The Etiology of Pneumonia in HIV-1-infected South African Children in the Era of Antiretroviral Treatment: Findings From the Pneumonia Etiology Research for Child Health (PERCH) Study

Abstract

Background: HIV-1 infection predisposes to an increased burden of pneumonia caused by community-acquired and opportunistic pathogens.

Methods: Within the context of the Pneumonia Etiology Research for Child Health case-control study of under 5 pneumonia, we investigated the etiology of World Health Organization-defined severe/very severe pneumonia requiring hospitalization in South African HIV-infected children. Nasopharyngeal-oropharyngeal swabs and blood, collected from cases and age- and season-matched HIV-infected controls attending outpatient antiretroviral therapy (ART) clinics, were analyzed using molecular diagnostic methods. Cases were also investigated for tuberculosis. Etiologic fractions among cases with radiologically confirmed pneumonia were derived using Bayesian analytic techniques.

Results: Of 115 HIV-infected cases, 89 (77.4%) had radiologically confirmed pneumonia. Severe immunosuppression (adjusted odds ratio, 32.60; 95% confidence interval, 7.25-146.64) was significantly associated with radiologically confirmed pneumonia. Cotrimoxazole prophylaxis (46.4% vs. 77.4%) and ART (28.2% vs. 83.1%) coverage were significantly lower in cases compared with ART-clinic controls. An etiologic agent was identified in 99.0% of the radiologically confirmed cases. The 'top 4' pathogens associated with radiologically confirmed pneumonia were Pneumocystis jirovecii [23.0%; 95% credible interval (CrI), 12.4%-31.5%], Staphylococcus aureus (10.6%; 95% CrI, 2.2%-20.2%), pneumococcus (9.5%; 95% CrI, 2.2%-18.0%) and respiratory syncytial virus (9.3%; 95% CrI, 2.2%-14.6%). Bacteremia (6.7%) and in-hospital death (10.1%) were frequent among those with radiologically confirmed disease.

Conclusions: Pneumocystis jirovecii, S. aureus, pneumococcus and respiratory syncytial virus contribute a considerable burden of radiologically confirmed pneumonia in South African HIV-infected children under 5 years. Expediting access to ART and cotrimoxazole prophylaxis would decrease the burden of pneumonia in these children.

FIGURE 1.

Integrated etiology results for HIV-infected cases with radiologically confirmed pneumonia. Sample size: n = 89. Adeno indicates adenovirus; B. pert, Bordetella pertussis; Boca, Human bocavirus; C. pneu, Chlamydophila pneumoniae; Cand sp, Candida species; HCoV, human coronavirus; HMPV, human metapneumovirus A/B; Legio, Legionella species; M. cat, Moraxella catarrhalis; M. pneu, Mycoplasma pneumoniae; NFGNR, Nonfermentative Gram-negative rods; N. men, Neisseria meningitidis; NoS, not otherwise specified (ie, pathogens not tested for); PV/EV, Parechovirus/Enterovirus; Rhino, human rhinovirus; and Salm sp, Salmonella species. Other Strep includes Streptococcus pyogenes and Enterococcus faecium. NFGNR includes Acinetobacter species and Pseudomonas species. Enterobacteriaceae includes E. coli, Enterobacter species, and Klebsiella species, excluding mixed Gram-negative rods. Radiologically confirmed defined as consolidation and/or other infiltrate on chest radiograph. Bacterial summary excludes Mtb. Pathogens estimated at the subspecies level but grouped to the species level for display (Parainfluenza virus type 1, 2, 3 and 4; S. pneumoniae PCV13 and S. pneumoniae non-PCV13 types; H. influenzae type b and H. influenzae non-b; influenza A, B, and C). Estimates, including subspecies and serotype disaggregation (eg, PCV13 type and non PCV13 type), are given in Table 3 (age-stratified analysis) and Supplemental Digital Content 7, http://links.lww.com/INF/D849 (pneumonia severity-stratified analysis) for the top 10 pathogens. Description of symbols: Line represents the 95% credible interval. The size of the symbol is scaled based on the ratio of the estimated EF to its standard error. Of 2 identical EF estimates, the estimate associated with a larger symbol is more informed by the data than the priors.