Theoretical origin of genetically homologous Plasmodium vivax malarial recurrences

Abstract

Malaria caused by Plasmodium vivax is being diagnosed with increasing frequency in Africa. Some southern countries where it has been detected are Angola, Botswana, Mozambique, Namibia, Zambia and Zimbabwe. Knowing the parasite origin of P. vivax infection recurrences (which can be reinfections, recrudescences or relapses) is important epidemiologically for malaria elimination in Africa. Although hypnozoites will no doubt be a source, we should try to determine how frequently the origin of non-reinfection recurrences of P. vivax malaria involving closely related parasites may be non-circulating merozoites rather than hypnozoites.

Malaria Elimination in Africa: Rethinking Strategies for Plasmodium vivax and Lessons from Botswana

“…These observations were seen in both the rodent P. berghei parasite and the human P. falciparum , indicating that the bone marrow and spleen are major sites for parasite development during the Plasmodium life cycle. The unique biology of P. vivax and P. ovale , i.e., having hypnozoite stages, presents an even greater intriguing scenario considering that this stage can cause relapse after several years [ 73 , 74 , 75 ]. Although malaria relapses are attributed to a hypnozoite source in the liver, the current understanding of the life cycle may point to there being additional sources of cryptic ‘ non-liver rejuvenants ’ of dormant parasites [ 76 ].…”

Putative Contribution of 8-Aminoquinolines to Preventing Recrudescence of Malaria

“…It does seem feasible, however [ 25 , 27 , 28 , 29 ]. Alternatively, non-circulating blood-stage merozoites (i.e., merozoites not detectable in peripheral blood) might be the source of more recrudescences (as opposed to relapses) than is readily apparent [ 30 , 31 ]. The latter possibility is not a new suggestion, but a long-standing idea ( Table 1 ) supported by the fact that intra-erythrocytic stages have, in the meantime, been shown to be hidden outside the peripheral circulation in vast numbers (compared to what must be relatively few hypnozoites) in individuals chronically infected by P. vivax [ 32 , 33 , 34 , 35 , 36 , 37 ].…”