Bacterial aetiology and outcome in children with severe pneumonia in Uganda.

BACKGROUND: Pneumonia is a major cause of morbidity and mortality in the 'under-5s' and in Uganda accounts for 10-30% of childhood deaths. Antibiotic resistance is increasing. OBJECTIVE: To describe the bacterial aetiology, antimicrobial sensitivity and outcome of severe pneumonia among children aged 2-59 months admitted to the Acute Care Unit, Mulago Hospital, Uganda. METHODS: A total of 157 children aged 2-59 months with symptoms of severe pneumonia according to WHO guidelines were recruited over a 4-month period in 2005/2006. Blood and induced sputum were obtained for culture, and chest radiographs were undertaken. Children were clinically classified as having severe or very severe pneumonia and were followed up for a maximum of 7 days. RESULTS: Bacteraemia was detected in 15.9% of patients with Staphylococcus aureus (36%) and Streptococcus pneumoniae (28%) were the organisms most commonly isolated. Bacteria were isolated from sputum in half of the children, the commonest organisms being Streptococcus pneumoniae (45.9%), Haemophilus influenzae (23.5%) and Klebsiella species (22.4%). Staphylococcus aureus had only 33.3% sensitivity to chloramphenicol and H. influenzae isolates were completely resistant. S. pneumoniae was sensitive to chloramphenicol in 87.4% of cases. The case fatality rate was 15.5%. Independent predictors of death were very severe pneumonia (OR 12.9, CI 2.5-65.8), hypoxaemia (SaO(2) <92%, OR 4.9, CI 1.2-19.5) and severe malnutrition (OR 16.5, CI 4.2-65.5). CONCLUSION: S. aureus, S. pneumoniae and H. influenzae are common bacterial causes of severe pneumonia. Chloramphenicol, the current first-line antibiotic for treating severe pneumonia in Ugandan children, is useful in pneumonia caused by S. pneumoniae but other common bacteria show resistance. The presence of severe malnutrition, hypoxaemia and very severe pneumonia increase the risk of death and should be considered in case management protocols.

HIV-1 ICD p24 antigen detection in ugandan infants: use in early diagnosis of infection and as a marker of disease progression.

The objective of this study was to determine the use of immune-complex dissociated (ICD) p24 antigen detection for the diagnosis and prognosis of HIV-1 infection in Ugandan children. Plasma collected prospectively from children born to HIV-1 infected Ugandan women was stored and later analyzed for the presence of neutralizable HIV-1 p24 antigen using the Coulter ICD p24 antigen and neutralization kits. HIV-1 infection status, disease progression, and survival of the children were determined. Specimens from 311 children born to HIV-1 infected women, including 138 HIV-1 infected children, and 113 children born to negative women were tested. Sixty-nine (50%) infected children were p24 antigen positive at least once. For early HIV-1 diagnosis, the specificity and positive predictive value of the assay were consistently high (>95% and >83% respectively), but the sensitivity was low (6-53%), especially in the first months of life. The presence of p24 antigenemia in the first two years of life was associated with poor survival (20%) by 80 months of age compared with infected children without antigenemia (43%, P < 0.001). Early detection of p24 antigen (6 months, P < 0.001). The data suggest that ICD p24 antigen detection is not a sensitive method for the determination of infant HIV-1 status in our cohort of HIV-1 infected Ugandan children tested in the first two years of life. There was a strong correlation, however, between the presence and time of onset of p24 antigenemia and mortality among HIV-1 infected children.

Effects of malaria infection in human immunodeficiency virus type 1-infected Ugandan children.

BACKGROUND: Malaria causes severe morbidity and mortality in many areas of Africa where HIV-1 infection is also prevalent. Immunosuppression is associated with both diseases but most reports do not find significant interactions between them. METHODS: A collaborative study of HIV-1 infection in Ugandan women and their infants was established between the Ministry of Health, Makerere University, Kampala, and Case Western Reserve University in 1988. Four hundred fifty-eight infants, including 77 HIV-1-infected, 232 seroreverter and 125 control children born to HIV-1-negative mothers and 24 of indeterminate status were followed closely from birth for 4 years. Data on these infants were reviewed with respect to episodes of general illness and infections, suspected and confirmed episodes of malaria, onset and frequency of malaria, use of chloroquine and occurrence of selected illnesses after episodes of febrile illnesses. Thick and thin blood smears for malaria were obtained from children with fever. RESULTS: There was no association between occurrence of febrile illnesses and childrens' HIV-1 category. The relative rates of occurrence were 1.0 (95% confidence interval (CI), 0.8 to 1.2) and 1.1 (95% CI 0.9 to 1.4) for the HIV seroreverter and control children compared with the HIV-infected children. Although there was no association (P = 0.83) between HIV-1 status and a smear being taken during a febrile episode, there was an increase in smears positive for malaria parasitemia among seroreverter (risk ratio, 1.5; 95% CI 1.1 to 1.9) and control infants (risk ratio, 1.6; 95% CI 1.2 to 2.2) compared with HIV-1-infected infants. The level of parasitemia was similar in each group. A greater proportion of malaria episodes among the HIV-infected group than among the control groups resulted in hospitalizations (P = 0.001) and blood transfusions (P = 0.02). There was a positive association between time to clinical AIDS and absence of malaria (adjusted for follow-up age) in infected children (P = 0.02). Use of chloroquine was similarly high in each HIV-1 category (80%). CONCLUSIONS: In this group of HIV-infected children there was no significant increase in malarial episodes as compared with their HIV-negative controls. The results suggest a possibility that malaria may offer some protection against HIV-1 progression or that chloroquine used to treat malaria may have a direct effect against the HIV-1 virus.

PIP: A prospective study of 458 infants from Kampala, Uganda, who were followed from birth to 48 months of age, documented a reduced risk of malaria in children infected with HIV-1. Included in the analysis were 77 HIV-infected children, 232 seroreverters, 125 HIV-negative children born to uninfected mothers, and 24 children of indeterminate HIV status. Thick and thin blood smears for malaria were obtained from children with fever. 51% of all children had at least 1 positive malaria smear during the study period, for a total of 653 documented malaria episodes. HIV-infected children had 3.5 episodes of malaria per 100 child months of observation compared with 5.0 episodes among seroreverters and 5.5 episodes among seronegative children. The relative rates of occurrence of malaria were 1.0 (95% confidence interval [CI], 0.8-1.2) in seroreverters and 1.1 (95% CI, 0.9-1.4) There was an increase in smears positive for malaria parasitemia among seroreverters (risk ratio, 1.5; 95% CI, 1.1-1.9) and HIV-negative controls (risk ratio, 1.6; 95% CI, 1.2-2.2) compared with HIV-infected children. Parasitemia levels during episodes of malaria were not significantly different between groups. Although the HIV-infected children had fewer episodes of malaria, they had a greater percentage of severe malaria episodes than controls and more frequent hospitalizations and blood transfusions per acute malarial episode. Within the HIV-positive group, mortality and progression to AIDS were delayed (although not significantly) among children who had malaria compared with those without malaria. It is possible that HIV-1 suppresses Plasmodium infection by creating a milieu that is suboptimal for parasite growth.