CD8+ T cells provide an immunologic signature of tuberculosis in young children.

RATIONALE: The immunologic events surrounding primary Mycobacterium tuberculosis infection and development of tuberculosis remain controversial. Young children who develop tuberculosis do so quickly after first exposure, thus permitting study of immune response to primary infection and disease. We hypothesized that M. tuberculosis-specific CD8(+) T cells are generated in response to high bacillary loads occurring during tuberculosis. OBJECTIVES: To determine if M. tuberculosis-specific T cells are generated among healthy children exposed to M. tuberculosis and children with tuberculosis. METHODS: Enzyme-linked immunosorbent spot assays were used to measure IFN-γ production in response to M. tuberculosis-specific proteins ESAT-6/CFP-10 by peripheral blood mononuclear cells and CD8(+) T cells isolated from Ugandan children hospitalized with tuberculosis (n = 96) or healthy tuberculosis contacts (n = 62). MEASUREMENTS AND MAIN RESULTS: The proportion of positive CD8(+) T-cell assays and magnitude of CD8(+) T-cell responses were significantly greater among young (<5 yr) tuberculosis cases compared with young contacts (P = 0.02, Fisher exact test, P = 0.01, Wilcoxon rank-sum, respectively). M. tuberculosis-specific T-cell responses measured in peripheral blood mononuclear cells were equivalent between groups. CONCLUSIONS: Among young children, M. tuberculosis-specific CD8(+) T cells develop in response to high bacillary loads, as occurs during tuberculosis, and are unlikely to be found after M. tuberculosis exposure. T-cell responses measured in peripheral blood mononuclear cells are generated after M. tuberculosis exposure alone, and thus cannot distinguish exposure from disease. In young children, IFN-γ-producing M. tuberculosis-specific CD8(+) T cells provide an immunologic signature of primary M. tuberculosis infection resulting in disease.

Aetiology, risk factors and immediate outcome of bacteriologically confirmed neonatal septicaemia in Mulago hospital, Uganda.

BACKGROUND: Neonatal septicaemia remains a major cause of morbidity and mortality. The aetiology, risk factors and outcome of this problem need to understood. OBJECTIVE: To determine the aetiology, risk factors and immediate outcome of bacteriologically confirmed neonatal septicaemia in Mulago hospital. METHODS: Blood cultures were aseptically obtained from neonates presenting with clinical sepsis by WHO criteria to Mulago during a five month period between July and November 2002. Blood was placed in Brain Heart Infusion media and incubated within 30 minutes. Subcultures were plated daily up to 7 days on blood, chocolate and MacConkey agar and incubated in aerobic and 5% carbon dioxide conditions. Pure colonies were identified by Gram stain and biochemical tests and antibiotic sensitivities were obtained. RESULTS: Gram positive organisms were predominant (69.2%) followed by E. coli (17%) and Group B Streptococci (GBS) (7%). Staphylococcus aureus and E. coli dominated isolates in early and late onset sepsis. S. aureus was more sensitive to gentamicin than to cloxacillin. The sensitivity of E. coli to ceftriaxone was 94.1%. Factors significantly associated with neonatal septicaemia were male sex, history of convulsions, hypoglycaemia, lack of antenatal care, late onset sepsis and umbilical pus discharge. Mortality in sepsis cases was 18.1%, and 84% of deaths occurred in the first 2 days of admission. Hypoglycaemia was significantly associated with death (p < 0.01). CONCLUSION: S. aureus predominates the aetiology of neonatal septicaemia followed by E.coli. Most deaths occur in the first 48 hours of admission and hypoglycaemia is significantly associated with death.