Early-life respiratory syncytial virus lower respiratory tract infection in a South African birth cohort: epidemiology and effect on lung health

Abstract

Summary Background Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection (LRTI) in children. Early-life RSV LRTI might affect long-term health but there are few data from low-income and middle-income countries. We investigated the epidemiology and effect of early-life RSV LRTI on lung health in a South African birth cohort. Methods We conducted the Drakenstein Child Health Study (DCHS), an ongoing birth cohort longitudinal study in the Western Cape province, South Africa. We enrolled pregnant women aged 18 years or older during their second trimester of pregnancy at two public health clinics. We followed up study children from birth to 2 years. The primary outcome of the study was LRTI and RSV LRTI. LRTI and wheezing episodes were identified through active surveillance; respiratory samples were tested for RSV and other pathogens. Wheezing was longitudinally identified by caregiver report and ascertainment at health facilities. Lung function was measured from 6 weeks to 2 years. We analysed the associations between RSV LRTI and subsequent LRTI, wheezing, and lung function using generalised estimating equations and mixed-effects linear regression. Findings We enrolled 1137 mothers between March 5, 2012, and March 31, 2015. Among their 1143 infants, accruing 2093 child-years of follow-up, there were 851 cases of LRTI (incidence 0·41 episodes per child-year, 95% CI 0·38–0·43). Admission to hospital owing to LRTI occurred in 169 (20%) cases (incidence 0·08 episodes per child-year, 0·07–0·09), with a case-fatality ratio of 0·5%. RSV was detected in 164 (21%) of 785 LRTI events with a specimen available for qPCR, an incidence of 0·08 episodes per child-year (0·07–0·09); highest at age 0–6 months (0·15 episodes per child-year, 0·12–0·19). Children with a first RSV LRTI were three times as likely to develop recurrent LRTI compared with those with non-RSV LRTI (0·32 [0·22–0·48] vs 0·10 [0·07– 0·16] episodes per child-year; p<0·0001), particularly following hospitalised RSV LRTI. RSV LRTI and hospitalisation for all-cause LRTI were independently associated with recurrent wheezing (adjusted incident rate ratio 1·41, 95% CI 1·25–1·59, for RSV LRTI and 1·48, 1·30–1·68, for hospitalisation). LRTI or recurrent LRTI was associated with impaired lung function, but a similar outcome was observed following RSV LRTI or non-RSV LRTI. All-cause LRTI was associated with an average 3% higher respiratory rate (95% CI 0·01–0·06; p=0·013) and lower compliance (–0·1, −0·18 to 0·02) at 2 years compared with no LRTI. Recurrent LRTI was associated with further increased respiratory rate (0·01, 0·001–0·02), resistance (0·77 hPa s L −1 , 0·07–1·47), and lower compliance (–0·6 mL hPa −1 , −0·09 to −0·02) with each additional event. Interpretation RSV LRTI was common in young infants and associated with recurrent LRTI, pa...

Factors associated with serious outcomes of pneumonia among children in a birth cohort in South Africa

“…From March 2012 to March 2015, 1137 pregnant women were enrolled; there were 1143 live births. Risk factors for and incidence of pneumonia in the cohort have been described [9,10]. In the first 2 years of life there were 174 episodes of hospitalized pneumonia.…”

“…We previously described incidence, severity and risk factors for pneumonia [9] and respiratory syncytial virus (RSV) pneumonia [10] in children under 2 years of age in the Drakenstein Child Health Study (DCHS), a birth cohort in South Africa. In this paper, we describe factors associated with pneumonia mortality or ICU admission in the first 2 years of life, and test whether the risk factors included in the PERCH severity score were associated with death or ICU admission in this cohort.…”

Pneumonia in Infancy and Risk for Asthma

“…Data from a South African birth cohort suggest that lower respiratory tract infections in infancy are associated with decreased lung function and recurrent wheeze. 27,28 Several different biological mechanisms could explain the association between pneumonia diagnosis and asthma, including direct damage to the lung parenchyma, immunomodulatory mechanisms, or disturbance of lung development during a critical phase. In mouse models, pneumococcal pneumonia has been shown to alter the expression of airway smooth muscle proteins, whereas RSV infection has been associated with immune modulation and airway hyperresponsiveness.…”

Satellite Symposia

“…A causal relationship between early life RSV LRTI and recurrent wheeze or asthma is hard to establish since both syndromes are complex and risk factors should be weighted differently for specific phenotypes and endotypes [8]. Still, there is a significant impact of RSV‐LRTI in the first year of life on recurrent wheeze, especially in the pre‐school years with tracking of low lung function values [9]. There are important implications for RSV prevention strategies, especially regarding any potential long‐term benefit from prophylaxis aimed at reducing post‐RSV recurrent wheezing and asthma [7].…”