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Amanda Murphy - One of the best experts on this subject based on the ideXlab platform.
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Where Chloroquine still works: the genetic make-up and susceptibility of Plasmodium vivax to Chloroquine Plus Primaquine in Bhutan
Malaria Journal, 2016Co-Authors: Sonam Wangchuk, Tobgyel Drukpa, Kinley Penjor, Tashi Peldon, Yeshey Dorjey, Kunzang Dorji, Vishal Chhetri, Hidayat Trimarsanto, Sheren To, Amanda MurphyAbstract:Background Bhutan has made substantial progress in reducing malaria incidence. The national guidelines recommend Chloroquine (CQ) and Primaquine (PQ) for radical cure of uncomplicated Plasmodium vivax , but the local efficacy has not been assessed. The impact of cases imported from India on the genetic make-up of the local vivax populations is currently unknown. Methods Patients over 4 years of age with uncomplicated P. vivax mono-infection were enrolled into a clinical efficacy study and molecular survey. Study participants received a standard dose of CQ (25 mg/kg over 3 days) followed by weekly review until day 28. On day 28 a 14-day regimen of PQ (0.25 mg/kg/day) was commenced under direct observation. After day 42, patients were followed up monthly for a year. The primary and secondary endpoints were risk of treatment failure at day 28 and at 1 year. Parasite genotyping was undertaken at nine tandem repeat markers, and standard population genetic metrics were applied to examine population diversity and structure in infections thought to be acquired inside or outside of Bhutan. Results A total of 24 patients were enrolled in the clinical study between April 2013 and October 2015. Eight patients (33.3 %) were lost to follow-up in the first 6 months and another eight patients lost between 6 and 12 months. No (0/24) treatment failures occurred by day 28 and no (0/8) parasitaemia was detected following PQ treatment. Some 95.8 % (23/24) of patients were aparasitaemic by day 2. There were no haemolytic or serious events. Genotyping was undertaken on parasites from 12 autochthonous cases and 16 suspected imported cases. Diversity was high ( H _ E 0.87 and 0.90) in both populations. There was no notable differentiation between the autochthonous and imported populations. Conclusions CQ and PQ remains effective for radical cure of P. vivax in Bhutan. The genetic analyses indicate that imported infections are sustaining the local vivax population, with concomitant risk of introducing drug-resistant strains.
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where Chloroquine still works the genetic make up and susceptibility of plasmodium vivax to Chloroquine Plus Primaquine in bhutan
Malaria Journal, 2016Co-Authors: Sonam Wangchuk, Tobgyel Drukpa, Kinley Penjor, Tashi Peldon, Yeshey Dorjey, Kunzang Dorji, Vishal Chhetri, Hidayat Trimarsanto, Sheren To, Amanda MurphyAbstract:Background Bhutan has made substantial progress in reducing malaria incidence. The national guidelines recommend Chloroquine (CQ) and Primaquine (PQ) for radical cure of uncomplicated Plasmodium vivax, but the local efficacy has not been assessed. The impact of cases imported from India on the genetic make-up of the local vivax populations is currently unknown.
Sonam Wangchuk - One of the best experts on this subject based on the ideXlab platform.
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Where Chloroquine still works: the genetic make-up and susceptibility of Plasmodium vivax to Chloroquine Plus Primaquine in Bhutan
Malaria Journal, 2016Co-Authors: Sonam Wangchuk, Tobgyel Drukpa, Kinley Penjor, Tashi Peldon, Yeshey Dorjey, Kunzang Dorji, Vishal Chhetri, Hidayat Trimarsanto, Sheren To, Amanda MurphyAbstract:Background Bhutan has made substantial progress in reducing malaria incidence. The national guidelines recommend Chloroquine (CQ) and Primaquine (PQ) for radical cure of uncomplicated Plasmodium vivax , but the local efficacy has not been assessed. The impact of cases imported from India on the genetic make-up of the local vivax populations is currently unknown. Methods Patients over 4 years of age with uncomplicated P. vivax mono-infection were enrolled into a clinical efficacy study and molecular survey. Study participants received a standard dose of CQ (25 mg/kg over 3 days) followed by weekly review until day 28. On day 28 a 14-day regimen of PQ (0.25 mg/kg/day) was commenced under direct observation. After day 42, patients were followed up monthly for a year. The primary and secondary endpoints were risk of treatment failure at day 28 and at 1 year. Parasite genotyping was undertaken at nine tandem repeat markers, and standard population genetic metrics were applied to examine population diversity and structure in infections thought to be acquired inside or outside of Bhutan. Results A total of 24 patients were enrolled in the clinical study between April 2013 and October 2015. Eight patients (33.3 %) were lost to follow-up in the first 6 months and another eight patients lost between 6 and 12 months. No (0/24) treatment failures occurred by day 28 and no (0/8) parasitaemia was detected following PQ treatment. Some 95.8 % (23/24) of patients were aparasitaemic by day 2. There were no haemolytic or serious events. Genotyping was undertaken on parasites from 12 autochthonous cases and 16 suspected imported cases. Diversity was high ( H _ E 0.87 and 0.90) in both populations. There was no notable differentiation between the autochthonous and imported populations. Conclusions CQ and PQ remains effective for radical cure of P. vivax in Bhutan. The genetic analyses indicate that imported infections are sustaining the local vivax population, with concomitant risk of introducing drug-resistant strains.
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where Chloroquine still works the genetic make up and susceptibility of plasmodium vivax to Chloroquine Plus Primaquine in bhutan
Malaria Journal, 2016Co-Authors: Sonam Wangchuk, Tobgyel Drukpa, Kinley Penjor, Tashi Peldon, Yeshey Dorjey, Kunzang Dorji, Vishal Chhetri, Hidayat Trimarsanto, Sheren To, Amanda MurphyAbstract:Background Bhutan has made substantial progress in reducing malaria incidence. The national guidelines recommend Chloroquine (CQ) and Primaquine (PQ) for radical cure of uncomplicated Plasmodium vivax, but the local efficacy has not been assessed. The impact of cases imported from India on the genetic make-up of the local vivax populations is currently unknown.
Awash Teklehaimanot - One of the best experts on this subject based on the ideXlab platform.
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therapeutic efficacy of Chloroquine and Chloroquine Plus Primaquine for the treatment of plasmodium vivax in ethiopia
Acta Tropica, 2010Co-Authors: Asnakew K Yeshiwondim, Afework H Tekle, Dereje O Dengela, Ambachew M Yohannes, Awash TeklehaimanotAbstract:Abstract Plasmodium vivax is the second most important cause of morbidity in Ethiopia. There is, however, little information on P. vivax resistance to Chloroquine and Chloroquine Plus Primaquine treatment although these drugs have been used as the first line treatment for over 50 years. We assessed the efficacy of standard Chloroquine and Chloroquine Plus Primaquine treatment for P. vivax infections in a randomized open-label comparative study in Debre Zeit and Nazareth in East Shoa, Ethiopia. A total of 290 patients with microscopically confirmed P. vivax malaria who presented to the outpatient settings of the two laboratory centers were enrolled: 145 patients were randomized to receive CQ and 145 to receive CQ + PQ treatment. Participants were followed-up for 28–157 days according to the WHO procedures. There were 12 (6.5%) lost to follow-up patients and 9 (3.1%) withdrawals. In all, 96% (277/290) of patients were analysed at day 28. Baseline characteristics were similar in all treatment groups. In all, 98.6% (275/277) of patients had cleared their parasitemia on day 3 with no difference in mean parasite clearance time between regimens (48.34 ± 17.68, 50.67 ± 15.70 h for the CQ and CQ + PQ group, respectively, P = 0.25). The cumulative incidence of therapeutic failure at day 28 by a life-table analysis method was 5.76% (95% CI: 2.2–14.61) and 0.75% (95% CI: 0.11–5.2%) in the CQ and CQ + PQ group, respectively (P = 0.19). The relapse rate was 8% (9/108) for the CQ group and 3% (4/132) for the comparison group (P = 0.07). The cumulative risk of relapse at day 157 by a life-table method was 61.8% (95% CI: 20.1–98.4%) in the CQ group, compared with 26.3% (95% CI: 7.5–29.4%) in the CQ + PQ group (P = 0.0038). The study confirms the emergence of CQ and PQ resistance/treatment failure in P. vivax malaria in Ethiopia. Although treatment failures were detected, they were similar between the treatment groups. We recommend regular monitoring and periodic evaluation of the efficacy of these antimalarial drugs in systematically selected sentinel sites to detect further development of resistance and to make timely national antimalarial drug policy changes.
Stephan Duparc - One of the best experts on this subject based on the ideXlab platform.
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Estimation of the Antirelapse Efficacy of Tafenoquine, Using Plasmodium vivax Genotyping.
The Journal of Infectious Diseases, 2015Co-Authors: Hans-peter Beck, Ronnatrai Rueangweerayut, Srivicha Krudsood, Rahel Wampfler, Nick Carter, Lyda Osorio, Marcus V. G. Lacerda, Alejandro Llanos-cuentas, Stephan DuparcAbstract:Prevention of relapse of Plasmodium vivax infection is a key treatment goal in malaria. Use of P. vivax genotyping in a multicenter, double-blind, randomized, placebo-controlled phase 2b study in Peru, India, Thailand, and Brazil allowed determination of genetically heterologous or homologous P. vivax infection recurrence following receipt of Chloroquine Plus one of 4 doses of tafenoquine (50, 100, 300, or 600 mg) or Chloroquine Plus Primaquine, compared with receipt of Chloroquine alone. The antihypnozoite efficacy of tafenoquine was evident as a reduction in homologous recurrences of P. vivax infection as drug doses were increased. No clear dose-response pattern was evident for heterologous recurrences of P. vivax infection. Rates of homologous recurrence of P. vivax infection appear to be clinically useful for comparing drug efficacy for the prevention of P. vivax infection relapse.; NCT01376167.
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tafenoquine Plus Chloroquine for the treatment and relapse prevention of plasmodium vivax malaria detective a multicentre double blind randomised phase 2b dose selection study
The Lancet, 2014Co-Authors: Alejandro Llanoscuentas, Marcus Vinícius Guimarães Lacerda, Ronnatrai Rueangweerayut, Srivicha Krudsood, Sanjay K Kochar, Preetam Arthur, Nuttagarn Chuenchom, Jorg J Mohrle, Sandeep Kumar Gupta, Stephan DuparcAbstract:Summary Background Clinical effectiveness of previous regimens to treat Plasmodium vivax infection have been hampered by compliance. We aimed to assess the dose–response, safety, and tolerability of single-dose tafenoquine Plus 3-day Chloroquine for P vivax malaria radical cure. Methods In this double-blind, randomised, dose-ranging phase 2b study, men and women (aged ≥16 years) with microscopically confirmed P vivax monoinfection (parasite density >100 to 7500 per μL blood). The primary efficacy endpoint was relapse-free efficacy at 6 months from initial dose (ie, clearance of initial infection without subsequent microscopically confirmed infection), analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01376167. Findings Between Sept 19, 2011, and March 25, 2013, 329 patients were randomly assigned to a treatment group (Chloroquine Plus tafenoquine 50 mg [n=55], 100 mg [n=57], 300 mg [n=57], 600 mg [n=56]; or to Chloroquine Plus Primaquine [n=50]; or Chloroquine alone [n=54]). Relapse-free efficacy at 6 months was 57·7% (95% CI 43–70) with tafenoquine 50 mg, 54·1% (40–66) with tafenoquine 100 mg, 89·2% (77–95) with tafenoquine 300 mg, 91·9% (80–97) with tafenoquine 600 mg, 77·3% (63–87) with Primaquine, and 37·5% (23–52) with Chloroquine alone. Tafenoquine 300 mg and 600 mg had better efficacy than Chloroquine alone (treatment differences 51·7% [95% CI 35–69], p Interpretation Single-dose tafenoquine 300 mg coadministered with Chloroquine for P vivax malaria relapse prevention was more efficacious than Chloroquine alone, with a similar safety profile. As a result, it has been selected for further clinical assessment in phase 3. Funding GlaxoSmithKline, Medicines for Malaria Venture.
Cor Jf Fontes - One of the best experts on this subject based on the ideXlab platform.
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Adherence to Plasmodium vivax malaria treatment in the Brazilian Amazon Region
Malaria Journal, 2011Co-Authors: Elza A Pereira, Edna Ay Ishikawa, Cor Jf FontesAbstract:Background Patients' adherence to malaria treatment is an important factor in determining the therapeutic response to anti-malarial drugs. It contributes to the patient's complete recovery and prevents the emergence of parasite resistance to anti-malarial drugs. In Brazil, the low compliance with malaria treatment probably explains the large number of Plasmodium vivax malaria relapses observed in the past years. The goal of this study was to estimate the proportion of patients adhering to the P. vivax malaria treatment with Chloroquine + Primaquine in the dosages recommended by the Brazilian Ministry of Health. Methods Patients who were being treated for P. vivax malaria with Chloroquine Plus Primaquine were eligible for the study. On the seventh day of taking Primaquine, they were visited at their home and were interviewed. The patients were classified as probably adherent, if they reported having taken all the medication as prescribed, in the correct period of time and dosage, and had no medication tablets remaining; probably non-adherent, if they reported not having taken the medication, in the correct period of time and dosage, and did not show any remaining tablets; and certainly non-adherent, if they showed any remaining medication tablets. Results 242 of the 280 patients reported having correctly followed the prescribed instructions and represented a treatment adherence frequency (CI95%) of 86.4% (81.7%-90.1%). Of the 38 patients who did not follow the recommendations, 27 (9.6%) were still taking the medication on the day of the interview and, therefore, still had Primaquine tablets left in the blister pack. These patients were then classified as certainly non-adherent to treatment. Although 11 patients did not show any tablets left, they reported incorrect use of the prescribed therapy regimen and were considered as probably non-adherent to treatment. Conclusions Compliance with the P. vivax malaria treatment is a characteristic of 242/280 patients in the surveyed region. However, the group of non-adherent patients can have an impact on the magnitude of transmission and relapses of P. vivax infections currently observed in the studied area. Simple practices can be introduced in the healthcare services in order to improve compliance with the treatment prescribed.