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The American Journal of Tropical... Sep 2023
Topics: Humans; Plasmodium vivax; Africa South of the Sahara
PubMed: 37640286
DOI: 10.4269/ajtmh.23-0523 -
FEMS Microbiology Reviews Jul 2022
Topics: Plasmodium falciparum; Plasmodium vivax
PubMed: 35767876
DOI: 10.1093/femsre/fuac015 -
The Journal of Clinical Investigation Oct 2023BACKGROUNDThe biology of Plasmodium vivax is markedly different from that of P. falciparum; how this shapes the immune response to infection remains unclear. To address...
BACKGROUNDThe biology of Plasmodium vivax is markedly different from that of P. falciparum; how this shapes the immune response to infection remains unclear. To address this shortfall, we inoculated human volunteers with a clonal field isolate of P. vivax and tracked their response through infection and convalescence.METHODSParticipants were injected intravenously with blood-stage parasites and infection dynamics were tracked in real time by quantitative PCR. Whole blood samples were used for high dimensional protein analysis, RNA sequencing, and cytometry by time of flight, and temporal changes in the host response to P. vivax were quantified by linear regression. Comparative analyses with P. falciparum were then undertaken using analogous data sets derived from prior controlled human malaria infection studies.RESULTSP. vivax rapidly induced a type I inflammatory response that coincided with hallmark features of clinical malaria. This acute-phase response shared remarkable overlap with that induced by P. falciparum but was significantly elevated (at RNA and protein levels), leading to an increased incidence of pyrexia. In contrast, T cell activation and terminal differentiation were significantly increased in volunteers infected with P. falciparum. Heterogeneous CD4+ T cells were found to dominate this adaptive response and phenotypic analysis revealed unexpected features normally associated with cytotoxicity and autoinflammatory disease.CONCLUSIONP. vivax triggers increased systemic interferon signaling (cf P. falciparum), which likely explains its reduced pyrogenic threshold. In contrast, P. falciparum drives T cell activation far in excess of P. vivax, which may partially explain why falciparum malaria more frequently causes severe disease.TRIAL REGISTRATIONClinicalTrials.gov NCT03797989.FUNDINGThe European Union's Horizon 2020 Research and Innovation programme, the Wellcome Trust, and the Royal Society.
Topics: Humans; Plasmodium vivax; Plasmodium falciparum; Malaria, Vivax; Malaria, Falciparum; Malaria; Lymphocyte Activation
PubMed: 37616070
DOI: 10.1172/JCI152463 -
The Indian Journal of Medical Research Jun 2021Plasmodium vivax (P. vivax) malaria is a major problem in various countries such as America, Southeast Asia, Africa and the Eastern Mediterranean. The major barrier in... (Review)
Review
Plasmodium vivax (P. vivax) malaria is a major problem in various countries such as America, Southeast Asia, Africa and the Eastern Mediterranean. The major barrier in controlling P. vivax malaria is its ability to remain in the liver as a hypnozoite form which is responsible for relapse of P. vivax malaria; hence it is necessary to target both the blood (schizont) as well as the liver (hypnozoite) stages of P. vivax to prevent its relapse. A number of factors limit the use of primaquine (PQ), the currently available therapy for P. vivax (hypnozoite stage), such as haemolysis in glucose-6-phosphate dehydrogenase-deficient patients and being contraindicated in pregnant women. Another problem associated with PQ is the poor adherence rate to the 14-day treatment regimen. Single-dose tafenoquine (TQ), an 8-aminoquinoline, has recently been approved by the U.S. FDA for the treatment of P. vivax malaria along with a blood schizonticidal. TQ is active against all stages of P. vivax lifecycle. In published studies, TQ is considered a better alternative to PQ in terms of adherence, but there are some concerns regarding its safety, efficacy and study designs of trials conducted on TQ. In this context, this review, discusses the potential safety concerns, efficacy data, summary and an appraisal of findings of the important published trials of TQ.
Topics: Aminoquinolines; Antimalarials; Female; Humans; Malaria, Vivax; Plasmodium vivax; Pregnancy; Primaquine; Recurrence
PubMed: 35662084
DOI: 10.4103/ijmr.IJMR_1167_19 -
Frontiers in Cellular and Infection... 2021After a century of constant failure to produce an culture of the most widespread human malaria parasite , recent advances have highlighted the difficulties to provide... (Review)
Review
After a century of constant failure to produce an culture of the most widespread human malaria parasite , recent advances have highlighted the difficulties to provide this parasite with a healthy host cell to invade, develop, and multiply under conditions. The actual level of understanding of the heterogeneous populations of cells-framed under the name 'reticulocytes'-and, importantly, their adequate progression from very immature reticulocytes to normocytes (mature erythrocytes) is far from complete. The volatility of its individual stability may suggest the reticulocyte as a delusory cell, particularly to be used for stable culture purposes. Yet, the recent relevance gained by a specific subset of highly immature reticulocytes has brought some hope. Very immature reticulocytes are characterized by a peculiar membrane harboring a plethora of molecules potentially involved in invasion and by an intracellular complexity dynamically changing upon its quick maturation into normocytes. We analyze the potentialities offered by this youngest reticulocyte subsets as an ideal host cell for .
Topics: Erythrocytes; Humans; Malaria, Vivax; Plasmodium vivax; Reticulocytes
PubMed: 34055670
DOI: 10.3389/fcimb.2021.675156 -
Journal of Mathematical Biology Dec 2023A characteristic of malaria in all its forms is the potential for superinfection (that is, multiple concurrent blood-stage infections). An additional characteristic of...
A characteristic of malaria in all its forms is the potential for superinfection (that is, multiple concurrent blood-stage infections). An additional characteristic of Plasmodium vivax malaria is a reservoir of latent parasites (hypnozoites) within the host liver, which activate to cause (blood-stage) relapses. Here, we present a model of hypnozoite accrual and superinfection for P. vivax. To couple host and vector dynamics for a homogeneously-mixing population, we construct a density-dependent Markov population process with countably many types, for which disease extinction is shown to occur almost surely. We also establish a functional law of large numbers, taking the form of an infinite-dimensional system of ordinary differential equations that can also be recovered by coupling expected host and vector dynamics (i.e. a hybrid approximation) or through a standard compartment modelling approach. Recognising that the subset of these equations that model the infection status of the human hosts has precisely the same form as the Kolmogorov forward equations for a Markovian network of infinite server queues with an inhomogeneous batch arrival process, we use physical insight into the evolution of the latter process to write down a time-dependent multivariate generating function for the solution. We use this characterisation to collapse the infinite-compartment model into a single integrodifferential equation (IDE) governing the intensity of mosquito-to-human transmission. Through a steady state analysis, we recover a threshold phenomenon for this IDE in terms of a parameter [Formula: see text] expressible in terms of the primitives of the model, with the disease-free equilibrium shown to be uniformly asymptotically stable if [Formula: see text] and an endemic equilibrium solution emerging if [Formula: see text]. Our work provides a theoretical basis to explore the epidemiology of P. vivax, and introduces a strategy for constructing tractable population-level models of malarial superinfection that can be generalised to allow for greater biological realism in a number of directions.
Topics: Animals; Humans; Plasmodium vivax; Superinfection; Mosquito Vectors; Malaria, Vivax; Malaria
PubMed: 38040981
DOI: 10.1007/s00285-023-02014-3 -
Parasitology Nov 2023Of the 5 human malarial parasites, and are the most prevalent species globally, while and are less prevalent and typically occur as mixed-infections. , previously... (Review)
Review
Of the 5 human malarial parasites, and are the most prevalent species globally, while and are less prevalent and typically occur as mixed-infections. , previously considered a non-human primate (NHP) infecting species, is now a cause of human malaria in Malaysia. The other NHP species, , , , , and cause malaria in primates, which are mainly reported in southeast Asia and South America. The non- NHP species also emerged and were found to cross-transmit from their natural hosts (NHP) – to human hosts in natural settings. Here we have reviewed and collated data from the literature on the NHPs-to-human-transmitting species. It was observed that the natural transmission of these NHP parasites to humans had been reported from 2010 onwards. This study shows that: (1) the majority of the non- NHP mixed species infecting human cases were from Yala province of Thailand; (2) mono/mixed infections with other human-infecting species were prevalent in Malaysia and Thailand and (3) and were found in Central and South America.
Topics: Animals; Humans; Malaria; Plasmodium knowlesi; Primates; Asia, Southeastern; Plasmodium vivax
PubMed: 37929579
DOI: 10.1017/S003118202300077X -
PLoS Neglected Tropical Diseases Mar 2020More than 200 million malaria clinical cases are reported each year due to Plasmodium vivax, the most widespread Plasmodium species in the world. This species has been...
More than 200 million malaria clinical cases are reported each year due to Plasmodium vivax, the most widespread Plasmodium species in the world. This species has been neglected and understudied for a long time, due to its lower mortality in comparison with Plasmodium falciparum. A renewed interest has emerged in the past decade with the discovery of antimalarial drug resistance and of severe and even fatal human cases. Nonetheless, today there are still significant gaps in our understanding of the population genetics and evolutionary history of P. vivax, particularly because of a lack of genetic data from Africa. To address these gaps, we genotyped 14 microsatellite loci in 834 samples obtained from 28 locations in 20 countries from around the world. We discuss the worldwide population genetic structure and diversity and the evolutionary origin of P. vivax in the world and its introduction into the Americas. This study demonstrates the importance of conducting genome-wide analyses of P. vivax in order to unravel its complex evolutionary history.
Topics: Genetic Variation; Genotype; Genotyping Techniques; Global Health; Humans; Malaria, Vivax; Plasmodium vivax
PubMed: 32150544
DOI: 10.1371/journal.pntd.0008072 -
Nature Communications Sep 2023Drugs targeting multiple stages of the Plasmodium vivax life cycle are needed to reduce the health and economic burdens caused by malaria worldwide....
Drugs targeting multiple stages of the Plasmodium vivax life cycle are needed to reduce the health and economic burdens caused by malaria worldwide. N-myristoyltransferase (NMT) is an essential eukaryotic enzyme and a validated drug target for combating malaria. However, previous PvNMT inhibitors have failed due to their low selectivity over human NMTs. Herein, we apply a structure-guided hybridization approach combining chemical moieties of previously reported NMT inhibitors to develop the next generation of PvNMT inhibitors. A high-resolution crystal structure of PvNMT bound to a representative selective hybrid compound reveals a unique binding site architecture that includes a selective conformation of a key tyrosine residue. The hybridized compounds significantly decrease P. falciparum blood-stage parasite load and consistently exhibit dose-dependent inhibition of P. vivax liver stage schizonts and hypnozoites. Our data demonstrate that hybridized NMT inhibitors can be multistage antimalarials, targeting dormant and developing forms of liver and blood stage.
Topics: Humans; Animals; Plasmodium vivax; Schizonts; Liver; Acyltransferases; Malaria, Vivax; Malaria, Falciparum
PubMed: 37669940
DOI: 10.1038/s41467-023-41119-7 -
Parasitology International Apr 2022Plasmodium vivax is the most widespread causative agent of human malaria in the world. Despite the ongoing implementation of malaria control programs, the rate of case... (Review)
Review
Plasmodium vivax is the most widespread causative agent of human malaria in the world. Despite the ongoing implementation of malaria control programs, the rate of case reduction has declined over the last 5 years. Hence, surveillance of malaria transmission should be in place to identify and monitor areas that require intensified malaria control interventions. Serological tools may offer additional insights into transmission intensity over parasite and entomological measures, especially as transmission levels decline. Antibodies can be detected in the host system for months to even years after parasite infections have been cleared from the blood, enabling malaria exposure history to be captured. Because the Plasmodium parasite expresses more than 5000 proteins, it is important to a) understand antibody longevity following infection and b) measure antibodies to more than one antigen in order to accurately inform on the exposure and/or immune status of populations. This review summarises current practices for surveillance of P. vivax malaria, the current state of research into serological exposure markers and their potential role for accelerating malaria elimination, and discusses further studies that need to be undertaken to see such technology implemented in malaria-endemic areas.
Topics: Antibodies, Protozoan; Fluorescent Antibody Technique; Humans; Malaria, Vivax; Plasmodium vivax
PubMed: 34728377
DOI: 10.1016/j.parint.2021.102492