Human malaria in immunocompromised mice: New in vivo model for chemotherapy studies

We have recently designed a new Plasmodium falciparum mouse model and docum ented its potential for the study of immune effector mechanisms, In order t o determine its value for drug studies, we evaluated its response to existi ng antimalarial drugs compared to that observed in humans. Immunocompromise d BXN (bg/bg xid/xid nu/nu) mice were infected with either the sensitive NF 54 strain or the multiresistant T24 strain and then treated with chloroquin e, quinine, mefloquine, or dihydroartemisinin. A parallelism was observed b etween previously reported human responses and P, falciparum-parasitized hu man red blood cell (huRBC)-BXN mouse responses to classical antimalarial dr ugs, measured in terms of speed of decrease in parasitemia and of morpholog ical alterations of the parasites, Mice infected with the sensitive strain were successfully cured after treatment with either chloroquine or mefloqui ne, In contrast, mice infected with the multiresistant strain failed to be cured by chloroquine or quinine but thereafter responded to dihydroartemisi nin treatment, The speed of parasite clearance and the morphological altera tions induced differed for each drug and matched previously reported observ ations, hence stressing the relevance of the model, These data thus suggest that P. falciparum-huRBC-BXN mice can provide a valuable in vivo system an d should be included in the short list of animals that can be used for the evaluation of P. falciparum responses to drugs.