This study focusses on characteristics and outcomes of ill returning travellers presenting to the emergency department after a stay in a malaria-endemic country.

Malaria (n = 40) was the most common specific diagnosis in the patients with systemic febrile illness, followed by influenza (n = 13) and rickettsiosis (n = 8). Plasmodium falciparum, the cause of severe (potentially lethal) malaria, was identified in 75.0% of the patients with malaria. Compared to the study of Siikamaki et al., who performed a similar retrospective study in the ED looking at febrile adults after travel to malaria-endemic areas, our data show a higher percentage of Plasmodium falciparum malaria (11.9% vs 3.5%) [8]. As the great majority of falciparum malaria occurs in the region Sub-Saharan Africa, this difference can be explained by the higher proportion of patients returning from this region in our study (68.4% vs only 41.8%). Our data are in concordance with data from Bottieau et al. (ITM), who included mainly ambulatory patients with fever after a stay in the tropics: sub-Saharan Africa was the most frequent region of exposure (68%) and falciparum malaria was recorded in 22.1% of patients [5]. Our study confirms that most cases of falciparum malaria in returning travelers occur when the prescribed regimen for chemoprophylaxis is not followed. Nevertheless, as no prophylactic regimen gives complete protection, malaria should always be excluded in patients with a relevant travel history up until months after their return, and both medical professionals and patients should be educated about this [12]. Although thrombocytopenia increases the likelihood for malaria, it should be used with caution when trying to determine if fever is due to malaria or to another acquired infection. Thrombocytopenia was also found in patients with viral (hantavirus, dengue, chikungunya, influenza A and varicella zoster virus) as well as bacterial (rickettsiosis and enteric fever) infections. Thirteen % of the patients in our study had severe falciparum malaria, compared to 7.7% of cases in a London registry and 25% in the Finnish ED study [8, 13].

Early diagnosis and treatment of malaria is of utmost importance, since delay in diagnosis is associated with fatal outcome [14]. When analyzing the history of the patients eventually having malaria, 5 patients mentioned previous clinical visits before malaria was considered in the differential diagnosis. For example, one patient presented after five days of illness (shivering and general weakness) at the general practitioner. No blood smear was performed and paracetamol was prescribed. On day nine of symptoms he presented with fever and change of consciousness at our emergency department with diagnoses of severe falciparum malaria. Admission at the intensive care was necessary.

It is important to stress that malaria may be acquired together with other pathogens that are endemic in the visited areas (e.g. bacteria, viruses, other parasites), and that symptoms can overlap. Therefore, additional diagnoses should always be considered, even when a diagnosis of malaria has already been made: a tropical co-infection may be present, may require specific therapy and may cause significant morbidity when left untreated [15]. In our study blood cultures were not taken in all patients, whereas this would have been more prudent. A recent retrospective study from Sweden on travellers diagnosed with malaria showed a low frequency of bacterial coinfection (positive blood cultures in 0.3% of patients (Salmonella Enteritidis and E. coli)) [16].

Although recognition and early treatment of life-threatening tropical diseases by the emergency physician is crucial, in our study only 22.5% of the patients had a ‘tropical’ diagnosis (additional file 1). This is higher to the study of Siikamäki et al. in which 10% of the patients suffered from a tropical infection, but lower than in the ITM study (39%) [5, 8]; the higher ITM percentage reflecting the selection of patients sent to ITM. The most frequent cosmopolitan infections we found were acute diarrhoea (18.2%), respiratory tract infections (5.1%) and ear, nose and throat infections (4.7%). Previous studies show that physicians should always remain vigilant to the possibility of a serious cosmopolitan bacterial infection (that can resemble tropical viral infection on clinical grounds) when facing a returning traveller, so that antimicrobial therapy can be started in time, awaiting results from additional testing [17].

When we looked at the prevalence of tropical disease according to geographical region of exposure, rickettsiosis (typical eschar (7 of 8 patients) and/or positive IgG antibody titer to Rickettsia conorii (3 of 8 patients) was almost exclusively seen after return from Sub-Saharan Africa (7 of 8 patients), especially South-Africa (6/8), based on epidemiological data presumably 6 cases of African tick-bite fever. Enteric fever was only found in Asia in our study (Southeast Asia [n = 1] and South-Central Asia [n = 1]). Dengue was diagnosed in 4 patients (1.6%), all after travels to Asia or Latin America. These data are in accordance with the GeoSentinel surveillance data, and emphasize the importance of the region of return when determining the prior probability for a specific disease [9].

For a large proportion of the travellers presenting at the ED (23.3%), the aetiology of illness remained unclear, which is consistent with other reports in and outside the ED (no specific diagnosis in respectively 25.1 and 24.4% of patients) [5, 8].

Mortality in returning travellers has been reported to range from 0.2 to 0.5% in other studies [4, 5, 7], and was mainly caused by falciparum malaria (case fatality ranging from 0.2 to 3% [14]), and occasionally by dengue, melioidosis, leptospirosis, enteric fever and Strongyloides hyperinfection syndromes [5, 18,19,20,21]. In our study none of the patients died.

Since this is a single-centred study performed in a tertiary care hospital, there are restrictions on generalisability to other non-tertiary centres. We used the blood smear test as a surrogate for illness in the returning travellers after a stay in a malaria-endemic country. Theoretically we may have missed some patients that erroneously did not have a blood smear, but we believe this is unlikely since training on imported diseases is organised on a yearly basis in our centre and the threshold to request a blood smear is low. We were not able to collect reliable data on pre-travel vaccination status and so we did not include it on our study. Furthermore inpatients presenting with diarrhoea; parasitic testing was not routinely performed. The indication was evaluated case by case. In our study, there were no diagnoses of parasitic diarrhoea (e.g. giardiasis or amebiasis) and this could be an underestimation. Finally, this study discusses the patient population before the onset of the Covid-19 pandemic. For now, it remains unclear if the pandemic will have a permanent influence on international travel and cause a shift in the epidemiology of diseases in returning travellers.