# Aetiological Fraction of Influenza, Respiratory Syncytial Virus and Other Respiratory Pathogens in Infants Aged < 1 Year Hospitalised With Respiratory and Non‐Respiratory Medical Illness in South Africa, 2016–2018

## TL;DR

The study finds that respiratory syncytial virus and influenza are major causes of hospitalization in infants in South Africa, highlighting the need for maternal immunization and improved nutrition.

## Contribution

This study quantifies the aetiological fractions of respiratory pathogens in infants hospitalized with both respiratory and non-respiratory illnesses in South Africa.

## Key findings

- Respiratory syncytial virus (RSV) had the highest aetiological fraction (94.0%) for respiratory illness hospitalization.
- Influenza and human metapneumovirus (HMPV) also showed high aetiological fractions for respiratory illness.
- Klebsiella pneumoniae was significantly associated with both respiratory and non-respiratory hospitalizations.

## Abstract

Understanding the contribution of pathogens to respiratory illness in infants is important to guide interventions. We assessed the aetiology of respiratory pathogens among infants hospitalised with respiratory and non‐respiratory illness.

We conducted an unmatched case–control study among infants aged < 1 year. Cases were admitted with acute respiratory and non‐respiratory illness in November 2016–October 2018. Controls were infants presenting for immunisation with no reported illness. Nasopharyngeal aspirates and blood were tested using multi‐pathogen real‐time PCR. Aetiological fraction (AF) was calculated using logistic regression, adjusting for HIV, age, season and pathogens with higher prevalence in cases than controls. Factors associated with respiratory illness hospitalisation were assessed using logistic regression.

Overall, 1214 cases (846 respiratory, 368 non‐respiratory) and 684 controls were included. Respiratory syncytial virus (RSV) (AF 94.0%), influenza (AF 72.6%) and human metapneumovirus (HMPV) (AF 74.9%) were significantly attributable to respiratory illness hospitalisation.
Klebsiella pneumoniae
had significant AF in both respiratory (AF 48.0%) and non‐respiratory (AF 60.7%) hospitalisation. HIV exposure (adjusted odds ratio [aOR] 1.5, 95% confidence interval [CI] 1.1–2.0) and living with HIV (aOR 6.6, 95%CI 2.1–20.5), underlying illness (aOR 4.8, 95%CI 1.3–17.6), malnutrition (aOR 6.0, 95%CI 4.0–8.9), infection with RSV (aOR 19.7, 95%CI 11.4–34.1), influenza (aOR 5.7, 95%CI 2.3–14.1) or HMPV (aOR 4.1, 95%CI 2.0–8.6) were associated with respiratory illness hospitalisation.

Maternal immunisation to prevent severe RSV and influenza illness in infants should be prioritised. In addition, improved infant nutrition and the prevention of HIV‐infection and HIV‐exposure could reduce the high burden of severe respiratory illness.