In the spring of 1965, a lone American set off for the jungles of Malaysia, sleeping by day and working by night. The official story is that “B.W.” was a surveyor with the U.S. army; it’s believed, however, that he was actually a CIA spy, dispatched to the Malaysian hilltops to eavesdrop on communists.
It remains unclear what B.W. accomplished in that jungle. But according to the medical literature, he definitely picked up something strange: a mean case of monkey malaria.
Two weeks after leaving Malaysia, B.W. landed in a Maryland hospital with a diagnosis of Plasmodium knowlesi, a form of malaria previously thought to only infect macaques.
He became the first person in recorded history to catchmonkey malaria in the wild, but he would not be the last. Today, five decades after B.W. came down with a fever, thousands of P. knowlesi cases have been reported across Southeast Asia, in every country but Laos. The vast majority have occurred in Malaysia, where the monkey parasite is now the leading cause of human malaria, and government officials recently announced that P. knowlesi caused 66 per cent of the country’s 3,923 malaria cases last year.
Once written off as a monkey problem, scientists now consider P. knowlesi to be the “fifth human malaria.” But even as the human toll ticks upward, the mystery around this strange disease lingers.
“It’s surprising how little we do know about P. knowlesi,” said Jonathan Cox, a medical geographer with the London School of Tropical Medicine and Hygiene, who is spearheading a project studying the disease’s emergence. “I don’t think it’s going to cause a pandemic or anything. But we don’t know enough about the risk factors to know exactly what we’re dealing with yet.”
Malaria is a disease caused by the parasite Plasmodium parasite and transmitted by mosquito bites. It is also one of the leading causes of death in the developing world, infecting nearly 200 million people every year and killing an estimated 584,000.
But few people realize there are actually more than 150 species of malaria parasites, each preferring a specific host; everything from mice to snakes to penguins. Before P. knowlesi came along, it was thought that only four malarias infected humans: P. vivax, P. malariae, P. ovale and — the deadliest of the bunch — P. falciparum.
Scientists have long known that P. knowlesi could infect monkeys, primarily long-tailed and pig-tailed macaques. They also knew from experiments that the parasite was capable of infecting humans — for a time, patients with neurosyphillis were purposely infected as a form of treatment — but nobody believed that “natural” P. knowlesi infections were happening outside the clinic or lab.
Even the CIA agent’s case was considered a fluke, with investigations at the time concluding it was a freak occurrence.
“The 1965 case was probably considered a curiousity,” said Dr. Christopher Plowe, a malaria expert with the University of Maryland. “We had no clue P. knowlesi was significant to human health.”
But then came the husband-and-wife team of Balbir Singh and Janet Cox-Singh, both malaria researchers who moved to Malaysian Borneo, where they started a lab at the University of Malaysia Sarawak.
Prior to leaving, Singh asked a World Health Organization colleague if there was anything interesting about malaria in Malaysia that he should investigate. “He said, ‘Look out for P. malariae,” Singh recalled.
P. malariae is one of the rarer forms of human malaria. But as the country made greater strides in fighting malaria — reducing its annual caseload from 60,000 in 1995 to less than 4,000 last year — it became increasingly clear that there was something odd about Malaysia’s P. malariae cases.
For one, patients were getting really sick, sometimes even dying — unusual for P. malariae, which is thought to cause milder disease. So Singh travelled by boat up the Rajang river to visit a hospital in the remote region of Malaysia where cases were clustering, bringing a handful of patient blood samples back to his lab.
Using what was then-considered novel gene sequencing technology, Singh quickly realized why these cases were so weird. They weren’t P. malariae at all; they were P. knowlesi.
“Initially, we thought it was just one or two cases,” said Singh. “But what we found out was that virtually everything that’s been identified as P. malariae has been P. knowlesi.”
Singh has since identified more than 1,200 cases and he now believes that P. malariae isn’t endemic to Malaysia at all. He explains that previous cases were probably misdiagnosed because the two malarias look so similar under the microscope.
For Singh, there are many important questions to answer still when it comes to P. knowlesi, including why, exactly, cases seem to be on the rise. His worst-case scenario is that P. knowlesi (still believed to be sporadically jumping from monkey to human) will evolve to start spreading human-to-human — a development that could pave the way for monkey malaria to spread beyond Southeast Asia and regions where macaques are prevalent.
Of the five human malarias, P. knowlesi is still a lower priority, accounting for a tiny proportion of the total human misery caused by this disease. But scientists know fully well that infectious diseases are always ready to send up new surprises.
“We can too often, as researchers, slip into a way of thinking that ‘Malaria is this’ or ‘Malaria is that,’” said David Conway, a malaria researcher at the London School of Hygiene and Tropical Medicine who also studies P. knowlesi. “But that can change — and it has changed.”