Operational effectiveness of tafenoquine and primaquine for the prevention of Plasmodium vivax recurrence in Brazil: a retrospective observational study

04 Mar 2024
Marcelo Brito, PhD; Rosilene Rufatto, BSc; José Diego Brito-Sousa, PhD; Felipe Murta, PhD; Vanderson Sampaio, PhD; Patrícia Balieiro, MSc; Djane Baía-Silva, PhD; Vanessa Castro, BSc; Brenda Alves, BSc; Aline Alencar, MD; Stephan Duparc, MD; Penny Grewal Daumerie, MBA; Isabelle Borghini-Fuhrer, PhD; Elodie Jambert, PharmD; Cássio Peterka, MSc; Francisco Edilson Lima Jr, MSc; Leonardo Carvalho Maia, BSc; Catherine Lucena Cruz, BSc; Bruna Maciele, BSc; Mariana Vasconcelos, MD; Myrna Machado, MSc; Elder Augusto Figueira, PhD; Antônio Alcirley Balieiro, PhD; Dhelio Batista Pereira, PhD; Marcus Lacerda, PhD.

Prevention of Plasmodium vivax malaria recurrence is essential for malaria elimination in Brazil. We evaluated the real-world effectiveness of an updated treatment algorithm for P vivax radical cure in the Brazilian Amazon.

In this non-interventional observational study, we used retrospective data from the implementation of a P vivax treatment algorithm at 43 health facilities in Manaus and Porto Velho, Brazil. The treatment algorithm consisted of chloroquine (25 mg/kg over 3 days) and point-of-care quantitative glucose-6-phosphate dehydrogenase (G6PD) testing followed by single-dose tafenoquine 300 mg (G6PD normal, aged ≥16 years, not pregnant and not breastfeeding), 7-day primaquine 0·5 mg/kg per day (G6PD intermediate or normal, aged ≥6 months, not pregnant, and not breastfeeding or breastfeeding for >1 month), or primaquine 0·75 mg/kg per week for 8 weeks (G6PD deficient, aged ≥6 months, not pregnant, and not breastfeeding or breastfeeding for >1 month). P vivax recurrences were identified from probabilistic linkage of routine patient records from the Brazilian malaria epidemiological surveillance system. Recurrence-free effectiveness at day 90 and day 180 was estimated using Kaplan–Meier analysis and hazard ratios (HRs) by multivariate analysis. This clinical trial is registered with ClinicalTrials.gov, NCT05096702, and is completed.

Records from Sept 9, 2021, to Aug 31, 2022, included 5554 patients with P vivax malaria. In all treated patients of any age and any G6PD status, recurrence-free effectiveness at day 180 was 75·8% (95% CI 74·0–77·6) with tafenoquine, 73·4% (71·9–75·0) with 7-day primaquine, and 82·1% (77·7–86·8) with weekly primaquine. In patients aged at least 16 years who were G6PD normal, recurrence-free effectiveness until day 90 was 88·6% (95% CI 87·2–89·9) in those who were treated with tafenoquine (n=2134) and 83·5% (79·8–87·4) in those treated with 7-day primaquine (n=370); after adjustment for confounding factors, the HR for recurrence following tafenoquine versus 7-day primaquine was 0·65 (95% CI 0·49–0·86; p=0·0031), with similar outcomes between the two treatments at day 180 (log-rank p=0·82). Over 180 days, median time to recurrence in patients aged at least 16 years who were G6PD normal was 92 days (IQR 76–120) in those treated with tafenoquine and 68 days (52–94) in those treated with 7-day primaquine.

In this real-world setting, single-dose tafenoquine was more effective at preventing P vivax recurrence in patients aged at least 16 years who were G6PD normal compared with 7-day primaquine at day 90, while overall efficacy at 180 days was similar. The public health benefits of the P vivax radical cure treatment algorithm incorporating G6PD quantitative testing and tafenoquine support its implementation in Brazil and potentially across South America.