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Primaquine

Significant efficacy of single low dose primaquine compared to stand alone artemisinin combination therapy in reducing gametocyte carriage in Cambodian patients with uncomplicated multidrug resistant Plasmodium falciparum malaria

March 19, 2020 - 09:13 -- Open Access
Author(s): 
Vantaux A, Kim S, Piv E, Chy S, Berne L, Khim N, Lek D, Siv S, Mukaka M, Taylor WR, Ménard D
Reference: 
Antimicrob Agents Chemother. 2020 Mar 16. pii: AAC.02108-19

Since 2012, single low dose of primaquine (SLDPQ, 0.25mg/kg) has been recommended with artemisinin-based combination therapies, as first-line treatment of acute uncomplicated Plasmodium falciparum malaria, to interrupt its transmission, especially in low transmission settings of multidrug, including artemisinin, resistance. Policy makers in Cambodia have been reluctant to implement this recommendation due to primaquine safety concerns and lack of data on its efficacy.

Corrigendum to: Hemolytic Dynamics of Weekly Primaquine Antirelapse Therapy Among Cambodians With Acute Plasmodium vivax Malaria With or Without Glucose-6-Phosphate Dehydrogenase Deficiency

February 22, 2020 - 17:12 -- Open Access
Author(s): 
Taylor WRJ, Kheng S, Muth S, Tor P, Kim S, Bjorge S, Topps N, Kosal K, Sothea K, Souy P, Char CM, Vanna C, Ly P, Khieu V, Christophel E, Kerleguer A, Pantaleo A, Mukaka M, Menard D, Baird JK
Reference: 
The Journal of Infectious Diseases, Volume 221, Issue 5, 1 March 2020, Page 854

In “Hemolytic Dynamics of Weekly Primaquine Antirelapse Therapy Among Cambodians With Acute Plasmodium vivax Malaria With or Without Glucose-6-Phosphate Dehydrogenase Deficiency” by Taylor et al [J Infect Dis 2019; 220(11): 1750–60], P values should be P < 0.001 where 0.000 is written. This has been updated in the article.

The authors regret these errors.

Mass drug administrations with dihydroartemisinin-piperaquine and single low dose primaquine to eliminate Plasmodium falciparum have only a transient impact on Plasmodium vivax: Findings from randomised controlled trials

February 14, 2020 - 16:53 -- Open Access
Author(s): 
Phommasone K, van Leth F, von Seidlein L, et al.
Reference: 
PLoS ONE 15(2): e0228190

Mass administrations of antimalarial drugs (MDA) have reduced the incidence and prevalence of P. falciparum infections in a trial in the Greater Mekong Subregion. Here we assess the impact of the MDA on P. vivax infections.

Optimal timing of primaquine to reduce Plasmodium falciparum gametocyte carriage when co-administered with artemether–lumefantrine

January 24, 2020 - 14:49 -- Open Access
Author(s): 
Seif Shekalaghe, Dominic Mosha, Ali Hamad, Thabit A. Mbaga, Michael Mihayo, Teun Bousema, Chris Drakeley and Salim Abdulla
Reference: 
Malaria Journal 2020 19:34, 21 January 2020

Primaquine is an important gametocytocidal drug that is combined with conventional malaria treatment for prevention of Plasmodium falciparum malaria transmission. Primaquine has been administered together on the first or the last day of conventional treatment but the impact of primaquine timing has never been examined. This study aimed to assess safety, efficacy and optimal timing of single full-dose (0.75 mg/kg) primaquine when added to a standard 6-dose regimen of artemether–lumefantrine (AL).

The use of ultrasensitive quantitative-PCR to assess the impact of primaquine on asymptomatic relapse of Plasmodium vivax infections: a randomized, controlled trial in Lao PDR

January 7, 2020 - 14:55 -- Open Access
Author(s): 
Koukeo Phommasone, Frank van Leth, Mayfong Mayxay, et al.
Reference: 
Malaria Journal 2020 19:4, 3 January 2020

Trials to assess the efficacy of the radical cure of Plasmodium vivax malaria with 8-aminoquinolines require that most post-treatment relapses are identified, but there is no consensus on the optimal duration of follow-up in either symptomatic or asymptomatic vivax malaria. The efficacy of a 14-day course of primaquine on the cumulative incidence of recurrent asymptomatic P. vivax infections detected by ultrasensitive quantitative PCR (uPCR) as a primary endpoint was assessed.

Coupling the Antimalarial Cell Penetrating Peptide TP10 to Classical Antimalarial Drugs Primaquine and Chloroquine Produces Strongly Hemolytic Conjugates

December 23, 2019 - 14:59 -- Open Access
Author(s): 
Aguiar L, Biosca A, Lantero E, Gut J, Vale N, Rosenthal PJ, Nogueira F, Andreu D, Fernàndez-Busquets X, Gomes P
Reference: 
Molecules 2019, 24(24), 4559

Recently, we disclosed primaquine cell penetrating peptide conjugates that were more potent than parent primaquine against liver stage Plasmodium parasites and non-toxic to hepatocytes. The same strategy was now applied to the blood-stage antimalarial chloroquine, using a wide set of peptides, including TP10, a cell penetrating peptide with intrinsic antiplasmodial activity. Chloroquine-TP10 conjugates displaying higher antiplasmodial activity than the parent TP10 peptide were identified, at the cost of an increased hemolytic activity, which was further confirmed for their primaquine analogues.

Killing of Plasmodium vivax by Primaquine and Tafenoquine

October 30, 2019 - 09:45 -- Open Access
Author(s): 
Miles B. Markus
Reference: 
Trends In Parasitology, Volume 35, ISSUE 11, P857-859, November 01, 2019

Primaquine administration results in H 2O 2 accumulation in bone marrow, where gametocytes and asexual parasites are therefore killed. This finding, by Camarda et al. , supports the theory that the nonperipheral blood origin of recurrent Plasmodium vivax malaria is both hypnozoites (relapse source) and merozoites (recrudescence source), not hypnozoites only.

Medical Condition: 

The efficacy of dihydroartemisinin-piperaquine and artemether-lumefantrine with and without primaquine on Plasmodium vivax recurrence: A systematic review and individual patient data meta-analysis

October 15, 2019 - 15:36 -- Open Access
Author(s): 
Robert J. Commons, Julie A. Simpson, Ric N. Price, et al.
Reference: 
PLoS Med 16(10): e1002928

Artemisinin-based combination therapy (ACT) is recommended for uncomplicated Plasmodium vivax malaria in areas of emerging chloroquine resistance. We undertook a systematic review and individual patient data meta-analysis to compare the efficacies of dihydroartemisinin-piperaquine (DP) and artemether-lumefantrine (AL) with or without primaquine (PQ) on the risk of recurrent P. vivax.

Medical Condition: 

Pharmacokinetics/pharmacodynamics of chloroquine and artemisinin-based combination therapy with primaquine

September 24, 2019 - 14:59 -- Open Access
Author(s): 
André Daher, Ghait Aljayyoussi, David G. Lalloo, et al.
Reference: 
Malaria Journal 2019 18:325, 23 September 2019

Activation of hypnozoites of vivax malaria causes multiple clinical relapses, which contribute to the Plasmodium vivax burden and continuing transmission. Artemisinin-based combination therapy (ACT) is effective against blood-stage P. vivax but requires co-administration with primaquine to achieve radical cure. The therapeutic efficacy of primaquine depends on the generation of a therapeutically active metabolite via cytochrome P450 2D6 (CYP2D6). Impaired CYP2D6 metabolism has been associated with primaquine treatment failure. This study investigated the association between impaired CYP2D6 genotypes, drug-exposure to the long-acting ACT component (schizonticidal drugs) and tolerance and efficacy.

Medical Condition: 

Modelling the benefits of long-acting or transmission-blocking drugs for reducing Plasmodium falciparum transmission by case management or by mass treatment

August 22, 2017 - 17:51 -- Open Access
Author(s): 
Michael T. Bretscher, Jamie T. Griffin, Azra C. Ghani and Lucy C. Okell
Reference: 
Malaria Journal 2017 16:341, 16 August 2017

These results emphasise the importance of increasing access to treatment for routine case management, and the potential value of choosing first-line anti-malarial treatment policies according to local malaria epidemiology to maximise impact on transmission.

Medical Treatment: 

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