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      Plasmodium knowlesi malaria: current research perspectives

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          Abstract

          Originally known to cause simian malaria, Plasmodium knowlesi is now known as the fifth human malaria species. Since the publishing of a report that largely focused on human knowlesi cases in Sarawak in 2004, many more human cases have been reported in nearly all of the countries in Southeast Asia and in travelers returning from these countries. The zoonotic nature of this infection hinders malaria elimination efforts. In order to grasp the current perspective of knowlesi malaria, this literature review explores the different aspects of the disease including risk factors, diagnosis, treatment, and molecular and functional studies. Current studies do not provide sufficient data for an effective control program. Therefore, future direction for knowlesi research is highlighted here with a final aim of controlling, if not eliminating, the parasite.

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          High sensitivity of detection of human malaria parasites by the use of nested polymerase chain reaction.

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            The genome of the simian and human malaria parasite Plasmodium knowlesi.

            Plasmodium knowlesi is an intracellular malaria parasite whose natural vertebrate host is Macaca fascicularis (the 'kra' monkey); however, it is now increasingly recognized as a significant cause of human malaria, particularly in southeast Asia. Plasmodium knowlesi was the first malaria parasite species in which antigenic variation was demonstrated, and it has a close phylogenetic relationship to Plasmodium vivax, the second most important species of human malaria parasite (reviewed in ref. 4). Despite their relatedness, there are important phenotypic differences between them, such as host blood cell preference, absence of a dormant liver stage or 'hypnozoite' in P. knowlesi, and length of the asexual cycle (reviewed in ref. 4). Here we present an analysis of the P. knowlesi (H strain, Pk1(A+) clone) nuclear genome sequence. This is the first monkey malaria parasite genome to be described, and it provides an opportunity for comparison with the recently completed P. vivax genome and other sequenced Plasmodium genomes. In contrast to other Plasmodium genomes, putative variant antigen families are dispersed throughout the genome and are associated with intrachromosomal telomere repeats. One of these families, the KIRs, contains sequences that collectively match over one-half of the host CD99 extracellular domain, which may represent an unusual form of molecular mimicry.
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              A prospective comparative study of knowlesi, falciparum, and vivax malaria in Sabah, Malaysia: high proportion with severe disease from Plasmodium knowlesi and Plasmodium vivax but no mortality with early referral and artesunate therapy.

              Plasmodium knowlesi commonly causes severe malaria in Malaysian Borneo, with high case-fatality rates reported. We compared risk, spectrum, and outcome of severe disease from P. knowlesi, Plasmodium falciparum, and Plasmodium vivax and outcomes following introduction of protocols for early referral and intravenous artesunate for all severe malaria. From September 2010 to October 2011 we prospectively assessed nonpregnant patients aged ≥12 years admitted to Queen Elizabeth Hospital (QEH), Sabah, with polymerase chain reaction-confirmed Plasmodium monoinfection. Standardized referral and prereferral intravenous artesunate were instituted at district hospitals. Severe malaria occurred in 38 of 130 (29%) patients with P. knowlesi, 13 of 122 (11%) with P. falciparum, and 7 of 43 (16%) with P. vivax. The commonest severity criteria in knowlesi malaria included parasitemia >100 000/µL (n = 18), jaundice (n = 20), respiratory distress (n = 14), hypotension (n = 13), and acute kidney injury (n = 9). On multivariate analysis, P. knowlesi was associated with a 2.96-fold (95% confidence interval, 1.19-7.38-fold) greater risk of severity than P. falciparum (P = .020); only parasitemia and schizontemia >10% independently predicted knowlesi severity. Risk of severe knowlesi malaria increased 11-fold with parasitemia >20 000/µL, and 28-fold with parasitemia >100 000/µL. Nearly all (92%) knowlesi malaria patients received oral artemisinin therapy; 36 of 38 (95%) and 39 of 92 (42%) with severe and nonsevere disease, respectively, also received ≥1 dose of intravenous artesunate. No deaths occurred from any species. Plasmodium knowlesi is the commonest cause of severe malaria at QEH, with parasitemia the major risk factor for severity. Early referral and treatment with artesunate was highly effective for severe malaria from all species and associated with zero mortality.
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                Author and article information

                Journal
                Infect Drug Resist
                Infect Drug Resist
                Infection and Drug Resistance
                Infection and Drug Resistance
                Dove Medical Press
                1178-6973
                2018
                10 August 2018
                : 11
                : 1145-1155
                Affiliations
                Department of Parasitology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia, lauyeeling@ 123456um.edu.my
                Author notes
                Correspondence: Yee Ling Lau Department of Parasitology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia, Tel +60 3 7967 4749, Fax +60 3 7967 4754, Email lauyeeling@ 123456um.edu.my
                Article
                idr-11-1145
                10.2147/IDR.S148664
                6089103
                30127631
                53dbdb3e-9857-42dd-b75d-57e4857758be
                © 2018 Amir et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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                Categories
                Review

                Infectious disease & Microbiology
                zoonosis,epidemiology,diagnosis,treatment,molecular,functional studies

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