Treatment outcome of imported cutaneous leishmaniasis among travelers and migrants infected with Leishmania major and Leishmania tropica: a retrospective study in European centers 2013 to 2019.

OBJECTIVES: Cutaneous leishmaniasis (CL) in Asia, Northern, and Sub-Saharan Africa is mainly caused by Leishmania major and Leishmania tropica. We describe and evaluate the treatment outcome of CL among travelers and migrants in Europe. METHODS: We conducted a retrospective study of parasitological confirmed CL cases caused by L. major and L. tropica during 2013-2019 in Europe. Data were collected from medical records and databases within the LeishMan network. RESULTS: Of 206 included cases of CL, 75 were identified as L. major and 131 as L. tropica. Of patients with L. tropica infection, 80% were migrants, whereas 53% of patients with L. major infection had been visiting friends and relatives. Among patients with L. tropica, 48% were younger than 15 years. Pentavalent antimony cured 73% (L. major) and 78% (L. tropica) of patients. The cure rate for intralesional administration was 86% and 67% for systemic, on L. tropica. Liposomal amphotericin B had a cure rate of 44-63%. CONCLUSION: L. major infections were mostly found in individuals visiting friends and relatives, whereas L. tropica were mainly identified in migrants. No patients with L. major relapsed. Pentavalent antimony, liposomal amphotericin B, and cryotherapy had cure rates in accordance with previous studies.

Mental distress and health-related quality of life in gambiense human African trypanosomiasis: a case-control study in the Democratic Republic of Congo.

BACKGROUND: The extent to which neuropsychiatric sequelae affects the mental health status and quality of life of former gambiense human African trypanosomiasis (gHAT) patients is not known. METHODS: We assessed anxiety, depression and health-related quality of life (HRQoL) in 93 patients and their age- and sex-matched controls using the Hospital Anxiety and Depression Scale, Becks Depression Inventory and the 36-item Short Form Health Survey in structured interviews in the Vanga health zone in the Democratic Republic of Congo. Data were analysed using Stata version 14.0. The degree of association between neurologic sequelae and mental distress was evaluated using the Student's t-test and χ2 or Fisher's exact tests, where appropriate, with a p-value <0.05 deemed to be statistically significant. RESULTS: We found that neurological sequelae persisted in former patients at least 15 y after treatment. Depression (p<0.001) and anxiety (p=0.001) were significantly higher in former patients with neurologic sequelae. The mean quality-of-life (QoL) scores were significantly lower for patients than in controls in the physical, emotional and mental health domains. CONCLUSIONS: The presence of neurological sequelae leads to mental distress and a diminished QoL in former gHAT patients. Minimising neurologic sequelae and incorporating psychosocial interventions should be essential management goals for gHAT.

Surveillance of leishmaniasis cases from 15 European centres, 2014 to 2019: a retrospective analysis.

BackgroundSurveillance of human leishmaniasis in Europe is mostly limited to country-specific information from autochthonous infections in the southern part. As at the end of 2021, no integrated analysis has been performed for cases seen across centres in different European countries.AimTo provide a broad perspective on autochthonous and imported leishmaniasis cases in endemic and non-endemic countries in Europe.MethodsWe retrospectively collected records from cutaneous, mucosal and visceral leishmaniasis cases diagnosed in 15 centres between 2014 and 2019. Centres were located in 11 countries: Belgium, France, Germany, Italy, the Netherlands, Norway, Portugal, Spain, Sweden, Switzerland and the United Kingdom. Data on country of infection, reason for travelling, infecting species, age and sex were analysed.ResultsWe obtained diagnostic files from 1,142 cases, of which 76%, 21% and 3% had cutaneous, visceral, and mucosal disease, respectively. Of these, 68% were men, and 32% women, with the median age of 37 years (range: 0-90) at diagnosis. Visceral leishmaniasis was mainly acquired in Europe (88%; 167/190), while cutaneous leishmaniasis was primarily imported from outside Europe (77%; 575/749). Sixty-two percent of cutaneous leishmaniasis cases from outside Europe were from the Old World, and 38% from the New World. Geographic species distribution largely confirmed known epidemiology, with notable exceptions.ConclusionsOur study confirms previous reports regarding geographic origin, species, and traveller subgroups importing leishmaniasis into Europe. We demonstrate the importance of pooling species typing data from many centres, even from areas where the aetiology is presumably known, to monitor changing epidemiology.

Clinical diversity and treatment results in Tegumentary Leishmaniasis: A European clinical report in 459 patients.

BACKGROUND: Cutaneous leishmaniasis (CL) is frequent in travellers and can involve oro-nasal mucosae. Clinical presentation impacts therapeutic management. METHODOLOGY: Demographic and clinical data from 459 travellers infected in 47 different countries were collected by members of the European LeishMan consortium. The infecting Leishmania species was identified in 198 patients. PRINCIPAL FINDINGS: Compared to Old World CL, New World CL was more frequently ulcerative (75% vs 47%), larger (3 vs 2cm), less frequently facial (17% vs 38%) and less frequently associated with mucosal involvement (2.7% vs 5.3%). Patients with mucosal lesions were older (58 vs 30 years) and more frequently immunocompromised (37% vs 3.5%) compared to patients with only skin lesions. Young adults infected in Latin America with L. braziliensis or L. guyanensis complex typically had an ulcer of the lower limbs with mucosal involvement in 5.8% of cases. Typically, infections with L. major and L. tropica acquired in Africa or the Middle East were not associated with mucosal lesions, while infections with L. infantum, acquired in Southern Europe resulted in slowly evolving facial lesions with mucosal involvement in 22% of cases. Local or systemic treatments were used in patients with different clinical presentations but resulted in similarly high cure rates (89% vs 86%). CONCLUSION/SIGNIFICANCE: CL acquired in L. infantum-endemic European and Mediterranean areas displays unexpected high rates of mucosal involvement comparable to those of CL acquired in Latin America, especially in immunocompromised patients. When used as per recommendations, local therapy is associated with high cure rates.

Long-term sequelae of congenital gambiense human African trypanosomiasis.

BACKGROUND: The clinical presentation of gambiense human African trypanosomias (gHAT) is generally considered to be the same among children and adults. In general, when describing the clinical presentation of children with gHAT, no differentiation is made between congenital gHAT and gHAT acquired later. There is a lack of knowledge regarding the signs and symptoms attributable to congenital gHAT and its long-term sequelae. METHODS: Following an evaluation of the hospital register for gHAT, the authors observed that six children born to mothers with gHAT during their pregnancies still had sequelae of the infection. The six mothers were interviewed about their respective pregnancies and the developmental history of the children borne to the infected mothers. Furthermore, the children then underwent a complete physical examination with a focus on neuropsychiatric signs and symptoms. RESULTS: Five of the six patients are still seriously disabled. Behavioral changes are present in four patients, tremor, speech impairment, involuntary movements and pathologic the Barrés test and Mingazzini test in three patients and convulsions, pyramidal signs and decreased muscle tonus in two patients. Two patients cannot work and one has a sphincter disorder. CONCLUSIONS: Our study suggests that congenital gHAT may lead to long-lasting sequelae in babies born to mothers treated after delivery. The risk of embryo toxicity of treatment of mothers with gHAT must be balanced against the risk of congenital gHAT with long-term sequelae.

Tracking stress via the computer mouse? Promises and challenges of a potential behavioral stress marker.

Computer mouse tracking offers a simple and cost-efficient way to gather continuous behavioral data and has mostly been utilized in psychological science to study cognitive processes. The present study extends the potential applicability of computer mouse tracking and investigates the feasibility of using computer mouse tracking for stress measurement. Drawing on first empirical results and theoretical considerations, we hypothesized that stress affects sensorimotor processes involved in mouse usage. To explore the relationship between stress and computer mouse usage, we conducted a between-participant field experiment in which N = 994 participants worked on four mouse tasks in a high-stress or low-stress condition. In the manipulation check, participants reported different stress levels between the two conditions. However, frequentist and machine learning data analysis approaches did not reveal a clear and systematic relationship between mouse usage and stress. These findings challenge the feasibility of using straightforward computer mouse tracking for generalized stress measurement.

Development and Pilot Test of a Virtual Reality Respiratory Biofeedback Approach.

Breathing exercises with biofeedback have benefits over breathing exercises without biofeedback. However, the traditional measurement of respiratory signals that is required as part of feeding back the breath incurs high cost and effort. We propose a novel virtual reality (VR) based approach to respiratory biofeedback that utilizes the positionally tracked hand controllers integrated into modern VR systems to capture and feedback the respiration-induced abdominal movements. In a randomized controlled laboratory study, we investigated the feasibility and efficacy of the developed biofeedback algorithm. In total, 72 participants performed a short breathing exercise in VR with or without respiratory biofeedback. The feedback integration resulted in a satisfactory user experience, a heightened breath awareness, a greater focus on slow diaphragmatic breathing and an increased respiratory sinus arrhythmia. This evidences that the novel biofeedback approach is low-cost, unobtrusive, usable and effective in increasing breath awareness and promoting slow diaphragmatic breathing in the context of VR-based breathing exercises. Future studies need to investigate the broader applicability and long-term effects.

Gambiense Human African Trypanosomiasis Sequelae after Treatment: A Follow-Up Study 12 Years after Treatment.

The clinical presentation of Human African Trypanosomiasis (HAT) due to Trypanosoma brucei gambiense is well known, but knowledge on long-term sequelae is limited. In the frame of studies conducted between 2004 and 2005 in the Democratic Republic of the Congo (DRC), the prevalence of HAT related signs and symptoms were evaluated before the start of treatment and at the end of treatment. To explore possible long-term sequelae, the same clinical parameters were assessed in 2017 in 51 first stage and 18 second stage HAT patients. Signs and symptoms 12-13 years after treatment were compared to before and immediately after treatment and to controls matched for sex and age (±5 years). In first stage HAT patients, the prevalence of all signs and symptoms decreased compared to before treatment but were still higher after 12-13 years than immediately at the end of treatment and in the control group. In second stage HAT patients, all HAT-specific findings had continuously decreased to the point where they were in the range of the healthy control group. In a selection of oligosymptomatic first stage HAT patients, no trypanosomes were detected in the blood by microscopic examination or PCR. An oligosymptomatic presentation of HAT due to the persistence of parasites in compartments, where first stage HAT medications do not penetrate, could not be ruled out.

Sleeping hearts: 12 years after a follow up study on cardiac findings due to sleeping sickness.

Both American Trypanosomiasis (Chagas disease) and Human African Trypanosomiasis (HAT) are diseases caused by single-celled flagellate protozoan parasites. While cardiac complications such as conduction problems and heart failure are very common in Chagas disease there is little known about the long-term effects of Human African Trypanosomiasis (HAT) on cardiac sequelae in Sub-Saharan Africa, where heart failure has become an increasing problem and growing burden. In the context of clinical trials conducted between 2004 and 2005 in the Democratic Republic of the Congo (DRC), the prevalence of HAT related signs and symptoms and an ECG were evaluated prior to the initiation of treatment. The object of this follow-up study in 2017 was to assess the prevalence of cardiac sequelae in the same 51 first stage and 18  second stage HAT patients 12-13 years after their treatment by conducting a clinical examination and an ECG. A control group matched by age (± 5 years), sex and whenever possible form the same village was enrolled. There were no significant differences in the prevalence of cardiac symptoms and in ECG findings between patients and their controls at the time of the follow-up evaluation. Repolarization changes disappeared or improved in 24.7% of HAT patients and were even less frequent than in the control group. Peripheral low voltage was the only parameter that increased over time in HAT patients and in three patients, new conduction problems in the ECG (ventricular bigeminy, RBBB, and bifascicular block) could be found, although none of these findings was clinically significant. However, the appearance of these conduction problems might represent an early indication of a HAT related cardiomyopathy or ongoing subclinical infection. This hypothesis would be supported by the findings of an older study in which antibodies (IFAT) against trypanosomiasis in 27% of Cameroonian patients with dilated cardiomyopathy compared to 2% in normal controls had been observed.

Glycaemic control among patients with type 2 diabetes followed in a rural African primary care setting - A reality check in the Democratic Republic of Congo.

AIMS: The aim of this study was to assess diabetes control in adult patients with type II diabetes and to evaluate its association with socio-economic characteristics in rural the Democratic Republic Congo (DRC). METHODS: We recruited patients ≥18 years in care for type II diabetes in a hospital in rural DRC. Socio-economic status, medical history and diabetes control were assessed through a structured questionnaire, a physical examination and laboratory tests, such as fasting glucose, HbA1c, serum creatinine and urine analysis. Uni- and multivariate logistic regression was used to assess for patient factors associated with diabetes control. RESULTS: 319 diabetic patients (212 men, 107 women) were enrolled. The target threshold of HbA1c level at 7.0% or below was met by 17.8% (19/107) of female and 12.3% (26/212) of male patients. The fasting plasma glucose level was <7.0mmol/l in 28.9% (31/107) and 36.3% (77/212) of women and men, respectively. Among participants with a fasting glucose <7.0mmol/l only 32.4% (35/108) had an HbA1c at 7.0% or below. None of the assessed socio-economic or lifestyle factors were predictive of diabetes control. CONCLUSIONS: In this study among diabetic patients in care at a rural hospital in DRC, less than one out of five had an HbA1c ≤7.0%. Fasting plasma glucose at study visit had poor correlation with HbA1c, only a third of patients with a fasting glucose level <7mmol/l had an HbA1c ≤7.0%.

The Flipside of Eradicating a Disease; Human African Trypanosomiasis in a Woman in Rural Democratic Republic of Congo: A Case Report.

Human African Trypanosomiasis (HAT) is a neglected disease caused by the protozoan parasites Trypanosoma brucei and transmitted by tsetse flies that progresses in two phases. Symptoms in the first phase include fever, headaches, pruritus, lymphadenopathy, and in certain cases, hepato- and splenomegaly. Neurological disorders such as sleep disorder, aggressive behavior, logorrhea, psychotic reactions, and mood changes are signs of the second stage of the disease. Diagnosis follows complex algorithms, including serological testing and microscopy. Our case report illustrates the course of events of a 41-year old woman with sleep disorder, among other neurological symptoms, whose diagnosis was made seven months after the onset of symptoms. The patient had consulted two different hospitals in Kinshasa and was on the verge of being discharged from a third due to negative laboratory test results. This case report highlights the challenges that may arise when a disease is on the verge of eradication.

Danger of Herbal Tea: A Case of Acute Cholestatic Hepatitis Due to Artemisia annua Tea.

Background: Artemisia annua is a Chinese medicinal herb. Artemisinin-derivatives are recommended as part of a combination treatment for uncomplicated malaria. Herbal and dietary supplements (HDS) are increasingly used worldwide and HDS-induced liver injury is becoming a growing concern. Case Report: We present the first case of severe acute cholestatic hepatitis due to the intake of Artemisia annua tea as chemoprophylaxis for malaria in a patient returning from Ethiopia. The patients presented with jaundice, elevated transaminases, and parameters of cholestasis (total bilirubin 186.6 µmol/L, conjugated bilirubin 168.5 µmol/L). A liver biopsy showed a portal hepatitis with lymphocytic infiltration of the bile ducts and diffuse intra-canalicular and intra-cytoplasmic bilirubinostasis. The toxicologic analysis of the Artemisia tea revealed the ingredients arteannuin b, deoxyartemisin, campher, and scopoletin. There were no other identifiable etiologies of liver disease. The Roussel Uclaf Causality Assessment Method (RUCAM) score assessed a "probably" causal relationship. Sequencing of genes encoding for hepatic transporters for bile acid homeostasis (BSEP, MDR3, and FIC1) found no genetic variants typically associated with hereditary cholestasis syndromes. Normalization of bilirubin occurred 3 months after the onset of disease. Conclusion: The use of artemisinin-derivatives for malaria prevention is ineffective and potentially harmful and should thus be discouraged. Moreover, the case demonstrates our as yet inadequate understanding of the pathophysiology and susceptibility to HDS induced liver injury.

Heart Rate Variability Biofeedback Based on Slow-Paced Breathing With Immersive Virtual Reality Nature Scenery.

This study investigated the benefits of using a virtual nature environment to administer immersive heart rate variability biofeedback (HRV-BF) based on slow-paced breathing. We compared the virtual reality (VR)-based HRV-BF with a standard implementation in a randomized controlled experiment with 60 healthy employees. After a cognitive stress induction, the participants performed a single-session of HRV-BF before repeating the cognitive stressor task. VR-based versus standard HRV-BF was comparable in terms of biofeedback performance (cardiac coherence and cardiac vagal tone). However, the VR-based implementation buffered perceived stress in the subsequent stressor task, increased relaxation self-efficacy more, reduced mind wandering, helped participants focus on the present moment, and helped preserve attentional resources. Potential long-term effects and generalizability need to be assessed in future research.

A blind passenger: a rare case of documented seroconversion in an Angiostrongylus cantonensis induced eosinophilic meningitis in a traveler visiting friends and relatives.

BACKGROUND: Eosinophilic meningitis (EOM) is a rare condition that is caused by various communicable and non-communicable factors. The rat-lungworm Angiostrongylus cantonensis, which is associated with consumption of raw or undercooked paratenic or intermediate hosts, is the most common cause of parasitic eosinophilic meningitis worldwide. While the majority of A. cantonensis cases are reported from endemic regions, cases in travelers pose a challenge to clinicians in non-endemic countries. Here we report a rare case of eosinophilic meningitis caused by A. cantonensis in a Swiss traveler who was diagnosed after returning from Thailand. CASE PRESENTATION: A 33-year old woman with a travel history to rural north-eastern Thailand presented to an emergency department in Switzerland with severe headache and vomiting. Eosinophilic meningitis was confirmed as the cause of the symptoms; however, serologic investigations failed to confirm an A. cantonensis infection on the first evaluation. Nevertheless, empirical treatment with an anthelminthic and steroid regimen led to a rapid alleviation of symptoms. Repeated serology confirmed seroconversion 2 weeks after treatment initiation. DISCUSSION: Parasitic etiology must be considered in returning travelers who present with symptoms compatible with a central nervous system infection. A thorough medical history, including types of food consumed, is paramount and can often suggest differential diagnosis. Neuroangiostrongyliasis is rare and might be missed if serology does not cover possible seroconversion.

Increased risk of chikungunya infection in travellers to Thailand during ongoing outbreak in tourist areas: cases imported to Europe and the Middle East, early 2019.

We report nine travellers with confirmed chikungunya virus infection, returning from tourist areas of Thailand to Sweden, Switzerland, the United Kingdom, Romania, Israel and France, diagnosed in January and February 2019. These sentinel tourists support the intensification of chikungunya virus circulation in Thailand and highlight the potential for importation to areas at risk of local transmission.

Double trouble: visceral leishmaniasis in twins after traveling to Tuscany - a case report.

BACKGROUND: Leishmaniasis is endemic in many countries worldwide, with a prevalence of 12 million people infected, and an estimated annual incidence of 500 000 visceral leishmaniasis cases. In Europe visceral leishmaniasis is considered endemic mainly in the Mediterranean countries and cases in non-endemic European countries north of the Alps have primarily been reported in returning travellers. The incubation period is typically described between 6 weeks to 6 months. The cases presented highlight the occurrence of longer incubation periods and illustrate the individual variability for progression from infection to disease. CASE PRESENTATION: We report the cases of 18-months-old twin girls living at the German-Swiss border, who developed visceral leishmaniasis 7 and 15 months after travelling to Tuscany. They presented with fever of unknown origin and pancytopenia. Both had splenomegaly and in the first case haemophagocytic lymphohistiocytosis or leukaemia was initially included in the differential diagnosis. Diagnosis of visceral leishmaniasis was confirmed by presence of intracytoplasmic localised leishmania parasites on bone marrow aspirate and/or positive leishmania serology. Both girls responded well to treatment with liposomal amphotericin B. The mother and two older siblings remained uninfected, while the father was diagnosed to be an asymptomatic carrier. CONCLUSION: Visceral leishmaniasis is an important differential diagnosis for fever of unknown origin and pancytopenia in young children living in countries with endemic disease and highlights the importance of obtaining a detailed travel history. Hemophagocytic lymphohistiocytosis and acute leukaemia present with similar symptoms and consequently are important differential diagnoses. Factors determining progression from infection to disease are not fully understood but younger age seems to be an important risk factor. Screening of siblings from affected individuals therefore may be warranted.

Health-seeking behaviour and treatment delay in patients with pulmonary tuberculosis in Switzerland: some slip through the net.

AIMS OF THE STUDY: To assess the health-seeking behaviour, the patient delay (onset of symptoms to first consultation) and the health system delay (first consultation to start of tuberculosis treatment) among patients with pulmonary tuberculosis (TB) diagnosed in Switzerland, and to assess the predictors of the various types of delay. METHODS: A survey among pulmonary TB patients was carried out in six cantons, covering 42% of all pulmonary adult TB cases notified in Switzerland. Data were collected by collaborators of the cantonal lung associations in charge of the follow-up of TB patients to investigate treatment seeking behaviour and to establish various delays and its predictors. Predictors of percentiles of delay (median and 75th percentile) were assessed using quantile regression. RESULTS: Among 252 eligible patients, 162 patients could be interviewed. Of these, 20.4% were born in Switzerland. Cough as a symptom was mentioned by 76% of the interviewed patients. Almost half of the 162 patients (46%) consulted first a general practitioner in an ambulatory care setting and 26% approached a hospital first. The median delay between symptom onset and first healthcare contact (patient delay) was 5.2 weeks, which is slightly longer than findings in other low prevalence countries. The interquartile range was 1.6 to 14.2 weeks. The median delay between first consultation in Switzerland and the start of TB treatment (health system delay) was 2 weeks. The interquartile range was 0.6 to 7.1 weeks. There were no clear predictors of patient delay. The main predictors of a longer median health system delay were the presence of fever (1.6 weeks, 95% confidence interval [CI] 0.5 to 2.6 weeks), having visited first a general practitioner or a paediatrician (1 week, 95% CI 0.1 to 1.9 weeks) and having seen three or four doctors before beginning TB treatment (2.9 weeks, 95% CI 0.7 to 5.1 weeks). A clear predictor of a shorter median health system delay was having undergone an X-ray at the first consultation (-2.9 weeks, 95% CI -4.8 to -0.9 weeks). Marginally significant for shorter delay was male sex (-2.6 weeks, 95% CI -5.4 to 0.1 weeks). CONCLUSIONS: No predictor of patient delay was found among the variables collected. For one fourth of the patients, the health system delay was longer than 7 weeks. General practitioners are commonly approached first, and they have to consider TB, also for patients not considered at high-risk for TB.

Liposomal amphotericin B treatment of Old World cutaneous and mucosal leishmaniasis: A literature review.

Old World cutaneous and mucosal leishmaniasis is a potentially serious disease. Systemic treatment approaches with pentavalent antimonials, liposomal amphotericin B, fluconazole and miltefosine are increasingly used despite the absence of supportive evidence - to date, no prospective clinical trials have been conducted for systemic treatment of these diseases. We performed a literature search to delineate the contemporary evidence for the use of liposomal amphotericin B, and found that although cure rates of 17/20 (85%) were achieved in immune competent patients with Old World cutaneous leishmaniasis and cure rates of 10/13 (77%) for Old World mucosal leishmaniasis due to L. infantum, the available data is highly limited with high variation in total treatment dosages. The presented findings reflect a lack of consensus on the optimal treatment dosage and on the schedule of application.