UNIVERSA MEDICINA pISSN: 1907-3062 / eISSN: 2407-2230 Univ Med 2025. 44:208-218 DOI: https://doi. org/10. 18051/UnivMed. REVIEW ARTICLE Threat of zoonotic malaria and strategy to overcome in Kalimantan (Indonesian Borne. bordering Malaysian Borneo Diana Natalia1,2* . Willy Handoko2 . Sari Rahmayanti2 . Tri Wahyudi2. Ayu Akida Abdul Rashid1 , and Paul Cliff Simon Divis1 Malaria Research Centre. Faculty of Medicine and Health Sciences. Universiti Malaysia Sarawak. Kota Samarahan. Sarawak. Malaysia Faculty of Medicine. Universitas Tanjungpura. Pontianak. West Kalimantan. Indonesia * Correspondence Author: diananatalia@medical. Cite this article as: Natalia D. Handoko W. Rahmayanti S. Wahyudi T. Rashid a. Divis PCS Threat of zoonotic malaria and strategy to overcome in Kalimantan (Indonesian Borne. bordering Malaysian Borneo. Univ Med 2025. 44:208-218 Date of first submission. November 20, 2024 Date of acceptance. June 10, 2025 Date of publised. June 17, 2025 ABSTRACT Indonesia aims to eradicate malaria by 2030. Indonesia has the second highest disease burden in the WHO South-East Asia region, after India, accounting for 9% of all malaria cases in 2024. Malaria cases have dropped dramatically due to national strategic plans and programs, and the Indonesian Ministry of Health has certified several districts as malaria-free zones. Malaria cases in Kalimantan (Indonesian Borne. , have declined during the last two decades. Nearly all regencies within these provinces have been declared as having low malaria endemic status (API<1 per 1000 peopl. , except for one regency in East Kalimantan Province, which showed a high endemicity level (API>5 per 1000 peopl. This reduced incidence, however, contrasts sharply with the zoonotic infection caused by the simian parasite Plasmodium knowlesi, which is prevalent in Malaysian Borneo. Only a few cases of P. knowlesi infection have been reported in South and Central Kalimantan Province since This difference between Kalimantan. Indonesia and Borneo. Malaysia appears contradictory given that both regions have a similar epidemiological risk of zoonotic malaria infection and share the same natural habitat. The references were tracked using various databases, such as Google Scholar. PubMed (MEDLINE) and other sources (Google engine and manual searching using a reference lis. This reviewAos objective was to describe current malaria and zoonotic malaria, mosquito vector prevalence, and the available data from case reports along the Kalimantan border in Indonesia during the malaria elimination phase, compared with malaria distribution in the neighbouring country. Malaysian Borneo. Keywords: Malaria, simian. Plasmodium. Kalimantan border, strategy, threat INTRODUCTION Malaria is a mosquito-borne disease caused by Plasmodium parasites. There are hundreds of Plasmodium species that have been described to infect a wide range of vertebrates, such as primates, rodents, reptiles, and birds. Five Plasmodium species, namely Plasmodium falciparum. ovale, and P. knowlesi, are known to infect humans and cause . While P. vivax is the most widely distributed species of human malaria. falciparum is known as the deadliest species. These Plasmodium species are transmitted by infected female Anopheles mosquitoes that bite humans and infect their red blood cells. Copyright@Author. - https://univmed. org/ejurnal/index. php/medicina/article/view/1672 Zoonotic malaria and strategy Malaria has been reported to be prevalent in more than 85 endemic countries, with an increase of 5 million cases in 2022 compared with 2021, resulting in 249 million malaria cases. Despite 9% decline in malaria cases between 2021 and 2022 in the WHO South-East Asia region, the disease still accounted for 2% of malaria cases Malaria cases and incidence have surged in Bangladesh. Myanmar, and Thailand, with India and Indonesia accounting for 94% of all malaria deaths. The Maldives and Sri Lanka received malaria-free status in 2016 and have maintained that status. Malaysia reported no indigenous infections for the fifth year consecutively and aimed for elimination, despite 2,500 P. knowlesi malaria cases being reported in . , . Every year, approximately two million cases of malaria are reported in Indonesia. , . In 2021 throughout the COVID-19 pandemic, a total of 811,636 new malaria cases with 1,412 deaths were . The post COVID-19 pandemic situation showed increased malaria cases in 2022 and 2023 (Figure . , where 98. 9% were confirmed by laboratory tests. Of these, 52% of cases were confirmed by standard microscopy and 48% by rapid diagnostic test (RDT). Most malaria cases occur in the eastern part of Indonesia (Papua. East Nusa Tenggara. West Nusa Tenggara. Maluku, part of Sulawes. accounting for more than 87% of 35 million national cases. In 2021 there were 3 Indonesian provinces with regencies of high endemicity . nnual parasite incidence (API) >5 per 1000 peopl. , namely East Nusa Tenggara . East Kalimantan . , and Papua . Recently, 33 provinces were declared to have malaria elimination status with decreased numbers of malaria cases over the . Overall. falciparum infections accounted for half of the total malaria cases in 2022, followed by P. 4%), mixed P. falciparum and P. 2%) and infections by other Plasmodium species . 2%). Infections caused by P. falciparum and P. vivax were common in Eastern Indonesia . %), while zoonotic malaria caused by P. knowlesi was also found in some regions of Sumatra and Kalimantan, but at low frequency. In Southeast Asia and South America, while some countries reported zero indigenous malaria cases by human Plasmodium species, there has been a challenge by the rise of zoonotic malaria Malaysia aimed for malaria elimination with no indigenous cases caused by human Plasmodium species since 2018, yet more than 17,000 cases of P. knowlesi infection and 48 deaths have been reported since 2017 and also contributing to 90. 5% of P. knowlesi cases worldwide in 2022. - . Besides P. knowlesi, other zoonotic malaria by non-human primate Plasmodium species have been progressively For example. cynomolgi and P. infections in Malaysia and Thailand . and infections with the New World monkey parasites brasilianum and P. simium in Brazil. Borneo, a hotspot of biodiversity, has already suffered huge deforestation that has endangered many species. Further decreasing biodiversity and bringing more people in closer contact with macaques and mosquitoes may dramatically increase the risk of emerging zoonotic infections, including P. knowlesi malaria. Indeed. Malaysian Sabah and Sarawak states, at the northern border of Indonesian Borneo, are among the main areas of P. knowlesi transmission to humans, representing more than 9000 cases reported between 2017 and 2019. In 2021, the World Health Organization (WHO) reported 3651 cases globally and 13 deaths from P. knowlesi malaria in Malaysia. Meanwhile, the global incidence of knowlesi has been reported to decrease by 24% . Given this background, this review aimed to describe the current epidemiology of malaria and zoonotic malaria, mosquito vector prevalence, and the available data from case reports along the Kalimantan border in Indonesia during the malaria elimination phase compared with malaria distribution in the neighbouring country. Malaysian Borneo. Geographical situation and population Borneo is the world's third biggest island, covering approximately 287,000 square miles, being located southeast of the Malay Peninsula and southwest of the Philippines. It is divided into four political regions, as shown in Figure 2. Kalimantan is in Indonesia. Sabah and Sarawak are in Malaysia, and the Sultanate of Brunei is situated north of Sabah. Indonesia is the major political component of the island. Borneo island has a tropical climate, often with high temperatures and high humidity. The island is located at the equator and has relatively constant temperatures throughout the year, between 2535oC. The island is known for its dense rainforests and diverse wildlife. Natalia D. Handoko W. Rahmayanti S, et al Figure 1. Malaria cases in Indonesia . Figure 2. Map of Borneo Island The map shows three bordering countries: Brunei. Malaysia (Sarawak and Sabah state. and Indonesia . ive Kalimantan province. Zoonotic malaria and strategy METHODS The present review on malaria and zoonotic malaria involved an extensive literature search that was performed in PubMed (MEDLINE) and Google Scholar using the keywords Aumalaria Kalimantan IndonesiaAy and Auplasmodium KalimantanAy. Data on malaria were obtained from the provincial Health Department and personal communication with malaria officers in both Indonesia and Malaysia. Publications older than ten years were excluded, as were those published in languages other than English, unless they were the primary source of literature and rare in Zoonotic malaria The natural zoonotic malaria infections were initially reported as early as the 1960s and 1970s in Peninsular Malaysia, and were extremely rare until a large focus of P. knowlesi infections was reported in Kapit Division in Sarawak. Malaysian Borneo, in 2004. Due to this, the causative organism has been recognized as the fifth Plasmodium species to affect humans. Since then, similar cases have been documented in all Southeast Asian countries except Timor Leste, as molecular diagnosis has advanced. , . Zoonotic infection caused by P. constitutes the predominant type of malaria in Malaysia, despite the absence of indigenous cases of human Plasmodium species infection since A study conducted in Kapit Division. Sarawak, involving 152 hospitalised patients revealed a 1. 8% case fatality rate for knowlesi malaria and 6. 5% for severe disease. From 2017 onwards. Malaysia has reported a total of 17,125 cases with 48 deaths attributed to P. In 2021 alone, 3,575 P. knowlesi cases and 13 deaths have been recorded. In comparison. Indonesia, the Philippines, and Thailand collectively reported 435 P. More recently human natural infections with P. and P. simiovale were reported among indigenous communities living near the forest fringe in various locations in Malaysia. Commonly employed molecular techniques have accurately identified Plasmodium species in malaria patients for effective drug therapy. This suggests that simian Plasmodium species might regularly infect humans, posing a risk of misdiagnosis as human Plasmodium infection when using standard microscopy methods. knowlesi isolated from humans can be easily misdiagnosed as P. falciparum or P. malariae due to the morphological similarities with these latter . Similarly, the asexual stage feature of cynomolgi is indistinguishable from P. vivax by microscopy identification. malariae also has . The microscopy method is costeffective and affordable, but its sensitivity is doubtful low parasitemia and a shortage of experienced microscopists. The natural hosts of simian Plasmodium species are very diverse, which include Old World and New World primates as presented in Table 1. , . The most considered types of simian malaria caused by P. and P. inui were originally harboured by longtailed macaques (Macaca fasciculari. , pig-tailed macaques (Macaca nemestrin. and banded leaf monkeys (Presbytis melolophu. A study in India reported the presence of P. and P. cynomolgi in Macaca radiata, as well as the occurrence of P. falciparum in M. mulatta and . A molecular analysis of malaria parasites in Malaysian Borneo led to the unexpected discovery of P. simiovale in wild . Previously. simiovale was thought to be restricted to Macaca sinica in Sri Lanka. Recent findings revealed its zoonotic potential, with P. simiovale infecting humans among indigenous communities living near forest fringes,. highlighting the need for enhanced surveillance and understanding of zoonotic malaria dynamics. Entomological surveillance identified most anopheline mosquitoes that transmit simian Plasmodium species to humans as belonging to the Leucosphyrus group. These include An. latens that has been incriminated as the vector of P. knowlesi in Sarawak. Malaysia. An. cracens in Peninsular Malaysia, and An. in Vietnam. An. cracens and An. have been suspected as vectors of P. and P. An. An. An. An. introlatus, and An. cracens are the known P. knowlesi vectors in Indonesia, while Kalimantan. An. An. leucosphyrus, and An. latens are reported as P. Recent entomological surveys in Sarawak revealed that more Anopheles species are being identified as vectors in areas with low frequencies of zoonotic malaria such as An. balabacensis and An. in Lawas district. and An. An. An. roperi and An. collessi in Betong district. Natalia D. Handoko W. Rahmayanti S, et al The Leucosphyrus group of Anopheles mosquitoes was previously exclusively known to be found in deep forests in Southeast Asia. The mosquito bites at dusk, when most people return home from the forest or plantations. A recent geospatial analysis revealed that it has followed simian hosts to the edge of forests, farms, and semi-urban regions as a result of deforestation. For example. An. balabacensis in Sabah. Malaysia, shifted its habitat from deep forest to fields, naturally shifting its breeding sites and raising its biting rates on humans. Alteration in vector habitats and their behaviour, along with increased proximity to macaques, make humans susceptible to zoonotic malaria infections, particularly forest-dwelling individuals. Prevalence of malaria in Kalimantan bordering Malaysia Malaria morbidity and fatality data in the Kalimantan border region have been frequently Zoonotic infections caused by P. knowlesi have been reported in certain regions of Kalimantan, though at very low frequencies. The first documented case involved an Australian traveller returning from South Kalimantan,. followed by four additional cases among gold miners in the same region. In 2016, another P. knowlesi infection was identified in a traditional gold miner in Central Kalimantan. Despite advancements in diagnostic testing and reporting procedures, accurately determining the burden of zoonosis malaria in Indonesia, particularly P. knowlesi infections, remains knowlesi is primarily a zoonosis, with human infections occurring among individuals who frequently farm or engage in forested areas near macaque Reported cases of P. infections in Indonesia are rare, with most detected through PCR in North Sumatra . 8%) and Aceh Besar . 27%). limited number of cases have also been reported in Central and South Kalimantan. There have been no reports of zoonotic malaria in West Kalimantan, despite its proximity to Malaysian Borneo, a region with a high prevalence of P. knowlesi infections. However, a study conducted in Kapuas Hulu Regency identified 16 Plasmodium-positive individuals using PCR assay targeting the 18S rRNA gene. Among these, five were confirmed as human Plasmodium species infections . vivax, 2 P. ovale, and 1 P. , while 11 infections could not be conclusively identified despite being positive for Plasmodium DNA. A BLAST search analysis of short 18S rRNA . -248 b. from these samples revealed seven simian Plasmodium species including P. inui, and P. This finding highlights the potential for simian Plasmodium infections in West Kalimantan, particularly near the border with Malaysian Borneo. Table 1. Simian Plasmodium species in Southeast Asia . Plasmodium species Natural host Macaques (M. Leaf monkeys (Presbytis melalopho. Macaques (M. Langur (Presbytis cristatus. Semnopithecus entellu. Macaques (M. Langur (Presbytis cristatus. Macaques (M. Macaques (M. Macaques (M. Macaques (M. Gibbon (Hylobates moloc. Gibbon (Hylobates la. Gibbon (Hylobates la. Gibbon (Hylobates la. Orangutan (Pongo pygmaeu. Orangutan (Pongo pygmaeu. Geographical distribution Malaysia. Indonesia. Philippines. Vietnam Malaysia. Indonesia. Taiwan. Cambodia. Sri Lanka Malaysia. Indonesia. Taiwan Malaysia. Philippines India. Sri Lanka Malaysia Sri Lanka Indonesia Malaysia Malaysia Malaysia Malaysia. Indonesia Malaysia. Indonesia Zoonotic malaria and strategy Entomological surveys across various regions in Kalimantan have identified various Anopheles mosquito species as malaria vectors. South Kalimantan. An. An. An. leucosphyrus, and An. balabacensis were incriminated as malaria vectors,. while An. An. peditaeniatus and An. tessellatus were . In Sebatik Island of North Kalimantan bordering the Sabah state of Malaysian Borneo. An. An. An. maculatus and An. were identified as vectors. Central Kalimantan was reported to exhibit diverse Anopheles species as malaria vectors, including An. An. An. An. An. An. An. umbrosus and An. Vagus. Prevalence of malaria in Malaysian Borneo Malaysia has made significant progress in malaria control, achieving zero indigenous cases caused by human Plasmodium species since 2018 as shown in Figure 3. However. cases have steadily increased, particularly in Sarawak and Sabah in Malaysian Borneo . , 42, 52-. and some regions of Peninsular Malaysia. In Sarawak, knowlesi malaria accounts for more than half of malaria admissions in certain hospitals,. while cases in Sabah have risen more than ten-fold. Since the first large focus of knowlesi infections in Sarawak in 2004 . , the importance of diagnosing zoonotic malaria has been widely recognized by clinicians and laboratory microscopists in high-risk areas. This has led to an increase in reported cases of P. knowlesi malaria across Malaysia (Figure . ,56, Due to the attempts at malaria elimination, molecular testing is increasingly used in surveillance studies to detect low-level illnesses. The effort by the Malaysian Ministry of Health to eliminate malaria has yielded significant success, with a marked reduction in P. falciparum and P. vivax cases. The use of molecular methods, such as nested PCR assay, revealed P. infections in humans previously misdiagnosed as AoP. malariaeAo in 2001-2006 in Sarawak, indicating that human P. knowlesi infections in human are not a "new" emerging disease. A spatiotemporal study in Kapit Division. Sarawak identified two P. knowlesi subpopulations associated with longtailed and pig-tailed macaque hosts (Cluster 1 and Cluster 2, respectivel. and linked to human activities and environmental changes. Cluster 1 knowlesi infections are linked to long-tailed macaques, which live near humans due to food availability and deforestation, whereas Cluster 2 infections are typically associated with activities in deep forest environments. Besides P. knowlesi, other simian Plasmodium species, including P. cynomolgi, and simiovale have been reported to infect humans in both Sabah and Sarawak,. in which both macaque species serve as the primary reservoir host for these parasites. Figure 3. Malaria cases in Malaysia from 2000 to 2021 . Natalia D. Handoko W. Rahmayanti S, et al Entomological studies in Malaysia have identified nine Anopheles species as malaria vectors, including An. An. An. An. An. An. An. An. leucosphyrus and An. A recent study in Sarawak indicates that Anopheles vectors of simian Plasmodium species extend beyond the Leucosphyrus Group. Examples include P. knowlesi in An. coatneyi in An. and P. cynomolgi in An. latens and An. Strategies to overcome malaria incidence in Kalimantan-Malaysian Borneo border In the Kalimantan-Malaysian Borneo border region, economic disparities between Indonesian provinces and Malaysian states have led to cross-border migration, impacting both trade and infectious disease dynamics. While Indonesians are drawn to Sarawak and Sabah in Malaysia by the economic opportunities and the movement of natural hosts such as wild macaques, these conditions raise concerns about the transmission of malaria between Kalimantan and Malaysian Borneo. Zoonotic malaria caused by P. knowlesi is a particularly concerning infectious disease in Malaysian Borneo, posing new challenges for healthcare systems and public health efforts. Despite the potential risks, there is a lack of systematic epidemiological data on human and zoonotic malaria in Kalimantan, the data coming mostly from presumptive diagnoses based on clinical symptoms. One possible reason for the lack of systematic epidemiological data in Kalimantan is the limited resources allocated to public health activities and surveillance. Additionally, the remote and rural areas in Kalimantan may pose logistical challenges for continuous surveillance, further contributing to the lack of comprehensive data on malaria. This lack of data hinders the understanding and control of malaria transmission in the region. In Indonesia, malaria surveillance relies on passive case detection by microscopic examination and rapid diagnostic tests (RDT. at primary health care centers. These tests are sufficient to detect clinical malaria caused by the two major species in Indonesia. falciparum and However, the identification of less common species, particularly at low-density parasitemia, is more challenging, which can lead to underdiagnosis. To pursue malaria elimination in Southeast Asia, molecular assays have increasingly been used to identify low-level infections in surveillance studies. In Malaysian Borneo, successful malaria control has dramatically reduced both P. falciparum and P. vivax cases but the numbers of P. knowlesi cases were increasingly detected by microscopy and initially thought to be the common P. infection replacing the former two. Nevertheless, species-specific PCR assay confirmed the presence of P. knowlesi infections among these P. malariae cases, including cases retrieved from 1996, implying that P. knowlesi in humans is not a AunewAy emerging disease. Malaysia is now moving towards the elimination phase with increased use of molecular tests and a similar pattern with a significant proportion of P. cases among malaria-infected populations has been observed. Indonesia will also launch sentinel surveillance of P. knowlesi that is already in the trial phase with strengthening of microscopy examination in the subdistrict health clinic laboratory, followed by cross-testing in district and provincial laboratories and PCR examination in the national laboratory. Active case finding through outreach or house-to-house visits by community health workers, distribution of LLINs, training, case and foci analysis, and migration surveillance are all critical and must be doubled to detect, treat, and reduce malaria cases efficiently. Stronger collaboration amongst ministries, particularly the Ministries of Health. Forestry and Environment, and Home Affairs, as well as the WHO, to sustain the malaria eradication programs and to meet the malaria elimination target by 2030, even though P. malaria in humans is not yet required for malaria-free certification. Even at low transmission rates, it will be difficult to declare a country as malaria-free if there is a risk of P. knowlesi malaria. To anticipate the risk of P. knowlesi and other simian malarias, more government collaboration across provinces, regencies, and cities is essential throughout Indonesia. Zoonotic malaria and strategy CONCLUSION REFERENCES