The Experts below are selected from a list of 270 Experts worldwide ranked by ideXlab platform
Nicholas J. White - One of the best experts on this subject based on the ideXlab platform.
-
use of Primaquine and glucose 6 phosphate dehydrogenase deficiency testing divergent policies and practices in malaria endemic countries
PLOS Neglected Tropical Diseases, 2018Co-Authors: Judith Recht, Elizabeth A. Ashley, Nicholas J. WhiteAbstract:Primaquine is the only available antimalarial drug that kills dormant liver stages of Plasmodium vivax and Plasmodium ovale malarias and therefore prevents their relapse ('radical cure'). It is also the only generally available antimalarial that rapidly sterilises mature P. falciparum gametocytes. Radical cure requires extended courses of Primaquine (usually 14 days; total dose 3.5-7 mg/kg), whereas transmissibility reduction in falciparum malaria requires a single dose (formerly 0.75 mg/kg, now a single low dose [SLD] of 0.25 mg/kg is recommended). The main adverse effect of Primaquine is dose-dependent haemolysis in glucose 6-phosphate dehydrogenase (G6PD) deficiency, the most common human enzymopathy. X-linked mutations conferring varying degrees of G6PD deficiency are prevalent throughout malaria-endemic regions. Phenotypic screening tests usually detect <30% of normal G6PD activity, identifying nearly all male hemizygotes and female homozygotes and some heterozygotes. Unfortunately, G6PD deficiency screening is usually unavailable at point of care, and, as a consequence, radical cure is greatly underused. Both haemolytic risk (determined by the prevalence and severity of G6PD deficiency polymorphisms) and relapse rates vary, so there has been considerable uncertainty in both policies and practices related to G6PD deficiency testing and use of Primaquine for radical cure. Review of available information on the prevalence and severity of G6PD variants together with countries' policies for the use of Primaquine and G6PD deficiency testing confirms a wide range of practices. There remains lack of consensus on the requirement for G6PD deficiency testing before prescribing Primaquine radical cure regimens. Despite substantially lower haemolytic risks, implementation of SLD Primaquine as a P. falciparum gametocytocide also varies. In Africa, a few countries have recently adopted SLD Primaquine, yet many with areas of low seasonal transmission do not use Primaquine as an antimalarial at all. Most countries that recommended the higher 0.75 mg/kg single Primaquine dose for falciparum malaria (e.g., most countries in the Americas) have not changed their recommendation. Some vivax malaria-endemic countries where G6PD deficiency testing is generally unavailable have adopted the once-weekly radical cure regimen (0.75 mg/kg/week for 8 weeks), known to be safer in less severe G6PD deficiency variants. There is substantial room for improvement in radical cure policies and practices.
-
open label crossover study of Primaquine and dihydroartemisinin piperaquine pharmacokinetics in healthy adult thai subjects
Antimicrobial Agents and Chemotherapy, 2014Co-Authors: Borimas Hanboonkunupakarn, Warunee Hanpithakpong, Podjanee Jittamala, Palang Chotsiri, Thanaporn Wattanakul, Salwaluk Panapipat, Elizabeth A. Ashley, Joel Tarning, Sasithon Pukrittayakamee, Nicholas J. WhiteAbstract:Dihydroartemisinin-piperaquine is an artemisinin-based combination treatment (ACT) recommended by the WHO for uncomplicated Plasmodium falciparum malaria, and it is being used increasingly for resistant vivax malaria where combination with Primaquine is required for radical cure. The WHO recently reinforced its recommendations to add a single dose of Primaquine to ACTs to reduce P. falciparum transmission in low-transmission settings. The pharmacokinetics of Primaquine and dihydroartemisinin-piperaquine were evaluated in 16 healthy Thai adult volunteers in a randomized crossover study. Volunteers were randomized to two groups of three sequential hospital admissions to receive 30 mg (base) Primaquine, 3 tablets of dihydroartemisinin-piperaquine (120/960 mg), and the drugs together at the same doses. Blood sampling was performed over 3 days following Primaquine and 36 days following dihydroartemisinin-piperaquine dosing. Pharmacokinetic assessment was done with a noncompartmental approach. The drugs were well tolerated. There were no statistically significant differences in dihydroartemisinin and piperaquine pharmacokinetics with or without Primaquine. Dihydroartemisinin-piperaquine coadministration significantly increased plasma Primaquine levels; geometric mean ratios (90% confidence interval [CI]) of Primaquine combined versus Primaquine alone for maximum concentration (Cmax), area under the concentration-time curve from 0 h to the end of the study (AUC0-last), and area under the concentration-time curve from 0 h to infinity (AUC0-∞) were 148% (117 to 187%), 129% (103 to 163%), and 128% (102 to 161%), respectively. This interaction is similar to that described recently with chloroquine and may result in an enhanced radical curative effect. (This study has been registered at ClinicalTrials.gov under registration no. NCT01525511.).
-
activities of artesunate and Primaquine against asexual and sexual stage parasites in falciparum malaria
Antimicrobial Agents and Chemotherapy, 2004Co-Authors: Sasithon Pukrittayakamee, Arun Chantra, Ralf Clemens, Kesinee Chotivanich, Sornchai Looareesuwan, Nicholas J. WhiteAbstract:The activities of Primaquine in combination with quinine or artesunate against asexual- and sexual-stage parasites were assessed in 176 adult Thai patients with uncomplicated Plasmodium falciparum malaria. Patients were randomized to one of the six following 7-day oral treatment regimens: (i) quinine alone, (ii) quinine with tetracycline, (iii) quinine with Primaquine at 15 mg/day, (iv) quinine with Primaquine at 30 mg/day, (v) artesunate alone, or (vi) artesunate with Primaquine. Clinical recovery occurred in all patients. There were no significant differences in fever clearance times, rates of P. falciparum reappearance, or recurrent vivax malaria between the six treatment groups. Patients treated with artesunate alone or in combination with Primaquine had significantly shorter parasite clearance times (mean +/- standard deviation = 65 +/- 18 versus 79 +/- 21 h) and lower gametocyte carriage rates (40 versus 62.7%) than those treated with quinine (P 0.2). Gametocytemia was detected in 98 patients (56% [22% before treatment and 34% after treatment]). Artesunate reduced the appearance of gametocytemia (relative risk [95% confidence interval] = 0.34 [0.17 to 0.70]), whereas combinations containing Primaquine resulted in shorter gametocyte clearance times (medians of 66 versus 271 h for quinine groups and 73 versus 137 h for artesunate groups; P < or = 0.038). These results suggest that artesunate predominantly inhibits gametocyte development whereas Primaquine accelerates gametocyte clearance in P. falciparum malaria.
Balbir Singh - One of the best experts on this subject based on the ideXlab platform.
-
Clinical and parasitological response to oral chloroquine and Primaquine in uncomplicated human Plasmodium knowlesi infections
Malaria Journal, 2010Co-Authors: Cyrus Daneshvar, Timothy Me Davis, Janet Cox-singh, Mohammad Z Rafa'ee, Siti K Zakaria, Paul Cs Divis, Balbir SinghAbstract:Background Plasmodium knowlesi is a cause of symptomatic and potentially fatal infections in humans. There are no studies assessing the detailed parasitological response to treatment of knowlesi malaria infections in man and whether antimalarial resistance occurs. Methods A prospective observational study of oral chloroquine and Primaquine therapy was conducted in consecutive patients admitted to Kapit Hospital, Sarawak, Malaysian Borneo with PCR-confirmed single P. knowlesi infections. These patients were given oral chloroquine for three days, and at 24 hours oral Primaquine was administered for two consecutive days, primarily as a gametocidal agent. Clinical and parasitological responses were recorded at 6-hourly intervals during the first 24 hours, daily until discharge and then weekly to day 28. Vivax malaria patients were studied as a comparator group. Results Of 96 knowlesi malaria patients who met the study criteria, 73 were recruited to an assessment of the acute response to treatment and 60 completed follow-up over 28 days. On admission, the mean parasite stage distributions were 49.5%, 41.5%, 4.0% and 5.6% for early trophozoites, late trophozoites, schizonts and gametocytes respectively. The median fever clearance time was 26.5 [inter-quartile range 16-34] hours. The mean times to 50% (PCT_50) and 90% (PCT_90) parasite clearance were 3.1 (95% confidence intervals [CI] 2.8-3.4) hours and 10.3 (9.4-11.4) hours. These were more rapid than in a group of 23 patients with vivax malaria 6.3 (5.3-7.8) hours and 20.9 (17.6-25.9) hours; P = 0.02). It was difficult to assess the effect of Primaquine on P. knowlesi parasites, due to the rapid anti-malarial properties of chloroquine and since Primaquine was administered 24 hours after chloroquine. No P. knowlesi recrudescences or re-infections were detected by PCR. Conclusions Chloroquine plus primaqine is an inexpensive and highly effective treatment for uncomplicated knowlesi malaria infections in humans and there is no evidence of drug resistance. Further studies using alternative anti-malarial drugs, including artemisinin derivatives, would be desirable to define optimal management strategies for P. knowlesi .
-
clinical and parasitological response to oral chloroquine and Primaquine in uncomplicated human plasmodium knowlesi infections
Malaria Journal, 2010Co-Authors: Cyrus Daneshvar, Timothy Me Davis, Siti K Zakaria, Paul Cs Divis, Janet Coxsingh, Mohammad Zakri Rafaee, Balbir SinghAbstract:Plasmodium knowlesi is a cause of symptomatic and potentially fatal infections in humans. There are no studies assessing the detailed parasitological response to treatment of knowlesi malaria infections in man and whether antimalarial resistance occurs. A prospective observational study of oral chloroquine and Primaquine therapy was conducted in consecutive patients admitted to Kapit Hospital, Sarawak, Malaysian Borneo with PCR-confirmed single P. knowlesi infections. These patients were given oral chloroquine for three days, and at 24 hours oral Primaquine was administered for two consecutive days, primarily as a gametocidal agent. Clinical and parasitological responses were recorded at 6-hourly intervals during the first 24 hours, daily until discharge and then weekly to day 28. Vivax malaria patients were studied as a comparator group. Of 96 knowlesi malaria patients who met the study criteria, 73 were recruited to an assessment of the acute response to treatment and 60 completed follow-up over 28 days. On admission, the mean parasite stage distributions were 49.5%, 41.5%, 4.0% and 5.6% for early trophozoites, late trophozoites, schizonts and gametocytes respectively. The median fever clearance time was 26.5 [inter-quartile range 16-34] hours. The mean times to 50% (PCT50) and 90% (PCT90) parasite clearance were 3.1 (95% confidence intervals [CI] 2.8-3.4) hours and 10.3 (9.4-11.4) hours. These were more rapid than in a group of 23 patients with vivax malaria 6.3 (5.3-7.8) hours and 20.9 (17.6-25.9) hours; P = 0.02). It was difficult to assess the effect of Primaquine on P. knowlesi parasites, due to the rapid anti-malarial properties of chloroquine and since Primaquine was administered 24 hours after chloroquine. No P. knowlesi recrudescences or re-infections were detected by PCR. Chloroquine plus primaqine is an inexpensive and highly effective treatment for uncomplicated knowlesi malaria infections in humans and there is no evidence of drug resistance. Further studies using alternative anti-malarial drugs, including artemisinin derivatives, would be desirable to define optimal management strategies for P. knowlesi.
Eugenie Poirot - One of the best experts on this subject based on the ideXlab platform.
-
safety and efficacy of adding a single low dose of Primaquine to the treatment of adult patients with plasmodium falciparum malaria in senegal to reduce gametocyte carriage a randomized controlled trial
Clinical Infectious Diseases, 2017Co-Authors: Roger Tine, Eugenie Poirot, Khadime Sylla, Babacar Faye, F Fall, Duolao Wang, Magatte Ndiaye, Jean Louis Ndiaye, B M GreenwoodAbstract:Introduction More information is needed about the safety of low-dose Primaquine in populations where G6PD deficiency is common. Methods Adults with Plasmodium falciparum malaria were randomized to receive 1 of 3 artemisinin combination therapies (ACTs) with or without Primaquine (0.25 mg/kg). Glucose-6-phosphate dehydrogenase (G6PD) status was determined using a rapid test. Patients were followed for 28 days to record hemoglobin concentration, adverse events, and gametocyte carriage. The primary end point was the change in Hb at day 7. Results In sum, 274 patients were randomized, 139 received an ACT alone, and 135 received an ACT + Primaquine. The mean reduction in Hb at day 7 was similar in each group, a difference in the ACT + PQ versus the ACT alone group of -0.04 g/dL (95% confidence interval [CI] -0.23, 0.31), but the effect of Primaquine differed according to G6PD status. In G6PD-deficient patients the drop in Hb was 0.63 g/dL (95% CI 0.03, 1.24) greater in those who received Primaquine than in those who received an ACT alone. In G6PD-normal patients, the reduction in Hb was 0.22 g/dL (95% CI -0.08, 0.52) less in those who received Primaquine (interaction P = .01). One G6PD normal patient who received Primaquine developed moderately severe anaemia (Hb < 8 g/dL). Dark urine was more frequent in patients who received Primaquine. Primaquine was associated with a 73% (95% CI 24-90) reduction in gametocyte carriage (P = .013). Conclusion Primaquine substantially reduced gametocyte carriage. However, the fall in Hb concentration at day 7 was greater in G6PD-deficient patients who received Primaquine than in those who did not and one patient who received Primaquine developed moderately severe anemia.
-
an assessment of the supply programmatic use and regulatory issues of single low dose Primaquine as a plasmodium falciparum gametocytocide for sub saharan africa
Malaria Journal, 2015Co-Authors: Ingrid Chen, Eugenie Poirot, Mark Newman, Deepika Kandula, Renee Shah, Jimee Hwang, Justin M Cohen, Roly Gosling, Luke RooneyAbstract:Global ambitions to eliminate malaria are intensifying, underscoring a critical need for transmission blocking tools. In 2012, the WHO recommended the use of 0.25 mg/kg of single low-dose (SLD) Primaquine to stop Plasmodium falciparum transmission. To ensure the availability of SLD Primaquine to countries in need of this tool, more information on the supply, programmatic, and regulatory barriers to the rollout of SLD Primaquine is required. Challenges to the rollout of SLD Primaquine in sub-Saharan Africa were established through semi-structured qualitative interviews with three Primaquine manufacturers, 43 key informants from Ethiopia, Senegal, Swaziland, Zambia, and Tanzania, and 16 malaria research experts. Sanofi and Remedica are the only two sources of SRA-approved Primaquine suitable for procurement by international donors. Neither manufacturer produces Primaquine tablet strengths suitable for the transmission blocking indication. In-country key informants revealed that the WHO weight-based recommendation to use SLD Primaquine is challenging to implement in actual field settings. Malaria programmes expressed safety concerns of SLD Primaquine use in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency, as well as potential interactions between Primaquine and co-morbidities, and drug-drug interactions with HIV and/or tuberculosis treatments. Regulatory processes are a major barrier to the rollout of SLD Primaquine, requiring multiple steps at both the country and global level. Despite these barriers, demand for SLD Primaquine is growing, and malaria researchers are interested in Primaquine deployment through mass screen and treat and/or mass drug administration campaigns. Demand for Primaquine as a transmission blocking agent is growing rapidly yet multiple barriers to SLD Primaquine use exist. Research is needed to define the therapeutic dose range, which will guide dosing regimens in the field, inform the development of new, lower strength Primaquine tablets and/or formulation(s), and allay programmatic safety concerns in individuals with G6PD deficiency. Potential interactions between Primaquine and co-morbidities and treatments should be explored. To minimize regulatory delays, countries need to prepare for product registration at an early stage, WHO prequalification for suitable Primaquine tablet strengths and/or new formulations should be sought, and in the meanwhile only Stringent Regulatory Authority (SRA)-approved Primaquine should be used.
-
Pharmacovigilance for single low-dose Primaquine: a practical approach
Malaria Journal, 2014Co-Authors: Eugenie Poirot, Ingrid Chen, Andy Stergachis, Feiko O. Ter Kuile, Philippe J Guerin, Roland GoslingAbstract:Establishing and strengthening pharmacovigilance in resource-limited settings provides a valuable opportunity to identify, quantify and address pertinent safety concerns regarding the use of single low-dose (SLD) Primaquine. While it is understood that Primaquine causes dose-dependent hemolysis in glucose-6-phosphate dehydrogenase (G6PD) deficient individuals with P. falciparum and P. vivax malaria, the extent of this risk when using low doses of Primaquine remains to be defined. Prospective pharmacovigilance methods are needed to confirm or refute these safety concerns that have likely hindered the uptake of the new WHO policy for SLD Primaquine. Pharmacovigilance in resource-limited settings is challenging, especially when attempting to identify unknown or poorly understood adverse drug reactions over weeks of follow-up. In contrast, the objectives of a pharmacovigilance program for SLD Primaquine are specific, measurable, and attainable within a short time frame. The nadir of Primaquine-induced hemolytic anemia, measurable by hemoglobin concentrations, has been shown to occur on or near day 7. Thus, it is expected that adverse drug reactions related to Primaquine can be captured within a week of drug administration by active surveillance methods involving patient follow-up. Furthermore, dark urine is a characteristic sign of acute hemolytic anemia, an easily identifiable and documentable symptom of hemolysis. Numerous pharmacovigilance efforts are ongoing, supporting individual countries in the collection of standardized SLD Primaquine safety data. These efforts seek to establish the expected fall in hemoglobin from baseline levels before treatment to levels seven days post-treatment and include G6PD testing and recording of adverse events using standard data collection instruments. Each participating in-country program or study site aims to collect data on 100-400 subjects depending on malaria endemicity and expected G6PD prevalence. We plan to collate data across these countries in a global database of individual patient data, contributing to the evidence-base for benefit-risk assessments of SLD Primaquine. As other 8-aminoquinoline drugs such as tafenoquine come to market, we will be faced with related safety concerns of dose-dependent hemolysis in G6PD-deficient individuals. Active pharmacovigilance and the establishment of a standardized database for SLD Primaquine not only provide opportunities to harmonize efforts, address unanswered questions regarding the safe use of SLD Primaquine, and assist programs planning widespread roll-out of SLD Primaquine in routine malaria case management they can also serve as a common platform for other current and future pharmacovigilance needs. The methods used in these efforts and the composition of this database will be described.
Sasithon Pukrittayakamee - One of the best experts on this subject based on the ideXlab platform.
-
Pharmacokinetic Interactions between Primaquine and Pyronaridine- Artesunate in Healthy Adult Thai Subjects
2016Co-Authors: Podjanee Jittamala, Borimas Hanboonkunupakarn, Elizabeth A. Ashley, Sasithon Pukrittayakamee, François Nosten, Joel Tarningb CAbstract:Pyronaridine-artesunate is a newly introduced artemisinin-based combination treatment which may be deployed together with Primaquine. A single-dose, randomized, three-sequence crossover study was conducted in healthy Thai volunteers to character-ize potential pharmacokinetic interactions between these drugs. Seventeen healthy adults received a single oral dose of prima-quine alone (30 mg base) and were then randomized to receive pyronaridine-artesunate alone (540180 mg) or pyronaridine-artesunate plus Primaquine in combination, with intervening washout periods between all treatments. The pharmacokinetic properties of Primaquine, its metabolite carboxyPrimaquine, artesunate, its metabolite dihydroartemisinin, and pyronaridine were assessed in 15 subjects using a noncompartmental approach followed by a bioequivalence evaluation. All drugs were well tolerated. The single oral dose of Primaquine did not result in any clinically relevant pharmacokinetic alterations to pyronari-dine, artesunate, or dihydroartemisinin exposures. There were significantly higher Primaquine maximum plasma drug concen-trations (geometric mean ratio, 30%; 90 % confidence interval [CI], 17 % to 46%) and total exposures (15%; 6.4 % to 24%) during coadministration with pyronaridine-artesunate than when Primaquine was given alone. Pyronaridine, like chloroquine and pip-eraquine, increases plasma Primaquine concentrations. (This study has been registered at ClinicalTrials.gov under registration no. NCT01552330.) Artemisinin-based combination therapy (ACT) is the recom-mended first-line treatment for uncomplicated Plasmodiu
-
open label crossover study of Primaquine and dihydroartemisinin piperaquine pharmacokinetics in healthy adult thai subjects
Antimicrobial Agents and Chemotherapy, 2014Co-Authors: Borimas Hanboonkunupakarn, Warunee Hanpithakpong, Podjanee Jittamala, Palang Chotsiri, Thanaporn Wattanakul, Salwaluk Panapipat, Elizabeth A. Ashley, Joel Tarning, Sasithon Pukrittayakamee, Nicholas J. WhiteAbstract:Dihydroartemisinin-piperaquine is an artemisinin-based combination treatment (ACT) recommended by the WHO for uncomplicated Plasmodium falciparum malaria, and it is being used increasingly for resistant vivax malaria where combination with Primaquine is required for radical cure. The WHO recently reinforced its recommendations to add a single dose of Primaquine to ACTs to reduce P. falciparum transmission in low-transmission settings. The pharmacokinetics of Primaquine and dihydroartemisinin-piperaquine were evaluated in 16 healthy Thai adult volunteers in a randomized crossover study. Volunteers were randomized to two groups of three sequential hospital admissions to receive 30 mg (base) Primaquine, 3 tablets of dihydroartemisinin-piperaquine (120/960 mg), and the drugs together at the same doses. Blood sampling was performed over 3 days following Primaquine and 36 days following dihydroartemisinin-piperaquine dosing. Pharmacokinetic assessment was done with a noncompartmental approach. The drugs were well tolerated. There were no statistically significant differences in dihydroartemisinin and piperaquine pharmacokinetics with or without Primaquine. Dihydroartemisinin-piperaquine coadministration significantly increased plasma Primaquine levels; geometric mean ratios (90% confidence interval [CI]) of Primaquine combined versus Primaquine alone for maximum concentration (Cmax), area under the concentration-time curve from 0 h to the end of the study (AUC0-last), and area under the concentration-time curve from 0 h to infinity (AUC0-∞) were 148% (117 to 187%), 129% (103 to 163%), and 128% (102 to 161%), respectively. This interaction is similar to that described recently with chloroquine and may result in an enhanced radical curative effect. (This study has been registered at ClinicalTrials.gov under registration no. NCT01525511.).
-
Pharmacokinetic Interactions between Primaquine and Pyronaridine-Artesunate in Healthy Adult Thai Subjects
Antimicrobial agents and chemotherapy, 2014Co-Authors: Podjanee Jittamala, Borimas Hanboonkunupakarn, Elizabeth A. Ashley, Sasithon Pukrittayakamee, François Nosten, Sue J. Lee, Praiya Thana, Kalayanee Chairat, Daniel Blessborn, Salwaluk PanapipatAbstract:Pyronaridine-artesunate is a newly introduced artemisinin-based combination treatment which may be deployed together with Primaquine. A single-dose, randomized, three-sequence crossover study was conducted in healthy Thai volunteers to characterize potential pharmacokinetic interactions between these drugs. Seventeen healthy adults received a single oral dose of Primaquine alone (30 mg base) and were then randomized to receive pyronaridine-artesunate alone (540-180 mg) or pyronaridine-artesunate plus Primaquine in combination, with intervening washout periods between all treatments. The pharmacokinetic properties of Primaquine, its metabolite carboxyPrimaquine, artesunate, its metabolite dihydroartemisinin, and pyronaridine were assessed in 15 subjects using a noncompartmental approach followed by a bioequivalence evaluation. All drugs were well tolerated. The single oral dose of Primaquine did not result in any clinically relevant pharmacokinetic alterations to pyronaridine, artesunate, or dihydroartemisinin exposures. There were significantly higher Primaquine maximum plasma drug concentrations (geometric mean ratio, 30%; 90% confidence interval [CI], 17% to 46%) and total exposures (15%; 6.4% to 24%) during coadministration with pyronaridine-artesunate than when Primaquine was given alone. Pyronaridine, like chloroquine and piperaquine, increases plasma Primaquine concentrations. (This study has been registered at ClinicalTrials.gov under registration no. NCT01552330.).
-
activities of artesunate and Primaquine against asexual and sexual stage parasites in falciparum malaria
Antimicrobial Agents and Chemotherapy, 2004Co-Authors: Sasithon Pukrittayakamee, Arun Chantra, Ralf Clemens, Kesinee Chotivanich, Sornchai Looareesuwan, Nicholas J. WhiteAbstract:The activities of Primaquine in combination with quinine or artesunate against asexual- and sexual-stage parasites were assessed in 176 adult Thai patients with uncomplicated Plasmodium falciparum malaria. Patients were randomized to one of the six following 7-day oral treatment regimens: (i) quinine alone, (ii) quinine with tetracycline, (iii) quinine with Primaquine at 15 mg/day, (iv) quinine with Primaquine at 30 mg/day, (v) artesunate alone, or (vi) artesunate with Primaquine. Clinical recovery occurred in all patients. There were no significant differences in fever clearance times, rates of P. falciparum reappearance, or recurrent vivax malaria between the six treatment groups. Patients treated with artesunate alone or in combination with Primaquine had significantly shorter parasite clearance times (mean +/- standard deviation = 65 +/- 18 versus 79 +/- 21 h) and lower gametocyte carriage rates (40 versus 62.7%) than those treated with quinine (P 0.2). Gametocytemia was detected in 98 patients (56% [22% before treatment and 34% after treatment]). Artesunate reduced the appearance of gametocytemia (relative risk [95% confidence interval] = 0.34 [0.17 to 0.70]), whereas combinations containing Primaquine resulted in shorter gametocyte clearance times (medians of 66 versus 271 h for quinine groups and 73 versus 137 h for artesunate groups; P < or = 0.038). These results suggest that artesunate predominantly inhibits gametocyte development whereas Primaquine accelerates gametocyte clearance in P. falciparum malaria.
-
Blood Stage Antimalarial Efficacy of Primaquine in Plasmodium vivax Malaria
The Journal of Infectious Diseases, 1994Co-Authors: Sasithon Pukrittayakamee, S. Vanijanonta, Arun Chantra, Ralf ClemensAbstract:The blood stage antimalarial efficacy of Primaquine (0.25 mg of base/kg of body weight/day over 14 days) and chloroquine (25 mg of base/kg over 3 days) were compared in 85 adult Thai men with acute Plasmodium vivax malaria. Most (75%) had at least one malaria episode previously. Parasite clearance times after Primaquine alone (n = 30) were slower than after chloroquine (n = 30) or combined chloroquine-Primaquine (n = 25), but all patients had a satisfactory initial therapeutic response. P. vivax malaria recurred in 10 (17%) of 60 patients followed for > or = 2 months and Plasmodium falciparum malaria developed in another 5 (8%) without reexposure to infection. Recurrences occurred or = 5 weeks later, suggesting relapse. Vivax malaria responds well initially to either Primaquine or chloroquine. The blood stage antimalarial activity of Primaquine may mask chloroquine resistance in combined regimens.
B M Greenwood - One of the best experts on this subject based on the ideXlab platform.
-
safety and efficacy of adding a single low dose of Primaquine to the treatment of adult patients with plasmodium falciparum malaria in senegal to reduce gametocyte carriage a randomized controlled trial
Clinical Infectious Diseases, 2017Co-Authors: Roger Tine, Eugenie Poirot, Khadime Sylla, Babacar Faye, F Fall, Duolao Wang, Magatte Ndiaye, Jean Louis Ndiaye, B M GreenwoodAbstract:Introduction More information is needed about the safety of low-dose Primaquine in populations where G6PD deficiency is common. Methods Adults with Plasmodium falciparum malaria were randomized to receive 1 of 3 artemisinin combination therapies (ACTs) with or without Primaquine (0.25 mg/kg). Glucose-6-phosphate dehydrogenase (G6PD) status was determined using a rapid test. Patients were followed for 28 days to record hemoglobin concentration, adverse events, and gametocyte carriage. The primary end point was the change in Hb at day 7. Results In sum, 274 patients were randomized, 139 received an ACT alone, and 135 received an ACT + Primaquine. The mean reduction in Hb at day 7 was similar in each group, a difference in the ACT + PQ versus the ACT alone group of -0.04 g/dL (95% confidence interval [CI] -0.23, 0.31), but the effect of Primaquine differed according to G6PD status. In G6PD-deficient patients the drop in Hb was 0.63 g/dL (95% CI 0.03, 1.24) greater in those who received Primaquine than in those who received an ACT alone. In G6PD-normal patients, the reduction in Hb was 0.22 g/dL (95% CI -0.08, 0.52) less in those who received Primaquine (interaction P = .01). One G6PD normal patient who received Primaquine developed moderately severe anaemia (Hb < 8 g/dL). Dark urine was more frequent in patients who received Primaquine. Primaquine was associated with a 73% (95% CI 24-90) reduction in gametocyte carriage (P = .013). Conclusion Primaquine substantially reduced gametocyte carriage. However, the fall in Hb concentration at day 7 was greater in G6PD-deficient patients who received Primaquine than in those who did not and one patient who received Primaquine developed moderately severe anemia.
