Rosetting Responses of Plasmodium-infected Erythrocytes to Antimalarials

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  • 1 Department of Parasitology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia;
  • | 2 Infectious Diseases Labs (ID Labs), Agency for Science, Technology and Research (A*STAR), Singapore;
  • | 3 Department of Microbiology and Immunology, University of Otago, Dunedin, Otago, New Zealand;
  • | 4 Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medical Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Tak, Thailand;
  • | 5 Nuffield Department of Medicine, University of Oxford, United Kingdom;
  • | 6 Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore;
  • | 7 School of Biological Sciences, Nanyang Technological University, Singapore

In malaria, rosetting is a phenomenon involving the cytoadherence of uninfected erythrocytes to infected erythrocytes (IRBC) harboring the late erythrocytic stage of Plasmodium spp. Recently, artesunate-stimulated rosetting has been demonstrated to confer a survival advantage to P. falciparum late-stage IRBC. This study investigated the rosetting response of P. falciparum and P. vivax clinical isolates to ex vivo antimalarial treatments. Brief exposure of IRBC to chloroquine, mefloquine, amodiaquine, quinine, and lumefantrine increased the rosetting rates of P. falciparum and P. vivax. Furthermore, the ex vivo combination of artesunate with mefloquine and piperaquine also resulted in increased the rosetting rates. Drug-mediated rosette-stimulation has important implications for the therapeutic failure of rapidly cleared drugs such as artesunate. However, further work is needed to establish the ramifications of increased rosetting rates by drugs with longer half-lifves, such as chloroquine, mefloquine, and piperaquine.

Author Notes

Address correspondence to Wenn-Chyau Lee, Department of Parasitology, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia, E-mail: leewc_88@hotmail.comor Laurent Rénia, A*STAR Infectious Diseases Laboratories, 8A Biomedical Grove, #03-06 Immunos, Singapore 138648, E-mail: renia_laurent@idlabs.a-star.edu.sg.

Financial support: W-C. L. and L. R. were supported by core funding from A*STAR. W-C. L. was also funded by the Open Fund-Young Individual Research grant OF-YIRG NMRC/OFYIRG/0070/2018. L. R. was also funded by A*STAR grant JCO-DP BMSI/15-800006-SIGN. B. R. was supported by a HRC e-ASIA grant (17/678) and a University of Otago Deans Bequest Grant. Shoklo Malaria Research Unit is part of the Mahidol-Oxford University Research Unit, supported by the Wellcome Trust Thailand/Laos Major Overseas Program Renewal (grant no. 106698).

Authors’ addresses: Wenn-Chyau Lee, Agency for Science, Technology and Research (A*STAR), Malaria, Singapore, E-mail: leewc_88@hotmail.com. Bruce Russel, University of Malaya, Parasitology, Kuala Lumpur, Malaysia, and University of Otago, Microbiology and Immunology, Dunedin, New Zealand, E-mail: b.russell@otago.ac.nz. Yee Ling Lau, University of Malaya, Parasitology, Faculty of Medicine, Kuala Lumpur, Malaysia, E-mail: lauyeeling@um.edu.my. Francois Nosten, Mahidol Oxford Tropical Medicine Research Unit, Shoklo Malaria Research Unit, 60/30 Bantung Road, Bangkok, Thailand, E-mail: francois@tropmedres.ac. Laurent Rénia, Agency for Science, Technology and Research (A*STAR), Singapore, Infectious Diseases Labs (ID Labs), Singapore, Nanyang Technological University, Singapore, Lee Kong Chian School of Medicine, Singapore, and Nanyang Technological University, Singapore, School of Biological Sciences, Singapore, E-mail: renia_laurent@idlabs.a-star.edu.sg.

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