The effect of antiretroviral therapy provision on all-cause, AIDS and non-AIDS mortality at the population level--a comparative analysis of data from four settings in Southern and East Africa.

OBJECTIVE: To provide a broad and up-to-date picture of the effect of antiretroviral therapy (ART) provision on population-level mortality in Southern and East Africa. METHODS: Data on all-cause, AIDS and non-AIDS mortality among 15-59 year olds were analysed from demographic surveillance sites (DSS) in Karonga (Malawi), Kisesa (Tanzania), Masaka (Uganda) and the Africa Centre (South Africa), using Poisson regression. Trends over time from up to 5 years prior to ART roll-out, to 4-6 years afterwards, are presented, overall and by age and sex. For Masaka and Kisesa, trends are analysed separately for HIV-negative and HIV-positive individuals. For Karonga and the Africa Centre, trends in AIDS and non-AIDS mortality are analysed using verbal autopsy data. RESULTS: For all-cause mortality, overall rate ratios (RRs) comparing the period 2-6 years following ART roll-out with the pre-ART period were 0.58 (5.9 vs. 10.2 deaths per 1000 person-years) in Karonga, 0.79 (7.2 vs. 9.1 deaths per 1000 person-years) in Kisesa, 0.61 (6.7 compared with 11.0 deaths per 1000 person-years) in Masaka and 0.79 (14.8 compared with 18.6 deaths per 1000 person-years) in the Africa Centre DSS. The mortality decline was seen only in HIV-positive individuals/AIDS mortality, with no decline in HIV-negative individuals/non-AIDS mortality. Less difference was seen in Kisesa where ART uptake was lower. CONCLUSIONS: Falls in all-cause mortality are consistent with ART uptake. The largest falls occurred where ART provision has been decentralised or available locally, suggesting that this is important

Early school failure predicts teenage pregnancy and marriage: A large population-based cohort study in northern Malawi.

BACKGROUND: School dropout has been linked to early pregnancy and marriage but less is known about the effect of school performance. We aimed to assess whether school performance influenced age at sexual debut, pregnancy and marriage, and from what age school drop-out and performance were associated with these later life events. METHODS: Data from 2007-2016 from a demographic surveillance site in northern Malawi with annual updating of schooling status and grades, and linked sexual behaviour surveys, were analysed to assess the associations of age-specific school performance (measured as age-for-grade) and status (in or out of school) on subsequent age at sexual debut, pregnancy and marriage. Landmark analysis with Cox regression was used to estimate hazard ratios of sexual debut, pregnancy and marriage by schooling at selected (landmark) ages, controlling for socio-economic factors. RESULTS: Information on at least one outcome was available for >16,000 children seen at ages 10-18. Sexual debut was available on a subset aged ≥15 by 2011. For girls, being out of school was strongly associated with earlier sexual debut, pregnancy and marriage. For example, using schooling status at age 14, compared to girls in primary, those who had dropped out had adjusted hazard ratios of subsequent sexual debut, pregnancy and marriage of 5.39 (95% CI 3.27-8.86), 2.39 (1.82-3.12), and 2.76 (2.08-3.67) respectively. For boys, the equivalent association with sexual debut was weak, 1.92 (0.81-4.55), but that with marriage was strong, 3.74 (2.28-6.11), although boys married later. Being overage-for-grade was not associated with sexual debut for girls or boys. For girls, being overage-for-grade from age 10 was associated with earlier pregnancy and marriage (e.g. adjusted hazard ratio 2.84 (1.32-6.17) for pregnancy and 3.19 (1.47-6.94) for marriage, for those ≥3 years overage compared to those on track at age 10). For boys, overage-for-grade was associated with earlier marriage from age 12, with stronger associations at older ages (e.g. adjusted hazard ratio 2.41 (1.56-3.70) for those ≥3 years overage compared to those on track at age 14). For girls ≥3 years overage at age 14, 39% were pregnant before they were 18, compared to 18% of those who were on track. The main limitation was the use of reported ages of sexual debut, pregnancy and marriage. CONCLUSIONS: School progression at ages as young as 10 can predict teenage pregnancy and marriage, even after adjusting for socio-economic factors. Early education interventions may reduce teenage pregnancy and marriage as well as improving learning

Changes in fertility at the population level in the era of ART in rural Malawi

Introduction: HIV reduces fertility through biological and social pathways, and antiretroviral treatment (ART) can ameliorate these effects. In northern Malawi, ART has been available since 2007 and lifelong ART is offered to all pregnant or breastfeeding HIV-positive women. Methods: Using data from the Karonga Health and Demographic Surveillance Site in Malawi from 2005 to 2014, we used total and age-specific fertility rates and Cox regression to assess associations between HIV and ART use and fertility. We also assessed temporal trends in in utero and breastfeeding HIV and ART exposure among live births. Results: From 2005 to 2014, there were 13,583 live births during approximately 78,000 person years of follow-up of women aged 15–49 years. The total fertility rate in HIV-negative women decreased from 6.1 [95% confidence interval (CI): 5.5 to 6.8] in 2005–2006 to 5.1 (4.8–5.5) in 2011–2014. In HIV-positive women, the total fertility rate was more stable, although lower, at 4.4 (3.2–6.1) in 2011–2014. In 2011–2014, compared with HIV-negative women, the adjusted (age, marital status, and education) hazard ratio was 0.7 (95% CI: 0.6 to 0.9) and 0.8 (95% CI: 0.6 to 1.0) for women on ART for at least 9 months and not (yet) on ART, respectively. The crude fertility rate increased with duration on ART up to 3 years before declining. The proportion of HIV-exposed infants decreased, but the proportion of ART-exposed infants increased from 2.4% in 2007–2010 to 3.5% in 2011–2014. Conclusions: Fertility rates in HIV-positive women are stable in the context of generally decreasing fertility. Despite a decrease in HIV-exposed infants, there has been an increase in ART-exposed infants

Changes in Fertility at the Population Level in the Era of ART in Rural Malawi.

INTRODUCTION: HIV reduces fertility through biological and social pathways, and antiretroviral treatment (ART) can ameliorate these effects. In northern Malawi, ART has been available since 2007 and lifelong ART is offered to all pregnant or breastfeeding HIV-positive women. METHODS: Using data from the Karonga Health and Demographic Surveillance Site in Malawi from 2005 to 2014, we used total and age-specific fertility rates and Cox regression to assess associations between HIV and ART use and fertility. We also assessed temporal trends in in utero and breastfeeding HIV and ART exposure among live births. RESULTS: From 2005 to 2014, there were 13,583 live births during approximately 78,000 person years of follow-up of women aged 15-49 years. The total fertility rate in HIV-negative women decreased from 6.1 [95% confidence interval (CI): 5.5 to 6.8] in 2005-2006 to 5.1 (4.8-5.5) in 2011-2014. In HIV-positive women, the total fertility rate was more stable, although lower, at 4.4 (3.2-6.1) in 2011-2014. In 2011-2014, compared with HIV-negative women, the adjusted (age, marital status, and education) hazard ratio was 0.7 (95% CI: 0.6 to 0.9) and 0.8 (95% CI: 0.6 to 1.0) for women on ART for at least 9 months and not (yet) on ART, respectively. The crude fertility rate increased with duration on ART up to 3 years before declining. The proportion of HIV-exposed infants decreased, but the proportion of ART-exposed infants increased from 2.4% in 2007-2010 to 3.5% in 2011-2014. CONCLUSIONS: Fertility rates in HIV-positive women are stable in the context of generally decreasing fertility. Despite a decrease in HIV-exposed infants, there has been an increase in ART-exposed infants

Reliability of reporting of HIV status and antiretroviral therapy usage during verbal autopsies: a large prospective study in rural Malawi.

OBJECTIVE: Verbal autopsies (VAs) are interviews with a relative or friend of the deceased; VAs are a technique used in surveillance sites in many countries with incomplete death certification. The goal of this study was to assess the accuracy and validity of data on HIV status and antiretroviral therapy (ART) usage reported in VAs and their influence on physician attribution of cause of death. DESIGN: This was a prospective cohort study. METHODS: The Karonga Health and Demographic Surveillance Site monitors demographic events in a population in a rural area of northern Malawi; a VA is attempted on all deaths reported. VAs are reviewed by clinicians, who, with additional HIV test information collected pre-mortem, assign a cause of death. We linked HIV/ART information reported by respondents during adult VAs to database information on HIV testing and ART use and analysed agreement using chi-square and kappa statistics. We used multivariable logistic regression to analyse factors associated with agreement. RESULTS: From 2003 to 2014, out of a total of 1,952 VAs, 80% of respondents reported the HIV status of the deceased. In 2013-2014, this figure was 99%. Of those with an HIV status known to the study, there was 89% agreement on HIV status between the VA and pre-mortem data, higher for HIV-negative people (92%) than HIV-positive people (83%). There was 84% agreement on whether the deceased had started ART, and 72% of ART initiation dates matched within 1 year. CONCLUSIONS: In this population, HIV/ART information was often disclosed during a VA and matched well with other data sources. Reported HIV/ART status appears to be a reliable source of information to help classification of cause of death

Unintended Childbearing and Child Growth in Northern Malawi

Objective The study aims to assess whether unintended children experience slower growth than intended children. Methods We analysed longitudinal data linked to the Karonga Health and Demographic Surveillance Site collected over three rounds between 2008 and 2011 on women's fertility intentions and anthropometric data of children. Using the prospective information on fertility intention we assessed whether unintended children are more likely to be stunted than intended children. We applied Propensity Score Matching technique to control for endogenous factors affecting both the probability that a family has an unwanted birth and a child with poor health outcomes. Results We found that 24 % of children from unwanted pregnancies were stunted compared with 18 % of mistimed pregnancies and 17 % of those from wanted pregnancies. However, these differences in probability of children being stunted, though in the expected direction, were not significant either for large or small families, after controlling for age. The number of children in the household was associated with stunting and boys were substantially more likely to be stunted than girls. Conclusion We found no significance difference in probability of being stunted by mother's fertility intention

Patterns and risk factors for deaths from external causes in rural Malawi over 10 years: a prospective population-based study.

BACKGROUND: Little is known about the pattern or risk factors for deaths from external causes in sub-Saharan Africa: there is a lack of reliable data, and public health priorities have been focussed on other causes. This study assessed the prevalence and risk factor for deaths from external causes in rural Malawi. METHODS: We analysed data from 2002-2012 from the Karonga demographic surveillance site which covers ~35,000 people in rural northern Malawi. Verbal autopsies with clinician coding are used to assign cause of death. Repeated annual surveys capture data on socio-economic factors. Using Poisson regression models we calculated age, sex and cause-specific rates and rate ratios of external deaths. We used a nested case-control study, matched on age, sex and time period, to investigate risk factors for these deaths, using conditional logistic regression. RESULTS: In 315,580 person years at risk (pyar) there were 2673 deaths, including 143 from external causes. The mortality rate from external causes was 47.1/100,000 pyar (95 % CI 32.5-68.2) among under-fives; 20.1/100,000 pyar (95 % CI 13.1-32.2) among 5-14 year olds; 46.3/100,000 pyar (95 % CI 35.8-59.9) among 15-44 year olds; and 98.7/100,000 pyar (95 % CI 71.8-135.7) among those aged ≥45 years. Drowning (including four deaths in people with epilepsy), road injury and suicide were the leading external causes. Adult males had the highest rates (100.7/100,000 pyar), compared to 21.8/100,000pyar in adult females, and the rate continued to increase with increasing age in men. Alcohol contributed to 21 deaths, all in adult males. Children had high rates of drowning (9.2/100,000 pyar, 95 % CI 5.5-15.6) but low rates of road injury (2.6/100,000 pyar, 95 % CI 1.0-7.0). Among 5-14 year olds, attending school was associated with fewer deaths from external causes than among those who had never attended school (adjusted OR 0.15, 95 % CI 0.08-0.81). Fishermen had increased risks of death from drowning and suicide compared to farmers. DISCUSSION: In this population the rate of deaths from external causes was lowest at age 5-14 years. Adult males had the highest rate of death from external causes, 5 times the rate in adult females. Drowning, road injury and suicide were the leading causes of death; alcohol consumption contributed to more than one quarter of the deaths in men CONCLUSIONS: The high proportion of alcohol-related deaths in men, the predominance of drowning, deaths linked to uncontrolled epilepsy, and the possible protective effect of school attendance suggest areas for intervention

Failing to progress or progressing to fail? Age-for-grade heterogeneity and grade repetition in primary schools in Karonga district, northern Malawi.

Timely progression through school is an important measure for school performance, completion and the onset of other life transitions for adolescents. This study examines the risk factors for grade repetition and establishes the extent to which age-for-grade heterogeneity contributes to subsequent grade repetition at early and later stages of school. Using data from a demographic surveillance site in Karonga district, northern Malawi, a cohort of 8174 respondents (ages 5-24 years) in primary school was followed in 2010 and subsequent grade repetition observed in 2011. Grade repetition was more common among those at early (grades 1-3) and later (grades 7-8) stages of school, with little variation by sex. Being under-age or over-age in school has different implications on schooling outcomes, depending on the stage of schooling. After adjusting for other risk factors, boys and girls who were under-age at early stages were at least twice as likely to repeat a grade as those at the official age-for-grade (girls: adjusted OR 2.06 p < 0.01; boys: adjusted OR 2.37 p < 0.01); while those over-age at early stages were about 30% less likely to repeat (girls: adjusted OR 0.65 p < 0.01; boys: adjusted OR 0.72 p < 0.01). Being under/over-age at later grades (4-8) was not associated with subsequent repetition but being over-age was associated with dropout. Other risk factors identified that were associated with repetition included both family-level factors (living away from their mother, having young children in the household, lower paternal education) and school-level factors (higher student-teacher ratio, proportion of female teachers and schools without access to water). Reducing direct and indirect costs of schooling for households; and improving school quality and resources at early stages of school may enable timely progression at early stages for greater retention at later stages

Sustained 10-year gain in adult life expectancy following antiretroviral therapy roll-out in rural Malawi: July 2005 to June 2014.

Background: Improved life expectancy in high HIV prevalence populations has been observed since antiretroviral therapy (ART) scale-up. However, it is unclear if the benefits are sustained, and the mortality among HIV-positive individuals not (yet) on ART is not well described. We assessed temporal change in mortality over 9 years in rural Malawi. Methods: Within a demographic surveillance site in northern rural Malawi, we combined demographic, HIV and ART uptake data. We calculated life expectancy using Kaplan-Meier estimates, and compared mortality rates and rate ratios using Poisson regression, by period of ART availability (July 2005-June 2008, July 2008-June 2011 and July 2011-June 2014). Results: Among 32 664 individuals there were 1424 deaths; 1930 individuals were known HIV-positive, of whom 1382 started ART. Overall, life expectancy at age 15 years increased by 10 years within 5 years of ART introduction, and plateaued. Age-standardized adult mortality rates declined from 11.3/1000 to 7.5/1000 person-years between the first and last time period. In July 2011-June 2014 compared with July 2005-June 2008, mortality declined in HIV-positive individuals on ART (rate ratio adjusted (aRR) for age, sex, location and education, 0.3; 95% confidence interval (CI) 0.2-0.5) and in those not (yet) on ART (aRR 0.3; 95%CI 0.1-0.5) but not in HIV-negative individuals (aRR 1.1; 95%CI 0.7-1.9). Conclusions: Total population adult life expectancy increased toward that of HIV-negative individuals by 2011 and remained raised. The reduction in all-cause and HIV-related mortality in HIV-positive individuals not (yet) on ART suggests ART uptake is occurring at an earlier disease stage, particularly in women

Profile: the Karonga Health and Demographic Surveillance System

The Karonga Health and Demographic Surveillance System (Karonga HDSS) in northern Malawi currently has a population of more than 35 000 individuals under continuous demographic surveillance since completion of a baseline census (2002–2004). The surveillance system collects data on vital events and migration for individuals and for households. It also provides data on cause-specific mortality obtained by verbal autopsy for all age groups, and estimates rates of disease for specific presentations via linkage to clinical facility data. The Karonga HDSS provides a structure for surveys of socio-economic status, HIV sero-prevalence and incidence, sexual behaviour, fertility intentions and a sampling frame for other studies, as well as evaluating the impact of interventions, such as antiretroviral therapy and vaccination programmes. Uniquely, it relies on a network of village informants to report vital events and household moves, and furthermore is linked to an archive of biological samples and data from population surveys and other studies dating back three decades