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.

COVID-19 Surveillance and Investigations in Workplaces - Seattle & King County, Washington, June 15-November 15, 2020.

Workplace activities involving close contact with coworkers and customers can lead to transmission of SARS-CoV-2, the virus that causes COVID-19 (1,2). Information on the approach to and effectiveness of COVID-19 workplace investigations is limited. In May 2020, Public Health - Seattle & King County (PHSKC), King County, Washington established a COVID-19 workplace surveillance and response system to enhance COVID-19 contact tracing and identify outbreaks in workplaces. During June 15-November 15, 2020, a total of 2,881 workplaces in King County reported at least one case of COVID-19. Among 1,305 (45.3%) investigated workplaces,* 524 (40.3%) met the definition of a workplace outbreak.† Among 306 (58.4%) workplaces with complete data,§ an average of 4.4 employee COVID-19 cases¶ (median = three; range = 1-65) were identified per outbreak, with an average attack rate among employees of 17.5%. PHSKC and the Washington State Department of Health optimized resources by establishing a classification scheme to prioritize workplace investigations as high, medium, or low priority based on workplace features observed to be associated with increased COVID-19 spread and workforce features associated with severe disease outcomes. High-priority investigations were significantly more likely than medium- and low-priority investigations to have two or more cases among employees (p<0.001), two or more cases not previously linked to the workplace (p<0.001), or two or more exposed workplace contacts not previously identified during case interviews (p = 0.002). Prioritization of workplace investigations allowed for the allocation of limited resources to effectively conduct workplace investigations to limit the potential workplace spread of COVID-19. Workplace investigations can also serve as an opportunity to provide guidance on preventing workplace exposures to SARS-CoV-2, facilitate access to vaccines, and strengthen collaborations between public health and businesses.

Patterns of Gender-Based Violence and Associations with Mental Health and HIV Risk Behavior Among Female Sex Workers in Mombasa, Kenya: A Latent Class Analysis.

Gender-based violence (GBV) is common among female sex workers (FSWs) and is associated with multiple HIV risk factors, including poor mental health, high-risk sexual behavior, and sexually transmitted infections (STIs). Prior studies have focused on GBV of one type (e.g. physical or sexual) or from one kind of perpetrator (e.g., clients or regular partners), but many FSWs experience overlapping types of violence from multiple perpetrators, with varying frequency and severity. We examined the association between lifetime patterns of GBV and HIV risk factors in 283 FSWs in Mombasa, Kenya. Patterns of GBV were identified with latent class analysis based on physical, sexual, or emotional violence from multiple perpetrators. Cross-sectional outcomes included depressive symptoms, post-traumatic stress disorder (PTSD) symptoms, disordered alcohol and other drug use, number of sex partners, self-reported unprotected sex, prostate-specific antigen (PSA) in vaginal secretions, and a combined unprotected sex indicator based on self-report or PSA detection. We also measured HIV/STI incidence over 12 months following GBV assessment. Associations between GBV patterns and each outcome were modeled separately using linear regression for mental health outcomes and Poisson regression for sexual risk outcomes. Lifetime prevalence of GBV was 87%. We identified 4 GBV patterns, labeled Low (21% prevalence), Sexual (23%), Physical/Moderate Emotional (18%), and Severe (39%). Compared to women with Low GBV, those with Severe GBV had higher scores for depressive symptoms, PTSD symptoms, and disordered alcohol use, and had more sex partners. Women with Sexual GBV had higher scores for disordered alcohol use than women with Low GBV, but similar sexual risk behavior. Women with Physical/Moderate Emotional GBV had more sex partners and a higher prevalence of unprotected sex than women with Low GBV, but no differences in mental health. HIV/STI incidence did not differ significantly by GBV pattern. The prevalence of GBV was extremely high in this sample of Kenyan FSWs, and different GBV patterns were associated with distinct mental health and sexual risk outcomes. Increased understanding of how health consequences vary by GBV type and severity could lead to more effective programs to reduce HIV risk in this vulnerable population.

Evaluation of the Isoniazid Preventive Therapy Care Cascade Among HIV-Positive Female Sex Workers in Mombasa, Kenya.

BACKGROUND: Kenyan female sex workers (FSWs) have a high HIV prevalence, increasing their tuberculosis (TB) risk. Despite recommendations that HIV-positive individuals be offered isoniazid preventive therapy (IPT), uptake has been limited. METHODS: In this longitudinal cohort of HIV-positive FSWs, we retrospectively characterized the IPT care cascade between March 2000 and January 2010, including reasons for cascade loss or appropriate exit. Cascade success required completion of 6 months of IPT. Baseline characteristics were assessed as potential correlates of cascade loss using multivariable logistic regression. RESULTS: Among 642 HIV-positive FSWs eligible for IPT evaluation, median age was 31 years (IQR 26-35) with median CD4 lymphocyte count of 409 (IQR 292-604) cells per cubic millimeter. There were 249 (39%) women who successfully completed 6 months of IPT, 157 (24%) appropriately exited the cascade, and 236 (37%) were cascade losses. Most cascade losses occurred at symptom screen (38%, 90/236), chest radiograph evaluation (28%, 66/236), or during IPT treatment (30%, 71/236). Twenty-nine women were diagnosed with tuberculosis, including one after IPT initiation. Most women initiating IPT completed the course (71%, 249/351); <5% had medication intolerance. Younger women [<25 and 25-35 vs. >35 years; adjusted odds ratio (AOR) 2.65, 95% confidence interval (CI): 1.46 to 4.80 and AOR 1.78, 95% CI: 1.13 to 2.80, respectively], and those evaluated for IPT after antiretroviral availability in 2004 (AOR 1.92, 95% CI: 1.31 to 2.81), were more likely to be cascade losses. CONCLUSIONS: Implementation of IPT among HIV-positive FSWs in Kenya is feasible. However, significant losses along the IPT care cascade underscore the need for strategies improving retention in care.

Brief Report: Association Between Menopause and Unprotected Sex in High-Risk HIV-Positive Women in Mombasa, Kenya.

OBJECTIVE: Many HIV-positive women now live well beyond menopause. Postmenopausal women are no longer at risk for pregnancy, and some studies suggest that they may use condoms less often than premenopausal women. This study tests the hypothesis that, in HIV-positive women who report trading sex for cash or in-kind payment, unprotected sex is more common at postmenopausal visits compared with premenopausal visits. DESIGN: Prospective cohort study of HIV-positive women ≥16 years old in Mombasa, Kenya. METHODS: At enrollment and monthly follow-up visits, participants completed a standardized interview. Study clinicians collected genital samples at enrollment and quarterly visits. Menopausal status was assessed annually. The primary outcome of unprotected sex was determined by detection of prostate specific antigen (PSA) in vaginal secretions. RESULTS: This study followed 404 HIV-positive women who contributed 2753 quarterly examination visits. Detection of PSA was less frequent at postmenopausal visits compared with premenopausal visits [55/554, 10.5% versus 394/2199, 17.9%; relative risk (RR) 0.58, 95% confidence interval (CI): 0.39 to 0.87]. Adjusting for age diminished the association between menopause and PSA detection (adjusted RR 0.73, 95% CI: 0.47 to 1.14). At visits where women reported sexual activity in the past week, they reported similar rates of 100% condom use at postmenopausal and premenopausal visits (RR 0.99, 95% CI: 0.87 to 1.13). CONCLUSIONS: In this population of high-risk HIV-positive Kenyan women, postmenopausal status was not associated with a greater risk of unprotected sex. The relationship between menopause and unprotected sex is likely context specific and may differ with varying risk groups, regions, and levels of exposure to sexual health education.

Genital HSV Shedding among Kenyan Women Initiating Antiretroviral Therapy.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

A Prospective Cohort Study of Intimate Partner Violence and Unprotected Sex in HIV-Positive Female Sex Workers in Mombasa, Kenya.

We conducted a prospective cohort study to test the hypothesis that intimate partner violence (IPV) is associated with unprotected sex in HIV-positive female sex workers in Mombasa, Kenya. Women completed monthly visits and quarterly examinations. Any IPV in the past year was defined as ≥1 act of physical, sexual, or emotional violence by the current or most recent emotional partner ('index partner'). Unprotected sex with any partner was measured by self-report and prostate specific antigen (PSA) test. Recent IPV was associated with significantly higher risk of unprotected sex (adjusted relative risk [aRR] 1.91, 95 % CI 1.32, 2.78, p = 0.001) and PSA (aRR 1.54, 95 % CI 1.17, 2.04, p = 0.002) after adjusting for age, alcohol use, and sexual violence by someone besides the index partner. Addressing IPV in comprehensive HIV programs for HIV-positive women in this key population is important to improve wellbeing and reduce risk of sexual transmission of HIV.

Genital Shedding of Resistant Human Immunodeficiency Virus-1 Among Women Diagnosed With Treatment Failure by Clinical and Immunologic Monitoring.

Background. The accumulation of human immunodeficiency virus (HIV) resistance mutations can compromise treatment outcomes and promote transmission of drug-resistant virus. We conducted a study to determine the duration and evolution of genotypic drug resistance in the female genital tract among HIV-1-infected women failing first-line therapy. Methods. Treatment failure was diagnosed based on World Health Organization (WHO) clinical or immunologic criteria, and second-line therapy was initiated. Stored plasma and genital samples were tested to determine the presence and timing of virologic failure and emergence of drug resistance. The median duration of genital shedding of genotypically resistant virus prior to regimen switch was estimated. Results. Nineteen of 184 women were diagnosed with treatment failure, of whom 12 (63.2%) had confirmed virologic failure at the switch date. All 12 women with virologic failure (viral load, 5855-1 086 500 copies/mL) had dual-class resistance in plasma. Seven of the 12 (58.3%) had genital HIV-1 RNA levels high enough to amplify (673-116 494 copies/swab), all with dual-class resistance. The median time from detection of resistance in stored samples to regimen switch was 895 days (95% confidence interval [CI], 130-1414 days) for plasma and 629 days (95% CI, 341-984 days) for genital tract secretions. Conclusions. Among women diagnosed with treatment failure using WHO clinical or immunologic criteria, over half had virologic failure confirmed in stored samples. Resistant HIV-1 RNA was shed in the genital tract at detectable levels for ≈1.7 years before failure diagnosis, with steady accumulation of mutations. These findings add urgency to the ongoing scale-up of viral load testing in resource-limited settings.

Prevalence and correlates of intimate partner violence in HIV-positive women engaged in transactional sex in Mombasa, Kenya.

We evaluated the prevalence and correlates of intimate partner violence (IPV) in the past year by a regular male partner in HIV-positive female sex workers (FSWs) in Mombasa, Kenya. This cross-sectional study included HIV-positive women ≥18 years old who reported engagement in transactional sex at the time of enrolment in the parent cohort. We asked 13 questions adapted from the World Health Organization survey on violence against women about physical, sexual, or emotional violence in the past year by the current or most recent emotional partner (index partner). We used standardised instruments to assess socio-demographic and behavioural characteristics as possible correlates of IPV. Associations between IPV and these correlates were evaluated using univariate and multivariate logistic regression. Overall, 286/357 women (80.4%) had an index partner, and 52/357 (14.6%, 95% confidence interval 10.9%-18.2%) reported IPV by that partner in the past year. In multivariate analysis, women with severe alcohol problems (adjusted odds ratio 4.39, 1.16-16.61) and those experiencing controlling behaviours by the index partner (adjusted odds ratio 4.98, 2.31-10.74) were significantly more likely to report recent IPV. Recent IPV was common in HIV-positive FSWs. Interventions targeting risk factors for IPV, including alcohol problems and partner controlling behaviours, could help to reduce recurrent violence and negative health outcomes in this key population.

Fetal head circumference, operative delivery, and fetal outcomes: a multi-ethnic population-based cohort study.

BACKGROUND: Operative delivery procedures, such as primary cesarean section, vacuum-assisted, and forceps-assisted vaginal delivery increase maternal and fetal morbidity, and the cost of care. We evaluated whether large fetal head circumference (FHC) independently increases risk of such interventions, as well as fetal distress or low Apgar score, in anatomically normal infants. METHODS: We conducted a population-based retrospective cohort study using Washington State birth certificate data. We included singleton, term infants born to nulliparous mothers from 2003-2009. We compared mode of delivery and fetal outcomes in 10,750 large-FHC (37-41 cm) infants relative to 10,750 average-FHC (34 cm) infants, frequency matched by birth-year. RESULTS: Large-FHC infants were nearly twice as likely to be delivered by primary cesarean section as average-FHC infants (unadjusted relative risk [RR] 1.84, 95% confidence interval [CI]: 1.77, 1.92). The RR for primary cesarean section associated with large-FHC was largest for mothers aged 19 years or less (RR 2.28; 95% CI: 1.99, 2.61), and smallest for mothers aged 35 years or greater (RR 1.51; 95% CI: 1.37, 1.66) [test of homogeneity, p < 0.001]. Large-FHC infants were at increased risk of vacuum-assisted vaginal delivery (RR 1.55; 95% CI: 1.43, 1.69), and forceps-assisted vaginal delivery (RR 1.61; 95% CI: 1.32, 1.97). There was no difference in risk of fetal distress (RR 0.97; 95% CI: 0.89, 1.07) for large-FHC versus average-FHC infants. Risk estimates were unaffected by adjustment for potential confounders. CONCLUSIONS: Nulliparous mothers of large-FHC infants are at increased risk of primary cesarean section, vacuum-assisted and forceps-assisted vaginal delivery relative to mothers of average-FHC infants. Maternal age modifies the association between FHC and primary cesarean section.

Incidence and correlates of Chlamydia trachomatis infection in a high-risk cohort of Kenyan women.

BACKGROUND: In Africa, data on Chlamydia trachomatis infection are scarce because reliable diagnosis is costly and not widely available. Our objective was to evaluate the incidence and correlates of C. trachomatis infection among high-risk Kenyan women. METHODS: We conducted prospective cohort analyses using data from a cohort of women who reported transactional sex. C. trachomatis testing was performed using the Gen-Probe Aptima GC/CT Detection System. We used Andersen-Gill proportional hazards modeling to evaluate correlates of C. trachomatis. RESULTS: 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, 5.0/100 person-years). There was a large difference in incidence by age group: those younger than 25 years had an incidence of 27.6 per 100 person-years (95% confidence interval [CI], 16.3-46.5), those 25 to 34 years old had an incidence of 8.4 per 100 person-years (95% CI, 6.4-11.0), and those 35 years and older had an incidence of 2.6 per 100 person-years (95% CI, 1.8-3.6). In multivariate analyses, younger age (<25 and 25-34 years vs. ≥35 years; hazard ratio [HR], 8.5 [95% CI, 4.1-17.7] and 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. CONCLUSIONS: The high incidence of C. trachomatis among younger high-risk women suggests the need for screening as an important public health intervention for this population.

Prevalence and correlates of genital warts in Kenyan female sex workers.

BACKGROUND: Our goal in the present study was to investigate the prevalence and correlates of genital warts in a population of female sex workers in Mombasa, Kenya. Because of the high prevalence of human immunodeficiency virus type 1 (HIV-1) in this population, we were particularly interested in the association between HIV-1 infection and genital warts. METHODS: We conducted a cross-sectional study of the prevalence and correlates of genital warts among high-risk women in Mombasa, Kenya. Between 2001 and 2007, 1182 women were enrolled, of whom 613 (51.4%) were HIV-1 seropositive. Chi square tests and logistic regression were used to examine the associations between genital warts and potential correlates. RESULTS: Genital warts were identified on clinical examination in 27 (2.3%) women. Women who were HIV-1 seropositive were nearly 8 times as likely to have genital warts compared with HIV-1-seronegative women (odds ratio, 7.69; 95% confidence interval, 2.30-25.6). CONCLUSION: Understanding the prevalence and correlates of genital warts will help to determine whether coverage for the wart-inducing subtypes 6 and 11 in a human papillomavirus vaccine is an important consideration in resource-limited countries.

Antiretroviral treatment interruptions predict female genital shedding of genotypically resistant HIV-1 RNA.

OBJECTIVES: Resistant viruses may emerge in the female genital tract during antiretroviral therapy (ART). Our objective was to identify predictors of drug-resistant HIV-1 RNA in genital secretions after initiation of nonnucleoside reverse transcriptase inhibitor-based therapy. DESIGN: We conducted a prospective cohort study with periodic evaluation of plasma and genital swab samples for HIV-1 RNA levels and antiretroviral resistance mutations. METHODS: First-line ART was initiated in 102 women. Plasma and genital HIV-1 RNA levels were measured at months 0, 3, 6, and 12. Genotypic resistance testing was performed for samples from all participants with RNA >1000 copies per milliliter at month 6 or 12. Cox regression analysis was used to identify factors associated with incident genital tract resistance. RESULTS: Detectable genital tract resistance developed in 5 women, all with detectable plasma resistance (estimated incidence, 5.5/100 person-years of observation). Treatment interruption >48 hours, adherence by pill count, adherence by visual analog scale, and baseline plasma viral load were associated with incident genital tract resistance. In multivariate analysis, only treatment interruption was associated with risk of detectable genital tract resistance (adjusted hazard ratio: 14.2; 95% confidence interval: 1.3 to 158.4). CONCLUSIONS: Treatment interruption >48 hours during nonnucleoside reverse transcriptase inhibitor-based therapy led to a significantly increased risk of detecting genotypically resistant HIV-1 RNA in female genital tract secretions. Patient- and program-level interventions to prevent treatment interruptions could reduce the risk of shedding-resistant HIV-1 during ART.