Malaria is no stranger to human civilisation – It has actively participated, whether we like it or not, in the history of our species pretty much as long as humans have been around (by humans I mean Homo sapiens because Neanderthal wasn’t around 40 00 years ago). Its victims have included nomadic Neolithic dwellers, early Chinese and Greeks, as well as princes and paupers. Malaria’s long reign of death and misery can be traced back to the cuneiform script on clay tablets from ancient Mesopotamia, which mentioned deadly periodic fevers suggestive of malaria. Even recently, Malarial antigen was detected in Egyptian remains dating from as far back as 3200 and 1304 BC.
Aside from Africa, Malaria can also thrive in tropical countries, and Malaysia being one of those tropical countries, has a very personal history with Malaria – in fact, syllable for syllable, the two words even sound similar.
Malaysia’s experience with Malaria has been very interesting for a few reasons; most of the cases of Malaria in the country, comes from just one state which is Sabah; and the least common of the Malaria-causing protozoa, P. knowlesi, happens to be one of the most common cause of Malaria in the country. That’s right, the rarest cause of Malaria in the world, happens to be one of the the most common cause of Malaria infection in Malaysia. In other parts of the world, Malaria is caused by the famous four Plasmodium species (which is also known as Human-only Plasmodium species) – P. falciparum, P. malariae, P. ovale, P. vivax.
The reason why P. knowlesi infection is so rare and special compared to the other 4 species of Plasmodium is because it is a zoonotic infection – infection that originates from an animal source or reservoir, unlike the other four which are limited to just human reservoir. In all countries where both the major monkey reservoir (Macaca fascicularis and M. nemestrina) and mosquito vector (Anopheles leucosphyrus group) are present, like Malaysia, Malaria from P. knowlesi infection is a looming existential threat.
A recent study which was published on the 19th of March 2019 in the journal of Clinical Infectious Disease, reported the incidence of all Plasmodium species in Sabah, including the zoonotic P. knowlesi, from the period of 2015 until 2017. What the study found was interesting and scary at the same time – while the country is approaching a complete elimination of human-only Plasmodium species, the incidence of P. knowlesi is increasing drastically.
Malaysia aims to eliminate Malaria by 2020, and with the recent report by the World Health Organization (WHO) that only 85 malaria cases occurred nationally in 2017, we seemed to be on the right track. However, that report only accounted for human-only Plasmodium species. The zoonotic P. knowlesi infection on the other hand, has made tremendous stride when it comes to infecting people as it is responsible for 817 out of 1018 (80%), 677 out of 771 (88%), and a staggering 2030 out of 2078 (98%) of the total malaria cases from 2015 to 2017. In contrast, for the same period of time, P. falciparum accounted for just 110 (11%), 45 (6%), and 23 (1%) of Malaria cases in 2015, 2016, and 2017 respectively.
What’s interesting about the 2015 – 2017 time frame is that the majority of the districts in Sabah experienced a decrease in P. knowlesi cases from 2015 to 2016; however, the incidence increased in 2017 in all districts except Kunak, with the highest number of cases occurred in Keningau and Ranau along the Crocker range, reporting 479 and 358 cases, respectively.
This indicates that the interventions implemented to control Malaria was successful at reducing the transmission of human-only Plasmodium species but did little to effectively address the complex factors that are likely contributing to the increase in zoonotic P. knowlesi infections.
So, why are we experiencing an increase inMalaria caused by P. knowlesi?
In an attempt to provide explanation for this worrying phenomenon, the team of Malaysian researchers suggested a few plausible theories.
As with other emerging zoonotic diseases, the increase in incidence of P. knowlesi in Sabah is likely driven by changes in human land use, leading to complex changes in transmission of the parasite between humans, the mosquito vectors and the macaque hosts. Sabah has undergone extensive deforestation, with around 30% of its primary forest area lost between 1973 and 2010. 21% of Sabah’s total area now are used for palm oil plantations. Among many other things deforestation is notorious for, it can result in a reduced biodiversity and it is possible that the loss of less efficient or dead-end hosts for Malaria, has contributed to a higher prevalence of P. knowlesi in the highly competent macaque hosts, with consequent spill-over of P. knowlesi to humans.
Deforestation can also enhance the vectors’ population and subsequently, malaria transmission by potentially increasing the amount of sunlight on breeding sites, changing composition of soil, or by changing Anopheles species distribution or behaviour.
The emergent of a competent vector
In Sabah, the mosquito species An. balabacensis is the primary vector of P. knowlesi and they can be found in villages, forests and farming sites, but with the rampant deforestation going on in Sabah, An. balabacensis has recently been shown to be most abundant in logged areas, with predatory host-seeking behaviour more prevalent at ground level. Combining its ability to adapt to changing environment and its behvaiour of seeking for hosts where humans would mostly be at, An. balabacensis can be considered as a highly competent vector successfully adapting to ecological changes, favouring the increased of zoonotic P. knowlesi transmission.
The Malaria immunity trade-off
As it turns out, our relentless pursuit in eradicating Human-only Plasmodium species is costing us something – being more and more defenceless against P. knowlesi infection. You see, having previously been infected by Human-only species such as P. vivax can have its silver lining as it confer ‘Heterologous immunity’ against P. knowlesi. Studies has demonstrated that P. vivax antibodies can inhibit P. knowlesi red cell invasion. Thus, the possibility that declining cross-protective immunity to P. vivax may contribute to the rising incidence of knowlesi malaria has important implications, highlighting the importance of regional molecular surveillance for P. knowlesi.
The changing of the season
In this study, the number of P. knowlesi cases decreased between 2015 and 2016, before increasing in 2017. This initial decrease may in part reflect a short-term impact on vector bionomics due to changing rainfall and weather patterns, with Sabah experiencing unusually low rainfall during this period as part of the worldwide El Niño weather phenomenon. Consistent with previous reports, the study found an increase in P. knowlesi incidence 3 months after higher rainfall.
A possibility of human to human transmission
The substantial increase in incidence of P. knowlesi in 2017 could also raise the possibility of an underlying human-to-human transmission (HTHT) taking place. While genetic analysis and modelling involving humans and macaques transmission remains zoonotic, HTHT has been experimentally demonstrated and should we witness another increment of cases, such possibility should not be discounted.
From this study, it is painfully obvious that P. knowlesi is posing a major challenge and an unprecedented level of threat to malaria control in Malaysia. While efforts on the elimination of the human-only malaria species must continue, current malaria prevention activities may need to be redesigned, or new approaches needs to be developed, to mitigate P. knowlesi transmission to humans. In parallel, public health policies need to focus on increasing awareness of knowlesi malaria, and ensure strategies are in place to enable prompt diagnosis and treatment, particularly in high-risk regions.
Hello Health Group does not provide medical advice, diagnosis or treatment.
Review Date: April 11, 2019 | Last Modified: April 11, 2019
Shearer FM, Huang Z, Weiss DJ, et al. Estimating geographical variation in the risk of zoonotic Plasmodium knowlesi infection in countries eliminating malaria. PLoS Negl Trop Dis 2016;10(8):e0004915.
William T, Jelip J, Menon J, et al. Changing epidemiology of malaria in Sabah, Malaysia: increasing incidence of Plasmodium knowlesi. Malar J 2014; 13: 390.
Rajahram GS, Barber BE, William T, et al. Falling Plasmodium knowlesi malaria death rate among adults despite rising incidence, Sabah, Malaysia, 2010-2014. Emerg Infect Dis 2016; 22(1): 41-8