Decentralising chronic disease management in sub-Saharan Africa: a protocol for the qualitative process evaluation of community-based integrated management of HIV, diabetes and hypertension in Tanzania and Uganda.

INTRODUCTION: Sub-Saharan Africa continues to experience a syndemic of HIV and non-communicable diseases (NCDs). Vertical (stand-alone) HIV programming has provided high-quality care in the region, with almost 80% of people living with HIV in regular care and 90% virally suppressed. While integrated health education and concurrent management of HIV, hypertension and diabetes are being scaled up in clinics, innovative, more efficient and cost-effective interventions that include decentralisation into the community are required to respond to the increased burden of comorbid HIV/NCD disease. METHODS AND ANALYSIS: This protocol describes procedures for a process evaluation running concurrently with a pragmatic cluster-randomised trial (INTE-COMM) in Tanzania and Uganda that will compare community-based integrated care (HIV, diabetes and hypertension) with standard facility-based integrated care. The INTE-COMM intervention will manage multiple conditions (HIV, hypertension and diabetes) in the community via health monitoring and adherence/lifestyle advice (medicine, diet and exercise) provided by community nurses and trained lay workers, as well as the devolvement of NCD drug dispensing to the community level. Based on Bronfenbrenner's ecological systems theory, the process evaluation will use qualitative methods to investigate sociostructural factors shaping care delivery and outcomes in up to 10 standard care facilities and/or intervention community sites with linked healthcare facilities. Multistakeholder interviews (patients, community health workers and volunteers, healthcare providers, policymakers, clinical researchers and international and non-governmental organisations), focus group discussions (community leaders and members) and non-participant observations (community meetings and drug dispensing) will explore implementation from diverse perspectives at three timepoints in the trial implementation. Iterative sampling and analysis, moving between data collection points and data analysis to test emerging theories, will continue until saturation is reached. This process of analytic reflexivity and triangulation across methods and sources will provide findings to explain the main trial findings and offer clear directions for future efforts to sustain and scale up community-integrated care for HIV, diabetes and hypertension. ETHICS AND DISSEMINATION: The protocol has been approved by the University College of London (UK), the London School of Hygiene and Tropical Medicine Ethics Committee (UK), the Uganda National Council for Science and Technology and the Uganda Virus Research Institute Research and Ethics Committee (Uganda) and the Medical Research Coordinating Committee of the National Institute for Medical Research (Tanzania). The University College of London is the trial sponsor. Dissemination of findings will be done through journal publications and stakeholder meetings (with study participants, healthcare providers, policymakers and other stakeholders), local and international conferences, policy briefs, peer-reviewed journal articles and publications. TRIAL REGISTRATION NUMBER: ISRCTN15319595.

Prevalence of subclinical pulmonary tuberculosis in adults in community settings: an individual participant data meta-analysis.

BACKGROUND: Subclinical pulmonary tuberculosis, which presents without recognisable symptoms, is frequently detected in community screening. However, the disease category is poorly clinically defined. We explored the prevalence of subclinical pulmonary tuberculosis according to different case definitions. METHODS: We did a one-stage individual participant data meta-analysis of nationally representative surveys that were conducted in countries with high incidence of tuberculosis between 2007 and 2020, that reported the prevalence of pulmonary tuberculosis based on chest x-ray and symptom screening in participants aged 15 years and older. Screening and diagnostic criteria were standardised across the surveys, and tuberculosis was defined by positive Mycobacterium tuberculosis sputum culture. We estimated proportions of subclinical tuberculosis for three case definitions: no persistent cough (ie, duration ≥2 weeks), no cough at all, and no symptoms (ie, absence of cough, fever, chest pain, night sweats, and weight loss), both unadjusted and adjusted for false-negative chest x-rays and uninterpretable culture results. FINDINGS: We identified 34 surveys, of which 31 were eligible. Individual participant data were obtained and included for 12 surveys (620 682 participants) across eight countries in Africa and four in Asia. Data on 602 863 participants were analysed, of whom 1944 had tuberculosis. The unadjusted proportion of subclinical tuberculosis was 59·1% (n=1149/1944; 95% CI 55·8-62·3) for no persistent cough and 39·8% (773/1944; 36·6-43·0) for no cough of any duration. The adjusted proportions were 82·8% (95% CI 78·6-86·6) for no persistent cough and 62·5% (56·6-68·7) for no cough at all. In a subset of four surveys, the proportion of participants with tuberculosis but without any symptoms was 20·3% (n=111/547; 95% CI 15·5-25·1) before adjustment and 27·7% (95% CI 21·0-36·4) after adjustment. Tuberculosis without cough, irrespective of its duration, was more frequent among women (no persistent cough: adjusted odds ratio 0·79, 95% CI 0·63-0·97; no cough: adjusted odds ratio 0·76, 95% CI 0·62-0·93). Among participants with tuberculosis, 29·1% (95% CI 25·2-33·3) of those without persistent cough and 23·1% (18·8-27·4) of those without any cough had positive smear examinations. INTERPRETATION: The majority of people in the community who have pulmonary tuberculosis do not report cough, a quarter report no tuberculosis-suggestive symptoms at all, and a quarter of those not reporting any cough have positive sputum smears, suggesting infectiousness. In high-incidence settings, subclinical tuberculosis could contribute considerably to the tuberculosis burden and to Mycobacterium tuberculosis transmission. FUNDING: Mr Willem Bakhuys Roozeboom Foundation.

Health insurance financing and patient retention in care at diabetics and hypertension clinics in Dar es Salaam and Pwani regions, Tanzania. A cohort study.

Hypertension and diabetes are chronic conditions that cause major morbidity and mortality worldwide. Whether health insurance financing is associated with improved retention in chronic care in Tanzania, is unknown. Our study establishes the effect of health insurance on retention and the determinants for retention in care among patients attending diabetes and hypertension clinics. We used a Cohort design to study participants enrolled in a cluster-randomized trial of integrated management of HIV, diabetes, and hypertension compared with standard vertical care in the INTE-AFRICA trial. Fifteen health facilities in Dar es Salam and Pwani regions were enrolled, with 1716 participants. Our sample size had 95% power to detect a 50% to 60% retention difference between the insured and uninsured groups (95% CI). We compared proportions using χ2 tests and obtained prevalence and rate ratios by Generalised Linear Models. We studied 1716 participants for 1612.3 Person-years (PY). At the study's end, 1351 persons were alive and retained in care. Among the insured participants (26.0%), females accounted for 65.9%. Middle-aged adults contributed 58.8% of insured participants. We observed high retention rates (retention incidence rate IR: 83.80/100 PY; 95% CI (79.40-88.40)). There was no difference in retention among insured and uninsured patients (adjusted rate ratio aRR: 1.00; 95% CI, 0.94-1.06). Being middle-aged or senior-aged adults compared to young adults, having diabetes alone or hypertension alone compared to both conditions, having the comorbidity of diabetes or hypertension with HIV compared to a single condition, and attending health centres and hospitals compared to dispensaries were significantly associated with retention in care. This study showed no effect of health insurance on retention in diabetic and hypertension care clinics. However, age, medical diagnosis, morbidity, and type of health facility attended were associated with retention in care.

Tobacco smoking clusters in households affected by tuberculosis in an individual participant data meta-analysis of national tuberculosis prevalence surveys: Time for household-wide interventions?

Tuberculosis (TB) and non-communicable diseases (NCD) share predisposing risk factors. TB-associated NCD might cluster within households affected with TB requiring shared prevention and care strategies. We conducted an individual participant data meta-analysis of national TB prevalence surveys to determine whether NCD cluster in members of households with TB. We identified eligible surveys that reported at least one NCD or NCD risk factor through the archive maintained by the World Health Organization and searching in Medline and Embase from 1 January 2000 to 10 August 2021, which was updated on 23 March 2023. We compared the prevalence of NCD and their risk factors between people who do not have TB living in households with at least one person with TB (members of households with TB), and members of households without TB. We included 16 surveys (n = 740,815) from Asia and Africa. In a multivariable model adjusted for age and gender, the odds of smoking was higher among members of households with TB (adjusted odds ratio (aOR) 1.23; 95% CI: 1.11-1.38), compared with members of households without TB. The analysis did not find a significant difference in the prevalence of alcohol drinking, diabetes, hypertension, or BMI between members of households with and without TB. Studies evaluating household-wide interventions for smoking to reduce its dual impact on TB and NCD may be warranted. Systematically screening for NCD using objective diagnostic methods is needed to understand the actual burden of NCD and inform comprehensive interventions.

Stability in care and risk of loss to follow-up among clients receiving community health worker-led differentiated HIV care: Results from a prospective cohort study in northern Tanzania.

BACKGROUND: HIV services in Tanzania are facility-based but facilities are often overcrowded. Differentiated care models (DCM) have been introduced into the National Guidelines. We piloted a Community Health Worker (CHW)-led HIV treatment club model (CHW-DCM) in an urban region, and assessed its effectiveness in comparison to the standard of care (SoC, facility-based model), in terms of stability in care, loss to follow-up (LTFU) and treatment adherence. METHODS: In two clinics in the Shinyanga region, clients established on ART (defined as stable clients by national guidelines as on first-line ART >6 months, undetectable viral load, no opportunistic infections or pregnancy, and good adherence) were offered CHW-DCM. This prospective cohort study included all stable clients who enrolled in CHW-DCM between July 2018 and March 2020 (CHW-DCM) and compared them to stable clients who remained in SoC during that period. Multivariable Cox regression models were used to analyse factors associated with continued stability in care and the risk of LTFU during 18 months of follow-up; treatment adherence was assessed by pill count and compared using Chi-square tests. RESULTS: Of 2472 stable clients, 24.5% received CHW-DCM and 75.5% SoC. CHW-DCM clients were slightly older (mean 42.8 vs. 37.9 years) and more likely to be female (36.2% vs. 32.2%). Treatment adherence was better among CHW-DCM than SoC: 96.6% versus 91.9% and 98.5% versus 92.2%, respectively (both p = 0.001). SoC clients were more likely to not remain stable over time than CHW-DCM (adjusted Hazard ratio [AHR] = 2.68; 95% CI: 1.86-3.90). There was no difference in LTFU (adjusted hazard ratio [AHR] = 1.54; 95%CI: 0.82-2.93). CONCLUSION: Clients attending CHW-DCM demonstrated better stability in care and treatment adherence than SoC, and the risk of LTFU was not increased. These findings demonstrate the potential of CHW in delivering community-based HIV services in the local Tanzanian context. These results could be used to extend this CHW-DCM model to similar settings.

Neutrophil-Lymphocyte and Platelet-Lymphocyte Ratios in Distinguishing Lung Cancer in People with HIV.

Objective: The neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) demonstrate good diagnostic accuracy in distinguishing lung cancer patients from healthy individuals, primarily in HIV-negative populations. We determined the sensitivity (Se), specificity (Sp), and area under the curve (AUC) of the NLR and PLR in discriminating between people living with HIV (PLWH) with and without lung cancer. Methods: This is a comparative analysis of secondary data. Cases were PLWH with lung cancer from a retrospective cohort treated at the Uganda Cancer Institute. Controls were unmatched PLWH without lung cancer who were randomly selected from three HIV clinics in Uganda. Se, Sp, and AUC analysis and determination of optimal cutoffs were performed using receiver operating characteristic (ROC) curves. Results: Of 115 PLWH (18 cases and 97 controls), 83 (72.2%) were female, 110 (95.7) were on ART, and the median (IQR) age was 46 (38-51) years. The median (IQR) NLR was higher among cases than controls (3.53 (3.14-7.71) vs. 0.92 (0.67-1.09), p < 0.001). Similarly, the PLR was higher among cases than controls (237.5 (177.8-361.6) vs. 123.6 (100.6-155.4), p=0.001). At a cutoff of 2.44, the respective Se, Sp, and AUC of the NLR were 87.5% (95% CI: 61.7%-98.4%), 100% (95% CI: 96.2%-100%), and 0.94 (95% CI: 0.85-1.00, p < 0.001). Similarly, the respective Se, Sp, and AUC for the PLR were 75% (95% CI: 47.6%-92.7%), 87.2% (95% CI: 78.8%-93.2%), and 0.81 (95% CI: 0.70-0.93, p < 0.001) at a cutoff of 196.3. Conclusion: The NLR and PLR discriminated PLWH with and without lung cancer and could be useful in PLWH with respiratory symptoms in whom lung cancer can easily be misdiagnosed as other lung pathology.

Leveraging Community Health Workers and a Responsive Digital Health System to Improve Vaccination Coverage and Timeliness in Resource-Limited Settings: Protocol for a Cluster Randomized Type 1 Effectiveness-Implementation Hybrid Study.

BACKGROUND: Tanzania is 1 of 20 countries where the majority of unvaccinated and undervaccinated children reside. Prior research identified substantial rural-urban disparities in the coverage and timeliness of childhood vaccinations in Tanzania, with children in rural settings being more likely to receive delayed or no vaccinations. Further research is necessary to identify effective and scalable interventions that can bridge rural-urban gaps in childhood vaccination while accounting for multifaceted barriers to vaccination. OBJECTIVE: This protocol describes a type 1 effectiveness-implementation hybrid study to evaluate Chanjo Kwa Wakati (timely vaccination in Kiswahili), a community-based digital health intervention to improve vaccination timeliness. The intervention combines human resources (community health workers), low-cost digital strategies (electronic communication, digital case management, and task automation), a vaccination knowledge intervention, and insights from behavioral economics (reminders and incentives) to promote timely childhood vaccinations. METHODS: The study will be conducted in 2 predominantly rural regions in Tanzania with large numbers of unvaccinated or undervaccinated children: Shinyanga and Mwanza. Forty rural health facilities and their catchment areas (clusters) will be randomized to an early or delayed onset study arm. From each cluster, 3 cohorts of mother-child dyads (1 retrospective cohort and 2 prospective cohorts) will be enrolled in the study. The timeliness and coverage of all vaccinations recommended during the first year of life will be observed for 1200 children (n=600, 50% intervention group children and n=600, 50% nonintervention group children). The primary effectiveness outcome will be the timeliness of the third dose of the pentavalent vaccine (Penta3). Quantitative surveys, vaccination records, study logs, fidelity checklists, and qualitative interviews with mothers and key informants will inform the 5 constructs of the reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) framework. The results will be used to develop an implementation blueprint to guide future adaptations and scale-up of Chanjo Kwa Wakati. RESULTS: The study was funded in August 2022. Data collection is expected to last from February 2024 to July 2027. CONCLUSIONS: This study will address the lack of rigorous evidence on the effectiveness of community-based digital health interventions for promoting vaccination coverage and timeliness among children from sub-Saharan Africa and identify potential implementation strategies to facilitate the deployment of vaccination promotion interventions in low- and middle-income countries. TRIAL REGISTRATION: ClinicalTrials.gov NCT06024317; https://www.clinicaltrials.gov/study/NCT06024317. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/52523.

The effectiveness of interventions to reduce cardio-metabolic risk factors among regular street food consumers in Dar es Salaam, Tanzania: The pre-post findings from a cluster randomized trial (Registered by Pan African clinical trial registry with trial # PACTR202208642850935).

INTRODUCTION: The healthy plate model (HPM) is a practical guide to modulate the portion of staple food in main meals, subsequently affecting the risks associated with Non-communicable Diseases include type2 diabetes mellitus (T2DM). OBJECTIVE: This study investigated the effectiveness of health information and the healthy plate model on cardio-metabolic risk factors, knowledge and attitude towards T2DM prevention measures. METHODS: A pre-post analysis, as part of a cluster randomized trial with street food vendors and their customers, was implemented in three randomly selected districts in Dar es Salaam, Tanzania. Two vendor-customer clusters each with 15 and more vendors from each district were randomly assigned to receive either T2DM health information only (Intervention package1 [IP1]) or IP1 plus a subsidized meal with vegetables and fruits, following the principles of the HPM (Intervention package2 [IP2]). Within the clusters the participants were informed on the importance of the intervention they received. An intervention period lasted for three months from 1st April to 31st June 2019. We applied Generalized Linear Mixed Models and Bayesian Modelling (for sensitivity analysis) to assess the effectiveness of the interventions. RESULTS: Overall, 336 (IP2 = 175 and IP1 = 161) out of 560 (280/arm) previous study participants participated in evaluation. Diastolic BP was lower among IP2 participants in the evaluation than baseline AßC = -4.1mmHg (95%CI:-5.42 to -2.76). After adjusting for the interaction between IP2 and age of the consumers, the BMI was significantly lower among IP2 in the evaluation than baseline AßC = -0.7kg/m2 (95%CI: -1.17 to -0.23). With interaction between IP2 and income, BMI was higher in the IP2 in the evaluation than baseline AßC = 0.73kg/m2 (95%CI: 0.08 to 1.38). Systolic and diastolic BP were significantly lower among IP1 in the evaluation than baseline AßC = -3.5mmHg (95%CI:-5.78 to -1.24) and AßC = -5.9mmHg (95%CI:-7.34 to -4.44) respectively. Both the knowledge scores and positive attitudes towards T2DM prevention measures were higher in the evaluation than baseline in both interventions arms. CONCLUSION: The positive effects on cardio-metabolic risk factors, knowledge and attitude were observed in both intervention arms. Due to interactions between IP2, age and income; designing interventions relating to food and cardio-metabolic risk factors, should consider combining socio-economic factors.

Integrated management of HIV, diabetes, and hypertension in sub-Saharan Africa (INTE-AFRICA): a pragmatic cluster-randomised, controlled trial.

BACKGROUND: In sub-Saharan Africa, health-care provision for chronic conditions is fragmented. The aim of this study was to determine whether integrated management of HIV, diabetes, and hypertension led to improved rates of retention in care for people with diabetes or hypertension without adversely affecting rates of HIV viral suppression among people with HIV when compared to standard vertical care in medium and large health facilities in Uganda and Tanzania. METHODS: In INTE-AFRICA, a pragmatic cluster-randomised, controlled trial, we randomly allocated primary health-care facilities in Uganda and Tanzania to provide either integrated care or standard care for HIV, diabetes, and hypertension. Random allocation (1:1) was stratified by location, infrastructure level, and by country, with a permuted block randomisation method. In the integrated care group, participants with HIV, diabetes, or hypertension were managed by the same health-care workers, used the same pharmacy, had similarly designed medical records, shared the same registration and waiting areas, and had an integrated laboratory service. In the standard care group, these services were delivered vertically for each condition. Patients were eligible to join the trial if they were living with confirmed HIV, diabetes, or hypertension, were aged 18 years or older, were living within the catchment population area of the health facility, and were likely to remain in the catchment population for 6 months. The coprimary outcomes, retention in care (attending a clinic within the last 6 months of study follow-up) for participants with either diabetes or hypertension (tested for superiority) and plasma viral load suppression for those with HIV (>1000 copies per mL; tested for non-inferiority, 10% margin), were analysed using generalised estimating equations in the intention-to-treat population. This trial is registered with ISCRTN 43896688. FINDINGS: Between June 30, 2020, and April 1, 2021 we randomly allocated 32 health facilities (17 in Uganda and 15 in Tanzania) with 7028 eligible participants to the integrated care or the standard care groups. Among participants with diabetes, hypertension, or both, 2298 (75·8%) of 3032 were female and 734 (24·2%) of 3032 were male. Of participants with HIV alone, 2365 (70·3%) of 3365 were female and 1000 (29·7%) of 3365 were male. Follow-up lasted for 12 months. Among participants with diabetes, hypertension, or both, the proportion alive and retained in care at study end was 1254 (89·0%) of 1409 in integrated care and 1457 (89·8%) of 1623 in standard care. The risk differences were -0·65% (95% CI -5·76 to 4·46; p=0·80) unadjusted and -0·60% (-5·46 to 4·26; p=0·81) adjusted. Among participants with HIV, the proportion who had a plasma viral load of less than 1000 copies per mL was 1412 (97·0%) of 1456 in integrated care and 1451 (97·3%) of 1491 in standard care. The differences were -0·37% (one-sided 95% CI -1·99 to 1·26; pnon-inferiority<0·0001 unadjusted) and -0·36% (-1·99 to 1·28; pnon-inferiority<0·0001 adjusted). INTERPRETATION: In sub-Saharan Africa, integrated chronic care services could achieve a high standard of care for people with diabetes or hypertension without adversely affecting outcomes for people with HIV. FUNDING: European Union Horizon 2020 and Global Alliance for Chronic Diseases.

Management of chronic conditions in resource limited settings: multi stakeholders' perception and experiences with receiving and providing integrated HIV, diabetes and hypertension services in Tanzania.

BACKGROUND: The rising prevalence of non-communicable diseases (NCDs) alongside the continuing high burden of HIV poses a serious challenge to middle- and low-income countries' healthcare systems. Pilot studies of integrated models of service delivery for HIV, hypertension and diabetes have demonstrated that they are feasible and acceptable among patients and care providers. This study assessed multi-stakeholders' perspectives of the delivery and receipt of integrated care in Tanzania. METHODS: A qualitative process evaluation was conducted in Dar es Salaam region of Tanzania where the integrated service delivery model was implemented from July to November 2021. In-depth interviews were held with seven key informants at the national, regional and district levels, eight healthcare providers, two researchers working at the integrated clinic and forty patients benefiting from integrated services at a large hospital. Three focus group discussions were held with community leaders and residents of the hospital's catchment area, and clinic level observations were conducted. Thematic analysis was conducted followed by the use of Bronfenbrenner's ecological model to identify factors pertinent to sustaining and scaling up of the integrated model. RESULTS: Participants of the study at all levels were aware of the increased prevalence of NCDs specifically for hypertension and diabetes and were concerned about the trend of increasing co-morbid conditions among people living with HIV (PLHIV). The integrated service delivery model was positively perceived by stakeholders because of its multiple benefits for both patients and the healthcare system. These include stigma and discrimination reduction, improved quality of care, efficient use of limited resources, cost and time saving, reduced duplication of services and fostering of early detection for undiagnosed conditions. The organisation of the clinic was critical in increased satisfaction. Several challenges were observed, which included costs for NCD services relative to free care for HIV and inconsistent availability of NCD medications. CONCLUSION: Stakeholders reported numerous benefits of the integrated service delivery model that are fundamental in improving the health of many Tanzanians living with NCDs and HIV. These benefits highlight the need for policy and decision-makers to sustain and expand the integrated service delivery model as a solution to many challenges facing the health system especially at the primary care level.

Reduction in mortality from HIV-related CNS infections in routine care in Africa (DREAMM): a before-and-after, implementation study.

BACKGROUND: Four decades into the HIV epidemic, CNS infection remains a leading cause of preventable HIV-related deaths in routine care. The Driving Reduced AIDS-associated Meningo-encephalitis Mortality (DREAMM) project aimed to develop, implement, and evaluate pragmatic implementation interventions and strategies to reduce mortality from HIV-related CNS infection. METHODS: DREAMM took place in five public hospitals in Cameroon, Malawi, and Tanzania. The main intervention was a stepwise algorithm for HIV-related CNS infections including bedside rapid diagnostic testing and implementation of WHO cryptococcal meningitis guidelines. A health system strengthening approach for hospitals was adopted to deliver quality care through a co-designed education programme, optimised clinical and laboratory pathways, and communities of practice. DREAMM was led and driven by local leadership and divided into three phases: observation (including situational analyses of routine care), training, and implementation. Consecutive adults (aged ≥18 years) living with HIV presenting with a first episode of suspected CNS infection were eligible for recruitment. The primary endpoint was the comparison of 2-week all-cause mortality between observation and implementation phases. This study completed follow-up in September, 2021. The project was registered on ClinicalTrials.gov, NCT03226379. FINDINGS: From November, 2016 to April, 2019, 139 eligible participants were enrolled in the observation phase. From Jan 9, 2018, to March 25, 2021, 362 participants were enrolled into the implementation phase. 216 (76%) of 286 participants had advanced HIV disease (209 participants had missing CD4 cell count), and 340 (69%) of 494 participants had exposure to antiretroviral therapy (ART; one participant had missing ART data). In the implementation phase 269 (76%) of 356 participants had a probable CNS infection, 203 (76%) of whom received a confirmed microbiological or radiological diagnosis of CNS infection using existing diagnostic tests and medicines. 63 (49%) of 129 participants died at 2 weeks in the observation phase compared with 63 (24%) of 266 in the implementation phase; and all-cause mortality was lower in the implementation phase when adjusted for site, sex, age, ART exposure (adjusted risk difference -23%, 95% CI -33 to -13; p<0·001). At 10 weeks, 71 (55%) died in the observation phase compared with 103 (39%) in the implementation phase (-13%, -24 to -3; p=0·01). INTERPRETATION: DREAMM substantially reduced mortality from HIV-associated CNS infection in resource-limited settings in Africa. DREAMM scale-up is urgently required to reduce deaths in public hospitals and help meet Sustainable Development Goals. FUNDING: European and Developing Countries Clinical Trials Partnership, French Agency for Research on AIDS and Viral Hepatitis. TRANSLATIONS: For the French and Portuguese translations of the abstract see Supplementary Materials section.

Latent tuberculosis in children and youth with type 1 diabetes mellitus in Dar es Salaam, Tanzania: a cross section survey.

BACKGROUND: Data for latent tuberculosis in patients with type 1 Diabetes in Africa is limited. We assessed the prevalence of latent tuberculosis in youth and children with type 1 Diabetes in Dar es Salaam -Tanzania. METHODS: Our cross-sectional study recruited children and youth with T1DM by stage of puberty, glycaemic control, and age at diagnosis from January to December 2021 in Dar es Salaam. Participants were screened for the presence of latent Tuberculosis using the QuantiFERON test. A positive test was considered to have latent TB. RESULTS: Of the 281 participants, the mean age was 19 (± 6) years, 51.2% were female, and 80.8% had either a primary or secondary level of education at baseline. The prevalence of latent TB was 14.9% and was slightly higher in females (52.4%) than in males. This difference, however, was insignificant (p > 0.05). On the other hand, the proportion of latent TB was significantly higher in uncontrolled HbA1c levels (76.2%) than in those with controlled HbA1c (23.8%) [p = 0.046]. Duration of diabetes and age at diagnosis did not affect the occurrence of latent Tuberculosis [p > 0.05]. Meanwhile, in the regression model, participants with latent TB were more likely to have uncontrolled HbA1c. [p = 0.045] CONCLUSIONS: Despite the methodological limitations, this survey highlights the high prevalence of latent TB among children and youth with diabetes; shouting for better control. These results clearly show the need to screen for Tuberculosis in children and youth with diabetes and start them on prevention as per protocol, especially in tuberculosis-endemic areas like Tanzania.

Antimicrobial susceptibility profile of oral and rectal microbiota of non-human primate species in Ghana: A threat to human health.

BACKGROUND: The potential for the transfer of zoonotic diseases, including bacteria between human and non-human primates (NHPs), is expected to rise. It is posited that NHPs that live in close contact with humans serve as sentinels and reservoirs for antibiotic-resistant bacteria. OBJECTIVES: The objective was to characterize the oral and rectal bacteria in Ghanaian NHPs and profile the antimicrobial susceptibility of the isolated bacteria. METHODS: Oral and rectal swabs were obtained from 40 immobilized wild and captive NHPs from 7 locations in Ghana. Standard bacteriological procedures were used in the isolation, preliminary identification, automated characterization and antimicrobial susceptibility test (AST) of bacteria using the Vitek 2 Compact system. RESULTS: Gram-negative bacteria dominated isolates from the rectal swabs (n = 76, 85.4%), whereas Gram-positive bacteria were more common in the oral swabs (n = 41, 82%). Staphylococcus haemolyticus (n = 7, 14%) was the most occurring bacterial species isolated from the oral swabs, whereas Escherichia coli (n = 32, 36%) dominated bacteria isolates from rectal swabs. Enterobacter spp. had the highest (39%) average phenotypic resistance to antimicrobials that were used for AST, whereas a trend of high resistance was recorded against norfloxacin, Ampicillin and Tetracycline in Gram-negative bacteria. Similarly, among Gram-positive bacteria, Staphylococcus spp. had the highest (25%) average phenotypic resistance to antimicrobials used for AST, and a trend of high resistance was recorded against penicillin G and oxacillin. CONCLUSIONS: This study has established that apparently healthy NHPs that live in anthropized environments in Ghana harbour zoonotic and antimicrobial resistant bacteria.

Association of diabetes, smoking, and alcohol use with subclinical-to-symptomatic spectrum of tuberculosis in 16 countries: an individual participant data meta-analysis of national tuberculosis prevalence surveys.

Background: Non-communicable diseases (NCDs) and NCD risk factors, such as smoking, increase the risk for tuberculosis (TB). Data are scarce on the risk of prevalent TB associated with these factors in the context of population-wide systematic screening and on the association between NCDs and NCD risk factors with different manifestations of TB, where ∼50% being asymptomatic but bacteriologically positive (subclinical). We did an individual participant data (IPD) meta-analysis of national and sub-national TB prevalence surveys to synthesise the evidence on the risk of symptomatic and subclinical TB in people with NCDs or risk factors, which could help countries to plan screening activities. Methods: In this systematic review and IPD meta-analysis, we identified eligible prevalence surveys in low-income and middle-income countries that reported at least one NCD (e.g., diabetes) or NCD risk factor (e.g., smoking, alcohol use) through the archive maintained by the World Health Organization and by searching in Medline and Embase from January 1, 2000 to August 10, 2021. The search was updated on March 23, 2023. We performed a one-stage meta-analysis using multivariable multinomial models. We estimated the proportion of and the odds ratio for subclinical and symptomatic TB compared to people without TB for current smoking, alcohol use, and self-reported diabetes, adjusted for age and gender. Subclinical TB was defined as microbiologically confirmed TB without symptoms of current cough, fever, night sweats, or weight loss and symptomatic TB with at least one of these symptoms. We assessed heterogeneity using forest plots and I2 statistic. Missing variables were imputed through multi-level multiple imputation. This study is registered with PROSPERO (CRD42021272679). Findings: We obtained IPD from 16 national surveys out of 21 national and five sub-national surveys identified (five in Asia and 11 in Africa, N = 740,815). Across surveys, 15.1%-56.7% of TB were subclinical (median: 38.1%). In the multivariable model, current smoking was associated with both subclinical (OR 1.67, 95% CI 1.27-2.40) and symptomatic TB (OR 1.49, 95% CI 1.34-1.66). Self-reported diabetes was associated with symptomatic TB (OR 1.67, 95% CI 1.17-2.40) but not with subclinical TB (OR 0.92, 95% CI 0.55-1.55). For alcohol drinking ≥ twice per week vs no alcohol drinking, the estimates were imprecise (OR 1.59, 95% CI 0.70-3.62) for subclinical TB and OR 1.43, 95% CI 0.59-3.46 for symptomatic TB). For the association between current smoking and symptomatic TB, I2 was high (76.5% (95% CI 62.0-85.4), while the direction of the point estimates was consistent except for three surveys with wide CIs. Interpretation: Our findings suggest that current smokers are more likely to have both symptomatic and subclinical TB. These individuals can, therefore, be prioritised for intensified screening, such as the use of chest X-ray in the context of community-based screening. People with self-reported diabetes are also more likely to have symptomatic TB, but the association is unclear for subclinical TB. Funding: None.

Factors Influencing Participation of Adults in Voluntary Medical Male Circumcision in Lindi Region, Tanzania.

Background: Voluntary Medical Male Circumcision (VMMC) is a surgical procedure done by a qualified medical personnel using anesthesia. In Tanzania, there is a gap between adult men who are not circumcised and adolescents. This calls for a review of the current situation of VMMC services in the community at large in order to inform policymakers and stakeholders involved in the fight against HIV and other sexually transmitted diseases. The present study explored the factors influencing utilisation of VMMC services among adult males in Lindi Region, Tanzania. Materials and methods: A cross-sectional study was conducted among adults male (15-49 years). Data were collected by using a structured modified measure evaluation quantitative Version 2 questionnaire using a Tablet/Android device with an Open Data Kit (ODK) application (Google Inc. California, USA). Results: The socio-demographic set up of the study participants was mainly composed of males less than 30yrs, single, unemployed, with primary education as the highest level of study and of a Muslim faith. Majority of the respondents (92%) recommended circumcision to a male family member who is not yet circumcised. The study showed that improved sexual performance (81%), penile hygiene (97%) and circumcision as a modern civilization (96%) to be the key factors that motivated respondents' utilisation of VMMC services. However, only 20.6% of the respondents could barely say that VMMC is a surgical procedure done by qualified medical personnel under anaesthesia. The major reasons for recommending the utilisation of VMMC services to their family members were the VMMC usefulness in preventing STIs (48.9%), cultural practices and norms (31.5%), improved penile hygiene (17.4%) and religious reasons (2.2%). Conclusion: VMMC is positively favoured by the local coastal communities of the Lindi region of Tanzania Mainland. Our findings may be inferred to reflect on the other neighbouring regions with similar sociocultural set ups such as Mtwara, Pwani, Rural Dar es Salaam and Tanga and the isles of Unguja and Pemba. Programs addressing VMMC may be well instituted in these local communities with high degree of favourability and success.

Scaling up integrated care for HIV and other chronic conditions in routine health care settings in sub-Saharan Africa: Field notes from Uganda.

Introduction: Integration of HIV and non-communicable disease (NCD) services is proposed to increase efficiency and coverage of NCD care in sub-Saharan Africa. Description: Between October 2018 to January 2020 in Tanzania and Uganda, working in partnership with health services, we introduced an integrated chronic care model for people with HIV, diabetes and hypertension. In this model, patients were able to access care from a single point of care, as opposed to the standard of siloed care from vertical clinics. When the study ended, routine clinical services adopted the integrated model. In this article, we discuss how the model transitioned post hand-over in Uganda and draw lessons to inform future scale-up. Discussion: The findings suggest potential for successful uptake of integrated chronic care by routine clinical services in sub-Saharan Africa. This approach may appeal to health care service providers and policy makers when they can quantify benefits that accrue from it, such as optimal utilization of health resources. For patients, integrated care may not appeal to all patients due to HIV-related stigma. Key considerations include good communication with patients, strong leadership, maintaining patient confidentiality and incorporating patient needs to facilitate successful uptake. Conclusion: Evidence on the benefits of integrated care remains limited. More robust evidence will be essential to guide scale-up beyond research sites.

Metformin for the prevention of diabetes among people with HIV and either impaired fasting glucose or impaired glucose tolerance (prediabetes) in Tanzania: a Phase II randomised placebo-controlled trial.

AIMS/HYPOTHESIS: In sub-Saharan Africa (SSA), 5% of adults are living with type 2 diabetes and this is rising sharply, with a greater increase among people with HIV. Evidence on the efficacy of prevention strategies in this cohort is scarce. We conducted a Phase II double-blind placebo-controlled trial that aimed to determine the impact of metformin on blood glucose levels among people with prediabetes (defined as impaired fasting glucose [IFG] and/or impaired glucose tolerance [IGT]) and HIV in SSA. METHODS: Adults (≥18 years old) who were stable in HIV care and found to have prediabetes (IFG and/or IGT) and who were attending hospitals in Dar es Salaam, Tanzania, were randomised to receive sustained-release metformin, 2000 mg daily, or matching placebo between 4 November 2019 and 21 July 2020. Randomisation used permuted blocks. Allocation was concealed in the trial database and made visible only to the Chief Pharmacist after consent was taken. All participants, research and clinical staff remained blinded to the allocation. Participants were provided with information on diet and lifestyle and had access to various health information following the start of the coronavirus disease 2019 (COVID-19) pandemic. Participants were followed up for 12 months. The primary outcome measure was capillary blood glucose measured 2 h following a 75 g glucose load. Analyses were by intention-to-treat. RESULTS: In total, 364 participants (182 in each arm) were randomised to the metformin or placebo group. At enrolment, in the metformin and placebo arms, mean fasting glucose was 6.37 mmol/l (95% CI 6.23, 6.50) and 6.26 mmol/l (95% CI 6.15, 6.36), respectively, and mean 2 h glucose levels following a 75 g oral glucose load were 8.39 mmol/l (95% CI 8.22, 8.56) and 8.24 mmol/l (95% CI 8.07, 8.41), respectively. At the final assessment at 12 months, 145/182 (79.7%) individuals randomised to metformin compared with 158/182 (86.8%) randomised to placebo indicated that they had taken >95% of their medicines in the previous 28 days (p=0.068). At this visit, in the metformin and placebo arms, mean fasting glucose levels were 6.17 mmol/l (95% CI 6.03, 6.30) and 6.30 mmol/l (95% CI 6.18, 6.42), respectively, and mean 2 h glucose levels following a 75 g oral glucose load were 7.88 mmol/l (95% CI 7.65, 8.12) and 7.71 mmol/l (95% CI 7.49, 7.94), respectively. Using a linear mixed model controlling for respective baseline values, the mean difference between the metformin and placebo group (metformin-placebo) was -0.08 mmol/l (95% CI -0.37, 0.20) for fasting glucose and 0.20 mmol/l (95% CI -0.17, 0.58) for glucose levels 2 h post a 75 g glucose load. Weight was significantly lower in the metformin arm than in the placebo arm: using the linear mixed model adjusting for baseline values, the mean difference in weight was -1.47 kg (95% CI -2.58, -0.35). In total, 16/182 (8.8%) individuals had a serious adverse event (Grade 3 or Grade 4 in the Division of Acquired Immunodeficiency Syndrome [DAIDS] adverse event grading table) or died in the metformin arm compared with 18/182 (9.9%) in the placebo arm; these events were either unrelated to or unlikely to be related to the study drugs. CONCLUSIONS/INTERPRETATION: Blood glucose decreased over time in both the metformin and placebo arms during the trial but did not differ significantly between the arms at 12 months of follow up. Metformin therapy was found to be safe for use in individuals with HIV and prediabetes. A larger trial with longer follow up is needed to establish if metformin can be safely used for the prevention of diabetes in people who have HIV. TRIAL REGISTRATION: The trial is registered on the International Standard Randomised Controlled Trial Number (ISRCTN) registry ( www.isrctn.com/ ), registration number: ISCRTN76157257. FUNDING: This research was funded by the National Institute for Health Research using UK aid from the UK Government to support global health research.

Effectiveness of provider-initiated versus client-initiated HIV testing by different health facility departments in Northern Tanzania.

BACKGROUND: HIV prevalence in Tanzania is still high at 4.7% among adults. Regular HIV testing is consistently advocated in the country to increase the level of awareness of HIV status, thus contributing to national HIV prevention. We report findings from three years of implementation of an HIV Test and Treat project utilizing provider-initiated and client-initiated testing and counselling (PITC and CITC). This study compared the effectiveness of PITC versus CITC in HIV case detection by the different departments of health facilities. METHOD: This retrospective cross-sectional study used health facility-based HIV testing data collected from adults aged 18 years and above between June 2017 - July 2019 in the Shinyanga region, Tanzania. Chi-square and logistic regression analysis were used to assess determinants of yield (HIV positivity). RESULTS: A total of 24,802 HIV tests were performed of which 15,814 (63.8%) were by PITC and 8,987 (36.2%) by CITC. Overall HIV positivity was 5.7%, higher among CITC at 6.6% than PITC at 5.2%. TB and IPD departments had the highest HIV positivity 11.8% and 7.8% respectively. Factors associated with a positive test were testing at a department in the facility compared to CITC, first-time test, and being or having been married compared to being single. CONCLUSION: Success in identifying HIV + patients was highest among people visiting the clinic for HIV testing (CITC) and first-time testers. With PITC, HIV + patient detection differed between departments, suggesting divergent risk profiles of respective clients and/or divergent HIV alertness of staff. This underscores the importance of increased targeting for PITC to identify HIV + patients.