Uganda Genome Resource Enables Insights into Population History and Genomic Discovery in Africa.

Genomic studies in African populations provide unique opportunities to understand disease etiology, human diversity, and population history. In the largest study of its kind, comprising genome-wide data from 6,400 individuals and whole-genome sequences from 1,978 individuals from rural Uganda, we find evidence of geographically correlated fine-scale population substructure. Historically, the ancestry of modern Ugandans was best represented by a mixture of ancient East African pastoralists. We demonstrate the value of the largest sequence panel from Africa to date as an imputation resource. Examining 34 cardiometabolic traits, we show systematic differences in trait heritability between European and African populations, probably reflecting the differential impact of genes and environment. In a multi-trait pan-African GWAS of up to 14,126 individuals, we identify novel loci associated with anthropometric, hematological, lipid, and glycemic traits. We find that several functionally important signals are driven by Africa-specific variants, highlighting the value of studying diverse populations across the region.

Which government policies to create sustainable food systems have the potential to simultaneously address undernutrition, obesity and environmental sustainability?

INTRODUCTION: A transformation of food systems is urgently needed, given their contribution to three ongoing and interlinked global health pandemics: (1) undernutrition and food insecurity, (2) obesity and non-communicable diseases (NCDs), and (3) climate change and biodiversity loss. As policymakers make decisions that shape food systems, this study aimed to identify and prioritise policies with double- or triple-duty potential to achieve healthier and more environmentally sustainable food systems. METHODS: This study undertook a 4-step methodological approach, including (i) a compilation of international policy recommendations, (ii) an online survey, (iii) four regional workshops with international experts and (iv) a ranking for prioritisation. Policies were identified and prioritised based on their double- or triple-duty potential, synergies and trade-offs. Using participatory and transdisciplinary approaches, policies were identified to have double- or triple-duty potential if they were deemed effective in tackling two or three of the primary outcomes of interest: (1) undernutrition, (2) obesity/NCDs and (3) environmental degradation. RESULTS: The desk review identified 291 recommendations for governments, which were merged and classified into 46 initially proposed policies. Based on the results from the online survey, 61% of those policies were perceived to have double- or triple-duty potential. During the workshops, 4 potential synergies and 31 trade-offs of these policies were identified. The final list of 44 proposed policies for healthier and more environmentally sustainable food systems created was divided into two main policy domains: 'food supply chains' and 'food environments'. The outcome with the most trade-offs identified was 'undernutrition', followed by 'environmental sustainability', and 'obesity/NCDs'. Of the top five expert-ranked food supply chain policies, two were perceived to have triple-duty potential: (a) incentives for crop diversification; (b) support for start-ups, and small- and medium-sized enterprises. For food environments, three of the top five ranked policies had perceived triple-duty potential: (a) affordability of healthier and more sustainable diets; (b) subsidies for healthier and more sustainable foods; (c) restrictions on children's exposure to marketing through all media. CONCLUSION: This study identified and prioritised a comprehensive list of double- and triple-duty government policies for creating healthier and more environmentally sustainable food systems. As some proposed policies may have trade-offs across outcomes, they should be carefully contextualised, designed, implemented and monitored.

Determinants of under-five mortality in informal settlements in Nairobi, Kenya from 2002 to 2018.

BACKGROUND: Childhood mortality persists as a significant public health challenge in low and middle-income countries and is uneven within countries, with poor communities such as urban informal settlements bearing the highest burden. There is limited literature from urban informal settlements on the risk factors of mortality. We assessed under-five mortality and associated risk factors from the period 2002 to 2018 in Nairobi urban informal settlements. METHODS: We used secondary data from the Nairobi Urban Health and Demographic Surveillance System (NUHDSS), a longitudinal surveillance platform that routinely collects individual and household-level data in two informal settlements (Viwandani and Korogocho) in Nairobi, Kenya. We used Kaplan-Meier curves to estimate overall survival and the Cox proportional hazard model with a frailty term to evaluate the impact of risk factors on survival time. RESULTS: Overall under-five survival rate was 96.8% and this improved from 82.6% (2002-2006) to 95% (2007-2012) and 98.4% (2012-2018). There was a reduced risk of mortality among children who had BCG vaccination, those born to a married mother or a mother not engaging in any income-generating activity (both from 2007 to 2011), children from singleton pregnancy, children born in Viwandani slum and ethnicity of the child. CONCLUSION: Under-five mortality is still high in urban informal settlements. Targeted public health interventions such as vaccinations and interventions empowering women such as single mothers, those with multiple pregnancies, and more impoverished slums are needed to further reduce under-five mortality in urban informal settlements.

The economic burden of type 2 diabetes on the public healthcare system in Kenya: a cost of illness study.

BACKGROUND: The burden of chronic non-communicable diseases (NCDs) is a growing public health concern. The availability of cost-of-illness data, particularly public healthcare costs for NCDs, is limited in Sub-Saharan Africa (SSA), yet such data evidence is needed for policy action. OBJECTIVE: The objective of this study was to estimate the economic burden of type 2 diabetes (T2D) on Kenya's public healthcare system in 2021 and project costs for 2045. METHODS: This was a cost-of-illness study using the prevalence-based bottom-up costing approach to estimate the economic burden of T2D in the year 2021. We further conducted projections on the estimated costs for the year 2045. The costs were estimated corresponding to the care, treatment, and management of diabetes and some diabetes complications based on the primary data collected from six healthcare facilities in Nairobi and secondary costing data from previous costing studies in low and middle-income countries (LMICs). The data capture and costing analysis were done in Microsoft Excel 16, and sensitivity analysis was conducted on all the parameters to estimate the cost changes. RESULTS: The total cost of managing T2D for the healthcare system in Kenya was estimated to be US$ 635 million (KES 74,521 million) in 2021. This was an increase of US$ 2 million (KES 197 million) considering the screening costs of undiagnosed T2D in the country. The major cost driver representing 59% of the overall costs was attributed to T2D complications, with nephropathy having the highest estimated costs of care and management (US$ 332 million (KES 36, 457 million). The total cost for T2D was projected to rise to US$ 1.6 billion (KES 177 billion) in 2045. CONCLUSION: This study shows that T2D imposes a huge burden on Kenya's healthcare system. There is a need for government and societal action to develop and implement policies that prevent T2D, and appropriately plan care for those diagnosed with T2D.

Discovery and fine-mapping of kidney function loci in first genome-wide association study in Africans.

Genome-wide association studies (GWAS) of kidney function have uncovered hundreds of loci, primarily in populations of European ancestry. We have undertaken the first continental African GWAS of estimated glomerular filtration rate (eGFR), a measure of kidney function used to define chronic kidney disease (CKD). We conducted GWAS of eGFR in 3288 East Africans from the Uganda General Population Cohort (GPC) and replicated in 8224 African Americans from the Women's Health Initiative. Loci attaining genome-wide significant evidence for association (P < 5 × 10-8) were followed up with Bayesian fine-mapping to localize potential causal variants. The predictive power of a genetic risk score (GRS) constructed from previously reported trans-ancestry eGFR lead single nucleotide polymorphism (SNPs) was evaluated in the Uganda GPC. We identified and validated two eGFR loci. At the glycine amidinotransferase (GATM) locus, the association signal (lead SNP rs2433603, P = 1.0 × 10-8) in the Uganda GPC GWAS was distinct from previously reported signals at this locus. At the haemoglobin beta (HBB) locus, the association signal (lead SNP rs141845179, P = 3.0 × 10-8) has been previously reported. The lead SNP at the HBB locus accounted for 88% of the posterior probability of causality after fine-mapping, but did not colocalise with kidney expression quantitative trait loci. The trans-ancestry GRS of eGFR was not significantly predictive into the Ugandan population. In the first GWAS of eGFR in continental Africa, we validated two previously reported loci at GATM and HBB. At the GATM locus, the association signal was distinct from that previously reported. These results demonstrate the value of performing GWAS in continental Africans, providing a rich genomic resource to larger consortia for further discovery and fine-mapping. The study emphasizes that additional large-scale efforts in Africa are warranted to gain further insight into the genetic architecture of CKD.

Effectiveness of self-financing patient-led support groups in the management of hypertension and diabetes in low- and middle-income countries: Systematic review.

OBJECTIVE: There is insufficient evidence on the role of self-financing patient support groups in the control of blood pressure (BP) and/or diabetes in low- and middle-income countries (LMICs). We conducted a systematic review to investigate the effectiveness of these groups in BP and glycaemic control. METHODS: We searched PubMed, Embase, SCOPUS, Web of Science, Global Health, African Journals Online, CINAHL and African Index Medicus for published peer-reviewed articles from inception up to November 2021. Grey literature was obtained from OpenGrey. Studies on patient support groups for hypertension and/or diabetes with a component of pooling financial resources, conducted in LMICs, were included. Narrative reviews, commentaries, editorials and articles published in languages other than English and French were excluded. Study quality and risk of bias were assessed using the National Institutes of Health Quality assessment tool and the revised Cochrane risk-of-bias tool. Results are reported according to PRISMA guidelines. RESULTS: Of 724 records screened, three studies met the criteria: two trials conducted in Kenya and a retrospective cohort study conducted in Cambodia. All studies reported improvement in BP control after 12 months follow-up with reductions in systolic BP of 23, 14.8, and 16.9 mmHg, respectively. Two studies reported diabetes parameters. The first reported improvement in HbA1c (reduction from baseline 10.8%, to 10.6% at 6 months) and random blood sugar (baseline 8.9 mmol/L, to 8.5 mmol/L at 6 months) but these changes did not achieve statistical significance. The second reported a reduction in fasting blood glucose (baseline-216 mg/dl, 12 months-159 mg/dl) in diabetic patients on medication. CONCLUSION: Self-financing patient support groups for diabetes and hypertension are potentially effective in the control of BP and diabetes in LMICs. More studies are needed to add to the scarce evidence base on the role of self-financing patient support groups.

Mobility limitations and emotional dysfunction in old age: The moderating effects of physical activity and social ties.

BACKGROUND: This study aims to examine the association between mobility limitations and emotional dysfunction among older Ghanaians and evaluate the buffering effect of physical activity (PA) and social ties in this association. METHODS: The analysis included 1201 adults aged ≥50 from the 2016-17 Aging, Health, Psychological Well-being, and Health-seeking Behavior study. The Medical Outcomes Study Short Form-36 (MOS SF-36) assessed mobility limitations and emotional dysfunction. We measured PA using the International Physical Activity Questionnaire Short Form (IPAQ-SF). Hierarchical OLS regressions were performed to evaluate the hypothesized direct and interactive relationships. RESULTS: The mean age of the sample was 66.2 (SD = 11.9), and 63.3% were women. After full adjustment for potential confounders, OLS regressions found that mobility limitations increased the risk of emotional dysfunction (ß = 0.113, p = 0.004). Moreover, social ties (ß = -0.157, p < 0.001) and PA (ß = -0.096, p < 0.001) were independently and negatively associated with emotional dysfunction. We finally found a significant effect modification of the association of mobility limitations with emotional dysfunction by PA (ß = -0.040, p < 0.002) and social ties (ß = -0.013, p = 0.013). CONCLUSIONS: Mobility-enhancing strategies such as engagement in positive behavioral choices, focusing on regular PA, and maintaining resourceful interpersonal social networks can mitigate the impact of mobility limitations on emotional dysfunction in later life.

Feasibility and acceptability of using biometric fingerprinting to track migrations and support retention in HIV prevention research in fishing population in East Africa.

INTRODUCTION: Fishing populations constitute a suitable key population amongst which to conduct HIV prevention trials due to very high HIV prevalence and incidence, however, these are highly mobile populations. We determined the feasibility and acceptability of using fingerprinting and geographical positioning systems to describe mobility patterns and retention among fisherfolks on the shoreline of Lake Victoria in South-western Uganda. METHODS: Between August 2015 and January 2017, two serial cross-sectional surveys were conducted during which fingerprinting of all residents aged 18-30 years on the shoreline of Lake Victoria was done. A mapper moving ahead of the survey team, produced village maps and took coordinates of every household. These were accessed by the survey team that assigned household and individual unique identifiers (ID) and collected demographic data. Using the assigned IDs, individuals were enrolled and their fingerprints scanned. The fingerprinting was repeated 6 months later in order to determine the participant's current household. If it was different from that at baseline, a new household ID was assigned which was used to map migrations both within and between villages. RESULTS: At both rounds, over 99% accepted to be fingerprinted. No fingerprinting faults were recorded at baseline and the level was under 1% at round two. Over 80% of the participants were seen at round two and of these, 16.3%, had moved to a new location whilst the majority, 85%, stayed within the same village. Movements between villages were mainly observed for those resident in large villages. Those who did not consider a fishing village to be their permanent home were less likely to be migrants than permanent residents (adjusted odds ratio = 0.37, 95%CI:0.15-0.94). CONCLUSION: Use of fingerprinting in fishing populations is feasible and acceptable. It is possible to track this mobile population for clinical trials or health services using this technology since most movements could be traced within and between villages.

Community perceptions on the factors in the social food environment that influence dietary behaviour in cities of Kenya and Ghana: a Photovoice study.

OBJECTIVE: To explore communities' perspectives on the factors in the social food environment that influence dietary behaviours in African cities. DESIGN: A qualitative study using participatory photography (Photovoice). Participants took and discussed photographs representing factors in the social food environment that influence their dietary behaviours. Follow-up in-depth interviews allowed participants to tell the 'stories' of their photographs. Thematic analysis was conducted, using data-driven and theory-driven (based on the socio-ecological model) approaches. SETTING: Three low-income areas of Nairobi (n 48) in Kenya and Accra (n 62) and Ho (n 32) in Ghana. PARTICIPANTS: Adolescents and adults, male and female aged ≥13 years. RESULTS: The 'people' who were most commonly reported as influencers of dietary behaviours within the social food environment included family members, friends, health workers and food vendors. They mainly influenced food purchase, preparation and consumption, through (1) considerations for family members' food preferences, (2) considerations for family members' health and nutrition needs, (3) social support by family and friends, (4) provision of nutritional advice and modelling food behaviour by parents and health professionals, (5) food vendors' services and social qualities. CONCLUSIONS: The family presents an opportunity for promoting healthy dietary behaviours among family members. Peer groups could be harnessed to promote healthy dietary behaviours among adolescents and youth. Empowering food vendors to provide healthier and safer food options could enhance healthier food sourcing, purchasing and consumption in African low-income urban communities.

Readiness of health facilities to deliver non-communicable diseases services in Kenya: a national cross-sectional survey.

BACKGROUND: Non-communicable diseases (NCDs) account for an estimated 71% of all global deaths annually and nearly 80% of these deaths occur in low- and middle-income countries. This study aimed to assess the readiness of existing healthcare systems at different levels of health care in delivering NCDs management and prevention services in Kenya. METHODS: A cross-sectional survey of 258 facilities was conducted between June 2019 and December 2020 using multistage sampling, examining facility readiness based on the availability of indicators such as equipment, diagnostic capacity, medicines and commodities, trained staff and guidelines for NCDs management. Readiness scores were calculated as the mean availability of tracer items expressed as a percentage and a cut-off threshold of ≥ 70% was used to classify facilities as "ready" to manage NCDs. Descriptive and bivariate analyses were performed to assess the readiness of facilities by type, level, and location settings. Logistic regressions were used to identify factors associated with the readiness of facilities to provide disease-specific services. RESULTS: Of the surveyed facilities, 93.8% offered chronic respiratory disease (CRD) diagnosis and/or management services, 82.2% diabetes mellitus, 65.1% cardiovascular disease (CVD), and only 24.4% cervical cancer screening services. The mean readiness scores for diabetes mellitus (71%; 95% CI: 67-74) and CVD (69%; 95% CI: 66-72) were relatively high. Although CRD services were reportedly the most widely available, its mean readiness score was low (48%; 95% CI: 45-50). The majority of facilities offering cervical cancer services had all the necessary tracer items available to provide these services. Modeling results revealed that private facilities were more likely to be "ready" to offer NCDs services than public facilities. Similarly, hospitals were more likely "ready" to provide NCDs services than primary health facilities. These disparities in service readiness extended to the regional and urban/rural divide. CONCLUSIONS: Important gaps in the current readiness of facilities to manage NCDs in Kenya at different levels of health care were revealed, showing variations by disease and healthcare facility type. A collective approach is therefore needed to bridge the gap between resource availability and population healthcare needs.

Perspectives on returning individual and aggregate genomic research results to study participants and communities in Kenya: a qualitative study.

BACKGROUND: A fundamental ethical challenge in conducting genomics research is the question of what and how individual level genetic findings and aggregate genomic results should be conveyed to research participants and communities. This is within the context of minimal guidance, policies, and experiences, particularly in Africa. The aim of this study was to explore the perspectives of key stakeholders' on returning genomics research results to participants in Kenya. METHODS: This qualitative study involved focus group discussions (FGDs) and in-depth interviews (IDIs) with 69 stakeholders. The purposively selected participants, included research ethics committee (REC) members (8), community members (44), community resource persons (8), and researchers (9). A semi-structured interview guide was used to facilitate discussions. Six FGDs and twenty-five (IDIs) were conducted among the different stakeholders. The issues explored in the interviews included: (1) views on returning results, (2) kind of results to be returned, (3) value of returning results to participants, and (4) challenges anticipated in returning results to participants and communities. The interviews were audio-recorded, transcribed verbatim, and coded in Nvivo 12 pro. Thematic and content analysis was conducted. RESULTS: Participants agreed on the importance of returning genomic results either as individual or aggregate results. The most cited reasons for returning of genomic results included recognizing participants' contribution to research, encouraging participation in future research, and increasing the awareness of scientific progress. Other aspects on how genomic research results should be shared included sharing easy to understand results in the shortest time possible and maintaining confidentiality when sharing sensitive results. CONCLUSIONS: This study identified key stakeholders' perspectives on returning genomic results at the individual and community levels in two urban informal settlements of Nairobi. The majority of the participants expect to receive feedback about their genomic results, and it is an obligation for researchers to see how to best fulfil it.

The African Genome Variation Project shapes medical genetics in Africa.

Given the importance of Africa to studies of human origins and disease susceptibility, detailed characterization of African genetic diversity is needed. The African Genome Variation Project provides a resource with which to design, implement and interpret genomic studies in sub-Saharan Africa and worldwide. The African Genome Variation Project represents dense genotypes from 1,481 individuals and whole-genome sequences from 320 individuals across sub-Saharan Africa. Using this resource, we find novel evidence of complex, regionally distinct hunter-gatherer and Eurasian admixture across sub-Saharan Africa. We identify new loci under selection, including loci related to malaria susceptibility and hypertension. We show that modern imputation panels (sets of reference genotypes from which unobserved or missing genotypes in study sets can be inferred) can identify association signals at highly differentiated loci across populations in sub-Saharan Africa. Using whole-genome sequencing, we demonstrate further improvements in imputation accuracy, strengthening the case for large-scale sequencing efforts of diverse African haplotypes. Finally, we present an efficient genotype array design capturing common genetic variation in Africa.

Prevalence and socio-demographic correlates of tobacco and alcohol use in four sub-Saharan African countries: a cross-sectional study of middle-aged adults.

BACKGROUND: Substance misuse is a global public health problem. In addition to social and economic concerns, consumption of tobacco and alcohol is associated with susceptibility to cardiovascular, respiratory, and infectious diseases, cancers, and risk of transition to substance use disorders. African data suggest regional differences in the prevalence and patterns of substance use, but a number of key questions remain. This cross-sectional population-based study of middle-aged adults aims to examine prevalence and socio-demographic correlates of substance use in four sub-Saharan African countries, in rural and urban settings. METHODS: Participants aged between 40 and 60 years were recruited from six research centres as part of the Africa Wits-INDEPTH partnership for Genomic Research study. Data on patterns of tobacco and alcohol consumption was captured, and the latter further assessed using the CAGE (cut-annoyed-guilty-eye) questionnaire. RESULTS: Data from 10,703 participants suggested that more men (68.4%) than women (33.3%) were current substance users. The prevalence of current smoking was significantly higher in men than in women (34.5% vs 2.1%, p < 0.001). Smokeless tobacco was used more by women than men (14.4% vs 5.3%, p < 0.001). Current smoking was associated with alcohol consumption in men, and smoking cessation in men was associated with being a former drinker, having higher socio-economic status, and if married or cohabiting. Current alcohol consumption was higher in men, compared to women (60.3% vs 29.3%), and highest in men from Soweto (70.8%) and women from Nanoro (59.8%). The overall prevalence of problematic alcohol consumption among men was 18.9%, and women 7.3%. Men were significantly more likely to develop problematic drinking patterns, and this was more common in those who were divorced or widowed, and in current smokers. CONCLUSIONS: Regional variation in the patterns and prevalence of substance use was observed across study sites, and in rural and urban settings. The high levels of substance use recorded in this study are of concern due to the increased risk of associated morbidities. Further longitudinal data will be valuable in determining trends in substance misuse in Africa.

Highly Diverse Hepatitis C Strains Detected in Sub-Saharan Africa Have Unknown Susceptibility to Direct-Acting Antiviral Treatments.

The global plan to eradicate hepatitis C virus (HCV) led by the World Health Organization outlines the use of highly effective direct-acting antiviral drugs (DAAs) to achieve elimination by 2030. Identifying individuals with active disease and investigation of the breadth of diversity of the virus in sub-Saharan Africa (SSA) is essential as genotypes in this region (where very few clinical trials have been carried out) are distinct from those found in other parts of the world. We undertook a population-based, nested case-control study in Uganda and obtained additional samples from the Democratic Republic of Congo (DRC) to estimate the prevalence of HCV, assess strategies for disease detection using serological and molecular techniques, and characterize genetic diversity of the virus. Using next-generation and Sanger sequencing, we aimed to identify strains circulating in East and Central Africa. A total of 7,751 Ugandan patients were initially screened for HCV, and 20 PCR-positive samples were obtained for sequencing. Serological assays were found to vary significantly in specificity for HCV. HCV strains detected in Uganda included genotype (g) 4k, g4p, g4q, and g4s and a newly identified unassigned g7 HCV strain. Two additional unassigned g7 strains were identified in patients originating from DRC (one partial and one full open reading frame sequence). These g4 and g7 strains contain nonstructural (ns) protein 3 and 5A polymorphisms associated with resistance to DAAs in other genotypes. Clinical studies are therefore indicated to investigate treatment response in infected patients. Conclusion: Although HCV prevalence and genotypes have been well characterized in patients in well-resourced countries, clinical trials are urgently required in SSA, where highly diverse g4 and g7 strains circulate.

Uptake of long acting reversible contraception following integrated couples HIV and fertility goal-based family planning counselling in Catholic and non-Catholic, urban and rural government health centers in Kigali, Rwanda.

BACKGROUND: When integrated with couples' voluntary HIV counselling and testing (CVCT), family planning including long acting reversible contraceptives (LARC) addresses prongs one and two of prevention of mother-to-child transmission (PMTCT). METHODS: In this observational study, we enrolled equal numbers of HIV concordant and discordant couples in four rural and four urban clinics, with two Catholic and two non-Catholic clinics in each area. Eligible couples were fertile, not already using a LARC method, and wished to limit or delay fertility for at least 2 years. We provided CVCT and fertility goal-based family planning counselling with the offer of LARC and conducted multivariate analysis of clinic, couple, and individual predictors of LARC uptake. RESULTS: Of 1290 couples enrolled, 960 (74%) selected LARC: Jadelle 5-year implant (37%), Implanon 3-year implant (26%), or copper intrauterine device (IUD) (11%). Uptake was higher in non-Catholic clinics (85% vs. 63% in Catholic clinics, p < 0.0001), in urban clinics (82% vs. 67% in rural clinics, p < 0.0001), and in HIV concordant couples (79% vs. 70% of discordant couples, p = .0005). Religion of the couple was unrelated to clinic religious affiliation, and uptake was highest among Catholics (80%) and lowest among Protestants (70%) who were predominantly Pentecostal. In multivariable analysis, urban location and non-Catholic clinic affiliation, Catholic religion of woman or couple, younger age of men, lower educational level of both partners, non-use of condoms or injectable contraception at enrollment, prior discussion of LARC by the couple, and women not having concerns about negative side effects of implant were associated with LARC uptake. CONCLUSIONS: Fertility goal-based LARC recommendations combined with couples' HIV counselling and testing resulted in a high uptake of LARC methods, even among discordant couples using condoms for HIV prevention, in Catholic clinics, and in rural populations. This model successfully integrates prevention of HIV and unplanned pregnancy.

HIV, HCMV and mycobacterial antibody levels: a cross-sectional study in a rural Ugandan cohort.

OBJECTIVES: A growing evidence base implicates human cytomegalovirus (HCMV) as a risk factor for TB disease. We investigated total IgG and mycobacteria-specific antibodies in a cross-sectional study nested within a rural Ugandan General Population Cohort (GPC), in relation to HIV infection and the magnitude of HCMV IgG response. METHODS: Sera from 2189 individuals (including 27 sputum-positive TB cases) were analysed for antibodies against mycobacteria (Ag85A, PPD, LAM, ESAT6/CFP10) and HCMV, tetanus toxoid (TT) and total IgG. RESULTS: Anti-mycobacterial antibodies increased with age until approximately 20 years, when they plateaued. Higher HCMV exposure (measured by IgG) was associated with lower levels of some anti-mycobacterial antibodies, but no increase in total IgG. HIV infection was associated with a decrease in all anti-mycobacterial antibodies measured and with an increase in total IgG. CONCLUSIONS: The increase in anti-mycobacterial antibodies with age suggests increasing exposure to non-tuberculous mycobacteria (NTM), and to M.tb itself. HIV infection is associated with decreased levels of all mycobacterial antibodies studied here, and high levels of HCMV IgG are associated with decreased levels of some mycobacterial antibodies. These findings point towards the importance of humoral immune responses in HIV/TB co-infection and highlight a possible role of HCMV as a risk factor for TB disease.

Trends of serum phospholipid fatty acids over time in rural Uganda: evidence of nutritional transition?

Non-communicable diseases are projected to become the most common causes of death in Africa by 2030. The impact on health of epidemiological and nutritional transitions in sub-Saharan Africa remains unclear. To assess the trends of dietary fatty acids over time in Uganda, we examined fatty acids in serum collected from individuals in rural south-west Uganda, at three time points over two decades. Independent cross-sectional samples of 915 adults and children were selected from the general population cohort in 1990 (n 281), 2000 (n 283) and 2008 (n 351). Serum phospholipid fatty acids were measured by GC. Multivariate regression analyses were performed to compare the geometric means of fatty acids by time period. Serum fatty acid profiling showed high proportions of SFA, cis-MUFA and industrial trans-fatty acids (iTFA), likely to be biomarkers of high consumption of palm oil and hydrogenated fats. In contrast, proportions of n-6 and n-3 PUFA from vegetable oils and fish were low. From 1990 to 2008, serum phospholipids showed increases in absolute amounts of SFA (17·3 % increase in adults and 26·4 % in children), MUFA (16·7 % increase in adults and 16·8 % in children) and n-6:n-3 PUFA (40·1 % increase in adults and 39·8 % in children). The amount of elaidic acid, iTFA from hydrogenated fats, increased in children (60·1 % increase). In this rural Ugandan population, we show evidence of unfavourable trends over time of dietary fatty acids.

Factors associated with vaccination completion and retention among HIV negative female sex workers enrolled in a simulated vaccine efficacy trial in Kampala, Uganda.

BACKGROUND: Female sex workers (FSWs) at substantial risk of HIV are potentially a suitable group for HIV prevention trials including vaccine trials. Few HIV vaccine preparatory studies have been conducted among FSWs in Sub-Saharan Africa (SSA); data are therefore limited on acceptability of vaccine trial procedures. We determined vaccination completion and one-year retention among FSWs in Kampala, Uganda. METHODS: We conducted a prospective study that simulated a vaccine efficacy trial among HIV negative FSWs (18-49 years). Hepatitis B vaccine (Engerix B) was used to mimic an HIV vaccine product. Volunteers received 1 ml intramuscular injection at 0, 1 and 6 months, and made additional visits (3 days post-vaccination and months 3, 9 and 12). They were censored at that visit if diagnosed as HIV positive or pregnant. We collected socio-demographic, behavioral and clinical data at baseline, 6 and 12 months and fitted Poisson regression models with robust standard error to find factors associated with vaccination completion and retention. RESULTS: We enrolled 290 volunteers (median age 27 years) of whom 230 reached a study end-point as follows: 7 became HIV infected, 11 became pregnant and 212 completed both the vaccination schedule and 12-month visit giving a retention of 77.9% (212/272). Vaccination completion was 82.4%. Non-retention at 1 year was more likely among those reporting symptoms of genital ulcer disease (GUD) in the past 3 months (IRR 1.90; 95% CI 1.09-3.32) and those < 35 years; (IRR 6.59; 95% CI 2.11-20.57). Non-completion of the vaccination schedule was associated with being < 35 years (IRR 13.10; 95% CI 1.89-90.92, reporting GUD symptoms (IRR 3.02; 95% CI 1.71-5.33) and reporting consistent condom use with new sexual partners (IRR 2.57; 95% CI 1.10-6.07). CONCLUSIONS: FSWs are at substantial risk of HIV infection and yet willing to participate in HIV vaccine and prevention research; young FSWs should be empowered, and those reporting GUD symptoms need close follow up to improve participation in future HIV vaccine trials.

Kaposi Sarcoma-Associated Herpesvirus in a Rural Ugandan Cohort, 1992-2008.

Background: The prevalence and titers of antibodies against Kaposi sarcoma-associated herpesvirus (KSHV) in rural Africa are not completely understood, nor are their trends over time in populations in which human immunodeficiency virus (HIV) is also endemic. We examined prevalence, titers, temporal trends, and determinants of anti-KSHV antibodies in each of 3 time periods (1990-1991, 1999-2000, and 2007-2008) within a long-standing, rural population-based cohort in southwestern Uganda. Methods: For each period, we measured antibodies to the K8.1 and ORF73 KSHV antigens in approximately 3000 people of all ages (1:1 sex ratio). Results: In all periods, KSHV prevalence increased rapidly through childhood to approximately 90% by age 15 years, plateauing at approximately 95% thereafter. Similarly, antibody titers, particularly against the lytic antigen K8.1, were among the highest seen and increased significantly with age, suggesting sustained viral replication in this population. Male sex was also independently associated with higher prevalence, whereas HIV coinfection was not. A modest reduction in prevalence among children was noted in the most recent period. Conclusions: KSHV seroprevalence and antibodies titers in this rural Ugandan population are the highest yet reported, perhaps reflecting frequent viral reactivation and persistently elevated transmission.

Relationship Between Anemia, Malaria Coinfection, and Kaposi Sarcoma-Associated Herpesvirus Seropositivity in a Population-Based Study in Rural Uganda.

We examined anemia and malaria as risk factors for Kaposi sarcoma-associated herpesvirus (KSHV) seropositivity and antibody levels in a long-standing rural Ugandan cohort, in which KSHV is prevalent. Samples from 4134 children, aged 1-17 years, with a sex ratio of 1:1, and 3149 adults aged 18-103 years, 41% of whom were males, were analyzed. Among children, malaria infection was associated with higher KSHV prevalence (61% vs 41% prevalence among malaria infected and uninfected, respectively); malaria was not assessed in adults. Additionally, lower hemoglobin level was associated with an increased prevalence of KSHV seropositivity, both in children and in adults.