Deforestation and non-human primate malarias will be a threat to malaria elimination in the future: Insights from Southeast Asia.

Malaria continues to be a global public health problem although it has been eliminated from many countries. Sri Lanka and China are two countries that recently achieved malaria elimination status, and many countries in Southeast Asia are currently in the pipeline for achieving the same goal by 2030. However, Plasmodium knowlesi, a non-human primate malaria parasite continues to pose a threat to public health in this region, infecting many humans in all countries in Southeast Asia except for Timor-Leste. Besides, other non-human primate malaria parasite such as Plasmodium cynomolgi and Plasmodium inui are infecting humans in the region. The non-human primates, the long-tailed and pig-tailed macaques which harbour these parasites are now increasingly prevalent in farms and forest fringes close by to the villages. Additionally, the Anopheles mosquitoes belonging to the Lecuosphyrus Group are also present in these areas which makes them ideal for transmitting the non-human primate malaria parasites. With changing landscape and deforestation, non-human primate malaria parasites will affect more humans in the coming years with the elimination of human malaria. Perhaps due to loss of immunity, more humans will be infected as currently being demonstrated in Malaysia. Thus, control measures need to be instituted rapidly to achieve the malaria elimination status by 2030. However, the zoonotic origin of the parasite and the changes of the vectors behaviour to early biting seems to be the stumbling block to the malaria elimination efforts in this region. In this review, we discuss the challenges faced in malaria elimination due to deforestation and the serious threat posed by non-human primate malaria parasites.

The threat of increased transmission of non-knowlesi zoonotic malaria in humans: a systematic review.

Of the 5 human malarial parasites, Plasmodium falciparum and Plasmodium vivax are the most prevalent species globally, while Plasmodium malariae, Plasmodium ovale curtisi and Plasmodium ovale wallikeri are less prevalent and typically occur as mixed-infections. Plasmodium knowlesi, previously considered a non-human primate (NHP) infecting species, is now a cause of human malaria in Malaysia. The other NHP Plasmodium species, Plasmodium cynomolgi, Plasmodium brasilianum, Plasmodium inui, Plasmodium simium, Plasmodium coatneyi and Plasmodium fieldi cause malaria in primates, which are mainly reported in southeast Asia and South America. The non-knowlesi NHP Plasmodium species also emerged and were found to cross-transmit from their natural hosts (NHP) ­ to human hosts in natural settings. Here we have reviewed and collated data from the literature on the NHPs-to-human-transmitting non-knowlesi Plasmodium species. It was observed that the natural transmission of these NHP parasites to humans had been reported from 2010 onwards. This study shows that: (1) the majority of the non-knowlesi NHP Plasmodium mixed species infecting human cases were from Yala province of Thailand; (2) mono/mixed P. cynomolgi infections with other human-infecting Plasmodium species were prevalent in Malaysia and Thailand and (3) P. brasilianum and P. simium were found in Central and South America.

Primate malaria of human importance.

Nonhuman primate (NHP) malaria poses a major threat to the malaria control programs. The last two decades have witnessed a paradigm shift in our understanding of the malaria caused by species other than the traditionally known human Plasmodium species - Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, and Plasmodium ovale. The emergence of the malaria parasite of long-tailed macaque monkeys, Plasmodium knowlesi, as the fifth malaria species of humans has made the scientific community consider the risk of other zoonotic malaria, such as Plasmodium cynomolgi, Plasmodium simium, Plasmodium inui, and others, to humans. The development of knowledge about P. knowlesi as a pathogen which was earlier only known to experimentally cause malaria in humans and rarely cause natural infection, toward its acknowledgment as a significant cause of human malaria and a threat of malaria control programs has been made possible by the use of advanced molecular techniques such as polymerase chain reaction and gene sequencing. This review explores the various aspects of NHP malaria, and the association of various factors with their emergence and potential to cause human malaria which are important to understand to be able to control these emerging infections.

Diversity of Anopheles species and zoonotic malaria vector of the Buton Utara Wildlife Sanctuary, Southeast Sulawesi, Indonesia.

BACKGROUND: The recent deforestation for agricultural, mining, and human re-settlement has significantly reduced the habitat of many non-human primates (NHPs) in Indonesia and intensifies interaction between the NHPs and humans and thus opening the possibility of pathogen spill-over. The emergence of zoonotic malaria, such as Plasmodium knowlesi, poses an immense threat to the current malaria control and elimination that aims for the global elimination of malaria by 2030. As malaria in humans and NHPs is transmitted by the female Anopheles mosquito, malaria vector control is very important to mitigate the spill-over of the malaria parasite to humans. The present study aims to explore the Anopheles species diversity in human settlements adjacent to the wildlife sanctuary forest in Buton Utara Regency, Southeast Sulawesi, Indonesia, and identify the species that potentially transmit the pathogen from monkey to human in the area. METHODS: Mosquito surveillance was conducted using larval and adult collection, and the collected mosquitoes were identified morphologically and molecularly using the barcoding markers, cytochrome oxidase subunit I (COI), and internal transcribed species 2 (ITS2) genes. Plasmodium sporozoite carriage was conducted on mosquitoes collected through human landing catch (HLC) and human-baited double net trap (HDNT). RESULTS: The results revealed several Anopheles species, such as Anopheles flavirostris (16.6%), Anopheles sulawesi (3.3%), Anopheles maculatus (3.3%), Anopheles koliensis (1.2%), and Anopheles vagus (0.4%). Molecular analysis of the sporozoite carriage using the primate-specific malaria primers identified An. sulawesi, a member of the Leucosphyrus group, carrying Plasmodium inui sporozoite. CONCLUSIONS: This study indicates that the transmission of zoonotic malaria in the area is possible and alerts to the need for mitigation efforts through a locally-tailored vector control intervention and NHPs habitat conservation.

Primate malaria: An emerging challenge of zoonotic malaria in Indonesia.

The emergence of zoonotic malaria in different parts of the world, including Indonesia poses a challenge to the current malaria control and elimination program that target global malaria elimination at 2030. The reported cases in human include Plasmodium knowlesi, P. cynomolgi and P. inui, in South and Southeast Asian region and P. brazilianum and P. simium in Latin America. All are naturally found in the Old and New-world monkeys, macaques spp. This review focuses on the currently available data that may represent primate malaria as an emerging challenge of zoonotic malaria in Indonesia, the distribution of non-human primates and the malaria parasites it carries, changes in land use and deforestation that impact the habitat and intensifies interaction between the non-human primate and the human which facilitate spill-over of the pathogens. Although available data in Indonesia is very limited, a growing body of evidence indicate that the challenge of zoonotic malaria is immense and alerts to the need to conduct mitigation efforts through multidisciplinary approach involving environmental management, non-human primates conservation, disease management and vector control.

Primate malarias as a model for cross-species parasite transmission.

Parasites regularly switch into new host species, representing a disease burden and conservation risk to the hosts. The distribution of these parasites also gives insight into characteristics of ecological networks and genetic mechanisms of host-parasite interactions. Some parasites are shared across many species, whereas others tend to be restricted to hosts from a single species. Understanding the mechanisms producing this distribution of host specificity can enable more effective interventions and potentially identify genetic targets for vaccines or therapies. As ecological connections between human and local animal populations increase, the risk to human and wildlife health from novel parasites also increases. Which of these parasites will fizzle out and which have the potential to become widespread in humans? We consider the case of primate malarias, caused by Plasmodium parasites, to investigate the interacting ecological and evolutionary mechanisms that put human and nonhuman primates at risk for infection. Plasmodium host switching from nonhuman primates to humans led to ancient introductions of the most common malaria-causing agents in humans today, and new parasite switching is a growing threat, especially in Asia and South America. Based on a wild host-Plasmodium occurrence database, we highlight geographic areas of concern and potential areas to target further sampling. We also discuss methodological developments that will facilitate clinical and field-based interventions to improve human and wildlife health based on this eco-evolutionary perspective.

Zoonotic malaria - global overview and research and policy needs.

The four main Plasmodium species that cause human malaria, Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, and Plasmodium ovale, are transmitted between humans by mosquito vectors belonging to the genus Anopheles. It has recently become evident that Plasmodium knowlesi, a parasite that typically infects forest macaque monkeys, can be transmitted by anophelines to cause malaria in humans in Southeast Asia. Plasmodium knowlesi infections are frequently misdiagnosed microscopically as P. malariae. Direct human to human transmission of P. knowlesi by anophelines has not yet been established to occur in nature. Knowlesi malaria must therefore be presently considered a zoonotic disease. Polymerase chain reaction is now the definitive method for differentiating P. knowlesi from P. malariae and other human malaria parasites. The origin of P. falciparum and P. vivax in African apes are examples of ancient zoonoses that may be continuing at the present time with at least P. vivax, and possibly P. malariae and P. ovale. Other non-human primate malaria species, e.g., Plasmodium cynomolgi in Southeast Asia and Plasmodium brasilianum and Plasmodium simium in South America, can be transmitted to humans by mosquito vectors further emphasizing the potential for continuing zoonoses. The potential for zoonosis is influenced by human habitation and behavior as well as the adaptive capabilities of parasites and vectors. There is insufficient knowledge of the bionomics of Anopheles vector populations relevant to the cross-species transfer of malaria parasites and the real extent of malaria zoonoses. Appropriate strategies, based on more research, need to be developed for the prevention, diagnosis, and treatment of zoonotic malaria.