Effects of probiotic saccharomyces bourlardii on cytokine levels and outcomes of childhood severe malaria: Study protocol for a randomized controlled trial

Abstract

Background: Severe malaria is acute malaria with signs of organ dysfunction and/or hyperparasitaemia. About 90% of the world’s severe and fatal malaria is estimated to affect young children in sub-Sahara Africa. Systemic complications and neuropathology in severe malaria include ‘cytokine storm hypothesis’. Probiotic immunomodulation may show therapeutic benefits in severe malaria.

Aim: This study aims to evaluate the effects of probiotic saccharomyces bourladii on serum cytokine levels (IL-6 and TNF), clinical course and outcome of children with severe malaria.

Methods: Participants shall be recruited based on WHO diagnostic criteria for severe malaria and their clinical-demographic data shall be obtained with a pretested questionnaire. The study design is randomized controlled trial (RCT); participants shall be randomized into two study sub-groups (intervention vs. control). All participants shall receive standard anti-malarial therapies. In addition, probiotic saccharomyces bourladii 250mg twice a day shall be administered to those in the intervention sub-group for 3 days. There after, their serum cytokines (IL-6 and TNF) shall be measured quantitatively by a Sandwich enzyme-linked immunosorbent assay (ELISA) technique. Primary outcomes shall be cytokine levels and length of stay (LOS) while secondary measures shall be coma scores, seizure, neurological deficits and mortality. The data shall be analyzed using SPSS version 26.0 statistical software for Windows. Both ‘intention-to-treat analysis’ and ‘analysis as per protocol’ shall be done. P-value< 0.05 shall be considered significant in all tests.

Discussion: At the end of this clinical trial, it is expected that the potential benefits of probiotic saccharomyces bourladii in modulating pro-inflammatory cytokines, averting systemic complications and reducing mortality in childhood severe malaria would have been verified.

Protocol No: ADM/E22/A/ VOL.VII/148312145; University of Benin Teaching Hospital’s Health Research Ethics Committee Approval; August 5th, 2022.