Search

Summary Background A large, double-blind, randomised, placebo-controlled trial of repeat BCG found 49% efficacy against leprosy but no protection against tuberculosis after 6–9 years’ follow-up in 1995. We report here additional follow-up, which resulted in greatly increased tuberculosis case numbers, and allowed subgroup analysis. Methods Nearly 47 000 individuals of all ages living in northern Malawi with a BCG vaccine scar were randomly assigned (1:1) between 1986 and 1989 to receive a second BCG or placebo. The investigators and project staff remained masked to all interventions. Enhanced passive surveillance ensured ascertainment of tuberculosis and leprosy to the end of 2018. Tuberculosis case definitions included rigorous microbiological or histological confirmation. Prespecified subgroup analyses were by tuberculosis type, age at vaccination, time since vaccination, previous tuberculin reactivity, HIV status and Mycobacterium tuberculosis lineage. The original trial is registered with ISRCTN registry, ISRCTN11311670. Findings In follow-up until Dec 31, 2018, 824 participants had developed tuberculosis, including 786 with pulmonary disease, of whom 383 (63%) of 607 with known HIV status were HIV positive. There was no effect of a second BCG overall (odds ratio [OR] 0·92; 95% CI 0·80–1·05), or for pulmonary (0·93; 0·81–1·07), or lymph node tuberculosis (0·60; 0·31–1·17). The OR was lower for those with known HIV-negative tuberculosis (0·77; 0·59–1·00), for those vaccinated as children (aged

Introduction Low high-density lipoprotein (HDL) is widely used as a marker of cardiovascular disease risk, although this relationship is not causal and is likely mediated through associations with other risk factors. Low HDL is extremely common in sub-Saharan African populations, and this has often been interpreted to indicate that these populations will have increased cardiovascular risk. We aimed to determine whether the association between HDL and other cardiovascular risk factors differed between populations in sub-Saharan Africa and the UK.Methods We compared data from adults living in Uganda and Malawi (n=26 216) and in the UK (n=8747). We examined unadjusted and adjusted levels of HDL and applied the WHO recommended cut-offs for prevalence estimates. We used spline and linear regression to assess the relationship between HDL and other cardiovascular risk factors.Results HDL was substantially lower in the African than in the European studies (geometric mean 0.9textendash1.2 mmol/L vs 1.3textendash1.8 mmol/L), with African prevalence of low HDL as high as 77geometric mean 3.3textendash3.9 mmol/L vs 4.6textendash5.4 mmol/L). In comparison with European studies the relationship between HDL and adiposity (body mass index, waist to hip ratio) was greatly attenuated in African studies and the relationship with non-HDL cholesterol reversed: in African studies low HDL was associated with lower non-HDL cholesterol. The association between sex and HDL was also different; using the WHO sex-specific definitions, low HDL was substantially more common among women (69textendash77 than men (41textendash59 in Uganda/Malawi.Conclusion The relationship between HDL and sex, adiposity and non-HDL cholesterol in sub-Saharan Africa is different from European populations. In sub-Saharan Africans low HDL is a marker of low overall cholesterol and sex differences are markedly attenuated. Therefore low HDL in isolation is unlikely to indicate raised cardiovascular risk and the WHO sex-based cut-offs are inappropriate.Data from the EXTEND study are available through application to the Peninsula Research Bank (https://exetercrfnihr.org/about/exeter-10000-prb/). For enquiries about access to the Exeter Family Study please contact BS (B.Shields@exeter.ac.uk). The MEIRU data are available through the LSHTM Research Data Compass (https://datacompass.lshtm.ac.uk/961/).

Accurate and affordable point-of-care diagnostics for tuberculosis (TB) are needed. Host serum protein signatures have been derived for use in primary care settings, however validation of these in secondary care settings is lacking. We evaluated serum protein biomarkers discovered in primary care cohorts from Africa reapplied to patients from secondary care. In this nested case-control study, concentrations of 22 proteins were quantified in sera from 292 patients from Malawi and South Africa who presented predominantly to secondary care. Recruitment was based upon intention of local clinicians to test for TB. The case definition for TB was culture positivity for Mycobacterium tuberculosis; and for other diseases (OD) a confirmed alternative diagnosis. Equal numbers of TB and OD patients were selected. Within each group, there were equal numbers with and without HIV and from each site. Patients were split into training and test sets for biosignature discovery. A nine-protein signature to distinguish TB from OD was discovered comprising fibrinogen, alpha-2-macroglobulin, CRP, MMP-9, transthyretin, complement factor H, IFN-gamma, IP-10, and TNF-alpha. This signature had an area under the receiver operating characteristic curve in the training set of 90% (95% CI 86–95%), and, after adjusting the cut-off for increased sensitivity, a sensitivity and specificity in the test set of 92% (95% CI 80–98%) and 71% (95% CI 56–84%), respectively. The best single biomarker was complement factor H [area under the receiver operating characteristic curve 70% (95% CI 64–76%)]. Biosignatures consisting of host serum proteins may function as point-of-care screening tests for TB in African hospitals. Complement factor H is identified as a new biomarker for such signatures.

Background The prevalence of excess adiposity, as measured by elevated body mass index (BMI) and waist-hip ratio (WHR), is increasing in sub-Saharan African (SSA) populations. This could add a considerable burden of cardiovascular and metabolic diseases for which these populations are currently ill-prepared. Evidence from white, European origin populations shows that higher adiposity leads to an adverse lipid profile; whether these associations are similar in all SSA populations requires further exploration. This study compared the association of BMI and WHR with lipid profile in urban Malawi with a contemporary cohort with contrasting socioeconomic, demographic, and ethnic characteristics in the United Kingdom (UK). Methods We used data from 1248 adolescents (mean 18.7 years) and 2277 Malawian adults (mean 49.8 years), all urban-dwelling, and from 3201 adolescents (mean 17.8 years) and 6323 adults (mean 49.7 years) resident in the UK. Adiposity measures and fasting lipids were assessed in both settings, and the associations of BMI and WHR with total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) were assessed by sex and age groups in both studies. Results Malawian female adults were more adipose and had more adverse lipid profiles than their UK counterparts. In contrast, Malawian adolescent and adult males were leaner and had more favourable lipid profiles than in the UK. Higher BMI and WHR were associated with increased TC, LDL-C and TG and reduced HDL-C in both settings. The magnitude of the associations of BMI and WHR with lipids was mostly similar or slightly weaker in the Malawian compared with the UK cohort in both adolescents and adults. One exception was the stronger association between increasing adiposity and elevated TC and LDL-C in Malawian compared to UK men. Conclusions Malawian adult women have greater adiposity and more adverse lipid profiles compared with their UK counterparts. Similar associations of adiposity with adverse lipid profiles were observed for Malawian and UK adults in most age and sex groups studied. Sustained efforts are urgently needed to address the excess adiposity and adverse lipid profiles in Malawi to mitigate a future epidemic of cardio-metabolic disease among the poorest populations.

Background: Low high-density lipoprotein (HDL) is widely used as a marker of cardiovascular disease risk, despite lack of evidence of a casual role. It is extremely common in sub-Saharan African populations, where reported cardiovascular risk is low. We aimed to determine whether the association between HDL and other cardiovascular risk factors differed between populations in sub-Saharan Africa and the UK. Methods: We compared data from adults living in Uganda and Malawi (n=26,216) and the UK (n=8,747). We examined unadjusted and adjusted levels of HDL, and applied WHO recommended cut-offs for prevalence estimates. We used spline and linear regression to assess the relationship between HDL and other cardiovascular risk factors. Findings: Geometric-mean HDL was substantially lower in the African than European studies (0.9-1.2mmol/l vs 1.3-1.8mmol/l), with African prevalence of low-HDL as high as 77%. In comparison to European studies the relationship between HDL and adiposity (BMI, waist-hip ratio) was greatly attenuated in African studies, and the relationship with non-HDL cholesterol reversed: low HDL was associated with lower non-HDL. The association between sex and HDL was also markedly different; using WHO sex-specific definitions low-HDL was substantially more common among women (69-77%) than men (41-59%) in Uganda/Malawi. Interpretation: The relationship between HDL and sex, adiposity and Non-HDL cholesterol in sub-Saharan Africa is markedly different from European populations. Low HDL is a marker of low overall cholesterol, and sex differences are markedly attenuated. Therefore low HDL may not be a reliable marker of cardiovascular risk in Sub-Saharan Africa, and WHO sex based cut-offs are inappropriate. Funding Statement: This work is funded by the National Institute of Health and Social Care (UK), NIHR Global Health Group 17/63/131. Declaration of Interests: All authors report no conflicts of interest in relation to this work. Ethics Approval Statement: The Ugandan cohort was approved by the Uganda Virus Research Institute Science and Ethics Committee and the Uganda National Council of Science and Technology. The Malawian study was approved by the National Health Sciences Research Committee of Malawi nd London School of Hygiene and Tropical Medicine Ethics Committee, UK.The Exeter 10,000 study was approved by the UK NHS Health Research Authority South West Ethics Committee. The Exeter Family Study was approved by the University of Exeter Research Ethics Committee, UK.

Background: Sub-Saharan Africa faces region-specific risk factors for chronic kidney disease (CKD), such as nephrotoxic herbal medicines, antiretroviral therapy and infections, in addition to hypertension and diabetes. However, large epidemiological studies from this area are scarce. Methods: In a cross-sectional survey of non-communicable diseases, we conducted a prevalence sub-study of CKD in two Malawian populations. Study participants (N=5264) of 18 years of age and above were recruited and data on demographics and CKD risk factors were collected. Glomerular filtration rate was estimated (eGFR) using the CKD-EPI equation. Results: The prevalence of eGFR2 was 1.4% (95% CI 1.1 – 1.7%) and eGFR2 was 20.6% (95% CI 19.5 – 21.7%). The rural area had higher age-standardized prevalence of both eGFR2, at 1.8% (95% CI 1.4 – 2.3) and eGFR 2 of 0.69 (95% CI 0.49–0.96; p=0.03). Of participants with eGFR2, 14 (19.4%) had no history of hypertension, diabetes or HIV, while 36 (50%) had a single risk factor of being hypertensive. Conclusions: Impaired renal function is prevalent, but lower than expected, in rural and urban Malawi. Further research is needed to increase understanding of CKD incidence, survival and validation of eGFR calculations in this population.

BackgroundEvidence from high-income countries shows that higher adiposity results in an adverse lipid profile, but it is unclear whether this association is similar in Sub-Saharan African (SSA) populations. This study aimed to assess the association between total and central adiposity measures and lipid profile in Malawi, exploring differences by sex and area of residence (rural/urban).MethodsData from 12,847 rural and 12,096 urban Malawian residents were used. The associations of body mass index (BMI) and waist-hip ratio (WHR) with fasting lipids (total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprote in-cholesterol (HDL-C) and triglycerides (TG)) were assessed by area and sex.ResultsA great proportion of adults have high BMI and WHR, and this was associated with adverse lipid profiles; higher BMI and WHR were linearly associated with increased TC, LDL-C and TG and reduced HDL-C. BMI was more strongly related to fasting lipids than was WHR. The associations of adiposity with adverse lipid profile were stronger in urban compared with rural residents.ConclusionsThe consistent associations observed of higher adiposity with adverse lipid profiles in females and males living in rural and urban areas of Malawi highlight the emerging adverse cardio-metabolic epidemic in this poor population. Our findings underline the potential utility of BMI in estimating cardiovascular risk and highlight the need for greater investment to understand the long-term health outcomes of obesity and adverse lipid profiles and the extent to which lifestyle changes and treatments effectively prevent and modify adverse cardio-metabolic outcomes.Key messagesHigher body mass index (BMI) and waist to hip ratio (WHR) are associated with increased total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C) and triglycerides (TG) and reduced high density lipoprotein-cholesterol (HDL-C) in a large sub-Saharan African population.Total adiposity is more strongly associated with adverse lipid profile than central adiposity.Despite the higher BMI and the less favourable lipid profile in urban residents, stronger associations between BMI and TC, LDL-C and TG are observed in rural than urban residents.

Background: \ud High dietary sodium intake is a major risk factor for hypertension. Data on population sodium intake are scanty in sub-Saharan Africa, despite a high hypertension prevalence in most countries.\ud \ud Objective: \ud We aimed to determine daily sodium intake in urban and rural communities in Malawi.\ud \ud Design: \ud In an observational cross-sectional survey, data were collected on estimated household-level per capita sodium intake, based on how long participants reported that a defined quantity of plain salt lasts in a household. In a subset of 2078 participants, 24-h urinary sodium was estimated from a morning spot urine sample.\ud \ud Results: \ud Of 29,074 participants, 52.8% of rural and 50.1% of urban individuals lived in households with an estimated per capita plain salt consumption >5 g/d. Of participants with urinary sodium data, 90.8% of rural and 95.9% of urban participants had estimated 24-h urinary sodium >2 g/d; there was no correlation between household per capita salt intake and estimated 24-h urinary sodium excretion. Younger adults were more likely to have high urinary sodium and to eat food prepared outside the home than were those over the age of 60 y. Households with a member with previously diagnosed hypertension had reduced odds (OR: 0.59; 95% CI: 0.51, 0.68) of per capita household plain salt intake >5 g/d, compared with those where hypertension was undiagnosed.\ud \ud Conclusions: \ud Sodium consumption exceeds the recommended amounts for most of the population in rural and urban Malawi. Population-level interventions for sodium intake reduction with a wide focus are needed, targeting both sources outside the home as well as home cooking. This trial was registered at clinicaltrials.gov as NCT03422185.

Background In Africa, albendazole and ivermectin are currently used in combination for annual mass drug administration (MDA) for lymphatic filariasis (LF) elimination. Rapid and sustained clearance is desirable for public health impact and elimination of LF. Increasing the dose and/or frequency of albendazole and ivermectin treatment may be more effective in clearing microfilariae than standard MDA. Methods We conducted a randomised controlled open label trial in northern Malawi comparing three modified treatment groups to standard dosage of ivermectin and albendazole in adults with confirmed circulating LF antigen and microfilaria. Participants were followed-up every 6 months for 2 years for repeat microfilarial counts and safety assessments. Results A total of 1851 adults were screened and 70 with microfilarial counts >80 microfilariae/ml were randomised. All treatment groups achieved a significant reduction of microfilariae levels by 12- and 24-months of follow-up. Doubling the standard dose and administering it twice yearly showed a non-significant tendency towards faster and more complete clearance. There were no serious adverse reactions. Conclusions In this small study, all regimens effectively cleared microfilaria. Standard treatment may be adequate in settings like Malawi but not in all endemic settings and larger studies are required to demonstrate benefit of higher dosages. [ClinicalTrials.gov identifier: NCT01213576].