Examining the Complex Relationship Between Tuberculosis and Other Infectious Diseases in Children

Abstract

Millions of children are exposed to tuberculosis (TB) each year, many of which become infected with Mycobacterium tuberculosis . Most children can immunologically contain or eradicate the organism without pathology developing. However, in a minority, the organism overcomes the immunological constraints, proliferates and causes TB disease. Each year a million children develop TB disease, with a quarter dying. While it is known that young children and those with immunodeficiencies are at increased risk of progression from TB infection to TB disease, our understanding of risk factors for this transition is limited. The most immunologically disruptive process that can happen during childhood is infection with another pathogen and yet the impact of co-infections on TB risk is poorly investigated. Many diseases have overlapping geographical distributions to TB and affect similar patient populations. It is therefore likely that infection with viruses, bacteria, fungi and protozoa may impact on the risk of developing TB disease following exposure and infection, although disentangling correlation and causation is challenging. As vaccinations also disrupt immunological pathways, these may also impact on TB risk. In this article we describe the pediatric immune response to M. tuberculosis and then review the existing evidence of the impact of co-infection with other pathogens, as well as vaccination, on the host response to M. tuberculosis . We focus on the impact of other organisms on the risk of TB disease in children, in particularly evaluating if co-infections drive host immune responses in an age-dependent way. We finally propose priorities for future research in this field. An improved understanding of the impact of co-infections on TB could assist in TB control strategies, vaccine development (for TB vaccines or vaccines for other organisms), TB treatment approaches and TB diagnostics.

Fatal central nervous system co-infection with SARS-CoV-2 and tuberculosis in a healthy child

“…Multiple studies have shown that viruses such as influenza, HIV, and measles can impair the ability of macrophages to contain mycobacterial growth, including Mycobacterium tuberculosis [26,27]. In a mouse model of influenza A and M. tuberculosis, co-infection resulted in enhanced mycobacterial growth in the lungs and decreased survival mediated by type I IFN signaling [28].…”

Fatal Central Nervous System Co-Infection with SARS-CoV-2 and Tuberculosis in a Healthy Child

“…Multiple studies have shown that viruses such as in uenza, HIV,and measles can impair the ability of macrophages to containmycobacterial growth, including Mycobacterium tuberculosis [18,19]. In a mouse model of in uenza A and M.tuberculosis, co-infection resulted in enhancedmycobacterial growth in the lungs and decreased survival mediatedby type I IFN signaling [20].Type I interferons also reduce theability of macrophages to respond to IFN-γ and control o ntracellular growth of M. tuberculosis [21].This child additionally had persistent lymphopenia, which is a riskfactor for severe tuberculosis [22].…”

Pediatric Tuberculosis: The Impact of “Omics” on Diagnostics Development

“…Thus, it is the dynamic balance between bacterial pathogenicity and the host immune system that determines the clinical presentation of TB disease. This balance is influenced by several factors including the infectious dose, virulence and persistence of the pathogen, host health and co-morbidities (HIV/AIDS, diabetes, and others), and the interplay between the innate and acquired immune system [ 6 , 7 , 8 , 9 , 10 ].…”