Artemisinin-naphthoquine plus lower-dose primaquine to treat and prevent recurrence of Plasmodium vivax malaria: an open-label randomized and non-inferiority trial
Abstract Background Plasmodium vivax malaria, with the widest geographic distribution, can cause severe disease and death. Primaquine is the main licensed antimalarial drug that can kill hypnozoites. The dose-dependent acute haemolysis in individuals with glucose-6-phospate dehydrogenase (G6PD) defi...
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| Format: | Article |
| Language: | English |
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BMC
2024-01-01
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| Series: | Parasites & Vectors |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13071-023-06058-8 |
| _version_ | 1797276708688101376 |
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| author | Hui Liu Jian-Wei Xu Dao-Wei Deng Bi Yaw Hkawn Shawng Nbwi Chun Wei Xing-Wu Zhou Jian-Xiong Li |
| author_facet | Hui Liu Jian-Wei Xu Dao-Wei Deng Bi Yaw Hkawn Shawng Nbwi Chun Wei Xing-Wu Zhou Jian-Xiong Li |
| author_sort | Hui Liu |
| collection | DOAJ |
| description | Abstract Background Plasmodium vivax malaria, with the widest geographic distribution, can cause severe disease and death. Primaquine is the main licensed antimalarial drug that can kill hypnozoites. The dose-dependent acute haemolysis in individuals with glucose-6-phospate dehydrogenase (G6PD) deficiency is the main safety concern when using primaquine. The recommended treatment regimen for P. vivax malaria is chloroquine plus primaquine for 14 days (CQPQ14) in Myanmar. The study aimed to evaluate the therapeutic efficacy, safety and adherence for the regimen of artemisinin-naphthoquine plus primaquine for 3 days (ANPQ3) in patients with P. vivax infections compared to those with CQPQ14. Methods The patients in the ANPQ3 group were given fixed-dose artemisinin-naphthoquine (a total 24.5 mg/kg bodyweight) plus a lower total primaquine dose (0.9 mg/kg bodyweight) for 3 days. The patients in the CQPQ14 group were given a total chloroquine dose of 30 mg/kg body weight for 3 days plus a total primaquine dose of 4.2 mg/kg bodyweight for 14 days. All patients were followed up for 365 days. Results A total of 288 patients completed follow-up, 172 in the ANPQ3 group and 116 in the CQPQ14 group. The first recurrence patients were detected by day 58 in both groups. By day 182, 16 recurrences had been recorded: 12 (7.0%) patients in the ANPQ3 group and 4 (3.4%) in the CQPQ14 group. The difference in recurrence-free patients was 3.5 (−8.6 to 1.5) percentage points between ANPQ3 and CQPQ14 group (P = 0.2946). By day 365, the percentage of recurrence-free patients was not significant between the two groups (P = 0.2257). Mean fever and parasite clearance time of ANPQ3 group were shorter than those in CQPQ14 group (P ≤ 0.001). No severe adverse effect was observed in ANPQ3 group, but five (3.9%) patients had acute haemolysis in CQPQ14 group (P = 0.013). Medication percentage of ANPQ3 group was significantly higher than that of CQPQ14 group (P < 0.0001). Conclusions Both ANPQ3 and CQPQ14 promised clinical cure efficacy, and the radical cure efficacy was similar between the ANPQ3 and CQPQ14 group. ANPQ3 clears fever and parasites faster than CQPQ14. ANPQ3 is safer and shows better patient adherence to the regimen for treatment of P. vivax malaria along the China-Myanmar border. Trial registration: ChiCTR-INR-17012523. Registered 31 August 2017, https://www.chictr.org.cn/showproj.html?proj=21352 Graphical Abstract |
| first_indexed | 2024-03-07T15:33:05Z |
| format | Article |
| id | doaj.art-d7f2fe6e53ce4c80b47731c81ce94cd5 |
| institution | Directory Open Access Journal |
| issn | 1756-3305 |
| language | English |
| last_indexed | 2024-03-07T15:33:05Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Parasites & Vectors |
| spelling | doaj.art-d7f2fe6e53ce4c80b47731c81ce94cd52024-03-05T16:21:39ZengBMCParasites & Vectors1756-33052024-01-0117111010.1186/s13071-023-06058-8Artemisinin-naphthoquine plus lower-dose primaquine to treat and prevent recurrence of Plasmodium vivax malaria: an open-label randomized and non-inferiority trialHui Liu0Jian-Wei Xu1Dao-Wei Deng2Bi Yaw3Hkawn Shawng Nbwi4Chun Wei5Xing-Wu Zhou6Jian-Xiong Li7Yunnan Institute of Parasitic Diseases, Yunnan Provincial Key Laboratory of Vector-Borne Disease Control and Research, Yunnan International Joint Laboratory of Tropical Infectious DiseasesYunnan Institute of Parasitic Diseases, Yunnan Provincial Key Laboratory of Vector-Borne Disease Control and Research, Yunnan International Joint Laboratory of Tropical Infectious DiseasesYunnan Institute of Parasitic Diseases, Yunnan Provincial Key Laboratory of Vector-Borne Disease Control and Research, Yunnan International Joint Laboratory of Tropical Infectious DiseasesLaiza City HospitalLaiza City HospitalYunnan Institute of Parasitic Diseases, Yunnan Provincial Key Laboratory of Vector-Borne Disease Control and Research, Yunnan International Joint Laboratory of Tropical Infectious DiseasesYunnan Institute of Parasitic Diseases, Yunnan Provincial Key Laboratory of Vector-Borne Disease Control and Research, Yunnan International Joint Laboratory of Tropical Infectious DiseasesYunnan Institute of Parasitic Diseases, Yunnan Provincial Key Laboratory of Vector-Borne Disease Control and Research, Yunnan International Joint Laboratory of Tropical Infectious DiseasesAbstract Background Plasmodium vivax malaria, with the widest geographic distribution, can cause severe disease and death. Primaquine is the main licensed antimalarial drug that can kill hypnozoites. The dose-dependent acute haemolysis in individuals with glucose-6-phospate dehydrogenase (G6PD) deficiency is the main safety concern when using primaquine. The recommended treatment regimen for P. vivax malaria is chloroquine plus primaquine for 14 days (CQPQ14) in Myanmar. The study aimed to evaluate the therapeutic efficacy, safety and adherence for the regimen of artemisinin-naphthoquine plus primaquine for 3 days (ANPQ3) in patients with P. vivax infections compared to those with CQPQ14. Methods The patients in the ANPQ3 group were given fixed-dose artemisinin-naphthoquine (a total 24.5 mg/kg bodyweight) plus a lower total primaquine dose (0.9 mg/kg bodyweight) for 3 days. The patients in the CQPQ14 group were given a total chloroquine dose of 30 mg/kg body weight for 3 days plus a total primaquine dose of 4.2 mg/kg bodyweight for 14 days. All patients were followed up for 365 days. Results A total of 288 patients completed follow-up, 172 in the ANPQ3 group and 116 in the CQPQ14 group. The first recurrence patients were detected by day 58 in both groups. By day 182, 16 recurrences had been recorded: 12 (7.0%) patients in the ANPQ3 group and 4 (3.4%) in the CQPQ14 group. The difference in recurrence-free patients was 3.5 (−8.6 to 1.5) percentage points between ANPQ3 and CQPQ14 group (P = 0.2946). By day 365, the percentage of recurrence-free patients was not significant between the two groups (P = 0.2257). Mean fever and parasite clearance time of ANPQ3 group were shorter than those in CQPQ14 group (P ≤ 0.001). No severe adverse effect was observed in ANPQ3 group, but five (3.9%) patients had acute haemolysis in CQPQ14 group (P = 0.013). Medication percentage of ANPQ3 group was significantly higher than that of CQPQ14 group (P < 0.0001). Conclusions Both ANPQ3 and CQPQ14 promised clinical cure efficacy, and the radical cure efficacy was similar between the ANPQ3 and CQPQ14 group. ANPQ3 clears fever and parasites faster than CQPQ14. ANPQ3 is safer and shows better patient adherence to the regimen for treatment of P. vivax malaria along the China-Myanmar border. Trial registration: ChiCTR-INR-17012523. Registered 31 August 2017, https://www.chictr.org.cn/showproj.html?proj=21352 Graphical Abstracthttps://doi.org/10.1186/s13071-023-06058-8Plasmodium vivax malariaArtemisinin-naphthoquinePrimaquineRadical cure efficacySafetyAdherence |
| spellingShingle | Hui Liu Jian-Wei Xu Dao-Wei Deng Bi Yaw Hkawn Shawng Nbwi Chun Wei Xing-Wu Zhou Jian-Xiong Li Artemisinin-naphthoquine plus lower-dose primaquine to treat and prevent recurrence of Plasmodium vivax malaria: an open-label randomized and non-inferiority trial Parasites & Vectors Plasmodium vivax malaria Artemisinin-naphthoquine Primaquine Radical cure efficacy Safety Adherence |
| title | Artemisinin-naphthoquine plus lower-dose primaquine to treat and prevent recurrence of Plasmodium vivax malaria: an open-label randomized and non-inferiority trial |
| title_full | Artemisinin-naphthoquine plus lower-dose primaquine to treat and prevent recurrence of Plasmodium vivax malaria: an open-label randomized and non-inferiority trial |
| title_fullStr | Artemisinin-naphthoquine plus lower-dose primaquine to treat and prevent recurrence of Plasmodium vivax malaria: an open-label randomized and non-inferiority trial |
| title_full_unstemmed | Artemisinin-naphthoquine plus lower-dose primaquine to treat and prevent recurrence of Plasmodium vivax malaria: an open-label randomized and non-inferiority trial |
| title_short | Artemisinin-naphthoquine plus lower-dose primaquine to treat and prevent recurrence of Plasmodium vivax malaria: an open-label randomized and non-inferiority trial |
| title_sort | artemisinin naphthoquine plus lower dose primaquine to treat and prevent recurrence of plasmodium vivax malaria an open label randomized and non inferiority trial |
| topic | Plasmodium vivax malaria Artemisinin-naphthoquine Primaquine Radical cure efficacy Safety Adherence |
| url | https://doi.org/10.1186/s13071-023-06058-8 |
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