Studies on malaria at two Malaysian universities.
WHILE Dr Balbir Singh and his team in Universiti Malaysia Sarawak have been building a picture of the parasite Plasmodium knowlesi in Sarawak, Dr Reuben Sharma has been tackling the problem from a slightly different angle at Universiti Putra Malaysia in Selangor.
A protozoologist by training, Dr Sharma’s niche is blood parasites, especially zoonotic ones – that is, those that occur in both animals and humans.
He spent his doctoral years in Cambridge, Britain, working on trypanosomes – a type of blood parasite that causes sleeping sickness, and Chagas disease, of which there are a number of species spread out over different geographical regions.
“But it’s not an important disease here. The most important blood parasite in Malaysia is malaria,” he says.
It was Dr Balbir’s 2004 publication in The Lancet that got Dr Sharma interested in P. knowlesi.
In their laboratory at UPM, Dr Sharma’s researchers have spent the past four years processing samples of monkey blood. Their primary aim: to scour the samples for P. knowlesi DNA, in order to try and figure out the prevalence rate for the disease in wild macaques.
This period has seen Dr Sharma’s team travel up and down the entire west coast of Malaysia.
They have been to every state from Penang down to Johor and analysed 800 samples of monkey blood, with 200 more awaiting processing in the laboratory freezer.
At the 6th Asean Congress of Tropical Medicine and Parasitology held in Kuala Lumpur recently, Dr Sharma told the audience that the prevalence rate of P. knowlesi in monkeys on the west coast of Peninsular Malaysia is 25%.
In some states, such as Perak or Negri Sembilan, the figure climbed to 35% – possibly because of more habitable areas for the parasite’s monkey hosts and mosquito vectors.
Importantly, Dr Sharma says, a number of cases were recorded at the forest fringes. Certain transmission hotspots were identified around plantations and suburban areas.
These locations represent a growing interface between wildlife and people – and scientists are trying to find out what risks this might entail.
Are monkeys emerging from the jungle because they are losing habitats to deforestation and urban development, or are they simply visiting farms for access to easy food?
What sort of factors do we need to look at that may increase the chances of human exposure to the parasite?
A monkey coming out of the jungle is not enough for transmission – so are the Anopheles mosquitoes that usually feed on monkeys in the jungle following them out?
Or are there different Anopheles vectors, more widespread in human inhabited areas, that are aiding transmission once the monkeys come out?
Many questions remain, and answering them will be important if we are to come up with an informed control strategy.
The next step is to determine the prevalence of monkey infections on the east coast and within the peninsula’s central forest spine interior. Another one of Dr Sharma’s long-term goals is to use molecular genetic tools to develop rapid diagnostic kits that can detect human infections of P. knowlesi.
Current detection methods like microscopy or serology tests are simply not specific enough, or practical to deploy. What is needed is a simple and relatively cheap tool like a lateral flow monoclonal antibody kit – the sort used in pregnancy tests – where you get a band of colour forming if the result is positive.
It would work by designing antibodies that bind to protein receptors found on the parasite’s surface. To do that, you would first need to know which protein receptors to target, so a lot of groundwork needs to be done.
And Dr Sharma has been spending a lot of time characterising genotypes – the various genetic variants within the genome of different strains of P. knowlesi.
One widespread variant he found co-exists both in monkeys and humans.
“That’s important, because if we wanted to come up with a drug or vaccine targeting a certain genotype, we would want to know which is the most dominant (genotype) within a population,” he says.
The fact that there are no such variants unique to humans indicates that, for the moment, P. knowlesi is still very much a zoonosis – a disease that can be transmitted from animals to humans. This means that even if we manage to eradicate the parasite in humans, monkeys would still act as its pool of hosts.
That has important implications for control strategies.
Malaysia has done an excellent job at controlling malaria. Worldwide, the disease is one of the world’s biggest killers, thought to kill one child every 30 seconds, and about 3,000 children every day.
This mostly occurs in sub-Saharan Africa, though; Malaysia is considered a “low contribution country” under the Global Malaria Action Plan, which aims to eradicate the parasitic disease by 2020.
The control strategies that got us here – insecticide-treated mosquito nets, residual spraying and treatment of malarial infections – won’t work in monkeys, which don’t sleep under nets or in houses.
And as the interface between wildlife and humans expands along with urban development, so too do the risk factors for human exposure to P. knowlesi.
Given the right precautions – vector control programmes, sensible town planning, management of monkey populations, and a healthcare system that is prepared to offer correct diagnoses and treatments – this is something Malaysia should have no problem handling.
However there is one question that looms: what if P. knowlesi becomes easily transmissible from human to human?
My cat gave me TB
Coming up: We explore the theory that, despite its relatively recent appearance on the scene, P. knowlesi is in fact very old – older, perhaps, than even the two most virulent human malarias – P. falciparum and P. vivax – endemic to South-East Asia.