ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
Kojom Foko LP, Arya A, Sharma A, Singh V , 2021. Epidemiology and clinical outcomes of severe Plasmodium vivax malaria in India. J Infect 82: 231–246.
-
2.
Price RN, Commons RJ, Battle KE, Thriemer K, Mendis K , 2020. Plasmodium vivax in the era of the shrinking P. falciparum map. Trends Parasitol 36: 560–570.
-
3.
The PLOS Neglected Tropical Diseases Staff , 2019. Correction: growing evidence of Plasmodium vivax across malaria-endemic Africa. PLoS Negl Trop Dis 13: e0007525.
-
4.
Hanboonkunupakarn B, White NJ, 2020. Advances and roadblocks in the treatment of malaria. Br J Clin Pharmacol bcp.14474.
-
5.
Awandu SS, Raman J, Makhanthisa TI, Kruger P, Frean J, Bousema T, Niemand J, Birkholtz L-M , 2018. Understanding human genetic factors influencing primaquine safety and efficacy to guide primaquine roll-out in a pre-elimination setting in southern Africa. Malar J 17: 120.
-
6.
Baird JK , 2019. 8-Aminoquinoline therapy for latent malaria. Clin Microbiol Rev 32: e00011–e00019.
-
7.
Ahmad SS, Rahi M, Sharma A , 2021. Relapses of Plasmodium vivax malaria threaten disease elimination: time to deploy tafenoquine in India? BMJ Glob Health 6: e004558.
-
8.
Recht J, Ashley EA, White NJ , 2018. Use of primaquine and glucose-6-phosphate dehydrogenase deficiency testing: divergent policies and practices in malaria endemic countries. PLoS Negl Trop Dis 12: e0006230.
-
9.
Camarda G et al.2019. Antimalarial activity of primaquine operates via a two-step biochemical relay. Nat Commun 10: 3226.
-
10.
Sarkar S, Biswas NK, Dey B, Mukhopadhyay D, Majumder PP , 2010. A large, systematic molecular-genetic study of G6PD in Indian populations identifies a new non-synonymous variant and supports recent positive selection. Infect Genet Evol 10: 1228–1236.
-
11.
Tripathi P, Agarwal S, Muthuswamy S, 2019. Prevalence and genetic characterization of glucose-6-phosphate dehydrogenase deficiency in anemic subjects from Uttar Pradesh, India. J Pediatr Genet 8: 47–53.
-
12.
Devendra R et al.2020. Prevalence and spectrum of mutations causing G6PD deficiency in Indian populations. Infect Genet Evol 86: 104597.
-
13.
Devendra R, Gupta V, Biradar SS, Bhat P, Hegde S, Hoti SL, Mukherjee MB, Hegde HV , 2020. G6PD A- is the major cause of G6PD deficiency among the Siddis of Karnataka, India. Ann Hum Biol 47: 55–58.
-
14.
Arunachalam AK, Sumithra S, Maddali M, Fouzia NA, Abraham A, George B, Edison ES , 2020. Molecular characterization of G6PD deficiency: report of three novel G6PD variants. Indian J Hematol Blood Transfus 36: 349–355.
-
15.
Danquah KO et al.2020. Molecular characterization of glucose-6-phosphate dehydrogenase: do single nucleotide polymorphisms affect hematological parameters in HIV-positive patients? J Trop Med 2020: 1–7.
-
16.
Bennett JW, Pybus BS, Yadava A, Tosh D, Sousa JC, McCarthy WF, Deye G, Melendez V, Ockenhouse CF , 2013. Primaquine failure and cytochrome P-450 2D6 in plasmodium vivax Malaria. N Engl J Med 369: 1381–1382.
-
17.
Zhou Y, Ingelman-Sundberg M, Lauschke V , 2017. Worldwide distribution of cytochrome P450 alleles: a meta-analysis of population-scale sequencing projects. Clin Pharmacol Ther 102: 688–700.
-
18.
Baird JK et al.2018. Association of impaired cytochrome P450 2D6 activity genotype and phenotype with therapeutic efficacy of Primaquine treatment for latent Plasmodium vivax malaria. JAMA Netw Open 1: e181449.
-
19.
Crews KR et al.Clinical Pharmacogenetics Implementation Consortium , 2014. Clinical pharmacogenetics implementation consortium guidelines for cytochrome P450 2D6 genotype and codeine therapy: 2014 update. Clin Pharmacol Ther 95: 376–382.
-
20.
Spring MD et al.2020. Prevalence of CYP2D6 genotypes and predicted phenotypes in a cohort of Cambodians at high risk for infections with Plasmodium vivax. Am J Trop Med Hyg 103: 756–759.
-
21.
Pandey AV, Sproll P , 2014. Pharmacogenomics of human P450 oxidoreductase. Front Pharmacol 5: 103.
-
22.
Bai Y, Li J, Wang X , 2017. Cytochrome P450 oxidoreductase deficiency caused by R457H mutation in POR gene in Chinese: case report and literature review. J Ovarian Res 10: 16.
-
23.
Constantino L, Paixão P, Moreira R, Portela MJ, Do Rosario VE, Iley J , 1999. Metabolism of primaquine by liver homogenate fractions. Exp Toxicol Pathol 51: 299–303.
-
24.
Pybus BS et al.2012. CYP450 phenotyping and accurate mass identification of metabolites of the 8-aminoquinoline, anti-malarial drug primaquine. Malar J 11: 259.
-
25.
Ariffin NM, Islahudin F, Kumolosasi E, Makmor-Bakry M , 2019. Effects of MAO-A and CYP450 on primaquine metabolism in healthy volunteers. Parasitol Res 118: 1011–1018.
-
26.
Gilad Y, Rosenberg S, Przeworski M, Lancet D, Skorecki K , 2002. Evidence for positive selection and population structure at the human MAO-A gene. Proc Natl Acad Sci USA 99: 862–867.
-
27.
Balciuniene J, Syvänen A-C, McLeod HL, Pettersson U, Jazin EE , 2001. The geographic distribution of monoamine oxidase haplotypes supports a bottleneck during the dispersion of modern humans from Africa. J Mol Evol 52: 157–163.
-
28.
Velazquez MNR, Parween S, Udhane SS, Pandey AV , 2019. Variability in human drug metabolizing cytochrome P450 CYP2C9, CYP2C19 and CYP3A5 activities caused by genetic variations in cytochrome P450 oxidoreductase. Pharmacol Toxicol 515: 133–138.
-
29.
Commons RJ, Simpson JA, Watson J, White NJ, Price RN , 2020. Estimating the proportion of Plasmodium vivax recurrences caused by relapse: a systematic review and meta-analysis. Am J Trop Med Hyg 103: 1094–1099.
-
30.
Sandee D, Morrissey K, Agrawal V, Tam HK, Kramer MA, Tracy TS, Giacomini KM, Miller WL , 2010. Effects of genetic variants of human P450 oxidoreductase on catalysis by CYP2D6 in vitro. Pharmacogenet Genomics 20: 677–686.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 15520 | 545 | 23 |
| Full Text Views | 236 | 108 | 2 |
| PDF Downloads | 137 | 17 | 3 |
Effects of Host Genetic Polymorphisms on the Efficacy of the Radical Cure Malaria Drug Primaquine
Minu Nain
Minu Nain
National Institute of Malaria Research, New Delhi, India;
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Mradul Mohan
Mradul Mohan
National Institute of Malaria Research, New Delhi, India;
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Amit Sharma
Amit Sharma
National Institute of Malaria Research, New Delhi, India;
Molecular Medicine, International Centre for Genetic Engineering and Biotechnology, New Delhi, India
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Current site
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PubMed
Molecular Medicine, International Centre for Genetic Engineering and Biotechnology, New Delhi, India
Search for other papers by Amit Sharma in
Current site
Google Scholar
PubMed
ABSTRACT.
Malaria is a major cause of death in low-income countries. Malaria relapses are caused by Plasmodium vivax–induced latent liver stage hypnozoites, and relapses contribute significantly to the total disease burden. The goal of malaria elimination is threatened in countries where P. vivax is endemic and relapses remain a key aspect of concern. Targeting of the hypnozoites is crucial for radical cure and this is achieved by primaquine (PQ). In addition to its anti-hypnozoite effects, PQ also possesses gametocidal activity against all malaria causing Plasmodium species and is hence a useful tool to curtail malaria transmission. It is well known that host glucose-6-phosphate dehydrogenase (G6PD) deficiency is associated with hemolysis after treatment with PQ. Multiple other host polymorphisms impact on PQ metabolism, potentially affecting drug efficacy. Being a prodrug, PQ requires host factors cytochrome P450 2D6 (CYP2D6), cytochrome P450 NADPH: oxidoreductase (CPR) and monoamine oxidase (MAO) for its metabolism and conversion to active form. The efficacy of PQ in the host is therefore dependent on genetic polymorphisms of these three host genes. The efficacy of PQ is important for clearing reservoirs of P. vivax infection. Here, we have analyzed the known spectrum of genetic polymorphisms for host genes that enable PQ metabolism. It is vital to delineate the polymorphisms that determine the ultimate efficacy of PQ for formulating better malaria elimination strategies in countries with severe malaria burden. Thus population-based studies of these gene variants will provide new insights into the role of host genetics on PQ treatment outcomes.
Author Notes
Authors’ addresses: Minu Nain and Mradul Mohan, National Institute of Malaria Research, New Delhi, India, E-mails: minu345r@gmail.com and mradul_mohan@yahoo.com. Amit Sharma, Molecular Medicine, International Centre for Genetic Engineering and Biotechnology, New Delhi, India, E-mail: directornimr@gmail.com.
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
Kojom Foko LP, Arya A, Sharma A, Singh V , 2021. Epidemiology and clinical outcomes of severe Plasmodium vivax malaria in India. J Infect 82: 231–246.
-
2.
Price RN, Commons RJ, Battle KE, Thriemer K, Mendis K , 2020. Plasmodium vivax in the era of the shrinking P. falciparum map. Trends Parasitol 36: 560–570.
-
3.
The PLOS Neglected Tropical Diseases Staff , 2019. Correction: growing evidence of Plasmodium vivax across malaria-endemic Africa. PLoS Negl Trop Dis 13: e0007525.
-
4.
Hanboonkunupakarn B, White NJ, 2020. Advances and roadblocks in the treatment of malaria. Br J Clin Pharmacol bcp.14474.
-
5.
Awandu SS, Raman J, Makhanthisa TI, Kruger P, Frean J, Bousema T, Niemand J, Birkholtz L-M , 2018. Understanding human genetic factors influencing primaquine safety and efficacy to guide primaquine roll-out in a pre-elimination setting in southern Africa. Malar J 17: 120.
-
6.
Baird JK , 2019. 8-Aminoquinoline therapy for latent malaria. Clin Microbiol Rev 32: e00011–e00019.
-
7.
Ahmad SS, Rahi M, Sharma A , 2021. Relapses of Plasmodium vivax malaria threaten disease elimination: time to deploy tafenoquine in India? BMJ Glob Health 6: e004558.
-
8.
Recht J, Ashley EA, White NJ , 2018. Use of primaquine and glucose-6-phosphate dehydrogenase deficiency testing: divergent policies and practices in malaria endemic countries. PLoS Negl Trop Dis 12: e0006230.
-
9.
Camarda G et al.2019. Antimalarial activity of primaquine operates via a two-step biochemical relay. Nat Commun 10: 3226.
-
10.
Sarkar S, Biswas NK, Dey B, Mukhopadhyay D, Majumder PP , 2010. A large, systematic molecular-genetic study of G6PD in Indian populations identifies a new non-synonymous variant and supports recent positive selection. Infect Genet Evol 10: 1228–1236.
-
11.
Tripathi P, Agarwal S, Muthuswamy S, 2019. Prevalence and genetic characterization of glucose-6-phosphate dehydrogenase deficiency in anemic subjects from Uttar Pradesh, India. J Pediatr Genet 8: 47–53.
-
12.
Devendra R et al.2020. Prevalence and spectrum of mutations causing G6PD deficiency in Indian populations. Infect Genet Evol 86: 104597.
-
13.
Devendra R, Gupta V, Biradar SS, Bhat P, Hegde S, Hoti SL, Mukherjee MB, Hegde HV , 2020. G6PD A- is the major cause of G6PD deficiency among the Siddis of Karnataka, India. Ann Hum Biol 47: 55–58.
-
14.
Arunachalam AK, Sumithra S, Maddali M, Fouzia NA, Abraham A, George B, Edison ES , 2020. Molecular characterization of G6PD deficiency: report of three novel G6PD variants. Indian J Hematol Blood Transfus 36: 349–355.
-
15.
Danquah KO et al.2020. Molecular characterization of glucose-6-phosphate dehydrogenase: do single nucleotide polymorphisms affect hematological parameters in HIV-positive patients? J Trop Med 2020: 1–7.
-
16.
Bennett JW, Pybus BS, Yadava A, Tosh D, Sousa JC, McCarthy WF, Deye G, Melendez V, Ockenhouse CF , 2013. Primaquine failure and cytochrome P-450 2D6 in plasmodium vivax Malaria. N Engl J Med 369: 1381–1382.
-
17.
Zhou Y, Ingelman-Sundberg M, Lauschke V , 2017. Worldwide distribution of cytochrome P450 alleles: a meta-analysis of population-scale sequencing projects. Clin Pharmacol Ther 102: 688–700.
-
18.
Baird JK et al.2018. Association of impaired cytochrome P450 2D6 activity genotype and phenotype with therapeutic efficacy of Primaquine treatment for latent Plasmodium vivax malaria. JAMA Netw Open 1: e181449.
-
19.
Crews KR et al.Clinical Pharmacogenetics Implementation Consortium , 2014. Clinical pharmacogenetics implementation consortium guidelines for cytochrome P450 2D6 genotype and codeine therapy: 2014 update. Clin Pharmacol Ther 95: 376–382.
-
20.
Spring MD et al.2020. Prevalence of CYP2D6 genotypes and predicted phenotypes in a cohort of Cambodians at high risk for infections with Plasmodium vivax. Am J Trop Med Hyg 103: 756–759.
-
21.
Pandey AV, Sproll P , 2014. Pharmacogenomics of human P450 oxidoreductase. Front Pharmacol 5: 103.
-
22.
Bai Y, Li J, Wang X , 2017. Cytochrome P450 oxidoreductase deficiency caused by R457H mutation in POR gene in Chinese: case report and literature review. J Ovarian Res 10: 16.
-
23.
Constantino L, Paixão P, Moreira R, Portela MJ, Do Rosario VE, Iley J , 1999. Metabolism of primaquine by liver homogenate fractions. Exp Toxicol Pathol 51: 299–303.
-
24.
Pybus BS et al.2012. CYP450 phenotyping and accurate mass identification of metabolites of the 8-aminoquinoline, anti-malarial drug primaquine. Malar J 11: 259.
-
25.
Ariffin NM, Islahudin F, Kumolosasi E, Makmor-Bakry M , 2019. Effects of MAO-A and CYP450 on primaquine metabolism in healthy volunteers. Parasitol Res 118: 1011–1018.
-
26.
Gilad Y, Rosenberg S, Przeworski M, Lancet D, Skorecki K , 2002. Evidence for positive selection and population structure at the human MAO-A gene. Proc Natl Acad Sci USA 99: 862–867.
-
27.
Balciuniene J, Syvänen A-C, McLeod HL, Pettersson U, Jazin EE , 2001. The geographic distribution of monoamine oxidase haplotypes supports a bottleneck during the dispersion of modern humans from Africa. J Mol Evol 52: 157–163.
-
28.
Velazquez MNR, Parween S, Udhane SS, Pandey AV , 2019. Variability in human drug metabolizing cytochrome P450 CYP2C9, CYP2C19 and CYP3A5 activities caused by genetic variations in cytochrome P450 oxidoreductase. Pharmacol Toxicol 515: 133–138.
-
29.
Commons RJ, Simpson JA, Watson J, White NJ, Price RN , 2020. Estimating the proportion of Plasmodium vivax recurrences caused by relapse: a systematic review and meta-analysis. Am J Trop Med Hyg 103: 1094–1099.
-
30.
Sandee D, Morrissey K, Agrawal V, Tam HK, Kramer MA, Tracy TS, Giacomini KM, Miller WL , 2010. Effects of genetic variants of human P450 oxidoreductase on catalysis by CYP2D6 in vitro. Pharmacogenet Genomics 20: 677–686.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 15520 | 545 | 23 |
| Full Text Views | 236 | 108 | 2 |
| PDF Downloads | 137 | 17 | 3 |