HIV/AIDS testing and counselling.

No abstract availabl

Tuberculosis and gender: exploring the patterns in a case control study in Malawi.

BACKGROUND: In many populations there is an excess of tuberculosis in young women and older men. We explored possible explanations for these patterns, concentrating on human immunodeficiency virus (HIV) status, pregnancy, smoking, cooking smoke exposure, contact with tuberculosis cases within the household or outside, and gender differences in health service usage and diagnostic delay. DESIGN: Case control study in Karonga District, Malawi. METHODS: Cases were new tuberculosis patients with bacteriological or histological evidence of tuberculosis. Controls were selected in the community using field-based random sampling. RESULTS: The study included 598 tuberculosis cases and 992 controls, with an excess of tuberculosis in young females and older males. This was more marked in HIV-positive individuals. HIV infection was a similarly strong risk factor for tuberculosis in both men and women. Tuberculosis was associated with having a family or household contact with tuberculosis for both men and women. For women, but not men, contacts outside the close family and household were also a risk factor for tuberculosis. Tuberculosis was not associated with current or recent pregnancy, or with smoking or smoke exposure. There were no differences between men and women in health service usage or delay. CONCLUSIONS: In this population, HIV infection and contacts with known tuberculosis patients are important determinants of the gender distribution of cases

Impact of changing diagnostic criteria for smear-positive tuberculosis: a cohort study in Malawi.

We assessed the impact on measured burden and outcomes of the revised World Health Organization and Malawi guidelines reclassifying people with single (including 'scanty') positive smears as smear-positive pulmonary tuberculosis cases. In a retrospective cohort in rural Malawi, 567 (34%) of 1670 smear-positive episodes were based on single positive smears (including 176 with scanty smears). Mortality rates and the proportion starting treatment were similar in those with two positive smears or single, non-scanty smears. Those with single scanty smears had higher mortality and a lower proportion starting treatment. The reclassification will increase the reported burden substantially, but should improve treatment access

Does antiretroviral treatment increase the infectiousness of smear-positive pulmonary tuberculosis?

BACKGROUND: Understanding of the effects of human immunodeficiency virus (HIV) infection and antiretroviral treatment (ART) on Mycobacterium tuberculosis transmission dynamics remains limited. We undertook a cross-sectional study among household contacts of smear-positive pulmonary tuberculosis (TB) cases to assess the effect of established ART on the infectiousness of TB. METHOD: Prevalence of tuberculin skin test (TST) positivity was compared between contacts of index cases aged 2-10 years who were HIV-negative, HIV-positive but not on ART, on ART for <1 year and on ART for 1 year. Random-effects logistic regression was used to take into account clustering within households. RESULTS: Prevalence of M. tuberculosis infection in contacts of HIV-negative patients, HIV-positive patients on ART 1 year and HIV-positive patients not on ART/on ART <1 year index cases was respectively 44%, 21% and 22%. Compared to contacts of HIV-positive index cases not on ART or recently started on ART, the odds of TST positivity was similar in contacts of HIV-positive index cases on ART 1 year (adjusted OR [aOR] 1.0, 95%CI 0.3-3.7). The odds were 2.9 times higher in child contacts of HIV-negative index cases (aOR 2.9, 95%CI 1.0-8.2). CONCLUSIONS: We found no evidence that established ART increased the infectiousness of smear-positive, HIV-positive index cases

Prevalence and risk factors for chronic kidney disease of unknown cause in Malawi: a cross-sectional analysis in a rural and urban population

Background: An epidemic of chronic kidney disease of unknown cause (CKDu) is occurring in rural communities in tropical regions of low-and middle-income countries in South America and India. Little information is available from Southern African countries which have similar climatic and occupational characteristics to CKDu-endemic countries. We investigated whether CKDu is prevalent in Malawi and identified its potential risk factors in this setting. / Methods: We conducted a cross-sectional study from January–August 2018 collecting bio samples and anthropometric data in two Malawian populations. The sample comprised adults > 18 years (n = 821) without diabetes, hypertension, and proteinuria. Estimates of glomerular filtration rate (eGFR) were calculated using the CKD-EPI equation. Linear and logistic regression models were applied with potential risk factors, to estimate risk of reduced eGFR. / Results: The mean eGFR was 117.1 ± 16.0 ml/min per 1.73m2 and the mean participant age was 33.5 ± 12.7 years. The prevalence of eGFR< 60 was 0.2% (95% confidence interval (95% CI) 0.1, 0.9); the prevalence of eGFR< 90 was 5% (95% CI =3.2, 6.3). We observed a higher prevalence in the rural population (5% (3.6, 7.8)), versus urban (3% (1.4, 6.7)). Age and BMI were associated with reduced eGFR< 90 [Odds ratio (OR) (95%CI) =3.59 (2.58, 5.21) per ten-year increment]; [OR (95%CI) =2.01 (1.27, 3.43) per 5 kg/m2 increment] respectively. No increased risk of eGFR < 90 was observed for rural participants [OR (95%CI) =1.75 (0.50, 6.30)]. / Conclusions: Reduced kidney function consistent with the definition of CKDu is not common in the areas of Malawi sampled, compared to that observed in other tropical or sub-tropical countries in Central America and South Asia. Reduced eGFR< 90 was related to age, BMI, and was more common in rural areas. These findings are important as they contradict some current hypothesis that CKDu is endemic across tropical and sub-tropical countries. This study has enabled standardized comparisons of impaired kidney function between and within tropical/subtropical regions of the world and will help form the basis for further etiological research, surveillance strategies, and the implementation and evaluation of interventions

Risk factors for Mycobacterium tuberculosis infection in 2-4 year olds in a rural HIV-prevalent setting.

BACKGROUND: Mycobacterium tuberculosis infection in children acts as a sentinel for infectious tuberculosis. OBJECTIVE: To assess risk factors associated with tuberculous infection in pre-school children. METHOD: We conducted a population-wide tuberculin skin test (TST) survey from January to December 2012 in Malawi. All children aged 2-4 years residing in a demographic surveillance area were eligible. Detailed demographic data, including adult human immunodeficiency virus (HIV) status, and clinical and sociodemographic data on all diagnosed tuberculosis (TB) patients were available. RESULTS: The prevalence of M. tuberculosis infection was 1.1% using a TST induration cut-off of 15 mm (estimated annual risk of infection of 0.3%). The main identifiable risk factors were maternal HIV infection at birth (adjusted OR [aOR] 3.6, 95%CI 1.1-12.2), having three or more adult members in the household over a lifetime (aOR 2.4, 95%CI 1.2-4.8) and living in close proximity to a known case of infectious TB (aOR 1.6, 95%CI 1.1-2.4), modelled as a linear variable across categories (>200 m, 100-200 m, <100 m, within household). Less than 20% of the infected children lived within 200 m of a known diagnosed case. CONCLUSION: Household and community risk factors identified do not explain the majority of M. tuberculosis infections in children in our setting

Methodological challenges in measuring vaccine effectiveness using population cohorts in low resource settings.

Post-licensure real world evaluation of vaccine implementation is important for establishing evidence of vaccine effectiveness (VE) and programme impact, including indirect effects. Large cohort studies offer an important epidemiological approach for evaluating VE, but have inherent methodological challenges. Since March 2012, we have conducted an open prospective cohort study in two sites in rural Malawi to evaluate the post-introduction effectiveness of 13-valent pneumococcal conjugate vaccine (PCV13) against all-cause post-neonatal infant mortality and monovalent rotavirus vaccine (RV1) against diarrhoea-related post-neonatal infant mortality. Our study sites cover a population of 500,000, with a baseline post-neonatal infant mortality of 25 per 1000 live births. We conducted a methodological review of cohort studies for vaccine effectiveness in a developing country setting, applied to our study context. Based on published literature, we outline key considerations when defining the denominator (study population), exposure (vaccination status) and outcome ascertainment (mortality and cause of death) of such studies. We assess various definitions in these three domains, in terms of their impact on power, effect size and potential biases and their direction, using our cohort study for illustration. Based on this iterative process, we discuss the pros and cons of our final per-protocol analysis plan. Since no single set of definitions or analytical approach accounts for all possible biases, we propose sensitivity analyses to interrogate our assumptions and methodological decisions. In the poorest regions of the world where routine vital birth and death surveillance are frequently unavailable and the burden of disease and death is greatest We conclude that provided the balance between definitions and their overall assumed impact on estimated VE are acknowledged, such large scale real-world cohort studies can provide crucial information to policymakers by providing robust and compelling evidence of total benefits of newly introduced vaccines on reducing child mortality

Child Mortality in Rural Malawi: HIV Closes the Survival Gap between the Socio-Economic Strata

BACKGROUND: As HIV-related deaths increase in a population the usual association between low socioeconomic status and child mortality may change, particularly as death rates from other causes decline. METHODS/PRINCIPAL FINDINGS: As part of a demographic surveillance system in northern Malawi in 2002-6, covering a population of 32,000, information was collected on socio-economic status of the households. Deaths were classified as HIV/AIDS-related or not by verbal autopsy. Poisson regression models were used to assess the association of socio-economic indicators with all-cause mortality, AIDS-mortality and non-AIDS mortality among children. There were 195 deaths in infants, 109 in children aged 1-4 years, and 38 in children aged 5-15. All-cause child mortality in infants and 1-4 year olds was similar in households with higher and lower socio-economic status. In infants 13% of deaths were attributed to AIDS, and there were no clear trends with socio-economic status for AIDS or non-AIDS causes. For 1-4 year olds 27% of deaths were attributed to AIDS. AIDS mortality was higher among those with better built houses, and lowest in those with income from farming and fishing, whereas non-AIDS mortality was higher in those with worse built houses, lowest in those with income from employment, and decreased with increasing household assets. CONCLUSIONS/SIGNIFICANCE: In this population, since HIV infection among adults was initially more common among the less poor, childhood mortality patterns have changed. The usual gap in survival between the poor and the less poor has been lost, but because the less poor have been disproportionately affected by HIV, rather than because of relative improvement in the survival of the poorest

Differences between naive and memory T cell phenotype in Malawian and UK adolescents: a role for Cytomegalovirus?

Background: Differences in degree of environmental exposure to antigens in early life have been hypothesized to lead to differences in immune status in individuals from different populations, which may have implications for immune responses in later years.Methods: Venous blood from HIV-negative adolescents and blood from the umbilical cords of babies, born to HIV-negative women, post-delivery was collected and analysed using flow cytometry. T cell phenotype was determined from peripheral blood lymphocytes and cytomegalovirus (CMV) seropositivity was assessed by ELISA in adolescents.Results: HIV-negative Malawian adolescents were shown to have a lower percentage of naive T cells (CD45RO-CD62L(hi)CD11a(lo)), a higher proportion of memory T cells and a higher percentage of CD28(-) memory (CD28(-)CD45RO(+)) T cells compared to age-matched UK adolescents. Malawian adolescents also had a lower percentage of central memory (CD45RA(-)CCR7(+)) T cells and a higher percentage of stable memory (CD45RA(+)CCR7(-)) T cells than UK adolescents. All of the adolescents tested in Malawi were seropositive for CMV (59/59), compared to 21/58 (36%) of UK adolescents. CMV seropositivity in the UK was associated with a reduced percentage of naive T cells and an increased percentage of CD28- memory T cells in the periphery. No differences in the proportions of naive and memory T cell populations were observed in cord blood samples from the two sites.Conclusion: It is likely that these differences between Malawian and UK adolescents reflect a greater natural exposure to various infections, including CMV, in the African environment and may imply differences in the ability of these populations to induce and maintain immunological memory to vaccines and natural infections