scholarly journals Prospective Study of Plasmodium vivax Malaria Recurrence after Radical Treatment with a Chloroquine-Primaquine Standard Regimen in Turbo, Colombia

2016 ◽  
Vol 60 (8) ◽  
pp. 4610-4619 ◽  
Author(s):  
Lina Zuluaga-Idárraga ◽  
Silvia Blair ◽  
Sheila Akinyi Okoth ◽  
Venkatachalam Udhayakumar ◽  
Paula L. Marcet ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Standard Regimen ◽  
High Genetic Diversity ◽  
Content Type ◽  
Longitudinal Observational Study ◽  
High Incidence ◽  
Plasmodium Vivax Malaria ◽  
Previous Infection ◽  
First Recurrence ◽  
Infection Episode

ABSTRACTPlasmodium vivaxrecurrences help maintain malaria transmission. They are caused by recrudescence, reinfection, or relapse, which are not easily differentiated. A longitudinal observational study took place in Turbo municipality, Colombia. Participants with uncomplicatedP. vivaxinfection received supervised treatment concomitantly with 25 mg/kg chloroquine and 0.25 mg/kg/day primaquine for 14 days. Incidence of recurrence was assessed over 180 days. Samples were genotyped, and origins of recurrences were established. A total of 134 participants were enrolled between February 2012 and July 2013, and 87 were followed for 180 days, during which 29 recurrences were detected. The cumulative incidence of first recurrence was 24.1% (21/87) (95% confidence interval [CI], 14.6 to 33.7%), and 86% (18/21) of these events occurred between days 51 and 110. High genetic diversity ofP. vivaxstrains was found, and 12.5% (16/128) of the infections were polyclonal. Among detected recurrences, 93.1% (27/29) of strains were genotyped as genetically identical to the strain from the previous infection episode, and 65.5% (19/29) of infections were classified as relapses. Our results indicate that there is a high incidence ofP. vivaxmalaria recurrence after treatment in Turbo municipality, Colombia, and that a large majority of these episodes are likely relapses from the previous infection. We attribute this to the primaquine regimen currently used in Colombia, which may be insufficient to eliminate hypnozoites.

scholarly journals Pharmacokinetics of Amodiaquine and Desethylamodiaquine in Pregnant and Postpartum Women with Plasmodium vivax Malaria

2011 ◽  
Vol 55 (9) ◽  
pp. 4338-4342 ◽  
Author(s):  
Marcus J. Rijken ◽  
Rose McGready ◽  
Vincent Jullien ◽  
Joel Tarning ◽  
Niklas Lindegardh ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Dosing Regimen ◽  
Noncompartmental Analysis ◽  
Time Data ◽  
Content Type ◽  
Concentration Time ◽  
Chromatography Tandem Mass Spectrometry ◽  
Pharmacokinetic Properties ◽  
Plasmodium Vivax Malaria ◽  
Liquid Chromatography Tandem Mass

ABSTRACTIn order to study the pharmacokinetic properties of amodiaquine and desethylamodiaquine during pregnancy, 24 pregnant women in the second and third trimesters of pregnancy and withPlasmodium vivaxmalaria were treated with amodiaquine (10 mg/kg of body weight/day) for 3 days. The same women were studied again at 3 months postpartum. Plasma was analyzed for amodiaquine and desethylamodiaquine by use of a liquid chromatography-tandem mass spectrometry method. Individual concentration-time data were evaluated using noncompartmental analysis. There were no clinically relevant differences in the pharmacokinetics of amodiaquine and desethylamodiaquine between pregnant (n= 24) and postpartum (n= 18) women. The results suggest that the current amodiaquine dosing regimen is adequate for the treatment ofP. vivaxinfections during pregnancy.

scholarly journals Antibodies to a Single, Conserved Epitope in Anopheles APN1 Inhibit Universal Transmission of Plasmodium falciparum and Plasmodium vivax Malaria

2013 ◽  
Vol 82 (2) ◽  
pp. 818-829 ◽  
Author(s):  
Jennifer S. Armistead ◽  
Isabelle Morlais ◽  
Derrick K. Mathias ◽  
Juliette G. Jardim ◽  
Jaimy Joy ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Plasmodium Vivax ◽  
Content Type ◽  
Block Transmission ◽  
Antibody Recognition ◽  
Protective Epitope ◽  
Product Profile ◽  
Plasmodium Vivax Malaria ◽  
Transmission Blocking Vaccines ◽  
Conserved Epitope

ABSTRACTMalaria transmission-blocking vaccines (TBVs) represent a promising approach for the elimination and eradication of this disease. AnAPN1 is a lead TBV candidate that targets a surface antigen on the midgut of the obligate vector of thePlasmodiumparasite, theAnophelesmosquito. In this study, we demonstrated that antibodies targeting AnAPN1 block transmission ofPlasmodium falciparumandPlasmodium vivaxacross distantly related anopheline species in countries to which malaria is endemic. Using a biochemical and immunological approach, we determined that the mechanism of action for this phenomenon stems from antibody recognition of a single protective epitope on AnAPN1, which we found to be immunogenic in murine and nonhuman primate models and highly conserved among anophelines. These data indicate that AnAPN1 meets the established target product profile for TBVs and suggest a potential key role for an AnAPN1-based panmalaria TBV in the effort to eradicate malaria.

scholarly journals Population Pharmacokinetic and Pharmacodynamic Modeling of Amodiaquine and Desethylamodiaquine in Women with Plasmodium vivax Malaria during and after Pregnancy

2012 ◽  
Vol 56 (11) ◽  
pp. 5764-5773 ◽  
Author(s):  
Joel Tarning ◽  
Palang Chotsiri ◽  
Vincent Jullien ◽  
Marcus J. Rijken ◽  
Martin Bergstrand ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Plasmodium Vivax ◽  
Plasma Concentrations ◽  
Inhibitory Effect ◽  
Biologically Active ◽  
Pharmacodynamic Modeling ◽  
Population Pharmacokinetic ◽  
Content Type ◽  
Plasmodium Vivax Malaria

ABSTRACTAmodiaquine is effective for the treatment ofPlasmodium vivaxmalaria, but there is little information on the pharmacokinetic and pharmacodynamic properties of amodiaquine in pregnant women with malaria. This study evaluated the population pharmacokinetic and pharmacodynamic properties of amodiaquine and its biologically active metabolite, desethylamodiaquine, in pregnant women withP. vivaxinfection and again after delivery. Twenty-seven pregnant women infected withP. vivaxmalaria on the Thai-Myanmar border were treated with amodiaquine monotherapy (10 mg/kg/day) once daily for 3 days. Nineteen women, with and withoutP. vivaxinfections, returned to receive the same amodiaquine dose postpartum. Nonlinear mixed-effects modeling was used to evaluate the population pharmacokinetic and pharmacodynamic properties of amodiaquine and desethylamodiaquine. Amodiaquine plasma concentrations were described accurately by lagged first-order absorption with a two-compartment disposition model followed by a three-compartment disposition of desethylamodiaquine under the assumption of completein vivoconversion. Body weight was implemented as an allometric function on all clearance and volume parameters. Amodiaquine clearance decreased linearly with age, and absorption lag time was reduced in pregnant patients. Recurrent malaria infections in pregnant women were modeled with a time-to-event model consisting of a constant-hazard function with an inhibitory effect of desethylamodiaquine. Amodiaquine treatment reduced the risk of recurrent infections from 22.2% to 7.4% at day 35. In conclusion, pregnancy did not have a clinically relevant impact on the pharmacokinetic properties of amodiaquine or desethylamodiaquine. No dose adjustments are required in pregnancy.

scholarly journals Efficacy of a Plasmodium vivax Malaria Vaccine Using ChAd63 and Modified Vaccinia Ankara Expressing Thrombospondin-Related Anonymous Protein as Assessed with Transgenic Plasmodium berghei Parasites

2013 ◽  
Vol 82 (3) ◽  
pp. 1277-1286 ◽  
Author(s):  
Karolis Bauza ◽  
Tomas Malinauskas ◽  
Claudia Pfander ◽  
Burcu Anar ◽  
E. Yvonne Jones ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Plasmodium Berghei ◽  
Malaria Vaccine ◽  
Protective Mechanisms ◽  
Content Type ◽  
Cell Responses ◽  
Malaria Vaccines ◽  
Modified Vaccinia Virus Ankara ◽  
Plasmodium Vivax Malaria ◽  
Antibody Titers

ABSTRACTPlasmodium vivaxis the world's most widely distributed malaria parasite and a potential cause of morbidity and mortality for approximately 2.85 billion people living mainly in Southeast Asia and Latin America. Despite this dramatic burden, very few vaccines have been assessed in humans. The clinically relevant vectors modified vaccinia virus Ankara (MVA) and the chimpanzee adenovirus ChAd63 are promising delivery systems for malaria vaccines due to their safety profiles and proven ability to induce protective immune responses againstPlasmodium falciparumthrombospondin-related anonymous protein (TRAP) in clinical trials. Here, we describe the development of new recombinant ChAd63 and MVA vectors expressingP. vivaxTRAP (PvTRAP) and show their ability to induce high antibody titers and T cell responses in mice. In addition, we report a novel way of assessing the efficacy of new candidate vaccines againstP. vivaxusing a fully infectious transgenicPlasmodium bergheiparasite expressingP. vivaxTRAP to allow studies of vaccine efficacy and protective mechanisms in rodents. Using this model, we found that both CD8+T cells and antibodies mediated protection against malaria using virus-vectored vaccines. Our data indicate that ChAd63 and MVA expressing PvTRAP are good preerythrocytic-stage vaccine candidates with potential for future clinical application.

scholarly journals Potential Immune Mechanisms Associated with Anemia in Plasmodium vivax Malaria: a Puzzling Question

2014 ◽  
Vol 82 (10) ◽  
pp. 3990-4000 ◽  
Author(s):  
Thiago Castro-Gomes ◽  
Luiza C. Mourão ◽  
Gisely C. Melo ◽  
Wuelton M. Monteiro ◽  
Marcus V. G. Lacerda ◽  
...  
Keyword(s):  
Immune Response ◽  
Plasmodium Vivax ◽  
Clinical Manifestations ◽  
Severe Illness ◽  
Content Type ◽  
Immunological Mechanisms ◽  
Plasmodium Vivax Malaria ◽  
Causative Agents ◽  
Strong Inflammatory Response ◽  
Considerable Morbidity

ABSTRACTThe 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 duringP. vivaxinfections.

scholarly journals Frequent Spread of Plasmodium vivax Malaria Maintains High Genetic Diversity at the Myanmar-China Border, Without Distance and Landscape Barriers

2017 ◽  
Vol 216 (10) ◽  
pp. 1254-1263 ◽  
Author(s):  
Eugenia Lo ◽  
Nancy Lam ◽  
Elizabeth Hemming-Schroeder ◽  
Jennifer Nguyen ◽  
Guofa Zhou ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Plasmodium Vivax ◽  
Vivax Malaria ◽  
High Genetic Diversity ◽  
Plasmodium Vivax Malaria

scholarly journals Monitoring the Efficacy of Chloroquine-Primaquine Therapy for Uncomplicated Plasmodium vivax Malaria in the Main Transmission Hot Spot of Brazil

2019 ◽  
Vol 63 (5) ◽  
Author(s):  
Simone Ladeia-Andrade ◽  
Maria José Menezes ◽  
Taís Nóbrega de Sousa ◽  
Ana Carolina R. Silvino ◽  
Jaques F. de Carvalho ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Vivax Malaria ◽  
Amazon Basin ◽  
Ex Vivo ◽  
Hot Spot ◽  
Radical Cure ◽  
Content Type ◽  
Plasmodium Vivax Malaria

ABSTRACT Emerging Plasmodium vivax resistance to chloroquine (CQ) may undermine malaria elimination efforts in South America. CQ-resistant P. vivax has been found in the major port city of Manaus but not in the main malaria hot spots across the Amazon Basin of Brazil, where CQ is routinely coadministered with primaquine (PQ) for radical cure of vivax malaria. Here we randomly assigned 204 uncomplicated vivax malaria patients from Juruá Valley, northwestern Brazil, to receive either sequential (arm 1) or concomitant (arm 2) CQ-PQ treatment. Because PQ may synergize the blood schizontocidal effect of CQ and mask low-level CQ resistance, we monitored CQ-only efficacy in arm 1 subjects, who had PQ administered only at the end of the 28-day follow-up. We found adequate clinical and parasitological responses in all subjects assigned to arm 2. However, 2.2% of arm 1 patients had microscopy-detected parasite recrudescences at day 28. When PCR-detected parasitemias at day 28 were considered, response rates decreased to 92.1% and 98.8% in arms 1 and 2, respectively. Therapeutic CQ levels were documented in 6 of 8 recurrences, consistent with true CQ resistance in vivo. In contrast, ex vivo assays provided no evidence of CQ resistance in 49 local P. vivax isolates analyzed. CQ-PQ coadministration was not found to potentiate the antirelapse efficacy of PQ over 180 days of surveillance; however, we suggest that larger studies are needed to examine whether and how CQ-PQ interactions, e.g., CQ-mediated inhibition of PQ metabolism, modulate radical cure efficacy in different P. vivax-infected populations. (This study has been registered at ClinicalTrials.gov under identifier NCT02691910.)

scholarly journals Chloroquine Remains Effective for Treating Plasmodium vivax Malaria in Pursat Province, Western Cambodia

2014 ◽  
Vol 58 (10) ◽  
pp. 6270-6272 ◽  
Author(s):  
Chanaki Amaratunga ◽  
Sokunthea Sreng ◽  
Sivanna Mao ◽  
Gregory S. Tullo ◽  
Jennifer M. Anderson ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Plasmodium Vivax ◽  
Vivax Malaria ◽  
Combination Therapies ◽  
Content Type ◽  
Plasmodium Vivax Malaria

ABSTRACTChloroquine (CQ) is used to treatPlasmodium vivaxmalaria in areas where CQ resistance has not been reported. The use of artemisinin (ART)-based combination therapies (ACTs) to treat CQ-sensitiveP. vivaxinfections is effective and convenient but may promote the emergence and worsening of ART resistance in sympatricPlasmodium falciparumpopulations. Here, we show that CQ effectively treatsP. vivaxmalaria in Pursat Province, western Cambodia, where ART-resistantP. falciparumis highly prevalent and spreading. (This study has been registered at ClinicalTrials.gov under registration no. NCT00663546.)

scholarly journals Therapeutic Responses of Plasmodium vivax Malaria to Chloroquine and Primaquine Treatment in Northeastern Myanmar

2014 ◽  
Vol 59 (2) ◽  
pp. 1230-1235 ◽  
Author(s):  
Lili Yuan ◽  
Ying Wang ◽  
Daniel M. Parker ◽  
Bhavna Gupta ◽  
Zhaoqing Yang ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Cumulative Incidence ◽  
Therapeutic Efficacy ◽  
Cumulative Risk ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Radical Cure ◽  
Content Type ◽  
Plasmodium Vivax Malaria

ABSTRACTChloroquine-primaquine (CQ-PQ) continues to be the frontline therapy for radical cure ofPlasmodium vivaxmalaria. Emergence of CQ-resistant (CQR)P. vivaxparasites requires a shift to artemisinin combination therapies (ACTs), which imposes a significant financial, logistical, and safety burden. Monitoring the therapeutic efficacy of CQ is thus important. Here, we evaluated the therapeutic efficacy of CQ-PQ forP. vivaxmalaria in northeast Myanmar. We recruited 587 patients withP. vivaxmonoinfection attending local malaria clinics during 2012 to 2013. These patients received three daily doses of CQ at a total dose of 24 mg of base/kg of body weight and an 8-day PQ treatment (0.375 mg/kg/day) commencing at the same time as the first CQ dose. Of the 401 patients who finished the 28-day follow-up, the cumulative incidence of recurrent parasitemia was 5.20% (95% confidence interval [CI], 3.04% to 7.36%). Among 361 (61%) patients finishing a 42-day follow-up, the cumulative incidence of recurrent blood-stage infection reached 7.98% (95% CI, 5.20% to 10.76%). The cumulative risk of gametocyte carriage at days 28 and 42 was 2.21% (95% CI, 0.78% to 3.64%) and 3.93% (95% CI, 1.94% to 5.92%), respectively. Interestingly, for all 15 patients with recurrent gametocytemia, this was associated with concurrent asexual stages. Genotyping of recurrent parasites at the merozoite surface protein 3α gene locus from 12 patients with recurrent parasitemia within 28 days revealed that 10 of these were the same genotype as at day 0, suggesting recrudescence or relapse. Similar studies in 70 patients in the same area in 2007 showed no recurrent parasitemias within 28 days. The sensitivity to chloroquine ofP. vivaxin northeastern Myanmar may be deteriorating.

scholarly journals High incidence of Plasmodium vivax malaria in newly arrived Eritrean refugees in Sweden since May 2014

2014 ◽  
Vol 19 (35) ◽  
Author(s):  
K Sondén ◽  
E Castro ◽  
L Trönnberg ◽  
C Stenström ◽  
A Tegnell ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Vivax Malaria ◽  
Young Men ◽  
Severe Anaemia ◽  
Symptom Duration ◽  
High Incidence ◽  
Plasmodium Vivax Malaria

Since May 2014, an increase in Plasmodium vivax malaria has been observed in Sweden. As of 31 August 2014, 105 malaria cases have been reported in newly arrived Eritrean refugees, 84 of them P. vivax. The patients were mainly young men and reported migration through Ethiopia and/or Sudan. Severe anaemia and long symptom duration reflect inadequate healthcare during migration. Countries currently hosting Eritrean refugees need to consider P. vivax malaria in this group of migrants.

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