Imported malaria and artemisinin-based combination therapy failure in travellers returning to Belgium: a retrospective study

Background: Malaria (Plasmodium spp) remains a top cause of travel-associated morbidity among European residents. Here, we describe recent trends of imported malaria to Belgium and characterize the first cases of P. falciparum failure to artemisinin-based combination therapy (ACT).

Methods: National surveillance data and registers from national reference laboratory were used to investigate malaria cases and ACT failures in the past 20 years. Recurrent infections were confirmed by pfmsp genotyping and polymorphisms in drug resistance-associated genes pfk13, pfcrt, pfmdr1, pfpm2, pfap2mu and pfubp1 were determined by sequencing or quantitative PCR.

Results: Annual malaria cases steadily increased in the last decade, reaching 428 in 2017 (all species). An estimated 15% of P. falciparum cases were severe. Between 2014 and 2017, 727 P. falciparum cases were reported and six non-immune travellers presented late recurrence. Five had hyperparasitaemia and/or signs of severe malaria at initial consultation. No mutations in ACT drug resistance markers were detected, although pfcrt-pfmdr1 haplotypes associated with lumefantrine tolerance were common.

Conclusions: The upward trend in imported malaria, the substantial proportion of severe cases and the emergence of ACT failures are sources of concern, although late failures were infrequent. Genetic analysis did not support parasitological resistance to ACT, suggesting prospective pharmacokinetic studies should assess adequacy of partner drug dosage and duration of treatment in non-immune populations.