Heterogeneity in Mycobacterium tuberculosis immunoreactivity in young children in Blantyre, Malawi: a community-based survey
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Background
As tuberculosis (TB) incidence declines, transmission increasingly concentrates into vulnerable populations. There is an urgent need for affordable surveillance strategies to monitor trends, identify high-risk groups and target interventions. Mycobacterium tuberculosis (Mtb) immunoreactivity surveys indirectly detect transmission and therefore undiagnosed infectious disease.
Methods
We conducted a cross-sectional community-based interferon-gamma release assay (IGRA) survey in children aged 1-4 years in Blantyre, Malawi. Community-representative participants were recruited using novel convenience sampling in health facilities alongside random household sampling, and tested for Mtb immunoreactivity using QFT-Plus IGRA. We constructed hierarchical Bayesian logistic regression models for IGRA positivity, with neighbourhood-level random effects.
Findings
Of 1,545 participants, 102 (6.6%) had a positive IGRA: an annual risk of Mtb infection (ARTI) of 2.7% (95% CrI 2.2-3.2%). Immunoreactivity was higher in the poorest third of households (8.7% vs 4.9%; adjusted odds ratio: 1.88, 95% CrI 1.08-3.01) compared to the richest, but was not associated with HIV exposure, malnutrition or reported household TB exposure. There was substantial between-neighbourhood heterogeneity (ARTI range 1.1-4.1%). There was no association between neighbourhood-level TB case notifications and ARTI.
Interpretation
An innovative convenience sampling approach identified a high burden and substantial spatial variation of recent TB transmission, which did not correspond to case notification rates. This strategy could support identification of high-risk populations, monitoring of trends and targeted public health interventions.
Funding
This work was funded by the Wellcome Trust [225482/Z/22/Z, 200901/Z/16/Z, 206575/Z/17/Z], and by UK aid from the UK government [to MDP, KCH, MYRH, ELC, PM; “Leaving no-one behind: transforming gendered pathways to health for TB”; 2018/S 196-443482]; however the views expressed do not necessarily reflect the UK government’s official policies.
Research in context
Evidence before this study
Tuberculin skin test surveys were widely used in the 20 th century to estimate population-level tuberculosis (TB) burden, particularly amongst school-aged children, but are limited by cross-reactivity with Bacillus Calmette-Guerin vaccination and non-tuberculous mycobacteria. For a previous meta-analysis we searched Medline Embase, Global Health databases, Science Citation Index Expanded, and Global Index Medicus, using terms related to Mycobacterium tuberculosis (Mtb) immunoreactivity and epidemiological study type (1/1/1993 to 31/12/2022; no language restrictions); we performed an updated search on 10/3/2026 restricted to interferon-gamma release assay (IGRA) surveys. Overall, we found four IGRA surveys which included results from children under five. None were designed to assess Mtb immunoreactivity as a measure of recent population-level transmission, and none reported neighbourhood-level data. From Malawi, we identified no community-representative Mtb immunoreactivity surveys from the past decade, and none using IGRA.
Added value of this study
We conducted a cross-sectional, community-representative IGRA survey among children under 5 years in Blantyre, Malawi, using pragmatic and scalable methodologies based on convenience clinic sampling and community satellite imagery. Because immunoreactivity in this age group reflects recent exposure, our study provides a proxy measure of ongoing transmission, and therefore of infectious TB disease within the community. We found a substantial burden of Mtb immunoreactivity in young children, and explore the individual- and neighbourhood-level risk factors associated with TB transmission, highlighting priority neighbourhoods for targeted interventions.
Implications of all the available evidence
Mtb immunoreactivity surveys have historically provided important insights into TB epidemiology, particularly in settings with falling incidence. Our findings suggest that a pragmatic methodology based on IGRA testing of young children may allow monitoring of trends and identification of high-risk groups and neighbourhoods, supporting targeted interventions in the pursuit of TB elimination.
