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Parasitology International Apr 2022Plasmodium vivax is the most geographically widespread human malaria parasite. Global malaria efforts have been less successful at reducing the burden of P. vivax... (Review)
Review
Plasmodium vivax is the most geographically widespread human malaria parasite. Global malaria efforts have been less successful at reducing the burden of P. vivax compared to P. falciparum, owing to the unique biology and related treatment complexity of P. vivax. As a result, P. vivax is now the dominant malaria parasite throughout the Asia-Pacific and South America causing up to 14 million clinical cases every year and is considered a major obstacle to malaria elimination. Key features circumventing existing malaria control tools are the transmissibility of asymptomatic, low-density circulating infections and reservoirs of persistent dormant liver stages (hypnozoites) that are undetectable but reactivate to cause relapsing infections and sustain transmission. In this review we summarise the new knowledge shaping our understanding of the global epidemiology of P. vivax infections, highlighting the challenges for elimination and the tools that will be required achieve this.
Topics: Disease Reservoirs; Humans; Liver; Malaria, Falciparum; Malaria, Vivax; Plasmodium vivax
PubMed: 34896312
DOI: 10.1016/j.parint.2021.102526 -
Cold Spring Harbor Perspectives in... Sep 2017is the second most prevalent cause of malaria worldwide and the leading cause of malaria outside of Africa. Although infections are seldom fatal clinical disease can be... (Review)
Review
is the second most prevalent cause of malaria worldwide and the leading cause of malaria outside of Africa. Although infections are seldom fatal clinical disease can be debilitating and imposes significant health and economic impacts on affected populations. Estimates of transmission and prevalence intensity can be problematic because many episodes of vivax originate from hypnozoite stages in the liver that have remained dormant from previous infections by an unknown mechanism. Lack of treatment options to clear hypnozoites and the ability to infect mosquitoes before disease symptoms present represent major challenges for control and eradication of vivax malaria. Compounding these challenges is the unique biology of and limited progress in development of experimental research tools, thereby hindering development of new drugs and vaccines. Renewed emphasis on vivax malaria research is beginning to make progress in overcoming some of these challenges.
Topics: Animals; Asymptomatic Infections; Humans; Malaria, Vivax; Plasmodium vivax
PubMed: 28490540
DOI: 10.1101/cshperspect.a025585 -
Parasitology International Dec 2021Plasmodium vivax is the most geographically widespread malaria parasite on the planet. This is largely because after mosquito transmission, P. vivax sporozoites can... (Review)
Review
Plasmodium vivax is the most geographically widespread malaria parasite on the planet. This is largely because after mosquito transmission, P. vivax sporozoites can invade hepatocytes and form latent liver stages known as hypnozoites. These persistent liver stages can activate weeks, months or even years after an infected individual suffers a primary clinical infection. Activation then leads to replication and liver stage schizont maturation that ultimately cause relapse of blood stage infection, disease, and onward transmission. Thus, the latent hypnozoite can lie in wait during times when onward transmission is unlikely due to conditions that do not favor the mosquito. For example, in temperate climates where mosquito prevalence is only seasonal. Furthermore, the elimination of hypnozoites is challenging since the hypnozoite reservoir is currently undetectable and not killed by most antimalarial drugs. Here, we review our current knowledge of the pre-erythrocytic stages of the malaria parasite - the sporozoite and liver stages, including the elusive and enigmatic hypnozoite. We focus on our understanding of sporozoite biology, the novel animal models that are available to study the hypnozoite and hypnozoite activation and the ongoing efforts to understand the biological makeup of the hypnozoite that allow for its persistence in the human host.
Topics: Animals; Disease Models, Animal; Liver; Malaria, Vivax; Plasmodium vivax; Sporozoites
PubMed: 34474178
DOI: 10.1016/j.parint.2021.102447 -
Trends in Parasitology May 2008Four Plasmodium species cause malaria in humans: Plasmodium vivax is the most widespread and results in pronounced morbidity. India (population >1 billion) is a major... (Review)
Review
Four Plasmodium species cause malaria in humans: Plasmodium vivax is the most widespread and results in pronounced morbidity. India (population >1 billion) is a major contributor to the burden of vivax malaria. With a resurgence in interest concerning the neglected burden of vivax malaria and the completion of the P. vivax genome, it is timely to review what is known concerning P. vivax in India. The P. vivax population is highly diverse in terms of relapse patterns, drug response and clinical profiles, and highly genetically variable according to studies of antigen genes, isoenzyme markers and microsatellites. The unique epidemiology of malaria in India, where P. vivax predominates over Plasmodium falciparum, renders this location ideal for studying the dynamics of co-infection.
Topics: Animals; Antimalarials; Drug Resistance; Genetic Variation; Humans; India; Malaria, Vivax; Plasmodium vivax
PubMed: 18403267
DOI: 10.1016/j.pt.2008.01.007 -
The Journal of Infectious Diseases May 2023
Topics: Humans; Plasmodium vivax; Mefloquine; Plasmodium cynomolgi; Antimalarials; Malaria, Vivax; Drug Resistance; Drug Resistance, Multiple
PubMed: 36478038
DOI: 10.1093/infdis/jiac470 -
Parasitology Nov 2018A curious aspect of the evolution of the hypnozoite theory of malarial relapse is its transmogrification from theory into 'fact', this being of historical, linguistic,... (Review)
Review
A curious aspect of the evolution of the hypnozoite theory of malarial relapse is its transmogrification from theory into 'fact', this being of historical, linguistic, scientific and sociological interest. As far as it goes, the hypnozoite explanation for relapse is almost certainly correct. I contend, however, that many of the genotypically homologous, non-reinfection, relapse-like Plasmodium vivax recurrences that researchers ascribe to hypnozoite activation are probably hypnozoite-independent. Indeed, some malariologists are starting to recognize that homologous P. vivax recurrences have most likely been overattributed to activation of hypnozoites. Hitherto identified, non-hypnozoite, possible plasmodial sources of recurrence that must be considered, besides circulating erythrocytic stages, include parasites in splenic dendritic cells, other cells in the spleen (in addition to infected erythrocytes there), bone marrow (importantly) and the skin. I argue that we need to take into account the possibility of a dual or multiple extra-vascular origin of P. vivax non-reinfection recurrences, not arbitrarily discount it. The existence of a P. vivax reservoir(s) is a topical subject and one of practical importance for malaria eradication. Pertinent drug-associated matters are also discussed, as is the dormancy-related significance of clues provided by blood-stage-induced malarial infection.
Topics: Animals; Antimalarials; Bone Marrow; Erythrocytes; Humans; Life Cycle Stages; Malaria, Vivax; Mice; Plasmodium vivax; Recurrence; Spleen
PubMed: 29564998
DOI: 10.1017/S003118201800032X -
Malaria Journal Jun 2020Vivax malaria is associated with significant morbidity and economic loss, and constitutes the bulk of malaria cases in large parts of Asia and South America as well as...
BACKGROUND
Vivax malaria is associated with significant morbidity and economic loss, and constitutes the bulk of malaria cases in large parts of Asia and South America as well as recent case reports in Africa. The widespread prevalence of vivax is a challenge to global malaria elimination programmes. Vivax malaria control is particularly challenged by existence of dormant liver stage forms that are difficult to treat and are responsible for multiple relapses, growing drug resistance to the asexual blood stages and host-genetic factors that preclude use of specific drugs like primaquine capable of targeting Plasmodium vivax liver stages. Despite an obligatory liver-stage in the Plasmodium life cycle, both the difficulty in obtaining P. vivax sporozoites and the limited availability of robust host cell models permissive to P. vivax infection are responsible for the limited knowledge of hypnozoite formation biology and relapse mechanisms, as well as the limited capability to do drug screening. Although India accounts for about half of vivax malaria cases world-wide, very little is known about the vivax liver stage forms in the context of Indian clinical isolates.
METHODS
To address this, methods were established to obtain infective P. vivax sporozoites from an endemic region in India and multiple assay platforms set up to detect and characterize vivax liver stage forms. Different hepatoma cell lines, including the widely used HCO4 cells, primary human hepatocytes as well as hepatocytes obtained from iPSC's generated from vivax patients and healthy donors were tested for infectivity with P. vivax sporozoites.
RESULTS
Both large and small forms of vivax liver stage are detected in these assays, although the infectivity obtained in these platforms are low.
CONCLUSIONS
This study provides a proof of concept for detecting liver stage P. vivax and provide the first characterization of P. vivax liver stage forms from an endemic region in India.
Topics: India; Life Cycle Stages; Liver; Malaria, Vivax; Plasmodium vivax
PubMed: 32571333
DOI: 10.1186/s12936-020-03284-8 -
PLoS Pathogens Feb 2020The absence of the Duffy protein at the surface of erythrocytes was considered for decades to confer full protection against Plasmodium vivax as this blood group is the... (Review)
Review
The absence of the Duffy protein at the surface of erythrocytes was considered for decades to confer full protection against Plasmodium vivax as this blood group is the receptor for the key parasite ligand P. vivax Duffy binding protein (PvDBP). However, it is now clear that the parasite is able to break through this protection and induce clinical malaria in Duffy-negative people, although the underlying mechanisms are still not understood. Here, we briefly review the evidence of Duffy-negative infections by P. vivax and summarize the current hypothesis at the basis of this invasion process. We discuss those in the perspective of malaria-elimination challenges, notably in African countries.
Topics: Africa; Antigens, Protozoan; Duffy Blood-Group System; Humans; Malaria, Vivax; Plasmodium vivax; Protozoan Proteins; Receptors, Cell Surface
PubMed: 32078643
DOI: 10.1371/journal.ppat.1008258 -
The Korean Journal of Parasitology Dec 2018Plasmodium vivax is more challenging to control and eliminate than P. falciparum due to its more asymptomatic infections with low parasite densities making diagnosis... (Review)
Review
Plasmodium vivax is more challenging to control and eliminate than P. falciparum due to its more asymptomatic infections with low parasite densities making diagnosis more difficult, in addition to its unique biological characteristics. The potential re-introduction of incidence cases, either through borders or via human migrations, is another major hurdle to sustained control and elimination. The Republic of Korea has experienced re-emergence of vivax malaria in 1993 but is one of the 32 malaria-eliminating countries to-date. Despite achieving successful nationwide control and elimination of vivax malaria, the evolutionary characteristics of vivax malaria isolates in the Republic of Korea have not been fully understood. In this review, we present an overview of the genetic variability of such isolates to increase understanding of the epidemiology, diversity, and dynamics of vivax populations in the Republic of Korea.
Topics: Communicable Diseases, Emerging; Epidemics; Genetic Variation; Humans; Malaria, Vivax; Plasmodium vivax; Republic of Korea
PubMed: 30630274
DOI: 10.3347/kjp.2018.56.6.545 -
Trends in Parasitology Feb 2018Malaria prevalence has declined in the past 10 years, especially outside of sub-Saharan Africa. However, the proportion of cases due to Plasmodium vivax is increasing,... (Review)
Review
Malaria prevalence has declined in the past 10 years, especially outside of sub-Saharan Africa. However, the proportion of cases due to Plasmodium vivax is increasing, accounting for up to 90-100% of the malaria burden in endemic regions. Nonetheless, investments in malaria research and control still prioritize Plasmodium falciparum while largely neglecting P. vivax. Specific biological features of P. vivax, particularly invasion of reticulocytes, occurrence of dormant liver forms of the parasite, and the potential for transmission of sexual-stage parasites prior to onset of clinical illness, promote its persistence and hinder development of research tools and interventions. This review discusses recent advances in P. vivax research, current knowledge of its unique biology, and proposes priorities for P. vivax research and control efforts.
Topics: Humans; Malaria, Vivax; Plasmodium vivax; Research
PubMed: 29153587
DOI: 10.1016/j.pt.2017.10.009