Is the BCG Vaccine Safe for Undernourished Individuals?

Abstract

<jats:p>Cellular immunity is critical for protection against tuberculosis, but its integrity is compromised during undernutrition. The present study was designed to evaluate if the attenuated mycobacterium BCG is a safe vaccine for undernourished individuals. An experimental model of undernutrition was established by subjecting BALB/c mice to dietary restriction. These animals received 70% of the amount of food consumed by the healthy control group and exhibited physiological alterations compatible with malnutrition, including body weight loss, reduced levels of triglycerides and glucose, and reduced lymphocyte numbers. Undernourished mice were immunized with BCG, and the mycobacterial loads in lymph nodes, spleen, liver, lungs, and thymus were determined. A much higher proportion of undernourished mice exhibited bacterial dissemination to the lymph nodes, spleen and liver. In addition, only undernourished animals had bacteria in the lungs and thymus. Concomitant with higher mycobacterial loads and more widespread BCG dissemination in undernourished mice, production of TNF-α, IFN-γ, and IL-10 was also diminished in these mice. Taken together, these results indicate that BCG infection is more severe in undernourished mice. Whether a similar phenomenon exists in undernourished children or not remains to be thoroughly investigated.</jats:p>

Malnutrition and vaccination in developing countries

“…Dissemination of live attenuated BCG has been described following vaccination of infants with HIV infection [69] or primary immunodeficiency [70], but does not appear to have been reported in HIV-uninfected malnourished infants. However, mice submitted to 10 days of dietary restriction prior to intradermal inoculation with BCG showed a higher frequency of BCG dissemination to lymph nodes and thymus than wellfed mice [71] and, interestingly, mycobacterial dissemination to the thymus has been shown to drive tolerance when pathogen-specific T cell responses are assessed in murine models [72]. This raises a theoretical concern that, if thymic BCG dissemination does occur in malnourished infants, they may fail to mount an effective T cell response to the vaccine; this warrants investigation in humans.…”

Nutritional status and immune response in murine experimental Jorge Lobo's disease

“…TNF‐α is a proinflammatory cytokine and its production and excessive release have been associated with the development of cachexia observed in patients with acute infection, similar to the present study. IL‐10 is an anti‐inflammatory mediator and a powerful immunosuppressant which can inhibit the synthesis of IFN‐γ, IL‐2 and IL‐12, as well as the proliferation of Th1 lymphocytes . An important finding of the present study was the marked reduction in the spontaneous production of IL‐2 in inoculated malnourished mice (G1) compared to the other groups, suggesting a deficient Th1 immune response during malnutrition in conjunction with infection.…”

“…In this model, mice are previously submitted to PCM and then inoculated with the causative agent of the disease. This model has been used successfully in other studies with the following pathogens: T. gondii , S. aureus and M. tuberculosis …”

“…Malnutrition is recognised as the main cause of acquired immunosuppression in the world and can increase the incidence of morbidity and mortality due to infections . These deleterious effects on immune function have been demonstrated clinically and in experimental studies on different diseases …”

“…The triad of nutrition, infection and immunity has been demonstrated in several studies on mice infected with Toxoplasma gondii , Schistosoma mansoni , Leishmania chagasi , Staphylococcus aureus and Mycobacterium tuberculosis, however, there are no studies investigating nutritional and immunological aspects in Jorge Lobo's disease.…”