Risk of Disease After Isoniazid Preventive Therapy for Mycobacterium tuberculosis Exposure in Young HIV-uninfected Children

Abstract

Background:The risk of developing tuberculosis (TB) disease in HIV-uninfected children after isoniazid preventive therapy (IPT) for a positive QuantiFERON-TB Gold In-Tube test (QFT-GIT) is unknown. The aim of this study was to evaluate risk of TB disease after IPT in young HIV-uninfected children with a positive QFT-GIT result, or household TB contact.Methods:HIV-uninfected South African infants aged 4–6 months were screened for enrolment in a TB vaccine trial. Baseline household TB contact and positive QFT-GIT result were exclusion criteria, and these infants were referred for IPT. Outcome data are reported for 36 months after IPT referral.Results:Four thousand seven hundred forty-nine infants were screened. Household TB contact was reported in 131 (2.8%) infants; 279 (6.0%) were QFT-GIT positive, and 138 of these 410 infants (34.0%) started IPT. Forty-four cases of TB disease (11.0%) were recorded within 991 child years of observation. TB disease incidence was 4.8 versus 3.6 per 100 child years in household exposed versus QFT-GIT-positive children [incidence rate ratio: 1.35; 95% confidence interval (CI): 0.67–2.88] and 2.4 versus 5.5 per 100 child years in children who received versus did not receive IPT, respectively (incidence rate ratio: 0.44; 95% CI: 0.17–0.96). Adjusted hazard ratio (Cox regression) for TB disease was 0.48 (95% CI: 0.21–1.05) for those who received IPT.Conclusion:In young HIV-uninfected children, the effect of IPT on risk of TB disease is similar, whether TB exposure was defined by household contact history or by positive QFT-GIT result. International IPT guidelines for HIV-uninfected children with a positive QFT-GIT result should be updated.

Serial QuantiFERON testing and tuberculosis disease risk among young children: an observational cohort study

“…IPT reduces the incidence of disease in M tuberculosis-infected or M tuberculosis-exposed children by more than 50% and is recommended in national and international guidelines. 12,13 However, implementation of IPT is poor in the resource-limited countries where effective tuberculosis prevention is most needed.…”

Impact of isoniazid preventive therapy on the evaluation of long-term effectiveness of infant MVA85A vaccination

“…We previously reported a lower effectiveness of IPT (52%) among a smaller group of infants with a history of household TB exposure and/or LTBI. 4 Differences in these estimates might be explained by differences in study population and the denominator and a clinical trial effect, whereby participants in this study were more rigorously followed and investigated for TB disease. However, the 85% effectiveness of IPT among children with LTBI reported here is equivalent to the 88% reported by Trauer et al 11 …”

“…Despite recommendations that children aged <5 years with latent tuberculous infection (LTBI) or close contact with a TB patient should receive IPT, linkage to care is poor in high TB burden countries 1,3. Three South African studies showed that respectively only 20%, 28% and 33% of children referred for IPT actually received it,4–6 which is similar to an estimate from Ethiopia (33%) 7. Health systems strengthening is needed to ensure IPT is administered when indicated.…”

Isoniazid preventive therapy for children in sub-Saharan Africa

“…A major step-up change in scaling up the implementation of IPT in sub-Saharan Africa is needed and will require several major obstacles to be overcome. [9][10][11] First, there are absence of comprehensive clear policies on IPT. Most countries do not have recommendations for screening, testing and treatment for LTBI and there is lack of harmonization of policy recommendations across countries and regions.…”