Introduction and Background of the Project

Introduction

While clinical malaria cases in the Asia-Pacific and the Americas have gone down >90% in the last decade, a shift in malaria species composition has been observed, with Plasmodium vivax now being the predominant species outside Africa. This shift may relate to the unique biology of P. vivax, including the relapsing phenotype from dormant liver stages (hypnozoites). In the light of the United Nations Sustainable Development Goals (By 2030, end the epidemics of AIDS, tuberculosis, malaria...") and in the era of pursuing malaria eradication, an effective strategy to handle P. vivax malaria is indispensable. Asymptomatic hypnozoite infections form a hidden parasite reservoir in the human population that can give rise to new symptomatic and transmissible malaria weeks, months or years after primary infection, without new infection through mosquito bites. Proper diagnostic tools to identify hypnozoite-infected individuals are currently lacking, and this is mentioned as a challenge in "WHO Global Technical Strategy for Malaria 2016–2030". 

Project objective

Identification of putative metabolite markers for malaria hypnozoite infection. 

Project design

Under our previous RFP (T2017-105) we pioneered an in vitro Proof-of-Concept (PoC) towards identifying targets for diagnostic tools for malaria hypnozoites, exploiting our unique experience in in vitro P. cynomolgi hypnozoite cultures (an accessible proxy to P. vivax with near identical biology), as well as in sensitive metabolomics. Specific metabolites have been identified and prioritized based on the unique signatures found in hypnozoite-enriched cultures. A second-phase in vivo feasibility study using the P. cynomolgi-rhesus monkey model is now warranted to determine whether the specific signatures detected in the in vitro PoC are confirmed in vivo and can thus be pursued in the subsequent development phase of a rapid diagnostic test for hypnozoite infection. 

How can your partnership (project) address global health challenges?

Diagnostic tools to identify hypnozoite carriers are urgently needed to further map the scale of the problem in the short-term and to allow for targeted drug treatment in the long-term. This approach of identifying and treating individuals infected with dormant malaria parasites prevents disease and further transmission of vivax malaria, while it also prevents unnecessary drug exposure of the non-infected individuals. Our unique approach would provide in vivo PoC for the development of such diagnostic tools and, if successful, further detailed planning for diagnostic tool development will be initiated. Once available, these important tools will significantly contribute to P. vivax malaria control and elimination. 

What sort of innovation are you bringing in your project?

We exploit our P. cynomolgi-rhesus monkey model to measure metabolites originating from hypnozoite infection. To obtain a broad quantitative profiling of metabolites, we will employ an innovative technology Capillary Electrophoresis-Mass Spectrometry. 

Role and Responsibility of Each Partner

Nagasaki University, Japan is responsible for designing and managing the metabolomic experiments. BPRC, Netherlands is responsible for all primate work as well as all hypnozoite culture work. National Institute of Technology, Kumamoto College, Japan supports the metabolome analyses. All partners will be co-responsible for data interpretation.