Earlier menarche is associated with a higher prevalence of Herpes simplex type-2 (HSV-2) in young women in rural Malawi.

Remarkably little is known about associations between age at menarche and sexually transmitted infections, although girls with earlier menarche tend to have earlier sexual debut and school drop-out, so an association might be expected. In a population-based survey of >3000 women aged 15-30 in northern Malawi we show that those with earlier menarche had earlier sexual debut, earlier marriage and were more often Herpes simplex type-2 (HSV-2) positive. Compared to those with menarche aged <14, the age-adjusted odds ratios for HSV-2 were 0.89 (95%CI 0.71-1.1), 0.71 (0.57-0.89) and 0.69 (0.54-0.89) for menarche aged 14, 15 and 16+ respectively. This association persisted after adjusting for socio-economic factors, including schooling, and for sexual behaviour. No such association was seen with HIV infection, which is much less common and less uniformly distributed than HSV-2 in this population. The extra vulnerability of girls with earlier menarche needs to be recognised. DOI: http://dx.doi.org/10.7554/eLife.01604.001

Earlier menarche is associated with a higher prevalence of Herpes simplex type-2 (HSV-2) in young women in rural Malawi

Remarkably little is known about associations between age at menarche and sexually transmitted infections, although girls with earlier menarche tend to have earlier sexual debut and school drop-out, so an association might be expected. In a population-based survey of &gt;3000 women aged 15–30 in northern Malawi we show that those with earlier menarche had earlier sexual debut, earlier marriage and were more often Herpes simplex type-2 (HSV-2) positive. Compared to those with menarche aged &lt;14, the age-adjusted odds ratios for HSV-2 were 0.89 (95%CI 0.71–1.1), 0.71 (0.57–0.89) and 0.69 (0.54–0.89) for menarche aged 14, 15 and 16+ respectively. This association persisted after adjusting for socio-economic factors, including schooling, and for sexual behaviour. No such association was seen with HIV infection, which is much less common and less uniformly distributed than HSV-2 in this population. The extra vulnerability of girls with earlier menarche needs to be recognised

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

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

Lusting, learning and lasting in school: sexual debut, school performance and dropout among adolescents in primary schools in Karonga district, northern Malawi.

Age at sexual debut is known to have implications for future sexual behaviours and health outcomes, including HIV infection, early pregnancy and maternal mortality, but may also influence educational outcomes. Longitudinal data on schooling and sexual behaviour from a demographic surveillance site in Karonga district, northern Malawi, were analysed for 3153 respondents between the ages of 12 and 25 years to examine the association between sexual debut and primary school dropout, and the role of prior school performance. Time to dropout was modelled using the Fine and Gray survival model to account for the competing event of primary school completion. To deal with the time-varying nature of age at sexual debut and school performance, models were fitted using landmark analyses. Sexual debut was found to be associated with a five-fold increase in rate of subsequent dropout for girls and a two-fold increase in dropout rate for boys (adjusted hazard ratio [aHR] of 5.27, CI 4.22-6.57, and 2.19, CI 1.77-2.7, respectively). For girls who were sexually active by age 16, only 16% ultimately completed primary schooling, compared with 70% aged 18 or older at sexual debut. Prior to sexual debut, girls had primary completion levels similar to those of boys. The association between sexual debut and school dropout could not be explained by prior poor school performance: the effect of sexual debut on dropout was as strong among those who were not behind in school as among those who were overage for their school grade. Girls who were sexually active were more likely to repeat a grade, with no effect being seen for boys. Pathways to dropout are complex and may differ for boys and girls. Interventions are needed to improve school progression so children complete primary school before sexual debut, and to improve sex education and contraception provision

Community-Level Knowledge and Perceptions of Stroke in Rural Malawi.

Background and Purpose- The incidence of stroke in Malawi is unknown but major risk factors, including hypertension, obesity, and diabetes mellitus, are highly prevalent. We sought to understand community-level knowledge about stroke. Methods- A population-based cross-sectional study was conducted in rural Malawi (2016-2017). Adults aged ≥15 years were randomly selected and interviewed about their knowledge and perceptions of stroke symptoms, risk factors, and prevention. Logistic regression was used to investigate sociodemographic factors associated with stroke knowledge. Results- Of 812 selected, 739 (91% response rate) were seen and consented; 57% were female, and the median age was 52.0 years. Knowledge of stroke was poor: 71% knew no (correct) risk factors. Witchcraft (20.6%) was mentioned as frequently as hypertension (19.8%) as a cause. Knowledge of stroke was greatest in the most educated and wealthy and lowest in men, the never married, and the youngest age group. HIV-positive individuals had higher knowledge of prevention (odds ratio, 2.91; 95% CI, 1.21-7.03) than HIV negative individuals. Conclusions- Knowledge about stroke is very low in this community, particularly among the least educated and poor. Programs to support prevention, early recognition, and timely hospital presentation after a stroke are needed

The two C-terminal tyrosines stabilize occluded Na/K pump conformations containing Na or K ions

Interactions of the three transported Na ions with the Na/K pump remain incompletely understood. Na/K pump crystal structures show that the extended C terminus of the Na,K–adenosine triphosphatase (ATPase) α subunit directly contacts transmembrane helices. Deletion of the last five residues (KETYY in almost all Na/K pumps) markedly lowered the apparent affinity for Na activation of pump phosphorylation from ATP, a reflection of cytoplasmic Na affinity for forming the occluded E1P(Na3) conformation. ATPase assays further suggested that C-terminal truncations also interfere with low affinity Na interactions, which are attributable to extracellular effects. Because extracellular Na ions traverse part of the membrane’s electric field to reach their binding sites in the Na/K pump, their movements generate currents that can be monitored with high resolution. We report here electrical measurements to examine how Na/K pump interactions with extracellular Na ions are influenced by C-terminal truncations. We deleted the last two (YY) or five (KESYY) residues in Xenopus laevis α1 Na/K pumps made ouabain resistant by either of two kinds of point mutations and measured their currents as 10-mM ouabain–sensitive currents in Xenopus oocytes after silencing endogenous Xenopus Na/K pumps with 1 µM ouabain. We found the low affinity inhibitory influence of extracellular Na on outward Na/K pump current at negative voltages to be impaired in all of the C-terminally truncated pumps. Correspondingly, voltage jump–induced transient charge movements that reflect pump interactions with extracellular Na ions were strongly shifted to more negative potentials; this signals a several-fold reduction of the apparent affinity for extracellular Na in the truncated pumps. Parallel lowering of Na affinity on both sides of the membrane argues that the C-terminal contacts provide important stabilization of the occluded E1P(Na3) conformation, regardless of the route of Na ion entry into the binding pocket. Gating measurements of palytoxin-opened Na/K pump channels additionally imply that the C-terminal contacts also help stabilize pump conformations with occluded K ions