Expanding the Use of Primaquine for the Radical Cure of Plasmodium vivax

Price, Ric N.; Douglas, Nicholas M.

doi:10.1093/cid/ciy236

Cited by 8 publications

(3 citation statements)

References 10 publications

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“…However, focal MDAs in Costa Rica can be made more effective. Currently, Costa Rica follows PAHO/WHO recommendations [24] to exclude breastfeeding women from malaria treatments, despite clinical evidence that suggests it is safe for this subpopulation and their breastfeeding children [25]. Thus, the 90% coverage of the BA MDA that we observed could be increased by at least 2% if breastfeeding mothers are included.…”

Section: Discussionmentioning

confidence: 84%

Malaria Elimination in Costa Rica: Changes in Treatment and Mass Drug Administration

et al. 2020

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Costa Rica is a candidate to eliminate malaria by 2020. The remaining malaria transmission hotspots are located within the Huétar Norte Region (HNR), where 90% of the country’s 147 malaria cases have occurred since 2016, following a 33-month period without transmission. Here, we examine changes in transmission with the implementation of a supervised seven-day chloroquine and primaquine treatment (7DCPT). We also evaluate the impact of a focal mass drug administration (MDA) in January 2019 at Boca Arenal, the town in HNR reporting the greatest local transmission. We found that the change to a seven-day treatment protocol, from the prior five-day program, was associated with a 98% reduction in malaria transmission. The MDA helped to reduce transmission, keeping the basic reproduction number, RT, significantly below 1, for at least four months. However, following new imported cases from Nicaragua, autochthonous transmission resumed. Our results highlight the importance of appropriate treatment delivery to reduce malaria transmission, and the challenge that highly mobile populations, if their malaria is not treated, pose to regional elimination efforts in Mesoamerica and México.

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Section: Discussionmentioning

confidence: 84%

Malaria Elimination in Costa Rica: Changes in Treatment and Mass Drug Administration

et al. 2020

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“…In some countries where P. falciparum and P. vivax are co-endemic such as Myanmar, Vietnam, Lao People's Democratic Republic, and Cambodia, P. vivax has become the dominant species between 2010 and 2021 (2,3). P. vivax infections can result in dormant liver-stage hypnozoites, which are not eradicated with standard malaria treatments (6). These infections carry an especially heavy individual and public health burden among pregnant women and children (7)(8)(9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

Liver-targeted polymeric prodrugs delivered subcutaneously improve tafenoquine therapeutic window for malaria radical cure

Pottenger,

Roy,

Srinivasan

et al. 2024

Sci. Adv.

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Approximately 3.3 billion people live with the threat of Plasmodium vivax malaria. Infection can result in liver-localized hypnozoites, which when reactivated cause relapsing malaria. This work demonstrates that an enzyme-cleavable polymeric prodrug of tafenoquine addresses key requirements for a mass administration, eradication campaign: excellent subcutaneous bioavailability, complete parasite control after a single dose, improved therapeutic window compared to the parent oral drug, and low cost of goods sold (COGS) at less than $1.50 per dose. Liver targeting and subcutaneous dosing resulted in improved liver:plasma exposure profiles, with increased efficacy and reduced glucose 6-phosphate dehydrogenase–dependent hemotoxicity in validated preclinical models. A COGS and manufacturability analysis demonstrated global scalability, affordability, and the ability to redesign this fully synthetic polymeric prodrug specifically to increase global equity and access. Together, this polymer prodrug platform is a candidate for evaluation in human patients and shows potential for P. vivax eradication campaigns.

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“…The only drugs currently effective against hypnozoites belong to the class of 8-aminoquinolines, primaquine and tafenoquine ( 3 , 4 ). Primaquine has been for many years the only approved drug for a radical cure, that is, the elimination of liver-stage hypnozoites in P. vivax and Plasmodium ovale infections ( 5 , 6 ). However, primaquine is usually prescribed to be taken once daily for 14 days, leading to efficacy issues related to poor treatment adherence ( 7 ).…”

Section: Introductionmentioning

confidence: 99%

A nanochitosan-D-galactose formulation increases the accumulation of primaquine in the liver

Gomes,

Ribeiro,

Sanches

et al. 2024

Antimicrob Agents Chemother

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Primaquine is the mainstream antimalarial drug to prevent Plasmodium vivax relapses. However, this drug can induce hemolysis in patients with glucose-6-phosphate dehydrogenase deficiency. Nanostructure formulations of primaquine loaded with D-galactose were used as a strategy to target the drug to the liver and decrease the hemolytic risks. Nanoemulsion (NE-Pq) and nanochitosan (NQ-Pq) formulations of primaquine diphosphate containing D-galactose were prepared and characterized by their physicochemistry properties. Pharmacokinetic and biodistribution studies were conducted using Swiss Webster mice. A single dose of 10 mg/kg of each nanoformulation or free primaquine solution was administered by gavage to the animals, which were killed at 0.5, 1, 2, 4, 8, and 24 hours. Blood samples and tissues were collected, processed, and analyzed by high-performance liquid chromatography. The nanoformulation showed sizes around 200 nm (NE-Pq) and 400 nm (NQ-Pq) and physicochemical stability for over 30 days. Free primaquine solution achieved higher primaquine Cmax in the liver than NE-Pq or NQ-Pq at 0.5 hours. However, the half-life and mean residence time (MRT) of primaquine in the liver were three times higher with the NQ-Pq formulation than with free primaquine, and the volume distribution was four times higher. Conversely, primaquine’s half-life, MRT, and volume distribution in the plasma were lower for NQ-Pq than for free primaquine. NE-Pq, on the other hand, accumulated more in the lungs but not in the liver. Galactose-coated primaquine nanochitosan formulation showed increased drug targeting to the liver compared to free primaquine and may represent a promising strategy for a more efficient and safer radical cure for vivax malaria.

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Expanding the Use of Primaquine for the Radical Cure of Plasmodium vivax

Cited by 8 publications

References 10 publications

Malaria Elimination in Costa Rica: Changes in Treatment and Mass Drug Administration

Malaria Elimination in Costa Rica: Changes in Treatment and Mass Drug Administration

Liver-targeted polymeric prodrugs delivered subcutaneously improve tafenoquine therapeutic window for malaria radical cure

A nanochitosan-D-galactose formulation increases the accumulation of primaquine in the liver

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