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Respiratory disease is the predominant cause of illness in children globally. We describe a unique multidisciplinary South African birth cohort, the Drakenstein Child Health Study (DCHS), to investigate the incidence, risk factors, aetiology and long-term impact of early lower respiratory tract infection (LRTI) on child health. Pregnant women from a poor, peri-urban community with high exposure to infectious diseases and environmental risk factors are enrolled with 1000 mother-child pairs followed for at least 5 years. Biomedical, environmental, psychosocial and demographic risk factors are longitudinally measured. Environmental exposures are measured using monitors placed at home visits. Lung function is measured in children at 6 weeks, annually and during LRTI episodes. Microbiological investigations including microbiome and multiplex PCR measures are done longitudinally and at LRTI episodes. The DCHS is a unique African birth cohort study that uses sophisticated measures to comprehensively investigate the early-life determinants of child health in an impoverished area of the world.
The DCHS is a population-based birth cohort study in the Drakenstein area in Paarl, a peri-urban area, 60 km outside Cape Town, South Africa. Pregnant women are enrolled in their second trimester and followed through childbirth; thereafter mother–child pairs are followed until children are at least 5 years old (figure 1). Maternal, paternal and child health are investigated through longitudinal measurements of risk factors in seven areas (environmental, infectious, nutritional, genetic, psychosocial, maternal and immunological) that may impact on child health. Intensive aetiological and risk factor investigations are done during an episode of childhood LRTI. Outline of study visits and samples collected. The local community of approximately 200 000 people is of low socio-economic status, live in informal housing or crowded conditions and have high levels of unemployment. Infectious diseases including pneumonia, HIV (antenatal prevalence approximately 30%) and tuberculosis (annual reported incidence 293/100 000) are common. There is a high prevalence of tobacco smoke exposure, alcohol misuse, malnutrition and other poverty-related exposures. Pneumonia is the predominant cause of childhood hospitalisation and death, with the estimated incidence similar to the reported LMIC incidence of 0.22 per child-year in early life.2 The population is stable, with little immigration or emigration. More than 90% of the population access healthcare in the public sector including antenatal and child health services. The public health system comprises 23 primary health clinics and one hospital, Paarl Hospital, where all births and hospital care occur. The well-established, free primary healthcare system provides childhood immunisations including 13-valent pneumococcal and H influenzae b vaccines as part of the national immunisation schedule. Consenting pregnant women are enrolled from two primary health clinics serving different populations—TC Newman (serving a mixed race population) and Mbekweni (serving a black African population). Pregnant women who are not enrolled are included in a control cohort; these mother–infant pairs are followed annually to compare outcomes with the active cohort. Antenatal and postnatal visits are at primary healthcare clinics, while birth, 6-week and annual study visits occur at Paarl hospital (figure 1). Fathers, as identified by mothers, are invited to participate in an antenatal study visit. Infants attend study visits synchronised with the national programme where feasible at 6, 10 and 14 weeks, and 6, 9, 18, 30, 36, 42, 54 and 60 months. Two home visits (antenatally and 4 months postnatally) are done to investigate environmental risk factors. Comprehensive data including biomedical, environmental, psychosocial, demographic, physical and mental health of the mother, father and child and intercurrent morbidity are collected. Specimens (blood, urine, stool, respiratory) are longitudinally taken (figure 1). Urine cotinine, to investigate tobacco smoke exposure, is longitudinally measured. Monitors measuring nitrogen dioxide, sulfur dioxide, carbon monoxide, volatile organic compounds and particulate matter (PM10) exposure over 24 h to 2 weeks are placed in homes; electrostatic dust collectors collect household dust over 2 weeks. Infant lung function, undertaken for the first time in an African setting, is measured at 6 weeks and annually at Paarl hospital. State-of-the-art measurements in unsedated children during sleep include tidal breathing, exhaled nitric oxide, forced oscillation technique and sulfur hexafluoride multiple breath washout. Lung function is also measured during a LRTI and 4–6 weeks thereafter. Chronic respiratory disease measurements include symptoms, clinical data, lung function and chest X-ray and ultrasound (during an LRTI). Child neurodevelopmental outcomes are assessed longitudinally with a subsample of infants undergoing brain MRI. All children have six monthly nasopharyngeal swabs (NPs) and stool specimens collected, while a subset intensive cohort have two weekly NPs and monthly stool samples in the first year. These specimens will enable longitudinal delineation of the child’s nasopharyngeal and stool microbiome using targeted (bacterial culture, multiplex real-time PCR for viral and bacterial pathogens) and non-targeted approaches (16srRNA gene sequencing). A similar approach is used for detailed investigation of LRTI aetiology on NP and induced sputum specimens. The maternal microbiome (stool, vaginal, skin, breast milk, NPs) is also studied perinatally (figure 1). The predictive value of the child’s microbiome for development of LRTI or chronic respiratory illness is a key area of study. Specimens from mothers, fathers, children and the environment are processed in a central research laboratory and stored at −80°C, creating a large biobank for future studies. Measurement of LRTI includes ambulatory and hospitalised pneumonia cases, severe or very severe pneumonia, as defined by WHO criteria. Strong surveillance systems have been established using healthcare workers, cell phones and active surveillance at health facilities. Trained community field workers promote community engagement and enable home visits even in areas where violent crime is common. Several strategies to promote cohort retention are used including automated study visit reminders, a close working relationship with clinical staff, a cell phone system enabling two-way communication with study participants at all times and regular follow-up synchronised with routine visits. Written informed consent from mothers is renewed annually; informed consent is also obtained from fathers. The study was approved by the Ethics Committee of the Faculty of Health Sciences, University of Cape Town, by Stellenbosch University and the Western Cape Provincial Research committee. The sample size of 1000 mother-infant pairs is designed to provide at least 550 pneumonia episodes for analyses of LRTI incidence and determinants. We estimate cumulative attrition over 5 years of 20% (including losses due to child mortality) and an expected incidence of LRTI similar to that reported in LMIC.2 This sample will provide adequate statistical power to detect relative associations of at least 1.5-fold for prevalent risk factors.
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