Schistosoma mansoni Infections in Young Children: When Are Schistosome Antigens in Urine,Eggs in Stool and Antibodies to Eggs First Detectable?

Background

In Uganda, control of intestinal schistosomiasis with preventive chemotherapy is typically focused towards treatment of school-aged children; the needs of younger children are presently being investigated as in lakeshore communities very young children can be infected. In the context of future epidemiological monitoring, we sought to compare the detection thresholds of available diagnostic tools for Schistosoma mansoni and estimate a likely age of first infection for these children.

Methods and Findings

A total of 242 infants and preschool children (134 boys and 108 girls, mean age 2.9 years, minimum 5 months and maximum 5 years) were examined from Bugoigo, a well-known disease endemic village on Lake Albert. Schistosome antigens in urine, eggs in stool and host antibodies to eggs were inspected to reveal a general prevalence of 47.5% (CI₉₅ 41.1–54.0%), as ascertained by a positive criterion from at least one diagnostic method. Although children as young as 6 months old could be found infected, the average age of infected children was between 3¼–3¾ years, when diagnostic techniques became broadly congruent.

Conclusion

Whilst different assays have particular (dis)advantages, direct detection of eggs in stool was least sensitive having a temporal lag behind antigen and antibody methods. Setting precisely a general age of first infection is problematic but if present Ugandan policies continue, a large proportion of infected children could wait up to 3–4 years before receiving first medication. To better tailor treatment needs for this younger ageclass, we suggest that the circulating cathodic antigen urine dipstick method to be used as an epidemiological indicator.     

Can Volunteer Community Health Workers Decrease Child Morbidity and Mortality in Southwestern Uganda? An Impact Evaluation

Background

The potential for community health workers to improve child health in sub-Saharan Africa is not well understood. Healthy Child Uganda implemented a volunteer community health worker child health promotion model in rural Uganda. An impact evaluation was conducted to assess volunteer community health workers'' effect on child morbidity, mortality and to calculate volunteer retention.

Methodology/Principal Findings

Two volunteer community health workers were selected, trained and promoted child health in each of 116 villages (population ∼61,000) during 2006–2009. Evaluation included a household survey of mothers at baseline and post-intervention in intervention/control areas, retrospective reviews of community health worker birth/child death reports and post-intervention focus group discussions. Retention was calculated from administrative records. Main outcomes were prevalence of recent child illness/underweight status, community health worker reports of child deaths, focus group perception of effect, and community health worker retention. After 18–36 months, 86% of trained volunteers remained active. Post-intervention surveys in intervention households revealed absolute reductions of 10.2% [95%CI (−17.7%, −2.6%)] in diarrhea prevalence and 5.8% [95%CI (−11.5%, −0.003%)] in fever/malaria; comparative decreases in control households were not statistically significant. Underweight prevalence was reduced by 5.1% [95%CI (−10.7%, 0.4%)] in intervention households. Community health worker monthly reports revealed a relative decline of 53% in child deaths (<5 years old), during the first 18 months of intervention. Focus groups credited community health workers with decreasing child deaths, improved care-seeking practices, and new income-generating opportunities.

Conclusions/Significance

A low-cost child health promotion model using volunteer community health workers demonstrated decreased child morbidity, dramatic mortality trend declines and high volunteer retention. This sustainable model could be scaled-up to sub-Saharan African communities with limited resources and high child health needs.     

Rates of anti-tuberculosis drug resistance in Kampala-Uganda are low and not associated with HIV infection

Background

Drug resistance among tuberculosis patients in sub-Saharan Africa is increasing, possibly due to association with HIV infection. We studied drug resistance and HIV infection in a representative sample of 533 smear-positive tuberculosis patients diagnosed in Kampala, Uganda.

Methods/Principal Findings

Among 473 new patients, multidrug resistance was found in 5 (1.1%, 95% CI 0.3–2.5) and resistance to any drug in 57 (12.1%, 9.3–15.3). Among 60 previously treated patients this was 7 (11.7%, 4.8–22.6) and 17 (28.3%; 17.5–41.4), respectively. Of 517 patients with HIV results, 165 (31.9%, 27.9–36.1) tested positive. Neither multidrug (adjusted odds ratio (OR^adj) 0.7; 95% CI 0.19–2.6) nor any resistance (OR^adj 0.7; 0.43–1.3) was associated with HIV status. Primary resistance to any drug was more common among patients who had worked in health care (OR^adj 3.5; 1.0–12.0).

Conclusion/Significance

Anti-tuberculosis drug resistance rates in Kampala are low and not associated with HIV infection, but may be associated with exposure during health care.     

PKCθ Regulates T Cell Motility via Ezrin-Radixin-Moesin Localization to the Uropod

Cell motility is a fundamental process crucial for function in many cell types, including T cells. T cell motility is critical for T cell-mediated immune responses, including initiation, activation, and effector function. While many extracellular receptors and cytoskeletal regulators have been shown to control T cell migration, relatively few signaling mediators have been identified that can modulate T cell motility. In this study, we find a previously unknown role for PKCθ in regulating T cell migration to lymph nodes. PKCθ localizes to the migrating T cell uropod and regulates localization of the MTOC, CD43 and ERM proteins to the uropod. Furthermore, PKCθ-deficient T cells are less responsive to chemokine induced migration and are defective in migration to lymph nodes. Our results reveal a novel role for PKCθ in regulating T cell migration and demonstrate that PKCθ signals downstream of CCR7 to regulate protein localization and uropod formation.     

Aetiology of Pulmonary Symptoms in HIV-Infected Smear Negative Recurrent PTB Suspects in Kampala,Uganda: A Cross-Sectional Study

Introduction

Previously treated TB patients with pulmonary symptoms are often considered recurrent TB suspects in the resource-limited settings, where investigations are limited to microscopy and chest x-ray. Category II anti-TB drugs may be inappropriate and may expose patients to pill burden, drug toxicities and drug-drug interactions.

Objective

To determine the causes of pulmonary symptoms in HIV-infected smear negative recurrent pulmonary tuberculosis suspects at Mulago Hospital, Kampala.

Methods

Between March 2008 and December 2011, induced sputum samples of 178 consented HIV-infected smear negative recurrent TB suspects in Kampala were subjected to MGIT and LJ cultures for mycobacteria at TB Reference Laboratory, Kampala. Processed sputum samples were also tested by PCR to detect 18S rRNA gene of P.jirovecii and cultured for other bacteria.

Results

Bacteria, M. tuberculosis and Pneumocystis jirovecii were detected in 27%, 18% and 6.7% of patients respectively and 53.4% of the specimens had no microorganisms. S. pneumoniae, M. catarrhalis and H. influenzae were 100% susceptible to chloramphenicol and erythromycin but co-trimoxazole resistant.

Conclusion

At least 81.5% of participants had no microbiologically-confirmed TB. However our findings call for thorough investigation of HIV-infected smear negative recurrent TB suspects to guide cost effective treatment.     

Assessment of Health Benefits and Cost-Effectiveness of 10-Valent and 13-Valent Pneumococcal Conjugate Vaccination in Kenyan Children

Background

The GAVI Alliance supported10-valent pneumococcal conjugate vaccine (PCV10) introduction in Kenya. We estimated the cost-effectiveness of introducing either PCV10 or the13-valent vaccine (PCV13) from a societal perspective and explored the incremental impact of including indirect vaccine effects.

Methods

The costs and effects of pneumococcal vaccination among infants born in Kenya in 2010 were assessed using a decision analytic model comparing PCV10 or PCV13, in turn, with no vaccination. Direct vaccine effects were estimated as a reduction in the incidence of pneumococcal meningitis, sepsis, bacteraemic pneumonia and non-bacteraemic pneumonia. Pneumococcal disease incidence was extrapolated from a population-based hospital surveillance system in Kilifi and adjustments were made for variable access to care across Kenya. We used vaccine efficacy estimates from a trial in The Gambia and accounted for serotype distribution in Kilifi. We estimated indirect vaccine protection and serotype replacement by extrapolating from the USA. Multivariable sensitivity analysis was conducted using Monte Carlo simulation. We assumed a vaccine price of US$ 3.50 per dose.

Findings

The annual cost of delivering PCV10 was approximately US$14 million. We projected a 42.7% reduction in pneumococcal disease episodes leading to a US$1.97 million reduction in treatment costs and a 6.1% reduction in childhood mortality annually. In the base case analysis, costs per discounted DALY and per death averted by PCV10, amounted to US$ 59 (95% CI 26–103) and US$ 1,958 (95% CI 866–3,425), respectively. PCV13 introduction improved the cost-effectiveness ratios by approximately 20% and inclusion of indirect effects improved cost-effectiveness ratios by 43–56%. The break-even prices for introduction of PCV10 and PCV13 are US$ 0.41 and 0.51, respectively.

Conclusions

Introducing either PCV10 or PCV13 in Kenya is highly cost-effective from a societal perspective. Indirect effects, if they occur, would significantly improve the cost-effectiveness.     

Factors Associated with Risky Sexual Practices among Female Sex Workers in Karnataka,India

Introduction

The objectives of this study are to develop a summary measure of risky sexual practice and examine the factors associated with this among female sex workers (FSWs) in Karnataka, India.

Materials and Methods

Data were drawn from special behavioral surveys (SBS) conducted in 2007 among 577 FSWs in two districts of Karnataka, India: Belgaum and Bangalore. FSWs were recruited using the two-stage probability sampling design. FSWs'' sexual practice was considered risky if they reported inconsistent condom use with any sexual partner and reported experience of one of the following vulnerabilities to HIV risk: anal sex, alcohol consumption prior to sex and concurrent sexual relationships.

Results

About 51% of FSWs had engaged in risky sexual practice. The odds of engaging in risky sex were higher among FSWs who were older (35+ years) than younger (18–25 years) (58% vs. 45%, Adjusted Odds Ratio (AOR): 2.0, 95% confidence interval (CI): 1.2–3.4), who were currently married than never married (61% vs. 51%, AOR: 4.8, 95% CI: 2.5–9.3), who were in sex work for 10+ years than those who were in sex work for less than five years (66% vs. 39%, AOR: 2.6, 95% CI: 1.6–4.2), and who had sex with 3+ clients/day than those who had sex with fewer clients (67% vs. 38%, AOR: 3.7, 95% CI:2.5–5.5).

Conclusion

FSWs who are older, currently married, practicing sex work for longer duration and with higher clientele were more likely to engage in risky sexual practices. HIV prevention programs should develop strategies to reach these most-at risk group of FSWs to optimize the effectiveness of such programs.     

Polymorphism, divergence, and the role of recombination in Saccharomyces cerevisiae genome evolution

A contentious issue in molecular evolution and population genetics concerns the roles of recombination as a facilitator of natural selection and as a potential source of mutational input into genomes. The budding yeast Saccharomyces cerevisiae, in particular, has injected both insights and confusion into this topic, as an early system subject to genomic analysis with subsequent conflicting reports. Here, we revisit the role of recombination in mutation and selection with recent genome-wide maps of population polymorphism and recombination for S. cerevisiae. We confirm that recombination-associated mutation does not leave a genomic signature in yeast and conclude that a previously observed, enigmatic, negative recombination-divergence correlation is largely a consequence of weak selection and other genomic covariates. We also corroborate the presence of biased gene conversion from patterns of polymorphism. Moreover, we identify significant positive relations between recombination and population polymorphism at putatively neutrally evolving sites, independent of other factors and the genomic scale of interrogation. We conclude that widespread natural selection across the yeast genome has left its imprint on segregating genetic variation, but that this signature is much weaker than in Drosophila and Caenorhabditis.