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Abstract Introduction Tuberculosis (TB) is an important cause of morbidity and mortality among people living with HIV (PLHIV). Current WHO-recommended strategies for diagnosing TB among hospitalized PLHIV rely on symptom screening and disease severity to assess eligibility for urine lipoarabinomannan lateral flow (LF-LAM) and molecular testing. Despite these recommendations, autopsy studies show a large burden of undiagnosed TB among admitted PLHIV. The EXULTANT trial aims to assess the impact of an expanded screening strategy using three specimens (sputum, stool, and urine) for TB diagnosis among PLHIV admitted to hospitals in two high HIV and TB burden African countries. Methods This is a multicenter, pragmatic, individually randomized controlled trial conducted across eleven hospitals in Tanzania and Mozambique. Participants in the intervention arm will be tested with Xpert MTB/RIF Ultra® from expectorated sputum, stool, and urine samples, with additional urine LF-LAM testing in the first 24 h after hospital admission, irrespective of the presence of the symptoms. The control arm will implement the WHO standard of care recommendations. Hospitalized adults (≥ 18 years) with a confirmed HIV-diagnosis, irrespective of antiretroviral (ART) therapy status or presence of TB symptoms will be assessed for eligibility at admission. Patients with a pre-existing TB diagnosis, those receiving anti-tuberculosis therapy or tuberculosis preventive treatment in the 6 months prior to enrolment, and those transferred from other hospitals will not be eligible. Also, participants admitted for traumatic reasons such as acute abdomen, maternal conditions, scheduled surgery, having a positive SARS-CoV2 test will be ineligible. The primary endpoint is the proportion of participants with microbiologically confirmed TB starting treatment within 3 days of enrolment. Discussion The EXULTANT trial investigates rapid implementation after admission of a new diagnostic algorithm using Xpert MTB/RIF Ultra® in several non-invasive specimens, in addition to LF-LAM, in hospitalized PLHIV regardless of TB symptoms. This enhanced strategy is anticipated to detect frequently missed TB cases in this population and is being evaluated as an implementable and scalable intervention. Trial registration Trial reference number: NCT04568967 (ClinicalTrials.gov) registered on 2020–09-29.

Abstract Background Of the 2 million children living with HIV globally, 90% live in sub-Saharan Africa. Despite antiretroviral therapy, longstanding HIV infection is associated with several chronic complications in children including growth failure, particularly stunting and delayed puberty. Vitamin D deficiency, which is highly prevalent among children living with HIV in sub-Saharan Africa, has further adverse impact on bone health. This trial aims to establish whether supplementation with vitamin D3 and calcium carbonate improves musculoskeletal health among peripubertal children living with HIV. This paper is an update to an already existing protocol that was previously published in Trials in 2022 and details changes in the trial outcomes. Methods/design We will conduct an individually randomised, double-blinded, placebo-controlled trial of weekly high-dose vitamin D3 (20,000 IU) plus daily calcium carbonate (500 mg) supplementation for 48 weeks. Eight hundred and forty children living with HIV aged 11–19 years taking ART for ≥ 6 months will be enrolled and followed up for 96 weeks. The primary outcome is DXA-measured total body less-head bone mineral density Z-score (TBLH-BMD) at 48 weeks and is an update to the previous primary outcome total body less-head bone mineral content adjusted for lean mass (TBLH-BMCLBM) Z-score. The primary outcome was updated to address the substantial differences in distributions of TBLH-BMCLBM Z-score between the two sites as a result of software differences of the DXA machines. Secondary outcomes are DXA-measured TBLH-BMD Z-score adjusted for height at 48 weeks a new secondary outcome, lumbar spine bone mineral apparent density Z-score, number of respiratory infections, lean muscle mass and grip-strength at 48 and 96 weeks, and TBLH-BMD Z-score at 96 weeks. Sub-studies will investigate the effect of the intervention on vitamin D3 pathway metabolites and markers of bone turnover, intestinal microbiota, and innate and acquired immune function. Discussion This is the largest trial to date of vitamin D supplementation in children living with HIV. Intervening to address deficits in bone accrual through childhood is critical for optimising adolescent and early adult bone health, and prevention of later adult osteoporotic fractures. Trial results will draw attention to the need to screen for and treat long-term comorbidities in children living with HIV in resource-limited settings. Trial registration Pan African Clinical Trials Registry PACTR20200989766029. Registered on September 3, 2020. URL of trial registry record: https://pactr.samrc.ac.za Trial status Participant follow-up completed; data analysis ongoing.

Summary: Background: Clinical severity scores can identify patients at risk of severe disease and death, and improve patient management. The modified early warning score (MEWS), the quick Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA), and the Universal Vital Assessment (UVA) were developed as risk-stratification tools, but they have not been fully validated in low-resource settings where fever and infectious diseases are frequent reasons for health care seeking. We assessed the performance of MEWS, qSOFA, and UVA in predicting mortality among febrile patients in the Lao PDR, Malawi, Mozambique, and Zimbabwe. Methods: We prospectively enrolled in- and outpatients aged ≥ 15 years who presented with fever (≥37.5 °C) from June 2018–March 2021. We collected clinical data to calculate each severity score. The primary outcome was mortality 28 days after enrolment. The predictive performance of each score was determined using area under the receiver operating curve (AUC). Findings: A total of 2797 participants were included in this analysis. The median (IQR) age was 32 (24–43) years, 38% were inpatients, and 60% (1684/2797) were female. By the time of follow-up, 7% (185/2797) had died. The AUC (95% CI) for MEWS, qSOFA and UVA were 0.67 (0.63–0.71), 0.68 (0.64–0.72), and 0.82 (0.79–0.85), respectively. The AUC comparison found UVA outperformed both MEWS (p

Objectives Hazardous drinking (HD) and substance use (SU) can lead to disinhibited behaviour and are both growing public health problems among Southern African youths. We investigated the prevalence of SU and HD and their association with risky sexual behaviour among youth in Zimbabwe.Design Data analysis from a population-based survey conducted between October 2021 and June 2022 to ascertain the outcomes of a cluster randomised trial (CHIEDZA: Trial registration number:NCT03719521). Trial Stage: Post-results.Setting 24 communities in three provinces in Zimbabwe.Participants Youth aged 18–24 years living in randomly selected households.Outcome measures HD was defined as an Alcohol Use Disorders Identification Test score ≥8, SU was defined as ever use of ≥1 commonly used substances in the local setting.Results Of 17 585 participants eligible for this analysis, 61% were women and the median age was 20 (IQR: 19–22) years. Overall, 4.5% and 7.0% of participants reported HD and SU, respectively. Men had a substantially higher prevalence than women of HD (8.2% vs 1.9%) and SU (15.1% vs 1.5%). Among men, after adjusting for socio-demographic factors, we found increased odds of having >1 sexual partner in those who engaged in SU (adjusted OR (aOR)=2.67, 95% CI: 2.21 to 3.22), HD (aOR=3.40, 95% CI: 2.71 to 4.26) and concurrent HD and SU (aOR=4.57,95% CI: 3.59 to 5.81) compared with those who did not engage in HD or SU. Similarly, there were increased odds of receiving/providing transactional sex among men who engaged in SU (aOR=2.51, 95% CI: 1.68 to 3.74), HD (aOR=3.60, 95% CI: 2.24 to 5.79), and concurrent HD and SU (aOR=7.74, 95% CI: 5.44 to 11.0). SU was associated with 22% increased odds of inconsistent condom use in men (aOR=1.22, 95% CI: 1.03 to 1.47). In women, the odds of having >1 sexual partner and having transactional sex were also increased among those who engaged in SU and HD.Conclusion SU and HD are associated with sexual behaviours that increase the risk of HIV acquisition in youth. Sexual and reproductive health interventions must consider HD and SU as potential drivers of risky sexual behaviour in youths.

Introduction A prototype lateral flow device detecting cytokine biomarkers interleukin (IL)-1α and IL-1β has been developed as a point-of-care test—called the Genital InFlammation Test (GIFT)—for detecting genital inflammation associated with sexually transmitted infections (STIs) and/or bacterial vaginosis (BV) in women. In this paper, we describe the rationale and design for studies that will be conducted in South Africa, Zimbabwe and Madagascar to evaluate the performance of GIFT and how it could be integrated into routine care.Methods and analysis We will conduct a prospective, multidisciplinary, multicentre, cross-sectional and observational clinical study comprising two distinct components: a biomedical (‘diagnostic study’) and a qualitative, modelling and economic (‘an integration into care study’) part. The diagnostic study aims to evaluate GIFT’s performance in identifying asymptomatic women with discharge-causing STIs (Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Trichomonas vaginalis (TV) and Mycoplasma genitalium (MG)) and BV. Study participants will be recruited from women attending research sites and family planning services. Several vaginal swabs will be collected for the evaluation of cytokine concentrations (ELISA), STIs (nucleic acid amplification tests), BV (Nugent score) and vaginal microbiome characteristics (16S rRNA gene sequencing). The first collected vaginal swab will be used for the GIFT assay which will be performed in parallel by a healthcare worker in the clinic near the participant, and by a technician in the laboratory. The integration into care study aims to explore how GIFT could be integrated into routine care. Four activities will be conducted: user experiences and/or perceptions of the GIFT device involving qualitative focus group discussions and in-depth interviews with key stakeholders; discrete choice experiments; development of a decision tree classification algorithm; and economic evaluation of defined management algorithms.Ethics and dissemination Findings will be reported to participants, collaborators and local government for the three sites, presented at national and international conferences, and disseminated in peer-reviewed publications.The protocol and all study documents such as informed consent forms were reviewed and approved by the University of Cape Town Human Research Ethics Committee (HREC reference 366/2022), Medical Research Council of Zimbabwe (MRCZ/A/2966), Comité d’Ethique pour la Recherche Biomédicale de Madagascar (N° 143 MNSAP/SG/AMM/CERBM) and the London School of Hygiene and Tropical Medicine ethics committee (LSHTM reference 28046).Before the start, this study was submitted to the Clinicaltrials.gov public registry (NCT05723484).Trial registration number NCT05723484.

ABSTRACTMultidrug-resistant tuberculosis (MDR-TB) management has become a serious global health challenge. Understanding its epidemic determinants on the regional level is crucial for developing effective control measures. We used whole genome sequencing data of 238 of Mycobacterium tuberculosis complex (MTBC) strains to determine drug resistance profiles, phylogeny, and transmission dynamics of MDR/rifampicin-resistant (RR) MTBC strains from Sierra Leone. Forty-two strains were classified as RR, 196 as MDR, 5 were resistant to bedaquiline (BDQ) and clofazimine (CFZ), but none was found to be resistant to fluoroquinolones. Sixty-one (26%) strains were resistant to all first-line drugs, three of which had additional resistance to BDQ/CFZ. The strains were classified into six major MTBC lineages (L), with strains of L4 being the most prevalent, 62% (n = 147), followed by L6 (Mycobacterium africanum) strains, (21%, n = 50). The overall clustering rate (using ≤d12 single-nucleotide polymorphism threshold) was 44%, stratified into 31 clusters ranging from 2 to 16 strains. The largest cluster (n = 16) was formed by sublineage 2.2.1 Beijing Ancestral 3 strains, which developed MDR several times. Meanwhile, 10 of the L6 strains had a primary MDR transmission. We observed a high diversity of drug resistance mutations, including borderline resistance mutations to isoniazid and rifampicin, and mutations were not detected by commercial assays. In conclusion, one in five strains investigated was resistant to all first-line drugs, three of which had evidence of BDQ/CFZ resistance. Implementation of interventions such as rapid diagnostics that prevent further resistance development and stop MDR-TB transmission chains in the country is urgently needed.IMPORTANCEA substantial proportion of MDR-TB strains in Sierra Leone were resistant against all first line drugs; however this makes the all-oral-six-month BPaLM regimen or other 6-9 months all oral regimens still viable, mainly because there was no FQ resistance.Resistance to BDQ was detected, as well as RR, due to mutations outside of the hotspot region. While the prevalence of those resistances was low, it is still cause for concern and needs to be closely monitored.

IntroductionGlobally adolescents and young adults (AYA) with tuberculosis (TB) face unique challenges. Until recently they have received little attention and few tailored interventions exist. To improve TB outcomes in this population, there is a need to implement tailored interventions. However, limited research has been conducted about how to meet the needs of AYA with tuberculosis. In this paper we present the findings of a qualitative study to explore the needs of AYA with TB in Zimbabwe and to identify interventions to optimize their engagement in TB care.MethodsWe conducted two participatory workshops with 16 AYA, aged 10-24 years diagnosed with TB to explore their experiences of TB disease and treatment. Through subsequent interviews with 15 of the same AYA and with two other key stakeholder groups (health care providers n = 11 and policy makers n = 9), we sought to identify areas of convergence and divergence about what youth-orientated services and policies would be effective in Zimbabwe. Qualitative data were analyzed iteratively and thematically.ResultsThe findings are presented to align with four levels of a socio-ecological framework: individual, community, health system and policy. All three stakeholder groups highlighted the unmet mental health and TB literacy needs of AYA, which are particularly acute early in their TB care journey, as well as the imperative of engendering family support and securing the continuity of educational or employment opportunities during and after receiving TB care. There was a consensus that clinical services needed to become more youth-centered by extending training for health care providers and investing in peer-delivered psychosocial support. More broadly, there was also a strong consensus that adolescent-specific TB policies require further development and implementation, accompanied by community-based TB education and awareness campaigns to emphasize the curability of TB and to reduce TB related stigma.ConclusionsThere is much to be done to improve TB care for AYA. We found that there is need for alignment on where investment is needed to support the development of context-appropriate and effective interventions. There is an opportunity to benefit from translational learning from other successful approaches, such as HIV, within the region. Implementation of evidence-based interventions and youth-friendly policies and programs are much needed to improve outcomes for AYA with TB.

Pakistan is one of the five highest tuberculosis burden countries globally. We estimated prevalence of adult bacteriologically confirmed pulmonary tuberculosis and annual risk of Mycobacterium tuberculosis (M. tuberculosis) infection in children aged 2-4 years in Karachi, Pakistan. The survey design enabled exploration of tuberculosis burden by whether the population had previously been exposed to widespread tuberculosis active case-finding (ACF) activities or not. We conducted a concurrent adult pulmonary tuberculosis prevalence survey and a child M. tuberculosis infection survey using interferon gamma release assays in four districts (Korangi, South, West and Central). A cluster-based unequal probability random sampling method was employed with the a priori plan to oversample Korangi district which had been the focus of tuberculosis ACF activities since 2011. We defined Korangi district as the 'prior ACF' zone and remaining districts as the 'no prior ACF' zone. Between March 2018 and May 2019, 34,962 adults (78·5% of those eligible) and 1,505 children (59·9%) participated. Overall estimated prevalence of bacteriologically confirmed pulmonary tuberculosis was 387 cases per 100,000 population (95% CI 276-498) with a prevalence of 421 cases [95% CI 276-567] per 100,000 in the 'no prior ACF' and 279 cases [95% CI 155-403] per 100,000 in the 'prior ACF' zone. We estimated the annual risk of M. tuberculosis infection in children to be 1·1% (95% CI 0·7-1·5) in the 'no prior ACF' zone and 0·6% (95% CI 0·3-1·1) in the 'prior ACF' zone. We observed consistent differences in the population distribution of tuberculosis between the 'prior ACF' and 'no prior' ACF zones with a trend towards lower estimates of burden and M. tuberculosis transmission in the 'prior ACF' zone. A plausible explanation is that intensive ACF activities that have been ongoing in Korangi district for the preceding years have noticeably reduced the burden of tuberculosis and transmission.

We determined the impact of the COVID-19 pandemic on mycobacterial diagnostic services. 40 laboratories from 22 countries completed an online questionnaire covering the redeployment of the laboratory infrastructure and/or staff for SARS-CoV-2 testing, staff shortages and supply chain disruptions. 28 laboratories reported monthly numbers of samples processed for mycobacterial investigations and monthly numbers of M. tuberculosis complex (MTBC) PCRs performed between October 1st 2018 and October 31st 2020. More than half (23/40) of the participating TB laboratories reported having performed COVID-19 diagnostics in the early phase of the pandemic, in part with negative impact on the mycobacterial service activities. All participating laboratories reported shortages of consumables and laboratory equipment due to supply chain issues. Average monthly sample numbers decreased by 24% between January 2020 and October 2020 compared to pre-pandemic averages. At the end of the study period, most participating laboratories had not returned to pre-pandemic average MTBC PCR throughput.

Youth living with HIV are at higher risk than adults of disengaging from HIV care. Differentiated models of care such as community delivery of antiretroviral therapy (ART) may improve treatment outcomes. We investigated outcomes across the HIV cascade among youth accessing HIV services in a community-based setting. This study was nested in a cluster-randomised controlled trial (CHIEDZA: Clinicaltrials.gov, Registration Number: NCT03719521) conducted in three provinces in Zimbabwe and aimed to investigate the impact of a youth-friendly community-based package of HIV services, integrated with sexual and reproductive health services for youth (16-24 years), on population-level HIV viral load (VL). HIV services included HIV testing, ART initiation and continuous care, VL testing, and adherence support. Overall 377 clients were newly diagnosed with HIV at CHIEDZA, and linkage to HIV care was confirmed for 265 (70.7%, 234 accessed care at CHIEDZA and 31 with other providers); of these 250 (94.3%) started ART. Among those starting ART at CHIEDZA who did not transfer out and had enough follow up time (>6 months), 38% (68/177) were lost-to-follow-up within six months. Viral suppression (HIV Viral Load

BackgroundWe investigated the clinical profile, complications, and outcomes of inpatients with COVID-19 at Parirenyatwa Hospital, Harare, across the first two waves of SARS-CoV-2 infection, and factors associated with mortality.MethodsWe conducted a prospective cohort study on all patients admitted to the COVID-19 unit. Data were extracted from medical records and negative binomial regression with robust standard errors was used to assess the association between sociodemographic and clinical characteristics and mortality. Cox Regression was used for sensitivity analysis.ResultsOf 563 people admitted with COVID-19 between 2 July 2020 and 19 March 2021, 214 (38.0%) died, 340 were discharged and 9 transferred. The median age was 56 (IQR 44-68) years and 53.8% were male. Overall, 38.8% experienced a complication, the most common being acute kidney injury (17.9%) and hyperglycaemia (13.1%). The most common comorbidity was hypertension (41.3%) followed by diabetes (28.6%), HIV (12.1%), cardiovascular disease (10.9%) and chronic kidney disease (7.8%). Among participants who stayed in the ward for more than 1 night, mortality was higher in patients with comorbidity compared to those without any comorbidity (38.7% vs 25.5%, risk ratio (RR) = 1.52 (95% CI 1.11, 2.07), p = 0.008). After adjusting for oxygen saturation, comorbidities, sex and pregnancy, mortality was higher in the second wave than in the first (adjusted RR 1.23, 95% CI 1.00-1.51, p = 0.05). In the second wave 57/161 (35.4%) deaths were attributed to lack of resources, mainly human resources.ConclusionThe mortality rate was high and clinical COVID-19 care needs to pay careful attention to patient monitoring for complications and management of comorbidities. This will require addressing the critical health workforce shortage issues. Prevention of COVID-19 including vaccination particularly among individuals with comorbidities remains a high priority.

The burden of non-communicable diseases (NCDs) in southern Africa is expanding and is superimposed on high HIV prevalence. Healthcare workers are a scarce resource; yet are vital to health systems. There are very limited studies on the burden of chronic conditions among healthcare workers in Africa, and none exploring multimorbidity (≥2 chronic conditions). We describe the epidemiology of infectious (HIV) and non-communicable chronic conditions, and multimorbidity, among Zimbabwean healthcare workers. Healthcare workers (≥18 years) in eight Zimbabwean provinces were invited to a voluntary, cross-sectional health-check, including HIV, diabetes, hypertension and mental health screening. Statistical analyses described the prevalence and risk factors for multimorbidity (two or more of HIV, diabetes, hypertension or common mental disorder) and each condition. Missing data were handled using multiple imputation. Among 6598 healthcare workers (July 2020-July 2022) participating in the health-check, median age was 37 years (interquartile range 29-44), 79% were women and 10% knew they were living with HIV. Half had at least one chronic condition: 11% were living with HIV, 36% had elevated blood pressure, 12% had elevated HbA1c and 11% had symptoms of common mental disorder. The overall prevalence of multimorbidity was 15% (95% CI: 13-17%); 39% (95% CI: 36-43%) among people aged 50 and older. Whilst most HIV was diagnosed and treated, other chronic conditions were usually undiagnosed or uncontrolled. Limiting our definition of multimorbidity to two or more screened conditions sought to reduce bias due to access to diagnosis, however, may have led to a lower reported prevalence than that found using a wider definition. Half of healthcare workers screened were living with a chronic condition; one in seven had multimorbidity. Other than HIV, most conditions were undiagnosed or untreated. Multisectoral action to implement contextually relevant, chronic disease services in Africa is urgently needed. Specific attention on health workers is required to protect and retain this critical workforce.

Health workers are essential for a functioning healthcare system, and their own health is often not addressed. During the COVID-19 pandemic health workers were at high risk of SARS-CoV-2 infection whilst coping with increased healthcare demand. Here we report the development, implementation, and uptake of an integrated health check combining SARS-CoV-2 testing with screening for other communicable and non-communicable diseases for health workers in Zimbabwe during the COVID-19 pandemic. Health checks were offered to health workers in public and private health facilities from July 2020 to June 2022. Data on the number of health workers accessing the service and yield of screening was collected. Workshops and in-depth interviews were conducted to explore the perceptions and experiences of clients and service providers. 6598 health workers across 48 health facilities accessed the service. Among those reached, 5215 (79%) were women, the median age was 37 (IQR: 29-44) years and the largest proportion were nurses (n = 2092, 32%). 149 (2.3%) healthcare workers tested positive for SARS-CoV-2. Uptake of screening services was almost 100% for all screened conditions except HIV. The most common conditions detected through screening were elevated blood pressure (n = 1249; 19%), elevated HbA1c (n = 428; 7.7%) and common mental disorder (n = 645; 9.8%). Process evaluation showed high acceptability of the service. Key enablers for health workers accessing the service included free and comprehensive service provision, and availability of reliable point-of-care screening methods. Implementation of a comprehensive health check for health workers was feasible, acceptable, and effective, even during a pandemic. Conventional occupational health programmes focus on infectious diseases. In a society where even health workers cannot afford health care, free comprehensive occupational health services may address unmet needs in prevention, diagnosis, and treatment for chronic non-communicable conditions.

Abstract Background Index-linked HIV testing for children, whereby HIV testing is offered to children of individuals living with HIV, has the potential to identify children living with undiagnosed HIV. The “Bridging the Gap in HIV Testing and Care for Children in Zimbabwe” (B-GAP) study implemented and evaluated the provision of index-linked HIV testing for children aged 2–18 years in Zimbabwe. We conducted a process evaluation to understand the considerations for programmatic delivery and scale-up of this strategy. Methods We used implementation documentation to explore experiences of the field teams and project manager who delivered the index-linked testing program, and to describe barriers and facilitators to index-linked testing from their perspectives. Qualitative data were drawn from weekly logs maintained by the field teams, monthly project meeting minutes, the project coordinator’s incident reports and WhatsApp group chats between the study team and the coordinator. Data from each of the sources was analysed thematically and synthesised to inform the scale-up of this intervention. Results Five main themes were identified related to the implementation of the intervention: (1) there was reduced clinic attendance of potentially eligible indexes due to community-based differentiated HIV care delivery and collection of HIV treatment by proxy individuals; (2) some indexes reported that they did not live in the same household as their children, reflecting the high levels of community mobility; (3) there were also thought to be some instances of ‘soft refusal’; (4) further, delivery of HIV testing was limited by difficulties faced by indexes in attending health facilities with their children for clinic-based testing, stigma around community-based testing, and the lack of familiarity of indexes with caregiver provided oral HIV testing; (5) and finally, test kit stockouts and inadequate staffing also constrained delivery of index-linked HIV testing. Conclusions There was attrition along the index-linked HIV testing cascade of children. While challenges remain at all levels of implementation, programmatic adaptations of index-linked HIV testing approaches to suit patterns of clinic attendance and household structures may strengthen implementation of this strategy. Our findings highlight the need to tailor index-linked HIV testing to subpopulations and contexts to maximise its effectiveness.

Background Youth have poorer HIV-related outcomes when compared to other age-groups. We describe the protocol for a cluster randomised trial (CRT) to evaluate the effectiveness of community-based, integrated HIV and sexual and reproductive health services for youth on HIV outcomes. Protocol The CHIEDZA trial is being conducted in three provinces in Zimbabwe, each with eight geographically demarcated areas (clusters) (total 24 clusters) randomised 1:1 to standard of care (existing health services) or to the intervention. The intervention comprises community-based delivery of HIV services including testing, antiretroviral therapy, treatment monitoring and adherence support as well as family planning, syndromic management of sexually transmitted infections (STIs), menstrual health management, condoms and HIV prevention and general health counselling. Youth aged 16–24 years living within intervention clusters are eligible to access CHIEDZA services. A CRT of STI screening (chlamydia, gonorrhoea and trichomoniasis) is nested in two provinces (16 of 24 clusters). The intervention is delivered over a 30-month period by a multidisciplinary team trained and configured to provide high-quality, youth friendly services. Outcomes will be ascertained through a population-based survey of 18–24-year-olds. The primary outcome is HIV viral load

Introduction Sexually transmitted infections (STIs) such as chlamydia, gonorrhoea, trichomoniasis, and syphilis, are associated with adverse birth outcomes. Treatment should be accompanied by partner services to prevent re-infection and break cycles of transmission. Partner services include the processes of partner notification (PN) as well as arranging for their attendance for testing and/or treatment. However, due to a complex mix of cultural, socio-economic, and health access factors, uptake of partner services is often very low, in many settings globally. Alternative strategies to facilitate partner services are therefore needed. The aim of this study is to assess the impact of a small financial incentive on uptake of partner services for STIs as part of antenatal care (ANC) services in Zimbabwe. Methods and analysis This trial will be embedded within a prospective interventional study in Harare, aiming to evaluate integration of point-of-care diagnostics for STIs into ANC settings. One thousand pregnant women will be screened for chlamydia, gonorrhoea, trichomoniasis, and syphilis. All individuals with STIs will be offered treatment, risk reduction counselling, and client PN. Each clinic day will be randomised 1:1 to be an incentive or non-incentive day. On incentive days, participants diagnosed with a curable STI will be offered a PN slip, that when returned will entitle their partners to $3 (USD) in compensation. On non-incentive days, regular PN slips with no incentive are provided. The primary outcome measure is the proportion of individuals with at least one partner who returns for partner services based on administrative records. Secondary outcomes will include the number of days between index case diagnosis and the partner attending for partner services, uptake of PN slips by pregnant women, adverse birth outcomes in index cases, partners who receive treatment, and intervention cost. Registration Pan African Clinical Trials Registry: PACTR202302702036850 (Approval date 18th February 2022).

Summary: Background: Young people are at high risk of sexually transmitted infections (STIs). We report STI testing uptake, prevalence and incidence within a community-based integrated HIV and sexual and reproductive health service for youth, being evaluated in a cluster randomised trial in Zimbabwe. Methods: This paper reports the intervention findings of the cluster randomised trial whereby STI testing was offered to all service attendees (16–24 years) in 12 intervention clusters over 12 months between October 5, 2020, and December 17, 2021, in Zimbabwe. Testing for Chlamydia trachomatis [CT] and Neisseria gonorrhoeae [NG] was offered to males and females with results available in one week and follow-up of test-positive clients by telephone. Trichomonas vaginalis [TV] testing was offered to females only with same day results and treatment. Youth testing positive for any STI were offered partner notification slips and free treatment for partners. This trial was registered with ISRCTN Registry, ISRCTN15013425. Findings: Overall, 8549/9891 (86.1%) eligible youth accepted CT/NG testing. Prevalence of CT and NG was 14.7% (95% CI 13.6–15.8) and 2.8% (95% CI 2.2–3.6) respectively. Combined prevalence of CT, NG or TV in women was 23.2% (95% CI 21.5–25.0). After adjusting for cluster, age and sex, the odds of NG were increased in those living with HIV (aOR 3.14, 95% CI 2.21–4.47). The incidence rate among those who initially tested negative for CT or NG was 25.6/100PY (95% CI 20.6–31.8). CT/NG treatment uptake was 924/1526 (60.6%). TV treatment uptake was 483/489 (98.8%). A partner returned for treatment for 103/1807 clients (5.7%). Interpretation: Our findings show high acceptability of STI testing among youth. STI prevalence was high particularly among females and youth with HIV, underscoring the need for integration of HIV and STI services. Funding: MRC/ESRC/DFID/NIHR (MR/T040327/1) and Wellcome Trust (206316/Z/17/Z).

Introduction COVID-19 vaccine acceptance research has mostly originated from high-income countries and reasons why youth may not get vaccinated may differ in low-income settings. Understanding vaccination coverage across different population groups and the sociocultural influences in healthcare delivery is important to inform targeted vaccination campaigns.Methods A population-based survey was conducted in 24 communities across three provinces (Harare, Bulawayo and Mashonaland East) in Zimbabwe between October 2021 and June 2022. Youth aged 18–24 years were randomly selected using multistage sampling. Sociodemographic characteristics, COVID-19 vaccination uptake and reasons for non-uptake were collected, and odds of vaccination was investigated using logistic regression.Results 17 682 youth were recruited in the survey (n=10 742, 60.8% female). The median age of participants was 20 (IQR: 19–22) years. Almost two thirds (n=10 652, 60.2%) reported receiving at least one dose of COVID-19 vaccine. A higher proportion of men than women had been vaccinated (68.9% vs 54.7%), and vaccination prevalence increased with age (23: 62.2%). Lack of time to get vaccinated, belief that the vaccine was unsafe and anxiety about side effects (particularly infertility) were the main reasons for not getting vaccinated. Factors associated with vaccination were male sex (OR=1.69, 95% CI 1.58 to 1.80), increasing age (>22 years: OR=1.12, 95% CI 1.04 to 1.21), education level (postsecondary: OR=4.34, 95% CI 3.27 to 5.76) and socioeconomic status (least poor: OR=1.32, 95% CI 1.20 to 1.47).Conclusion This study found vaccine inequity across age, sex, educational attainment and socioeconomic status among youth. Strategies should address these inequities by understanding concerns and tailoring vaccine campaigns to specific groups.

Introduction: Sexually transmitted infections (STIs) such as chlamydia, gonorrhoea, trichomoniasis, and syphilis, are associated with adverse birth outcomes. Treatment should be accompanied by partner services to prevent re-infection and break cycles of transmission. Partner services include the processes of partner notification (PN) as well as arranging for their attendance for testing and/or treatment. However, due to a complex mix of cultural, socio-economic, and health access factors, uptake of partner services is often very low, in many settings globally. Alternative strategies to facilitate partner services are therefore needed. The aim of this study is to assess the effect of a small financial incentive on improving uptake of partner services for STIs as part of antenatal care (ANC) services in Zimbabwe. Methods and analysis: This trial will be embedded within a prospective interventional study in Harare, aiming to evaluate integration of point-of-care diagnostics for STIs into ANC settings. One thousand pregnant women will be screened for chlamydia, gonorrhoea, trichomoniasis, and syphilis. All individuals with STIs will be offered treatment, risk reduction counselling, and client PN. Each clinic day will be randomised 1:1 to be an incentive or non-incentive day. On incentive days, participants diagnosed with a curable STI will be offered a PN slip, that when returned will entitle their partners to $3 (USD) in compensation. On non-incentive days, regular PN slips with no incentive are provided. The primary outcome measure is the proportion of individuals with at least one partner who returns for partner services based on administrative records. Secondary outcomes will include the number of days between index case diagnosis and the partner attending for partner services, uptake of PN slips by pregnant women, adverse birth outcomes in index cases, partners who receive treatment, and intervention cost. Registration: Pan African Clinical Trials Registry: PACTR202302702036850 (Approval date 18th February 2022).

Introduction Sexually transmitted infections (STIs) can cause serious morbidity, including pelvic inflammatory disease, and adverse pregnancy outcomes. In low/middle-income countries, limited laboratory infrastructure has resulted in a syndrome-based approach being used for management of STIs, which has poor sensitivity and specificity, leading to considerable underdiagnosis and overtreatment. The WHO has called for development and evaluation of strategies to inform replacement of syndromic management by diagnostic testing.The aim of this project is to evaluate a strategy of point-of-care testing for six STIs in antenatal care (ANC) in Zimbabwe.Methods and analysis A prospective interventional study will be conducted in ANC clinics in Harare province, Zimbabwe. One thousand pregnant women will be recruited when registering for routine ANC. Alongside routine HIV and syphilis testing, participants will be offered an integrated screening package including testing for Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Trichomonas vaginalis (TV) and hepatitis B. All individuals with STIs will receive treatment, partner notification services, risk reduction counselling and referral if needed according to national guidelines. Gonorrhoea samples will be cultured and tested for antimicrobial resistance as per WHO enhanced gonococcal antimicrobial surveillance programme guidelines.The primary outcome measure is the composite prevalence of CT, NG, TV, syphilis and hepatitis B. A mixed-methods process evaluation and economic evaluation will be conducted to understand the acceptability, feasibility and cost-effectiveness of integrated STI testing, compared with standard of care (syndromic management).Ethics and dissemination The study protocol was approved by the Medical Research Council of Zimbabwe, the Biomedical Research and Training Institute Institutional Review Board, and the London School of Hygiene & Tropical Medicine Research Ethics Committee. Results will be submitted to open-access peer-reviewed journals, presented at academic meetings and shared with participating communities and with national and international policymaking bodies.Trial registration number NCT05541081

Abstract Background Point-of-care testing for sexually transmitted infections (STIs) may improve diagnosis and treatment of STIs in low- and middle-income counties. We explored the facilitators and barriers to point-of-care testing for Chlamydia trachomatis (CT) and Neisseria gonorrhoea (NG) for youth in community-based settings in Zimbabwe. Methods This study was nested within a cluster randomised trial of community-based delivery of integrated HIV and sexual and reproductive health services for youth aged 16 to 24 years. On-site CT/NG testing on urine samples using the Xpert® CT/NG test was piloted in four intervention clusters, with testing performed by service providers. On-site testing was defined as sample processing on the same day and site as sample collection. Outcomes included proportion of tests processed on-site, time between sample collection and collection of results, and proportion of clients receiving treatment. In-depth interviews were conducted with nine service providers and three staff members providing study co-ordination or laboratory support to explore facilitators and barriers to providing on-site CT/NG testing. Results Of 847 Xpert tests, 296 (35.0%) were performed on-site. Of these, 61 (20.6%) were positive for CT/NG; one (1.6%) received same day aetiological treatment; 33 (54.1%) presented later for treatment; and 5 (8.2%) were treated as a part of syndromic management. There was no difference in the proportion of clients who were treated whether their sample was processed on or off-site (64% (39/61) vs 60% (66/110); p = 0.61). The median (IQR) number of days between sample collection and collection of positive results was 14 (7–35) and 14 (7–52.5) for samples processed on and off-site, respectively, The interviews revealed four themes related to the provision of on-site testing associated with the i) diagnostic device ii) environment, iii) provider, and iv) clients. Some of the specific barriers identified included insufficient testing capacity, inadequate space, as well as reluctance of clients to wait for their results. Conclusions In addition to research to optimise the implementation of point-of-care tests for STIs in resource-limited settings, the development of new platforms to reduce analytic time will be necessary to scale up STI testing and reduce the attrition between testing and treatment. Trial registration Registered in clinical trials.gov ( NCT03719521 ).

Abstract Background Of the 2 million children living with HIV globally, 90% live in sub-Saharan Africa. Despite antiretroviral therapy, longstanding HIV infection is associated with several chronic complications in children including growth failure, particularly stunting and delayed puberty. Vitamin D deficiency, which is highly prevalent among children living with HIV in sub-Saharan Africa, has a further adverse impact on bone health. This trial aims to establish whether supplementation with vitamin D3 and calcium carbonate improves musculoskeletal health among peripubertal children living with HIV. Methods/design We will conduct an individually randomised, double-blinded, placebo-controlled trial of weekly high-dose vitamin D3 (20,000 IU) plus daily calcium carbonate (500mg) supplementation for 48 weeks. Eight hundred and forty children living with HIV aged 11–19 years taking ART for ≥6 months will be enrolled and followed up for 96 weeks. The primary outcome is total body less-head bone mineral content for lean mass adjusted for height (TBLH-BMCLBM) Z-score at 48 weeks, measured by dual-energy X-ray absorptiometry (DEXA). Secondary outcomes are DEXA-measured lumbar spine bone mineral apparent density Z-score, number of respiratory infections, lean muscle mass and grip strength at 48 and 96 weeks and TBLH-BMCLBM Z-scores at 96 weeks. Sub-studies will investigate the effect of the intervention on vitamin D3 pathway metabolites and markers of bone turnover, intestinal microbiota, and innate and acquired immune function. Discussion This is the largest trial to date of vitamin D supplementation in children living with HIV. Intervening to address deficits in bone accrual in childhood is critical for optimising adolescent and early adult bone health and prevention of later adult osteoporotic fractures. Trial results will draw attention to the need to screen for and treat long-term comorbidities in children living with HIV in resource-limited settings. Trial registration Pan African Clinical Trials Registry PACTR20200989766029 . Registered on 3 September 2020

With COVID-19 no longer categorized as a public health emergency of international concern, vaccination strategies and priority groups for vaccination have evolved. Africa Centres for Diseases Prevention and Control proposed the '100-100-70%' strategy which aims to vaccinate all healthcare workers, all vulnerable groups, and 70% of the general population. Understanding whether healthcare workers were reached during previous vaccination campaigns and what can be done to address concerns, anxieties, and other influences on vaccine uptake, will be important to optimally plan how to achieve these ambitious targets. In this mixed-methods study, between June 2021 and July 2022 a quantitative survey was conducted with healthcare workers accessing a comprehensive health check in Zimbabwe to determine whether and, if so, when they had received a COVID-19 vaccine. Healthcare workers were categorized as those who had received the vaccine 'early' (before 30.06.2021) and those who had received it 'late' (after 30.06.2021). In addition, 17 in-depth interviews were conducted to understand perceptions and beliefs about COVID-19 vaccines. Of the 3,086 healthcare workers employed at 43 facilities who participated in the study, 2,986 (97%, 95% CI [92%-100%]) reported that they had received at least one vaccine dose. Geographical location, older age, higher educational attainment and having a chronic condition was associated with receiving the vaccine early. Qualitatively, (mis)information, infection risk perception, quasi-mandatory vaccination requirements, and legitimate concerns such as safety and efficacy influenced vaccine uptake. Meeting the proposed 100-100-70 target entails continued emphasis on strong communication while engaging meaningfully with healthcare workers' concerns. Mandatory vaccination may undermine trust and should not be a substitute for sustained engagement.

Abstract Background Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are the most common bacterial sexually transmitted infections (STIs) worldwide. In the absence of affordable point-of-care STI tests, WHO recommends STI testing based on risk factors. This study aimed to develop a prediction tool with a sensitivity of > 90% and efficiency (defined as the percentage of individuals that are eligible for diagnostic testing) of

Background: Treatment for urinary tract infections (UTIs) is usually empiric and is based on local antimicrobial resistance data. These data, however, are scarce in low-resource settings. The aim of this study is to determine the impact of antibiotic treatment on clinical and bacteriological outcomes in patients presenting with UTI symptoms to primary care in Harare. Methods: This cohort study enrolled participants presenting with UTI symptoms to 10 primary healthcare clinics in Harare between July 2019 and July 2020. A questionnaire was administered and a urine sample was collected for culture. If the urine culture showed growth of ≥105 colony forming units/mL of a uropathogen, a follow up visit at 7-21 days was conducted. Results: The analysis included 168 participants with a median age of 33.6 years (IQR 25.1-51.4) and of whom 131/168 (78.0%) were female. Effective treatment was taken by 54/168 (32.1%) participants. The urine culture was negative at follow up in 41/54 (75.9%) of participants who took appropriate treatment and in 33/114 (28.9%, p

Introduction The WHO End-TB Strategy calls for the development of novel diagnostics to detect tuberculosis (TB) earlier and more accurately. Better diagnostics, together with tools to predict disease progression, are critical for achieving WHO End-TB targets. The Early Risk Assessment in TB Contacts by new diagnoStic tEsts (ERASE-TB) study aims to evaluate novel diagnostics and testing algorithms for early TB diagnosis and accurate prediction of disease progression among household contacts (HHCs) exposed to confirmed index cases in Mozambique, Tanzania and Zimbabwe.Methods and analysis A total of 2100 HHCs (aged ≥10 years) of adults with microbiologically-confirmed pulmonary TB will be recruited and followed up at 6-month intervals for 18–24 months. At each time point, a WHO symptom screen and digital chest radiograph (dCXR) will be performed, and blood and urine samples will be collected. Individuals screening positive (WHO symptom screen or dCXR) will be requested to provide sputum for Xpert MTB/Rif Ultra. At baseline, HHCs will also be screened for HIV, diabetes (HbA1c), chronic lung disease (spirometry), hypertension and anaemia. Study outcomes will be coprevalent TB (diagnosed at enrolment), incident TB (diagnosed during follow-up) or no TB at completion of follow-up. Novel diagnostics will be validated using fresh and biobanked samples with a nested case–control design. Cases are defined as HHCs diagnosed with TB (for early diagnosis) or with incident TB (for prediction of progression) and will be matched by age, sex and country to HHCs who remain healthy (controls). Statistical analyses will include assessment of diagnostic accuracy by constructing receiver operating curves and calculation of sensitivity and specificity.Ethics and dissemination ERASE-TB has been approved by regulatory and ethical committees in each African country and by each partner organisation. Consent, with additional assent for participants

Background: Healthcare workers (HCWs) have experienced anxiety and psychological distress during the COVID-19 pandemic. We established and report findings from an occupational health programme for HCWs in Zimbabwe that offered screening for SARS-CoV-2 with integrated screening for comorbidities including common mental disorder (CMD) and referral for counselling. Methods: Quantitative outcomes were fearfulness about COVID-19, the Shona Symptom Questionnaire (SSQ-14) score (cutpoint 8/14) and the number and proportion of HCWs offered referral for counselling, accepting referral and counselled. We used chi square tests to identify factors associated with fearfulness, and logistic regression was used to model the association of fearfulness with wave, adjusting for variables identified using a DAG. Qualitative data included 18 in-depth interviews, two workshops conducted with HCWs and written feedback from counsellors, analysed concurrently with data collection using thematic analysis. Results: Between 27 July 2020–31 July 2021, spanning three SARS-CoV-2 waves, the occupational health programme was accessed by 3577 HCWs from 22 facilities. The median age was 37 (IQR 30–43) years, 81.9% were women, 41.7% said they felt fearful about COVID-19 and 12.1% had an SSQ-14 score ≥ 8. A total of 501 HCWs were offered referral for counselling, 78.4% accepted and 68.9% had ≥1 counselling session. Adjusting for setting and role, wave 2 was associated with increased fearfulness over wave 1 (OR = 1.26, 95% CI 1.00–1.60). Qualitative data showed high levels of anxiety, psychosomatic symptoms and burnout related to the pandemic. Mental wellbeing was affected by financial insecurity, unmet physical health needs and inability to provide quality care within a fragile health system. Conclusions: HCWs in Zimbabwe experience a high burden of mental health symptoms, intensified by the COVID-19 pandemic. Sustainable mental health interventions must be multisectoral addressing mental, physical and financial wellbeing.

Background Overuse of antibiotics is one of the main drivers for antimicrobial resistance (AMR). Globally, most antibiotics are prescribed in the outpatient setting. This survey aimed to explore attitudes and practices with regards to microbiology tests, AMR and antibiotic prescribing among healthcare providers at public primary health clinics in Harare, Zimbabwe. Methods This cross-sectional survey was conducted in nine primary health clinics located in low-income suburbs of Harare between October and December 2020. In Zimbabwe, primary health clinics provide nurse-led outpatient care for acute and chronic illnesses. Healthcare providers who independently prescribe antibiotics and order diagnostic tests were invited to participate. The survey used self-administered questionnaires. A five-point Likert scale was used to determine attitudes and beliefs. Results A total of 91 healthcare providers agreed to participate in the survey. The majority of participants (62/91, 68%) had more than 10 years of work experience. Most participants reported that they consider AMR as a global (75/91, 82%) and/or national (81/91, 89%) problem, while 52/91 (57%) considered AMR to be a problem in their healthcare facilities. A fifth of participants (20/91, 22%) were unsure if AMR was a problem in their clinics. Participants felt that availability of national guidelines (89/89, 100%), training sessions on antibiotic prescribing (89/89, 100%) and regular audit and feedback on prescribing (82/88, 93%) were helpful interventions to improve prescribing. Conclusions These findings support the need for increased availability of data on AMR and antibiotic use in primary care. Educational interventions, regular audit and feedback, and access to practice guidelines may be useful to limit overuse of antibiotics.

Abstract Introduction Index-linked HIV testing, targeted at sexual contacts or children of individuals with HIV, may improve yield and efficiency. The B-GAP study evaluated index-linked testing approaches in health facility and community-based settings. This paper reports on a qualitative study to understand factors that affect uptake of index-linked HIV testing for children and adolescents. Methods We conducted four focus group discussions (FGDs) with caregivers who had their children tested through B-GAP and one FGD with providers who offered index-linked HIV testing to indexes. We aimed to understand enabling and inhibiting factors in the decision-making process. Translated and transcribed transcripts were read for familiarisation. Following initial coding, analytical memos were written to identify emerging key themes across the data. Results Our findings showed there was inadequate emphasis on paediatric HIV in routine care which had a negative impact on subsequent uptake of testing for children. Once the decision to test had been made, access to facilities was sometimes challenging and alleviated by community-based testing. A key finding was that HIV testing is not a discrete event but a process that was influenced by relationships with other family members and children themselves. These relationships raised complex issues that could prevent or delay the testing process. Conclusion There is a need to improve messaging on the importance of HIV testing for children and adolescents and to provide support to caregivers and their families in order to improve testing uptake. Addressing access barriers through the provision of community-based testing and implementing a family-centred approach can optimise index-linked testing.

Pathogen-based factors associated with tuberculosis (TB) in eastern Sudan are not well defined. We investigated genetic diversity, drug resistance, and possible transmission clusters of Mycobacterium tuberculosis complex (MTBC) strains by using a genomic epidemiology approach. We collected 383 sputum specimens at 3 hospitals in 2014 and 2016 from patients with symptoms suggestive of TB; of these, 171 grew MTBC strains. Whole-genome sequencing could be performed on 166 MTBC strains; phylogenetic classification revealed that most (73.4%; n = 122) belonged to lineage 3 (L3). Genome-based cluster analysis showed that 76 strains (45.9%) were grouped into 29 molecular clusters, comprising 2–8 strains/patients. Of the strains investigated, 9.0% (15/166) were multidrug resistant (MDR); 10 MDR MTBC strains were linked to 1 large MDR transmission network. Our findings indicate that L3 strains are the main causative agent of TB in eastern Sudan; MDR TB is caused mainly by transmission of MDR L3 strains.

There is substantial unmet need for family planning (FP) among women living with HIV (WLHIV), leading to unintended pregnancies and may contribute indirectly to increasing the risk of transmission of HIV. This review aims to determine whether integration of FP into HIV testing and care results in increased use of contraception, a reduction in unmet need for FP, improved use of safer conception methods and a reduction in unintended pregnancies in low and middle-income countries. A systematic review was undertaken incorporating studies from PubMed, EMBASE, CINAHL, Web of Science and Global Health, the International AIDS Society Abstract Archive, the World STI & HIV Congress Abstract Archive and the Conference on Retroviruses and Opportunistic Infections Abstract Archive published between 2016 and 2021, updating previous systematic reviews. After screening, 13 studies were included, 11 conducted in sub-Saharan Africa and 2 in India. The primary outcome of the review was contraceptive uptake and secondary outcomes included unmet need for FP, safer conception and unintended pregnancy. Integrated FP-HIV facilities were found to increase dual contraceptive use by at least 8% in five studies and modern contraceptive use by at least 8% in four studies. Findings from two studies suggested integration decreased the unmet need for contraception. Limited data prevented a conclusion from being drawn regarding whether integration increases safer conception. There was no evidence of integration reducing unintended pregnancies. The median quality score of studies was 3/9. Overall, integrated facilities have the potential of improving reproductive health of women accessing HIV services in LMICs. FP may be enhanced by including a safer conception component for WLHIV.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021251008, identifier: CRD42021251008.

The End TB strategy recommends social protection to mitigate socio-economic impacts of tuberculosis. Zimbabwe started implementing a conditional cash transfer (CCT) programme for people on drug resistant tuberculosis (DR-TB) treatment in 2013. We aimed to determine the proportion of people receiving CCT and effectiveness of CCT in improving treatment outcomes, explore their experiences with registering for CCT and understand the impact of CCT from the perspective of beneficiaries. Data from 2014-2021 were extracted from TB registers and CCT payment records within the National TB Programme. Sixteen in-depth interviews were conducted with people who were completing treatment or had completed treatment within two months. Poisson regression, adjusted for province, year of treatment, age and sex was used to investigate associations between receiving CCT and successful treatment outcomes among people who were in DR-TB care for ≥3 months after treatment initiation. Qualitative data were analyzed using thematic analysis. A total of 481 people were included in the quantitative study. Of these, 53% (254/481) received CCT at some point during treatment. People who exited DR-TB care within three months were 73% less likely to receive CCT than those who did not (prevalence ratio (PR) = 0.27 [95%CI: 0.18-0.41]). Among those who were alive and in care three months after treatment initiation, CCT recipients were 32% more likely to have successful outcomes than those who did not (adjusted PR = 1.32, [95%CI: 1.00-1.75]). Qualitative results revealed lack of knowledge about availability of CCT among people with DR-TB and missed opportunities by healthcare providers to provide information about availability of CCT. Delays and inconsistencies in disbursements of CCT were frequent themes. CCT were associated with successful treatment outcomes. Improvements in coverage, timeliness and predictability of disbursements are recommended.

Abstracts: Background: By the end of July 2021 Zimbabwe, has reported over 100,000 SARS-CoV-2 infections. The true number of SARS-CoV-2 infections is likely to be much higher. We conducted a seroprevalence survey to estimate the prevalence of past SARS-CoV-2 in three high-density communities in Harare, Zimbabwe before and after the second wave of SARS-CoV-2. Methods: Between November 2020 and April 2021 we conducted a cross-sectional study of randomly selected households in three high-density communities (Budiriro, Highfield and Mbare) in Harare. Consenting participants answered a questionnaire and a dried blood spot sample was taken. Samples were tested for anti-SARS-CoV-2 nucleocapsid antibodies using the Roche e801 platform. Findings: A total of 2340 individuals participated in the study. SARS-CoV-2 antibody results were available for 70·1% (620/885) and 73·1% (1530/2093) of eligible participants in 2020 and 2021. The median age was 22 (IQR 10-37) years and 978 (45·5%) were men. SARS-CoV-2 seroprevalence was 19·0% (95% CI 15·1-23·5%) in 2020 and 53·0% (95% CI 49·6-56·4) in 2021. The prevalence ratio was 2·47 (95% CI 1·94-3·15) comparing 2020 with 2021 after adjusting for age, sex, and community. Almost half of all participants who tested positive reported no symptoms in the preceding six months. Interpretation: Following the second wave, one in two people had been infected with SARS-CoV-2 suggesting high levels of community transmission. Our results suggest that 184,800 (172,900-196,700) SARS-CoV-2 infections occurred in these three communities alone, greatly exceeding the reported number of cases for the whole city. Further seroprevalence surveys are needed to understand transmission during the current third wave despite high prevalence of past infections. Funding: GCRF, Government of Canada, Wellcome Trust, Bavarian State Ministry of Sciences, Research, and the Arts

Abstract Introduction In sub‐Saharan Africa, less than half of young people know their HIV status. HIV self‐testing (HIVST) is a testing strategy with the potential to offer privacy and autonomy. We aimed to understand the uptake and acceptability of different HIV testing options for youth in Harare, Zimbabwe. Methods This study was nested within a cluster randomized trial of a youth‐friendly community‐based integrated HIV and sexual and reproductive health intervention for youth aged 16–24 years. Three HIV testing options were offered: (1) provider‐delivered testing; (2) HIVST on site in a private booth without a provider present; and (3) provision of a test kit to test off site. Descriptive statistics and proportions were used to investigate the uptake of HIV testing in a client sample. A focus group discussion (FGD) with intervention providers alongside in‐depth interviews, paired interviews and FGDs with a selected sample of youth clients explored uptake and acceptability of the different HIV testing strategies. Thematic analysis was used to analyse the qualitative data. Results Between April and June 2019, 951 eligible clients were tested for HIV: 898 (94.4%) chose option 1, 30 (3.25%) chose option 2 and 23 (2.4%) chose option 3. Option 1 clients cited their trust in the service and a desire for immediate counselling, support and guidance from trusted providers as the reasons for their choice. Young people were not confident in their expertise to conduct HIVST. Concerns about limited privacy, confidentiality and lack of support in the event of an HIV‐positive result were barriers for off‐site HIVST. Conclusions In the context of supportive, trusted and youth‐friendly providers, youth clients overwhelmingly preferred provider‐delivered HIV testing over client‐initiated HIVST or HIVST off site. This highlights the importance of listening to youth to improve engagement in testing. While young people want autonomy in choosing when, where and how to test, they do not want to necessarily test on their own. They desire quality in‐person counselling, guidance and support, alongside privacy and confidentiality. To increase the appeal of HIVST for youth, greater provision of access to private spaces is required, and accessible pre‐ and post‐test counselling and support may improve uptake.

Objective Urinary tract infections (UTIs) are common in primary care. The yield of urine cultures in patients with UTI symptoms can be considerably different between high-income and low-income settings. This study aimed to explore possible causes of negative urine cultures in patients presenting with symptoms of UTI to primary health clinics in Harare.Design Cross-sectional study.Setting Nine primary health clinics in Harare, Zimbabwe.Participants Adults presenting with symptoms of UTIs between March and July 2020.Primary outcome measures Urine samples underwent dipstick testing, microscopy, culture, and testing for sexually transmitted infections (STIs) using GeneXpert and for the presence of antibiotic residues using an antibiotic bioassay. The primary outcomes were the number and proportion of participants with evidence of STIs, prior antibiotic exposure, leucocyturia and UTIs.Results The study included 425 participants with a median age of 37.3 years, of whom 275 (64.7%) were women. Leucocyturia was detected in 130 (30.6%, 95% CI 26.2% to 35.2%) participants, and 96 (22.6%, 95% CI 18.7% to 26.9%) had a positive urine culture for a uropathogen. Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis were detected in 43/425 (10.1%, 95% CI 7.4% to 13.4%), 37/425 (8.7%, 95% CI 6.2% to 11.8%) and 14/175 (8.0%, 95% CI 4.4% to 13.1%) participants, respectively. Overall, 89 (20.9%, 95% CI 17.2% to 25.1%) participants reported either having taken prior antibiotics or having had a positive urine bioassay. In 170 (40.0%, 95% CI 35.3% to 44.8%) participants, all of the tests that were performed were negative.Conclusions This study found a high prevalence of STIs and evidence of prior antimicrobial use as possible explanations for the low proportion of positive urine cultures.

Abstract Background Drug-resistant tuberculosis (TB) is a major public health concern threathing the success of TB control efforts, and this is particularily problematic in Central Asia. Here, we present the first analysis of the population structure of Mycobacterium tuberculosis complex isolates in the Central Asian republics Uzbekistan, Tajikistan, and Kyrgyzstan. Methods The study set consisted of 607 isolates with 235 from Uzbekistan, 206 from Tajikistan, and 166 from Kyrgyzstan. 24-loci MIRU-VNTR (Mycobacterial Interspersed Repetitive Units - Variable Number of Tandem Repeats) typing and spoligotyping were combined for genotyping. In addition, phenotypic drug suceptibility was performed. Results The population structure mainly comprises strains of the Beijing lineage (411/607). 349 of the 411 Beijing isolates formed clusters, compared to only 33 of the 196 isolates from other clades. Beijing 94–32 (n = 145) and 100–32 (n = 70) formed the largest clusters. Beijing isolates were more frequently multidrug-resistant, pre-extensively resistant (pre-XDR)- or XDR-TB than other genotypes. Conclusions Beijing clusters 94–32 and 100–32 are the dominant MTB genotypes in Central Asia. The relative size of 100–32 compared to previous studies in Kazakhstan and its unequal geographic distribution support the hypothesis of its more recent emergence in Central Asia. The data also demonstrate that clonal spread of resistant TB strains, particularly of the Beijing lineage, is a root of the so far uncontroled MDR-TB epidemic in Central Asia.

Resistance to Tuberculosis drugs has become a major threat to the control of tuberculosis (TB) globally. We conducted the first nation-wide drug resistance survey to investigate the level and pattern of resistance to first-line TB drugs among newly and previously treated sputum smear-positive TB cases. We also evaluated associations between potential risk factors and TB drug resistance. Using the World Health Organization (WHO) guidelines on conducting national TB surveys, we selected study participants from 33 health facilities from across the country, grouped into 29 clusters, and included them into the survey. Between April 2016 and June 2017, a total of 927 patients (859 new and 68 previously treated) were enrolled in the survey. Mycobacterium tuberculosis complex (MTBC) isolates were successfully cultured from 598 (65.5%) patient samples and underwent DST, 550 from newly diagnosed and 48 from previously treated patients. The proportion of patients who showed resistance to any of the TB drugs tested was 25.2% (95% CI; 21.8–28.9). The most frequent resistance was to Streptomycin (STR) (12.3%), followed by Isoniazid (INH) (10.4%), with Rifampicin (RIF), showing the least resistance of 2.4%. Resistance to Isoniazid and Rifampicin (multi-drug resistance) was found in 19 (3.2%; 95% CI: 1.9–4.9) isolates. Prevalence of multidrug resistance was 7 (1.3%; 95% CI: 0.5–2.6) among newly diagnosed and 12 (25.0%; 95% CI: 13.6–39.6) among previously treated patients. At both univariate and multivariate analysis, MDR-TB was positively associated with previous history of TB treatment (OR = 5.09, 95% CI: 1.75–14.75, p = 0.003); (OR = 5.41, 95% CI: 1.69–17.30, p = 0.004). The higher levels of MDR-TB and overall resistance to any TB drug among previously treated patients raises concerns about adherence to treatment. This calls for strengthening existing TB programme measures to ensure a system for adequately testing and monitoring TB drug resistance.

BackgroundHealthcare workers are disproportionately affected by COVID-19. In low- and middle- income countries, they may be particularly impacted by underfunded health systems, lack of personal protective equipment, challenging working conditions and barriers in accessing personal healthcare.MethodsIn this cross-sectional study, occupational health screening was implemented at the largest public sector medical centre in Harare, Zimbabwe, during the "first wave" of the country's COVID-19 epidemic. Clients were voluntarily screened for symptoms of COVID-19, and if present, offered a SARS-CoV-2 nucleic acid detection assay. In addition, measurement of height, weight, blood pressure and HbA1c, HIV and TB testing, and mental health screening using the Shona Symptom Questionnaire (SSQ-14) were offered. An interviewer-administered questionnaire ascertained client knowledge and experiences related to COVID-19.ResultsBetween 27th July and 30th October 2020, 951 healthcare workers accessed the service; 210 (22%) were tested for SARS-CoV-2, of whom 12 (5.7%) tested positive. Clients reported high levels of concern about COVID-19 which declined with time, and faced barriers including lack of resources for infection prevention and control. There was a high prevalence of largely undiagnosed non-communicable disease: 61% were overweight or obese, 34% had a blood pressure of 140/90mmHg or above, 10% had an HbA1c diagnostic of diabetes, and 7% had an SSQ-14 score consistent with a common mental disorder. Overall 8% were HIV-positive, with 97% previously diagnosed and on treatment.ConclusionsCases of SARS-CoV-2 in healthcare workers mirrored the national epidemic curve. Implementation of comprehensive occupational health services during a pandemic was feasible, and uptake was high. Other comorbidities were highly prevalent, which may be risk factors for severe COVID-19 but are also important independent causes of morbidity and mortality. Healthcare workers are critical to combatting COVID-19; it is essential to support their physical and psychological wellbeing during the pandemic and beyond.

ObjectiveThe experiences of frontline healthcare professionals are essential in identifying strategies to mitigate the disruption to healthcare services caused by the COVID-19 pandemic.MethodsWe conducted a cross-sectional study of TB and HIV professionals in low and middle-income countries (LMIC). Between May 12 and August 6, 2020, we collected qualitative and quantitative data using an online survey in 11 languages. We used descriptive statistics and thematic analysis to analyse responses.Findings669 respondents from 64 countries completed the survey. Over 40% stated that it was either impossible or much harder for TB and HIV patients to reach healthcare facilities since COVID-19. The most common barriers reported to affect patients were: fear of getting infected with SARS-CoV-2, transport disruptions and movement restrictions. 37% and 28% of responses about TB and HIV stated that healthcare provider access to facilities was also severely impacted. Strategies to address reduced transport needs and costs-including proactive coordination between the health and transport sector and cards that facilitate lower cost or easier travel-were presented in qualitative responses. Access to non-medical support for patients, such as food supplementation or counselling, was severely disrupted according to 36% and 31% of HIV and TB respondents respectively; qualitative data suggested that the need for such services was exacerbated.ConclusionPatients and healthcare providers across numerous LMIC faced substantial challenges in accessing healthcare facilities, and non-medical support for patients was particularly impacted. Synthesising recommendations of frontline professionals should be prioritised for informing policymakers and healthcare service delivery organisations.

BackgroundActive case finding (ACF) may be valuable in tuberculosis (TB) control, but questions remain about its optimum implementation in different settings. For example, smear microscopy misses up to half of TB cases, yet is cheap and detects the most infectious TB cases. What, then, is the incremental value of using more sensitive and specific, yet more costly, tests such as Xpert MTB/RIF in ACF in a high-burden setting?Methods and findingsWe constructed a dynamic transmission model of TB, calibrated to be consistent with an urban slum population in India. We applied this model to compare the potential cost and impact of 2 hypothetical approaches following initial symptom screening: (i) 'moderate accuracy' testing employing a microscopy-like test (i.e., lower cost but also lower accuracy) for bacteriological confirmation and (ii) 'high accuracy' testing employing an Xpert-like test (higher cost but also higher accuracy, while also detecting rifampicin resistance). Results suggest that ACF using a moderate-accuracy test could in fact cost more overall than using a high-accuracy test. Under an illustrative budget of US$20 million in a slum population of 2 million, high-accuracy testing would avert 1.14 (95% credible interval 0.75-1.99, with p = 0.28) cases relative to each case averted by moderate-accuracy testing. Test specificity is a key driver: High-accuracy testing would be significantly more impactful at the 5% significance level, as long as the high-accuracy test has specificity at least 3 percentage points greater than the moderate-accuracy test. Additional factors promoting the impact of high-accuracy testing are that (i) its ability to detect rifampicin resistance can lead to long-term cost savings in second-line treatment and (ii) its higher sensitivity contributes to the overall cases averted by ACF. Amongst the limitations of this study, our cost model has a narrow focus on the commodity costs of testing and treatment; our estimates should not be taken as indicative of the overall cost of ACF. There remains uncertainty about the true specificity of tests such as smear and Xpert-like tests in ACF, relating to the accuracy of the reference standard under such conditions.ConclusionsOur results suggest that cheaper diagnostics do not necessarily translate to less costly ACF, as any savings from the test cost can be strongly outweighed by factors including false-positive TB treatment, reduced sensitivity, and foregone savings in second-line treatment. In resource-limited settings, it is therefore important to take all of these factors into account when designing cost-effective strategies for ACF.

Introduction Fever commonly leads to healthcare seeking and hospital admission in sub-Saharan Africa and Asia. There is only limited guidance for clinicians managing non-malarial fevers, which often results in inappropriate treatment for patients. Furthermore, there is little evidence for estimates of disease burden, or to guide empirical therapy, control measures, resource allocation, prioritisation of clinical diagnostics or antimicrobial stewardship. The Febrile Illness Evaluation in a Broad Range of Endemicities (FIEBRE) study seeks to address these information gaps.Methods and analysis FIEBRE investigates febrile illness in paediatric and adult outpatients and inpatients using standardised clinical, laboratory and social science protocols over a minimum 12-month period at five sites in sub-Saharan Africa and Southeastern and Southern Asia. Patients presenting with fever are enrolled and provide clinical data, pharyngeal swabs and a venous blood sample; selected participants also provide a urine sample. Laboratory assessments target infections that are treatable and/or preventable. Selected point-of-care tests, as well as blood and urine cultures and antimicrobial susceptibility testing, are performed on site. On day 28, patients provide a second venous blood sample for serology and information on clinical outcome. Further diagnostic assays are performed at international reference laboratories. Blood and pharyngeal samples from matched community controls enable calculation of AFs, and surveys of treatment seeking allow estimation of the incidence of common infections. Additional assays detect markers that may differentiate bacterial from non-bacterial causes of illness and/or prognosticate illness severity. Social science research on antimicrobial use will inform future recommendations for fever case management. Residual samples from participants are stored for future use.Ethics and dissemination Ethics approval was obtained from all relevant institutional and national committees; written informed consent is obtained from all participants or parents/guardians. Final results will be shared with participating communities, and in open-access journals and other scientific fora. Study documents are available online (https://doi.org/10.17037/PUBS.04652739).

Background: Assessment of the effectiveness of tuberculosis control strategies requires the periodic measurement of M. tuberculosis transmission in populations, which is notoriously difficult. One well-established method is to measure the prevalence of infectious pulmonary tuberculosis in the population which is then repeated at a second time point after a period of ‘intervention’, such as scale up of the Search-Treat-Prevent strategy of the Zero TB Cities initiative, allowing for a ‘before and after’ comparison. Protocol: The concurrent adult pulmonary tuberculosis prevalence survey (using digital radiography and Xpert MTB/RIF Ultra) and child M. tuberculosis infection survey (using QuantiFERON-TB® Gold Plus) will primarily provide a baseline measure of the burden of adult infectious tuberculosis in Karachi and assess whether a large-scale interferon gamma release assay survey in children aged 2 to 4 years is feasible. The target population for the prevalence survey is comprised of a stratified random sample of all adults aged 15 years and above and all children aged 2 to 4 years resident in four districts in Karachi. The survey procedures and analyses to estimate pulmonary tuberculosis prevalence are based on the World Health Organization methodology for tuberculosis prevalence surveys. Ethics and dissemination: The study protocol has been approved by the Interactive Research Development / The Indus Hospital Research Centre Research Ethics Committee in Karachi, Pakistan and the London School of Hygiene & Tropical Medicine Research Ethics Committee. Due to non-representative sampling in this setting, where a large proportion of the population are illiterate and are reluctant to provide fingerprints due to concerns about personal security, verbal informed consent will be obtained from each eligible participant or guardian. Results will be submitted to international peer-reviewed journals, presented at international conferences and shared with participating communities and with the Provincial and National TB programme.

Antimicrobial resistance (AMR) is compromising our ability to successfully treat infections. There are few data on gram-negative AMR prevalence in sub-Saharan Africa especially from the outpatient setting. This study aims to investigate the prevalence of and underlying molecular mechanisms for AMR in gram-negative bacilli causing urinary tract infections (UTIs) in Zimbabwe. Risk factors for AMR and how AMR impacts on clinical outcomes will also be investigated. Adults presenting with UTI symptoms at primary health clinics in Harare will be included. A questionnaire will be administered, and urine samples will be collected for culture. Participants with positive urine cultures will be followed up at 7-14 days post-enrolment. All participants will also be followed by telephone at 28 days to determine clinical outcomes. Bacterial identification and antibiotic susceptibility testing will be performed on positive cultures. The results from this study will be used to inform policy and development of treatment recommendations. Whole genome sequencing results will provide a better understanding of the prevalent resistance genes in Zimbabwe, of the spread of successful clones, and potentially will contribute to developing strategies to tackle AMR.

Abstract Background Human immunodeficiency virus (HIV)-related chronic lung disease (CLD) among children is associated with substantial morbidity, despite antiretroviral therapy. This may be a consequence of repeated respiratory tract infections and/or dysregulated immune activation that accompanies HIV infection. Macrolides have anti-inflammatory and antimicrobial properties, and we hypothesised that azithromycin would reduce decline in lung function and morbidity through preventing respiratory tract infections and controlling systemic inflammation. Methods/design We are conducting a multicentre (Malawi and Zimbabwe), double-blind, randomised controlled trial of a 12-month course of weekly azithromycin versus placebo. The primary outcome is the mean change in forced expiratory volume in 1 second (FEV1) z-score at 12 months. Participants are followed up to 18 months to explore the durability of effect. Secondary outcomes are FEV1 z-score at 18 months, time to death, time to first acute respiratory exacerbation, number of exacerbations, number of hospitalisations, weight for age z-score at 12 and 18 months, number of adverse events, number of malaria episodes, number of bloodstream Salmonella typhi infections and number of gastroenteritis episodes. Participants will be followed up 3-monthly, and lung function will be assessed every 6 months. Laboratory substudies will be done to investigate the impact of azithromycin on systemic inflammation and on development of antimicrobial resistance as well as impact on the nasopharyngeal, lung and gut microbiome. Discussion The results of this trial will be of clinical relevance because there are no established guidelines on the treatment and management of HIV-associated CLD in children in sub-Saharan Africa, where 80% of the world’s HIV-infected children live and where HIV-associated CLD is highly prevalent. Trial registration ClinicalTrials.gov, NCT02426112 . Registered on 21 April 2015.

Introduction In the UK, several hundred patients notified with tuberculosis (TB) die every year. The aim of this article is to describe trends in deaths among notified TB patients, explore risk factors associated with death and compare all-cause mortality in TB patients with age-specific mortality rates in the general UK population. Methods We used 2001–2014 data from UK national TB surveillance to explore trends and risk factors for death, and population mortality data to compare age-specific death rates among notified TB patients with annual death rates in the UK general population. Results The proportion of TB patients in the UK who died each year declined steadily from 7.1% in 2002 to 5.5% in 2014. One in five patients (21.3%) was diagnosed with TB post-mortem. Where information was available, almost half of the deaths occurred within 2 months of starting treatment. Risk factors for death included demographic, disease-specific and social risk factors. Age had by far the largest effect, with patients aged ≥80 years having a 70 times increased risk of death compared with those aged

Introduction The number of new paediatric infections per year has declined in sub-Saharan Africa due to prevention-of-mother-to-child HIV transmission programmes; many children and adolescents living with HIV remain undiagnosed. In this protocol paper, we describe the methodology for evaluating an index-linked HIV testing approach for children aged 2–18 years in health facility and community settings in Zimbabwe.Methods and analysis Individuals attending for HIV care at selected primary healthcare clinics (PHCs) will be asked if they have any children aged 2–18 years in their households who have not been tested for HIV. Three options for HIV testing for these children will be offered: testing at the PHC; home-based testing performed by community workers; or an oral mucosal HIV test given to the caregiver to test the children at home. All eligible children will be followed-up to ascertain whether HIV testing occurred. For those who did not test, reasons will be determined, and for those who tested, the HIV test result will be recorded. The primary outcome will be uptake of HIV testing. The secondary outcomes will be preferred HIV testing method, HIV yield, prevalence and proportion of those testing positive linking to care and having an undetectable viral load at 12 months. HIV test results will be stratified by sex and age group, and factors associated with uptake of HIV testing and choice of HIV testing method will be investigated.Ethics and dissemination Ethical approval for this study was granted by the Medical Research Council of Zimbabwe, the London School of Hygiene and Tropical Medicine and the Institutional Review Board of the Biomedical Research and Training Institute. Study results will be presented at national policy meetings and national and international research conferences. Results will also be published in international peer-reviewed scientific journals and disseminated to study communities at the end of study.

Despite being fundamental to all treatment decisions, the breakpoints that define susceptibility and resistance to conventional anti-tuberculosis (TB) drugs were traditionally defined based on expert opinion as opposed to modern microbiological principles. As a result, the breakpoints for several key drugs (i.e. amikacin, levofloxacin, and moxifloxacin) were too high, resulting in the systematic misclassification of a proportion of resistant strains as susceptible. Moreover, a recent systematic review of clinical outcome data prompted the World Health Organization (WHO) to make significant changes to its treatment guidelines. For example, capreomycin and kanamycin are no longer recommended for TB treatment because their use correlates with worse clinical outcomes. This history notwithstanding, robust breakpoints still do not exist for bedaquiline and delamanid six years after their approval. This was compounded by the fact that access to both agents for drug-susceptibility testing had initially been restricted. It is incumbent upon the European Medicines Agency, the United States Food and Drug Administration, and WHO to ensure that drug developers generate the necessary data to set breakpoints as a prerequisite for the approval of new agents. Keywords: Tuberculosis, Drug resistance, Minimum inhibitory concentration, Breakpoint, Bedaquiline, Delamanid

BACKGROUND:High quality diagnostic services are crucial for tuberculosis (TB) diagnosis, treatment and control. A strong laboratory quality management system (QMS) is critical to ensuring the quality of testing and results. Recent initiatives to improve TB laboratory quality have focused on low and middle-income countries, but similar issues also apply to high-income countries. METHODS AND FINDINGS:Using a multipronged approach reviews of facilities, equipment, processes (purchasing, pre-analytic, analytic and post-analytic), staff, health and safety, documentation, information management and organization based on the ISO 15189 and the twelve quality system essentials were conducted between October 2015 and January 2016 at the National TB Reference Laboratory in Germany. Outcome assessment included proportion of smear positive slides, proportion of contaminated liquid cultures and DNA contamination rates before and after implementation of QMS. The odds ratio for these outcomes was calculated using a before/after comparison. Reviews highlighted deficiencies across all twelve quality system essentials and were addressed in order of priority and urgency. Actions aimed at improving analytical quality, health and safety and information management were prioritised for initial implementation in parallel with each other. The odds ratio for a sample to be tested as microscopically positive increased by 2.08 (95%CI 1.41-3.06) comparing the time before with the time after implementation of quality managed fluorescence microscopy. Liquid culture contamination rates decreased from 23.6- 7.6% in April-July 2016 to

INTRODUCTION:A simple cost-effective strategy to pre-screen for targeted HIV testing can have substantial benefit in high burden and resource limited settings. A 4-item (previous hospitalisation, orphanhood, poor health status, and recurring skin problems) screening tool to identify adolescents living with HIV has previously shown high sensitivity in healthcare facility settings. We validated this screening tool in a community setting, in Harare, Zimbabwe in a community-based HIV prevalence survey. METHODS:A community-based HIV prevalence survey was conducted among individuals aged 8-17 years with guardian consent and child assent and residing in 7 communities during the period February 2015 to December 2015. Participants without previously diagnosed HIV were evaluated for the probability of having HIV using the screening tool. HIV status was defined using an anonymous HIV test which was done using Oral Mucosal Transudate (OMT). A questionnaire was also administered to ascertain self-reported HIV status and screening tool items. The validity of a 4-item screening tool was tested. Sensitivity and specificity of the screening tool was assessed against the HIV status based on OMT result. RESULTS:Prevalence survey participants were 5386 children who had an HIV test result, aged 8-17 years. However, 5384, who did not report testing HIV positive and responded to all screening tool item questions were included in the validation. Their median age was 12 (IQR: 10-15) years, 2515 (46.7%) were male. HIV prevalence was 1.3% (95% CI:1.0-1.8%). The 4-item screening tool had poor accuracy with an area under the receiver operating curve of 0.65(95% CI: 0.60-0.72) at a cut-off score≥1. Its sensitivity was 56.3% (95% CI:44.0-68.1%) and specificity of 75.1% (95% CI:73.9-76.3%), PPV of 2.9% (95% CI:2.1-3.9%) and a NPV of 99.2% (95% CI:98.9-99.5%). The number needed to test to diagnose one child using the screening tool was 55% lower than universal testing for HIV. CONCLUSION:Use of the 4-item screening tool could be a strategy that can be adopted to identify children living with HIV in a community setting in resource limited settings by reducing the number needed to test compared to universal testing since it is inexpensive, easy to administer and not harmful. However, screening items adapted to a community setting need to be explored to improve the performance of the screening tool.