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.

Mid-level healthcare workers knowledge on non-communicable diseases in Tanzania: a district-level pre-and post-training assessment.

INTRODUCTION: Over the past two decades, Tanzania's burden of non-communicable diseases has grown disproportionately, but limited resources are still prioritized. A trained human resource for health is urgently needed to combat these diseases. However, continuous medical education for NCDs is scarce. This paper reports on the mid-level healthcare workers knowledge on NCDs. We assessed the knowledge to measure the effectiveness of the training conducted during the initiation of a Package for Essential Management of Severe NCDs (PEN Plus) in rural district hospitals in Tanzania. METHODS: The training was given to 48 healthcare employees from Dodoma Region's Kondoa Town Council District Hospital. For a total of five (5) days, a fundamental course on NCDs featured in-depth interactive lectures and practical workshops. Physicians from Tanzania's higher education institutions, tertiary university hospitals, research institutes, and medical organizations served as trainers. Before and after the training, a knowledge assessment comprising 28 questions was administered. Descriptive data analysis to describe the characteristics of the specific knowledge on physiology, diagnosis and therapy of diabetes mellitus, rheumatic fever, heart disease, and sickle cell disease was done using Stata version 17 (STATA Corp Inc., TX, USA). RESULTS: Complete assessment data for 42 out of the 48 participants was available. Six participants did not complete the training and the assessment. The mean age of participants was 36.9 years, and slightly above half (52%) were above 35 years. Two-thirds (61.9%) were female, and about half (45%) were nurses. The majority had the experience of working for more than 5 years, and the average was 9.4 years (+/- 8.4 years). Overall, the trainees' average scores improved after the training (12.79 vs. 16.05, p < 0.0001) out of 28 possible scores. Specifically, trainees' average scores were better in treatment than in diagnosis, except for sickle cell disease (1.26 vs. 1.83). Most were not able to diagnose rheumatic heart disease (47.6% able) compared to diabetes mellitus (54.8% able) or sickle cell disease (64.3% able) at baseline. The proportion of trainees with adequate knowledge of the treatment of sickle cell disease and diabetes mellitus was 35% and 38.1%, respectively, and there was a non-statistical difference after training. Those working for less than 5 years had a higher proportion of adequate knowledge (30.8%) compared to their more experienced colleagues (6.9%). After the training, participants' knowledge of NCDs increased by three times (i.e., aPR 3, 95% CI = 1.1, 1.5, and 6.0). CONCLUSION AND RECOMMENDATIONS: PEN Plus training improved the knowledge of healthcare workers at Kondoa Town Council District Hospital. Training is especially needed among nurses and those with a longer duration of work. Continuing education for human resources for health on the management of NCDs is highly recommended in this setting.

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.

Retention in care for type 2 diabetes management in Sub-Saharan Africa: A systematic review.

OBJECTIVE: Diabetes prevalence has risen rapidly in Sub-Saharan Africa, but rates of retention in diabetes care are poorly understood. We conducted a systematic review and meta-analysis to determine rates of retention in care of persons with type 2 diabetes. METHODS: We searched MEDLINE, Global Health and CINAHL online databases for cohort studies and randomised control trials (RCTs) published up to 12 October 2021, that reported retention in or attrition from care for patients with type 2 diabetes in Sub-Saharan Africa. Retention was defined as persons diagnosed with diabetes who were alive and in care or with a known outcome, while attrition was defined as loss from care. RESULTS: From 6559 articles identified, after title and abstract screening, 209 articles underwent full text review. Forty six papers met the inclusion criteria, comprising 22,610 participants. Twenty one articles were of RCTs of which 8 trials had 1 year or more of follow-up and 25 articles were of non-randomised studies of which 19 had 12 months or more of follow-up. A total of 11 studies (5 RCTs and 6 non-randomised) were assessed to be of good quality. Sixteen RCTs were done in secondary or tertiary care settings. Their pooled retention rate (95% CI) was 80% (77%, 84%) in the control arm. Four RCTs had been done in primary care settings and their pooled retention rate (95% CI) was 53% (45%, 62%) in the control arm. The setting of one trial was unclear. For non-randomised studies, retention rates (95% CI) were 68% (62%, 75%) among 19 studies done in secondary and tertiary care settings, and 40% (33%, 49%) among the 6 studies done in primary care settings. CONCLUSION: Rates of retention in care of people living with diabetes are poor in primary care research settings.

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.

Energy expenditure and intensity of ritual jumping-dancing in male Maasai.

OBJECTIVES: Traditional jumping-dance rituals performed by Maasai men involve prolonged physical exertion that may contribute significantly to overall physical activity level. We aimed to objectively quantify the metabolic intensity of jumping-dance activity and assess associations with habitual physical activity and cardiorespiratory fitness (CRF). METHODS: Twenty Maasai men (18-37 years) from rural Tanzania volunteered to participate in the study. Habitual physical activity was monitored using combined heart rate (HR) and movement sensing over 3 days, and jumping-dance engagement was self-reported. A 1-h jumping-dance session resembling a traditional ritual was organized, during which participants' vertical acceleration and HR were monitored. An incremental, submaximal 8-min step test was performed to calibrate HR to physical activity energy expenditure (PAEE) and assess CRF. RESULTS: Mean (range) habitual PAEE was 60 (37-116) kJ day-1 kg-1 , and CRF was 43 (32-54) mL O2 min-1 kg-1 . The jumping-dance activity was performed at an absolute HR of 122 (83-169) beats·min-1 , and PAEE of 283 (84-484) J min-1 kg-1 or 42 (18-75)% when expressed relative to CRF. The total PAEE for the session was 17 (range 5-29) kJ kg-1 , ~28% of the daily total. Self-reported engagement in habitual jumping-dance frequency was 3.8 (1-7) sessions/week, with a total duration of 2.1 (0.5-6.0) h/session. CONCLUSIONS: Intensity during traditional jumping-dance activity was moderate, but on average sevenfold higher than habitual physical activity. These rituals are common, and can make a substantial contribution to overall physical activity in Maasai men, and thus be promoted as a culture-specific activity to increase energy expenditure and maintain good health in this population.

Management of type 1 diabetes in low- and middle-income countries: Comparative health system assessments in Kyrgyzstan, Mali, Peru and Tanzania.

AIMS: To describe and compare the health system responses for type 1 diabetes in Kyrgyzstan, Mali, Peru and Tanzania. METHODS: The Rapid Assessment Protocol for Insulin Access, a multi-level assessment of the health system, was implemented in Kyrgyzstan, Mali, Peru and Tanzania using document reviews, site visits and interviews to assess the delivery of care and access to insulin. RESULTS: Despite the existence of noncommunicable or diabetes strategies and Universal Health Coverage policies including diabetes-related supplies, this has not necessarily translated into access to insulin or diabetes care for all. Insulin and related supplies were often unavailable and unaffordable. Across the four countries test strips and insulin, when paid for by the individual, represented respectively 48-82% and 25-36% of total costs. Care was mainly delivered at tertiary-level hospitals by specialists. Only Kyrgyzstan had data collection systems integrated into the Ministry of Health structure. In addition, issues with healthcare worker training and education and empowerment of people with diabetes were present in these health systems. CONCLUSIONS: People with type 1 diabetes in these countries face different barriers, including the cost of insulin and care. Given the renewed attention to diabetes on the global health agenda tailored health system responses for type 1 diabetes are needed. Insulin should be prioritized as it is the foundation of type 1 diabetes care, but other elements of care and support need to be fostered by different actors.

Impact of early diagnosis of impaired glucose regulation in tuberculosis: Comparison of clinical outcomes in people with tuberculosis in Tanzania.

OBJECTIVE: Diabetes mellitus (DM) has been known to compromise tuberculosis (TB) treatment outcomes. Association data are limited for early hyperglycaemia detection and TB treatment outcomes. Thus, we assessed treatment outcomes including time to sputum conversion and death in TB participants with or without hyperglycaemia. METHODS: A prospective cohort study recruited TB participants receiving anti-TB treatment at health facilities in Tanzania between October 2019 and September 2020. Hyperglycaemia was defined as having pre-existing DM or pre-treatment random blood glucose of ≥7.8 mmol/L, in combination categorised as impaired glucose regulation (IGR). Those with IGR were further screened for hyperglycaemia severity using glycated haemoglobin. In case of unknown status, participants were tested for HIV. Time to death was determined at 6 months of TB treatment. RESULTS: Of 1344 participants, 187 (13.9%) had IGR, of whom 44 (23.5%) were HIV co-infected. Overall treatment success was 1206 (89.7%), and was similar among participants with or without IGR (p > 0.05). Time to death for participants with and without IGR was 18 versus 28 days (p = 0.870), respectively. Age ≥ 40 years (p = 0.038), bacteriological positive (p = 0.039), HIV (p = 0.009), or recurrent TB (p = 0.017) predicted death or treatment success during TB treatment in adjusted multivariable models. CONCLUSION: IGR did not influence clinical outcomes in TB patients with or without IGR in a programme of early IGR diagnosis and integration TB, HIV and DM care. Early detection and co-management of multi-morbidities among people diagnosed with TB may reduce likelihood of poor treatment outcomes in a programmatic setting.

Survival of children and youth with type 1 diabetes mellitus in Tanzania.

INTRODUCTION: Survival from type 1 diabetes Mellitus is low in lower-income countries with underdeveloped health systems. Support programs from partners like life for a child (LFAC) and changing diabetes in children (CDiC) were implemented in Tanzania in 2005 to provide diabetes care to children and youth. No evaluation of survival has been done since their implementation. OBJECTIVE: To assess the survival of children and youth living with diabetes mellitus (CYLDM) in Tanzania. METHODS: A retrospective data collection from 39 clinics of CYLDM was done by extracting data from the diabetes registry between 1991 and 2019. Three cohort were analyzed (1) Cohort 1991-2004 (pre-implementation), (2) Cohort 2005-2010 (during implementation), and (3) 2011-2019 (after the implementation of LFAC/CDiC). Data were analyzed using STATA-version 14. RESULTS: A total of 3822 data of CYLDM were extracted, mean age at diagnosis was 13.8 (±5) years. Approximately fifty-one percent (50.8%) were male. The total observation time was 28 years, and the Median duration of diabetes of 5 (IQR2, 8) years. Total death was 95 (3%), with a mean age at death of 17.7 (SD 4.7) years. The last cohort (2011-2019) had more diagnosis 2353 (72.7%), as compared to the <2005 cohort with only 163(5%). The survival improved from 59% before 2005 to 69% in the last cohort (2011-2019). CONCLUSION: The implemented programs have facilitated the diagnosis and retention of CYLDM in the health care system. In doing so, it has also increased the survival probability in Tanzania compared to the early 90s.

Clinical-demographic markers for improving diabetes mellitus diagnosis in people with tuberculosis in Tanzania.

BACKGROUND: Tuberculosis (TB) control is threatened by an increasing prevalence of diabetes mellitus (DM), particularly in endemic countries. Screening for DM is not routinely implemented in Tanzania; therefore, we aimed to screen for DM at TB diagnosis using clinical-demographic markers. METHODS: Our cross-sectional study recruited TB patients who received anti-TB treatment between October 2019 and September 2020 at health care facilities in three regions from Tanzania. Patients were screened for DM using DM symptoms (polydipsia, polyphagia and polyuria) and random blood glucose (RBG) testing. Patients with a history of DM and those with no history of DM but an RBG ≥ 7.8 mmol/L had point-of-care glycated haemoglobin (HbA1c) testing, and were considered to have DM if HbA1c was ≥ 48 mmol/mol. RESULTS: Of 1344 TB patients, the mean age was 41.0 (± 17.0) years, and 64.7% were male. A total of 1011 (75.2%) had pulmonary TB, and 133 (10.4%) had at least one DM symptom. Overall, the prevalence of DM was 7.8%, of which 36 (2.8%) TB patients with no history of DM were newly diagnosed with DM by RBG testing. TB/DM patients were older than those with only TB (50.0 ± 14.0 years vs 40.0 ± 17.0 years, p < 0.001). Patients with RBG ≥ 7.8 mmol/L were more likely to have pulmonary TB (p = 0.003), age ≥ 35 years (p = 0.018), and have at least one DM symptom (p < 0.001). There was a substantial agreement (Kappa = 0.74) between the on-site glucometer and point-of-care HbA1c tests in detecting DM range of hyperglycemia. CONCLUSION: The implementation of clinical-demographic markers and blood glucose screening identified the overall prevalence of DM and those at risk of DM in TB patients. Clinical-demographic markers are independent predictors for DM range hyperglycemia and highlight the importance of further diagnostic testing and early co-management of TB and DM.

The circadian rhythm of calcium and bone homeostasis in Maasai.

OBJECTIVES: Ethnic groups differ in prevalence of calcium-related diseases. Differences in the physiology and the endogenous circadian rhythm (CR) of calcium and bone homeostasis may play a role. Thus, we aimed to investigate details of CR pattern in calcium and bone homeostasis in East African Maasai. METHODS: Ten clinically healthy adult Maasai men and women from Tanzania were examined. Blood samples were collected every 2nd hour for 24 h. Serum levels of total calcium, albumin, parathyroid hormone (PTH), 25(OH)D, creatinine, C-terminal telopeptide (CTX), bone-specific alkaline phosphatase (BSAP), procollagen type 1 N-terminal propeptide (P1NP), and osteocalcin were measured. Circadian patterns were derived from graphic curves of medians, and rhythmicity was assessed with Fourier analysis. RESULTS: PTH-levels varied over the 24 h exhibiting a bimodal pattern. Nadir level corresponded to 65% of total 24-h mean. CTX and P1NP showed 24-h variations with a morning nadir and nocturnal peak with nadir levels corresponding to 23% and 79% of the 24-h mean, respectively. Albumin-corrected calcium level was held in a narrow range and alterations were corresponding to alterations in PTH. There was no distinct pattern in 24-h variations of 25(OH)D, creatinine, osteocalcin, or BSAP. CONCLUSIONS: All participants showed pronounced 24-h variations in PTH and bone turnover markers CTX and P1NP. These findings support that Maasai participants included in this study have typical patterns of CR in calcium and bone homeostasis consistent with findings from other ethnic populations.

Directly measured aerobic fitness in male Maasai of Tanzania.

OBJECTIVES: The agro-pastoralist Maasai of East Africa are highly physically active, but their aerobic fitness has so far only been estimated using heart rate (HR) response to submaximal exercise and not directly measured. Thus, we aimed to measure aerobic fitness directly using respiratory gas analysis in a group of Maasai, and habitual physical activity energy expenditure (PAEE) as explanatory variable. METHODS: In total, 21 (10 rural, 11 semi-urban) of 30 volunteering Tanzanian Maasai men were eligible to participate. Respiratory gas exchange was measured during a graded exercise test until exhaustion on a stationary bicycle to determine aerobic fitness. Maximal effort criteria were at least two of the following (1) leveling off, (2) respiratory exchange ratio (RER) >1.10, and (3) maximum HR within 10 bpm of age-estimated maximum HR. Habitual PAEE was estimated using combined accelerometry and HR monitoring. Anthropometry, biochemistry, blood pressure, resting HR, and dietary intake information were collected for background information. RESULTS: Mean age was 43.2 (range 26-60) years, and hemoglobin was higher in the rural versus semi-urban Maasai (16.9 vs. 15.4 g/dl, p = .02). Mean aerobic fitness (34.4 vs. 33.3 mlO2 /min/kg, p = .79), and mean PAEE (58.5 vs. 52.9 kJ/day/kg, p = .64) were similar in rural and semi-urban Maasai, respectively. CONCLUSIONS: Aerobic fitness was low to moderate in male rural and semi-urban Maasai. This may be explained by relatively low PAEE in comparison to previous objectively measured activity levels in Maasai, which indicates recent lifestyle changes.

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%). Five hundred and eighty-two of 2273 (25.6%) participants had two or all three chronic conditions and 1691/2273 (74.4%) had a single condition. During the study, 84/2239 (3.8%) participants acquired a second or third condition. The mean service costs per month of managing two conditions in a single participant were $39.11 (95% CI 33.99, 44.33), $32.18 (95% CI 30.35, 34.07) and $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.

ß-cell dysfunction and insulin resistance in relation to pre-diabetes and diabetes among adults in north-western Tanzania: a cross-sectional study.

OBJECTIVE: Studies on phenotypes of diabetes in Africa are inconsistent. We assessed the role of ß-cell dysfunction and insulin resistance on pre-diabetes and diabetes. METHODS: We included 1890 participants with mean age of 40.6 (SD11.9) years in a cross-sectional study among male and female adults in Tanzania during 2016 to 2017. Data on C-reactive protein (CRP), alpha-acid glycoprotein (AGP), HIV, oral glucose tolerance test (OGTT), body composition and insulin were collected. Insulinogenic index and HOMA-IR were used to derive an overall marker of ß-cell dysfunction and insulin resistance which was categorised as follows: normal ß-cell function and insulin sensitivity, isolated ß-cell dysfunction, isolated insulin resistance, and combined ß-cell dysfunction and insulin resistance. Pre-diabetes and diabetes were defined as 2-hour OGTT glucose between 7.8-11.0 and ≥ 11.1 mmol/L, respectively. Multinomial regression assessed the association of ß-cell dysfunction and insulin resistance with outcome measures. RESULTS: ß-cell dysfunction, insulin resistance, and combined ß-cell dysfunction and insulin resistance were associated with higher pre-diabetes risk. Similarly, isolated ß-cell dysfunction (adjusted relative risk ratio (aRRR) 4.8 (95% confidence interval (CI) 2.5, 9.0), isolated insulin resistance (aRRR 3.2 (95% CI 1.5, 6.9), and combined ß-cell dysfunction and insulin resistance (aRRR 35.9 (95% CI 17.2, 75.2) were associated with higher diabetes risk. CRP, AGP and HIV were associated with higher diabetes risk, but fat mass was not. 31%, 10% and 33% of diabetes cases were attributed to ß-cell dysfunction, insulin resistance, and combined ß-cell dysfunction and insulin resistance, respectively. CONCLUSIONS: ß-cell dysfunction seemed to explain most of diabetes cases compared to insulin resistance in this population. Cohort studies on evolution of diabetes in Africa are needed to confirm these results.

Integrating diabetes, hypertension and HIV care in sub-Saharan Africa: a Delphi consensus study on international best practice.

BACKGROUND: Although HIV continues to have a high prevalence among adults in sub-Saharan Africa (SSA), the burden of noncommunicable diseases (NCD) such as diabetes and hypertension is increasing rapidly. There is an urgent need to expand the capacity of healthcare systems in SSA to provide NCD services and scale up existing chronic care management pathways. The aim of this study was to identify key components, outcomes, and best practice in integrated service provision for the prevention, identification and treatment of HIV, hypertension and diabetes. METHODS: An international, multi stakeholder e-Delphi consensus study was conducted over two successive rounds. In Round 1, 24 participants were asked to score 27 statements, under the headings 'Service Provision' and 'Benefits of Integration', by importance. In Round 2, the 16 participants who completed Round 1 were shown the distribution of scores from other participants along with the score that they attributed to an outcome and were asked to reflect on the score they gave, based on the scores of the other participants and then to rescore if they wished to. Nine participants completed Round 2. RESULTS: Based on the Round 1 ranking, 19 of the 27 outcomes met the 70% threshold for consensus. Four additional outcomes suggested by participants in Round 1 were added to Round 2, and upon review by participants, 22 of the 31 outcomes met the consensus threshold. The five items participants scored from 7 to 9 in both rounds as essential for effective integrated healthcare delivery of health services for chronic conditions were improved data collection and surveillance of NCDs among people living with HIV to inform integrated NCD/HIV programme management, strengthened drug procurement systems, availability of equipment and access to relevant blood tests, health education for all chronic conditions, and enhanced continuity of care for patients with multimorbidity. CONCLUSIONS: This study highlights the outcomes which may form key components of future complex interventions to define a model of integrated healthcare delivery for diabetes, hypertension and HIV in sub-Saharan Africa.

Costs and outcomes of "intermediate" vs "minimal" care for youth-onset type 1 diabetes in six countries.

OBJECTIVE: Data are needed to demonstrate that providing an "intermediate" level of type 1 diabetes (T1D) care is cost-effective compared to "minimal" care in less-resourced countries. We studied these care scenarios in six countries. METHODS: We modeled the complications/costs/mortality/healthy life years (HLYs) associated with "intermediate" care including two blood glucose tests/day (mean HbA1c 9.0% [75 mmol/mol]) in three lower-gross domestic product (GDP) countries (Mali, Tanzania, Pakistan), or three tests/day (mean HbA1c 8.5% [69 mmol/mol]) in three higher-GDP countries (Bolivia, Sri Lanka, Azerbaijan); and compared findings to "minimal" care (mean HbA1c 12.5% [113 mmol/mol]). A discrete time Markov illness-death model with age and calendar-year-dependent transition probabilities was developed, with inputs of 30 years of complications and Standardized Mortality Rate data from the youth cohort in the Pittsburgh Epidemiology of Diabetes Complications Study, background mortality, and costs determined from international and local prices. RESULTS: Cumulative 30 years incidences of complications were much lower for "intermediate care" than "minimal care", for example, for renal failure incidence was 68.1% (HbA1c 12.5%) compared to 3.9% (9%) and 2.4% (8.5%). For Mali, Tanzania, Pakistan, Bolivia, Sri Lanka, and Azerbaijan, 30 years survival was 50.1%/52.7%/76.7%/72.5%/82.8%/89.2% for "intermediate" and 8.5%/10.1%/39.4%/25.8%/45.5%/62.1% for "minimal" care, respectively. The cost of a HLY gained as a % GDP/capita was 141.1%/110.0%/52.3%/41.8%/17.0%/15.6%, respectively. CONCLUSIONS: Marked reductions in complications rates and mortality are achievable with "intermediate" T1D care achieving mean clinic HbA1c of 8.5% to 9% (69-75 mmol/mol). This is also "very cost-effective" in four of six countries according to the WHO "Fair Choices" approach which costs HLYs gained against GDP/capita.

Transient Hyperglycemia in Patients With Tuberculosis in Tanzania: Implications for Diabetes Screening Algorithms.

BACKGROUND: Diabetes mellitus (DM) increases tuberculosis risk while tuberculosis, as an infectious disease, leads to hyperglycemia. We compared hyperglycemia screening strategies in controls and patients with tuberculosis in Dar es Salaam, Tanzania. METHODS: Consecutive adults with tuberculosis and sex- and age-matched volunteers were included in a case-control study between July 2012 and June 2014. All underwent DM screening tests (fasting capillary glucose [FCG] level, 2-hour CG [2-hCG] level, and glycated hemoglobin A1c [HbA1c] level) at enrollment, and cases were tested again after receipt of tuberculosis treatment. Association of tuberculosis and its outcome with hyperglycemia was assessed using logistic regression analysis adjusted for sex, age, body mass index, human immunodeficiency virus infection status, and socioeconomic status. Patients with tuberculosis and newly diagnosed DM were not treated for hyperglycemia. RESULTS: At enrollment, DM prevalence was significantly higher among patients with tuberculosis (n = 539; FCG level > 7 mmol/L, 4.5% of patients, 2-hCG level > 11 mmol/L, 6.8%; and HbA1c level > 6.5%, 9.3%), compared with controls (n = 496; 1.2%, 3.1%, and 2.2%, respectively). The association between hyperglycemia and tuberculosis disappeared after tuberculosis treatment (adjusted odds ratio [aOR] for the FCG level: 9.6 [95% confidence interval {CI}, 3.7-24.7] at enrollment vs 2.4 [95% CI, .7-8.7] at follow-up; aOR for the 2-hCG level: 6.6 [95% CI, 4.0-11.1] vs 1.6 [95% CI, .8-2.9]; and aOR for the HbA1c level, 4.2 [95% CI, 2.9-6.0] vs 1.4 [95% CI, .9-2.0]). Hyperglycemia, based on the FCG level, at enrollment was associated with tuberculosis treatment failure or death (aOR, 3.3; 95% CI, 1.2-9.3). CONCLUSIONS: Transient hyperglycemia is frequent during tuberculosis, and DM needs confirmation after tuberculosis treatment. Performance of DM screening at tuberculosis diagnosis gives the opportunity to detect patients at risk of adverse outcome.