Routine immunization uptake and timeliness in young children exposed to multidrug-resistant tuberculosis: A secondary analysis of the Tuberculosis Child Multidrug-Resistant Preventive Therapy multi-site randomised controlled trial

BACKGROUND: The Expanded Programme on Immunization (EPI) reduces vaccine preventable disease-related childhood morbidity and mortality. Vaccine coverage and timeliness are crucial to maximise protection in children < 5 years old. This is especially important for children living in households affected by human immunodeficiency virus (HIV) and tuberculosis. METHODS: Tuberculosis Child Multidrug-Resistant Preventive Therapy (TB-CHAMP), a randomised controlled trial of multidrug-resistant tuberculosis (MDR-TB) prevention, enrolled participants at five sites across South Africa between 26 Sep 2017 and 21 Jan 2023. In this secondary exploratory analysis, we analysed the coverage and timeliness of EPI vaccinations due by 12 months of age and associations between delayed/non-vaccinations and pre-defined factors relating to child participant, adult MDR-TB index patient, and household. Early, on-time, and delayed vaccinations were defined as > 5 days before, within 28 days of, and > 28 days after the projected dates, respectively. Modified Poisson regression was used to assess factors associated with delayed/non-vaccination and vaccination completeness. The COVID-19 period was defined as the 6 months after the start of South African lockdown. RESULTS: Of 922 enrolled children, 814 children < 5 years with complete immunisation records were included. There was equal sex distribution, median age was 2.5 years (IQR 1.2-3.8), 35% were HIV-exposed, and 1% living with HIV. EPI coverage was over 80% across all vaccine types, excluding measles, with a trend towards an increase in delayed doses and non-vaccination as children aged. Two-dose measles vaccination coverage was 70.6% with 11.3% not having any measles vaccination. We found associations between delayed/non-vaccination with the primary caregiver being the MDR-TB index patient, lower household socioeconomic status and the site where children enrolled. We did not observe increased delays and non-vaccination during the COVID-19 period. CONCLUSIONS: EPI coverage in this vulnerable population was reasonable, except for measles, which was low. There was a trend towards increasing delays and non-vaccination with age. Targeting vaccination interventions at households affected by TB and poorer households emphasising caregiver education on routine vaccination especially as children age is important. TRIAL REGISTRATION: South African National Clinical Trials Register (SANCTR) (RefDOH270117530) and UK's Clinical Study Registry (Ref ISRCTN92634082, https://doi.org/10.1186/ISRCTN92634082.