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Background: The HPTN 052 trial confirmed that antiretroviral therapy (ART) can nearly eliminate HIV transmission from successfully treated HIV-infected individuals within couples. Here, we present the mathematical modeling used to inform the design and monitoring of a new trial aiming to test whether widespread provision of ART is feasible and can substantially reduce population-level HIV incidence. Methods and Findings: The HPTN 071 (PopART) trial is a three-arm cluster-randomized trial of 21 large population clusters in Zambia and South Africa, starting in 2013. A combination prevention package including home-based voluntary testing and counseling, and ART for HIV positive individuals, will be delivered in arms A and B, with ART offered universally in arm A and according to national guidelines in arm B. Arm C will be the control arm. The primary endpoint is the cumulative three-year HIV incidence. We developed a mathematical model of heterosexual HIV transmission, informed by recent data on HIV-1 natural history. We focused on realistically modeling the intervention package. Parameters were calibrated to data previously collected in these communities and national surveillance data. We predict that, if targets are reached, HIV incidence over three years will drop by >60% in arm A and >25% in arm B, relative to arm C. The considerable uncertainty in the predicted reduction in incidence justifies the need for a trial. The main drivers of this uncertainty are possible community-level behavioral changes associated with the intervention, uptake of testing and treatment, as well as ART retention and adherence. Conclusions: The HPTN 071 (PopART) trial intervention could reduce HIV population-level incidence by >60% over three years. This intervention could serve as a paradigm for national or supra-national implementation. Our analysis highlights the role mathematical modeling can play in trial development and monitoring, and more widely in evaluating the impact of treatment as prevention. [ABSTRACT FROM AUTHOR]

Background: The Stop TB Partnership target for tuberculosis is to have reduced the prevalence of tuberculosis by 50% comparing 2015 to 1990. This target is challenging as few prevalence surveys have been conducted, especially in high burden tuberculosis and HIV countries. Current tuberculosis control strategies in high HIV prevalent settings are therefore based on limited epidemiological evidence and more evidence is needed from community-based surveys to inform improved policy formulation. Methods and Findings: 8044 adults were sampled from 2 sub-districts (wards) in Lusaka province, Zambia. Questionnaires were used to screen for symptoms, respiratory samples were obtained for culture and oral secretions collected for HIV testing. 79 individuals were found to have Mycobacterium tuberculosis in their sputum, giving an adjusted overall prevalence of tuberculosis of 870/100,000 (95% CI 570-1160/100,000). The adjusted overall prevalence of HIV was 28.61% (95% CI 26.04-31.19). HIV- infection was significantly associated with prevalent tuberculosis (Adj OR 2.3, 95% CI 1.42-3.74) and the population attributable fraction of HIV for prevalent tuberculosis was 36%. Symptoms such as prolonged cough (adj OR 12.72, 95% CI 7.05-22.94) and fever (Adj OR 2.04, 95%CI 1.23-3.39), were associated with prevalent tuberculosis, but 8 (10%) individuals with prevalent tuberculosis denied having any symptoms at all and only 34 (43%) would have been classified as a TB suspect by current guidelines. Conclusions: Undiagnosed tuberculosis is a challenge for tuberculosis control and new approaches are needed if we are to reach international targets. Epidemiological studies can inform screening algorithms for both detection and prevention of active tuberculosis. [ABSTRACT FROM AUTHOR]

Introduction: The use of antigen rapid tests (Ag-RDTs) for self-testing is an important element of the COVID-19 control strategy and has been widely supported. However, scale-up of self-testing for COVID-19 in sub-Saharan Africa is still insufficient and there is limited evidence on the acceptability of self-testing and agreement between Ag-RDT self-testing and Ag-RDT testing by professional users. A joint collaboration (Botnar Research Centre for Child Health-European & Developing countries Clinical Trials Partnership)was established between Lesotho and Zambia to address these gaps in relation to Ag-RDT self-testing and contribute to increasing its use in the region. Methods: A cross-sectional study was conducted with qualitative and quantitative data analysis. Firstly, 14 in-depth cognitive interviews (5 in Zambia and 9 in Lesotho) were performed to assess the participants' understanding of the instructions for use (IFU) for self-testing. In a second step, evaluation of test agreement between Ag-RDT self-testing and Ag-RDT testing by professional user using SD Biosensor STANDARD Q COVID-19 Ag-RDT was performed. In Zambia, usability and acceptability of self-testing were also assessed. Results: Cognitive interviews in Lesotho and Zambia showed overall good understanding of IFU. In Zambia, acceptability of self-testing was high, though some participants had difficulties in conducting certain steps in the IFU correctly. Agreement between Ag-RDT self-test and Ag-RDT by professional users in Lesotho (428 participants) and Zambia (1136 participants) was high, 97.3% (403/414, 95% CI: 95.3–98.7) and 99.8% (1116/1118, 95% CI: 99.4–100) respectively. Conclusion: Findings from this study support the use of Ag-RDT self-testing within COVID-19 control strategies in sub-Saharan Africa, contributing to increase the testing capacity and access in hard-to reach settings. [ABSTRACT FROM AUTHOR]

Introduction: The HPTN071 (PopART) for Youth (P-ART-Y) study evaluated the acceptability and uptake of a community-level combination HIV prevention package including universal testing and treatment (UTT) among young people in Zambia and South Africa. We determined whether a four-question primary care level screening tool, validated for use in clinical settings, could enhance community (door-to-door) identification of undiagnosed HIV-positive younger adolescents (aged 10–14) who are frequently left out of HIV interventions. Method: Community HIV-care Providers (CHiPs) contacted and consented adolescents in their homes and offered them participation in the PopART intervention. CHiPs used a four question-screening tool, which included: history of hospital admission; recurring skin problems; poor health in last 3 months; and death of at least one parent. A "yes" response to one or more questions was classified as being "at risk" of being HIV-positive. Rapid HIV tests were offered to all children. Data were captured through an electronic data capture device from August 2016 to December 2017. The sensitivity, specificity, positive predictive value and negative predictive value were estimated for the screening tool, using the rapid HIV test result as the gold standard. Results: In our 14 study sites, 33,710 adolescents aged 10–14 in Zambia and 8,610 in South Africa participated in the study. About 1.3% (427/33,710) and 1.2% (106/8,610) self-reported to be HIV positive. Excluding the self-reported HIV-positive, we classified 11.3% (3,746/33,283) of adolescents in Zambia and 17.5% (1,491/8,504) in South Africa as "at risk". In Zambia the estimated sensitivity was 35.3% (95% CI 27.3%-44.2%) and estimated specificity was 88.9% (88.5%-89.2%). In South Africa the sensitivity was 72.3% (26.8%-94.9%) and specificity was 82.5% (81.6–83.4%). Conclusion: The sensitivity of the screening tool in a community setting in Zambia was low, so this tool should not be considered a substitute for universal testing where that is possible. In South Africa the sensitivity was higher, but with a wide confidence interval. Where universal testing is not possible the tool may help direct resources to adolescents more likely to be living with undiagnosed HIV. Trial registration: Clinical Trial Number:NCT01900977. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) prevalence remains persistently high in many settings, with new or expanded interventions required to achieve substantial reductions. The HIV Prevention Trials Network (HPTN) 071 (PopART) community-randomised trial randomised 14 communities to receive the "PopART" intervention during 2014 to 2017 (7 arm A and 7 arm B communities) and 7 communities to receive standard-of-care (arm C). The intervention was delivered door-to-door by community HIV care providers (CHiPs) and included universal HIV testing, facilitated linkage to HIV care at government health clinics, and systematic TB symptom screening. The Tuberculosis Reduction through Expanded Anti-retroviral Treatment and Screening (TREATS) study aimed to measure the impact of delivering the PopART intervention on TB outcomes, in communities with high HIV and TB prevalence. Methods and findings: The study population of the HPTN 071 (PopART) trial included individuals aged ≥15 years living in 21 urban and peri-urban communities in Zambia and South Africa, with a total population of approximately 1 million and an adult HIV prevalence of around 15% at the time of the trial. Two sputum samples for TB testing were provided to CHiPs by individuals who reported ≥1 TB suggestive symptom (a cough for ≥2 weeks, unintentional weight loss ≥1.5 kg in the last month, or current night sweats) or that a household member was currently on TB treatment. Antiretroviral therapy (ART) was offered universally at clinics in arm A and according to local guidelines in arms B and C. The TREATS study was conducted in the same 21 communities as the HPTN 071 (PopART) trial between 2017 and 2022, and TB prevalence was a co-primary endpoint of the TREATS study. The primary comparison was between the PopART intervention (arms A and B combined) and the standard-of-care (arm C). During 2019 to 2021, a TB prevalence survey was conducted among randomly selected individuals aged ≥15 years (approximately 1,750 per community in arms A and B, approximately 3,500 in arm C). Participants were screened on TB symptoms and chest X-ray, with diagnostic testing using Xpert-Ultra followed by culture for individuals who screened positive. Sputum eligibility was determined by the presence of a cough for ≥2 weeks, or ≥2 of 5 "TB suggestive" symptoms (cough, weight loss for ≥4 weeks, night sweats, chest pain, and fever for ≥2 weeks), or chest X-ray CAD4TBv5 score ≥50, or no available X-ray results. TB prevalence was compared between trial arms using standard methods for cluster-randomised trials, with adjustment for age, sex, and HIV status, and multiple imputation was used for missing data on prevalent TB. Among 83,092 individuals who were eligible for the survey, 49,556 (59.6%) participated, 8,083 (16.3%) screened positive, 90.8% (7,336/8,083) provided 2 sputum samples for Xpert-Ultra testing, and 308 (4.2%) required culture confirmation. Overall, estimated TB prevalence was 0.92% (457/49,556). The geometric means of 7 community-level prevalence estimates were 0.91%, 0.70%, and 0.69% in arms A, B, and C, respectively, with no evidence of a difference comparing arms A and B combined with arm C (adjusted prevalence ratio 1.14, 95% confidence interval, CI [0.67, 1.95], p = 0.60). TB prevalence was higher among people living with HIV than HIV–negative individuals, with an age-sex-community adjusted odds ratio of 2.29 [95% CI 1.54, 3.41] in Zambian communities and 1.61 [95% CI 1.13, 2.30] in South African communities. The primary limitations are that the study was powered to detect only large reductions in TB prevalence in the intervention arm compared with standard-of-care, and the between-community variation in TB prevalence was larger than anticipated. Conclusions: There was no evidence that the PopART intervention reduced TB prevalence. Systematic screening for TB that is based on symptom screening alone may not be sufficient to achieve a large reduction in TB prevalence over a period of several years. Including chest X-ray screening alongside TB symptom screening could substantially increase the sensitivity of systematic screening for TB. Trial registration: The TREATS study was registered with ClinicalTrials.gov Identifier: NCT03739736 on November 14, 2018. The HPTN 071 (PopART) trial was registered at ClinicalTrials.gov under number NCT01900977 on July 17, 2013. In a population based cohort study, Eveline Klinkenberg and colleagues examine the impact of the PopART intervention on TB prevalence in Zambia and South Africa. Author summary: Why was this study done?: Tuberculosis (TB) prevalence remains persistently high in many settings, with new or expanded interventions required to achieve substantial reductions. The HIV Prevention Trials Network (HPTN) 071 Population Effects of Antiretroviral Therapy to Reduce HIV Transmission (PopART) community-randomised trial, conducted in 21 Zambian and South African communities (2013 to 2018), provided an opportunity to test whether the PopART intervention—universal testing and universal treatment for HIV combined with universal symptom screening for TB—could reduce TB prevalence. The Tuberculosis Reduction through Expanded Anti-retroviral Treatment and Screening (TREATS) study measured the impact of the PopART intervention on TB prevalence, comparing 14 communities that received the PopART intervention during 2014 to 2017 with 7 communities that received standard-of-care. What did the researchers do and find?: We conducted a TB prevalence survey during 2019 to 2021, among around 50,000 randomly selected individuals aged ≥15 years in the 21 urban and peri-urban communities that were included in the HPTN 071 (PopART) trial. Overall, estimated TB prevalence was 0.92% (457/49,556). There was no evidence of a difference in TB prevalence between the PopART intervention and standard-of-care communities, with an adjusted prevalence ratio of 1.14, 95% confidence interval (CI) [0.67, 1.95]. TB prevalence was around 2 times higher among HIV–positive than HIV–negative individuals, adjusted for age, sex, and community, and several times higher among men than women. What do these findings mean?: This study found no evidence that the PopART intervention reduced TB prevalence, compared with standard-of-care. Systematic screening for TB that is based on symptom screening alone may not be sufficient to achieve a large reduction in TB prevalence over a period of a few years. Including chest X-ray screening alongside TB symptom screening could substantially increase the sensitivity of systematic screening for TB, and several years of delivering such a strategy might be able to achieve a considerable reduction in TB prevalence. [ABSTRACT FROM AUTHOR]

Background: The growing population of adolescents and young people (AYP) aged 15 to 24 in sub-Saharan Africa face a high burden of HIV in many settings. Unintended pregnancies among adolescent girls in the region remain high. Nonetheless, the sexual and reproductive health (SRH) service needs of AYP have remained underserved. We conducted a cluster-randomised trial (CRT) to estimate the impact of community-based, peer-led SRH service provision on knowledge of HIV status and other SRH outcomes, including met need for contraceptives. Methods and findings: Yathu Yathu was a cluster-randomised trial (CRT) conducted from 2019 to 2021 in 2 urban communities in Lusaka, Zambia. The communities were divided into 20 zones (approximately 2,350 AYP/zone) that were randomly allocated to the Yathu Yathu intervention or control arm. In each intervention zone, a community-based hub, staffed by peer support workers, was established to provide SRH services. In 2019, a census was conducted in all zones; all consenting AYP aged 15 to 24 were given a Yathu Yathu card, which allowed them to accrue points for accessing SRH services at the hub and health facility (intervention arm) or the health facility only (control arm). Points could be exchanged for rewards, thus acting as an incentive to use SRH services in both arms. We conducted a cross-sectional survey in 2021 to estimate the impact of Yathu Yathu on the primary outcome: knowledge of HIV status (self-reporting living with HIV or HIV testing in the last 12 months) and secondary outcomes, including use of pre-exposure prophylaxis (PrEP) in the last 12 months, current use of antiretroviral therapy (ART), and met need for contraceptive services. The sampling was stratified on sex and age group, and we analysed data at cluster-level using a two-stage process recommended for CRTs with <15 clusters/arm. A total of 1,989 AYP consented to participate in the survey (50% male); consent was similar across arms (63% consent/arm). Across zones, knowledge of HIV status ranged from 63.6% to 81.2% in intervention zones and 35.4% to 63.0% in control zones. Adjusting for age, sex, and community, knowledge of HIV status was higher in the intervention arm compared to control (73.3% versus 48.4%, respectively, adjusted prevalence ratio (PR) 1.53 95% CI 1.36, 1.72; p < 0.001). By age and sex, results were similar. There was no evidence for impact on any secondary outcomes, including current use of ART and met need for contraceptives. There were no adverse events reported in either arm. A key limitation of our trial is that approximately 35% of the AYP randomly selected for participation in the endline survey could not be reached. Conclusions: Delivering community-based, peer-led SRH services increased knowledge of HIV status among AYP, both males and females, compared with the control arm. Scaling up the highly effective Yathu Yathu strategy has the potential to make a substantial contribution to increasing access to HIV prevention and care services for young people. However, additional implementation research is needed to understand how to improve uptake of broader SRH services, beyond uptake of HIV testing. Trial registration: ISRCTN75609016, clinicaltrials.gov number NCT04060420 Bernadette Hensen and colleagues investigate whether community-based delivery of sexual and reproductive health services by peers increased knowledge of HIV status among adolescents and young people in Zambia. Author summary: Why was this study done?: Adolescents and young people (AYP) have limited access to sexual and reproductive health (SRH) services; rigorous evidence of strategies, co-developed with young people, that improve access to these services is needed. This trial was done to investigate whether community-based delivery of SRH services by peers would increase knowledge of HIV status among AYP aged 15 to 24 in Lusaka, Zambia. What did the researchers do and find?: Through spaces in the community (called hubs), peer support workers, a nurse and supervisor, delivered a range of SRH services, including HIV testing, comprehensive sexuality education, and contraceptives, daily to AYP aged 15 to 24. Service delivery through hubs was complemented by incentives, namely the collection of points for services accessed and the ability to use these points to "buy" rewards, such as soap, toothbrush, and toothpaste. After approximately 24 months, we compared knowledge of HIV status (defined as either self-reporting knowing ones HIV–positive status or having HIV tested in the previous 12 months) between random selections of AYP aged 15 to 24 (N = 1,989) living in areas that received the Yathu Yathu intervention and in areas that did not receive the intervention. We found that knowledge of status was considerably higher in the intervention areas (73.3%) as compared to the non-intervention areas (48.4%), but that there was no difference in uptake of other SRH services, such as linkage to PrEP for the prevention of HIV. What do these findings mean?: These findings show that community-based hubs that deliver a range of SRH services and are complemented by incentives can increase knowledge of HIV status. Additional research is needed to improve delivery of other services, including linkage to prevention and care services, and access to contraceptive services. [ABSTRACT FROM AUTHOR]

Background: Mental health is a critical and neglected public health problem for adolescents in sub-Saharan Africa. In this paper we aim to determine the prevalence of depressive symptoms and the association with HIV risk behaviours in adolescents aged 15–19 years in Zambia and SA. Methods: We conducted a cross-sectional survey from August-November 2017 in seven control communities of HPTN 071 (PopART) trial (a community-randomised trial of universal HIV testing and treatment), enrolling approximately 1400 eligible adolescents. HIV-status was self-reported. Depressive symptoms were measured with the Short Mood and Feelings Questionnaire (SMFQ), with a positive screen if adolescents scored ≥12. We fitted a logistic regression model to identify correlates of depressive symptoms with subgroup analyses among those who self-reported ever having had sex, by gender and country. Results: Out of 6997 households approached, 6057 (86.6%) were enumerated. 2546 adolescents were enumerated of whom 2120 (83.3%) consented to participate and were administered the SMFQ. The prevalence of depressive symptoms was 584/2120 (27.6%) [95%CI: 25.7%-29.5%]. Adolescents in SA were less likely to experience depressive symptoms (Adjusted Odds Ratio [AOR] = 0.63 (95% CI: 0.50, 0.79), p-value<0.0001). Female adolescents (AOR = 1.46 (95% CI: 1.19, 1.81), p-value<0.0001); those who reported ever having sex and being forced into sex (AOR = 1.80 (95% CI: 1.45, 2.23), p-value<0.001) and AOR = 1.67 (95% CI: 0.99, 2.84); p-value = 0.057 respectively) were more likely to experience depressive symptoms. Among 850 (40.1%) adolescents who self-reported to ever having had sex; those who used alcohol/drugs during their last sexual encounter were more likely to experience depressive symptoms (AOR = 2.18 (95% CI: 1.37, 3.47); p-value = 0.001), whereas those who reported using a condom were less likely to experience depressive symptoms (AOR = 0.74 (95% CI: 0.55, 1.00); p-value = 0.053). Conclusion: The prevalence of depressive symptoms among adolescents ranged from 25–30% and was associated with increased HIV-risk behaviour. [ABSTRACT FROM AUTHOR]

Background: Female genital schistosomiasis (FGS) is a neglected and disabling gynecological disease that can result from infection with the parasitic trematode Schistosoma haematobium. Accurate diagnosis of FGS is crucial for effective case management, surveillance and control. However, current methods for diagnosis and morbidity assessment can be inaccessible to those at need, labour intensive, costly and unreliable. Molecular techniques such as PCR can be used to reliably diagnose FGS via the detection of Schistosoma DNA using cervicovaginal lavage (CVL) samples as well as lesser-invasive vaginal self-swab (VSS) and cervical self-swab samples. PCR is, however, currently unsuited for use in most endemic settings. As such, in this study, we assessed the use of a rapid and portable S. haematobium recombinase polymerase amplification (Sh-RPA) isothermal molecular diagnostic assay, coupled with simplified sample preparation methodologies, to detect S. haematobium DNA using CVL and VSS samples provided by patients in Zambia. Methodology/Principal findings: VSS and CVL samples were screened for FGS using a previously developed Sh-RPA assay. DNA was isolated from VSS and CVL samples using the QIAamp Mini kit (n = 603 and 527, respectively). DNA was also isolated from CVL samples using two rapid and portable DNA extraction methods: 1) the SpeedXtract Nucleic Acid Kit (n = 223) and 2) the Extracta DNA Tissue Prep Kit (n = 136). Diagnostic performance of the Sh-RPA using VSS DNA extacts (QIAamp Mini kit) as well as CVL DNA extracts (QIAamp Mini kit, SpeedXtract Nucleic Acid Kit and Extracta DNA Tissue Prep Kit) was then compared to a real-time PCR reference test. Results suggest that optimal performance may be achieved when the Sh-RPA is used with PuVSS samples (sensitivity 93.3%; specificity 96.6%), however no comparisons between different DNA extraction methods using VSS samples could be carried out within this study. When using CVL samples, sensitivity of the Sh-RPA ranged between 71.4 and 85.7 across all three DNA extraction methods when compared to real-time PCR using CVL samples prepared using the QIAamp Mini kit. Interestingly, of these three DNA extraction methods, the rapid and portable SpeedXtract method had the greatest sensitivity and specificity (85.7% and 98.1%, respectively). Specificity of the Sh-RPA was >91% across all comparisons. Conclusions/Significance: These results supplement previous findings, highlighting that the use of genital self-swab sampling for diagnosing FGS should be explored further whilst also demonstrating that rapid and portable DNA isolation methods can be used to detect S. haematobium DNA within clinical samples using RPA. Although further development and assessment is needed, it was concluded that the Sh-RPA, coupled with simplified sample preparation, shows excellent promise as a rapid and sensitive diagnostic tool capable of diagnosing FGS at the point-of-care in resource-poor schistosomiasis-endemic settings. Author summary: Female genital schistosomiasis (FGS) is a neglected gynecological disease that can result from infection with the parasitic trematode Schistosoma haematobium. In addition to disabling FGS-associated pathologies, S. haematobium infection has also been associated with sexually transmitted infections (STIs), cervical dysplasia and HIV transmission.Accurate diagnosis of FGS is crucial for effective case management, surveillance and control. However, current methods for diagnosis and morbidity assessment can be inaccessible to those at need, labour intensive, costly and unreliable. Molecular techniques such as PCR can be used to reliably diagnose FGS via the detection of Schistosoma DNA using cervicovaginal lavage (CVL) samples as well as lesser-invasive vaginal self-swab (VSS) and cervical self-swab samples. PCR is, however, currently unsuited for use in most endemic settings. As such, in this study, we assessed the use of a rapid and portable S. haematobium recombinase polymerase amplification (Sh-RPA) molecular diagnostic assay, coupled with simplified sample preparation methods that can be carried out in resourse-poor settings, to diagnose FGS using CVL and VSS samples.Performance of the Sh-RPA was excellent when compared to real-time PCR across all comparisons, even when using simplified sample preparation methods. Of note, optimal performance of the Sh-RPA may be achieved when used with the lesser-invasive VSS samples. The Sh-RPA therefore shows promise as a rapid and sensitive diagnostic tool capable of diagnosing FGS at the point-of-care in schistosomiasis-endemic settings. [ABSTRACT FROM AUTHOR]

Background: Assays and multi-assay algorithms (MAAs) have been developed for population-level cross-sectional HIV incidence estimation. These algorithms use a combination of serologic and/or non-serologic biomarkers to assess the duration of infection. We evaluated the performance of four MAAs for individual-level recency assessments. Methods: Samples were obtained from 220 seroconverters (infected <1 year) and 4,396 non-seroconverters (infected >1 year) enrolled in an HIV prevention trial (HPTN 071 [PopART]); 28.6% of the seroconverters and 73.4% of the non-seroconverters had HIV viral loads ≤400 copies/mL. Samples were tested with two laboratory-based assays (LAg-Avidity, JHU BioRad-Avidity) and a point-of-care assay (rapid LAg). The four MAAs included different combinations of these assays and HIV viral load. Seroconverters on antiretroviral treatment (ART) were identified using a qualitative multi-drug assay. Results: The MAAs identified between 54 and 100 (25% to 46%) of the seroconverters as recently-infected. The false recent rate of the MAAs for infections >2 years duration ranged from 0.2%-1.3%. The MAAs classified different overlapping groups of individuals as recent vs. non-recent. Only 32 (15%) of the 220 seroconverters were classified as recent by all four MAAs. Viral suppression impacted the performance of the two LAg-based assays. LAg-Avidity assay values were also lower for seroconverters who were virally suppressed on ART compared to those with natural viral suppression. Conclusions: The four MAAs evaluated varied in sensitivity and specificity for identifying persons infected <1 year as recently infected and classified different groups of seroconverters as recently infected. Sensitivity was low for all four MAAs. These performance issues should be considered if these methods are used for individual-level recency assessments. [ABSTRACT FROM AUTHOR]

Mathematical models are powerful tools in HIV epidemiology, producing quantitative projections of key indicators such as HIV incidence and prevalence. In order to improve the accuracy of predictions, such models need to incorporate a number of behavioural and biological heterogeneities, especially those related to the sexual network within which HIV transmission occurs. An individual-based model, which explicitly models sexual partnerships, is thus often the most natural type of model to choose. In this paper we present PopART-IBM, a computationally efficient individual-based model capable of simulating 50 years of an HIV epidemic in a large, high-prevalence community in under a minute. We show how the model calibrates within a Bayesian inference framework to detailed age- and sex-stratified data from multiple sources on HIV prevalence, awareness of HIV status, ART status, and viral suppression for an HPTN 071 (PopART) study community in Zambia, and present future projections of HIV prevalence and incidence for this community in the absence of trial intervention. Author summary: In this paper we present PopART-IBM, an individual-based model used to simulate HIV transmission in communities in high prevalence settings. We show that PopART-IBM can simulate transmission over a span of decades in a large community in less than a minute. This computational efficiency allows us to calibrate the model within an inference framework, and we show an illustrative example of calibration using an adaptive population Monte Carlo Approximate Bayesian Computation algorithm for a community in Zambia that was part of the HPTN-071 (PopART) trial. We compare the detailed model output to real-world data collected during the trial from this community. Finally, we project how the HIV epidemic would have changed over time in this community if no intervention from the trial had occurred. [ABSTRACT FROM AUTHOR]

Background: Given the potentially causal association of female genital schistosomiasis (FGS) with HIV-1 infection, improved diagnostics are urgently needed to scale-up FGS surveillance. The BILHIV (bilharzia and HIV) study assessed the performance of home-based self-collection methods (cervical and vaginal swabs) compared to cervicovaginal lavage (CVL) for the detection of Schistosoma DNA by real-time polymerase chain reaction (PCR). Methods: Between January and August 2018, a consecutive series of female participants from the Population-Cohort of the previous HIV prevention trial HPTN 071 (PopART), resident in Livingstone, Zambia were invited to take part in BILHIV if they were 18–31 years old, non-pregnant and sexually active. Genital self-collected swabs and a urine specimen were obtained and a questionnaire completed at home visits. CVL was obtained at clinic follow-up. Results: 603 women self-collected genital swabs. Of these, 527 women had CVL performed by a mid-wife during clinic follow-up. Schistosoma DNA was more frequently detected in genital self-collected specimens (24/603, 4.0%) compared to CVL (14/527, 2.7%). Overall, 5.0% (30/603) women had female genital schistosomiasis, defined as a positive PCR by any genital sampling method (cervical swab PCR, vaginal swab PCR, or CVL PCR) and 95% (573/603) did not have a positive genital PCR. The sensitivity of any positive genital self-collected swab against CVL was 57.1% (95% CI 28.9–82.3%), specificity 97.3% (95.5–98.5%). In a subset of participants with active schistosome infection, determined by detectable urine Circulating Anodic Antigen (CAA) (15.1%, 91/601), positive PCR (4.3%, 26/601), or positive microscopy (5.5%, 33/603), the sensitivity of any positive self-collected specimen against CVL was 88.9% (51.8–99.7%). Conclusions: Genital self-sampling increased the overall number of PCR-based FGS diagnoses in a field setting, compared with CVL. Home-based sampling may represent a scalable alternative method for FGS community-based diagnosis in endemic resource limited settings. Author summary: Female Genital schistosomiasis (FGS) is a neglected and disabling disease that results when eggs from the waterborne parasite Schistosoma haematobium are trapped in the human reproductive tract. Current female genital schistosomiasis (FGS) diagnostic strategies are limited because they require expertise and equipment that may not be readily available in low income settings. Improved and accessible diagnostics are urgently needed to scale-up FGS surveillance. This is especially important as FGS has been associated with HIV-1 infection. The BILHIV (bilharzia and HIV) study assessed the performance of home-based self-collection methods (cervical and vaginal swabs) compared with a clinic-based cervicovaginal lavage (CVL) performed by a medical professional. Both methods used real-time polymerase chain reaction (PCR) to detect Schistosoma DNA. We found that, in a field setting, self-collected genital and cervical swabs increased the overall number of PCR-based FGS diagnoses, compared with clinically collected CVL. We report the sensitivity of self-collected swabs for the diagnosis of FGS, compared with CVL. We found that the sensitivity of self-collected genital swabs was high in a subset of women with active schistosome infection. We suggest that home-based self-sampling may represent a scalable community-based sampling platform for FGS community-based diagnosis in endemic resource limited settings. [ABSTRACT FROM AUTHOR]

Background: In 2014, the Joint United Nations Programme on HIV/AIDS (UNAIDS) set the 90-90-90 targets: that 90% of people living with HIV know their HIV status, that 90% of those who know their HIV-positive status are on antiretroviral therapy (ART), and that 90% of those on treatment are virally suppressed. The aim was to reach these targets by 2020. We assessed the feasibility of achieving the first two targets, and the corresponding 81% ART coverage target, as part of the HIV Prevention Trials Network (HPTN) 071 Population Effects of Antiretroviral Therapy to Reduce HIV Transmission (PopART) community-randomized trial.Methods and Findings: The study population was individuals aged ≥15 years living in 14 urban and peri-urban "PopART intervention" communities in Zambia and South Africa (SA), with a total population of approximately 600,000 and approximately 15% adult HIV prevalence. Community HIV care providers (CHiPs) delivered the PopART intervention during 2014-2017. This was a combination HIV prevention package including universal home-based HIV testing, referral of HIV-positive individuals to government HIV clinic services that offered universal ART (Arm A) or ART according to national guidelines (Arm B), and revisits to HIV-positive individuals to support linkage to HIV care and retention on ART. The intervention was delivered in 3 "rounds," each about 15 months long, during which CHiPs visited all households and aimed to contact all individuals aged ≥15 years at least once. In Arm A in Round 3 (R3), 67% (41,332/61,402) of men and 86% (56,345/65,896) of women in Zambia and 56% (17,813/32,095) of men and 71% (24,461/34,514) of women in SA participated in the intervention, among 193,907 residents aged ≥15 years. Following participation, HIV status was known by 90% of men and women in Zambia and by 78% of men and 85% of women in SA. The median time from CHiP referral of HIV-positive individuals to ART initiation was approximately 3 months. By the end of R3, an estimated 95% of HIV-positive women and 85% of HIV-positive men knew their HIV status, and among these individuals, approximately 90% of women and approximately 85% of men were on ART. ART coverage among all HIV-positive individuals was approximately 85% in women and approximately 75% in men, up from about 45% at the start of the study. ART coverage was lowest among men aged 18 to 34 and women aged 15 to 24 years, and among mobile individuals/in-migrants. Findings from Arm B were similar. The main limitations to our study were that estimates of testing and treatment coverage among men relied on considerable extrapolation because, in each round, approximately one-third of men did not participate in the PopART intervention; that our findings are for a service delivery model that was relatively intensive; and that we did not have comparable data from the 7 "standard-of-care" (Arm C) communities.Conclusions: Our study showed that very high HIV testing and treatment coverage can be achieved through persistent delivery of universal testing, facilitated linkage to HIV care, and universal treatment services. The ART coverage target of 81% was achieved overall, after 4 years of delivery of the PopART intervention, though important gaps remained among men and young people. Our findings are consistent with previously reported findings from southern and east Africa, extending their generalisability to urban settings with high rates of in-migration and mobility and to Zambia and SA.Trial Registration: ClinicalTrials.gov NCT01900977. [ABSTRACT FROM AUTHOR]

Introduction: Zambia has made substantial investments in health systems capacity, yet it remains unclear whether improved service quality improves outcomes. We investigated the association between health system capacity and use of prevention of mother-to-child HIV transmission (PMTCT) services in Zambia. Materials and methods: We analyzed data from two studies conducted in rural and semi-urban Lusaka Province in 2014–2015. Health system capacity, our primary exposure, was measured with a validated balanced scorecard approach. Based on WHO building blocks for health systems strengthening, we derived overall and domain-specific facility scores (range: 0–100), with higher scores indicating greater capacity. Our outcome, community-level maternal antiretroviral drug use at 12 months postpartum, was measured via self-report in a large cohort study evaluating PMTCT program impact. Associations between health systems capacity and our outcome were analyzed via linear regression. Results: Among 29 facilities, median overall facility score was 72 (IQR:67–74). Median domain scores were: patient satisfaction 75 (IQR 71–78); human resources 85 (IQR:63–87); finance 50 (IQR:50–67); governance 82 (IQR:74–91); service capacity 77 (IQR:68–79); service provision 60 (IQR:52–76). Our programmatic outcome was measured from 804 HIV-infected mothers. Median community-level antiretroviral use at 12 months was 81% (IQR:69–89%). Patient satisfaction was the only domain score significantly associated with 12-month maternal antiretroviral use (β:0.22; p = 0.02). When we excluded the human resources and finance domains, we found a positive association between composite 4-domain facility score and 12-month maternal antiretroviral use in peri-urban but not rural facilities. Conclusions: In these Zambian health facilities, patient satisfaction was positively associated with maternal antiretroviral 12 months postpartum. The association between overall health system capacity and maternal antiretroviral drug use was stronger in peri-urban versus rural facilities. Additional work is needed to guide strategic investments for improved outcomes in HIV and broader maternal-child health region-wide. [ABSTRACT FROM AUTHOR]

Background: HPTN071(PopART) is a 3-arm community-randomised study in 21 peri-urban/urban communities in Zambia and the Western Cape of South Africa, with high HIV prevalence and high mobility especially among young adults. In Arm A communities, from November 2013 community HIV care providers (CHiPs) have delivered the “PopART” universal-test-and-treat (UTT) package in annual rounds, during which they visit all households and offer HIV testing. CHiPs refer HIV-positive (HIV+) individuals to routine HIV clinic services, where universal ART (irrespective of CD4 count) is offered, with re-visits to support linkage to care. The overall goal is to reduce population-level adult HIV incidence, through achieving high HIV testing and treatment coverage. Methods and findings: The second annual round was June 2015-October 2016. Included in analysis are all individuals aged ≥15 years who consented to participate, with extrapolation to the total population. Our three main outcomes are (1) knowledge of HIV+ status (2) ART coverage, by the end of Round 2 (R2) and compared with the start of R2, and (3) retention on ART on the day of consenting to participate in R2. We used “time-to-event” methods to estimate the median time to start ART after referral to care. CHiPs visited 45,631 households during R2, ~98% of the estimated total across the four communities, and for 94% (43,022/45,631) consent was given for all household members to be listed on the CHiPs’ electronic register; 120,272 individuals aged ≥15 years were listed, among whom 64% of men (37,265/57,901) and 86% (53,516/62,371) of women consented to participate in R2. We estimated there were 6,521 HIV+ men and 10,690 HIV+ women in the total population of visited households; and that ~80% and ~90% of HIV+ men and women respectively knew their HIV+ status by the end of R2, fairly similar across age groups but lower among those who did not participate in Round 1 (R1). Among those who knew their HIV+ status, ~80% of both men and women were on ART by the end of R2, close to 90% among men aged ≥45 and women aged ≥35 years, but lower among younger adults, those who were resident in R1 but did not participate in R1, and those who were newly resident in the area of the community in which they were living in R2. Overall ART coverage was ~65% among HIV+ men and ~75% among HIV+ women, compared with the cumulative 90–90 target of 81%. Among those who reported ever taking ART, 93% of men and 95% of women self-reported they were on ART and missed 0 pills in the last 3 days. The median time to start ART after referral to care was ~6 months in R2, similar across the age range 25–54 years, compared with ~9.5 months in R1. The two main limitations to our findings were that a comparison with control-arm communities cannot be made until the end of the study; and that to extrapolate to the total population, assumptions were required about individuals who were resident, but did not participate, in R2. Conclusions: Overall coverage against the 90–90 targets was high after two years of intervention, but was lower among men, individuals aged 18–34 years, and those who did not participate in R1. Our findings reflect the relative difficulties for CHiPs to contact men at home, compared with women, and that it is challenging to reach high levels of testing and treatment coverage in communities with substantial mobility and in-migration. The shortened time to start ART after referral to care in R2, compared with R1, was likely attributable to multiple factors including an increased focus of the CHiPs on linkage to care; increasing community acceptance and understanding of the CHiPs, and of ART and UTT, with time; increased coordination with the clinics to facilitate linkage; and clinic improvements. [ABSTRACT FROM AUTHOR]

Introduction: WHO recommends antiretroviral treatment (ART) for all HIV-positive individuals. This study evaluated the association between baseline CD4 count and attrition in a cohort of HIV positive adults initiating ART at three department of health (DOH) clinics routinely providing ART at baseline CD4 counts >500cells/μL for the HPTN 071 (PopART) trial. Methods: All clients attending the DOH clinics were managed according to standard care guidelines with the exception that those starting ART outside of pertinent local guidelines signed research informed consent. DOH data on all HIV-positive adult clients recorded as having initiated ART between January 2014 and November 2015 at the three study clinics was analysed. Attrition, included clients lost to follow up or died, and was defined as ‘being three or more months late for an antiretroviral pharmacy pick-up appointment’. All clients were followed until attrition, transfer out or end May 2016. Results: A total of 2423 clients with a median baseline CD4 count of 328 cells/μL (IQR 195–468) were included of whom 631 (26.0%) experienced attrition and 140 (5.8%) were TFO. Attrition was highest during the first six months of ART (IR 38.3/100 PY; 95% CI 34.8–42.1). Higher attrition was found amongst those with baseline CD4 counts > 500 cells/μL compared to those with baseline CD4 counts of 0–500 cells/μL (aHR 1.26, 95%CI 1.05 to 1.52) This finding was confirmed on subset analyses when restricted to individuals non-pregnant at baseline and when restricted to individuals with follow up of > 12months. Conclusions: Attrition in this study was high, particularly during the first six months of treatment. Attrition was highest amongst clients starting ART at baseline CD4 counts > 500 cells/μL. Strategies to improve retention amongst ART clients, particularly those starting ART at baseline CD4 counts >500cells/μL, need strengthening. Improved monitoring of clients moving in and out of ART care and between clinics will assist in better understanding attrition and ART coverage in high burden countries. [ABSTRACT FROM AUTHOR]

Background: Providing HIV testing at health facilities remains the most common approach to ensuring access to HIV treatment and prevention services for the millions of undiagnosed HIV-infected individuals in sub-Saharan Africa. We sought to explore the costs of providing these services across three southern African countries with high HIV burden. Methods: Primary costing studies were undertaken in 54 health facilities providing HIV testing services (HTS) in Malawi, Zambia and Zimbabwe. Routinely collected monitoring and evaluation data for the health facilities were extracted to estimate the costs per individual tested and costs per HIV-positive individual identified. Costs are presented in 2016 US dollars. Sensitivity analysis explored key drivers of costs. Results: Health facilities were testing on average 2290 individuals annually, albeit with wide variations. The mean cost per individual tested was US$5.03.9 in Malawi, US$4.24 in Zambia and US$8.79 in Zimbabwe. The mean cost per HIV-positive individual identified was US$79.58, US$73.63 and US$178.92 in Malawi, Zambia and Zimbabwe respectively. Both cost estimates were sensitive to scale of testing, facility staffing levels and the costs of HIV test kits. Conclusions: Health facility based HIV testing remains an essential service to meet HIV universal access goals. The low costs and potential for economies of scale suggests an opportunity for further scale-up. However low uptake in many settings suggests that demand creation or alternative testing models may be needed to achieve economies of scale and reach populations less willing to attend facility based services. [ABSTRACT FROM AUTHOR]

Background: The Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 targets require that, by 2020, 90% of those living with HIV know their status, 90% of known HIV-positive individuals receive sustained antiretroviral therapy (ART), and 90% of individuals on ART have durable viral suppression. The HPTN 071 (PopART) trial is measuring the impact of a universal testing and treatment intervention on population-level HIV incidence in 21 urban communities in Zambia and South Africa. We report observational data from four communities in Zambia to assess progress towards the UNAIDS targets after 1 y of the PopART intervention.Methods and Findings: The PopART intervention comprises annual rounds of home-based HIV testing delivered by community HIV-care providers (CHiPs) who also support linkage to care, ART retention, and other services. Data from four communities in Zambia receiving the full intervention (including immediate ART for all individuals with HIV) were used to determine proportions of participants who knew their HIV status after the CHiP visit; proportions linking to care and initiating ART following referral; and overall proportions of HIV-infected individuals who knew their status (first 90 target) and the proportion of these on ART (second 90 target), pre- and post-intervention. We are not able to assess progress towards the third 90 target at this stage of the study. Overall, 121,130 adults (59,283 men and 61,847 women) were enumerated in 46,714 households during the first annual round (December 2013 to June 2015). Of the 45,399 (77%) men and 55,703 (90%) women consenting to the intervention, 80% of men and 85% of women knew their HIV status after the CHiP visit. Of 6,197 HIV-positive adults referred by CHiPs, 42% (95% CI: 40%-43%) initiated ART within 6 mo and 53% (95% CI: 52%-55%) within 12 mo. In the entire population, the estimated proportion of HIV-positive adults who knew their status increased from 52% to 78% for men and from 56% to 87% for women. The estimated proportion of known HIV-positive individuals on ART increased overall from 54% after the CHiP visit to 74% by the end of the round for men and from 53% to 73% for women. The estimated overall proportion of HIV-positive adults on ART, irrespective of whether they knew their status, increased from 44% to 61%, compared with the 81% target (the product of the first two 90 targets). Coverage was lower among young men and women than in older age groups. The main limitation of the study was the need for assumptions concerning knowledge of HIV status and ART coverage among adults not consenting to the intervention or HIV testing, although our conclusions were robust in sensitivity analyses.Conclusions: In this analysis, acceptance of HIV testing among those consenting to the intervention was high, although linkage to care and ART initiation took longer than expected. Knowledge of HIV-positive status increased steeply after 1 y, almost attaining the first 90 target in women and approaching it in men. The second 90 target was more challenging, with approximately three-quarters of known HIV-positive individuals on ART by the end of the annual round. Achieving higher test uptake in men and more rapid linkage to care will be key objectives during the second annual round of the intervention.Trial Registration: ClinicalTrials.gov NCT01900977. [ABSTRACT FROM AUTHOR]

Background: The current cost of Xpert MTB RIF (Xpert) consumables is such that algorithms are needed to select which patients to prioritise for testing with Xpert. Objective: To evaluate two algorithms for prioritisation of Xpert in primary health care settings in a high TB and HIV burden setting. Method: Consecutive, presumptive TB patients with a cough of any duration were offered either Xpert or Fluorescence microscopy (FM) test depending on their CXR score or HIV status. In one facility, sputa from patients with an abnormal CXR were tested with Xpert and those with a normal CXR were tested with FM (“CXR algorithm”). CXR was scored automatically using a Computer Aided Diagnosis (CAD) program. In the other facility, patients who were HIV positive were tested using Xpert and those who were HIV negative were tested with FM (“HIV algorithm”). Results: Of 9482 individuals pre-screened with CXR, Xpert detected TB in 2090/6568 (31.8%) with an abnormal CXR, and FM was AFB positive in 8/2455 (0.3%) with a normal CXR. Of 4444 pre-screened with HIV, Xpert detected TB in 508/2265 (22.4%) HIV positive and FM was AFB positive in 212/1920 (11.0%) in HIV negative individuals. The notification rate of new bacteriologically confirmed TB increased; from 366 to 620/ 100,000/yr and from 145 to 261/100,000/yr at the CXR and HIV algorithm sites respectively. The median time to starting TB treatment at the CXR site compared to the HIV algorithm site was; 1(IQR 1-3 days) and 3 (2-5 days) (p<0.0001) respectively. Conclusion: Use of Xpert in a resource-limited setting at primary care level in conjunction with pre-screening tests reduced the number of Xpert tests performed. The routine use of Xpert resulted in additional cases of confirmed TB patients starting treatment. However, there was no increase in absolute numbers of patients starting TB treatment. Same day diagnosis and treatment commencement was achieved for both bacteriologically confirmed and empirically diagnosed patients where Xpert was used in conjunction with CXR. [ABSTRACT FROM AUTHOR]

Reflecting on a Policy Forum article by Till Bärnighausen and colleagues, the HPTN 071 (PopART) Study Team consider ethical and study power concerns and the importance of the trial’s future findings. [ABSTRACT FROM AUTHOR]

Introduction: In many low income countries, the delivery of quality health services is hampered by health system-wide barriers which are often interlinked, however empirical evidence on how to assess the level and scope of these barriers is scarce. A balanced scorecard is a tool that allows for wider analysis of domains that are deemed important in achieving the overall vision of the health system. We present the quantitative results of the 12 months follow-up study applying the balanced scorecard approach in the BHOMA intervention with the aim of demonstrating the utility of the balanced scorecard in evaluating multiple building blocks in a trial setting. Methods: The BHOMA is a cluster randomised trial that aims to strengthen the health system in three rural districts in Zambia. The intervention aims to improve clinical care quality by implementing practical tools that establish clear clinical care standards through intensive clinic implementations. This paper reports the findings of the follow-up health facility survey that was conducted after 12 months of intervention implementation. Comparisons were made between those facilities in the intervention and control sites. STATA version 12 was used for analysis. Results: The study found significant mean differences between intervention(I) and control (C) sites in the following domains: Training domain (Mean I:C; 87.5.vs 61.1, mean difference 23.3, p = 0.031), adult clinical observation domain (mean I:C; 73.3 vs.58.0, mean difference 10.9, p = 0.02 ) and health information domain (mean I:C; 63.6 vs.56.1, mean difference 6.8, p = 0.01. There was no gender differences in adult service satisfaction. Governance and motivation scores did not differ between control and intervention sites. Conclusion: This study demonstrates the utility of the balanced scorecard in assessing multiple elements of the health system. Using system wide approaches and triangulating data collection methods seems to be key to successful evaluation of such complex health intervention. Trial number: ClinicalTrials.gov NCT01942278 [ABSTRACT FROM AUTHOR]

Objective: To determine the sensitivity and specificity of a Computer Aided Diagnosis (CAD) program for scoring chest x-rays (CXRs) of presumptive tuberculosis (TB) patients compared to Xpert MTB/RIF (Xpert). Method: Consecutive presumptive TB patients with a cough of any duration were offered digital CXR, and opt out HIV testing. CXRs were electronically scored as normal (CAD score ≤60) or abnormal (CAD score>60) using a CAD program. All patients regardless of CAD score were requested to submit a spot sputum sample for testing with Xpert and a spot and morning sample for testing with LED Fluorescence Microscopy-(FM). Results: Of 350 patients with evaluable data, 291 (83.1%) had an abnormal CXR score by CAD. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of CXR compared to Xpert were 100% (95%CI 96.2–100), 23.2% (95%CI 18.2–28.9), 33.0% (95%CI 27.6–38.7) and 100% (95% 93.9–100), respectively. The area under the receiver operator curve (AUC) for CAD was 0.71 (95%CI 0.66–0.77). CXR abnormality correlated with smear grade (r = 0.30, p<0.0001) and with Xpert CT(r = 0.37, p<0.0001). Conclusions: To our knowledge this is the first time that a CAD program for TB has been successfully tested in a real world setting. The study shows that the CAD program had high sensitivity but low specificity and PPV. The use of CAD with digital CXR has the potential to increase the use and availability of chest radiography in screening for TB where trained human resources are scarce. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) and human immunodeficiency virus (HIV) represent two of the greatest health threats in African prisons. In 2010, collaboration between the Centre for Infectious Disease Research in Zambia, the Zambia Prisons Service, and the National TB Program established a TB and HIV screening program in six Zambian prisons. We report data on the prevalence of TB and HIV in one of the largest facilities: Lusaka Central Prison. Methods: Between November 2010 and April 2011, we assessed the prevalence of TB and HIV amongst inmates entering, residing, and exiting the prison, as well as in the surrounding community. The screening protocol included complete history and physical exam, digital radiography, opt-out HIV counseling and testing, sputum smear and culture. A TB case was defined as either bacteriologically confirmed or clinically diagnosed. Results: A total of 2323 participants completed screening. A majority (88%) were male, median age 31 years and body mass index 21.9. TB symptoms were found in 1430 (62%). TB was diagnosed in 176 (7.6%) individuals and 52 people were already on TB treatment at time of screening. TB was bacteriologically confirmed in 88 cases (3.8%) and clinically diagnosed in 88 cases (3.8%). Confirmed TB at entry and exit interventions were 4.6% and 5.3% respectively. Smear was positive in only 25% (n = 22) of bacteriologically confirmed cases. HIV prevalence among inmates currently residing in prison was 27.4%. Conclusion: Ineffective TB and HIV screening programs deter successful disease control strategies in prison facilities and their surrounding communities. We found rates of TB and HIV in Lusaka Central Prison that are substantially higher than the Zambian average, with a trend towards concentration and potential transmission of both diseases within the facility and to the general population. Investment in institutional and criminal justice reform as well as prison-specific health systems is urgently required. [ABSTRACT FROM AUTHOR]

Background: In South Africa the estimated incidence of all forms of tuberculosis (TB) for 2008 was 960/100000. It was reported that all South Africans lived in districts with Directly Observed Therapy, Short-course. However, the 2011 WHO report indicated South Africa as the only country in the world where the TB incidence is still rising. Aims: To report the results of a TB prevalence survey and to determine the speed of TB case detection in the study communities. Methods: In 2005 a TB prevalence survey was done to inform the sample size calculation for the ZAMSTAR (Zambia South Africa TB and AIDS Reduction) trial. It was a cluster survey with clustering by enumeration area; all households were visited within enumeration areas and informed consent obtained from eligible adults. A questionnaire was completed and a sputum sample collected from each adult. Samples were inoculated on both liquid mycobacterium growth indicator tube (MGIT) and Löwenstein-Jensen media. A follow-up HIV prevalence survey was done in 2007. Results: In Community A, the adjusted prevalence of culture positive TB was 32/1000 (95%CI 25–41/1000) and of smear positive TB 8/1000 (95%CI 5–13/1000). In Community B, the adjusted prevalence of culture positive TB was 24/1000 (95%CI 17–32/1000) and of smear positive TB 9/1000 (95%CI 6–15/1000). In Community A the patient diagnostic rate was 0.38/person-year while in community B it was 0.30/person-year. In both communities the adjusted HIV prevalence was 25% (19–30%). Discussion: In both communities a higher TB prevalence than national estimates and a low patient diagnostic rate was calculated, suggesting that cases are not detected at a sufficient rate to interrupt transmission. These findings may contribute to the rising TB incidence in South Africa. The TB epidemic should therefore be addressed rapidly and effectively, especially in the presence of the concurrently high HIV prevalence. [ABSTRACT FROM AUTHOR]

Introduction: There is growing interest in health system performance and recently WHO launched a report on health systems strengthening emphasising the need for close monitoring using system-wide approaches. One recent method is the balanced scorecard system. There is limited application of this method in middle- and low-income countries. This paper applies the concept of balanced scorecard to describe the baseline status of three intervention districts in Zambia. Methodology: The Better Health Outcome through Mentoring and Assessment (BHOMA) project is a randomised step-wedged community intervention that aims to strengthen the health system in three districts in the Republic of Zambia. To assess the baseline status of the participating districts we used a modified balanced scorecard approach following the domains highlighted in the MOH 2011 Strategic Plan. Results: Differences in performance were noted by district and residence. Finance and service delivery domains performed poorly in all study districts. The proportion of the health workers receiving training in the past 12 months was lowest in Kafue (58%) and highest in Luangwa district (77%). Under service capacity, basic equipment and laboratory capacity scores showed major variation, with Kafue and Luangwa having lower scores when compared to Chongwe. The finance domain showed that Kafue and Chongwe had lower scores (44% and 47% respectively). Regression model showed that children's clinical observation scores were negatively correlated with drug availability (coeff −0.40, p = 0.02). Adult clinical observation scores were positively association with adult service satisfaction score (coeff 0.82, p = 0.04) and service readiness (coeff 0.54, p = 0.03). Conclusion: The study applied the balanced scorecard to describe the baseline status of 42 health facilities in three districts of Zambia. Differences in performance were noted by district and residence in most domains with finance and service delivery performing poorly in all study districts. This tool could be valuable in monitoring and evaluation of health systems. [ABSTRACT FROM AUTHOR]

Background: Although historically tuberculosis (TB) has been associated with poverty, few analytical studies from developing countries have tried to: 1. assess the relative impact of poverty on TB after the emergence of HIV; 2. explore the causal mechanism underlying this association; and 3. estimate how many cases of TB could be prevented by improving household socioeconomic position (SEP). Methods and Findings: We undertook a case-control study nested within a population-based TB and HIV prevalence survey conducted in 2005-2006 in two Zambian communities. Cases were defined as persons (15+ years of age) culture positive for M. tuberculosis. Controls were randomly drawn from the TB-free participants enrolled in the prevalence survey. We developed a composite index of household SEP combining variables accounting for four different domains of household SEP. The analysis of the mediation pathway between household SEP and TB was driven by a pre-defined conceptual framework. Adjusted Population Attributable Fractions (aPAF) were estimated. Prevalent TB was significantly associated with lower household SEP [aOR = 6.2, 95%CI: 2.0-19.2 and aOR = 3.4, 95%CI: 1.8-7.6 respectively for low and medium household SEP compared to high]. Other risk factors for prevalent TB included having a diet poor in proteins [aOR = 3.1, 95%CI: 1.1-8.7], being HIV positive [aOR = 3.1, 95%CI: 1.7-5.8], not BCG vaccinated [aOR = 7.7, 95%CI: 2.8-20.8], and having a history of migration [aOR = 5.2, 95%CI: 2.7-10.2]. These associations were not confounded by household SEP. The association between household SEP and TB appeared to be mediated by inadequate consumption of protein food. Approximately the same proportion of cases could be attributed to this variable and HIV infection (aPAF = 42% and 36%, respectively). Conclusions: While the fight against HIV remains central for TB control, interventions addressing low household SEP and, especially food availability, may contribute to strengthen our control efforts. [ABSTRACT FROM AUTHOR]

Introduction: The utility of T-cell based interferon-gamma release assays for the diagnosis of latent tuberculosis infection remains unclear in settings with a high burden of tuberculosis. Objectives: To determine risk factors associated with positive QuantiFERON-TB Gold In-Tube (QFT-GIT) and tuberculin skin test (TST) results and the level of agreement between the tests; to explore the hypotheses that positivity in QFT-GIT is more related to recent infection and less affected by HIV than the TST. Methods: Adult household contacts of tuberculosis patients were invited to participate in a cross-sectional study across 24 communities in Zambia and South Africa. HIV, QFT-GIT and TST tests were done. A questionnaire was used to assess risk factors. Results: A total of 2,220 contacts were seen. 1,803 individuals had interpretable results for both tests, 1,147 (63.6%) were QFT-GIT positive while 725 (40.2%) were TST positive. Agreement between the tests was low (kappa = 0.24). QFT-GIT and TST results were associated with increasing age (adjusted OR [aOR] for each 10 year increase for QFT-GIT 1.15; 95% CI: 1.06- 1.25, and for TST aOR: 1.10; 95% CI 1.01-1.20). HIV positivity was less common among those with positive results on QFT-GIT (aOR: 0.51; 95% CI: 0.39-0.67) and TST (aOR: 0.61; 95% CI: 0.46-0.82). Smear positivity of the index case was associated with QFT-GIT (aOR: 1.25; 95% CI: 0.90-1.74) and TST (aOR: 1.39; 95% CI: 0.98-1.98) results. We found little evidence in our data to support our hypotheses. Conclusion: QFT-GIT may not be more sensitive than the TST to detect risk factors associated with tuberculous infection. We found little evidence to support the hypotheses that positivity in QFT-GIT is more related to recent infection and less affected by HIV than the TST. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization recommends the screening of all people living with HIV for tuberculosis (TB) disease, followed by TB treatment, or isoniazid preventive therapy (IPT) when TB is excluded. However, the difficulty of reliably excluding TB disease has severely limited TB screening and IPT uptake in resource-limited settings. We conducted an individual participant data meta-analysis of primary studies, aiming to identify a sensitive TB screening rule. Methods and Findings: We identified 12 studies that had systematically collected sputum specimens regardless of signs or symptoms, at least one mycobacterial culture, clinical symptoms, and HIV and TB disease status. Bivariate random-effects meta-analysis and the hierarchical summary relative operating characteristic curves were used to evaluate the screening performance of all combinations of variables of interest. TB disease was diagnosed in 557 (5.8%) of 9,626 people living with HIV. The primary analysis included 8,148 people living with HIV who could be evaluated on five symptoms from nine of the 12 studies. The median age was 34 years. The best performing rule was the presence of any one of: current cough (any duration), fever, night sweats, or weight loss. The overall sensitivity of this rule was 78.9% (95% confidence interval [CI] 58.3%-90.9%) and specificity was 49.6% (95% CI 29.2%-70.1%). Its sensitivity increased to 90.1% (95% CI 76.3%-96.2%) among participants selected from clinical settings and to 88.0% (95% CI 76.1%-94.4%) among those who were not previously screened for TB. Negative predictive value was 97.7% (95% CI 97.4%-98.0%) and 90.0% (95% CI 88.6%-91.3%) at 5% and 20% prevalence of TB among people living with HIV, respectively. Abnormal chest radiographic findings increased the sensitivity of the rule by 11.7% (90.6% versus 78.9%) with a reduction of specificity by 10.7% (49.6% versus 38.9%). Conclusions: Absence of all of current cough, fever, night sweats, and weight loss can identify a subset of people living with HIV who have a very low probability of having TB disease. A simplified screening rule using any one of these symptoms can be used in resource-constrained settings to identify people living with HIV in need of further diagnostic assessment for TB. Use of this algorithm should result in earlier TB diagnosis and treatment, and should allow for substantial scale-up of IPT. [ABSTRACT FROM AUTHOR]

Background: Interferon gamma release assays (IGRA) are replacing the tuberculin skin test (TST) as a diagnostic tool for Mycobacterium tuberculosis infection. However research into the test's performance in the high HIV-TB burden setting is scarce. This study aimed to define the sensitivity of an IGRA, QuantiFERON-TBH Gold In-Tube (QGIT), in adult Zambian patients with active smear-positive tuberculosis. Secondary outcomes focussed on the effect of HIV on the test's performance. Principal Findings: Patients attending government health clinics were recruited within 1 month of starting treatment for TB. Subjects were tested with QGIT and TST. T lymphocyte counts were estimated (CD3+, CD4+, CD8+). QGIT was performed for 112 subjects. 83/112 were QGIT positive giving an overall sensitivity of 74% [95%CI: 66,82]. A marked decrease in sensitivity was observed in HIV positive patients with 37/59 (63%) being QGIT positive compared to 31/37 (84%) HIV negative patients [chi2 p = 0.033]. Low CD4+ count was associated with increases in both indeterminate and false-negative results. Low CD4+ count in combination with high/normal CD8+ count was associated with false-negative results. TST was recorded for 92 patients, 62/92 were positive, giving a sensitivity of 67% [95%CI: 58,77]. Although there was little difference in the overall sensitivities, agreement between TST and QGIT was poor. Conclusions: QGIT was technically feasible with results in HIV negative subjects comparable to those achieved elsewhere. However, where under-treated HIV is prevalent, an increased proportion of both indeterminate and false-negative QGIT results can be expected in patients with active TB. The implications of this for the diagnosis of LTBI by QGIT is unclear. The diagnostic and prognostic relevance of IGRAs in high burden settings needs to be better characterised. [ABSTRACT FROM AUTHOR]

Objectives:To determine the prevalence and correlates of alcohol dependence disorders in persons receiving treatment for HIV and Tuberculosis (TB) at 16 Primary Health Care centres (PHC) across Zambia. Methods:649 adult patients receiving treatment for HIV and/or TB at PHCs in Zambia (363 males, 286 females) were recruited between 1st December 2009 and 31st January 2010. Data on socio-demographic variables, clinical disease features (TB and HIV), and psychopathological status were collected. The Mini International Neuropsychiatric Interview (MINI) was used to diagnose alcohol dependence disorder. Correlates of alcohol dependence were analyzed for men only, due to low prevalence in women. Univariable and multivariable logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI), using general estimating equations to allow for within-PHC clustering. Results:The prevalence of alcohol dependence was 27.2% (95%CI: 17.7-39.5%) for men and 3.9% (95%CI: 1.4-0.1%) for women. Factors associated with alcohol dependence disorder in men included being single, divorced or widowed compared with married (adjusted OR = 1.47, 95%CI: 1.00-2.14) and being unemployed (adjusted OR=1.30, 95%CI: 1.01-1.67). The highest prevalence of alcohol dependence was among HIV-test unknown TB patients (34.7%), and lowest was among HIV positive patients on treatment but without TB (14.1%), although the difference was not statistically significant (p=0.38). Conclusions:Male TB/HIV patients in this population have high prevalence of alcohol dependence disorder, and prevalence differs by HIV/TB status. Further work is needed to explore interventions to reduce harmful drinking in this population. [ABSTRACT FROM AUTHOR]