Blood pressure levels among children in rural Uganda: results from 1913 children in a general population survey.

Despite increasing levels of adult hypertension in sub-Saharan Africa (SSA), there is limited information on elevated blood pressure among children in SSA. We described the distribution of blood pressure among children in rural Uganda and estimated hypertension prevalence. We conducted a cross-sectional study in south-western Uganda, collecting demographic, anthropometric and blood pressure measurements from children aged 6-12 years. Children with elevated blood pressure (systolic and/or diastolic blood pressure greater or equal to the 95th percentile for age, height and sex) were invited for two further assessments 6-18 months later. We described blood pressure distribution at first assessment, assessed associations with demographic and anthropometric characteristics and estimated prevalence of hypertension as defined by having elevated blood pressure on three separate occasions months apart. Blood pressure (BP) was measured in 1913 children (50% male, 3% overweight or obese, 22% stunted) at the first assessment. Mean (SD) systolic and diastolic BP at first assessment was 113.4 mmHg (±10.8) and 69.5 mmHg (±8.3), respectively, and 44.2% had elevated BP. Older age, higher BMI, and being female were associated with higher BP, and stunted height was associated with lower BP. An estimated 7.8% [95% CI:(6.6-9.1)], (males: 6.8%, females: 9.0%), had elevated BP on three separate occasions, and were considered hypertensive. High blood pressure levels among adults in SSA may be set early in life. In this study, obesity (a common lifestyle modifiable risk factor in other settings) was largely irrelevant. More research is needed to understand the main drivers for elevated blood pressure in SSA further.

Prevalence and Factors Associated With Liver Fibrosis Among Adult HIV-Infected Patients Attending Urban and Rural Care Clinics in Uganda.

BACKGROUND: Liver fibrosis is common among HIV-infected patients. Risk factors vary by location. Understanding this variation may inform prevention strategies. We compared the prevalence and correlates of liver fibrosis among HIV-infected patients attending care clinics in Uganda. METHODS: This was a cross-sectional study involving 2030 HIV-infected patients attending care clinics in urban and rural Uganda. Liver fibrosis was defined as liver stiffness measurement (LSM) >7.1 KPa. Proportions and correlates of liver fibrosis were assessed and compared using logistic regression stratified by gender and site. RESULTS: Prevalence of liver fibrosis was higher among participants in the rural clinic (15% vs 11%; P = .017). History of tobacco use (urban P = .022; rural P = .035) and serologic evidence of hepatitis C infection (HCV; urban P = .028; rural P = .03) was associated with liver fibrosis in all men. Elevated liver transaminases (urban P = .002; rural P = .028) and increasing age (urban P = .008; rural P = .052) were risk factors among all women. Tobacco use among women was only a risk factor in those attending the rural clinic (P = .003), and detectable HIV viral load (P = .002) for men in the urban clinic. CONCLUSIONS: Liver fibrosis is prevalent among HIV-infected persons in Uganda. HIV viral suppression and avoiding tobacco may be strategies to prevent liver fibrosis and cancer risk.

The Molecular Epidemiology and Transmission Dynamics of HIV Type 1 in a General Population Cohort in Uganda.

The General Population Cohort (GPC) in south-western Uganda has a low HIV-1 incidence rate (<1%). However, new infections continue to emerge. In this research, 3796 HIV-1 pol sequences (GPC: n = 1418, non-GPC sites: n = 1223, Central Uganda: n = 1010 and Eastern Uganda: n = 145) generated between 2003-2015 were analysed using phylogenetic methods with demographic data to understand HIV-1 transmission in this cohort and inform the epidemic response. HIV-1 subtype A1 was the most prevalent strain in the GPC area (GPC and non-GPC sites) (39.8%), central (45.9%) and eastern (52.4%) Uganda. However, in the GPC alone, subtype D was the predominant subtype (39.1%). Of the 524 transmission clusters identified by Cluster Picker, all large clusters (≥5 individuals, n = 8) involved individuals from the GPC. In a multivariate analysis, clustering was strongly associated with being female (adjusted Odds Ratio, aOR = 1.28; 95% CI, 1.06-1.54), being >25 years (aOR = 1.52; 95% CI, 1.16-2.0) and being a resident in the GPC (aOR = 6.90; 95% CI, 5.22-9.21). Phylogeographic analysis showed significant viral dissemination (Bayes Factor test, BF > 3) from the GPC without significant viral introductions (BF < 3) into the GPC. The findings suggest localized HIV-1 transmission in the GPC. Intensifying geographically focused combination interventions in the GPC would contribute towards controlling HIV-1 infections.

Liver function tests and fibrosis scores in a rural population in Africa: a cross-sectional study to estimate the burden of disease and associated risk factors.

OBJECTIVES: Liver disease is a major cause of morbidity and mortality in sub-Saharan Africa, but its prevalence, distribution and aetiology have not been well characterised. We therefore set out to examine liver function tests (LFTs) and liver fibrosis scores in a rural African population. DESIGN: We undertook a cross-sectional survey of LFTs. We classified abnormal LFTs based on reference ranges set in America and in Africa. We derived fibrosis scores (aspartate aminotransferase (AST) to Platelet Ratio Index (APRI), fibrosis-4, gamma-glutamyl transferase (GGT) to platelet ratio (GPR), red cell distribution width to platelet ratio and S-index). We collected information about alcohol intake, and infection with HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV). SETTING: We studied a population cohort in South-Western Uganda. PARTICIPANTS: Data were available for 8099 adults (median age 30 years; 56% female). RESULTS: The prevalence of HBV, HCV and HIV infection was 3%, 0.2% and 8%, respectively. The prevalence of abnormal LFTs was higher based on the American reference range compared with the African reference range (eg, for AST 13% vs 3%, respectively). Elevated AST/ALT ratio was significantly associated with self-reported alcohol consumption (p<0.001), and the overall prevalence of AST/ALT ratio >2 was 11% (suggesting alcoholic hepatitis). The highest prevalence of fibrosis was predicted by the GPR score, with 24% of the population falling above the threshold for fibrosis. There was an association between the presence of HIV or HBV and raised GPR (p=0.005) and S-index (p<0.001). By multivariate analysis, elevated LFTs and fibrosis scores were most consistently associated with older age, male sex, being under-weight, HIV or HBV infection and alcohol consumption. CONCLUSIONS: Further work is required to determine normal reference ranges for LFTs in this setting, to evaluate the specificity and sensitivity of fibrosis scores and to determine the aetiology of liver disease.

Monoclonal B-cell lymphocytosis in a hospital-based UK population and a rural Ugandan population: a cross-sectional study.

BACKGROUND: Reported incidence of B-cell malignancies shows substantial geographical variation, being more common in the Americas and Europe than in Africa. This variation might reflect differences in diagnostic capability, inherited susceptibility, and infectious exposures. Monoclonal B-cell lymphocytosis (MBL) is a precursor lesion that can be screened for in apparently healthy people, allowing comparison of prevalence across different populations independently of health-care provision. We aimed to compare the prevalence and phenotypic characteristics of MBL in age-and-sex-matched populations from rural Uganda and the UK. METHODS: In this cross-sectional study, we recruited volunteers aged at least 45 years who were seronegative for HIV-1 from the established Ugandan General Population Cohort and obtained their whole-blood samples. We also obtained blood samples from anonymised waste material of age-and-sex-matched individuals (aged >45 years, with a normal blood count and no history of cancer) in the UK. We used flow cytometry to determine the presence of MBL, defined according to standard diagnostic criteria, in the samples and compared differences in the proportion of cases with chronic lymphocytic leukaemia (CLL)-phenotype MBL and CD5-negative MBL, as well as differences in absolute monoclonal B-cell count between the two cohorts. FINDINGS: Between Jan 15 and Dec 18, 2012, we obtained samples from 302 Ugandan volunteers and 302 UK individuals who were matched by age and sex to the Ugandan population. Overall MBL prevalence was higher in the Ugandan participants (42 [14%] individuals) than in the UK cohort (25 [8%]; p=0·038). CLL-phenotype MBL was detected in three (1%) Ugandan participants and 21 (7%) UK participants (p=0·00021); all three Ugandan participants had absolute monoclonal B-cell count below one cell per µL, whereas the 21 UK participants had a median absolute number of circulating neoplastic cells of 4·6 (IQR 2-12) cells per µL. The prevalence of CD5-negative MBL was higher in the Ugandan cohort (41 [14%], of whom two [5%] also had CLL-phenotype MBL) than in the UK cohort (six [2%], of whom two [33%] also had CLL-phenotype MBL; p<0·0001), but the median absolute B-cell count was similar (227 [IQR 152-345] cells per µL in the Ugandan cohort vs 135 [105-177] cells per µL in the UK cohort; p=0·13). INTERPRETATION: MBL is common in both Uganda and the UK, but the substantial phenotypic differences might reflect fundamental differences in the pathogenesis of B-cell lymphoproliferative disorders. FUNDING: UK Medical Research Council and UK Department for International Development.

Correction: Prevalence of Dyslipidaemia and Associated Risk Factors in a Rural Population in South-Western Uganda: A Community Based Survey.

[This corrects the article DOI: 10.1371/journal.pone.0126166.].

Prevalence of dyslipidaemia and associated risk factors in a rural population in South-Western Uganda: a community based survey.

BACKGROUND: The burden of dyslipidaemia is rising in many low income countries. However, there are few data on the prevalence of, or risk factors for, dyslipidaemia in Africa. METHODS: In 2011, we used the WHO Stepwise approach to collect cardiovascular risk data within a general population cohort in rural south-western Uganda. Dyslipidaemia was defined by high total cholesterol (TC) ≥ 5.2 mmol/L or low high density lipoprotein cholesterol (HDL-C) <1 mmol/L in men, and <1.3 mmol/L in women. Logistic regression was used to explore correlates of dyslipidaemia. RESULTS: Low HDL-C prevalence was 71.3% and high TC was 6.0%. In multivariate analysis, factors independently associated with low HDL-C among both men and women were: decreasing age, tribe (prevalence highest among Rwandese tribe), lower education, alcohol consumption (comparing current drinkers to never drinkers: men adjusted (a)OR=0.44, 95%CI=0.35-0.55; women aOR=0.51, 95%CI=0.41-0.64), consuming <5 servings of fruit/vegetable per day, daily vigorous physical activity (comparing those with none vs those with 5 days a week: men aOR=0.83 95%CI=0.67-1.02; women aOR=0.76, 95%CI=0.55-0.99), blood pressure (comparing those with hypertension to those with normal blood pressure: men aOR=0.57, 95%CI=0.43-0.75; women aOR=0.69, 95%CI=0.52-0.93) and HIV infection (HIV infected without ART vs. HIV negative: men aOR=2.45, 95%CI=1.53-3.94; women aOR=1.88, 95%CI=1.19-2.97). The odds of low HDL-C was also higher among men with high BMI or HbA1c ≤ 6%, and women who were single or with abdominal obesity. Among both men and women, high TC was independently associated with increasing age, non-Rwandese tribe, high waist circumference (men aOR=5.70, 95%CI=1.97-16.49; women aOR=1.58, 95%CI=1.10-2.28), hypertension (men aOR=3.49, 95%CI=1.74-7.00; women aOR=1.47, 95%CI=0.96-2.23) and HbA1c >6% (men aOR=3.00, 95%CI=1.37-6.59; women aOR=2.74, 95%CI=1.77-4.27). The odds of high TC was also higher among married men, and women with higher education or high BMI. CONCLUSION: Low HDL-C prevalence in this relatively young rural population is high whereas high TC prevalence is low. The consequences of dyslipidaemia in African populations remain unclear and prospective follow-up is required.

Genetic characterization of Greek population isolates reveals strong genetic drift at missense and trait-associated variants.

Isolated populations are emerging as a powerful study design in the search for low-frequency and rare variant associations with complex phenotypes. Here we genotype 2,296 samples from two isolated Greek populations, the Pomak villages (HELIC-Pomak) in the North of Greece and the Mylopotamos villages (HELIC-MANOLIS) in Crete. We compare their genomic characteristics to the general Greek population and establish them as genetic isolates. In the MANOLIS cohort, we observe an enrichment of missense variants among the variants that have drifted up in frequency by more than fivefold. In the Pomak cohort, we find novel associations at variants on chr11p15.4 showing large allele frequency increases (from 0.2% in the general Greek population to 4.6% in the isolate) with haematological traits, for example, with mean corpuscular volume (rs7116019, P=2.3 × 10(-26)). We replicate this association in a second set of Pomak samples (combined P=2.0 × 10(-36)). We demonstrate significant power gains in detecting medical trait associations.

Urbanicity and lifestyle risk factors for cardiometabolic diseases in rural Uganda: a cross-sectional study.

BACKGROUND: Urban living is associated with unhealthy lifestyles that can increase the risk of cardiometabolic diseases. In sub-Saharan Africa (SSA), where the majority of people live in rural areas, it is still unclear if there is a corresponding increase in unhealthy lifestyles as rural areas adopt urban characteristics. This study examines the distribution of urban characteristics across rural communities in Uganda and their associations with lifestyle risk factors for chronic diseases. METHODS AND FINDINGS: Using data collected in 2011, we examined cross-sectional associations between urbanicity and lifestyle risk factors in rural communities in Uganda, with 7,340 participants aged 13 y and above across 25 villages. Urbanicity was defined according to a multi-component scale, and Poisson regression models were used to examine associations between urbanicity and lifestyle risk factors by quartile of urbanicity. Despite all of the villages not having paved roads and running water, there was marked variation in levels of urbanicity across the villages, largely attributable to differences in economic activity, civil infrastructure, and availability of educational and healthcare services. In regression models, after adjustment for clustering and potential confounders including socioeconomic status, increasing urbanicity was associated with an increase in lifestyle risk factors such as physical inactivity (risk ratio [RR]: 1.19; 95% CI: 1.14, 1.24), low fruit and vegetable consumption (RR: 1.17; 95% CI: 1.10, 1.23), and high body mass index (RR: 1.48; 95% CI: 1.24, 1.77). CONCLUSIONS: This study indicates that even across rural communities in SSA, increasing urbanicity is associated with a higher prevalence of lifestyle risk factors for cardiometabolic diseases. This finding highlights the need to consider the health impact of urbanization in rural areas across SSA. Please see later in the article for the Editors' Summary.

Effect of HSV-2 on population-level trends in HIV incidence in Uganda between 1990 and 2007.

OBJECTIVE: To assess the long-term effects of population-level HSV-2 infection on HIV incidence. METHODS: Data from a population-based cohort in south-western Uganda were used to estimate HIV incidence from 1990 to 2007. Stored blood samples were tested for HSV-2, and the impact of HSV-2 prevalence and incidence on HIV incidence was estimated by calculating population attributable fractions (PAFs). The association between population-level annual HIV incidence and annual HSV-2 incidence/prevalence was analysed using linear regression. RESULTS: HIV incidence declined over time among men, from 8.72/1000 person-years (pyr) in 1990 to 4.85/1000 pyr in 2007 (P-trend <0.001). In contrast, there was no decline in HIV incidence among women (4.86/1000 pyr in 1990 to 6.74/1000 pyr in 2007, P-trend = 0.18). PAFs of incident HIV attributable to HSV-2 were high (60% in males; 70% in females). There was no evidence of an association between long-term trends in HIV incidence and HSV-2 prevalence or incidence. CONCLUSION: Assuming a causal relationship, a substantial proportion of new HIV infections in this population are attributable to HSV-2. The study did not find an effect of HSV-2 prevalence/incidence on trends in HIV incidence. HIV incidence did not vary much during the study period. This may partly explain the lack of association.

The general population cohort in rural south-western Uganda: a platform for communicable and non-communicable disease studies.

The General Population Cohort (GPC) was set up in 1989 to examine trends in HIV prevalence and incidence, and their determinants in rural south-western Uganda. Recently, the research questions have included the epidemiology and genetics of communicable and non-communicable diseases (NCDs) to address the limited data on the burden and risk factors for NCDs in sub-Saharan Africa. The cohort comprises all residents (52% aged ≥13years, men and women in equal proportions) within one-half of a rural sub-county, residing in scattered houses, and largely farmers of three major ethnic groups. Data collected through annual surveys include; mapping for spatial analysis and participant location; census for individual socio-demographic and household socioeconomic status assessment; and a medical survey for health, lifestyle and biophysical and blood measurements to ascertain disease outcomes and risk factors for selected participants. This cohort offers a rich platform to investigate the interplay between communicable diseases and NCDs. There is robust infrastructure for data management, sample processing and storage, and diverse expertise in epidemiology, social and basic sciences. For any data access enquiries you may contact the director, MRC/UVRI, Uganda Research Unit on AIDS by email to mrc@mrcuganda.org or the corresponding author.

Concurrent sexual partnerships and associated factors: a cross-sectional population-based survey in a rural community in Africa with a generalised HIV epidemic.

BACKGROUND: Although concurrent sexual partnerships may play an important role in HIV transmission in Africa, the lack of an agreed definition of concurrency and of standard methodological approaches has hindered studies. In a long-standing general population cohort in rural Uganda we assessed the prevalence of concurrency and investigated its association with sociodemographic and behavioural factors and with HIV prevalence, using the new recommended standard definition and methodological approaches. METHODS: As part of the 2010 annual cohort HIV serosurvey among adults, we used a structured questionnaire to collect information on sociodemographic and behavioural factors and to measure standard indicators of concurrency using the recommended method of obtaining sexual-partner histories. We used logistic regression to build a multivariable model of factors independently associated with concurrency. RESULTS: Among those eligible, 3,291 (66%) males and 4,052 (72%) females participated in the survey. Among currently married participants, 11% of men and 25% of women reported being in a polygynous union. Among those with a sexual partner in the past year, the proportion reporting at least one concurrent partnership was 17% in males and 0.5% in females. Polygyny accounted for a third of concurrency in men and was not associated with increased HIV risk. Among men there was no evidence of an association between concurrency and HIV prevalence (but too few women reported concurrency to assess this after adjusting for confounding). Regarding sociodemographic factors associated with concurrency, females were significantly more likely to be younger, unmarried, and of lower socioeconomic status than males. Behavioural factors associated with concurrency were young age at first sex, increasing lifetime partners, and a casual partner in the past year (among men and women) and problem drinking (only men). CONCLUSIONS: Our findings based on the new standard definition and methodological approaches provide a baseline for measuring changes in concurrency and HIV incidence in future surveys, and a benchmark for other studies. As campaigns are now widely conducted against concurrency, such surveys and studies are important in evaluating their effectiveness in decreasing HIV transmission.

Epidemiology of hypertension in low-income countries: a cross-sectional population-based survey in rural Uganda.

OBJECTIVE: Population-based data on burden of hypertension are crucial for planning and implementation of prevention and control strategies but are often limited in developing countries in Africa. We assessed the prevalence of hypertension and related risk factors in a population cohort in rural Uganda initially established for HIV surveys. METHODS: In a cross-sectional population-based survey of hypertension and related risk factors in 2009, trained field staff administered a questionnaire and obtained a single measurement of blood pressure, BMI, waist and hip circumference, waist/hip ratio (WHR) and random plasma glucose. All members of the population cohort aged 13 years and above were eligible for survey participation. Logistic regression was used to evaluate factors associated with high blood pressure, defined as SBP (mmHg) ≥ 140 or DBP ≥ 90. RESULTS: Of the 4801 men and 5372 women who were eligible, 2719 (56.6%) men and 3959 (73.7%) women participated in the survey. The prevalence of high blood pressure was 22.0%, age standardized to the local population. Factors that were independently associated with high blood pressure were increasing age, BMI and elevated glucose in both sexes, extremes of education level (none and secondary or above) among men, and being unmarried and waist circumference ≥ 80 cm among women. Levels of reported hypertension were very low, with nine out 10 people unaware of their condition. CONCLUSION: The use of established research infrastructure, for example, community HIV surveys, can help to generate the population-based data on the prevalence of hypertension and related risk factors needed to inform planning and implementation of effective prevention and control strategies in low-income countries. There is an urgent need to strengthen health services in responding effectively to the large burden of undetected hypertension.

Distribution of hyperglycaemia and related cardiovascular disease risk factors in low-income countries: a cross-sectional population-based survey in rural Uganda.

BACKGROUND: Data on non-communicable disease (NCD) burden are often limited in developing countries in Africa but crucial for planning and implementation of prevention and control strategies. We assessed the prevalence of related cardiovascular disease risk factors (hyperglycaemia, high blood pressure and obesity) in a longstanding population cohort in rural Uganda. METHODS: Trained field staff conducted a cross-sectional population-based survey of cardiovascular disease risk indicators using a questionnaire and simple measurements of body mass index (BMI), waist and hip circumference, waist/hip ratio (WHR), blood pressure and random plasma glucose. All members of the population cohort aged ≥13 years were eligible to participate in the survey. RESULTS: Of the 4801 males and 5372 females who were eligible, 2719 (56.6%) males and 3959 (73.7%) females participated in the survey. Male and female participants had a mean standard deviation (SD) age of 31.8 (18.4) years and 33.7 (17.6) years, respectively. The observed prevalences of probable diabetes (glucose >11.0 mmol/l) and probable hyperglycaemia (7.0-11.0 mmol/l) were 0.4 and 2.9%, respectively. Less than 1% of males and 4% of females were obese (BMI ≥30 kg/m(2)), with 3.6% of males and 14.5% of females being overweight (BMI 25.0-29.9 kg/m(2)). However, in women, the prevalence of abdominal obesity was high (71.3% as measured by WHR and 31.2% as measured by waist circumference). The proportions of male and female current regular smokers were low (13.7 and 0.9%, respectively). The commonest cardiovascular disease risk factor was high blood pressure, with an observed prevalence of 22.5% in both sexes. CONCLUSIONS: Population-based data on the burden of related cardiovascular disease risk factors can aid in the planning and implementation of an effective response to the double burden of communicable diseases and NCDs in this rural population of a low-income country undergoing epidemiological transition.

Nutritional status of children living in a community with high HIV prevalence in rural Uganda: a cross-sectional population-based survey.

OBJECTIVES: To assess the nutritional status of children in a rural community with high HIV prevalence in rural Uganda and to examine the impact of HIV infection at the individual and population level. Methods Cross-sectional population-based survey of children aged 0-12 in a cohort comprising the residents of 25 neighbouring villages in rural southwest Uganda. Anthropometric indicators of nutritional status (height for age, weight for age and weight for height) were assessed in relation to children's HIV serostatus, maternal HIV serostatus and maternal vital status. Children with a Z score of <-2 were defined as undernourished, with a Z score <-2 for weight for age defining underweight, for height for age defining stunting and for weight for height defining wasting. RESULTS: Of 5951 children surveyed, 91% underwent anthropometric measurement: 30% were underweight, 42% stunted and 10% wasted. HIV seroprevalence among children aged 2-12 was 0.7%. The prevalence of underweight was significantly higher in HIV-positive than in HIV-negative children (52%vs. 30%), as was the prevalence of stunting (68%vs. 42%), but there was no significant difference in the prevalence of wasting (4%vs. 9%). There were no significant differences in the prevalences of indicators of undernutrition in children classified by maternal HIV and vital status. CONCLUSIONS: Chronic childhood undernutrition is common in this rural community. HIV infection had a direct effect in worsening children's nutritional status, but no indirect effect in terms of maternal HIV infection or maternal death. The population-level impact of childhood HIV infection on nutritional status is limited on account of the low HIV prevalence in children. The response to undernutrition in children in Africa requires action on many fronts: not only delivering community-wide HIV and nutritional interventions but also addressing the many interacting factors that contributed to childhood undernutrition before the HIV era and still do so now.