Plasmodium knowlesi, a simian malaria parasite responsible for all recent indigenous cases of mal... more Plasmodium knowlesi, a simian malaria parasite responsible for all recent indigenous cases of malaria in Malaysia, infects humans throughout Southeast Asia. There are two genetically distinct subpopulations of Plasmodium knowlesi in Malaysian Borneo, one associated with long-tailed macaques (termed cluster 1) and the other with pig-tailed macaques (cluster 2). A prospective study was conducted to determine whether there were any between-subpopulation differences in clinical and laboratory features, as well as in epidemiological characteristics. Over 2 years, 420 adults admitted to Kapit Hospital, Malaysian Borneo with knowlesi malaria were studied. Infections with each subpopulation resulted in mostly uncomplicated malaria. Severe disease was observed in 35/298 (11.7%) of single cluster 1 and 8/115 (7.0%) of single cluster 2 infections (p = 0.208). There was no clinically significant difference in outcome between the two subpopulations. Cluster 1 infections were more likely to be as...
Human infections with Plasmodium knowlesi, a malaria parasite of Macaca fascicularis and Macaca n... more Human infections with Plasmodium knowlesi, a malaria parasite of Macaca fascicularis and Macaca nemestrina (long-tailed and pig-tailed macaques respectively), occur throughout Southeast Asia, especially Malaysian Borneo. Other naturally-acquired human infections with malaria parasites from macaques in Southeast Asia are P. cynomolgi, P. inui-like, P. coatneyi and P. simiovale. In Sarawak, Malaysian Borneo, M. fascicularis and M. nemestrina from only the Kapit Division have been examined previously for malaria parasites. In order to determine the distribution of P. knowlesi and other zoonotic malaria parasites, 73 macaque blood samples derived from 7 other administrative divisions in Sarawak were studied. Of 45 blood samples from M. fascicularis and 28 from M. nemestrina tested by nested PCR assays, 23 (51.1%) M. fascicularis and 15 (53.6%) M. nemestrina samples were positive for Plasmodium DNA. Thirty-two of these macaques from 7 divisions sampled, harboured either single (n = 12), ...
Plasmodium knowlesi and Plasmodium cynomolgi are two malaria parasites naturally transmissible be... more Plasmodium knowlesi and Plasmodium cynomolgi are two malaria parasites naturally transmissible between humans and wild macaque through mosquito vectors, while Plasmodium inui can be experimentally transmitted from macaques to humans. One of their major natural hosts, the long-tailed macaque (Macaca fascicularis), is host to two other species of Plasmodium (Plasmodium fieldi and Plasmodium coatneyi) and is widely distributed in Southeast Asia. This study aims to determine the distribution of wild macaques infected with malarial parasites by examining samples derived from seven populations in five countries across Southeast Asia. Plasmodium knowlesi, P. cynomolgi, P. coatneyi, P. inui and P. fieldi, were detected using nested PCR assays in DNA samples from 276 wild-caught long-tailed macaques. These samples had been derived from macaques captured at seven locations, two each in the Philippines (n = 68) and Indonesia (n = 70), and one each in Cambodia (n = 54), Singapore (n = 40) and L...
There were only four species of Plasmodium that were thought to cause malaria in humans until a l... more There were only four species of Plasmodium that were thought to cause malaria in humans until a large number of human infections by Plasmodium knowlesi, a malaria parasite typically found in long-tailed and pig-tailed macaques, were reported in 2004 in Malaysian Borneo. Since then, cases of knowlesi malaria have been reported throughout South-east Asia and also in travellers returning from the region. This article describes the molecular, entomological and epidemiological data which indicate that P. knowlesi is an ancient parasite that is primarily zoonotic, and there are three highly divergent sub-populations. It also describes the detection methods for P. knowlesi, which is morphologicaly similar to P. malariae, and the clinical features and treatment of this malaria parasite that is potentially fatal.
Infection with Plasmodium knowlesi, a zoonotic primate malaria, is a growing human health problem... more Infection with Plasmodium knowlesi, a zoonotic primate malaria, is a growing human health problem in Southeast Asia. P. knowlesi is being used in malaria vaccine studies, and a number of proteins are being considered as candidate malaria vaccine antigens, including the Apical Membrane Antigen 1 (AMA1). In order to determine genetic diversity of the ama1 gene and to identify epitopes of AMA1 under strongest immune selection, the ama1 gene of 52 P. knowlesi isolates derived from human infections was sequenced. Sequence analysis of isolates from two geographically isolated regions in Sarawak showed that polymorphism in the protein is low compared to that of AMA1 of the major human malaria parasites, P. falciparum and P. vivax. Although the number of haplotypes was 27, the frequency of mutations at the majority of the polymorphic positions was low, and only six positions had a variance frequency higher than 10%. Only two positions had more than one alternative amino acid. Interestingly,...
BackgroundCytoadherence of infected red blood cells to brain endothelium is causally implicated i... more BackgroundCytoadherence of infected red blood cells to brain endothelium is causally implicated in malarial coma, one of the severe manifestations of falciparum malaria. Cytoadherence is mediated by specific binding of variant parasite antigens, expressed on the surface of infected erythrocytes, to endothelial receptors including, ICAM-1, VCAM and CD36. In fatal cases of severe falciparum malaria with coma, blood vessels in the brain are characteristically congested with infected erythrocytes. Brain sections from a fatal case of knowlesi malaria, but without coma, were similarly congested with infected erythrocytes. The objective of this study was to determine the binding phenotype ofPlasmodium knowlesiinfected human erythrocytes to recombinant human ICAM-1, VCAM and CD36.MethodsFive patients with PCR-confirmedP. knowlesimalaria were recruited into the study with consent between April and August 2010. Pre-treatment venous blood was washed and culturedex vivoto increase the proportio...
Davis TME, Singh B, Choo KE, Ibrahim J, Sulaiman SA, Kadir ZA, Ismail R (University of Western Au... more Davis TME, Singh B, Choo KE, Ibrahim J, Sulaiman SA, Kadir ZA, Ismail R (University of Western Australia, Fremantle Hospital, Fremantle, Western Australia, Australia. Universiti Sains Malaysia, Kubang Kerian, Kota Bharu; General Hospital, Kota Bharu, Kuala Krai Hospital, Kuala Krai; Kelantan, Malaysia) Dynamic assessment of parathyroid function in acute malaria. J Intern Med 1998; 243: 349–54.ObjectivesTo investigate the dynamic parathyroid response to rapidly induced, sustained hypocalcaemia in patients with acute malaria and in healthy volunteers.DesignSerum intact parathormone (PTH) concentrations were measured on samples taken before and during a variable‐rate tri‐sodium citrate infusion designed to ‘clamp’ the whole blood ionised calcium concentration 0.20 mmol L−1 below baseline for 120 min.SubjectsSix Malaysian patients aged 17–42 years with acute malaria, four of whom were restudied in convalescence, and 12 healthy controls aged 19–36 years.Main outcome measuresWhole‐blood i...
Plasmodium knowlesi is typically found in nature in macaques and has recently been recognized as ... more Plasmodium knowlesi is typically found in nature in macaques and has recently been recognized as the fifth species of Plasmodium causing malaria in human populations in south-east Asia. A case of knowlesi malaria is described in a Swedish man, who became ill after returning from a short visit to Malaysian Borneo in October 2006. His P. knowlesi infection was not detected using a rapid diagnostic test for malaria, but was confirmed by PCR and molecular characterization. He responded rapidly to treatment with mefloquine. Evaluation of rapid diagnostic kits with further samples from knowlesi malaria patients are necessary, since early identification and appropriate anti-malarial treatment of suspected cases are essential due to the rapid growth and potentially life-threatening nature of P. knowlesi. Physicians should be aware that knowlesi infection is an important differential diagnosis in febrile travellers, with a recent travel history to forested areas in south-east Asia, including...
Background The misdiagnosis of Plasmodium knowlesi by microscopy has prompted a re-evaluation of ... more Background The misdiagnosis of Plasmodium knowlesi by microscopy has prompted a re-evaluation of the geographic distribution, prevalence and pathogenesis of this species using molecular diagnostic tools. In this report, a specific probe for P. knowlesi, that can be used in a previously described TaqMan real-time PCR assay for detection of Plasmodium spp., and Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae and Plasmodium ovale, was designed and validated against clinical samples. Methods A hydrolysis probe for a real-time PCR assay was designed to recognize a specific DNA sequence within the P. knowlesi small subunit ribosomal RNA gene. The sensitivity, linearity and specificity of the assay were determined using plasmids containing P. knowlesi DNA and genomic DNA of P. falciparum, P. knowlesi, P. malariae, P. ovale and P. vivax isolated from clinical samples. DNA samples of the simian malaria parasites Plasmodium cynomolgi and Plasmodium inui that can infect humans und...
Plasmodium knowlesi, a simian malaria parasite responsible for all recent indigenous cases of mal... more Plasmodium knowlesi, a simian malaria parasite responsible for all recent indigenous cases of malaria in Malaysia, infects humans throughout Southeast Asia. There are two genetically distinct subpopulations of Plasmodium knowlesi in Malaysian Borneo, one associated with long-tailed macaques (termed cluster 1) and the other with pig-tailed macaques (cluster 2). A prospective study was conducted to determine whether there were any between-subpopulation differences in clinical and laboratory features, as well as in epidemiological characteristics. Over 2 years, 420 adults admitted to Kapit Hospital, Malaysian Borneo with knowlesi malaria were studied. Infections with each subpopulation resulted in mostly uncomplicated malaria. Severe disease was observed in 35/298 (11.7%) of single cluster 1 and 8/115 (7.0%) of single cluster 2 infections (p = 0.208). There was no clinically significant difference in outcome between the two subpopulations. Cluster 1 infections were more likely to be as...
Human infections with Plasmodium knowlesi, a malaria parasite of Macaca fascicularis and Macaca n... more Human infections with Plasmodium knowlesi, a malaria parasite of Macaca fascicularis and Macaca nemestrina (long-tailed and pig-tailed macaques respectively), occur throughout Southeast Asia, especially Malaysian Borneo. Other naturally-acquired human infections with malaria parasites from macaques in Southeast Asia are P. cynomolgi, P. inui-like, P. coatneyi and P. simiovale. In Sarawak, Malaysian Borneo, M. fascicularis and M. nemestrina from only the Kapit Division have been examined previously for malaria parasites. In order to determine the distribution of P. knowlesi and other zoonotic malaria parasites, 73 macaque blood samples derived from 7 other administrative divisions in Sarawak were studied. Of 45 blood samples from M. fascicularis and 28 from M. nemestrina tested by nested PCR assays, 23 (51.1%) M. fascicularis and 15 (53.6%) M. nemestrina samples were positive for Plasmodium DNA. Thirty-two of these macaques from 7 divisions sampled, harboured either single (n = 12), ...
Plasmodium knowlesi and Plasmodium cynomolgi are two malaria parasites naturally transmissible be... more Plasmodium knowlesi and Plasmodium cynomolgi are two malaria parasites naturally transmissible between humans and wild macaque through mosquito vectors, while Plasmodium inui can be experimentally transmitted from macaques to humans. One of their major natural hosts, the long-tailed macaque (Macaca fascicularis), is host to two other species of Plasmodium (Plasmodium fieldi and Plasmodium coatneyi) and is widely distributed in Southeast Asia. This study aims to determine the distribution of wild macaques infected with malarial parasites by examining samples derived from seven populations in five countries across Southeast Asia. Plasmodium knowlesi, P. cynomolgi, P. coatneyi, P. inui and P. fieldi, were detected using nested PCR assays in DNA samples from 276 wild-caught long-tailed macaques. These samples had been derived from macaques captured at seven locations, two each in the Philippines (n = 68) and Indonesia (n = 70), and one each in Cambodia (n = 54), Singapore (n = 40) and L...
There were only four species of Plasmodium that were thought to cause malaria in humans until a l... more There were only four species of Plasmodium that were thought to cause malaria in humans until a large number of human infections by Plasmodium knowlesi, a malaria parasite typically found in long-tailed and pig-tailed macaques, were reported in 2004 in Malaysian Borneo. Since then, cases of knowlesi malaria have been reported throughout South-east Asia and also in travellers returning from the region. This article describes the molecular, entomological and epidemiological data which indicate that P. knowlesi is an ancient parasite that is primarily zoonotic, and there are three highly divergent sub-populations. It also describes the detection methods for P. knowlesi, which is morphologicaly similar to P. malariae, and the clinical features and treatment of this malaria parasite that is potentially fatal.
Infection with Plasmodium knowlesi, a zoonotic primate malaria, is a growing human health problem... more Infection with Plasmodium knowlesi, a zoonotic primate malaria, is a growing human health problem in Southeast Asia. P. knowlesi is being used in malaria vaccine studies, and a number of proteins are being considered as candidate malaria vaccine antigens, including the Apical Membrane Antigen 1 (AMA1). In order to determine genetic diversity of the ama1 gene and to identify epitopes of AMA1 under strongest immune selection, the ama1 gene of 52 P. knowlesi isolates derived from human infections was sequenced. Sequence analysis of isolates from two geographically isolated regions in Sarawak showed that polymorphism in the protein is low compared to that of AMA1 of the major human malaria parasites, P. falciparum and P. vivax. Although the number of haplotypes was 27, the frequency of mutations at the majority of the polymorphic positions was low, and only six positions had a variance frequency higher than 10%. Only two positions had more than one alternative amino acid. Interestingly,...
BackgroundCytoadherence of infected red blood cells to brain endothelium is causally implicated i... more BackgroundCytoadherence of infected red blood cells to brain endothelium is causally implicated in malarial coma, one of the severe manifestations of falciparum malaria. Cytoadherence is mediated by specific binding of variant parasite antigens, expressed on the surface of infected erythrocytes, to endothelial receptors including, ICAM-1, VCAM and CD36. In fatal cases of severe falciparum malaria with coma, blood vessels in the brain are characteristically congested with infected erythrocytes. Brain sections from a fatal case of knowlesi malaria, but without coma, were similarly congested with infected erythrocytes. The objective of this study was to determine the binding phenotype ofPlasmodium knowlesiinfected human erythrocytes to recombinant human ICAM-1, VCAM and CD36.MethodsFive patients with PCR-confirmedP. knowlesimalaria were recruited into the study with consent between April and August 2010. Pre-treatment venous blood was washed and culturedex vivoto increase the proportio...
Davis TME, Singh B, Choo KE, Ibrahim J, Sulaiman SA, Kadir ZA, Ismail R (University of Western Au... more Davis TME, Singh B, Choo KE, Ibrahim J, Sulaiman SA, Kadir ZA, Ismail R (University of Western Australia, Fremantle Hospital, Fremantle, Western Australia, Australia. Universiti Sains Malaysia, Kubang Kerian, Kota Bharu; General Hospital, Kota Bharu, Kuala Krai Hospital, Kuala Krai; Kelantan, Malaysia) Dynamic assessment of parathyroid function in acute malaria. J Intern Med 1998; 243: 349–54.ObjectivesTo investigate the dynamic parathyroid response to rapidly induced, sustained hypocalcaemia in patients with acute malaria and in healthy volunteers.DesignSerum intact parathormone (PTH) concentrations were measured on samples taken before and during a variable‐rate tri‐sodium citrate infusion designed to ‘clamp’ the whole blood ionised calcium concentration 0.20 mmol L−1 below baseline for 120 min.SubjectsSix Malaysian patients aged 17–42 years with acute malaria, four of whom were restudied in convalescence, and 12 healthy controls aged 19–36 years.Main outcome measuresWhole‐blood i...
Plasmodium knowlesi is typically found in nature in macaques and has recently been recognized as ... more Plasmodium knowlesi is typically found in nature in macaques and has recently been recognized as the fifth species of Plasmodium causing malaria in human populations in south-east Asia. A case of knowlesi malaria is described in a Swedish man, who became ill after returning from a short visit to Malaysian Borneo in October 2006. His P. knowlesi infection was not detected using a rapid diagnostic test for malaria, but was confirmed by PCR and molecular characterization. He responded rapidly to treatment with mefloquine. Evaluation of rapid diagnostic kits with further samples from knowlesi malaria patients are necessary, since early identification and appropriate anti-malarial treatment of suspected cases are essential due to the rapid growth and potentially life-threatening nature of P. knowlesi. Physicians should be aware that knowlesi infection is an important differential diagnosis in febrile travellers, with a recent travel history to forested areas in south-east Asia, including...
Background The misdiagnosis of Plasmodium knowlesi by microscopy has prompted a re-evaluation of ... more Background The misdiagnosis of Plasmodium knowlesi by microscopy has prompted a re-evaluation of the geographic distribution, prevalence and pathogenesis of this species using molecular diagnostic tools. In this report, a specific probe for P. knowlesi, that can be used in a previously described TaqMan real-time PCR assay for detection of Plasmodium spp., and Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae and Plasmodium ovale, was designed and validated against clinical samples. Methods A hydrolysis probe for a real-time PCR assay was designed to recognize a specific DNA sequence within the P. knowlesi small subunit ribosomal RNA gene. The sensitivity, linearity and specificity of the assay were determined using plasmids containing P. knowlesi DNA and genomic DNA of P. falciparum, P. knowlesi, P. malariae, P. ovale and P. vivax isolated from clinical samples. DNA samples of the simian malaria parasites Plasmodium cynomolgi and Plasmodium inui that can infect humans und...
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