Etiology of Childhood Pneumonia: What We Know, and What We Need to Know!

Childhood community acquired pneumonia continues to be an important clinical problem at the individual, institutional and community levels. Determination of microbial etiology is critical to develop evidence-based management (therapeutic and prophylactic) decisions. For decades, the approach to this relied on culture of lung aspirate specimens obtained from children with radiographically confirmed pneumonia, before administering antibiotics. Such studies revealed the major bacteria associated with pneumonia, prompting the World Health Organization to develop a highly sensitive clinical definition of pneumonia and advocate empiric antibiotic therapy; in order to save lives (focusing on community settings lacking resources for diagnostic tests). However, it spawned research studies conducted in/from/by institutions enrolling children with the relatively non-specific WHO definition of pneumonia. Specificity got further compromised by abandoning lung aspiration and using naso/oro pharyngeal specimens; even in children who had received antibiotics. This led to the recovery of viruses more often than bacteria. The use of highly sensitive molecular based diagnostics (especially PCR) facilitated the detection of multiple organisms (bacteria, viruses, atypical organisms and even fungal species); making it difficult to attribute etiology in individual cases. This challenge was sought to be addressed through the multi-site PERCH Study (Pneumonia Etiology Research for Child Health), designed as a case-control study to conclusively determine the etiology of pneumonia. However, despite a slew of publications, the answer to the central question of etiology has not emerged so far. Since none of the PERCH Study sites was located in India, the Community Acquired Pneumonia Etiology Study (CAPES) was conducted at Chandigarh. This turned out to be the largest single-centre pneumonia etiology study, and generated a wealth of data. This article summarizes the current challenges in pneumonia etiology research; outlines the key observations from the PERCH and CAPES projects, as well as other important studies; and suggests a way forward for pneumonia etiology research in the current era.