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Malaria Journal May 2008Plasmodium vivax is a major cause of malaria and is still primarily treated with chloroquine. Chloroquine inhibits the polymerization of haem to inert haemozoin. Free... (Comparative Study)
Comparative Study
BACKGROUND
Plasmodium vivax is a major cause of malaria and is still primarily treated with chloroquine. Chloroquine inhibits the polymerization of haem to inert haemozoin. Free haem monomers are thought to catalyze oxidative damage to the Plasmodium spp. trophozoite, the stage when haemoglobin catabolism is maximal. However preliminary in vitro observations on P. vivax clinical isolates suggest that only ring stages (early trophozoites) are sensitive to chloroquine. In this study, the stage specific action of chloroquine was investigated in synchronous cryopreserved isolates of P. vivax.
METHODS
The in vitro chloroquine sensitivity of paired ring and trophozoite stages from 11 cryopreserved P. vivax clinical isolates from Thailand and two Plasmodium falciparum clones (chloroquine resistant K1 and chloroquine sensitive FC27) was measured using a modified WHO microtest method and fluorometric SYBR Green I Assay. The time each stage was exposed to chloroquine treatment was controlled by washing the chloroquine off at 20 hours after the beginning of treatment.
RESULTS
Plasmodium vivax isolates added to the assay at ring stage had significantly lower median IC50s to chloroquine than the same isolates added at trophozoite stage (median IC50 12 nM vs 415 nM p < 0.01). Although only 36% (4/11) of the SYBR Green I assays for P. vivax were successful, both microscopy and SYBR Green I assays indicated that only P. vivax trophozoites were able to develop to schizonts at chloroquine concentrations above 100 nM.
CONCLUSION
Data from this study confirms the diminished sensitivity of P. vivax trophozoites to chloroquine, the stage thought to be the target of this drug. These results raise important questions about the pharmacodynamic action of chloroquine, and highlight a fundamental difference in the activity of chloroquine between P. vivax and P. falciparum.
Topics: Animals; Antimalarials; Benzothiazoles; Chloroquine; Diamines; Drug Resistance; Humans; Inhibitory Concentration 50; Microscopy; Organic Chemicals; Parasitic Sensitivity Tests; Plasmodium falciparum; Plasmodium vivax; Quinolines; Trophozoites
PubMed: 18505560
DOI: 10.1186/1475-2875-7-94 -
The Korean Journal of Parasitology Oct 2009Plasmodium vivax, a protozoan malaria parasite of humans, represents a major public health concern in the Republic of Korea (= South Korea). However, little is known... (Review)
Review
Plasmodium vivax, a protozoan malaria parasite of humans, represents a major public health concern in the Republic of Korea (= South Korea). However, little is known about the genetic properties and population structures of the P. vivax isolates circulating in South Korea. This article reviews known polymorphic genetic markers in South Korean isolates of P. vivax and briefly summarizes the current issues surrounding the gene and population structures of this parasite. The critical genetic characteristics of major antigens of the parasite, such as circumsporozoite protein (CSP), merozoite surface protein 1 (MSP-1) and MSP-3, Duffy binding protein (DBP), apical membrane antigen 1 (AMA-1), and GAM-1, are also discussed.
Topics: Amino Acid Sequence; Animals; Antigens, Protozoan; Base Sequence; Humans; Malaria, Vivax; Molecular Sequence Data; Plasmodium vivax; Polymorphism, Genetic; Protozoan Proteins; Republic of Korea; Sequence Alignment
PubMed: 19885335
DOI: 10.3347/kjp.2009.47.S.S51 -
Potential immune mechanisms associated with anemia in Plasmodium vivax malaria: a puzzling question.Infection and Immunity Oct 2014The pathogenesis of malaria is complex, generating a broad spectrum of clinical manifestations. One of the major complications and concerns in malaria is anemia, which... (Review)
Review
The pathogenesis of malaria is complex, generating a broad spectrum of clinical manifestations. One of the major complications and concerns in malaria is anemia, which is responsible for considerable morbidity in the developing world, especially in children and pregnant women. Despite its enormous health importance, the immunological mechanisms involved in malaria-induced anemia remain incompletely understood. Plasmodium vivax, one of the causative agents of human malaria, is known to induce a strong inflammatory response with a robust production of immune effectors, including cytokines and antibodies. Therefore, it is possible that the extent of the immune response not only may facilitate the parasite killing but also may provoke severe illness, including anemia. In this review, we consider potential immune effectors and their possible involvement in generating this clinical outcome during P. vivax infections.
Topics: Anemia; Humans; Malaria, Vivax; Plasmodium vivax
PubMed: 25092911
DOI: 10.1128/IAI.01972-14 -
ACS Infectious Diseases Apr 2018To develop new drugs and vaccines for malaria elimination, it will be necessary to discover biological interventions, including small molecules that act against...
To develop new drugs and vaccines for malaria elimination, it will be necessary to discover biological interventions, including small molecules that act against Plasmodium vivax exoerythrocytic forms. However, a robust in vitro culture system for P. vivax is still lacking. Thus, to study exoerythrocytic forms, researchers must have simultaneous access to fresh, temperature-controlled patient blood samples, as well as an anopheline mosquito colony. In addition, researchers must rely on native mosquito species to avoid introducing a potentially dangerous invasive species into a malaria-endemic region. Here, we report an in vitro culture system carried out on site in a malaria-endemic region for liver stage parasites of P. vivax sporozoites obtained from An. darlingi, the main malaria vector in the Americas. P. vivax sporozoites were obtained by dissection of salivary glands from infected An. darlingi mosquitoes and purified by Accudenz density gradient centrifugation. HC04 liver cells were exposed to P. vivax sporozoites and cultured up to 9 days. To overcome low P. vivax patient parasitemias, potentially lower mosquito vectorial capacity, and humid, nonsterile environmental conditions, a new antibiotic cocktail was included in tissue culture to prevent contamination. Culturing conditions supported exoerythrocytic (EEF) P. vivax liver stage growth up to 9 days and allowed for maturation into intrahepatocyte merosomes. Some of the identified small forms were resistant to atovaquone (1 μM) but sensitive to the phosphatidylinositol 4-kinase inhibitor, KDU691 (1 μM). This study reports a field-accessible EEF production process for drug discovery in a malaria-endemic site in which viable P. vivax sporozoites are used for drug studies using hepatocyte infection. Our data demonstrate that the development of meaningful, field-based resources for P. vivax liver stage drug screening and liver stage human malaria experimentation in the Amazon region is feasible.
Topics: Animals; Anopheles; Cell Culture Techniques; Cell Line; Hepatocytes; Humans; Parasitology; Peru; Plasmodium vivax; Salivary Glands
PubMed: 29542317
DOI: 10.1021/acsinfecdis.7b00198 -
Research in Immunology Oct 1991
Review
Topics: Animals; Host-Parasite Interactions; Humans; Immunity, Active; Malaria, Vivax; Plasmodium vivax; Recurrence; Reticulocytes
PubMed: 1817289
DOI: 10.1016/0923-2494(91)90140-e -
Antimicrobial Agents and Chemotherapy 2014Data on chloroquine (CQ)-resistant Plasmodium vivax in Latin America is limited, even with the current research efforts to sustain an efficient malaria control program...
Data on chloroquine (CQ)-resistant Plasmodium vivax in Latin America is limited, even with the current research efforts to sustain an efficient malaria control program in all these countries where P. vivax is endemic and where malaria still is a major public health issue. This study estimated in vivo CQ resistance in patients with uncomplicated P. vivax malaria, with use of CQ and primaquine simultaneously, in the Brazilian Amazon. Of a total of 135 enrolled subjects who accomplished the 28-day follow-up, parasitological failure was observed in 7 (5.2%) patients, in whom plasma CQ and desethylchloroquine (DCQ) concentrations were above 100 ng/dl. Univariate analysis showed that previous exposure to malaria and a higher initial mean parasitemia were associated with resistance but not with age or gender. In the multivariate analysis, only high initial parasitemia remained significant. Hemoglobin levels were similar at the beginning of the follow-up and were not associated with parasitemia. However, at day 3 and day 7, hemoglobin levels were significantly lower in patients presenting CQ resistance. The P. vivax dhfr (pvdhfr), pvmrp1, pvmdr1, and pvdhps gene mutations were not related to resistance in this small sample. P. vivax CQ resistance is already a problem in the Brazilian Amazon, which could be to some extent associated with the simultaneous report of anemia triggered by this parasite, a common complication of the disease in most of the areas of endemicity.
Topics: Anemia; Antimalarials; Brazil; Chloroquine; Drug Resistance; Female; Humans; Malaria, Vivax; Male; Plasmodium vivax
PubMed: 24165179
DOI: 10.1128/AAC.02279-12 -
International Journal For Parasitology Jan 2016The invasion of CD71+ reticulocytes by Plasmodium vivax is a crucial yet poorly characterised event. The application of flow cytometry to ex vivo invasion assays...
The invasion of CD71+ reticulocytes by Plasmodium vivax is a crucial yet poorly characterised event. The application of flow cytometry to ex vivo invasion assays promises to facilitate the quantitative analysis of P. vivax reticulocyte invasion. However, current protocols suffer from a low level of sensitivity due to the absence of a particular design for P. vivax cell tropism. Importantly, merozoite invasion into contaminating red blood cells from the schizont inoculum (auto-invasion) may confound the analysis. Here we present a stable two-color flow cytometry assay for the accurate quantification of P. vivax merozoite invasion into intracellularly labelled CD71+ reticulocytes. Various enzymatic treatments, antibodies and invasion inhibitory molecules were used to successfully demonstrate the utility of this method. Fluorescent labelling of red blood cells did not affect the invasion and early intra-erythrocytic development of P. vivax. Importantly, this portable field assay allows for the economic usage of limited biological material (parasites and reticulocytes) and the intracellular labeling of the target cells reduces the need for highly purified schizont inoculums. This assay will facilitate the study of P. vivax merozoite biology and the testing of vaccine candidates against vivax malaria.
Topics: Antigens, CD; Bacteriological Techniques; Base Sequence; Erythrocytes; Flow Cytometry; High-Throughput Screening Assays; Humans; Malaria, Vivax; Plasmodium vivax; Receptors, Transferrin; Reticulocytes
PubMed: 26385436
DOI: 10.1016/j.ijpara.2015.08.003 -
Advances in Parasitology 2013
Topics: Animals; Disease Susceptibility; Genomics; Humans; Malaria Vaccines; Malaria, Vivax; Plasmodium vivax
PubMed: 23384626
DOI: 10.1016/B978-0-12-407826-0.00050-3 -
The Korean Journal of Parasitology Jun 2011The use of sulfadoxine and pyrimethamine (SP) for treatment of vivax malaria is uncommon in most malarious areas, but Plasmodium vivax isolates are exposed to SP because...
The use of sulfadoxine and pyrimethamine (SP) for treatment of vivax malaria is uncommon in most malarious areas, but Plasmodium vivax isolates are exposed to SP because of mixed infections with other Plasmodium species. As P. vivax is the most prevalent species of human malaria parasites in Iran, monitoring of resistance of the parasite against the drug is necessary. In the present study, 50 blood samples of symptomatic patients were collected from 4 separated geographical regions of south-east Iran. Point mutations at residues 57, 58, 61, and 117 were detected by the PCR-RFLP method. Polymorphism at positions 58R, 117N, and 117T of P. vivax dihydrofolate reductase (Pvdhfr) gene has been found in 12%, 34%, and 2% of isolates, respectively. Mutation at residues F57 and T61 was not detected. Five distinct haplotypes of the Pvdhfr gene were demonstrated. The 2 most prevalent haplotypes were F57S58T61S117 (62%) and F57S58T61N117 (24%). Haplotypes with 3 and 4 point mutations were not found. The present study suggested that P. vivax in Iran is under the pressure of SP and the sensitivity level of the parasite to SP is diminishing and this fact must be considered in development of malaria control programs.
Topics: Amino Acid Substitution; Antimalarials; Drug Combinations; Drug Resistance; Haplotypes; Humans; Iran; Malaria, Vivax; Mutation, Missense; Plasmodium vivax; Polymorphism, Genetic; Pyrimethamine; Sulfadoxine; Tetrahydrofolate Dehydrogenase
PubMed: 21738267
DOI: 10.3347/kjp.2011.49.2.125 -
Malaria Journal Dec 2012Plasmodium vivax has traditionally been considered virtually absent from Western and Central Africa, due to the absence of the Duffy blood group in most of the...
BACKGROUND
Plasmodium vivax has traditionally been considered virtually absent from Western and Central Africa, due to the absence of the Duffy blood group in most of the population living in these areas. Recent reports, however, suggest the circulation of P. vivax in sub-Saharan Africa.
METHODS
Giemsa/Field-stained smears from febrile patients recruited in five different cities (Goundam, Tombouctou, Gao, Bourem and Kidal) pertaining to three regions from Northern Mali were examined. Nested-PCR and DNA sequence analyses of selected samples were performed to fully confirm the presence of P. vivax infections.
RESULTS
Results demonstrated the presence of P. vivax infections in close to 30% of the cases as detected by Giemsa/Field-stained smears and nested-PCR and DNA-sequence analyses of selected samples unequivocally confirmed the presence of P. vivax.
CONCLUSIONS
The diagnostics of this human malaria parasite should be taken into account in the context of malaria control and elimination efforts, not only in Mali, but also in sub-Saharan Africa.
Topics: DNA, Protozoan; Duffy Blood-Group System; Humans; Malaria, Vivax; Mali; Molecular Epidemiology; Phylogeny; Plasmodium vivax; Polymerase Chain Reaction; RNA, Protozoan
PubMed: 23217064
DOI: 10.1186/1475-2875-11-405