UC Davis

Disseminated disease from non-typhoidal Salmonella contributes to significant morbidity and mortality globally, especially for children who are immunocompromised due to malnutrition and vitamin A deficiency. Despite successful implementation of standard care, antibiotic therapy can be sub-therapeutic if the immune response is blunted. Better treatment regimens are needed that consider the immune status of the host.

To determine whether vitamin A supplementation during treatment of disseminated disease could improve morbidity and mortality in at-risk populations, I utilized a mouse model of invasive non-typhoidal Salmonella disease and sub-therapeutic antibiotic therapy to assess the effect of vitamin A supplementation on the morbidity and mortality of both vitamin A-deficient (VAD) and control mice.

I found that adding vitamin A treatment to antibiotic therapy early during infection improved outcomes significantly for VAD male mice, as indicated by increased survival, less weight loss, and decreased systemic bacterial levels in the spleen, liver, and blood. These results are impactful, as they suggest that a clinical study assessing vitamin A as a treatment in at-risk children may improve outcomes during disseminated disease from non-typhoidal Salmonella.

Globally, clinical recommendations support preventative vitamin A supplementation for decreasing morbidity and mortality of diarrhea. However, invasive non-typhoidal Salmonella disease often presents as a fever in the absence of diarrhea. I worked with Tanzanian collaborators familiar with at-risk populations and local health systems to develop a clinical trial concept note that consider my findings from the mouse study in the context of previous literature to inform a clinical trial design. This work is impactful, since it can contribute to the implementation of a multisite, double-blind, placebo-controlled, randomized control trial, with the purpose of improving care for vulnerable populations.