Epidemiological and clinical studies of viral pneumonia in young children in Bhaktapur, Nepal.

Abstract

Pneumonia remains the leading cause of illness and death in children less than 5 years of age in low-and-middle-income countries. Both bacteria and viruses are major causes of pneumonia in children. The disease burden attributed to the different respiratory pathogens varies with season and between regions. Knowledge of the relative importance of each agent is essential for adequate case management as well as prevention strategies, such as development of vaccines. This thesis focuses on respiratory viruses as causes of pneumonia. The basis for the present thesis is: 1) a cross-sectional study of 2,219 children with community-acquired pneumonia as defined under the Integrated Management of Childhood Illness (IMCI) program in the World Health Organization and 2) a case-control study of 680 pneumonia cases and 680 matched controls. Study subjects were included at a field clinic in Bhaktapur, Nepal. A nasopharyngeal aspirate was collected from each child at inclusion and examined for seven respiratory viruses using a commercial multiplex reverse transcription polymerase chain reaction (PCR) assay. The aim of the large cross-sectional study was to obtain information on the frequency of these seven common respiratory viruses and their seasonal distribution over a three-year period. Moreover, the study was designed to obtain information on clinical characteristics and outcomes of the pneumonia episodes and how the individual respiratory viruses were associated with these factors. The case-control study was undertaken to measure the degree to which the individual viruses were associated with IMCI defined pneumonia. We identified at least one virus in a large proportion (40%) of the children with pneumonia. Respiratory syncytial virus (RSV), influenza A, and parainfluenza virus (PIV) type 3 were most frequently detected among the seven viruses in the three-year study. The epidemics of infection with individual respiratory viruses contributed substantially to the observed pneumonia epidemics. RSV occurred in yearly epidemics in relation to the rainy season or during the winter. We also found that RSV infection was associated with signs of severe illness; the children infected with RSV more frequently had severe pneumonia and, among infants, low oxygen saturation, compared to children who were RSV negative. Among cases with non-severe pneumonia, the children with RSV infection had longer time to recovery and increased risk of treatment failure compared to the other children. The case-control study revealed that all the seven viruses were associated with pneumonia but that the strength of this association varied. RSV, PIV type 3 and influenza A were most strongly associated with pneumonia. Our findings indicate that these viruses are important causes of pneumonia in young children in Bhaktapur. Although influenza A and PIV type 3, like RSV, were among the most common viruses and were strongly associated with pneumonia, RSV was by far the most frequently detected virus over the three-year period and children infected with RSV had the most severe clinical presentations and outcomes. This supports the notion that development of a safe and effective RSV vaccine should be a priority for prevention of pneumonia in young children in low-and-middle-income countries.