Public Health Concern and Initiatives on the Priority Action Towards Non-Communicable Diseases in Tanzania

Tanzania is already facing challenges caused by existing burden of communicable diseases, and the growing trend of non-communicable diseases (NCDs), which raises a lot of concerns and challenges. The objective of this review is to provide broad insight of the “silent epidemic” of NCDs, existing policies, strategies and interventions, and recommendations on prioritized actions. A review of existing literature including published articles, technical reports, and proceedings from national and international NCDs meetings was carried out. The burden, existing interventions, socio-economic impact, lessons learnt, and potential for expanding cost effective interventions in Tanzania were explored. Challenges to catch up with global\ud momentum on NCD agenda were identified and discussed. The review has indicated that the burden of NCDs and its underlying risk factors in Tanzania is alarming, and affects people of all socio-economic status. The\ud costs of health care for managing NCDs are high, and thus impoverishing the already poor people. The country\ud leadership has a high political commitment; there are policies and strategies, which need to be implemented to\ud address the growing NCD burden. In conclusion, NCDs in Tanzania are a silent rising health burden and has\ud enormous impact on an individual and country’s social-economical status. From the experience of other countries, interventions for NCDs are affordable, feasible and some are income generating. Multi-sectoral approach, involving national and international partners has a unique role in intensifying action on NCDs.\ud Tanzania should strategize on implementation research on how to adapt the interventions and apply multisectoral\ud approach to control and prevent NCDs in the country.\u

Red meat consumption and its association with hypertension and hyperlipidaemia among adult Maasai pastoralists of Ngorongoro Conservation Area, Tanzania

Background: Red meat is an important dietary source of protein and other essential nutrients. Its high intake has been associated with an increased risk of cardiovascular morbidity and mortality, including hypertension (HTN) and hyperlipidaemia (HLP). Despite being physically active, the Maasai at Ngorongoro Conservation Area (NCA) depend heavily on animals' products as their staple food with fewer intakes of vegetables or fruits due to restriction from carrying out agricultural activities within the NCA. This study aimed at determining the prevalence of HTN and HLP and their association with red meat consumption among adult Maasai of NCA. Methods: A community-based cross-sectional study was conducted in October 2018 using multistage sampling technique. Eight hundred and ninety-four (894) participants enrolled from seven villages in three wards within NCA Data were collected using a modified WHO NCDs-STEPS tool. Anthropometric measurements, blood pressure (BP) measurements, and blood samples for glucose and cholesterol tests were obtained from the study participants. Crude and adjusted prevalence ratio (PR) for factors associated with HTN and HLP were estimated using Ordinal and Bayesian logistic regression models, respectively. Results: The prevalence of HLP was 23.7 percent. The levels were higher among males than were among the females (29.0% vs. 20.1%, p = 0.002). The prevalence of HTN and pre-HTN (elevated BP) were 9.8 and 37.0 percent, respectively. Both HTN and elevated BP were higher among males than were among females (hypertensive [10.9% vs. 9.0%]; elevated BP [44.0% vs. 32.1%], p<0.001). The prevalence of HLP was significantly associated with level II (PR = 1.56, 95%CrI: 1.10–2.09) and level III (PR = 1.64, 95%CrI: 1.08–2.41) of red meat consumption as opposed to level I. Conclusion: The prevalence of hyperlipidaemia and elevated BP were high among NCA Maasai. We found a significant association between red meat consumption and hyperlipidaemia. Further follow-up studies are warranted to establish a temporal relationship between red meat consumption and both conditions

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

The acceptability of integrated healthcare services for HIV and non-communicable diseases: experiences from patients and healthcare workers in Tanzania.

BACKGROUND: In sub-Saharan Africa, the prevalence of non-communicable diseases (NCDs) has risen sharply amidst a high burden of communicable diseases. An integrated approach to HIV and NCD care offers the potential of strengthening disease control programmes. We used qualitative methods to explore patients' and care-providers' experiences and perspectives on the acceptability of integrated care for HIV-infection, diabetes mellitus (DM), and hypertension (HT) in Tanzania. METHODS: A qualitative study was conducted in selected health facilities in Dar es Salaam and Coastal regions, which had started to provide integrated care and management for HIV, DM, and HT using a single research clinic for patients with one or more of these conditions. In-depth interviews were held with patients and healthcare providers at three time points: At enrolment (prior to the patient receiving integrated care, at the mid-line and at the study end). A minimum of 16 patients and 12 healthcare providers were sampled for each time point. Observation was also carried out in the respective clinics during pre- and mid-line phases. The Theoretical Framework of Acceptability (TFA) underpinned the structure and interpretation of the combined qualitative and observational data sets. RESULTS: Patients and healthcare providers revealed a positive attitude towards the integrated care delivery model at the mid-line and at study end-time points. High acceptability was related to increased exposure to service integration in terms of satisfaction with the clinic setup, seating arrangements and the provision of medical care services. Satisfaction also centred on the patients' freedom to move from one service point to another, and to discuss the services and their own health status amongst themselves. Adherence to medication and scheduling of clinic appointments appeared central to the patient-provider relationship as an aspect in the provision of quality services. Multi-condition health education, patient time and cost-saving, and detection of undiagnosed disease conditions emerged as benefits. On the other hand, a few challenges included long waiting times and limited privacy in lower and periphery health facilities due to infrastructural limitations. CONCLUSION: The study reveals a continued high level of acceptability of the integrated care model among study participants in Tanzania. This calls for evaluation in a larger and a comparative study. Nevertheless, much more concerted efforts are necessary to address structural challenges and maximise privacy and confidentiality

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

Cryptococcal Meningitis Screening and Community-based Early Adherence Support in People With Advanced Human Immunodeficiency Virus Infection Starting Antiretroviral Therapy in Tanzania and Zambia: A Cost-effectiveness Analysis.

BACKGROUND: A randomized trial demonstrated that among people living with late-stage human immunodeficiency virus (HIV) infection initiating antiretroviral therapy, screening serum for cryptococcal antigen (CrAg) combined with adherence support reduced all-cause mortality by 28%, compared with standard clinic-based care. Here, we present the cost-effectiveness. METHODS: HIV-infected adults with CD4 count <200 cells/μL were randomized to either CrAg screening plus 4 weekly home visits to provide adherence support or to standard clinic-based care in Dar es Salaam and Lusaka. The primary economic outcome was health service care cost per life-year saved as the incremental cost-effectiveness ratio (ICER), based on 2017 US dollars. We used nonparametric bootstrapping to assess uncertainties and univariate deterministic sensitivity analysis to examine the impact of individual parameters on the ICER. RESULTS: Among the intervention and standard arms, 1001 and 998 participants, respectively, were enrolled. The annual mean cost per participant in the intervention arm was US$339 (95$331-$347), resulting in an incremental cost of the intervention of US$77 (95% CI, $66-$88). The incremental cost was similar when analysis was restricted to persons with CD4 count <100 cells/μL. The ICER for the intervention vs standard care, per life-year saved, was US$70 (95$43-$211) for all participants with CD4 count up to 200 cells/μL and US$91 (95% CI, $49-$443) among those with CD4 counts <100 cells /μL. Cost-effectveness was most sensitive to mortality estimates. CONCLUSIONS: Screening for cryptococcal antigen combined with a short period of adherence support, is cost-effective in resource-limited settings

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

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. 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. 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. 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. The trial is registered on the International Standard Randomised Controlled Trial Number (ISRCTN) registry ( www.isrctn.com/ ), registration number: ISCRTN76157257. This research was funded by the National Institute for Health Research using UK aid from the UK Government to support global health research

Dynamic ploidy changes drive fluconazole resistance in human cryptococcal meningitis.

BACKGROUND Cryptococcal meningitis (CM) causes an estimated 180,000 deaths annually, predominantly in sub-Saharan Africa, where most patients receive fluconazole (FLC) monotherapy. While relapse after FLC monotherapy with resistant strains is frequently observed, the mechanisms and impact of emergence of FLC resistance in human CM are poorly understood. Heteroresistance (HetR) - a resistant subpopulation within a susceptible strain - is a recently described phenomenon in Cryptococcus neoformans (Cn) and Cryptococcus gattii (Cg), the significance of which has not previously been studied in humans. METHODS A cohort of 20 patients with HIV-associated CM in Tanzania was prospectively observed during therapy with either FLC monotherapy or in combination with flucytosine (5FC). Total and resistant subpopulations of Cryptococcus spp. were quantified directly from patient cerebrospinal fluid (CSF). Stored isolates underwent whole genome sequencing and phenotypic characterization. RESULTS Heteroresistance was detectable in Cryptococcus spp. in the CSF of all patients at baseline (i.e., prior to initiation of therapy). During FLC monotherapy, the proportion of resistant colonies in the CSF increased during the first 2 weeks of treatment. In contrast, no resistant subpopulation was detectable in CSF by day 14 in those receiving a combination of FLC and 5FC. Genomic analysis revealed high rates of aneuploidy in heteroresistant colonies as well as in relapse isolates, with chromosome 1 (Chr1) disomy predominating. This is apparently due to the presence on Chr1 of ERG11, which is the FLC drug target, and AFR1, which encodes a drug efflux pump. In vitro efflux levels positively correlated with the level of heteroresistance. CONCLUSION Our findings demonstrate for what we believe is the first time the presence and emergence of aneuploidy-driven FLC heteroresistance in human CM, association of efflux levels with heteroresistance, and the successful suppression of heteroresistance with 5FC/FLC combination therapy. FUNDING This work was supported by the Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology 097377/Z/11/Z and the Daniel Turnberg Travel Fellowship

Patient and health provider costs of integrated HIV, diabetes and hypertension ambulatory health services in low-income settings — an empirical socio-economic cohort study in Tanzania and Uganda

Background: Integration of health services might be an efficient strategy for managing multiple chronic conditions in sub-Saharan Africa, considering the scope of treatments and synergies in service delivery. Proven to promote compliance, integration may lead to increased economies-of-scale. However, evidence on the socio-economic consequences of integration for providers and patients is lacking. We assessed the clinical resource use, staff time, relative service efficiency and overall societal costs associated with integrating HIV, diabetes and hypertension services in single one-stop clinics where persons with one or more of these conditions were managed. Methods: 2273 participants living with HIV infection, diabetes, or hypertension or combinations of these conditions were enrolled in 10 primary health facilities in Tanzania and Uganda and followed-up for up to 12 months. We collected data on resources used from all participants and on out-of-pocket costs in a sub-sample of 1531 participants, while a facility-level costing study was conducted at each facility. Health worker time per participant was assessed in a time-motion morbidity-stratified study among 228 participants. The mean health service cost per month and out-of-pocket costs per participant visit were calculated in 2020 US$prices. Nested bootstrapping from these samples accounted for uncertainties. A data envelopment approach was used to benchmark the efficiency of the integrated services. Last, we estimated the budgetary consequences of integration, based on prevalence-based projections until 2025, for both country populations. Results: Their average retention after 1 year service follow-up was 1911/2273 (84.1$39.11 (95% CI 33.99, 44.33), $32.18 (95$22.65 (95% CI 21.86, 23.43) for the combinations of HIV and diabetes and of HIV and hypertension, diabetes and hypertension, respectively. These costs were 34.4% (95% CI 17.9%, 41.9%) lower as compared to managing any two conditions separately in two different participants. The cost of managing an individual with all three conditions was 48.8% (95% CI 42.1%, 55.3%) lower as compared to managing these conditions separately. Out-of-pocket healthcare expenditure per participant per visit was $7.33 (95% CI 3.70, 15.86). This constituted 23.4% (95% CI 9.9, 54.3) of the total monthly service expenditure per patient and 11.7% (95% CI 7.3, 22.1) of their individual total household income. The integrated clinics’ mean efficiency benchmark score was 0.86 (range 0.30–1.00) suggesting undercapacity that could serve more participants without compromising quality of care. The estimated budgetary consequences of managing multi-morbidity in these types of integrated clinics is likely to increase by 21.5% (range 19.2–23.4%) in the next 5 years, including substantial savings of 21.6% on the provision of integrated care for vulnerable patients with multi-morbidities. Conclusion: Integration of HIV services with diabetes and hypertension control reduces both health service and household costs, substantially. It is likely an efficient and equitable way to address the increasing burden of financially vulnerable households among Africa’s ageing populations. Additional economic evidence is needed from longer-term larger-scale implementation studies to compare extended integrated care packages directly simultaneously with evidence on sustained clinical outcomes

Ethical issues in intervention studies on the prevention and management of diabetes and hypertension in sub-Saharan Africa

Conducting intervention studies in Africa, where medicines supply for chronic conditions is inequitable and patchy, raises major ethical issues. Here we discuss what should the ethical approach be for a research programme in terms of provision of a steady and sustainable supply of medicines for patients with diabetes and hypertension