High Cancer Burden Among Antiretroviral Therapy Users in Malawi: a Record Linkage Study of Observational HIV Cohorts and Cancer Registry Data.

Background With antiretroviral therapy (ART), AIDS-defining cancer incidence has declined and non-AIDS defining cancers are now more frequent among HIV-infected populations in high-income countries. In sub-Saharan Africa, limited epidemiological data describe cancer burden among ART users. Methods We used probabilistic algorithms to link cases from the population-based cancer registry with electronic medical records supporting ART delivery in the Malawi's two largest HIV cohorts, Lighthouse Trust (LT; 2007-2010) and Queen Elizabeth Central Hospital (QECH; 2000-2010). Age-adjusted cancer incidence rates (IR) and 95% confidence intervals were estimated by cancer site, early versus late incidence periods (4 -24 and >24 months after ART start), and WHO stage among naïve ART initiators enrolled for at least 90 days. Results We identified 4,346 cancers among 28,576 persons. Most people initiated ART at advanced WHO stage (LT stage 3/4: 55%; QECH stage 3/4: 66%); 12% of patients had prevalent malignancies at ART initiation, which were predominantly AIDS-defining eligibility criteria for initiating ART. Kaposi sarcoma (KS) had the highest IR (634.7 per 100,000 person-years), followed by cervical cancer (36.6). KS incidence was highest during the early period 4-24 months after ART initiation. Non-AIDS defining cancers (NADC) accounted for 6% of new cancers. Conclusions Under historical ART guidelines, NADC were observed at low rates, and were eclipsed by high KS and cervical cancer burden. Cancer burden among Malawian ART users does not yet mirror high-income countries. Integrated cancer screening and management in HIV clinics, especially for KS and cervical cancer, remain important priorities in the current Malawi context

Seasonally variant stable isotope baseline characterisation of Malawi's Shire River Basin to support integrated water resources management

Integrated Water Resources Management (IWRM) is vital to the future of Malawi and motivates this study's provision of the first stable isotope baseline characterization of the Shire River Basin (SRB). The SRB drains much of Southern Malawi and receives the sole outflow of Lake Malawi whose catchment extends over much of Central and Northern Malawi (and Tanzania and Mozambique). Stable isotope (283) and hydrochemical (150) samples were collected in 2017-2018 and analysed at Malawi's recently commissioned National Isotopes Laboratory. Distinct surface water dry-season isotope enrichment and wet-season depletion are shown with minor retention of enriched signatures ascribed to Lake Malawi influences. Isotopic signatures corroborate that wet-season river flows mostly arise from local precipitation, with dry-season flows supported by increased groundwater contributions. Groundwater signatures follow a local meteoric water line of limited spread suggesting recharge by local precipitation predominantly during the peak months of the wet-season. Relatively few dry-season groundwater samples displayed evaporative enrichment, although isotopic seasonality was more pronounced in the lowlands compared to uplands ascribed to amplified climatic effects. These signatures serve as isotopic diagnostic tools that valuably informed a basin conceptual model build and, going forward, may inform key identified Malawian IWRM concerns. The isotopic baseline establishes a benchmark against which future influences from land use, climate change and water mixing often inherent to IWRM schemes may be forensically assessed. It thereby enables both source-water protection and achievement of Sustainable Development Goal 6

Impact of monovalent rotavirus vaccine on diarrhoea-associated post-neonatal infant mortality in rural communities in Malawi: a population-based birth cohort study

Background: Rotavirus is a major contributor to child mortality. The effect of rotavirus vaccine on diarrhoea mortality has been estimated in middle-income but not low-income settings, where mortality is high and vaccine effectiveness in reducing admissions to hospital is lower. Empirical population-based mortality studies have not been done in any setting. Malawi introduced monovalent rotavirus vaccine (RV1) in October, 2012. We aimed to investigate the impact and effectiveness of the RV1 vaccine in reducing diarrhoea-associated mortality in infants aged 10–51 weeks. Methods: In this population-based cohort study, we included infants born between Jan 1, 2012, and June 1, 2015, in Mchinji, Central Malawi and analysed data on those surviving 10 weeks. Individual vaccination status was extracted from caregiver-held records or report at home visits at 4 months and 1 year of age. Survival to 1 year was confirmed at home visit, or cause of death ascertained by verbal autopsy. We assessed impact (1 minus mortality rate ratio following vs before vaccine introduction) using Poisson regression. Among vaccine-eligible infants (born from Sept 17, 2012), we assessed effectiveness (1 minus hazard ratio) using Cox regression. Findings: Between Jan 1, 2012, and June 1, 2015, we recruited 48 672 livebirths in Mchinji, among whom 38 518 were vaccine-eligible and 37 570 survived to age 10 weeks. Two-dose versus zero-dose effectiveness analysis included 28 141 infants, of whom 101 had diarrhoea-associated death before 1 year of age. Diarrhoea-associated mortality declined by 31% (95% CI 1–52; p=0·04) after RV1 introduction. Effectiveness against diarrhoea-mortality was 34% (95% CI –28 to 66; p=0·22). Interpretation: RV1 was associated with substantial reduction in diarrhoea-associated deaths among infants in this rural sub-Saharan African setting. These data add considerable weight to evidence showing the impact of rotavirus vaccine programmes. Funding: Wellcome Trust and GlaxoSmithKline Biologicals

Water-isotope capacity building and demonstration in a developing world context : isotopic baseline and conceptualization of a Lake Malawi catchment

Developing countries such as Malawi require improved access to isotope tracer tools to better characterize and manage water resources threatened by land development, deforestation and climate change. This is the first published study to use an isotope facility developed in Malawi for this purpose, instead of relying upon sample analyses from abroad. Results from this new facility are used to evaluate an important Lake Malawi catchment in the Rift Valley. This work successfully established a stable-isotope baseline, hydrochemical signatures, and system conceptualization against which future policy change and management strategies may be measured. Precipitation isotopic composition was consistent with the Global Meteoric Water Line, but varied, confirming different precipitation systems nationally. Groundwater largely followed a Local MeteoricWater Line, with limited isotopic variation indicating predominant areal groundwater recharge, but with dry-season evaporative enrichment of groundwater near Lake Malawi. Surface-water isotopes widely varied with local precipitation, suggesting the latter accounted for wet-season river flows, but upstream dambo (complex wetlands occupying a shallow, seasonal waterlogged depression) helped sustain dry-season flows. Isotope capacity reinforced water-resource conceptualization and provenance in a hydrologically complex, but not atypical, Rift Valley system, exhibiting a noted complexity of groundwater-surface-water interactions. The latter, critical to integrated water resource management, requires more focused study, to which an expanded array of isotopes will contribute to tracking Sustainable Development Goal 6 targets. This study and future catchment studies should help underpin Malawian water-resource policy implementation on several identified fronts

Impact of monovalent rotavirus vaccine on diarrhoea-associated post-neonatal infant mortality in rural communities in Malawi: a population-based birth cohort study.

BACKGROUND: Rotavirus is a major contributor to child mortality. The effect of rotavirus vaccine on diarrhoea mortality has been estimated in middle-income but not low-income settings, where mortality is high and vaccine effectiveness in reducing admissions to hospital is lower. Empirical population-based mortality studies have not been done in any setting. Malawi introduced monovalent rotavirus vaccine (RV1) in October, 2012. We aimed to investigate the impact and effectiveness of the RV1 vaccine in reducing diarrhoea-associated mortality in infants aged 10-51 weeks. METHODS: In this population-based cohort study, we included infants born between Jan 1, 2012, and June 1, 2015, in Mchinji, Central Malawi and analysed data on those surviving 10 weeks. Individual vaccination status was extracted from caregiver-held records or report at home visits at 4 months and 1 year of age. Survival to 1 year was confirmed at home visit, or cause of death ascertained by verbal autopsy. We assessed impact (1 minus mortality rate ratio following vs before vaccine introduction) using Poisson regression. Among vaccine-eligible infants (born from Sept 17, 2012), we assessed effectiveness (1 minus hazard ratio) using Cox regression. FINDINGS: Between Jan 1, 2012, and June 1, 2015, we recruited 48 672 livebirths in Mchinji, among whom 38 518 were vaccine-eligible and 37 570 survived to age 10 weeks. Two-dose versus zero-dose effectiveness analysis included 28 141 infants, of whom 101 had diarrhoea-associated death before 1 year of age. Diarrhoea-associated mortality declined by 31% (95% CI 1-52; p=0·04) after RV1 introduction. Effectiveness against diarrhoea-mortality was 34% (95% CI -28 to 66; p=0·22). INTERPRETATION: RV1 was associated with substantial reduction in diarrhoea-associated deaths among infants in this rural sub-Saharan African setting. These data add considerable weight to evidence showing the impact of rotavirus vaccine programmes. FUNDING: Wellcome Trust and GlaxoSmithKline Biologicals

Population impact and effectiveness of monovalent rotavirus vaccination in urban Malawian children 3 years after vaccine introduction: ecological and case-control analyses

Background. Rotavirus vaccines have been introduced in many low-income African countries including Malawi in 2012. Despite early evidence of vaccine impact, determining persistence of protection beyond infancy, the utility of the vaccine against specific rotavirus genotypes, and effectiveness in vulnerable subgroups is important. Methods. We compared rotavirus prevalence in diarrheal stool and hospitalization incidence before and following rotavirus vaccine introduction in Malawi. Using case-control analysis, we derived vaccine effectiveness (VE) in the second year of life and for human immunodeficiency virus (HIV)–exposed and stunted children. Results. Rotavirus prevalence declined concurrent with increasing vaccine coverage, and in 2015 was 24% compared with prevaccine mean baseline in 1997–2011 of 32%. Since vaccine introduction, population rotavirus hospitalization incidence declined in infants by 54.2% (95% confidence interval [CI], 32.8–68.8), but did not fall in older children. Comparing 241 rotavirus cases with 692 test-negative controls, VE was 70.6% (95% CI, 33.6%–87.0%) and 31.7% (95% CI, −140.6% to 80.6%) in the first and second year of life, respectively, whereas mean age of rotavirus cases increased from 9.3 to 11.8 months. Despite higher VE against G1P[8] than against other genotypes, no resurgence of nonvaccine genotypes has occurred. VE did not differ significantly by nutritional status (78.1% [95% CI, 5.6%–94.9%] in 257 well-nourished and 27.8% [95% CI, −99.5% to 73.9%] in 205 stunted children; P = .12), or by HIV exposure (60.5% [95% CI, 13.3%–82.0%] in 745 HIV-unexposed and 42.2% [95% CI, −106.9% to 83.8%] in 174 exposed children; P = .91). Conclusions. Rotavirus vaccination in Malawi has resulted in reductions in disease burden in infants <12 months, but not in older children. Despite differences in genotype-specific VE, no genotype has emerged to suggest vaccine escape. VE was not demonstrably affected by HIV exposure or stunting

Antiretroviral pharmacokinetics in mothers and breastfeeding infants from 6 to 24 weeks post partum: results of the BAN Study

An intensive, prospective, open-label pharmacokinetic (PK) study in a subset of HIV-infected mothers and their uninfected infants enrolled in the Breastfeeding, Antiretroviral, and Nutrition study was performed to describe drug exposure and antiviral response