Zoonotic Malaria – Global Overview and Research and Policy Needs

Abstract

The four main Plasmodium species that cause human malaria, Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, and Plasmodium ovale, are transmitted between humans by mosquito vectors belonging to the genus Anopheles. It has recently become evident that Plasmodium knowlesi, a parasite that typically infects forest macaque monkeys, can be transmitted by anophelines to cause malaria in humans in Southeast Asia. Plasmodium knowlesi infections are frequently misdiagnosed microscopically as P. malariae. Direct human to human transmission of P. knowlesi by anophelines has not yet been established to occur in nature. Knowlesi malaria must therefore be presently considered a zoonotic disease. Polymerase chain reaction is now the definitive method for differentiating P. knowlesi from P. malariae and other human malaria parasites. The origin of P. falciparum and P. vivax in African apes are examples of ancient zoonoses that may be continuing at the present time with at least P. vivax, and possibly P. malariae and P. ovale. Other non-human primate malaria species, e.g., Plasmodium cynomolgi in Southeast Asia and Plasmodium brasilianum and Plasmodium simium in South America, can be transmitted to humans by mosquito vectors further emphasizing the potential for continuing zoonoses. The potential for zoonosis is influenced by human habitation and behavior as well as the adaptive capabilities of parasites and vectors. There is insufficient knowledge of the bionomics of Anopheles vector populations relevant to the cross-species transfer of malaria parasites and the real extent of malaria zoonoses. Appropriate strategies, based on more research, need to be developed for the prevention, diagnosis, and treatment of zoonotic malaria.

Role of indoleamine 2,3-dioxygenase in health and disease

“…plants and animals, including humans) for food and survival. Parasitic infections, which can cause severe and debilitating diseases such as malaria, disproportionally affect those in low-income tropical and subtropical regions [491]. The impact of these infections is exacerbated by the lack of effective vaccines, coupled with difficulties in vector control and the increased drug resistance of various parasites.…”

Molecular interactions governing host-specificity of blood stage malaria parasites

“…Second, though rare, ape-to-human P. vivax transmission has been reported in Central Africa [8]. Finally, P. vivax has been secondarily transmitted from humans to New World monkeys multiple times, yielding a post-Columbian host shift (deemed P. simium ) less than 500 years ago [12,53,54]. These observations suggest that further research into the host promiscuity of P. vivax is warranted.…”

“…The pre-civilization origins of both P. falciparum [5,6] and P. vivax [7,8]—pandemic malaria parasites, which underlie the majority of human malaria infections globally [2,9]—have recently been traced to African great apes, and cross-species transmission of other malaria parasites continues to this day (Figure 1). Indeed, the observation that most, if not all, contemporary human malaria parasites originated in non-human primate hosts has compelled the scientific community to ask whether these zoonotic reservoirs could impede malaria control efforts by acting as a source of recurrent human infection [10–12]. …”

Malaria diagnosis for malaria elimination

“…Malaria diagnosis must be strengthened given the importance of continuing progress against this disease and the global investment in malaria elimination. Methods for detecting human as opposed to mosquito [3,4] or nonhuman primate malaria [5] infections will be favored here. Aspects of malaria diagnosis beyond the focus of this review include monitoring antimalarial drug resistance markers and developing products to assess glucose-6-phosphate dehydrogenase deficiency (G6PDd) to improve safety of primaquine (and ultimately tafenoquine) treatment of P. vivax and P. ovale hypnozoites.…”