Plasmodium cynomolgi in humans: current knowledge and future directions of an emerging zoonotic malaria parasite

Abstract

Plasmodium cynomolgi ( Pcy ), a simian malaria parasite, is a recent perfect example of emerging zoonotic transfer in human. This review summarizes the current knowledge on the epidemiology of natural Pcy infections in humans, mosquitoes and monkeys, along with its biological, clinical and drug sensitivity patterns. Knowledge gaps and further studies on Pcy in humans are also discussed. This parasite currently seems to be geographically limited in South-East Asia (SEA) with a global prevalence in human ranging from 0 to 1.4%. The Pcy infections were reported in local SEA populations and European travelers, and range from asymptomatic carriage to mild/moderate attacks with no evidence of pathognomonic clinical and laboratory patterns but with Pcy strain-shaped clinical differences. Geographical distribution and competence of suitable mosquito vectors and non-primate hosts, globalization, climate change, and increased intrusion of humans into the habitat of monkeys are key determinants to emergence of Pcy parasites in humans, along with its expansion outside SEA. Sensitization/information campaigns coupled with training and assessment sessions of microscopists and clinicians on Pcy are greatly needed to improve data on the epidemiology and management of human Pcy infection. There is a need for development of sensitive and specific molecular tools for individual diagnosis and epidemiological studies. The development of safe and efficient anti-hypnozoite drugs is the main therapeutic challenge for controlling human relapsing malaria parasites. Experience gained from P. knowlesi malaria, development of integrated measures and strategies—ideally with components related to human, monkeys, mosquito vectors, and environment—could be very helpful to prevent emergence of Pcy malaria in humans through disruption of transmission chain from monkeys to humans and ultimately contain its expansion in SEA and potential outbreaks in a context of malaria elimination. Supplementary Information The online version contains supplementary material available at 10.1007/s15010-022-01952-2.

Malaria in pregnancy in India: a 50-year bird’s eye

“…LM is the standard and reports pinpointed that Po and Pm infections are misdiagnosed as Pv and Pf infections using LM in the country ( 124 , 125 ). It is worth determining the extent and characterizing these species in MiP as previous studies showed their ability to elicit SM and noted pathophysiological differences between P. ovale curtisi and P. ovale wallikeri ( 4 , 126–129 ).…”

“…This burden has significantly increased compared to previous years, partially due to the current COVID-19 pandemics ( 2 , 3 ). Malaria is due to five Plasmodium species that are transmitted to human through infecting bites of female Anopheles mosquitoes ( 4 ). Plasmodium falciparum ( Pf ) and Plasmodium vivax ( Pv ) are the predominant malaria species around the world; Pf is the most severe and dangerous species while Pv is the most geographically spread but can also induce severe clinical attacks ( 5 , 6 ).…”

Transcriptional responses of brain endothelium toPlasmodium falciparumpatient-derived isolatesin vitro

“…The majority of symptomatic infections result in mild febrile cases of uncomplicated malaria (UM), as severe disease only occurs in 1-2% of all cases 2 . Out of the eight Plasmodium spp that have been reported to cause either direct or zoonotic infection in humans, P. falciparum is considered a major driver of severe disease and mortality 3,4 . Cerebral malaria (CM) is a severe neurological complication of malaria infection that is a major cause of death, with mortality estimated between 15-25% and clinical manifestations including unarousable coma and seizures 5,6 .…”

Gene expression of macaques infected with malaria species of zoonotic concern

“…Although pathogenicity in crab-eating macaques is less consistent than in rhesus macaques, these monkeys still variably develop severe symptoms and clinical presentation in response to P. coatneyi 20 . In contrast, P. cynomolgi has been found to naturally infect a range of primate hosts in Southeast Asia, including various macaque species 26 . Alongside the established simian zoonotic P. knowlesi , both P. cynomolgi 4, 27–30 and P. coatneyi 30 parasites were recently found in blood samples of humans, though the latter appears to be far rarer, as supported by prior failed attempts to experimentally infect people 31 .…”