Alternative Invasion Mechanisms and Host Immune Response to  Plasmodium vivax  Malaria: Trends and Future Directions

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Abstract

Plasmodium vivax malaria is a neglected tropical disease, despite being more geographically widespread than any other form of malaria. The documentation of P. vivax infections in different parts of Africa where Duffy-negative individuals are predominant suggested that there are alternative pathways for P. vivax to invade human erythrocytes. Duffy-negative individuals may be just as fit as Duffy-positive individuals and are no longer resistant to P. vivax malaria. In this review, we describe the complexity of P. vivax malaria, characterize pathogenesis and candidate invasion genes of P. vivax, and host immune responses to P. vivax infections. We provide a comprehensive review on parasite ligands in several Plasmodium species that further justify candidate genes in P. vivax. We also summarize previous genomic and transcriptomic studies related to the identification of ligand and receptor proteins in P. vivax erythrocyte invasion. Finally, we identify topics that remain unclear and propose future studies that will greatly contribute to our knowledge of P. vivax.

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Comparative genomics of the neglected human malaria parasite Plasmodium vivax.

Jane M-R Carlton, John H. Adams, Joana C. Silva … (2008)

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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Vivax malaria: neglected and not benign.

Nicholas Anstey, Carlos Guerra, Shunmay Yeung … (2007)

Plasmodium vivax threatens almost 40% of the world's population, resulting in 132-391 million clinical infections each year. Most of these cases originate from Southeast Asia and the Western Pacific, although a significant number also occurs in Africa and South America. Although often regarded as causing a benign and self-limiting infection, there is increasing evidence that the overall burden, economic impact, and severity of disease from P. vivax have been underestimated. Malaria control strategies have had limited success and are confounded by the lack of access to reliable diagnosis, emergence of multidrug resistant isolates, the parasite's ability to transmit early in the course of disease and relapse from dormant liver stages at varying time intervals after the initial infection. Progress in reducing the burden of disease will require improved access to reliable diagnosis and effective treatment of both blood-stage and latent parasites, and more detailed characterization of the epidemiology, morbidity, and economic impact of vivax malaria. Without these, vivax malaria will continue to be neglected by ministries of health, policy makers, researchers, and funding bodies.

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Determinants of relapse periodicity in Plasmodium vivax malaria

Nicholas J. White (2011)

Plasmodium vivax is a major cause of febrile illness in endemic areas of Asia, Central and South America, and the horn of Africa. Plasmodium vivax infections are characterized by relapses of malaria arising from persistent liver stages of the parasite (hypnozoites) which can be prevented only by 8-aminoquinoline anti-malarials. Tropical P. vivax relapses at three week intervals if rapidly eliminated anti-malarials are given for treatment, whereas in temperate regions and parts of the sub-tropics P. vivax infections are characterized either by a long incubation or a long-latency period between illness and relapse - in both cases approximating 8-10 months. The epidemiology of the different relapse phenotypes has not been defined adequately despite obvious relevance to malaria control and elimination. The number of sporozoites inoculated by the anopheline mosquito is an important determinant of both the timing and the number of relapses. The intervals between relapses display a remarkable periodicity which has not been explained. Evidence is presented that the proportion of patients who have successive relapses is relatively constant and that the factor which activates hypnozoites and leads to regular interval relapse in vivax malaria is the systemic febrile illness itself. It is proposed that in endemic areas a large proportion of the population harbours latent hypnozoites which can be activated by a systemic illness such as vivax or falciparum malaria. This explains the high rates of vivax following falciparum malaria, the high proportion of heterologous genotypes in relapses, the higher rates of relapse in people living in endemic areas compared with artificial infection studies, and, by facilitating recombination between different genotypes, contributes to P. vivax genetic diversity particularly in low transmission settings. Long-latency P. vivax phenotypes may be more widespread and more prevalent than currently thought. These observations have important implications for the assessment of radical treatment efficacy and for malaria control and elimination.

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Journal

Journal ID (nlm-ta): Microorganisms

Journal ID (iso-abbrev): Microorganisms

Journal ID (publisher-id): microorganisms

Title: Microorganisms

Publisher: MDPI

ISSN (Electronic): 2076-2607

Publication date (Electronic): 23 December 2020

Publication date Collection: January 2021

Volume: 9

Issue: 1

Electronic Location Identifier: 15

Affiliations

[1 ]Biological Sciences, University of North Carolina, Charlotte, NC 28223, USA; Kpestana@ 123456uncc.edu (K.P.); Junya.tomida@ 123456uncc.edu (J.T.)

[2 ]Ethiopian Public Health Institute, Addis Ababa 1000, Ethiopia; Abnetabas@ 123456gmail.com

[3 ]Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa 1000, Ethiopia; Lgolassa@ 123456gmail.com

Author notes

[* ]Correspondence: Dkepple@ 123456uncc.edu (D.K.); Eugenia.Lo@ 123456uncc.edu (E.L.)

[†]

These authors equally contributed to this work.

Author information

Daniel Kepple https://orcid.org/0000-0003-0566-3623

Kareen Pestana https://orcid.org/0000-0001-9775-5378

Junya Tomida https://orcid.org/0000-0002-0813-5757

Eugenia Lo https://orcid.org/0000-0002-5631-4709

Article

Publisher ID: microorganisms-09-00015

DOI: 10.3390/microorganisms9010015

PMC ID: 7822457

PubMed ID: 33374596

SO-VID: e5dee740-7468-4a0e-b2c3-eadf7e15e8b9

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Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

Alternative Invasion Mechanisms and Host Immune Response to Plasmodium vivax Malaria: Trends and Future Directions

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Abstract

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Malaria vaccine development

Most cited references 171

Comparative genomics of the neglected human malaria parasite Plasmodium vivax.

Vivax malaria: neglected and not benign.

Determinants of relapse periodicity in Plasmodium vivax malaria

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