Status of Primaquine

Alving, Alf S.; Arnold, Major John; Robinson, Major Donald H.

doi:10.1001/jama.1952.72930340017010

Cited by 38 publications

(6 citation statements)

References 3 publications

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“…Primaquine was synthesized during World War II and was first widely used as a curative agent for vivax malaria during the Korean War [13]. It acts in the liver on hypnozoites of P. vivax and P. ovale and has similar activity against incubating P. falciparum in the liver, but doses required for this effect seem to be higher [12,[14][15][16].…”

Section: Discussionmentioning

confidence: 99%

Primaquine as Prophylaxis for Malaria for Nonimmune Travelers: A Comparison with Mefloquine and Doxycycline

Schwartz

Regev‐Yochay

1999

Clinical Infectious Diseases

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Malaria prophylaxis for travelers is a controversial issue. The commonly used regimens are associated with side effects, low compliance, or low efficacy, which have raised concern regarding their use. In addition, they are inefficient against the tissue stage of the parasite and thus do not prevent relapses of Plasmodium vivax infection. Primaquine is aimed at the pre-erythrocytic stage and thus may be a potential causal-prophylactic treatment that can abolish the need for long postexposure therapy. During 1995-1998, we followed retrospectively travelers who joined rafting trips to an area in Ethiopia where both P. vivax and Plasmodium falciparum are hyperendemic. Of the 106 travelers who received primaquine, 5.7% developed malaria; of the 19 doxycycline recipients, 53% developed malaria; and of the 25 mefloquine recipients, 52% developed P. vivax malaria (>/=3 months after return from the area of endemicity). Primaquine was well tolerated, and only 1 withdrawal from therapy (due to gastrointestinal symptoms) was reported. Primaquine was shown to be a safe and effective prophylactic drug against both P. falciparum malaria and P. vivax malaria in travelers.

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Section: Discussionmentioning

confidence: 99%

Primaquine as Prophylaxis for Malaria for Nonimmune Travelers: A Comparison with Mefloquine and Doxycycline

Schwartz

Regev‐Yochay

1999

Clinical Infectious Diseases

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“…14 Primaquine was the preferred 8-aminoquinoline based on estimates of its toxicity compared with pamaquine, so chloroquine-primaquine combinations were tested and found effective. 15 Just as quinine showed genuine synergy when simultaneously used in combination with pamaquine, a similar synergistic effect for concurrent medication was observed with chloroquine and primaquine. 7 This was exploited by the mass treatment of .…”

Section: Chloroquine Combinationsmentioning

confidence: 90%

Historical 8-Aminoquinoline Combinations: Not All Antimalarial Drugs Work Well Together

Shanks

2022

The American Journal of Tropical Medicine and Hygiene

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Since their first use in the 1920s, 8-aminoquinolines have been known to have important toxicities such as methemoglobinemia and hemolysis. An empiric pamaquine (plasmochin) combination with quinine was widely used in the British military with relatively little toxicity. Attempts to use pamaquine with a new synthetic antimalarial drug (atabrine, quinacrine) in the 1930–1940s, however, resulted in hemolytic reactions and some deaths from renal failure. An improved 8-aminoquinoline, primaquine, was particularly effective against Plasmodium vivax relapses when combined with either quinine or chloroquine. When used in reduced daily doses (15 mg) over 2 weeks, it was safely given to many thousands of U.S. soldiers returning from Korea. CP tablets (chloroquine 300 mg, primaquine 45 mg weekly) were widely used during the Vietnam War with few hemolytic reactions and no known deaths. Efficacy and toxicity of 8-aminoquinolines is determined in part by the selection of appropriate partner drugs

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“…They described no serious adverse reactions and characterized the therapy as "well tolerated." Soon thereafter a published trial of posttravel PART was undertaken aboard two troop ships repatriating American soldiers from the Korean Peninsula during September 1951 (183). The trial involved 3,536 soldiers, 426 of whom were African-Americans.…”

Section: Primaquinementioning

confidence: 99%

8-Aminoquinoline Therapy for Latent Malaria

2019

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SUMMARYThe technical genesis and practice of 8-aminoquinoline therapy of latent malaria offer singular scientific, clinical, and public health insights. The 8-aminoquinolines brought revolutionary scientific discoveries, dogmatic practices, benign neglect, and, finally, enduring promise against endemic malaria. The clinical use of plasmochin—the first rationally synthesized blood schizontocide and the first gametocytocide, tissue schizontocide, and hypnozoitocide of any kind—commenced in 1926. Plasmochin became known to sometimes provoke fatal hemolytic crises. World War II delivered a newer 8-aminoquinoline, primaquine, and the discovery of glucose-6-phosphate dehydrogenase (G6PD) deficiency as the basis of its hemolytic toxicity came in 1956. Primaquine nonetheless became the sole therapeutic option against latent malaria. After 40 years of fitful development, in 2018 the U.S. Food and Drug Administration registered the 8-aminoquinoline called tafenoquine for the prevention of all malarias and the treatment of those that relapse. Tafenoquine also cannot be used in G6PD-unknown or -deficient patients. The hemolytic toxicity of the 8-aminoquinolines impedes their great potential, but this problem has not been a research priority. This review explores the complex technical dimensions of the history of 8-aminoquinolines. The therapeutic principles thus examined may be leveraged in improved practice and in understanding the bright prospect of discovery of newer drugs that cannot harm G6PD-deficient patients.

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Status of Primaquine

Cited by 38 publications

References 3 publications

Primaquine as Prophylaxis for Malaria for Nonimmune Travelers: A Comparison with Mefloquine and Doxycycline

Primaquine as Prophylaxis for Malaria for Nonimmune Travelers: A Comparison with Mefloquine and Doxycycline

Historical 8-Aminoquinoline Combinations: Not All Antimalarial Drugs Work Well Together

8-Aminoquinoline Therapy for Latent Malaria

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