This study provided evidence of a sustained decrease in the prevalence of Plasmodium spp. carriage over at least one year following an MSAT campaign. The MSAT also noticeably reduced the incidence of symptomatic P. vivax infections in participants for more than 12 months. Relapses, and to a lesser degree reinfections, are the most likely source of P. vivax infections, and are a source of ongoing transmission. In French Guiana, P. vivax infections generally relapse after a short interval (up to 90 days, and generally around 28 days) 19. Therefore, the MSAT campaign including a radical cure of chloroquine and 14 days of primaquine will block transmission by clearing P. vivax gametocytes and also hypnozoites. Nearly half of the P. vivax cases in the studied area were previously reported to be caused by latent hypnozoites in patients who had not benefited from primaquine as a radical cure 4. The obstacles to primaquine administration were mainly logistical (samples for G6PD testing were shipped by canoe and drugs delivery followed a complex pharmaceutical approval process) 4,10. In addition, patients feel better after chloroquine treatment, and do not usually return to the health centre for G6PD testing and primaquine treatment. For these reasons, this MSAT campaign with dedicated teams including cultural health mediators increased primaquine delivery to 100% of P. vivax carriers who had no contraindication for its use. This approach was rapid and suitable for local populations, including a personalized follow-up. Despite this, only 60.7% of the primaquine-treated cases reported adherence to the complete 14-day course. This is a long period of treatment and follow-up did not include a daily visit to supervise primaquine intake. This poor adherence could explain why relapses were observed in MSAT participants. Single-dose tafenoquine, which was successfully evaluated in neighbouring Brazil, could be a solution to increase medication adherence 21. However, tafenoquine involves stronger side-effects in case of G6PD deficiency than for primaquine, and this treatment is not yet available in French Guiana.
Several Mass Drug Administration (MDAs) including mass primaquine administrations have been used to eliminate P. vivax throughout the world 22. When MDA achieved high coverage and was associated with vector control measures, it was described as an effective means to decrease incidence 22. However, data are scarce about its efficiency on asymptomatic carriage and therefore on the reservoir9,23. MDA of primaquine showed a good tolerability, despite high levels of G6PD deficiency in some regions of the world 22. In our study, participants with severe G6PD deficiency and pregnant women were only prescribed chloroquine treatment in cases of P. vivax carriage. However, these populations did not reveal significantly more relapses or carriage in our study. The difficulty to detect such a difference could be explained by the lack of statistical power, given the low number of patients with G6PD deficiency in the study samples. This study not only allowed a reduction of Plasmodium spp. carriage, but also enabled us to determine the G6PD status of a large part of this population living in a high malaria-risk area. These values have been recorded carefully in the health centre. This will enable participants to benefit from a faster primaquine treatment administration in the future.
This is the first Amazonia-based study to evaluate the efficiency of a MSAT campaign involving PCR diagnosis followed by a treatment of all Plasmodium spp. carriers. Contrary to the studies of Phommasone et al. in Myanmar and Garfield et al. in Nicaragua, we did not observe any resurgence of P. vivax infections during the 12-month follow-up 24,25. This may be due to the radical cure with 14 days (30mg/day) of primaquine treatment. Indeed, participants of Phommasone et al. MDA study participants received three-day courses of dihydroartemisidine-piperaquine and only a single dose of primaquine used as gametocytocide that does not target P. vivax hypnozoites 25. The treatment in the study by Garfield et al. was also shorter than that prescribed in our study, with a three-day course of chloroquine and a five-day course of primaquine (15mg/day) 24. However, P. vivax carriers in our study had a higher risk for P. vivax infection and a shorter median time before the next infection compared to participants without P. vivax carriage. This could be due to a higher global risk for malaria when living in specific areas such as a remote neighbourhood, or socio-demographic parameters such as high malaria-risk activities (hunting, fishing or farming in the forest), as previously described 10. It is also important to note that although primaquine coverage was 100% at the first MSAT intervention, medication adherence to 14 days of primaquine was low (around 60%); this figure should be taken with caution due to a possible memory bias (patients were asked about primaquine adherence one year after treatment). Similarly, data regarding behaviours in cases of fever during the 2nd MSAT identified a lack of medical consultation for malaria testing (56% of patients with fever presented for malaria testing), and this despite health education provided by dedicated teams during the 1st MSAT. In routine care, primaquine coverage was also low
In our transborder context, this kind of intervention must be repeated and coordinated with our Brazilian neighbour in order to be effective over the long term, and avoid new infections in this territory. It is also important to target mobile populations. In this respect, the ongoing MALAKIT project seeks to provide a kit for auto-testing and auto-treatment, and aims to control malaria in mobile gold miner populations 26. Efforts are also being made to develop and maintain a cross-border observatory on vector-borne disease (notably by the French-Brazilian Joint International Laboratory “Sentinela”) and a political commitment to eliminating this disease, with regular meetings and the implementation of specific measures in the field 27.
The efforts made to engage the empowerment and participation of the communities at all levels led the local population to accept and willingly participate in the MSAT campaigns. Communication via cultural community mediators who know local culture, languages and community mobilization made it possible to build confidence about MSAT and increased adherence 28. Door-to-door distribution of medication and the follow-up of carriers were effective in targeting all positive cases and improved the care of malaria patients. It was also easier for cultural mediators to explain directly to patients that the drugs had to be taken regularly, even by those who were asymptomatic and did not feel sick, in order to protect their household and community and eventually defeat malaria transmission. Being close to the inhabitants was also a logical approach given the logistical difficulties and the high cost of transport from houses to the health centre in this area. However, primaquine treatment adherence remains particularly challenging.
Although MSAT implementation was a success, it has a number of limitations. MSAT activities were conducted during the day, making it difficult to reach adult men who were at work, hunting or fishing. In addition, these communities move around a vast border territory for family purposes (ex: Amerindians moving between Brazil and French Guiana) or for subsistence. Finally, during the first intervention, a major seasonal malaria epidemic was reported. This outbreak may have resulted in an overestimation of MSAT efficiency. However, results of passive monitoring of non-participants of the study were a good indication of the impact on the number on symptomatic cases of MSAT strategy.