The high burden of Pneumocystis carinii pneumonia in African HIV-1-infected children hospitalized for severe pneumonia
Ruffini, D.D.; Madhi, S.A.
Aids 16(1): 105-112
2002
ISSN/ISBN: 0269-9370 PMID: 11741167 DOI: 10.1097/00002030-200201040-00012Document Number: 243915
To estimate RNA viral load patterns over age in vertically infected children that account for between- and within-individual variation, treatment and assay cut-off detection level. To investigate possible sex-based differences. A total of 118 infected children with 894 RNA viral load measurements enrolled in the European Collaborative Study were prospectively followed from birth for up to 15 years. Fractional polynomial and mixed effects models with censored data to assess the non-linear pattern of viral load over age, allowing for repeated measures. The RNA viral load peaked at approximately 3 months of age, and gradually declined thereafter. The sex by age interaction was significant (chi2 = 19.7, P < 0.001); viral load peaked higher for girls than boys, but after 4 years the RNA load was consistently 0.25-0.5 log10 lower for girls than boys. The effects of sex and treatment on viral load vary over age (chi2 = 6.31, P = 0.043). Sex differences in RNA viral load relating to measurement without treatment were more pronounced than those under treatment. Disease progression was more rapid for girls than for boys up to the age of 4 years, and less rapid thereafter; the overall difference was not statistically significant. Differences in RNA viral load over age between untreated boys and girls may have implications for policies for the initiation of antiretroviral therapy, but do not seem to translate into differences in progression to serious disease. The findings would suggest underlying biological explanations, which need further investigation. To evaluate the burden of Pneumocystis carinii pneumonia (PCP) and the usefulness of induced sputum and nasopharyngeal aspirates (NPA) in diagnosing PCP in African children in whom the use of bronchoalveolar lavage is unavailable. Children aged 2-24 months who were either known or suspected of being HIV-1 infected and who were hospitalized for severe pneumonia were investigated for P. carinii using induced sputum and NPA. P. carinii identification was performed using a direct monoclonal antibody immunofluorescent stain. A group of children who subsequently died also had lung biopsies performed. P. carinii cysts were identified in 51 out of 105 (48.6%) children either from induced sputum (37/105, 35.2%) or NPA (26/101, 25.7%) samples, or from both. Neither clinical nor laboratory tests were useful in distinguishing between HIV-1-infected children with and without PCP. Twenty-eight per cent (14/51) of HIV-1-infected children who developed PCP had a history of being on cotrimoxazole prophylaxis at the time of their illness. Mortality rates of HIV-1-infected children with and without PCP were equally high (27.5 and 27.8%, respectively). Histological evidence of PCP and cytomegalovirus pneumonia was observed on post-mortem lung biopsy in eight out of 18 (44.4%) children each. Using post-mortem lung histology as a reference, the sensitivity and specificity for induced sputum and NPA in diagnosing PCP were 75 and 80%, respectively. Strategies to reduce the high burden of PCP, which can successfully be diagnosed using NPA and induced sputum, in HIV-1-infected children hospitalized with severe pneumonia are urgently warranted in Africa.