Insights from Pranay Sinna MD on a multicenter prospective cohort study on household contacts.
Chest x-ray showing cavity at right lung and interstitial infiltrate both lung due to Tuberculosis infection.
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Undernutrition and tuberculosis (TB) pose a risk among household contacts (HHCs) in India. These findings reveal a heightened risk of TB progression among undernourished individuals, emphasizing the need for cost-effective nutritional interventions to reduce TB incidence.
Out of 857 HHCs enrolled, 27.9% had a BMI below 18.5 kg/m², with a median BMI of 22.03 kg/m². During a median follow-up of 24 months, 18 incident TB cases occurred, with 10 cases among those with BMI < 18.5 kg/m². Kaplan-Meier analysis revealed a higher risk of TB progression in undernourished individuals (HR: 3.16, 95% CI: 1.25–8.02), while adjusting for age, sex, and HIV status showed an adjusted HR of 0.85 (95% CI: 0.73–0.98). There was no significant association between BMI and IGRA conversion.
“Undernutrition has been linked to blunting of both innate and adaptive immune responses to TB,” according to Sinha. “Indeed, undernutrition is the leading cause of secondary immunodeficiency in the world, far exceeding HIV/AIDS. Indeed, we have begun referring to the effect of undernutrition on immunity as nutritionally acquired immunodeficiency syndrome (N-AIDS). Undernourished individuals usually have an array of nutrient deficiencies which affect a range of physiological processes that affect the immune system. These include mechanisms that affect phagocytosis of the bacilli in the lungs, antigen presentation, and adaptive immune response.”
To carry out a prospective cohort analysis, we enlisted household contacts (HHCs) within 2 months of the Primary Index Case (PWTB) diagnosis. All HHCs, irrespective of their IGRA status, underwent tuberculosis disease screening at the outset. Those HHCs diagnosed with prevalent TB via liquid culture, GeneXpert, or microscopy upon enrollment were excluded. Participants were sourced from five diverse study sites across India, both epidemiologically and geographically.
“The RATIONS trial published in 2023 provides empirical evidence that an inexpensive food basket accompanied by multivitamin tablets can reduce the risk of TB among household contacts by as much as 40%,” according to Sinha. “The risk for progression is the highest in the first year of exposure so nutritional support must not be delayed. Not only would robust nutritional interventions reduce the risk of disease progression, they would also mitigate the nutritional shock due to catastrophic health expenditures that is experienced by approximately half of households with TB.”
The study's small sample size limited subgroup and multivariable analyses. Four household contacts (HHCs) developing TB within a week of enrollment suggest concurrent TB may cause weight loss, potentially reversing causality. However, rapid progression to primary TB due to nutrition-related immunodeficiency is also possible. Missing data on diabetes, alcohol/tobacco use, and micronutrient deficiencies hamper understanding of TB risk factors. Larger studies are crucial to validate and understand the interplay between undernutrition and TB risk. Longitudinal data collection and extended Cox models with time-dependent variables are recommended.
The findings underscore the significance of addressing undernutrition among vulnerable populations. Rectifying nutritional deficiencies is projected to yield substantial benefits in TB eradication efforts, with cost-effectiveness likely. There is a critical need to prioritize operational and policy research to identify cost-effective nutritional interventions for reducing TB incidence.
Reference
Sinah P, Ezhumalai K, Du X, et. al. Undernourished Household Contacts Are at Increased Risk of Tuberculosis (TB) Disease, but not TB Infection— a Multicenter Prospective Cohort Analysis, Clinical Infectious Diseases. Published April 23, 2024. Accessed April 26, 2024. Doi: https://doi.org/10.1093/cid/ciae149
