Heterogeneity in Mycobacterium tuberculosis immunoreactivity in young children in Blantyre, Malawi: A community-based survey
11 affiliations
- 1Clinical Research Department, London School of Hygiene & Tropical Medicine, London, United Kingdom
- 2Malawi Liverpool Wellcome Research Programme, Blantyre, Malawi
- 3Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom
- 4Helse Nord TB Initiative, Kamuzu University of Health Sciences, Blantyre, Malawi
- 5School of Medicine, University of St Andrews, St Andrews, United Kingdom
- 6Department of Paediatrics, Queen Elizabeth Central Hospital, Blantyre, Malawi
- 7Department of Infectious Disease, Imperial College London, London, United Kingdom
- 8Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Stellenbosch University, Stellenbosch, South Africa
- 9Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, United Kingdom
- 10Malawi National Tuberculosis and Leprosy Elimination Programme, Lilongwe, Malawi
- 11School of Health and Wellbeing, University of Glasgow, Glasgow, United Kingdom
Abstract
As tuberculosis (TB) incidence declines, transmission becomes increasingly concentrated in vulnerable populations and neighbourhoods. There is an urgent need for affordable surveillance strategies to monitor trends, identify high-risk groups and target interventions. TB disease prevalence surveys are no longer cost-effective in monitoring epidemiological trends as countries target TB elimination, while passive surveillance methodologies such as case-notification rates (CNRs) are biased by healthcare access disparities. Mycobacterium tuberculosis (Mtb) immunoreactivity surveys indirectly measure transmission and therefore undiagnosed infectious TB, and may provide valuable information to TB programmes globally. We conducted a pragmatic hybrid clinic- and household-based cross-sectional interferon-gamma release assay (IGRA) survey in healthy children aged 1–4 years in 33 high-burden neighbourhoods Blantyre, Malawi. Participants were recruited using novel convenience sampling in health facilities, alongside random household sampling guided by satellite imagery, and tested for Mtb immunoreactivity using QFT-Plus IGRA. We constructed hierarchical Bayesian logistic regression models for IGRA positivity, with neighbourhood-level random effects. 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. Measuring Mtb immunoreactivity in young children, using innovative recruitment strategies, revealed a high burden of immunoreactivity suggestive of recent TB transmission. Children in the poorest households were at highest risk, highlighting the importance of social and economic inequity in driving the TB epidemic. Case notification rates may not reflect the areas with the highest transmission, and Mtb immunoreactivity surveillance may support identification of high-risk populations, monitoring of trends and targeting of public health interventions.
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BibTeX
@article{rickman2026heterogeneity,
title = {{Heterogeneity in Mycobacterium tuberculosis immunoreactivity in young children in Blantyre, Malawi: A community-based survey}},
author = {Hannah M. Rickman and Mphatso D. Phiri and Hannah Mbale and Helena R. A. Feasey and Marriott Nliwasa and George Chagaluka and James A. Seddon and Henry C. Mwandumba and Katherine C. Horton and Marc Y. R. Henrion and Tisungane Mwenyenkulu and Kuzani N. Mbendera and Emily S. Nightingale and Elizabeth L. Corbett and Peter MacPherson},
journal = {PLOS Global Public Health},
year = {2026},
month = oct,
doi = {10.1371/journal.pgph.0007269},
url = {https://journals.plos.org/globalpublichealth/article?id=10.1371/journal.pgph.0007269},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Heterogeneity in Mycobacterium tuberculosis immunoreactivity in young children in Blantyre, Malawi: A community-based survey
AU - Hannah M. Rickman
AU - Mphatso D. Phiri
AU - Hannah Mbale
AU - Helena R. A. Feasey
AU - Marriott Nliwasa
AU - George Chagaluka
AU - James A. Seddon
AU - Henry C. Mwandumba
AU - Katherine C. Horton
AU - Marc Y. R. Henrion
AU - Tisungane Mwenyenkulu
AU - Kuzani N. Mbendera
AU - Emily S. Nightingale
AU - Elizabeth L. Corbett
AU - Peter MacPherson
PY - 2026
DA - 2026/10/09
JO - PLOS Global Public Health
DO - 10.1371/journal.pgph.0007269
UR - https://journals.plos.org/globalpublichealth/article?id=10.1371/journal.pgph.0007269
AB - As tuberculosis (TB) incidence declines, transmission becomes increasingly concentrated in vulnerable populations and neighbourhoods. There is an urgent need for affordable surveillance strategies to monitor trends, identify high-risk groups and target interventions. TB disease prevalence surveys are no longer cost-effective in monitoring epidemiological trends as countries target TB elimination, while passive surveillance methodologies such as case-notification rates (CNRs) are biased by healthcare access disparities. Mycobacterium tuberculosis (Mtb) immunoreactivity surveys indirectly measure transmission and therefore undiagnosed infectious TB, and may provide valuable information to TB programmes globally. We conducted a pragmatic hybrid clinic- and household-based cross-sectional interferon-gamma release assay (IGRA) survey in healthy children aged 1–4 years in 33 high-burden neighbourhoods Blantyre, Malawi. Participants were recruited using novel convenience sampling in health facilities, alongside random household sampling guided by satellite imagery, and tested for Mtb immunoreactivity using QFT-Plus IGRA. We constructed hierarchical Bayesian logistic regression models for IGRA positivity, with neighbourhood-level random effects. 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. Measuring Mtb immunoreactivity in young children, using innovative recruitment strategies, revealed a high burden of immunoreactivity suggestive of recent TB transmission. Children in the poorest households were at highest risk, highlighting the importance of social and economic inequity in driving the TB epidemic. Case notification rates may not reflect the areas with the highest transmission, and Mtb immunoreactivity surveillance may support identification of high-risk populations, monitoring of trends and targeting of public health interventions.
SN - 2767-3375
ER -