Malaria, man, monkeys and mosquitoes… oh my!
By Patricia Hului
In the 1960s, an American army surveyor on a five-week mapping exercise in the jungle near Temerloh, Pahang returned to the US with a fever.
Diagnosing his blood by microscopy, they believed that he had picked up Plasmodium malariae. A blood sample was taken and sent to Atlanta where they were running drug trials on this malaria strain.
Thereafter, they injected the strain into human volunteers, observing that their fevers peaked at 24 hours… not the expected 72 hours for P malariae.
The researchers then injected the infected blood into rhesus macaques known to be immune to P malariae. The animals died, however, revealing instead that the parasites were not P malariae as originally suspected, but a kind of monkey malaria, P knowlesi.
But what was an American army surveyor doing a mapping exercise in the Malayan jungle by himself in the first place?
According to Universiti Malaysia Sarawak (Unimas) lecturer Professor Dr Balbir Singh, rumour had it that the so-called surveyor was actually a CIA agent working on a secret mission against the communist insurgency at the time.
The ‘CIA agent’ became the first reported case confirming that humans could get malaria from monkeys by mosquito bite instead.
This finding did not come to light, however, until after Dr Balbir and his team confirmed that besides the four species of Plasmodium parasites known to cause malaria in humans – P falciparum, P vivax, P ovale and P malariae – there was in fact a fifth one, and that it could be transmitted by mosquito from monkeys to humans.
The founding director of the Malaria Research Centre (MRC) Unimas said the fifth species P knowlesi could cause severe malaria and death compared to its benign lookalike, P malariae.
“Our laboratory technologists were trained to identify the three major malaria parasites found in Malaysia; P falciparum, P vivax and P malariae,” shared Dr Balbir, who has been investigating malaria for three decades.
Upon re-examination of the blood samples collected, it was found the technologists were misdiagnosing P knowlesi as P malariae because these two parasites looked similar under the microscope.
He added, “The only way to correctly identify each species is by using molecular detection methods, or DNA tests, that have been developed.”
The 61-year-old scientist shared how he and his team began their investigations into the little-known species of malaria parasite when they noticed atypical malaria records in Kapit division back in 1999.
“The main cause of human malaria in Sarawak has been P vivax, followed by P falciparum and P malariae,” said Balbir. “However, in Kapit there were more P malariae cases than P falciparum.”
What’s more, P malariae typically exhibits a low parasite count and is a benign infection that does not normally require hospitalisation.
“But all the cases in Kapit were hospitalised and some patients had high numbers of parasites in their blood.”
The Unimas team then obtained the DNA sequence for the parasite, comparing it with other sequences deposited in an online database called GenBank.
“When this was done, it caused great excitement in the laboratory because the DNA sequence was 99.6 percent identical with that of P knowlesi.”
He shared that this malaria parasite was typically found in long-tailed and pig-tailed macaques.
“The macaques were a good host for this parasite as they did not become ill by it.”
These were confirmed with further DNA sequencing of seven other P malariae isolates. Dr Balbir’s team also developed a molecular detection test for P knowlesi, conducting a study at Kapit Hospital starting 2000.
From the 208 blood samples collected at Kapit Hospital, 141 (68 per cent) of the samples were diagnosed as P malariae under microscopy, the conventional method of analysing malaria at the time. When they ran the same samples under molecular tests, however, they discovered that none of the samples identified as P malariae, but 120 (58 per cent) were in fact P knowlesi.
“This was a landmark discovery since it was generally believed that malaria was not a zoonosis; an infection originating from an animal.”
According to Dr Balbir and his team’s findings from Kapit, moreover, knowlesi malaria does not occur within the communities in the longhouses.
He stated, “People get infected when they are bitten by mosquitoes in the forest or the forest fringe in the evenings when they venture into the jungle to hunt or return from the farm land.”
Dr Balbir explained that the finding of the fifth human malaria parasite had resulted not only in the rewriting of medical textbooks but changed the way infections are diagnosed.
“Due to the rapid multiplication of P knowlesi in the blood – 24 hours compared to 72 hours for P malariae – and the potential to cause severe malaria and death, these patients can now be recognised as having knowlesi malaria and treatment can be administered more urgently.”
According to Dr Balbir, this change in treatment and management policy has resulted in lives being saved, especially in Sabah and Sarawak where P knowlesi is now the most common cause of human malaria.
Dr Balbir was speaking to 300 people during a public talk ‘Malaria, man, monkeys and mosquitoes’ hosted by the Faculty of Medicine and Health Sciences Unimas at Pustaka Negeri Sarawak on Aug 18.
Since he and his research team made the landmark discovery in 2004, they have made subsequent key discoveries which have highlighted knowlesi malaria as a life-threatening zoonotic disease prevalent throughout Southeast Asia.
His contributions to science in Malaysia were recognised by the Academy of Sciences Malaysia when they selected him as one of the Top Research Scientists Malaysia in 2012 and invited him to become a Fellow of the Academy of Sciences Malaysia in 2015.