Malaria is endemic in Malaysia and has been around for more than a century. The parasitic infection is due to the Plasmodium species, which include P. falciparum, P. vivax, P. ovale and P. malariae. The parasite has two hosts: humans and the Anopheles mosquitoes that transmit the infection.
There are increasing reports of monkey malaria, most of which are due to P. knowlesi, and which has established itself as the fifth Plasmodium species that infects humans. It has not been determined whether P. knowlesi is naturally transmitted from one human to another by the mosquito, without the natural intermediate host (monkeys). As such, P. knowlesi is still considered a zoonotic infection i.e. an infection that is transmitted from animal to human. Mixed infections of P. knowlesi with other Plasmodium species have also been reported.
Malaysia has the highest cases
According to the World Health Organization (WHO), Malaysia has the highest incidence of P. knowlesi infection in the world. There were 4,553 and 204 cases reported from Sabah and Sarawak, and Peninsular Malaysia from 2004 to 2016 respectively. The infection has also been reported in Indonesia, Thailand, Myanmar, Singapore, the Philippines, Vietnam, Brunei and China with 465, 37, 33, six, five, three, one and one cases respectively.
The first case of P. knowlesi was reported in 1965 in a man who returned to the United States after a visit to Peninsular Malaysia. According to WHO data, P. knowlesi accounted for 1,523 (69%) of the 2,206 human malarial infections in Malaysia in 2016, with 1,264 men and 259 women infected by P. knowlesi.
The natural hosts of P.knowlesi are the macaque and banded leaf monkeys. The people who are at risk of acquiring the infection include farmers, timber camp workers, hunters, security personnel and travellers to forests or their fringes. Data from Sabah report that patients with P. knowlesi infections are older than those with P. falciparum and P. vivax infections, with 80% of those infected being males. There is a bimodal distribution among females with peaks at 12 and 52 years of age.
The Anopheles mosquito species, which are the vectors, are found in slow running streams, animal foot paths, ground pools and collections of stagnant water. The increase in the reported P.knowlesi infections have been attributed to improved diagnosis; reduction of human malaria cases; reduction in immunity due to decreased incidence of human malaria; and changes in land use that have led to increased likelihood of transmission of zoonotic infection due to closer association with monkey hosts or access to infected mosquitoes. Of the Plasmodium species, P. knowlesi has the shortest reproduction cycle, which means that the level of parasites in the blood (parasitaemia) increases very quickly.
The Anopheles mosquito species, which are vectors for the malaria parasites, are found in collections of
stagnant water, slow running streams and ground pools.
Infections with P. knowlesi are of a wide spectrum, ranging from asymptomatic to fatal infection. The common clinical features are fever, chills, headache, muscle ache, poor appetite, joint pains, cough, abdominal pain and diarrhoea.
These features are not different from P. falciparum and P. vivax infections. Studies from Sabah and Sarawak report that more than 10% have severe infection, with a case fatality rate of about 1%.
The complications of severe infection include jaundice, acute kidney failure, low blood pressure and acute respiratory disease. Low platelet counts are very common, and together with parasitaemia and increasing age, are associated with severe infection.
Diagnosis and treatment
The diagnosis of malaria is often made by microscopic examination of a blood film. The microscopic features of P. knowlesi are similar to that of P. falciparum and P. malariae in the early and later stages of infection respectively. Many P. knowlesi infections have been mistakenly identified as P. malariae infections.
Molecular detection methods are the most accurate and sensitive tests for identification of P. knowlesi. However, these techniques are relatively expensive, not rapid and are not readily available in all healthcare facilities.
In short, the diagnosis of P. knowlesi infections poses challenges. Infections with P. knowlesi are very sensitive to treatment with artemisinins and moderately sensitive to chloroquine and mefloquine.
Some answers, but many unanswered
A recent report addressed the issue of "Individual-level factors associated with the risk of acquiring human P. knowlesi malaria in Malaysia". (Source: Grigg MJ et al, Lancet Planetary Health Vol 1, June 2017)
The factors associated with an increased risk of symptomatic P. knowlesi infection were age 15 years or older, males, plantation work, sleeping outside, travel, being aware of the presence of monkeys in the preceding four weeks and having open eaves or gaps in walls.
There was increased risk for P. knowlesi infection with a farming occupation, clearing vegetation and having long grass around the house, but these factors did not increase the risk of other Plasmodium species infection.
G6PD deficiency, residual insecticide spraying of household walls, presence of young sparse forest and rice paddy around the house appeared to decrease the risk of P. knowlesi infection.
Human P. knowlesi infections are still a zoonosis. However, there are indications that human to human infection can occur, and is probably occurring, albeit inefficiently.
This is evidenced by mixed infections with human malaria species i.e. P. falciparum, P. vivax and P. malariae, and from laboratory and genomic studies.
Could human to human transmission of P. knowlesi become more common?
It could with time and adaptation of the parasite.
The malaria eradication programme has resulted in a decline in the incidence rate, from 23.47 to 7.58 per 100,000 population in 2010 and 2015 respectively.
The mortality rate declined from 0.12 to 0.03 per 100,000 population in 2010 and 2015 respectively.
The next step
At this rate, the country is on track to eliminating human-only species malaria by 2020. How P. knowlesi could impact on the malaria eradication programme is a question that needs addressing. However, there are many unanswered questions as the vector dynamics, its longevity, and probably its flight range are not well known.