Undernutrition, nutritionally acquired immunodeficiency, and tuberculosis control

Nutrition is essential to life, health, and protection from disease. Pneumocystis jiroveci pneumonia—the first opportunistic infection associated with AIDS and indicative of advanced immunosuppression—was initially described in undernourished infants in wartime Europe.1 Undernutrition increases the frequency, severity, and fatality of many infections (including tuberculosis (TB)), while infections in turn worsen undernutrition.2 Undernutrition is the commonest cause of secondary immunodeficiency worldwide, which affects both innate and adaptive immunity, and this has been termed nutritionally acquired immune deficiency syndrome.3 Immunodeficiency related to malnutrition contributes to nearly half of deaths from common childhood infections in children under 5 years.4

Undernutrition in adults is an under-recognised driver of TB epidemics, which are declining only slowly in high burden countries despite treatment programmes.5 Large cohort studies have consistently shown a strong, inverse, and exponential relation between body mass index and incidence of TB.6 In the most recent study, new cases of TB were 12 times higher in people with a low body mass index (BMI<18.5), relative to those with normal BMI (18.5-25) after other factors were adjusted for (adjusted hazard ratio =12.43, 95% confidence interval 5.75 to 26.95).7 People with a low BMI and latent TB have lower levels of protective cytokines.8

Undernutrition contributes most to incidence of TB in high burden countries with a lower HIV prevalence, such as those in South East Asia.9 In India, which has the highest number of incident cases of TB globally, undernutrition is a coepidemic, with more than a third of adults having a low body mass index.9 Around 55% of the annual incidence of TB (more than a million new cases) in India has been estimated to be attributable to undernutrition,10 and modelling suggests that reducing adult undernutrition could cut new cases by up to 71% in certain states.11 Contacts of patients with multidrug resistant TB are at high risk of similar infection, and maintaining adequate nutrition12 in them would be prudent in addition to the current strategy of close observation.

Undernutrition is a widely prevalent comorbidity in people with TB13 and increases the risk of more severe disease,14 death,15 delayed sputum conversion,16 drug induced hepatotoxicity,17 malabsorption of anti-TB drugs,18 and relapse after cure.19 Severe undernutrition (BMI <16) was documented at diagnosis in more than half of patients with pulmonary TB in rural India, and serious levels of undernutrition persisted even after effective treatment.20 The World Health Organization’s recent guideline made recommendations for nutritional support in patients with TB,21 and these need to be acted on by those managing TB treatment programmes. Although a systematic review published this year found that there was insufficient research to judge whether food supplementation improves treatment outcomes, the summary risk ratio for death in supplemented patients who were HIV negative (0.18, 95% CI 0.02 to 1.48) is promising, and larger pragmatic trials are urgently needed.22

WHO’s End TB strategy aims to reduce the incidence of TB by 90% by 2035.23 A third of the world’s population are estimated to have latent TB infection.24 With well functioning cell mediated immunity, only 5%-15% of people with latent infection will develop active TB over a lifetime,24 implying protection of around 90%. To meet the ambitious incidence reduction targets we need to ensure that latent TB infection remains latent by tackling undernutrition and other risk factors for progression to active disease. In a unique sociomedical experiment in the UK between 1918 and 1943, social interventions—of which adequate nutrition was considered the most important—nearly eliminated TB in children born in the Papworth village settlement for patients with TB and their families.12 In German prisoner-of-war camps during the second world war, British soldiers given a Red Cross ration of 1000 calories and 30 g proteins in addition to the poor camp diet had a 93% lower incidence of TB than their Russian counterparts, who received no ration—a risk reduction comparable to that of an effective vaccine14

Undernourished people in countries with a high burden of TB and battling food inflation, need urgent access to the oral “vaccine” of a balanced adequate diet; it is polyvalent, increasing immunity to many other pathogens, and can be manufactured in farms and dispensed over the counter safely to men, women, and children. In many cases, TB is a nutritional disease that can be prevented by placing nutrition (including adult nutrition) at the heart of the global developmental and public health agenda and implementing appropriate economic and agricultural policies, social protection measures, and targeted nutritional interventions. It’s time for the new vision of TB control to also focus on this measurable, preventable, and reversible coepidemic of undernutrition. To continue neglecting nutrition is incompatible with any vision of human development, public health, patient centred care, or the ultimate goal of TB control.