Discussion
malaria, parasitaemia, infections
MALARIA, ADVERSE EVENT, INFECTIONS, MALARIA
The trial found that it is feasible and effective to give forest goers antimalarial chemoprophylaxis with artemether–lumefantrine. Antimalarial chemoprophylaxis with artemether–lumefantrine had a large impact on the proportions of participants with subsequent parasitaemia: 3% among those who received chemoprophylaxis compared with 17% in the control group. A marked impact on parasitaemia occurred irrespective of whether participants were PCR-positive on enrolment. The large differences in outcome between the treatment groups strongly suggest that the forest goers adhered to their respective regimens, in concordance with the other measures of adherence reported. Adverse events reported by trial participants receiving artemether–lumefantrine and multivitamin were similar, reinforcing the well known safety and tolerability of artemether–lumefantrine.Most infections were with The findings come at a time when forested regions have become some of the last remaining foci of malaria transmission in southeast Asia. A range of interventions to interrupt malaria transmission has been tried with mixed success in the Greater Mekong subregion.The study was conducted in 2020 during the first year of the COVID-19 pandemic, which made access to study sites difficult. Repeated lockdowns prohibited large gatherings, including sensitisation meetings with forest goers, and required unusual flexibility from all members of the study team throughout the study period. The well balanced baseline characteristics of both study groups indicate that the randomisation was achieved successfully despite the constraints. Restrictions due to COVID-19 slowed enrolment and follow-up, and thus the trial had to be stopped before reaching the planned sample size once the grants came to an end. Despite this, we believe the statistically significant and approximately six-fold difference between study groups in subsequent infections is sufficiently reliable evidence from which to report a real effect of the intervention. The COVID-19 pandemic had no noticeable negative impact on malaria control in Cambodia, despite valid concerns that diagnosis and treatment would be undermined. Quite the opposite has occurred, and clinical malaria has reached unprecedented low levels in Cambodia, while numbers of malaria diagnostic tests performed suggests this observation is not due to under-reporting. Our study detected only 11 clinical malaria cases, which was insufficient to detect statistically significant differences between study groups.Given the nature of forest work, DOT could not be provided by a trained health worker, and instead smart DOT was used, whereby the first dose was observed by a health worker and subsequent doses supervised by a volunteer forest worker in each group. This meant the study was conducted closer to a real-world setting. Despite this, high participant adherence was achieved, which is supported by the finding that the large majority of malaria cases occurred in the control group.The antimalarial regimen used in this study for chemoprophylaxis did not include 8-aminoquinolines required for the prevention of Limitations of artemether–lumefantrine are the relatively short duration of the prophylactic effect compared with other ACTs, the dependence on concomitant intake of a fat, and the twice daily dosing. Advantages of artemether–lumefantrine for chemoprophylaxis in Cambodia are the antimalarial efficacy, that it is not used as first-line antimalarial treatment, and the very good safety and tolerability profile. Good tolerability and an excellent safety profile were especially important as the participants receiving it would be otherwise healthy and thus potentially less likely to accept drug-related symptoms than patients with clinical malaria. In other studies,In conclusion, this study demonstrated that chemoprophylaxis with artemether–lumefantrine was acceptable, well tolerated, and reduced by approximately six-fold the number of subsequent malaria infections over a 3-month period. Malaria chemoprophylaxis among high-risk groups such as forest goers is a valuable additional tool for malaria elimination in the Greater Mekong subregion.