Consensus definitions in imported human schistosomiasis: a GeoSentinel and TropNet Delphi study.

Terminology in schistosomiasis is not harmonised, generating misunderstanding in data interpretation and clinical descriptions. This study aimed to achieve consensus on definitions of clinical aspects of schistosomiasis in migrants and returning travellers. We applied the Delphi method. Experts from institutions affiliated with GeoSentinel and TropNet, identified through clinical and scientific criteria, were invited to participate. Five external reviewers revised and pilot-tested the statements. Statements focusing on the definitions of acute or chronic; possible, probable, or confirmed; active; and complicated schistosomiasis were managed through REDCap and replies managed in a blinded manner. Round 1 mapped the definitions used by experts; subsequent rounds were done to reach consensus, or quantify disagreement, on the proposed statements. Data were analysed with percentages, medians, and IQRs of a 5-point Likert scale. The study was terminated on the basis of consensus or stability-related and time-related criteria. 28 clinicians and scientists met the criteria for experts. 25 (89%) of 28 experts replied to Round 1, 18 (64%) of 28 to Round 2, 19 (68%) of 28 to Round 3, and 21 (75%) of 28 to at least two rounds. High-level consensus (79-100% agreement and IQRs ≤1) was reached for all definitions. Consensus definitions will foster harmonised scientific and clinical communication and support future research and development of management guidelines for schistosomiasis.

Tecovirimat for the treatment of severe Mpox in Germany.

BACKGROUND: In May 2022, a multi-national mpox outbreak was reported in several non-endemic countries. The only licensed treatment for mpox in the European Union is the orally available small molecule tecovirimat, which in Orthopox viruses inhibits the function of a major envelope protein required for the production of extracellular virus. METHODS: We identified presumably all patients with mpox that were treated with tecovirimat in Germany between the onset of the outbreak in May 2022 and March 2023 and obtained demographic and clinical characteristics by standardized case report forms. RESULTS: A total of twelve patients with mpox were treated with tecovirimat in Germany in the study period. All but one patient identified as men who have sex with men (MSM) who were most likely infected with mpox virus (MPXV) through sexual contact. Eight of them were people living with HIV (PLWH), one of whom was newly diagnosed with HIV at the time of mpox, and four had CD4+ counts below 200/µl. Criteria for treatment with tecovirimat included severe immunosuppression, severe generalized and/or protracted symptoms, a high or increasing number of lesions, and the type and location of lesions (e.g., facial or oral soft tissue involvement, imminent epiglottitis, or tonsillar swelling). Patients were treated with tecovirimat for between six and 28 days. Therapy was generally well-tolerated, and all patients showed clinical resolution. CONCLUSIONS: In this cohort of twelve patients with severe mpox, treatment with tecovirimat was well tolerated and all individuals showed clinical improvement.

Clinical Characteristics and Outcomes Among Travelers With Severe Dengue : A GeoSentinel Analysis.

BACKGROUND: Dengue virus is a flavivirus transmitted by Aedes mosquitoes and is an important cause of illness worldwide. Data on the severity of travel-associated dengue illness are limited. OBJECTIVE: To describe the epidemiology, clinical characteristics, and outcomes among international travelers with severe dengue or dengue with warning signs as defined by the 2009 World Health Organization classification (that is, complicated dengue). DESIGN: Retrospective chart review and analysis of travelers with complicated dengue reported to GeoSentinel from January 2007 through July 2022. SETTING: 20 of 71 international GeoSentinel sites. PATIENTS: Returning travelers with complicated dengue. MEASUREMENTS: Routinely collected surveillance data plus chart review with abstraction of clinical information using predefined grading criteria to characterize the manifestations of complicated dengue. RESULTS: Of 5958 patients with dengue, 95 (2%) had complicated dengue. Eighty-six (91%) patients had a supplemental questionnaire completed. Eighty-five of 86 (99%) patients had warning signs, and 27 (31%) were classified as severe. Median age was 34 years (range, 8 to 91 years); 48 (56%) were female. Patients acquired dengue most frequently in the Caribbean (n = 27 [31%]) and Southeast Asia (n = 21 [24%]). Frequent reasons for travel were tourism (46%) and visiting friends and relatives (32%). Twenty-one of 84 (25%) patients had comorbidities. Seventy-eight (91%) patients were hospitalized. One patient died of nondengue-related illnesses. Common laboratory findings and signs were thrombocytopenia (78%), elevated aminotransferase (62%), bleeding (52%), and plasma leakage (20%). Among severe cases, ophthalmologic pathology (n = 3), severe liver disease (n = 3), myocarditis (n = 2), and neurologic symptoms (n = 2) were reported. Of 44 patients with serologic data, 32 confirmed cases were classified as primary dengue (IgM+/IgG-) and 12 as secondary (IgM-/IgG+) dengue. LIMITATIONS: Data for some variables could not be retrieved by chart review for some patients. The generalizability of our observations may be limited. CONCLUSION: Complicated dengue is relatively rare in travelers. Clinicians should monitor patients with dengue closely for warning signs that may indicate progression to severe disease. Risk factors for developing complications of dengue in travelers need further prospective study. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention, International Society of Travel Medicine, Public Health Agency of Canada, and GeoSentinel Foundation.

Frequency of IRF5+ dendritic cells is associated with the TLR7-induced inflammatory cytokine response in SARS-CoV-2 infection.

The SARS-CoV-2 infection leads to enhanced inflammation driven by innate immune responses. Upon TLR7 stimulation, dendritic cells (DC) mediate the production of inflammatory cytokines, and in particular of type I interferons (IFN). Especially in DCs, IRF5 is a key transcription factor that regulates pathogen-induced immune responses via activation of the MyD88-dependent TLR signaling pathway. In the current study, the frequencies of IRF5+ DCs and the association with innate cytokine responses in SARS-CoV-2 infected individuals with different disease courses were investigated. In addition to a decreased number of mDC and pDC subsets, we could show reduced relative IRF5+ frequencies in mDCs of SARS-CoV-2 infected individuals compared with healthy donors. Functionally, mDCs of COVID-19 patients produced lower levels of IL-6 in response to in vitro TLR7 stimulation. IRF5+ mDCs more frequently produced IL-6 and TNF-α compared to their IRF5- counterparts upon TLR7 ligation. The correlation of IRF5+ mDCs with the frequencies of IL-6 and TNF-α producing mDCs were indicators for a role of IRF5 in the regulation of cytokine responses in mDCs. In conclusion, our data provide further insights into the underlying mechanisms of TLR7-dependent immune dysfunction and identify IRF5 as a potential immunomodulatory target in SARS-CoV-2 infection.

Sotrovimab in Hospitalized Patients with SARS-CoV-2 Omicron Variant Infection: a Propensity Score-Matched Retrospective Cohort Study.

In vitro data suggest the monoclonal antibody sotrovimab may have lost inhibitory capability against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant. We aimed to provide real-life data on clinical outcomes in hospitalized patients. We retrospectively analyzed patients who were treated at the University Medical Center Hamburg-Eppendorf, Germany, between December 2021 and June 2022. Out of all 1,254 patients, 185 were treated with sotrovimab: 147 patients received sotrovimab monotherapy, and 38 received combination treatment with sotrovimab and remdesivir. We compared in-hospital mortality for the different treatment regimens for patients treated on regular wards and the intensive care unit separately and performed propensity score matching by age, sex, comorbidities, immunosuppression, and additional dexamethasone treatment to select patients who did not receive antiviral treatment for comparison. No difference in in-hospital mortality was observed between any of the treatment groups and the respective control groups. These findings underline that sotrovimab adds no clinical benefit for hospitalized patients with SARS-CoV-2 Omicron variant infections. IMPORTANCE This study shows that among hospitalized patients with SARS-CoV-2 Omicron variant infection at risk of disease progression, treatment with sotrovimab alone or in combination with remdesivir did not decrease in-hospital mortality. These real-world clinical findings in combination with previous in vitro data about lacking neutralizing activity of sotrovimab against SARS-CoV-2 Omicron variant do not support sotrovimab as a treatment option in these patients.

Screening for Monkeypox Infection in Asymptomatic High-Risk-Behaviour Men Having Sex with Men (MSM).

Background: Since the outbreak of monkeypox in formerly non-endemic countries, we have included a screening for monkeypox in our sexually transmitted diseases (STD) routine in patients with high-risk behavior, as it is mainly transmitted through close skin to mucous membrane contact with infected individuals. Methods: Between 16 June 2022 and 14 July 2022, we screened 53 MSM with high-risk behavior for monkeypox acquisition in an observational prospective cohort trial. We complemented the throat and anal swabs for chlamydia and gonococci with monkeypox using polymerase chain reaction (PCR). In addition, all patients participated in a questionnaire survey about their risk behavior and previous STD in their medical history. Results: None of the 53 participants had tested positive for the monkeypox virus. One patient was diagnosed with syphilis and one with an oral and anorectal chlamydia infection. Conclusions: STD screening in high-risk populations is a valuable tool to detect asymptomatic patients for chlamydia, gonococci, HIV, hepatitis B and C and syphilis. Based on our small cohort, monkeypox screening in asymptomatic MSM patients in areas of low prevalence does not seem to be an appropriate approach to deal with the ongoing outbreak. Therefore, we recommend to focus more on vaccinations, targeted nonstigmatizing information and behavior recommendation for risk populations, and to engage further investigations.

Clinical characteristics and comparison of longitudinal qPCR results from different specimen types in a cohort of ambulatory and hospitalized patients infected with monkeypox virus.

BACKGROUND: The ongoing monkeypox virus outbreak includes at least 7553 confirmed cases in previously non-endemic countries worldwide as of July 2022. Clinical presentation has been reported as highly variable, sometimes lacking classically described systemic symptoms, and only small numbers of cutaneous lesions in most patients. The aim of this study was to compare clinical data with longitudinal qPCR results from lesion swabs, oropharyngeal swabs and blood in a well characterized patient cohort. METHODS: 16 male patients (5 hospitalized, 11 outpatients) were included in the study cohort and serial testing for monkeypox virus-DNA carried out in various materials throughout the course of disease. Laboratory analysis included quantitative PCR, next-generation sequencing, immunofluorescence tests and virus isolation in cell culture. RESULTS: All patients were male, between age 20 and 60, and self-identified as men having sex with men. Two had a known HIV infection, coinciding with an increased number of lesions and viral DNA detectable in blood. In initial- and serial testing, lesion swabs yielded viral DNA-loads at, or above 106 cp/ml and only declined during the third week. Oropharyngeal swabs featured lower viral loads and returned repeatedly negative in some cases. Viral culture was successful only from lesion swabs but not from oropharyngeal swabs or plasma. DISCUSSION: The data presented underscore the reliability of lesion swabs for monkeypox virus-detection, even in later stages of the disease. Oropharyngeal swabs and blood samples alone carry the risk of false negative results, but may hold value in pre-/asymptomatic cases or viral load monitoring, respectively.

Evidence of surface contamination in hospital rooms occupied by patients infected with monkeypox, Germany, June 2022.

The extent of monkeypox virus environmental contamination of surfaces is unclear. We examined surfaces in rooms occupied by two monkeypox patients on their fourth hospitalisation day. Contamination with up to 105 viral copies/cm2 on inanimate surfaces was estimated by PCR and the virus was successfully isolated from surfaces with more than 106 copies. These data highlight the importance of strict adherence of hospital staff to recommended protective measures. If appropriate, pre-exposure or early post-exposure vaccination should be considered for individuals at risk.

[Parasites - important endemic and imported pathogens]. / Parasiten ­ wichtige endemische und importierte Erreger.

Parasites are a diverse group of pathogens; they range from unicellular protozoa (e. g. Giardia lamblia) to tapeworms that can grow several meters long. Parasites have adapted to humans over millions of years and cause a wide, colorful variety of diseases. Due to increasing travel and climate change, previously rare pathogens occur more frequently in patients in Germany.Often the history, clinical findings and imaging are suggestive of the causative parasite and the suspected diagnosis only needs to be confirmed with pathogen detection in order to initiate targeted therapy. Nonetheless, the diagnosis is often delayed due to lack of experience of attending clinicians with parasitic infections.In this review article we give an overview of the epidemiology, transmission, diagnosis and treatment of some of the most common parasitic infections that are endemic, or regularly imported to Germany. We also discuss current and future challenges in the diagnosis, treatment and control of these pathogens.

[Visceral leishmaniasis mimicking Felty's syndrome in rheumatoid arthritis treated with methotrexate and etanercept]. / Imitation eines Felty-Syndroms durch eine viszerale Leishmaniasis bei rheumatoider Arthritis unter Therapie mit Methotrexat und Etanercept.

Visceral leishmaniasis (VL) is a chronic parasitic disease caused by pathogens of the genus Leishmania, which can mimic numerous diseases. The leading symptoms of VL (splenomegaly, pancytopenia, fever) can be misinterpreted, especially if autoantibodies are detected, and lead to the misdiagnosis of an underlying rheumatic disease (e.g. systemic lupus erythematosus, Felty's syndrome). Proinflammatory cytokines such as tumour necrosis factor alpha (TNF-α) play an important role in infection control. In this context, there are increasing reports of VL as an opportunistic infection during treatment with anti-TNF­α agents. A case of VL mimicking Felty's syndrome in a patient with rheumatoid arthritis treated with methotrexate and etanercept is presented.

Attitudes, practices, and obstacles towards influenza vaccination for international travelers among travel health advisors in Germany: A questionnaire-based survey.

BACKGROUND: Influenza is the most frequent vaccine-preventable infection in travelers, and both national and international guidelines recommend considering seasonal influenza vaccination (SIV) not only for those with risk factors for complications but for all travelers. However, vaccination coverage may be hampered by a lack of awareness among travelers and health care providers and limited vaccine availability outside the local influenza season. METHODS: We identified travel health advisors in databases of German medical professional societies and invited them to complete an online questionnaire between April and May 2021. RESULTS: Among 1085 travel health advisors contacted by email, 253 (23.3%) completed the online questionnaire. Most of them recommend SIV for travelers older than 60 years or those with comorbidities regardless of the travel destination or the influenza season in Germany. However, only very few respondents stated that they had regular access to SIV in June (n = 16, 6.5%), July (n = 10, 4.0%), and August (n = 17, 6.9%), respectively. While most participants (n = 197, 79.4%) stated that they would vaccinate more travelers if they had SIV regularly available outside the German influenza season, only eleven respondents (4.4%) have previously ordered SIV produced for the southern hemisphere, which was attributed mainly to logistic barriers. CONCLUSIONS: Travel health advisors in Germany recommend SIV for a considerable proportion of travelers. While most of them see a necessity to vaccinate throughout the year, availability of SIV outside the German season is very limited. Current organizational barriers must be overcome to increase vaccination coverage among international travelers.

Patient Characteristics and Clinical Course of COVID-19 Patients Treated at a German Tertiary Center during the First and Second Waves in the Year 2020.

In this study, we directly compared coronavirus disease 2019 (COVID-19) patients hospitalized during the first (27 February-28 July 2020) and second (29 July-31 December 2020) wave of the pandemic at a large tertiary center in northern Germany. Patients who presented during the first (n = 174) and second (n = 331) wave did not differ in age (median [IQR], 59 years [46, 71] vs. 58 years [42, 73]; p = 0.82) or age-adjusted Charlson Comorbidity Index (median [IQR], 2 [1, 4] vs. 2 [0, 4]; p = 0.50). During the second wave, a higher proportion of patients were treated as outpatients (11% [n = 20] vs. 20% [n = 67]), fewer patients were admitted to the intensive care unit (43% [n = 75] vs. 29% [n = 96]), and duration of hospitalization was significantly shorter (median days [IQR], 14 [8, 34] vs. 11 [5, 19]; p < 0.001). However, in-hospital mortality was high throughout the pandemic and did not differ between the two periods (16% [n = 27] vs. 16% [n = 54]; p = 0.89). While novel treatment strategies and increased knowledge about the clinical management of COVID-19 may have resulted in a less severe disease course in some patients, in-hospital mortality remained unaltered at a high level. These findings highlight the unabated need for efforts to hamper severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) transmission, to increase vaccination coverage, and to develop novel treatment strategies to prevent mortality and decrease morbidity.

Clinical Presentation and Disease Course of 37 Consecutive Cases of Progressive Multifocal Leukoencephalopathy (PML) at a German Tertiary-Care Hospital: A Retrospective Observational Study.

Background: Progressive multifocal leukoencephalopathy (PML) caused by JCV is a rare but frequently fatal disease of the central nervous system, usually affecting immunocompromised individuals. Our study aims to expand the data on patient characteristics, diagnosis, clinical course, possible PML-directed treatment, and outcome of patients with PML at a German tertiary-care hospital. Methods:In this single-center observational cohort study, 37 consecutive patients with a confirmed diagnosis of PML seen at the University Medical Center Hamburg-Eppendorf from 2013 until 2019 were retrospectively analyzed by chart review with a special focus on demographics, risk factors, and clinical aspects as well as PML-directed treatment and survival. Results:We identified 37 patients with definite, probable, and possible PML diagnosis. 36 patients (97%) had underlying immunosuppressive disorders such as HIV/AIDS (n = 17; 46%), previous treatment with monoclonal antibodies (n = 6; 16%), hematological or oncological malignancies (n = 6; 16%), sarcoidosis (n = 5; 14%), solid organ transplantation (n = 1; 3%), and diagnosis of mixed connective tissue disease (n = 1; 3%). In only one patient no evident immunocompromised condition was detected (n = 1; 3%). Treatment attempts to improve the outcome of PML were reported in 13 patients (n = 13; 35%). Twenty seven percent of patients were lost to follow-up (n = 10). Twenty four-month survival rate after diagnosis of PML was 56% (n = 15). Conclusion: This interdisciplinary retrospective study describes epidemiology, risk factors, clinical course, and treatment trials in patients with PML at a German tertiary-care hospital. Acquired immunosuppression due to HIV-1 constituted the leading cause of PML in this monocenter cohort.

Travel-related infections presenting in Europe: A 20-year analysis of EuroTravNet surveillance data.

BACKGROUND: Disease epidemiology of (re-)emerging infectious diseases is changing rapidly, rendering surveillance of travel-associated illness important. METHODS: We evaluated travel-related illness encountered at EuroTravNet clinics, the European surveillance sub-network of GeoSentinel, between March 1, 1998 and March 31, 2018. FINDINGS: 103,739 ill travellers were evaluated, including 11,239 (10.8%) migrants, 89,620 (86.4%) patients seen post-travel, and 2,880 (2.8%) during and after travel. Despite increasing numbers of patient encounters over 20 years, the regions of exposure by year of clinic visits have remained stable. In 5-year increments, greater proportions of patients were migrants or visiting friends and relatives (VFR); business travel-associated illness remained stable; tourism-related illness decreased. Falciparum malaria was amongst the most-frequently diagnosed illnesses with 5,254 cases (5.1% of all patients) and the most-frequent cause of death (risk ratio versus all other illnesses 2.5:1). Animal exposures requiring rabies post-exposure prophylaxis increased from 0.7% (1998-2002) to 3.6% (2013-2018). The proportion of patients with seasonal influenza increased from zero in 1998-2002 to 0.9% in 2013-2018. There were 44 cases of viral haemorrhagic fever, most during the past five years. Arboviral infection numbers increased significantly as did the range of presenting arboviral diseases, dengue and chikungunya diagnoses increased by 2.6% and 1%, respectively. INTERPRETATION: Travel medicine must adapt to serve the changing profile of travellers, with an increase in migrants and persons visiting relatives and friends and the strong emergence of vector-borne diseases, with potential for further local transmission in Europe. FUNDING: This project was supported by a cooperative agreement (U50CK00189) between the Centers for Disease Control and Prevention to the International Society of Travel Medicine (ISTM) and funding from the ISTM and the Public Health Agency of Canada.

Sustained Response After Remdesivir and Convalescent Plasma Therapy in a B-Cell-Depleted Patient With Protracted Coronavirus Disease 2019 (COVID-19).

We provide detailed clinical, virological, and immunological data of a B-cell-depleted patient treated with obinutuzumab for follicular lymphoma with protracted coronavirus disease 2019 (COVID-19) and viremia. A sustained response was achieved after 2 courses of remdesivir and subsequent convalescent plasma therapy. Immunocompromised patients might require combined and prolonged antiviral treatment regimens.