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.

Changes in self-reported risky sexual behaviour indicators among adults receiving regular risk reduction counselling and optional initiation of pre-exposure prophylaxis in an HIV vaccine preparedness study in Masaka, Uganda.

BACKGROUND: HIV risk reduction counselling may reduce risk-taking behaviours. Yet, concerns remain about risk compensation among individuals initiating pre-exposure prophylaxis (PrEP). OBJECTIVE: We assessed changes in risky sexual behaviour indicators among HIV vaccine preparedness study participants who received regular risk reduction counselling and referral for PrEP in Masaka, Uganda. METHODS: Adults (18-39 years) at high risk of HIV infection were enrolled in the study between July 2018 and December 2021. Data were collected on socio-demographic factors (baseline) and self-reported sexual risk behaviours (baseline, six monthly). HIV testing and risk-reduction counselling and referral for PrEP were done quarterly. Participants who had completed at least 1 year of follow-up were included in the analysis. Proportional differences and McNemar chi-square tests were used to assess changes in the prevalence of self-reported risky sexual behaviour indicators between baseline and 1 year. Logistic regression was used to assess the predictors of unchanged/increased HIV risk at 1 year. RESULTS: Three hundred participants [132 (44%) females, 152 (51%) aged ≤24 years] were included in this analysis. Eighty-one (27%) participants initiated PrEP at 1 year. Compared to baseline, there were significant reductions in the prevalence of the following self-reported HIV risk indicators at 1 year (overall, among non-PrEP initiators, and among PrEP initiators): transactional sex, ≥6 sexual partners, unprotected sex with ≥3 partners, sex while drunk, and sexually transmitted infection diagnosis/treatment. Percentage differences ranged from 10% for individuals reporting at least six sexual partners to 30% for those reporting unprotected sex with three or fewer sexual partners. There was weak evidence of association between female gender and unchanged/increased HIV risk at 1 year (adjusted OR: 1.35, 95% CI (0.84-2.17)). No other indicators, including PrEP use, were associated with unchanged/increased HIV risk at 1 year. CONCLUSION: Regular risk-reduction counselling may reduce risky sexual behaviour, while PrEP initiation may not lead to risk compensation.

Social engagement and survival in people aged 50 years and over living with HIV and without HIV in Uganda: a prospective cohort study.

This study examined the association between social engagement and survival in people with or without HIV aged 50 years and over in Uganda. We analysed two waves of a survey from two sites in Uganda to assess predictors of mortality between waves. The first wave was conducted between 2009 and 2010 while the second wave was conducted between 2012 and 2013. A standardised questionnaire adapted from the World Health Organization study on global AGEing and adult health (SAGE) was administered through face-to-face interviews at both survey waves. Cox proportional hazards models and Nelson-Aalen cumulative hazards functions were used to investigate associations between the strength of participants' social ties, using distance and intimacy metrics, and their social engagement with mortality between waves. Of the original 510 participants, 63 (12.3%) died between waves. Being more socially engaged and able to provide in-kind or financial contributions to family or friends were protective. After adjusting for covariates neither social tie measure was predictive of mortality. There were no significant differences in social engagement and survival by HIV status. Further research is needed in African settings on the relationship between social relationships and subsequent mortality in older adults to assess if improved social relationships could moderate mortality.

Timing of Most Recent Health Care Visit by Older People Living With and Without HIV.

The objective of this article is to document factors associated with the recency of health-care service utilization by people aged 50 years and over living with and without HIV in Uganda. A survey was conducted with 510 Ugandans aged 50 and older, living with and without HIV. The survey included information on sociodemographic characteristics, health state, self-reported chronic conditions, and timing of most recent visit to a health-care facility (time since last visit [TSLV]). We use ordinal logistic regression to identify independent factors associated TSLV. Independent factors associated with TSLV (>6 months) include age, OR = 2.40 [95% CI 1.08-5.37] for those aged 80 years and above, urban respondents, OR = 0.6 [95%CI 0.38-0.94], HIV-positive respondents, OR = 0.33 [95%CI 0.18-0.59], and better health. To understand the meaning of these finding, further investigation should examine (a) how best to define and measure older persons' health-care service needs and (b) older persons' decision-making processes around the timing of their access to health-care facilities.

Population based haematology reference ranges for old people in rural South-West Uganda.

BACKGROUND: Haematology reference values are needed to interpret haematology results and make clinical decisions, but these have not been established for old people in sub-Saharan Africa. The objective of this study was to establish haematology reference values for people aged 50 years and above in Uganda, to compare the haematology reference values for those aged 65 years and over with those less than 65 years and to compare these haematology reference values with established haematology reference values for old people from high income countries. METHODS: A total of 1449 people aged 50 years and above were recruited from the Medical Research Council/Uganda Virus Research Institute general population cohort between January 2012 and January 2013 (response rate 72.3 %). From the blood samples collected, we did haematology, HIV testing and malaria tests. We also obtained stool samples and tested them for hookworm infection. Questionnaire data were obtained through interviews. In the analysis, we excluded those with HIV infection, malaria infection, hookworm infection and those not feeling well at the time of recruitment. Medians and reference ranges for 12 haematology parameters were determined, based on the Clinical Laboratory and Standards institute's guidelines. RESULTS: In total, 903 people aged 50 years and above were included in the analysis with the majority 545 (60.3 %) being female. Men had significant difference in median haemoglobin, haematocrit, erythrocytes counts and white blood cells counts, which were higher than those of women. Women had significant difference in mean platelet counts and neutrophil percentages which were higher than those of men. Comparing those aged 65+ and those aged less than 65 years, the following parameters were significantly lower in those aged above 65 years: haemoglobin, haematocrit, erythrocytes counts, platelets and mean corpuscular volume. Compared to the reference intervals from old people in high income countries, all the haematology parameters from our study population were low. CONCLUSION: The differences between haematology reference ranges in old people compared to adults and the very old (65+) compared to those between 50 and 65 call for more population based studies using nationwide surveys to be carried out among old people in other study settings in Uganda and the rest of Africa to explore the differences in haematology reference ranges between these different age groups with a view of establishing whether there is need to have separate reference range for these different categories of old people.

Chronic disease, risk factors and disability in adults aged 50 and above living with and without HIV: findings from the Wellbeing of Older People Study in Uganda.

BACKGROUND: Data on the prevalence of chronic conditions, their risk factors, and their associations with disability in older people living with and without HIV are scarce in sub-Saharan Africa. OBJECTIVES: In older people living with and without HIV in sub-Saharan Africa: 1) to describe the prevalence of chronic conditions and their risk factors and 2) to draw attention to associations between chronic conditions and disability. METHODS: Cross-sectional individual-level survey data from people aged 50 years and over living with and without HIV were analyzed from three study sites in Uganda. Diagnoses of chronic conditions were made through self-report, and disability was determined using the WHO Disability Assessment Schedule (WHODAS). We used ordered logistic regression and calculated predicted probabilities to show differences in the prevalence of multiple chronic conditions across HIV status, age groups, and locality. We used linear regression to determine associations between chronic conditions and the WHODAS. RESULTS: In total, 471 participants were surveyed; about half the respondents were living with HIV. The prevalence of chronic obstructive pulmonary disease and eye problems (except for those aged 60-69 years) was higher in the HIV-positive participants and increased with age. The prevalence of diabetes and angina was higher in HIV-negative participants. The odds of having one or more compared with no chronic conditions were higher in women (OR 1.6, 95% CI 1.1-2.3) and in those aged 70 years and above (OR 2.1, 95% CI 1.2-3.6). Sleep problems (coefficient 14.2, 95% CI 7.3-21.0) and depression (coefficient 9.4, 95% CI 1.2-17.0) were strongly associated with higher disability scores. CONCLUSION: Chronic conditions are common in older adults and affect their functioning. Many of these conditions are not currently addressed by health services in Uganda. There is a need to revise health care policy and practice in Uganda to consider the health needs of older people, particularly as the numbers of people living into older age with HIV and other chronic conditions are increasing.

Gender perspectives in care provision and care receipt among older people infected and affected by HIV in Uganda.

The objective of this study was to examine gender roles in the provision and receipt of care among older Ugandans. Survey data on care work were collected in 2009-2010 from 510 older people infected or affected by HIV/AIDS, at one rural and one semi-urban site. The questionnaire was adapted from the WHO Study on global AGEing and adult health survey. The type of care work done by older men and women for children in their households differs, yet, both men and women are taking on various types of care work. Women were more likely to report taking part in health/personal and physical care, whereas men were more likely to report providing financial assistance. Some older people, particularly women, were providing care at the same time as needing care. The finding on reciprocity of care suggests the need for further studies focused on how the reciprocity of care may affect health and well-being in older age.

Older people's perception of anemia in rural southwest Uganda.

OBJECTIVE: To describe older people's perceptions of anemia in a rural Ugandan population. METHOD: Quantitative and qualitative data on anemia were collected from participants aged ≥50 years from January 2012 to January 2013 using questionnaires and in-depth interviews. Quantitative data were collected from 1,455 participants. Qualitative data were collected from 10 people who were purposively selected. Data were analyzed using STATA software and thematic content analysis. RESULTS: 33.8% men and 17.4% women had anemia. Older people perceived themselves to be anemic because of symptoms and beliefs about causes. Those with anemia were more likely to perceive that they had anemia (18.4% vs. 10.2%, p < .001). Poor diet, diseases, poor living conditions, and over work were mentioned as causes of anemia. Use of traditional methods for treating anemia was common. DISCUSSION: Anemia prevention and control programs in Uganda should target older people and correct misconceptions about the causes and treatment of anemia.

Prevalence, types, risk factors and clinical correlates of anaemia in older people in a rural Ugandan population.

BACKGROUND: Studies conducted in high income countries have shown that anaemia is a common medical condition among older people, but such data are scarce in Africa. The objectives of this study were to estimate the prevalence, types, risk factors and clinical correlates of anaemia in older people. METHODS: Participants were aged (≥ 50) years recruited from a general population cohort from January 2012 to January 2013. Blood samples were collected for assessing hemoglobin, serum ferritin, serum vitamin B12, serum folate, C-reactive protein, malaria infection and stool samples for assessment of hookworm infection. HIV status was assessed using an algorithm for HIV rapid testing. Questionnaires were used to collect data on sociodemographic characteristics and other risk factors for anaemia. RESULTS: In total, 1449 people participated (response rate 72.3%). The overall prevalence of anaemia was 20.3 % (95% CI 18.2-22.3%), and this was higher for males (24.1%, 95% CI=20.7-27.7%) than females (17.5%, 95% CI=15.0-20.1%). In males, the prevalence of anaemia increased rapidly with age almost doubling between 50 and 65 years (p-trend<0.001). Unexplained anaemia was responsible for more than half of all cases (59.7%). Anaemia was independently associated with infections including malaria (OR 3.49, 95% CI 1.78-6.82), HIV (OR 2.17, 1.32-3.57) heavy hookworm infection (OR 3.45, 1.73-6.91), low fruit consumption (OR 1.55, 1.05-2.29) and being unmarried (OR 1.37 , 95% CI 1.01-1.89). However, the odds of anaemia were lower among older people with elevated blood pressure (OR 0.47, 95% CI 0.29-0.77). CONCLUSION: Anaemia control programmes in Uganda should target older people and should include interventions to treat and control hookworms and educational programs on diets that enhance iron absorption. Clinicians should consider screening older people with HIV or malaria for anaemia. Further studies should be done on unexplained anaemia and serum ferritin levels that predict iron deficiency anaemia in older people.

Patients' worries before starting antiretroviral therapy and their association with treatment adherence and outcomes: a prospective study in rural Uganda, 2004 - 2009.

BACKGROUND: In HIV-infected persons, good adherence to antiretroviral therapy (ART) is essential for successful treatment outcomes. Patients' worries before starting ART may affect their ART adherence and treatment outcomes. METHODS: Between 2004 and 2009, HIV-infected individuals in a prospective cohort study in rural Uganda were assessed for ART eligibility. A counsellor explained the ART eligibility criteria, adherence and side effects, and recorded the patients' worries related to ART. Every quarter, patients who initiated ART had clinical, immunological (CD4 cell counts) and virological (viral loads) assessments, and data were collected on ART adherence using patients' self-reports and pill counts. We describe the patients' worries and examine their association with ART adherence, and immunological and virological outcomes. RESULTS: We assessed 421 patients, 271 (64%) were females, 318 (76%) were aged 30 years and above and 315 (75%) were eligible for ART. 277 (66%) reported any worry, and the proportions were similar by sex, age group and ART eligibility status. The baseline median CD4 counts and viral loads were similar among patients with any worry and those with no worry. The commonest worries were: fear of HIV serostatus disclosure; among 69 (16%) participants, lack of food when appetite improved after starting ART; 50 (12%), concurrent use of other medications; 33 (8%), adherence to ART; 28 (7%) and problems concerning condom use; 27 (6%). After 24 months or more on ART, patients who reported any worry had made more scheduled ART refill visits than patients who reported no worry (p<0.01), but the annual CD4 cell increases were similar (p=0.12). After one year on ART, patients who reported any worry had greater virological suppression than patients who reported no worry (p<0.05). CONCLUSIONS: Despite the lack of significant associations of worries with unfavourable ART outcomes, physicians and counsellors should assist patients in overcoming their worries that can cause stress and discomfort. Food supplements may be desirable for some patients initiating ART.

Mean Corpuscular Volume as a Marker for Adherence to Zidovudine-Containing Therapy in HIV-Infected Adults.

OBJECTIVES: To assess whether mean corpuscular volume (MCV) is useful in detecting non-adherence to AZTcontaining therapy. DESIGN: Observational study within randomised controlled trial. METHODS: We combined data from two treatment arms in SPARTAC, an RCT of short-course cART in primary HIV infection, classifying participants as responders (HIV-RNA decrease ≥1 log(10) or reaching <400copies/ml) or nonresponders following cART initiation. We assessed the sensitivity and specificity of using different percentage increases in MCV for accurately differentiating between responders and non-responders. We further examined changes in MCV levels up to 24 weeks after protocol-indicated cART cessation. RESULTS: Of 119 participants included in this analysis, 73 (61%) were women, 71 of whom were randomised in Africa. Ninety-eight (88%) and 84 (85%) were classified as responders at 4 and 12 weeks respectively following cART initiation. MCV increased by a mean 3% and 1% at week 4, and 14% and <1% at 12 weeks for responders and non-responders. A 2% MCV increase at 4 weeks had 62% sensitivity and specificity for identifying virological response. At 12 weeks, an 8% increase had 89% sensitivity and specificity. In responders, MCV remained lower for individuals in African compared to non-African sites throughout and rose from 85 vs 90 fL at cART start to 96 vs 103 fL at 12 weeks post-initiation then fell to 88 vs 93 fL and 86 vs 89 fL at 12 and 48 weeks post-cessation. CONCLUSION: In low-income countries, where HIV RNA may be unavailable, 12-weekly MCV measurements may be useful in monitoring adherence to AZT-containing regimens.

Using verbal autopsy to assess the prevalence of HIV infection among deaths in the ART period in rural Uganda: a prospective cohort study, 2006-2008.

BACKGROUND: Verbal autopsy is important for detecting causes of death including HIV in areas with inadequate vital registration systems. Before antiretroviral therapy (ART) introduction, a verbal autopsy study in rural Uganda found that half of adult deaths assessed were in HIV-positive individuals. We used verbal autopsy to compare the proportion of HIV-positive adult deaths in the periods before and after ART introduction. METHODS: Between 2006 and 2008, all adult (≥ 13 years) deaths in a prospective population-based cohort study were identified by monthly death registration, and HIV serostatus was determined through annual serosurveys. A clinical officer interviewed a relative of the deceased using a verbal autopsy questionnaire. Two clinicians independently reviewed the questionnaires and classified the deaths as HIV-positive or not. A third clinician was the tie-breaker in case of nonagreement. The performance of the verbal autopsy tool was assessed using HIV serostatus as the gold standard of comparison. We compared the proportions of HIV-positive deaths as assessed by verbal autopsy in the early 1990s and the 2006-2008 periods. RESULTS: Of 333 deaths among 12,641 adults of known HIV serostatus, 264 (79.3%) were assessed by verbal autopsy, of whom 59 (22.3%) were HIV-seropositive and 68 (25.8%) were classified as HIV-positive by verbal autopsy. Verbal autopsy had a specificity of 90.2% and positive predictive value of 70.6% for identifying deaths among HIV-infected individuals, with substantial interobserver agreement (80.3%; kappa statistic = 0.69). The HIV-attributable mortality fraction estimated by verbal autopsy decreased from 47.0% (pre-ART period) to 25.8% (ART period), p < 0.001. CONCLUSIONS: In resource-limited settings, verbal autopsy can provide a good estimate of the prevalence of HIV infection among adult deaths. In this rural population, the proportion of deaths identified by verbal autopsy as HIV-positive declined between the early 1990s and the 2006-2008 period. Verbal autopsy findings can inform policy on HIV health care needs.

Anaemia in a rural Ugandan HIV cohort: prevalence at enrolment, incidence, diagnosis and associated factors.

OBJECTIVES: To determine the prevalence and incidence of anaemia in HIV-positive and negative individuals; to identify risk factors for anaemia, prior to the introduction of HAART; and to determine the validity of the clinical diagnosis of anaemia. METHODS: Between 1990 and 2003, we followed a rural population based cohort of HIV-infected and uninfected participants. Prevalence and incidence of anaemia were determined clinically and by laboratory measurements. The sensitivity, specificity and predictive values of clinical diagnosis were calculated. RESULTS: The prevalence of anaemia at enrolment was 18.9% among HIV-positive and 12.9% among HIV-negative participants (P = 0.065). Incidence of anaemia increased with HIV disease progression, from 103 per 1000 person-years of observation among those with CD4 counts >500 to 289 per 1000 person-years of observation among those with CD4 counts <200. Compared to laboratory diagnosis, the clinical diagnosis of anaemia had a sensitivity of 17.8%, specificity of 96.8%, a positive predictive value of 50.6% and a negative predictive value of 86.4%. Being female, low CD4 cell counts, HIV-positive, wasting syndrome, WHO stage 3 or 4, malaria, fever, pneumonia and oral candidiasis were associated with prevalent anaemia. CONCLUSIONS: Anaemia prevalence and incidence were higher among HIV-positive than negative participants. Compared to laboratory diagnosis, clinical detection of anaemia had a low sensitivity. Clinicians working in settings with limited laboratory support must be conscious of the risk of anaemia when managing HIV/AIDS patients, particularly when using antiretroviral drugs which by themselves may cause anaemia as a side effect. We recommend that haemoglobin should be measured before starting ART and monthly for the first three months.