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As Southeast Asia progresses towards malaria elimination, Plasmodium knowlesi threatens to derail its hard-won gains. Over the past five years, Malaysia has reported 2,000 to 3,000 P. knowlesi cases annually, despite sustaining zero indigenous human malaria cases since 2018.
Cases of P. knowlesi in humans are correlated with the presence of long-tailed macaques and pig-tailed macaques. The Anopheles mosquitoes that transmits P. knowlesi malaria tend to bite outdoors and can be found across different locations. While macaques are the natural hosts of P.knowlesi, it can be passed to humans through the bites of infected mosquitoes. Generally, adult males working in the agricultural sector are most likely to be exposed to P. knowlesi, although cases have also been reported among women and children. Left untreated, P. knowlesi malaria can lead to life-threatening complications including acute kidney failure, respiratory distress, and intravascular haemolysis.
The State of P. knowlesi in Southeast Asia
Cases of P. knowlesi have been detected in all countries across Southeast Asia, with the exception of Timor-Leste. As surveillance improves in recent years, the number of reported cases has also increased, especially in Malaysia.
Malaysia’s malaria elimination strategy centered efforts to eliminate malaria in Peninsular Malaysia by 2015, with Sabah and Sarawak to follow by 2020. These goals were achieved sooner than expected, with zero non-zoonotic malaria cases reported since 2018. However, Malaysia’s malaria-free certification has been delayed on account of its many P. knowlesi cases, with nearly 19,000 cases reported since 2018. As P. knowlesi is a form of malaria, certification from the World Health Organization is hindered under current guidelines.
Elsewhere, such as in Sumatra and Kalimantan of Indonesia, surveillance for P. knowlesi is improving though case detection and identification of malaria cases among forest-going populations remain challenging. In Thailand, while P. knowlesi infections are notifiable, protocol for its management does not vary from that of routine human malaria cases.
Current Challenges: Case Diagnosis and Health-seeking Behaviour
PCR testing is the gold standard for the diagnosis of P. knowlesi. However, its accessibility is hindered by the limited resources and expertise in areas of greatest need. Such systems are under development in Indonesia, while countries facing resource constraints may rely upon a central laboratory, which makes prompt diagnosis challenging.
Challenges remain in malaria prevention practices across the region, particularly on the use of insecticide-treated nets (ITNs), indoor residual spraying (IRS), and repellents. Compliance and usage figures from studies in Thailand and Malaysia indicate high usage rates of ITNs, however these levels of acceptance are not universally seen across the region. Studies have found that forest workers view ITNs as being impractical, as mosquito nets often require supporting structures that are not always available outdoors. In some cultures, hammock nets may be preferred. In Cambodia, rural communities have improvised their own solutions, from combining nets for coverage to setting up posts to support bed nets. Unfortunately, these interventions are insufficient to contain zoonotic malaria.
Recommendations
Eliminating P. knowlesi will require a multisectoral approach rather than merely adopting existing methods used against non-zoonotic malaria. The presence of the zoonotic element necessitates the adoption of a One Health policy that recognises the interconnectedness of human behaviour, primate behaviour, and mosquito control in controlling zoonotic malaria.
Human behaviour
Knowledge gaps surrounding P. knowlesi remain across rural communities where the parasite is endemic. A survey among the Orang Asli of Peninsular Malaysia found high bed net use, though only half of surveyed users understood their role in the prevention of malaria transmission, indicating a need for more tailored health education. Additionally, health education should be extended beyond rural communities, with warnings clearly communicated to visitors entering malaria-endemic areas to minimise outdoor activities, especially during active mosquito-biting periods. Creating lasting cultural norms such as these require a better understanding of health-seeking behaviour in rural communities.
Primate behaviour
Communities in forest-adjacent areas, or villages at risk, often face higher exposure risks because of their proximity to monkey reservoirs and Anopheles mosquitoes. Owing to the role of macaques in P. knowlesi transmission, any attempt to eliminate zoonotic malaria would be incomplete without understanding simian behavioural patterns and responses to environmental changes. Deforestation and human intrusion into deeper parts of the forest have resulted in macaques coexisting near human settlements. The absence of their natural predators in areas where humans exist further incentivises anthropogenic behaviour in macaques. Encouragingly, efforts to discourage macaques from associating with humans persist today and these are complemented with efforts to alter human behaviour in parallel.
Mosquito control
As mosquito nets by themselves are insufficient to eliminate transmission of P. knowlesi to humans, alternative methods of vector control have been attempted. In the Malaysian states of Sabah and Sarawak, novel formulations of outdoor residual sprays were examined for suitability and have seen some success in reducing mosquito numbers, though the impact on P. knowlesi infections was not measured. Trials on the use of spatial emanators have similarly produced positive results, though further testing under a wider range of experimental conditions remains necessary.
Advancing the One Health Approach
The intersection of humans, animals, and the environment is a frontier that the region can ill afford to ignore, as the threat of zoonotic malaria comes into focus. While international cooperation is strengthening, addressing zoonotic malaria will require more than traditional approaches — it demands strategies that bridge human, animal, and environmental health through a One Health lens. With coordinated, cross‑sectoral action, the region can safeguard hard‑won gains and move decisively toward a malaria‑free future.
