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BACKGROUND:Antimicrobial resistance is an emerging global health issue. Data on the epidemiology of multidrug-resistant organisms are scarce for Africa, especially in HIV-infected individuals who often have frequent contact with healthcare. We investigated the prevalence of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) carriage in stool among HIV-infected children attending an HIV outpatient department in Harare, Zimbabwe. METHODS:We recruited children who were stable on antiretroviral therapy (ART) attending a HIV clinic from August 2014 to June 2015. Information was collected on antibiotic use and hospitalization. Stool was tested for ESBL-E through combination disc diffusion. API20E identification and antimicrobial susceptibility was performed on the positive samples followed by whole genome sequencing. RESULTS:Stool was collected from 175/202 (86.6 %) children. Median age was 11 [inter-quartile range (IQR) 9-12] years. Median time on ART was 4.6 years (IQR 2.4-6.4). ESBL-Es were found in 24/175 samples (13.7 %); 50 % of all ESBL-Es were resistant to amoxicillin-clavulanate, 100 % to co-trimoxazole, 45.8 % to chloramphenicol, 91.6 % to ceftriaxone, 20.8 % to gentamicin and 62.5 % to ciprofloxacin. ESBL-Es variously encoded CTX-M, OXA, TEM and SHV enzymes. The odds of ESBL-E carriage were 8.5 times (95 % CI 2.2-32.3) higher in those on ART for less than one year (versus longer) and 8.5 times (95 % CI 1.1-32.3) higher in those recently hospitalized for a chest infection. CONCLUSION:We found a 13.7 % prevalence of ESBL-E carriage in a population where ESBL-E carriage has not been described previously. Antimicrobial resistance (AMR) in Africa merits further study, particularly given the high HIV prevalence and limited diagnostic and therapeutic options available.

Background: Young people are at particularly high risk of acquiring sexually transmitted infections (STIs). We conducted a trial to investigate the effect of a community-based intervention that included STI screening among youth on population-level prevalence of STIs in Zimbabwe., Methods: STICH was a parallel-arm, cluster-randomised controlled trial nested within CHIEDZA, a trial of community-based integrated HIV and sexual and reproductive health services for youth in Zimbabwe. STICH was conducted in Harare and Bulawayo provinces with eight clusters in each province, randomised 1:1 to control (existing health services) or to the intervention: community-based screening and treatment for Chlamydia trachomatis and Neisseria gonorrhoeae (males and females) and Trichomonas vaginalis (females only) offered over 12 months to intervention cluster residents aged 16-24 years who were attending CHIEDZA. Outcomes were ascertained through a population-level survey immediately after the intervention period, which included young people aged 18-24 years who lived in randomly selected households in each of the 16 clusters. The primary outcome was population prevalence of any (one or more) of the three STIs; secondary outcomes were prevalence of each of the three STIs. The STICH trial is registered with ISRCTN registry, ISRCTN15013425, and the CHIEDZA trial is registered with ClinicalTrials.gov, NCT03719521., Findings: From Oct 6, 2021, to March 8, 2022, 6361 randomly sampled young people were recruited into the outcome survey (median age 20 years [IQR 19-22], 3500 female and 2101 male, 3066 in intervention clusters and 3295 in control clusters). 5601 participants were included in the primary outcome analysis (2756 in intervention clusters and 2845 in control clusters). In the intervention clusters, 612 (22·2%) of 2756 participants reported that they had attended CHIEDZA and 298 (10·8%) had been tested for C trachomatis and N gonorrhoeae. In the control clusters, 113 (4·0%) of 2845 participants had attended CHIEDZA and 40 (1·4%) had been tested for C trachomatis and N gonorrhoeae. In the outcome survey, the cluster-level geometric mean prevalence of the primary outcome (any of C trachomatis, N gonorrhoeae, and T vaginalis) was 19·07% (geometric standard deviation [GSD] 1·20) in the intervention arm versus 19·95% (GSD 1·10) in the control arm (risk ratio [RR] 0·93 [95% CI 0·78-1·10]; p=0·35). There was no difference between arms in geometric mean prevalence of C trachomatis (12·86% [GSD 1·14] in the intervention arm vs 12·94% [GSD 1·15] in the control arm, RR 0·97 [95% CI 0·84-1·11]; p=0·60) or T vaginalis (7·06% [GSD 1·48] vs 6·20% [1·38], RR 1·09 [95% CI 0·74-1·60]; p=0·66). N gonorrhoeae prevalence was significantly lower in the intervention arm, with a 43% risk reduction (geometric mean 1·65% [GSD 1·77] vs 2·87% [1·43], RR 0·57 [95% CI 0·34-0·96]; p=0·036)., Interpretation: Our study showed high population prevalence of curable STIs. Community-based STI screening appeared to reduce population-level prevalence of N gonorrhoeae, but not of C trachomatis or T vaginalis, probably due to low intervention coverage. Future research is needed on the effects of screening interventions on morbidity, antimicrobial resistance, and re-infection rates., Funding: Medical Research Council, Economic and Social Research Council, Department for International Development, National Institute for Health and Care Research, and the Wellcome Trust., Competing Interests: Declaration of interests KM has received funding from FIND to validate a novel lateral flow assay for gonorrhoea and a loan of a GeneXpert Machine. KM is also the recipient of a Wellcome Trust grant for a clinical PhD fellowship assessing point-of-care testing for STIs (Grant number 225468/Z/22/Z). All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Youth in Southern Africa face a high burden of HIV and sexually transmitted infections, yet they exhibit low uptake of health care services., Objective: The Zvatinoda! intervention, co-designed with youth, aims to increase the demand for and utilization of health services among 18-24-year-olds in Chitungwiza, Zimbabwe., Methods: The intervention utilized mobile phone-based discussion groups, complemented by "ask the expert" sessions. Peer facilitators, supported by an "Auntie," led youth in anonymous online chats on health topics prioritized by the participants. Feedback on youth needs was compiled and shared with health care providers. The intervention was tested in a 12-week feasibility study involving 4 groups of 7 youth each, totaling 28 participants (n=14, 50%, female participants), to evaluate feasibility and acceptability. Mixed methods process evaluation data included pre- and postintervention questionnaires (n=28), in-depth interviews with participants (n=15) and peer facilitators (n=4), content from discussion group chats and expert guest sessions (n=24), facilitators' debrief meetings (n=12), and a log of technical challenges. Descriptive quantitative analysis and thematic qualitative analysis were conducted. The RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework was adapted to analyze and present findings on (1) reach, (2) potential efficacy, (3) adoption, (4) implementation, and (5) maintenance., Results: Mobile delivery facilitated engagement with diverse groups, even during COVID-19 lockdowns (reach). Health knowledge scores improved from pre- to postintervention across 9 measures. Preintervention scores varied from 14% (4/28) for contraception to 86% (24/28) for HIV knowledge. After the intervention, all knowledge scores reached 100% (28/28). Improvements were observed across 10 sexual and reproductive health (SRH) self-efficacy measures. The most notable changes were in the ability to start a conversation about SRH with older adults in the family, which increased from 50% (14/28) preintervention to 86% (24/28) postintervention. Similarly, the ability to use SRH services even if a partner does not agree rose from 57% (16/28) preintervention to 89% (25/28) postintervention. Self-reported attendance at a health center in the past 3 months improved from 32% (9/28) preintervention to 86% (24/28) postintervention (potential efficacy). Chat participation varied, largely due to network challenges and school/work commitments. The key factors facilitating peer learning were interaction with other youth, the support of an older, knowledgeable "Auntie," and the anonymity of the platform. As a result of COVID-19 restrictions, regular feedback to providers was not feasible. Instead, youth conveyed their needs to stakeholders through summaries of key themes from chat groups and a music video presented at a final in-person workshop (adoption and implementation). Participation in discussions decreased over time. To maintain engagement, introducing an in-person element was suggested (maintenance)., Conclusions: The Zvatinoda! intervention proved both acceptable and feasible, showing promise for enhancing young people's knowledge and health-seeking behavior. Potential improvements include introducing in-person discussions once the virtual group has established rapport and enhancing feedback and dialog with service providers., (©Constance Ruth Sina Mackworth-Young, Privillage Charashika, Zvatinoda Youth Advisory Group, Leyla Larsson, Olivia Jane Wilding-Davies, Nikita Simpson, Anna Sorrel Kydd, Theonevus Tinashe Chinyanga, Rashida Abbas Ferrand, Aveneni Mangombe, Karen Webb, Aoife Margaret Doyle. Originally published in JMIR Formative Research (https://formative.jmir.org), 24.09.2024.)

Background: Globally, the increasing use of digital technologies such as mobile phones and the internet has allowed for the development of innovative mobile health interventions, particularly for reaching and engaging with youth. However, there is a risk that using such technologies may exclude those who lack access to them., Objective: In this study, we investigated the sociodemographic factors associated with mobile phone ownership, internet use, and social media use among youth in Zimbabwe., Methods: A population-based prevalence survey was conducted in 24 urban and periurban communities across 3 provinces of Zimbabwe (Harare, Mashonaland East, and Bulawayo). Youths aged 18 to 24 years resident in randomly selected households in the study communities completed an interviewer-administered questionnaire. The primary outcomes were mobile phone ownership and current internet and social media use. A household wealth indicator was developed using principal components analysis, based on household asset ownership. Multivariable logistic regression was used to investigate the factors associated with each primary outcome. Age, sex, and province were considered a priori confounders. Household wealth, marital status, education level, employment status, time lived at current address, and HIV status were included in the final multivariable model if there was an age-, sex-, and province-adjusted association with a primary outcome on univariable analysis at a significance level of P<.10., Results: Of the 17,636 participants assessed for the primary outcome, 16,370 (92.82%) had access to a mobile phone, and 15,454 (87.63%) owned a mobile phone. Among participants with access to a mobile phone, 58.61% (9594/16,370) and 57.79% (9460/16,370), respectively, used internet and social media at least weekly. Older age (adjusted odds ratio [aOR] 1.76, 95% CI 1.55-2.00), increasing wealth (ranging from aOR 1.85, 95% CI 1.58-2.16, for wealth quintile 2 to aOR 3.80, 95% CI 3.00-4.80, for wealth quintile 5, with quintile 1 as reference), and higher education level (secondary: aOR 1.96, 95% CI 1.60-2.39; tertiary: aOR 8.36, 95% CI 5.29-13.20) were associated with mobile phone ownership. Older age, male sex, increasing wealth, having never been married, higher education level, being in education or formal employment, and having lived at the same address for ≥2 years were associated with higher levels of internet and social media use., Conclusions: While mobile phone ownership was near-universal, over one-third of youths in urban and periurban settings did not have access to the internet and social media. Access to the internet and social media use were strongly associated with household wealth and education level. Mobile health interventions must ensure that they do not amplify existing inequalities in access to health care. Such interventions must be accompanied by alternative strategies to engage and enroll individuals without internet or social media access to prevent the exclusion of young people by sex and socioeconomic status., (©Kevin Martin, Rachel Wei Chun Peh, Mandikudza Tembo, Constancia Vimbayi Mavodza, Aoife M Doyle, Chido Dziva Chikwari, Ethel Dauya, Tsitsi Bandason, Steven Azizi, Victoria Simms, Rashida A Ferrand. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 23.09.2024.)

Background: Stunting and pubertal delay are common among children growing up with human immunodeficiency virus (HIV) and are associated with bone and muscle impairments. We investigated factors associated with bone density and muscle function in adolescents living with HIV (ALWH)., Methods: The VITALITY trial (PACTR202009897660297) investigated whether vitamin D and calcium supplementation improves musculoskeletal health among ALWH. A total of 842 ALWH aged 11-19 years, established on antiretroviral therapy (ART) for ≥6 months, were enrolled from HIV clinics in Zambia and Zimbabwe. Clinical history and examination were undertaken, and serum 25-hydroxyvitamin D 3 (25[OH]D 3 ) was measured. Dual-energy X-ray absorptiometry measured total-body-less-head bone mineral density adjusted for height (TBLH-BMD HT ), and lumbar spine bone mineral apparent density (LS-BMAD) z scores. The association between a priori-defined covariates and musculoskeletal outcomes were investigated using baseline enrollment data and multivariable logistic regression., Results: TBLH-BMD HT   z scores were impaired (mean, -1.42 for male and -0.63 female participants), as were LS-BMAD z scores (mean -1.15 for male and -0.47 for female participants). In bivariate analysis, early pubertal stage, less physical activity, and older age at ART initiation were associated with lower TBLH-BMD HT   z scores. Younger age, early pubertal stage, and low socioeconomic status were associated with lower LS-BMAD z scores. Grip-strength-for-height and jump-power-for-height z scores were associated with lower TBLH-BMD HT and LS-BMAD z scores. Low dietary vitamin D and calcium were associated with lower adjusted TBLH-BMD HT   z scores. Lower 25(OH)D 3 was associated with lower adjusted TBLH-BMD HT and LS-BMAD z scores., Conclusions: Deficits in bone density are common in ALWH. Vitamin D and calcium supplementation and promotion of exercise may improve musculoskeletal health among perinatally infected ALWH., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objective: Cluster randomised trials (CRTs) are used for evaluating health-related interventions in low-income and middle-income countries (LMICs) but raise complex ethical issues. To inform the development of future ethics guidance, we aim to characterise CRTs conducted exclusively in LMICs by examining the types of clusters, settings, author affiliations and primary clinical focus and to evaluate adherence to trial registration and ethics reporting requirements over time., Design: A systematic scoping review using the Preferred Reporting Items for Systematic Review and Meta-Analyses Extension for Scoping Reviews., Data Sources: We searched MEDLINE between 1 January 2017 and 17 August 2022., Eligibility Criteria for Selecting Studies: We included primary reports of CRTs evaluating health-related interventions, conducted exclusively in LMICs and published in English between 2017 and 2022., Data Extraction and Synthesis: Data were extracted by one reviewer; a second reviewer verified accuracy by extracting data from 10% of the reports. Results were summarised overall and categorised by country's economic level or publication year., Results: Among 800 identified CRTs, 400 (50.0%) randomised geographical areas and 373 (46.6%) were conducted in Africa. 30 (3.7%) had no authors with an LMIC affiliation, and 246 (30.8%) had neither first nor last author with an LMIC affiliation. The relative frequency of first or last authors holding an LMIC affiliation increases as a country's economic level increases. Most CRTs focused on reducing maternal and neonatal disorders (106, 13.3%). 670 (83.8%) CRTs reported trial registration, 786 (98.2%) reported research ethics committee review and 757 (94.6%) reported consent statements. Among the 757 CRTs, 46 (6.1%) reported a waiver or no consent and, among these, 10 (21.7%) did not provide a rationale. Gatekeepers were identified in 403 (50.4%) CRTs. No meaningful trends were observed in adherence to trial registration or ethics reporting requirements over time., Conclusion: Our findings suggest existing inequity in authorship practices. There is high adherence to trial registration and ethics reporting requirements, although greater attention to reporting a justification for using a waiver of consent is needed., Competing Interests: Competing interests: CW receives consulting income from Cardialen and Eli Lilly & Company. Other authors declare no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Khan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Multimorbidity is an emerging challenge for health systems globally. It is commonly defined as the co-occurrence of two or more chronic conditions in one person, but its meaning remains a lively area of academic debate, and the utility of the concept beyond high-income settings is uncertain. This article presents the findings from an interdisciplinary research initiative that drew together 60 academic and applied partners working in 10 African countries to answer the questions: how useful is the concept of multimorbidity within Africa? Can the concept be adapted to context to optimise its transformative potentials? During a three-day concept-building workshop, we investigated how the definition of multimorbidity was understood across diverse disciplinary and regional perspectives, evaluated the utility and limitations of existing concepts and definitions, and considered how to build a more context-sensitive, cross-cutting description of multimorbidity. This iterative process was guided by the principles of grounded theory and involved focus- and whole-group discussions during the workshop, thematic coding of workshop discussions, and further post-workshop development and refinement. Three thematic domains emerged from workshop discussions: the current focus of multimorbidity on constituent diseases; the potential for revised concepts to centre the priorities, needs, and social context of people living with multimorbidity (PLWMM); and the need for revised concepts to respond to varied conceptual priorities amongst stakeholders. These themes fed into the development of an expanded conceptual model that centres the catastrophic impacts multimorbidity can have for PLWMM, families and support structures, service providers, and health systems., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Dixon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: HIV infection and its treatment compromises skeletal development (growth and maturation). Skeletal maturity is assessed as bone age (BA) on hand and wrist radiographs. BA younger than chronological age (CA) indicates delayed development. We conducted a cross-sectional study to determine differences between BA and CA (i.e., skeletal maturity deviation [SMD]), and risk factors associated with SMD in peripubertal children with and without HIV established on antiretroviral therapy (ART) including use of tenofovir disoproxil fumarate (TDF)., Methods: Children with HIV taking ART for at least two years and a comparison group of HIV-negative children, aged 8-16 years and frequency-matched by age and sex, were recruited from HIV clinics and local schools in the same catchment area, in Harare, Zimbabwe. BA was assessed from non-dominant hand-wrist radiographs using the Tanner Whitehouse 3 method. Negative SMD values correspond to delayed development, i.e., BA younger than CA. Multivariable linear regression models determined factors associated with SMD overall, and in children with HIV., Results: In total, 534 participants (54% males) were included; by design CA was similar in males and females, whether living with or without HIV. Mean (SD) SMD was more negative in CWH than in HIV-negative children in both males [-1.4(1.4) vs. -0.4(1.1) years] and females [-1.1(1.3) vs. -0.0(1.2) years]. HIV infection and weight-for-age Z-score<-2 were associated with more negative SMD in both males and females after adjusting for socio-economic status, orphanhood, pubertal stage, and calcium intake. Age at ART initiation was associated with SMD in both males and females with those starting ART later more delayed: starting ART aged 4-8 years 1.14 (-1.84, -0.43), or over 8 years 1.47 (-2.30, -0.65) (p-value for trend < 0.001). Similar non-significant trends were seen in males. TDF exposure TDF exposure whether < 4years or ≥ 4 years was not associated with delayed development., Conclusion: Perinatally-acquired HIV infection and being underweight were independently associated with delayed skeletal maturation in both males and females. Starting ART later was independently associated with skeletal maturation delay in CWH. Given the known effects of delayed development on later health, it is important to find interventions to ensure healthy weight gain through early years and in CWH to initiate ART as early as possible., (© 2024. The Author(s).)

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 D 3 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 D 3 (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-BMC LBM ) Z-score. The primary outcome was updated to address the substantial differences in distributions of TBLH-BMC LBM 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 D 3 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., (© 2024. The Author(s).)

Background: Chronic lung disease (CLD) is common among children with HIV (CWH) including in those taking antiretroviral therapy (ART). Azithromycin has both antimicrobial and anti-inflammatory effects and has been effective in improving lung function in a variety of lung diseases. We investigated lung function trajectories among CWH with CLD on ART enrolled in a randomized controlled trial of adjuvant azithromycin. We also investigated factors that modified the effect of azithromycin on lung function., Methods: The study used data from a double-blinded placebo-controlled trial conducted in Malawi and Zimbabwe of 48 weeks on azithromycin (BREATHE: ClinicalTrials.gov NCT02426112) among CWH aged 6 to 19 years taking ART for at least six months who had a forced expiratory volume in one second (FEV 1 ) z-score <-1.0. Participants had a further follow-up period of 24 weeks after intervention cessation. FEV 1 , forced vital capacity (FVC) and FEV 1 /FVC were measured at baseline, 24, 48 and 72-weeks and z-scores values calculated. Generalized estimating equations (GEE) models were used to determine the mean effect of azithromycin on lung-function z-scores at each follow-up time point., Results: Overall, 347 adolescents (51% male, median age 15 years) were randomized to azithromycin or placebo. The median duration on ART was 6.2 (interquartile range: 3.8-8.6) years and 56.2% had an HIV viral load < 1000copies/ml at baseline. At baseline, the mean FEV 1 z-score was - 2.0 (0.7) with 44.7% (n = 155) having an FEV 1 z-score <-2, and 10.1% had microbiological evidence of azithromycin resistance. In both trial arms, FEV 1 and FVC z-scores improved by 24 weeks but appeared to decline thereafter. The adjusted overall mean difference in FEV 1 z-score between the azithromycin and placebo arms was 0.004 [-0.08, 0.09] suggesting no azithromycin effect and this was similar for other lung function parameters. There was no evidence of interaction between azithromycin effect and baseline age, lung function, azithromycin resistance or HIV viral load., Conclusion: There was no observed azithromycin effect on lung function z-scores at any time point suggesting no therapeutic effect on lung function., Trial Registration: ClinicalTrials.gov NCT02426112. First registered on 24/04/2015., (© 2024. The Author(s).)

Introduction: Chronic lung disease is a major cause of morbidity in African children with HIV infection; however, the microbial determinants of HIV-associated chronic lung disease (HCLD) remain poorly understood. We conducted a case-control study to investigate the prevalence and densities of respiratory microbes among pneumococcal conjugate vaccine (PCV)-naive children with (HCLD +) and without HCLD (HCLD-) established on antiretroviral treatment (ART)., Methods: Nasopharyngeal swabs collected from HCLD + (defined as forced-expiratory-volume/second < -1.0 without reversibility postbronchodilation) and age-, site-, and duration-of-ART-matched HCLD- participants aged between 6-19 years enrolled in Zimbabwe and Malawi (BREATHE trial-NCT02426112) were tested for 94 pneumococcal serotypes together with twelve bacteria, including Streptococcus pneumoniae (SP), Staphylococcus aureus (SA), Haemophilus influenzae (HI), Moraxella catarrhalis (MC), and eight viruses, including human rhinovirus (HRV), respiratory syncytial virus A or B, and human metapneumovirus, using nanofluidic qPCR (Standard BioTools formerly known as Fluidigm). Fisher's exact test and logistic regression analysis were used for between-group comparisons and risk factors associated with common respiratory microbes, respectively., Results: A total of 345 participants (287 HCLD + , 58 HCLD-; median age, 15.5 years [IQR = 12.8-18], females, 52%) were included in the final analysis. The prevalence of SP (40%[116/287] vs. 21%[12/58], p = 0.005) and HRV (7%[21/287] vs. 0%[0/58], p = 0.032) were higher in HCLD + participants compared to HCLD- participants. Of the participants positive for SP (116 HCLD + & 12 HCLD-), 66% [85/128] had non-PCV-13 serotypes detected. Overall, PCV-13 serotypes (4, 19A, 19F: 16% [7/43] each) and NVT 13 and 21 (9% [8/85] each) predominated. The densities of HI (2 × 10 4 genomic equivalents [GE/ml] vs. 3 × 10 2 GE/ml, p = 0.006) and MC (1 × 10 4 GE/ml vs. 1 × 10 3 GE/ml, p = 0.031) were higher in HCLD + compared to HCLD-. Bacterial codetection (≥ any 2 bacteria) was higher in the HCLD + group (36% [114/287] vs. (19% [11/58]), (p = 0.014), with SP and HI codetection (HCLD + : 30% [86/287] vs. HCLD-: 12% [7/58], p = 0.005) predominating. Viruses (predominantly HRV) were detected only in HCLD + participants. Lastly, participants with a history of previous tuberculosis treatment were more likely to carry SP (adjusted odds ratio (aOR): 1.9 [1.1 -3.2], p = 0.021) or HI (aOR: 2.0 [1.2 - 3.3], p = 0.011), while those who used ART for ≥ 2 years were less likely to carry HI (aOR: 0.3 [0.1 - 0.8], p = 0.005) and MC (aOR: 0.4 [0.1 - 0.9], p = 0.039)., Conclusion: Children with HCLD + were more likely to be colonized by SP and HRV and had higher HI and MC bacterial loads in their nasopharynx. The role of SP, HI, and HRV in the pathogenesis of CLD, including how they influence the risk of acute exacerbations, should be studied further., Trial Registration: The BREATHE trial (ClinicalTrials.gov Identifier: NCT02426112 , registered date: 24 April 2015)., (© 2024. The Author(s).)

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. 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. Households with incomes per capita below US$1.90/day were considered 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. TB-affected households were more likely to report episodes of TB and household members requiring care than non-TB households. The proportions of impoverished households were 81% (non-TB), 88% (DS-TB) and 94% (DR-TB) 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 33% (55/168) of TB-affected compared to 14% (12/88) non-TB households. Overall, 133 (50%) households experienced loss of livelihood, with TB-affected households almost twice as likely to experience loss of livelihood; adjusted prevalence ratio (aPR = 1.78 [95%CI:1.09-2.89]). The effect of TB on livelihood was most pronounced in poorest households (aPR = 2.61, [95%CI:1.47-4.61]). TB-affected households experienced greater socioeconomic losses compared to non-TB households. Multisectoral social protection is crucial to mitigate impacts of TB and other shocks, especially targeting poorest households., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Timire et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Despite being integral to women's well-being, achieving good menstrual health (MH) remains a challenge. This study examined MH services uptake (including information, analgesics, and a choice of MH products - the menstrual cup and reusable pads) and sustained use of MH products within an integrated sexual and reproductive health intervention for young people in Zimbabwe., Methods: This mixed-methods study was nested within a cluster randomised trial of integrated sexual and reproductive health services (CHIEDZA) for youth in three provinces (Harare, Mashonaland East, and Bulawayo). The study collected qualitative and quantitative data from 27,725 female clients aged 16-24 years, who accessed CHIEDZA from April 2019 - March 2022. Using a biometric (fingerprint recognition) identification system, known as SIMPRINTS, uptake of MH information, products, and analgesics and other services was tracked for each client. Descriptive statistics and logistic regression were used to investigate MH service uptake and product choice and use over time, and the factors associated with these outcomes. Thematic analysis of focus group discussions and interviews were used to further explore providers' and participants' experiences of the MH service and CHIEDZA intervention., Results: Overall, 36,991 clients accessed CHIEDZA of whom 27,725 (75%) were female. Almost all (n = 26,448; 95.4%) took up the MH service at least once: 25433 took up an MH product with the majority (23,346; 92.8%) choosing reusable pads. The uptake of cups varied across province with Bulawayo province having the highest uptake (13.4%). Clients aged 20-24 years old were more likely to choose cups than reusable pads compared with those aged 16-19 years (9.4% vs 6.0%; p < 0.001). Over the implementation period, 300/1819 (16.5%) of clients swapped from the menstrual cup to reusable pads and 83/23346 (0.4%) swapped from reusable pads to the menstrual cup. Provision of the MH service encouraged uptake of other important SRH services. Qualitative findings highlighted the provision of free integrated SRH and MH services that included a choice of MH products and analgesics in a youth-friendly environment were key to high uptake and overall female engagement with SRH services., Conclusions: High uptake demonstrates how the MH service provided much needed access to MH products and information. Integration of MH within an SRH intervention proved central to young women accessing other SRH services., (© 2024. The Author(s).)

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., Competing Interests: Declaration of interests CJC and RAF acknowledge funding from the Wellcome Trust. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

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., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Chido Dziva Chikwari has been a guest Editor for Plos Global Public Health. The other authors have declared that no competing interests exist., (Copyright: © 2024 Dziva Chikwari et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Fryatt et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Calderwood et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Marambire et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Taruvinga et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Competing Interests: Competing interests: None declared.

Partner notification (PN) is considered integral to the management of sexually transmitted infections (STI). Patient-referral is a common PN strategy and relies on index cases notifying and encouraging their partners to access treatment; however, it has shown limited efficacy. We conducted a mixed methods study to understand young people's experiences of PN, particularly the risks and challenges encountered during patient-referral. All young people (16-24 years) attending a community-based sexual and reproductive health service in Zimbabwe who were diagnosed with an STI were counselled and offered PN slips, which enabled their partners to access free treatment at the service. PN slip uptake and partner treatment were recorded. Among 1807 young people (85.0% female) offered PN slips, 745 (41.2%) took up ≥1 PN slip and 103 partners (5.7%) returned for treatment. Most participants described feeling ill-equipped to counsel and persuade their partners to seek treatment. Between June and August 2021, youth researchers conducted in-depth interviews with 41 purposively selected young people diagnosed with an STI to explore their experiences of PN. PN posed considerable social risks, threatening their emotional and physical safety. Except for a minority in long-term, publicly acknowledged relationships, participants did not expect PN would achieve successful outcomes. Public health discourse, which constructs PN as "the right thing to do", influenced participants to adopt narratives that concealed the difficulties of PN and their unmet needs. Urgent interrogation is needed of whether PN is a suitable or constructive strategy to continue pursuing with young people. To improve the outcomes of preventing reinfection and onward transmission of STIs, we must consider developing alternative strategies that better align with young people's lived experiences. Plain language summary Partner notification is a public health strategy used to trace the sexual partners of people who have received a sexually transmitted infection (STI) diagnosis. It aims to interrupt the chains of STI transmission and prevent reinfection by treating both the person diagnosed and their sexual partners. The least effective but most common partner notification strategy used in many resource-limited settings is called "patient referral". This involves a sexual healthcare provider encouraging the person diagnosed to give a "partner notification slip" to their potentially exposed sexual partner/s and persuading them to access treatment. This research sought to better understand young people's experiences of partner notification, particularly the risks and challenges they faced during patient-referral.All young people (16-24 years) attending a community-based sexual and reproductive health service in Zimbabwe who were diagnosed with an STI were counselled and offered PN slips, which enabled their partners to access free treatment at the service. Young people trained as researchers interviewed 41 young people who had received a STI diagnosis to explore their experiences of partner notification.Only a small number (5.7%) of the partners of those who took a slip attended the service for treatment. Most participants felt they did not have the preparation, skills, or resources to persuade their partners to seek treatment. Many described negative experiences during and after partner notification, including relationship breakdown, reputation damage, and physical violence.These findings suggest that we should reconsider if partner notification is suitable or effective for use with young people. We should explore alternative approaches that do not present risks to young people's social, emotional, and physical safety and well-being.

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 <1000 copies/ml in those living with HIV and proportion who test positive for STIs (for the nested trial). A detailed process and cost evaluation of the trial will be conducted., Ethics and Dissemination: The trial 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 policy-making bodies., Trial Registration: https://clinicaltrials.gov/: NCT03719521., Competing Interests: No competing interests were disclosed., (Copyright: © 2023 Dziva Chikwari C et al.)

Background: The COVID-19 pandemic has disrupted global health supply chains including manufacturing, storage, and delivery of essential medicines, testing kits, personal protective equipment, and laboratory reagents. We sought to document how pandemic impacted the procurement, prices, and supply chain of medical products in Zimbabwe., Methods: We conducted semistructured in-depth key informant interviews with 36 health system stakeholders in Zimbabwe involved in medicine procurement. Respondents included pharmacists, regulatory officers, and procurement and supply chain management professionals from public and private sectors., Results: Before the COVID-19 pandemic, respondents described experiencing long-standing resource constraints, medicine shortages, foreign currency shortages, and supply chain inefficiencies. The pandemic exacerbated this situation due to supply constraints, export restrictions, medicine shortages, and movement restrictions that disrupted logistical and stock management systems. Competitive bidding and tendering processes experienced reduced participation by international suppliers. Significant price increases were initially observed among internationally shipped medicines and for personal protective equipment to cover additional freight costs. COVID-19 pandemic impacts were moderated by reduced patient demand and lower health services utilization, resulting in fewer supply shocks and less price volatility. Further, health system adaptations such as switching treatment regimens, modifying dispensing schedules based on stock availability, redistributing stock of medicines among facilities, and new service delivery models such as integrated outreach services helped ensure continued patient access to medicines., Conclusions: Our findings highlight the need for policies that ensure continuity in access to health services and medical products, even during a pandemic, by avoiding blanket restrictions on medical product exports and imports. Pooled procurement, especially at regional and global levels, with long-term service agreements may help achieve greater resiliency to supply and price shocks from supply chain disruptions. Interventions across manufacturing, trade, and regulatory policy and service delivery models are also needed for supply chain resiliency., (© Yemeke et al.)

Impaired linear growth and slower pubertal growth can be associated with perinatal HIV infection. We characterised growth relative to population norms, among the full adolescent period in southern Africa to better understand processes leading to morbidity in adulthood. We conducted a secondary analysis of 945 adolescents aged 8-20 years from urban Malawi and Zimbabwe; we included children with HIV (CWH), an uninfected comparison group from a cohort study, and CWH with co-morbid chronic lung disease (CLD) from a randomised controlled trial. We used latent class analysis of anthropometric Z-scores generated from British 1990 reference equations at two annual time-points, to identify growth trajectory profiles and used multinomial logistic regression to identify factors associated with growth profiles. Growth faltering (one or more of weight-for-age, height-for-age, or BMI-for-age Z-scores < -2) occurred in 38% (116/303) of CWH from the cohort study, 62% (209/336) of CWH with CLD, and 14% (44/306) of HIV-uninfected participants. We identified seven different growth profiles, defined, relatively, as (1) average growth, (2) tall not thin, (3) short not thin, (4) stunted not thin, (5) thin not stunted, (6) thin and stunted and (7) very thin and stunted. Females in profile 3 exhibited the highest body fat percentage, which increased over 1 year. Males at older age and CWH especially those with CLD were more likely to fall into growth profiles 4-7. Improvements in height-for-age Z-scores were observed in profiles 6-7 over 1 year. Interventions to target those with the worst growth faltering and longer-term follow-up to assess the impact on adult health are warranted.

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)., Competing Interests: No competing interests were disclosed., (Copyright: © 2023 Martin K et al.)

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)., Competing Interests: Authors declare no competing interests., (© 2023 The Author(s).)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Competing Interests: We declare no competing interests.

Background: The scale-up of antiretroviral therapy programmes has resulted in increased life expectancy of people with HIV in Africa. Little is known of the menopausal experiences of African women, including those living with HIV. We aimed to determine the prevalence and severity of self-reported menopause symptoms in women at different stages of menopause transition, by HIV status, and evaluate how symptoms are related to health-related quality of life (HRQoL). We further sought to understand factors associated with menopause symptoms., Methods: A cross-sectional study recruited women resident in Harare, Zimbabwe, sampled by age group (40-44/45-49/50-54/55-60 years) and HIV status. Women recruited from public-sector HIV clinics identified two similarly aged female friends (irrespective of HIV status) with phone access. Socio-demographic and medical details were recorded and women staged as pre-, peri- or post-menopause. The Menopausal Rating Scale II (MRS), which classified symptom severity, was compared between those with and without HIV. Linear and logistic regression determined factors associated with menopause symptoms, and associations between symptoms and HRQoL., Results: The 378 women recruited (193[51.1%] with HIV), had a mean (SD) age of 49.3 (5.7) years; 173 (45.8%), 51 (13.5%) and 154 (40.7%) were pre-, peri and post-menopausal respectively. Women with HIV reported more moderate (24.9% vs. 18.1%) and severe (9.7% vs. 2.6%) menopause symptoms than women without HIV. Peri-menopausal women with HIV reported higher MRS scores than those pre- and post-menopausal, whereas in HIV negative women menopausal stage was not associated with MRS score (interaction p-value = 0.014). With increasing severity of menopause symptoms, lower mean HRQoL scores were observed. HIV (OR 2.02[95% CI 1.28, 3.21]), mood disorders (8.80[2.77, 28.0]), ≥ 2 falls/year (4.29[1.18, 15.6]), early menarche (2.33[1.22, 4.48]), alcohol consumption (2.16[1.01, 4.62]), food insecurity (1.93[1.14, 3.26]) and unemployment (1.56[0.99, 2.46]), were all associated with moderate/severe menopause symptoms. No woman reported use of menopausal hormone therapy., Conclusions: Menopausal symptoms are common and negatively impact HRQoL. HIV infection is associated with more severe menopause symptoms, as are several modifiable factors, including unemployment, alcohol consumption, and food insecurity. Findings highlight an unmet health need in ageing women in Zimbabwean, especially among those living with HIV., (© 2023. The Author(s).)

Objective: To explore the impact of the Coronavirus disease 2019 (COVID-19) pandemic on the quality of medical products in Zimbabwe, including market risks for substandard and falsified products and impacts on quality assurance activities., Design: Qualitative study based on in-depth key informant interviews., Setting: Health system stakeholders across the medical product supply chain in Zimbabwe., Participants: 36 key informants were interviewed between April and June 2021., Results: We found that the COVID-19 pandemic disrupted quality assurance and regulatory activities of medical products in Zimbabwe, resulted in observations of poor-quality personal protective equipment (PPE) and other COVID-19-related products and led to increased risks to quality. Risks to quality due to COVID-19-related disruptions included increased layers of agents in the supply chain and an influx of non-traditional suppliers. COVID-19-related movement restrictions reduced access to health facilities and thus may have increased the usage of the informal market where smuggled and unregistered medical products are sold with less oversight by the regulator. Most reports of poor-quality medical products were for PPE, such as masks and infrared thermometers, used for the COVID-19 response. Besides these reports, many participants stated that the quality of essential medicines in the formal sector, not related to COVID-19, had largely been maintained during the pandemic due to the regulator's stringent quality assurance process. Incentives for suppliers to maintain quality to retain large donor-funded contracts, and the need for local wholesalers and distributors to comply with quality-related aspects of distribution agreements with global manufacturers of brand-name medical products, mitigated threats to quality., Conclusions: The COVID-19 pandemic presented opportunities and market risks for circulation of substandard and falsified medical products in Zimbabwe. There is a need for policymakers to invest in measures to safeguard the quality of medical products during emergencies and to build resiliency against future supply chain shocks., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

An estimated 25% of South African women live with human immunodeficiency virus (HIV). Antiretroviral therapy roll-out has improved life expectancy, so many more women now reach menopause. We aimed to quantify changes in bone mineral density (BMD) during the menopausal transition in urban-dwelling South African women with and without HIV and determine whether HIV infection modified the effect of menopause on BMD changes. A 5-year population-based longitudinal study recruited women aged 40-60 years residing in Soweto and collected demographic and clinical data, including HIV status, anthropometry, and BMD, at baseline and at 5-year follow-up. All women were staged as pre-, peri-, or postmenopausal at both time points. Multivariable linear regression assessed relationships and interactions between HIV infection, menopause, and change in BMD. At baseline, 450 women had mean age 49.5 (SD 5.7) years, 65 (14.4%) had HIV, and 140 (31.1%), 119 (26.4%), and 191 (42.4%) were pre-, peri-, and postmenopausal, respectively; 34/205 (13.6%) women ≥50 years had a total hip (TH) or lumbar spine (LS) T-score ≤ -2.5. At follow-up 38 (8.4%), 84 (18.7%), and 328 (72.9%) were pre-, peri-, and postmenopausal. Those with HIV at baseline lost more total body (TB) BMD (mean difference -0.013 [95% confidence interval -0.026, -0.001] g/cm 2 , p = 0.040) and gained more weight 1.96 [0.32, 3.60] kg; p = 0.019 than HIV-uninfected women. After adjusting for age, baseline weight, weight change, and follow-up time, the transition from pre- to postmenopause was associated with greater TB BMD losses in women with HIV (-0.092 [-0.042, -0.142] g/cm 2 ; p = 0.001) than without HIV (-0.038 [-0.016, -0.060] g/cm 2 , p = 0.001; interaction p = 0.034). Similarly, in women who were postmenopausal at both time points, those with HIV lost more TB BMD (-0.070 [-0.031, -0.108], p = 0.001) than women without HIV (-0.036 [-0.015, -0.057], p = 0.001, interaction p = 0.049). Findings were consistent but weaker at the LS and TH. Menopause-related bone loss is greater in women with HIV, suggesting women with HIV may be at greater risk of osteoporotic fractures. HIV services should consider routine bone health assessment in midlife women as part of long-term HIV care delivery. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)., (© 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

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., (© 2023. The Author(s).)

Objectives: HIV infection impairs bone density in children living with HIV (CLWH). We aimed to determine the prevalence of self-reported fracture (past or current), associated risk factors and disability, by HIV status in Zimbabwean children., Design: Cross-sectional study., Methods: We recruited CLWH aged 8-16 years taking antiretroviral therapy (ART) for ≥2 years from HIV clinics, and HIV-uninfected children from schools in Harare. Interviewer-administered questionnaires collected data on fracture site and management, sociodemographics, dietary calcium and vitamin D, physical activity and HIV history. Dual-energy X-ray absorptiometry (DXA) measured size-adjusted bone density., Results: We recruited 303 CLWH [mean (SD) age 12.5 (2.5) years; 50% female] and 306 children without HIV [12.5 (2.5) years; 51% female]. Median age at HIV diagnosis in CLWH was 3.0 years [interquartile range (IQR) 1.2, 5.9], and median ART duration 8.1 years [IQR 6.2, 9.5]. 53.8% CLWH had self-reported disability and/or functional impairment, vs. 29.4% children without HIV. Fracture prevalence was 5.9% with no difference by HIV status [21/306 (6.9%) vs. 14/303 (4.6%), P  = 0.24]. Male sex was associated with fractures. Low size-adjusted bone density ( Z -score < -2) was associated with prevalent fractures in CLWH {risk ratio [RR] 1.14 (95% confidence interval (CI) -0.02, 2.29]}, but not in children without HIV [RR -0.04 (-2.00, 1.91)], P -interaction = 0.27. All sought medical attention for their fracture(s), but CLWH were less often admitted to hospital [2/14 (14.3%) vs. 7/21 (33.3%)]., Conclusion: Prevalent fractures may be associated with low lumbar spine bone density in CLWH. Fracture surveillance and strategies to reduce future fracture risk are warranted as CLWH enter adulthood., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Multimorbidity has been framed as a pressing global health challenge that exposes the limits of systems organised around single diseases. This article seeks to expand and strengthen current thinking around multimorbidity by analysing its construction within the field of global health. We suggest that the significance of multimorbidity lies not only in challenging divisions between disease categories but also in what it reveals about the culture and history of transnational biomedicine. Drawing on social research from sub-Saharan Africa to ground our arguments, we begin by describing the historical processes through which morbidity was made divisible in biomedicine and how the single disease became integral not only to disease control but to the extension of biopolitical power. Multimorbidity, we observe, is hoped to challenge single disease approaches but is assembled from the same problematic, historically-loaded categories that it exposes as breaking down. Next, we highlight the consequences of such classificatory legacies in everyday lives and suggest why frameworks and interventions to integrate care have tended to have limited traction in practice. Finally, we argue that efforts to align priorities and disciplines around a standardised biomedical definition of multimorbidity risks retracing the same steps. We call for transdisciplinary work across the field of global health around a more holistic, reflexive understanding of multimorbidity that foregrounds the culture and history of translocated biomedicine, the intractability of single disease thinking, and its often-adverse consequences in local worlds. We outline key domains within the architecture of global health where transformation is needed, including care delivery, medical training, the organisation of knowledge and expertise, global governance, and financing., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Background: Long-term azithromycin (AZM) treatment reduces the frequency of acute respiratory exacerbation in children and adolescents with HIV-associated chronic lung disease (HCLD). However, the impact of this treatment on the respiratory bacteriome is unknown., Method: African children with HCLD (defined as forced expiratory volume in 1 s z-score (FEV1z) less than - 1.0 with no reversibility) were enrolled in a placebo-controlled trial of once-weekly AZM given for 48-weeks (BREATHE trial). Sputum samples were collected at baseline, 48 weeks (end of treatment) and 72 weeks (6 months post-intervention in participants who reached this timepoint before trial conclusion). Sputum bacterial load and bacteriome profiles were determined using 16S rRNA gene qPCR and V4 region amplicon sequencing, respectively. The primary outcomes were within-participant and within-arm (AZM vs placebo) changes in the sputum bacteriome measured across baseline, 48 weeks and 72 weeks. Associations between clinical or socio-demographic factors and bacteriome profiles were also assessed using linear regression., Results: In total, 347 participants (median age: 15.3 years, interquartile range [12.7-17.7]) were enrolled and randomised to AZM (173) or placebo (174). After 48 weeks, participants in the AZM arm had reduced sputum bacterial load vs placebo arm (16S rRNA copies/µl in log 10 , mean difference and 95% confidence interval [CI] of AZM vs placebo - 0.54 [- 0.71; - 0.36]). Shannon alpha diversity remained stable in the AZM arm but declined in the placebo arm between baseline and 48 weeks (3.03 vs. 2.80, p = 0.04, Wilcoxon paired test). Bacterial community structure changed in the AZM arm at 48 weeks compared with baseline (PERMANOVA test p = 0.003) but resolved at 72 weeks. The relative abundances of genera previously associated with HCLD decreased in the AZM arm at 48 weeks compared with baseline, including Haemophilus (17.9% vs. 25.8%, p < 0.05, ANCOM ω = 32) and Moraxella (1% vs. 1.9%, p < 0.05, ANCOM ω = 47). This reduction was sustained at 72 weeks relative to baseline. Lung function (FEV1z) was negatively associated with bacterial load (coefficient, [CI]: - 0.09 [- 0.16; - 0.02]) and positively associated with Shannon diversity (0.19 [0.12; 0.27]). The relative abundance of Neisseria (coefficient, [standard error]: (2.85, [0.7], q = 0.01), and Haemophilus (- 6.1, [1.2], q < 0.001) were positively and negatively associated with FEV1z, respectively. An increase in the relative abundance of Streptococcus from baseline to 48 weeks was associated with improvement in FEV1z (3.2 [1.11], q = 0.01) whilst an increase in Moraxella was associated with decline in FEV1z (-2.74 [0.74], q = 0.002)., Conclusions: AZM treatment preserved sputum bacterial diversity and reduced the relative abundances of the HCLD-associated genera Haemophilus and Moraxella. These bacteriological effects were associated with improvement in lung function and may account for reduced respiratory exacerbations associated with AZM treatment of children with HCLD. Video Abstract., (© 2023. The Author(s).)

HIV infection has multi-system adverse effects in children, including on the growing skeleton. We aimed to determine the association between chronic HIV infection and bone architecture (density, size, strength) in peripubertal children. We conducted a cross-sectional study of children aged 8 to 16 years with HIV (CWH) on antiretroviral therapy (ART) and children without HIV (CWOH) recruited from schools and frequency-matched for age strata and sex. Outcomes, measured by tibial peripheral quantitative computed tomography (pQCT), included 4% trabecular and 38% cortical volumetric bone mineral density (vBMD), 4% and 38% cross-sectional area (CSA), and 38% stress-strain index (SSI). Multivariable linear regression tested associations between HIV status and outcomes, stratified by sex and puberty (Tanner 1-2 versus 3-5), adjusting for age, height, fat mass, physical activity, and socioeconomic and orphanhood statuses. We recruited 303 CWH and 306 CWOH; 50% were female. Although CWH were similar in age to CWOH (overall mean ± SD 12.4 ± 2.5 years), more were prepubertal (ie, Tanner 1; 41% versus 23%). Median age at ART initiation was 4 (IQR 2-7) years, whereas median ART duration was 8 (IQR 6-10) years. CWH were more often stunted (height-for-age Z-score <-2) than those without HIV (33% versus 7%). Both male and female CWH in later puberty had lower trabecular vBMD, CSA (4% and 38%), and SSI than those without HIV, whereas cortical density was similar. Adjustment explained some of these differences; however, deficits in bone size persisted in CWH in later puberty (HIV*puberty interaction p = 0.035 [males; 4% CSA] and p = 0.029 [females; 38% CSA]). Similarly, puberty further worsened the inverse association between HIV and bone strength (SSI) in both males (interaction p = 0.008) and females (interaction p = 0.004). Despite long-term ART, we identified deficits in predicted bone strength in those living with HIV, which were more overt in the later stages of puberty. This is concerning, as this may translate to higher fracture risk later in life. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)., (© 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)