Journals RSS : Gourt

Women's HIV Disclosure to Family and Friends

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

Substantial Multiclass Transmitted Drug Resistance and Drug-Relevant Polymorphisms Among Treatment-Naïve Behaviorally HIV-Infected Youth

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

Lay Health Workers and HIV Care in Rural Lesotho: A Report from the Field

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

Entry into Care and Clinician Management of Acute HIV Infection in New York City

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

Disclosure and Nondisclosure Among People Newly Diagnosed with HIV: An Analysis from a Stress and Coping Perspective

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

Development and Pilot Testing of a Standardized Training Program for a Patient-Mentoring Intervention to Increase Adherence to Outpatient HIV Care

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

Behavioral and Serologic Survey of Men Who Have Sex with Men in Beijing, China: Implication for HIV Intervention

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

Linkages to Care for Newly Diagnosed Individuals Who Test HIV Positive in Nonprimary Care Settings

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

HIV Symptom Distress and Anxiety Sensitivity in Relation to Panic, Social Anxiety, and Depression Symptoms Among HIV-Positive Adults

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

What HIV-Positive Young Women Want from Behavioral Interventions: A Qualitative Approach

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

Relapse of Intravenous Drug Use Triggered by Enfuvirtide, a Parenteral Antiretroviral Medication

AIDS Patient Care and STDs Feb 2012, Vol. 26, No. 2: 71-72.

Change in Fibrosis Score as a Predictor of Mortality Among HIV-Infected Patients with Viral Hepatitis

AIDS Patient Care and STDs Feb 2012, Vol. 26, No. 2: 73-80.

Causes of Hospitalization and Perceived Access to Care Among Persons Newly Diagnosed with HIV Infection: Implications for HIV Testing Programs

AIDS Patient Care and STDs Feb 2012, Vol. 26, No. 2: 81-86.

Sexual Risk Behaviors and Acceptability of HIV Pre-Exposure Prophylaxis Among HIV-Negative Gay and Bisexual Men in Serodiscordant Relationships: A Mixed Methods Study

AIDS Patient Care and STDs Feb 2012, Vol. 26, No. 2: 87-94.

Alcohol and Marijuana Use Outcomes in the Healthy Choices Motivational Interviewing Intervention for HIV-Positive Youth

AIDS Patient Care and STDs Feb 2012, Vol. 26, No. 2: 95-100.

Task-Shifting to Community Health Workers: Evaluation of the Performance of a Peer-Led Model in an Antiretroviral Program in Uganda

AIDS Patient Care and STDs Feb 2012, Vol. 26, No. 2: 101-107.

The Impact of Stigma on Medication Adherence Among HIV-Positive Adolescent and Young Adult Females and the Moderating Effects of Coping and Satisfaction with Health Care

AIDS Patient Care and STDs Feb 2012, Vol. 26, No. 2: 108-115.

Development of a Framework for HIV/AIDS Prevention Programs in African American Churches

AIDS Patient Care and STDs Feb 2012, Vol. 26, No. 2: 116-124.

HIV/AIDS and STD Updates

AIDS Patient Care and STDs Feb 2012, Vol. 26, No. 2: 125-127.

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Anti-Mullerian Hormone: A Potential New Tool in Epidemiologic Studies of Female Fecundability

The objective of the present commentary is to suggest that epidemiologists explore the use of anti-Müllerian hormone (AMH) as a new measurement tool in fecundability studies. The authors briefly summarize the advantages and limitations of the 3 current approaches to studies of fecundability. All 3 approaches involve the collection of time-to-pregnancy or attempt-time data, and most are limited to participants who plan their pregnancies. AMH is produced by ovarian follicles during their early growth stages and is measured clinically to assess ovarian reserve (the number of remaining oocytes). Unlike time to pregnancy, serum AMH level can be assessed regardless of pregnancy-attempt status. Measurements are not significantly affected by phase of the menstrual cycle, oral contraceptive use, or early pregnancy. The authors suggest that AMH measurement can be a valuable addition to traditionally designed fecundability studies. In addition, this hormone should be investigated as an independent measure of fecundability in studies that focus on exposures hypothesized to target the ovary.

Bias in Observational Studies of Prevalent Users: Lessons for Comparative Effectiveness Research From a Meta-Analysis of Statins

Randomized clinical trials (RCTs) are usually the preferred strategy with which to generate evidence of comparative effectiveness, but conducting an RCT is not always feasible. Though observational studies and RCTs often provide comparable estimates, the questioning of observational analyses has recently intensified because of randomized-observational discrepancies regarding the effect of postmenopausal hormone replacement therapy on coronary heart disease. Reanalyses of observational data that excluded prevalent users of hormone replacement therapy led to attenuated discrepancies, which begs the question of whether exclusion of prevalent users should be generally recommended. In the current study, the authors evaluated the effect of excluding prevalent users of statins in a meta-analysis of observational studies of persons with cardiovascular disease. The pooled, multivariate-adjusted mortality hazard ratio for statin use was 0.77 (95% confidence interval (CI): 0.65, 0.91) in 4 studies that compared incident users with nonusers, 0.70 (95% CI: 0.64, 0.78) in 13 studies that compared a combination of prevalent and incident users with nonusers, and 0.54 (95% CI: 0.45, 0.66) in 13 studies that compared prevalent users with nonusers. The corresponding hazard ratio from 18 RCTs was 0.84 (95% CI: 0.77, 0.91). It appears that the greater the proportion of prevalent statin users in observational studies, the larger the discrepancy between observational and randomized estimates.

Environmental and Urinary Markers of Prenatal Exposure to Drinking Water Disinfection By-Products, Fetal Growth, and Duration of Gestation in the PELAGIE Birth Cohort (Brittany, France, 2002-2006)

Although prenatal exposure to water disinfection by-products does not appear to affect the duration of gestation, its impact on fetal growth remains an open question. The authors studied the associations between prenatal exposure to disinfection by-products and fetal growth restriction (FGR) and preterm birth in the PELAGIE cohort, a French birth cohort comprising 3,421 pregnant women recruited between 2002 and 2006. Exposure was assessed by estimating levels of trihalomethanes (THMs) in tap water during pregnancy and maternal water use and by measuring maternal urinary levels of trichloroacetic acid (TCAA) during early pregnancy in a nested case-control design that compared 174 FGR cases, 114 preterm births, and 399 controls. Higher uptake of THMs (especially brominated THMs) was associated with a higher risk of FGR. Women with TCAA detected in their urine (>0.01 mg/L) had a higher risk of FGR than those with TCAA levels below the detection limit (adjusted odds ratio = 1.8, 95% confidence interval: 0.9, 3.7) and had an odds ratio for preterm birth below 1 (adjusted odds ratio = 0.8, 95% confidence interval: 0.3, 2.6). Results from this prospective study, the first to use a biomarker of disinfection by-product exposure, suggest that prenatal exposure affects fetal growth, but the causal agent or agents remain to be identified.

Invited Commentary: Biomarkers of Exposure to Drinking Water Disinfection By-Products--Are We Ready Yet?

Studies of the relation between exposure to drinking water disinfection by-products and pregnancy outcomes have been limited by the complexity of the exposure itself (consisting of hundreds of different chemicals), the diverse pathways contributing to exposure, and the difficulty in assessing behavioral determinants of exposure. Therefore, exposure biomarkers offer great promise of enhancing exposure assessment, the limiting factor in the quality and conclusiveness of epidemiologic studies. However, there are significant conceptual and logistical challenges in developing biomarkers for the various constituents of concern that are sensitive to typical variation in exposure, reflective of the time periods of interest, not susceptible to interference from exposures other than water, not subject to reverse causality by correlates of adverse pregnancy outcomes, reflective of the chemicals of interest, and feasible for large-scale epidemiologic studies. Urinary trichloroacetic acid has been the leading candidate exposure biomarker for over a decade, and the first attempt to incorporate it into an epidemiologic study (Am J Epidemiol. 2012;175(4):263–275) is notable—the considerable limitations notwithstanding. In future efforts, investigators need to combine biomarker development with substantive epidemiologic studies to improve on this initial effort and prepare for more definitive research.

Is Childhood Asthma Associated With Educational Level and Longest-Held Occupation?

Children with asthma can experience chronic morbidity that may interfere with education and career progression. The authors investigated retrospectively whether a history of childhood asthma is associated with educational level and longest-held occupation, by gender. Cross-sectional analysis included a nationally representative sample of 10,452 adults aged ≥20 years who participated in the US National Health and Nutrition Examination Survey (2001–2004). Logistic regression was used to assess associations between a childhood-asthma history and educational level, employment, and longest-held occupation. An estimated 6.9% of men and 5.8% of women had a childhood-asthma history. Persons with a childhood-asthma history tended to have a higher educational level than those with no asthma history. Among those who ever worked, and after adjustment for age and race/ethnicity, men with a childhood-asthma history were more likely to work in health-diagnosing occupations, other professional occupations, and as cooks; women with a childhood-asthma history were more likely to work in management-related, entertainment-related, and health service occupations. Compared with those with no asthma history, persons with a childhood-asthma history tended to achieve a higher educational level and, if they worked, were more likely to work in particular occupations.

Passive Cigarette Smoke Exposure During Various Periods of Life, Genetic Variants, and Breast Cancer Risk Among Never Smokers

The association between passive cigarette smoke exposure and breast cancer risk is inconclusive and may be modified by genotype. The authors investigated lifetime passive cigarette smoke exposures, 36 variants in 12 carcinogen-metabolizing genes, and breast cancer risk among Ontario, Canada, women who had never smoked (2003–2004). DNA (saliva) was available for 920 breast cancer cases and 960 controls. Detailed information about passive smoke exposure was collected for multiple age periods (childhood, teenage years, and adulthood) and environments (home, work, and social). Adjusted odds ratios and 95% confidence intervals were estimated by multivariable logistic regression, and statistical interactions were assessed using the likelihood ratio test. Among postmenopausal women, most associations between passive smoke and breast cancer risk were null, whereas among premenopausal women, nonsignificant positive associations were observed. Significant interactions were observed between certain types of passive smoke exposure and genetic variants in CYP2E1, NAT2, and UGT1A7. While these interactions were statistically significant, the magnitudes of the effect estimates were not consistent or easily interpretable, suggesting that they were perhaps due to chance. Although the results of this study were largely null, it is possible that premenopausal women exposed to passive smoke or carrying certain genetic variants may be at higher risk of breast cancer.

Mortality Among Young Injection Drug Users in San Francisco: A 10-Year Follow-up of the UFO Study

This study examined associations between mortality and demographic and risk characteristics among young injection drug users in San Francisco, California, and compared the mortality rate with that of the population. A total of 644 young (<30 years) injection drug users completed a baseline interview and were enrolled in a prospective cohort study, known as the UFO ("U Find Out") Study, from November 1997 to December 2007. Using the National Death Index, the authors identified 38 deaths over 4,167 person-years of follow-up, yielding a mortality rate of 9.1 (95% confidence interval: 6.6, 12.5) per 1,000 person-years. This mortality rate was 10 times that of the general population. The leading causes of death were overdose (57.9%), self-inflicted injury (13.2%), trauma/accidents (10.5%), and injection drug user-related medical conditions (13.1%). Mortality incidence was significantly higher among those who reported injecting heroin most days in the past month (adjusted hazard ratio = 5.8, 95% confidence interval: 1.4, 24.3). The leading cause of death in this group was overdose, and primary use of heroin was the only significant risk factor for death observed in the study. These findings highlight the continued need for public health interventions that address the risk of overdose in this population in order to reduce premature deaths.

A Nationwide Cohort Study on the Incidence of Meningioma in Women Using Postmenopausal Hormone Therapy in Finland

The authors conducted a nationwide cohort study to evaluate the association between postmenopausal hormone therapy and meningioma incidence in Finland. All women who had used hormone therapy at least for 6 months at the age of 50 years or older during 1994–2009 were included. Women who had used postmenopausal hormone therapy were identified from the medical reimbursement register of the Social Insurance Institution (131,480 estradiol users and 131,248 estradiol-progestin users), and meningioma cases were identified from the Finnish Cancer Registry. During the average 9 years of follow-up, 289 estradiol users and 196 estradiol-progestin users were diagnosed with meningioma. Ever use of estradiol-only therapy was associated with an increased risk of meningioma (standardized incidence ratio = 1.29, 95% confidence interval: 1.15, 1.44). Among women who had been using estradiol-only therapy for at least 3 years, the incidence of meningioma was 1.40-fold higher (95% confidence interval: 1.18, 1.64; P < 0.001) than in the background population. In contrast, this risk was not increased in users of combination therapy (standardized incidence ratio = 0.93, 95% confidence interval: 0.80, 1.06). There was no difference in risk between continuous and sequential use of hormone therapy. Estradiol-only therapy was accompanied with a slightly increased risk of meningioma.

Brazilian Longitudinal Study of Adult Health (ELSA-Brasil): Objectives and Design

Although low- and middle-income countries still bear the burden of major infectious diseases, chronic noncommunicable diseases are becoming increasingly common due to rapid demographic, epidemiologic, and nutritional transitions. However, information is generally scant in these countries regarding chronic disease incidence, social determinants, and risk factors. The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) aims to contribute relevant information with respect to the development and progression of clinical and subclinical chronic diseases, particularly cardiovascular diseases and diabetes. In this report, the authors delineate the study’s objectives, principal methodological features, and timeline. At baseline, ELSA-Brasil enrolled 15,105 civil servants from 5 universities and 1 research institute. The baseline examination (2008–2010) included detailed interviews, clinical and anthropometric examinations, an oral glucose tolerance test, overnight urine collection, a 12-lead resting electrocardiogram, measurement of carotid intima-media thickness, echocardiography, measurement of pulse wave velocity, hepatic ultrasonography, retinal fundus photography, and an analysis of heart rate variability. Long-term biologic sample storage will allow investigation of biomarkers that may predict cardiovascular diseases and diabetes. Annual telephone surveillance, initiated in 2009, will continue for the duration of the study. A follow-up examination is scheduled for 2012–2013.

Regression Calibration When Foods (Measured With Error) Are the Variables of Interest: Markedly Non-Gaussian Data With Many Zeroes

Regression calibration has been described as a means of correcting effects of measurement error for normally distributed dietary variables. When foods are the items of interest, true distributions of intake are often positively skewed, may contain many zeroes, and are usually not described by well-known statistical distributions. The authors considered the validity of regression calibration assumptions where data are non-Gaussian. Such data (including many zeroes) were simulated, and use of the regression calibration algorithm was evaluated. An example used data from Adventist Health Study 2 (2002–2008). In this special situation, a linear calibration model does (as usual) at least approximately correct the parameter that captures the exposure-disease association in the "disease" model. Poor fit in the calibration model does not produce biased calibrated estimates when the "disease" model is linear, and it produces little bias in a nonlinear "disease" model if the model is approximately linear. Poor fit will adversely affect statistical power, but more complex linear calibration models can help here. The authors conclude that non-Gaussian data with many zeroes do not invalidate regression calibration. Irrespective of fit, linear regression calibration in this situation at least approximately corrects bias. More complex linear calibration equations that improve fit may increase power over that of uncalibrated regressions.

Credible Mendelian Randomization Studies: Approaches for Evaluating the Instrumental Variable Assumptions

As with other instrumental variable (IV) analyses, Mendelian randomization (MR) studies rest on strong assumptions. These assumptions are not routinely systematically evaluated in MR applications, although such evaluation could add to the credibility of MR analyses. In this article, the authors present several methods that are useful for evaluating the validity of an MR study. They apply these methods to a recent MR study that used fat mass and obesity-associated (FTO) genotype as an IV to estimate the effect of obesity on mental disorder. These approaches to evaluating assumptions for valid IV analyses are not fail-safe, in that there are situations where the approaches might either fail to identify a biased IV or inappropriately suggest that a valid IV is biased. Therefore, the authors describe the assumptions upon which the IV assessments rely. The methods they describe are relevant to any IV analysis, regardless of whether it is based on a genetic IV or other possible sources of exogenous variation. Methods that assess the IV assumptions are generally not conclusive, but routinely applying such methods is nonetheless likely to improve the scientific contributions of MR studies.

Taking Advantage of the Strengths of 2 Different Dietary Assessment Instruments to Improve Intake Estimates for Nutritional Epidemiology

With the advent of Internet-based 24-hour recall (24HR) instruments, it is now possible to envision their use in cohort studies investigating the relation between nutrition and disease. Understanding that all dietary assessment instruments are subject to measurement errors and correcting for them under the assumption that the 24HR is unbiased for usual intake, here the authors simultaneously address precision, power, and sample size under the following 3 conditions: 1) 1–12 24HRs; 2) a single calibrated food frequency questionnaire (FFQ); and 3) a combination of 24HR and FFQ data. Using data from the Eating at America’s Table Study (1997–1998), the authors found that 4–6 administrations of the 24HR is optimal for most nutrients and food groups and that combined use of multiple 24HR and FFQ data sometimes provides data superior to use of either method alone, especially for foods that are not regularly consumed. For all food groups but the most rarely consumed, use of 2–4 recalls alone, with or without additional FFQ data, was superior to use of FFQ data alone. Thus, if self-administered automated 24HRs are to be used in cohort studies, 4–6 administrations of the 24HR should be considered along with administration of an FFQ.

A Comparison of Self-Reported Analgesic Use and Detection of Urinary Ibuprofen and Acetaminophen Metabolites by Means of Metabonomics: The INTERMAP Study

Information on dietary supplements, medications, and other xenobiotics in epidemiologic surveys is usually obtained from questionnaires and is subject to recall and reporting biases. The authors used metabolite data obtained from hydrogen-1 (or proton) nuclear magnetic resonance (1H NMR) analysis of human urine specimens from the International Study of Macro-/Micro-Nutrients and Blood Pressure (INTERMAP Study) to validate self-reported analgesic use. Metabolic profiling of two 24-hour urine specimens per individual was carried out for 4,630 participants aged 40–59 years from 17 population samples in Japan, China, the United Kingdom, and the United States (data collection, 1996–1999). 1H NMR-detected acetaminophen and ibuprofen use was low (~4%) among East Asian population samples and higher (>16%) in Western population samples. In a comparison of self-reported acetaminophen and ibuprofen use with 1H NMR-detected acetaminophen and ibuprofen metabolites among 496 participants from Chicago, Illinois, and Belfast, Northern Ireland, the overall rate of concordance was 81%–84%; the rate of underreporting was 15%–17%; and the rate of underdetection was approximately 1%. Comparison of self-reported unspecified analgesic use with 1H NMR-detected acetaminophen and ibuprofen metabolites among 2,660 Western INTERMAP participants revealed similar levels of concordance and underreporting. Screening for urinary metabolites of acetaminophen and ibuprofen improved the accuracy of exposure information. This approach has the potential to reduce recall bias and other biases in epidemiologic studies for a range of substances, including pharmaceuticals, dietary supplements, and foods.

Re: "Socioeconomic Differences in Cardiometabolic Factors: Social Casusation or Health-Related Selection? Evidence from the Whitehall II Cohort Study, 1991-2004"

The Authors Reply

Translation and validation of the German version of the Bournemouth Questionnaire for Neck Pain.

Background: Clinical outcome measures are important tools to monitor patient improvement during treatment as well as to document changes for research purposes. The short-form Bournemouth questionnaire for neck pain patients (BQN) was developed from the biopsychosocial model and measures pain, disability, cognitive and affective domains. It has been shown to be a valid and reliable outcome measure in English, French and Dutch and more sensitive to change compared to other questionnaires. The purpose of this study was to translate and validate a German version of the Bournemouth questionnaire for neck pain patients. Methods: German translation and back translation into English of the BQN was done independently by four persons and overseen by an expert committee. Face validity of the German BQN was tested on 30 neck pain patients in a single chiropractic practice. Test-retest reliability was evaluated on 31 medical students and chiropractors before and after a lecture. The German BQN was then assessed on 102 first time neck pain patients at two chiropractic practices for internal consistency, external construct validity, external longitudinal construct validity and sensitivity to change compared to the German versions of the Neck Disability Index (NDI) and the Neck Pain and Disability Scale (NPAD). Results: Face validity testing lead to minor changes to the German BQN. The Intraclass Correlation Coefficient for the test-retest reliability was 0.99. The internal consistency was strong for all 7 items of the BQN with Cronbach alpha's of .79 and .80 for the pre and post-treatment total scores. External construct validity and external longitudinal construct validity using Pearson's correlation coefficient showed statistically significant correlations for all 7 scales of the BQN with the other questionnaires. The German BQN showed greater responsiveness compared to the other questionnaires for all scales. Conclusions: The German BQN is a valid and reliable outcome measure that has been successfully translated and culturally adapted. It is shorter, easier to use, and more responsive to change than the NDI and NPAD.Key WordsBournemouth Questionnaire; Outcome Assessment; Neck Pain; Chiropractic; Validity of Results

The Five Eras of Chiropractic & the future of chiropractic as seen through the eyes of a participant observer.

Chiropractic has endured a turbulent history, marked by tremendous advances in areas such as education and licensing while marred by interprofessional conflict and a poor public image. The prolonged interprofessional conflict was instrumental in shaping the culture of chiropractic. These obstacles have long-since been removed although there are lingering effects from them.This article examines the chiropractic profession's history by dividing it into five Eras and suggests that there are three options available for the future of the profession. One: maintaining the status quo. Two: uniting under an evidence based scientific approach as partners in the health care delivery system that has buried the "one-cause, one-cure" sacred cow. The steps required to achieve this outcome are outlined. Three: openly dividing the profession into evidence based practitioners and subluxation based practitioners. Adopting this option would allow each branch of the profession to move forward in the health care delivery system unhindered by the other.It is unclear which option the profession will choose and whether the profession is mature enough to follow option two remains to be seen. What is evident is that the time to act is now.

Management of people with acute low-back pain: a survey of Australian chiropractors

IntroductionChiropractors commonly provide care to people with acute low-back pain (LBP). The aim of this survey was to determine how chiropractors intend to support and manage people with acute LBP and if this management is in accordance with two recommendations from an Australian evidence-based acute LBP guideline. The two recommendations were directed at minimising the use of plain x-ray and encouraging the patient to stay active. Methods: This is a cross sectional survey of chiropractors in Australia. This paper is part of the ALIGN study in which a targeted implementation strategy was developed to improve the management of acute LBP in a chiropractic setting. This implementation strategy was subsequently tested in a cluster randomised controlled trial. In this survey phase of the ALIGN study we approached a random sample of 880 chiropractors in three States of Australia. The mailed questionnaire consisted of five patient vignettes designed to represent people who would typically present to chiropractors with acute LBP. Four vignettes represented people who, according to the guideline, would not require a plain lumbar x-ray, and one vignette represented a person with a suspected vertebral fracture. Respondents were asked, for each vignette, to indicate which investigation(s) they would order, and which intervention(s) they would recommend or undertake. Results: Of the 880 chiropractors approached, 137 were deemed ineligible to participate, mostly because they were not currently practising, or mail was returned to sender. We received completed questionnaires from 274 chiropractors (response rate of 37%). Male chiropractors made up 66% of respondents, 75% practised in an urban location and their mean number of years in practice was 15. Across the four vignettes where an x-ray was not indicated 68% (95% Confidence Intervals (CI): 64%, 71%) of chiropractors responded that they would order or take an x-ray. In addition 51% (95%CI: 47%, 56%) indicated they would give advice to stay active when it was indicated. For the vignette where a fracture was suspected, 95% (95% CI: 91%, 97%) of chiropractors would order an x-ray. Conclusion: The intention of chiropractors surveyed in this study shows low adherence to two recommendations from an evidence-based guideline for acute LBP. Quality of care for these patients could be improved through effective implementation of evidence-based guidelines. Further research to find cost-effective methods to increase implementation is warranted.

Prevalence of pain-free weeks in chiropractic subjects with low back pain - a longitudinal study using data gathered with text messages

IntroductionThe use of automated text messages has made it possible to identify different courses of low back pain (LBP), and it has been observed that pain often fluctuates and that absolute recovery is rather rare. The purpose of this study was to describe the prevalence of pain-free weeks and pain-free periods in subjects with non-specific LBP treated by chiropractors, and to compare subjects from two different countries in these aspects. Methods: Data were obtained from two practice-based multicentre prospective outcome studies, one Danish and one Swedish, involving subjects being treated by chiropractors for non-specific LBP. Over 18 weeks, subjects answered a weekly automated text message question on the number of days in the past week that they had experienced bothersome LBP, i.e. a number between 0 and 7. The number of weeks in a row without any LBP at all ("zero weeks") as well as the maximum number of zero weeks in a row was determined for each individual. Comparisons were made between the two study samples. Estimates are presented as percentages with 95% confidence intervals. Results: In the Danish and the Swedish populations respectively, 93/110 (85%) and 233/262 (89%) of the subjects were eligible for analysis. In both groups, zero weeks were rather rare and were most commonly (in 40% of the zero weeks) reported as a single isolated week. The prevalence of pain free periods, i.e. reporting a maximum of 0, 1 or 2, or 3-6 zero weeks in a row, were similar in the two populations (20-31%). Smaller percentages were reported for ≥ 7 zero weeks in a row. There were no significant differences between the two study groups. Conclusion: It was uncommon that chiropractic subjects treated for non-specific LBP experienced an entire week without any LBP at all over 18 weeks. When this occurred, it was most commonly reported for brief periods only. Hence, recovery in the sense that patients become absolutely pain free is rare, even in a primary care population.

Prognostic factors for short-term improvement in acute and persistent musculoskeletal pain consulters in primary care.

Background: Given the costs associated with the management of musculoskeletal pain in primary care, predicting the course of these conditions remains a research priority. Much of the research into prognostic indicators however considers musculoskeletal conditions in terms of single pain sites whereas in reality, many patients present with pain in more than one site. The aim of this study was to identify prognostic factors for early improvement in primary care consulters with acute and persistent musculoskeletal conditions across a range of pain sites. Methods: Consecutive patients with a new episode of musculoskeletal pain completed self-report questionnaires at baseline, and then again at the 4/5th treatment visit, and if they were still consulting, at the 10th visit. The outcome was defined as patient self-report improvement sufficient to make a meaningful difference. Independent predictors of outcome were identified using multivariate regression analyses. Results: Acute (<7 weeks) patients, on average, had more severe conditions in terms of pain, disability, anxiety and work fear-avoidance behaviour than patients with persistent (≥7 weeks) pain, but were more likely to be better by the 4/5th visit. Several variables at baseline were associated with improvement at the 4/5th visit, but the predictive models were weak and unable to discriminate between patients who were improved and those who were not. In contrast, it was possible to elicit a predictive model for improvement later on at the 10th visit, but only in patients with persistent pain. Being employed, reporting a decline in work fear-avoidance behaviour at the 4/5th visit, and being better by the 4/5th visit, were all independently associated with improvement. This model accounted for 34.3% (p < 0.001) of the variation in observed improvement, and had good discriminative ability (the area under receiver operating characteristic (ROC) curve was 0.80 (95%CI 0.73 to 0.86)) and approximate balance in correctly identifying improved and non-improved cases (79.0% and 68% respectively). Conclusions: We were unable to identify baseline characteristics that predicted early outcome in musculoskeletal pain patients. However, early self-reported improvement and decline in work fear-avoidance behaviour as predictors of later improvement highlighted the importance of speedy recovery in persistent musculoskeletal pain consulters. Our findings reinforce the elusive nature of baseline predictors, and the need for more emphasis on early changes as prognostic predictors in musculoskeletal conditions.

Application of a Diagnosis-Based Clinical Decision Guide in Patients with Low Back Pain

Background: Low back pain (LBP) is common and costly. Development of accurate and efficacious methods of diagnosis and treatment has been identified as a research priority. A diagnosis-based clinical decision guide (DBCDG; previously referred to as a diagnosis-based clinical decision rule) has been proposed which attempts to provide the clinician with a systematic, evidence-based means to apply the biopsychosocial model of care. The approach is based on three questions of diagnosis. The purpose of this study is to present the prevalence of findings using the DBCDG in consecutive patients with LBP. Methods: Demographic, diagnostic and baseline outcome measure data were gathered on a cohort of LBP patients examined by one of three examiners trained in the application of the DBCDG. Results: Data were gathered on 264 patients. Signs of visceral disease or potentially serious illness were found in 2.7%. Centralization signs were found in 41%, lumbar and sacroiliac segmental signs in 23% and 27%, respectively and radicular signs were found in 24%. Clinically relevant myofascial signs were diagnosed in 10%. Dynamic instability was diagnosed in 63%, fear beliefs in 40%, central pain hypersensitivity in 5%, passive coping in 3% and depression in 3%. Conclusion: The DBCDG can be applied in a busy private practice environment. Further studies are needed to investigate clinically relevant means to identify central pain hypersensitivity, poor coping and depression, correlations and patterns among the diagnostic components of the DBCDG as well as inter-examiner reliability and efficacy of treatment based on the DBCDG.

Attitudes towards Chiropractic: An Analysis of Written Comments from a Survey of North American Orthopaedic Surgeons

Background: There is increasing interest by chiropractors in North America regarding integration into mainstream healthcare; however, there is limited information about attitudes towards the profession among conventional healthcare providers, including orthopaedic surgeons. Methods: We administered a 43-item cross-sectional survey to 1000 Canadian and American orthopaedic surgeons that inquired about demographic variables and their attitudes towards chiropractic. Our survey included an option for respondants to include written comments, and our present analysis is restricted to these comments. Two reviewers, independantly and in duplicate, coded all written comments using thematic analysis. Results: 487 surgeons completed the survey (response rate 49%), and 174 provided written comments. Our analysis revealed 8 themes and 24 sub-themes represented in surgeons' comments. Reported themes were: variability amongst chiropractors (n = 55); concerns with chiropractic treatment (n = 54); areas where chiropractic is perceived as effective (n = 43); unethical behavior (n = 43); patient interaction (n = 36); the scientific basis of chiropractic (n = 26); personal experiences with chiropractic (n = 21); and chiropractic training (n = 18). Common sub-themes endorsed by surgeon's were diversity within the chiropractic profession as a barrier to increased interprofessional collaboration, endorsement for chiropractic treatment of musculoskeletal complaints, criticism for treatment of non-musculoskeletal complaints, and concern over whether chiropractic care was evidence-based. Conclusions: Our analysis identified a number of issues that will have to be considered by the chiropractic profession as part of its efforts to further integrate chiropractic into mainstream healthcare.

Retraction: A descriptive study of a manual therapy intervention within a randomised controlled trial for hamstring and lower limb injury prevention

The journal has been informed by its publisher BioMed Central that contrary to the statement in this article [Wayne Hoskins, Henry Pollard, Chiropractic & Osteopathy 2010, 18:23], they have been advised by the authors' institution Macquarie University, that its Human Research Ethics Committee did not approve this study. Because the study was conducted without institutional ethics committee approval it has been retracted.

Case management of chiropractic patients with cervical brachialgia: A survey of French chiropractors.

Background: Not much is known about the French chiropractic profession on, for example, level of consensus on clinical issues.ObjectivesThe first objective was to investigate if French chiropractors' management choices appeared reasonable for various neck problem scenarios. The second objective was to investigate if there was agreement between chiropractors on the patient management. The third objective was to see to which degree and at what stages chiropractors would consider to interact with other health-care practitioners, such as physiotherapists, general practitioners and specialists.MethodA questionnaire was sent to a randomly selected sample of all French chiropractors known to the national chiropractic college. It consisted of an invitation to participate in the study, a brief case description, and drawings of five stages of how a case of neck pain gradually evolves into a brachialgia to end up with a compromised spinal cord. Each stage offered five management choices. Participants were asked at what stages patients would be treated solely by the chiropractor and when patients would be referred out for second opinion or other care without chiropractic treatment, plus an open ended option, resulting in a "five-by-six" table. The percentages of respondents choosing the different management strategies were identified for the different scenarios and the 95% confidence intervals were calculated. There was a pre hoc agreement on when chiropractic care would or would not be suitable. Consensus was arbitrarily defined as "moderate" when 50- 69% of respondents agreed on the same management choice and as "excellent" when 70% or more provided the same answer. It was expected that inter professional contacts would be rare. Results: The response rate was 53% out of 254 potential participants. The first two uncomplicated cases would generally have been treated by the chiropractors. As the patient worsened, the responses tended towards external assistance and for the most severe case, the majority of respondents would have referred the patient out. There was excellent consensus for the two extreme cases (the most benign and the most severe), moderate consensus for the cases next to these two and least agreement relating to the "middle" case. Inter-professional collaboration was contemplated mainly for the severe case. Conclusion: The French chiropractors who participated in this study seem to have a similar approach to patients with neck pain that gradually develops into a brachialgia and worsens. However, it is not known if the large group of non-participants in the study would agree with this treatment strategy.

The lived experience of fibromyalgia in female patients, a phenomenological study.

Background: Fibromyalgia is a chronic syndrome with no cure. A thorough understanding of the illness experience is therefore key in the palliative care of patients with this condition. In search for supportive treatments fibromyalgia patients often attend a chiropractor or other manual therapist. Knowledge of the meaning and reality of living with this condition to the patient could be considered essential to any health care practitioner playing a role in the management. This study aimed to gain a better understanding of the subjective experience of fibromyalgia, focusing on the personal, occupational and social impact of the condition on patients' lives. This included exploring the patients' views about the future. Methods: This study employed descriptive phenomenology and adopted Husserl's concept of transcendental subjectivity or "bracketing". This qualitative study involved semi-structured interviews and was undertaken to obtain rich data that reflected the essence of the participants' experience. Participants consisted of six female volunteers, diagnosed with fibromyalgia by the University Hospital Gent, Belgium. Data were analysed using a thematic framework. Results: Fibromyalgia pervaded all aspects of life. Four main themes arose from data analysis, namely; the impact of fibromyalgia on patients' occupational and personal life, the impact on their future and aspects of social interaction. Nearly all participants had stopped working, giving rise to feelings of uselessness and loss of identity. Leisure activities were also greatly affected. Fibromyalgia was said to alter family bonds, some of which were reinforced, others were broken. The diagnosis was seen as a relief, marking an end to a period of uncertainty. Participants reported ambivalence in interaction. Despite some positive encounters, frustration arising from perceived incomprehension dominated. Consequently patients preferred not to share their experiences. Conclusions: The study revealed the negative impact of fibromyalgia on patients' lives as comprising of great complexity and individuality. Several implications for health care practitioners can be extrapolated, including the need of a more efficient diagnostic process and increased education about the fibromyalgia experience. Further studies are required to better clarify the multifaceted nature of living with the condition.

Relationship of Climate, Geography, and Geology to the Incidence of Rift Valley Fever in Kenya during the 2006-2007 Outbreak.

Relationship of Climate, Geography, and Geology to the Incidence of Rift Valley Fever in Kenya during the 2006-2007 Outbreak. Am J Trop Med Hyg. 2012 Feb;86(2):373-380 Authors: Hightower A, Kinkade C, Nguku PM, Anyangu A, Mutonga D, Omolo J, Njenga MK, Feikin DR, Schnabel D, Ombok M, Breiman RF Abstract Abstract. We estimated Rift Valley fever (RVF) incidence as a function of geological, geographical, and climatological factors during the 2006-2007 RVF epidemic in Kenya. Location information was obtained for 214 of 340 (63%) confirmed and probable RVF cases that occurred during an outbreak from November 1, 2006 to February 28, 2007. Locations with subtypes of solonetz, calcisols, solonchaks, and planosols soil types were highly associated with RVF occurrence during the outbreak period. Increased rainfall and higher greenness measures before the outbreak were associated with increased risk. RVF was more likely to occur on plains, in densely bushed areas, at lower elevations, and in the Somalia acacia ecological zone. Cases occurred in three spatial temporal clusters that differed by the date of associated rainfall, soil type, and land usage. PMID: 22302875 [PubMed - as supplied by publisher]

The Safety of Yellow Fever Vaccine 17D or 17DD in Children, Pregnant Women, HIV+ Individuals, and Older Persons: Systematic Review.

The Safety of Yellow Fever Vaccine 17D or 17DD in Children, Pregnant Women, HIV+ Individuals, and Older Persons: Systematic Review. Am J Trop Med Hyg. 2012 Feb;86(2):359-72 Authors: Thomas RE, Lorenzetti DL, Spragins W, Jackson D, Williamson T Abstract Abstract. Yellow fever vaccine provides long-lasting immunity. Rare serious adverse events after vaccination include neurologic or viscerotropic syndromes or anaphylaxis. We conducted a systematic review of adverse events associated with yellow fever vaccination in vulnerable populations. Nine electronic bibliographic databases and reference lists of included articles were searched. Electronic databases identified 2,415 abstracts for review, and 32 abstracts were included in this review. We identified nine studies of adverse events in infants and children, eight studies of adverse events in pregnant women, nine studies of adverse events in human immunodeficiency virus-positive patients, five studies of adverse events in persons 60 years and older, and one study of adverse events in individuals taking immunosuppressive medications. Two case studies of maternal-neonate transmission resulted in serious adverse events, and the five passive surveillance databases identified very small numbers of cases of yellow fever vaccine-associated viscerotropic disease, yellow fever vaccine-associated neurotropic disease, and anaphylaxis in persons ≥ 60 years. No other serious adverse events were identified in the other studies of vulnerable groups. PMID: 22302874 [PubMed - in process]

Assessing the risk of international spread of yellow Fever virus: a mathematical analysis of an urban outbreak in asuncion, 2008.

Assessing the risk of international spread of yellow Fever virus: a mathematical analysis of an urban outbreak in asuncion, 2008. Am J Trop Med Hyg. 2012 Feb;86(2):349-58 Authors: Johansson MA, Arana-Vizcarrondo N, Biggerstaff BJ, Gallagher N, Marano N, Staples JE Abstract Abstract. Yellow fever virus (YFV), a mosquito-borne virus endemic to tropical Africa and South America, is capable of causing large urban outbreaks of human disease. With the ease of international travel, urban outbreaks could lead to the rapid spread and subsequent transmission of YFV in distant locations. We designed a stochastic metapopulation model with spatiotemporally explicit transmissibility scenarios to simulate the global spread of YFV from a single urban outbreak by infected airline travelers. In simulations of a 2008 outbreak in Asunción, Paraguay, local outbreaks occurred in 12.8% of simulations and international spread in 2.0%. Using simple probabilistic models, we found that local incidence, travel rates, and basic transmission parameters are sufficient to assess the probability of introduction and autochthonous transmission events. These models could be used to assess the risk of YFV spread during an urban outbreak and identify locations at risk for YFV introduction and subsequent autochthonous transmission. PMID: 22302873 [PubMed - in process]

A Three-Component Biomarker Panel for Prediction of Dengue Hemorrhagic Fever.

A Three-Component Biomarker Panel for Prediction of Dengue Hemorrhagic Fever. Am J Trop Med Hyg. 2012 Feb;86(2):341-348 Authors: Brasier AR, Ju H, Garcia J, Spratt HM, Victor SS, Forshey BM, Halsey ES, Comach G, Sierra G, Blair PJ, Rocha C, Morrison AC, Scott TW, Bazan I, Kochel TJ, The Venezuelan Dengue Fever Working Group Abstract Abstract. Dengue virus infections are a major cause of morbidity in tropical countries. Early detection of dengue hemorrhagic fever (DHF) may help identify individuals that would benefit from intensive therapy. Predictive modeling was performed using 11 laboratory values of 51 individuals (38 DF and 13 DHF) obtained on initial presentation using logistic regression. We produced a robust model with an area under the curve of 0.9615 that retained IL-10 levels, platelets, and lymphocytes as the major predictive features. A classification and regression tree was developed on these features that were 86% accurate on cross-validation. The IL-10 levels and platelet counts were also identified as the most informative features associated with DHF using a Random Forest classifier. In the presence of polymerase chain reaction-proven acute dengue infections, we suggest a complete blood count and rapid measurement of IL-10 can assist in the triage of potential DHF cases for close follow-up or clinical intervention improving clinical outcome. PMID: 22302872 [PubMed - as supplied by publisher]

Molecular detection and typing of dengue viruses from archived tissues of fatal cases by rt-PCR and sequencing: diagnostic and epidemiologic implications.

Molecular detection and typing of dengue viruses from archived tissues of fatal cases by rt-PCR and sequencing: diagnostic and epidemiologic implications. Am J Trop Med Hyg. 2012 Feb;86(2):335-40 Authors: Bhatnagar J, Blau DM, Shieh WJ, Paddock CD, Drew C, Liu L, Jones T, Patel M, Zaki SR Abstract Abstract. Diagnosis of dengue virus (DENV) infection in fatal cases is challenging because of the frequent unavailability of blood or fresh tissues. For formalin-fixed, paraffin-embedded (FFPE) tissues immunohistochemistry (IHC) can be used; however, it may not be as sensitive and serotyping is not possible. The application of reverse transcription-polymerase chain reaction (RT-PCR) for the detection of DENV in FFPE tissues has been very limited. We evaluated FFPE autopsy tissues of 122 patients with suspected DENV infection by flavivirus and DENV RT-PCR, sequencing, and DENV IHC. The DENV was detected in 61 (50%) cases by RT-PCR or IHC. The RT-PCR and sequencing detected DENV in 60 (49%) cases (DENV-1 in 16, DENV-2 in 27, DENV-3 in 8, and DENV-4 in 6 cases). No serotype could be identified in three cases. The IHC detected DENV antigens in 50 (40%) cases. The RT-PCR using FFPE tissue improves detection of DENV in fatal cases and provides sequence information useful for typing and epidemiologic studies. PMID: 22302871 [PubMed - in process]

Factors associated with dengue mortality in latin america and the Caribbean, 1995-2009: an ecological study.

Factors associated with dengue mortality in latin america and the Caribbean, 1995-2009: an ecological study. Am J Trop Med Hyg. 2012 Feb;86(2):328-34 Authors: Díaz-Quijano FA, Waldman EA Abstract Abstract. In this study, we aimed to estimate the effect that environmental, demographic, and socioeconomic factors have on dengue mortality in Latin America and the Caribbean. To that end, we conducted an observational ecological study, analyzing data collected between 1995 and 2009. Dengue mortality rates were highest in the Caribbean (Spanish-speaking and non-Spanish-speaking). Multivariate analysis through Poisson regression revealed that the following factors were independently associated with dengue mortality: time since identification of endemicity (adjusted rate ratio [aRR] = 3.2 [for each 10 years]); annual rainfall (aRR = 1.5 [for each 10(3) L/m(2)]); population density (aRR = 2.1 and 3.2 for 20-120 inhabitants/km(2) and > 120 inhabitants/km(2), respectively); Human Development Index > 0.83 (aRR = 0.4); and circulation of the dengue 2 serotype (aRR = 1.7). These results highlight the important role that environmental, demographic, socioeconomic, and biological factors have played in increasing the severity of dengue in recent decades. PMID: 22302870 [PubMed - in process]

Human Risk of Infection with Borrelia burgdorferi, the Lyme Disease Agent, in Eastern United States.

Human Risk of Infection with Borrelia burgdorferi, the Lyme Disease Agent, in Eastern United States. Am J Trop Med Hyg. 2012 Feb;86(2):320-327 Authors: Diuk-Wasser MA, Hoen AG, Cislo P, Brinkerhoff R, Hamer SA, Rowland M, Cortinas R, Vourc'h G, Melton F, Hickling GJ, Tsao JI, Bunikis J, Barbour AG, Kitron U, Piesman J, Fish D Abstract Abstract. The geographic pattern of human risk for infection with Borrelia burgdorferi sensu stricto, the tick-borne pathogen that causes Lyme disease, was mapped for the eastern United States. The map is based on standardized field sampling in 304 sites of the density of Ixodes scapularis host-seeking nymphs infected with B. burgdorferi, which is closely associated with human infection risk. Risk factors for the presence and density of infected nymphs were used to model a continuous 8 km×8 km resolution predictive surface of human risk, including confidence intervals for each pixel. Discontinuous Lyme disease risk foci were identified in the Northeast and upper Midwest, with a transitional zone including sites with uninfected I. scapularis populations. Given frequent under- and over-diagnoses of Lyme disease, this map could act as a tool to guide surveillance, control, and prevention efforts and act as a baseline for studies tracking the spread of infection. PMID: 22302869 [PubMed - as supplied by publisher]

Leptospirosis in american samoa 2010: epidemiology, environmental drivers, and the management of emergence.

Leptospirosis in american samoa 2010: epidemiology, environmental drivers, and the management of emergence. Am J Trop Med Hyg. 2012 Feb;86(2):309-19 Authors: Lau CL, Dobson AJ, Smythe LD, Fearnley EJ, Skelly C, Clements AC, Craig SB, Fuimaono SD, Weinstein P Abstract Abstract. Leptospirosis has recently been reported as an emerging disease worldwide, and a seroprevalence study was undertaken in American Samoa to better understand the drivers of transmission. Antibodies indicative of previous exposure to leptospirosis were found in 15.5% of 807 participants, predominantly against three serovars that were not previously known to occur in American Samoa. Questionnaires and geographic information systems data were used to assess behavioral factors and environmental determinants of disease transmission, and logistic regression was used to identify factors associated with infection. Many statistically significant factors were consistent with previous studies, but we also showed a significant association with living at lower altitudes (odds ratio [OR] = 1.53, 95% confidence interval [CI]: 1.03-2.28), and having higher numbers of piggeries around the home (OR = 2.63, 95% CI: 1.52-4.40). Our findings support a multifaceted approach to combating the emergence of leptospirosis, including modification of individual behavior, but importantly also managing the evolving environmental drivers of risk. PMID: 22302868 [PubMed - in process]

Comparative analysis of severe pediatric and adult leptospirosis in sao paulo, Brazil.

Comparative analysis of severe pediatric and adult leptospirosis in sao paulo, Brazil. Am J Trop Med Hyg. 2012 Feb;86(2):306-8 Authors: Spichler A, Athanazio DA, Vilaça P, Seguro A, Vinetz J, Leake JA Abstract Abstract. Although leptospirosis may be fatal in childhood, the experience of many clinicians working in disease-endemic areas is that classic Weil's disease and death are less common among pediatric patients. The aim of the study was to ascertain disease spectrum and outcome differences in severe pediatric and adult leptospirosis in a large at-risk population. Epidemiologic, clinical, and laboratory data were obtained on hospitalized cases from São Paulo during 2004-2006. A total of 42 case-patients < 18 years of age and 328 case-patients ≥ 18 years of age were tested during the study. Compared with children, adults had higher rates of jaundice (P = 0.01), elevated serum bilirubin levels (P < 0.01), oliguria (P = 0.02), and elevated creatinine levels (P = 0.01) but not for thrombocytopenia or pulmonary involvement. The overall case-fatality rate was 27% (adult) versus 5% (pediatric) (P < 0.01). Severe pediatric leptospirosis may be less likely to show all classic features of Weil's disease and may be less fatal than in adults. PMID: 22302867 [PubMed - in process]

Factors Associated with Resistance to Schistosoma mansoni Infection in an Endemic Area of Bahia, Brazil.

Factors Associated with Resistance to Schistosoma mansoni Infection in an Endemic Area of Bahia, Brazil. Am J Trop Med Hyg. 2012 Feb;86(2):296-305 Authors: Oliveira RR, Figueiredo JP, Cardoso LS, Jabar RL, Souza RP, Wells MT, Carvalho EM, Fitzgerald DW, Barnes KC, Araújo MI, Glesby MJ Abstract Abstract. Detailed knowledge of factors associated with resistance to Schistosoma mansoni infection in endemic areas might facilitate more effective schistosomiasis control. We conducted a cross-sectional study of persons resistant to schistosomiasis and found no association between socioeconomic status and resistance to infection. Mononuclear cells of resistant subjects produced higher levels of interleukin-5 (IL-5), IL-13 and interferon-γ upon stimulation with soluble egg antigen (SEA) compared with infected persons. When stimulated with Sm21.6 or Sm22.6, levels of IL-10 were higher in cell culture of resistant persons. Levels of IgE against soluble adult worm antigen (SWAP) and against interleukin-4-inducing principle from S. mansoni eggs (IPSE) and levels of IgG4 against SWAP, SEA, and Sm22.6 were lower in the resistant group compared with the susceptible group. Our data suggest that socioeconomic status could not fully explain resistance to S. mansoni infection observed in the studied area. However, a mixture of Th1 and Th2 immune responses and low levels of specific IgG4 against parasite antigens could be mediating resistance to infection. PMID: 22302866 [PubMed - as supplied by publisher]

Sexually Transmitted Infections in Newly Arrived Refugees: Is Routine Screening for Neisseria gonorrheae and Chlamydia trachomatis Infection Indicated?

Sexually Transmitted Infections in Newly Arrived Refugees: Is Routine Screening for Neisseria gonorrheae and Chlamydia trachomatis Infection Indicated? Am J Trop Med Hyg. 2012 Feb;86(2):292-5 Authors: Stauffer WM, Painter J, Mamo B, Kaiser R, Weinberg M, Berman S Abstract Abstract. More than 340 million cases of bacterial and protozoal sexually transmitted infections (STIs) occur annually. Approximately 70,000 refugees arrive in the United States on a yearly basis. Refugees are a particularly disenfranchised and vulnerable population. The prevalence of Chlamydia and gonorrhea in refugee populations has not been described, and the utility of routine screening is unknown. We performed a descriptive evaluation of 25,779 refugees who completed a screening medical examination in Minnesota during 2003-2010. A total of 18,516 (72%) refugees were tested for at least one STI: 183 (1.1%) of 17,235 were seropositive for syphilis, 15 (0.6%) of 2,512 were positive for Chlamydia, 5 (0.2%) of 2,403 were positive for gonorrhea, 136 (2.0%) of 6,765 were positive for human immunodeficiency virus, and 6 (0.1%) of 5,873 were positive for multiple STIs. Overall prevalence of Chlamydia (0.6%) and gonorrhea (0.2%) infection was low, which indicated that routine screening may not be indicated. However, further research on this subject is encouraged. PMID: 22302865 [PubMed - in process]

Prediction of child health by household density and asset-based indices in impoverished indigenous villages in rural panama.

Prediction of child health by household density and asset-based indices in impoverished indigenous villages in rural panama. Am J Trop Med Hyg. 2012 Feb;86(2):280-91 Authors: Halpenny CM, Koski KG, Valdés VE, Scott ME Abstract Abstract. Chronic infection over a 16-month period and stunting of preschool children were compared between more spatially dense versus dispersed households in rural Panamá. Chronic protozoan infection was associated with higher household density, lower household wealth index, poor household water quality, yard defecation, and the practice of not washing hands with soap before eating. Models for chronic diarrhea confirmed the importance of household wealth, water quality, sanitation, and hygiene practices. Furthermore, chronic protozoan infection was an important predictor for low height-for-age, along with low household wealth index scores, but not household density. Thus, despite better access to health related infrastructure in the more densely populated households, chronic protozoan infection was more common, and was associated with higher rates of child stunting, compared with more dispersed households. PMID: 22302864 [PubMed - in process]

Non-invasive assessment of fibrosis using color Doppler ultrasound in patients with hepatitis C virus in the Amazon rainforest, Brazil.

Non-invasive assessment of fibrosis using color Doppler ultrasound in patients with hepatitis C virus in the Amazon rainforest, Brazil. Am J Trop Med Hyg. 2012 Feb;86(2):273-9 Authors: Leão J, Brock M, Castilho M, Scariot A, Scariot A, Braga W Abstract Abstract. The purpose of this study was to correlate morphologic and hemodynamic Doppler ultrasound findings as indicators of the degree of inflammation and fibrosis and to diagnose chronic vital hepatitis complications and progression. A prospective, descriptive study of a case series was conducted that analyzed Doppler ultrasound images of the liver and portal system and used the portal vein congestion index, hepatic and splenic artery impedance indices, and the liver vascular index. Of 50 patients positive for antibodies against hepatitis C virus, morphologic changes highlighted increased hepatic parenchyma echogenicity in 24%, and increased gall blander echogenicity and wall thickness in 4%. The most common hemodynamic changes observed were reduced flow velocity in the portal vein trunk in 26%, congestion index changes in 12%, liver vascular index changes in 16%, and splenic and hepatic artery impedance index changes in 14%. These indices were shown to be associated with alanine aminotransferase levels, which suggested that they are important liver damage indicators in the early phase of infection with hepatitis C virus. PMID: 22302863 [PubMed - in process]

Pseudotumoral form of neuroschistosomiasis: report of three cases in ganzi, china.

Pseudotumoral form of neuroschistosomiasis: report of three cases in ganzi, china. Am J Trop Med Hyg. 2012 Feb;86(2):268-72 Authors: Wan H, Masataka H, Zhang LP, Zheng DF Abstract Abstract. The authors report three rare cases of neuroschistosomiasis lacking extracranial involvement. No parasitic eggs were detected in the stool with the Kato-Katz thick smear methods. Computed tomography of the brains showed hypodense signals, and magnetic resonance imaging showed isointense signals on T1-weighted images, hyperintense signals on T2-weighted images, and intensely enhancing nodules in the brain after intravenous administration of gadolinium. High-grade gliomas were suspected, and operations or radiosurgery was performed. Cerebral schistosomiasis was confirmed in all cases by biopsy of the brain lesions, revealing granulomas containing embedded Schistosoma japonicum eggs. All cases were definitively diagnosed as brain schistosomiasis japonica. Praziquantel and corticosteroids were administered, and the prognoses were good for all case patients. Although the aforementioned pattern of imaging examinations is not present in all cases of neuroschistosomiasis, a diagnosis of neuroschistosomiasis should be considered when this pattern of imaging is observed; cerebrospinal fluid serological exams are also recommended. PMID: 22302862 [PubMed - in process]

Recurrent disseminated intravascular coagulation caused by intermittent dosing of rifampin.

Recurrent disseminated intravascular coagulation caused by intermittent dosing of rifampin. Am J Trop Med Hyg. 2012 Feb;86(2):264-7 Authors: Havey TC, Cserti-Gazdewich C, Sholzberg M, Keystone JS, Gold WL Abstract Abstract. Daily rifampin therapy is associated with minimal adverse effects, but administration on an intermittent or interrupted basis has been associated with severe immunoallergic reactions such as hemolytic anemia, acute renal failure, and disseminated intravascular coagulation. We describe a patient with Mycobacterium leprae infection who experienced recurrent episodes of disseminated intravascular coagulation after intermittent exposures to rifampin, and review eight previously reported cases of rifampin-associated disseminated intravascular coagulation. In six (75%) cases, previous exposure to rifampin was reported and seven (87.5%) patients were receiving the medication on an intermittent or interrupted basis. Clinical features of rifampin-associated disseminated intravascular coagulation included fever, hypotension, abdominal pain, and vomiting within hours of ingestion. Average time to reaction was 3-6 doses if rifampin was being administered on a monthly schedule. Three (37.5%) of eight reported cases were fatal. A complete history of previous exposure to rifampin is recommended before intermittent therapy with this medication. PMID: 22302861 [PubMed - in process]

An Unusual Cutaneous Tumor: African Histoplasmosis following Mudbaths: Case Report and Review.

An Unusual Cutaneous Tumor: African Histoplasmosis following Mudbaths: Case Report and Review. Am J Trop Med Hyg. 2012 Feb;86(2):261-3 Authors: Tsiodras S, Drogari-Apiranthitou M, Pilichos K, Leventakos K, Kelesidis T, Buitrago MJ, Petrikkos G, Panayiotides I Abstract Abstract. African histoplasmosis, caused by Histoplasma capsulatum var. duboisii, is endemic in Africa. The disease usually involves the skin, subcutaneous tissue, and bones. A case of African histoplasmosis presenting as a cutaneous tumor and non-healing wound in a 66-year-old immunocompetent male residing in Africa, the first ever reported following mudbaths and acupuncture, is hereby reported. Diagnosis was confirmed by means of polymerase chain reaction performed on tissue material. The patient was started on long-term itraconazole therapy and he responded well. African histoplasmosis should be included in the differential diagnosis of non-healing wounds or tumor-like lesions, especially in the context of mudbaths in an endemic area. PMID: 22302860 [PubMed - in process]

Unusual presentations of pediatric neurobrucellosis.

Unusual presentations of pediatric neurobrucellosis. Am J Trop Med Hyg. 2012 Feb;86(2):258-60 Authors: Budnik I, Fuchs I, Shelef I, Krymko H, Greenberg D Abstract Abstract. Neurobrucellosis is an uncommon complication of pediatric brucellosis. Acute meningitis and encephalitis are the most common clinical manifestations, however symptoms may be protean and diagnosis requires a high index of suspicion in patients from endemic areas. Diagnosis is often based on neurological symptoms, serology, and suggestive brain imaging because cerebrospinal fluid culture yields are low. Two cases of pediatric neurobrucellosis with unusual clinical and radiologic findings are presented. PMID: 22302859 [PubMed - in process]

Saw-scaled viper bites in sri lanka: is it a different subspecies? Clinical evidence from an authenticated case series.

Saw-scaled viper bites in sri lanka: is it a different subspecies? Clinical evidence from an authenticated case series. Am J Trop Med Hyg. 2012 Feb;86(2):254-7 Authors: Gnanathasan A, Rodrigo C, Peranantharajah T, Coonghe A Abstract Abstract. The saw-scaled viper (SSV) (Echis carinatus) is considered to be a highly venomous snake in Sri Lanka despite any published clinical justification. Being a rarity, the clinical profile of SSV bites is not well established in Sri Lanka. We report a series of 48 (n-48) SSV bites from the Northern Province of Sri Lanka. The majority (65%) of victims had evidence of local envenoming at the site of the bite; however, 29% showed spontaneous bleeding and 71% had coagulopathy. There were no deaths in the series. The envenoming was mild in contrast to the mortality and significant morbidity associated with SSV bites in West Africa and some parts of India. These observations need to be further explored with laboratory studies to identify the venom components, study of morphological characteristics, and genetic profiling of the Sri Lankan SSV to see if it is different from the subspecies found elsewhere. PMID: 22302858 [PubMed - in process]

Infectious Etiologies of Acute Febrile Illness among Patients Seeking Health Care in South-Central Cambodia.

Infectious Etiologies of Acute Febrile Illness among Patients Seeking Health Care in South-Central Cambodia. Am J Trop Med Hyg. 2012 Feb;86(2):246-53 Authors: Kasper MR, Blair PJ, Touch S, Sokhal B, Yasuda CY, Williams M, Richards AL, Burgess TH, Wierzba TF, Putnam SD Abstract Abstract. The agents of human febrile illness can vary by region and country suggesting that diagnosis, treatment, and control programs need to be based on a methodical evaluation of area-specific etiologies. From December 2006 to December 2009, 9,997 individuals presenting with acute febrile illness at nine health care clinics in south-central Cambodia were enrolled in a study to elucidate the etiologies. Upon enrollment, respiratory specimens, whole blood, and serum were collected. Testing was performed for viral, bacterial, and parasitic pathogens. Etiologies were identified in 38.0% of patients. Influenza was the most frequent pathogen, followed by dengue, malaria, and bacterial pathogens isolated from blood culture. In addition, 3.5% of enrolled patients were infected with more than one pathogen. Our data provide the first systematic assessment of the etiologies of acute febrile illness in south-central Cambodia. Data from syndromic-based surveillance studies can help guide public health responses in developing nations. PMID: 22302857 [PubMed - in process]

Predictors of Acute Bacterial Meningitis in Children from a Malaria-Endemic Area of Papua New Guinea.

Predictors of Acute Bacterial Meningitis in Children from a Malaria-Endemic Area of Papua New Guinea. Am J Trop Med Hyg. 2012 Feb;86(2):240-245 Authors: Laman M, Manning L, Greenhill AR, Mare T, Michael A, Shem S, Vince J, Lagani W, Hwaiwhanje I, Siba PM, Mueller I, Davis TM Abstract Abstract. Predictors of acute bacterial meningitis (ABM) were assessed in 554 children in Papua New Guinea 0.2-10 years of age who were hospitalized with culture-proven meningitis, probable meningitis, or non-meningitic illness investigated by lumbar puncture. Forty-seven (8.5%) had proven meningitis and 36 (6.5%) had probable meningitis. Neck stiffness, Kernig's and Brudzinski's signs and, in children < 18 months of age, a bulging fontanel had positive likelihood ratios (LRs) ≥ 4.3 for proven/probable ABM. Multiple seizures and deep coma were less predictive (LR = 1.5-2.1). Single seizures and malaria parasitemia had low LRs (≤ 0.5). In logistic regression including clinical variables, Kernig's sign and deep coma were positively associated with ABM, and a single seizure was negatively associated (P ≤ 0.01). In models including microscopy, neck stiffness and deep coma were positively associated with ABM and parasitemia was negatively associated with ABM (P ≤ 0.04). In young children, a bulging fontanel added to the model (P < 0.001). Simple clinical features predict ABM in children in Papua New Guinea but malaria microscopy augments diagnostic precision. PMID: 22302856 [PubMed - as supplied by publisher]

Verbal autopsy for neurological diseases.

Verbal autopsy for neurological diseases. Am J Trop Med Hyg. 2012 Feb;86(2):237-9 Authors: Mateen FJ, Kalter HD Abstract Abstract. Verbal autopsy is an interview-based technique to determine the cause distribution of death in a population. The use of verbal autopsy for understanding neurological diseases is crucial to burden of disease analyses in many countries, particularly in locations where civil registration systems are non-functioning or absent. We review the purposes, strengths, and weaknesses in the use of verbal autopsy for neurological diseases. PMID: 22302855 [PubMed - in process]

Detection and Transmission of Dientamoeba fragilis from Environmental and Household Samples.

Detection and Transmission of Dientamoeba fragilis from Environmental and Household Samples. Am J Trop Med Hyg. 2012 Feb;86(2):233-6 Authors: Stark D, Roberts T, Marriott D, Harkness J, Ellis JT Abstract Abstract. Dientamoeba fragilis is a commonly occurring pathogenic protozoan often detected at higher rates in stool samples than Giardia intestinalis. However, little is known about its life cycle and mode of transmission. A total of 210 environmental and household samples were examined for the presence of D. fragilis by culture and polymerase chain reaction. Of 100 environmental samples, D. fragilis was detected only in untreated sewage. In the household samples D. fragilis was detected in 30% of household contacts tested and was not detected in any domestic pets. This study provides evidence that environmental transmission of D. fragilis is unlikely and that pets played no role in transmission of the disease in this study. Direct transmission from infected persons is the most likely mode of transmission for D. fragilis. The study also highlights the need for household contacts to be screened, given the propensity of close contacts to become infected with the organism. PMID: 22302854 [PubMed - in process]

Mannose-Binding Lectin and Toll-Like Receptor Polymorphisms and Chagas Disease in Chile.

Mannose-Binding Lectin and Toll-Like Receptor Polymorphisms and Chagas Disease in Chile. Am J Trop Med Hyg. 2012 Feb;86(2):229-232 Authors: Weitzel T, Zulantay I, Danquah I, Hamann L, Schumann RR, Apt W, Mockenhaupt FP Abstract Abstract. Mannose-binding lectin (MBL) and Toll-like receptor (TLR) polymorphisms may influence susceptibility and manifestation of Trypanosoma cruzi infection. In northern Chile, we examined 61 asymptomatic patients with chronic Chagas disease (CD), 64 patients with chronic Chagas cardiomyopathy (CCC), and 45 healthy individuals. Low-producer MBL2*B genotypes were more common in CD patients (48%) than healthy individuals (31%; adjusted odds ratio = 2.3, 95% confidence interval = 1.01-5.4, P = 0.047) but did not differ with manifestation. In contrast, the heterozygous Toll-like receptor 4 (TLR4)-deficiency genotype D299G/T399I occurred more frequently in asymptomatic (14.8%) than CCC patients (3.1%; P = 0.02). TLR1-I602S, TLR2-R753Q, TLR6-S249P, and MAL/TIRAP-S180L did not associate with CD or CCC. These findings support the complement system to be involved in defense against Trypanosoma cruzi infection and indicate that curbed TLR4 activation might be beneficial in preventing CCC. PMID: 22302853 [PubMed - as supplied by publisher]

Evaluation of the Solar Water Disinfection Process (SODIS) Against Cryptosporidium parvum Using a 25-L Static Solar Reactor Fitted with a Compound Parabolic Collector (CPC).

Evaluation of the Solar Water Disinfection Process (SODIS) Against Cryptosporidium parvum Using a 25-L Static Solar Reactor Fitted with a Compound Parabolic Collector (CPC). Am J Trop Med Hyg. 2012 Feb;86(2):223-8 Authors: Fontán-Sainz M, Gómez-Couso H, Fernández-Ibáñez P, Ares-Mazás E Abstract Abstract. Water samples of 0, 5, and 30 nephelometric turbidity units (NTU) spiked with Cryptosporidium parvum oocysts were exposed to natural sunlight using a 25-L static solar reactor fitted with a compound parabolic collector (CPC). The global oocyst viability was calculated by the evaluation of the inclusion/exclusion of the fluorogenic vital dye propidium iodide and the spontaneous excystation. After an exposure time of 8 hours, the global oocyst viabilities were 21.8 ± 3.1%, 31.3 ± 12.9%, and 45.0 ± 10.0% for turbidity levels of 0, 5, and 30 NTU, respectively, and these values were significantly lower (P < 0.05) that the initial global viability of the isolate (92.1 ± 0.9%). The 25-L static solar reactor that was evaluated can be an alternative system to the conventional solar water disinfection process for improving the microbiological quality of drinking water on a household level, and moreover, it enables treatment of larger volumes of water (> 10 times). PMID: 22302852 [PubMed - in process]

Systemic Antibody Responses to the Immunodominant p23 Antigen and p23 Polymorphisms in Children with Cryptosporidiosis in Bangladesh.

Systemic Antibody Responses to the Immunodominant p23 Antigen and p23 Polymorphisms in Children with Cryptosporidiosis in Bangladesh. Am J Trop Med Hyg. 2012 Feb;86(2):214-222 Authors: Borad AJ, Allison GM, Wang D, Ahmed S, Karim MM, Kane AV, Moy J, Hibberd PL, Rao Ajjampur SS, Kang G, Calderwood SB, Ryan ET, Naumova E, Khan WA, Ward HD Abstract Abstract. Cryptosporidium is a major cause of diarrhea in children in developing countries. However, there is no vaccine available and little is known about immune responses to protective antigens. We investigated antibody responses to p23, a putative vaccine candidate, in children in Bangladesh with cryptosporidiosis and diarrhea (cases) and uninfected children with diarrhea (controls), and p23 gene polymorphisms in infecting species. Serum IgM, IgG, and IgA responses to p23 were significantly greater in cases than controls after three weeks of follow-up. Cases with acute diarrhea had significantly greater serum IgA and IgM responses than those with persistent diarrhea, which suggested an association with protection from prolonged disease. The p23 sequences were relatively conserved among infecting species and subtype families. Although most children were infected with Cryptosporidium hominis, there was a cross-reactive antibody response to C. parvum antigen. These results support further development of p23 as a vaccine candidate. PMID: 22302851 [PubMed - as supplied by publisher]

Different Patterns of pfcrt and pfmdr1 Polymorphisms in P. falciparum Isolates from Nigeria and Brazil: The Potential Role of Antimalarial Drug Selection Pressure.

Different Patterns of pfcrt and pfmdr1 Polymorphisms in P. falciparum Isolates from Nigeria and Brazil: The Potential Role of Antimalarial Drug Selection Pressure. Am J Trop Med Hyg. 2012 Feb;86(2):211-3 Authors: Gbotosho GO, Folarin OA, Bustamante C, Pereira da Silva LH, Mesquita E, Sowunmi A, Zalis MG, Oduola AM, Happi CT Abstract Abstract. The effect of antimalarial drug selection on pfcrt and pfmdr1 polymorphisms in Plasmodium falciparum isolates from two distinct geographical locations was determined in 70 and 18 P. falciparum isolates from Nigeria and Brazil, respectively, using nested polymerase chain reaction and direct DNA sequencing approaches. All isolates from Brazil and 72% from Nigeria harbored the mutant SVMNT and CVIET pfcrt haplotype, respectively. The pfcrt CVMNT haplotype was also observed in (7%) of the Nigerian samples. One hundred percent (100%) and 54% of the parasites from Brazil and Nigeria, respectively, harbored wild-type pfmdr1Asn86. We provide first evidence of emergence of the CVMNT haplotype in West Africa. The high prevalence of pfcrt CVIET and SVMNT haplotypes in Nigeria and Brazil, respectively, is indicative of different selective pressure by chloroquine and amodiaquine. Continuous monitoring of pfcrt SVMNT haplotype is required in endemic areas of Africa, where artesunate-amodiaquine combination is used for treatment of acute uncomplicated malaria. PMID: 22302850 [PubMed - in process]

Compliance, Safety, and Effectiveness of Fixed-Dose Artesunate-Amodiaquine for Presumptive Treatment of Non-Severe Malaria in the Context of Home Management of Malaria in Madagascar.

Compliance, Safety, and Effectiveness of Fixed-Dose Artesunate-Amodiaquine for Presumptive Treatment of Non-Severe Malaria in the Context of Home Management of Malaria in Madagascar. Am J Trop Med Hyg. 2012 Feb;86(2):203-210 Authors: Ratsimbasoa A, Ravony H, Vonimpaisomihanta JA, Raherinjafy R, Jahevitra M, Rapelanoro R, Rakotomanga JD, Malvy D, Millet P, Ménard D Abstract Abstract. Home management of malaria is recommended for prompt, effective antimalarial treatment in children less than five years of age. Compliance, safety, and effectiveness of the new fixed-dose artesunate-amodiaquine regimen used to treat suspected malaria were assessed in febrile children enrolled in a 24-month cohort study in two settings in Madagascar. Children with fever were asked to visit community health workers. Presumptive antimalarial treatment was given and further visits were scheduled for follow-up. The primary endpoint was the risk of clinical/parasitologic treatment failure. Secondary outcomes included fever/parasite clearance, change in hemoglobin levels, and frequency of adverse events. The global clinical cure rate was 98.4% by day 28 and 97.9% by day 42. Reported compliance was 83.4%. No severe adverse effects were observed. This study provides comprehensive data concerning the clinical cure rate obtained with artesunate-amodiaquine and evidence supporting the scaling up of home management of malaria. PMID: 22302849 [PubMed - as supplied by publisher]

Performance of Two Malaria Rapid Diagnostic Tests in Febrile Adult Patients with and without Human Immunodeficiency Virus-1 Infection in Blantyre, Malawi.

Performance of Two Malaria Rapid Diagnostic Tests in Febrile Adult Patients with and without Human Immunodeficiency Virus-1 Infection in Blantyre, Malawi. Am J Trop Med Hyg. 2012 Feb;86(2):199-202 Authors: Chinkhumba J, Nyanda M, Skarbinski J, Mathanga DP Abstract Abstract. The performance of two histidine-rich protein type-2-based malaria rapid diagnostic tests (mRDTs) was examined in a rural area with a high prevalence of malaria and human immunodeficiency virus type-1 (HIV-1) infection in 113 and 445 febrile patients ≥ 15 years of age with and without HIV-1 infection, respectively. Patients were tested for HIV-1 infection by using a standard assay and for Plasmodium falciparum by using two mRDTs and microscopy. When microscopy was used as the gold standard, both mRDTs performed similarly in patients with and without HIV-1 infection: Bioline SD Malaria Antigen P.f, sensitivity 94.4% (95% confidence interval [CI]: 81.3-99.3%) versus 97.1% (95% CI:92.8-99.2%) and specificity 50.6% (95% CI: 39.0-62.2%) versus 47.2% (95% CI: 41.4-53.1%); and ICT diagnostics Malaria Pf, sensitivity 94.4% (95% CI: 81.3-99.3%) versus 97.1% (95% CI: 92.8-99.2%) and specificity 50.6% (95% CI:39.0-62.2%) versus 50.3% (95% CI: 44.4-56.1%). Infection with HIV-1 does not appear to affect the performance of these histidine-rich protein type-2 (HRP-2)-based mRDTs. PMID: 22302848 [PubMed - in process]

False-Negative Rapid Diagnostic Tests for Malaria and Deletion of the Histidine-Rich Repeat Region of the hrp2 Gene{dagger}.

False-Negative Rapid Diagnostic Tests for Malaria and Deletion of the Histidine-Rich Repeat Region of the hrp2 Gene{dagger}. Am J Trop Med Hyg. 2012 Feb;86(2):194-8 Authors: Koita OA, Doumbo OK, Ouattara A, Tall LK, Konaré A, Diakité M, Diallo M, Sagara I, Masinde GL, Doumbo SN, Dolo A, Tounkara A, Traoré I, Krogstad DJ Abstract Abstract. We identified 480 persons with positive thick smears for asexual Plasmodium falciparum parasites, of whom 454 had positive rapid diagnostic tests (RDTs) for the histidine-rich protein 2 (HRP2) product of the hrp2 gene and 26 had negative tests. Polymerase chain reaction (PCR) amplification for the histidine-rich repeat region of that gene was negative in one-half (10/22) of false-negative specimens available, consistent with spontaneous deletion. False-negative RDTs were found only in persons with asymptomatic infections, and multiplicities of infection (MOIs) were lower in persons with false-negative RDTs (both P < 0.001). These results show that parasites that fail to produce HRP2 can cause patent bloodstream infections and false-negative RDT results. The importance of these observations is likely to increase as malaria control improves, because lower MOIs are associated with false-negative RDTs and false-negative RDTs are more frequent in persons with asymptomatic infections. These findings suggest that the use of HRP2-based RDTs should be reconsidered. PMID: 22302847 [PubMed - in process]

How do we best diagnose malaria in Africa?

How do we best diagnose malaria in Africa? Am J Trop Med Hyg. 2012 Feb;86(2):192-3 Authors: Rosenthal PJ PMID: 22302846 [PubMed - in process]

Recommendations for Publication of Viral Genetic Data and Sample Access for Novel Viruses and Strains.

Recommendations for Publication of Viral Genetic Data and Sample Access for Novel Viruses and Strains. Am J Trop Med Hyg. 2012 Feb;86(2):189-191 Authors: Arrigo NC, Briese T, Calisher CH, Drebot MA, Hjelle B, Leduc JW, Powers AM, Repik PM, Roehrig JT, Schmaljohn CS, Tesh RB, Weaver SC PMID: 22302845 [PubMed - as supplied by publisher]

Leptospirosis after typhoon.

Leptospirosis after typhoon. Am J Trop Med Hyg. 2012 Feb;86(2):187-8 Authors: Lin CY, Chiu NC, Lee CM Abstract Abstract. Leptospirosis is a zoonotic disease with protean manifestations. A 35-year-old male presented with pneumonia after the Typhoon Morakot. Skin rash, conjunctival suffusion, and subconjunctival hemorrhage led us to the diagnosis of leptospirosis and the microscopic agglutination test confirmed the diagnosis. This patient well demonstrated the picture of conjunctival suffusion and reminded us of the alertness of leptospirosis after a typhoon. PMID: 22302844 [PubMed - in process]

Superantigen profiles of emm and emm-like typeable and nontypeable pharyngeal streptococcal isolates of South India

Background: The major virulence factors determining the pathogenicity of streptococcal strains include M protein encoded by emm and emm-like (emmL) genes and superantigens. In this study, the distribution of emm, emmL and superantigen genes was analyzed among the streptococcal strains isolated from the patients of acute pharyngitis. Methods: The streptococcal strains were isolated from the throat swabs of 1040 patients of acute pharyngitis. The emm and emmL genes were PCR amplified from each strain and sequenced to determine the emm types. The dot-blot hybridization was performed to confirm the pathogens as true emm nontypeable strains. The presence of eleven currently known superantigens was determined in all the strains by multiplex PCR. Results: Totally, 124 beta-hemolytic streptococcal strains were isolated and they were classified as group A streptococcus (GAS) [15.3% (19/124)], group C streptococcus (GCS) [59.7% (74/124)] and group G streptococcus (GGS) [25.0% (31/124)]. Among 124 strains, only 35 strains were emm typeable and the remaining 89 strains were emm nontypeable. All GAS isolates were typeable, whereas most of the GCS and GGS strains were nontypeable. These nontypeable strains belong to S. anginosus [75.3% (67/89)] and S. dysgalactiae subsp. equisimilis [24.7% (22/89)]. The emm and emmL types identified in this study include emm12.0 (28.6%), stG643.0 (28.6%), stC46.0 (17.0%), emm30.11 (8.5%), emm3.0 (2.9%), emm48.0 (5.7%), st3343.0 (2.9%), emm107.0 (2.9%) and stS104.2 (2.9%). Various superantigen profiles were observed in typeable as well as nontypeable strains. Conclusions: Multiplex PCR analysis revealed the presence of superantigens in all the typeable strains irrespective of their emm types. However, the presence of superantigen genes in emm and emmL nontypeable strains has not been previously reported. In this study, presence of at least one or a combination of superantigen coding genes was identified in all the emm and emmL nontypeable strains. Thus, the superantigens may inevitably play an important role in the pathogenesis of these nontypeable strains in the absence of the primary virulence factor, M protein.

Genotypes and serotype distribution of macrolide resistant invasive and non- invasive Streptococcus pneumoniae isolates from Lebanon

Background: This study determined macrolide resistance genotypes in clinical isolates of Streptococcus pneumoniae from multiple medical centers in Lebanon and assessed the serotype distribution in relation to these mechanism(s) of resistance and the source of isolate recovery. Methods: Forty four macrolide resistant and 21 macrolide susceptible S. pneumoniae clinical isolates were tested for antimicrobial susceptibility according to CLSI guidelines (2008) and underwent molecular characterization. Serotyping of these isolates was performed by Multiplex PCR-based serotype deduction using CDC protocols. PCR amplification of macrolide resistant erm (encoding methylase) and mef (encoding macrolide efflux pump protein) genes was carried out. Results: Among 44 isolates resistant to erythromycin, 35 were resistant to penicillin and 18 to ceftriaxone. Examination of 44 macrolide resistant isolates by PCR showed that 16 isolates harbored the erm(B) gene, 8 isolates harbored the mef gene, and 14 isolates harbored both the erm(B) and mef genes. There was no amplification by PCR of the erm(B) or mef genes in 6 isolates. Seven different capsular serotypes 2, 9V/9A,12F, 14,19A, 19F, and 23, were detected by multiplex PCR serotype deduction in 35 of 44 macrolide resistant isolates, with 19F being the most prevalent serotype. With the exception of serotype 2, all serotypes were invasive. Isolates belonging to the invasive serotypes 14 and 19F harbored both erm(B) and mef genes. Nine of the 44 macrolide resistant isolates were non-serotypable by our protocols. Conclusion: Macrolide resistance in S. pneumoniae in Lebanon is mainly through target site modification but is also mediated through efflux pumps, with serotype 19F having dual resistance and being the most prevalent and invasive.

Enteric alpha defensins in norm and pathology

Microbes living in the mammalian gut exist in constant contact with immunity system that prevents infection and maintains homeostasis. Enteric alpha defensins play an important role in regulation of bacterial colonization of the gut, as well as in activation of pro- and anti-inflammatory responses of the adaptive immune system cells in lamina propria. This review summarizes currently available data on functions of mammalian enteric alpha defensins in the immune defense and changes in their secretion in intestinal inflammatory diseases and cancer.

Assessment of the requisites of microbiology based infectious disease training under the pressure of consultation needs

Background: Training of infectious disease (ID) specialists is structured on classical clinical microbiology training in Turkey and ID specialists work as clinical microbiologists at the same time. Hence, this study aimed to determine the clinical skills and knowledge required by clinical microbiologists. Methods: A cross-sectional study was carried out between June 1, 2010 and September 15, 2010 in 32 ID departments in Turkey. Only patients hospitalized and followed up in the ID departments between January-June 2010 who required consultation with other disciplines were included. Results: A total of 605 patients undergoing 1343 consultations were included, with pulmonology, neurology, cardiology, gastroenterology, nephrology, dermatology, haematology, and endocrinology being the most frequent consultation specialties. The consultation patterns were quite similar and were not affected by either the nature of infections or the critical clinical status of ID patients. Conclusions: The results of our study show that certain internal medicine subdisciplines such as pulmonology, neurology and dermatology appear to be the principal clinical requisites in the training of ID specialists, rather than internal medicine as a whole.

Antimutagenic and free radical scavenger effects of leaf extracts from Accacia salicina

Background: Three extracts were prepared from the leaves of Accacia salicina; ethyl acetate (EA), chloroform (Chl) and petroleum ether (PE) extracts and was designed to examine antimutagenic, antioxidant potenty and oxidative DNA damage protecting activity. Methods: Antioxidant activity of A. salicina extracts was determined by the ability of each extract to protect against plasmid DNA strand scission induced by hydroxyl radicals. An assay for the ability of these extracts to prevent mutations induced by various oxidants in Salmonella typhimurium TA102 and TA 104 strains was conducted. In addition, nonenzymatic methods were employed to evaluate anti-oxidative effects of tested extracts. Results: These extracts from leaf parts of A. salicina showed no mutagenicity either with or without the metabolic enzyme preparation (S9). The highest protections against methylmethanesulfonate induced mutagenicity were observed with all extracts and especially chloroform extract. This extract exhibited the highest inhibitiory level of the Ames response induced by the indirect mutagen 2- aminoanthracene. All extracts exhibited the highest ability to protect plasmid DNA against hydroxyl radicals induced DNA damages. The ethyl acetate (EA) and chloroform (Chl) extracts showed with high TEAC values radical of 0.95 and 0.81 mM respectively, against the ABTS.+. Conclusion: The present study revealed the antimutagenic and antioxidant potenty of plant extract from Accacia salicina leaves.

Infection control practice in countries with limited resources

Nosocomial infections and their control are a world-wide challenge. The prevalence of nosocomial infections is generally higher in developing countries with limited resources than industrialized countries. In this paper we aimed to further explain the differences with regard to infection control challenges between Turkey, a country with "limited" resources, and the Netherlands, a country with "reasonable" resources. Infrastructure of hospitals, low compliance of hand hygiene, understaffing, overcrowding, heavy workload, misuse of personal protective equipments, late establishment of infection control programme are major problems in limited-resources countries. These problems cause high infection rates and spread of multi-drug resistant pathogens. To improve the control and prevention of infections in countries with limited resources, a multi-facet approach is needed.

Cholestatic Hepatitis in a patient with Typhoid Fever - A case report

Typhoid fever is a very common infectious disease, particularly in developing countries such as Sri Lanka. Although multiple organs are known to be affected by the disease, hepatic involvement could be considered the most important as studies have showed that it is associated with a higher relapse rate. We report a young patient who presented with fever and jaundice and found to have cholestatic hepatitis secondary to typhoid fever.

Decrease in Shiga-like toxin expression using a minimal inhibitory concentration of rifampicin followed by bactricidal gentamicin treatment enhances survival of Escherichia coli O157:H7-infected BALB/c mice

Background: Treatment of Escherichia coli O157:H7 infections with antimicrobial agents is controversial due to an association with potentially fatal sequelae. The production of Shiga toxins is believed to be central to the pathogenesis of this organism. Therefore, decreasing the expression of these toxins prior to bacterial eradication may provide a safer course of therapy. Methods: The utility of decreasing Shiga toxin gene expression in E. coli O157:H7 with rifampicin prior to bacterial eradication with gentamicin was evaluated in vitro using real-time reverse-transcription polymerase chain reaction. Toxin release from treated bacterial cells was assayed for with reverse passive latex agglutination. The effect of this treatment on the survival of E. coli O157:H7-infected BALB/c mice was also monitored. Results: Transcription of Shiga toxin-encoding genes was considerably decreased as an effect of treating E. coli O157:H7 in vitro with the minimum inhibitory concentration (MIC) of rifampicin followed by the minimum bactericidal concentration (MBC) of gentamicin (> 99% decrease) compared to treatment with gentamicin alone (50-75% decrease). The release of Shiga toxins from E. coli O157:H7 incubated with the MIC of rifampicin followed by addition of the MBC of gentamicin was decreased as well. On the other hand, the highest survival rate in BALB/c mice infected with E. coli O157:H7 was observed in those treated with the in vivo MIC equivalent dose of rifampicin followed by the in vivo MBC equivalent dose of gentamicin compared to mice treated with gentamicin or rifampicin alone. Conclusions: The use of non-lethal expression-inhibitory doses of antimicrobial agents prior to bactericidal ones in treating E. coli O157:H7 infection is effective and may be potentially useful in human infections with this agent in addition to other Shiga toxin producing E. coli strains.

Rapid PCR detection of group A streptococcus from flocked throat swabs: a retrospective clinical study

Background: Rapid diagnosis of GAS pharyngitis may improve patient care by ensuring that patients with GAS pharyngitis are treated quickly and also avoiding unnecessary use of antibiotics in those without GAS infection. Very few molecular methods for detection of GAS in clinical throat swab specimens have been described. Methods: We performed a study of a laboratory-developed internally-controlled rapid Group A streptococcus (GAS) PCR assay using flocked swab throat specimens. We compared the GAS PCR assay to GAS culture results using a collection of archived throat swab samples obtained during a study comparing the performance of conventional and flocked throat swabs. Results: The sensitivity of the GAS PCR assay as compared to the reference standard was 96.0% (95% CI 90.1% to 98.4%), specificity 98.6% (95% CI 95.8% to 99.5%), positive predictive value (PPV) 96.9% (95% CI 91.4% to 99.0%) and negative predictive value (NPV) of 98.1% (95% CI 95.2% to 99.2%). For conventional swab cultures, sensitivity was 96.0% (95% CI 90.1% to 98.4%), specificity 100% (95% CI 98.2% to 100%), PPV 100%, (95% CI 96.1% to 100%) and NPV 98.1% (95% CI 95.2% to 99.3%) Conclusions: In this retrospective study, the GAS PCR assay appeared to perform as well as conventional throat swab culture, the current standard of practice. Since the GAS PCR assay, including DNA extraction, can be performed in approximately 1 hour, prospective studies of this assay are warranted to evaluate the clinical impact of the assay on management of patients with pharyngitis.

Correlation between antibutyrylcholinesterasic and antioxidant activities of three aqueous extracts from Tunisian Rhus pentaphyllum

For centuries, plants have been used in traditional medicines and there has been recent interest in the chemopreventive properties of compounds derived from plants. In the present study, we investigated the antibutyrylcholinestrasic (anti-BuChE) and antioxidant (against some free radicals) activities of extracts from Rhus pentaphyllum. Aqueous extracts were prepared from powdered R. pentaphyllum roots, leaves and seeds and characterized for the presence of tannins, flavonoids and coumarins. Seeds aqueous extract contained the highest quantities of both flavonoids and tannins (21.12% and 17.45% respectively). In the same way, seeds extracts displayed remarkable inhibition against BuChE over 95%, at 100 μg/ml and with IC50 0.74 μg/ml. In addition, compared to leaves and roots extracts, seeds aqueous extract revealed relatively strong antiradical activity towards the ABTS .+ (IC50 = 0.25 μg/ml) and DPPH (IC50 = 2.71 μg/ml) free radicals and decreased significantly the reactive oxygen species such O2 .- (IC50 = 2.9 μg/ml) formation evaluated by the non-enzymatic generating O2 .- system (Nitroblue tetrazolium/riboflavine). These data suggest that the anti-BuChE activities mechanism of these extracts occurs through a free radical scavenging capacities.The present study indicates that extracts of Rhus pentaphyllum leaves, seeds and roots are a significant source of compounds, such as tannins, flavonoids and coumarins, with anti-BuChE and antioxidant activities, and thus may be useful for chemoprevention.

Entecavir versus lamivudine in the treatment of chronic hepatitis B patients with hepatic decompensation.

Entecavir versus lamivudine in the treatment of chronic hepatitis B patients with hepatic decompensation. Antivir Ther. 2011 Dec 20; Authors: Hsu YC, Mo LR, Chang CY, Perng DS, Tseng CH, Lo GH, Tai CM, Lin CW, Hsu CC, Hsu CY, Huang SC, Lin JT Abstract BACKGROUND: Lamivudine has been widely used in chronic hepatitis B patients with hepatic decompensation, but its use is limited by drug resistance. This outcome research aimed to investigate the comparative efficacy and safety of entecavir versus lamivudine in decompensated patients. METHODS: Between November 2004 and February 2010, 126 consecutive treatment-naive patients received either entecavir (n=53) or lamivudine (n=73) for decompensated chronic hepatitis B. All patients presented with both hyperbilirubinaemia and coagulopathy. Primary outcome was mortality within 1 year; secondary outcomes included liver-related mortality, biochemical and virological response, and improvement of hepatic dysfunction. RESULTS: Both treatment groups were comparable in baseline characteristics. A total of 19 (35.8%) entecavir and 33 (45.2%) lamivudine receivers expired within 1 year, respectively (P=0.29, log rank test). Age (hazard ratio [HR] 1.04 per year, 95% CI 1.01, 1.06), cirrhosis (HR 2.07, 95% CI 1.02, 4.23), and international normalized ratio for prothrombin time (HR 1.44, 95% CI 1.20, 1.74) were independent baseline predictors for all-cause mortality. Antiviral therapy was also unrelated to liver-specific death. However, more patients taking entecavir tended to attain aminotransferase normalization (76.5% versus 52.5%; P=0.05) and viral DNA undetectability (100% versus 58.3%; P=0.06). Moreover, entecavir was associated with significantly greater reduction of the model for end-stage liver disease scores (median 10.0 versus 4.3; P=0.02). Overall, 3 (7.5%) lamivudine but no entecavir users acquired drug resistance in 1 year (P=0.25). CONCLUSIONS: Entecavir as compared with lamivudine is similar in the effect on short-term mortality but is associated with greater clinical improvement among chronic hepatitis survivors who recovered from hepatic decompensation. PMID: 22301517 [PubMed - as supplied by publisher]

Interleukin 28B genetic polymorphisms and viral factors help identify HCV genotype-1 patients who benefit from 24-week pegylated interferon plus ribavirin therapy.

Interleukin 28B genetic polymorphisms and viral factors help identify HCV genotype-1 patients who benefit from 24-week pegylated interferon plus ribavirin therapy. Antivir Ther. 2011 Dec 20; Authors: Liu CH, Liang CC, Liu CJ, Tseng TC, Lin CL, Yang SS, Su TH, Hsu SJ, Lin JW, Chen JH, Chen PJ, Chen DS, Kao JH Abstract BACKGROUND: Interleukin 28B (IL28B) single nucleotide polymorphism (SNP) genotypes and viral factors can predict sustained virological response (SVR) in HCV genotype-1 (HCV-1) patients receiving 48 weeks of pegylated interferon and ribavirin. Whether these factors would identify those patients who can benefit from a shorter duration of therapy remains unclear. METHODS: Treatment-naive HCV-1 patients (n=662) receiving 24 or 48 weeks of combination therapy were enrolled. Baseline demographic data, HCV viral load, IL28B SNP genotypes (rs8099917), duration of therapy and rapid virological response (RVR) were evaluated to predict SVR. The SVR rates were further stratified by the independent factors and compared. RESULTS: The IL28B rs8099917 TT genotype, low baseline viral load (HCV RNA≤600,000 IU/ml), RVR and 48-week therapy independently predicted SVR. In RVR patients with the IL28B rs8099917 TT genotype, the SVR rate of 24-week therapy was comparable to 48-week therapy (95% versus 99%; P=0.21) at low baseline viral load, but was inferior to 48-week therapy (70% versus 97%; P<0.001) at high baseline viral load. In non-RVR patients, the SVR rate of 24-week therapy was inferior to 48-week therapy for those with the IL28B rs8099917 TT genotype but high baseline viral load (23% versus 62%; P<0.001), and those with the IL28B rs8099917 GT/GG genotype but low baseline viral load (0% versus 33%; P=0.02). CONCLUSIONS: HCV-1 patients simultaneously bearing the IL28B rs8099917 TT genotype, low baseline viral load and RVR can benefit from a shorter duration of combination therapy. PMID: 22301466 [PubMed - as supplied by publisher]

Evolution of HIV-1 genotype in plasma RNA and peripheral blood mononuclear cells proviral DNA after interruption and resumption of antiretroviral therapy.

Evolution of HIV-1 genotype in plasma RNA and peripheral blood mononuclear cells proviral DNA after interruption and resumption of antiretroviral therapy. Antivir Ther. 2011 Dec 19; Authors: Imaz A, Olmo M, Peñaranda M, Gutiérrez F, Romeu J, Larrousse M, Domingo P, Oteo JA, Niubó J, Curto J, Vilallonga C, Masiá M, López-Aldeguer J, Iribarren JA, Podzamczer D, Abstract BACKGROUND: Structured antiretroviral therapy interruption (TI) is discouraged because of poorer AIDS and non-AIDS-related outcomes, but is often inevitable in clinical practice. Certain strategies could reduce the emergence of resistance mutations related to TI. METHODS: A total of 106 HIV-1-infected patients on stable HAART with undetectable plasma viral load were randomized to therapy continuation (n=50) or CD4(+) T-cell-guided TI (n=56). Staggered interruption involved stopping non-nucleoside reverse transcriptase inhibitors (NNRTIs) 7 days before the nucleoside backbone. Genotypic resistance testing (GRT) was performed on proviral DNA from peripheral blood mononuclear cells (PBMCs) at baseline and before each TI, and on plasma RNA after each TI. RESULTS: At baseline, GRT on PBMCs detected mutations in nine patients and only two major mutations were identified. GRT on plasma samples performed after TIs showed nucleoside reverse transcriptase inhibitors (NRTI), NNRTI and protease inhibitor major resistance associated mutations in 10/56, 3/46 and 1/8 patients receiving these drugs, respectively. Only in two patients had the same mutations been observed in GRT on PBMCs at baseline. Three patients presented virological failure after resumption of therapy, all receiving NNRTIs. In one of them, resistance mutations detected at failure had been also observed previously in GRT on plasma after TI. CONCLUSIONS: Staggered interruption of NNRTIs 7 days before the nucleoside backbone does not avoid resistance emergence completely, but does not necessarily lead to virological failure after treatment resumption. Plasma HIV-1 RNA genotype after the interruption and the patient's treatment history seem to be more useful than baseline proviral DNA genotype to assess the risk of virological failure after restarting therapy. PMID: 22301439 [PubMed - as supplied by publisher]

Multiclass primary antiretroviral drug resistance in a patient presenting HIV-1/2 dual infection.

Multiclass primary antiretroviral drug resistance in a patient presenting HIV-1/2 dual infection. Antivir Ther. 2012 Jan 25; Authors: Castro E, Recordon-Pinson P, Cavassini M, Fleury H PMID: 22301389 [PubMed - as supplied by publisher]

Potent immune activation in chronic hepatitis C patients upon administration of an oral inducer of endogenous interferons that acts via Toll-like receptor 7.

Potent immune activation in chronic hepatitis C patients upon administration of an oral inducer of endogenous interferons that acts via Toll-like receptor 7. Antivir Ther. 2011 Dec 19; Authors: Boonstra A, Liu BS, Groothuismink ZM, Bergmann JF, de Bruijne J, Hotho DM, Hansen BE, van Vliet AA, van de Wetering de Rooij J, Fletcher SP, Bauman LA, Rahimy M, Appleman JR, Freddo JL, Reesink HW, de Knegt RJ, Janssen HL Abstract BACKGROUND: ANA773, an oral prodrug of a small-molecule Toll-like receptor (TLR)7 agonist, induces a dose-related decrease in serum HCV RNA levels in chronic hepatitis C patients. METHODS: The prodrug ANA773 was administered to healthy individuals and chronic hepatitis C patients. At different time points during the course of treatment, modulation of the phenotype and function of peripheral leukocytes were evaluated to determine the role of distinct immune cells on the clinical outcome of therapy. RESULTS: Early after administration of the TLR7 agonist, a mild transient reduction of the number of lymphocytes was observed in both healthy individuals and chronic hepatitis C patients. Moreover, repeated administration of ANA773 resulted in transiently reduced numbers of myeloid and plasmacytoid dendritic cells (DC) in blood. Interestingly, reduced plasmacytoid DC numbers as well as increased serum interferon (IFN)-α and IFN-γ inducible protein (IP)-10 levels were observed only in virological responders (≥1 log(10) IU/ml reduction of HCV RNA levels upon ANA773 treatment), but were absent in virological non-responders. In vitro stimulation of peripheral blood mononuclear cells from virological responders showed a high frequency of IFN-α-producing plasmacytoid DC upon stimulation in vitro with ANA773, whereas no IFN-α was induced in non-responders. CONCLUSIONS: These findings indicate that the viral load decline in chronic hepatitis C patients treated with the TLR7 agonist ANA773 is likely due to intrinsic differences in the induction of endogenous IFNs and IFN-stimulated gene products (IFN-α and IP-10) upon TLR7 ligation. PMID: 22301364 [PubMed - as supplied by publisher]

High-resolution melting and real-time PCR for quantification and detection of drug-resistant HBV mutants in a single amplicon.

High-resolution melting and real-time PCR for quantification and detection of drug-resistant HBV mutants in a single amplicon. Antivir Ther. 2011 Dec 16; Authors: Hsiao CC, Chang J, Wu JY, Liu WH, Han SY, Chen PJ, Yeh SH Abstract BACKGROUND: Antiviral therapy by nucleoside/nucleotide analogues (NAs) effectively reduces HBV replication in chronic hepatitis B (CHB) patients. Because long-term NA treatments will eventually select for drug-resistant mutants, early detection of mutants and frequent monitoring of viral loads is crucial for successful NA therapy. Because no efficient test for one-tube quantification and qualification of various HBV-resistant mutants exists, we propose to use high-resolution melting (HRM) analysis in combination with real-time PCR to achieve this unmet need. METHODS: We developed a single amplicon for detecting HBV mutants resistant to lamivudine (LMV), adefovir (ADV) and entecavir (ETV), which are commonly used for CHB treatment. Our design consists of two steps: real-time PCR for viral quantification, and hybridization probe HRM analysis for detection of specific drug-resistant mutants. RESULTS: Assay quantification was accurate (R=0.98) for viral loads from 10(3) to 10(9) copies/ml. HRM analysis produced distinct melting temperatures that clearly distinguished the mutants, rtM204V/I (LMV), rtA181V and rtN236T (ADV), and rtT184G and rtM250V (ETV), from their respective wild types. The assay detected mutants at only 10-25% of the HBV population. The clinical applicability of this assay was tested in a pilot study with serial samples from patients receiving LMV treatment. CONCLUSIONS: Flexibility, speed and cost-efficiency are additional benefits unique to our assay. The clinical sample results further support the feasibility of applying our design to frequent and long-term monitoring of CHB patients receiving NA treatments in the clinical setting. PMID: 22301217 [PubMed - as supplied by publisher]

Novel agents for the treatment of HIV-2 infection.

Novel agents for the treatment of HIV-2 infection. Antivir Ther. 2012 Jan 25; Authors: Peterson K, Rowland-Jones S Abstract Many of the antiretrovirals used against HIV-1 are either ineffective or less effective in HIV-2 infection. There is in vitro evidence of the potency of maraviroc and several investigational agents against HIV-2. We conclude that, whilst specific boosted protease inhibitors combined with nucleoside analogues should still be considered the mainstays of HIV-2 treatment, maraviroc, T-1249, TAK-779 and AMD3100, as well as raltegravir, could contribute to regimens for treatment-experienced individuals. Factors bearing on the use and timing of these alternative agents are discussed. PMID: 22301192 [PubMed - as supplied by publisher]

HIV-1 Tat protein impairs adipogenesis and induces the expression and secretion of proinflammatory cytokines in human SGBS adipocytes.

HIV-1 Tat protein impairs adipogenesis and induces the expression and secretion of proinflammatory cytokines in human SGBS adipocytes. Antivir Ther. 2011 Dec 16; Authors: Díaz-Delfín J, Domingo P, Wabitsch M, Giralt M, Villarroya F Abstract BACKGROUND: HIV-1 Tat protein has been shown to play multiple roles in the pathogenesis of AIDS; however, there is no information currently available on its effects on adipose tissue alterations. We have studied the effects of Tat on SGBS adipocytes to gain insight on its role on the development of lipodystrophy. METHODS: SGBS preadipocytes were exposed to Tat during and after differentiation. Acquisition of adipocyte morphology, expression of gene markers of adipogenesis and inflammation, release of adipokines and cytokines to the medium, and glucose uptake were measured. The action of Tat on tumour necrosis factor (TNF)-α-regulated messenger RNA expression was determined in differentiated adipocytes. The capacity of rosiglitazone, resveratrol and parthenolide to influence the action of Tat was also assessed. RESULTS: Tat treatment reduced the number of SGBS preadipocytes that acquired adipocyte morphology. It also led to repression of adipogenic gene expression and induced the coordinate expression and release of proinflammatory cytokines in human adipose cells. Moreover, combined treatment with Tat and TNF-α produced an additive effect on the repression of adipocyte genes. The observed effects of Tat on gene transcription in adipocytes were due, in part, to TNF-α that was secreted as a consequence of intracellular exposure to Tat. CONCLUSIONS: Tat impairs adipogenesis in human SGBS preadipocytes and increases the expression and release of proinflammatory cytokines. Positive crosstalk between Tat and TNF-α contributes to the anti-adipogenic and proinflammatory effects. HIV-1 Tat protein may play a role in the adipose tissue alterations that ultimately lead to lipoatrophy and systemic metabolic disturbances observed in HIV-1-infected patients. PMID: 22301094 [PubMed - as supplied by publisher]

Effect of abacavir on acute changes in biomarkers associated with cardiovascular dysfunction.

Effect of abacavir on acute changes in biomarkers associated with cardiovascular dysfunction. Antivir Ther. 2011 Dec 16; Authors: Patel P, Bush T, Overton T, Baker J, Hammer J, Kojic E, Conley L, Henry K, Brooks JT, Abstract BACKGROUND: This study examined the effect of abacavir on acute changes in biomarkers associated with cardiovascular dysfunction. METHODS: Among the Study to Understand the Natural History of HIV/AIDS in the Era of Effective therapy (SUN) participants, we identified 25 individuals (cases) who were HLA-B5701-negative and who had ≥2 weeks without abacavir exposure at one visit and ≥2 weeks with abacavir exposure at the consecutive visit while maintaining viral suppression. We identified 43 individuals (controls) similarly unexposed and exposed to tenofovir. We assessed concentrations of prothrombin fragment F(1+2), D-dimer, high-sensitivity C-reactive protein, interleukin-8, intercellular adhesion molecule-1, vascular adhesion molecule-1, E-selectin, P-selectin, serum amyloid A and serum amyloid P. We examined the median percentage change of these biomarkers from the unexposed to exposed state among cases and controls compared with the expected assay variability using a sign test, and compared changes among cases with controls using the Wilcoxon rank-sum test. RESULTS: Baseline characteristics were similar between cases and controls: median age 45 versus 46 years, 80% versus 81% male, 64% versus 63% non-Hispanic White and median CD4(+) T-cell count 538 versus 601 cells/mm(3), respectively. Mean exposure times were 65 and 15 weeks for abacavir and tenofovir, respectively. We observed no significant changes in biomarkers from the unexposed to exposed state among cases or controls compared with the expected assay variability. We found that no biomarkers were significantly increased among cases compared with controls; however, prothrombin fragment F(1+2) was significantly lower among controls (P=0.035). CONCLUSIONS: In virologically suppressed contemporary HIV-infected patients, abacavir exposure was not associated with increases in biomarkers associated with increased cardiovascular risk. PMID: 22301072 [PubMed - as supplied by publisher]

Prognosis of 2009 A(H1N1) influenza in hospitalized pregnant women in a context of early diagnosis and antiviral therapy.

Prognosis of 2009 A(H1N1) influenza in hospitalized pregnant women in a context of early diagnosis and antiviral therapy. Antivir Ther. 2011 Dec 16; Authors: Paño-Pardo JR, Rodríguez-Baño J, Martínez-Sánchez N, Viasus D, Fariñas MC, Leyes M, López-Medrano F, Pachón J, Torre-Cisneros J, Oteo JA, Pumarola T, García-Gasalla M, Ortega L, Segura F, Carratalá J, Abstract BACKGROUND: Initial reports suggested that novel A(H1N1) influenza virus (2009 A[H1N1]v) infection was significantly more severe in pregnant than in non-pregnant women. In Spain, antiviral therapy was recommended for pregnant women from the beginning of the 2009 pandemic. METHODS: The prospective cohort study included consecutive pregnant and non-pregnant women of reproductive age with a proven diagnosis of 2009 A(H1N1)v admitted to any of the 13 participating Spanish hospitals between 12 June and 10 November 2009. RESULTS: In total, 98 pregnant and 112 non-pregnant women with proven 2009 A(H1N1)v hospitalized during the study period were included. Influenza was more severe among non-pregnant patients than pregnant patients with respect to outcomes of both intensive care unit admission (18% versus 2%; P<0.001) and death (5 versus 0; P=0.06). Pregnant women had fewer associated comorbid conditions other than pregnancy (18% versus 44%; P<0.001); they were also admitted earlier than non-pregnant women (median days since onset of symptoms: 2 versus 3; P<0.001) and a higher percentage received early antiviral therapy (41% versus 28%; P=0.03). Neither a multivariate nor a matched cohort analysis found pregnancy to be associated with greater severity than that associated with hospitalized, seriously ill non-pregnant women. CONCLUSIONS: 2009 A(H1N1)v influenza was not associated with worse outcomes in hospitalized pregnant women compared with non-pregnant ones of reproductive age in a context of early diagnosis and antiviral therapy. PMID: 22301005 [PubMed - as supplied by publisher]

The vitamin D receptor gene bAt (CCA) haplotype impairs the response to pegylated-interferon/ribavirin-based therapy in chronic hepatitis C patients.

The vitamin D receptor gene bAt (CCA) haplotype impairs the response to pegylated-interferon/ribavirin-based therapy in chronic hepatitis C patients. Antivir Ther. 2011 Dec 14; Authors: Baur K, Mertens JC, Schmitt J, Iwata R, Stieger B, Frei P, Seifert B, Ferrari HA, von Eckardstein A, Müllhaupt B, Geier A, Abstract BACKGROUND: Chronic hepatitis C infection is a major cause of end-stage liver disease. Therapy outcome is influenced by 25-OH vitamin D deficiency. To further address this observation, our study investigates the impact of the vitamin D receptor (NR1I1) haplotype and combined effects of plasma vitamin D levels in a well-described cohort of hepatitis C patients. METHODS: A total of 155 chronic hepatitis C patients were recruited from the Swiss Hepatitis C Cohort Study for NR1I1 genotyping and plasma 25-OH vitamin D level measurement. NR1I1 genotype data and combined effects of plasma 25-OH vitamin D level were analysed regarding therapy response (sustained virological response). RESULTS: A strong association was observed between therapy non-response and the NR1I1 CCA (bAt) haplotype consisting of rs1544410 (BsmI) C, rs7975232 (ApaI) C and rs731236 (TaqI) A alleles. Of the HCV patients carrying the CCA haplotype, 50.3% were non-responders (odds ratio [OR] 1.69, 95% CI 1.07, 2.67; P=0.028). A similar association was observed for the combinational CCCCAA genotype (OR 2.94, 95% CI 1.36, 6.37; P=0.007). The combinational CCCCAA genotype was confirmed as an independent risk factor for non-response in multivariate analysis (OR 2.50, 95% CI 1.07, 5.87; P=0.034). Analysing combined effects, a significant impact of low 25-OH vitamin D levels on sustained virological response were only seen in patients with the unfavourable NR1I1 CCA (bAt) haplotype (OR for non-SVR 3.55; 95% CI 1.005, 12.57; P=0.049). CONCLUSIONS: NR1I1 vitamin D receptor polymorphisms influence response to pegylated-interferon/ribavirin-based therapy in chronic hepatitis C and exert an additive genetic predisposition to previously described low 25-OH vitamin D serum levels. PMID: 22300961 [PubMed - as supplied by publisher]

Evidence for a shift to anaerobic metabolism in adipose tissue in efavirenz-containing regimens for HIV with different nucleoside backbones.

Evidence for a shift to anaerobic metabolism in adipose tissue in efavirenz-containing regimens for HIV with different nucleoside backbones. Antivir Ther. 2011 Dec 13; Authors: McGee KC, Shahmanesh M, Boothby M, Nightingale P, Gathercole LL, Tripathi G, Harte AL, Shojaee-Moradie F, Umpleby AM, Das S, Al-Daghri NM, McTernan PG, Tomlinson JW Abstract BACKGROUND: Antiretroviral (ARV) treatment has been associated with abnormalities in lipid and mitochondrial metabolism. We compared patterns of gene expression in the subcutaneous adipose tissue (SAT) of HIV-positive subjects before and after 18-24 months of ARV therapy with HIV-negative controls. METHODS: HIV patients naive to ARV were randomized to receive zidovudine (AZT), lamivudine (3TC) with efavirenz (EFV) or tenofovir disoproxil fumarate (TDF) with emtricitabine (FTC) and EFV. Healthy controls (n=15) were matched for age, ethnicity and gender. Patients on a regimen containing abacavir (ABC), 3TC and EFV for 18-24 months were also tested. Genes involved in adipocyte glucocorticoid, lipid and mitochondrial metabolism, and adipocyte differentiation, were profiled with real-time PCR. RESULTS: AZT led to increased visceral adipose tissue (VAT; P=0.012) and VAT:SAT ratio (P=0.036), whereas TDF increased SAT (P=0.047) and peripheral fat/lean body mass ratio (P=0.017). HIV treatment-naive patients had lower plasma lipoprotein lipase (LPL) activity (P=0.0001) versus controls (remaining below controls after ARV; P=0.038-0.0001). The overall pattern of gene expression was similar across all treatment groups, being most marked with AZT and least with TDF. There was up-regulation of peroxisome proliferator-activated receptor-γ coactivator-1α, uncoupling protein-2 and hexose 6-phosphate dehydrogenase, and down-regulation of nuclear respiratory factor-1, cytochrome oxidase B, cytochrome c oxidase-4, uncoupling protein-3, 11β-hydroxysteroid dehydrogenase type-1, glucocorticoid receptor-α, fatty acid synthase, fatty acid binding protein-4, LPL and hormone sensitive lipase (18-24 months post-treatment versus pretreatment levels and controls; P<0.05 to <0.0001). CONCLUSIONS: The decreased expression of genes involved in lipid and mitochondrial metabolism 18-24 months post-ARV treatment in SAT of HIV patients, in conjunction with the increase in uncoupling protein-2 and decrease in cytochrome oxidase B gene expression, provides evidence of mitochondrial dysfunction and a shift to anaerobic metabolism within SAT in EFV-containing ARV regimens. PMID: 22300946 [PubMed - as supplied by publisher]

Continuous interferon-α2b infusion in combination with ribavirin for chronic hepatitis C in treatment-experienced patients.

Continuous interferon-α2b infusion in combination with ribavirin for chronic hepatitis C in treatment-experienced patients. Antivir Ther. 2011 Dec 13; Authors: Roomer R, Bergmann JF, Boonstra A, Hansen BE, Haagmans BL, Kwadijk-de Gijsel S, van Vuuren AJ, de Knegt RJ, Janssen HL Abstract BACKGROUND: Sustained virological response (SVR) rates in previous non-responders to pegylated interferon (PEG-IFN)-α and ribavirin for chronic HCV remain low (~10%). We hypothesize that continuous subcutaneous delivery of fully potent interferon (IFN)-α2b via an external pump will lead to stable blood concentrations and thereby prevent subtherapeutic trough levels associated with viral breakthrough. The aims of the study were to assess safety, tolerability and virological response in patients who were previous PEG-IFN-α/ribavirin non-responders. METHODS: We randomized 30 HCV genotype 1 (n=24) and genotype 4 (n=6) patients to receive 6, 9 or 12 million units (MU) IFN-α2b daily by continuous subcutaneous administration using an insulin pump (MiniMed(®) 508; Medtronic Inc., Minneapolis, MN, USA) in combination with ribavirin (1,000-1,600 mg) for 48 weeks. RESULTS: The magnitude of viral decline in the 12 MU group after 4 weeks of treatment was 2.67 log HCV RNA compared with 1.21 and 1.27 log HCV RNA in the 9 and 6 MU groups, respectively (P=0.001). In the intention-to-treat analysis, the SVR rate was 20% (6/30). The per-protocol SVR rate was 25% (6/24), of which four out of six patients in the high-dose arm achieved SVR. Adverse events appeared dose-dependent, were mostly mild-to-moderate and were typical of IFN therapy. Five patients developed irritation and/or abscesses at the injection site. Six serious adverse events were reported in five patients. CONCLUSIONS: Continuous delivery of IFN-α2b can induce a strong dose-dependent viral suppression. This could be an effective approach in conjunction with, or as lead-in therapy prior to, treatment with a direct antiviral agent. PMID: 22300892 [PubMed - as supplied by publisher]

The prevalence of darunavir-associated mutations in HIV-1-infected children in the UK.

The prevalence of darunavir-associated mutations in HIV-1-infected children in the UK. Antivir Ther. 2011 Dec 15; Authors: Donegan KL, Walker AS, Dunn D, Judd A, Pillay D, Menson E, Lyall H, Tudor-Williams G, Gibb DM, , Abstract BACKGROUND: We examined the prevalence of ritonavir-boosted darunavir (DRV) resistance-associated mutations (RAMs) in HIV-infected children in the UK to determine the drug's potential clinical utility as a first-line or second-line protease inhibitor (PI). METHODS: The prevalence of DRV RAMs, identified from IAS 2010 and Stanford, and the Stanford susceptibility score, were estimated in PI-naive and PI-experienced children in the Collaborative HIV Paediatric Study and the UK HIV Drug Resistance Database 1998-2008. Associations between type/duration of PI exposure and area under the viraemia curve on PI with the number of RAMs were investigated using multivariate Poisson regression. RESULTS: A total of 17/417 (4%) children with a resistance test when PI-naive had one IAS DRV RAM, and 1 had a Stanford mutation; none had multiple DRV RAMs. A total of 177 PI-experienced children had a test after a median 2.7 years (IQR 1.1-5.2) on PIs; 19 (11%) had one IAS DRV RAM, 7 (4%) had two RAMs, 1 (0.6%) had three RAMs and 1 (0.6%) had four RAMs. DRV RAMs were independently associated with increased years on a PI, a larger area under the viraemia curve since starting PIs, and any exposure to PIs other than lopinavir (all P≤0.05). Only 6 (3%) PI-experienced children had intermediate-level DRV/ritonavir resistance; none had high-level resistance. CONCLUSIONS: DRV resistance was negligible in PI-naive children and those with lopinavir PI exposure alone. However resistance increased with increasing time, and with higher levels of viraemia, on PIs. Once-daily DRV/ritonavir would be valuable as a second PI or an alternative first PI, particularly if coformulated with a booster in an appropriate formulation for children. PMID: 22300840 [PubMed - as supplied by publisher]

Control of HBV replication by antiviral microRNAs transferred by lentiviral vectors for potential cell and gene therapy approaches.

Control of HBV replication by antiviral microRNAs transferred by lentiviral vectors for potential cell and gene therapy approaches. Antivir Ther. 2011 Dec 13; Authors: Kumar M, Follenzi A, Garforth S, Gupta S Abstract BACKGROUND: Because molecular mechanisms regulating host cell and virus interactions are not fully understood, we further defined roles of antiviral microRNAs (miRNAs) in HBV replication. METHODS: We studied small interfering RNA sequences inserted into the miR-30 backbone in cell systems. Antiviral sequences were cloned into lentiviral vectors upstream of a green fluorescent protein reporter. Transduced cells included HepG2 or HepG2 2.2.15 cell lines and hTERT-FH-B fetal human liver cells. HBV replication was analysed by several assays. RESULTS: In 2.2.15 cells treated with constructs primarily targeting HBV polymerase and surface antigen or HBV polymerase and X open reading frames, HBV core protein, HBV DNA and HBV RNA expression decreased. This antiviral effect was more pronounced when the two constructs were expressed together. Similarly, antiviral constructs decreased HBV replication in HepG2 cells transduced with adenoviral vector to express HBV. Although antiviral sequences were expressed in hTERT-FH-B cells, these cells were non-permissive for HBV, possibly owing to expression of miRNAs reported to inhibit HBV replication, whereas these miRNAs were absent in HepG2 cells. Expression of antiviral miRNAs did not affect cell viability or proliferation and no deleterious changes were observed in expression of native cellular miRNAs. Moreover, expression of antiviral miRNA did not affect engraftment and survival of transplanted cells in mice. CONCLUSIONS: Identification of effective antiviral miRNAs and transfer of suitable constructs by lentiviral vectors will be helpful for pathophysiological studies of host cell-virus interactions. Simultaneously, this will advance potential mechanisms for cell/gene therapy in those afflicted with chronic hepatitis and refractory liver disease. PMID: 22300804 [PubMed - as supplied by publisher]

Increased CD34(+)/KDR(+) cells are not associated with carotid artery intima-media thickness progression in chronic HIV-positive subjects.

Increased CD34(+)/KDR(+) cells are not associated with carotid artery intima-media thickness progression in chronic HIV-positive subjects. Antivir Ther. 2011 Dec 16; Authors: Papasavvas E, Hsue P, Reynolds G, Pistilli M, Hancock A, Martin JN, Deeks SG, Montaner LJ Abstract BACKGROUND: Endothelial progenitor cells (EPCs) are involved in the endothelium repair. Low circulating EPC levels are predictive of cardiovascular events in HIV-negative subjects. The impact of HIV infection on EPCs, and the role of EPCs in HIV-associated cardiovascular disease, is not known. We hypothesized that circulating EPCs would be inversely associated with carotid artery intima-media thickness (c-IMT) changes in HIV-infected subjects. METHODS: EPCs (CD34(+)/KDR(+), CD133(+)/KDR(+) and CD34(+)/CD133(+)/KDR(+)) were defined retrospectively by flow cytometry in cryopreserved peripheral blood mononuclear cells collected longitudinally from 66 chronic HIV-infected subjects and cross-sectionally from 50 at-risk HIV-negative subjects. The HIV-infected subjects participated in the Study of the Consequences of the Protease Inhibitor Era (SCOPE) cohort, were receiving antiretroviral therapy (59/66) and had two sequential measurements of c-IMT 1 year apart. Two distinct groups of HIV-infected subjects were identified a priori: rapid c-IMT progressors (subjects with rapid c-IMT progression, n=13, Δc-IMT>0.2 mm) and slow c-IMT progressors (subjects with slow or no c-IMT progression, n=53, Δc-IMT<0.2 mm). RESULTS: Although cryopreservation reduced sensitivity of detection, EPC frequency in HIV-infected subjects was still significantly higher compared to at-risk HIV-negative subjects (CD34(+)/KDR(+); P=0.01) and correlated positively with CD4(+) T-cell count (CD34(+)/KDR(+), r=0.27; P=0.03). No association was found between the change of EPC frequencies over time (ΔEPC) and Δc-IMT or between EPC frequencies and c-IMT or Δc-IMT. CONCLUSIONS: The lack of an association between EPCs and c-IMT in our cohort does not support HIV-associated reductions in EPC frequency as a cause of accelerated atherosclerosis. PMID: 22300770 [PubMed - as supplied by publisher]

Antivirals for management of herpes zoster including ophthalmicus: a systematic review of high-quality randomized controlled trials.

Antivirals for management of herpes zoster including ophthalmicus: a systematic review of high-quality randomized controlled trials. Antivir Ther. 2011 Dec 15; Authors: McDonald EM, de Kock J, Ram FS Abstract BACKGROUND: There is lack of consensus from randomized controlled trials on the efficacy of antivirals in the management of herpes zoster. Therefore, a systematic review and meta-analysis was undertaken to provide better understanding of effectiveness of antivirals in management of herpes zoster. METHODS: A total of 12 randomized controlled trials with 7,277 patients were included in the review. Trials compared one antiviral to another (aciclovir, valaciclovir, famciclovir or brivudin) for a minimum of 7 days in immunocompetent patients presenting with herpes zoster diagnosed within 72 h of symptom onset. Primary outcome was reduction in pain. RESULTS: Compared with aciclovir, valaciclovir showed significant reduction in herpes-zoster-associated pain up to 112 days. The largest risk reduction in pain (36%) was seen at 21-30 days (relative risk [RR] 0.64, 95% CI 0.59, 0.70) with number needed to treat to benefit (NNT) of 3 (95% CI 2.7, 3.8). Famciclovir was also superior to aciclovir with a 46% reduction in risk of pain at 28-30 days (RR 0.54, 95% CI 0.48, 0.68) with NNT of 3 (95% CI 2, 5). Time to lesion healing and adverse effect profile was comparable. CONCLUSIONS: Evidence from quality trials have shown significant reduction in risk of pain with valaciclovir and famciclovir for management of herpes zoster including ophthalmicus. Valaciclovir or famciclovir should be preferred treatment options in patients with herpes zoster as they both provide significant reduction in risk of herpes-zoster-associated pain. Furthermore, the superior pharmacokinetics and more convenient dosing regimens with the use of valaciclovir and famciclovir clearly make them the preferred treatment option. PMID: 22300753 [PubMed - as supplied by publisher]

Is a single dose of meningococcal serogroup C conjugate vaccine sufficient for protection? Experience from the Netherlands

Background: The first meningococcal serogroup C (MenC) conjugate vaccine was licensed in 1999 and introduced in the United Kingdom. Countries that have implemented the MenC vaccine since then in their national immunisation programmes use different schedules. Nevertheless, all involved countries seem to experience substantial declines in the incidence of MenC disease.DiscussionSince 2001, the MenC conjugate vaccine has been implemented in the Netherlands by offering a single dose to all children aged 14 months. Prior to the introduction of the vaccine into the national immunisation programme, a catch-up vaccination campaign was initiated in which a single dose of the MenC conjugate vaccine was offered to all children aged from 14 months up to and including 18 years. Since then, there has been no report of any case of MenC disease among immunocompetent vaccinees. Administration of a single dose of MenC conjugate vaccine after infancy could be beneficial considering the already complex immunisation schedules with large numbers of vaccinations in the first year of life. The present paper deals with the advantages and critical aspects of a single dose of the MenC conjugate vaccine.SummaryA single dose of MenC conjugate vaccine at the age of 14 months in combination with a catch up vaccine campaign appeared to be a successful strategy to prevent MenC disease in the Netherlands, thereby confirming that a single dose of the vaccine could sufficiently protect against disease. Nevertheless, this approach can only be justified in countries with a relatively low incidence of serogroup C meningococcal disease in the first year of life. Furthermore, a good surveillance programme is recommended for timely detection of vaccine breakthroughs and outbreaks among non-vaccinees, since long-term protection after a single dose in the second year of life cannot currently be guaranteed.

Group B streptococcal carriage, serotype distribution and antibiotic susceptibilities in pregnant women at the time of delivery in a refugee population on the Thai - Myanmar border

Background: Group B Streptococcus (GBS) is the leading cause of neonatal sepsis in the developed world. Little is known about its epidemiology in the developing world, where the majority of deaths from neonatal infections occur. Maternal carriage of GBS is a prerequisite for the development of early onset GBS neonatal sepsis but there is a paucity of carriage data published from the developing world, in particular South East Asia. Methods: We undertook a cross sectional study over a 13 month period in a remote South East Asian setting on the Thai-Myanmar border. During labour, 549 mothers had a combined vaginal rectal swab taken for GBS culture. All swabs underwent both conventional culture as well as PCR for GBS detection. Cultured GBS isolates were serotyped by latex agglutination, those that were negative or had a weak positive reaction and those that were PCR positive but culture negative were additionally tested using multiplex PCR based on the detection of GBS capsular polysaccharide genes. Results: The GBS carriage rate was 12.0% (95% CI: 9.4-15.0), with 8.6% positive by both culture and PCR and an additional 3.5% positive by PCR alone. Serotypes, Ia, Ib, II, III, IV, V, VI and VII were identified, with II the predominant serotype. All GBS isolates were susceptible to penicillin, ceftriaxone and vancomycin and 43/47 (91.5%) were susceptible to erythromycin and clindamycin. Conclusions: GBS carriage is not uncommon in pregnant women living on the Thai-Myanmar border with a large range of serotypes represented.

A large, population-based study of age-related associations between vaginal pH and human papillomavirus infection

Background: Vaginal pH is related to genital tract inflammation and changes in the bacterial flora, both suggested cofactors for persistence of human papillomavirus (HPV) infection. To evaluate the relationship between vaginal pH and HPV, we analyzed data from our large population-based study in Guanacaste, Costa Rica. We examined vaginal pH and the risk of HPV infection, cytological abnormalities, and C. trachomatis infection. Methods: Our study included 9,165 women aged 18-97 at enrollment with a total of 28,915 visits (mean length of follow-up = 3.4 years). Generalized estimating equations were used to evaluate the relationship between vaginal pH and HPV infection (both overall and single versus multiple types) and low-grade squamous intraepithelial lesions (LSIL), the cytomorphic manifestation of HPV infection. The relationship between enrollment vaginal pH and C. trachomatis infection was assessed by logistic regression. Results were stratified by age at visit. Results: Detection of HPV was positively associated with vaginal pH, mainly in women <35 years (p-trend = 0.009 and 0.007 for women aged <25 and 25-34 years, respectively). Elevated vaginal pH was associated with 30% greater risk of infection with multiple HPV types and with LSIL, predominantly in women younger than 35 and 65+ years of age. Detection of C. trachomatis DNA was associated with increased vaginal pH in women <25 years (OR 2.2 95% CI 1.0-5.0). Conclusions: Our findings suggest a possible association of the cervical microenvironment as a modifier of HPV natural history in the development of cervical precancer and cancer. Future research should include studies of vaginal pH in a more complex assessment of hormonal changes and the cervicovaginal microbiome as they relate to the natural history of cervical neoplasia.

Measurement of the plasma levels of antibodies against the polymorphic vaccine candidate apical membrane antigen 1 in a malaria-exposed population

Background: Establishing antibody correlates of protection against malaria in human field studies and clinical trials requires, amongst others, an accurate estimation of antibody levels. For polymorphic antigens such as apical membrane antigen 1 (AMA1), this may be confounded by the occurrence of a large number of allelic variants in nature. Methods: To test this hypothesis, plasma antibody levels in an age-stratified cohort of naturally exposed children from a malaria-endemic area in Southern Ghana were determined by indirect ELISA. Titres against four single PfAMA1 alleles were compared with those against three different allele mixtures presumed to have a wider repertoire of epitope specificities. Associations of antibody levels with the incidence of clinical malaria as well as with previous exposure to parasites were also examined. Results: Antibody titres against PfAMA1 alleles generally increased with age/exposure while antibody specificity for PfAMA1 variants decreased, implying that younger children ([less than or equal to] 5 years) elicit a more strain-specific antibody response compared to older children. Antibody titre measurements against the FVO and 3D7 AMA1 alleles gave the best titre estimates as these varied least in pair-wise comparisons with titres against all PfAMA1 allele mixtures. There was no association between antibody levels against any capture antigen and either clinical malaria incidence or parasite density. Conclusions: The current data shows that levels of naturally acquired antigen-specific antibodies, especially in infants and young children, are dependent on the antigenic allele used for measurement. This may be relevant to the interpretation of antibody titre data from measurements against single PfAMA1 alleles, especially in studies involving infants and young children who have experienced fewer infections.

Inter-rater agreement in the assessment of abnormal chest X-ray findings for tuberculosis between two Asian countries

Background: Inter-rater agreement in the interpretation of chest X-ray (CXR) films is crucial for clinical and epidemiological studies of tuberculosis. We compared the readings of CXR films used for a survey of tuberculosis between raters from two Asian countries. Methods: Of the 11,624 people enrolled in a prevalence survey in Hanoi, Viet Nam, in 2003, we studied 258 individuals whose CXR films did not exclude the possibility of active tuberculosis. Follow-up films obtained from accessible individuals in 2006 were also analyzed. Two Japanese and two Vietnamese raters read the CXR films based on a coding system proposed by Den Boon et al. and another system newly developed in this study. Inter-rater agreement was evaluated by kappa statistics. Marginal homogeneity was evaluated by the generalized estimating equation (GEE). Results: CXR findings suspected of tuberculosis differed between the four raters. The frequencies of infiltrates and fibrosis/scarring detected on the films significantly differed between the raters from the two countries (P < 0.0001 and P = 0.0082, respectively, by GEE). The definition of findings such as primary cavity, used in the coding systems also affected the degree of agreement. Conclusions: CXR findings were inconsistent between the raters with different backgrounds. High inter-rater agreement is a component necessary for an optimal CXR coding system, particularly in international studies. An analysis of reading results and a thorough discussion to achieve a consensus would be necessary to achieve further consistency and high quality of reading.

Influenza vaccination of healthcare workers in acute-care hospitals: a case-control study of its effect on hospital-acquired influenza among patients

Background: In acute-care hospitals, no evidence of a protective effect of healthcare worker (HCW) vaccination on hospital-acquired influenza (HAI) in patients has been documented. Our study objective was to ascertain the effectiveness of influenza vaccination of HCW on HAI among patients. Methods: A nested case-control investigation was implemented in a prospective surveillance study of influenza-like illness (ILI) in a tertiary acute-care university hospital. Cases were patients with virologically-confirmed influenza occurring >=72 h after admission, and controls were patients with ILI presenting during hospitalisation with negative influenza results after nasal swab testing. Four controls per case, matched per influenza season (2004-05, 2005-06 and 2006-07), were randomly selected. Univariate and multivariate conditional logistic regression models were fitted to assess factors associated with HAI among patients. Results: In total, among 55 patients analysed, 11 (20%) had laboratory-confirmed HAI. The median HCW vaccination rate in the units was 36%. The median proportion of vaccinated HCW in these units was 11.5% for cases vs. 36.1% for the controls (P = 0.11); 2 (20%) cases and 21 (48%) controls were vaccinated against influenza in the current season (P = 0.16). The proportion of >=35% vaccinated HCW in short-stay units appeared to protect against HAI among patients (odds ratio = 0.07; 95% confidence interval 0.005-0.98), independently of patient age, influenza season and potential influenza source in the units. Conclusions: Our observational study indicates a shielding effect of more than 35% of vaccinated HCW on HAI among patients in acute-care units. Investigations, such as controlled clinical trials, are needed to validate the benefits of HCW vaccination on HAI incidence in patients.

Clinical features and risk factors for severe and critical pregnant women with 2009 pandemic H1N1 influenza infection in China

Background: 2009 pandemic H1N1 (pH1N1) influenza posed an increased risk of severe illness among pregnant women. Data on risk factors associated with death of pregnant women and neonates with pH1N1 infections are limited outside of developed countries. Methods: Retrospective observational study in 394 severe or critical pregnant women admitted to a hospital with pH1N1 influenza from Sep. 1, 2009 to Dec. 31, 2009. rRT-PCR testing was used to confirm infection. In-hospital mortality was the primary endpoint of this study. Univariable logistic analysis and multivariate logistic regression analysis were used to investigate the potential factors on admission that might be associated with the maternal and neonatal mortality. Results: 394 pregnant women were included, 286 were infected with pH1N1 in the third trimester. 351 had pneumonia, and 77 died. A PaO2/FiO2 [less than or equal to] 200 (odds ratio (OR), 27.16; 95% confidence interval (CI), 2.64-279.70) and higher BMI (i.e. [greater than or equal to]30) on admission (OR, 1.26; 95% CI, 1.09 to 1.47) were independent risk factors for maternal death. Of 211 deliveries, 146 neonates survived. Premature delivery (OR, 4.17; 95% CI, 1.19-14.56) was associated neonatal mortality. Among 186 patients who received mechanical ventilation, 83 patients were treated with non-invasive ventilation (NIV) and 38 were successful with NIV. The death rate was lower among patients who initially received NIV than those who were initially intubated (24/83, 28.9% vs 43/87, 49.4%; p = 0.006). Septic shock was an independent risk factor for failure of NIV. Conclusions: Severe hypoxemia and higher BMI on admission were associated with adverse outcomes for pregnant women. Preterm delivery was a risk factor for neonatal death among pregnant women with pH1N1 influenza infection. NIV may be useful in selected pregnant women without septic shock.

Immune reconstitution inflammatory syndrome from Penicillium marneffei in an HIV-infected child: A case report and review of literature

BackgroundsDisseminated Penicillium marneffei infection is one of the most common HIV-related opportunistic infections in Southeast Asia. Immune reconstitution inflammatory syndrome (IRIS) is a complication related to antiretroviral therapy (ART)-induced immune restoration. The aim of this report is to present a case of HIV-infected child who developed an unmasking type of IRIS caused by disseminated P. marneffei infection after ART initiation.Case presentationA 14-year-old Thai HIV-infected girl presented with high-grade fever, multiple painful ulcerated oral lesions, generalized non-pruritic erythrematous skin papules and nodules with central umbilication, and multiple swollen, warm, and tender joints 8 weeks after ART initiation. At that time, her CD4+ cell count was 7.2% or 39 cells/mm3. On admission, her repeated CD4+ cell count was 11% or 51 cells/mm3 and her plasma HIV-RNA level was <50 copies/mL. Her skin biopsy showed necrotizing histiocytic granuloma formation with neutrophilic infiltration in the upper and reticular dermis. Tissue sections stained with hematoxylin and eosin (H&E), periodic acid-Schiff (PAS), and Grocott methenamine silver (GMS) stain revealed numerous intracellular and extracellular, round to oval, elongated, thin-walled yeast cells with central septation. The hemoculture, bone marrow culture, and skin culture revealed no growth of fungus or bacteria. Our patient responded well to intravenous amphotericin B followed by oral itraconazole. She fully recovered after 4-month antifungal treatment without evidence of recurrence of disease. Conclusions: IRIS from P. marneffei in HIV-infected people is rare. Appropriate recognition and properly treatment is important for a good prognosis.

Infection control management of patients with suspected highly infectious diseases in emergency departments: data from a survey in 41 facilities in 14 European countries

Background: In Emergency and Medical Admission Departments (EDs and MADs), prompt recognition and appropriate infection control management of patients with Highly Infectious Diseases (HIDs, e.g. Viral Hemorrhagic Fevers and SARS) are fundamental for avoiding nosocomial outbreaks. Methods: The EuroNHID (European Network for Highly Infectious Diseases) project collected data from 41 EDs and MADs in 14 European countries, located in the same facility as a national/regional referral centre for HIDs, using specifically developed checklists, during on-site visits from February to November 2009. Results: Isolation rooms were available in 34 facilities (82,9%): these rooms had anteroom in 19, dedicated entrance in 15, negative pressure in 17, and HEPA filtration of exhausting air in 12. Only 6 centres (14,6%) had isolation rooms with all characteristics. Personnel trained for the recognition of HIDs was available in 24 facilities; management protocols for HIDs were available in 35. Conclusions: Preparedness level for the safe and appropriate management of HIDs is partially adequate in the surveyed EDs and MADs.

The role of facemasks and hand hygiene in the prevention of influenza transmission in households: results from a cluster randomised trial; Berlin, Germany, 2009-2011.

Background: Previous controlled studies on the effect of non-pharmaceutical interventions (NPI) - namely the use of facemasks and intensified hand hygiene - in preventing household transmission of influenza have not produced definitive results. We aimed to investigate efficacy, acceptability, and tolerability of NPI in households with influenza index patients. Methods: We conducted a cluster randomized controlled trial during the pandemic season 2009/10 and the ensuing influenza season 2010/11. We included households with an influenza positive index case in the absence of further respiratory illness within the preceding 14 days. Study arms were wearing a facemask and practicing intensified hand hygiene (MH group), wearing facemasks only (M group) and none of the two (control group). Main outcome measure was laboratory confirmed influenza infection in a household contact. We used daily questionnaires to examine adherence and tolerability of the interventions. Results: We recruited 84 households (30 control, 26 M and 28 MH households) with 82, 69 and 67 household contacts, respectively. In 2009/10 all 41 index cases had a influenza A (H1N1)pdm09 infection, in 2010/11 24 had an A (H1N1)pdm09 and 20 had a B infection. The total secondary attack rate was 16% (35/218). In intention-to-treat analysis there was no statistically significant effect of the M and MH interventions on secondary infections. When analysing only households where intervention was implemented within 36 hours after symptom onset of the index case, secondary infection in the pooled M and MH groups was significantly lower compared to the control group (adjusted odds ratio 0.16, 95% CI, 0.03-0.92). In a per-protocol analysis odds ratios were significantly reduced among participants of the M group (adjusted odds ratio, 0.30, 95% CI, 0.10-0.94). With the exception of MH index cases in 2010/11 adherence was good for adults and children, contacts and index cases. Conclusions: Results suggest that household transmission of influenza can be reduced by the use of NPI, such as facemasks and intensified hand hygiene, when implemented early and used diligently. Concerns about acceptability and tolerability of the interventions should not be a reason against their recommendation.The study was registered with ClinicalTrials.gov (Identifier NCT00833885).

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Epidemiologic Approaches to Injury and Violence

This volume of Epidemiologic Reviews features 13 articles covering a variety of injury problems and research topics. In this commentary, the authors highlight the remarkable achievements in injury control and the important role the Haddon Matrix has played in understanding injury causation and developing preventive strategies; comment on the individual articles included in this volume in the broad categories of research methods, childhood injury, motor-vehicle-related injury, alcohol-related injury, intentional injury, and occupational injury; and outline research gaps and future directions in injury epidemiology and prevention.

Classifying External Causes of Injury: History, Current Approaches, and Future Directions

The International Classification of Diseases (ICD) is used to categorize diseases, injuries, and external causes of injury, and it is a key epidemiologic tool enabling storage and retrieval of data from health and vital records to produce core international mortality and morbidity statistics. The ICD is updated periodically to ensure the classification system remains current, and work is now under way to develop the next revision, ICD-11. It has been almost 20 years since the last ICD edition was published and over 60 years since the last substantial structural revision of the external causes chapter. Revision of such a critical tool requires transparency and documentation to ensure that changes made to the classification system are recorded comprehensively for future reference. In this paper, the authors provide a history of the development of external causes classification and outline the external cause structure. They discuss approaches to manage ICD-10 deficiencies and outline the ICD-11 revision approach regarding the development of, rationale for, and implications of proposed changes to the chapter. Through improved capture of external cause concepts in ICD-11, a stronger evidence base will be available to inform injury prevention, treatment, rehabilitation, and policy initiatives to ultimately contribute to a reduction in injury morbidity and mortality.

Measuring the Population Burden of Fatal and Nonfatal Injury

The value of measuring the population burden of fatal and nonfatal injury is well established. Population health metrics are important for assessing health status and health-related quality of life after injury and for integrating mortality, disability, and quality-of-life consequences. A frequently used population health metric is the disability-adjusted life-year. This metric was launched in 1996 in the original Global Burden of Disease and Injury study and has been widely adopted by countries and health development agencies alike to identify the relative magnitude of different health problems. Apart from its obvious advantages and wide adherence, a number of challenges are encountered when the disability-adjusted life-year is applied to injuries. Validation of disability-adjusted life-year estimates for injury has been largely absent. This paper provides an overview of methods and existing knowledge regarding the population burden of injury measurement. The review of studies that measured burden of injury shows that estimates of the population burden remain uncertain because of a weak epidemiologic foundation; limited information on incidence, outcomes, and duration of disability; and a range of methodological problems, including definition and selection of incident and fatal cases, choices in selection of assessment instruments and timings of use for nonfatal injury outcomes, and the underlying concepts of valuation of disability. Recommendations are given for methodological refinements to improve the validity and comparability of future burden of injury studies.

Network Meta-analysis to Evaluate the Effectiveness of Interventions to Increase the Uptake of Smoke Alarms

This study is the first known to use network meta-analysis to simultaneously evaluate the effectiveness of interventions to increase the prevalence of functioning smoke alarms in households with children. The authors identified 24 primary studies from a systematic review of reviews and of more recently published primary studies, of which 23 (17 randomized controlled trials and 6 nonrandomized comparative studies) were included in 1 of the following 2 network meta-analyses: 1) possession of a functioning alarm: interventions that were more "intensive" (i.e., included components providing equipment (with or without fitting), home inspection, or both, in addition to education) generally were more effective. The intervention containing all of the aforementioned components was identified as being the most likely to be the most effective (probability (best) = 0.66), with an odds ratio versus usual care of 7.15 (95% credible interval: 2.40, 22.73); 2) type of battery-powered alarms: ionization alarms with lithium batteries were most likely to be the best type for increasing functioning possession (probability (best) = 0.69). Smoke alarm promotion programs should ensure they provide the combination of interventions most likely to be effective.

Roadway Characteristics and Pediatric Pedestrian Injury

Changing the built environment is a sound, but often underutilized approach to injury control. The authors reviewed the literature and conducted a meta-analysis to synthesize the evidence on the association of roadway characteristics with risk of pediatric pedestrian injury. To synthesize the data, they converted results to odds ratios based on direct results or abstracted outcomes and used Bayesian meta-analytic approaches by modeling outcomes as the logit of a normally distributed set of outcomes with vague prior distributions for the central measure of effect and its variance. On the basis of 10 studies of roadway features restricted exclusively to pediatric populations, the synthesized effect estimate for the association of roadway characteristics with pedestrian injury risk was 2.5 (95% credible interval: 1.8, 3.2). The probability of a new study showing an association between the built roadway and pediatric pedestrian injury was nearly 100%. The authors concluded that the built environment is directly related to the risk of pedestrian injury. This review and meta-analysis suggests that even modest interventions to the built roadway environment may result in meaningful reductions in the risk of pediatric pedestrian injury.

Interventions to Reduce Risks Associated With Vehicle Incompatibility

Occupants of smaller, lighter passenger cars are more likely to be killed or injured in collisions with larger, heavier sport utility vehicles and light trucks than in collisions with other cars. Interventions are needed to reduce this vehicle "incompatibility" and its consequences. The authors conducted a systematic literature review to identify evaluations of interventions to reduce incompatibility. They reviewed engineering, biomedical, and other technical literature. To be included, a study must have 1) evaluated an intervention to reduce vehicle incompatibility, or its consequences, in a crash; 2) reported new research; and 3) been published in English from 1990 to 2010. Seventeen studies met the inclusion criteria. Interventions were designed to reduce the aggressivity of larger vehicles or improve the crashworthiness of smaller vehicles. Effective interventions included 1) modified bumper heights, 2) improved side strength of smaller vehicles, 3) side-impact air bags, 4) changes to vehicle stiffness, and 5) modifications of other front-end structures. Some of the interventions shown to be effective are now in wide use. However, others have yet to be required by regulators or voluntarily agreed to by manufacturers. If larger, heavier vehicles remain on the nation's roads, countermeasures will be needed to reduce risks for occupants of other vehicles.

Marijuana Use and Motor Vehicle Crashes

Since 1996, 16 states and the District of Columbia in the United States have enacted legislation to decriminalize marijuana for medical use. Although marijuana is the most commonly detected nonalcohol drug in drivers, its role in crash causation remains unsettled. To assess the association between marijuana use and crash risk, the authors performed a meta-analysis of 9 epidemiologic studies published in English in the past 2 decades identified through a systematic search of bibliographic databases. Estimated odds ratios relating marijuana use to crash risk reported in these studies ranged from 0.85 to 7.16. Pooled analysis based on the random-effects model yielded a summary odds ratio of 2.66 (95% confidence interval: 2.07, 3.41). Analysis of individual studies indicated that the heightened risk of crash involvement associated with marijuana use persisted after adjustment for confounding variables and that the risk of crash involvement increased in a dose-response fashion with the concentration of 11-nor-9-carboxy-delta-9-tetrahydrocannabinol detected in the urine and the frequency of self-reported marijuana use. The results of this meta-analysis suggest that marijuana use by drivers is associated with a significantly increased risk of being involved in motor vehicle crashes.

Motor Vehicle Deaths Among American Indian and Alaska Native Populations

In the United States, the American Indian and Alaska Native (AI/AN) population has the highest motor vehicle death rate, which is significantly greater than that of any other race or ethnic group. To better understand why this significant disparity exists and how to eliminate it, the authors conducted a systematic review of the published scientific literature. Included studies were published between January 1, 1990, and January 31, 2011, and identified risk factors, or implemented and tested interventions, targeting motor vehicle deaths among the AI/AN population. Only 14 papers met the study’s inclusion criteria. Most of the epidemiologic studies explored alcohol use as a risk factor for deaths of both motor vehicle occupants and pedestrians; few studies addressed risk factors specifically for pedestrians. All of the intervention studies focused on mitigating risks for motor vehicle occupants. On the basis of the authors’ review, injury prevention interventions that are multifaceted and involve partnerships to change policy, the environment, and individual behavior can effectively mitigate motor-vehicle-related deaths among AI/ANs. Priority should be given to implementing interventions that address pedestrian safety and to sound investment in the states with the highest AI/AN motor vehicle death rates because reducing their burden can dramatically reduce the overall disparity.

The Role of Race/Ethnicity in Alcohol-attributable Injury in the United States

A substantial proportion of injuries worldwide are attributable to alcohol consumption, and US estimates indicate that the drinking patterns of racial/ethnic groups vary considerably. The authors reviewed evidence from 19 publications regarding racial/ethnic differences in overall alcohol-attributable injury as well as percent blood alcohol content positivity for injury deaths in the United States. They found that Native Americans evidence higher rates of alcohol-attributable motor vehicle crash fatality, suicide, and falls compared with other racial/ethnic groups; conversely, Asians evidence lower rates of alcohol-attributable injury than other racial/ethnic groups. The rate of alcohol positivity and intoxication among Hispanics is disproportionately high relative to estimates of alcohol use. Black subgroups also evidence higher rates of alcohol positivity than would be expected given estimates of alcohol use, including for alcohol positivity among drivers of fatally injured black children and homicide. These findings highlight the continued need for public health focus on Native American populations with respect to alcohol consumption and injury. Further, the disparity in alcohol-attributable injury mortality among black and Hispanic groups relative to their reported rates of alcohol consumption is an overlooked area of research. The authors review potential social determinants of racial/ethnic disparities in alcohol-attributable injuries and identify directions for further research on these patterns.

Does the Alcohol Make Them Do It? Dating Violence Perpetration and Drinking Among Youth

Strong evidence links alcohol use to partner violence perpetration among adults, but the relation between youth alcohol use and dating violence perpetration (DVP) is not as well studied. The authors used meta-analytic procedures to evaluate current knowledge on the association between alcohol use and DVP among youth. The authors reviewed 28 studies published in 1985–2010; most (82%) were cross-sectional. Alcohol use was measured in 3 main ways: 1) frequency or quantity of use, 2) frequency of heavy episodic drinking, or 3) problem use. Collectively, results support the conclusion that higher levels of alcohol use are positively associated with youth DVP. With fixed-effects models, the combined odds ratios for DVP for frequency/quantity, heavy episodic drinking, and problem use were 1.23 (95% confidence interval (CI): 1.16, 1.31), 1.47 (95% CI: 1.17, 1.85), and 2.33 (95% CI: 1.94, 2.80), respectively. This association persisted even after accounting for heterogeneity and publication bias. No studies were designed to assess the immediate temporal association between drinking and DVP. Future research should assess whether there are acute or pharmacologic effects of alcohol use on youth DVP. Furthermore, few studies have been hypothesis driven, controlled for potential confounding, or examined potential effect measure modification. Studies designed to investigate the youth alcohol–DVP link specifically, and whether results vary by individuals’ gender, developmental stage, or culture, are needed.

Peer Victimization Among School-aged Children With Chronic Conditions

Peer victimization is a common problem among school-aged children, and those with chronic conditions are at an increased risk. A systematic review of the literature was carried out to explore the increased risk of peer victimization among children with chronic conditions compared with others, considering a variety of chronic conditions; and to assess intervention programs designed to reduce negative attitudes or peer victimization at school toward children with chronic conditions. Various data sources were used (PubMed, ERIC, PsycINFO, Web of Science), and 59 studies published between 1991 and 2011 and mainly carried out in North American and European countries were included in the review. A higher level of peer victimization among children with chronic conditions was shown for each type of condition explored in this review (psychiatric diagnoses, learning difficulties, physical and motor impairments, chronic illnesses, and overweight). Despite a substantial number of studies having shown a significant association between chronic conditions and peer victimization, intervention studies aiming to reduce bullying among these children were rarely evaluated. The findings of this review suggest a growing need to develop and implement specific interventions targeted at reducing peer victimization among children with chronic conditions.

Suicide in Asia: Opportunities and Challenges

Asian countries account for approximately 60% of the world’s suicides, but there is a great mismatch in the region between the scale of the problem and the resources available to tackle it. Despite certain commonalities, the continent itself is culturally, economically, and socially diverse. This paper reviews current epidemiologic patterns of suicide, including suicide trends, sociodemographic factors, urban/rural living, suicide methods, sociocultural religious influences, and risk and protective factors in Asia, as well as their implications. The observed epidemiologic distributions of suicides reflect complex interplays among the traditional value/culture system, rapid economic transitions under market globalization, availability/desirability of suicide methods, and sociocultural permission/prohibitions regarding suicides. In general, compared with Western countries, Asian countries still have a higher average suicide rate, lower male-to-female suicide gender ratio, and higher elderly-to-general-population suicide ratios. The role of mental illness in suicide is not as important as that in Western countries. In contrast, aggravated by access to lethal means in Asia (e.g., pesticide poisoning and jumping), acute life stress (e.g., family conflicts, job and financial security issues) plays a more important role than it does in Western countries. Some promising suicide prevention programs in Asia are illustrated. Considering the specific socioeconomic and cultural aspects of the region, community-based suicide intervention programs integrating multiple layers of intervention targets may be the most feasible and cost-effective strategy in Asia, with its populous areas and limited resources.

Humanitarian Relief Workers and Trauma-related Mental Illness

Humanitarian relief work is a growing field characterized by ongoing exposure to primary and secondary trauma, which has implications for workers’ occupational mental health. This paper reviews and summarizes research to date on mental health effects of relief work. Twelve studies on relief workers and 5 studies on organizations that employ relief workers are examined to determine whether relief work is a risk factor for trauma-related mental illness. Although studies are inconsistent regarding methods and outcomes documenting trauma-related mental illness among relief workers, it appears that relief workers, compared with the general population, experience elevated trauma rates and suffer from more posttraumatic stress disorder, depression, and anxiety. Organizations that employ relief workers have varying approaches to train for these risks, and more support in the field is needed.

An Aging Workforce and Injury in the Construction Industry

The relatively large birth cohort between 1946 and 1964, combined with the economic recession in the first decade of the 21st century, have led to an increase in the proportion of older workers in the US workplace. Understanding the health and safety needs of an aging workforce will be critical, especially in the construction industry, where physical job demands are high. This paper reviews the epidemiologic literature on the impact of age on injury among workers in the construction industry in terms of cause, type, and cost. PubMed was searched by using the following terms: older workers, construction, construction industry, injury, and age. The available studies reported that, among the construction industry workforce, older age at injury was related to higher injury costs but not to number of injuries. The higher injury costs associated with worker age are likely due in part to the severity of the injuries sustained by older workers. Identification of injury trends and subsequent analytical research efforts designed to ascertain factors associated with injury among older construction workers are needed for employers to effectively manage a health and safety program that addresses the needs of the aging worker.

Volume 140 Issue 03

Epidemiology Infection, Volume 140 Issue 03 Epidemiology 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 scope includes the zoonoses, tropical infections, food hygiene, vaccine studies, statistics and the clinical, social and public-health aspects of infectious disease. It has become the key international 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.

HYG volume 140 issue 3 Cover and Front matter

Miscellaneous Epidemiology & Infection, Volume 140 Issue 03, pp f1-f2Abstract

HYG volume 140 issue 3 Cover and Back matter

Miscellaneous Epidemiology & Infection, Volume 140 Issue 03, pp b1-b3Abstract

Livestock veterinarians at high risk of acquiring methicillin-resistant Staphylococcus aureus ST398

Review Articles C. GARCIA-GRAELLS, J. ANTOINE, J. LARSEN, B. CATRY, R. SKOV, O. DENIS, Epidemiology & Infection, Volume 140 Issue 03, pp 383-389Abstract

USA300 methicillin-resistant S. aureus (USA300 MRSA) colonization and the risk of MRSA infection in residents of extended-care facilities

Research Articles S. M. SHURLAND, O. C. STINE, R. A. VENEZIA, M. ZHAN, J. P. FURUNO, R. R. MILLER, M.-C. ROGHMANN, Epidemiology & Infection, Volume 140 Issue 03, pp 390-399Abstract

Clinical significance of methicillin-resistant Staphylococcus aureus colonization in residents in community long-term-care facilities in Spain

Research Articles A. MANZUR, E. RUIZ DE GOPEGUI, M. DOMINGUEZ, D. MARISCAL, L. GAVALDA, J. L. PEREZ, F. SEGURA, M. PUJOL, the Spanish Network for Research in Infectious Diseases null, Epidemiology & Infection, Volume 140 Issue 03, pp 400-406Abstract

Space–time pattern of hepatitis A in Spain, 1997–2007

Research Articles D. GOMEZ-BARROSO, C. VARELA, R. RAMIS, J. L. DEL BARRIO, F. SIMÓN, Epidemiology & Infection, Volume 140 Issue 03, pp 407-416Abstract

Determinants of anti-hepatitis A antibody seroprevalence in 2- to 19-year-olds in the USA using NHANES 2007–2008

Research Articles E. VELASCO-MONDRAGON, I. LINDONG, F. KAMANGAR, Epidemiology & Infection, Volume 140 Issue 03, pp 417-425Abstract

Changes in measles seroepidemiology of healthcare workers in southern Taiwan

Research Articles T. S. HO, S. M. WANG, L. R. WANG, C. C. LIU, Epidemiology & Infection, Volume 140 Issue 03, pp 426-431Abstract

Molecular and phylogenetic analysis of Greek measles 2010 strains

Research Articles A. MELIDOU, G. GIOULA, V. POGKA, M. EXINDARI, A. MOUTOUSSI, D. SGOURAS, K. PAPADAKOS, D. CHATZIDIMITRIOU, D. KARABAXOGLOU, A. MENTIS, N. MALISIOVAS, Epidemiology & Infection, Volume 140 Issue 03, pp 432-438Abstract

Mumps outbreak in Israel's highly vaccinated society: are two doses enough?

Research Articles E. ANIS, I. GROTTO, L. MOERMAN, B. WARSHAVSKY, P. E. SLATER, B. LEV, Epidemiology & Infection, Volume 140 Issue 03, pp 439-446Abstract

An outbreak of rubella in the Federation of Bosnia and Herzegovina between December 2009 and May 2010 indicates failure to vaccinate during wartime (1992–1995)

Research Articles M. HUKIC, J. M. HÜBSCHEN, M. SEREMET, I. SALIMOVIC-BESIC, M. MULAOMEROVIC, N. MEHINOVIC, S. KARAKAS, E. CHARPENTIER, C. P. MULLER, Epidemiology & Infection, Volume 140 Issue 03, pp 447-453Abstract

Infection and immunity for human parvovirus B19 in patients with febrile exanthema

Research Articles M. S. PEDRANTI, P. BARBERO, C. WOLFF, L. M. GHIETTO, M. ZAPATA, M. P. ADAMO, Epidemiology & Infection, Volume 140 Issue 03, pp 454-461Abstract

African horse sickness in The Gambia: circulation of a live-attenuated vaccine-derived strain

Brief Report C. A. L. OURA, P. A. S. IVENS, K. BACHANEK-BANKOWSKA, A. BIN-TARIF, D. B. JALLOW, C. SAILLEAU, S. MAAN, P. C. MERTENS, C. A. BATTEN, Epidemiology & Infection, Volume 140 Issue 03, pp 462-465Abstract

Age factor and implication of human papillomavirus type-specific prevalence in women with normal cervical cytology

Research Articles C. H. LAI, A. CHAO, C. J. CHANG, C. C. HUANG, L. C. WANG, S. HSUEH, C. T. LIN, T. I. WU, M. S. JAO, H. H. CHOU, Epidemiology & Infection, Volume 140 Issue 03, pp 466-473Abstract

The risk of airborne influenza transmission in passenger cars

Brief Report L. D. KNIBBS, L. MORAWSKA, S. C. BELL, Epidemiology & Infection, Volume 140 Issue 03, pp 474-478Abstract

Geographical gradient of mean age of dengue haemorrhagic fever patients in northern Thailand

Research Articles Y. NAGAO, A. TAWATSIN, S. THAMMAPALO, U. THAVARA, Epidemiology & Infection, Volume 140 Issue 03, pp 479-490Abstract

Under-recognition and reporting of dengue in Cambodia: a capture–recapture analysis of the National Dengue Surveillance System

Research Articles S. VONG, S. GOYET, S. LY, C. NGAN, R. HUY, V. DUONG, O. WICHMANN, G. W. LETSON, H. S. MARGOLIS, P. BUCHY, Epidemiology & Infection, Volume 140 Issue 03, pp 491-499Abstract

Costs of illness due to endemic cholera

Research Articles C. POULOS, A. RIEWPAIBOON, J. F. STEWART, J. CLEMENS, S. GUH, M. AGTINI, D. SUR, Z. ISLAM, M. LUCAS, D. WHITTINGTON, the DOMI Cholera COI Study Group null, Epidemiology & Infection, Volume 140 Issue 03, pp 500-509Abstract

Genetic characterization of Vibrio cholerae O1 strains isolated in Zambia during 1996–2004 possessing the unique VSP-II region of El Tor variant

Research Articles N. A. BHUIYAN, S. NUSRIN, M. ANSARUZZAMAN, A. ISLAM, M. SULTANA, M. ALAM, M. A. ISLAM, A. CRAVIOTO, A. K. MUKHOPADHYAY, G. B. NAIR, J. C. L. MWASNA, H. P. ENDTZ, Epidemiology & Infection, Volume 140 Issue 03, pp 510-518Abstract

First reported foodborne outbreak associated with microsporidia, Sweden, October 2009

Research Articles V. DECRAENE, M. LEBBAD, S. BOTERO-KLEIVEN, A.-M. GUSTAVSSON, M. LÖFDAHL, Epidemiology & Infection, Volume 140 Issue 03, pp 519-527Abstract

Wide dissemination of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella spp. in acute care and rehabilitation hospitals

Research Articles A. KOHLENBERG, F. SCHWAB, H. RÜDEN, Epidemiology & Infection, Volume 140 Issue 03, pp 528-534Abstract

Acinetobacter calcoaceticus – Acinetobacter baumannii complex species in clinical specimens in Singapore

Brief Report T. H. KOH, T. T. TAN, C. T. KHOO, S. Y. NG, T. Y. TAN, L-Y. HSU, E. E. OOI, T. J. K. VAN DER REIJDEN, L. DIJKSHOORN, Epidemiology & Infection, Volume 140 Issue 03, pp 535-538Abstract

Emergence of metallo-β-lactamase IMP-14 and VIM-2 in Pseudomonas aeruginosa clinical isolates from a tertiary-level hospital in Thailand

Brief Report C. PIYAKUL, R. TIYAWISUTSRI, K. BOONBUMRUNG, Epidemiology & Infection, Volume 140 Issue 03, pp 539-541Abstract

Effectiveness of environmental decontamination as an infection control measure

Research Articles M. BANI-YAGHOUB, R. GAUTAM, D. DÖPFER, C. W. KASPAR, R. IVANEK, Epidemiology & Infection, Volume 140 Issue 03, pp 542-553Abstract

Transmission dynamics of primary pneumonic plague in the USA

Research Articles A. F. HINCKLEY, B. J. BIGGERSTAFF, K. S. GRIFFITH, P. S. MEAD, Epidemiology & Infection, Volume 140 Issue 03, pp 554-560Abstract

Transmission of Streptococcus pneumoniae in adults may occur through saliva

Brief Report H. LEVINE, S. ZARKA, R. DAGAN, T. SELA, V. ROZHAVSKI, D. I. COHEN, R. D. BALICER, Epidemiology & Infection, Volume 140 Issue 03, pp 561-565Abstract

Haemophilus influenzae type b infection, vaccination, and H. influenzae carriage in children in Minnesota, 2008–2009

Research Articles S. A. LOWTHER, N. SHINODA, B. A. JUNI, M. J. THEODORE, X. WANG, S. L. JAWAHIR, M. L. JACKSON, A. COHN, R. DANILA, R. LYNFIELD, the Hib Survey Team null, Epidemiology & Infection, Volume 140 Issue 03, pp 566-574Abstract

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.

Isolation and Molecular Characterization of Escherichia coli O157 from Broiler and Human Samples