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Background Identifying the causes of Acute Undifferentiated Febrile Illness (AUFI) is key to improve the management of returning travellers with fever. We evaluated a BioFire®FilmArray® prototype panel of multiplex nucleic acid amplification tests (NAAT) targeting different relevant pathogens in travellers returning with fever. Methods Prospective, multicentre study to evaluate a prototype panel in whole blood samples of adult international travellers presenting with AUFI in three European travel Clinics/Hospitals (November 2017–November 2019). We evaluated 15 target analytes: Plasmodium spp., Plasmodium falciparum, Plasmodium knowlesi, Plasmodium malariae, Plasmodium ovale, Plasmodium vivax, chikungunya virus, dengue virus, Zika virus, Anaplasma phagocytophilum, Borrelia spp., Leptospira spp., Orientia tsutsugamushi, Rickettsia spp. and Salmonella spp. Results were compared with composite reference standards (CRSs) for each target infection, including direct methods [smear microscopy, rapid diagnostic test (RDT), reference NAAT and blood cultures] and indirect methods (paired serology). Findings Among 455 travellers with AUFI, 229 target infections were diagnosed; the prototype panel detected 143 (overall sensitivity and specificity of 62.5 and 99.8%, respectively). The panel identified all Plasmodium infections (n = 82). Sensitivity for dengue (n = 71) was 92.9, 80.8 and 68.5% compared with RDT, NAAT and CRS, respectively. Compared with direct methods and CRS, respectively, the prototype panel detected 4/4 and 4/6 chikungunya, 2/2 and 4/29 Leptospira spp., 1/1 and 1/6 O. tsutsugamushi and 2/2 and 2/55 Rickettsia spp., but 0/2 and 0/10 Zika, 0/1 and 0/11 A. phagocytophylum and 0/3 Borrelia spp. diagnosed by serology and only 1/7 Salmonella spp. diagnosed by blood cultures. 77/86 (89.5%) infections not detected by the panel were diagnosed by serology. Interpretation The prototype panel allowed rapid and reliable diagnosis for malaria, dengue and chikungunya. Further improvements are needed to improve its sensitivity for Zika and important travel-related bacterial infections.

Objectives Given the scarcity of data regarding prevalence of various infectious diseases in Latin-American countries, our study aims to assess the burden of T. cruzi, S. stercoralis, HIV and viral hepatitis in Latin-American migrants, with a focus on Bolivian migrants. Methods We performed a retrospective observational study of 565 screening evaluations in adults (≥18 years) carried out at our International Healthcare referral service in Barcelona. We reviewed structured clinical records and microbiological results of patients attended between February 2012 and April 2015. Results The median age was 35 years and 74% were women. Of the population screened, 87% were of Bolivian origin. We found a 48% prevalence of T. cruzi, 16% of S. stercoralis, 0.2% of HIV, 0.2% HBV and 0.2% HCV. Conclusions These results support the relevance of screening for T. cruzi and S. stercoralis in Bolivian migrants but challenge the pertinence of systematic screening for HBV in this population.

Background Diagnosis of undifferentiated non-malaria fevers (NMF) in returning travellers is a great challenge. Currently, there is no consensus about the use of empirical antibiotics in returning travellers with undifferentiated NMF. Although studies in endemic areas showed that a wide range of pathogens implicated in undifferentiated NMF are treatable with doxycycline, the role of doxycycline in returning travellers with fever still has to be explored. Methods Prospective European multicentre cohort study of febrile international travellers (November 2017—November 2019). Immunological and molecular diagnostic techniques for doxycycline responding illnesses (DRI) agents such as Anaplasma phagocytophilum, spotted fever group Rickettsia spp., typhus group Rickettsia spp., Coxiella burnetii, Bartonella spp., Orientia tsutsugamushi, Borrelia miyamotoi, Borrelia recurrentis and Leptospira spp. were systematically performed in all patients with undifferentiated NMF. We estimated the prevalence and predictive factors of DRI in returning travellers with undifferentiated NMF. Results Among 347 travellers with undifferentiated NMF, 106 (30·5%) were finally diagnosed with DRI. Only 57 (53·8%) of the 106 DRI infections were diagnosed by the standard of care. The main causes of DRI were: 55 (51·9%) Rickettsia spp., 16 (15·1%) C. burnetii; 15 (14·2%) Bartonella spp.; 13 (12·3%) Leptospira spp. and 10 (9·5%) A. phagocytophilum. The only predictive factor associated with DRI was presenting an eschar (aOR 39·52, 95%CI 4·85–322·18). Features of dengue such as retro-orbital pain (aOR 0·40, 95%CI 0·21–0·76) and neutropenia (aOR 0·41, 95%CI 0·21–0·79) were negatively associated with DRI. Conclusions Although DRI are responsible for 30% of undifferentiated NMF cases in travellers, those are seldom recognized during the first clinical encounter. Empirical treatment with doxycycline should be considered in returning travellers with undifferentiated fever and negative tests for malaria and dengue, particularly when presenting severe illness, predictive factors for rickettsiosis or no features of dengue.

Background Etiological diagnosis of febrile illnesses in returning travelers is a great challenge, particularly when presenting with no focal symptoms [acute undifferentiated febrile illnesses (AUFI)], but is crucial to guide clinical decisions and public health policies. In this study, we describe the frequencies and predictors of the main causes of fever in travelers. Methods Prospective European multicenter cohort study of febrile international travelers (November 2017–November 2019). A predefined diagnostic algorithm was used ensuring a systematic evaluation of all participants. After ruling out malaria, PCRs and serologies for dengue, chikungunya and Zika viruses were performed in all patients presenting with AUFI ≤ 14 days after return. Clinical suspicion guided further microbiological investigations. Results Among 765 enrolled participants, 310/765 (40.5%) had a clear source of infection (mainly traveler’s diarrhea or respiratory infections), and 455/765 (59.5%) were categorized as AUFI. AUFI presented longer duration of fever (p Conclusions Over 40% of returning travelers with AUFI were diagnosed with malaria or dengue, infections that can be easily diagnosed by rapid diagnostic tests. Arboviruses were the most common cause of AUFI (above malaria) and most cases were diagnosed during Aedes spp. high season. This is particularly relevant for those areas at risk of introduction of these pathogens. Empirical antibiotic regimens including doxycycline or azithromycin should be considered in patients with AUFI, after ruling out malaria and arboviruses.

Different diagnostic tests were evaluated in a cluster of six European travellers with acute schistosomiasis (AS) acquired in Mozambique. Adult worm and soluble egg antibodies, circulating anodic antigen (CAA) and DNA detection allowed early confirmation of AS. CAA permitted monitoring treatment response and Sm1-7 polymerase chain reaction allowed identification of Schistosoma mansoni complex.

BACKGROUND: Delayed haemolysis is a frequent adverse event after treatment with artesunate (AS). Removing once-infected "pitted" erythrocytes by the spleen is the most accepted mechanism of haemolysis in these cases. However, an increasing number of cases with positive direct antiglobulin test (DAT) haemolysis after AS have been reported. METHODS: All malaria cases seen at Hospital Clinic of Barcelona between 2015 and 2017 were retrospectively reviewed. Clinical, parasitological and laboratory data from patients treated with intravenous artesunate-specifically looking for delayed haemolysis and DAT-was collected. RESULTS: Among the 36 severe malaria patients treated with artesunate at the hospital, 10 (27.8%) developed post-artesunate delayed haemolysis. Out of these, DAT was performed in six, being positive in four of them (at least 40%). DAT was positive only for complement-without IgG-suggesting drug-dependent immune-haemolytic anaemia of the immune-complex type. Three of the four patients were treated with corticosteroids and two also received blood transfusion, with a complete recovery. CONCLUSIONS: Drug-induced auto-immune phenomena in post-artesunate delayed haemolysis may be underreported and must be considered. The role of corticosteroids should be reassessed.

Background Although tick-borne pathogens have been reported as an important cause of imported fever, the incidence of Anaplasma phagocytophilum, the causative agent of human granulocytic anaplasmosis (HGA), in travellers is unknown. Methods We conducted a prospective cohort study to investigate the aetiologies of fever in returning travellers (November 2017—July 2019). Polymerase chain reaction for msp2 gene amplification and indirect immunofluorescence assay for A. phagocitophilum were performed in all returning travellers with undifferentiated non-malarial fever. Results Among 141 travellers included, 8 patients were diagnosed with probable or confirmed HGA. The overall incidence rate of HGA was 19.9 cases/1000 person—week of travel. The main destination of travel was Asia, accounting for 62.5% patients with HGA. Co-infections were found in 37.5% of patients with HGA. Conclusions Diagnosis of HGA and empirical treatment with doxycycline should be considered in travellers with fever.

After returning from Kenya, a 20-year-old Caucasian girl presented with multiple itching and burning erythematous skin lesions in her limbs, which progressively evolved to pustulous linear lesions, some of them with mirror distribution. Toxic ‘dermatitis linearis’ due to Paederus spp. was confirmed by the identification of rove beetles.

The emergence of Zika virus (ZIKV) represents a threat with consequences on maternal and children's health. We aimed to assess the clinical and epidemiological characteristics of pregnant women returning from ZIKV affected areas, and the effects of maternal ZIKV infection on birth outcomes and children's health. This was a hospital-based prospective observational study conducted at the Hospital Clínic of Barcelona and Hospital Sant Joan de Déu, Barcelona, Spain, from January 2016 to February 2020. One hundred and ninety-five pregnant women who had travelled to ZIKV affected areas during pregnancy were recruited. Four women (2.1%) had a confirmed ZIKV infection, 40 women (20.5%) a probable infection, and 151 (77.4%) were negative for ZIKV. Among the ZIKV confirmed cases, a pregnant woman suffered a miscarriage, highly plausible to be associated with ZIKV infection. Brain cysts and microcalcifications were detected in 7% of fetuses or infants from women with confirmed or probable ZIKV infection. Neurodevelopmental delay in the language function was found in 33.3% out of the 21 children evaluated. These findings contribute to the understanding of ZIKV prevalence estimates, and the impact of maternal ZIKV infection on pregnancy outcomes and children's health. Results highlight the importance of long-term surveillance in pregnant travellers and their children. This work was supported by the Government of Spain [grant number PI16/0123, ISCIII-AES Proyectos de Investigación en Salud, 2016]; a predoctoral fellowship from “la Caixa” Foundation (ID 100010434) [fellowship LCF/BQ/ES17/11600006]; the Ministry of Science, Innovation and Universities, Government of Spain through a Ramon y Cajal Grant [RYC-2013-14,512]; RICET, a Tropical Disease Cooperative Research Network in Spain [RD12/0018/0010] cofounded by ISCIII and the Fondo Europeo de Desarrollo Regional (FEDER); the Departament d’Universitats I Recerca de la Generalitat de Catalunya, Spain, AGAUR [grant 2017SGR924]; and ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya. Sí

Dear Editor, the changing epidemiology of Zika virus infection has been described before and in this letter we would like to show how the local epidemiology of Zika in Cuba is reflected in imported cases in returning travellers to Barcelona. The spread of the 2015 Zika epidemic was mostly reported in South America and the Caribbean. While increasing numbers of cases raised in South-America, Cuba was still free of cases. On 2nd March 2016 the first imported case from Cuba (Artemisa province) was reported. The first autochthonous case was reported on 16th March 2016 in La Habana. Onwards, cases were reported in Camagüey, Cienfuegos, Guantánamo, Havana and Santiago. During 2017 transmission has been reported in municipalities of Arroyo Naranjo and Regla in the province of Havana .

Background Zika virus has created a major epidemic in Central and South America, especially in Brazil, during 2015–16. The infection is strongly associated with fetal malformations, mainly microcephaly, and neurological symptoms in adults. During the preparation of the Rio de Janeiro Olympic Games in 2016, members of Olympic Delegations worldwide expressed their concern about the health consequences of being infected with Zika virus. A major risk highlighted by the scientific community was the impact on the spreading of the virus into new territories immediately after the Games. Objectives To detect real-time incidence of symptoms compatible with arboviral diseases and other tropical imported diseases among the Spanish Olympic Delegation (SOD) attending the Rio Olympic Games in 2016. Methods We developed a surveillance platform based on a mobile application installed in participant’s smartphones that monitored the health status of the SOD through a daily interactive check of the user health status including geo-localization data. The results were evaluated by a study physician on-call through a web-based platform monitoring system. Participants presenting severe symptoms or those compatible with Zika infection prompted an alarm in the system triggering specialized medical assistance and allowing early detection and control of the introduction of arboviral diseases in Spain. Summary of the results The system was downloaded by 189 participants and used by 143 of them (76%). Median age was 38 years (IQR 16), and 134 (71%) were male. Mean duration of travel was 19 days (+/-9SD). During the Games the highest accumulated incidence observed was for headache: 6.06% cough: 5.30% and conjunctivitis: 3.03%. The incidence rate of cough during the Olympic Games was 1.1% per day per person, followed by headache 0.8% and 0.4% conjunctivitis or diarrhea. In our cohort we observed that non-athletes experienced more incidence of symptoms, except for incidence of cough which was the same in the two groups (1.1%). No participants reported symptoms fulfilling Zika definition case. Conclusion Our system did not find cases fulfilling Zika definition amongst participants of the SOD during the Games, consistent with limited cases of Zika in Rio during the Games. The app showed good usability and the web based monitoring platform allowed to manage infectious cases in real-time. The overall system has proven to serve as a real-time surveillance platform for detecting symptoms that could be present in tropical imported diseases, especially arboviral diseases, contributing to the preparedness for the introduction of vector borne-diseases in non-endemic countries.

Trip Doctor(R), a Smartphone-based app monitoring system, was developed to detect infections among travelers in real-time. For testing, 106 participants were recruited (62.2% male, mean age 36 years (SD = 11)). Majority of trips were for tourism and main destinations were in South East Asia. Mean travel duration was 14 days (SD = 10). Diarrhea was the most frequently reported symptom (15.5%). The system demonstrated adequate usability and is ready to be used on a larger scale.

An expatriate to Ivory Coast (supposedly allergic to artemether-lumefantrine) was diagnosed with severe malaria in Spain. Parasitemia increased from 2% up to 21% within 24 h under quinine (10 mg/kg) and clindamycin (450 mg/8 h) combination treatment. Molecular profiling of the patient revealed the presence of molecular markers of quinine and other antimalarials resistance. Additionally, multiple copies of pfpm2 gene were also noticed in the patient sample, despite the absence of piperaquine drug pressure in Ivory Coast. Parasitemia was cleared with artesunate (2.4 mg/kg) under a desensitization protocol. Nevertheless, detection of early treatment failure is needed mainly in cases of suspected antimalarial resistance.

A 39-year-old caucasian man presented to our hospital in Barcelona with fever, dry cough, headache and weight loss of 4 kg. Symptoms started 5 days after returning from a 21-day travel to Malaysia. His physical examination was unremarkable except for a splenomegaly. Laboratory tests showed mild elevation of transaminases, elevated levels of lactate dehydrogenase (468 UI/L) and a normal blood cell count. Blood cultures, thick and thin blood smear and serologic tests for dengue, chikungunya, HIV, cytomegalovirus, Epstein-Barr virus, herpes virus 6, parvovirus B19, Toxoplasma spp and Rickettsia conorii were negative.

We evaluated the risk for the Spanish Olympic Team acquiring Zika virus in Rio de Janeiro, Brazil, during 2016. We recruited 117 team members, and all tested negative for Zika virus. Lack of cases in this cohort supports the minimum risk estimates made before the Games. This work was supported by La Caixa Foundation and the Spanish Olympic Committee. The laboratory work was supported by RICET (Network Biomedical Research on Tropical Diseases), RD16CIII/003/003. Sí

We evaluated the microbiological diagnosis in 14 patients with epidemiological and clinical suspicion of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) attended in a non-endemic area between June 2015 and January 2017. While no MERS-CoV was detected, other respiratory viruses were identified in 12 cases and Mycoplasma pneumoniae in 1 case.

BACKGROUND: Leptospirosis is an important zoonosis worldwide, nevertheless is often poor recognized in non tropical settings. In Thailand is becoming an emerging disease and Chiang Mai could become a popular spot to acquire the disease amongst travelers. METHODS: We describe three cases of imported leptospirosis undifferentiated fever after travelling to Thailand during the summer of 2015 diagnosed at two Spanish hospitals. RESULTS: Our three patients probably acquired leptospirosis while swimming in freshwater around Chiang Mai, a Thailand's northern region with moderate incidence of leptopirosis. Travelers had normal white blood cell counts and low platelets, suggesting leptospirosis after ruling out other imported diseases such as malaria, dengue or typhoid. CONCLUSION: As recent findings point out, low platelets and normal white blood cell counts are clinical features that could help the clinician to suspect Leptospirosis infection. It should be always considered as a cause of fever, particularly if travelers come from a tropical country and have had contact with water or flooding, especially during rainy season.

A 38-year-old Senegalese man with no travel history for the last 2 years presented with fever and acute kidney injury with nephrotic syndrome after an elective splenectomy. Diagnosis of membranoproliferative glomerulonephritis due to a chronic mixed Plasmodium infection triggered by splenectomy in a patient with hyperreactive malarial splenomegaly was confirmed.

Blackwater fever was typically reported after quinine administration, although it is poor recognized in patients receiving artesunate. This case describes a blackwater fever in a non-immune patient after artesunate for severe malaria. It highlights the importance of monitoring haemolytic parameters in severe malaria to avoid renal impairment or severe anaemia.