Epidemiology of multimorbidity in low-income countries of sub-Saharan Africa: Findings from four population cohorts.

We investigated prevalence and demographic characteristics of adults living with multimorbidity (≥2 long-term conditions) in three low-income countries of sub-Saharan Africa, using secondary population-level data from four cohorts; Malawi (urban & rural), The Gambia (rural) and Uganda (rural). Information on; measured hypertension, diabetes and obesity was available in all cohorts; measured hypercholesterolaemia and HIV and self-reported asthma was available in two cohorts and clinically diagnosed epilepsy in one cohort. Analyses included calculation of age standardised multimorbidity prevalence and the cross-sectional associations of multimorbidity and demographic/lifestyle factors using regression modelling. Median participant age was 29 (Inter quartile range-IQR 22-38), 34 (IQR25-48), 32 (IQR 22-53) and 37 (IQR 26-51) in urban Malawi, rural Malawi, The Gambia, and Uganda, respectively. Age standardised multimorbidity prevalence was higher in urban and rural Malawi (22.5%;95% Confidence intervals-CI 21.6-23.4%) and 11.7%; 95%CI 11.1-12.3, respectively) than in The Gambia (2.9%; 95%CI 2.5-3.4%) and Uganda (8.2%; 95%CI 7.5-9%) cohorts. In multivariate models, females were at greater risk of multimorbidity than males in Malawi (Incidence rate ratio-IRR 1.97, 95% CI 1.79-2.16 urban and IRR 2.10; 95%CI 1.86-2.37 rural) and Uganda (IRR- 1.60, 95% CI 1.32-1.95), with no evidence of difference between the sexes in The Gambia (IRR 1.16, 95% CI 0.86-1.55). There was strong evidence of greater multimorbidity risk with increasing age in all populations (p-value <0.001). Higher educational attainment was associated with increased multimorbidity risk in Malawi (IRR 1.78; 95% CI 1.60-1.98 urban and IRR 2.37; 95% CI 1.74-3.23 rural) and Uganda (IRR 2.40, 95% CI 1.76-3.26), but not in The Gambia (IRR 1.48; 95% CI 0.56-3.87). Further research is needed to study multimorbidity epidemiology in sub-Saharan Africa with an emphasis on robust population-level data collection for a wide variety of long-term conditions and ensuring proportionate representation from men and women, and urban and rural areas.

Identification and characterisation of diabetes in Uganda: protocol for the nested, population-based 'Diabetes in low-resource Populations' (DOP) Study.

INTRODUCTION: Sub-Saharan Africa is experiencing an increasing burden of diabetes, but there are little reliable data, particularly at the community level, on the true prevalence or why this condition affects young and relatively lean individuals. Moreover, the detection of diabetes in Africa remains poor, not only due to a lack of resources but because the performance of available diagnostic tests is unclear. METHODS: This research aims to (1) determine the prevalence and risk factors of diabetes in a rural Ugandan population, (2) use clinical and biochemical markers to define different diabetes phenotypes and (3) study the progression of diabetes in this population. We will also assess the utility of the widely used tests (glycated haemoglobin (HbA1c), oral glucose tolerance test (OGTT) and fasting glucose) in diagnosing diabetes. DESIGN: This is a population-based study nested within the longstanding general population cohort in southwestern Uganda. We will undertake a population survey to identify individuals with diabetes based on fasting glucose, HbA1c, OGTT results or history of pre-existing diabetes. PARTICIPANTS: The study intends to enrol up to 11 700 individuals aged 18 years and above, residing within the study area and not pregnant or within 6 months post-delivery date. All participants will have detailed biophysical and biochemical/metabolic measurements. Individuals identified to have diabetes and a random selection of controls will have repeat tests to test reproducibility before referral and enrolment into a diabetic clinic. Participants will then be followed up for 1 year to assess the course of the disease, including response to therapy and diabetes-related complications. CONCLUSIONS: These data will improve our understanding of the burden of diabetes in Uganda, the risk factors that drive it and underlying pathophysiological mechanisms, as well as better ways to detect this condition. This will inform new approaches to improve the prevention and management of diabetes. ETHICS AND DISSEMINATION: This study protocol was approved by the Uganda Virus Research Institute Research Ethics Committee (REC) (number: G.C./127/21/09/858), the London School of Hygiene and Tropical Medicine REC (number: 26638) and the Uganda National Council for Science and Technology (protocol number: HS1791ES). Written informed consent will be obtained from all participants before being enrolled on to the study and conducting study-related procedures. Research findings will be disseminated in policy briefs, seminars, local and international conferences and publications in peer-reviewed open-access journals. As part of the dissemination plans, findings will also be disseminated to patient care groups and to clinicians. TRIAL REGISTRATION NUMBER: NCT05487079.

Thirty years of change in HIV incidence among adults in the Kyamulibwa General Population Cohort in rural southwest Uganda, 1989-2021.

OBJECTIVES: To document the changes in HIV incidence over thirty years in Kalungu district, Uganda. METHODS: Since 1989, residents aged ≥15 years old have been tested for HIV, and data were collected on HIV risk factors annually and later, biennially in the Kyamulibwa open cohort. In the 2019-2021 survey, people living with HIV self-reported on knowledge of their HIV status, antiretroviral therapy (ART) use, and their most recent viral load data were obtained from health facilities. The HIV seroconversion dates were randomly imputed between the last negative and first positive test dates using a uniform distribution. RESULTS: Among 20,959 residents who were HIV-negative, 669 seroconverted within 176,659 person-years. Data showed a downward trend in age-adjusted HIV incidence over 30 years (P <0.001) even though HIV prevalence steadily increased with ART availability from 2004. Comparing 1990-1992 and 1996-1998, HIV incidence declined by 43% (0.79 to 0.45/100 person-years, P = 0.002). Between 1999 and 2011, the incidence remained stable at 0.49/100 person-years (95% confidence interval: 0.41-0.58) in men but slowly increased in women (average age-adjusted hazard ratio = 1.13 per 3 years, 95% confidence interval: 1.03-1.24; trend P-value = 0.02). After 2011, however, the incidence trends reversed and continued to decline in men and women and in all age groups. CONCLUSION: Facilitating HIV testing and timely ART initiation, and supporting ART adherence must be emphasized alongside sustainable prevention measures.

Uganda Genome Resource: A rich research database for genomic studies of communicable and non-communicable diseases in Africa.

The Uganda Genome Resource (UGR) is a well-characterized genomic database with a range of phenotypic communicable and non-communicable diseases and risk factors generated from the Uganda General Population Cohort (GPC), a population-based open cohort established in 1989. The UGR comprises genotype data on ∼5,000 and whole-genome sequence data on ∼2,000 Ugandan GPC individuals from 10 ethno-linguistic groups. Leveraging other platforms at MRC/UVRI and LSHTM Uganda Research Unit, there is opportunity for additional sample collection to expand the UGR to advance scientific discoveries. Here, we describe UGR and highlight how it is providing opportunities for discovery of novel disease susceptibility genetic loci, refining association signals at new and existing loci, developing and testing polygenic scores to determine disease risk, assessing causal relations in diseases, and developing capacity for genomics research in Africa. The UGR has the potential to develop to a comparable level of European and Asian large-scale genomic initiatives.

Association of impaired kidney function with mortality in rural Uganda: results of a general population cohort study.

OBJECTIVE: To determine the association between baseline kidney function and subsequent all-cause mortality. DESIGN AND SETTING: A general population-based cohort study from rural Uganda. PARTICIPANTS: People aged 18 years and above with measured baseline estimated glomerular filtration rate (eGFR), recruited from survey rounds in 2011-2012 or 2014-2015 and followed up to March 2019. OUTCOME MEASURE: The primary outcome was all-cause mortality, identified through reports from community health workers and verified by verbal autopsy. The association between baseline eGFR category and mortality was determined using multivariable Cox regression. RESULTS: Of 5812 participants in both rounds, we included 5678 (97.7%) participants with kidney function and mortality data; the median age was 36 years (IQR 24-50), 60.7% were female, 10.3% were hypertensive, 9.8% were HIV-positive and 1.5% were diabetic. During a median follow-up of 5.0 years (IQR 3.7-6.0) there were 140 deaths. In age-adjusted and sex-adjusted analyses, eGFR <45 mL/min/1.73 m2 at baseline was associated with a 5.97 (95% CI 2.55 to 13.98) increased risk of mortality compared with those with baseline eGFR >90 mL/min/1.73 m2. After inclusion of additional confounders (HIV, body mass index, diabetes, hypertension, alcohol and smoking status) into the model, eGFR <45 mL/min/1.73 m2 at baseline remained strongly associated with mortality (HR 6.12, 95% CI 2.27 to 16.45), although the sample size fell to 3102. Test for trend showed strong evidence (p<0.001) that the rate of mortality increased progressively as the category of baseline kidney function decreased. When very high eGFR was included as a separate category in age-adjusted and sex-adjusted analyses, baseline eGFR ≥120 mL/min/1.73 m2 was associated with increased risk of mortality (HR 2.68, 95% CI 1.47 to 4.87) compared with the reference category of 90-119 mL/min/1.73 m2. CONCLUSION: In a prospective cohort in rural Uganda we found that impaired baseline kidney function was associated with subsequently increased total mortality. Improved understanding of the determinants of kidney disease and its progression is needed in order to inform interventions for prevention and treatment.