Brazil: the first real-world use of new protocol for P. vivax case management

Representatives of the Brazilian Ministry of Health and Dr Dhelio Pereira, Director of Clinical Research at the Tropical Medicine Research Center of Rondonia (CEPEM) discuss the results of Phase I of TRuST and the next steps

1. What has Phase I of TRuST revealed so far?

Dhelio Pereira: Introduction of the G6PD test brought greater safety not only for the use of tafenoquine, but also for choosing the appropriate therapeutic regimen of primaquine. The few cases that resulted in haemolysis in this period were caused by inappropriate use of primaquine for patients with intermediate or low G6PD activity. 

Ministry of Health: The first phase of the study indicated that in medium and higher-level units, tafenoquine was used appropriately in more than 95% of cases, although there were challenges for local health services in organizing the training of professionals and monitoring of patients who had used the drug.

2. What are the next steps in this study?

DP: The results of the first phase were presented to the Independent Study Oversight Committee, which advised the Ministry of Health, MMV and the researchers to expand the study to the second phase. The new tools were introduced at lower-level health facilities including those in rural areas following training on the G6PD test and new treatment algorithm. Now all malaria diagnostic sites in the municipalities of Manaus and Porto Velho offer G6PD testing and tafenoquine.

3. How will the evidence generated be used?

MOH: The study will provide data on the implementation of tafenoquine in these two municipalities. A second study being carried out alongside TRuST, known as QualiTRuST, will provide findings on the perception of health professionals and patients. The Ministry of Health will bring this together with an evaluation of the process made at the local level, an evaluation by specialists, a cost-effectiveness and budget-impact analysis and a pharmacovigilance assessment to form a submission to the National Commission on Health Technologies (CONITEC). CONITEC will then make an assessment as to whether to incorporate tafenoquine and the G6PD test into the national health system, or Sistema Único de Saúde (SUS), for patients over 16 years of age.

DP: The evidence generated will help us better understand the challenges of implementing tafenoquine in the public health service and its acceptance by health workers and the population, as well as evaluate the costs and logistics of material distribution and data collection in the Amazonia region. This information will also be invaluable to other countries that are looking at whether to implement the G6PD test and tafenoquine.

4. How can tafenoquine support the country’s efforts to eliminate malaria (transmission, adherence, preventing relapse)?

MOH: The ability to treat hypnozoites and gametocytes in a single dose promotes better treatment adherence and, consequently, will help to reduce the transmission of P. vivax malaria. Furthermore, although there is no significant difference between the efficacy of tafenoquine and primaquine (a drug used for decades in Brazil), better adherence may also lead to a lower percentage of relapses in patients over 16 years of age with normal G6PD activity.

5. Is adherence to a 7-day treatment a challenge?

DP: In regions where the number of cases of P. vivax malaria is decreasing, knowledge about the disease also decreases and the importance of completing primaquine treatment is no longer valued, reducing adherence.

6. Which specific strategies are needed to improve adherence of primaquine within affected communities?

MOH: Health education actions with better targeting and accessible language for the affected populations, as well as the follow-up of treatment in locations with a lower level of transmission will be crucially important to ensure all patients understand the importance of completing the prescribed 7-day treatment regimen. To support this, we need operational capacity.

7. What has it been like to work with MMV on this project?

DP:  have been lucky enough to work with various teams within MMV, working on pre-clinical drug and compound development, diagnostic support, transmission blocking drug development and clinical trials, and now, on the implementation of two products, tafenoquine and the G6PD test. Everyone at MMV is a model of dedication, technical quality and love for what they do. Being in a malaria transmission region and being able to bring cutting-edge solutions to the local population in collaboration with MMV makes me proud and inspired to work harder and better.