Bacterial and Respiratory Viral Interactions in the Etiology of Acute Otitis Media in HIV-infected and HIV-uninfected South African Children

Shabir A Madhi, Niresha Govender, Kishen Dayal, Raghavendra Devadiga, Melissa K Van Dyke, Nadia van Niekerk, Clare Louise Cutland, Peter V Adrian, Marta C Nunes, Shabir A Madhi, Niresha Govender, Kishen Dayal, Raghavendra Devadiga, Melissa K Van Dyke, Nadia van Niekerk, Clare Louise Cutland, Peter V Adrian, Marta C Nunes

Abstract

Background: Bacteria and respiratory viruses are implicated in the pathogenesis of acute otitis media (AOM); however, data from low-middle income countries are sparse. We investigated the etiology of AOM in HIV-infected (HIV+), HIV-uninfected (HIV-) and HIV-exposed clinically asymptomatic for HIV-infection (HEU) South African children.

Methods: Children ≥3 months to <5 years of age with AOM were enrolled between May 2009 and April 2010 (NCT01031082). Middle ear fluid samples were cultured for bacteria; antibacterial susceptibility was done and serotyping undertaken for Streptococcus pneumoniae and Haemophilus influenzae. Nasopharyngeal aspirates were analyzed for respiratory viruses using immunofluorescence assay and polymerase chain reaction.

Results: Of 260 AOM episodes (HIV+:15; HIV-:182; HEU:63), bacteria were found in 54.6%, including Haemophilus influenzae (30.8%), 98.8% of which were nontypeable, and Streptococcus pneumoniae (20.4%), Staphylococcus aureus (15.8%), Moraxella catarrhalis (5.0%) and Streptococcus pyogenes (1.5%). Nonsusceptibility of Streptococcus pneumoniae to penicillin was 64.2%. Respiratory viruses were detected in 74.2% of cases. Human rhinovirus was most frequently detected (37.7%), followed by adenovirus (14.2%) and human bocavirus (11.5%) overall and irrespective of HIV status. Respiratory viruses were identified concurrently with S. pneumoniae, H. influenzae, M. catarrhalis (76.9-78.8%) and Staphylococcus aureus (63.4%) cultured from middle ear fluid, as well as in 72.0% of episodes negative for any bacteria.

Conclusion: The study suggests that respiratory viruses and pathogenic bacteria play an important role in the development of AOM in children. A similar spectrum of pathogens was observed independently of HIV status. Vaccines targeting both nontypeable Haemophilus influenzae and S. pneumoniae may have a broad impact on AOM in South Africa.

Conflict of interest statement

SAM, NG, NvN, CLC, PVA and MCN declare that their institution received grants to conduct trials from the GlaxoSmithKline group of companies/various pharmaceutical companies; SAM has undertaken consultancy and received payment for lectures including service on speakers bureaus for various pharmaceutical companies; KD declares no conflict of interest; RD and MVD are/were employed by the GlaxoSmithKline group of companies at the time of this study. MVD also holds stock ownership from the sponsoring company. This study was sponsored and funded by GlaxoSmithKline Biologicals S.A., Rixensart, Belgium. GlaxoSmithKline Biologicals SA was involved in all stages of the study conduct and analysis, and also took charge of all costs associated with the development and the publishing of the manuscript.

Figures

FIGURE 1.
FIGURE 1.
A, Bacterial etiology of acute otitis media episodes by age groups. B, Viral etiology of acute otitis media episodes by age groups.
FIGURE 2.
FIGURE 2.
Seasonal distribution of acute otitis media episodes (N = 260). IFA indicates immunofluorescence assay; PCR, polymerase chain reaction.

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