Provenance of "after the fact" harmonised community-based demographic and HIV surveillance data from ALPHA cohorts

Background: Data about data, metadata, for describing Health and Demographic Surveillance System (HDSS) data have often received insufficient attention. This thesis studied how to develop provenance metadata within the context of HDSS data harmonisation - the network for Analysing Longitudinal Population-based HIV/ AIDS data on Africa (ALPHA). Technologies from the data documentation community were customised, among them: A process model - Generic Longitudinal Business Process Model (GLBPM), two metadata standards - Data Documentation Initiative (DDI) and Standard for Data and Metadata eXchange (SDMX) and a data transformations description language - Structured Data Transform Language (SDTL). Methods: A framework with three complementary facets was used: Creating a recipe for annotating primary HDSS data using the GLBPM and DDI; Approaches for documenting data transformations. At a business level, prospective and retrospective documentation using GLBPM and DDI and retrospectively recovering the more granular details using SDMX and SDTL; Requirements analysis for a user-friendly provenance metadata browser. Results: A recipe for the annotation of HDSS data was created outlining considerations to guide HDSS on metadata entry, staff training and software costs. Regarding data transformations, at a business level, a specialised process model for the HDSS domain was created. It has algorithm steps for each data transformation sub-process and data inputs and outputs. At a lower level, the SDMX and SDTL captured about 80% (17/21) of the variable level transformations. The requirements elicitation study yielded requirements for a provenance metadata browser to guide developers. Conclusions: This is a first attempt ever at creating detailed metadata for this resource or any other similar resources in this field. HDSS can implement these recipes to document their data. This will increase transparency and facilitate reuse thus potentially bringing down costs of data management. It will arguably promote the longevity and wide and accurate use of these data

Data for the paper on "Early school failure predicts teenage pregnancy and marriage: a large population-based cohort study in Northern Malawi"

The data originate from a demographic surveillance site (DSS) in Karonga district in northern Malawi covering a population of >35,000 individuals from approx. 8000 households since 2002. This is run by MEIRU (Malawi Epidemiology and Intervention Research Unit). Annual individual and household-level socio-demographic and schooling data were combined with data on participants’ sexual behaviour, including age at sexual debut, pregnancy and marriage to examine the relationship between school progression (drop-out and age-for-grade) and sexual debut, pregnancy and marriage

Preservation of individuals’ privacy in shared COVID-19 related data

Preprint VersionThis paper provides insight into how restricted data can be incorporated in an open-be-default-by-design digital infrastructure for scientific data. We focus, in particular, on the ethical component of FAIRER (Findable, Accessible, Interoperable, Ethical, and Reproducible) data, and the pseudo-anonymization and anonymization of COVID-19 datasets to protect personally identifiable information (PII). First we consider the need for the customisation of the existing privacy preservation techniques in the context of rapid production, integration, sharing and analysis of COVID-19 data. Second, the methods for the pseudo-anonymization of direct identification variables are discussed. We also discuss different pseudo-IDs of the same person for multi-domain and multi-organization. Essentially, pseudo-anonymization and its encrypted domain specific IDs are used to successfully match data later, if required and permitted, as well as to restore the true ID (and authenticity) in individual cases of a patient's clarification.Third, we discuss application of statistical disclosure control (SDC) techniques to COVID-19 disease data. To assess and limit the risk of re-identification of individual persons in COVID-19 datasets (that are often enriched with other covariates like age, gender, nationality, etc.) to acceptable levels, the risk of successful re-identification by a combination of attribute values must be assessed and controlled. This is done using statistical disclosure control for anonymization of data. Lastly, we discuss the limitations of the proposed techniques and provide general guidelines on using disclosure risks to decide on appropriate modes for data sharing to preserve the privacy of the individuals in the datasets

The effect of BCG revaccination on all-cause mortality beyond infancy: 30-year follow-up of a population-based, double-blind, randomised placebo-controlled trial in Malawi.

BACKGROUND: Trials of BCG vaccination to prevent or reduce severity of COVID-19 are taking place in adults, some of whom have been previously vaccinated, but evidence of the beneficial, non-specific effects of BCG come largely from data on mortality in infants and young children, and from in-vitro and animal studies, after a first BCG vaccination. We assess all-cause mortality following a large BCG revaccination trial in Malawi. METHODS: The Karonga Prevention trial was a population-based, double-blind, randomised controlled in Karonga District, northern Malawi, that enrolled participants between January, 1986, and November, 1989. The trial compared BCG (Glaxo-strain) revaccination versus placebo to prevent tuberculosis and leprosy. 46 889 individuals aged 3 months to 75 years were randomly assigned to receive BCG revaccination (n=23 528) or placebo (n=23 361). Here we report mortality since vaccination as recorded during active follow-up in northern areas of the district in 1991-94, and in a demographic surveillance follow-up in the southern area in 2002-18. 7389 individuals who received BCG (n=3746) or placebo (n=3643) lived in the northern follow-up areas, and 5616 individuals who received BCG (n=2798) or placebo (n=2818) lived in the southern area. Year of death or leaving the area were recorded for those not found. We used survival analysis to estimate all-cause mortality. FINDINGS: Follow-up information was available for 3709 (99·0%) BCG recipients and 3612 (99·1%) placebo recipients in the northern areas, and 2449 (87·5%) BCG recipients and 2413 (85·6%) placebo recipients in the southern area. There was no difference in mortality between the BCG and placebo groups in either area, overall or by age group or sex. In the northern area, there were 129 deaths per 19 694 person-years at risk in the BCG group (6·6 deaths per 1000 person-years at risk [95% CI 5·5-7·8]) versus 133 deaths per 19 111 person-years at risk in the placebo group (7·0 deaths per 1000 person-years at risk [95% CI 5·9-8·2]; HR 0·94 [95% CI 0·74-1·20]; p=0·62). In the southern area, there were 241 deaths per 38 399 person-years at risk in the BCG group (6·3 deaths per 1000 person-years at risk [95% CI 5·5-7·1]) versus 230 deaths per 38 676 person-years at risk in the placebo group (5·9 deaths per 1000 person-years at risk [95% CI 5·2-6·8]; HR 1·06 [95% CI 0·88-1·27]; p=0·54). INTERPRETATION: We found little evidence of any beneficial effect of BCG revaccination on all-cause mortality. The high proportion of deaths attributable to non-infectious causes beyond infancy, and the long time interval since BCG for most deaths, might obscure any benefits. FUNDING: British Leprosy Relief Association (LEPRA); Wellcome Trust

Data resource profile: network for analysing longitudinal population-based HIV/AIDS data on Africa (ALPHA Network)

The Network for Analysing Longitudinal Population-based HIV/AIDS data on Africa (ALPHA Network, http://alpha.lshtm.ac.uk/) brings together ten population-based HIV surveillance sites in eastern and southern Africa, and is coordinated by the London School of Hygiene and Tropical Medicine (LSHTM). It was established in 2005 and aims to (i) broaden the evidence base on HIV epidemiology for informing policy, (ii) strengthen the analytical capacity for HIV research, and (iii) foster collaboration between network members. All study sites, some starting in the late 1980s and early 1990s, conduct demographic surveillance in populations that range from approximately 20 to 220 thousand individuals. In addition, they conduct population-based surveys with HIV testing, and verbal autopsy interviews with relatives of deceased residents. ALPHA Network datasets have been used for studying HIV incidence, sexual behaviour and the effects of HIV on mortality, fertility, and household composition. One of the network’s substantive focus areas is the monitoring of AIDS mortality and HIV services coverage in the era of antiretroviral therapy. Service use data are retrospectively recorded in interviews and supplemented by information from record linkage with medical facilities in the surveillance areas. Data access is at the discretion of each of the participating sites, but can be coordinated by the network

BCG re-vaccination in Malawi: 30-year follow-up of a large, randomised, double-blind, placebo-controlled trial.

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 <5 years, 0·74; 0·41-1·35; aged 5-14 years, 0·77; 0·60-0·99), and for cases arising at least 20 years after vaccination (0·79; 0·63-1·01). There were no differences by tuberculin status at vaccination, or lineage. There was no evidence of protection against leprosy beyond 10 years after vaccination (although there have been only nine diagnostically certain cases since 1995). INTERPRETATION: There was no evidence that repeat BCG vaccination provides appreciable protection against overall tuberculosis in this rural African population with a high prevalence of HIV. Subgroup effects should not be overinterpreted given the multiple analyses done. However, the evidence for modest protection against HIV-negative tuberculosis, and for a delayed benefit in those vaccinated as children, is consistent with other observations in the literature. FUNDING: LEPRA, Wellcome Trust, Bill & Melinda Gates Foundation

TSCQ study: a randomized, controlled, open-label trial of daily trimethoprim-sulfamethoxazole or weekly chloroquine among adults on antiretroviral therapy in Malawi: study protocol for a randomized controlled trial.

BACKGROUND: Before antiretroviral therapy (ART) became widely available in sub-Saharan Africa, several studies demonstrated that daily trimethoprim-sulfamethoxazole (TS) prophylaxis reduced morbidity and mortality among HIV-infected adults. As a result, the World Health Organization (WHO) recommended administering TS prophylaxis to this group. However, the applicability of the results to individuals taking ART and living in sub-Saharan Africa has not been definitively evaluated. This study aims to determine if TS prophylaxis benefits HIV-infected Malawian adults after a good response to ART. If TS prophylaxis does indeed show benefit, it is important to determine if this is due to its antibacterial and/or antimalarial properties. METHODS/DESIGN: A randomized, controlled, open-label, phase III trial of continued standard of care prophylaxis with daily trimethoprim-sulfamethoxazole (TS) compared to discontinuation of standard of care TS prophylaxis and starting weekly chloroquine (CQ) prophylaxis or discontinuation of standard of care TS prophylaxis. The study will randomize 1400-1500 HIV-infected adults (equally divided over the three study arms) with a nondetectable viral load and a CD4 count of 250/mm(3) or more from antiretroviral therapy clinics in Blantyre and Zomba. The expected rate of primary endpoint events of death and WHO stage 3 and 4 events is 6.8 per 100 person-years of follow-up in all participants. Assuming the number of events follows a Poisson distribution and average participant follow-up after 10 % loss to follow-up is 41.6 months, the study will have approximately 85 % power to rule out a reduction of 35 % or more in primary endpoint events in the TS or CQ arms compared to discontinuation of TS prophylaxis-i.e., to show that discontinuation of TS prophylaxis is noninferior to either TS or CQ, with a noninferiority margin of 35 %. Ethical and regulatory approvals were obtained from the University of Malawi College of Medicine Research Ethics Committee; the Malawi Pharmacy, Medicines and Poisons Board; and the University of Maryland Baltimore Institutional Review Board. DISCUSSION: The study began recruitment activities at the Ndirande site in November 2012. The sponsor agreed to extend and expand the study in early 2015, and a second site, Zomba, was added for recruitment and follow-up in mid-2015. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01650558 (registered on 6 July 2012). PROTOCOL VERSION: Letter of amendment #1 to the DAIDS-ES 10822 TSCQ Malawi Protocol, Version 4.0, 16 December 2014

Malawi Epidemiology and Intervention Research Unit Non-Communicable Disease Survey data, 2013-2017

Data from a cross-sectional survey on non-communicable diseases and their risk factors carried out between 2013 and 2017 in one rural and one urban site in Malawi by the Malawi Epidemiology Intervention Research Unit (MEIRU). Data also include some anthropometric measures and laboratory test results, and self-report data relating to socio-economic status

Plasmodium falciparum: PCR detection and genotyping of isolates from peripheral, placental, and cord blood of pregnant Malawian women and their infants

Polymerase chain reaction (PCR) is both a sensitive means of detecting malaria parasitaemia, and a simple tool for identifying genetic differences in parasites infecting human subjects. We compared PCR to microscopy in detection of Plasmodium falciparum infection in peripheral, placental and cord blood samples collected from 131 pregnant Malawian women and their infants in 1997-99. Infections detected by species-specific PCR were genotyped at the merozoite surface protein I and 2 loci, and minimum numbers of infecting genotypes determined. PCR was of similar sensitivity to microscopy in detecting peripheral and placental infection, and placental blood PCR was 100% specific compared to placental histology. Cord blood parasitaemia was more frequently detected by PCR than microscopy, 20% versus 6%. Genotype numbers in peripheral blood (mean 2-36; range 1-5), placental blood (mean 2-41; range 1-6) and cord (mean 2.14; range 1-4) were similar. The frequency of detection of each allelic family did not differ between sites. Genotypes from different sites in each patient were compared. In 69% of women, genotypes were detected in peripheral blood and not placenta, or vice versa, suggesting possible differential sequestration of different parasite populations. Cord blood genotypes were usually a subset of those in peripheral and placental blood, but, in some cases, genotypes were found in cord blood that were absent from the mother. Transplacental infection before term, and clearance of maternal infection, is postulated