be-IMPACT: Interdisciplinary Malaria Prevention, surveillAnce & Care in Travelers in Belgium

Malaria is a disease, caused by Plasmodium parasites transmitted to humans by the bite of an infected Anopheles mosquito, that can have life-threatening consequences if not timely diagnosed and effectively treated. The global malaria burden had rapidly and substantially declined since 2000, following intensification of vector control activities and improved case management by the introduction of artemisinin-based combination therapies (ACTs) - a combination of potent and short-acting artemisinin derivatives with a long active partner drug - as first-line treatment worldwide. Progress stalled, however, in 2016, followed by an increase in malaria cases, with the largest annual rise occurring during the COVID-19 pandemic due to disruptions in health services (1, 2). In 2022, there were an estimated 249 million malaria cases and 608,000 deaths in 85 malaria endemic countries, with over 90% of the burden in sub-Saharan Africa (SSA), where Plasmodium falciparum largely predominates (3). In addition to this worrisome stagnation, resistance of P. falciparum parasites to artemisinin derivatives has recently emerged and spread in East Africa (4–6) after it was first observed more than a decade ago in Southeast Asia (SEA). Resistance to artemisinin derivatives results in delayed clearance of P. falciparum parasites, with immediate life-threatening consequences in patients with severe malaria. Moreover, it compromises the protection of the partner drug, as persistent parasites can be exposed to this single drug during its longer tail of elimination. Any reduced susceptibility of parasites to the artemisinin component and/or the partner drug can lead to early or late ACT failure and is associated with mutations in the K13 gene among others. Under the current status quo, rates of failure are soon likely to surpass the WHO 10%-threshold in regions of East Africa, which should lead health authorities to change the first-line therapy (7, 8). Unfortunately, new ACT regimens and classes of antimalarials are still under investigation, with very few affordable therapeutic options available to treat failing resistant cases. In the short term, rapidly mounting resistance to ACT can jeopardize all efforts of malaria control in SSA, including in the Great Lakes region and East Africa which are considered hotspots of resistance (6) and popular destinations for Belgian travelers (9). Indeed, malaria has been for a long time a top cause of travel-related morbidity and mortality in non-endemic settings like Belgium (10, 11). But in contrast to the global decline during the 2000-2016 period, a continuous rise in the number of malaria cases was observed since the late 2000’s in Belgium, like elsewhere in Europe (9, 12). Studies in Europe have attributed this to reduced attention to preventive measures by international travelers in general, and especially in the growing group of immigrants from endemic countries traveling home to visit their friends and relatives (VFRs) (13, 14). VFRs are reported to travel more frequently than other groups to rural areas where the risk of contracting malaria is higher and the health infrastructure poorer; they are usually staying longer than people visiting for touristic purposes only; and perhaps most importantly, they often do not seek pre-travel advice (15, 16). Most recent estimates obtained before the COVID-19 pandemic, indicated that about 25,000 cases of travel-related malaria occurred annually outside endemic regions (17), 5,375 in Europe (18), the vast majority being African migrant VFR residing in Europe and returning from travels in sub-Saharan Africa (19–21). Malaria is therefore a critical emergency in Europe if not diagnosed and treated promptly.