Correlates of isoniazid preventive therapy failure in child household contacts with infectious tuberculosis in high burden settings in Nairobi, Kenya - a cohort study.

Background: Sub-Saharan Africa continues to document high pediatric tuberculosis (TB) burden, especially among the urban poor. One recommended preventive strategy involves tracking and isoniazid preventive therapy (IPT) for children under 5 years in close contact with infectious TB. However, sub-optimal effectiveness has been documented in diverse settings. We conducted a study to elucidate correlates to IPT strategy failure in children below 5 years in high burden settings.

Methods: A prospective longitudinal cohort study was done in informal settlings in Nairobi, where children under 5 years in household contact with recently diagnosed smear positive TB adults were enrolled. Consent was sought. Structured questionnaires administered sought information on index case treatment, socio-demographics and TB knowledge. Contacts underwent baseline clinical screening exclude TB and/or pre-existing chronic conditions. Contacts were then put on daily isoniazid for 6 months and monitored for new TB disease, compliance and side effects. Follow-up continued for another 6 months.

Results: At baseline, 428 contacts were screened, and 14(3.2%) had evidence of TB disease, hence excluded. Of 414 contacts put on IPT, 368 (88.8%) completed the 1 year follow-up. Operational challenges were reported by 258(70%) households, while 82(22%) reported side effects. Good compliance was documented in 89% (CI:80.2-96.2). By endpoint, 6(1.6%) contacts developed evidence of new TB disease and required definitive anti-tuberculosis therapy. The main factor associated with IPT failure was under-nutrition of contacts (p = 0.023).

Conclusion: Under-nutrition was associated with IPT failure for child contacts below 5 years in high burden, resource limited settings. IPT effectiveness could be optimized through nutrition support of contacts.