Primaquine for preventing relapse in people with Plasmodium vivax malaria treated with chloroquine.
Ontology highlight
ABSTRACT:
SUBMITTER: Galappaththy GN
PROVIDER: S-EPMC6532739 | biostudies-literature | 2013 Oct
REPOSITORIES: biostudies-literature
Publications
Primaquine for preventing relapse in people with Plasmodium vivax malaria treated with chloroquine.
Galappaththy Gawrie N L GN Tharyan Prathap P Kirubakaran Richard R
The Cochrane database of systematic reviews 20131026 10
<h4>Background</h4>Plasmodium vivax infections are an important contributor to the malaria burden worldwide. The World Health Organization recommends a 14-day course of primaquine (0.25 mg/kg/day, giving an adult dose of 15 mg/day) to eradicate the liver stage of the parasite and prevent relapse of the disease. Many people find a 14-day primaquine regimen difficult to complete, and there is a potential risk of haemolytic anaemia in people with glucose-6-phosphate-dehydrogenase enzyme (G6PD) defi ...[more]
Similar Datasets
Project description: Not available
| S-EPMC6611223 | biostudies-literature
Project description: Not available
| S-EPMC8094590 | biostudies-literature
Project description:BackgroundTafenoquine, a single-dose therapy for Plasmodium vivax malaria, has been associated with relapse prevention through the clearance of P. vivax parasitemia and hypnozoites, termed "radical cure."MethodsWe performed a phase 3, prospective, double-blind, double-dummy, randomized, controlled trial to compare tafenoquine with primaquine in terms of safety and efficacy. The trial was conducted at seven hospitals or clinics in Peru, Brazil, Colombia, Vietnam, and Thailand and involved patients with normal glucose-6-phosphate dehydrogenase (G6PD) enzyme activity and female patients with moderate G6PD enzyme deficiency; all patients had confirmed P. vivax parasitemia. The patients were randomly assigned, in a 2:1 ratio, to receive a single 300-mg dose of tafenoquine or 15 mg of primaquine once daily for 14 days (administered under supervision); all patients received a 3-day course of chloroquine and were followed for 180 days. The primary safety outcome was a protocol-defined decrease in the hemoglobin level (>3.0 g per deciliter or ≥30% from baseline or to a level of <6.0 g per deciliter). Freedom from recurrence of P. vivax parasitemia at 6 months was the primary efficacy outcome in a planned patient-level meta-analysis of the current trial and another phase 3 trial of tafenoquine and primaquine (per-protocol populations), and an odds ratio for recurrence of 1.45 (tafenoquine vs. primaquine) was used as a noninferiority margin.ResultsA protocol-defined decrease in the hemoglobin level occurred in 4 of 166 patients (2.4%; 95% confidence interval [CI], 0.9 to 6.0) in the tafenoquine group and in 1 of 85 patients (1.2%; 95% CI, 0.2 to 6.4) in the primaquine group, for a between-group difference of 1.2 percentage points (95% CI, -4.2 to 5.0). In the patient-level meta-analysis, the percentage of patients who were free from recurrence at 6 months was 67.0% (95% CI, 61.0 to 72.3) among the 426 patients in the tafenoquine group and 72.8% (95% CI, 65.6 to 78.8) among the 214 patients in the primaquine group. The efficacy of tafenoquine was not shown to be noninferior to that of primaquine (odds ratio for recurrence, 1.81; 95% CI, 0.82 to 3.96).ConclusionsAmong patients with normal G6PD enzyme activity, the decline in hemoglobin level with tafenoquine did not differ significantly from that with primaquine. Tafenoquine showed efficacy for the radical cure of P. vivax malaria, although tafenoquine was not shown to be noninferior to primaquine. (Funded by GlaxoSmithKline and Medicines for Malaria Venture; GATHER ClinicalTrials.gov number, NCT02216123 .).
| S-EPMC6657225 | biostudies-literature
Project description:PurposePharmacogenes have an influence on biotransformation pathway and clinical outcome of primaquine and chloroquine which are often prescribed to treat Plasmodium vivax infection. Genetic variation may impact enzyme activity and/or transporter function and thereby contribute to relapse. The aim of the study was to assess allele, genotype frequencies and the association between pharmacogenes variation and primaquine response in Thai patients infected with Plasmodium vivax.Patients and methodsFifty-one patients were genotyped for 74 variants in 18 genes by Sequenom MassARRAY® and Taqman® SNP Real-Time PCR.ResultsSNP frequencies were not significantly different between relapse (n=4) and non-relapse (n=47) patients. However, the CYP2C19 c.681G>A, the frequency of the A-allele that defines the non-functional CYP2C19*2 haplotype was significantly higher compared to the G-allele (OR=5.14, p=0.021). Patients heterozygous for ABCG2 c.421C>A had a higher odds ratio (OR=8.75, p=0.071) and the frequency of the G-allele of UGT2B7 c.372G>A was higher compared to the A-allele (OR=3.75, p=0.081). CYP2C19, ABCG2 and UGT2B7 emerged as potential high priority genes.ConclusionDecreased activity of CYP2C19, ABCG2 and UGT2B7 in combination with CYP2D6 intermediate or poor metabolizer status may expose patients to a higher risk of Plasmodium vivax relapse. Further investigations are warranted to substantiate these findings.
| S-EPMC6966953 | biostudies-literature
Project description:BACKGROUND:Chloroquine/primaquine is the current therapy to eliminate Plasmodium vivax infection in the Amazon region. AIMS:This study investigates CYP1A2, CYP2C8, CYP2C9, CYP3A4 and CYP3A5 genetic polymorphisms influence on cloroquine/primaquine treatment. PATIENTS & METHODS:Generalized estimating equations analyses were performed to determine the genetic influence in parasitemia and/or gametocytemia clearance over treatment time in 164 patients. RESULTS:An effect of CYP2C8 low-activity alleles on treatment was observed (p = 0.01). From baseline to first day of treatment, wild-type individuals achieved greater reduction of gametocytes than low-activity allele carriers. CYP2C9 and CYP3A5 genes showed a trend for gametocytemia and parasitemia clearance rates. CONCLUSION:Future studies should be performed to access the extent of CYP2C8, CYP2C9 and CYP3A5 gene polymorphisms influence on cloroquine/primaquine treatment.
| S-EPMC7099632 | biostudies-literature
Project description:BackgroundIn most of the Americas, the recommended treatment to prevent relapse of Plasmodium vivax malaria is primaquine at a total dose of 3.5 mg per kilogram of body weight, despite evidence of only moderate efficacy.MethodsIn this trial conducted in Brazil, we evaluated three primaquine regimens to prevent relapse of P. vivax malaria in children at least 5 years of age and in adults with microscopy-confirmed P. vivax monoinfection. All the patients received directly observed chloroquine for 3 days (total dose, 25 mg per kilogram). Group 1 received a total primaquine dose of 3.5 mg per kilogram (0.5 mg per kilogram per day) over 7 days with unobserved administration; group 2 received the same regimen as group 1 but with observed administration; and group 3 received a total primaquine dose of 7.0 mg per kilogram over 14 days (also 0.5 mg per kilogram per day) with observed administration. We monitored the patients for 168 days.ResultsWe enrolled 63 patients in group 1, 96 in group 2, and 95 in group 3. The median age of the patients was 22.4 years (range, 5.4 to 79.8). By day 28, three P. vivax recurrences were observed: 2 in group 1 and 1 in group 2. By day 168, a total of 70 recurrences had occurred: 24 in group 1, 34 in group 2, and 12 in group 3. No serious adverse events were noted. On day 168, the percentage of patients without recurrence was 58% (95% confidence interval [CI], 44 to 70) in group 1, 59% (95% CI, 47 to 69) in group 2, and 86% (95% CI, 76 to 92) in group 3. Survival analysis showed a difference in the day 168 recurrence-free percentage of 27 percentage points (97.5% CI, 10 to 44; P<0.001) between group 1 and group 3 and a difference of 27 percentage points (97.5% CI, 12 to 42; P<0.001) between group 2 and group 3.ConclusionsThe administration of primaquine at a total dose of 7.0 mg per kilogram had higher efficacy in preventing relapse of P. vivax malaria than a total dose of 3.5 mg per kilogram through day 168. (Supported by the U.S. Agency for International Development; ClinicalTrials.gov number, NCT03610399.).
| S-EPMC9132489 | biostudies-literature
Project description:BackgroundChloroquine has been recommended for Plasmodium vivax infections for >60 years, but resistance is increasing. To guide future therapies, the cumulative benefits of using slowly eliminated (chloroquine) vs rapidly eliminated (artesunate) antimalarials, and the risks and benefits of adding radical cure (primaquine) were assessed in a 3-way randomized comparison conducted on the Thailand-Myanmar border.MethodsPatients with uncomplicated P. vivax malaria were given artesunate (2 mg/kg/day for 5 days), chloroquine (25 mg base/kg over 3 days), or chloroquine-primaquine (0.5 mg/kg/day for 14 days) and were followed for 1 year. Recurrence rates and their effects on anemia were compared.ResultsBetween May 2010 and October 2012, 644 patients were enrolled. Artesunate cleared parasitemia significantly faster than chloroquine. Day 28 recurrence rates were 50% with artesunate (112/224), 8% with chloroquine (18/222; P < .001), and 0.5% with chloroquine-primaquine (1/198; P < .001). Median times to first recurrence were 28 days (interquartile range [IQR], 21-42) with artesunate, 49 days (IQR, 35-74) with chloroquine, and 195 days (IQR, 82-281) with chloroquine-primaquine. Recurrence by day 28, was associated with a mean absolute reduction in hematocrit of 1% (95% confidence interval [CI], .3%-2.0%; P = .009). Primaquine radical cure reduced the total recurrences by 92.4%. One-year recurrence rates were 4.51 (95% CI, 4.19-4.85) per person-year with artesunate, 3.45 (95% CI, 3.18-3.75) with chloroquine (P = .002), and 0.26 (95% CI, .19-.36) with chloroquine-primaquine (P < .001).ConclusionsVivax malaria relapses are predominantly delayed by chloroquine but prevented by primaquine.Clinical trials registrationNCT01074905.
| S-EPMC6206118 | biostudies-literature
Project description:AimThe association of transporters gene polymorphisms with chloroquine/primaquine malaria treatment response was investigated in a Brazilian population.Patients & methodsTotally, 164 Plasmodium vivax malaria infected patients were included. Generalized estimating equations were performed to determine gene influences on parasitemia and/or gametocytemia clearance over treatment time.ResultsSignificant interaction between SLCO2B1 genotypes and treatment over time for parasitemia clearance rate on day 2 were observed (p FDR = 0.002). SLCO1A2 and SLCO1B1 gene treatment over time interactions were associated with gametocytemia clearance rate (p FDR = 0.018 and p FDR = 0.024). ABCB1, ABCC4 and SLCO1B3 were not associated with treatment response.ConclusionThe present work presents the first pharmacogenetic report of an association between chloroquine/primaquine responses with OATP transporters.
| S-EPMC7099631 | biostudies-literature
Project description:BackgroundThe effect of primaquine in preventing Plasmodium vivax relapses from dormant stages is well established. For Plasmodium ovale, the relapse characteristics and the use of primaquine is not as well studied. We set to evaluate the relapsing properties of these 2 species, in relation to primaquine use among imported malaria cases in a nonendemic setting.MethodsWe performed a nationwide retrospective study of malaria diagnosed in Sweden 1995-2019, by reviewing medical records of 3254 cases. All episodes of P. vivax (n = 972) and P. ovale (n = 251) were selected for analysis.ResultsFirst time relapses were reported in 80/857 (9.3%) P. vivax and 9/220 (4.1%) P. ovale episodes, respectively (P < .01). Without primaquine, the risk for relapse was higher in P. vivax, 20/60 (33.3%), compared to 3/30 (10.0%) in P. ovale (hazard ratio [HR] 3.5, 95% confidence interval [CI] 1.0-12.0). In P. vivax, patients prescribed primaquine had a reduced risk of relapse compared to episodes without relapse preventing treatment, 7.1% vs 33.3% (HR 0.2, 95% CI .1-.3). In P. ovale, the effect of primaquine on the risk of relapse did not reach statistical significance, with relapses seen in 2.8% of the episodes compared to 10.0% in patients not receiving relapse preventing treatment (HR 0.3, 95% CI .1-1.1).ConclusionsThe risk of relapse was considerably lower in P. ovale than in P. vivax infections indicating different relapsing features between the two species. Primaquine was effective in preventing P. vivax relapse. In P. ovale, relapse episodes were few, and the supportive evidence for primaquine remains limited.
| S-EPMC8994585 | biostudies-literature
Project description:We evaluated the efficacy of chloroquine and primaquine on uncomplicated Plasmodium vivax malaria in Cruzeiro do Sul, Brazil, in 2014. Patients ≥ 5 years of age with either fever or history of fever, and laboratory-confirmed P. vivax monoinfection received chloroquine (total dose = 25 mg/kg) and primaquine (total dose = 3.5 mg/kg), and were followed up for 168 days (24 weeks). We used microsatellite genotyping to differentiate recurrent infections caused by heterologous parasites from those caused by homologous ones. No new P. vivax episode occurred by Day 28 among 119 enrolled patients, leading to Day 28, with adequate clinical and parasitological response (ACPR) of 100% (95% confidence interval [CI] = 96.7-100%). Twenty-eight P. vivax episodes occurred by Day 168, with uncorrected ACPR of 69.9% (95% CI = 59.5-79.0%). Fifteen of these episodes were caused by either homologous haplotypes or haplotypes that could not be determined. Excluding the 13 recurrent episodes caused by heterologous parasites, Day 168 microsatellite-corrected ACPR was estimated at 81.2% (95% CI = 71.0-89.1%). Chloroquine and primaquine remain efficacious to treat acute uncomplicated P. vivax infection, but moderate recurrence rates were observed within 24 weeks of follow-up.
| S-EPMC5094218 | biostudies-literature