The Etiology of Childhood Pneumonia in Mali: Findings From the Pneumonia Etiology Research for Child Health (PERCH) Study

Abstract

Background: We present findings from the Pneumonia Etiology Research for Child Health (PERCH) site in Bamako, Mali.

Methods: Cases were patients 28 days to 59 months of age, admitted to hospital with severe or very severe pneumonia (2005 World Health Organization definition). Community controls were frequency matched by age. Both provided nasopharyngeal and oropharyngeal swabs for multiplex polymerase chain reaction and Streptococcus pneumoniae culture. Cases underwent blood culture and induced sputum culture for Mycobacterium tuberculosis. A subset had pleural fluid and lung aspirates collected for culture and polymerase chain reaction. Primary analyses included participants with negative or unknown HIV status (HIV-) and cases with abnormal chest radiographs (CXR+). Cases and controls were compared using logistic regression adjusting for age. Etiologic fractions were calculated by a Bayesian nested partially latent class analysis, the PERCH integrated analysis.

Results: Between January 1, 2012, and January 14, 2014, we enrolled 241 CXR+/HIV- cases and 725 HIV- controls. Compared with controls, cases were more likely to have moderate-to-severe wasting (43.1% vs. 14.1%, P < 0.001) and stunting (26.6% vs. 9.4%, P < 0.001). Predominant etiologies were respiratory syncytial virus [24.0%; 95% credible interval (CrI): 18.3%-31.1%], S. pneumoniae (15.2%; 95% CrI: 9.5-21.6), human metapneumovirus (11.8%; 95% CrI: 8.3%-16.2%) and parainfluenza virus type 3 (9.0%; 95% CrI: 5.8%-13.3%). Case fatality was 13.3%, with Staphylococcus aureus, Pneumocystis jirovecii and Haemophilus influenzae type b predominating (40% of fatal cases).

Conclusions: PERCH uncovered high case fatality among children with severe pneumonia in Mali, highlighting a role for new interventions (eg, respiratory syncytial virus vaccines) and a need to improve vaccine coverage and strengthen healthcare delivery.

FIGURE 1.

Case and control enrollment flow diagram. *Cases were systematically sampled during prespecified morning and evening shifts, and a maximum of 4–6 children were enrolled per shift. ¥Thirteen children had lower chest wall indrawing and wheeze and underwent a bronchodilator challenge; whether lower chest wall indrawing persisted was not recorded because quota had been met. Therefore, it is unknown whether these children met the criteria for severe/very severe pneumonia. δSecondary analysis includes 653 HIV-uninfected children and compares those with positive and negative CXR. †Primary analysis includes 241 children without known HIV infection [includes 164 (68%) whose HIV test was negative, and 77 (32%) whose HIV test was unknown] and had CXRs that met the WHO case definition of consolidation and/or other infiltrate along with 725 frequency-matched controls. ‡Includes 285 (39%) whose HIV test was negative, and 440 (61%) whose HIV test was unknown.

FIGURE 2.

NP/OP PCR prevalence and odds ratios by pathogen among CXR+, HIV-uninfected cases and HIV-uninfected controls. Pathogens are ordered alphabetically among bacteria and then viruses and fungi. *Prevalence defined using NP/OP PCR density thresholds for 4 pathogens: P. jirovecii, 4 log₁₀ copies/mL; H. influenzae, 5.9 log₁₀ copies/mL; CMV, 4.9 log₁₀ copies/mL; S. pneumoniae, 6.9 log₁₀ copies/mL). NP/OP PCR results based on positivity are given in Table, Supplementary Digital Content 4, http://links.lww.com/INF/E14. Odds ratios adjusted for age (months), site and presence of other pathogens detected by NP/OP PCR. Adeno indicates Adenovirus; B. pert, Bordetella pertussis; Boca, Human bocavirus; C. pneu, Chlamydophila pneumoniae; CMV, cytomegalovirus; Flu, influenza virus; HCoV, human coronavirus; Hib, Haemophilus influenzae type b; Hi non-b, Haemophilus influenzae non-b; HMPV, human metapneumovirus A/B; Legio, Legionella; M. cat, Moraxella catarrhalis; M. pneu, Mycoplasma pneumoniae; NVT, non PCV13 vaccine type; Para, Parainfluenza virus; P. jirov, Pneumocystis jirovecii; PV/EV, parechovirus/enterovirus; Rhino, rhinovirus; RSV, Respiratory syncytial virus A/B; S. aur, Staphylococcus aureus; S. pneu, Streptococcus pneumoniae; Salm sp, Salmonella spp.; VT, PCV-13 vaccine type.

FIGURE 3.

Etiology of severe and very severe pneumonia among CXR+, HIV-uninfected cases using the integrated analysis method. Other Strep includes Streptococcus pyogenes and Enterococcus faecium. NFGNR includes Acinetobacter spp. and Pseudomonas spp. Enterobacteriaceae includes E. coli, Enterobacter spp., and Klebsiella spp., excluding mixed gram-negative rods. Vaccine-preventable disease includes S. pneumoniae PCV-13 type, H. influenzae type b and B. pertussis. CXR+ defined as consolidation and/or other infiltrate on chest radiograph. Bacterial summary excludes MTB. Pathogens estimated at the subspecies level are presented grouped and disaggregated (Parainfluenza virus type 1, 2, 3 and 4; S. pneumoniae PCV 13 and S. pneumoniae non-PCV 13 types; H. influenzae type b and H. influenzae non-b; influenza A, B, and C). Description of symbols: Color of symbols: Red = bacteria; Blue = viruses; Gray = other. 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. Adeno indicates Adenovirus; B. pert, Bordetella pertussis; Boca, Human bocavirus; C. pneu, Chlamydophila pneumoniae; Cand sp, Candida species; CMV, cytomegalovirus; Entrb, Enterobacteriaceae; Flu, influenza virus A, B and C; H. inf, Haemophilus influenzae; HCoV, Coronavirus; HMPV, human metapneumovirus A/B; Legio, Legionella species; M. cat, Moraxella catarrhalis; M. pneu, Mycoplasma pneumoniae; Mtb, Mycobacterium tuberculosis; NFGNR, nonfermentative gram-negative rods; N. men, Neisseria meningitidis; NoS, not otherwise specified (ie, pathogens not tested for); P. jirov, Pneumocystis jirovecii; Para, parainfluenza virus types 1, 2, 3 and 4; PV/EV, parechovirus/enterovirus; Rhino, human rhinovirus; RSV, respiratory syncytial virus A/B; S. aur, Staphylococcus aureus; S. pneu, Streptococcus pneumoniae; Salm sp, Salmonella spp.; VPD, vaccine-preventable disease.