Plasmodium knowlesi

Plasmodium knowlesi
Scientific classification
Kingdom:	Protista;
Phylum:	Apicomplexa;
Class:	Aconoidasida;
Order:	Haemosporida;
Family:	Plasmodiidae;
Genus:	Plasmodium;
Species:	P. knowlesi;
Binomial name
	Plasmodium knowlesi;

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Marjan Khan M.B.B.S.[2]

Overview

Plasmodium knowlesi is a simian parasite that cause malaria; the natural hosts are macaques.^[1] Human cases of Plasmodium knowlesi malaria have been reported throughout the Southeast Asia; most cases have been reported from Malaysia, particularly the eastern Malaysian states of Sabah and Sarawak.^[2] this malaria is generally acquired in forest or forest-fringe areas; those at risk include farmers, plantation workers, and individuals undertaking other activities in forested areas. Adult population is commonly affected more than children and the mortality increases as the age increases. ^[3]

Epidemiology

Reports of human P. knowlesi infections are confined to Southeast Asia,^[4]^[5] particularly Malaysia,^[6] but there are also reports on the Thai-Burmese border.^[7] A fifth of the cases of malaria diagnosed in Sarawak, Malaysian Borneo are due to P. knowlesi.^[6]

P. knowlesi infection is normally considered an infection of long-tailed (Macaca fascicularis) and pig-tailed (M. nemestrina) macaques, but humans who work at the forest fringe or enter the rainforest to work are at risk of being infected with P. knowlesi.
The first case of naturally acquired human infection with P. knowlesi was reported in 1965 in a United States national working in Malaysia.^[8]
The mosquito Anopheles latens is attracted to both macaques and humans and has been shown to be the main vector transmitting P. knowlesi to humans in the Kapit Division of Sarawak, Malaysian Borneo^[9]. Within the monkey population in Peninsular Malaysia, A. hackeri, is believed to be the main vector of 'P. knowlesi' : although 'A. hackeri' is capable of transmitting malaria to humans,^[10] it is not normally attracted to humans and therefore cannot be an important vector for transmission.^[11]

Transmission and risk factors for infection

Human-mosquito-human transmission has been demonstrated in the laboratory setting but has not yet been proven to occur in the natural environment.^[12]
Cases of P. knowlesi in humans have been reported to occur in clusters, affecting individuals of all ages.
Transmission is predominantly zoonotic but it appears possible that human-mosquito-human transmission may occur (at least to some degree) in endemic areas.^[13]
Risk factors for acquiring P. knowlesi infection include:^[14]

Male gender
Age greater than 15 years
Sleeping outside
Proximity to monkeys in the preceding four weeks
Presence of open eaves or gaps in walls
Presence of long grass around dwelling

Protective factors against P. knowlesi infection in one study included:^[14]

G6PD deficiency
Residual insecticide spraying of household walls
Presence of sparse forest or rice paddies around the house
Use of bed nets was not protective

children Less than 15 years accounted for only 10 % of all P. knowlesi cases in Sabah, Malaysia, between 2010 and 2014.^[15]
Transfusion-transmitted P. knowlesi malaria has been reported in Malaysia.^[16]

Diagnosis

P. knowlesi infections is diagnosed by examining thick and thin blood films in the same way as other malarias.
The appearance of P. knowlesi is similar to that of P. malariae and is unlikely to be correctly diagnosed except by using molecular detection assays ^[6]
Reporting of P. knowlesi as the more benign P. malariae has been associated with failure to recognize severe malaria and consequent delayed initiation of parenteral therapy, with fatal outcomes.
P. knowlesi malaria should be suspected in the setting of febrile illness after exposure to regions where P. knowlesi malaria is endemic.
The approach to diagnosis of P. knowlesi malaria consists of microscopy to guide immediate clinical management, followed by confirmatory testing with PCR.
PCR is the gold standard diagnostic tool with high sensitivity and specificity.^[17]
Microscopy is a sensitive tool for the detection of level of parasitemia and to know the life cycle stages of Plasmodium knowlesi.
Microscopy can not be used for the differentiation of different species of Plasmodium , as the blood stages of P. knowlesi resemble P. malariae and the ring stages resemble P. falciparum.^[18]
Patients in endemic regions of P. knowlesi malaria with microscopy findings resembling P. malariae should be treated for P. knowlesi infection.
Rapid diagnostic tests (RDTs) are useful for excluding P. falciparum infection but have low sensitivity for detection of P. knowlesi infection, especially at the low parasite densities commonly causing clinical disease.^[19]

Treatment

P. knowlesi infection responds well to treatment with chloroquine and primaquine.^[6]