Genetic susceptibility to tuberculosis in Africans: a genome-wide scan.

Human genetic variation is an important determinant of the outcome of infection with Mycobacterium tuberculosis. We have conducted a two-stage genome-wide linkage study to search for regions of the human genome containing tuberculosis-susceptibility genes. This approach uses sibpair families that contain two full siblings who have both been affected by clinical tuberculosis. For any chromosomal region containing a major tuberculosis-susceptibility gene, affected sibpairs inherit the same parental alleles more often than expected by chance. In the first round of the screen, 299 highly informative genetic markers, spanning the entire human genome, were typed in 92 sibpairs from The Gambia and South Africa. Seven chromosomal regions that showed provisional evidence of coinheritance with clinical tuberculosis were identified. To identify whether any of these regions contained a potential tuberculosis-susceptibility gene, 22 markers from these regions were genotyped in a second set of 81 sibpairs from the same countries. Markers on chromosomes 15q and Xq showed suggestive evidence of linkage (lod = 2.00 and 1.77, respectively) to tuberculosis. The potential identification of susceptibility loci on both chromosomes 15q and Xq was supported by an independent analysis designated common ancestry using microsatellite mapping. These results indicate that genome-wide linkage analysis can contribute to the mapping and identification of major genes for multifactorial infectious diseases of humans. An X chromosome susceptibility gene may contribute to the excess of males with tuberculosis observed in many different populations.

Management of children with tuberculosis admitted to a pediatric intensive care unit.

OBJECTIVES: To review the incidence, clinical features, ventilatory support and outcome of children with tuberculosis (TB) admitted to a Pediatric Intensive Care Unit (PICU) in a region with an high incidence of TB. MATERIALS AND METHODS: The study was performed in a PICU situated in a province with a extremely high incidence of TB (> 700 new cases/ 100000/year). This is a retrospective descriptive study of TB admissions to the PICU in a 4-year period. Data regarding indications for admission, clinical picture, duration of ventilation, PICU and hospital stay were collected from patient files. Outcome measures included mortality and long term morbidity. RESULTS: Of the 1862 children admitted to the hospital for TB during the 4 years, 57 (3.1%) required PICU admission (1 to 6% of annual admissions). Of these 57 children 41 (72%) were admitted for respiratory failure. In 12 cases TB was the cause of the respiratory failure, 17 cases suffered from other respiratory diseases and in 12 cases the cause was nonrespiratory disease of which TB meningitis (n=8) was the most common. Mechanical ventilation was indicated in 43 (75%) patients who were ventilated for 7.3+/-11.5 days. The duration of PICU admission was 10.2+/-2.4 days whereas the duration of hospitalization was 70.3+/-148.9 days. The PICU mortality was 23% with TB meningitis having the highest mortality of 75%. CONCLUSIONS: In a region with a high incidence of TB, tuberculous patients constitute up to 6% of PICU admissions. A high degree of suspicion for the diagnosis is needed because in 30% of our cases the diagnosis was not initially considered.