scholarly journals Plasmodium vivax Chloroquine Resistance and Anemia in the Western Brazilian Amazon

2013 ◽  
Vol 58 (1) ◽  
pp. 342-347 ◽  
Author(s):  
Marly M. Marques ◽  
Monica R. F. Costa ◽  
Franklin S. Santana Filho ◽  
José L. F. Vieira ◽  
Margareth T. S. Nascimento ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Univariate Analysis ◽  
Control Program ◽  
Brazilian Amazon ◽  
Small Sample ◽  
Chloroquine Resistance ◽  
Public Health Issue ◽  
Content Type

ABSTRACTData on chloroquine (CQ)-resistantPlasmodium vivaxin Latin America is limited, even with the current research efforts to sustain an efficient malaria control program in all these countries whereP. vivaxis endemic and where malaria still is a major public health issue. This study estimatedin vivoCQ resistance in patients with uncomplicatedP. vivaxmalaria, 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. TheP. vivaxdhfr(pvdhfr),pvmrp1,pvmdr1, andpvdhpsgene mutations were not related to resistance in this small sample.P. vivaxCQ 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.

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 Reduced Polymorphism in the Kelch Propeller Domain in Plasmodium vivax Isolates from Cambodia

2014 ◽  
Vol 59 (1) ◽  
pp. 730-733 ◽  
Author(s):  
Jean Popovici ◽  
Sokheng Kao ◽  
Leanghor Eal ◽  
Sophalai Bin ◽  
Saorin Kim ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Plasmodium Vivax ◽  
Preliminary Data ◽  
Mutant Allele ◽  
Chloroquine Resistance ◽  
Wild Type ◽  
Nonsynonymous Mutation ◽  
Content Type

ABSTRACTPolymorphism in the ortholog gene of thePlasmodium falciparumK13 gene was investigated inPlasmodium vivaxisolates collected in Cambodia. All of them were Sal-1 wild-type alleles except two (2/284, 0.7%), andP. vivaxK12 polymorphism was reduced compared to that of theP. falciparumK13 gene. Both mutant allele isolates had the same nonsynonymous mutation at codon 552 (V552I) and were from Ratanak Kiri province. These preliminary data should encourage additional studies for associating artemisinin or chloroquine resistance and K12 polymorphism.

scholarly journals Role of Toxoplasma gondii Chloroquine Resistance Transporter in Bradyzoite Viability and Digestive Vacuole Maintenance

mBio ◽  
2019 ◽  
Vol 10 (4) ◽  
Author(s):  
Geetha Kannan ◽  
Manlio Di Cristina ◽  
Aric J. Schultz ◽  
My-Hang Huynh ◽  
Fengrong Wang ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Chronic Infection ◽  
Chloroquine Resistance ◽  
Congenital Defects ◽  
Functional Link ◽  
Content Type ◽  
Chloroquine Resistance Transporter

ABSTRACT Toxoplasma gondii is a ubiquitous pathogen that can cause encephalitis, congenital defects, and ocular disease. T. gondii has also been implicated as a risk factor for mental illness in humans. The parasite persists in the brain as slow-growing bradyzoites contained within intracellular cysts. No treatments exist to eliminate this form of parasite. Although proteolytic degradation within the parasite lysosome-like vacuolar compartment (VAC) is critical for bradyzoite viability, whether other aspects of the VAC are important for parasite persistence remains unknown. An ortholog of Plasmodium falciparum chloroquine resistance transporter (CRT), TgCRT, has previously been identified in T. gondii. To interrogate the function of TgCRT in chronic-stage bradyzoites and its role in persistence, we knocked out TgCRT in a cystogenic strain and assessed VAC size, VAC digestion of host-derived proteins and parasite autophagosomes, and the viability of in vitro and in vivo bradyzoites. We found that whereas parasites deficient in TgCRT exhibit normal digestion within the VAC, they display a markedly distended VAC and their viability is compromised both in vitro and in vivo. Interestingly, impairing VAC proteolysis in TgCRT-deficient bradyzoites restored VAC size, consistent with a role for TgCRT as a transporter of products of digestion from the VAC. In conjunction with earlier studies, our current findings suggest a functional link between TgCRT and VAC proteolysis. This study provides further evidence of a crucial role for the VAC in bradyzoite persistence and a new potential VAC target to abate chronic Toxoplasma infection. IMPORTANCE Individuals chronically infected with the intracellular parasite Toxoplasma gondii are at risk of experiencing reactivated disease that can result in progressive loss of vision. No effective treatments exist for chronic toxoplasmosis due in part to a poor understanding of the biology underlying chronic infection and a lack of well-validated potential targets. We show here that a T. gondii transporter is functionally linked to protein digestion within the parasite lysosome-like organelle and that this transporter is necessary to sustain chronic infection in culture and in experimentally infected mice. Ablating the transporter results in severe bloating of the lysosome-like organelle. Together with earlier work, this study suggests the parasite’s lysosome-like organelle is vital for parasite survival, thus rendering it a potential target for diminishing infection and reducing the risk of reactivated disease.

scholarly journals Expression Levels of pvcrt-o and pvmdr-1 Are Associated with Chloroquine Resistance and Severe Plasmodium vivax Malaria in Patients of the Brazilian Amazon

PLoS ONE ◽  
2014 ◽  
Vol 9 (8) ◽  
pp. e105922 ◽  
Author(s):  
Gisely C. Melo ◽  
Wuelton M. Monteiro ◽  
André M. Siqueira ◽  
Siuhelem R. Silva ◽  
Belisa M. L. Magalhães ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Vivax Malaria ◽  
Brazilian Amazon ◽  
Chloroquine Resistance ◽  
Expression Levels ◽  
Plasmodium Vivax Malaria

scholarly journals Simultaneous Administration of 2-Aminoethyl Diphenylborinate and Chloroquine Reverses Chloroquine Resistance in Malaria Parasites

2015 ◽  
Vol 59 (5) ◽  
pp. 2890-2892 ◽  
Author(s):  
Ehab Mossaad ◽  
Wakako Furuyama ◽  
Masahiro Enomoto ◽  
Satoru Kawai ◽  
Katsuhiko Mikoshiba ◽  
...  
Keyword(s):  
Chloroquine Resistance ◽  
Infection Model ◽  
Simultaneous Administration ◽  
Plasmodium Chabaudi ◽  
Content Type ◽  
Mouse Infection Model ◽  
Complete Reversal ◽  
The Mean

ABSTRACTA nearly complete reversal of chloroquine (CQ) resistance in the CQ-resistantPlasmodium falciparumK-1 strain, with a significant decrease in the mean ± standard deviation (SD) 50% inhibitory concentration (IC50) from 1,050 ± 95 nM to 14 ± 2 nM, was achievedin vitroby the simultaneous administration of 2-aminoethyl diphenylborinate (2-APB). The CQ resistance-reversing activity of 2-APB, which showed the same efficacy as verapamil, was also observed in anin vivomouse infection model with the CQ-resistantPlasmodium chabaudiAS(30CQ) strain.

scholarly journals In vitro chloroquine resistance for Plasmodium vivax isolates from the Western Brazilian Amazon

2013 ◽  
Vol 12 (1) ◽  
pp. 226 ◽  
Author(s):  
Yonne F Chehuan ◽  
Monica RF Costa ◽  
Jacqueline S Costa ◽  
Maria GC Alecrim ◽  
Fátima Nogueira ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Brazilian Amazon ◽  
Chloroquine Resistance

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 Emergence of Plasmodium vivax Resistance to Chloroquine in French Guiana

2019 ◽  
Vol 63 (11) ◽  
Author(s):  
Lise Musset ◽  
Christophe Heugas ◽  
Richard Naldjinan ◽  
Denis Blanchet ◽  
Pascal Houze ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Therapeutic Efficacy ◽  
French Guiana ◽  
Gene Copy Number ◽  
Chloroquine Resistance ◽  
World Health ◽  
Gene Copy ◽  
Content Type ◽  
Gene Copy Number Variation ◽  
Health Organization

ABSTRACT In South America, Plasmodium vivax resistance to chloroquine was recently reported in Brazil and Bolivia. The objective of this study was to collect data on chloroquine resistance in French Guiana by associating a retrospective evaluation of therapeutic efficacy with an analysis of recurrent parasitemia from any patients. Patients with P. vivax infection, confirmed by microscopy and a body temperature of ≥37.5°C, were retrospectively identified at Cayenne Hospital between 2009 and 2015. Follow-up and treatment responses were performed according to the World Health Organization protocol. Parasite resistance was confirmed after dosage of a plasma concentration of chloroquine and microsatellite characterization. The pvmdr1 and pvcrt-o genes were analyzed for sequence and gene copy number variation. Among the 172 patients followed for 28 days, 164 presented adequate clinical and parasitological responses. Eight cases of treatment failures were identified (4.7%; n = 8/172), all after 14 days. The therapeutic efficacy of chloroquine was estimated at 95.3% (95% confidence interval [CI], 92.5 to 98.1%; n = 164/172). Among the eight failures, five were characterized: two cases were true P. vivax chloroquine resistance (1.2%; 95% CI, 0 to 2.6%; n = 2/172), and three cases were found with subtherapeutic concentrations of chloroquine. No particular polymorphism in the Plasmodium vivax pvmdr1 and pvcrt-o genes was identified in the resistant parasites. This identified level of resistance of P. vivax to chloroquine in French Guiana does not require a change in therapeutic recommendations. However, primaquine should be administered more frequently to limit the spread of resistance, and there is still a need for a reliable molecular marker to facilitate the monitoring of P. vivax resistance to chloroquine.

scholarly journals Gene Models, Expression Repertoire, and Immune Response of Plasmodium vivax Reticulocyte Binding Proteins

2015 ◽  
Vol 84 (3) ◽  
pp. 677-685 ◽  
Author(s):  
Jenni Hietanen ◽  
Anongruk Chim-ong ◽  
Thanprakorn Chiramanewong ◽  
Jakub Gruszczyk ◽  
Wanlapa Roobsoong ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Significant Negative Correlation ◽  
Protein Coding ◽  
Content Type ◽  
Immune Pressure ◽  
The Family ◽  
Genes Encoding ◽  
Gene Models

Members of thePlasmodium vivaxreticulocyte binding protein (PvRBP) family are believed to mediate specific invasion of reticulocytes byP. vivax. In this study, we performed molecular characterization of genes encoding members of this protein family. Through cDNA sequencing, we constructed full-length gene models and verified genes that are protein coding and those that are pseudogenes. We also used quantitative PCR to measure theirin vivotranscript abundances in clinicalP. vivaxisolates. Like genes encoding related invasion ligands ofP. falciparum,Pvrbpexpression levels vary broadly across different parasite isolates. Through antibody measurements, we found that host immune pressure may be the driving force behind the distinctly high diversity of one of the family members, PvRBP2c. Mild yet significant negative correlation was found between parasitemia and the PvRBP2b antibody level, suggesting that antibodies to the protein may interfere with invasion.

scholarly journals Endocarditis Caused by Highly Penicillin-Resistant Viridans Group Streptococci: Still Room for Vancomycin-Based Regimens

2019 ◽  
Vol 63 (8) ◽  
Author(s):  
Juan M. Pericàs ◽  
Ruvandhi Nathavitharana ◽  
Cristina Garcia-de-la-Mària ◽  
Carles Falces ◽  
Juan Ambrosioni ◽  
...  
Keyword(s):  
Bactericidal Activity ◽  
Treatment Options ◽  
Content Type ◽  
High Level ◽  
Viridans Group Streptococci ◽  
Time Kill

ABSTRACT Optimal treatment options remain unknown for infective endocarditis (IE) caused by penicillin-resistant (PEN-R) viridans group streptococcal (VGS) strains. The aims of this study were to report two cases of highly PEN-R VGS IE, perform a literature review, and evaluate various antibiotic combinations in vitro and in vivo. The following combinations were tested by time-kill studies and in the rabbit experimental endocarditis (EE) model: PEN-gentamicin, ceftriaxone-gentamicin, vancomycin-gentamicin, daptomycin-gentamicin, and daptomycin-ampicillin. Case 1 was caused by Streptococcus parasanguinis (PEN MIC, 4 μg/ml) and was treated with vancomycin plus cardiac surgery. Case 2 was caused by Streptococcus mitis (PEN MIC, 8 μg/ml) and was treated with 4 weeks of vancomycin plus gentamicin, followed by 2 weeks of vancomycin alone. Both patients were alive and relapse-free after ≥6 months follow-up. For the in vitro studies, except for daptomycin-ampicillin, all combinations demonstrated both synergy and bactericidal activity against the S. parasanguinis isolate. Only PEN-gentamicin, daptomycin-gentamicin, and daptomycin-ampicillin demonstrated both synergy and bactericidal activity against the S. mitis strain. Both strains developed high-level daptomycin resistance (HLDR) during daptomycin in vitro passage. In the EE studies, PEN alone failed to clear S. mitis from vegetations, while ceftriaxone and vancomycin were significantly more effective (P < 0.001). The combination of gentamicin with PEN or vancomycin increased bacterial eradication compared to that with the respective monotherapies. In summary, two patients with highly PEN-R VGS IE were cured using vancomycin-based therapy. In vivo, regimens of gentamicin plus either β-lactams or vancomycin were more active than their respective monotherapies. Further clinical studies are needed to confirm the role of vancomycin-based regimens for highly PEN-R VGS IE. The emergence of HLDR among these strains warrants caution in the use of daptomycin therapy for VGS IE.

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