Serosurveillance to Monitor Onchocerciasis Elimination: The Ugandan Experience

Uganda is the only African country whose onchocerciasis elimination program uses a two-pronged approach of vector control and mass drug distribution. The Ugandan program relies heavily upon the use of serosurveys of children to monitor progress toward elimination. The program has tested over 39,000 individuals from 11 foci for Onchocerca volvulus exposure, using the Ov16 ELISA test. The data show that the Ov16 ELISA is a useful operational tool to monitor onchocerciasis transmission interruption in Africa at the World Health Organization (WHO) recommended threshold of < 0.1% in children. The Ugandan experience has also resulted in a re-examination of the statistical methods used to estimate the boundary of the upper 95% confidence interval for the WHO prevalence threshold when all samples tested are negative. This has resulted in the development of Bayesian and hypergeometric statistical methods that reduce the number of individuals who must be tested to meet the WHO criterion.     

Evaluating the feasibility and uptake of a community‐led HIV testing and multi‐disease health campaign in rural Uganda

Introduction: Multi‐disease community health campaigns can be effective for population‐wide HIV testing in a research setting (SEARCH: NCT01864603). We sought to evaluate feasibility and uptake of a community‐led health campaign (CLHC) planned and implemented by village leaders and local clinic workers in Uganda. Methods: Over five months in 2014, locally elected village leaders and Ministry of Health (MoH) clinic staff in a rural parish in Uganda planned a census followed by a CLHC, after training by two SEARCH trial consultants and by leaders from a neighbouring parish that had previously participated in a SEARCH health campaign. We defined feasibility as: (1) elected leaders’ participation in training and implementation of pre‐campaign census and mobilization activities; (2) implementation of all campaign activities by MoH‐funded, local clinic staff; and (3) community participation in the campaign, including point‐of‐care screening for HIV, malaria, hypertension and diabetes, and same‐day referral for male circumcision and family planning (FP). Costing of all salaries and supplies was conducted. Results: Elected leaders from all eight villages in the parish participated in CLHC training. They and local clinic staff met monthly to select and plan CLHC services. Village leaders then leveraged existing volunteer health teams to perform a door‐to‐door census, enumerating 5,202 parish residents over 2 weeks. 2,753 (53%) residents participated in the 6‐day CLHC. Of 1,584 adult participants, 1,474 (93%) tested for HIV: 105/1,474 (7.1%) tested HIV positive. 27% (751/2,753) of participants reported fever and underwent malaria rapid diagnostic testing: 5.3% (40/751) tested positive. Among adults screened, 19% (271/1,452) were hypertensive, and 3% (18/637) had a random blood sugar >11.1 mmol/L. Of 805 men and boys (>10 years), 91 (11%) accepted same‐day clinic referral and underwent medical circumcision. Of 900 women offered same‐day long‐term FP referrals, 25 accepted. The CLHC cost, including census, mobilization and testing services, was $23,597 ($8.57/participant). C onclusions: Elected village leaders successfully planned and conducted a 6‐day multi‐disease health campaign with service provision by local clinic staff that reached over half of a rural Ugandan community. These data suggest it is feasible for local leaders and clinics to adopt a multi‐disease health campaign approach to scale‐up HIV testing in rural Africa.     

SVEP1 plays a crucial role in epidermal differentiation

SVEP1 is a recently identified multidomain cell adhesion protein, homologous to the mouse polydom protein, which has been shown to mediate cell‐cell adhesion in an integrin‐dependent manner in osteogenic cells. In this study, we characterized SVEP1 function in the epidermis. SVEP1 was found by qRT‐PCR to be ubiquitously expressed in human tissues, including the skin. Confocal microscopy revealed that SVEP1 is normally mostly expressed in the cytoplasm of basal and suprabasal epidermal cells. Downregulation of SVEP1 expression in primary keratinocytes resulted in decreased expression of major epidermal differentiation markers. Similarly, SVEP1 downregulation was associated with disturbed differentiation and marked epidermal acanthosis in three‐dimensional skin equivalents. In contrast, the dispase assay failed to demonstrate significant differences in adhesion between keratinocytes expressing normal vs low levels of SVEP1. Homozygous Svep1 knockout mice were embryonic lethal. Thus, to assess the importance of SVEP1 for normal skin homoeostasis in vivo, we downregulated SVEP1 in zebrafish embryos with a Svep1‐specific splice morpholino. Scanning electron microscopy revealed a rugged epidermis with perturbed microridge formation in the centre of the keratinocytes of morphant larvae. Transmission electron microscopy analysis demonstrated abnormal epidermal cell‐cell adhesion with disadhesion between cells in Svep1‐deficient morphant larvae compared to controls. In summary, our results indicate that SVEP1 plays a critical role during epidermal differentiation.     

Comparative study of catheter drainage and needle aspiration in management of large liver abscesses

Objective  

To compare the effectiveness of percutaneous catheter drainage (PCD) and percutaneous needle aspiration (PNA) in the management of large (>10 cm diameter) liver abscesses.     

Competition for self ligands restrains homeostatic proliferation of naive CD4 T cells

T cell antigen receptor (TCR) diversity is a critical feature of adaptive immunity. However, restriction of TCR diversity is a potential risk during immune reconstitution by homeostatic proliferation. What peripheral mechanisms are in place to maintain TCR diversity during recovery from lymphopenia? Here, we examine competition between several monoclonal CD4 T cell populations in RAG(-/-) and TCR Tg RAG(-/-) environments. The results suggest that specific self ligands constitute a critical limiting resource essential for homeostatic proliferation of naive CD4 T cells. In addition, T cells ignore large numbers of competitors as long as their TCR specificity is different and other non-MHC resources are not limiting. Therefore, the numbers of self ligands expressed in the periphery set the limits on TCR diversity.     

Universal nevirapine upon presentation in labor to prevent mother-to-child HIV transmission in high prevalence settings

OBJECTIVE: To assess the uptake of and adherence to nevirapine to prevent mother-to-child HIV transmission among women of unknown HIV serostatus presenting in labor. We also assessed preliminary efficacy of the approach. DESIGN: Women of unknown HIV serostatus presenting in labor were offered single-dose nevirapine in a prospective cohort study. Two additional contemporaneous comparison populations were also studied. METHODS: We measured uptake by counting the number of women that accepted enrollment when offered. We measured adherence with cord blood nevirapine assay. We measured preliminary efficacy with HIV DNA polymerase chain reaction of infant blood spots at 4-6 weeks of life. RESULTS: Of 1591 women approached in labor, 634 (40%) took up the intervention and received nevirapine, of whom 185 (29%) were HIV infected. Of 179 cord blood specimens from HIV-exposed infants that could be evaluated, 178 (99.4%) had nevirapine detected. This was higher than the 73 of 98 (74%) adherence rate observed in a comparison cohort in which women self-administered nevirapine before presenting to the labor ward (P < 0.001). Of 145 available infant specimens, 17 (11.7%) showed evidence of infection at 4-6 weeks, compared with 12 of 60 (20%) infants born immediately prior to study commencement whose HIV-infected mothers did not receive nevirapine (P < 0.05). CONCLUSIONS: Nevirapine without HIV testing upon presentation in labor was accepted by two-fifths of women. Because therapy is directly observed, adherence is nearly perfect. Labor ward dosing to enhance nevirapine coverage should be considered as an adjunct to antenatal nevirapine administration for prevention of mother-to-child transmission of HIV.     

The use of the hydrodynamic HBV animal model to study HBV biology and anti-viral therapy.

A simple reproducible and versatile small animal model for hepatitis B virus (HBV) infection is still unavailable. We have generated a simple transient liver-targeted transgenic mouse. Hydrodynamics tail vein injection of a head-to-tail dimer of adw HBV genome (pHBVadwHTD) into immunocompetent mice generated HBsAg and HBeAg expression in both serum and hepatocytes, followed by seroconversion. The injection of pHBVadwHTD into SCID mice generated prolonged HBsAg and HBeAg antigenemia and HBV viremia. Our results demonstrate that hydrodynamic injection of naked DNA could support the generation of HBV particles. We used this model for the assessment of anti-viral agents. Administration of our human monoclonal antibodies, HBV-Ab17(XTL) and HBV-Ab19(XTL), as well as Lamivudine (3TC) treatment suppressed HBV viremia. The model presented herein supports long and stable expression of HBV and will enable determination of various biological questions related to HBV life cycle, mutants and could enhance the development of anti-viral reagents.