Answer to Parasite Case of the Week 592: Plasmodium malariae; likely recrudescent infection, given that he has been without symptoms for > 2 months since his last travel to sub-Saharan Africa. While P. knowlesi is also in the differential based on the morphologic overlap between P. knowlesi and P. vivax, the long period of time since his travel to SE Asia would be atypical for P. knowlesi infection.
Some of the classic P. malariae features seen in this case are the small size of the infected red blood cells, schizonts with only 6-12 merozoites, band forms, and a basket form:
Recrudescence - seen primarily with P. malariae infection, but can also be seen with other Plasmodium species that lack hypnozoites.
Recrudescence refers to recurrence of infection. With P. malariae, recrudescence is thought to be due to the indolent growth of this parasite, enabling survival for many years, even with chloroquine treatment. Chloroquine is the drug of choice for P. malariae infections, and it is preferentially concentrated in the food vacuoles of metabolically active trophozoites. Here it binds to hematin and prevents its polymerization, resulting in oxidative stress to the parasite and eventual lysis. Given the low growth and metabolism of P. malariae asexual stages, some trophozoites can escape the action of chloroquine and later cause disease recrudescence. Recrudescence is different than relapse (see below) in that it doesn't result from activation of hypnozoites.
Relapse - seen with P. ovale and P. vivax infection.
Relapse is due to activation of dormant hypnozoites in the liver.
The final mystery in this case is the location in which the patient acquired infection. He had traveled to Ethiopia, Nigeria and Cameroon approximately 2 months prior to symptom onset, but according to the United States CDC, P. malariae is not found in appreciable amounts in these countries. What the CDC doesn't note in these lists, however, is that P. malariae is found throughout sub-Saharan Africa, and is present in all of the areas where P. falciparum is found. P. malariae is also found in parts of Asia and South America, so he could have acquired infection from many of his previous travels.
Thanks again to Drs. Decollings and Nikolic for donating this interesting case!