Oral Presentation First Malaria World Congress 2018

Development of serological markers for detecting recent exposure to Plasmodium vivax malaria (#214)

Rhea J Longley 1 2 , Michael White 3 , Eizo Takashima 4 , Jessica Brewster 1 , Masayuki Morita 4 , Matthias Harbers 5 , Leanne Robinson 1 2 6 , Shih-Jung (Zoe) Liu 1 2 , Connie S. N. Li Wai Suen 1 2 , Wai-Hong Tham 1 2 , Julie Healer 1 2 , Xavier C. Ding 7 , Iveth J Gonzalez 7 , James Kazura 8 , Marcus Lacerda 9 , Jetsumon Sattabongkot 10 , Takafumi Tsuboi 4 , Ivo Mueller 1 2 3
  1. Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
  2. Department of Medical Biology, University of Melbourne, Parkville, Australia
  3. Malaria: Parasites & Hosts Unit, Institute Pasteur, Paris, France
  4. Division of Malaria Research, Proteo-Science Center, Ehime University, Matsuyama, Japan
  5. RIKEN Center for Life Science Technologies, Yokohama, Japan
  6. Burnet Institute, Melbourne, VIC, Australia
  7. Foundation of Innovative New Diagnostics, Geneva, Switzerland
  8. Case Western Reserve University, Cleveland, United States
  9. Fundac√£o de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil
  10. Mahidol Vivax Research Unit, Mahidol University, Bangkok

The change of focus from control of malaria to its elimination brings with it a number of challenges, one being the dominance of the species Plasmodium vivax in regions with decreasing transmission. Such P. vivax cases are often asymptomatic and infections of low-density, so escape detection via traditional surveillance methods. Furthermore, hypnozoites (arrested liver-stages), cannot be detected even using sensitive molecular tools, and hence new diagnostic tools will be required to stop transmission and achieve elimination of this species. Here, we have identified and validated a panel of serological markers able to detect recent exposure to P. vivax malaria, and therefore indirectly identify individuals with a high chance of harbouring hypnozoites. We screened over 300 P. vivax protein constructs for their ability to induce IgG responses in individuals exposed to P. vivax malaria in Thailand and Brazil, and determined the kinetic profile of these responses over 9-months in the absence of any recurrent infections. Candidate serological markers were down-selected based on high immunogenicity, similar estimated antibody longevity between the two geographic sites and low levels of individual variation in IgG responses. 60 down-selected proteins were further validated in three independent observational cohorts conducted in Thailand, Brazil and the Solomon Islands. By measuring antibody responses at the last visit of these cohorts, we were able to confirm a strong association of antibody titers with time since P. vivax exposure. We have selected a final panel of 8 P. vivax proteins that can accurately classify whether an individual has had a P. vivax infection within the last 9 months or not, with more than 80% sensitivity and specificity. These novel serological exposure markers have the potential to dramatically increase our ability to efficiently target limited resources for malaria control and to conduct focal drug administration programs as part of an elimination strategy.