Novel point-of-care cytokine biomarker lateral flow test for the screening for sexually transmitted infections and bacterial vaginosis: study protocol of a multicentre multidisciplinary prospective observational clinical study to evaluate the performance and feasibility of the Genital InFlammation Test (GIFT).

INTRODUCTION: A prototype lateral flow device detecting cytokine biomarkers interleukin (IL)-1α and IL-1ß 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.

Impact of the COVID-19 pandemic on the real-world diagnostic infrastructure for tuberculosis-An ESGMYC collaborative study.

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.

Beyond tuberculosis: a person-centred and rights-based approach to screening for household contacts.

Households affected by tuberculosis have syndemic vulnerability, reflecting a concentration of and interactions between multiple biomedical, psychosocial, and structural determinants of health. Traditional approaches to tuberculosis screening do not address pre-existing risks, such as undernutrition and other chronic conditions, or the indirect effects of tuberculosis, such as loss of livelihood. These pre-existing risks and consequences not only perpetuate the global tuberculosis epidemic but, for those affected, lead to poor health and deepen poverty. We propose reimagining tuberculosis screening as an opportunity to deliver a contextually relevant package of services that address the needs of households affected by tuberculosis. This approach puts people and their rights at the centre of efforts to end tuberculosis, and has equity at the core. This approach could support progress towards universal health coverage, benefiting communities and health systems. Leadership, flexibility in funding allocation, and innovative care models will be required to realise this approach at scale.

Differentiated care for youth in Zimbabwe: Outcomes across the HIV care cascade.

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 <1000 copies/ml) among those who had a test at 6 months was 90% (96/107). In addition 1162 clients previously diagnosed with HIV accessed CHIEDZA; 714 (61.4%) had a VL test, of whom 565 (79.1%) were virally suppressed. This study shows that provision of differentiated services for youth in the community is feasible. Linkage to care and retention during the initial months of ART was the main challenge and needs concerted attention to achieve the ambitious 95-95-95 UNAIDS targets.

Molecular determinants of multidrug-resistant tuberculosis in Sierra Leone.

Multidrug-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. IMPORTANCE: A 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.

Evaluation of a comprehensive health check offered to frontline health workers in Zimbabwe.

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.

Prevalence of chronic conditions and multimorbidity among healthcare workers in Zimbabwe: Results from a screening intervention.

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.

Clinical characteristics and outcomes of patients admitted with COVID-19 at a public-sector hospital over the first two waves of SARS-CoV-2 infection in Harare, Zimbabwe: A prospective cohort study.

BACKGROUND: We 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. METHODS: We 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. RESULTS: Of 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. CONCLUSION: The 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.

Prevalence of hypertension and high-normal blood pressure among young adults in Zimbabwe: findings from a large, cross-sectional population-based survey.

BACKGROUND: Hypertension is the greatest driver of cardiovascular mortality and onset might be in youth. We aimed to investigate the prevalence of and risk factors for elevated blood pressure (hypertension ≥140 mm Hg systolic, ≥90 mm Hg diastolic, or both) and high-normal blood pressure (130-139 mm Hg systolic, 85-89 mm Hg diastolic, or both) among youth in Zimbabwe. METHODS: A population-based, cross-sectional survey of randomly sampled youth aged 18-24 years from 24 urban and peri-urban communities in three provinces (Harare, Bulawayo, and Mashonaland East) in Zimbabwe was conducted between Oct 4, 2021, and June 2, 2022. Standardised questionnaires were used by research assistants to collect sociodemographic, behavioural, and clinical data. Height, bodyweight, and blood pressure were recorded. Three seated blood pressure measurements were taken at standardised timepoints during participant interview using a digital sphygmomanometer and cuffs sized on mid-upper arm circumference. The association of potential risk factors with elevated blood pressure was examined using multivariable logistic regression. FINDINGS: 17 682 (94·4%) of 18 729 eligible participants were recruited, 17 637 (99·7%) of whom had complete data, and 16 883 (95·7%) of whom were included in the final study sample after excluding 754 (4·3%) pregnant women. The median age was 20 years (IQR 19-22), 9973 (59·1%) participants were female, and 6910 (40·9%) were male. The prevalence of hypertension was 7·4% (95% CI 7·0-7·8) and high-normal blood pressure was 12·2% (11·7-12·7). Overall, prevalence of hypertension was higher in men (8·7% [95% CI 8·2-9·6]) than in women (6·6% [6·0-6·9]), but with age increased to similar levels (at age 18 years 7·3% [6·2-8·6] and 4·3% [3·5-5·2]; at age 23-24 years 10·9% [9·3-12·6] and 9·5% [8·4-10·7] in men and women, respectively). After adjusting for factors associated with hypertension in the crude analysis, hypertension was associated with male sex (adjusted odds ratio 1·53 [95% CI 1·36-1·74]), increasing age (age 19-20 years 1·20 [1·00-1·44]; age 21-22 years 1·45 [1·20-1·75]; age 23-24 years 1·90 [1·57-2·30], vs age 18 years), and BMI of 30·0 kg/m2 or more (1·94 [1·53-2·47] vs 18·5-24·9 kg/m2). A BMI of 18·5 kg/m2 or less (0·79 [0·63-0·98] vs 18·5-24·9 kg/m2) and living with HIV (0·71 [0·55-0·92]) were associated with lower odds of hypertension. INTERPRETATION: Prevalence of elevated blood pressure is high among urban and peri-urban youth in Zimbabwe and increases rapidly with age. Further research is needed to understand drivers of blood pressure elevation and the extent of target organ damage in youth in Zimbabwe and similar sub-Saharan African settings, to guide implementation of prevention and management strategies. FUNDING: Wellcome Trust.

Emergence of bedaquiline-resistant tuberculosis and of multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis strains with rpoB Ile491Phe mutation not detected by Xpert MTB/RIF in Mozambique: a retrospective observational study.

BACKGROUND: In 2021, an estimated 4800 people developed rifampicin-resistant tuberculosis in Mozambique, 75% of which went undiagnosed. Detailed molecular data on rifampicin-resistant and multidrug-resistant (MDR) tuberculosis are not available. Here, we aimed at gaining precise data on the determinants of rifampicin-resistant and MDR tuberculosis in Mozambique. METHODS: In this retrospective observational study, we performed whole-genome sequencing of 704 rifampicin-resistant Mycobacterium tuberculosis complex (Mtbc) strains submitted to the National Tuberculosis Reference Laboratory (NTRL) in Maputo, Mozambique, between 2015 and 2021. Phylogenetic strain classification, genomic resistance prediction, and cluster analysis were performed. FINDINGS: Between Jan 1, 2015, and July 31, 2021, 2606 Mtbc isolates with an isoniazid or rifampicin resistance were identified in the NTRL biobank, of which, 1483 (56·9%) were from men, 1114 (42·7%) from women, and nine (0·4%) were unknown. Genome-based drug-resistant prediction classified 704 Mtbc strains as rifampicin resistant. 628 (89%) of the 704 Mtbc strains were classified MDR; of those, 146 (23%) were pre-extensively drug resistant (pre-XDR; additional fluoroquinolone resistance), and 24 (4%) extensively drug resistant (XDR; combined fluoroquinolone and bedaquiline resistance). Overall, 61 (9%) of 704 strains revealed resistance to bedaquiline: five (7%) of 76 rifampicin resistant plus bedaquiline resistant, 32 (7%) of 458 MDR plus bedaquiline resistant, and 24 (100%) of 24 XDR. Prevalence of bedaquiline resistance increased from 3% in 2016 to 14% in 2021. The cluster rate (12 single-nucleotide polymorphism threshold) was 42% for rifampicin-resistant strains, 78% for MDR strains, 94% for pre-XDR strains, and 96% for XDR Mtbc strains. 31 (4%) of 704 Mtbc strains, belonging to a diagnostic escape outbreak strain previously described in Eswatini (group_56), had an rpoB Ile491Phe mutation which is not detected by Xpert MTB/RIF (no other rpoB mutation). Of these, 23 (74%) showed additional resistance to bedaquiline, 13 (42%) had bedaquiline and fluoroquinolone resistance, and two (6%) were bedaquiline, fluoroquinolone, and delamanid resistant. INTERPRETATION: Pre-XDR resistance is highly prevalent among MDR Mtbc strains in Mozambique and so is bedaquiline resistance; and the frequency of bedaquiline resistance quadrupled over time and was found even in Mtbc strains without fluoroquinolone resistance. Importantly, strains with Ile491Phe mutation were frequent, accounting for 31% (n=10) of MDR plus bedaquiline-resistant strains and 54% (n=13) of XDR Mtbc strains. Given the current diagnostic algorithms and treatment regimens, both the emergence of rifampicin resistance due to Ile491Phe and bedaquiline resistance might jeopardise MDR tuberculosis prevention and care unless sequencing-based technology is rolled out. The potential cross border spread of diagnostic escape strains needs further investigation. FUNDING: The German Ministry of Health through the Seq_MDRTB-Net project, the Deutsche Forschungsgemeinschaft under Germany's Excellence Strategy Precision Medicine in Inflammation and the Research Training Group 2501 TransEvo, the Leibniz Science Campus Evolutionary Medicine of the Lung, and the German Ministry of Education and Research via the German Center for Infection Research.

Higher loss of livelihood and impoverishment in households affected by tuberculosis compared to non-tuberculosis affected households in Zimbabwe: a cross-sectional study.

Introduction: Tuberculosis (TB) disproportionally affects poor people, leading to income and non-income losses. Measures of socioeconomic impact of TB, e.g. impoverishment and patient costs are inadequate to capture non-income losses. We applied impoverishment and a multidimensional measure on TB and non-TB affected households in Zimbabwe. Methods: We conducted a cross-sectional study in 270 households: 90 non-TB; 90 drug-susceptible TB (DS-TB), 90 drug-resistant TB (DR-TB) during the COVID-19 pandemic (2020-2021). Household data included ownership of assets, number of household members, income and indicators on five capital assets: financial, human, social, natural and physical. We determined proportions of impoverished households for periods 12 months prior and at the time of the interview. Households with incomes below US$1.90/day were considered to be impoverished. We used principal component analysis on five capital asset indicators to create a binary outcome variable indicating loss of livelihood. Log-binomial regression was used to determine associations between loss of livelihood and type of household. Results: TB-affected households reported higher previous episodes of TB and household members requiring care than non-TB households. Households that were impoverished 12 months prior to the study were: 21 non-TB (23%); 40 DS-TB (45%); 37 DR-TB (41%). The proportions increased to 81%, 88% and 94%, respectively by the time of interview. Overall, 56% (152/270) of households sold assets: 44% (40/90) non-TB, 58% (52/90) DS-TB and 67% (60/90) DR-TB. Children's education was affected in 31% (56/180) of TB-affected compared to 13% (12/90) non-TB households. Overall, 133(50%) households experienced loss of livelihood, with TB-affected households twice as likely to experience loss of livelihood; adjusted prevalence ratio (aPR=2.02 (95%CI:1.35-3.03)). The effect of TB on livelihood was most pronounced in poorest households (aPR=2.64, (95%CI:1.29-5.41)). Conclusions: TB-affected households experienced greater socioeconomic losses compared to non-TB households. Multidimensional measures of TB are crucial to inform multisectoral approaches to mitigate impacts of TB and other shocks.

Exploring COVID-19 vaccine uptake among healthcare workers in Zimbabwe: A mixed methods study.

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.

Financial incentives to improve uptake of partner services for sexually transmitted infections in Zimbabwe antenatal care: protocol for a cluster randomised trial.

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 18 th February 2022).

Feasibility and economic costs of syphilis self-testing to expand test uptake among gay, bisexual and transgender men: results from a randomised controlled trial in Zimbabwe.

BACKGROUND: Access to syphilis testing and treatment is frequently limited for men who have sex with men (MSM). A two-armed randomised controlled trial compared feasibility and costs of facility-based syphilis testing with self-testing among MSM in Zimbabwe. METHODS: This randomised controlled trial was conducted in Harare, with participants randomised 1:1. Syphilis self-testing was offered in community-based settings. The primary outcome was the relative proportion of individuals taking up testing. Total incremental economic provider and user costs, and cost per client tested, diagnosed and treated were assessed using ingredients-based costing in 2020US$. RESULTS: A total of 100 men were enrolled. The two groups were similar in demographics. The mean age was 26years. Overall, 58% (29/50) and 74% (37/50) of facility- and self-testing arm participants, respectively, completed syphilis testing. A total of 28% of facility arm participants had a reactive test, with 50% of them returning for confirmatory testing yielding 28% reactivity. In the self-testing arm, 67% returned for confirmatory testing, with a reactivity of 16%. Total provider costs were US$859 and US$736, and cost per test US$30 and US$15 for respective arms. Cost per reactive test was US$107 and US$123, and per client treated US$215 and US$184, respectively. The syphilis test kit was the largest cost component. Total user cost per client per visit was US$9. CONCLUSION: Syphilis self-testing may increase test uptake among MSM in Zimbabwe. However, some barriers limit uptake including lack of self-testing and poor service access. Bringing syphilis testing services to communities, simplifying service delivery and increasing self-testing access through community-based organisations are useful strategies to promote health-seeking behaviours among MSM.

Evaluation of a community-based aetiological approach for sexually transmitted infections management for youth in Zimbabwe: intervention findings from the STICH cluster randomised trial.

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).

Coping with drug resistant tuberculosis alongside COVID-19 and other stressors in Zimbabwe: A qualitative study.

Households in low-resource settings are more vulnerable to events which adversely affect their livelihoods, including shocks e.g. death of family members, droughts and more recently COVID-19. Drug Resistant Tuberculosis (DR-TB) is another shock that inflicts physical, psychological and socioeconomic burden on individuals and households. We describe experiences and coping strategies among people affected by DR-TB and their households in Zimbabwe during the COVID-19 pandemic, 2020-2021. We purposively selected 16 adults who had just completed or were completing treatment for DR-TB for in-depth interviews. We transcribed audio-recordings verbatim and translated the transcripts into English. Data were coded both manually and using NVivo 12 (QSR International), and were analysed thematically. Health seeking from providers outside the public sector, extra-pulmonary TB and health system factors resulted in delayed DR-TB diagnosis and treatment and increased financial drain on households. DR-TB reduced productive capacity and narrowed job opportunities leading to income loss that continued even after completion of treatment. Household livelihood was further adversely affected by lockdowns due to COVID-19, outbreaks of bird flu and cattle disease. Stockouts of DR-TB medicines, common during COVID-19, exacerbated loss of productive time and transport costs as medication had to be accessed from other clinics. Reversible coping strategies included: reducing number of meals; relocating in search of caregivers and/or family support; spending savings; negotiating with school authorities to keep children in school. Some households adopted irreversible coping strategies e.g. selling productive assets and withdrawing children from school. DR-TB combined with COVID-19 and other stressors and pushed households into deeper poverty and vulnerability. Multisectoral approaches that combine health systems and socioeconomic interventions are crucial to mitigate diagnostic delays and suffering, and meaningfully support people with DR-TB and their households to compensate the loss of livelihoods during and post DR-TB treatment.

The effect of a comprehensive typhoid conjugate vaccine campaign on antimicrobial prescribing in children in Harare, Zimbabwe: a mixed methods study.

BACKGROUND: Vaccines prevent infections and could subsequently reduce antimicrobial use. A 1-week mass vaccination campaign was done with Typbar-TCV (Bharat Biotech, Hyderabad, India) between Feb 25 and March 4, 2019. We investigated whether this typhoid conjugate vaccine campaign could affect antimicrobial prescribing in children presenting to primary care in Harare, Zimbabwe. METHODS: In this mixed methods study, data for acute paediatric outpatient consultations between Jan 1, 2018, and March 31, 2020, were collected from five clinics in Harare. Interrupted time series analysis was done to compare prescription data before and after the campaign. To contextualise findings, qualitative data were collected between April 20, 2021, and July 20, 2022, comprising ethnographic research (ie, workshops, surveys, observations, and interviews) in 14 clinics. Ethnographic data were used for thematic analysis. The primary outcome was monthly antimicrobial prescriptions in children aged 6 months to 15 years, normalised by the number of trauma events in all age groups. FINDINGS: In the data collection period, 27 107 paediatric consultations were recorded. 17 951 (66·2%) of 27 107 children were prescribed antimicrobials. Despite the perceived reduction in typhoid cases and a decreasing trend in the prescription of antimicrobials commonly used to treat typhoid (ie, ciprofloxacin and azithromycin), mass vaccination with Typbar-TCV did not affect the total rate of antimicrobials (adjusted rate ratio, 1·20, 95% CI 0·70-2·05, p=0·51) or the rate of typhoid antimicrobials prescribed (0·93, 0·44-1·96, p=0·85). Unsafe water sources and insufficient diagnostic services were reported to contribute to the continued disease burden and antimicrobial prescription. INTERPRETATION: Non-specific febrile illness caused by confirmed or suspected typhoid is a common cause of antimicrobial use in endemic areas. Although effective in preventing typhoid fever, we were unable to identify any effect of Typbar-TCV on antimicrobial prescribing. Ethnographic research showed the effect of contextual factors on antimicrobial prescribing, including concerns regarding safe water access, appropriate sewage disposal, health-care and diagnostic availability. To realise effects beyond disease burden reduction, holistic approaches addressing these concerns are needed so that the value of vaccines mitigating the effects of antimicrobial use as a driver of antimicrobial resistance is fully achieved. FUNDING: Wellcome Trust. TRANSLATION: For the Shona translation of the abstract see Supplementary Materials section.

Addressing sociodemographic disparities in COVID-19 vaccine uptake among youth in Zimbabwe.

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 (<19 years: 57.5%, 20-22: 61.5%, >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.

Exploring COVID-19 vaccine uptake among healthcare workers in Zimbabwe: A mixed methods study.

With COVID-19 no longer categorized as a public health emergency of international concern, vaccination strategies and priority groups for vaccination have evolved. Africa Centers 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 2905 healthcare workers employed at 37 facilities who participated in the study, 2818 (97%, 95% CI [92%-102%]) 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.

Feasibility and Usability of Mobile Technology to Assist HIV Self-Testing in Youth in Zimbabwe: A Mixed-Methods Study.

PURPOSE: Mobile technology is increasingly being used to widen access to and support the delivery of public health interventions. Human immunodeficiency viruses (HIV) self-testing (HIVST) enables individuals to have autonomy. We evaluated the feasibility of a novel application called ITHAKA to support HIVST among youth aged 16-24 years in Zimbabwe. METHODS: This study was nested within a trial of community-based delivery of integrated HIV and sexual and reproductive health services called CHIEDZA. Youth accessing CHIEDZA were offered provider-delivered HIV testing or HIVST supported by ITHAKA, either on a tablet on-site at a community centre or on their mobile phone off-site. ITHAKA incorporated pre and post-test counselling, and instructions for conducting the test and the appropriate actions to take depending on test result, including reporting HIV test results to health providers. The outcome was completion of the testing journey. Semistructured interviews with CHIEDZA providers explored the perceptions of and experiences with the application. RESULTS: Between April and September 2019, of the 2,181 youth who accepted HIV testing in CHIEDZA, 128 (5.8%) initiated HIVST (the remainder opting for provider-delivered testing) using ITHAKA. Nearly all who performed HIVST on-site (108/109 (99.1%)) compared to only 9/19 (47.4%) who tested off-site completed their testing journey. Low digital literacy, lack of agency, erratic network coverage, lack of dedicated phone ownership, the limited functionality of smartphones challenged implementation of ITHAKA. DISCUSSION: Digitally supported HIVST had low uptake among youth. The feasibility and usability of digital interventions should be carefully assessed before implementation, paying careful attention to digital literacy, network availability, and access to devices.