Yield and Coverage of Active Case Finding Interventions for Tuberculosis Control:A Systematic Review and Meta-analysis.

Background. Active case finding (ACF) for tuberculosis (TB) is a key strategy to reduce diagnostic delays, expedite treatment, and prevent transmission. Objective. Our objective was to identify the populations, settings, screening and diagnostic approaches that optimize coverage (proportion of those targeted who were screened) and yield (proportion of those screened who had active TB) in ACF programs. Methods. We performed a comprehensive search to identify studies published from 1980-2016 that reported the coverage and yield of different ACF approaches. For each outcome, we conducted meta-analyses of single proportions to produce estimates across studies, followed by meta-regression to identify predictors. Findings. Of 3,972 publications identified, 224 met criteria after full-text review. Most individuals who were targeted successfully completed screening, for a pooled coverage estimate of 93.5%. The pooled yield of active TB across studies was 3.2%. Settings with the highest yield were internally-displaced persons camps (15.6%) and healthcare facilities (6.9%). When compared to symptom screening as the reference standard, studies that screened individuals regardless of symptoms using microscopy, culture, or GeneXpert®MTB/RIF (Xpert) had 3.7% higher case yield. In particular, microbiological screening (usually microscopy) as the initial test, followed by culture or Xpert for diagnosis had 3.6% higher yield than symptom screening followed by microscopy for diagnosis. In a model adjusted for use of Xpert testing, approaches targeting persons living with HIV (PLWH) had a 4.9% higher yield than those targeting the general population. In all models, studies targeting children had higher yield (4.8%-5.7%) than those targeting adults. Conclusion. ACF activities can be implemented successfully in various populations and settings. Screening yield was highest in internally-displaced person and healthcare settings, and among PLWH and children. In high-prevalence settings, ACF approaches that screen individuals with laboratory tests regardless of symptoms have higher yield than approaches focused on symptomatic individuals

A prospective study of vaginal trichomoniasis and HIV-1 shedding in women on antiretroviral therapy

<p>Abstract</p> <p>Background</p> <p><it>Trichomonas vaginalis </it>has been associated with increased vaginal HIV-1 RNA shedding in antiretroviral therapy (ART)-naïve women. The effect of trichomoniasis on vaginal HIV-1 shedding in ART-treated women has not been characterized. We tested the hypothesis that <it>T. vaginalis </it>infection would increase vaginal HIV-1 RNA shedding in women on ART, and that successful treatment would reduce vaginal HIV-1 RNA levels.</p> <p>Methods</p> <p>We conducted a prospective cohort study including monthly follow-up of 147 women receiving ART in Mombasa, Kenya. Those with <it>T. vaginalis </it>infection, defined by the presence of motile trichomonads on vaginal saline wet mount, received treatment with single dose metronidazole (2 g). Test of cure was performed at the next monthly visit. Using the pre-infection visit as the reference category, we compared detection of vaginal HIV-1 RNA before versus during and after infection using generalized estimating equations. A cut-off of 100 HIV-1 RNA copies/swab was used as the lower limit for linear quantitation.</p> <p>Results</p> <p>Among 31 women treated for trichomoniasis, the concentration of vaginal HIV-1 RNA was above the limit for quantitation before, during, and after <it>T. vaginalis </it>infection in 4 (13% [95% CI 4% - 30%]), 4 (13% [95% CI 4% - 30%]), and 5 (16% [95% confidence interval {CI} 5% - 34%]) women respectively. After adjusting for potential confounding factors, we could detect no difference in the likelihood of detecting vaginal HIV-1 RNA before versus during infection (odds ratio [OR] 1.41, 95% CI 0.23 - 8.79, p = 0.7). In addition, detection of HIV-1 RNA was similar before infection versus after successful treatment (OR 0.68, 95% CI (0.13 - 3.45), p = 0.6).</p> <p>Conclusion</p> <p>Detection of vaginal HIV-1 RNA during ART was uncommon at visits before, during and after <it>T. vaginalis </it>infection.</p

Epidemiological linkages between sexually transmitted infections

Thesis (Ph.D.)--University of Washington, 2014INTRODUCTION: Interactions between STIs can be complex and difficult to disentangle. These conditions share a common group of sexual risk factors, which may lead to the identification of non-causal associations. Studies that aim to determine the temporal sequence of STIs require prospective data collection with frequent STI assessment, as well as careful control for potential confounding factors. We conducted three studies to further characterize the complex inter-relationships between several STIs including HIV, utilizing data from a cohort of female sex workers (FSWs) in Mombasa, Kenya. The specific aims of these studies were: 1) To explore the contribution (population attributable risk percent) of STIs to HIV acquisition among Kenyan FSWs, and how this has changed over time since the cohort was established 2) To assesses the incidence and correlates of Chlamydia trachomatis infection among HIV-seropositive and seronegative women enrolled in the cohort and 3) To determine the effect of incident HSV-2 on subsequent BV episodes among HIV-seronegative women. METHODS: We conducted longitudinal follow-up and prospective cohort analyses to complete the three specific aims. The study was conducted within the Mombasa cohort, an established, open cohort study of high-risk women. Follow-up began in February 1993, with over 3500 women enrolled to date. The eligibility criteria to join the cohort are: age 16 - 50 years, residing in the Mombasa area, self-identifying as exchanging sex for payment in cash or in kind, and able to provide informed consent. Participants were seen monthly at the research clinic, where a standardized interview addressing past medical and sexual history is administered. They also receive a physical and pelvic examination, with collection of genital samples to test for STIs. RESULTS: Aim 1: Between 1993 and 2012, 1,964 women contributed 6,135 person-years of follow-up. The overall PAR% for each infection was; prevalent HSV-2 (48.3%), incident HSV-2 (4.5%), BV (15.1%), intermediate microbiota (7.5%), vaginal yeast (6.4%), T. vaginalis (1.1%), N. gonorrhoeae (0.9%), non-specific cervicitis (0.7%), GUD (0.8%), genital warts (-0.2%). The PAR% for prevalent HSV-2 (40.4%, 61.8%, 58.4%, 48.3%) and BV (17.1%, 19.5%, 14.7%, 17.1%), were high but did not change significantly over time. The PAR% for trichomoniasis, gonorrhea, GUD and genital warts all remained <3% across the four study periods. Aim 2: Between August 2006 and December 2010, 865 women contributed 2011 person-years of observation. Sixty-four women experienced 101 episodes of C. trachomatis infection (incidence rate of 5.0/100 person-years). In multivariate analyses, younger age (<25 years and 25-34 years versus ≥35 years; hazard ratio [HR] 8.49 95% CI 4.1-17.7 and HR 2.9 95% CI 1.7-5.0 respectively), depot medroxyprogesterone acetate use (HR 1.8 95% CI 1.1-3.0) and recent Neisseria gonorrhoeae infection (HR 3.3 95% CI 1.5-7.4) were significantly associated with increased risk of acquiring C. trachomatis infection. Aim 3: Between 1993 and December 2010, one hundred and sixty four of 406 HSV-2/HIV-1-seronegative Kenyan women acquired HSV-2, incidence rate 21/100 person-years. Incident HSV-2 was associated with increased likelihood of BV (adjusted OR 1.28; 95% CI 1.05-1.56; p=0.01). CONCLUSION: At the population level, abnormal vaginal microbiota and HSV-2 have consistently been the largest contributors to these high-risk women's risk for HIV acquisition over the past 20 years. Interventions that prevent these conditions would benefit women's health generally, and also hold potential for reducing HIV risk in women. Secondly, we found a high incidence of C. trachomatis among younger high-risk women suggesting the need for screening as an important public health intervention for this population. Finally, our findings strengthen the evidence for a causal link between genital HSV-2 infection and disruption of the vaginal microbiota

Preference of specimen collection methods for human papillomavirus detection for cervical cancer screening: a cross-sectional study of high-risk women in Mombasa, Kenya

Abstract Objectives Self-collection of genital specimens for high-risk types of human papillomavirus (hrHPV) detection may increase cervical cancer screening uptake. We hypothesized that women would prefer self-collection to clinician-collection of genital specimens. To test this hypothesis, and women’s preference between two different self-collection approaches, a total of 199 women were enrolled in a cross-sectional study in Mombasa, Kenya. Materials and methods Participants provided self-collected specimens using the Evalyn cytobrush (Rovers) stored in a dry tube and the Viba cytobrush (Rovers) stored in wet Aptima media (Hologic). A clinician also collected cervical specimens for hrHPV testing and for cytology, and performed visual inspection using acetic acid. A post-examination questionnaire assessed preferences for the different methods of specimen collection. To test the difference in proportions for each collection method, we performed an exact binomial probability test, under the null hypothesis that women would prefer each specimen-collection method equally. Results Most women preferred clinician-collection over self-collection (68% versus 32%, p < 0.01). For self-collection, dry-self collection with the Evalyn brush was preferred over the wet-selection with the Viba brush (53% versus 27%, p < 0.01). There was no association between preference for self-collection and preference for a particular self-collection cytobrush. Conclusion Further research to understand and address obstacles to self-collection of genital specimens may be needed to improve the uptake of self-collection for cervical cancer screening, especially in settings with poor access to trained healthcare providers

Genital HSV Shedding among Kenyan Women Initiating Antiretroviral Therapy.

Genital ulcer disease (GUD) prevalence increases in the first month of antiretroviral treatment (ART), followed by a return to baseline prevalence by month 3. Since most GUD is caused by herpes simplex virus type 2 (HSV-2), we hypothesized that genital HSV detection would follow a similar pattern after treatment initiation.We conducted a prospective cohort study of 122 HSV-2 and HIV-1 co-infected women with advanced HIV disease who initiated ART and were followed closely with collection of genital swab specimens for the first three months of treatment.At baseline, the HSV detection rate was 32%, without significant increase in genital HSV detection noted during the first month or the third month of ART. HIV-1 shedding declined during this period; no association was also noted between HSV and HIV-1 shedding during this period.Because other studies have reported increased HSV detection in women initiating ART and we have previously reported an increase in GUD during early ART, it may be prudent to counsel HIV-1 infected women initiating ART that HSV shedding in the genital tract may continue after ART initiation

Prevalence and predictors of unmet contraceptive need in HIV-positive female sex workers in Mombasa, Kenya.

ObjectivesFemale sex workers (FSWs) in sub-Saharan Africa are a key population for HIV prevention and treatment interventions, but less attention is given to their family planning needs. We evaluated the prevalence and predictors of unmet contraceptive need in HIV-positive FSWs.Study designThis cross-sectional analysis used data from an existing longitudinal study of FSWs in Mombasa, Kenya. This analysis included women who were HIV positive, age ≥18 years, pre-menopausal, not currently pregnant or desiring pregnancy, and reported exchanging sex for cash or in-kind payment at the time of enrollment. Unmet contraceptive need was defined as non-use of modern non-barrier contraceptives and not currently trying to become pregnant. Poisson regression was used to identify factors independently associated with unmet contraceptive need.ResultsAmong 346 HIV-positive FSWs, 125 (36.1%) reported modern non-barrier contraceptive use, leaving 221 (63.9%, 95%CI 58.8-68.9%) with unmet contraceptive need. Condom use was the only form of contraception for 129 (37.3%) participants. In unadjusted analyses, unmet contraceptive need was associated with physical abuse in the past year by someone other than a regular partner (PR 1.2, 95%CI 1.0-1.5), desire for (more) children (PR 1.3, 95%CI 1.1-1.5), and having 2-3 previous pregnancies compared to 0-1 prior pregnancies (PR 0.8, 95%CI 0.6-0.9). In adjusted analyses, lower number of previous pregnancies and having desire for future children remained significantly associated with a higher prevalence of unmet contraceptive need.ConclusionsUnmet need for modern non-barrier contraception was found in two-thirds of HIV-positive FSWs who reported that they were not currently trying to become pregnant, and was higher in women with the lowest number of prior pregnancies (0-1 prior pregnancies) and in those reporting desire for (more) children in the future. These findings highlight the need for concerted efforts to identify and eliminate barriers to contraceptive use in FSWs living with HIV

Principles, practices and knowledge of clinicians when assessing febrile children: a qualitative study in Kenya

Abstract Background Clinicians in low resource settings in malaria endemic regions face many challenges in diagnosing and treating febrile illnesses in children. Given the change in WHO guidelines in 2010 that recommend malaria testing prior to treatment, clinicians are now required to expand the differential when malaria testing is negative. Prior studies have indicated that resource availability, need for additional training in differentiating non-malarial illnesses, and lack of understanding within the community of when to seek care play a role in effective diagnosis and treatment. The objective of this study was to examine the various factors that influence clinician behavior in diagnosing and managing children presenting with fever to health centres in Kenya. Methods A total of 20 clinicians (2 paediatricians, 1 medical officer, 2 nurses, and 15 clinical officers) were interviewed, working at 5 different government-sponsored public clinic sites in two areas of Kenya where malaria is prevalent. Clinicians were interviewed one-on-one using a structured interview technique. Interviews were then analysed qualitatively for themes. Results The following five themes were identified: (1) Strong familiarity with diagnosis of malaria and testing for malaria; (2) Clinician concerns about community understanding of febrile illness, use of traditional medicine, delay in seeking care, and compliance; (3) Reliance on clinical guidelines, history, and physical examination to diagnose febrile illness and recognize danger signs; (4) Clinician discomfort with diagnosis of primary viral illness leading to increased use of empiric antibiotics; and (5) Lack of resources including diagnostic testing, necessary medications, and training modalities contributes to the difficulty clinicians face in assessing and treating febrile illness in children. These themes persisted across all sites, despite variation in levels of medical care. Within these themes, clinicians consistently expressed a need for reliable basic testing, especially haemograms and bacterial cultures. Clinicians discussed the use of counseling and education to improve community understanding of febrile illness in order to decrease preventable deaths in children. Conclusion Results of this study suggest that since malarial testing has become more widespread, clinicians working in resource-poor environments still face difficulty when evaluating a child with fever, especially when malaria testing is negative. Improving access to additional diagnostics, continuing medical education, and ongoing evaluation and revision of clinical guidelines may lead to more consistent management of febrile illness by providers, and may potentially decrease prescription of unnecessary antibiotics. Additional interventions at the community level may also have an important role in managing febrile illness, however, more studies are needed to identify targets for intervention at both the clinic and community levels

Association between non-barrier modern contraceptive use and condomless sex among HIV-positive female sex workers in Mombasa, Kenya: A prospective cohort analysis

<div><p>Background</p><p>As access to antiretroviral therapy in sub-Saharan Africa continues to expand, more women with HIV can expect to survive through their reproductive years. Modern contraceptives can help women choose the timing and spacing of childbearing. However, concerns remain that women with HIV who use non-barrier forms of modern contraception may engage in more condomless sex because of their decreased risk of unintended pregnancy. We examined whether non-barrier modern contraceptive use by HIV-positive female sex workers was associated with increased frequency of recent condomless sex, measured by detection of prostate-specific antigen (PSA) in vaginal secretions.</p><p>Methods</p><p>Women who were HIV-positive and reported transactional sex were included in this analysis. Pregnant and post-menopausal follow-up time was excluded, as were visits at which women reported trying to get pregnant. At enrollment and quarterly follow-up visits, a pelvic speculum examination with collection of vaginal secretions was conducted for detection of PSA. In addition, women completed a structured face-to-face interview about their current contraceptive methods and sexual risk behavior at enrollment and monthly follow-up visits. Log-binomial generalized estimating equations regression was used to test for associations between non-barrier modern contraceptive use and detection of PSA in vaginal secretions and self-reported condomless sex. Data from October 2012 through September 2014 were included in this analysis.</p><p>Results</p><p>Overall, 314 women contributed 1,583 quarterly examination visits. There was minimal difference in PSA detection at contraceptive-exposed versus contraceptive-unexposed visits (adjusted relative risk [aRR] 1.28, 95% confidence interval [95% CI] 0.93–1.76). There was a higher rate of self-reported condomless sex at visits where women reported using modern contraceptives, but this difference was not statistically significant after adjustment for potential confounding factors (aRR 1.59, 95% CI 0.98–2.58).</p><p>Conclusion</p><p>Non-barrier methods of modern contraception were not associated with increased risk of objective evidence of condomless sex.</p></div

Baseline Characteristics of HSV-2-Seropositive Women Initiating ART.

<p>Baseline Characteristics of HSV-2-Seropositive Women Initiating ART.</p