Incidence and Risk Factors for Influenza lower respiratory tract infection in a South African Birth Cohort

Hapeela, Nchimunya

Incidence and Risk Factors for Influenza lower respiratory tract infection in a South African Birth Cohort

Thesis / Dissertation

2026

Publisher

University of Cape Town

Department

Department of Paediatrics and Child Health

Faculty

Faculty of Health Sciences

Abstract

Background: Lower respiratory tract infection (LRTI) is a significant cause of morbidity and mortality in children under five years, particularly in low- and middle-income countries (LMICs). However, data on the incidence and risk factors for influenza-associated LRTI in young children in these settings are limited. This study prospectively investigated the incidence of and risk factors for influenza-associated LRTI from birth through early childhood, in a South African birth cohort, the Drakenstein Child Health Study (DCHS). Methods: Children enrolled in the DCHS between May 2012 to September 2015 were followed from birth up to 5 years of age. Data on socio-economic status, maternal and infant characteristics, and LRTI episodes were collected. Quantitative real-time polymerase chain reaction (qPCR) was used to identify respiratory organisms, including the influenza virus associated with each LRTI episode. Influenza-associated LRTI was defined as the presence of clinical LRTI symptoms with a laboratory-confirmed influenza infection (qPCR cycle threshold <40 for at least one influenza target gene). Generalized estimating equations (GEE) models were used to assess associations between potential risk factors and influenza-associated LRTI. Results: Among 1143 live births, 51% (586/1143) were male, 17% (189/1143) were born premature, and 22% (248/1143) were HIV-exposed uninfected, while two were living with HIV. The population experienced high levels of socio-economic disadvantages, with 61% (695/1143) of mothers having an education below secondary level, and 86% (982/1143) of households earning less than 5,000 South African rands per month. Maternal smoking and alcohol use during pregnancy were reported by 28% (323/1142) and 13% (137/1067) of mothers, respectively. None of the mothers received influenza vaccination during pregnancy, and no child was vaccinated against influenza through the study, although coverage for other routine childhood vaccines exceeded 98%. iv Overall, 47% (521/1108) of children experienced LRTI episodes (incidence rate of 22 episodes per 100 child-year, [95% CI 21, 23]). Among 472 children with qPCR results, 70 influenza-associated LRTI episodes occurred in 64 children (14%); incidence rate: 1.4 episodes per 100 child-year, [95% CI:1.1, 1.8] per 100 child-years. Of these 64 children with influenza-associated LRTI, 13% (9/70) required hospitalization, and one influenza-associated LRTI death was recorded among the hospitalized. Risk factors for all-cause LRTI included lower maternal education, maternal HIV, prenatal alcohol use, preterm birth, male sex, and winter birth. After adjusting for other factors, influenza-associated LRTI was significantly associated with older age (odds ratio for a one-month increase in age: 1.02, [95% CI: 1.00-1.04]) and winter season. Conclusion: Influenza remains a significant cause of LRTI, particularly among children affected by socio-economic disadvantages and maternal HIV exposure, and during the winter season. Expanding maternal and early childhood influenza vaccination programs, alongside broader public health interventions addressing underlying social vulnerabilities, could meaningfully reduce influenza-associated LRTI and improve child health outcomes.