# Impact of Marasmic Malnutrition on Visceral Leishmaniasis: Progression and Treatment Efficacy in a Murine Model

## TL;DR

Malnutrition worsens leishmaniasis infection and treatment outcomes in mice, with partial improvement seen after refeeding.

## Contribution

This study demonstrates how marasmic malnutrition impacts Leishmania infection progression and drug efficacy in a murine model.

## Key findings

- Malnourished mice had lower spleen parasite load but higher liver parasite load compared to controls.
- Refeeding partially reversed infection status but did not fully restore health.
- Malnutrition reduced treatment efficacy, though refed mice showed improved parasite load reduction.

## Abstract

Background/Objectives: Malnutrition and visceral leishmaniasis are major public health problems that are responsible for millions of deaths across many countries. Leishmaniasis development and progression are associated with the host immune status. In this context, malnutrition can directly affect the course of leishmaniasis, impairing several components of the immune system. Moreover, malnutrition directly interferes with the tropism of Leishmania in organs, affecting host susceptibility. Therefore, this work aimed to evaluate the influence of nutritional status on the establishment, progression, and treatment of Leishmania infantum infection in malnourished and refed mice. Methods: BALB/c mice were fed either a control or restricted diet, infected with L. infantum promastigotes, and treated with meglumine antimoniate, the standard drug for treating visceral leishmaniasis. The effects of infection were evaluated through limiting dilution analysis (LDA). Results: Compared with control mice, malnourished and refed mice presented a lower parasitic load in the spleen, which correlated with spleen atrophy, and the refeeding process partially reversed but did not fully rescue the infection status. Both groups presented a high parasitic load in the liver. Marasmic malnutrition appeared to impair the efficacy of leishmaniasis treatment; however, the refed groups exhibited a robust decrease in the parasite load, which was comparable to that in the control group subjected to treatment. Conclusions: Our data suggested that marasmic malnutrition affects the establishment and progression of Leishmania infection, in addition to reducing the efficacy of standard treatment. Furthermore, the refeeding intervention used did not fully reverse the observed effects. These findings highlight the potential importance of nutritional interventions in the clinical management of visceral leishmaniasis in malnourished populations.