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Factors Associated with Prevalent Hepatitis C Infection Among HIV-Infected Women with No Reported History of Injection Drug Use: The Women's Interagency HIV Study (WIHS)

AIDS Patient Care and STDs , Vol. 0, No. 0.

A Study of HIV Provider Attitudes Toward HLA-B*5701 Testing in the United States

AIDS Patient Care and STDs , Vol. 0, No. 0.

The Use of Second-Generation Antipsychotics and the Changes in Physical Growth in Children and Adolescents with Perinatally Acquired HIV

AIDS Patient Care and STDs , Vol. 0, No. 0.

Hepatitis C Virus Is Infrequently Evaluated and Treated in an Urban HIV Clinic Population

AIDS Patient Care and STDs , Vol. 0, No. 0.

Change in Quality of Life after Being Diagnosed with HIV: A Multicenter Longitudinal Study

AIDS Patient Care and STDs , Vol. 0, No. 0.

HIV Prevention Interventions in Chennai, India: Are Men Who Have Sex with Men Being Reached?

AIDS Patient Care and STDs , Vol. 0, No. 0.

Disclosure of Complementary and Alternative Medicine Use to Health Care Providers among HIV-Infected Women

AIDS Patient Care and STDs , Vol. 0, No. 0.

Barriers to Free Antiretroviral Treatment Access for Female Sex Workers in Chennai, India

AIDS Patient Care and STDs , Vol. 0, No. 0.

An Evidence-Based Review of Treatment-Related Determinants of Patients' Nonadherence to HIV Medications

AIDS Patient Care and STDs , Vol. 0, No. 0.

Early Patterns of Adherence in Adolescents Initiating Highly Active Antiretrovial Therapy Predict Long-Term Adherence, Virologic, and Immunologic Control

AIDS Patient Care and STDs Oct 2009, Vol. 23, No. 10: 799-801.

Antiretroviral Adherence and Pharmacokinetics: Review of Their Roles in Sustained Virologic Suppression

AIDS Patient Care and STDs Oct 2009, Vol. 23, No. 10: 803-807.

Cardiovascular Risk Assessment in Antiretroviral-Naïve HIV Patients

AIDS Patient Care and STDs Oct 2009, Vol. 23, No. 10: 809-813.

Long-Term Combination Antiretroviral Therapy Is Associated with the Risk of Coronary Plaques in African Americans with HIV Infection

AIDS Patient Care and STDs Oct 2009, Vol. 23, No. 10: 815-824.

Health System and Personal Barriers Resulting in Decreased Utilization of HIV and STD Testing Services among At-Risk Black Men Who Have Sex with Men in Massachusetts

AIDS Patient Care and STDs Oct 2009, Vol. 23, No. 10: 825-835.

Does Self-Report Data on HIV Primary Care Utilization Agree with Medical Record Data for Socially Marginalized Populations in the United States?

AIDS Patient Care and STDs Oct 2009, Vol. 23, No. 10: 837-843.

HIV-Specific Health Care Utilization and Mortality among Tuberculosis/HIV Coinfected Persons

AIDS Patient Care and STDs Oct 2009, Vol. 23, No. 10: 845-851.

Changes in At-Risk Behavior for HIV Infection among HIV-Positive Persons in Italy

AIDS Patient Care and STDs Oct 2009, Vol. 23, No. 10: 853-858.

HIV-Infected Adults from Minority Ethnic Groups Are Willing to Participate in Research If Asked

AIDS Patient Care and STDs Oct 2009, Vol. 23, No. 10: 859-865.

Barriers to Access to Antiretroviral Treatment in Mozambique, as Perceived by Patients and Health Workers in Urban and Rural Settings

AIDS Patient Care and STDs Oct 2009, Vol. 23, No. 10: 867-875.

Consequences of Drug Abuse and HIV/AIDS in China: Recommendations for Integrated Care of HIV-Infected Drug Users

AIDS Patient Care and STDs Oct 2009, Vol. 23, No. 10: 877-884.

Egocentric Networks of Chinese Men Who Have Sex with Men: Network Components, Condom Use Norms, and Safer Sex

AIDS Patient Care and STDs Oct 2009, Vol. 23, No. 10: 885-893.

Antiviral Briefs

AIDS Patient Care and STDs Oct 2009, Vol. 23, No. 10: 895-897.

HIV/AIDS and STD Updates

AIDS Patient Care and STDs Oct 2009, Vol. 23, No. 10: 899-901.

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Towards Reducing Disparities in Disparities Research

Discovery Properties of Genome-wide Association Signals From Cumulatively Combined Data Sets

Genetic effects for common variants affecting complex disease risk are subtle. Single genome-wide association (GWA) studies are typically underpowered to detect these effects, and combination of several GWA data sets is needed to enhance discovery. The authors investigated the properties of the discovery process in simulated cumulative meta-analyses of GWA study-derived signals allowing for potential genetic model misspecification and between-study heterogeneity. Variants with null effects on average (but also between-data set heterogeneity) could yield false-positive associations with seemingly homogeneous effects. Random effects had higher than appropriate false-positive rates when there were few data sets. The log-additive model had the lowest false-positive rate. Under heterogeneity, random-effects meta-analyses of 2–10 data sets averaging 1,000 cases/1,000 controls each did not increase power, or the meta-analysis was even less powerful than a single study (power desert). Upward bias in effect estimates and underestimation of between-study heterogeneity were common. Fixed-effects calculations avoided power deserts and maximized discovery of association signals at the expense of much higher false-positive rates. Therefore, random- and fixed-effects models are preferable for different purposes (fixed effects for initial screenings, random effects for generalizability applications). These results may have broader implications for the design and interpretation of large-scale multiteam collaborative studies discovering common gene variants.

Meta- and Pooled Analyses of the Methylenetetrahydrofolate Reductase (MTHFR) C677T Polymorphism and Colorectal Cancer: A HuGE-GSEC Review

Worldwide, over 1 million cases of colorectal cancer (CRC) were reported in 2002, with a 50% mortality rate, making CRC the second most common cancer in adults. Certain racial/ethnic populations continue to experience a disproportionate burden of CRC. A common polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene has been associated with a lower risk of CRC. The authors performed both a meta-analysis (29 studies; 11,936 cases, 18,714 controls) and a pooled analysis (14 studies; 5,068 cases, 7,876 controls) of the C677T MTHFR polymorphism and CRC, with stratification by racial/ethnic population and behavioral risk factors. There were few studies on different racial/ethnic populations. The overall meta-analysis odds ratio for CRC for persons with the TT genotype was 0.83 (95% confidence interval (CI): 0.77, 0.90). An inverse association was observed in whites (odds ratio = 0.83, 95% CI: 0.74, 0.94) and Asians (odds ratio = 0.80, 95% CI: 0.67, 0.96) but not in Latinos or blacks. Similar results were observed for Asians, Latinos, and blacks in the pooled analysis. The inverse association between the MTHFR 677TT polymorphism and CRC was not significantly modified by smoking status or body mass index; however, it was present in regular alcohol users only. The MTHFR 677TT polymorphism seems to be associated with a reduced risk of CRC, but this may not hold true for all populations.

Genetic Variations in Xenobiotic Metabolic Pathway Genes, Personal Hair Dye Use, and Risk of Non-Hodgkin Lymphoma

From 1996 to 2000, the authors conducted a population-based case-control study among Connecticut women to test the hypothesis that genetic variation in xenobiotic metabolic pathway genes modifies the relation between hair dye use and risk of non-Hodgkin lymphoma. No effect modifications were found for women who started using hair dyes in 1980 or afterward. For women who started using hair dye before 1980 as compared with never users, a statistically significantly increased risk of non-Hodgkin lymphoma was found for carriers of CYP2C9 Ex3-52C>T TT/CT genotypes (odds ratio (OR) = 2.9, 95% confidence interval (CI): 1.4, 6.1), CYP2E1 -332T>A AT/AA genotypes (OR = 2.0, 95% CI: 1.2, 3.4), a homozygous or heterozygous 3-base-pair deletion in intron 6 of GSTM3 (OR = 2.3, 95% CI: 1.3, 4.1), GSTP1 Ex5-24A>G AA genotypes (OR = 1.8, 95% CI: 1.1, 2.9), or NAT2 genotypes conferring intermediate/rapid acetylator status (OR = 1.6, 95% CI: 1.0, 2.7). The observed associations were mainly seen for follicular lymphoma. In contrast, no significantly increased risk was observed for starting hair dye use before 1980 (relative to never use) among women who were homozygous wild-type for the CYP2C9, CYP2E1, or GSTM3 polymorphisms, women carrying 1 or 2 copies of the variant GSTP1 allele, or women who were slow NAT2 acetylators. A possible role of genetic variation in xenobiotic metabolism in the carcinogenicity of hair dye use needs to be confirmed in larger studies.

Body Size, Recreational Physical Activity, and B-Cell Non-Hodgkin Lymphoma Risk Among Women in the California Teachers Study

Nutritional status and physical activity are known to alter immune function, which may be relevant to lymphomagenesis. The authors examined body size measurements and recreational physical activity in relation to risk of B-cell non-Hodgkin lymphoma (NHL) in the prospective California Teachers Study. Between 1995 and 2007, 574 women were diagnosed with incident B-cell NHL among 121,216 eligible women aged 22–84 years at cohort entry. Multivariable-adjusted relative risks and 95% confidence intervals were estimated by fitting Cox proportional hazards models for all B-cell NHL combined and for the 3 most common subtypes: diffuse large B-cell lymphoma, follicular lymphoma, and B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma. Height was positively associated with risk of all B-cell NHLs (for >1.70 vs. 1.61–1.65 m, relative risk = 1.50, 95% confidence interval: 1.16, 1.96) and chronic lymphocytic leukemia/small lymphocytic lymphoma (relative risk = 1.93, 95% confidence interval: 1.09, 3.41). Weight and body mass index at age 18 years were positive predictors of B-cell NHL risk overall. These findings indicate that greater height, which may reflect genetics, early life immune function, infectious exposures, nutrition, or growth hormone levels, may play a role in NHL etiology. Adiposity at age 18 years may be more relevant to NHL etiology than that in later life.

Genetic Variation in the Progesterone Receptor and Metabolism Pathways and Hormone Therapy in Relation to Breast Cancer Risk

The relevance of progesterone to breast carcinogenesis is highlighted by evidence indicating that use of combined estrogen-progesterone therapy (EPT) is more strongly related to breast cancer risk than is use of unopposed estrogen therapy. However, few investigators have assessed how genetic variation in progesterone-related genes modifies the effect of EPT on risk. In an analysis combining data from 2 population-based case-control studies of postmenopausal breast cancer (1,296 cases and 1,055 controls) conducted in Washington State in 1997–1999 and 2000–2004, the authors evaluated how 51 single nucleotide polymorphisms in 7 progesterone-related genes (AKR1C1, AKR1C2, AKR1C3, CYP3A4, SRD5A1, SRD5A2, and PGR) influenced breast cancer risk. There was no appreciable association with breast cancer risk overall for any single nucleotide polymorphism. For rs2854482 in AKR1C2, carrying 1 or 2 A alleles was associated with a 2.0-fold increased breast cancer risk in EPT users (95% confidence interval: 1.0, 4.0) but not in never users (Pheterogeneity = 0.03). For rs12387 in AKR1C3, the presence of 1 or 2 G alleles was associated with a 1.5-fold increased risk among EPT users (95% confidence interval: 1.1, 2.2) but not in never users (Pheterogeneity = 0.02). Interpretation of these subgroup associations must await the results of similar studies conducted in other populations.

Physical Activity's Impact on the Association of Fat and Fiber Intake With Survival After Breast Cancer

This study examined whether, after a breast cancer diagnosis, high intake of animal fat was associated with increased breast cancer mortality and high intake of fiber was associated with decreased breast cancer mortality. Participants were 3,846 US female nurses diagnosed with stages I–III breast cancer between 1976 and 2001 and followed until death or May 2006. Breast cancer mortality was calculated according to dietary intake quintiles first assessed at least 12 months after diagnosis and was cumulatively averaged and updated. There were 446 breast cancer deaths. In simple models adjusted for time since diagnosis, age, and energy intake, animal fat intake was associated with increased breast cancer death, and cereal fiber intake was associated with reduced breast cancer death. However, no associations were found in fully adjusted models: for animal fat, the relative risks for increasing quintiles were 1.00, 0.89, 0.86, 0.85, and 0.89 (95% confidence interval: 0.61, 1.28), P = 0.68; for cereal fiber, they were 1.00, 0.95, 0.76, 0.81, and 1.00 (95% confidence interval: 0.71, 1.40), P = 0.59. Results of simple models adjusted additionally for physical activity were similar to those for full multivariate models. Results show that physical activity strongly confounds the association between diet and survival.

Postmenopausal Breast Cancer Risk and Dietary Patterns in the E3N-EPIC Prospective Cohort Study

Since evidence relating diet to breast cancer risk is not sufficiently consistent to elaborate preventive proposals, the authors examined the association between dietary patterns and breast cancer risk in a large French cohort study. The analyses included 2,381 postmenopausal invasive breast cancer cases diagnosed during a median 9.7-year follow-up period (1993–2005) among 65,374 women from the E3N-EPIC cohort. Scores for dietary patterns were obtained by factor analysis, and breast cancer hazard ratios were estimated by Cox proportional hazards regression for the highest quartile of dietary pattern score versus the lowest. Two dietary patterns were identified: "alcohol/Western" (essentially meat products, French fries, appetizers, rice/pasta, potatoes, pulses, pizza/pies, canned fish, eggs, alcoholic beverages, cakes, mayonnaise, and butter/cream) and "healthy/Mediterranean" (essentially vegetables, fruits, seafood, olive oil, and sunflower oil). The first pattern was positively associated with breast cancer risk (hazard ratio = 1.20, 95% confidence interval (CI): 1.03, 1.38; P = 0.007 for linear trend), especially when tumors were estrogen receptor-positive/progesterone receptor-positive. The "healthy/Mediterranean" pattern was negatively associated with breast cancer risk (hazard ratio = 0.85, 95% CI: 0.75, 0.95; P = 0.003 for linear trend), especially when tumors were estrogen receptor-positive/progesterone receptor-negative. Adherence to a diet comprising mostly fruits, vegetables, fish, and olive/sunflower oil, along with avoidance of Western-type foods, may contribute to a substantial reduction in postmenopausal breast cancer risk.

Association of Perfluorooctanoic Acid and Perfluorooctane Sulfonate With Serum Lipids Among Adults Living Near a Chemical Plant

Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are compounds that do not occur in nature but have been widely used since World War II and persist indefinitely in the environment. They are present in the serum of Americans with median levels of 4 ng/mL and 21 ng/mL, respectively. PFOA has been positively associated with cholesterol in several studies of workers. A cross-sectional study of lipids and PFOA and PFOS was conducted among 46,294 community residents aged 18 years or above, who drank water contaminated with PFOA from a chemical plant in West Virginia. The mean levels of serum PFOA and PFOS in 2005–2006 were 80 ng/mL (median, 27 ng/mL) and 22 ng/mL (median, 20 ng/mL), respectively. All lipid outcomes except high density lipoprotein cholesterol showed significant increasing trends by increasing decile of either compound; high density lipoprotein cholesterol showed no association. The predicted increase in cholesterol from lowest to highest decile for either compound was 11–12 mg/dL. The odds ratios for high cholesterol (≥240 mg/dL), by increasing quartile of PFOA, were 1.00, 1.21 (95% confidence interval (CI): 1.12, 1.31), 1.33 (95% CI: 1.23, 1.43), and 1.40 (95% CI: 1.29, 1.51) and were similar for PFOS quartiles. Because these data are cross-sectional, causal inference is limited. Nonetheless, the associations between these compounds and lipids raise concerns, given their common presence in the general population.

Correlates of Multiple Chronic Disease Behavioral Risk Factors in Canadian Children and Adolescents

The authors assessed individual, social, and school correlates of multiple chronic disease behavioral risk factors (physical inactivity, sedentary behavior, tobacco smoking, alcohol drinking, and high body mass index) in a representative sample of Canadian youth aged 10–15 years (mean = 12.5 years) attending public schools. Cross-sectional data (n = 1,747) from cycle 4 (2000–2001) of the National Longitudinal Survey of Children and Youth were used. Ordinal regression models were constructed to investigate associations between selected covariates and multiple behavioral risk-factor levels (0/1, 2, 3, or 4/5 risk factors). Older age (odds ratio (OR) = 1.95, 95% confidence interval (CI): 1.21, 3.13), caregiver smoking (OR = 1.49, 95% CI: 1.09, 2.03), reporting that most/all of one's peers smoked (OR = 7.31, 95% CI: 4.00, 13.35) or drank alcohol (OR = 3.77, 95% CI: 2.18, 6.53), and living in a lone-parent family (OR = 1.94, 95% CI: 1.31, 2.88) increased the likelihood of having multiple behavioral risk factors. Youth with high self-esteem (OR = 0.92, 95% CI: 0.85, 0.99) and youth from families with postsecondary education (OR = 0.58, 95% CI: 0.41, 0.82) were less likely to have a higher number of risk factors. Although several individual and social characteristics were associated with multiple behavioral risk factors, no school-related correlates emerged. These variables should be considered when planning prevention programs.

The Aftermath of Hip Fracture: Discharge Placement, Functional Status Change, and Mortality

The authors prospectively explored the consequences of hip fracture with regard to discharge placement, functional status, and mortality using the Survey on Assets and Health Dynamics Among the Oldest Old (AHEAD). Data from baseline (1993) AHEAD interviews and biennial follow-up interviews were linked to Medicare claims data from 1993–2005. There were 495 postbaseline hip fractures among 5,511 respondents aged ≥69 years. Mean age at hip fracture was 85 years; 73% of fracture patients were white women, 45% had pertrochanteric fractures, and 55% underwent surgical pinning. Most patients (58%) were discharged to a nursing facility, with 14% being discharged to their homes. In-hospital, 6-month, and 1-year mortality were 2.7%, 19%, and 26%, respectively. Declines in functional-status-scale scores ranged from 29% on the fine motor skills scale to 56% on the mobility index. Mean scale score declines were 1.9 for activities of daily living, 1.7 for instrumental activities of daily living, and 2.2 for depressive symptoms; scores on mobility, large muscle, gross motor, and cognitive status scales worsened by 2.3, 1.6, 2.2, and 2.5 points, respectively. Hip fracture characteristics, socioeconomic status, and year of fracture were significantly associated with discharge placement. Sex, age, dementia, and frailty were significantly associated with mortality. This is one of the few studies to prospectively capture these declines in functional status after hip fracture.

Optimizing Influenza Sentinel Surveillance at the State Level

Influenza-like illness data are collected via an Influenza Sentinel Provider Surveillance Network at the state level. Because participation is voluntary, locations of the sentinel providers may not reflect optimal geographic placement. The purpose of this study was to determine the "best" locations for sentinel providers in Iowa by using a maximal coverage model (MCM) and to compare the population coverage obtained with that of the current sentinel network. The authors used an MCM to maximize the Iowa population located within 20 miles (32.2 km) of 1–143 candidate sites and calculated the coverage provided by each additional site. The first MCM location covered 15% of the population; adding a second increased coverage to 25%. Additional locations provided more coverage but with diminishing marginal returns. In contrast, the existing 22 Iowa sentinel locations covered 56% of the population, the same coverage achieved with just 10 MCM sites. Using 22 MCM sites covered more than 75% of the population, an improvement over the current site placement, adding nearly 600,000 Iowa residents. Given scarce public health resources, MCMs can help surveillance efforts by prioritizing recruitment of sentinel locations.

Analyses of Injury Count Data: Some Do's and Don'ts

The analysis of injury data requires different considerations from the analysis of other types of outcomes because an individual can experience the outcome many times. When describing injury patterns using numerator-only data (e.g., proportion of upper-extremity injuries vs. lower-extremity injuries), simple comparisons of proportions are inappropriate because 1) individuals are compared with themselves and 2) multiple testing increases the potential for incorrect inference. Bootstrapping (resampling) techniques can be used to determine confidence intervals and whether the frequencies significantly differ across categories. When describing injury rates, the authors suggest plotting the observed injury rate against the number of exposures to obtain a visual representation of the heterogeneity of risk across individuals. Because the distribution of injury rates is often skewed, some research questions may be best addressed by comparing the weighted median injury rates instead of the weighted mean injury rates (which are given by standard formulae). Again, resampling techniques can be used to obtain a null distribution for injury rates in order to determine whether there are subjects who have unexpectedly high injury rates. More advanced analyses are required to account for multiplicity.

Applying Quantitative Bias Analysis to Epidemiologic Data: By Timothy L. Lash, Matthew P. Fox, and Aliza K. Fink

Statistical Modeling for Biomedical Researchers: A Simple Introduction to the Analysis of Complex Data, 2nd Edition: By William D. Dupont

Re: "Determinants of Quality of Interview and Impact on Risk Estimates in a Case-Control Study of Bladder Cancer"

Three Authors Reply

Re: "Methods of Covariate Selection: Directed Acyclic Graphs and the Change-in-Estimate Procedure"

Three of the Authors Reply

Why do ineffective treatments seem helpful? A brief review

After any therapy, when symptoms improve, healthcare providers (and patients) are tempted to award credit to treatment. Over time, a particular treatment can seem so undeniably helpful that scientific verification of efficacy is judged an inconvenient waste of time and resources. Unfortunately, practitioners' accumulated, day-to-day, informal impressions of diagnostic reliability and clinical efficacy are of limited value. To help clarify why even treatments entirely lacking in direct effect can seem helpful, I will explain why real signs and symptoms often improve, independent of treatment. Then, I will detail quirks of human perception, interpretation, and memory that often make symptoms seem improved, when they are not. I conclude that healthcare will grow to full potential only when judgments of clinical efficacy routinely are based in properly scientific, placebo-controlled, outcome analysis.

Pain patterns and descriptions in patients with radicular pain: Does the pain necessarily follow a specific dermatome?

Background: It is commonly stated that nerve root pain should be expected to follow a specific dermatome and that this information is useful to make the diagnosis of radiculopathy. There is little evidence in the literature that confirms or denies this statement. The purpose of this study is to describe and discuss the diagnostic utility of the distribution of pain in patients with cervical and lumbar radicular pain. Methods: Pain drawings and descriptions were assessed in consecutive patients diagnosed with cervical or lumbar nerve root pain. These findings were compared with accepted dermatome maps to determine whether they tended to follow along the involved nerve root's dermatome. Results: Two hundred twenty-six nerve roots in 169 patients were assessed. Overall, pain related to cervical nerve roots was non-dermatomal in over two-thirds (69.7%) of cases. In the lumbar spine, the pain was non-dermatomal in just under two-thirds (64.1%) of cases. The majority of nerve root levels involved non-dermatomal pain patterns except C4 (60.0% dermatomal) and S1 (64.9% dermatomal). The sensitivity (SE) and specificity (SP) for dermatomal pattern of pain are low for all nerve root levels with the exception of the C4 level (Se 0.60, Sp 0.72) and S1 level (Se 0.65, Sp 0.80), although in the case of the C4 level, the number of subjects was small (n = 5). Conclusion: In most cases nerve root pain should not be expected to follow along a specific dermatome, and a dermatomal distribution of pain is not a useful historical factor in the diagnosis of radicular pain. The possible exception to this is the S1 nerve root, in which the pain does commonly follow the S1 dermatome.

Cervical spondylosis with spinal cord encroachment: should preventive surgery be recommended?

Background: It has been stated that individuals who have spondylotic encroachment on the cervical spinal cord without myelopathy are at increased risk of spinal cord injury if they experience minor trauma. Preventive decompression surgery has been recommended for these individuals. The purpose of this paper is to provide the non-surgical spine specialist with information upon which to base advice to patients. The evidence behind claims of increased risk is investigated as well as the evidence regarding the risk of decompression surgery. Methods: A literature search was conducted on the risk of spinal cord injury in individuals with asymptomatic cord encroachment and the risk and benefit of preventive decompression surgery. Results: Three studies on the risk of spinal cord injury in this population met the inclusion criteria. All reported increased risk. However, none were prospective cohort studies or case-control studies, so the designs did not allow firm conclusions to be drawn. A number of studies and reviews of the risks and benefits of decompression surgery in patients with cervical myelopathy were found, but no studies were found that addressed surgery in asymptomatic individuals thought to be at risk. The complications of decompression surgery range from transient hoarseness to spinal cord injury, with rates ranging from 0.3% to 60%. Conclusion: There is insufficient evidence that individuals with spondylotic spinal cord encroachment are at increased risk of spinal cord injury from minor trauma. Prospective cohort or case-control studies are needed to assess this risk. There is no evidence that prophylactic decompression surgery is helpful in this patient population. Decompression surgery appears to be helpful in patients with cervical myelopathy, but the significant risks may outweigh the unknown benefit in asymptomatic individuals. Thus, broad recommendations for decompression surgery in suspected at-risk individuals cannot be made. Recommendations to individual patients must consider possible unique circumstances.

The Nordic Maintenance Care Program: case management of chiropractic patients with low back pain - defining the patients suitable for various management strategies

Background: Maintenance care is a well known concept among chiropractors, although there is little knowledge about its exact definition, its indications and usefulness. As an initial step in a research program on this phenomenon, it was necessary to identify chiropractors' rationale for their use of maintenance care. Previous studies have identified chiropractors' choices of case management strategies in response to different case scenarios. However, the rationale for these management strategies is not known. In other words, when presented with both the case, and different management strategies, there was consensus on how to match these, but if only the management strategies were provided, would chiropractors be able to define the cases to fit these strategies? The objective with this study was to investigate if there is a common pattern in Finnish chiropractors' case management of patients with low back pain (LBP), with special emphasis on long-term treatment. Methods: Information was obtained in a structured workshop. Fifteen chiropractors, members of the Finnish Chiropractors' Union, and present at the general assembly, participated throughout the entire workshop session. These were divided into five teams each consisting of 3 people. A basic case of a patient with low back pain was presented together with six different management strategies undertaken after one month of treatment. Each team was then asked to describe one (or several) suitable case(s) for each of the six strategies, based on the aspects of 1) symptoms/findings, 2) the low back pain history in the past year, and 3) other observations. After each session the people in the groups were changed. Responses were collected as key words on flip-over boards. These responses were grouped and counted. Results: There appeared to be consensus among the participants in relation to the rationale for at least four of the management strategies and partial consensus on the rationale for the remaining two. In relation to maintenance care, the patient's past history was important but also the doctor-patient relationship. Conclusion: These results confirm that there is a pattern among Nordic chiropractors in how they manage patients with LBP. More information is needed to define the "cut-point" for the indication of prolonged care.

Cervicocephalic kinesthetic sensibility and postural balance in patients with nontraumatic chronic neck pain - a pilot study

Background: Although cervical pain is widespread, most victims are only mildly and occasionally affected. A minority, however, suffer chronic pain and/or functional impairments. Although there is abundant literature regarding nontraumatic neck pain, little focuses on diagnostic criteria. During the last decade, research on neck pain has been designed to evaluate underlying pathophysiological mechanisms, without noteworthy success. Independent researchers have investigated postural balance and cervicocephalic kinesthetic sensibility among patients with chronic neck pain, and have (in most cases) concluded the source of the problem is a reduced ability in the neck's proprioceptive system. Here, we investigated cervicocephalic kinesthetic sensibility and postural balance among patients with nontraumatic chronic neck pain. Methods: Ours was a two-group, observational pilot study of patients with complaints of continuous neck pain during the 3 months prior to recruitment. Thirteen patients with chronic neck pain of nontraumatic origin were recruited from an institutional outpatient clinic. Sixteen healthy persons were recruited as a control group. Cervicocephalic kinesthetic sensibility was assessed by exploring head repositioning accuracy and postural balance was measured with computerized static posturography. Results: Parameters of cervicocephalic kinesthetic sensibility were not reduced. However, in one of six test movements (flexion), global repositioning errors were significantly larger in the experimental group than in the control group (p < .05). Measurements did not demonstrate any general impaired postural balance, and varied substantially among participants in both groups. Conclusion: In patients with nontraumatic chronic neck pain, we found statistically significant global repositioning errors in only one of six test movements. In this cohort, we found no evidence of impaired postural balance.Head repositioning accuracy and computerized static posturography are imperfect measures of functional proprioceptive impairments. Validity of (and procedures for using) these instruments demand further investigation.Trial registrationCurrent Controlled Trials ISRCTN96873990

The Nordic Maintenance Care Program - An interview study on the use of maintenance care in a selected group of Danish chiropractors

Background: Although maintenance care appears to be relatively commonly used among chiropractors, the indications for its use are incompletely understood. A questionnaire survey was recently carried out among Swedish chiropractors in order to identify their choice of various management strategies, including maintenance care. That study revealed a common pattern of choice of strategies. However, it would be necessary to verify these findings in another study population and to obtain some additional information best collected through an interview.ObjectivesThe main aim of the present study was to attempt to reproduce the findings in the Swedish study and to obtain more information on the use of maintenance care.MethodA group of 11 chiropractors were selected because they used maintenance care. They were interviewed using the questionnaire from the previous Swedish survey. The questionnaire consisted of a simple description of a hypothetical patient with low back pain and nine possible ways in which the case could develop ("scenarios"). They could choose between six different management strategies for each scenario. In addition, the chiropractors were encouraged to provide their own definition of maintenance care in an open-ended question. Interviews were taped, transcribed and analyzed. For the open-ended question, statements were identified relating to six pre hoc defined topics on the inclusion criteria/rationale for maintenance care, the frequency of treatments, and the duration of the maintenance care program. Results: The open-ended question revealed that in patients with low back pain, maintenance care appears to be offered to prevent new events. The rationale was to obtain optimal spinal function. There appears to be no common convention on the frequency of treatments and duration of the treatment program was not mentioned by any of the interviewees. Conclusion: The results from the questionnaire in the Danish survey showed that the response pattern for the nine scenarios was similar to that obtained in the Swedish survey. There seems to be relative agreement between chiropractors working in different countries and sampled through different methods in relation to their choice of management strategies in patients with low back pain. However, more precise information is needed on the indications for maintenance care and its treatment program, before proceeding to studying its clinical validity.

A demographic and epidemiological study of a Mexican chiropractic college public clinic

Background: Descriptive studies of chiropractic patients are not new, several have been performed in the U.S., Australia, Canada, and Europe. None have been performed in a Latin American country. The purpose of this study is to describe the patients who visited a Mexican chiropractic college public clinic with respect to demographics and clinical characteristics. Methods: This study was reviewed and approved by the IRB of Parker College of Chiropractic and the Universidad Estatal del Valle de Ecatepec (UNEVE). Five hundred patient files from the UNEVE public clinic from May 2005 to May 2007 were selected from an approximate total number of 3,700. Information was collected for demographics, chief complaints, associated complaints, and previous care sought. Results: The sample comprised 306 (61.2%) female. Most files (44.2%) were in the age range of 40–59 years (mean of 43.4 years). The most frequent complaints were lumbar pain (29.2%) and extremity pain (28.0%), most commonly the knee. Most (62.0%) described their complaints as greater than one year. Trauma (46.6%) was indicated as the initial cause. Mean VAS score was 6.26/10 with 20% rated at 8/10. Conclusion: Demographic results compared closer to studies conducted with private clinicians (females within the ages of 40–59). The primary complaint and duration was similar to previous studies (low back pain and chronic), except in this population the cause was usually initiated by trauma. The most striking features were the higher number of extremity complaints and the marked increased level of VAS score (20% rated as 8/10).

How to select a chiropractor for the management of athletic conditions

Background: Chiropractors are an integral part of the management of musculoskeletal injuries. A considerable communication gap between the chiropractic and medical professions exists. Subsequently referring allopathic practitioners lack confidence in picking a chiropractic practitioner with appropriate management strategies to adequately resolve sporting injuries. Subsequently, the question is often raised: "how do you find a good chiropractor?".DiscussionBest practice guidelines are increasingly suggesting that musculoskeletal injuries should be managed with multimodal active and passive care strategies. Broadly speaking chiropractors may be subdivided into "modern multimodal" or "classical" (unimodal) in nature. The modern multimodal practitioner is better suited to managing sporting injuries by incorporating passive and active care management strategies to address three important phases of care in the continuum of injury from the acute inflammation/pain phase to the chronic/rehabilitation phase to the injury prevention phase. In contrast, the unimodal, manipulation only and typically spine only approach of the classical practitioner seems less suited to the challenges of the injured athlete. Identifying what part of the philosophical management spectrum a chiropractor falls is important as it is clearly not easily evident in most published material such as Yellow Pages advertisements.SummaryIdentifying a chiropractic practitioner who uses multimodal treatment of adequate duration, who incorporates active and passive components of therapy including exercise prescription whilst using medical terminology and diagnosis without mandatory x-rays or predetermined treatment schedules or prepaid contracts of care will likely result in selection of a chiropractor with the approach and philosophy suited to appropriately managing athletic conditions. Sporting organizations and associations should consider using similar criteria as a minimum standard to allow participation in health care team selections.

The clinical aspects of the acute facet syndrome: results from a structured discussion among European chiropractors

Background: The term 'acute facet syndrome' is widely used and accepted amongst chiropractors, but poorly described in the literature, as most of the present literature relates to chronic facet joint pain. Therefore, research into the degree of consensus on the subject amongst a large group of chiropractic practitioners was seen to be a useful contribution. Methods: During the annual congress of The European Chiropractors Union (ECU) in 2008, the authors conducted a workshop involving volunteer chiropractors. Topics were decided upon in advance, and the participants were asked to form into groups of four or five. The groups were asked to reach consensus on several topics relating to a basic case of a forty-year old man, where an assumption was made that his pain originated from the facet joints. First, the participants were asked to agree on a maximum of three keywords on each of four topics relating to the presentation of pain: 1. location, 2. severity, 3. aggravating factors, and 4. relieving factors. Second, the groups were asked to agree on three orthopaedic and three chiropractic tests that would aid in diagnosing pain from the facet joints. Finally, they were asked to agree on the number, frequency and duration of chiropractic treatment. Results: Thirty-four chiropractors from nine European countries participated. They described the characteristics of an acute, uncomplicated facet syndrome as follows: local, ipsilateral pain, occasionally extending into the thigh with pain and decreased range of motion in extension and rotation both standing and sitting. They thought that the pain could be relieved by walking, lying with knees bent, using ice packs and taking non-steroidal anti-inflammatory drugs, and aggravated by prolonged standing or resting. They also stated that there would be no signs of neurologic involvement or antalgic posture and no aggravation of pain from sitting, flexion or coughing/sneezing. Conclusion: The chiropractors attending the workshop described the characteristics of an acute, uncomplicated lumbar facet syndrome in much the same way as chronic pain from the facet joints has been described in the literature. Furthermore, the acute, uncomplicated facet syndrome was considered to have an uncomplicated clinical course, responding quickly to spinal manipulative therapy.

The Nordic Maintenance Care Program: when do chiropractors recommend secondary and tertiary preventive care for low back pain?

Background: Among chiropractors the use of long-term treatment is common, often referred to as "maintenance care". Although no generally accepted definition exists, the term has a self-explanatory meaning to chiropractic clinicians. In public health terms, maintenance care can be considered as both secondary and tertiary preventive care. The objective of this study was to explore what factors chiropractors consider before recommending maintenance care to patients with low back pain (LBP).MethodStructured focus group discussions with Swedish chiropractors were used to discuss pre-defined cases. A questionnaire was then designed on the basis of the information obtained. In the questionnaire, respondents were asked to grade the importance of several factors when considering recommending maintenance care to a patient. The grading was done on a straight line ranging from "Very important" to "Not at all important". All members of the Swedish Chiropractors' Association (SCA) were invited to participate in the discussions and in the questionnaire survey. Results: Thirty-six (22%) of SCA members participated in the group discussions and 129 (77%) returned the questionnaires. Ninety-eight percent of the questionnaire respondents claimed to believe that chiropractic care can prevent future relapses of back pain. According to the group discussions tertiary preventive care would be considered appropriate when a patient improves by 75% or more. According to the results of the questionnaire survey, two factors were considered as "very important" by more than 70% of the respondents in recommending secondary preventive care, namely frequency past year and frequency past 10 years of the low back pain problem. Eight other factors were considered "very important" by 50–69% of the respondents, namely duration (over the past year and of the present attack), treatment (effect and durability), lifestyle, work conditions, and psychosocial factors (including attitude). Conclusion: The vast majority of our respondents believe that chiropractic treatment can prevent relapses of back pain. When recommending secondary preventive care, past frequency of the problem is considered. For tertiary preventive care, the patient needs to improve considerably before a recommendation of maintenance care is made.

Rapid Molecular Detection of Opisthorchis viverrini in Human Fecal Samples by Real-Time Polymerase Chain Reaction.

Rapid Molecular Detection of Opisthorchis viverrini in Human Fecal Samples by Real-Time Polymerase Chain Reaction. Am J Trop Med Hyg. 2009 Nov;81(5):917-20 Authors: Intapan PM, Thanchomnang T, Lulitanond V, Pongsaskulchoti P, Maleewong W Real-time fluorescence resonance energy transfer (FRET) polymerase chain reaction (PCR) supplemented with melting curve analysis is a highly sensitive and fast method offering a high throughput. We report the development of a real-time FRET PCR for molecular detection of Opisthorchis viverrini in human fecal samples. The diagnostic sensitivity, specificity, accuracy, and positive and negative predictive values of this method were 97.5%, 100%, 98.9%, 100%, and 98.2%, respectively. The sensitivity was not significantly different from that of the quantified formalin-ethyl acetate concentration technique, the gold standard (P > 0.05). The procedure has potential for diagnosis of human opisthorchiasis in disease-endemic areas, for large epidemiologic investigations involving at risk populations, and monitoring eradication programs of the liver fluke, which causes hepatobiliary diseases and induces cholangiocarcinoma. PMID: 19861632 [PubMed - in process]

Immunologic profiles of persons recruited for a randomized, placebo-controlled clinical trial of hookworm infection.

Immunologic profiles of persons recruited for a randomized, placebo-controlled clinical trial of hookworm infection. Am J Trop Med Hyg. 2009 Nov;81(5):911-6 Authors: Blount D, Hooi D, Feary J, Venn A, Telford G, Brown A, Britton J, Pritchard D Data from epidemiologic studies suggest that hookworm infections, in establishing an immunologic phenotype conducive to parasite survival, may protect against the development of allergic disease. We describe immunologic findings from a clinical study designed to investigate the safety of iatrogenic hookworm infection in participants with allergic rhinitis. The low, relatively safe level of hookworm infection used in this study was immunogenic, inducing eosinophilia and a significant specific IgG response. Importantly, no potentiation of IgE responses to the environmental allergens to which the participants were sensitized was seen. However, no evidence of systemic immune regulation was seen in infected participants. This finding may indicate that the level of infection or the frequency of infection may have to be altered in future trials to induce a therapeutically conducive immunologic phenotype. PMID: 19861631 [PubMed - in process]

Prevalence of Leptospira spp. in Urban Rodents from a Groceries Trade Center of Medellin, Colombia.

Prevalence of Leptospira spp. in Urban Rodents from a Groceries Trade Center of Medellin, Colombia. Am J Trop Med Hyg. 2009 Nov;81(5):906-10 Authors: Agudelo-Flórez P, Londoño AF, Quiroz VH, Angel JC, Moreno N, Loaiza ET, Muñoz LF, Rodas JD Leptospirosis is a widely distributed zoonosis, and rats are its most common source of infection. Our goal was to determine the frequency for Leptospira infection in rodents in a farmers market in the city of Medellin. We performed a descriptive transversal study sampling 254 rodents. Rodents were bled and killed, and kidneys samples were taken. Supernatants of macerated kidneys were cultured on Fletcher medium. Microagglutination tests (MATs) with 11 serovars were also carried out in rat serum, and a polymerase chain reaction (PCR) specific for pathogenic species was used to test each bacterial culture. All animals were identified as Rattus norvegicus; 25% and 20% were positive by MAT and culture, respectively. PCR tests of 12 isolates were positive for pathogenic serovars, and 4 of them were confirmed as L. interrogans by sequencing. These data show the role of this natural carrier and shedder of pathogenic leptospires in the epidemiology of urban leptospirosis in Colombia. PMID: 19861630 [PubMed - in process]

Micro-Positron Emission Tomography in the Evaluation of Trypanosoma cruzi-Induced Heart Disease: Comparison with Other Modalities.

Micro-Positron Emission Tomography in the Evaluation of Trypanosoma cruzi-Induced Heart Disease: Comparison with Other Modalities. Am J Trop Med Hyg. 2009 Nov;81(5):900-5 Authors: Prado CM, Fine EJ, Koba W, Zhao D, Rossi MA, Tanowitz HB, Jelicks LA Noninvasive assessment of cardiac structure and function is essential to understand the natural course of murine infection with Trypanosoma cruzi. Magnetic resonance imaging (MRI) and echocardiography have been used to monitor anatomy and function; positron emission tomography (PET) is ideal for monitoring metabolic events in the myocardium. Mice infected with T. cruzi (Brazil strain) were imaged 15-100 days post infection (dpi). Quantitative (18)F-FDG microPET imaging, MRI and echocardiography were performed and compared. Tracer ((18)F-FDG) uptake was significantly higher in infected mice at all days of infection, from 15 to 100 dpi. Dilatation of the right ventricular chamber was observed by MRI from 30 to 100 dpi in infected mice. Echocardiography revealed significantly reduced ejection fraction by 60 dpi. Combination of these three complementary imaging modalities makes it possible to noninvasively quantify cardiovascular function, morphology, and metabolism from the earliest days of infection through the chronic phase. PMID: 19861629 [PubMed - in process]

Long-Term Relapse Risk of Multibacillary Leprosy after Completion of 2 Years of Multiple Drug Therapy (WHO-MDT) in Cebu, Philippines.

Long-Term Relapse Risk of Multibacillary Leprosy after Completion of 2 Years of Multiple Drug Therapy (WHO-MDT) in Cebu, Philippines. Am J Trop Med Hyg. 2009 Nov;81(5):895-9 Authors: Balagon MF, Cellona RV, Cruz ED, Burgos JA, Abalos RM, Walsh GP, Saunderson PR, Walsh DS From 1987 to 1994, we enrolled 500 subjects completing 2-year WHO multiple drug therapy (MDT) for multibacillary leprosy in a prospective relapse study. Relapse was defined as new skin lesions and an increase in the bacterial index (BI) >/= 2+ (>/= 100x) at any single slit-skin smear site. At the study end in 2006, follow-up was 6,401 subject-years, a mean of 12.8 years/subject. We observed 23 relapses, 6-16 years after MDT (mean, 10.5 years; 95% confidence interval [CI], 9.2-11.8), peaking in Years 11-12 (> 1%/year). The cumulative risk was 6.6% (95% CI, 5.0-8.2%). In a subset of 181 subjects with pre-MDT average BI >/= 4+, 11 relapses occurred (cumulative risk, 10.1%). In mouse footpad assays, Mycobacterium leprae from relapsed subjects were rifampin and clofazimine sensitive. Taken together, the data suggest relapses are related to activation of dormant organisms (persisters) not killed by MDT rather than new infection. PMID: 19861628 [PubMed - in process]

Persistence of Mycobacterium ulcerans Disease (Buruli Ulcer) in the Historical Focus of Kasongo Territory, the Democratic Republic of Congo.

Persistence of Mycobacterium ulcerans Disease (Buruli Ulcer) in the Historical Focus of Kasongo Territory, the Democratic Republic of Congo. Am J Trop Med Hyg. 2009 Nov;81(5):888-894 Authors: Suykerbuyk P, Wambacq J, Phanzu DM, Haruna H, Nakazawa Y, Ooms K, Kamango K, Stragier P, Singa JN, Ekwanzala F, De Herdt E, De Maeyer P, Kestens L, Portaels F Fifty years after the last report of Mycobacterium ulcerans infections (Buruli ulcer [BU]) in Kasongo Territory, Maniema Province, Democratic Republic of Congo (DRC), we conducted a small-scale cross-sectional survey to assess if this historical BU focus was still active and if so to explore the disease epidemiology. Seventy-five active and inactive BU cases were identified on clinical grounds of which two of 28 BU active cases were laboratory confirmed. We used a modified BU02 form to reconstruct the local disease dynamics and we believe that the horrific conflict in eastern DRC and exceptional flooding were the most likely causes of the re-emergence of the disease. There is a need in the DRC to decentralize and integrate surveillance and control activities at local level to increase the effectiveness of patient management. PMID: 19861627 [PubMed - as supplied by publisher]

Household characteristics associated with handwashing with soap in rural bangladesh.

Household characteristics associated with handwashing with soap in rural bangladesh. Am J Trop Med Hyg. 2009 Nov;81(5):882-7 Authors: Luby SP, Halder AK, Tronchet C, Akhter S, Bhuiya A, Johnston RB Handwashing with soap prevents diarrhea and respiratory disease, but it is rarely practiced in high-need settings. Among 100 randomly selected villages in rural Bangladesh, field workers enrolled 10 households per village and observed and recorded household activities for 5 hours. Field workers observed 761 handwashing opportunities among household members in 527 households who had just defecated or who cleaned a child's anus who had defecated. In the final multivariate analysis, having water available at the place to wash hands after toileting (odds ratio = 2.2, 95% confidence interval 1.3, 4.0) and having soap available at the place to wash hands after toileting (odds ratio = 2.1, 95% confidence interval 1.3, 3.4) were associated with washing both hands with soap after fecal contact. Interventions that improve the presence of water and soap at the designated place to wash hands would be expected to improve handwashing behavior and health. PMID: 19861626 [PubMed - in process]

Population seroprevalence of hepatitis e virus antibodies in rural bangladesh.

Population seroprevalence of hepatitis e virus antibodies in rural bangladesh. Am J Trop Med Hyg. 2009 Nov;81(5):875-81 Authors: Labrique AB, Zaman K, Hossain Z, Saha P, Yunus M, Hossain A, Ticehurst J, Nelson KE Hepatitis E virus (HEV) causes a substantial burden of sporadic and epidemic disease worldwide. HEV infections result in serious morbidity and mortality, especially among pregnant women, and have significant economic costs. Few population-based studies have characterized the epidemiology of HEV. A rural Bangladeshi population was studied to determine the age- and gender- specific population seroprevalence of antibodies to HEV. Of 1,134 specimens tested from a representative, random population sample, 255 (22.5%) were anti-HEV IgG seropositive. Seroprevalence was lower among women (19.7%) than among men (25.8%). We found anti-HBc (hepatitis B core) in 380 of 1080(35.2%) tested, anti-HCV (hepatitis C) in 14 of 917(1.5%) tested, and anti-HAV (hepatitis A) in 116 of 124(93.5%) tested individuals. Our data suggest that viral hepatitis, especially HEV, remains an under-recognized and significant public health problem in rural Bangladeshi populations, warranting further attention. PMID: 19861625 [PubMed - in process]

Coverage of and Influences on Timely Administration of Hepatitis B Vaccine Birth Dose in Remote Rural Areas of the People's Republic of China.

Coverage of and Influences on Timely Administration of Hepatitis B Vaccine Birth Dose in Remote Rural Areas of the People's Republic of China. Am J Trop Med Hyg. 2009 Nov;81(5):869-74 Authors: Zhou Y, Wang H, Zheng J, Zhu X, Xia W, Hipgrave DB A survey was conducted in 2006 to assess the coverage and timeliness of the birth dose of hepatitis B vaccine (HepB(1)) and related influences among children in rural areas of Guangxi, Guizhou, Tibet, and Shaanxi provinces, People's Republic of China. A total of 3,390 children born in 2004 were surveyed in four counties in each province, where a project to strengthen routine immunization is being implemented by the China Ministry of Health, supported by the United National Children's Fund. Two-stage stratified cluster sampling was undertaken to select those surveyed. A questionnaire was administered to parents or guardians and vaccination records were assessed. HepB(1) administration was timely for 31.6% of the sample. Timeliness of HepB(1) for children delivered at home (13%) was lower than for children born at county-level or higher facilities (54%) (odds ratio [OR] = 6.52, (95% confidence interval [CI] = 5.29-8.04, P < 10 (-3)), at township hospitals (49%, OR = 7.14, 95% CI = 5.68-8.98, P < 10 (-3)), or private clinics (59%, OR = 5.64, 95% CI = 3.68-8.64, P < 10 (-3)). Children of Tibetan (24.8%, OR = 0.16, 95% CI = 0.12-0.21, P < 10 (-4)), Zhuang (27.8%, OR = 0.73, 95% CI = 0.57-0.94, P < 0.02) or Meng, Miao, and Hui ethnicity (14.2%, OR = 0.36, 95% CI = 0.29-0.45, P < 10 (-4)) were less likely than children of Han ethnicity (33.2%) to have received a timely birth dose. Children lacking vaccination registration cards (OR = 0.64, 95% CI = 0.51-0.80, P < 10 (-4)) and children whose parents or guardians did not know the importance of timely HepB immunization (OR = 0.62, 95% CI = 0.46-0.84, P < 10 (-2)) were also less likely to have received a timely birth dose. Parental knowledge and prioritization of birth-dosing was low among children who did not receive it. The timeliness of HepB(1) should improve with increasing rates of hospital delivery, training of birth attendants, increasing staff and community awareness of the importance of the birth dose, and by focusing on vulnerable groups. PMID: 19861624 [PubMed - in process]

Chikungunya virus isolated from a returnee to Japan from sri lanka: isolation of two sub-strains with different characteristics.

Chikungunya virus isolated from a returnee to Japan from sri lanka: isolation of two sub-strains with different characteristics. Am J Trop Med Hyg. 2009 Nov;81(5):865-8 Authors: Lim CK, Nishibori T, Watanabe K, Ito M, Kotaki A, Tanaka K, Kurane I, Takasaki T A large-scale epidemic of chikungunya (CHIK) fever occurred in several Indian Ocean islands in 2004 and spread to India and Sri Lanka. In December 2006, a returnee to Japan from Sri Lanka developed an acute febrile illness. The patient was confirmed to have CHIK fever after reverse transcription-polymerase chain reaction, and specific IgM and IgG detection. CHIK virus was isolated from the serum specimen collected at the acute stage. The isolated virus developed two different sizes of plaques. Two sub-strains with different genetic and biological characteristics were obtained by plaque purification from one isolate. The entire genome was sequenced and phylogenetic analysis of the E1 genome showed that the sub-strains were of the Central/East African genotype, and were closely related to recent isolates in India. This is the first report of CHIK virus genome sequences isolated from a patient infected in Sri Lanka. PMID: 19861623 [PubMed - in process]

Phylogeny of Triatoma sherlocki (Hemiptera: Reduviidae: Triatominae) Inferred from Two Mitochondrial Genes Suggests Its Location Within the Triatoma brasiliensis Complex.

Phylogeny of Triatoma sherlocki (Hemiptera: Reduviidae: Triatominae) Inferred from Two Mitochondrial Genes Suggests Its Location Within the Triatoma brasiliensis Complex. Am J Trop Med Hyg. 2009 Nov;81(5):858-864 Authors: Mendonça VJ, da Silva MT, de Araújo RF, Júnior JM, Júnior MB, Almeida CE, Costa J, Graminha MA, Cicarelli RM, da Rosa JA The phylogenetic position of Triatoma sherlocki within triatomines group was inferred by analyzing mtDNA fragments of Cyt B and 16S ribosomal RNA by using maximum parsimony and Bayesian analysis. Despite being differentiated from members of the T. brasiliensis complex on morphologic grounds, molecular phylogenetic analysis suggests T. sherlocki is a member of this complex; moreover, it was placed as a sister species of T. melanica. These suggestions were supported by robust credibility rates. Hence, we show evidence for the paraphyletic group of the "Triatoma brasiliensis complex," which should be composed of T. brasiliensis brasiliensis, T. brasiliensis macromelasoma, T. juazeirensis, T. melanica, and T. sherlocki. PMID: 19861622 [PubMed - as supplied by publisher]

Blood Sources of Mosquitoes Collected from Urban and Peri-Urban Environments in Eastern Australia with Species-Specific Molecular Analysis of Avian Blood Meals.

Blood Sources of Mosquitoes Collected from Urban and Peri-Urban Environments in Eastern Australia with Species-Specific Molecular Analysis of Avian Blood Meals. Am J Trop Med Hyg. 2009 Nov;81(5):849-857 Authors: Jansen CC, Webb CE, Graham GC, Craig SB, Zborowski P, Ritchie SA, Russell RC, van den Hurk AF To identify the hosts of mosquitoes collected from urban and peri-urban habitats in eastern Australia, 1,180 blood fed mosquitoes representing 15 species were analyzed by enzyme-linked immunosorbent assay and molecular techniques. Four common and epidemiologically important species could be classified according to their host-feeding patterns: Aedes aegypti was anthropophilic, Ae. vigilax was mammalophilic, Culex quinquefasciatus was ornithophilic, and Cx. annulirostris was opportunistic, readily feeding on birds and mammals. Mitochondrial cytochrome b DNA sequence data showed that more than 75% of avian blood meals identified from Cx. annulirostris collected from Brisbane, Newcastle, and Sydney originated from ducks (Order Anseriformes, Family Anatidae). More than 75% of avian blood meals from Cx. quinquefasciatus from Cairns belonged to one of three Passerine species, namely Sphecotheres vieilloti (figbird), Sturnus tristis (common myna), and Philemon buceroides (helmeted friarbird). This study demonstrates associations between vectors in Australia and vertebrate hosts of endemic and exotic arboviruses. PMID: 19861621 [PubMed - as supplied by publisher]

Effects of Latitude and Longitude on the Population Structure of Culex pipiens s.l., Vectors of West Nile Virus in North America.

Effects of Latitude and Longitude on the Population Structure of Culex pipiens s.l., Vectors of West Nile Virus in North America. Am J Trop Med Hyg. 2009 Nov;81(5):842-848 Authors: Edillo F, Kiszewski A, Manjourides J, Pagano M, Hutchinson M, Kyle A, Arias J, Gaines D, Lampman R, Novak R, Foppa I, Lubelcyzk C, Smith R, Moncayo A, Spielman A, We assessed the structure and latitudinal selection that might result in sensitivities to critical day-lengths that trigger diapause between Culex pipiens populations distributed along North-South and East-West axes in eastern North America. Strong population structure between Cx. p. pipiens and Cx. p. quinquefasciatus existed. Among Cx. p. pipiens, a 100-km increase in the latitudinal change resulted in an increased square root of F(ST) by 0.002. A 100-km increase in the longitudinal change caused an increased square root of F(ST) by 0.035. A lack of latitudinal influence on the structure between Cx. p. pipiens populations suggests a uniform signal using the 12 microsatellite markers, which might increase the risk of West Nile virus (WNV) transmission toward northern areas because of longer breeding season, extend host-seeking period, and larger population size. Northern Cx. p. pipiens may have undergone additional generations before diapause is triggered, magnifying population size when WNV amplification is peaking. PMID: 19861620 [PubMed - as supplied by publisher]

Phase 1 Trial of the Dengue Virus Type 4 Vaccine Candidate rDEN4{Delta}30-4995 in Healthy Adult Volunteers.

Phase 1 Trial of the Dengue Virus Type 4 Vaccine Candidate rDEN4{Delta}30-4995 in Healthy Adult Volunteers. Am J Trop Med Hyg. 2009 Nov;81(5):834-841 Authors: Wright PF, Durbin AP, Whitehead SS, Ikizler MR, Henderson S, Blaney JE, Thumar B, Ankrah S, Rock MT, McKinney BA, Murphy BR, Schmidt AC rDEN4Delta30-4995 is a live attenuated dengue virus type 4 (DENV4) vaccine candidate specifically designed as a further attenuated derivative of the rDEN4Delta30 parent virus. In a previous study, 5 of 20 vaccinees who received 10(5) plaque-forming units (PFU) of rDEN4Delta30 developed a transient elevation of the serum alanine aminotransferase (ALT) level and an asymptomatic maculopapular rash developed in 10 of 20. In the current study, 28 healthy adult volunteers were randomized to receive 10(5) PFU of rDEN4Delta30-4995 (20) or placebo (8) as a single subcutaneous injection. The vaccine was safe, well-tolerated, and immunogenic. An asymptomatic generalized maculopapular rash and elevations in ALT levels were observed in 10% of the rDEN4Delta30-4995 vaccinees. None of the rDEN4Delta30-4995 vaccinees became viremic, yet 95% developed a four-fold or greater increase in neutralizing antibody titers. Thus, rDEN4Delta30-4995 was demonstrated to be safe, highly attenuated, and immunogenic. However, an asymptomatic localized erythematous rash at the injection site was seen in 17/20 rDEN4Delta30-4995 vaccinees. Therefore, alternative DENV4 vaccine strains were selected for further clinical development. PMID: 19861619 [PubMed - as supplied by publisher]

Dengue Plaque Reduction Neutralization Test (PRNT) in Primary and Secondary Dengue Virus Infections: How Alterations in Assay Conditions Impact Performance.

Dengue Plaque Reduction Neutralization Test (PRNT) in Primary and Secondary Dengue Virus Infections: How Alterations in Assay Conditions Impact Performance. Am J Trop Med Hyg. 2009 Nov;81(5):825-833 Authors: Thomas SJ, Nisalak A, Anderson KB, Libraty DH, Kalayanarooj S, Vaughn DW, Putnak R, Gibbons RV, Jarman R, Endy TP Dengue virus (DENV) infection is a worsening global health problem. The plaque reduction neutralization test (PRNT) is currently considered to be the "gold standard" to characterize and quantify circulating levels of anti-DENV neutralizing antibody (NAb). Many variations of the PRNT are currently in use and neither the assay nor its performance conditions have been standardized or harmonized between laboratories. We used a well-characterized panel of acute and late convalescent follow-up sera samples from children experiencing primary and secondary DENV infections to evaluate the performance of the dengue PRNT under a variety of testing conditions. Investigators varied cell type, control virus passage, and the use of complement across multiple assay runs of the same sample panel. Our findings indicate wide variation in PRNT titer results in response to varied testing conditions. PMID: 19861618 [PubMed - as supplied by publisher]

Translational regulation by the 3' untranslated region of the dengue type 2 virus genome.

Translational regulation by the 3' untranslated region of the dengue type 2 virus genome. Am J Trop Med Hyg. 2009 Nov;81(5):817-24 Authors: Wei Y, Qin C, Jiang T, Li X, Zhao H, Liu Z, Deng Y, Liu R, Chen S, Yu M, Qin E The role of the 3'untranslated region (UTR) of the dengue virus (DENV) genome during viral translation remains to be elucidated. We assessed the contribution of well-defined RNA elements in the 3'UTR of DENV-2 to viral translation using a virus-induced reporting gene system and deoxyribozymes (DRzs) targeting the 3'UTR of the DENV-2 genome. Results show that mRNAs carrying a deletion of repeated conserved sequence (RCS2)-CS2 are translated less efficiently than wild type mRNAs. However, mRNAs with a deletion of CS1-stem loop (SL) are translated more efficiently. Thus, CS1-SL and RCS2-CS2 may have different effects on translational regulation. Additionally, the translation-suppressing effect of CS1-SL or the SL element is further confirmed in DENV-2-infected cells using DRzs. Mutagenesis studies show that, rather than the secondary structure, nucleotides 10663-10677 and 10709-10723 are responsible for translational suppression of SL. Overall, our results demonstrate that sequences and elements within the DENV-2 3'UTR regulate viral translation. PMID: 19861617 [PubMed - in process]

Prevalence and genetic heterogeneity of bartonella strains cultured from rodents from 17 provinces in Thailand.

Prevalence and genetic heterogeneity of bartonella strains cultured from rodents from 17 provinces in Thailand. Am J Trop Med Hyg. 2009 Nov;81(5):811-6 Authors: Bai Y, Kosoy MY, Lerdthusnee K, Peruski LF, Richardson JH To study the distribution and diversity of Bartonella in rodents from Thailand, 330 rodents belonging to 13 species were tested. The majority (80.6%) of rodents examined belonged to the genus Rattus. Bartonellae were cultured from 41.5% of the rodents with a wide range of prevalence by host species and regions. Sequencing of gltA revealed diverse Bartonella strains. Bartonellae from Rattus spp. belonged to 23 variants and clustered with Bartonella coopersplainensis, Bartonella elizabethae, Bartonella phoceensis, Bartonella rattimassiliensis, Bartonella tribocorum, and an unknown geno-group. Bartonellae from Bandicota spp. belonged to six variants and clustered with B. coopersplainensis, B. rattimassilliensis, and B. tribocorum. Three variants from Mus spp. clustered with B. coopersplainensis or B. rattimassilliensis. The only isolate from a Berylmys berdmorei fell into the B. tribocorum group. The observations highlight the need to study these agents for their role in human febrile illnesses of unknown etiology in Thailand and elsewhere in Asia. PMID: 19861616 [PubMed - in process]

Interleukin-1 Beta Single-Nucleotide Polymorphism's C Allele is Associated with Elevated Risk of Gastric Cancer in Helicobacter pylori-Infected Peruvians.

Interleukin-1 Beta Single-Nucleotide Polymorphism's C Allele is Associated with Elevated Risk of Gastric Cancer in Helicobacter pylori-Infected Peruvians. Am J Trop Med Hyg. 2009 Nov;81(5):804-810 Authors: Gehmert S, Velapatiño B, Herrera P, Balqui J, Santivañez L, Cok J, Vargas G, Combe J, Passaro DJ, Wen S, Meyer F, Berg DE, Gilman RH Particular alleles of the interleukin-1B (IL-1B) gene have been correlated with increased risk of atrophic gastritis and gastric cancer in the populations of East Asia and Europe. No such data exist from Peru, a developing country with a population genotypically different from others studied and with a high prevalence of Helicobacter pylori infection and gastric cancer. We conducted a case-control study comparing 334 hospitalized patients with atrophic gastritis or gastric cancer with 158 nonatrophic gastritis patients (controls). Conditional logistic regression analysis revealed that an increased risk of atrophic gastritis (odds ratio, 5.60) and gastric cancer (odds ratio, 2.36) was associated with the IL-1B-511 C allele. Our study is the first to establish this allele as a risk for these conditions. Given the high prevalence of H. pylori and recurrence rate after treatment, IL-1B-511 single-nucleotide polymorphism analysis may identify those individuals who would benefit most from robust H. pylori eradication efforts in Peru. PMID: 19861615 [PubMed - as supplied by publisher]

Geographic Distribution and Prevalence of Schistosomiasis and Soil-Transmitted Helminths among Schoolchildren in Mozambique.

Geographic Distribution and Prevalence of Schistosomiasis and Soil-Transmitted Helminths among Schoolchildren in Mozambique. Am J Trop Med Hyg. 2009 Nov;81(5):799-803 Authors: Augusto G, Nalá R, Casmo V, Sabonete A, Mapaco L, Monteiro J Schistosomiasis and soil-transmitted helminths (STHs) are most prevalent in developing countries. In Mozambique, the first and only national survey of the distribution and prevalence of schistosomiasis and STHs was conducted in 1952 and 1957. Only occasional surveys in restricted areas have been conducted since the 1950s. The objective of our survey was to update information on the geographic distribution and prevalence of schistosomiasis and STHs in this country. During August 2005-June 2007, the Schistosomiasis and STH Laboratory of National Institutes of Health of the Ministry of Health undertook an epidemiologic survey among schoolchildren. A total of 83,331 persons attending primary schools were sampled. The mean age was 11.36 years (range: 7-22 years). Stool and urine samples were collected and examined by using Kato-Katz and filtration and Ritchie and Willis techniques. Results indicate a widespread occurrence of Schistosoma haematobium (overall prevalence = 47.0%) and STHs (prevalence = 53.5%). Prevalence varied dramatically across the country, with the highest prevalence in districts in northern provinces (Cabo Delgado, Niassa, Nampula, and Zambezia) and in certain provincial capital cities. Districts in the southern region of the country were less affected. Schistosoma mansoni was less common, with prevalence of 1%. We conclude that schistosomiasis and STHs are widely distributed in Mozambique and confirm the need for a national helminth control program. PMID: 19861614 [PubMed - in process]

Integrating NTD Mapping Protocols: Can Surveys for Trachoma and Urinary Schistosomiasis Be Done Simultaneously?

Integrating NTD Mapping Protocols: Can Surveys for Trachoma and Urinary Schistosomiasis Be Done Simultaneously? Am J Trop Med Hyg. 2009 Nov;81(5):793-8 Authors: King JD, Eigege A, Richards F, Jip N, Umaru J, Deming M, Miri E, McFarland D, Emerson PM We determined whether the school-based "disease mapping" methodology used to assess urinary schistosomiasis (SCH) is useful for determining trachoma interventions and whether the district-based approach recommended for trachoma is useful for SCH control programs. We conducted two separate integrated surveys in eight districts of central Nigeria: school based and district based. A total of 17,189 children were examined for trachoma and 16,238 children were examined for hematuria from 363 schools and 2,149 households. School surveys identified 67 communities warranting praziquantel drug treatment of SCH and 142 trachoma-endemic communities warranting trachoma control activities. In district-level estimates, we identified 24 communities for praziquantel treatment and 0 for trachoma intervention. Integrating trachoma into SCH school-based surveys, and SCH into trachoma surveys, was quick and easy, but in this setting, school-based surveys were more useful for identifying communities where intervention is warranted. PMID: 19861613 [PubMed - in process]

Spatial distribution of female genital mutilation in Nigeria.

Spatial distribution of female genital mutilation in Nigeria. Am J Trop Med Hyg. 2009 Nov;81(5):784-92 Authors: Kandala NB, Nwakeze N, Kandala SN The harmful effects of female genital mutilation (FGM) on women are recognized worldwide. Although it is practiced by persons of all socioeconomic backgrounds, there are differences within countries and between communities. The aim of this study was to use the 2003 Nigeria Demographic and Health Survey data to determine the spatial distribution of the prevalence of FGM and associated risk factors. Data were available for 7,620 women; 1,673 (22.0%) interviewed had had FGM and 2,168 women had living children, of whom 485 (22.4%) daughters had undergone FGM. Unmarried women were more likely to report a lower prevalence of FGM. Modernization (education and high socioeconomic status) had minimal impact on the likelihood of FGM, but education plays an important role in the mother's decision not to circumcise her daughter. It follows from these findings that community factors have a large effect on FGM, with individual factors having little effect on the distribution of FGM. PMID: 19861612 [PubMed - in process]

A simplified, low-cost method for polarized light microscopy.

A simplified, low-cost method for polarized light microscopy. Am J Trop Med Hyg. 2009 Nov;81(5):782-3 Authors: Maude RJ, Buapetch W, Silamut K Malaria pigment is an intracellular inclusion body that appears in blood and tissue specimens on microscopic examination and can help in establishing the diagnosis of malaria. In simple light microscopy, it can be difficult to discern from cellular background and artifacts. It has long been known that if polarized light microscopy is used, malaria pigment can be much easier to distinguish. However, this technique is rarely used because of the need for a relatively costly polarization microscope. We describe a simple and economical technique to convert any standard light microscope suitable for examination of malaria films into a polarization microscope. PMID: 19861611 [PubMed - in process]

Influence of tropical climate conditions on the quality of antihypertensive drugs from rwandan pharmacies.

Influence of tropical climate conditions on the quality of antihypertensive drugs from rwandan pharmacies. Am J Trop Med Hyg. 2009 Nov;81(5):776-81 Authors: Twagirumukiza M, Cosijns A, Pringels E, Remon JP, Vervaet C, Van Bortel L The objective of this study was to assess the quality of antihypertensive drugs and to investigate the influence of tropical storage conditions. Drug content and in vitro dissolution tests were performed on 10 test formulations (from Rwanda) and 6 reference formulations (from Belgium or France) after purchase and after 6-month storage under long-term (25 +/- 2 degrees C and 60 +/- 5% relative humidity [RH]) and accelerated (40 +/- 2 degrees C and 75 +/- 5% RH) testing conditions. Twenty percent of test formulations were of substandard content at the time of purchase. After 6 months at accelerated testing conditions, 7 of 10 test formulations were substandard in content and 8 were substandard for the combined criteria of drug content and dissolution, whereas no reference drug became substandard. This study shows that, apart from some drugs being already substandard from purchase, accelerated testing conditions (simulating tropical climate) have deleterious effects on the majority of antihypertensive drug formulations found in the Rwandan market. PMID: 19861610 [PubMed - in process]

Seasonal Pattern of Pneumonia Mortality among Under-Five Children in Nairobi's Informal Settlements.

Seasonal Pattern of Pneumonia Mortality among Under-Five Children in Nairobi's Informal Settlements. Am J Trop Med Hyg. 2009 Nov;81(5):770-5 Authors: Ye Y, Zulu E, Mutisya M, Orindi B, Emina J, Kyobutungi C Using longitudinal data from the Nairobi Urban and Demographic Surveillance System (NUHDSS), we examined the seasonal pattern of pneumonia mortality among under-five children living in Nairobi's slums. We included 17,787 under-five children resident in the NUHDSS from January 1, 2003 to December 31, 2005 in the analysis. Four hundred thirty-six deaths were observed and cause of death was ascertained by verbal autopsy for 377 of these deaths. Using Poisson regression, we modeled the quarterly mortality risk for pneumonia. The overall person-years (PYs) were 21,804 giving a mortality rate of 20.1 per 1,000 PYs in the study population. Pneumonia was the leading cause of death contributing 25.7% of the total deaths. Pneumonia mortality was highest in the second quarter (risk ratio [RR] = 2.3, confidence interval [CI]: 1.2-4.2 compared with the fourth quarter). The study provides evidence that pneumonia-related mortality among under-fives in Nairobi's slums is higher from April to June corresponding to the rainy season and the beginning of the cold season. PMID: 19861609 [PubMed - in process]

Budd-Chiari syndrome as a vascular complication of amebic liver abscess.

Budd-Chiari syndrome as a vascular complication of amebic liver abscess. Am J Trop Med Hyg. 2009 Nov;81(5):768-9 Authors: Méchaï F, Aoun O, Ficko C, Barruet R, Imbert P, Rapp C Amebiasis remains a major public health issue in most of the world. Amebic liver abscess is the most common extraintestinal manifestation. A complication such as venous obstruction associated with amebiais is rare. We report a thrombosis in hepatic veins associated with amebic hepatic abscess in a traveler. PMID: 19861608 [PubMed - in process]

Absence of asymptomatic malaria infections in previously high endemic areas of sri lanka.

Absence of asymptomatic malaria infections in previously high endemic areas of sri lanka. Am J Trop Med Hyg. 2009 Nov;81(5):763-7 Authors: Fernando SD, Abeyasinghe RR, Galappaththy GN, Rajapaksa LC As the goal of malaria elimination from Sri Lanka is currently being pursued, this study was planned to determine the prevalence of asymptomatic malaria infections. Five health areas in Trincomalee and Kurunegala districts that reported high prevalence in the recent past were purposively selected. The smallest administrative units (GN divisions) having high malaria risk within each area were identified. From these divisions, 20% of the population was randomly selected for blood smear examination and in a 50% sub-sample polymerase chain reaction (PCR) assay was performed. A population of 3,730 from 13 GN divisions was sampled. Thick and thin Giemsa-stained blood smears were negative for malaria parasites. The PCR carried out in 50% of the study sample was also negative for malaria parasites. The findings illustrate the absence of asymptomatic carriers in previously high transmission areas and it appears that achieving malaria elimination in Sri Lanka by 2015 is feasible. PMID: 19861607 [PubMed - in process]

Histopathology of Fatal Respiratory Distress Caused by Plasmodium vivax Malaria.

Histopathology of Fatal Respiratory Distress Caused by Plasmodium vivax Malaria. Am J Trop Med Hyg. 2009 Nov;81(5):758-762 Authors: Valecha N, Pinto RG, Turner GD, Kumar A, Rodrigues S, Dubhashi NG, Rodrigues E, Banaulikar SS, Singh R, Dash AP, Baird JK An otherwise healthy 20-year-old woman in Goa, India, received antibiotics after a diagnosis of upper respiratory tract infection. One week later, vivax malaria was diagnosed at a health center, but the patient developed respiratory distress and lost consciousness. She arrived at emergency department in shock, breathless, and comatose. She died within minutes. Two independent laboratories later confirmed Plasmodium vivax by microscopy (140,000/muL) and by nested and real-time polymerase chain reaction methods. Post-mortem examination showed congestion of alveolar capillaries by heavy monocytic infiltrates, along with diffuse damage to alveolar membranes consistent with acute respiratory distress syndrome. Parasites seen in lung tissue were roughly proportionate to both peripheral hyperparasitemia and those seen in other organs without lesions. In this patient, vivax malaria caused a rapidly fatal respiratory distress. PMID: 19861606 [PubMed - as supplied by publisher]

Malaria diagnosis by a polymerase chain reaction-based assay using a pooling strategy.

Malaria diagnosis by a polymerase chain reaction-based assay using a pooling strategy. Am J Trop Med Hyg. 2009 Nov;81(5):754-7 Authors: Bharti AR, Letendre SL, Patra KP, Vinetz JM, Smith DM Pooling clinical specimens reduces the number of assays needed when screening for infectious diseases. Polymerase chain reaction (PCR)-based assays are the most sensitive tests to diagnose malaria, but its high cost limits its use. We adapted a pooling platform that could reduce the number of assays needed to detect malaria infection. To evaluate this platform, two sets of 100 serum samples, with 1% and 5% malaria prevalence, were tested. DNA, extracted from pooled samples, was amplified by malaria-specific PCR. Additional validation was performed by determining the level of PCR detection based on 1:10 and 1:100 dilution. The platform correctly detected all malaria samples in the two test matrices. The use of stored serum samples also has important implications for studies investigating malaria prevalence rates retrospectively. Field studies, using serum and whole blood specimens, are needed to validate this technique for the adaptation of these methods for clinical utility. PMID: 19861605 [PubMed - in process]

Sex affects the steady-state pharmacokinetics of primaquine but not doxycycline in healthy subjects.

Sex affects the steady-state pharmacokinetics of primaquine but not doxycycline in healthy subjects. Am J Trop Med Hyg. 2009 Nov;81(5):747-53 Authors: Binh VQ, Chinh NT, Thanh NX, Cuong BT, Quang NN, Dai B, Travers T, Edstein MD We evaluated whether sex affects the steady-state pharmacokinetics of the antimalarial drugs, primaquine and doxycycline, in healthy subjects. Seventeen male and 17 female healthy Vietnamese subjects were administered 30 mg (base) of primaquine daily for 14 days. After a 2-week washout period, 14 male and 14 female subjects were administered 100 mg (base) of doxycycline daily for 14 days. Women had significantly higher median values of C(max) (212 versus 122 ng/mL, P< 0.001) and AUC(0-24) (1,909 versus 917 ng . h/mL, P < 0.001) of primaquine compared with men. Other than a longer t(max) in women, no sex-related differences were seen in the pharmacokinetics of doxycycline. The primaquine pharmacokinetic data suggest that women have increased exposure to primaquine, which may put them at increased risk for toxicity when administered the same maintenance dose as men. The similar pharmacokinetics of doxycycline between the two sexes justifies the same maintenance dose. PMID: 19861604 [PubMed - in process]

Successful Sporozoite Challenge Model in Human Volunteers with Plasmodium vivax Strain Derived from Human Donors.

Successful Sporozoite Challenge Model in Human Volunteers with Plasmodium vivax Strain Derived from Human Donors. Am J Trop Med Hyg. 2009 Nov;81(5):740-746 Authors: Herrera S, Fernández O, Manzano MR, Murrain B, Vergara J, Blanco P, Palacios R, Vélez JD, Epstein JE, Chen-Mok M, Reed ZH, Arévalo-Herrera M Successful establishment of a Plasmodium vivax sporozoite challenge model in humans is described. Eighteen healthy adult, malaria-naïve volunteers were randomly allocated to Groups A-C and exposed to 3 +/- 1, 6 +/- 1, and 9 +/- 1 bites of Anopheles albimanus mosquitoes infected with P. vivax, respectively. Seventeen volunteers developed signs and symptoms consistent with malaria, and geometric mean prepatent periods of 11.1 days (9.3-11) for Group A; 10.8 days (9.8-11.9) for Group B; and 10.6 days (8.7-12.4) for Group C, with no statistically significant difference among groups (Kruskal-Wallis, P = 0.70). One volunteer exposed to eight mosquito bites did not develop a parasitemia. No differences in parasite density were observed and all individuals successfully recovered after anti-malarial treatment. None of the volunteers developed parasite relapses within an 18-month follow-up. In conclusion, malaria-naive volunteers can be safely and reproducibly infected with bites of 2-10 An. albimanus mosquitoes carrying P. vivax sporozoites. This challenge method is suitable for vaccine and anti-malarial drug testing. PMID: 19861603 [PubMed - as supplied by publisher]

African tick bite Fever in a taiwanese traveler returning from South Africa: molecular and serologic studies.

African tick bite Fever in a taiwanese traveler returning from South Africa: molecular and serologic studies. Am J Trop Med Hyg. 2009 Nov;81(5):735-9 Authors: Tsai KH, Lu HY, Huang JH, Fournier PE, Mediannikov O, Raoult D, Shu PY We report the first imported case of African tick bite fever (ATBF) in a patient from Taiwan who returned from a 10-day trip to South Africa. Diagnosis was confirmed by polymerase chain reaction (PCR) from eschar biopsies. Portions of rickettsial ompA (491 bp) and ompB (273 bp) genes were amplified and subsequent sequencing of PCR product showed its 100% identity with R. africae. Microimmunofluorescence (MIF) assay of patient's serum on Days 14 and 46 after the onset of illness revealed IgG seroconversion when tested with spotted fever group (SFG) rickettsiae antigens, including R. africae. The patient clinically improved on the third day of 14-day treatment with a combination of ciprofloxacin and minocycline. Based on the patient's travel history and chronology of clinical symptoms, we strongly suspect that the tick-biting event occurred in Kruger National Park. PMID: 19861602 [PubMed - in process]

Tache noire in african tick bite Fever.

Tache noire in african tick bite Fever. Am J Trop Med Hyg. 2009 Nov;81(5):733-4 Authors: Tappe D, Dobler G, Stich A PMID: 19861601 [PubMed - in process]

Syndromic approach to treatment of snake bite in Sri Lanka based on results of a prospective national hospital-based survey of patients envenomed by identified snakes.

Related Articles Syndromic approach to treatment of snake bite in Sri Lanka based on results of a prospective national hospital-based survey of patients envenomed by identified snakes. Am J Trop Med Hyg. 2009 Oct;81(4):725-31 Authors: Ariaratnam CA, Sheriff MH, Arambepola C, Theakston RD, Warrell DA Of 860 snakes brought to 10 hospitals in Sri Lanka with the patients they had bitten, 762 (89%) were venomous. Russell's vipers (Daboia russelii) and hump-nosed pit vipers (Hypnale hypnale) were the most numerous and H. hypnale was the most widely distributed. Fifty-one (6%) were misidentified by hospital staff, causing inappropriate antivenom treatment of 13 patients. Distinctive clinical syndromes were identified to aid species diagnosis in most cases of snake bite in Sri Lanka where the biting species is unknown. Diagnostic sensitivities and specificities of these syndromes for envenoming were 78% and 96% by Naja naja, 66% and 100% by Bungarus caeruleus, 14% and 100% by Daboia russelii, and 10% and 97% by Hypnale hypnale, respectively. Although only polyspecific antivenoms are used in Sri Lanka, species diagnosis remains important to anticipate life-threatening complications such as local necrosis, hemorrhage and renal and respiratory failure and to identify likely victims of envenoming by H. hypnale who will not benefit from existing antivenoms. The technique of hospital-based collection, labeling and preservation of dead snakes brought by bitten patients is recommended for rapid assessment of a country's medically-important herpetofauna. PMID: 19815895 [PubMed - indexed for MEDLINE]

Flea diversity and infestation prevalence on rodents in a plague-endemic region of Uganda.

Related Articles Flea diversity and infestation prevalence on rodents in a plague-endemic region of Uganda. Am J Trop Med Hyg. 2009 Oct;81(4):718-24 Authors: Amatre G, Babi N, Enscore RE, Ogen-Odoi A, Atiku LA, Akol A, Gage KL, Eisen RJ In Uganda, the West Nile region is the primary epidemiologic focus for plague. The aims of this study were to 1) describe flea-host associations within a plague-endemic region of Uganda, 2) compare flea loads between villages with or without a history of reported human plague cases and between sampling periods, and 3) determine vector loads on small mammal hosts in domestic, peridomestic, and sylvatic settings. We report that the roof rat, Rattus rattus, is the most common rodent collected in human dwellings in each of the 10 villages within the two districts sampled. These rats were commonly infested with efficient Y. pestis vectors, Xenopsylla cheopis and X. brasiliensis in Arua and Nebbi districts, respectively. In peridomestic and sylvatic areas in both districts, the Nile rat, Arvicanthus niloticus, was the most abundant rodent and hosted the highest diversity of flea species. When significant temporal differences in flea loads were detected, they were typically lower during the dry month of January. We did not detect any significant differences in small mammal abundance or flea loads between villages with our without a history of human plague, indicating that conditions during inter-epizootic periods are similar between these areas. Future studies are needed to determine whether flea abundance or species composition changes during epizootics when humans are most at risk of exposure. PMID: 19815894 [PubMed - indexed for MEDLINE]

Spatial variation of Yersinia pestis from Yunnan Province of China.

Related Articles Spatial variation of Yersinia pestis from Yunnan Province of China. Am J Trop Med Hyg. 2009 Oct;81(4):714-7 Authors: Zhang Z, Hai R, Song Z, Xia L, Liang Y, Cai H, Liang Y, Shen X, Zhang E, Xu J, Yu D, Yu XJ Yunnan Province of China is considered the site of origin for modern plague. We analyzed the genotypes of eight Yersinia pestis strains isolated from three counties in Yunnan Province by pulse field gel electrophoresis (PFGE). PFGE showed that strains isolated from the same site were identical regardless of hosts or year of isolation. However, Y. pestis strains isolated from geographically distinct loci were genetically divergent. Whole genome sequences of two strains from two foci in Yunnan showed that the genetic variation of Y. pestis strains was caused by genome rearrangement. We concluded that Y. pestis strains in each epidemic focus in Yunnan were a clonal population and selected by host environments. The genomic variability of the Y. pestis strains from different foci were caused by genome rearrangement, which may provide a positive selective advantage for Y. pestis to adapt to its host environments. PMID: 19815893 [PubMed - indexed for MEDLINE]

Intra-cystic drug concentration of albendazole sulphoxide in patients with Echinococcus granulosus cysts.

Related Articles Intra-cystic drug concentration of albendazole sulphoxide in patients with Echinococcus granulosus cysts. Am J Trop Med Hyg. 2009 Oct;81(4):712-3 Authors: Capan M, Keltner S, Thalhammer F, Winkler S, Jäger W, Zeitlinger M, Ramharter M Albendazole therapy--alone or in combination with surgery--remains the standard of care for human echinococcosis depending on the stage of disease. However, only limited data are available on target site concentrations in liver cysts and data for non-liver cysts are lacking. We report on intra-cystic concentrations of the biologically active metabolite albendazole sulphoxide in non-liver cysts indicating a relative intra-cystic drug concentration of 48-156% compared with plasma levels. These data are evidence for a satisfactory penetration of albendazole sulphoxide into Echinococcus cysts localized in other organs than the liver and underline the usefulness of albendazole therapy for this indication. PMID: 19815892 [PubMed - indexed for MEDLINE]

Macrofilaricidal activity and amelioration of lymphatic pathology in bancroftian filariasis after 3 weeks of doxycycline followed by single-dose diethylcarbamazine.

Related Articles Macrofilaricidal activity and amelioration of lymphatic pathology in bancroftian filariasis after 3 weeks of doxycycline followed by single-dose diethylcarbamazine. Am J Trop Med Hyg. 2009 Oct;81(4):702-11 Authors: Mand S, Pfarr K, Sahoo PK, Satapathy AK, Specht S, Klarmann U, Debrah AY, Ravindran B, Hoerauf A In a placebo controlled trial, the effects of 21- and 10-day doxycycline treatments (200 mg/day) followed by single dose diethylcarbamazine (administered 4 months post treatment) on depletion of Wolbachia endobacteria from Wuchereria bancrofti, filaricidal activity, and amerlioration of scrotal lymph vessel dilation were studied in 57 men from Orissa, India. The 21-day doxycycline course reduced Wolbachia in W. bancrofti by 94% before diethylcarbamazine administration. After 12 months, all patients with this treatment were amicrofilaremic and different from the 10-day doxycycline (42.9%) and placebo (37.5%) groups, and significantly fewer were positive for scrotal worm nests (6.7%) compared with 10-day doxycycline (60%) and placebo (66.7%). Average scrotal lymph vessel diameters were reduced from 0.7 cm pre-treatment to 0.02 cm in patients after 21 days of treatment, while no significant changes were seen in the other groups. This latter feature confirms the beneficial effects of doxycycline on lymphatic dilation and thus adds to the existing evidence that doxycycline, in addition to being macrofilaricidal, may be used to prevent or reverse lymphatic pathology. PMID: 19815891 [PubMed - indexed for MEDLINE]

Clinical factors predictive of encephalitis caused by Angiostrongylus cantonensis.

Related Articles Clinical factors predictive of encephalitis caused by Angiostrongylus cantonensis. Am J Trop Med Hyg. 2009 Oct;81(4):698-701 Authors: Sawanyawisuth K, Takahashi K, Hoshuyama T, Sawanyawisuth K, Senthong V, Limpawattana P, Intapan PM, Wilson D, Tiamkao S, Jitpimolmard S, Chotmongkol V Angiostrongylus cantonensis is mainly caused eosinophilic meningitis in humans, whereas a minority of patients develop encephalitic angiostrongyliasis (EA). EA is an extremely fatal condition, and the clinical factors predictive of EA have never been reported. A comparison study was conducted in a hospital situated in an endemic area of Thailand. We enrolled 14 and 80 angiostrongyliasis patients who developed encephalitis and meningitis, respectively. Logistic regression analysis was used to assess the clinical variables predictive of encephalitis. Age (adjusted odds ratio [OR], 1.22; 95% confidence interval [CI], 1.05-1.42), duration of headache (adjusted OR, 1.26; 95% CI, 1.03-1.55), and fever > 38.0 degrees C (adjusted OR, 37.05; 95% CI, 1.59-862.35) were identified as statistically significant factors for EA prediction. Elderly patients with angiostrongyliasis experiencing fever and prolonged headaches were at the highest risk of developing EA. PMID: 19815890 [PubMed - indexed for MEDLINE]

The microscopic agglutination test (MAT) is an unreliable predictor of infecting Leptospira serovar in Thailand.

Related Articles The microscopic agglutination test (MAT) is an unreliable predictor of infecting Leptospira serovar in Thailand. Am J Trop Med Hyg. 2009 Oct;81(4):695-7 Authors: Smythe LD, Wuthiekanun V, Chierakul W, Suputtamongkol Y, Tiengrim S, Dohnt MF, Symonds ML, Slack AT, Apiwattanaporn A, Chueasuwanchai S, Day NP, Peacock SJ A prospective study in Thailand identified 106 patients with culture-proven leptospirosis. The accuracy of the microscopic agglutination test (MAT) in predicting the infecting serovar was evaluated in 78/106 (74%) patients with a diagnostic titer. MAT correctly determined the infecting serovar in 26 cases (33%), indicating that this assay is a poor predictor of infecting serovar in our setting. PMID: 19815889 [PubMed - indexed for MEDLINE]

Seroprevalence of Q fever in the United States, 2003-2004.

Related Articles Seroprevalence of Q fever in the United States, 2003-2004. Am J Trop Med Hyg. 2009 Oct;81(4):691-4 Authors: Anderson AD, Kruszon-Moran D, Loftis AD, McQuillan G, Nicholson WL, Priestley RA, Candee AJ, Patterson NE, Massung RF We performed serum testing for IgG antibodies against Coxiella burnetii (phase I and phase II) and analyzed questionnaire data from 4,437 adults > or = 20 years of age who participated in the National Health and Nutrition Examination Survey 2003-2004 survey cycle. National Q fever seroprevalence was determined by enzyme-linked immunosorbent assay and confirmed by using immunofluorescent antibody testing. Overall seroprevalence for Coxiella burnetii was 3.1% (95% confidence interval [CI] = 2.1-4.3%) among 4,437 adults > or = 20 years of age. Coxiella burnetii age-adjusted antibody prevalence was higher for men than for women (3.8%, 95% CI = 2.7-5.2% versus 2.5%, 95% CI = 1.5-3.7%, respectively, P < 0.05). Mexican Americans had a significantly higher antibody prevalence (7.4%, 95% CI = 6.6-8.3%) than either non-Hispanic whites (2.8%, 95% CI = 1.7-4.3%) or non-Hispanic blacks (1.3%, 95% CI = 0.6-2.5%) (P < 0.001). Multivariate analysis showed that the risk for Q fever antibody positivity increased with age and was higher among persons who were foreign-born, male, and living in poverty. These findings indicate that the national seroprevalence of Q fever in the United States is higher than expected on the basis of case numbers reported to the Centers for Disease Control and Prevention from state health departments. Potential differences in risk for exposure by race/ethnicity warrant further study. PMID: 19815888 [PubMed - indexed for MEDLINE]

Comparative efficacy of BioUD to other commercially available arthropod repellents against the ticks Amblyomma americanum and Dermacentor variabilis on cotton cloth.

Related Articles Comparative efficacy of BioUD to other commercially available arthropod repellents against the ticks Amblyomma americanum and Dermacentor variabilis on cotton cloth. Am J Trop Med Hyg. 2009 Oct;81(4):685-90 Authors: Bissinger BW, Zhu J, Apperson CS, Sonenshine DE, Watson DW, Roe RM BioUD is an arthropod repellent that contains the active ingredient 2-undecanone originally derived from wild tomato plants. Repellency of BioUD was compared with five commercially available arthropod repellents against the ticks Amblyomma americanum (L.) and Dermacentor variabilis Say in two-choice bioassays on treated versus untreated cotton cheesecloth. Overall mean percentage repellency against both species was greatest for and did not differ significantly between BioUD (7.75% 2-undecanone) and products containing 98.1% DEET, 19.6% IR3535, and 30% oil of lemon eucalyptus. Products containing 5% and 15% Picaridin and 0.5% permethrin were also repellent compared with untreated controls but to a lesser degree than BioUD. The four most active repellents at the same concentrations used before were directly compared in head-to-head bioassays on cotton cheesecloth. BioUD provided significantly greater overall mean percentage repellency than IR3535 for A. americanum and D. variabilis. BioUD was significantly more repellent than oil of lemon eucalyptus for A. americanum but did not differ significantly in repellency against D. variabilis. No statistically significant difference in overall mean percentage repellency was found between BioUD and DEET for A. americanum or D. variabilis. In a 7-week time course bioassay, BioUD applied to cotton cheesecloth and held at room temperature provided 5 weeks of > 90% repellency against A. americanum. PMID: 19815887 [PubMed - indexed for MEDLINE]

Development of field-based real-time reverse transcription-polymerase chain reaction assays for detection of Chikungunya and O'nyong-nyong viruses in mosquitoes.

Related Articles Development of field-based real-time reverse transcription-polymerase chain reaction assays for detection of Chikungunya and O'nyong-nyong viruses in mosquitoes. Am J Trop Med Hyg. 2009 Oct;81(4):679-84 Authors: Smith DR, Lee JS, Jahrling J, Kulesh DA, Turell MJ, Groebner JL, O'Guinn ML Chikungunya (CHIK) and O'nyong-nyong (ONN) are important emerging arthropod-borne diseases. Molecular diagnosis of these two viruses in mosquitoes has not been evaluated, and the effects of extraneous mosquito tissue on assay performance have not been tested. Additionally, no real-time reverse transcription-polymerase chain reaction (RT-PCR) assay exists for detecting ONN virus (ONNV) RNA. We describe the development of sensitive and specific real-time RT-PCR assays for detecting CHIK and ONN viral RNA in mosquitoes, which have application for field use. In addition, we compared three methods for primer/probe design for assay development by evaluating their sensitivity and specificity. This comparison resulted in development of virus-specific assays that could detect less than one plaque-forming unit equivalent of each of the viruses in mosquitoes. The use of these assays will aid in arthropod-borne disease surveillance and in the control of the associated diseases. PMID: 19815886 [PubMed - indexed for MEDLINE]

Crimean-Congo hemorrhagic fever virus as a nosocomial pathogen in Iran.

Related Articles Crimean-Congo hemorrhagic fever virus as a nosocomial pathogen in Iran. Am J Trop Med Hyg. 2009 Oct;81(4):675-8 Authors: Mardani M, Keshtkar-Jahromi M, Ataie B, Adibi P Crimean-Congo hemorrhagic fever (CCHF) is a viral disease with several different modes of transmission. We describe the manifestations, outcome, and likely modes of transmission for three nosocomial cases. All three cases were healthcare workers (two men and one woman). They had fever, myalgia, and petechia. Disseminated intravascular coagulation resulted in the death occurred in the woman. Because this disease is manifested with non-specific influenza-like symptoms, diagnosis can be difficult. Data for these patients can be used to investigate airborne or sexual transmission of this virus, although neither route was substantiated for these patients. Use of universal precautions and early case detection are the most helpful strategy for preventing nosocomial transmission of CCHF. PMID: 19815885 [PubMed - indexed for MEDLINE]

Development of an Alamar Blue viability assay in 384-well format for high throughput whole cell screening of Trypanosoma brucei brucei bloodstream form strain 427.

Related Articles Development of an Alamar Blue viability assay in 384-well format for high throughput whole cell screening of Trypanosoma brucei brucei bloodstream form strain 427. Am J Trop Med Hyg. 2009 Oct;81(4):665-74 Authors: Sykes ML, Avery VM There is an urgent need for new compounds for the drug development pipeline for treatment of patients with African sleeping sickness. One approach for identifying such compounds is by high throughput screening (HTS) of compound collections. For time and cost considerations, there is a need for the development of an assay that uses at least 384-well formats. To our knowledge, there are currently no viability assays for whole cell screening of trypanosomes in the 384-well plate format. We have developed and optimized an Alamar Blue viability assay in a 384-well format for Trypanosoma brucei brucei bloodstream form strain 427 (BS427). The assay had a Z' > 0.5 and tolerated a final dimethyl-sulfoxide concentration of 0.42%. Drug sensitivity was compared with those reported from previously developed 96-well methods and was found to be comparable. The sensitivity and cost benefit of the Alamar Blue assay make it an excellent candidate for HTS application. PMID: 19815884 [PubMed - indexed for MEDLINE]

Clinical course of monoclonal and oligoclonal gammopathies in patients infected with Orientia tsutsugamushi.

Related Articles Clinical course of monoclonal and oligoclonal gammopathies in patients infected with Orientia tsutsugamushi. Am J Trop Med Hyg. 2009 Oct;81(4):660-4 Authors: Park DS, Cho JH, Lee JH, Lee KE Although we have encountered many cases of monoclonal gammopathies (MGs) or oligoclonal gammopathies (OGs) in patients with Orientia tsutsugamushi infections, the clinical course of MG/OG associated with these infections has rarely been reported. We serially monitored 18 cases of MG/OG that appeared in the acute phase or early convalescent phase of scrub typhus. All MGs/OGs associated with infection with O. tsutsugamushi disappeared 7-15 weeks after treatment with doxycycline. In three cases of scrub typhus, MGs/OGs appeared before seropositive conversion (presence of antibodies against O. tsutsugamushi) and disappeared before seronegative conversion. Understanding our cases may be helpful for relevant clinical counseling and making appropriate medical decisions to avoid unnecessary invasive or cost-intensive diagnostic procedures for MGs/OGs in scrub typhus, especially in disease-endemic areas. We also suggest that 2-4 months after antibiotic treatment might be the optimal follow-up time to observe the disappearance of MGs/OGs associated with O. tsutsugamushi infections. PMID: 19815883 [PubMed - indexed for MEDLINE]

Molecular epidemiology of Chagas disease in the wild transmission cycle: the evaluation in the sylvatic vector Mepraia spinolai from an endemic area of Chile.

Related Articles Molecular epidemiology of Chagas disease in the wild transmission cycle: the evaluation in the sylvatic vector Mepraia spinolai from an endemic area of Chile. Am J Trop Med Hyg. 2009 Oct;81(4):656-9 Authors: Coronado X, Rozas M, Botto-Mahan C, Ortíz S, Cattan PE, Solari A The sylvatic transmission cycle of Chagas disease in Chile is composed of wild mammals and insects of the genus Mepraia. We determined infection rates and Trypanosoma cruzi genotypes in Mepraia spinolai. We collected 227 insects from two ecologically contrasting areas to assess T. cruzi infection. Polymerase chain reaction (PCR)-amplified minicircle DNAs were characterized by Southern blot and hybridization tests with genotype-specific probes. Infection in insects from the more fertile area was almost 2-fold higher than in the poorer area. The genotype TCI was the most prevalent and other genotypes such as TCIIb, TCIId, and TCIIe were found at lower rates. The areas differed in their genotype distribution but not in their genotype diversity. We suggest that the difference in abundance and richness of mammals between the areas may be producing the detected infection levels in vectors. Our results are compared with those reported for mammals from the same area. PMID: 19815882 [PubMed - indexed for MEDLINE]

Feeding and defecation patterns of Rhodnius nasutus (Hemiptera; Reduviidae), a triatomine native to an area endemic for Chagas disease in the state of Ceará, Brazil.

Related Articles Feeding and defecation patterns of Rhodnius nasutus (Hemiptera; Reduviidae), a triatomine native to an area endemic for Chagas disease in the state of Ceará, Brazil. Am J Trop Med Hyg. 2009 Oct;81(4):651-5 Authors: Oliveira TG, Carvalho-Costa FA, Sarquis O, Lima MM The importance of Rhodnius nasutus in the transmission of Chagas disease in northeastern Brazil was investigated regarding feeding and defecation patterns of this triatomine under laboratory conditions. An average of 30 samples were studied for each instar, from fourth-instar nymphs onward. On average, 86.4% started feeding after less than 10 minutes. In terms of the duration of feeding, 53.3% of fourth instar nymphs, 81.9% of fifth-instar nymphs, 21.9% of males, and 36.7% of females fed for more than 15 minutes. In all groups, there were insects that defecated and urinated during feeding; adult males defecated the most and fourth instar nymphs defecated the least. The results demonstrate that R. nasutus may be considered an efficient T. cruzi vector because it avidly searches for a food source, has a lengthy feeding time with low probability of interruption during feeding, and achieves a high percentage of engorgement. PMID: 19815881 [PubMed - indexed for MEDLINE]

Effect of peridomestic environments on repeated infestation by preadult Aedes aegypti in urban premises in Nha Trang City, Vietnam.

Related Articles Effect of peridomestic environments on repeated infestation by preadult Aedes aegypti in urban premises in Nha Trang City, Vietnam. Am J Trop Med Hyg. 2009 Oct;81(4):645-50 Authors: Tsuzuki A, Vu TD, Higa Y, Nguyen TY, Takagi M To determine the effect of peridomestic environments on Aedes aegypti infestation in urban premises, we conducted two consecutive surveys in the hot-dry and cool-wet seasons. Most Ae. aegypti pupae (79%) were recovered from premises where preadult forms (larvae and/or pupae) had been detected in both surveys. Hence, repeated infestation appears to be a useful parameter to identify premises associated with a high potential risk of dengue transmission. Multivariate analysis revealed that not only the persistent presence of containers discarded outdoors, wells, large plastic buckets, jars, and concrete toilet basins in the premises (adjusted odds ratios [aORs] = 63.3, 23.3, 22.5, 6.6, and 5.6, respectively) but also the presence of six or more residents was significantly associated with repeated infestation (aOR = 6.1). Premises with six or more residents along with specific container types from which a large number of pupae were recovered should be targeted in dengue-control programs. PMID: 19815880 [PubMed - indexed for MEDLINE]

Hemostatic changes in Vietnamese children with mild dengue correlate with the severity of vascular leakage rather than bleeding.

Related Articles Hemostatic changes in Vietnamese children with mild dengue correlate with the severity of vascular leakage rather than bleeding. Am J Trop Med Hyg. 2009 Oct;81(4):638-44 Authors: Wills B, Tran VN, Nguyen TH, Truong TT, Tran TN, Nguyen MD, Tran VD, Nguyen VV, Dinh TT, Farrar J The mechanisms underlying the bleeding manifestations and coagulopathy associated with dengue remain unclear, in part because of the focus of much previous work on severe disease without an appropriate comparison group. We describe detailed clinical and laboratory profiles for a large group of children with dengue of all severities, and a group with similar non-dengue febrile illnesses, all followed prospectively from early presentation through to recovery. Among the dengue-infected patients but not the controls, thrombocytopenia, increased partial thromboplastin times and reduced fibrinogen concentrations were apparent from an early stage, and these abnormalities correlated strongly with the severity and timing of vascular leakage but not bleeding. There was little evidence of procoagulant activation. The findings do not support a primary diagnosis of disseminated intravascular coagulation to explain the intrinsic coagulopathy. An alternative biologically plausible hypothesis is discussed. PMID: 19815879 [PubMed - indexed for MEDLINE]

Statins fail to improve outcome in experimental cerebral malaria and potentiate Toll-like receptor-mediated cytokine production by murine macrophages.

Related Articles Statins fail to improve outcome in experimental cerebral malaria and potentiate Toll-like receptor-mediated cytokine production by murine macrophages. Am J Trop Med Hyg. 2009 Oct;81(4):631-7 Authors: Helmers AJ, Gowda DC, Kain KC, Liles WC Cerebral malaria is responsible for a large proportion of the estimated one million deaths caused by Plasmodium falciparum malaria annually. This disease is associated with excessive pro-inflammatory cytokine production resulting from dysregulated host responses to infection. On the basis of reports indicating potent activity against host-mediated inflammatory disorders such as sepsis, we examined the activity of statins (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors) on malaria-associated inflammation in vivo and in vitro. Simvastatin failed to improve survival or alter parasitemia in C57BL/6 mice infected with Plasmodium berghei ANKA, an experimental model of cerebral malaria. In vitro statin treatment potentiated production of tumor necrosis factor and interleukin-6 by murine peritoneal macrophages in response to P. falciparum glycosylphosphatidyl inositol, a Toll-like receptor 2 (TLR2) ligand. Statin treatment also potentiated pro-inflammatory cytokine production stimulated by a panel of TLR2 and TLR4 ligands. Our results indicate that statins fail to confer protection in experimental cerebral malaria and potentiate TLR-mediated pro-inflammatory cytokine production by primary murine macrophages. PMID: 19815878 [PubMed - indexed for MEDLINE]

Non-destructive determination of age and species of Anopheles gambiae s.l. using near-infrared spectroscopy.

Related Articles Non-destructive determination of age and species of Anopheles gambiae s.l. using near-infrared spectroscopy. Am J Trop Med Hyg. 2009 Oct;81(4):622-30 Authors: Mayagaya VS, Michel K, Benedict MQ, Killeen GF, Wirtz RA, Ferguson HM, Dowell FE Determining malaria vector species and age is crucial to measure malaria risk. Although different in ecology and susceptibility to control, the African malaria vectors Anopheles gambiae sensu stricto and An. arabiensis are morphologically similar and can be differentiated only by molecular techniques. Furthermore, few reliable methods exist to estimate the age of these vectors, which is a key predictor of malaria transmission intensity. We evaluated the use of near-infrared spectroscopy (NIRS) to determine vector species and age. This non-destructive technique predicted the species of field-collected mosquitoes with approximately 80% accuracy and predicted the species of laboratory-reared insects with almost 100% accuracy. The relative age of young or old females was predicted with approximately 80% accuracy, and young and old insects were predicted with > or = 90% accuracy. For applications where rapid assessment of the age structure and species composition of wild vector populations is needed, NIRS offers a valuable alternative to traditional methods. PMID: 19815877 [PubMed - indexed for MEDLINE]

Pharmacokinetic profiles of artesunate after single intravenous doses at 0.5, 1, 2, 4, and 8 mg/kg in healthy volunteers: a phase I study.

Related Articles Pharmacokinetic profiles of artesunate after single intravenous doses at 0.5, 1, 2, 4, and 8 mg/kg in healthy volunteers: a phase I study. Am J Trop Med Hyg. 2009 Oct;81(4):615-21 Authors: Li Q, Cantilena LR, Leary KJ, Saviolakis GA, Miller RS, Melendez V, Weina PJ The pharmacokinetics of good manufacturing process injection of artesunate (AS) were evaluated after single doses at 0.5, 1, 2, 4, and 8 mg/kg with a 2-minute infusion in 40 healthy subjects. Drug concentrations were analyzed by validated liquid chromatography and mass spectrometry system (LC-MS/MS) procedures. The drug was immediately converted to dihydroartemisinin (DHA), with elimination half-lives ranging 0.12-0.24 and 1.15-2.37 hours for AS and DHA, respectively. Pharmacokinetic model-dependent analysis is suitable for AS, whereas DHA fits both model-dependent and -independent methods. Although DHA concentration was superior to that of AS with a 1.12-1.87 ratio of area under the curve (AUC)(DHA/AS), peak concentration of AS was much higher than that of DHA, with a 2.80- to 4.51-fold ratio of peak concentration (C(max AS/DHA)). Therefore, AS effectiveness has been attributed not only to its rapid hydrolysis to DHA, but also to itself high initial C(max). PMID: 19815876 [PubMed - indexed for MEDLINE]

Assessing the impact of indoor residual spraying on malaria morbidity using a sentinel site surveillance system in Western Uganda.

Related Articles Assessing the impact of indoor residual spraying on malaria morbidity using a sentinel site surveillance system in Western Uganda. Am J Trop Med Hyg. 2009 Oct;81(4):611-4 Authors: Bukirwa H, Yau V, Kigozi R, Filler S, Quick L, Lugemwa M, Dissanayake G, Kamya M, Wabwire-Mangen F, Dorsey G A single round of indoor residual spraying (IRS) using lambda-cyhalothrin was implemented in a district of Uganda with moderate transmission intensity in 2007. Individual patient data were collected from one health facility within the district 8 months before and 16 months after IRS. There was a consistent decrease in the proportion of patients diagnosed with clinical malaria after IRS for patients < 5 and > 5 years of age (52% versus 26%, P < 0.001 and 36% versus 23%, P < 0.001, respectively). There was a large decrease in the proportion of positive blood smears in the first 4 months after IRS for patients < 5 (47% versus 14%, P < 0.001) and > 5 (26% versus 9%, P < 0.001) years of age, but this effect waned over the subsequent 12 months. IRS was effective in reducing malaria morbidity, but this was not sustained beyond 1 year for the proportion of blood smears read as positive. PMID: 19815875 [PubMed - indexed for MEDLINE]

Resurgence of Plasmodium vivax malaria in the Republic of Korea during 2006-2007.

Related Articles Resurgence of Plasmodium vivax malaria in the Republic of Korea during 2006-2007. Am J Trop Med Hyg. 2009 Oct;81(4):605-10 Authors: Jun G, Yeom JS, Hong JY, Shin EH, Chang KS, Yu JR, Oh S, Chung H, Park JW Plasmodium vivax malaria, which re-emerged in the Republic of Korea (ROK) in 1993, had decreased since 2001. However, case numbers began to increase again in 2005. The number of cases rose 54.0% in 2006, but the rate of increase slowed down in 2007. Among the total of 4,206 cases of P. vivax malaria during 2006-2007, 756 cases (18.0%) were ROK military personnel, 891 cases (21.2%) were veterans, and 2,559 cases (60.8%) were civilians. The rapid increase during this period was mostly contributed by the western part of the malaria-risk areas that is under the influence of adjacent North Korea. Local transmission cases in ROK have also increased gradually and the transmission period seemingly became longer. Chemoprophylaxis in the military should be re-assessed in view of chloroquine-resistance. Continuous surveillance and monitoring are warranted to prevent further expansion of P. vivax malaria caused by climate change in ROK. PMID: 19815874 [PubMed - indexed for MEDLINE]

Biological resistance of hydroxychloroquine for Plasmodium vivax malaria in the Republic of Korea.

Related Articles Biological resistance of hydroxychloroquine for Plasmodium vivax malaria in the Republic of Korea. Am J Trop Med Hyg. 2009 Oct;81(4):600-4 Authors: Lee SW, Lee M, Lee DD, Kim C, Kim YJ, Kim JY, Green MD, Klein TA, Kim HC, Nettey H, Ko DH, Kim H, Park I The Republic of Korea (ROK) Army instituted a vivax malaria chemoprophylaxis program (hydroxychloroquine [HCQ] 400 mg per week) in 1997 that was expanded to nearly 200,000 soldiers by 2007, raising concerns for the emergence of drug-resistant vivax malaria. Therefore, a study of whole blood HCQ concentrations for all malaria patients admitted to four ROK Army hospitals was conducted from June through September 2007. For all 142 vivax malaria patients enrolled, fevers returned to normal by Day 3 post-treatment and all thin blood films were negative for parasites by Day 7. Pre-treatment whole blood concentrations of HCQ for 14 patients were > 100 ng/mL. Eight of the patients were enrolled in the ROK Army chemoprophylaxis program that reported taking HCQ as directed, with the last pill taken > or = 4 days before diagnosis. Although there was no evidence of clinical resistance, chemoprophylaxis data indicates the biological resistance or tolerance to HCQ in ROK. PMID: 19815873 [PubMed - indexed for MEDLINE]

Severe imported malaria in adults: retrospective study of 20 cases.

Related Articles Severe imported malaria in adults: retrospective study of 20 cases. Am J Trop Med Hyg. 2009 Oct;81(4):595-9 Authors: González A, Nicolás JM, Muñoz J, Castro P, Mas J, Valls ME, Coma JR, Aibar J, Gascon J Severe imported malaria is an important problem in many countries in which this disease is not endemic. This retrospective study describes the characteristics of 20 adults with severe imported malaria admitted to our intensive care unit from 1991 through 2007. All episodes were caused by Plasmodium falciparum and all patients had returned from sub-Saharan Africa, except for one transfusion recipient. All persons were considered non-immune, and none had taken appropriate chemoprophylaxis. The median time between the initiation of symptoms and the diagnosis was seven days. Five patients died (mortality rate = 25%). A higher frequency of unrousable coma and acidosis and a higher median Apache II score at admission was noted in the persons who died. Mortality by severe malaria remains high despite high quality management, which highlights the importance of chemoprophylaxis and early diagnosis and treatment. PMID: 19815872 [PubMed - indexed for MEDLINE]

Adaptation of a Thai multidrug-resistant C2A clone of Plasmodium falciparum to Aotus monkeys and its preliminary in vivo antimalarial drug efficacy-resistance profile.

Related Articles Adaptation of a Thai multidrug-resistant C2A clone of Plasmodium falciparum to Aotus monkeys and its preliminary in vivo antimalarial drug efficacy-resistance profile. Am J Trop Med Hyg. 2009 Oct;81(4):587-94 Authors: Obaldía N, Milhous W, Kyle D A multidrug-resistant (MDR) clone of Plasmodium falciparum (C2A) from Thailand was adapted through serial passage to Aotus monkeys. During adaptation, the parasite showed resistance to a single 20 or 40 mg/kg oral dose of mefloquine (MQ). Infection was only cured when MQ was administered orally at 40 mg/kg once in combination with intravenous artesunic acid at 20 mg/kg for 3 days. Similarly, the parasite clone was found to be resistant to quinine, failing at 20 mg/kg orally for 5 days in combination with an experimental dihydrofolate reductase (DHFR) inhibitor (WR297608) at 10, 20, or 40 mg/kg orally for 3 days, and with atovaquone/proguanil at 25 mg/kg for 3 days. This new model will allow in vivo testing of new antimalarial compounds or their combinations against a currently circulating MDR P. falciparum strain. PMID: 19815871 [PubMed - indexed for MEDLINE]

Aspergillus flavus brain abscesses associated with hepatic amebiasis in a non-neutropenic man in Senegal.

Related Articles Aspergillus flavus brain abscesses associated with hepatic amebiasis in a non-neutropenic man in Senegal. Am J Trop Med Hyg. 2009 Oct;81(4):583-6 Authors: Brun S, Fekkar A, Busse A, Seilhean D, Lecsö M, Adler D, Prodanovic H, Mazier D, Datry A A non-neutropenic man living in Senegal was repatriated to France for liver amebic abscesses associated with brain abscesses presumed to be of amebic origin. Surprisingly, the post-mortem examinations of brain abscesses showed Aspergillus flavus. The route of infection by A. flavus in this particular context is discussed. PMID: 19815870 [PubMed - indexed for MEDLINE]

Sensitive, specific, and rapid detection of Leishmania donovani DNA by loop-mediated isothermal amplification.

Related Articles Sensitive, specific, and rapid detection of Leishmania donovani DNA by loop-mediated isothermal amplification. Am J Trop Med Hyg. 2009 Oct;81(4):578-82 Authors: Takagi H, Itoh M, Islam MZ, Razzaque A, Ekram AR, Hashighuchi Y, Noiri E, Kimura E We have applied a loop-mediated isothermal amplification (LAMP) technique to detect Leishmania donovani DNA. The LAMP technique detected 1 fg of L. donovani DNA, which was 10-fold more sensitive than a conventional polymerase chain reaction (PCR). All nested PCR-positive blood samples from visceral leishmaniasis patients were positive with the LAMP technique, and DNA samples from L. infantum, L. major, L. mexicana, L. tropica, L. braziliensis, Plasmodium falciparum, and healthy humans were negative with the LAMP technique. The advantages of the LAMP method are its shorter reaction time, a lack of requirement of sophisticated equipment, and visual judgment of positivity based on the turbidity of reaction mixture. Our LAMP technique can be a better alternative to a conventional PCR, especially under field conditions. PMID: 19815869 [PubMed - indexed for MEDLINE]

Vector incrimination of sand flies in the most important visceral leishmaniasis focus in Iran.

Related Articles Vector incrimination of sand flies in the most important visceral leishmaniasis focus in Iran. Am J Trop Med Hyg. 2009 Oct;81(4):572-7 Authors: Oshaghi MA, Ravasan NM, Javadian EA, Mohebali M, Hajjaran H, Zare Z, Mohtarami F, Rassi Y The prevalence, host preference, and rate of Leishmania spp. infection of sand fly species are important parameters for incrimination of parasite vectors. We applied polymerase chain reaction (PCR)-based and enzyme-linked immunosorbent assay (ELISA) methods to detect Leishmania spp. parasites and blood meals within individual sand flies in the most important visceral leishmaniasis (VL) focus in northwestern Iran. Leishmania spp. minicircles (kinetoplast DNA) were found in 14 (0.9%) of 1,569 female specimens. Sequence analysis of 650 basepairs of an internal transcribed spacer ribosomal DNA gene identified L. infantum/L. donovani in 12 specimens and L. adleri-like parasites in 2 specimens. Nine (64.3%) of 14 of the Leishmania spp.-positive sand flies were Phlebotomus perfeliewi transcaucasicus. Blood meal identification of host DNA within sand flies by PCR-based and ELISA methods showed that 30% and 28%, respectively, were positive for human blood. Results of this study showed that P. perfeliewi transcaucasicus is the most prevalent, infected, and anthropophagic sand fly and plays a major role in VL transmission in the region studied. PMID: 19815868 [PubMed - indexed for MEDLINE]

Molecular epidemiology of American tegumentary leishmaniasis in Panama.

Related Articles Molecular epidemiology of American tegumentary leishmaniasis in Panama. Am J Trop Med Hyg. 2009 Oct;81(4):565-71 Authors: Miranda A, Carrasco R, Paz H, Pascale JM, Samudio F, Saldaña A, Santamaría G, Mendoza Y, Calzada JE American tegumentary leishmaniasis is an increasing public health problem in Panama. This study describes the clinical characteristics and the molecular epidemiology of leishmaniasis in Panama over a 5-year period (2004-2008). Additionally, we applied a polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP)-based assay to identify Leishmania species in clinical isolates, skin scrapings, and sandflies specimens. Whereas 60.3% of cases were detected with conventional parasitologic techniques (smear or in vitro culture), the PCR detected 72% positive patients. Our clinical-epidemiologic data corroborate the high incidence of L. (Viannia) panamensis and provide evidence of peridomestic and/or domestic transmission. Mucosal involvement was observed in 4.2% of the patients. The overall natural infection rate with Leishmania in 103 pools of sandflies was 0.46%. Lutzomyia gomezi and Lutzomya panamensis were the prevalent species incriminated as vectors at the capture sites in central Panama. This study contributes to a better knowledge of the current epidemiology of tegumentary leishmaniasis in Panama. PMID: 19815867 [PubMed - indexed for MEDLINE]

Tegumentary leishmaniasis as the cause of immune reconstitution inflammatory syndrome in a patient co-infected with human immunodeficiency virus and Leishmania guyanensis.

Related Articles Tegumentary leishmaniasis as the cause of immune reconstitution inflammatory syndrome in a patient co-infected with human immunodeficiency virus and Leishmania guyanensis. Am J Trop Med Hyg. 2009 Oct;81(4):559-64 Authors: Chrusciak-Talhari A, Ribeiro-Rodrigues R, Talhari C, Silva RM, Ferreira LC, Botileiro SF, Santos LO, Dietze R, Talhari S We report a case of immune reconstitution inflammatory syndrome (IRIS) in a 32-year-old man infected with human immunodeficiency virus and Leishmania guyanensis. Three months after initiation of highly active anti-retroviral therapy (HAART), the patient had disseminated cutaneous leishmaniasis and started anti-leishmanial therapy. The patient's leishmaniasis manifestations during HAART ranged form an anergic response (46 CD4+ T cells/microL) to a disseminated cutaneous leishmaniasis (112 CD4+ T cells/microL). Eight weeks later (168 CD4+ T cells/microL, skin biopsy specimens showed inflammatory infiltrates with no detectable amastigotes. The patient then became comatose. Prednisone therapy (60 mg/day) was initiated with a significant improvement within 48 hours. Three months later (CD4+ T cell count = 184 cell/microL), localized, classic, cutaneous leishmaniasis developed in the patient and anti-leishmanial treatment was re-introduced. On that occasion, frequency of T regulatory cells was 1.82% of all CD4+ cells. Our data suggest a pivotal role for CD4+ T cells in the onset of IRIS and lesion ulceration and their association with a low frequency of T regulatory cells. PMID: 19815866 [PubMed - indexed for MEDLINE]

Co-Infection of Leishmania (Viannia) braziliensis and HIV: report of a case of mucosal leishmaniasis in Cochabamba, Bolivia.

Related Articles Co-Infection of Leishmania (Viannia) braziliensis and HIV: report of a case of mucosal leishmaniasis in Cochabamba, Bolivia. Am J Trop Med Hyg. 2009 Oct;81(4):555-8 Authors: Torrico F, Parrado R, Castro R, Marquez CJ, Torrico MC, Solano M, Reithinger R, García AL We describe the first case of Leishmania/HIV co-infection reported in Bolivia. Initially hospitalized with a diagnosis of pneumonia and bronchitis, the patient had numerous cutaneous and mucosal lesions caused by Leishmania (Viannia) braziliensis. The patient was also diagnosed as severely immunocompromised because of HIV infection. PMID: 19815865 [PubMed - indexed for MEDLINE]

Vestibular-evoked myogenic potential (VEMP) in the evaluation of schistosomal myeloradiculopathy.

Related Articles Vestibular-evoked myogenic potential (VEMP) in the evaluation of schistosomal myeloradiculopathy. Am J Trop Med Hyg. 2009 Oct;81(4):551-4 Authors: Felipe L, Gonçalves DU, Tavares MC, Sousa-Pereira SR, Antunes CM, Lambertucci JR Schistosomal myeloradiculopathy (SMR) is the most severe and disabling form of schistosomiasis. The diagnosis is based on clinical, laboratory, and image data. Vestibular-evoked myogenic potential (VEMP) is a neurophysiologic test that assesses the vestibulospinal pathway through acoustic or galvanic stimuli. The aim of this study was to evaluate cervical spinal abnormalities in patients with SMR. Fifty-two subjects were evaluated, of whom 29 had SMR and 30 did not (normal control). Normal VEMP was observed in all volunteers without SMR. Abnormal VEMP was recorded in 34% of the group with SMR. After treatment, abnormal VEMP was found in 80% of those with persistent neurologic abnormalities. VEMP is a functional test, and the alteration may precede image abnormalities. This procedure may be useful for early diagnosis of schistosomal cervical spinal cord involvement. PMID: 19815864 [PubMed - indexed for MEDLINE]

Cervical schistosomiasis as a risk factor of cervical uterine dysplasia in a traveler.

Related Articles Cervical schistosomiasis as a risk factor of cervical uterine dysplasia in a traveler. Am J Trop Med Hyg. 2009 Oct;81(4):549-50 Authors: Dzeing-Ella A, Mechaï F, Consigny PH, Zerat L, Viard JP, Lecuit M, Lortholary O Female genital schistosomiasis (FGS) may be under-recognized in endemic areas as a cause of cervical dysplasia, neoplasia, infertility, and as a facilitator of the transmission of HIV. To the best of our knowledge, few cases of FGS mimicking neoplasia have been reported in travelers. We report a clinical case of a 34-year-old white woman who presented with a severe cervical dysplasia, without any features of human papilloma virus infection, 2 years after bathing in a waterfall, a source of schistosomiasis, in Mali. Schistosomes eggs were found on the conization. Management included conization and medical treatment, resulting in a full clinical and histologic recovery. FGS should be kept in mind as a possible cause of cervical dysplasia in endemic areas. Medical treatment with praziquantel improves this condition. PMID: 19815863 [PubMed - indexed for MEDLINE]

Peripheral rim enhancement in tuberculous mediastinal lymph nodes.

Related Articles Peripheral rim enhancement in tuberculous mediastinal lymph nodes. Am J Trop Med Hyg. 2009 Oct;81(4):548 Authors: Jayakrishnan B, Al-Rawas OA PMID: 19815862 [PubMed - indexed for MEDLINE]

Cerebral malaria: a new way forward with magnetic resonance imaging (MRI).

Related Articles Cerebral malaria: a new way forward with magnetic resonance imaging (MRI). Am J Trop Med Hyg. 2009 Oct;81(4):545-7 Authors: Looareesuwan S, Laothamatas J, Brown TR, Brittenham GM Magnetic resonance studies offer a new way through the impasse that now seems to block further progress in disentangling the pathogenesis and improving the treatment of cerebral malaria, a catastrophic neurologic complication of infection with Plasmodium falciparum. The underlying mechanisms responsible for coma in cerebral malaria are still unknown and the relative contributions of the microvascular sequestration of infected erythrocytes, the inflammatory response to P. falciparum, disordered hemostasis, and other factors remain controversial. For more than a century, neuropathologic studies have provided the basis for concepts of causation of cerebral malaria. Magnetic resonance techniques now offer non-invasive means of determining essential anatomic, metabolic, biochemical, and functional features of the brain in patients with cerebral malaria during life that could transform our understanding of the pathogenesis of cerebral malaria and lead to the development of new neuroprotective treatments. PMID: 19815861 [PubMed - indexed for MEDLINE]

Activity of tannins from Stryphnodendron adstringens on Cryptococcus neoformans: effects on growth, capsule size and pigmentation

Background: Stryphnodendron adstringens (Mart.) Coville, Leguminosae, also known in Brazil as barbatimao, is rich in tannins and many flavan-3-ols and proanthocyanidins such as prodelphinidins and prorobinetinidins. Previous studies have demonstrated several pharmacological properties of tannins from barbatimao, including anti-candidal activity. Methods: The antifungal activity of proanthocyanidin polymeric tannins from Stryphnodendron adstringens (subfraction F2.4) was evaluated against three strains of Cryptococcus neoformans with different capsule expressions, using the broth microdilution technique, light microscopy and transmission electron microscopy. The effect of subfraction F2.4 on C. neoformans and melanoma mammalian cells pigmentation was also evaluated. Results: Although susceptibility assays revealed MIC values quite similar (between 2.5 and 5.0 ug/ml), analyses of MFC values revealing that the acapsular mutant Cap 67 was more susceptible to be killed by the subfraction F2.4 (MFC = 20 ug/ml) than the two tested capsular strains (T1-444 and ATCC 28957) (MFC > 160 ug/ml). Optical and electron microscopy experiments revealed relevant alterations in cell shape and size in all strains treated with 1 and 2.5 ug/ml of subfraction F2.4. Capsule size of the capsular strains decreased drastically after subfraction F2.4 treatment. In addition, ultrastructural alterations such as cell wall disruption, cytoplasm extraction, mitochondria swelling, increase in the number of cytoplasmic vacuoles and formation of membranous structures in the cytoplasm were also observed in treated yeasts. Incubation with subfraction F2.4 also decreased C. neoformans pigmentation, however, did not interfere in melanization of B16F10 mammalian cells. Conclusion: Our data indicate that tannins extracted from S. adstringens interfered with growth, capsule size and pigmentation, all important virulence factors of C. neoformans, and may be considered as a putative candidate for the development of new antifungal agents.

Application of a high throughput Alamar blue biofilm susceptibility assay to Staphylococcus aureus biofilms

Background: Staphylococcus aureus and S. epidermidis biofilms differ in structure, growth and regulation, and thus the high-throughput method of evaluating biofilm susceptibility that has been published for S. epidermidis cannot be applied to S. aureus without first evaluating the assay's reproducibility and reliability with S. aureus biofilms. Methods: Staphylococcus aureus biofilms were treated with eleven approved antibiotics, lysostaphin, or Conflikt®, exposed to the oxidation reduction indicator Alamar blue, and reduction relative to untreated controls was determined visually and spectrophotometrically. The minimum biofilm inhibitory concentration (MBIC) was defined as ≤ 50% Alamar blue reduction and a purple/blue well 60 min after the addition of Alamar blue. Because all of the approved antibiotics had MBICs >128 μg/ml (most >2048 μg/ml), lysostaphin and Conflikt®, with relatively low MBICs, were used to correlate Alamar blue reduction with 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) reduction and viable counts (CFU/ml) for S. aureus ATCC 29213 and three clinical isolates. Alamar blue's stability and lack of toxicity allowed CFU/ml to be determined from the same wells as Alamar blue absorbances. Results: Overall, Alamar blue reduction had excellent correlation with XTT reduction and with CFU/ml. For ATCC 29213 and two clinical isolates treated with lysostaphin or Conflikt®, Alamar blue reduction had excellent correlation with XTT reduction (r = 0.93-0.99) and with CFU/ml (r = 0.92-0.98). For one of the clinical isolates, the results were moderately correlated for Conflikt® (r = 0.76, Alamar blue vs. XTT; r = 0.81, Alamar blue vs. CFU/ml) and had excellent correlation for lysostaphin (r = 0.95, Alamar blue vs. XTT; r = 0.97, Alamar blue vs. CFU/ml). Conclusion: A reliable, reproducible method for evaluating biofilm susceptibility was successfully applied to S. aureus biofilms. The described method provides researchers with a simple, nontoxic, relatively inexpensive, high throughput measure of viability after drug treatment. A standardized biofilm Alamar blue assay should greatly increase the rate of discovery of S. aureus biofilm specific agents.

Empiric antibiotic therapy in acute uncomplicated urinary tract infections and fluoroquinolone resistance: a prospective observational study

Background: The aims of this study were to determine the antimicrobial susceptibility patterns of urinary isolates from community acquired acute uncomplicated urinary tract infections (uUTI) and to evaluate which antibiotics were empirically prescribed in the outpatient management of uUTI. Methods: Among the patients which were admitted to outpatient clinics of Ankara University Medical Faculty, Ibni-Sina Hospital during 2005-2006, a total of 429 women between the age of 18 and 65 years old who were clinically diagnosed with uUTI and to whom prescribed empirical antibiotics were enrolled in this prospective observational study. Patients' demographical data, urine culture results, resistance rates to antimicrobial agents and prescribed empiric antimicrobial therapy were analyzed. Results: Totally 390 (90.9%) patients among all study population were requested for urine culture by their physicians. 150 (38.5%) of these urine cultures were positive. The most common isolated uropathogen was Escherichia coli (E. coli) (71.3%). The variations of uropathogens according to age and menopause status were not significantly different.The resistance rates of E. coli isolates for ampicillin, ampicillin-sulbactam, amoxicillin-clavulonate, cefuroxime, ceftriaxone, fluoroquinolones (FQ), co-trimoxazole (TMP-SMX) and gentamicin were 55.1%, 32.7%, 32.7%, 23.4%, 15.9%, 25.2%, 41.1%, 6.1% respectively. FQ were the most common prescribed antibiotics (77.9%) (P < 0.001), followed by TMP-SMX (10.7%), fosfomycin (9.2%), nitrofurantoin (2.1%). Treatment durations were statistically longer than the recommended 3-day course (P < 0.001). Conclusion: Empirical use of FQ in uUTI should be discouraged because of increased antimicrobial resistance rates.

Prevalence and antimicrobial resistance pattern of bacterial meningitis in Egypt

Infectious diseases are the leading cause of morbidity and mortality in the developing world. In Egypt bacterial diseases constitute a great burden, with several particular bacteria sustaining the leading role of multiple serious infections. This article addresses profound bacterial agents causing a wide array of infections including but not limited to pneumonia and meningitis. The epidemiology of such infectious diseases and the prevalence of Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae are reviewed in the context of bacterial meningitis. We address prevalent serotypes in Egypt, antimicrobial resistance patterns and efficacy of vaccines to emphasize the importance of periodic surveillance for appropriate preventive and treatment strategies.

Correction: Antifungal treatment for invasive Candida infections: a mixed treatment comparison meta-analysis

No description available

Fatal Chromobacterium violaceum septicaemia in northern Laos, a modified oxidase test and post-mortem forensic family G6PD analysis

Background: Chromobacterium violaceum is a Gram negative facultative anaerobic bacillus, found in soil and stagnant water, that usually has a violet pigmented appearance on agar culture. It is rarely described as a human pathogen, mostly from tropical and subtropical areas.Case presentationA 53 year-old farmer died with Chromobacterium violaceum septicemia in Laos. A modified oxidase method was used to demonstrate that this violacious organism was oxidase positive. Forensic analysis of the glucose-6-phosphate dehydrogenase genotypes of his family suggest that the deceased patient did not have this possible predisposing condition. Conclusion: C. violaceum infection should be included in the differential diagnosis in patients presenting with community-acquired septicaemia in tropical and subtropical areas. The apparently neglected but simple modified oxidase test may be useful in the oxidase assessment of other violet-pigmented organisms or of those growing on violet coloured agar.

Antifungal treatment for invasive Candida infections: a mixed treatment comparison meta-analysis

ObjectivesInvasive fungal infections are a major cause of mortality among patients at risk. Treatment guidelines vary on optimal treatment strategies. We aimed to determine the effects of different antifungal therapies on global response rates, mortality and safety. Methods: We searched independently and in duplicate 10 electronic databases from inception to May 2009. We selected any randomized trial assessing established antifungal therapies for confirmed cases of invasive candidiasis among predominantly adult populations. We performed a meta-analysis and then conducted a Bayesian mixed treatment comparison to differentiate treatment effectiveness. Sensitivity analyses included dosage forms of amphotericin B and fluconazole compared to other azoles. Results: Our analysis included 11 studies enrolling a total of 965 patients. For our primary analysis of global response rates, we pooled 7 trials comparing azoles to amphotericin B, Relative Risk [RR] 0.87 (95% Confidence Interval [CI], 0.78–0.96, P = 0.007, I2 = 43%, P = 0.09. We also pooled 2 trials of echinocandins versus amphotericin B and found a pooled RR of 1.10 (95% CI, 0.99–1.23, P = 0.08). One study compared anidulafungin to fluconazole and yielded a RR of 1.26 (95% CI, 1.06–1.51) in favor of anidulafungin. We pooled 7 trials assessing azoles versus amphotericin B for all-cause mortality, resulting in a pooled RR of 0.88 (95% CI, 0.74–1.05, P = 0.17, I2 = 0%, P = 0.96). Echinocandins versus amphotericin B (2 trials) for all-cause mortality resulted in a pooled RR of 1.01 (95% CI, 0.84–1.20, P = 0.93). Anidulafungin versus fluconazole resulted in a RR of 0.73 (95% CI, 0.48–1.10, P = 0.34). Our mixed treatment comparison analysis found similar within-class effects across all interventions. Adverse event profiles differed, with amphotericin B exhibiting larger adverse event effects. Conclusion: Treatment options appear to offer preferential effects on response rates and mortality. When mycologic data are available, therapy should be tailored.

Hospital-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) in Italy

The aim of our study was to trace the dynamic changes of hospital-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) lineages in Italy, comparing the genotypic backgrounds of contemporary isolates over a period of 17 years, with those of a sample of early MRSA strains from 1980.In total, 301 non-repetitive MRSA clinical isolates, recovered from 19 Italian hospitals between 1990 and 2007 were selected and analyzed for their antibiotic resistance, typed by PFGE and SCCmec, grouped into clonal-types and further characterized using Multi Locus Sequence Typing (MLST). A sample of fifteen early MRSA strains from 1980 was also used for comparison.The most interesting feature was the recent increase of ST228-MRSA-I (formerly the Italian clone; PFGE E) over the period 2000–2007 (57%), when compared to the period 1990–1999 (29%), and its stability to date, associated with a decrease of the highly epidemic ST247-MRSA-IA (formerly the Iberian clone; PFGE A), (23% from 1990 to 1999, 6% from 2000 to 2007). ST1-MRSA-I (1 out of 2 strains carrying ccrA2B2), ST8-MRSA-I (4 strains), ST15-MRSA-I (1 out of 4 carrying ccrA2B2) and ST30-MRSA-I (2 out of 5 carrying no ccrAB-types and ccrC) were the predominant earliest STs among the MRSA strains in 1980.A temporal shift in the susceptibility levels to glycopeptides was observed: strains with vancomycin MIC of ≥ 2 mg/L increased from 19.4% to 35.5%.In conclusion, we describe the alternation of MRSA clones that occurred in hospitals from 1990 to 2007 and the increase of the glycopeptide MIC levels, reflecting a worldwide trend. We document the detection of ST1, ST8, ST15 and ST30 in the 1980 isolates; we hypothesize their possible latency and their appearance as the current CA-MRSA clones.

Genetic relatedness and molecular characterization of multidrug resistant Acinetobacter baumannii isolated in central Ohio, USA

Background: Over the last decade, nosocomial infections due to Acinetobacter baumannii have been described with an increasing trend towards multidrug resistance, mostly in intensive care units. The aim of the present study was to determine the clonal relatedness of clinical isolates and to elucidate the genetic basis of imipenem resistance. Methods: A. baumannii isolates (n = 83) originated from two hospital settings in central Ohio were used in this study. Pulsed-field gel electrophoresis genotyping and antimicrobial susceptibility testing for clinically relevant antimicrobials were performed. Resistance determinants were characterized by using different phenotypic (accumulation assay for efflux) and genotypic (PCR, DNA sequencing, plasmid analysis and electroporation) approaches. Results: The isolates were predominantly multidrug resistant (>79.5%) and comprised of thirteen unique pulsotypes, with genotype VII circulating in both hospitals. The presence of blaOXA-23 in 13% (11/83) and ISAba1 linked blaOXA-66 in 79.5% (66/83) of clinical isolates was associated with high level imipenem resistance. In this set of OXA producing isolates, multidrug resistance was bestowed by blaADC-25, class 1 integron-borne aminoglycoside modifying enzymes, presence of sense mutations in gyrA/parC and involvement of active efflux (with evidence for the presence of adeB efflux gene). Conclusion: This study underscores the major role of carbapenem-hydrolyzing class D β-lactamases, and in particular the acquired OXA-23, in the dissemination of imipenem-resistant A. baumannii. The co-occurrence of additional resistance determinant could also be a significant threat.

Isolation and identification of antimicrobial compound from Mentha longifolia L. leaves grown wild in Iraq

Background: Mentha longifolia L. (Lamiaceae) leaves have been traditionally implemented in the treatment of minor sore throat and minor mouth or throat irritation by the indigenous people of Iraq, although the compounds responsible for the medicinal properties have not been identified. In the present study, an antimicrobial compound was isolated and characterized, and its biological activity was assessed. Methods: The compound was isolated and characterized from the extracted essential oil using different spectral techniques: TLC, FTIR spectra and HPLC. Antimicrobial activity of the compound was assessed using both disc diffusion and microdilution method in 96 multi-well microtiter plates. Results: A known compound was isolated from the essential oil of the plant and was identified as (-) menthol. The isolated compound was investigated for its antimicrobial activity against seven selected pathogenic and non-pathogenic microorganisms: Staphylococcus aureus, Streptococcus mutans, Streptococcus faecalis, Streptococcus pyogenis, Lactobacillus acidophilus, Pseudomonas aeruginosa and the yeast Candida albicans. Menthol at different concentrations (1:1, 1:5, 1:10, 1:20) was active against all tested bacteria except for P. aeruginosa, and the highest inhibitory effect was observed against S. mutans (zone of inhibition: 25.3 mm) using the disc diffusion method. Minimal inhibitory concentration MIC values ranged from 15.6–125.0 μg/ml, and the most promising results were observed against S. aureus and S. mutans (MIC 15.6 μg/ml) while, S. faecalis, S. pyogenis and L. acidophilus ranked next (MIC 31.2 μg/ml). Furthermore, menthol achieved considerable antifungal activity against the yeast C. albicans (zone of inhibition range: 7.1–18.5 mm; MIC: 125.0). Conclusion: The isolation of an antimicrobial compound from M. longifolia leaves validates the use of this plant in the treatment of minor sore throat and minor mouth or throat irritation.

Two types of drug-resistant hepatitis B viral strains emerging alternately and their susceptibility to combination therapy with entecavir and adefovir.

Related Articles Two types of drug-resistant hepatitis B viral strains emerging alternately and their susceptibility to combination therapy with entecavir and adefovir. Antivir Ther. 2009;14(6):873-7 Authors: Kurashige N, Ohkawa K, Hiramatsu N, Oze T, Yakushijin T, Mochizuki K, Hosui A, Miyagi T, Ishida H, Tatsumi T, Kanto T, Takehara T, Hayashi N The most serious problem of nucleoside/nucleotide analogue therapy for hepatitis B virus (HBV) infection is the emergence of drug-resistant mutant virus. Here, we describe a patient with chronic hepatitis B infection with a complex drug-resistant mutant virus during sequential therapy with lamivudine (3TC), entecavir (ETV) and adefovir dipivoxil (ADV). The patient was a 52-year-old male with positive hepatitis B e antigen and high HBV DNA (>7.6 log(10) copies/ml). Initial 3TC monotherapy offered little benefit and 3TC resistance was established by the virus with rtA181T and not rtM204V/I. HBV DNA was reduced slightly by replacement with ETV monotherapy and was followed by virological breakthrough. At that time, rtA181T was undetectable and the virus with rtM204V and rtL180M became predominant. ETV resistance was established by an additional rtS202G mutation. Efficacy of subsequent combination therapy with ADV and 3TC was limited because of reappearance of the virus with rtA181T, which might confer cross-resistance to 3TC and ADV. Final combination therapy with ETV and ADV reduced HBV DNA to 3.7 log(10) copies/ml for 5 months, which was the most effective therapy for this patient. Thus, two kinds of mutant viruses (rtM204V-related and rtA181T-related) appeared alternately in this patient. Combination therapy with ETV and ADV might have been effective because these drugs share therapeutic roles, that is, ETV affects the rtA181T-related virus and ADV affects the rtM204V-related virus. This is the first report suggesting clinical significance of combination therapy with ETV and ADV for controlling replication of the complex drug-resistant mutant HBV. PMID: 19812452 [PubMed - in process]

Telbivudine in the treatment of chronic hepatitis B: experience in HIV type-1-infected patients naive for antiretroviral therapy.

Related Articles Telbivudine in the treatment of chronic hepatitis B: experience in HIV type-1-infected patients naive for antiretroviral therapy. Antivir Ther. 2009;14(6):869-72 Authors: Milazzo L, Caramma I, Lai A, Violin M, De Maddalena C, Cesari M, Galli M, Balotta C BACKGROUND: Telbivudine is a potent inhibitor of hepatitis B virus (HBV) replication without anti-HIV type-1 (HIV-1) activity demonstrated in vitro; however, very few clinical data on HIV-1-infected patients are available at present. Because it represents a therapeutic option in HIV-1-HBV-coinfected patients who do not require antiretroviral therapy, we strictly monitored three HIV-1-HBV-coinfected patients treated with telbivudine monotherapy for chronic hepatitis B. METHODS: We performed molecular analysis of HBV DNA and of HIV-1 reverse transcriptase and protease RNA and DNA sequences in three HIV-1-HBV-coinfected patients treated with telbivudine monotherapy. RESULTS: Despite a transient and deep reduction of HIV-1 RNA, observed in two of the three patients studied, no genotypic resistance mutations were detected on both HIV-1 and HBV viruses. CONCLUSIONS: Telbivudine therapy for 24 weeks showed a potent anti-HBV activity in HIV-1-positive, hepatitis B e antigen-positive patients with high HBV viraemia. No direct anti-HIV-1 activity of telbivudine was demonstrated and no genotypic resistance mutations to anti-HIV-1 drugs was found; however, the transient but deep reduction of HIV RNA, after telbivudine introduction, deserves further investigation and a strict monitoring of HIV-1 viraemia in HIV-1-infected patients on treatment with this drug. PMID: 19812451 [PubMed - in process]

Lower limb high arterial flow induced by tenofovir and emtricitabine treatment.

Related Articles Lower limb high arterial flow induced by tenofovir and emtricitabine treatment. Antivir Ther. 2009;14(6):865-7 Authors: Periard D, Yerly P, Hayoz D, Mazzolai L, Widmeier A, Cavassini M Here, we describe a case of an HIV-infected patient with right lower limb oedema that appeared after initiation of tenofovir and emtricitabine treatment. The patient was fully investigated by serial heart and vessel echo-Doppler examination. Oedema of the lower limb was attributed to a transient drug-induced fivefold increase in peripheral artery flow, which was induced by a reduction in peripheral arterial resistance. The possible mechanisms of disease are discussed. PMID: 19812450 [PubMed - in process]

Efficacy and safety of darunavir/ritonavir in treatment-experienced HIV type-1 patients in the POWER 1, 2 and 3 trials at week 96.

Related Articles Efficacy and safety of darunavir/ritonavir in treatment-experienced HIV type-1 patients in the POWER 1, 2 and 3 trials at week 96. Antivir Ther. 2009;14(6):859-64 Authors: Arastéh K, Yeni P, Pozniak A, Grinsztejn B, Jayaweera D, Roberts A, Hoy J, De Meyer S, Vangeneugden T, Tomaka F BACKGROUND: Long-term (96-week) efficacy and safety of the protease inhibitor (PI) darunavir coadministered with low-dose ritonavir (DRV/r) was evaluated in HIV type-1 (HIV-1)-infected patients with extensive prior treatment experience in the POWER 1, 2 and 3 trials. METHODS: Patients with HIV-1 RNA>/=1,000 copies/ml and >/=1 primary PI mutation were randomized to receive either DRV/r 600/100 mg twice daily plus an optimized background regimen (OBR), or an investigator-selected control PI (CPI) plus OBR (POWER 3 was a DRV/r 600/100 mg twice daily single-arm study). The proportion of patients with HIV-1 RNA<50 copies/ml at week 96 was assessed (intent-to-treat [ITT], time-to-loss of virological response algorithm). RESULTS: In total, 467 patients received DRV/r 600/100 mg twice daily; 124 patients received CPI(s). At week 96, 39% of DRV/r patients in POWER 1 and 2 (pooled analysis) versus 9% of CPI patients achieved HIV-1 RNA<50 copies/ml (ITT, time-to-loss of virological response algorithm; P<0.001). A similar proportion of DRV/r patients (42%) in POWER 3 achieved HIV-1 RNA<50 copies/ml at week 96. Mean absolute CD4(+) T-cell count increase for DRV/r at 96 weeks was 133 cells/mm(3) in POWER 1 and 2 and 103 cells/mm(3) in POWER 3. Grade 2-4 treatment-emergent adverse events at least possibly related to DRV/r (>/=2% incidence, excluding laboratory abnormalities) were diarrhoea (3%), vomiting (3%), nausea (2%) and headache (2%). CONCLUSIONS: Treatment with DRV/r 600/100 mg twice daily was well tolerated and led to sustained virological and immunological responses in treatment-experienced HIV-1-infected patients over 96 weeks. PMID: 19812449 [PubMed - in process]

Statin therapy and changes in hip circumference among HIV-infected participants in the ALLRT Cohort.

Related Articles Statin therapy and changes in hip circumference among HIV-infected participants in the ALLRT Cohort. Antivir Ther. 2009;14(6):853-8 Authors: Brown TT, Smurzynski M, Wu K, Bosch RJ, McComsey GA BACKGROUND: We aimed to determine whether statin exposure in antiretroviral-treated individuals is associated with increases in hip circumference compared with HIV treatment without concomitant statin use. METHODS: This was a prospective multicentre cohort study involving individuals who had received antiretroviral therapy for at least 40 weeks and who were enrolled in the AIDS Clinical Trials Group Longitudinal Linked Randomized Trials cohort. There were 2,223 participants in the statin-unexposed group and 371 in the statin-exposed group. The main outcome measure was change in hip circumference at week 32. RESULTS: The 32-week change in hip circumference in the statin-exposed group was 0.60 cm greater (95% confidence interval 0.11-1.10; P=0.02) than in the statin-unexposed group after adjustment for age, gender, race, baseline body mass index and thymidine analogue exposure. CONCLUSIONS: Our findings support the hypothesis that statins might be beneficial in lipoatrophy. Given the limited treatment options for this important problem, further studies are needed to confirm this effect and to determine its clinical significance. PMID: 19812448 [PubMed - in process]

Genetic analysis and putative role in resistance to antivirals of the human cytomegalovirus DNA polymerase UL44 processivity factor.

Related Articles Genetic analysis and putative role in resistance to antivirals of the human cytomegalovirus DNA polymerase UL44 processivity factor. Antivir Ther. 2009;14(6):847-52 Authors: Boutolleau D, Deback C, Bressollette-Bodin C, Conan F, Aït-Arkoub Z, Imbert-Marcille BM, Agut H BACKGROUND: The human cytomegalovirus (HCMV) DNA polymerase is composed of the UL54 catalytic subunit and the UL44 accessory protein. UL44 increases the processivity of polymerase along the DNA template during replication and, incidentally, is a substrate for the UL97 phosphotransferase. The molecular mechanisms of HCMV resistance to antiviral drugs interfering with viral DNA synthesis reported so far only rely on the presence of amino acid changes within the UL97 and UL54 viral enzymes. We aimed to describe the natural polymorphism of UL44 and to analyse the changes of its amino acids potentially associated with HCMV resistance to antivirals. METHODS: The full-length UL44 gene sequence was compared to that of four reference strains (including the AD169 strain) and 43 clinical strains from patients who had not received any previous anti-HCMV treatment, and 25 blood samples from 15 HCMV-infected patients experiencing therapeutic failure and exhibiting genotypic traits of HCMV resistance to antivirals. RESULTS: Overall, seven different amino acid changes associated with natural polymorphisms were identified among the 433 residues of the UL44 protein, occurring at a frequency of 2.1% for five of them and 10.6% for the double change G296S+L319I. The analysis of the HCMV strains exhibiting genotypic resistance to antivirals did not show any changes in UL44 that had significant association with resistance mutations of UL97 and/or UL54. CONCLUSIONS: UL44 processivity factor exhibits a very low polymorphism that does not concern the assumed functional domains of the protein. From this preliminary study, UL44 does not seem to be involved in HCMV resistance to antivirals. PMID: 19812447 [PubMed - in process]

Insulin resistance impairs sustained virological response rate to pegylated interferon plus ribavirin in HIV-hepatitis C virus-coinfected patients: HOMAVIC-ANRS HC02 Study.

Related Articles Insulin resistance impairs sustained virological response rate to pegylated interferon plus ribavirin in HIV-hepatitis C virus-coinfected patients: HOMAVIC-ANRS HC02 Study. Antivir Ther. 2009;14(6):839-45 Authors: Cacoub P, Carrat F, Bédossa P, Lambert J, Pénaranda G, Pol S, Halfon P BACKGROUND: The aim of this study was to assess the effect of insulin resistance (IR) on the response to hepatitis C virus (HCV) therapy in HIV-HCV-coinfected patients. METHODS: A total of 238 HIV-HCV-coinfected patients (74% male, mean +/-sd age 40 +/-5 years, mean alcohol intake <50 g/day and 38% HCV genotype 2 or 3), treated by standard or pegylated interferon-alpha2b plus ribavirin during 48 weeks were studied. Liver biopsies were assessed before treatment. Patients were considered to have IR when the homeostasis model assessment of IR (HOMA-IR) was >2.5. Multiple logistic regression with stepwise selection was used to estimate independent factors associated with sustained virological response (SVR). RESULTS: IR was present in 32% and significant liver fibrosis (Metavir>/=F2) in 74% of patients. Patients with SVR (96/238 [40%]) were more likely to be infected with HCV genotype 2 or 3 (54% versus 27%; P<0.0001), and had more severe liver fibrosis (>/=F3; 45% versus 30%; P=0.03). By multivariate analysis, a HOMA-IR>2.5 had a negative effect on the SVR (odds ratio 0.49 [95% confidence interval 0.26-0.92]; P=0.05). CONCLUSIONS: A high HOMA-IR level is frequently found in HIV-HCV-coinfected patients and is associated with a reduced SVR rate. Improving insulin sensitivity might be a useful adjunct to HCV therapy in HIV-HCV-coinfected patients. PMID: 19812446 [PubMed - in process]

Pharmacokinetics, safety and tolerability of a single oral dose of maraviroc in HIV-negative subjects with mild and moderate hepatic impairment.

Related Articles Pharmacokinetics, safety and tolerability of a single oral dose of maraviroc in HIV-negative subjects with mild and moderate hepatic impairment. Antivir Ther. 2009;14(6):831-7 Authors: Abel S, Davis JD, Ridgway CE, Hamlin JC, Vourvahis M BACKGROUND: Maraviroc is the first CCR5 antagonist and only oral entry inhibitor approved for the treatment of HIV type-1 infection. Maraviroc is extensively metabolized, primarily by cytochrome P450 3A4 and hence its pharmacokinetics might be affected by impaired hepatic function. The objective of this study was to evaluate the pharmacokinetics of maraviroc in subjects with mild or moderate hepatic impairment compared with subjects with normal hepatic function. Safety and tolerability were also assessed. METHODS: This was an open-label, non-randomized, single-centre, parallel-group study. A total of 24 subjects with mild (n=8) or moderate (n=8) hepatic impairment, or normal hepatic function (n=8) received a single dose of 300 mg maraviroc. RESULTS: Relative to those with normal hepatic function, the geometric mean ratio (90% confidence interval) for the maximum observed plasma concentration (C(max)) of maraviroc was 111% (74.6-166) and 132% (89.6-194) for those with mild and moderate hepatic impairment, respectively; the area under the concentration-time curve from time 0 to the last quantifiable concentration (AUC(last)) was 125% (84.7-185) and 146% (100-212); oral clearance was 89% (53.2-150) and 83% (49.2-139); and renal clearance was 94% (70.5-126) and 131% (98.6-173), respectively. Maraviroc was well tolerated in all subjects. CONCLUSIONS: Although differences in maraviroc pharmacokinetics were noted in subjects with hepatic impairment compared with those with normal hepatic function, these do not currently support a dose modification. The single 300 mg dose of maraviroc was well tolerated by subjects with normal and impaired hepatic function. PMID: 19812445 [PubMed - in process]

Combined effect of C-reactive protein and stavudine on adipogenesis.

Related Articles Combined effect of C-reactive protein and stavudine on adipogenesis. Antivir Ther. 2009;14(6):819-29 Authors: Stankov MV, Schmidt RE, Behrens GM BACKGROUND: Subcutaneous fat wasting in HIV therapy is primarily associated with the use of stavudine (d4T) and zidovudine (AZT). We hypothesized that C-reactive protein (CRP) might have an additive effect on nucleoside reverse transcriptase inhibitor (NRTI)-mediated peripheral fat loss. METHODS: 3T3-F442A cells were exposed to AZT (6 muM), d4T (3 muM) and/or CRP (0.5 mug/ml) during differentiation. Differentiation was assessed by real-time PCR measurement of peroxisome proliferator-activated receptor (PPAR)gamma and CCAAT/enhancer-binding protein (C/EBP)alpha, by quantification of triglyceride accumulation and by determination of adiponectin expression and secretion. In addition, parameters of lipid accumulation, lipolysis, cell viability and apoptosis were examined. RESULTS: When preadipocytes were induced to differentiate in the presence of only AZT, d4T or CRP, only AZT significantly impaired adipogenic differentiation. When combined, d4T+CRP also led to reduced triacylglycerol accumulation, an effect not explained by CRP-induced apoptosis or cell death, but instead confirmed by reduced PPARgamma and C/EBPalpha expression and decreased expression of factors involved in lipogenesis, such as fatty acid synthase and acetyl-coenzyme A carboxylase. We observed further reduction in adiponectin expression and secretion when adipocytes were differentiated in the presence of AZT or d4T together with CRP. Addition of rosiglitazone (1 muM) had no effect on reduced adipogenesis, but partially rescued the effects of d4T and d4T+CRP on adiponectin production. CONCLUSIONS: We conclude that CRP at levels circulating in patients with HIV infection might promote the anti-adipogenic potential of d4T, a cooperative effect that could account for the in vivo observed variability in the development of lipoatrophy. PMID: 19812444 [PubMed - in process]

alpha-Galactosylceramide in chronic hepatitis B infection: results from a randomized placebo-controlled Phase I/II trial.

Related Articles alpha-Galactosylceramide in chronic hepatitis B infection: results from a randomized placebo-controlled Phase I/II trial. Antivir Ther. 2009;14(6):809-818 Authors: Woltman AM, Ter Borg MJ, Binda RS, Sprengers D, von Blomberg BM, Scheper RJ, Hayashi K, Nishi N, Boonstra A, van der Molen R, Janssen HL BACKGROUND: The glycosphingolipid alpha-galactosylceramide (alpha-GalCer) is known to stimulate invariant natural killer T-cells (iNKTs) and is able to induce powerful antiviral immune responses. The present dose-escalating randomized placebo-controlled Phase I/II trial aimed to investigate antiviral activity and safety of alpha-GalCer as a novel class of treatment for chronic hepatitis B patients. METHODS: Patients were randomly assigned to 0.1 mug/kg (n=8), 1 mug/kg (n=6) or 10 mug/kg (n=6) alpha-GalCer or placebo (n=7) treatment. RESULTS: Almost all alpha-GalCer-treated patients showed a rapid and strong decrease in natural killer T-cell (NKT) numbers. Patients with high baseline NKT numbers showed immune activation, including natural killer cell activation, increased serum tumour necrosis factor-alpha and interleukin-6 levels, and development of fever. Three patients demonstrated a transient decrease in hepatitis B virus (HBV) DNA. Only one alpha-GalCer-treated patient had a sustained decrease in HBV DNA at the end of follow-up. Four patients discontinued therapy because of fever shortly after drug administration. No significant side effects were observed. CONCLUSIONS: alpha-GalCer (0.1-10 mug/kg) used as monotherapy for chronic hepatitis B infection resulted in a strong decrease of NKTs, but did not clearly affect HBV DNA and alanine aminotransferase levels. alpha-GalCer was poorly tolerated and is unlikely to be suitable as an alternative monotherapy to the current treatment regimen. PMID: 19812443 [PubMed - as supplied by publisher]

Stimulation of the interleukin-1 receptor and Toll-like receptor 2 inhibits hepatitis B virus replication in hepatoma cell lines in vitro.

Related Articles Stimulation of the interleukin-1 receptor and Toll-like receptor 2 inhibits hepatitis B virus replication in hepatoma cell lines in vitro. Antivir Ther. 2009;14(6):797-808 Authors: Thompson AJ, Colledge D, Rodgers S, Wilson R, Revill P, Desmond P, Mansell A, Visvanathan K, Locarnini S BACKGROUND: Toll-like receptors (TLRs) are a key component of the innate immune system and TLR2 has been shown to be involved in the immunopathogenesis of hepatitis B virus (HBV) infection in vivo. We investigated the role of TLR2 stimulation of virus-infected hepatocyte cell lines as a potential antiviral mechanism in vitro. METHODS: The hepatoblastoma cell line HepG2 was transduced with recombinant HBV baculoviruses and the hepatoma cell line Huh-7 was transiently transfected with complimentary DNA clones of HBV. HBV viral replication was quantified after stimulation with interleukin (IL)-1beta and Pam-2-Cys, a synthetic TLR2 ligand, by measuring intracellular core-associated single-stranded HBV DNA using Southern blot hybridization, as well as viral nucleocapsid formation using a non-denaturing immunoblot method. RESULTS: Stimulation of both cell lines in vitro with IL-1beta and Pam-2-Cys, both known to induce expression of the pro inflammatory cytokines tumour necrosis factor-alpha and IL-8 via a nuclear factor-kappaB dependent pathway, resulted in the inhibition of HBV DNA replication in the transduced HepG2 cells by up to 90% and nucleocapsid formation in the transiently transfected Huh-7 cells by up to 30%, when compared with mock-treated cells. CONCLUSIONS: Hepatoma cell lines expressed functional IL-1 receptor and TLR2 receptors, which when stimulated led to a signalling cascade that inhibited HBV replication. These data support an active role for hepatocytes in inhibiting HBV replication and provide a rationale for the development of TLR agonists as potentially novel antiviral agents. PMID: 19812442 [PubMed - in process]

The course of inactive hepatitis B in hepatitis-C-coinfected patients treated with interferon and ribavirin.

Related Articles The course of inactive hepatitis B in hepatitis-C-coinfected patients treated with interferon and ribavirin. Antivir Ther. 2009;14(6):789-96 Authors: Viganò M, Aghemo A, Iavarone M, Rumi MG, Agnelli F, Lampertico P, Donato MF, Colombo M BACKGROUND: Interferon (IFN) combined with ribavirin (RBV) is an effective therapy for hepatitis C virus (HCV)-infected patients. Those who are coinfected with hepatitis B virus (HBV), however, might suffer from HBV reactivation. The aim of this study was to assess HBV reactivation in HCV-coinfected inactive HBV carriers following IFN/RBV. METHODS: A total of 32 HBV carriers with 4 log(10) copies/ml (range 5.2-6.5 log(10) copies/ml); however, these patients had no ALT flare either on treatment (n=2) or off treatment (n=1). During follow-up, 8 (36%) treated patients and 4 controls lost serum hepatitis B surface antigen (HBsAg; annual rate 6.5% versus 6.9%; P-value non-significant), whereas 4 and 2 patients seroconverted to antibodies against HBsAg, respectively. Hepatocellular carcinoma developed in 1 patient with SVR and 1 non-responder under nucleoside therapy for HBV, both with cirrhosis. No patient clinically decompensated. CONCLUSIONS: Inactive HBV carriers coinfected with HCV might achieve an SVR following IFN/RBV. Combination therapy carries a low risk of on- and off-treatment HBV reactivation and does not prevent HBsAg seroclearance. PMID: 19812441 [PubMed - in process]

Smoking motivations and quitting motivations among HIV-infected smokers.

Related Articles Smoking motivations and quitting motivations among HIV-infected smokers. Antivir Ther. 2009;14(6):781-787 Authors: Peretti-Watel P, Garelik D, Baron G, Spire B, Ravaud P, Duval X, BACKGROUND: The aim of this study was to examine smoking motivation and motivation to quit, and determinants of these motivations among HIV-infected cigarette smokers. METHODS: We conducted a 1-day cross-sectional survey on cigarette smoking in a representative sample of HIV-infected outpatients of French hospitals. A cluster analysis was used to characterize respondents' smoking motivation. A logistic regression was performed to study the factors associated with motivation to quit, including the clusters describing smoking motives. RESULTS: We found four clusters of smoking motivation. These included intellectual/emotional support (22% of respondents), automatic/stress relief (22%; characterized by heavy smoking and strong dependency); weight control (29%; characterized by frequent symptoms of fat accumulation because of antiretroviral therapy) and pleasure/conviviality (27%; corresponding to 'lighter' smokers). In the logistic regression model, among other significant covariates (cigarette consumption level, tobacco dependence and perceived risk of developing a smoking-related disease), the automatic/stress relief cluster was negatively correlated to the motivation to quit (odds ratio 0.39), whereas the weight control cluster was strongly associated to this motivation (odds ratio 2.87). CONCLUSIONS: The diversity of HIV-infected smokers' profiles suggests that different types of anti-tobacco measures should be implemented in this population, such as information campaigns on specific risks incurred by HIV-infected smokers, non-specific and comprehensive measures for those for whom smoking is combined with other difficulties, and alternative therapeutic solutions for those who smoke to deal with lipodystrophy. PMID: 19812440 [PubMed - as supplied by publisher]

Virological and immunological responses to efavirenz or boosted lopinavir as first-line therapy for patients with HIV.

Related Articles Virological and immunological responses to efavirenz or boosted lopinavir as first-line therapy for patients with HIV. Antivir Ther. 2009;14(6):771-779 Authors: Young J, Bucher HC, Guenthard HF, Rickenbach M, Fux CA, Hirschel B, Cavassini M, Vernazza P, Bernasconi E, Battegay M, BACKGROUND: Efavirenz and lopinavir boosted with ritonavir are both recommended as first-line therapies for patients with HIV when combined with two nucleoside reverse transcriptase inhibitors. It is uncertain which therapy is more effective for patients starting therapy with an advanced infection. METHODS: We estimated the relative effect of these two therapies on rates of virological and immunological failure within the Swiss HIV Cohort Study and considered whether estimates depended on the CD4(+) T-cell count when starting therapy. We defined virological failure as either an incomplete virological response or viral rebound after viral suppression and immunological failure as failure to achieve an expected CD4(+) T-cell increase calculated from EuroSIDA statistics. RESULTS: Patients starting efavirenz (n=660) and lopinavir (n=541) were followed for a median of 4.5 and 3.1 years, respectively. Virological failure was less likely for patients on efavirenz, with the adjusted hazard ratio (95% confidence interval) of 0.63 (0.50-0.78) then multiplied by a factor of 1.00 (0.90-1.12) for each 100 cells/mm(3) decrease in CD4(+) T-cell count below the mean when starting therapy. Immunological failure was also less likely for patients on efavirenz, with the adjusted hazard ratio of 0.68 (0.51-0.91) then multiplied by a factor of 1.29 (1.14-1.46) for each 100 cells/mm(3) decrease in CD4(+) T-cell count below the mean when starting therapy. CONCLUSIONS: Virological failure is less likely with efavirenz regardless of the CD4(+) T-cell count when starting therapy. Immunological failure is also less likely with efavirenz; however, this advantage disappears if patients start therapy with a low CD4(+) T-cell count. PMID: 19812439 [PubMed - as supplied by publisher]

Oxidant stress in HIV-infected women from the Women's Interagency HIV Study.

Related Articles Oxidant stress in HIV-infected women from the Women's Interagency HIV Study. Antivir Ther. 2009;14(6):763-9 Authors: Glesby MJ, Hoover DR, Raiszadeh F, Lee I, Shi Q, Milne G, Sanchez SC, Gao W, Kaplan RC, Morrow JD, Anastos K BACKGROUND: Oxidant stress contributes to the pathogenesis of multiple conditions and can be assessed by measuring plasma F(2)-isoprostane concentrations. We hypothesized that oxidant stress is associated with plasma homocysteine concentration and risk factors for atherosclerosis in HIV-infected women. METHODS: We measured plasma F(2)-isoprostane concentrations in a cross-sectional study of 249 HIV-infected women attending the Bronx (NY, USA) site of the Women's Interagency HIV Study and assessed associations with plasma homocysteine concentration and other metabolic parameters by linear regression. RESULTS: In multivariate analysis, hepatitis C virus (HCV) viraemia, waist circumference, homocysteine concentration and serum aspartate aminotransferase level were positively associated with log F(2)-isoprostane concentration (all P<0.005). There was a trend for an inverse association between log F(2)-isoprostane and CD4(+) T-cell percentage (P=0.06). Among women with HCV infection, the FIB-4 index, an indirect marker of liver fibrosis derived from routine laboratory tests, was positively associated with log F(2)-isoprostane concentration. CONCLUSIONS: In this cross-sectional study of HIV-infected women, plasma F(2)-isoprostane concentration was positively associated with homocysteine concentration, as well as HCV infection, abdominal obesity and aspartate aminotransferase level. PMID: 19812438 [PubMed - in process]

Surveillance for neuraminidase-inhibitor-resistant influenza viruses in Japan, 1996-2007.

Related Articles Surveillance for neuraminidase-inhibitor-resistant influenza viruses in Japan, 1996-2007. Antivir Ther. 2009;14(6):751-761 Authors: Tashiro M, McKimm-Breschkin JL, Saito T, Klimov A, Macken C, Zambon M, Hayden FG, BACKGROUND: High usage of the neuraminidase inhibitor (NAI) oseltamivir in Japan since 2003 led the Neuraminidase Inhibitor Susceptibility Network to assess the susceptibility of community isolates of influenza viruses to oseltamivir and zanamivir. METHODS: Isolates were tested by the enzyme inhibition assay and by neuraminidase (NA) sequence analysis. RESULTS: Among 1,141 A(H3N2) viruses and 171 type B viruses collected in Japan during the 2003-2004 season, 3 (0.3%) A(H3N2) isolates showed high 50% inhibitory concentrations (IC(50)) to oseltamivir. Each possessed a known resistance NA mutation at R292K or E119V. During the 2004-2005 season, no resistance was found among 567 influenza A(H3N2) or 60 A(H1N1) isolates, but 1 of 58 influenza B isolates had an NAI resistance mutation (D197N). Sequence analysis found that 4 (3%) of 132 A(H1N1) viruses from 2005-2006 had known NA resistance mutations (all H274Y), but no additional resistant isolates were detected from that or the subsequent 2006-2007 season. Concurrent testing of a selection of 500 influenza B viruses from 2000 to 2006 showed significant variations between seasons in both oseltamivir and zanamivir IC(50) values, but no persistent increases over this period. CONCLUSIONS: Our findings suggested possible low-level transmission of resistant variants from oseltamivir-treated patients in several seasons in Japan but no sustained reductions in NAI susceptibility or consistently increased frequency of detecting resistant variants for any strain or subtype, despite high levels of drug use. In particular, although oseltamivir-resistant A(H1N1) viruses with the H274Y mutation spread globally in 2007-2008, we found little evidence for increasing levels of resistant A(H1N1) variants in Japan in preceding years. PMID: 19812437 [PubMed - as supplied by publisher]

Dengue vaccine development and dengue viral neutralization and enhancement assays.

Related Articles Dengue vaccine development and dengue viral neutralization and enhancement assays. Antivir Ther. 2009;14(6):739-49 Authors: Jin X, Block OT, Rose R, Schlesinger J Dengue fever is a major tropical infectious disease that affects 50-100 million people each year. Its complications, namely dengue haemorrhagic fever and dengue shock syndrome, disproportionately afflict children and young adults. The primary goal of several vaccines now in development is to elicit protective neutralizing antibody responses; however, the exact definition of such responses remain unclear. Here, we review briefly the historical aspects of dengue vaccine development and current candidate dengue vaccines, and discuss various laboratory assays for gauging the neutralizing antibody responses to infection or vaccination, or both. We conclude that modification of current neutralization assays is required to improve the correlation between neutralization end point determinations and protection against secondary heterotypic dengue infections. PMID: 19812436 [PubMed - in process]

Host genetics influences on HIV type-1 disease.

Related Articles Host genetics influences on HIV type-1 disease. Antivir Ther. 2009;14(6):731-8 Authors: Fellay J HIV host genetic studies seek to describe as comprehensively as possible the effect of human genetic variation on the individual response to HIV type-1 (HIV-1) infection. Many associations between specific gene variants and HIV-1 disease outcomes have been reported over the past 15 years. Although most of them have yet to be confirmed or have been proven false-positives, the identification of several definitive genotype-phenotype associations has shed new light on HIV-1 pathogenesis. This review discusses these results in the context of the new genome-wide approaches that now make it possible to globally assess the influence of the host genome on HIV-1-related outcomes. PMID: 19812435 [PubMed - in process]

Uptake of meningococcal conjugate vaccine among adolescents in large managed care organizations, United States, 2005: Demand, supply and seasonality.

Background: In February 2005, the US Advisory Committee on Immunization Practices recommended the new meningococcal conjugate vaccine (MCV4) for routine use among 11- to 12-year-olds (at the preadolescent health-care visit), 14- to 15-year-olds (before high-school entry), and groups at increased risk. Vaccine distribution started in March; however, in July, the manufacturer reported inability to meet demand and widespread MCV4 shortages were reported. Our objectives were to determine early uptake patterns among target (11-12 and 14-15 year olds) and non-target (13- plus 16-year-olds) age groups. A post hoc analysis was conducted to compare seasonal uptake patterns of MCV4 with polysaccharide meningococcal (MPSV4) and tetanus diphtheria (Td) vaccines. Methods: We analyzed data for adolescents 11-16 years from five managed care organizations participating in the Vaccine Safety Datalink (VSD). For MCV4, we estimated monthly and cumulative coverage during 2005 and calculated risk ratios. For MPSV4 and Td, we combined 2003 and 2004 data and compared their seasonal uptake patterns with MCV4. Results: Coverage for MCV4 during 2005 among the 623,889 11-16 years olds was 10%. Coverage for 11-12 and 14-15 year olds was 12% and 11%, respectively, compared with 8% for 13- plus 16-year-olds (p<0.001). Of the 64,272 MCV4 doses administered from March-December 2005, 73% were administered June-August. Fifty-nine percent of all MPSV4 doses and 38% of all Td doses were administered during June-August. Conclusions: A surge in vaccine uptake between June and August was observed among adolescents for MCV4, MPSV4 and Td vaccines. The increase in summer-time vaccinations and vaccination of non-targeted adolescents coupled with supply limitations likely contributed to the reported shortages of MCV4 in 2005.

Downregulation of MIP-1alpha/CCL3 with praziquantel treatment in Schistosoma haematobiumand HIV-1 co-infected individuals in a rural community in Zimbabwe

Background: Chemokines have been reported to play an important role in granulomatous inflammation during Schistosoma mansoni infection. However there is less information on their role in Schistosoma haematobium infection, or on the effect of concurrent HIV-1 infection, as a potential modifying influence. Methods: To determine levels of MIP-1α/CCL3 chemokine in plasma of S. haematobium and HIV-1 co-infected and uninfected individuals in a rural black Zimbabwean community.A cohort was established of HIV-1 and schistosomiasis infection and co-infection comprising 379 participants. Outcome measures consisted of HIV-1 and schistosomiasis status and levels of MIP-1α/CCL3 in plasma at baseline and three months post treatment. An association was established between MIP-1α/CCL3 plasma levels with HIV-1 and S. haematobium infections. Results: A total of 379 adults formed the established cohort comprising 76 (20%) men and 303 (80%) women. Mean age was 33.25, range 17 - 62 years. The median MIP-1α/CCL3 plasma concentration was significantly higher in S. haematobium infected compared with uninfected individuals (p = 0.029). In contrast, there was no difference in the median MIP-1α/CCL3 levels between HIV-1 positive and negative individuals (p = 0.631). MIP-1α/CCL3 concentration in plasma was significantly reduced at three months after treatment with praziquantel (p = 000). Conclusion: The results of our study show that the MIP-1α/CCL3 levels were positively associated with S. haematobium egg counts at baseline but not with HIV-1 infection status. MIP-1α/CCL3 levels were significantly reduced at three months post treatment with praziquantel. We therefore conclude that MIP-1α/CCL3 is produced during infection with S haematobium. S. haematobium infection is associated with increased MIP-1α/CCL3 levels in an egg intensity-dependent manner and treatment of S. haematobium is associated with a reduction in MIP-1α/CCL3.

Acute sensorineural hearing loss and severe otalgia due to scrub typhus

Background: Scrub typhus is an acute febrile illness caused by Orientia tsutsugamushi.Case presentationsWe encountered a patient with sensorineural hearing loss complicating scrub typhus, and three patients with scrub typhus who complained of otalgia, which was sudden onset, severe, paroxysmal, intermittent yet persistent pain lasting for several seconds, appeared within 1 week after the onset of fever and rash. The acute sensorineural hearing loss and otalgia were resolved after antibiotic administration. Conclusion: When patients in endemic areas present with fever and rash and have sensorineural hearing loss or otalgia without otoscopic abnormalities, clinicians should suspect scrub typhus and consider empirical antibiotic therapy.

Immune control of HIV-1 infection after therapy interruption: immediate versus deferred antiretroviral therapy

Background: The optimal stage for initiating antiretroviral therapies in HIV-1 bearing patients is still a matter of debate. Methods: We present computer simulations of HIV-1 infection aimed at identifying the pro et contra of immediate as compared to deferred Highly Active Antiretroviral Therapy (HAART). Results: Our simulations highlight that a prompt specific CD8+ cytotoxic T lymphocytes response is detected when therapy is delayed. Compared to very early initiation of HAART, in deferred treated patients CD8+ T cells manage to mediate the decline of viremia in a shorter time and, at interruption of therapy, the virus experiences a stronger immune pressure. We also observe, however, that the immunological effects of the therapy fade with time in both therapeutic regimens. Thus, within one year from discontinuation, viral burden recovers to the value at which it would level off in the absence of therapy.In summary, simulations show that immediate therapy does not prolong the disease-free period and does not confer a survival benefit when compared to treatment started during the chronic infection phase. Conclusion: Our conclusion is that, since there is no therapy to date that guarantees life-long protection, deferral of therapy should be preferred in order to minimize the risk of adverse effects, the occurrence of drug resistances and the costs of treatment.

Newly formed cystic lesions for the development of pneumomediastinum in Pneumocystis jirovecii pneumonia

Background: Pneumocystis jirovecii, formerly named Pneumocystis carinii, is one of the most common opportunistic infections in human immunodeficiency virus (HIV)-infected patients.Case presentationsWe encountered two cases of spontaneous pneumomediastinum with subcutaneous emphysema in HIV-infected patients being treated for Pneumocystis jirovecii pneumonia with trimethoprim/sulfamethoxazole. Conclusion: Clinicians should be aware that cystic lesions and bronchiectasis can develop in spite of trimethoprim/sulfamethoxazole treatment for P. jirovecii pneumonia. The newly formed bronchiectasis and cyst formation that were noted in follow up high resolution computed tomography (HRCT) but were not visible on HRCT at admission could be risk factors for the development of pneumothorax or pneumomediastinum with subcutaneous emphysema in HIV-patients.

Protective measures and H5N1-seroprevalence among personnel tasked with bird collection during an outbreak of avian influenza A/H5N1 in wild birds, Ruegen, Germany, 2006

Background: In Germany, the first outbreak of highly pathogenic avian influenza A/H5N1 occurred among wild birds on the island of Ruegen between February and April 2006. The aim of this study was to investigate the use of recommended protective measures and to measure H5N1-seroprevalence among personnel tasked with bird collection. Methods: Inclusion criteria of our study were participation in collecting wild birds on Ruegen between February and March 2006. Study participants were asked to complete a questionnaire, and to provide blood samples. For evaluation of the use of protective measures, we developed a personal protective equipment (PPE)-score ranging between 0 and 9, where 9 corresponds to a consistent and complete use of PPE. Sera were tested by plaque neutralization (PN) and microneutralization (MN) assays. Reactive sera were reanalysed in the World Health Organization-Collaborating Centre (WHO-CC) using MN assay. Results: Of the eligible personnel, consisting of firemen, government workers and veterinarians, 61% (97/154) participated in the study. Of those, 13% reported having always worn all PPE-devices during bird collection (PPE-score: 9). Adherence differed between firemen (mean PPE-score: 6.6) and government workers (mean PPE-score: 4.5; p = 0.006). The proportion of personnel always adherent to wearing PPE was lowest for masks (19%). Of the participants, 18% had received seasonal influenza vaccination prior to the outbreak. There were no reports of influenza-like illness. Five sera initially H5-reactive by PN assay were negative by WHO-CC confirmatory testing. Conclusion: Gaps and variability in adherence demonstrate the risk of exposure to avian influenza under conditions of wild bird collection, and justify serological testing and regular training of task personnel.

Barriers to the care of HIV-infected children in rural Zambia: a cross-sectional analysis

Background: Successful antiretroviral treatment programs in rural sub-Saharan Africa may face different challenges than programs in urban areas. The objective of this study was to identify patient characteristics, barriers to care, and treatment responses of HIV-infected children seeking care in rural Zambia. Methods: Cross-sectional analysis of HIV-infected children seeking care at Macha Hospital in rural southern Zambia. Information was collected from caretakers and medical records. Results: 192 HIV-infected children were enrolled from September 2007 through September 2008, 28% of whom were receiving antiretroviral therapy (ART) at enrollment. The median age was 3.3 years for children not receiving ART (IQR 1.8, 6.7) and 4.5 years for children receiving ART (IQR 2.7, 8.6). 91% travelled more than one hour to the clinic and 26% travelled more than 5 hours. Most participants (73%) reported difficulties accessing the clinic, including insufficient money (60%), lack of transportation (54%) and roads in poor condition (32%). The 54 children who were receiving ART at study enrollment had been on ART a median of 8.6 months (IQR: 2.7, 19.5). The median percentage of CD4+ T cells was 12.4 (IQR: 9.2, 18.6) at the start of ART, and increased to 28.6 (IQR: 23.5, 36.1) at the initial study visit. However, the proportion of children who were underweight decreased only slightly, from 70% at initiation of ART to 61% at the initial study visit. Conclusion: HIV-infected children in rural southern Zambia have long travel times to access care and may have poorer weight gain on ART than children in urban areas. Despite these barriers, these children had a substantial rise in CD4+ T cell counts in the first year of ART although longer follow-up may indicate these gains are not sustained.

Influenza activity in Cambodia during 2006-2008

Background: There is little information about influenza disease among the Cambodian population. To better understand the dynamics of influenza in Cambodia, the Cambodian National Influenza Center (NIC) was established in August 2006. To continuously monitor influenza activity, a hospital based sentinel surveillance system for ILI (influenza like illness) with a weekly reporting and sampling scheme was established in five sites in 2006. In addition, hospital based surveillance of acute lower respiratory infection (ALRI) cases was established in 2 sites. Methods: The sentinel sites collect weekly epidemiological data on ILI patients fulfilling the case definition, and take naso-pharyngeal specimens from a defined number of cases per week. The samples are tested in the Virology Unit at the Institut Pasteur in Phnom Penh. From each sample viral RNA was extracted and amplified by a multiplex RT-PCR detecting simultaneously influenza A and influenza B virus. Influenza A viruses were then subtyped and analyzed by hemagglutination inhibition assay. Samples collected by the ALRI system were tested with the same approach. Results: From 2006 to 2008, influenza circulation was observed mainly from June to December, with a clear seasonal peak in October shown in the data from 2008. Conclusion: Influenza activity in Cambodia occurred during the rainy season, from June to December, and ended before the cool season (extending usually from December to February). Although Cambodia is a tropical country geographically located in the northern hemisphere, influenza activity has a southern hemisphere transmission pattern. Together with the antigenic analysis of the circulating strains, it is now possible to give better influenza vaccination recommendation for Cambodia.

Identification and genotyping of bacteria from paired vaginal and rectal samples from pregnant women indicates similarity between vaginal and rectal microflora

Background: The vaginal microflora is important for maintaining vaginal health and preventing infections of the reproductive tract. The rectum has been suggested as the major source for the colonisation of the vaginal econiche. Methods: To establish whether the rectum can serve as a possible bacterial reservoir for colonisation of the vaginal econiche, we cultured vaginal and rectal specimens from pregnant women at 35-37 weeks of gestation, identified the isolates to the species level with tRNA intergenic length polymorphism analysis (tDNA-PCR) and genotyped the isolates for those subjects from which the same species was isolated simultaneously vaginally and rectally, by RAPD-analysis.One vaginal and one rectal swab were collected from a total of each of 132 pregnant women at 35-37 weeks of gestation. Swabs were cultured on Columbia CNA agar and MRS agar. For each subject 4 colonies were selected for each of both sites, i.e. 8 colonies in total. Results: Among the 844 isolates that could be identified by tDNA-PCR, a total of 63 bacterial species were present, 9 (14%) only vaginally, 26 (41%) only rectally, and 28 (44%) in both vagina and rectum. A total of 121 (91.6%) of 132 vaginal samples and 51 (38.6%) of 132 rectal samples were positive for lactobacilli. L. crispatus was the most frequently isolated Lactobacillus species from the vagina (40% of the subjects were positive), followed by L. jensenii (32%), L. gasseri (30%) and L. iners (11%). L. gasseri was the most frequently isolated Lactobacillus species from the rectum (15%), followed by L. jensenii (12%), L. crispatus (11%) and L. iners (2%).A total of 47 pregnant women carried the same species vaginally and rectally. This resulted in 50 vaginal/rectal pairs of the same species, for a total of eight different species. For 34 of the 50 species pairs (68%), isolates with the same genotype were present vaginally and rectally and a high level of genotypic diversity within species per subject was also established. Conclusion: It can be concluded that there is a certain degree of correspondence between the vaginal and rectal microflora, not only with regard to species composition but also with regard to strain identity between vaginal and rectal isolates.These results support the hypothesis that the rectal microflora serves as a reservoir for colonisation of the vaginal econiche.

Initial psychological responses to Influenza A, H1N1 ("Swine flu")

Background: The outbreak of the pandemic flu, Influenza A H1N1 (Swine Flu) in early 2009, provided a major challenge to health services around the world. Previous pandemics have led to stockpiling of goods, the victimisation of particular population groups, and the cancellation of travel and the boycotting of particular foods (e.g. pork). We examined initial behavioural and attitudinal responses towards Influenza A, H1N1 ("Swine flu") in the six days following the WHO pandemic alert level 5, and regional differences in these responses. Methods: 328 respondents completed a cross-sectional Internet or paper-based questionnaire study in Malaysia (N = 180) or Europe (N = 148). Measures assessed changes in transport usage, purchase of preparatory goods for a pandemic, perceived risk groups, indicators of anxiety, assessed estimated mortality rates for seasonal flu, effectiveness of seasonal flu vaccination, and changes in pork consumption Results: 26% of the respondents were 'very concerned' about being a flu victim (42% Malaysians, 5% Europeans, p < .001). 36% reported reduced public transport use (48% Malaysia, 22% Europe, p < .001), 39% flight cancellations (56% Malaysia, 17% Europe, p < .001). 8% had purchased preparatory materials (e.g. face masks: 8% Malaysia, 7% Europe), 41% Malaysia (15% Europe) intended to do so (p < .001). 63% of Europeans, 19% of Malaysians had discussed the pandemic with friends (p < .001). Groups seen as at 'high risk' of infection included the immune compromised (mentioned by 87% respondents), pig farmers (70%), elderly (57%), prostitutes/highly sexually active (53%), and the homeless (53%). In data collected only in Europe, 64% greatly underestimated the mortality rates of seasonal flu, 26% believed seasonal flu vaccination gave protection against swine flu. 7% had reduced/stopped eating pork. 3% had purchased anti-viral drugs for use at home, while 32% intended to do so if the pandemic worsened. Conclusion: Initial responses to Influenza A show large regional differences in anxiety, with Malaysians more anxious and more likely to reduce travel and to buy masks and food. Discussions with family and friends may reinforce existing anxiety levels. Particular groups (homosexuals, prostitutes, the homeless) are perceived as at greater risk, potentially leading to increased prejudice during a pandemic. Europeans underestimated mortality of seasonal flu, and require more information about the protection given by seasonal flu inoculation.

The Burden of Mental Disorders

In the last decade, there has been an increase in interest in the burden of chronic and disabling health conditions that are not necessarily fatal, such as the mental disorders. This review systematically summarizes data on the burden associated with 11 major mental disorders of adults. The measures of burden include estimates of prevalence, mortality associated with the disorders, disabilities and impairments related to the disorders, and costs. This review expands the range of mental disorders considered in a report on the global burden of disease, updates the literature, presents information on the range and depth of sources of information on burden, and adds estimates of costs. The purpose is to provide an accessible guide to the burden of mental disorders, especially for researchers and policy makers who may not be familiar with this subfield of epidemiology.

Dementia of the Alzheimer Type

Dementia of the Alzheimer type is a progressive, fatal neurodegenerative condition characterized by deterioration in cognition and memory, progressive impairment in the ability to carry out activities of daily living, and a number of neuropsychiatric symptoms. This narrative review summarizes the literature regarding descriptive epidemiology, clinical course, and characteristic neuropathological changes of dementia of the Alzheimer type. Although there are no definitive imaging or laboratory tests, except for brain biopsy, for diagnosis, brief screening instruments and neuropsychiatric test batteries used to assess the disease are discussed. Insufficient evidence exists for the use of biomarkers in clinical practice for diagnosis or disease management, but promising discoveries are summarized. Optimal treatment requires both nonpharmacological and pharmacological interventions, yet none have been shown to modify the disease's clinical course. This review describes the current available options and summarizes promising new avenues for treatment. Issues related to the care of persons with dementia of the Alzheimer type, including caregiver burden, long-term care, and the proliferation of dementia special care units, are discussed. Although advances have been made, more research is needed to address the gaps in our understanding of the disease.

Dementia Prevention: Methodological Explanations for Inconsistent Results

The prevention of neurodegenerative dementias, such as Alzheimer disease, is a growing public health concern, because of a lack of effective curative treatment options and a rising global prevalence. Various potential risk or preventive factors have been suggested by epidemiologic research, including modifiable lifestyle factors, such as social contacts, leisure activities, physical exercise, and diet, as well as some preventive pharmacologic strategies, such as hormone replacement therapy, nonsteroidal antiinflammatory drugs, and Ginkgo biloba. Some factors have been targeted by interventions tested in randomized controlled trials, but many of the results are in conflict with observational evidence. The aim of this paper is to review the epidemiologic data linking potential protective factors to dementia or cognitive decline and to discuss the methodological limitations that could explain conflicting results. A thorough review of the literature suggests that, even if there are consistent findings from large observational studies regarding preventive or risk factors for dementia, few randomized controlled trials have been designed specifically to prove the protective effects of interventions based on such factors on dementia incidence. Because of the multifactorial origin of dementia, it appears that multidomain interventions could be a suitable candidate for preventive interventions, but designing such trials remains very challenging for researchers.

Schizophrenia: A Concise Overview of Incidence, Prevalence, and Mortality

Recent systematic reviews have encouraged the psychiatric research community to reevaluate the contours of schizophrenia epidemiology. This paper provides a concise overview of three related systematic reviews on the incidence, prevalence, and mortality associated with schizophrenia. The reviews shared key methodological features regarding search strategies, analysis of the distribution of the frequency estimates, and exploration of the influence of key variables (sex, migrant status, urbanicity, secular trend, economic status, and latitude). Contrary to previous interpretations, the incidence of schizophrenia shows prominent variation between sites. The median incidence of schizophrenia was 15.2/100,000 persons, and the central 80% of estimates varied over a fivefold range (7.7–43.0/100,000). The rate ratio for males:females was 1.4:1. Prevalence estimates also show prominent variation. The median lifetime morbid risk for schizophrenia was 7.2/1,000 persons. On the basis of the standardized mortality ratio, people with schizophrenia have a two- to threefold increased risk of dying (median standardized mortality ratio = 2.6 for all-cause mortality), and this differential gap in mortality has increased over recent decades. Compared with native-born individuals, migrants have an increased incidence and prevalence of schizophrenia. Exposures related to urbanicity, economic status, and latitude are also associated with various frequency measures. In conclusion, the epidemiology of schizophrenia is characterized by prominent variability and gradients that can help guide future research.

Population-based Cohort Studies on Premorbid Cognitive Function in Schizophrenia

Many previous studies have found associations between poor cognitive function and schizophrenia. However, the majority of these studies used retrospective data, leading to the possibility of selection and recall biases. Retrospective studies are also unable to distinguish whether cognitive deficits exist prior to the onset of schizophrenia, suggesting that they are important in etiology, or following onset, suggesting that they are secondary to the disorder or its treatment. The current review used a systematic search strategy to identify and summarize the results of all studies that have used population-based cohorts to examine associations between prospectively collected data on premorbid cognitive functioning in childhood or adolescence and subsequent risk for schizophrenia. Three broad categories of study have addressed these questions: birth cohort designs with cognitive testing during childhood, army conscript designs with cognitive performance measured at conscription, and studies using school grades. Birth cohort and conscript studies are consistent in reporting strong associations between poor performance on cognitive batteries and increased risk of schizophrenia. Studies on school performance have been less consistent, although the largest such study showed strong associations across all school subjects. In conclusion, children and adolescents with poor cognitive abilities in childhood are at increased risk of schizophrenia. This suggests that poor cognitive function is either directly causal or associated with causal factors that are involved in etiology.

Psychosis and Place

One important line of epidemiologic inquiry implicating social context in the etiology of psychosis is the examination of spatial variation in the distribution of psychotic illness. The authors conducted a systematic review of evidence from urbanicity and neighborhood studies regarding spatial variation in the incidence of psychosis in developed countries since 1950. A total of 44 studies (20 of urbanicity and 24 of neighborhood) were culled from three databases with similar time frames: Medline (1950–2007), PsychInfo (1950–2007), and Sociological Abstracts (1952–2007). With a special emphasis on social factors potentially relevant to etiology, the authors elucidated contributions, limitations, and issues related to study design, measurement, and theory. Evidence from both arenas supports a possible etiologic role for social context. Studies of urbanicity indicate that early-life exposure may be important; dose-response relations, spatial patterning of schizophrenia, and interactions with other factors may exist. Neighborhood studies indicate heterogeneity in rates, hint at spatial patterning of schizophrenia, and offer intriguing evidence implying more proximal social (as opposed to physical) exposures. The authors encourage the exploration of social pathways engaging theory, methodological advances, and the life-course perspective. They also propose a conceptual shift from studies of spatial variation in outcomes to research addressing the etiologic effect of exposures shaped by place as a reservoir of risk or resilience.

Blues from the Neighborhood? Neighborhood Characteristics and Depression

Unipolar major depression ranks among the leading contributors to the global burden of disease. Although established risk factors for depression include a variety of individual-level characteristics, neighborhood etiologic factors have been relatively understudied, with several such attributes (neighborhood socioeconomic status, physical conditions, services/amenities, social capital, social disorder) possessing plausible linkages to depression. Using the PubMed database (1966–2008) and the Social Sciences Citation Index database (1956–2008), the author undertook a systematic review of the published literature on the associations between these characteristics and depression in adults. Across studies, the evidence generally supports harmful effects of social disorder and, to a lesser extent, suggests protective effects for neighborhood socioeconomic status. Few investigations have explored the relations for neighborhood physical conditions, services/amenities, and social capital, and less consistently point to salutary effects. The unsupportive findings may be attributed to the lack of representative studies within and across societies or to methodological gaps, including lack of control for other neighborhood/non-neighborhood exposures and lack of implementation of more rigorous methodological approaches. Establishing mediating pathways and effect-modifying factors will vitally advance understanding of neighborhood effects on depression. Overall, addressing these gaps will help to identify what specific neighborhood features matter for depression, how, and for whom, and will contribute to curtailing the burden of disease associated with this major disorder.

The Relation between Work-related Psychosocial Factors and the Development of Depression

This review is based on a literature search made in January 2007 on request by the Danish National Board of Industrial Injuries. The search in PubMed, EMBASE, and PsycINFO resulted in more than 1,000 publications. This was reduced to 14 after the titles, abstracts, and papers were evaluated by using the following criteria: 1) a longitudinal study, 2) exposure to work-related psychosocial factors, 3) the outcome a measure of depression, 4) relevant statistical estimates, and 5) nonduplicated publication. Of the 14 studies, seven used standardized diagnostic instruments as measures of depression, whereas the other seven studies used self-administered questionnaires. The authors found moderate evidence for a relation between the psychological demands of the job and the development of depression, with relative risks of approximately 2.0. However, indication of publication bias weakens the evidence. Social support at work was associated with a decrease in risk for future depression, as all four studies dealing with this exposure showed associations with relative risks of about 0.6. Even if this literature study has identified work-related psychosocial factors that in high-quality epidemiologic studies predict depression, studies are still needed that assess in more detail the duration and intensity of exposure necessary for developing depression.

Suicide and Suicidal Behavior

Suicidal behavior is a leading cause of injury and death worldwide. Information about the epidemiology of such behavior is important for policy-making and prevention. The authors reviewed government data on suicide and suicidal behavior and conducted a systematic review of studies on the epidemiology of suicide published from 1997 to 2007. The authors' aims were to examine the prevalence of, trends in, and risk and protective factors for suicidal behavior in the United States and cross-nationally. The data revealed significant cross-national variability in the prevalence of suicidal behavior but consistency in age of onset, transition probabilities, and key risk factors. Suicide is more prevalent among men, whereas nonfatal suicidal behaviors are more prevalent among women and persons who are young, are unmarried, or have a psychiatric disorder. Despite an increase in the treatment of suicidal persons over the past decade, incidence rates of suicidal behavior have remained largely unchanged. Most epidemiologic research on suicidal behavior has focused on patterns and correlates of prevalence. The next generation of studies must examine synergistic effects among modifiable risk and protective factors. New studies must incorporate recent advances in survey methods and clinical assessment. Results should be used in ongoing efforts to decrease the significant loss of life caused by suicidal behavior.

Comorbid Forms of Psychopathology: Key Patterns and Future Research Directions

The purpose of this review is to systematically appraise the peer-reviewed literature about clustered forms of psychopathology and to present a framework that can be useful for studying comorbid psychiatric disorders. The review focuses on four of the most prevalent types of mental health problems: anxiety, depression, conduct disorder, and substance abuse. The authors summarize existing empirical research on the distribution of concurrent and sequential comorbidity in children and adolescents and in adults, and they review existing knowledge about exogenous risk factors that influence comorbidity. The authors include articles that used a longitudinal study design and used psychiatric definitions of the disorders. A total of 58 articles met the inclusion criteria and were assessed. Current evidence demonstrates a reciprocal, sequential relation between most comorbid pairs, although the mechanisms that mediate such links remain to be explained. Methodological concerns include the inconsistency of measurement of the disorders across studies, small sample sizes, and restricted follow-up times. Given the significant mental health burden placed by comorbid disorders, and their high prevalence across populations, research on the key risk factors for clustering of psychopathology is needed.

Volume 137 Issue 12

Epidemiology and Infection, Volume 137 Issue 12 Increased frequency in 2007 - now 8 issues per year! Epidemiology and Infection publishes original reports and reviews on all aspects of infection in humans and animals. Particular emphasis is given to the epidemiology, prevention and control of infectious diseases. The field covered is broad and includes the zoonoses, tropical infections, food hygiene, vaccine studies, statistics and the clinical, social and public-health aspects of infectious disease. Papers covering microbiology and immunology which have an epidemiological relevance are part of this broad field. Papers come from medical and veterinary scientists worldwide. It has become the key periodical in which to find the latest reports on recently discovered infections and new technology. For those concerned with policy and planning for the control of infections, the papers on mathematical modelling of epidemics caused by historical, current and emergent infections, will be of particular value. To celebrate 100 years of the journal, a series of important papers has been selected and each, together with a modern commentary on the paper by an expert, will be published on-line. This journal has now moved over to electronic submission, using the Scholar One system. Click here to go to the submission website. Guidance on how to upload your manuscript is available on the site by clicking "User Tutorials". Online manuscript submission (now) available, please go to http://mc.manuscriptcentral.com/cup/hyg

HYG volume 137 issue 12 Cover and Front matter

Miscellaneous Epidemiology and Infection, Volume 137 Issue 12 , pp f1-f2Abstract

HYG volume 137 issue 12 Cover and Back matter

Miscellaneous Epidemiology and Infection, Volume 137 Issue 12 , pp b1-b2Abstract

Surveillance for antimicrobial resistant organisms: potential sources and magnitude of bias

Review ArticlesO. R. REMPEL, K. B. LAUPLAND, Epidemiology and Infection, Volume 137 Issue 12 , pp 1665-1673Abstract

Surveillance for severe community-associated methicillin-resistant Staphylococcus aureus infection

Research ArticlesP. WIERSMA, M. TOBIN D'ANGELO, W. R. DALEY, J. TUTTLE, K. E. ARNOLD, S. M. RAY, J. L. LADSON, S. N. BULENS, C. L. DRENZEK, Epidemiology and Infection, Volume 137 Issue 12 , pp 1674-1678Abstract

Rates of Stenotrophomonas maltophilia colonization and infection in relation to antibiotic cycling protocols

Brief ReportA. L. PAKYZ, B. M. FARR, Epidemiology and Infection, Volume 137 Issue 12 , pp 1679-1683Abstract

Humoral immunity to respiratory syncytial virus in young and elderly adults

Brief ReportC. TERROSI, G. Di GENOVA, B. MARTORELLI, M. VALENTINI, M. G. CUSI, Epidemiology and Infection, Volume 137 Issue 12 , pp 1684-1686Abstract

The lack of protective immunity against RSV in the elderly

Article CommentaryO. SCHILDGEN, Epidemiology and Infection, Volume 137 Issue 12 , pp 1687-1690Abstract

Estimation of incidence of tuberculosis infection in health-care workers using repeated interferon-γ assays

Research ArticlesT. YOSHIYAMA, N. HARADA, K. HIGUCHI, Y. NAKAJIMA, H. OGATA, Epidemiology and Infection, Volume 137 Issue 12 , pp 1691-1698Abstract

Data mining of tuberculosis patient data using multiple correspondence analysis

Research ArticlesT. W. RENNIE, W. ROBERTS, Epidemiology and Infection, Volume 137 Issue 12 , pp 1699-1704Abstract

Household clustering of gastroenteritis

Research ArticlesK. LEDER, M. SINCLAIR, A. FORBES, D. WAIN, Epidemiology and Infection, Volume 137 Issue 12 , pp 1705-1712Abstract

Massive outbreak of viral gastroenteritis associated with consumption of municipal drinking water in a European capital city

Research ArticlesD. WERBER, D. LAUŠEVIĆ, B. MUGOŠA, Z. VRATNICA, L. IVANOVIĆ-NIKOLIĆ, L. ŽIŽIĆ, A. ALEXANDRE-BIRD, L. FIORE, F. M. RUGGERI, I. DI BARTOLO, A. BATTISTONE, B. GASSILLOUD, S. PERELLE, D. NITZAN KALUSKI, M. KIVI, R. ANDRAGHETTI, K. G. J. POLLOCK, Epidemiology and Infection, Volume 137 Issue 12 , pp 1713-1720Abstract

Norovirus outbreaks in nursing homes: the evaluation of infection control measures

Research ArticlesI. H. M. FRIESEMA, H. VENNEMA, J. C. M. HEIJNE, C. M. de JAGER, G. MORROY, J. H. T. C. van den KERKHOF, E. J. M. de COSTER, B. A. WOLTERS, H. L. G. ter WAARBEEK, E. B. FANOY, P. F. M. TEUNIS, R. van der LINDE, Y. T. H. P. van DUYNHOVEN, Epidemiology and Infection, Volume 137 Issue 12 , pp 1722-1733Abstract

Estimation of sample sizes for pooled faecal sampling for detection of Salmonella in pigs

Research ArticlesM. E. ARNOLD, A. J. C. COOK, Epidemiology and Infection, Volume 137 Issue 12 , pp 1734-1741Abstract

Danish strategies to control Campylobacter in broilers and broiler meat: facts and effects

Research ArticlesH. ROSENQUIST, L. BOYSEN, C. GALLIANO, S. NORDENTOFT, S. ETHELBERG, B. BORCK, Epidemiology and Infection, Volume 137 Issue 12 , pp 1742-1750Abstract

Higher rate of culture-confirmed Campylobacter infections in Australia than in the USA: is this due to differences in healthcare-seeking behaviour or stool culture frequency?

Research ArticlesH. VALLY, G. HALL, E. SCALLAN, M. D. KIRK, F. J. ANGULO, Epidemiology and Infection, Volume 137 Issue 12 , pp 1751-1758Abstract

A measles outbreak in the Irish traveller ethnic group after attending a funeral in England, March–June 2007

Research ArticlesS. COHUET, A. BUKASA, R. HEATHCOCK, J. WHITE, K. BROWN, M. RAMSAY, G. FRASER, Epidemiology and Infection, Volume 137 Issue 12 , pp 1759-1765Abstract

GIS-based spatial, temporal, and space–time analysis of haemorrhagic fever with renal syndrome

Research ArticlesW. WU, J.-Q. GUO, Z.-H. YIN, P. WANG, B.-S. ZHOU, Epidemiology and Infection, Volume 137 Issue 12 , pp 1766-1775Abstract

Cytomegalovirus seroprevalence and ‘cytomegalovirus-safe’ seropositive blood donors

Research ArticlesK. G. BADAMI, S. McQUILKAN-BICKERSTAFFE, J. E. WELLS, M. PARATA, Epidemiology and Infection, Volume 137 Issue 12 , pp 1776-1780Abstract

Multiple risk factors associated with a large statewide increase in cryptosporidiosis

Research ArticlesA. L. VALDERRAMA, M. C. HLAVSA, A. CRONQUIST, S. COSGROVE, S. P. JOHNSTON, J. M. ROBERTS, M. L. STOCK, L. XIAO, K. XAVIER, M. J. BEACH, Epidemiology and Infection, Volume 137 Issue 12 , pp 1781-1788Abstract

A modified case-control study of cryptosporidiosis (using non- Cryptosporidium -infected enteric cases as controls) in a community setting

Research ArticlesK. D. M. PINTAR, F. POLLARI, D. WALTNER-TOEWS, D. F. CHARRON, S. A. McEWEN, A. FAZIL, A. NESBITT, Epidemiology and Infection, Volume 137 Issue 12 , pp 1789-1799Abstract

Meta-analysis of a polymorphic surface glycoprotein of the parasitic protozoa Cryptosporidium parvum and Cryptosporidium hominis

Research ArticlesG. WIDMER, Epidemiology and Infection, Volume 137 Issue 12 , pp 1800-1808Abstract

Seroepidemiology of Toxoplasma infection in a metropolitan region of Brazil

Research ArticlesG. C. V. R. FERNANDES, R. S. AZEVEDO, M. AMAKU, A. L. F. YU, E. MASSAD, Epidemiology and Infection, Volume 137 Issue 12 , pp 1809-1815Abstract

Pathogen burden and cortisol profiles over the day

Research ArticlesA. STEPTOE, Å. GYLFE, A. SHAMAEI-TOUSI, S. BERGSTROM, B. HENDERSON, Epidemiology and Infection, Volume 137 Issue 12 , pp 1816-1824Abstract

Contribution of migrant coffee labourers infected with Onchocerca volvulus to the maintenance of the microfilarial reservoir in an ivermectin-treated area of Mexico.

Background: Since 1991, in Mexico, ivermectin has been administered twice a year to all residents in the onchocerciasis endemic foci which are mainly located in the coffee growing areas. However, the presence of a potentially infected itinerant seasonal labour force which is not treated regularly could jeopardise the attainment of the 85% coverage which is the present target for elimination of the disease. Methods: The prevalence and intensity of Onchocerca volvulus microfilariae (mf), as well as their transmission from humans to vectors, were assessed during the coffee planting-clearing and harvesting seasons of 1997–1998, and 1998–1999 in two localities (I and II) of Southern Chiapas, Mexico, which regularly receive an influx of untreated migrant coffee labourers. Results: Localities I and II had, respectively, an average of 391 (± 32) and 358 (± 14) resident inhabitants, and 70 (± 52) and 498 (± 289) temporary labourers. The ratio of migrants to residents ranged from 0.1:1 in locality I to 2.4:1 in locality II. The proportion of infected Simulium ochraceum s.l. parous flies was significantly lower in locality I than in locality II, and significantly higher during the stay of the migrants than before their arrival or after their departure. Parity and infection were higher in May-July than in November-February (in contrast with the latter being typically considered as the peak onchocerciasis transmission season by S. ochraceum s.l.). Conclusion: The presence of significant numbers of untreated and potentially infected migrants may contribute to ongoing transmission, and their incorporation into ivermectin programmes should be beneficial for the attainment of the elimination goals of the regional initiative. However, the possibility that the results also reflect transmission patterns for the area cannot be excluded and these should be analyzed further.

Epidemiology and psycho-social aspects Of onchocercal skin diseases in northeastern Nigeria

Background: Observations were made on the prevalence of onchocerciasis and Onchocercal Skin Diseases (OSD); frequency of occurrence and anatomical distribution of OSD in the Hawal River Valley, an established onchocerciasis endemic focus in north-eastern Nigeria. Methods: Symptoms of OSD were diagnosed in 5 844 subjects using Rapid Assessment Method (RAM) while 1 479 of the subjects chosen from alternate households had their skin biopsies examined for active microfilariae of Onchocerca volvulus. Also, Focal Group Discussions (FGD) were conducted at the Health District levels. Results: O. volvulus was recorded in (19.0%) and OSD in (43.8%) of the subjects. The Mantel-Haenszel test for linear association showed a close agreement between onchocerciasis prevalence and the rate of OSD (χ2 = 3.93; p < 0.05). The various forms of OSD occurred in the order: CPOD (17.7%), APOD (9.9%), DPM (9.0%), LOD (7.0%) and ATR (3.1%). The overall frequency of occurrence of various symptoms of OSD on different anatomical locations showed the locations in descending order of occurrence as lower limbs (24.6%), upper limbs (21.3%), buttocks (19.9%), shoulder & neck (19.1%), abdomen and trunk (11.3%), backside (10.6), and 'other' sites (7.5%). The Focal Group Discussion (FGD) revealed the most worrisome consequences of OSD as social isolation of victims (31.3%), shame and low self esteem (22.7%) and high cost of medication (15.6%). Conclusion: It is recommended that Onchocerciasis control programmes in the Hawal River Valley and any other focus with high incidence of OSD should incorporate an aspect that would address the anxiety and depression caused by various OSD lesions since they carry lots of psycho-social implications. This would increase acceptance and compliance of the target population. The classification criteria of onchocerciasis endemicity should be based on either or both of the O. volvulus and onchocercal skin disease burden of any community and no longer on O. volvulus parasitic infection rate alone.

Contributions of different mosquito species to the transmission of lymphatic filariasis in central Nigeria: Implications for monitoring infection by PCR in mosquito pools

Background: Members of the Anopheles gambiae complex are important vectors of lymphatic filariasis (LF) in sub-Saharan Africa, but little is known about the relative contributions of all mosquitoes to lymphatic filariasis transmission in this area. Methods: Over a 28 month period, mosquitoes were collected from 13 villages in Plateau and Nasarawa states in central Nigeria and dissected to determine W. bancrofti infection status. Wings and legs from a subset of the mosquitoes visually identified as A. gambiae s.l. were identified by PCR as either A. gambiae s.s. or A. arabiensis. Results: A. gambiae s.s peaked in abundance during the rainy season while A. arabiensis predominated during drier parts of the year. Both species were found equally likely to be infected with the developing stages (L1-L3) of W. bancrofti (9.2% and 11.1%, respectively). Fewer A. funestus (1.1%, p < 0.001) were infected than A. gambiae s.l. Conclusion: Understanding the relative contributions of morphologically indistinguishable species to LF transmission is essential if PCR is to be performed on mosquito pools. In the study area, the use of mosquito pools composed of A. gambiae sibling species would not be problematic, as both A. gambiae s.s. and A. arabiensis contribute equally to LF transmission.

Monitoring lymphatic filariasis interventions: Adult mosquito sampling, and improved PCR - based pool screening method for Wuchereria bancrofti infection in Anopheles mosquitoes

Background: Monitoring and evaluation are essential to the successful implementation of mass drug administration programmes for LF elimination. Monitoring transmission when it is low requires both large numbers of mosquito vectors and sensitive methods for detecting Wuchereria bancrofti infections in them. PCR-based methods are preferred over classical dissections but the best protocol so far achieved detection of one L3 Wuchereria bancrofti larva in a pool of 35–50 Anopheles mosquitoes. It also lacks consistency and remains still a costly tool. Hence we decided to improve upon this to achieve detection in a pool of 100 or more by enhancing the quality of the template DNA. Prior to this we also evaluated three vector sampling methods in the context of numbers for monitoring. Methods: Human landing, pyrethrium spray and light traps catches were conducted concurrently at sites in an LF endemic district in Ghana and the numbers obtained compared. Two DNA extraction methods; Bender buffer and phenol/chloroform purification, and DNAeasy Tissue kit (Quaigen Inc) were used on pools of 25, 50, 75 100 and 150 mosquitoes each seeded with one L3 or its quivalent amount of DNA. Then another set of extracted DNA by the two methods was subjected to Dynal bead purification method (using capture oligonucleotide primers). These were used as template DNA in PCR to amplify W. bancrofti sequences. The best PCR result was then evaluated in the field at five sites by comparing its results (infections per 1000 mosquitoes) with that of dissection of roughly equal samples sizes. Results: The largest numbers of mosquitoes were obtained with the human landing catches at all the sites sampled. Although PCR detection of one L3 in pools of 25, 50 and 75 mosquitoes was consistent irrespective of the extraction method, that of one L3 in 100 was only achieved with the kit-extracted DNA/Dynal bead purification method. Infections were found at only two sites by both dissection and pool-screening being 14.3 and 19 versus 13.4 and 20.1 per 1000 Anopheles mosquitoes respectively, which were not statistically significantDiscussion and conclusionHLC still remains the best option for sampling for the large numbers of mosquitoes required for monitoring transmission during MDA programmes, when vector population densities are high and classical indices of transmission are required. One – in – 100 detection is an improvement on previous PCR pool-screening methods, which in our opinion was a result of the introduction of the extra step of parasite DNA capture using Dynal/beads. As pool sizes increase the insects DNA will swamp parasite DNA making the latter less available for an efficient PCR, therefore we propose either additional steps of parasite DNA capture or real-time PCR to improve further the pool screening method. The study also attests also to the applicability of Katholi et al's algorithm developed for determining onchocerciasis prevalence in LF studies.

The geographical distribution of lymphatic filariasis infection in Malawi

Mapping distribution of lymphatic filariasis (LF) is a prerequisite for planning national elimination programmes. Results from a nation wide mapping survey for lymphatic filariasis (LF) in Malawi are presented. Thirty-five villages were sampled from 23 districts excluding three districts (Karonga, Chikwawa and Nsanje) that had already been mapped and Likoma, an Island, where access was not possible in the time frame of the survey. Antigenaemia prevalence [based on immunochromatographic card tests (ICT)] ranged from 0% to 35.9%. Villages from the western side of the country and distant from the lake tended to be of lower prevalence. The exception was a village in Mchinji district on the Malawi-Zambia border where a prevalence of 18.2% was found. In contrast villages from lake shore districts [Salima, Mangochi, Balaka and Ntcheu (Bwanje valley)] and Phalombe had prevalences of over 20%.A national map is developed which incorporates data from surveys in Karonga, Chikwawa and Nsanje districts, carried out in 2000. There is a marked decline in prevalence with increasing altitude. Further analysis revealed a strong negative correlation (R2 = 0.7 p < 0.001) between altitude and prevalence. These results suggest that the lake shore, Phalombe plain and the lower Shire valley will be priority areas for the Malawi LF elimination programme. Implications of these findings as regards implementing a national LF elimination programme in Malawi are discussed.

Social mobilisation, drug coverage and compliance and adverse reactions in a Mass Drug Administration (MDA) Programme for the Elimination of Lymphatic Filariasis in Sri Lanka

Background: In Sri Lanka filariasis is endemic in Southern, Western and North Western provinces covering eight districts designated as implementation units in the Programme for the Elimination of Lymphatic Filariasis (PELF). Despite control activities over sixty years including multidose diethylcarbamazine, 6 mg/kg treatment microfilaria rates had persisted at low levels. Following systematic social mobilisation the first MDA with DEC albendazole combination was conducted in 2002. Methods: We investigated the extent social mobilisation had reached the people, their drug compliance and adverse reactions. Three localities were selected from each district to pick target population samples for pre-tested questionnaire. Three teams each with six people visited one district each day. One team worked from three starting points in one locality. A member applied eight part questionnaire to one family member totalling 150–160 people from one locality. Questions included social mobilisation, drug compliance and adverse reactions. Results: Information was disseminated by television, radio, banners and leaflets, to a lesser extent by people. Information reached more people in the periphery than in Colombo. 35.2% from Colombo municipality were unaware of the MDA. Drug coverage was 79.6%, home delivery 71.7% and delivery centres 7.9%. 35.6% in Colombo district and 53.4% from Colombo municipality did not receive drugs. Drugs were consumed by 71.4%. 28.6% who did not comply included 20.4% who did not receive them. 91.4% showed no adverse reactions, 7.5% were mild, 1.1% recovered with home remedies. Conclusion: Drug compliance showed significant positive correlation with awareness of the MDA. Door to door delivery was more successful than delivery from centres. More delivery centres conveniently located would have rectified this disparity. Poor awareness and compliance in Colombo and urban areas could be rectified with separate strategy for urban areas. More time for MDA and trained adequate manpower would ensure coverage to achieve elimination.

Pan LF-ELISA using BmR1 and BmSXP recombinant antigens for detection of lymphatic filariasis

Background: Anti-filarial IgG4 antibody has been shown to be a good marker for detection of lymphatic filaria infection. Previous studies demonstrated that anti-filarial IgG4 assay using BmR1 recombinant antigen was highly specific and sensitive for detection of brugian filariasis. For bancroftian filariasis, an equivalent assay employing recombinant antigen expressed from the ORF of SXP1 gene has been reported. In order to detect infections by all species of lymphatic filarial, BmR1 and BmSXP recombinant antigens were employed in the development of a pan LF-ELISA. Methods: BmR1 was previously produced while BmSXP recombinant antigen was produced by cloning the ORF of SXP1 gene from a Brugia malayi cDNA library, followed by expression in a bacterial expression system. Subsequently, each of the purified recombinant antigens (BmR1 and BmSXP) and mixture of different ratios of the two antigens (1:1, 2:1 and 1:2) were tested using IgG4-ELISA with various categories of infection and normal human serum samples. Results: The results showed that both recombinant antigens were highly specific (99%–100%). For detection of brugian filariasis, BmR1 antigen alone and the mixture of BmR1 with BmSXP (1:1) gave 98% sensitivity; while BmSXP antigen alone showed 84% sensitivity. For detection of bancroftian filariasis, BmSXP antigen was more sensitive (95%) than assays using either BmR1 or mixtures of the two recombinant antigens. Conclusion: A sensitive and specific pan LF-ELISA for detection of lymphatic filariasis was successfully developed using two adjacent wells, each separately coated with BmR1 and BmSXP.

Multicentre evaluations of two new rapid IgG4 tests (WB rapid and panLF rapid) for detection of lymphatic filariasis

In the global effort to eliminate lymphatic filariasis (LF), rapid field-applicable tests are useful tools that will allow on-site testing to be performed in remote places and the results to be obtained rapidly. Exclusive reliance on the few existing tests may jeopardize the progress of the LF elimination program, thus the introduction of other rapid tests would be useful to address this issue. Two new rapid immunochromatographic IgG4 cassette tests have been produced, namely WB rapid and panLF rapid, for detection of bancroftian filariasis and all three species of lymphatic filaria respectively. WB rapid was developed using BmSXP recombinant antigen, while PanLF rapid was developed using BmR1 and BmSXP recombinant antigens. A total of 165 WB rapid and 276 panLF rapid tests respectively were evaluated at USM and the rest were couriered to another university in Malaysia (98 WB rapid, 129 panLF rapid) and to universities in Indonesia (56 WB rapid, 62 panLF rapid), Japan (152 of each test) and India (18 of each test) where each of the tests underwent independent evaluations in a blinded manner. The average sensitivities of WB rapid and panLF rapid were found to be 97.6% (94%–100%) and 96.5% (94%–100%) respectively; while their average specificities were both 99.6% (99%–100%). Thus this study demonstrated that both the IgG4 rapid tests were highly sensitive and specific, and would be useful additional tests to facilitate the global drive to eliminate this disease.

Health Related Quality of Life, an appropriate indicator to assess the impact of morbidity management and disability prevention activities towards elimination of lymphatic filariasis

Background: Lymphatic filariasis has been identified as one of the six diseases that can be potentially eliminated. Global programme to eliminate lymphatic filariasis has been launched, applying principal strategies of mass drug administration to interrupt transmission and morbidity management to prevent disability. The strategy for mass drug administration has been clearly laid out and guidelines have been well documented for implementation, monitoring and evaluation of the programme but such a guideline is warranted for morbidity management and disability prevention activities.DiscussionHealth Related Quality of Life, a multidimensional construct referring to patients' perceptions of the impact of disease and treatment on their physical, psychological and social function and well being is crucial in the evaluation of health care interventions. Lymphatic filariasis has a wide clinical spectrum and disability is more pronounced in the advanced stages of lymphoedema and hydrocele. Since the advanced stages of lymphoedema are not reversible, morbidity management and disability prevention activities can lessen the disabilities due to secondary infections and there by improve the quality of life of the patient. Thus, an improvement in quality of life is considered to be important as a primary outcome in the determination of therapeutic benefit. Therefore it can be used as an indicator to assess the impact of morbidity management and disability prevention activities in global programme to eliminate lymphatic filariasis.SummaryDisease specific Health Related Quality of Life instrument can be used to measure the longitudinal changes in quality of life of patients following the intervention. High responsiveness, clinical relevance to patients and its sensitiveness to detect small changes are the merits of disease specific instrument. Morbidity management and disability prevention activities under filariasis elimination programme aim at improving the quality of life of patients with irreversible manifestations. Therefore there is an urgent need to develop an instrument to assess the health related quality of life, specific for lymphatic filariasis by incorporating all the difficulties and problems caused to patients by the disease in the physical, mental and social domains of health.

Delivery strategy of mass annual single dose DEC administration to eliminate Lymphatic filariasis in the urban areas of Pondicherry, South India : 5 years of experience

Background: The recommended strategy for elimination of Lymphatic filariasis is single-dose, once-yearly mass treatment with anti-filarial drugs and the program is in operation on a national level in India. Rate of coverage and consumption is the most crucial factor in the success of Mass Drug Administration (MDA) program. In spite of massive efforts, the program demonstrated sub-optimal coverage and consumption in urban areas than rural. The involvement of Anganwadi workers (AWWs) of the Integrated Child Development Scheme (ICDS) as communicators and drug distributors was attempted to enhance the coverage and consumption in urban areas and the results presented here. Methods: An annual single dose MDA program was launched under the auspices of Freedom From Filariasis (FFF) program in Pondicherry, India, in the year 1997 and continued for five years. A questionnaire survey was carried out following all the treatment rounds (TRs) for assessing coverage of distribution and consumption Five percent of randomly selected households constituted the sample. All the members available in the selected household at the time of interview formed the respondent of the study. Results: The coverage of drug distribution during the TRs varied from 74.3 to 95.4 percent and consumption rate from 52.9 to 78.8. Among the respondents, 71% were aware of the MDA program and the source of information for 62.8% of them was through personal communication by the AWW. It was observed that 33.2% of the respondents who accepted the drug did so based on the trust on the AWW as a government representative. The main reason for non-consumption in all TRs was fear of side reaction (25.4 – 42.2%). Conclusion: The delivery-strategy of health information and Diethylcarbamazine (DEC) drug to the urban community using the AWWs could achieve relatively higher coverage and consumption than reported in other urban areas. In order to achieve the optimum level, it is imperative to equip the AWWs with current knowledge and skills, and design innovative Information, Education and Communication (IEC) campaign to target the less compliant groups. The beneficial effect of this delivery strategy may be used in similar urban settings to achieve the elimination of LF.

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