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PA-810 Ethiopian plasmodium vivax hypnozoites formation dynamics and their susceptibility to reference antimalarial drugs
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  1. Fanta Sogore,
  2. Ousmaila Diakite,
  3. Fatalmoudou Tandina,
  4. Mohamed Maiga,
  5. Abdoulaye A Djimde,
  6. Laurent Dembele
  1. University of Sciences Techniques and Technologies of Bamako, Mali

Abstract

Background One of the key obstacles to malaria elimination is largely attributed to Plasmodium vivax’s ability to form resilient hypnozoites in the host liver that cause relapsing infections. As a result, interruption of P. vivax transmission is difficult. P. vivax transmission occurs in Duffy-positive individuals and have been mainly thought to be absent in Africa. However, increasing studies using molecular tools detected P. vivax among Duffy-negative individuals in various African countries. Studies on the African P. vivax has been severely limited because most of malaria control program focus mainly on falciparum malaria. In addition, there is a scarcity of laboratory infrastructures to overcome the biological obstacles posed by P. vivax.

Methods Herein, we established field transmission of Ethiopian P. vivax for routine sporozoite supply followed by liver stage infection in Mali leveraging the EDCTP funded HypnoBio - TMA2017CDF-1892 outcome.

Furthermore, we evaluated local P. vivax hypnozoites and schizonts susceptibilities to reference antimalarial drugs. The study enabled the assessment of local African P. vivax hypnozoite production dynamics.

Results Our data displayed the ability of the African P. vivax to produce hypnozoite forms ex-vivo at different rates per field isolate. We report that while tafenoquine (1μM) potently inhibited both hypnozoites and schizont forms; atovaquone (0.25μM) and the phosphatidylinositol-4-OH kinase (PI4K)-specific inhibitor KDU691 (0.5μM) showed no activity against hypnozoites forms. Unlike hypnozoites forms, P. vivax schizont stages were fully susceptible to both atovaquone (0.25μM) and the (PI4K)-specific inhibitor KDU691 (0.5μM).

Conclusion Together, the data revealed the importance of the local platform for further biological investigation and implementation of drug discovery program on the African P. vivax clinical isolates.

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