Plasmodium cynomolgi zoonosis

Plasmodium cynomolgi, the most recent NHP parasite infecting humans, was cultivated in vitro in the early 1980s (Nguyen-Dinh et al., Reference Nguyen-Dinh, Gardner, Campbell, Skinner and Collins1981). Plasmodium cynomolgi infections are predominantly found in macaque monkeys like Macaca fascicularis (long-tailed macaque) and Macaca nemestrina (pig-tailed macaque) (Fig. 1) (Chua et al., Reference Chua, Ong, Malleret, Suwanarusk, Kosaisavee, Zeeman, Cooper, Tan, Zhang, Tan, Abas, Yip, Elliot, Joyner, Cho, Breyer, Baran, Lange, Maher, Nosten, Bodenreider, Yeung, Mazier, Galinski, Dereuddre-Bosquet, Le Grand, Kocken, Rénia, Kyle, Diagana, Snounou, Russell and Bifani2019). However, P. cynomolgi infections are also reported in experimental and rare natural zoonotic infections in humans (Eyles et al., Reference Eyles, Coatney and Getz1960; Kuvin et al., Reference Kuvin, Beye, Stohlman, Contacos and Coatney1962; Bennett and Warren, Reference Bennett and Warren1965; Garnham, Reference Garnham1966). The first recorded P. cynomolgi infection was in M. fascicularis in Indonesia in 1907, which was later acquired naturally by humans throughout southeast Asia from various macaque monkeys (Coatney et al., Reference Coatney, Collins, Warren and Contacos1971; Kotepui et al., Reference Kotepui, Masangkay, Kotepui and Milanez2021). In terms of morphological and biological features, P. cynomolgi is nearly identical to its sister taxon P. vivax with its asexual replication, i.e. 48 h, the period between infection and the appearance of parasites in the blood (prepatent period), and the existence of a dormant stage (hypnozoites) (Fig. 1) (Cross et al., Reference Cross, Hsu-Kuo and Lien1973; Most, Reference Most1973; Druilhe et al., Reference Druilhe, Trape, Leroy, Godard and Gentilini1980). Both P. cynomolgi and P. vivax prefer to infect reticulocytes and have Schuffner's dot-modified infected erythrocyte membrane (Bykersma, Reference Bykersma2021). The experimental and accidental infection of humans with P. cynomolgi was shown half a century ago, with the suspicion that this simian parasite might infect humans and that an actual zoonotic outbreak would occur in the future (Cross et al., Reference Cross, Hsu-Kuo and Lien1973; Most, Reference Most1973; Druilhe et al., Reference Druilhe, Trape, Leroy, Godard and Gentilini1980).

The first accidental P. cynomolgi (P. cynomolgi bastianellii) infection in humans was reported in the Laboratory of Parasite Chemotherapy, National Institute of Allergy and Infectious Diseases, while studying the P. cynomolgi subspecies in rhesus monkeys (Macaca mulatta). Four accidental infections by this simian malaria occurred among laboratory workers, proving that one particular ‘B strain’ of P. cynomolgi could produce malaria in humans (Eyles et al., Reference Eyles, Coatney and Getz1960). The first naturally acquired P. cynomolgi human infection was reported in Hulu Terengganu, Peninsular Malaysia, in 2011, near a small forest crowded with macaques (Ta et al., Reference Ta, Hisam, Lanza, Jiram, Ismail and Rubio2014). The infection was initially diagnosed as P. malariae/P. knowlesi and later as P. vivax by microscopy and molecular methods. However, re-examination was performed via nested multiplex-polymerase chain reaction (PCR) followed by a parallel nested PCR for Plasmodium genus amplification, confirming the P. cynomolgi infection with asexual stages (Ta et al., Reference Ta, Hisam, Lanza, Jiram, Ismail and Rubio2014). In this region (Peninsular Malaysia), Anopheles cracens is the predominant mosquito species in Peninsular Malaysia and is hence suspected as a vector for the transmission of P. cynomolgi. A detailed survey conducted between 2011 and 2014 in 7 states of Malaysia identified 9 mono-infections of P. cynomolgi (8.8%) from multiple districts out of the 102 malaria-positive samples (Table 1) (Yap et al., Reference Yap, Hossain, Nada-Raja, Ngui, Muslim, Hoh, Khaw, Kadir, Simon Divis, Vythilingam, Singh and Lim2021). This study also reported the infections of other zoonotic Plasmodium species: P. coatneyi and P. inui, with ~3% prevalence of 102 malaria-positive individuals (Table 1) (Yap et al., Reference Yap, Hossain, Nada-Raja, Ngui, Muslim, Hoh, Khaw, Kadir, Simon Divis, Vythilingam, Singh and Lim2021). A malariometric study conducted in Cambodia between 2013 and 2016 reported that out of 1361 asymptomatic malaria-positive patients, 21 (~1.6%) were asymptomatic carriers of NHP malarial parasites (Imwong et al., Reference Imwong, Madmanee, Suwannasin, Kunasol, Peto, Tripura, von Seidlein, Nguon, Davoeung, Day, Dondorp and White2019). Of these 21 patients, 52.4% of asymptomatic patients had P. cynomolgi mono-infections, while ~9.6% carried mixed-infections of P. cynomolgi and P. vivax (Imwong et al., Reference Imwong, Madmanee, Suwannasin, Kunasol, Peto, Tripura, von Seidlein, Nguon, Davoeung, Day, Dondorp and White2019). From 2013 to 2017, a study of 1047 malaria-positive patients in Kapit, Malaysia, reported mixed-infections of P. cynomolgi and P. knowlesi in 6 clinical cases (~0.6%) in Sarawak, Malaysian Borneo (Raja et al., Reference Raja, Hu, Kadir, Mohamad, Rosli, Wong, Hii, Simon Divis and Singh2020). Another study conducted in 2015 in Sabah, Malaysia, identified 2 asymptomatic P. cynomolgi mono-infections (3.07%) out of 54 malaria-positive cases (Grignard et al., Reference Grignard, Shah, Chua, William, Drakeley and Fornace2019). In Thailand during 2007–2018, out of 1180 symptomatic malaria patients reported via species-specific nested PCR, 9 were P. cynomolgi (0.76% prevalence) co-infections with P. vivax (0.59%), P. falciparum (0.09%) and P. vivax + P. knowlesi (0.09%) (Table 1) (Putaporntip et al., Reference Putaporntip, Kuamsab, Pattanawong, Yanmanee, Seethamchai and Jongwutiwes2021). Most P. cynomolgi cases were reported in areas where macaques were in close proximity to humans (wild or domesticated). The study could not determine if P. cynomolgi caused symptomatic infections or coexisted asymptomatically with other human malarial parasites (Putaporntip et al., Reference Putaporntip, Kuamsab, Pattanawong, Yanmanee, Seethamchai and Jongwutiwes2021).

Owing to the high prevalence of nocturnal mosquitoes and macaques, Thailand and similar regions may be a potential infection source for P. cynomolgi transmission to humans. In 2018, a traveller with a P. cynomolgi symptomatic infection was reported to have visited Thailand and Peninsular Malaysia (Hartmeyer et al., Reference Hartmeyer, Stensvold, Fabricius, Marmolin, Hoegh, Nielsen, Kemp and Vestergaard2019). Another study conducted in Thailand in 2021 to probe simian Plasmodium species in blood samples of malaria patients reported 21 mono-infections with P. cynomolgi (Putaporntip et al., Reference Putaporntip, Kuamsab, Seethamchai, Pattanawong, Rojrung, Yanmanee, Weng Cheng and Jongwutiwes2022). These 2 reports from Thailand highlight the occurrence of P. cynomolgi in diverse malaria-endemic areas of Thailand (Hartmeyer et al., Reference Hartmeyer, Stensvold, Fabricius, Marmolin, Hoegh, Nielsen, Kemp and Vestergaard2019; Putaporntip et al., Reference Putaporntip, Kuamsab, Seethamchai, Pattanawong, Rojrung, Yanmanee, Weng Cheng and Jongwutiwes2022). Further, Yala province in Thailand reported the highest number of mixed-infections (n = 17) of P. cynomolgi with other Plasmodium species (Fig. 3A) (Putaporntip et al., Reference Putaporntip, Kuamsab, Pattanawong, Yanmanee, Seethamchai and Jongwutiwes2021, Reference Putaporntip, Kuamsab, Seethamchai, Pattanawong, Rojrung, Yanmanee, Weng Cheng and Jongwutiwes2022). A recent systematic survey between 1946 and 2020 in southeast Asian countries compared the prevalence of P. cynomolgi infections in humans, mosquitoes and macaques in natural settings (Kotepui et al., Reference Kotepui, Masangkay, Kotepui and Milanez2021). The study demonstrated that the pooled proportion of naturally acquired P. cynomolgi was highest in macaques (47%), followed by mosquitoes (18%) and humans (1%) (Kotepui et al., Reference Kotepui, Masangkay, Kotepui and Milanez2021). Given this, P. cynomolgi transmission from mosquitoes to humans is likely constrained by the presence of macaque and Anopheles bite rates with their susceptibility (Kotepui et al., Reference Kotepui, Masangkay, Kotepui and Milanez2021).

Plasmodium inui zoonosis

Plasmodium inui, a quartan-type parasite, infects Old World monkeys with a typical 72 h quartan periodicity. Plasmodium inui natural hosts are macaques (Macaca nigra, Macaca cyclopis, M. fascicularis, M. mulatta, M. nemestrina, and Macaca radiate), and the primate infections are reported throughout Asia, including southern India, southeast Asia and Taiwan (Fig. 1; Table 2) (Eyles, Reference Eyles1963; Coatney et al., Reference Coatney, Collins, Warren and Contacos1971). One vector responsible for P. inui transmission – Anopheles leucosphyrus (a vector of human malaria in Sarawak, Borneo) was identified in 1962, which was caught while biting a man, showing the possibility of transmission of a monkey infection to humans in nature (Coatney et al., Reference Coatney, Collins, Warren and Contacos1971). Following this, 2 volunteers established the experimental natural transmission of P. inui to man via bites of infected mosquitoes (Anopheles stephensi/Anopheles maculatus) (Coatney et al., Reference Coatney, Chin, Contacos and King1966). In 2020, an epidemiologic and entomological study from Pahang, Malaysia, revealed 2 natural, asymptomatic mono-infections of P. inui by nested PCR (Liew et al., Reference Liew, Bukhari, Jeyaprakasam, Phang, Vythilingam and Lau2021). All the tested individuals were participants who underwent forest training in 2020. The primers aimed at asexual and sexual 18S rRNA genes confirmed infection with P. inui (Liew et al., Reference Liew, Bukhari, Jeyaprakasam, Phang, Vythilingam and Lau2021). Anopheles cracens and An. leucosphyrus were shown to be the possible vector of monkey infection and transmission to humans in the wild. Both cases experienced minimal symptoms, and the parasitaemia was undetectable for short periods. Hence, the quartan P. inui parasite could be self-limiting in humans since it was not detected approximately 8 months after a patient's exposure to an infectious mosquito bite (Liew et al., Reference Liew, Bukhari, Jeyaprakasam, Phang, Vythilingam and Lau2021). According to a surveillance study, there was a 66.7% predominance of P. inui in all macaques tested in Pahang (26/39 macaques sampled), suggesting that humans may get infected with P. inui via vector-borne transmission from infected macaques to humans (Amir et al., Reference Amir, Shahari, Liew, de Silva, Khan, Lai, Snounou, Abdullah, Gani, Rovie-Ryan and Lau2020; Liew et al., Reference Liew, Bukhari, Jeyaprakasam, Phang, Vythilingam and Lau2021). In 2021, blood samples from malaria patients in 5 malaria-endemic regions of Thailand confirmed the natural transmission of P. inui in 19 patients out of all reported human and other infections (Putaporntip et al., Reference Putaporntip, Kuamsab, Seethamchai, Pattanawong, Rojrung, Yanmanee, Weng Cheng and Jongwutiwes2022). Most patients infected with P. inui had concurrent infections with other Plasmodium species (Fig. 3B) (Putaporntip et al., Reference Putaporntip, Kuamsab, Seethamchai, Pattanawong, Rojrung, Yanmanee, Weng Cheng and Jongwutiwes2022). Further, in 2011 and 2014, the blood samples from 14 villages in 7 states in Malaysia of indigenous populations of various sub-tribes recorded 3 P. inui infections while searching for P. cynomolgi cases (Table 2) (Yap et al., Reference Yap, Hossain, Nada-Raja, Ngui, Muslim, Hoh, Khaw, Kadir, Simon Divis, Vythilingam, Singh and Lim2021). However, another study conducted from 2014 to 2015 from communities in Sarawak, Malaysian Borneo regions did not detect any P. inui and P. cynomolgi infections in humans (Siner et al., Reference Siner, Liew, Kadir, Mohamad, Thomas, Zulkarnaen and Singh2017). The locations of reported mono- and mixed-infections of P. inui in humans are shown in Fig. 3B.

Plasmodium simium zoonosis

Plasmodium simium was first identified in 1951 in the blood smear of Alouatta clamitans (brown howler monkeys) collected in the Atlantic Forest in Brazil (Fonseca, Reference Fonseca1951; Deane et al., Reference Deane, Deane and Ferreira Neto1966). Plasmodium simium is found in south Brazil, where it is found among woolly spider monkeys (Brachyteles arachnoids), capuchin monkeys (Cebus and Sapajus sp.), arboreal howler monkeys (Alouatta sp.) and black-fronted titi monkeys (Callicebus nigrifrons) (Fig. 1) (Coatney et al., Reference Coatney, Collins, Warren and Contacos1971). The first suspected natural infection of a human by P. simium was from Brazil (Deane et al., Reference Deane, Deane and Ferreira Neto1966). The infection was suspected on the basis that it had occurred in a forest reserve outside São Paulo where P. simium was known to be transmitted along with the morphological characteristics of the parasite (Deane et al., Reference Deane, Deane and Ferreira Neto1966). After half a decade, in 2015–2016, an epidemiological investigation of malaria patients in Rio de Janeiro, Brazil, reported a total of 28 mono-infections of P. simium out of 49 autochthonous malaria cases indicative of P. simium zoonosis in Brazil, although initially misdiagnosed as P. vivax (Fig. 3C; Table 2) (Brasil et al., Reference Brasil, Zalis, De Pina-Costa, Siqueira, Júnior, Silva, Areas, Pelajo-Machado, De Alvarenga, Da Silva Santelli, Albuquerque, Cravo, Santos De Abreu, Peterka, Zanini, Suárez Mutis, Pissinatti, Lourenço-de-Oliveira, De Brito, De Fátima Ferreira-da-Cruz, Culleton and Daniel-Ribeiro2017). The mitochondrial genome of these cases indicated that P. simium was most closely related to the South American P. vivax parasite (Brasil et al., Reference Brasil, Zalis, De Pina-Costa, Siqueira, Júnior, Silva, Areas, Pelajo-Machado, De Alvarenga, Da Silva Santelli, Albuquerque, Cravo, Santos De Abreu, Peterka, Zanini, Suárez Mutis, Pissinatti, Lourenço-de-Oliveira, De Brito, De Fátima Ferreira-da-Cruz, Culleton and Daniel-Ribeiro2017). The P. simium sequence revealed that it is similar to P. vivax, corroborating earlier claims that it originated from a host switch from humans to monkeys. Further, a study identified 7 distinct haplotypes from 22 human blood isolates (infected with P. vivax identified by microscopy) from Atlantic Forest inhabitants in Espírito Santo, Brazil (Fig. 3C). Of these 7 isolates, 2 isolates when shared with samples obtained from simians had an identical sequence to P. simium (Table 2) (Buery et al., Reference Buery, Rodrigues, Natal, Salla, Loss, Vicente, Rezende, Duarte, Fux, Malafronte, Falqueto and Cerutti2017). This suggests that P. simium has been endemic in the Atlantic region but may have been incorrectly diagnosed as P. vivax due to the lack of any reliable diagnostic molecular techniques (Brasil et al., Reference Brasil, Zalis, De Pina-Costa, Siqueira, Júnior, Silva, Areas, Pelajo-Machado, De Alvarenga, Da Silva Santelli, Albuquerque, Cravo, Santos De Abreu, Peterka, Zanini, Suárez Mutis, Pissinatti, Lourenço-de-Oliveira, De Brito, De Fátima Ferreira-da-Cruz, Culleton and Daniel-Ribeiro2017; Buery et al., Reference Buery, Rodrigues, Natal, Salla, Loss, Vicente, Rezende, Duarte, Fux, Malafronte, Falqueto and Cerutti2017). Plasmodium simium then adapted to the monkeys, and now occasionally infects humans in the region due to opportunistic infections (de Oliveira et al., Reference de Oliveira, Rodrigues, Early, Duarte, Buery, Bueno, Catão-Dias, Cerutti, Rona, Neafsey and Ferreira2021; Mourier et al., Reference Mourier, de Alvarenga, Kaushik, de Pina-Costa, Douvropoulou, Guan, Guzmán-Vega, Forrester, de Abreu, Júnior, de Souza Junior, Moreira, Hirano, Pissinatti, Ferreira-da-Cruz, de Oliveira, Arold, Jeffares, Brasil, de Brito, Culleton, Daniel-Ribeiro and Pain2021). The primary vector in this area is suspected to be the Anopheles (kerteszia) cruzi which is found almost exclusively in the Atlantic region and can feed on both monkeys in the canopy and humans at the ground level (Deane et al., Reference Deane, Deane and Ferreira Neto1966, 196; Brasil et al., Reference Brasil, Zalis, De Pina-Costa, Siqueira, Júnior, Silva, Areas, Pelajo-Machado, De Alvarenga, Da Silva Santelli, Albuquerque, Cravo, Santos De Abreu, Peterka, Zanini, Suárez Mutis, Pissinatti, Lourenço-de-Oliveira, De Brito, De Fátima Ferreira-da-Cruz, Culleton and Daniel-Ribeiro2017). The isolates of P. simium from the New World monkeys and humans have a close genome-wide association with P. vivax from the New World. The genome-wide divergence between P. simium and New World P. vivax is negligible compared to intraspecific polymorphism in P. vivax populations of South America (de Oliveira et al., Reference de Oliveira, Rodrigues, Early, Duarte, Buery, Bueno, Catão-Dias, Cerutti, Rona, Neafsey and Ferreira2021). The differences between P. vivax and P. simium are focused on large deletions in the P. simium Duffy-binding protein 1 and reticulocyte-binding protein 2a genes which are usually present in all human-derived isolates (Mourier et al., Reference Mourier, de Alvarenga, Kaushik, de Pina-Costa, Douvropoulou, Guan, Guzmán-Vega, Forrester, de Abreu, Júnior, de Souza Junior, Moreira, Hirano, Pissinatti, Ferreira-da-Cruz, de Oliveira, Arold, Jeffares, Brasil, de Brito, Culleton, Daniel-Ribeiro and Pain2021). There are only 2 unique single-nucleotide polymorphisms (SNPs) in the P. simium mitochondrial genome, differentiating it from P. vivax (Brasil et al., Reference Brasil, Zalis, De Pina-Costa, Siqueira, Júnior, Silva, Areas, Pelajo-Machado, De Alvarenga, Da Silva Santelli, Albuquerque, Cravo, Santos De Abreu, Peterka, Zanini, Suárez Mutis, Pissinatti, Lourenço-de-Oliveira, De Brito, De Fátima Ferreira-da-Cruz, Culleton and Daniel-Ribeiro2017; Rodrigues et al., Reference Rodrigues, Valdivia, De Oliveira, Alves, Duarte, Cerutti-Junior, Buery, Brito, De Souza, Hirano, Malafronte, Ladeia-Andrade, Mita, Santamaria, Calzada, Kawamoto, Raijmakers, Mueller, Pacheco, Escalante, Felger and Ferreira2018). Further, a recent study also identified 8 P. simium-specific SNPs out of 9 infected humans using an inexpensive tool specific to diagnose P. simium infections (De Alvarenga et al., Reference De Alvarenga, Culleton, De Pina-Costa, Rodrigues, Bianco, Silva, Nunes, De Souza, Hirano, Moreira, Pissinatti, De Abreu, Lisboa Areas, Lourenço-de-Oliveira, Zalis, Ferreira-da-Cruz, Brasil, Daniel-Ribeiro and De Brito2018). Hence, it can be speculated that gene deletions in human-derived isolates and other genetic changes in the P. simium genome may have helped to invade human red blood cells (RBCs), thus explaining the basis of recent zoonotic infections (de Oliveira et al., Reference de Oliveira, Rodrigues, Early, Duarte, Buery, Bueno, Catão-Dias, Cerutti, Rona, Neafsey and Ferreira2021; Mourier et al., Reference Mourier, de Alvarenga, Kaushik, de Pina-Costa, Douvropoulou, Guan, Guzmán-Vega, Forrester, de Abreu, Júnior, de Souza Junior, Moreira, Hirano, Pissinatti, Ferreira-da-Cruz, de Oliveira, Arold, Jeffares, Brasil, de Brito, Culleton, Daniel-Ribeiro and Pain2021).

Plasmodium brasilianum zoonosis

In New World monkeys, P. brasilianum is a simian parasite that causes quartan fever (Fig. 1) (Contacos et al., Reference Contacos, Lunn, Coatney, Kilpatrick and Jones1963). Plasmodium brasilianum was identified in at least 35 species of New World primates in Central and South America (Chaves et al., Reference Chaves, Dolz, Ibarra-Cerdeña, Núñez, Ortiz-Malavasi, Bernal-Valle and Gutiérrez-Espeleta2022). The genetic and morphological characteristics of P. brasilianum are indistinguishable from those of P. malariae (Contacos et al., Reference Contacos, Lunn, Coatney, Kilpatrick and Jones1963; Fandeur et al., Reference Fandeur, Volney, Peneau and De Thoisy2000). Thus, P. brasilianum and P. malariae may specialize in different hosts but remain members of the same quartan malarial species. This anthropozoonotic parasite can easily circulate between humans or NHPs (Contacos et al., Reference Contacos, Lunn, Coatney, Kilpatrick and Jones1963). Investigations in the 1960s supported the theory that P. brasilianum could experimentally infect humans from monkeys and vice versa (Coatney et al., Reference Coatney, Collins, Warren and Contacos1971). A comparison of the circumsporozoite protein and ribosomal small subunit (18S) in parasites of 75 P. malariae-positive patients revealed 16% with parasites that were nearly identical to the strain of P. brasilianum of infected monkeys from French Guiana (Fandeur et al., Reference Fandeur, Volney, Peneau and De Thoisy2000; Lalremruata et al., Reference Lalremruata, Magris, Vivas-Martínez, Koehler, Esen, Kempaiah, Jeyaraj, Perkins, Mordmüller and Metzger2015). These studies indicate that P. brasilianum is endemic to Latin America and that P. brasilianum and P. malariae parasites can spread quickly between humans and monkeys, serving as a natural reservoir for malaria (Lalremruata et al., Reference Lalremruata, Magris, Vivas-Martínez, Koehler, Esen, Kempaiah, Jeyaraj, Perkins, Mordmüller and Metzger2015). The presence of P. brasilianum has already been established in howler monkeys in Central America (Costa Rica) (Chinchilla et al., Reference Chinchilla, Guerrero, Gutiérrez and Sánchez2006). Interestingly, a group identified 3 samples with 99% identity with P. malariae/P. brasilianum from human clinical samples in Costa Rica (Fig. 3C; Table 2) (Calvo et al., Reference Calvo, Morera, Dolz, Solorzano-Morales and Herrero2015). The analysis revealed a 99% identity with P. malariae isolated from atypical human cases in Asia, and a 99% identity with a sequence of P. brasilianum isolated from a non-human monkey of Guiana (Calvo et al., Reference Calvo, Morera, Dolz, Solorzano-Morales and Herrero2015). Similarly, another study demonstrated the genomic sequence identity of 99.70% in mitochondrial and apicoplast genomes of P. brasilianum with P. malariae (Talundzic et al., Reference Talundzic, Ravishankar, Nayak, Patel, Olsen, Sheth, Batra, Loparev, Vannberg, Udhayakumar and Barnwell2017). Additionally, it is established that while belonging to the radiation of human P. malariae strains, P. brasilianum does not represent a separate lineage and that P. brasilianum likely emerged after the human infection was transmitted to New World monkeys (Plenderleith et al., Reference Plenderleith, Liu, Li, Loy, Mollison, Connell, Ayouba, Esteban, Peeters, Sanz, Morgan, Wolfe, Ulrich, Sachse, Calvignac-Spencer, Leendertz, Shaw, Hahn and Sharp2022).

Plasmodium fieldi zoonosis

Plasmodium fieldi asexual cycle is 48 h (Fig. 1). Bonnet macaques (Macaca radiata), long-tailed macaques (M. fascicularis), baboons (Papio doguera), rhesus macaques (M. mulatta) and pig-tailed macaques (M. nemestrina) are noted as natural hosts and reservoirs of P. fieldi (Eyles, Reference Eyles1963). In 2021, P. fieldi was reported to be capable of cross-transmission between macaques and humans under natural conditions (Putaporntip et al., Reference Putaporntip, Kuamsab, Seethamchai, Pattanawong, Rojrung, Yanmanee, Weng Cheng and Jongwutiwes2022). While examining the symptomatic malaria patients in Thailand, a P. fieldi infection was diagnosed in 3 out of 5271 tested patients (Putaporntip et al., Reference Putaporntip, Kuamsab, Seethamchai, Pattanawong, Rojrung, Yanmanee, Weng Cheng and Jongwutiwes2022). All P. fieldi-infected patients had concurrent infections with other Plasmodium species and responded well to chloroquine or artemisinin–mefloquine combination therapy (Table 2) (Putaporntip et al., Reference Putaporntip, Kuamsab, Seethamchai, Pattanawong, Rojrung, Yanmanee, Weng Cheng and Jongwutiwes2022). A study conducted in Thailand determining the prevalence of different Plasmodium species in NHPs reported that of 93 macaque blood samples examined, P. inui (35%) and P. fieldi (30%) were the most prevalent species in malaria-positive macaques, presenting them as the natural reservoir and a potential public health concern to the local population (Fungfuang et al., Reference Fungfuang, Udom, Tongthainan, Kadir and Singh2020). The geographical distribution of reported P. fieldi infections in humans is depicted in Fig. 3B.

Plasmodium coatneyi zoonosis

Plasmodium coatneyi is commonly found in long-tailed macaques (M. fascicularis), and unlike other simian parasites, P. coatneyi shares morphological features to P. falciparum (Fig. 1) (Eyles, Reference Eyles1963; Fungfuang et al., Reference Fungfuang, Udom, Tongthainan, Kadir and Singh2020). A detailed study conducted between 2011 and 2014 in 7 states of Malaysia showed 3 mono-infections (2.17%) of P. coatneyi among 645 samples that tested positive for malaria (Table 2) (Yap et al., Reference Yap, Hossain, Nada-Raja, Ngui, Muslim, Hoh, Khaw, Kadir, Simon Divis, Vythilingam, Singh and Lim2021). This study highlighted the existence of naturally acquired human infection with P. coatneyi, a species earlier believed to be incapable of infecting humans through infected monkey blood or mosquito bites (Yap et al., Reference Yap, Hossain, Nada-Raja, Ngui, Muslim, Hoh, Khaw, Kadir, Simon Divis, Vythilingam, Singh and Lim2021). The geographical spread of P. coatneyi in humans is shown in Fig. 3B.