Tuberculosis susceptibility and protection in children
Robindra Basu Roy1, Elizabeth Whittaker2, James A Seddon2
1Centre for International Child Health, Department of Paediatrics, Imperial College London, London, UK; Vaccines and Immunity Theme MRC Unit The Gambia at London School of Hygiene and Tropical Medicine, Fajara, The Gambia.
Insights
Children under 5 are highly susceptible to tuberculosis (TB) disease. Identifying biomarkers like monocyte-to-lymphocyte ratio can help develop new TB vaccines for children.
Area of Science:
- Pediatric infectious diseases
- Immunology
- Vaccinology
Background:
- Children under 5 are highly susceptible to tuberculosis (TB) infection, disease, and mortality.
- Risk of TB increases again in adolescence, with a protective effect observed in children aged 5-10 years.
- Neonatal Bacillus Calmette-Guérin (BCG) vaccination offers the clearest proven benefit against TB.
Purpose of the Study:
- To identify host immune correlates of risk for developing tuberculosis in children.
- To guide the development of novel tuberculosis vaccines for pediatric populations.
- To contribute to the World Health Organization's goal of eliminating childhood TB deaths.
Main Methods:
- Analysis of large case-control cohorts comprising over 15,000 children and adolescents.
- Investigation of potential biomarkers including monocyte-to-lymphocyte ratio, CD4 T cell counts, and blood RNA signatures.
Main Results:
- Identified the monocyte-to-lymphocyte ratio, activated CD4 T cell count, and a blood RNA signature as potential correlates of risk for TB development.
- Highlighted distinct susceptibility patterns across different pediatric age groups.
Conclusions:
- Specific immune and molecular signatures correlate with tuberculosis risk in children.
- Further research into these correlates is crucial for developing effective pediatric TB vaccines.
- Understanding age-specific susceptibility is key to achieving global TB elimination goals in children.
Abstract:
Children represent both a clinically important population susceptible to tuberculosis and a key group in whom to study intrinsic and vaccine-induced mechanisms of protection. After exposure to Mycobacterium tuberculosis, children aged under 5 years are at high risk of progressing first to tuberculosis infection, then to tuberculosis disease and possibly disseminated forms of tuberculosis, with accompanying high risks of morbidity and mortality. Children aged 5-10 years are somewhat protected, until risk increases again in adolescence. Furthermore, neonatal BCG programmes show the clearest proven benefit of vaccination against tuberculosis. Case-control comparisons from key cohorts, which recruited more than 15 000 children and adolescents in total, have identified that the ratio of monocytes to lymphocytes, activated CD4 T cell count, and a blood RNA signature could be correlates of risk for developing tuberculosis. Further studies of protected and susceptible populations are necessary to guide development of novel tuberculosis vaccines that could facilitate the achievement of WHO's goal to eliminate deaths from tuberculosis in childhood.
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