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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.

We describe a patient presenting with eosinophilia and liver lesions. A juvenile Fasciola gigantica emerged through the skin, an occurrence which has been only described in two patients so far. Ectopic manifestations usually appear shortly after infection, whereas the time before emergence was more than 1 year in our patient.

A couple presented with fever and strikingly similar symptoms starting exactly on the same day after returning from an adventurous journey in Peru. Symptom onset was 12 days after exposure to bats from a hollow tree. The further evolution underscores the disparate disease course of Histoplasmosis in different individuals, despite similar radiological findings. Our case highlights the importance of careful history taking in returning travelers since exposure to bat (or fowl) excrement can be easily overlooked.

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.

Background Benznidazole is an effective drug in the trypanocidal treatment of acute and chronic indeterminate Chagas’ disease (CD). However, adverse drug reactions (ADR) are common and frequently cause patients to discontinue treatment. Objectives We hypothesized that antioxidant supplementation could mitigate benznidazole-induced toxicity. Methods We co-supplemented an adult traveller with chronic indeterminate CD who experienced benznidazole ADR with ascorbic acid (AA), 1000 mg/day. We measured selected serum biomarkers of oxidative stress [total antioxidant status (TAS), total oxidative status (TOS), nuclear factor erythroid 2-related factor 2 (Nrf2), malondialdehyde (MDA), extracellular glutathione peroxidase (GPX3), catalase (CAT) and total superoxide dismutase (T-SOD)] at timepoints before and throughout benznidazole treatment and after AA co-supplementation. Results AA co-supplementation effectively mitigated benznidazole-induced ADR during the aetiological treatment of chronic indeterminate CD. The kinetics of serum biomarkers of oxidative stress suggested significantly decreased oxidative insult in our patient. Conclusions We hypothesize that the key pathophysiological mechanism of benznidazole-associated toxicity is oxidative stress, rather than hypersensitivity. AA co-supplementation may improve adherence to benznidazole treatment of chronic indeterminate (or acute) CD. Oxidative stress biomarkers have the potential to guide the clinical management of CD. Prospective studies are needed to establish the benefit of antioxidant co-supplementation to benznidazole treatment of CD in reducing benznidazole toxicity, parasite clearance and the prevention of end-organ damage.

Background: Data on rabies post-exposure prophylaxis (PEP) and the use of human rabies immunoglobulins (HRIG) in Belgium are scarce. The main objective of this study was to evaluate the timely administration of HRIG after rabies exposure. The secondary objective was to evaluate the adequate antibody response following PEP. Methods: We reviewed all medical records from July 2017 to June 2018 of patients seeking care at, or referred to, the Institute of Tropical Medicine and the University Hospital, Antwerp for the administration of human rabies immunoglobulins following potential rabies exposure abroad or in Belgium. A timely response was defined as starting HRIG with a delay of 5.0 IU/mL in case of bat-related exposure and >3.0 IU/mL in case of exposure to other animals. Titers were measured 10 days after the last PEP vaccine dose, using the rapid fluorescent focus inhibition test (RFFIT). Results: Of the 92 cases treated with HRIG, 75 were evaluated. The majority of injuries were acquired in Asia (n = 26,34%) and in Western Europe (n = 18, 24%), of which 17 in Belgium. The five most frequently recorded countries overseas were Indonesia (n = 13), Thailand (n = 7), Morocco (n = 4), Peru (n = 3) and Costa Rica (n = 3). Administration of immunoglobulins was related to injuries by dogs (36%), monkeys (25%) or bats (22%). A timely response was observed in 16 (21,33%) and in 55 (73,33%) of subjects receiving HRIG (5.0 IU/ml. In 38 of 47 (81%) cases related to other animals the RFFIT titer was >3.0 IU/ml. All low-responders received additional rabies injections. Conclusion: This study showed a substantial time delay between the animal-related risk and the administration of HRIG, in particular when the injury occurred abroad. More targeted communication about the risks of rabies and preventable measures may reduce this delay. Furthermore, the antibody response was inadequate in some cases following full PEP administration according to the Belgian recommendation.

Background Information on human filariasis in international travelers is scarce. We describe the epidemiology, clinical presentation, and outcome of these infections in a reference travel clinic over the past decades. Methods We reviewed all cases of filariasis diagnosed at the Institute of Tropical Medicine, Antwerp, Belgium, from 1994 to 2018. Diagnosis was obtained by either parasitological methods (confirmed) or strict clinical case definitions (probable). We assessed the characteristics of cases at diagnosis and response to therapy within 3–12 months. Results A total of 320 patients (median age: 41 years; 71% males) were diagnosed with 327 filarial infections (Wuchereria bancrofti = 6, Onchocerca volvulus = 33, Loa loa = 150, Mansonella perstans = 130, unspecified species = 8). Diagnosis was confirmed in 213/320 (67%) patients. European long-term travelers accounted for 166 patients (52%) and visitors/migrants from tropical countries for another 110 (34%). Central Africa was the likely region of acquisition for 294 (92%) patients. The number of filariasis cases decreased from 21.5/year on average in the 1990s to 6.3/year in the past decade, when loiasis became predominant. Cases reported symptoms in >80% of all filarial infections but mansonellosis (45/123 single infections; 37%). Lymphatic filariasis and onchocerciasis cases responded well to conventional therapy. However, 30% of patients with loiasis and mansonellosis experienced treatment failure (with diethylcarbamazine and levamisole-mebendazole, respectively). Conclusions The burden and species distribution of filariasis in travelers evolved in the past decades. Most presentations were symptomatic. Case management would benefit from more effective therapies for loiasis and mansonellosis.

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.

ispartof: OPEN FORUM INFECTIOUS DISEASES vol:7 issue:5 ispartof: location:United States status: published

Borreliabacterien zijn verantwoordelijk voor de ziekte van Lyme of Lyme-borreliose. De mens wordt besmet via een beet van een geinfecteerde teek. De meeste besmettingen komen voort na beten van nymfen (

Visceral pentastomiasis is usually found incidentally during surgery. We describe a case of visceral pentastomiasis discovered during inguinoscrotal hernia surgery for a man from Benin, Africa. Because surgical removal of nymphs is needed for symptomatic patients only, this patient's asymptomatic pentastomiasis was not treated and he recovered from surgery uneventfully.

Background Amebiasis is a protozoal infection caused by Entamoeba histolytica, while the morphologically indistinguishable E. dispar is considered as non-pathogenic. Polymerase chain reaction (PCR) assays are necessary to differentiate both species. The most common clinical presentations of E. histolytica disease are amebic colitis and amebic liver abscess, but asymptomatic infection is also possible. We assessed the frequency and pattern of clinical symptoms and microscopic features in travelers/migrants associated with E. histolytica intestinal infection and compared them to those found in individuals with E. dispar infection. Methods We conducted a retrospective study at the travel clinic of the Institute of Tropical Medicine, Antwerp, Belgium on travelers/migrants found from 2006 to 2016 positive for Entamoeba histolytica/dispar through antigen detection and/or through microscopy confirmed by PCR. All files of individuals with a positive PCR for E. histolytica (= cases) and a random selection of an equal number of Entamoeba dispar carriers (= controls) were reviewed. We calculated the sensitivity, specificity and likelihood ratios (LRs) of clinical symptoms (blood in stool, mucus in stool, watery diarrhea, abdominal cramps, fever or any of these 5 symptoms) and of microscopic features (presence of trophozoites in direct and in sodium acetate-acetic acid-formalin (SAF)-fixed stool smears) to discriminate between E. histolytica and E. dispar infection. Results Of all stool samples positive for Entamoeba histolytica/dispar for which PCR was performed (n = 810), 30 (3.7%) were true E. histolytica infections, of which 39% were asymptomatic. Sensitivity, specificity and positive LRs were 30%, 100% and 300 (p 0.007) for presence of blood in stool; 22%, 100% and 222 (p 0.03) for mucus in stool; 44%, 90% and 4.7 (p 0.009) for cramps and 14%, 97% and 4.8 (p = 0.02) for trophozoites in direct smears. For watery diarrhea, fever and for trophozoites in SAF fixated smears results were non-significant. Conclusions E. histolytica infection was demonstrated in a small proportion of travelers/migrants with evidence of Entamoeba histolytica/dispar infection. In this group, history of blood and mucus in stool and cramps had good to strong confirming power (LR+) for actual E. histolytica infection. Trophozoites were also predictive for true E. histolytica infection but in direct smears only., Author summary In the present work, we found that E. histolytica intestinal infections are rarely diagnosed among travelers and migrants presenting in a national reference travel clinic in Europe. Microscopic finding of cysts or trophozoites and antigen testing cannot discriminate between Entamoeba histolytica/dispar infection, which leads to overdiagnosis of E. histolytica infections in low resource settings where PCR is not available. We found visualization of trophozoites under the microscope helpful in discriminating between E. histolytica and E. dispar infection in direct smears. Hematophagy is a very rare finding but in our experience was always associated with E. histolytica infection. In a context where only microscopy is available, a patient presenting with blood or mucus in stool or cramps should anyhow be treated as amoebiasis if Entamoeba histolytica/dispar cysts/trophozoites are found. Nevertheless it is worth noting that a sizeable proportion of E. histolytica cases were asymptomatic. Last, our study suggests that E. dispar might be pathogenic but symptoms in E. histolytica infected patients were clearly more often suggestive of intestinal tissue invasion.

More than 2 million people fleeing conflict, persecution, and poverty applied for asylum between 2015 and 2016 in the European Union. Due to this, medical practitioners in recipient countries may be facing a broader spectrum of conditions and unusual presentations not previously encountered, including a wide range of infections with pulmonary involvement. Tuberculosis is known to be more common in migrants and has been covered broadly in other publications. The scope of this review was to provide an overview of exotic infections with pulmonary involvement that could be encountered in refugees and migrants and to briefly describe their epidemiology, diagnosis, and management. As refugees and migrants travel from numerous countries and continents, it is important to be aware of the various organisms that might cause disease according to the country of origin. Some of these diseases are very rare and geographically restricted to certain regions, while others have a more cosmopolitan distribution. Also, the spectrum of severity of these infections can vary from very benign to severe and even life-threatening. We will also describe infectious and noninfectious complications that can be associated with HIV infection as some migrants might originate from high HIV prevalence countries in sub-Saharan Africa. As the diagnosis and treatment of these diseases can be challenging in certain situations, patients with suspected infection might require referral to specialized centers with experience in their management. Additionally, a brief description of noncommunicable pulmonary diseases will be provided.

Background Rapid diagnostic test (RDT) detecting the nonstructural 1 (NS1) antigen is increasingly used for dengue diagnosis in endemic and nonendemic settings, but its clinical utility has not been studied in travel clinic practice. Methods From August 2012 to July 2016, travelers returning from the tropics with fever were evaluated in the Institute of Tropical Medicine (Antwerp, Belgium) with the routine use of NS1 antigen RDT that provided results within 1 hour. We determined the diagnostic performance, assessed the management of patients with a positive RDT result, and compared it with that of historical cases of dengue diagnosed from 2000 to 2006, when only antibody detection assays were available. Results Of 335 travelers evaluated for fever, 54 (16%) were diagnosed with dengue, including 1 severe case. Nonstructural 1 antigen RDT was performed in 308 patients. It was truly positive in 43 of 52 tested dengue cases and falsely positive in only 1 of the 256 nondengue cases; therefore, sensitivity was 82.7% (95% confidence interval [CI], 74.4%–93.0%) and specificity was 99.6% (95% CI, 98.8%–100%). Only 3 (7%) of the 43 febrile travelers “immediately” diagnosed by RDT were admitted, and only 2 (5%) were given empirical antibacterial treatment, without adverse outcome. Admission and antibiotic prescription rates were significantly higher in the historical cases (n = 43) diagnosed by antibody detection (33%, P = .006 and 26%, P = .014, respectively), although the frequency of severe dengue was similar. Conclusions In our practice, the diagnostic performance of NS1 antigen RDT substantially contributed in withholding unnecessary hospitalization and antibiotherapy in dengue patients.

Such abnormalities were common during infection and enabled accurate stratification of the risk for death. Electrolyte and Metabolic Disturbances in Ebola, By using data from a 2015 clinical trial on Ebola convalescent-phase plasma in Guinea, we assessed the prevalence of electrolyte and metabolic abnormalities at admission and their predictive value to stratify patients into risk groups. Patients underwent testing with a point-of-care device. We used logistic regression to construct a prognostic model and summarized the predictive value with the area under the receiver operating curve. Abnormalities were common among patients, particularly hypokalemia, hypocalcemia, hyponatremia, raised creatinine, high anion gap, and anemia. Besides age and PCR cycle threshold value, renal dysfunction, low calcium levels, and low hemoglobin levels were independently associated with increased risk for death. A prognostic model using all 5 factors was highly discriminatory (area under the receiver operating curve 0.95; 95% CI 0.90–0.99) and enabled the definition of risk criteria to guide targeted care. Most patients had a very low (80%) risk for death.

Although infection with Toxocara canis or T. catis (commonly referred as toxocariasis) appears to be highly prevalent in (sub)tropical countries, information on its frequency and presentation in returning travelers and migrants is scarce. In this study, we reviewed all cases of asymptomatic and symptomatic toxocariasis diagnosed during post-travel consultations at the reference travel clinic of the Institute of Tropical Medicine, Antwerp, Belgium. Toxocariasis was considered as highly probable if serum Toxocara-antibodies were detected in combination with symptoms of visceral larva migrans if present, elevated eosinophil count in blood or other relevant fluid and reasonable exclusion of alternative diagnosis, or definitive in case of documented seroconversion. From 2000 to 2013, 190 travelers showed Toxocara-antibodies, of a total of 3436 for whom the test was requested (5.5%). Toxocariasis was diagnosed in 28 cases (23 symptomatic and 5 asymptomatic) including 21 highly probable and 7 definitive. All but one patients were adults. Africa and Asia were the place of acquisition for 10 and 9 cases, respectively. Twelve patients (43%) were short-term travelers (< 1 month). Symptoms, when present, developed during travel or within 8 weeks maximum after return, and included abdominal complaints (11/23 symptomatic patients, 48%), respiratory symptoms and skin abnormalities (10 each, 43%) and fever (9, 39%), often in combination. Two patients were diagnosed with transverse myelitis. At presentation, the median blood eosinophil count was 1720/μL [range: 510–14160] in the 21 symptomatic cases without neurological complication and 2080/μL [range: 1100–2970] in the 5 asymptomatic individuals. All patients recovered either spontaneously or with an anti-helminthic treatment (mostly a 5-day course of albendazole), except both neurological cases who kept sequelae despite repeated treatments and prolonged corticotherapy. Toxocariasis has to be considered in travelers returning from a (sub)tropical stay with varying clinical manifestations or eosinophilia. Prognosis appears favorable with adequate treatment except in case of neurological involvement., Author Summary Toxocariasis is a zoonosis of worldwide distribution caused by dog (Toxocara canis) or cat (T. catis) roundworm that can be fully asymptomatic or may cause significant disease such as a the systemic syndrome called visceral larva migrans as well as neurological or eye manifestations. Toxocariasis prevails in tropical areas, but information about this disease in travelers and migrants is scarce. In this study, we describe in detail a case series of 28 international travelers, mostly adults, diagnosed with toxocariasis from 2000 to 2013 at the reference travel clinic of the Institute of Tropical Medicine of Antwerp, Belgium. We found this infection in all types of travelers returning from any part of the world. Clinical symptoms, when present, varied widely and an increase of the blood eosinophil count was almost always present. Morbidity was substantial and 2 patients had severe neurological complications. Diagnosis was difficult in travelers because the illness often resembled other tropical infections. Recovery was, however, complete, either spontaneously or with anti-parasitic drugs, except in both cases with neurological involvement. Toxocariasis is one of the numerous parasitic infections to consider in travelers returning from the tropics with any type of symptoms or with an increased blood eosinophil count.