References
- Sinton JA, Bird W: Studies in malaria with special reference to
treatment; plasmoquine in treatment of malaria. Indian J Med Research
1928, 16: 159.
- Sinton JA, Smith S, Potinger D. Studies in malaria, with special
reference to treatment. XII. Further researches into treatment of
chronic benign tertian malaria with plasmoquine and quinine. Indian J
Med Res. 1930; 17: 793.
- Orachowatz D. Toxicity, cyanosis induced by plasmochin treatment of
malaria. Arch f Schiffs u Tropen Hyg 1928; 32: 119-21.
- Hardgrove M, Applebaum IL. Plasmochin toxicity; analysis of 258 cases.
Ann Intern Med. 1946 Jul;25:103-12.
- Recht J, Ashley EA, White NJ. Safety of 8-aminoquinoline antimalarial
medicines. Geneva, World Health Organization, 2014.
- Baird JK. 8-Aminoquinoline therapy for latent malaria. Clin Microbiol
Rev. 2019; 32: e00011-19.
- Alving AS, Craige B, Pullman TN, Whorton CM, Jones R, Eichelberger L.
Procedures used at Stateville Penitentiary for the testing of
potential antimalarial agents. J Clin Invest 1948; 27: Suppl 2.
- Boyd MF. The influence of sporozoite dosage in vivax malaria, Am J
Trop Med. 1940; 20: 279-86.
- Hill E, Amatuzio DS. Southwest Pacific vivax malaria; clinical
features and observations concerning duration of clinical activity. Am
J Trop Med Hyg. 1949; 29: 203-14.
- Most H, Kane CA, Lavietes PH, London IM, Schroeder EF, Hayman DM.
Combined quinine-plasmochin treatment of vivax malaria; effect of
relapse rate. Am J Med Sci. 1946; 212: 550-60.
- Craige B, Jones R, Whorton M, Pullman TN, Alving AS, Eichelberger L.
Clinical standardization of Pamaquin (Plasmochin) in mosquito-induced
vivax malaria, Chesson strain, a preliminary report. J Clin Invest
1948; 27: 309-315
- White NJ. Anti-malarial drug effects on parasite dynamics in vivax
malaria. Malar J. 2021; 20: 161.
- Christianson HB, Gordon HH, Daniels WB, Lippincott SW. Afebrile
parasitemia in imported vivax malaria. Am J Publ Hlth 1946; 36:
759-761.
- Chaumeau V, Kajeechiwa L, Fustec B, Landier J, Nyo SN, Hsel SN,
Phatharakokordbun P, Kittiphanakun P, Nosten S, Thwin MM, Tun SW,
Wiladphaingern J, Cottrell G, Parker DM, Minh MC, Kwansomboon N,
Metaane S, Montazeau C, Kunjanwong K, Sawasdichai S, Andolina C, Ling
C, Haohankhunnatham W, Christiensen P, Wanyatip S, Konghahong K,
Cerqueira D, Imwong M, Dondorp AM, Chareonviriyaphap T, White NJ,
Nosten FH, Corbel V. The contribution of asymptomatic Plasmodium
infections to the transmission of malaria in Kayin state, Myanmar. J
Infect Dis 2019; 219:1499-1509.
- Alving AS, Hankey DD, Coatney GR, Jones R Jr, Coker WG, Garrison PL,
Donovan WN. Korean vivax malaria. II. Curative treatment with
pamaquine and primaquine. Am J Trop Med Hyg. 1953; 2: 970-6.
- Pybus BS, Sousa JC, Jin X, Ferguson JA, Christian RE, Barnhart R,
Vuong C, Sciotti RJ, Reichard GA, Kozar MP, Walker LA, Ohrt C,
Melendez V. CYP450 phenotyping and accurate mass identification of
metabolites of the 8-aminoquinoline, anti-malarial drug primaquine.
Malar J. 2012; 11: 259.
- Camarda G, Jirawatcharadech P, Priestley RS, Saif A, March S, Wong
MHL, Leung S, Miller AB, Baker DA, Alano P, Paine MJI, Bhatia SN,
O’Neill PM, Ward SA, Biagini GA. Antimalarial activity of primaquine
operates via a two-step biochemical relay. Nat Commun. 2019 ;10:
e3226.
- Bennett JW, Pybus BS, Yadava A, Tosh D, Sousa JC, McCarthy WF, Deye G,
Melendez V, Ockenhouse CF. Primaquine failure and cytochrome P-450 2D6
in Plasmodium vivax malaria. N Engl J Med. 2013; 369:1381-2.
- Baird JK, Louisa M, Noviyanti R, Ekawati L, Elyazar I, Subekti D,
Chand K, Gayatri A, Instiaty, Soebianto S, Crenna-Darusallam C, Djoko
D, Hasto BD, Meriyenes D, Wesche D, Nelwan EJ, Sutanto I, Sudoyo H,
Setiabudy R. Association of Impaired Cytochrome P450 2D6 Activity
Genotype and Phenotype with Therapeutic Efficacy of Primaquine
Treatment for Latent Plasmodium vivax Malaria. JAMA Netw Open.
2018;1:e181449.
- Umbreit J. Methemoglobin–it’s not just blue: a concise review. Am J
Hematol. 2007; 82: 134-44.
- Sutanto I, Tjahjono B, Basri H, Taylor WR, Putri FA, Meilia RA,
Setiabudy R, Nurleila S, Ekawati LL, Elyazar I, Farrar J, Sudoyo H,
Baird JK. Randomized, open-label trial of primaquine against vivax
malaria relapse in Indonesia. Antimicrob Agents Chemother. 2013; 57:
1128-35.
- Chu CS, Phyo AP, Turner C, Win HH, Poe NP, Yotyingaphiram W, Thinraow
S, Wilairisak P, Raksapraidee R, Carrara VI, Paw MK, Wiladphaingern J,
Proux S, Bancone G, Sriprawat K, Lee SJ, Jeeyapant A, Watson J,
Tarning J, Imwong M, Nosten F, White NJ. Chloroquine versus
dihydroartemisinin-piperaquine with standard high-dose primaquine
given either for 7 days or 14 days in Plasmodium vivax malaria.
Clin Infect Dis. 2019; 68: 1311-9.
- Alving AS, Pullman TN, Craige B, Jones R, Whorton CM, Eichelberger L.
The clinical trial of eighteen analogues of pamaquin (plasmochin) in
vivax malaria (Chesson strain). J Clin Invest. 1948; 27: 34-45.
- Edgcomb JH, Arnold J, Yount EH, Alving AS, Eichelberger L, Jeffery G,
et al. Primaquine, SN 13272, a new curative agent in vivax malaria; a
preliminary report. J Natl Malar Soc. 1950; 9: 285-92.
- Cooper WC, Myatt AV, Hernandez T, Jeffery GM, Coatney GR. Studies in
human malaria. XXXI. Comparison of primaquine, isopentaquine, SN-3883,
and pamaquine as curative agents against Chesson strain vivax malaria.
Am J Trop Med Hyg 1953; 2: 949-57.
- Brewer GJ, Tarlov AR, Kellermeyer RW, Alving AS. The hemolytic effect
of primaquine. XV. Role of methemoglobin. J Lab Clin Med 1962; 59:
905-17.
- Beutler E. G6PD deficiency. Blood. 1994; 84: 3613-36.
- Chu CS, Watson JA, Phyo AP, Win HH, Yotyingaphiram W, Thinraow S, Soe
NL, Aung AA, Wilaisrisak P, Kraft K, Imwong M, Hanpithakpong W,
Blessborn D, Tarning J, Proux S, Ling C, Nosten FH, White NJ.
Determinants of primaquine and carboxyprimaquine exposures in children
and adults with Plasmodium vivax malaria. Antimicrob Agents Chemother. 2021:AAC0130221.
doi:10.1128/AAC.01302-21.
- Llanos-Cuentas A, Lacerda MVG, Hien TT, Vélez ID, Namaik-Larp C, Chu
CS, et al. Tafenoquine versus primaquine to prevent relapse ofPlasmodium vivax malaria. N Engl J Med. 2019; 380: 229-41.
- Walsh DS, Wilairatana P, Tang DB, Heppner DG Jr, Brewer TG, Krudsood
S, Silachamroon U, Phumratanaprapin W, Siriyanonda D, Looareesuwan S.
Randomized trial of 3-dose regimens of tafenoquine (WR238605) versus
low-dose primaquine for preventing Plasmodium vivax malaria
relapse. Clin Infect Dis. 2004; 39: 1095-103.
- Llanos-Cuentas A, Lacerda MV, Rueangweerayut R, Krudsood S, Gupta SK,
Kochar SK, Arthur P, Chuenchom N, Möhrle JJ, Duparc S, Ugwuegbulam C,
Kleim JP, Carter N, Green JA, Kellam L. Tafenoquine plus chloroquine
for the treatment and relapse prevention of Plasmodium vivax malaria
(DETECTIVE): a multicentre, double-blind, randomised, phase 2b
dose-selection study. Lancet 2014; 383: 1049-58.
- Nelwan EJ, Ekawati LL, Tjahjono B, Setiabudy R, Sutanto I, Chand K,
Ekasari T, Djoko D, Basri H, Taylor WR, Duparc S, Subekti D, Elyazar
I, Noviyanti R, Sudoyo H, Baird JK. Randomized trial of primaquine
hypnozoitocidal efficacy when administered with artemisinin-combined
blood schizontocides for radical cure of Plasmodium vivax in
Indonesia. BMC Med. 2015; 13: 294.
- Earle DP, Jr, Bigelow FS, Zubrod CH, Kane C. Studies on the
chemotherapy of the human malarias. IX. Effect of pamaquine on the
blood cells of man. J Clin Invest 1948; 27:121–129.
- Chairat K, Jittamala P, Hanboonkunupakarn B, Pukrittayakamee S,
Hanpithakpong W, Blessborn D, White NJ, Day NPJ, Tarning J.
Enantiospecific pharmacokinetics and drug-drug interactions of
primaquine and blood-stage antimalarial drugs. J Antimicrob Chemother
2018; 73: 3102-3113.
- Berliner RW, Earle DP, Jr, Taggart JV, Welch WJ, Zubrod CG, Knowlton
P, Atchley JA, Shannon JA. Studies on the chemotherapy of the human
malarias. VII. The antimalarial activity of pamaquine. J Clin Invest
1948; 27:108 –113.
- Alving AS, Arnold J, Hockwald RS, Clayman CB, Dern RJ, Beutler E,
Flanagan CL. Potentiation of the curative action of primaquine in
vivax malaria by quinine and chloroquine. J Lab Clin Med 1955;
46:301–306.
- Clayman CB, Arnold J, Hockwald RS, Yount EH, Edgcomb JH, Alving AS.
Status of primaquine. III. Toxicity of primaquine in Caucasians. JAMA
1952; 149:1563–1568.
- Finch CA. Methemoglobinemia and sulfhemoglobinemia. N Engl J Med 1948;
239: 470-8.
- Fletcher KA, Evans DA, Gilles HM, Greaves J, Bunnag D, Harinasuta T.
Studies on the pharmacokinetics of primaquine. Bull World Health
Organ. 1981; 59: 407-12.
- Fryauff DJ, Baird JK, Basri H, Sumawinata I, Purnomo, Richie TL, Ohrt
CK, Mouzin E, Church CJ, Richards AL, et al. Randomised
placebo-controlled trial of primaquine for prophylaxis of falciparum
and vivax malaria. Lancet. 1995; 346: 1190-3.
- Baird JK, Lacy MD, Basri H, Barcus MJ, Maguire JD, Bangs MJ,
Gramzinski R, Sismadi P, Krisin, Ling J, Wiady I, Kusumaningsih M,
Jones TR, Fryauff DJ, Hoffman SL; United States Naval Medical Research
Unit 2 Clinical Trials Team. Randomized, parallel placebo-controlled
trial of primaquine for malaria prophylaxis in Papua, Indonesia. Clin
Infect Dis. 2001; 33: 1990-7.
- Lacerda MVG, Llanos-Cuentas A, Krudsood S, Lon C, Saunders DL,
Mohammed R,Yilma D, Batista Pereira D, Espino FEJ, Mia RZ, Chuquiyauri
R, Val F, Casapía M, Monteiro WM, Brito MAM, Costa MRF, Buathong N,
Noedl H, Diro E, Getie S, Wubie KM, Abdissa A, Zeynudin A, Abebe C,
Tada MS, Brand F, Beck HP, Angus B, Duparc S, Kleim JP, Kellam LM,
Rousell VM, Jones SW, Hardaker E, Mohamed K, Clover DD, Fletcher K,
Breton JJ, Ugwuegbulam CO, Green JA, Koh GCKW. Single-Dose Tafenoquine
to Prevent Relapse of Plasmodium vivax Malaria. N Engl J Med.
2019; 380: 215-228.
- Nelwan EJ, Ekawati LL, Tjahjono B, Setiabudy R, Sutanto I, Chand K,
Ekasari T, Djoko D, Basri H, Taylor WR, Duparc S, Subekti D, Elyazar
I, Noviyanti R, Sudoyo H, Baird JK. Randomized trial of primaquine
hypnozoitocidal efficacy when administered with artemisinin-combined
blood schizontocides for radical cure of Plasmodium vivax in
Indonesia. BMC Med. 2015; 13: 294.Legends to FiguresFigure 1. Haemoglobin - methaemoglobin interconversion. The major
factor contributing to reduction of methaemoglobin back to haemoglobin
is the activity of the red cell NADH cytochrome B5 MetHb reductase.
MetHb: methaemoglobin.
Figure 2: The figures show increasing levels of methaemoglobinaemia (as
a proportion of the corresponding haemoglobin concentration) during
radical curative treatment of vivax malaria with primaquine. On the left
(Figure 2A) primaquine 30mg base/day was given to adults for 14 days
either concurrently with quinine, or 28 days after a treatment dose of
dihydroartemisinin-piperaquine (from Sutanto et al (21)). On the right
(Figure 2B) primaquine was given to adults and children either at a dose
of 0.5mg base/kg /day for 14 days or 1mg/kg/day for 7 days and patients
were randomized to receive concurrent chloroquine or
dihydroartemisinin-piperaquine (from Chu et al (22))
Figure 3: During the clinical investigations, conducted over 70 years
ago in the USA, to develop new 8-aminoquinolines 18 different compounds
were evaluated in addition to pamaquine, and later primaquine (23-25).
Each was administered for 14 days concurrently with quinine. The
volunteers were infected by multiple bites of A. quadrimaculatusinfected with the Chesson strain of P. vivax . The figure shows
the relationship between the radical cure proportion and the average
blood methaemoglobin concentration (%) measured in the last 4 days of
treatment. The size of the circles is proportional to the number
recruited as shown in the inset box.
Figure 4: Dose-response relationships for primaquine and tafenoquine in
generating methaemoglobinaemia (21,22, 24-26, 28-32). The dose shown is
the daily adult dose of primaquine, whereas for tafenoquine the dose
shown is the total dose administered. The size of the circles is
proportional to the number of patients or volunteers recruited as shown
in the inset box.
Figure 5: Studies conducted during the development of primaquine which
assessed the average methaemoglobin concentration (%) as a proportion
of the haemoglobin concentration in the last 4 days of treatment in
relation to the dosing of plasmoquine (pamaquine) (left) and primaquine
(right) (11,33,37). These initial observations suggested that
methaemoglobinaemia following primaquine, but not plasmoquine, was
attenuated by concomitant administration of chloroquine or quinine.
However, later studies (summarized in Figure 6) did not confirm this.
The size of the circles is proportional to the number of patients or
volunteers recruited as shown in the inset box.
Figure 6: More recent studies in which methaemoglobinaemia has been
assessed after different dose regimens of primaquine whether given alone
(26,39-41), or in combination with antimalarial drugs (18, 34, 37, 38),
either to healthy volunteers, in antimalarial prophylaxis, or in the
treatment of vivax malaria (15,19,21,22,24-26,28-32,37,42,43). These do
not suggest attenuation of primaquine induced methaemoglobinaemia by
concomitant antimalarial drugs (as reported by Clayman et al (37)), nor
are there differences between healthy subjects and patients with
malaria. The size of the circles is proportional to the number of
patients or volunteers recruited as shown in the inset box.
Figure 7: Mean values of haemoglobin (g/dL) and methaemoglobin (%) in
12 normal and 12 African A- G6PD deficient volunteers given primaquine
(from Brewer et al (26)).