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Malarial parasite plasmodium knowlesi, no monkey business

KUALA LUMPUR: The malarial parasite Plasmodium knowlesi is no monkey business.

The deadly microscopic parasite, which is transmitted to humans from monkeys (particularly macaques) through the anopheles leucosphyrus group of mosquito's bites, has increasingly become a threat to mankind in the tropics - accounting for tens of thousands of reported cases in Southeast Asia-wide to date.

Revealing this, Malaysian Society of Parasitology and Tropical Medicine (MSPTM) president Dr Sam Mohan told the New Straits Times that unaware to many, plasmodium knowlesi was becoming a bane as the primates were increasingly displaced from their natural habitat.

This, he said, was a result of rapid deforestation for economic development, which forced the primates to migrate closer to populated human dwellings in modernised towns and cities to survive.

"Typically, the parasites are maintained in low numbers in the natural monkey hosts from each mosquito bite.

"At the same time, these mosquitoes pick-up the infected blood from the monkeys and transmit the parasites to humans, dwelling close to the primate colony, during their next bite and easily multiply by the thousands in human blood.

"There on, the parasites continuously infect humans when they encounter the mosquitoes that also feed on monkeys during forest-related activities," said Dr Sam.

MSPTM's biggest concern, he added, was that many cases in Southeast Asia may be undiagnosed or unreported owing to lack of health checks by the authorities.

Thus, at least 32 deaths from plasmodium knowlesi - 18 of whom were males - were documented from Sabah and Sarawak.

Plasmodium knowlesi infections were strictly confined within the Southeast Asian region due to the limited natural distributions of the monkey hosts and the particular type of anopheles leucosphyrus group of mosquitoes.

"The detection of Plasmodium knowlesi in patients require the use of the molecular laboratory polymerase chain reaction (PCR) method, due to its undistinguished morphological characteristics with other parasite species.

"In hospitals across Malaysia, microscopy is still the gold standard for laboratory diagnosis of malaria for all species.

"The use of the PCR molecular method is mainly for research or molecular epidemiological studies and specific confirmatory cases," Dr Sam said this in conjunction with the recent 'MSPTM Annual Scientific Conference 2021'.

He noted that the molecular epidemiological studies conducted in Malaysia from 2004 to 2019, cumulatively identified 5,776 plasmodium knowlesi infections.

Thailand recorded 34 cases, Myanmar and the Philippines five each, Singapore and Kalimantan in Indonesia one each, Sumatera in Indonesia 392, Cambodia two, Vietnam 38 and Laos ten, for the same period.

However, based on microscopy, Dr Sam said that out of the 3,565 average annual malaria cases in Malaysia, between 2016 and 2020, 85 per cent were due to plasmodium knowlesi.

Of this figure, he said 88 per cent of plasmodium knowlesi cases occurred in east Malaysia, with Sabah reporting 55 per cent, followed by Sarawak (33 per cent), Kelantan (three per cent), Perak (three per cent) and Pahang (two per cent).

Dr Sam said the National Malaria Elimination Strategic Plan aimed to eliminate indigenous human malaria, especially malaria caused by human parasites plasmodium falciparum and plasmodium vivax, since 2011.

"We are aware that zoonotic malaria caused by plasmodium knowlesi has steadily increased.

"All plasmodium knowlesi malaria patients acquired the infections when performing activities in the dense forests and fringes, which involve mainly agriculture,

plantation and logging activities, when they were exposed to the Anopheles mosquitoes that fed on wild infected monkeys," Dr Sam said.

"Plasmodium knowlesi requires 24 hours to complete its development cycle in red blood cells before invading new cells, making it the fastest malaria parasite to multiply in humans.

"Delayed laboratory diagnosis and treatment will cause the patients to develop severe disease and potentially death due to high parasite burden," Dr Sam said.

To combat the spread of plasmodium knowlesi, health authorities had begun conducting studies to understand the biology of plasmodium knowlesi and the epidemiology of the disease.

"For almost two decades, since the large focus of natural infections reported in Sarawak in 2004, current significant findings showed that the evolution of this parasite was complex, indicating that there are at least three genetically divergent plasmodium knowlesi infecting humans.

"Two of these divergent parasites infect humans in east Malaysia - each associated with long-tailed macaque and pig-tailed macaque species, respectively.

"Whole genome data of these parasites isolated from patients indicate that two independent zoonosis are occurring sympatrically over there.

"One divergent plasmodium knowlesi is exclusively found in Peninsular Malaysia, mainly due to the geographical barrier of the South China Sea that separates the parasites in the monkeys from those in east Malaysia," he said.

Entomological studies also showed that there were many anopheles mosquito species responsible for transmitting plasmodium knowlesi to humans.

The anopheles balabacensis is the main vector in many regions in Sabah, while various species have been incriminated as potential vectors in Sarawak, like anopheles latens in Kapit, anopheles latens and anopheles donaldi in Lawas, and anopheles latens, anopheles introlatus, anopheles roperi and anopheles collesi in Betong.

"Anopheles cracens, however, are still the main vector for plasmodium knowlesi in Peninsular Malaysia," he said.

Meanwhile, Universiti Malaysia Sarawak's Malaria Research Centre director Dr Paul Cliff Simon Divis warned that malaria was a mandatory notifiable disease under the Malaysian Infectious Disease Prevention and Control Act 1988.

"Active and passive surveillances are being routinely performed by the district health offices to control the disease, which include plasmodium knowlesi parasite.

"PCR-based detection should be continuously applied in the surveillance especially on asymptomatic patients.

"While this molecular detection method is time-consuming and costly, collaboration between the Health Ministry and other agencies such as the universities, should be continuously emphasised to combat this zoonotic disease," said Dr Paul.

Additionally, he said, there ought to be greater public awareness through health education on monkeys malaria by Plasmodium knowlesi among people who were at high risk.

"Understanding the behaviour and habitat of the mosquitoes in essential, therefore, it is important for people to take precautions when engaging activities at the forest or forest fringe.

"Traditional methods such as applying mosquito repellents and wear long clothes to cover our skin are still effective to prevent mosquito bites.

"It is also recommended that farmers or plantation workers who spend the nights at the farms should sleep under insecticide-treated bed nets," he said.

Dr Paul advised those living in areas that were endemic for zoonotic malaria to be aware about the classical symptoms like fever, chills and rigours, and seek immediate treatment.

He called for further research to understand the biology of anopheles mosquitoes to control their abundance in the forest.

"Currently, a radiation technique that sterilizes male aedes mosquitoes is being tested in many countries as part of global health efforts to control diseases like dengue.

"Perhaps, similar technique can also be applied to anopheles mosquitoes for similar reasons," he said.

Dr Paul hoped that the discovery of a new malaria vaccine, Mosquirix, by the World Health Organisation, would be able to combat plasmodium falciparum malaria.

"But will it work on monkey malaria?" he asked.

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