Oxidative stress in malaria and typhoid fever: A scoping review of the pathogenic mechanisms and therapeutic implications

Abstract

Oxidative stress is a key factor in the pathogenesis of many infectious diseases, including typhoid fever and malaria. Co-infection with these diseases poses a particular challenge, as both are associated with increased production of reactive species that can damage tissues, trigger oxidative stress, and exacerbate disease. To cope with this oxidative insult, cells have a defense system consisting of antioxidant molecules that can terminate the oxygen radical cascade and render toxic metabolites innocuous. However, lack of complete understanding of the pathophysiology of malaria and typhoid fever continues to hinder efforts aimed at eradicating these diseases. In this review, we examine the current understanding of oxidative stress in the context of malaria and typhoid fever, and its implications for disease pathogenesis and treatment. The search and data extraction strategy used in this scoping review involved a structured approach to identify relevant studies related to the topic. Studies were included that investigated ROS production, antioxidant responses, and the effect of pharmacological interventions on oxidative stress markers. The search was conducted using electronic databases, including PubMed, ScienceDirect, and Directory of Open Access Journals (DOAJ), and involved an extensive literature search of studies published between January 2000 and May 2024. The review identified potential avenues for research with evidence that both malaria and typhoid fever elevate oxidative stress levels, which are further exacerbated in co-infections. The endogenous antioxidant response is activated but may not be sufficient to neutralize ROS completely. Moreover, commonly used antimalarial and antibacterial drugs influence oxidative and antioxidant dynamics, which may have implications for treatment efficacy and disease progression. Understanding the oxidative-antioxidant balance in malaria and/or typhoid fever may open new avenues for adjunctive therapies and vaccines targeting oxidative stress. It is thus important to consider the oxidative-antioxidant balance during treatment of malaria and typhoid fever patients.