The Etiology of Pneumonia in HIV-uninfected Children in Kilifi, Kenya: Findings From the Pneumonia Etiology Research for Child Health (PERCH) Study

Abstract

Background: In the 1980s, Streptococcus pneumoniae and Haemophilus influenzae were identified as the principal causes of severe pneumonia in children. We investigated the etiology of severe childhood pneumonia in Kenya after introduction of conjugate vaccines against H. influenzae type b, in 2001, and S. pneumoniae, in 2011.

Methods: We conducted a case-control study between August 2011 and November 2013 among residents of the Kilifi Health and Demographic Surveillance System 28 days to 59 months of age. Cases were hospitalized at Kilifi County Hospital with severe or very severe pneumonia according to the 2005 World Health Organization definition. Controls were randomly selected from the community and frequency matched to cases on age and season. We tested nasal and oropharyngeal samples, sputum, pleural fluid, and blood specimens and used the Pneumonia Etiology Research for Child Health Integrated Analysis, combining latent class analysis and Bayesian methods, to attribute etiology.

Results: We enrolled 630 and 863 HIV-uninfected cases and controls, respectively. Among the cases, 282 (44%) had abnormal chest radiographs (CXR positive), 33 (5%) died in hospital, and 177 (28%) had diagnoses other than pneumonia at discharge. Among CXR-positive pneumonia cases, viruses and bacteria accounted for 77% (95% CrI: 67%-85%) and 16% (95% CrI: 10%-26%) of pneumonia attribution, respectively. Respiratory syncytial virus, S. pneumoniae and H. influenza, accounted for 37% (95% CrI: 31%-44%), 5% (95% CrI: 3%-9%), and 6% (95% CrI: 2%-11%), respectively.

Conclusions: Respiratory syncytial virus was the main cause of CXR-positive pneumonia. The small contribution of H. influenzae type b and pneumococcus to pneumonia may reflect the impact of vaccine introductions in this population.

FIGURE 1.

Recruitment flow chart. Left, Case recruitment. Right, Control recruitment.

FIGURE 2.

Top 10 causes of radiologically confirmed pneumonia in HIV-uninfected cases, stratified by age, severity and CXR findings. Radiologically confirmed pneumonia defined by the presence of any of consolidation, pleural effusion or other infiltrate on chest radiograph. Description of symbols: Line represents the 95% credible interval. The size of the symbol is scaled based on the ratio of the estimated etiologic fraction to its standard error. Of 2 identical etiologic fraction estimates, the estimate associated with a larger symbol is more informed by the data than the priors. Panel C Stratified by WHO 2005 pneumonia case classification: severe pneumonia, cough or difficulty in breathing and lower chest wall indrawing without any danger sign; and very severe pneumonia, cough or difficulty in breathing and any danger sign. Flu indicates influenza virus A, B and C; H. inf, Haemophilus influenzae; HMPV, human metapneumovirus A/B; Mtb, Mycobacterium tuberculosis; NoS, not otherwise specified (ie, pathogens not tested for); P. jirov, P. jirovecii; Para, parainfluenza virus types 1, 2, 3 and 4; PV/EV, parechovirus/enterovirus; Rhino, Human rhinovirus; S. pneu, Streptococcus pneumoniae.

FIGURE 3.

Primary discharge diagnoses for children 28 days to 59 months of age admitted at the study hospital during the PERCH study. WHO Pneumonia classification (2005): severe pneumonia, cough or difficulty in breathing and lower chest wall indrawing without any danger sign; and very severe pneumonia, cough or difficulty in breathing and any danger sign. Abnormal chest radiograph: presence of any of consolidation, pleural effusion or other infiltrate on chest radiograph. Discharge diagnoses (primary and secondary) are recorded in a standard computer form at discharge by nonstudy clinicians during discharge. The most appropriate diagnoses are selected from a predefined list based on the diagnosis recorded during the course of the admission. At the study hospital bronchiolitis is differentiated at discharge diagnosis as part of a longitudinal surveillance program in Kilifi for RSV. In PERCH, children with wheeze/bronchiolitis were excluded from the study only if their case-defining symptoms (usually lower chest wall indrawing) resolved after bronchodilator treatment.