Résumé
La primaquine, une amino-8-quinoléine, est un antipaludique relativement méconnu et sous-utilisé en Afrique francophone. Ce médicament possède des activités antipaludiques sur les schizontes hépatiques de toutes les espèces plasmodiales spécifiques de l’homme, les schizontes intraérythrocytaires asexués de Plasmodium vivax et, à un moindre degré, de Plasmodium falciparum, sur les gamétocytes matures de P. falciparum et sur les hypnozoïtes de P. vivax et Plasmodium ovale. L’utilité thérapeutique de la primaquine est limitée par le risque d’anémie hémolytique aiguë. Suite aux recommandations récemment formulées par l’Organisation mondiale de la santé (OMS), nous proposons d’examiner l’utilité de la primaquine en Afrique francophone afin d’améliorer la lutte contre le paludisme et de progresser vers son élimination. Deux indications ont été retenues par l’OMS. La première indication consiste à associer les bithérapies à base d’artémisinine à la primaquine en dose unique et faible (0,25 mg base/kg) pour éliminer les parasites asexués et sexués de P. falciparum. Ce schéma thérapeutique est bien toléré et présente peu de risques, même chez les individus légèrement ou modérément déficients en glucose-6-phosphate déshydrogénase (G6PD). Cette stratégie pourrait endiguer la transmission dans une zone en Afrique où l’incidence du paludisme à P. falciparum a considérablement baissé. Le traitement radical de P. vivax et de P. ovale est la seconde indication retenue par l’OMS. Le schéma thérapeutique de référence de 14 jours (0,25 à 0,5 mg base/kg par jour) est efficace, mais il n’est pas préconisé chez les patients déficients en G6PD. Des études cliniques seront nécessaires pour mieux définir la place de la primaquine pour le traitement radical chez les patients déficitaires en G6PD en Afrique. Sans la primaquine, l’élimination éventuelle du paludisme à P. vivax et à P. ovale semble extrêmement difficile. Des données épidémiologiques mises à jour sur la G6PD, l’antigène Duffy et la répartition actuelle et le poids du paludisme à P. vivax et à P. ovale sont nécessaires pour l’utilisation rationnelle de la primaquine sur le continent africain. En outre, des essais cliniques sur la primaquine s’imposent en Afrique.
Abstract
Primaquine, an 8-aminoquinoline, is a relatively unknown and underutilized drug in French-speaking African countries. It acts against the liver stage parasites of all human malaria species, asexual blood stages of Plasmodium vivax and, to a lesser degree, Plasmodium falciparum; P. falciparum mature gametocytes, and P. vivax and Plasmodium ovale hypnozoites. Gastrointestinal disturbances are its most common side effects. The clinical utility of primaquine is limited due to its hematological side effects in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency and other contraindications (pregnant woman, breastfeeding woman, infants less than 6 months old). In the light of the recent recommendations of the World Health Organization (WHO), we propose to examine how primaquine can be used in French-speaking Africa to improve malaria control and move towards malaria elimination. Two indications supported by the WHO are of relevance in Africa. First, artemisinin-based combination therapies and primaquine given as a single low dose (0.25 mg base/kg) are effective to kill asexual and sexual parasites of P. falciparum, are well-tolerated, and have very little risk even in mild to moderate G6PD-deficient patients. This strategy may be helpful to contain transmission in an area in Africa where P. falciparum malaria incidence has decreased considerably. There is an ethical concern in administering primaquine as a gametocytocide as it does not confer any direct benefit to the treated patient. However, the single low-dose primaquine is most likely associated with very low risk for adverse hematological effects, and WHO recommends its use even without prior G6PD testing. In our opinion, clinical studies including G6PD test should be conducted to assess the safety of low-dose primaquine in African patients. Second, primaquine is effective and necessary for radical treatment of P. vivax and P. ovale, but the standard 14-day treatment (0.25–0.5 mg base/kg/day) is not recommended in patients with G6PD deficiency. Prior G6PD testing is required before prescribing primaquine for radical treatment. The use of primaquine for radical treatment in patients without contraindications does not raise any major ethical problem since the probability of relapse in patients who do not receive anti-hypnozoite treatment can be relatively high and each relapse can cause or aggravate anemia, especially in children. In our opinion, patients with mild or moderate G6PD deficiency should not be treated with primaquine at present. Further clinical studies are necessary to define the role of this drug for radical treatment in G6PD-deficient African patients. Without primaquine, the eventual elimination of P. vivax and P. ovale malaria appears to be very difficult. Updated epidemiological data on G6PD, Duffy antigen, and the current distribution of and burden due to P. vivax and P. ovale are required for a rational use of primaquine in the African continent. Moreover, clinical studies on primaquine are required in Africa.
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Briolant, S., Pradines, B. & Basco, L.K. Place de la primaquine dans la lutte contre le paludisme en Afrique francophone. Bull. Soc. Pathol. Exot. 110, 198–206 (2017). https://doi.org/10.1007/s13149-017-0556-z
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DOI: https://doi.org/10.1007/s13149-017-0556-z
Mots clés
- Paludisme
- Plasmodium falciparum
- Plasmodium vivax
- Plasmodium ovale
- Chimiorésistance
- Primaquine
- Déficience en G6PD
- Antigène Duffy
- Afrique francophone