Evaluation of Test of Cure Procedures in Mice Treated for Plasmodium Berghei Infections

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Abstract
Summary In an effort to elucidate the state of immunity acquired by mice given curative treatment for a malaria infection, white mice infected with Plasmodium berghei were treated with primaquine diphosphate and subsequently exposed to various infectivity procedures for determining whether plasmodia had been completely eradicated or merely reduced to subpatent, chronic levels. Test of cure procedures included: (a) serial blood smears continuing at intervals for 5 weeks; (b) subinoculation of blood into recipients; (c) splenectomy of donors with subinoculation of spleens into recipient mice; and (d) sacrifice of donors with subinoculation of total organ content into recipients. Blood examination was an adequate criterion for demonstrating radical cure in mice following primaquine therapy since all mice presumed cured on the basis of post-treatment blood smears failed to transmit the infection to recipients inoculated with their blood or organs. Splenectomy did not produce relapses in any of the cured mice. An apparent attenuation of the infection was noted in recipients of blood and organs from treated animals. One group of mice, with parasitemias on one or more occasions following therapy, apparently underwent spontaneous cure since they failed to transmit the infection to recipients by any infectivity procedure employed. Furthermore, splenectomy did not evoke relapses in these animals. Therefore, although serial blood smears taken after treatment are adequate for selection of mice uncured by drug therapy, the parasitemia state of such mice cannot be relied on for prognosticating the ultimate infection status of the animal and its consequent immune response to challenge infections.