Strengthening molecular surveillance for the epidemiology of vivax malaria

Background Plasmodium vivax is the predominant cause of malaria in many endemic countries outside of Africa. However, the transmission dynamics of this parasite are not well understood, complicated in part by the hidden liver and spleen reservoirs. P. vivax relapses from reactivation of dormant-liver stages complicate recurrence classification in treatment surveys as well as the characterisation of P. vivax incidence. Molecular tools have the potential to decipher this complexity by informing on the relatedness (measured with Identity-by-descent (IBD)) between infections to provide a better understanding of transmission, recurrence origin (and treatment efficacy) and, ultimately, the main reservoirs of infection. However, establishing a molecular surveillance framework for P. vivax brings species-specific challenges that will require appropriate research and development tailored to different endemic needs. My PhD project will develop and validate novel molecular surveillance tools with modular utilities for different endemic settings and associated needs. Methods There are four aims within my PhD project. The first two aims will focus on the development and optimisation of laboratory protocols for P. vivax molecular surveillance, whilst the last two aims will demonstrate the application of the tool. In Study 1, I will develop a new laboratory protocol using MinION sequencing for rapid detection of imported P. vivax infections for use in low-transmission settings. In Study 2, I will evaluate and optimise an existing high-throughput Illumina-based laboratory protocol for determining P. vivax relatedness (IBD) to support low-yield dried blood spot samples. In Study 3, I will apply the IBD-determining protocol to compare and contrast the diversity of within-host splenic versus circulating P. vivax parasites. In Study 4, I will apply the IBD-determining protocol for spatial and temporal surveillance of P. vivax transmission and spread in Indonesia. Significance Molecular surveillance has great potential to inform National Malaria Control Programs on the efficacy of current interventions and to prioritise resource allocation for rapid and effective transmission reduction. My PhD project will support a more flexible framework for P. vivax molecular surveillance for use in different malaria endemic settings. As proof-of-concept, my research will apply the utility of molecular surveillance methods to evaluate the epidemiology of hidden P. vivax spleen stage as well as P. vivax transmission dynamic in Indonesia. This will provide critical knowledge advancements on how P. vivax parasites are spreading and where the main reservoirs are.