The Epidemiology of Herpes Simplex Virus Type-2 Infection among Pregnant Women in Rural Mysore Taluk, India

To assess the prevalence and determinants of herpes simplex virus type 2 (HSV-2) infections among pregnant women attending mobile antenatal health clinic in rural villages in Mysore Taluk, India. Methods. Between January and September 2009, 487 women from 52 villages participated in this study. Each participant consented to provide a blood sample for HSV-2 and HIV testing and underwent an interviewer-administered questionnaire. Results. HSV-2 prevalence was 6.7% (95% confidence interval (CI) 4.4–9.0), and one woman tested positive for HIV.The median age of women was 20 years and 99% of women reported having a single lifetime sex partner.Women whose sex partner traveled away from home had 2.68 (CI: 1.13–6.34) times the odds of being HSV-2 seropositive compared to women whose sex partner did not travel. Having experienced genital lesions was also associated with HSV-2 infection ( value = 0.08). Conclusion.The 6.7% HSV-2 prevalence was similar to results obtained in studies among pregnant women in other parts of India. It appeared that most women in this study contracted HSV-2 from their spouses and few regularly used condoms. This finding highlights the need for public health policies to increase awareness and education about prevention methods among women and men living in rural India

A Pre-mRNA–Associating Factor Links Endogenous siRNAs to Chromatin Regulation

In plants and fungi, small RNAs silence gene expression in the nucleus by establishing repressive chromatin states. The role of endogenous small RNAs in metazoan nuclei is largely unknown. Here we show that endogenous small interfering RNAs (endo-siRNAs) direct Histone H3 Lysine 9 methylation (H3K9me) in Caenorhabditis elegans. In addition, we report the identification and characterization of nuclear RNAi defective (nrde)-1 and nrde-4. Endo-siRNA–driven H3K9me requires the nuclear RNAi pathway including the Argonaute (Ago) NRDE-3, the conserved nuclear RNAi factor NRDE-2, as well as NRDE-1 and NRDE-4. Small RNAs direct NRDE-1 to associate with the pre-mRNA and chromatin of genes, which have been targeted by RNAi. NRDE-3 and NRDE-2 are required for the association of NRDE-1 with pre-mRNA and chromatin. NRDE-4 is required for NRDE-1/chromatin association, but not NRDE-1/pre-mRNA association. These data establish that NRDE-1 is a novel pre-mRNA and chromatin-associating factor that links small RNAs to H3K9 methylation. In addition, these results demonstrate that endo-siRNAs direct chromatin modifications via the Nrde pathway in C. elegans

Evaluating risk factors and synergistic effects of two common HIV-1 coinfections: schistosomiasis and trichomoniasis

Thesis (Ph.D.)--University of Washington, 2018Introduction: HIV-1 coinfections have long been suspected of catalyzing the HIV-1 epidemic by increasing HIV-1 transmission or acquisition risk. The geographical distribution of coinfections may explain why some regions have been more heavily impacted by HIV-1. The primary objective of this dissertation was to expand our understanding of two common HIV-1 coinfections that have been hypothesized to increase the risk of HIV-1 transmission and acquisition: schistosomiasis and trichomoniasis. The specific aims of this dissertation were 1) Identify correlates of T. vaginalis infection within a population of HIV-1 serodiscordant heterosexual couples, 2) Estimate the association between schistosomiasis and HIV-1 acquisition, 3) Evaluate the impact of schistosome coinfection on HIV-1 set-point genital viral load levels, and 4) Evaluate the association between schistosome coinfection and HIV-1 set-point plasma viral load levels. Methods: To conduct these analyses, we used data from four cohort studies: the Partners in Prevention HSV/HIV Transmission Study, the Couples Observational Study, the Partners PrEP Study, and the Mombasa Cohort. All analyses utilized data from multiple cohorts. For all cohorts, a large amount of individual-level information was collected, including characteristics associated with HIV-1 acquisition risk and the prevalence of coinfections, permitting thorough adjustment for possible confounding factors. Results and Conclusions: Correlates of T. vaginalis infection: In a cross-sectional analysis of 8,155 HIV-1 serodiscordant couples, the strongest predictor of a prevalent T. vaginalis infection was having an infected sexual partner. Thus, concurrent treatment of sexual partners is critical to prevent reinfection. Among women, having a circumcised male partner was associated with reduced T. vaginalis risk while bacterial vaginosis (detected via Nugent Score) was associated with an increased risk, so expanding male circumcision programs and bacterial vaginosis treatment has the potential to reduce the prevalence of trichomoniasis. Schistosomiasis and HIV-1 acquisition risk: In nested case-control analyses including 575 HIV-1 seroconverters and 1,675 controls, S. mansoni infection was not associated with an increased the risk of HIV-1 acquisition. In addition, S. haematobium infection was not associated with a statistically significant increase in HIV-1 acquisition risk, though our result suggested that women with S. haematobium could face a moderate increased risk of HIV-1 acquisition. Schistosomiasis and set point HIV-1 RNA viral loads: Schistosomiasis was not associated with increased plasma HIV-1 viral loads. Our results do not support the hypothesis that schistosome coinfection increases the rate of HIV-1 disease progression. Schistosomiasis and genital HIV-1 RNA viral loads: Schistosomiasis was not associated with increased genital HIV-1 viral loads. Our results do not support the hypothesis that schistosome coinfection increases HIV-1 transmission risk

Timing of adverse events among voluntary medical male circumcision clients: Implications from routine service delivery in Zimbabwe.

BACKGROUND:Timing of routine follow-up visits after adult male circumcision (MC) differs by country and method. Most men do not attend all routine follow-up visits. This cross-sectional study aimed to further understanding of AE timing within a large-scale, routine, MC program to improve patient safety. METHODS:From 2013-2017, ZAZIC consortium performed 192,575 MCs in Zimbabwe; the reported adverse event (AE) rate was 0.3%. Three scheduled, routine, follow-up visits intend to identify AEs. For surgical MC, visits were days 2, 7 and 42 post-procedure. For PrePex (device-based), visits were days 7, 14 and 49. Descriptive statistics explored characteristics of those patients with AEs. For each MC method, chi-square tests were used to evaluate associations between AE timing (days from MC to AE diagnosis) and factors of interest (age, AE type, severity). RESULTS:Of 421 AEs, 290 (69%) were surgical clients: 55 (19%) AEs were ≤2 days post-MC; 169 (58%) between 3-7 days; 47 (16%) between days 8-14; and 19 (7%) were ≥15 post-MC. Among surgical clients, bleeding was most common AE on/before Day 2 while infections predominated in other follow-up periods (p<0.001). Younger surgical MC patients with AEs experienced AEs later than older clients (p<0.001). Among 131 (31%) PrePex clients with AEs, 46 (35%) were ≤2 days post-MC; 59 (45%) between 3-7 days; 16 (12%) between days 8-14; and 10 (7%) ≥15 post-MC. For PrePex clients, device displacements were more likely to occur early while late AEs were most commonly infections (p<0.001). CONCLUSION:Almost 23% of surgical and 8% of PrePex AEs occurred after Visit 2. Later AEs were likely infections. Clinicians, clients, and caregivers should be more effectively counseled that complications may arise after initial visits. Messages emphasizing attention to wound care until complete healing could help ensure client safety. Younger boys, ages 10-14, and their caregivers would benefit from improved, targeted, post-operative counseling

Implementing voluntary medical male circumcision using an innovative, integrated, health systems approach: experiences from 21 districts in Zimbabwe

Background: Despite increased support for voluntary medical male circumcision (VMMC) to reduce HIV incidence, current VMMC progress falls short. Slow progress in VMMC expansion may be partially attributed to emphasis on vertical (stand-alone) over more integrated implementation models that are more responsive to local needs. In 2013, the ZAZIC consortium began implementation of a 5-year, integrated VMMC program jointly with Ministry of Health and Child Care (MoHCC) in Zimbabwe. Objective: To explore ZAZIC’s approach emphasizing existing healthcare workers and infrastructure, increasing program sustainability and resilience. Methods: A process evaluation utilizing routine quantitative data. Interviews with key MoHCC informants illuminate program strengths and weaknesses. Methods: A process evaluation utilizing routine quantitative data. Interviews with key MoHCC informants illuminate program strengths and weaknesses. Results: In start-up and year 1 (March 2013–September, 2014), ZAZIC expanded from two to 36 static VMMC sites and conducted 46,011 VMMCs; 39,840 completed from October 2013 to September 2014. From October 2014 to September 2015, 44,868 VMMCs demonstrated 13% increased productivity. In October, 2015, ZAZIC was required by its donor to consolidate service provision from 21 to 10 districts over a 3-month period. Despite this shock, 57,282 VMMCs were completed from October 2015 to September 2016 followed by 44,414 VMMCs in only 6 months, from October 2016 to March 2017. Overall, ZAZIC performed 192,575 VMMCs from March 2013 to March, 2017. The vast majority of VMMCs were completed safely by MoHCC staff with a reported moderate and severe adverse event rate of 0.3%. Conclusion: The safety, flexibility, and pace of scale-up associated with the integrated VMMC model appears similar to vertical delivery with potential benefits of capacity building, sustainability and health system strengthening. These models also appear more adaptable to local contexts. Although more complicated than traditional approaches to program implementation, attention should be given to this country-led approach for its potential to spur positive health system changes, including building local ownership, capacity, and infrastructure for future public health programming

The impact of routine data quality assessments on electronic medical record data quality in Kenya

<div><p>Background</p><p>Routine Data Quality Assessments (RDQAs) were developed to measure and improve facility-level electronic medical record (EMR) data quality. We assessed if RDQAs were associated with improvements in data quality in KenyaEMR, an HIV care and treatment EMR used at 341 facilities in Kenya.</p><p>Methods</p><p>RDQAs assess data quality by comparing information recorded in paper records to KenyaEMR. RDQAs are conducted during a one-day site visit, where approximately 100 records are randomly selected and 24 data elements are reviewed to assess data completeness and concordance. Results are immediately provided to facility staff and action plans are developed for data quality improvement. For facilities that had received more than one RDQA (baseline and follow-up), we used generalized estimating equation models to determine if data completeness or concordance improved from the baseline to the follow-up RDQAs.</p><p>Results</p><p>27 facilities received two RDQAs and were included in the analysis, with 2369 and 2355 records reviewed from baseline and follow-up RDQAs, respectively. The frequency of missing data in KenyaEMR declined from the baseline (31% missing) to the follow-up (13% missing) RDQAs. After adjusting for facility characteristics, records from follow-up RDQAs had 0.43-times the risk (95% CI: 0.32–0.58) of having at least one missing value among nine required data elements compared to records from baseline RDQAs. Using a scale with one point awarded for each of 20 data elements with concordant values in paper records and KenyaEMR, we found that data concordance improved from baseline (11.9/20) to follow-up (13.6/20) RDQAs, with the mean concordance score increasing by 1.79 (95% CI: 0.25–3.33).</p><p>Conclusions</p><p>This manuscript demonstrates that RDQAs can be implemented on a large scale and used to identify EMR data quality problems. RDQAs were associated with meaningful improvements in data quality and could be adapted for implementation in other settings.</p></div

The association between facility characteristics and the risk that records contained missing values during baseline RDQAs.

<p>The association between facility characteristics and the risk that records contained missing values during baseline RDQAs.</p