Can treatment of P. vivax lead to a unexpected appearance of falciparum malaria?

Of 994 patients admitted to the Bangkok Hospital for Tropical Diseases for P. vivax malaria, 104 (10.5%) experienced appearance of Plasmodiumfalciparum following drug treatment for P. vivax . In all patients, P. falciparum parasites were not found by microscopic examination upon admission. The mean time for P. falciparum appearance was 12.6 days after the commencement of chloroquine treatment. Patients experiencing appearance of P. falciparum had significantly lower hematocrit, and greater initial P. vivax parasite counts. We use a mathematical model to explore the consequences of chloroquine treatment of such mixed infections. Both clinical results and features of the model suggest that such "hidden infections" may be quite common, and that the appearance of P. falciparum may be stimulated by treatment of P. vivax.

Review and recent progress: the mathematical modeling of mixed species Plasmodium infections.

Mathematical modeling serves numerous uses in biology, notably in the exploration of phenomena that are difficult to observe empirically. Here, I review recent progress in modeling the blood-stage dynamics of mixed-species Plasmodium infections, namely P. malariae-P. falciparum and P. vivax- P. falciparum mixed infections. Modeling reproduces features of such infections found in nature including the asymmetry of parasite blood-stage densities, inter-specific suppression, and parasite asexual-form recrudescence following long-standing sub-patency. Several findings which merit clinical attention are presented: the ability of P. malariae and P. vivax to reduce the peak parasitemia of co-infecting P. falciparum, and the potential recrudescence of a low-level P. falciparum infection following a P. malariae infection or P. vivax infection or relapse. The action of antimalarial drugs is discussed, highlighting some potential complications in treating mixed-species malaria infections. Most notably, if a mixed-species infection is misdiagnosed as a single-species P. vivax infection, treatment can lead to the dangerous appearance of "hidden" P. falciparum.

Hidden Plasmodium falciparum infections.

Mixed infection of P. vivax and P. falciparum malaria frequently recorded in field survey. However mixed infection was frequently misdiagnosed as single infection due to low parasite density, difficult species identification and procedure error of microscopic examination. Our previous report showed high rates (32-33%) of P vivax infection following treatment of previously assumed to be only P. falciparum infection. In a study of 992 patients with initial presentation with P. falciparum, we found that 104 (10.5%) of patients had P. falciparum appearing during 28 days in the hospital (ranged 1-28 days) following chloroquine treatment for P. vivax. The potential for P. falciparum appearing following elimination of P. vivax must be considered in malaria treatment.