MENINGITIS in children, HIV infections, AIDS, CELLULAR immunity
Abstract
Over a million children are infected by the human immunodeficiency virus (HIV); most of whom live in the developing world. Bacterial meningitis is a serious infection of childhood that is 10 times more common in resource-constrained settings than well-resourced countries, and the outcome is worse. This paper reviews the relationship of bacterial meningitis to HIV infection and also the effect of HIV status on antibiotic sensitivity to common causes of childhood meningitis. The combined effects on outcome and long-term sequelae of meningitis are discussed and illustrated with results from Malawi and Southern Africa. [ABSTRACT FROM AUTHOR]
Sepako, Enoch, Glennie, Sarah J., Jambo, Kondwani C., Mzinza, David, Iwajomo, Oluwadamilola H., Banda, Dominic, van Oosterhout, Joep J., A. Williams, Neil, Gordon, Stephen B., and Heyderman, Robert S.
Subjects
THERAPEUTICS, HIV infections, T cells, ANTIRETROVIRAL agents, STREPTOCOCCUS pneumoniae, DISEASES in adults, CELLULAR immunity
Abstract
HIV-infected African adults are at a considerably increased risk of life-threatening invasive pneumococcal disease (IPD) which persists despite antiretroviral therapy (ART). Defects in naturally acquired pneumococcal-specific T-cell immunity have been identified in HIV-infected adults. We have therefore determined the extent and nature of pneumococcal antigen-specific immune recovery following ART. HIV-infected adults were followed up at 3, 6 and 12 months after initiating ART. Nasopharyngeal swabs were cultured to determine carriage rates. Pneumococcal-specific CD4 T-cell immunity was assessed by IFN-γ ELISpot, proliferation assay, CD154 expression and intracellular cytokine assay. S. pneumoniae colonization was detected in 27% (13/48) of HIV-infected patients prior to ART. The rates remained elevated after 12 months ART, 41% (16/39) (p = 0.17) and significantly higher than in HIV-uninfected individuals (HIVneg 14%(4/29); p = 0.0147). CD4+ T-cell proliferative responses to pneumococcal antigens increased significantly to levels comparable with HIV-negative individuals at 12 months ART (p = 0.0799). However, recovery of the pneumococcal-specific CD154 expression was incomplete (p = 0.0015) as were IFN-γ ELISpot responses (p = 0.0040) and polyfunctional CD4+ T-cell responses (TNF-α, IL-2 and IFN-γ expression) (p = 0.0040) to a pneumolysin-deficient mutant strain. Impaired control of pneumococcal colonisation and incomplete restoration of pneumococcal-specific immunity may explain the persistently higher risk of IPD amongst HIV-infected adults on ART. Whether vaccination and prolonged ART can overcome this immunological defect and reduce the high levels of pneumococcal colonisation requires further evaluation. [ABSTRACT FROM AUTHOR]