Non-human Primate Malaria Parasite Research Articles

Time to drop the term ‘simian malaria parasites’

The term ‘simian malaria parasites’ has crept into the modern malaria literature as a synonym for ‘non-human primate malaria parasites’, most commonly referring to species of Plasmodium infective to Old World monkeys. As humans are also simians, we contend that this usage is erroneous, and should not be used.

Defining malaria risks among forest workers in Aceh, Indonesia: a formative assessment

BackgroundFollowing a dramatic decline of malaria cases in Aceh province, geographically-based reactive case detection (RACD) was recently evaluated as a tool to improve surveillance with the goal of malaria elimination. While RACD detected few cases in households surrounding index cases, engaging in forest work was identified as a risk factor for malaria and infections from Plasmodium knowlesi—a non-human primate malaria parasite—were more common than expected. This qualitative formative assessment was conducted to improve understanding of malaria risk from forest work and identify strategies for targeted surveillance among forest workers, including adapting reactive case detection.MethodsBetween June and August, 2016, five focus groups and 18 in-depth interviews with forest workers and key informants were conducted in each of four subdistricts in Aceh Besar and Aceh Jaya districts. Themes included: types of forest activities, mobility of workers, interactions with non-human primates, malaria prevention and treatment-seeking behaviours, and willingness to participate in malaria surveys at forest work sites and using peer-referral.ResultsReported forest activities included mining, logging, and agriculture in the deep forest and along the forest fringe. Forest workers, particularly miners and loggers, described often spending weeks to months at work sites in makeshift housing, rarely utilizing mosquito prevention and, upon fever, self-medicating and seeking care from traditional healers or pharmacies rather than health facilities. Non-human primates are frequently observed near work sites, and most forest work locations are within a day’s journey of health clinics. Employers and workers expressed interest in undertaking malaria testing and in participating in survey recruitment by peer-referral and at work sites.ConclusionsDiverse groups of forest workers in Aceh are potentially exposed to malaria through forest work. Passive surveillance and household-based screening may under-estimate malaria burden due to extended stays in the forest and health-seeking behaviours. Adapting active surveillance to specifically target forest workers through work-site screening and/or peer-referral appears promising for addressing currently undetected infections.

Asymptomatic Natural Human Infections With the Simian Malaria Parasites Plasmodium cynomolgi and Plasmodium knowlesi.

BackgroundIn Southeast Asia, Plasmodium knowlesi, a parasite of long-tailed macaques (Macaca fascicularis), is an important cause of human malaria. Plasmodium cynomolgi also commonly infects these monkeys, but only one naturally acquired symptomatic human case has been reported previously.MethodsMalariometric studies involving 5422 subjects (aged 6 months to 65 years) were conducted in 23 villages in Pailin and Battambang, western Cambodia. Parasite detection and genotyping was conducted on blood samples, using high-volume quantitative PCR (uPCR).ResultsAsymptomatic malaria parasite infections were detected in 1361 of 14732 samples (9.2%). Asymptomatic infections with nonhuman primate malaria parasites were found in 21 individuals living close to forested areas; P. cynomolgi was found in 11, P. knowlesi was found in 8, and P. vivax and P. cynomolgi were both found in 2. Only 2 subjects were female, and 14 were men aged 20–40 years. Geometric mean parasite densities were 3604 parasites/mL in P. cynomolgi infections and 52488 parasites/mL in P. knowlesi infections. All P. cynomolgi isolates had wild-type dihydrofolate reductase genes, in contrast to the very high prevalence of mutations in the human malaria parasites. Asymptomatic reappearance of P. cynomolgi occurred in 2 subjects 3 months after the first infection.ConclusionsAsymptomatic naturally acquired P. cynomolgi and P. knowlesi infections can both occur in humans.Clinical Trials RegistrationNCT01872702.

Outbreak of human malaria caused by Plasmodium simium in the Atlantic Forest in Rio de Janeiro: a molecular epidemiological investigation.

Malaria was eliminated from southern and southeastern Brazil over 50 years ago. However, an increasing number of autochthonous episodes attributed to Plasmodium vivax have recently been reported from the Atlantic Forest region of Rio de Janeiro state. As the P vivax-like non-human primate malaria parasite species Plasmodium simium is locally enzootic, we performed a molecular epidemiological investigation to determine whether zoonotic malaria transmission is occurring. We examined blood samples from patients presenting with signs or symptoms suggestive of malaria as well as from local howler monkeys by microscopy and PCR. Samples were included from individuals if they had a history of travel to or resided in areas within the Rio de Janeiro Atlantic Forest, but not if they had malaria prophylaxis, blood transfusion or tissue or organ transplantation, or had travelled to known malaria endemic areas in the preceding year. Additionally, we developed a molecular assay based on sequencing of the parasite mitochondrial genome to distinguish between P vivax and P simium, and applied this assay to 33 cases from outbreaks that occurred in 2015, and 2016. A total of 49 autochthonous malaria cases were reported in 2015-16. Most patients were male, with a mean age of 44 years (SD 14·6), and 82% lived in urban areas of Rio de Janeiro state and had visited the Atlantic Forest for leisure or work-related activities. 33 cases were used for mitochondrial DNA sequencing. The assay was successfully performed for 28 samples, and all were shown to be P simium, indicative of zoonotic transmission of this species to human beings in this region. Sequencing of the whole mitochondrial genome of three of these cases showed that P simium is most closely related to P vivax parasites from South America. The malaria outbreaks in this region were caused by P simium, previously considered to be a monkey-specific malaria parasite, related to but distinct from P vivax, and which has never conclusively been shown to infect people before. This unequivocal demonstration of zoonotic transmission, 50 years after the only previous report of P simium in people, leads to the possibility that this parasite has always infected people in this region, but that it has been consistently misdiagnosed as P vivax because of an absence of molecular typing techniques. Thorough screening of local non-human primates and mosquitoes (Anopheline) is required to evaluate the extent of this newly recognised zoonotic threat to public health and malaria elimination in Brazil. Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado de Rio de Janeiro, The Brazilian National Council for Scientific and Technological Development (CNPq), JSPS Grant-in-Aid for scientific research, Secretary for Health Surveillance of the Brazilian Ministry of Health, Global Fund, Fundaçao de amparo à pesquisa do estado de Minas Gerais (Fapemig), and PRONEX Program of the CNPq.

An improved Plasmodium cynomolgi genome assembly reveals an unexpected methyltransferase gene expansion

Background: Plasmodium cynomolgi, a non-human primate malaria parasite species, has been an important model parasite since its discovery in 1907. Similarities in the biology of P. cynomolgi to the closely related, but less tractable, human malaria parasite P. vivax make it the model parasite of choice for liver biology and vaccine studies pertinent to P. vivax malaria. Molecular and genome-scale studies of P. cynomolgi have relied on the current reference genome sequence, which remains highly fragmented with 1,649 unassigned scaffolds and little representation of the subtelomeres. Methods: Using long-read sequence data (Pacific Biosciences SMRT technology), we assembled and annotated a new reference genome sequence, PcyM, sourced from an Indian rhesus monkey. We compare the newly assembled genome sequence with those of several other Plasmodium species, including a re-annotated P. coatneyi assembly. Results: The new PcyM genome assembly is of significantly higher quality than the existing reference, comprising only 56 pieces, no gaps and an improved average gene length. Detailed manual curation has ensured a comprehensive annotation of the genome with 6,632 genes, nearly 1,000 more than previously attributed to P. cynomolgi. The new assembly also has an improved representation of the subtelomeric regions, which account for nearly 40% of the sequence. Within the subtelomeres, we identified more than 1300 Plasmodium interspersed repeat ( pir) genes, as well as a striking expansion of 36 methyltransferase pseudogenes that originated from a single copy on chromosome 9. Conclusions: The manually curated PcyM reference genome sequence is an important new resource for the malaria research community. The high quality and contiguity of the data have enabled the discovery of a novel expansion of methyltransferase in the subtelomeres, and illustrates the new comparative genomics capabilities that are being unlocked by complete reference genomes.

An improved Plasmodium cynomolgi genome assembly reveals an unexpected methyltransferase gene expansion.

Plasmodium cynomolgi, a non-human primate malaria parasite species, has been an important model parasite since its discovery in 1907. Similarities in the biology of P. cynomolgi to the closely related, but less tractable, human malaria parasite P. vivax make it the model parasite of choice for liver biology and vaccine studies pertinent to P. vivax malaria. Molecular and genome-scale studies of P. cynomolgi have relied on the current reference genome sequence, which remains highly fragmented with 1,649 unassigned scaffolds and little representation of the subtelomeres. Methods: Using long-read sequence data (Pacific Biosciences SMRT technology), we assembled and annotated a new reference genome sequence, PcyM, sourced from an Indian rhesus monkey. We compare the newly assembled genome sequence with those of several other Plasmodium species, including a re-annotated P. coatneyi assembly. The new PcyM genome assembly is of significantly higher quality than the existing reference, comprising only 56 pieces, no gaps and an improved average gene length. Detailed manual curation has ensured a comprehensive annotation of the genome with 6,632 genes, nearly 1,000 more than previously attributed to P. cynomolgi. The new assembly also has an improved representation of the subtelomeric regions, which account for nearly 40% of the sequence. Within the subtelomeres, we identified more than 1300 Plasmodium interspersed repeat ( pir) genes, as well as a striking expansion of 36 methyltransferase pseudogenes that originated from a single copy on chromosome 9. The manually curated PcyM reference genome sequence is an important new resource for the malaria research community. The high quality and contiguity of the data have enabled the discovery of a novel expansion of methyltransferase in the subtelomeres, and illustrates the new comparative genomics capabilities that are being unlocked by complete reference genomes.

Non-human Primate Malaria Parasites: out of the forest and into the laboratory - CORRIGENDUM.

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Non-human primate malaria parasites: out of the forest and into the laboratory.

The study of malaria in the laboratory relies on either the in vitro culture of human parasites, or the use of non-human malaria parasites in laboratory animals. In this review, we address the use of non-human primate malaria parasite species (NHPMPs) in laboratory research. We describe the features of the most commonly used NHPMPs, review their contribution to our understanding of malaria to date, and discuss their potential contribution to future studies.

Humans frequently exposed to a range of non-human primate malaria parasite species through the bites of Anopheles dirus mosquitoes in South-central Vietnam.

BackgroundRecent studies have described natural human infections of the non-human primate parasites Plasmodium knowlesi and Plasmodium cynomolgi. In Southeast Asia, mosquitoes of the Anopheles leucosphyrus group bite both humans and monkeys in the forest and thus offer a possible route for Plasmodium species to bridge the species barrier. In this study we analysed the species composition of malarial sporozoites infecting the salivary glands of Anopheles dirus in order to determine their potential role as bridge vectors of Plasmodium parasites from monkeys to humans.MethodsMosquitoes were collected in the forest and forest fringe area of Khanh Phu commune by human-baited landing collection. Anopheles species were determined on the basis of morphologic features. Sporozoite-infected salivary glands were applied to filter paper and dried in an ambient atmosphere, before storage in closed vials at 4–6 °C. Detection and identification of Plasmodium species in salivary glands were carried out by nested-PCR of the small subunit ribosomal RNA gene.ResultsSix species of Plasmodium parasites were detected by PCR, of which P. vivax was the most common, followed by P. knowlesi, P. inui, P. cynomolgi, P. coatneyi and P. falciparum. Twenty-six of the 79 sporozoite infected mosquitoes showed multiple infections, most of which were a combination of P. vivax with one or more of the non-human primate Plasmodium species.ConclusionsThese results suggest that humans overnighting in this forest are frequently inoculated with both human and non-human primate malaria parasites, leading to a situation conducive for the emergence of novel zoonotic malaria.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-015-0995-y) contains supplementary material, which is available to authorized users.

The Origin of Malarial Parasites in Orangutans

BackgroundRecent findings of Plasmodium in African apes have changed our perspectives on the evolution of malarial parasites in hominids. However, phylogenetic analyses of primate malarias are still missing information from Southeast Asian apes. In this study, we report molecular data for a malaria parasite lineage found in orangutans.Methodology/Principal FindingsWe screened twenty-four blood samples from Pongo pygmaeus (Kalimantan, Indonesia) for Plasmodium parasites by PCR. For all the malaria positive orangutan samples, parasite mitochondrial genomes (mtDNA) and two antigens: merozoite surface protein 1 42 kDa (MSP-142) and circumsporozoite protein gene (CSP) were amplified, cloned, and sequenced. Fifteen orangutans tested positive and yielded 5 distinct mitochondrial haplotypes not previously found. The haplotypes detected exhibited low genetic divergence among them, indicating that they belong to one species. We report phylogenetic analyses using mitochondrial genomes, MSP-142 and CSP. We found that the orangutan malaria parasite lineage was part of a monophyletic group that includes all the known non-human primate malaria parasites found in Southeast Asia; specifically, it shares a recent common ancestor with P. inui (a macaque parasite) and P. hylobati (a gibbon parasite) suggesting that this lineage originated as a result of a host switch. The genetic diversity of MSP-142 in orangutans seems to be under negative selection. This result is similar to previous findings in non-human primate malarias closely related to P. vivax. As has been previously observed in the other Plasmodium species found in non-human primates, the CSP shows high polymorphism in the number of repeats. However, it has clearly distinctive motifs from those previously found in other malarial parasites.ConclusionThe evidence available from Asian apes indicates that these parasites originated independently from those found in Africa, likely as the result of host switches from other non-human primates.

Human Malaria Parasites: Are We Ready for a New Species?

There are four well-established human malaria parasites, although a nonhuman primate malaria parasite, Plasmodium knowlesi, can also infect humans [1]. Plasmodium ovale is one of the human malaria parasites, but it traditionally receives little attention because of its mild disease and relatively low infection rate. An intriguing and provocative report in this issue of the Journal by Sutherland et al. raises the possibility of two distinct parasite species under the name P. ovale.

Malaria and Hepatocystis Species in Wild Macaques, Southern Thailand

Southeast Asian macaques are natural hosts for a number of nonhuman primate malaria parasites; some of these can cause diseases in humans. We conducted a cross-sectional survey by collecting 99 blood samples from Macaca fascicularis in southern Thailand. Giemsa-stained blood films showed five (5.1%) positive samples and six (6.1%) isolates had positive test results by polymerase chain reaction. A phylogenetic tree inferred from the A-type sequences of the small subunit ribosomal RNA gene confirmed Plasmodium inui in five macaques; one of these macaques was co-infected with P. coatneyi. Hepatocystis, a hemoprotozoan parasite transmitted by Culicoides, was identified in an isolate that was confirmed by analysis of mitochondrial cytochrome b sequences. All malaria-infected monkeys lived in mangrove forests, but no infected monkeys were found in an urban area. These findings indicate regional differences in malaria distribution among these macaques, as well as differences in potential risk of disease transmission to humans.

Circumsporozoite protein gene of Plasmodium simium, a Plasmodium vivax-like monkey malaria parasite.

The circumsporozoite (CS) protein, a species-specific sporozoite surface protein and a vaccine candidate antigen, has been characterized from malaria parasites that naturally cause infections in humans, monkeys and chimpanzees [1-7]. Because of the related structural features of repetitive and nonrepetitive sequences the CS protein genes have also been used as markers for studies of evolutionary relatedness of malaria parasites [8]. The CS protein genes of the nonhuman primate malaria parasites Plasmodium brazilianurn and Plasmodium reichenowi, which are considered to be evolutionarily related to the human malaria parasites Plasrnodium malariae and Plasmodium falciparum, respectively, have been characterized and shown to bear structural and antigenic similarity [4,7]. Plasmodium simium is a nonhuman malaria parasite both morphologically and biologically similar to the human malaria parasite Plasmo-

Suppressive and Causal Prophylactic Activity of Floxacrine in Various Avian Malaria Models

Floxacrine, a 7-chloro-10-hydroxy-3(4-trifluoromethylphenyl)-3, 4-dihydroacridine-1,9-(2H, 10H)-dione and various standard malarials were found to be distinctly less active against avian malaria parasites than against rodent or nonhuman primate malaria parasites. Especially the suppressive action against asexual stages of P. gallinaceum, P. praecox and P. cathemerium was markedly reduced in comparison with that ascertained in mice infected with P. berghei. Similar results were observed in sporozoite-induced infections of P. gallinaceum and P. cathemerium respectively. Expressed as quotient of calculated causal prophylactic activity (CPD50) floxacrine was 42 and pyrimethamine 54 times more active against P. berghei yoelii than P. gallinaceum. The blood schizontocidal effect of floxacrine proved superior to that of mefloquine, chloroquine and mepacrine, whereas the causal prophylactic activity was slightly inferior to that of pyrimethamine but superior to that of primaquine. In vitro floxacrine revealed no effect against sporozoites of P. gallinaceum even at concentrations of 100 mcg/ml.