Predictors of TB disease in HIV-exposed children from Southern Africa.

BACKGROUND: P1041 was a randomised, placebo-controlled isoniazid prophylaxis trial in South Africa. We studied predictors for TB in HIV-exposed children participating in the P1041 trial.METHODS: We included data from entry until Week 108. Predictors considered were type of housing, overcrowding, age, sex, ethnicity, tobacco exposure, weight-for-age percentile Z-score (WAZ), CD4%, viral load (VL), antiretroviral therapy (ART) and number of household smokers.RESULTS: Of 543 HIV-positive (HIV+) and 808 HIV-exposed uninfected (HEU) infants at entry, median age was 96 days (interquartile range: 92-105). Of 1,351 caregivers, 125 (9%) had a smoking history, and 62/1,351 reported current smoking. In 594/1,351 (44%) households, there was at least one smoker. Smoking caregivers consumed 1-5 cigarettes daily. In the HIV+ cohort, significant baseline TB predictors after adjusting covariates were as follows: WAZ (adjusted hazard ratio [aHR] 0.76, P = 0.002) and log10 HIV RNA copies/ml (aHR 1.50, P = 0.009). Higher CD4% (aHR 0.88, P = 0.002) and ART (aHR 0.50, P = 0.006) were protective. In the HEU cohort, smoking exposure was associated with reduced TB-free survival on univariate analysis, but not after adjustment in the multivariate model.CONCLUSION: Low WAZ and high VL were strong predictors of TB disease or death. Rising CD4 percentage and being on ART were protective in the HIV+ cohort.

Source case identification in HIV-exposed infants and tuberculosis diagnosis in an isoniazid prevention study.

BACKGROUND: Identifying source cases of children exposed to tuberculosis (TB) is challenging. We examined the time-point of obtaining contact information of TB source cases in human immunodeficiency virus (HIV) infected and HIV-exposed uninfected (HEU) children in a randomised, placebo-controlled trial of pre-exposure to isoniazid prophylaxis. METHODS: A total of 543 HIV-infected and 808 HEU infants without TB exposure aged 3-4 months were enrolled between 2004 and 2008. At 3-monthly follow-up, infants were evaluated for TB and care givers were asked about new TB exposure. RESULTS: In total, 128 cases of TB disease and 40 deaths were recorded among 19% (105/543) of the HIV-infected and 8% (63/808) of the HEU children; 229 TB contact occasions were reported in 205/1351 (15%) children, of which 83% (189/229) were in the household. Of the 189 household contacts, 108 (53%) underwent microbiological evaluations; 81% (87/108) were positive. HIV-infected and HEU infants had similar frequencies of TB contact: in 48% of infants with definite TB, 58% with probable TB and 43% with possible TB. Of 128 children diagnosed with TB, a TB contact was identified for 59. Of these, 29/59 (49%) were identified at or after the child's TB diagnosis. CONCLUSION: TB source cases are often identified at or after a child's TB diagnosis. More effort is required for earlier detection.