ArticleMalaria journal2018
Primaquine ineligibility in anti-relapse therapy of Plasmodium vivax malaria: the problem of G6PD deficiency and cytochrome P-450 2D6 polymorphisms.
Article in Malaria journal, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
51 citing papers in PubMed, 2 syntheses or guidelines pooled it, 92 citations in OpenAlex.
- The Impact of Emerging Plasmodium knowlesi on Accurate Diagnosis by Light Microscopy: A Systematic Review and Modeling Analysis.The American journal of tropical medicine and hygiene · 2023Pooled it
- Quantification of glucose-6-phosphate dehydrogenase activity by spectrophotometry: A systematic review and meta-analysis.PLoS medicine · 2020Pooled it
- Higher-Dose Primaquine to Prevent Relapse ofThe New England journal of medicine · 2022Trial
- Superinfection and the hypnozoite reservoir for Plasmodium vivax: a multitype branching process approximation.Journal of mathematical biology · 2026Article
- Amplicon-based DNA sequencing to characterize Duffy antigen polymorphisms and analysis of Duffy blood system and glucose-6-phosphate dehydrogenase deficiency in Mauritania.PLoS neglected tropical diseases · 2025Article
- How CYP2D6 Polymorphism Modulates the Community-Wide Risk of Plasmodium vivax Infection: A Panel Study in Amazonian Brazil.The Journal of infectious diseases · 2025Article
- Hotspot districts of persistentThe Lancet regional health. Southeast Asia · 2025Article
- Malaria vaccines: a new era of prevention and control.Nature reviews. Microbiology · 2024Review
- Monoamine oxidase-A (MAO-A) low-expression variants and increased risk of Plasmodium vivax malaria relapses.The Journal of antimicrobial chemotherapy · 2024Article
- Effectiveness of an Unsupervised Primaquine Regimen for Preventing Plasmodium vivax Malaria Relapses in Northeast Myanmar: A Single-Arm Nonrandomized Observational Study.The Journal of infectious diseases · 2024Observational
- Optimal balance of benefit versus risk for tafenoquine in the treatment of Plasmodium vivax malaria.Malaria journal · 2024Review
- Transfection Models to InvestigatePathogens (Basel, Switzerland) · 2023Review
- Biology and epidemiology ofParasite epidemiology and control · 2023Review
- Individual variation in Plasmodium vivax malaria risk: Are repeatedly infected people just unlucky?PLoS neglected tropical diseases · 2023Review
- Vivax malaria: a possible stumbling block for malaria elimination in India.Frontiers in public health · 2023Review
- Cytochrome P450 2D6 (CYP2D6) and glucose-6-phosphate dehydrogenase (G6PD) genetic variations in Thai vivax malaria patients: Implications for 8-aminoquinoline radical cure.PLoS neglected tropical diseases · 2022Article
- Article
- Developing sero-diagnostic tests to facilitate Plasmodium vivax Serological Test-and-Treat approaches: modeling the balance between public health impact and overtreatment.BMC medicine · 2022Article
- Mechanistic Modeling of Primaquine Pharmacokinetics, Gametocytocidal Activity, and Mosquito Infectivity.Clinical pharmacology and therapeutics · 2022Article
- Liver-stage fate determination inFrontiers in microbiology · 2022Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 3 countries.
Funding
Abstract
The hypnozoite reservoir of Plasmodium vivax represents both the greatest obstacle and opportunity for ultimately eradicating this species. It is silent and cannot be diagnosed until it awakens and provokes a clinical attack with attendant morbidity, risk of mortality, and opportunities for onward transmission. The only licensed drug that kills hypnozoites is primaquine, which attacks the hypnozoite reservoir but imposes serious obstacles in doing so-at hypnozoitocidal doses, it invariably causes a threatening acute haemolytic anaemia in patients having an inborn deficiency in glucose-6-phosphate dehydrogenase (G6PD), affecting about 8% of people living in malaria endemic nations. That problem excludes a large number of people from safe and effective treatment of the latent stage of vivax malaria: the G6PD deficient, pregnant or lactating women, and young infants. These groups were estimated to comprise 14.3% of populations resident in the 95 countries with endemic vivax malaria. Another important obstacle regarding primaquine in the business of killing hypnozoites is its apparent metabolism to an active metabolite exclusively via cytochrome P-450 isozyme 2D6 (CYP2D6). Natural polymorphisms of this allele create genotypes expressing impaired enzymes that occur in over 20% of people living in Southeast Asia, where more than half of P. vivax infections occur globally. Taken together, the estimated frequencies of these primaquine ineligibles due to G6PD toxicity or impaired CYP2D6 activity composed over 35% of the populations at risk of vivax malaria. Much more detailed work is needed to refine these estimates, derive probabilities of error for them, and improve their ethnographic granularity in order to inform control and elimination strategy and tactics.
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Registered trials
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