Therapeutic efficacy of pyronaridine-artesunate (Pyramax) in treating Plasmodium vivax malaria in the central highlands of Vietnam.
| Title: | Therapeutic efficacy of pyronaridine-artesunate (Pyramax) in treating Plasmodium vivax malaria in the central highlands of Vietnam. |
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| Authors: | Manh ND; Vietnam People's Army Military Institute of Preventive Medicine, Hanoi, Vietnam.; Thanh NV; Vietnam People's Army Military Institute of Preventive Medicine, Hanoi, Vietnam.; Quang HH; Vietnam Ministry of Health Institute of Malariology, Parasitology and Entomology, Qui Nhon, Vietnam.; Van NTT; Vietnam People's Army Military Institute of Preventive Medicine, Hanoi, Vietnam.; San NN; Vietnam People's Army Military Institute of Preventive Medicine, Hanoi, Vietnam.; Phong NC; Vietnam People's Army Military Institute of Preventive Medicine, Hanoi, Vietnam.; Birrell GW; Australian Defense Force Malaria and Infectious Disease Institute, Brisbane, Australia.; Edgel KA; U.S. Naval Medical Research Unit INDO PACIFIC, Singapore.; Martin NJ; U.S. Naval Medical Research Unit INDO PACIFIC, Singapore.; Edstein MD; Australian Defense Force Malaria and Infectious Disease Institute, Brisbane, Australia.; Chavchich M; Australian Defense Force Malaria and Infectious Disease Institute, Brisbane, Australia. |
| Source: | Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2024 Sep 04; Vol. 68 (9), pp. e0004424. Date of Electronic Publication: 2024 Jul 24. |
| Publication Type: | Journal Article; Clinical Trial; Research Support, U.S. Gov't, Non-P.H.S. |
| Language: | English |
| Journal Info: | Publisher: American Society for Microbiology Country of Publication: United States NLM ID: 0315061 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1098-6596 (Electronic) Linking ISSN: 00664804 NLM ISO Abbreviation: Antimicrob Agents Chemother Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Washington, American Society for Microbiology |
| MeSH Terms: | Malaria, Vivax*/drug therapy ; Malaria, Vivax*/parasitology ; Naphthyridines*/therapeutic use ; Antimalarials*/therapeutic use ; Artesunate*/therapeutic use ; Plasmodium vivax*/drug effects ; Plasmodium vivax*/genetics ; Artemisinins*/therapeutic use; Primaquine/therapeutic use ; Polymorphism, Single Nucleotide/genetics ; Protozoan Proteins/genetics ; Drug Resistance/genetics ; Humans ; Vietnam ; Adult ; Male ; Adolescent ; Child ; Female ; Middle Aged ; Young Adult ; Child, Preschool ; Membrane Transport Proteins |
| Abstract: | The emergence and spread of chloroquine-resistant Plasmodium vivax have necessitated the assessment of alternative blood schizonticidal drugs. In Vietnam, chloroquine-resistant P. vivax malaria has been reported. In an open-label, single-arm trial, the safety, tolerability, and efficacy of pyronaridine-artesunate (Pyramax, PA) was evaluated in Dak Nong province, Vietnam. A 3-day course of PA was administered to adults and children (≥20 kg) infected with P. vivax. Patients also received primaquine (0.25 mg/kg daily for 14 days). PA was well tolerated with transient asymptomatic increases in liver transaminases. The per-protocol proportion of patients with day 42 PCR-unadjusted adequate clinical and parasitological response was 96.0% (95% CI, 84.9%-99.0%, n = 48/50). The median parasite clearance time was 12 h (range, 12-36 h), with a median fever clearance time of 24 h (range, 12-60 h). Single nucleotide polymorphisms (SNPs) as potential genetic markers of reduced drug susceptibility were analyzed in three putative drug resistance markers, Pvcrt-o, Pvmdr1, and PvK12. Insertion at position K10 of the Pvcrt-o gene was found in 74.6% (44/59) of isolates. Pvmdr1 SNPs at Y976F and F1076L were present in 61% (36/59) and 78% (46/59), respectively. Amplification of Pvmdr1 gene (two copies) was found in 5.1% (3/59) of parasite samples. Only 5.1% (3/59) of isolates had mutation 552I of the PvK12 gene. Overall, PA rapidly cleared P. vivax blood asexual stages and was highly efficacious in treating vivax malaria, with no evidence of artemisinin resistance found. PA provides an alternative to chloroquine treatment for vivax malaria in Vietnam.; Clinical Trials: This study is registered with the Australian New Zealand Clinical Trials Registry as ACTRN12618001429246. |
| Competing Interests: | The authors declare no conflict of interest. |
| References: | Malar J. 2011 Oct 11;10:297. (PMID: 21989376); N Engl J Med. 2012 Apr 5;366(14):1298-309. (PMID: 22475593); Clin Infect Dis. 2020 May 6;70(10):2187-2195. (PMID: 31251812); Antimicrob Agents Chemother. 2021 Nov 17;65(12):e0027621. (PMID: 34570647); Antimicrob Agents Chemother. 2014 Jul;58(7):3889-94. (PMID: 24777099); Am J Trop Med Hyg. 2020 Sep;103(3):1088-1093. (PMID: 32524960); Malar J. 2011 Nov 10;10:339. (PMID: 22074219); Am J Trop Med Hyg. 2003 Jul;69(1):14-8. (PMID: 12932090); PLoS One. 2016 Feb 05;11(2):e0148172. (PMID: 26849445); Antimicrob Agents Chemother. 2019 Sep 23;63(10):. (PMID: 31358594); Antimicrob Agents Chemother. 2019 Feb 26;63(3):. (PMID: 30602520); Antimicrob Agents Chemother. 2015 Dec 14;60(3):1450-8. (PMID: 26666916); Malar J. 2012 Oct 26;11:355. (PMID: 23101492); Lancet. 2018 Apr 7;391(10128):1378-1390. (PMID: 29606364); PLoS One. 2007 Oct 31;2(10):e1089. (PMID: 17971853); PLoS One. 2011 Jan 18;6(1):e14501. (PMID: 21267072); J Infect Dis. 2005 Jan 15;191(2):272-7. (PMID: 15609238); Acta Trop. 2011 Feb;117(2):69-75. (PMID: 20933490); Antimicrob Agents Chemother. 2016 Jun 20;60(7):3884-90. (PMID: 26926629); Antimicrob Agents Chemother. 2011 Sep;55(9):4412-5. (PMID: 21730120); Antimicrob Agents Chemother. 2004 Nov;48(11):4075-83. (PMID: 15504824); PLoS Med. 2021 Jun 15;18(6):e1003669. (PMID: 34129601); Lancet. 1989 Nov 18;2(8673):1183-4. (PMID: 2572903); Antimicrob Agents Chemother. 2015 Jan;59(1):730-3. (PMID: 25385109); Nature. 2014 Jan 2;505(7481):50-5. (PMID: 24352242); J Infect Dis. 2008 Nov 15;198(10):1558-64. (PMID: 18808339); Eur J Clin Pharmacol. 2008 Oct;64(10):993-8. (PMID: 18600318); Antimicrob Agents Chemother. 2017 Mar 24;61(4):. (PMID: 28137815); Clin Infect Dis. 2011 Mar 1;52(5):612-20. (PMID: 21292666); Lancet Infect Dis. 2010 Jun;10(6):405-16. (PMID: 20510281); Lancet Infect Dis. 2019 Jan;19(1):91-101. (PMID: 30587297); Malar J. 2012 Jan 09;11:12. (PMID: 22230294); Trends Parasitol. 2020 Jun;36(6):560-570. (PMID: 32407682); Malar J. 2019 Apr 2;18(1):114. (PMID: 30940150); Antimicrob Agents Chemother. 2015 Dec;59(12):7411-9. (PMID: 26392501); Lancet Infect Dis. 2019 Sep;19(9):952-961. (PMID: 31345710); Trends Parasitol. 2009 May;25(5):220-7. (PMID: 19349210); N Engl J Med. 2013 Oct 3;369(14):1381-2. (PMID: 24088113); Am J Trop Med Hyg. 2016 Dec 28;95(6 Suppl):15-34. (PMID: 27402513); Antimicrob Agents Chemother. 2015 Jan;59(1):505-13. (PMID: 25385096); PLoS Med. 2008 Jun 17;5(6):e127. (PMID: 18563961); Lancet. 2010 Apr 24;375(9724):1457-67. (PMID: 20417857); Cochrane Database Syst Rev. 2013 Oct 25;(10):CD008492. (PMID: 24163021); Antimicrob Agents Chemother. 2008 Jul;52(7):2657-9. (PMID: 18443118); Malar J. 2022 Dec 31;21(1):401. (PMID: 36587210); Antimicrob Agents Chemother. 2021 Jul 16;65(8):e0009521. (PMID: 34031050); Lancet Microbe. 2022 Aug;3(8):e598-e605. (PMID: 35654079); Am J Trop Med Hyg. 2018 Jul;99(1):65-72. (PMID: 29741150); Lancet Infect Dis. 2014 Oct;14(10):982-91. (PMID: 25213732); Int J Parasitol Drugs Drug Resist. 2017 Aug;7(2):181-190. (PMID: 28384505); Int J Parasitol Drugs Drug Resist. 2021 Apr;15:9-24. (PMID: 33360105); Int J Parasitol Drugs Drug Resist. 2021 Aug;16:23-37. (PMID: 33957488); Trop Med Int Health. 2002 Oct;7(10):858-64. (PMID: 12358621); Malar J. 2013 Feb 21;12:70. (PMID: 23433102) |
| Grant Information: | WUN D1430 US Department of Defense Health Program |
| Contributed Indexing: | Keywords: Plasmodium vivax; Pyramax; Vietnam; antimalarial drug resistance; molecular markers; pyronaridine-artesunate |
| Substance Nomenclature: | 0 (Naphthyridines); 0 (Antimalarials); 60W3249T9M (Artesunate); TD3P7Q3SG6 (pyronaridine); 0 (Artemisinins); MVR3634GX1 (Primaquine); 0 (Protozoan Proteins); 0 (Crt-o protein, Plasmodium vivax); 0 (Membrane Transport Proteins) |
| Entry Date(s): | Date Created: 20240724 Date Completed: 20240904 Latest Revision: 20250730 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC11373200 |
| DOI: | 10.1128/aac.00044-24 |
| PMID: | 39046237 |
| Database: | MEDLINE |
Journal Article; Clinical Trial; Research Support, U.S. Gov't, Non-P.H.S.