Poster Presentation First Malaria World Congress 2018

Investigating human to mosquito transmission of artemisinin-resistant parasites in the induced blood stage malaria model  (#472)

Zuleima Pava 1 , Katharine Collins 1 2 , Rebecca Watts 1 , Fiona Amante 1 , Maria Rebelo 1 , Hayley Mitchell 1 , Matthew Adams 1 , Greg Robinson 1 , Melanie Rampton 1 , Claire Wang 3 , Jörg J. Möhrle 4 , James McCarthy 1
  1. QIMR, Herston, QLD, Australia
  2. Radboud Institute for Health Science, Nijmegen, Netherlands
  3. Queensland Paediatric Infectious Diseases Laboratory, Centre for Children's Health Research, Brisbane, QLD, Australia
  4. Medicines for Malaria Venture, Geneve, Switzerland

Background: Investigation of human-mosquito transmission of artemisinin-resistant parasites is a priority to contain the spread of drug resistance. An artemisinin-resistance induced blood stage malaria (IBSM) model has been established, where subjects are infected with a P. falciparum artemisinin-resistant strain “K13” (R539T). The present study aimed to describe the dynamics of gametocytemia and the effect of atovaquone/proguanil (A/P) on transmission to Anopheles stephensi mosquitoes

Methods: This work is an exploratory component of a randomised trial (ACTRN12617001394336) where subjects were inoculated with either ~2,800 of K13 (n=7) or 3D7 (artemisinin sensitive; n=3) parasites and received a single-dose of artesunate (2 mg/kg) on day 9 post-inoculation. First recrudescent infections were treated with piperaquine and second recrudescence with A/P. Expression of female (pfs25) and male (pfMGET) gametocyte markers were measured from day 9 onwards by qRT-PCR. The 6 subjects with the highest level of pfs25 transcripts were selected to investigate transmission by performing direct feeding assay (DFA) and membrane feeding assay (MFA) on day 23 post-inoculation. Gametocytes were enriched by Percoll gradient prior to MFA. Midguts were dissected 8 days later, and infection was determined by qPCR.

Results: The 6 subjects with highest gametocytemia were all infected with K13 (~49 – 1,749 female gametocytes/mL; 5 – 716 male gametocytes/mL). Two subjects received A/P prior to DFA/MFA and did not infect mosquitoes. The four subjects who did not receive A/P prior to DFA/MFA infected between 20% (18/89) and 97% (98/101) of mosquitoes by MFA, and between 3% (1/30) and 10% (3/30) of mosquitoes by DFA.

Conclusion: Artemisinin-resistant parasites are transmissible to mosquitoes after a single dose of artesunate.  A/P appears to block transmission to mosquitoes, although is not gametocytocidal. The IBSM model could be used to test the transmission-blocking activity of licensed and investigational antimalarials.