Plasmodium knowlesi and other zoonotic malaria species in Sabah, Malaysia: Molecular detection, red blood cell interactions, and exposure trends within a longitudinal cohort

Plasmodium knowlesi is a pathogenic malaria parasite in humans, with a risk of severe and fatal disease equivalent to that of P. falciparum in co-endemic areas, especially if optimal treatment is delayed. It is now the most common etiological agent for malaria in Malaysia, and is increasing in incidence, with the state of Sabah reporting over 2000 confirmed cases in 2018.
Due to the difficulties with microscopic diagnosis of P. knowlesi and limited data on transient infections, the true infection prevalence of zoonotic malaria species in co-endemic areas and the related disease burden remain poorly understood. Therefore, it is imperative to evaluate currently used nucleic acid-based detection methods for differentiating P. knowlesi from human-only Plasmodium species as Malaysia continues progress to eliminate the latter. In addition, surveillance for other zoonotic species such as P. cynomolgi, also known to cause human infections, will further inform malaria public health activities.
This project also aims to determine the cumulative incidence and delineate specific factors for P. knowlesi exposure and infection within a unique high-risk cohort. In addition, this study will enable a first-time assessment of efficacy and adherence to prophylactic doxycycline currently given to this group; as well as evaluation of the seroprevalence and incidence of malaria compared to other causes of acute febrile illnesses after exposure to different environmental landscapes. Lastly, this project hopes to contribute to current understanding of the pathophysiology of knowlesi malaria by investigating intercellular interactions; i.e. red blood cells and neutrophil extracellular traps.