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      Host Cell Tropism and Adaptation of Blood-Stage Malaria Parasites: Challenges for Malaria Elimination

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          Abstract

          At least four malaria parasite species from the Plasmodium genus besides P. falciparum and P. vivax may be transmitted in humans. The molecular determinants of host cell tropism are unique among these species.

          Abstract

          Plasmodium falciparum and Plasmodium vivax account for most of the mortality and morbidity associated with malaria in humans. Research and control efforts have focused on infections caused by P. falciparum and P. vivax, but have neglected other malaria parasite species that infect humans. Additionally, many related malaria parasite species infect nonhuman primates (NHPs), and have the potential for transmission to humans. For malaria elimination, the varied and specific challenges of all of these Plasmodium species will need to be considered. Recent advances in molecular genetics and genomics have increased our knowledge of the prevalence and existing diversity of the human and NHP Plasmodium species. We are beginning to identify the extent of the reservoirs of each parasite species in humans and NHPs, revealing their origins as well as potential for adaptation in humans. Here, we focus on the red blood cell stage of human infection and the host cell tropism of each human Plasmodium species. Determinants of tropism are unique among malaria parasite species, presenting a complex challenge for malaria elimination.

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          Comparative genomics of the neglected human malaria parasite Plasmodium vivax.

          The human malaria parasite Plasmodium vivax is responsible for 25-40% of the approximately 515 million annual cases of malaria worldwide. Although seldom fatal, the parasite elicits severe and incapacitating clinical symptoms and often causes relapses months after a primary infection has cleared. Despite its importance as a major human pathogen, P. vivax is little studied because it cannot be propagated continuously in the laboratory except in non-human primates. We sequenced the genome of P. vivax to shed light on its distinctive biological features, and as a means to drive development of new drugs and vaccines. Here we describe the synteny and isochore structure of P. vivax chromosomes, and show that the parasite resembles other malaria parasites in gene content and metabolic potential, but possesses novel gene families and potential alternative invasion pathways not recognized previously. Completion of the P. vivax genome provides the scientific community with a valuable resource that can be used to advance investigation into this neglected species.
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            Key gaps in the knowledge of Plasmodium vivax, a neglected human malaria parasite.

            Plasmodium vivax is geographically the most widely distributed cause of malaria in people, with up to 2.5 billion people at risk and an estimated 80 million to 300 million clinical cases every year--including severe disease and death. Despite this large burden of disease, P vivax is overlooked and left in the shadow of the enormous problem caused by Plasmodium falciparum in sub-Saharan Africa. The technological advances enabling the sequencing of the P vivax genome and a recent call for worldwide malaria eradication have together placed new emphasis on the importance of addressing P vivax as a major public health problem. However, because of this parasite's biology, it is especially difficult to interrupt the transmission of P vivax, and experts agree that the available methods for preventing and treating infections with P vivax are inadequate. It is thus imperative that the development of new methods and strategies become a priority. Advancing the development of such methods needs renewed emphasis on understanding the biology, pathogenesis, and epidemiology of P vivax. This Review critically examines what is known about P vivax, focusing on identifying the crucial gaps that create obstacles to the elimination of this parasite in human populations.
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              High sensitivity of detection of human malaria parasites by the use of nested polymerase chain reaction

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                Author and article information

                Journal
                Cold Spring Harb Perspect Med
                Cold Spring Harb Perspect Med
                cshperspectmed
                cshperspectmed
                Cold Spring Harbor Perspectives in Medicine
                Cold Spring Harbor Laboratory Press (Cold Spring Harbor, New York )
                2157-1422
                November 2017
                : 7
                : 11
                : a025494
                Affiliations
                [1 ]Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115
                Author notes
                [2]

                These authors contributed equally to this work.

                Editors: Dyann F. Wirth and Pedro L. Alonso

                Additional Perspectives on Malaria: Biology in the Era of Eradication available at www.perspectivesinmedicine.org

                Article
                PMC5666624 PMC5666624 5666624 a025494
                10.1101/cshperspect.a025494
                5666624
                28213436
                624af483-7f20-40b0-9bc0-4fcd4f8143b7
                Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved
                History
                Page count
                Pages: 18
                Categories
                107
                Perspectives

                Comments

                Malaria vaccine development collection topic 5) Identifying and developing the new generation of malaria vaccines - Unraveling host-parasite interactions. See https://www.scienceopen.com/collection/malariavaccine

                We are only beginning to identify the extent of the reservoirs of P. vivax (as well as P. falciparium) in humans and other primates. Here, Lim and collaborators focus on the host cell tropism of each human Plasmodium spp. species. 

                2018-10-09 23:53 UTC
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