Publications by authors named "Stefan Schmiedel"

70 Publications

Psittacosis in a traveller.

J Travel Med 2021 Apr 14. Epub 2021 Apr 14.

German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Germany.

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http://dx.doi.org/10.1093/jtm/taab062DOI Listing
April 2021

Malaria in the Time of COVID-19: Do Not Miss the Real Cause of Illness.

Trop Med Infect Dis 2021 Mar 26;6(2). Epub 2021 Mar 26.

I. Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.

We report a case of malaria in a patient asymptomatically co-infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In the current ongoing coronavirus pandemic, co-infections with unrelated life-threatening febrile conditions may pose a particular challenge to clinicians. The current situation increases the risk for cognitive biases in medical management.
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http://dx.doi.org/10.3390/tropicalmed6020040DOI Listing
March 2021

Comparison of clinical characteristics and disease outcome of COVID-19 and seasonal influenza.

Sci Rep 2021 03 11;11(1):5803. Epub 2021 Mar 11.

I. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany.

While several studies have described the clinical course of patients with coronavirus disease 2019 (COVID-19), direct comparisons with patients with seasonal influenza are scarce. We compared 166 patients with COVID-19 diagnosed between February 27 and June 14, 2020, and 255 patients with seasonal influenza diagnosed during the 2017-18 season at the same hospital to describe common features and differences in clinical characteristics and course of disease. Patients with COVID-19 were younger (median age [IQR], 59 [45-71] vs 66 [52-77]; P < 0001) and had fewer comorbidities at baseline with a lower mean overall age-adjusted Charlson Comorbidity Index (mean [SD], 3.0 [2.6] vs 4.0 [2.7]; P < 0.001) than patients with seasonal influenza. COVID-19 patients had a longer duration of hospitalization (mean [SD], 25.9 days [26.6 days] vs 17.2 days [21.0 days]; P = 0.002), a more frequent need for oxygen therapy (101 [60.8%] vs 103 [40.4%]; P < 0.001) and invasive ventilation (52 [31.3%] vs 32 [12.5%]; P < 0.001) and were more frequently admitted to the intensive care unit (70 [42.2%] vs 51 [20.0%]; P < 0.001) than seasonal influenza patients. Among immunocompromised patients, those in the COVID-19 group had a higher hospital mortality compared to those in the seasonal influenza group (13 [33.3%] vs 8 [11.6%], P = 0.01). In conclusion, we show that COVID-19 patients were younger and had fewer baseline comorbidities than seasonal influenza patients but were at increased risk for severe illness. The high mortality observed in immunocompromised COVID-19 patients emphasizes the importance of protecting these patient groups from SARS-CoV-2 infection.
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http://dx.doi.org/10.1038/s41598-021-85081-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970952PMC
March 2021

Frequent neurocognitive deficits after recovery from mild COVID-19.

Brain Commun 2020 23;2(2):fcaa205. Epub 2020 Nov 23.

Institute of Neuroimmunology and Multiple Sclerosis, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany.

Neuropsychiatric complications associated with coronavirus disease 2019 caused by the Coronavirus SARS-CoV-2 (COVID-19) are increasingly appreciated. While most studies have focussed on severely affected individuals during acute infection, it remains unclear whether mild COVID-19 results in neurocognitive deficits in young patients. Here, we established a screening approach to detect cognitive deficiencies in post-COVID-19 patients. In this cross-sectional study, we recruited 18 mostly young patients 20-105 days (median, 85 days) after recovery from mild to moderate disease who visited our outpatient clinic for post-COVID-19 care. Notably, 14 (78%) patients reported sustained mild cognitive deficits and performed worse in the Modified Telephone Interview for Cognitive Status screening test for mild cognitive impairment compared to 10 age-matched healthy controls. While short-term memory, attention and concentration were particularly affected by COVID-19, screening results did not correlate with hospitalization, treatment, viremia or acute inflammation. Additionally, Modified Telephone Interview for Cognitive Status scores did not correlate with depressed mood or fatigue. In two severely affected patients, we excluded structural or other inflammatory causes by magnetic resonance imaging, serum and cerebrospinal fluid analyses. Together, our results demonstrate that sustained sub-clinical cognitive impairments might be a common complication after recovery from COVID-19 in young adults, regardless of clinical course that were unmasked by our diagnostic approach.
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http://dx.doi.org/10.1093/braincomms/fcaa205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717144PMC
November 2020

Seroprevalence of SARS-CoV-2 antibodies among hospital workers in a German tertiary care center: A sequential follow-up study.

Int J Hyg Environ Health 2021 03 30;232:113671. Epub 2020 Nov 30.

I. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany; German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Germany.

We sequentially assessed the presence of SARS-CoV-2 IgG antibodies in 1253 hospital workers including 1026 HCWs at the University Medical Center Hamburg-Eppendorf at three time points during the early phase of the epidemic. By the end of the study in July 2020, the overall seroprevalence was 1.8% (n = 22), indicating the overall effectiveness of infection control interventions in mitigating coronavirus disease 2019 (COVID-19) in hospital workers.
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http://dx.doi.org/10.1016/j.ijheh.2020.113671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832715PMC
March 2021

[New developments in outpatient parenteral antibiotic therapy (OPAT)].

Dtsch Med Wochenschr 2020 11 17;145(23):1688-1694. Epub 2020 Nov 17.

Long term intravenous antibiotic therapy is required for the treatment of selected infections. Outpatient parenteral antibiotic therapy (OPAT) allows patients who require intravenous treatment to be treated outside of the hospital with equal efficacy and safety as in-hospital; prolonged intravenous antibiotic therapy is required for the treatment of selected infections. OPAT is particularly beneficial for patients. Staying at home and resuming everyday life lead to significantly higher patient satisfaction and quality of life. Furthermore, the risk of nosocomial infections can be reduced, especially through multi-resistant pathogens. Outpatient prescriptions shorten the inpatient length of stay and costs can be saved. Additionally the reception capacities of hospitals will be increased.
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http://dx.doi.org/10.1055/a-1114-3990DOI Listing
November 2020

Sustained response after remdesivir and convalescent plasma therapy in a B-cell depleted patient with protracted COVID-19.

Clin Infect Dis 2020 Oct 26. Epub 2020 Oct 26.

Department of Medicine, Gastroenterology and Hepatology, with the Sections Infectious Diseases and Tropical Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

We provide detailed clinical, virological and immunological data of a B-cell depleted patient treated with obinutuzumab for follicular lymphoma with protracted COVID-19 and viremia. A sustained response was achieved after two courses of remdesivir and subsequent convalescent plasma therapy. Immunocompromised patients might require combined and prolonged antiviral treatment regimens.
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http://dx.doi.org/10.1093/cid/ciaa1637DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665388PMC
October 2020

Case Report: Acute Vision Loss in a Young Returning Traveler with Dengue Fever.

Am J Trop Med Hyg 2020 11;103(5):2026-2028

I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Ocular complications are rare in patients with dengue fever, but may cause permanent loss of vision. We present the case of a 29-year-old German woman who developed severe acute vision loss because of dengue-associated maculopathy after traveling to Vietnam and Cambodia. Initially, the optical coherence tomography showed detachment of the retinal pigment epithelium, a central shift in the retinal pigmentation and intraretinal cysts. The patient was hospitalized and treated with a short course of intravenous prednisolone. Vision improved, and the patient showed full recovery at 9 months after the onset. This case highlights the importance of awareness and adequate management for ocular involvement in patients with dengue fever, including travelers.
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http://dx.doi.org/10.4269/ajtmh.20-0562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646753PMC
November 2020

Defining the CD39/CD73 Axis in SARS-CoV-2 Infection: The CD73 Phenotype Identifies Polyfunctional Cytotoxic Lymphocytes.

Cells 2020 07 22;9(8). Epub 2020 Jul 22.

First Department of Medicine, Section Infectious Diseases, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.

The ectonucleotidases CD39 and CD73 regulate immune responses by balancing extracellular ATP and adenosine in inflammation and are likely to be involved in the pathophysiology of COVID-19. Here, we analyzed CD39 and CD73 on different lymphocyte populations in a small cohort of COVID-19 patients and in healthy individuals. We describe a significantly lower level of expression of CD73 on cytotoxic lymphocyte populations, including CD8 T, natural killer T (NKT), and natural killer (NK) cells, during COVID-19. Interestingly, the decrease of CD73 on CD8 T cells and NKT cells correlated with serum ferritin levels. Furthermore, we observed distinct functional differences between the CD73 and CD73 subsets of CD8 T cells and NKT cells with regard to cytokine/toxin secretion. In COVID-19 patients, the majority of the CD73CD8 T cells were capable of secreting granzyme B, perforin, tumor necrosis factor (TNF-α) or interferon-gamma (IFN-γ). To conclude, in this first study of CD39 and CD73 expression of lymphocytes in COVID-19, we show that CD8 T cells and NKT cells lacking CD73 possess a significantly higher cytotoxic effector functionality compared to their CD73 counterparts. Future studies should investigate differences of cellular CD39 and CD73 expression in patients at different disease stages and their potential as prognostic markers or targets for immunomodulatory therapies.
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http://dx.doi.org/10.3390/cells9081750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464076PMC
July 2020

Autopsy Findings and Venous Thromboembolism in Patients With COVID-19: A Prospective Cohort Study.

Ann Intern Med 2020 08 6;173(4):268-277. Epub 2020 May 6.

University Medical Center Hamburg-Eppendorf, Hamburg, Germany (D.W., J.S., M.L., S.S., C.E., A.H., F.H., H.M., I.K., A.S.S., C.B., G.D., A.N., D.F., S.P., S.S., C.B., M.M.A., M.A., K.P., S.K.).

Background: The new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused more than 210 000 deaths worldwide. However, little is known about the causes of death and the virus's pathologic features.

Objective: To validate and compare clinical findings with data from medical autopsy, virtual autopsy, and virologic tests.

Design: Prospective cohort study.

Setting: Autopsies performed at a single academic medical center, as mandated by the German federal state of Hamburg for patients dying with a polymerase chain reaction-confirmed diagnosis of COVID-19.

Patients: The first 12 consecutive COVID-19-positive deaths.

Measurements: Complete autopsy, including postmortem computed tomography and histopathologic and virologic analysis, was performed. Clinical data and medical course were evaluated.

Results: Median patient age was 73 years (range, 52 to 87 years), 75% of patients were male, and death occurred in the hospital ( = 10) or outpatient sector ( = 2). Coronary heart disease and asthma or chronic obstructive pulmonary disease were the most common comorbid conditions (50% and 25%, respectively). Autopsy revealed deep venous thrombosis in 7 of 12 patients (58%) in whom venous thromboembolism was not suspected before death; pulmonary embolism was the direct cause of death in 4 patients. Postmortem computed tomography revealed reticular infiltration of the lungs with severe bilateral, dense consolidation, whereas histomorphologically diffuse alveolar damage was seen in 8 patients. In all patients, SARS-CoV-2 RNA was detected in the lung at high concentrations; viremia in 6 of 10 and 5 of 12 patients demonstrated high viral RNA titers in the liver, kidney, or heart.

Limitation: Limited sample size.

Conclusion: The high incidence of thromboembolic events suggests an important role of COVID-19-induced coagulopathy. Further studies are needed to investigate the molecular mechanism and overall clinical incidence of COVID-19-related death, as well as possible therapeutic interventions to reduce it.

Primary Funding Source: University Medical Center Hamburg-Eppendorf.
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http://dx.doi.org/10.7326/M20-2003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7240772PMC
August 2020

Relapsing cutaneous leishmaniasis in a patient requiring TNF-α-inhibitor Infliximab for Takayasu-arteritis: Case report and review of the literature.

Travel Med Infect Dis 2020 Sep - Oct;37:101700. Epub 2020 Apr 25.

I. Department of Medicine, Division of Infectious Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Leishmaniasis is a protozoan parasitic infection that can manifest as visceral or cutaneous disease. Immunosuppression, mainly through TNF-α) inhibition, is a risk factor for complicated leishmaniasis that is becoming increasingly known. Here, we present a case of cutaneous leishmaniasis (CL) in a patient who suffers from advanced Takayasu-Arteritis, requiring TNF-α inhibition with infliximab. The primary CL lesions in this 47-year-old, female patient were caused by Leishmaniapanamensis and occurred after a touristic trip to Panama on her right foot. The lesions first resolved under treatment with liposomal amphotericin B. However, ten months later, the patient returned with relapsing lesions requiring further treatment. We discuss the challenges and risks of leishmaniasis in patients with TNF-α inhibition and the rare phenomenon of relapsing CL and the management hereof. We review published cases of CL associated with TNF-α inhibition. A growing body of evidence now suggests that especially CL (and visceral leishmaniasis (VL)) can be associated with TNF-α inhibition. The host response to leishmaniasis is of the Th1-type and TNF-α and interferon-gamma expression are crucial for disease control. Inversely, TNF-α inhibition can lead to complicated and relapsing progression of leishmanial infection. Therefore, we propose that CL and VL should be considered in at-risk patients receiving immunosuppressants.
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http://dx.doi.org/10.1016/j.tmaid.2020.101700DOI Listing
April 2020

Safety and immunogenicity of a modified vaccinia virus Ankara vector vaccine candidate for Middle East respiratory syndrome: an open-label, phase 1 trial.

Lancet Infect Dis 2020 07 21;20(7):827-838. Epub 2020 Apr 21.

First Department of Medicine, Division of Infectious Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Department for Clinical Immunology of Infectious Diseases, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany; German Center for Infection Research, Hamburg-Lubeck-Borstel-Riems, Germany. Electronic address:

Background: The Middle East respiratory syndrome coronavirus (MERS-CoV) causes a respiratory disease with a case fatality rate of up to 35%. Given its potential to cause a public health emergency and the absence of efficacious drugs or vaccines, MERS is one of the WHO priority diseases warranting urgent research and development of countermeasures. We aimed to assess safety and tolerability of an anti-MERS-CoV modified vaccinia virus Ankara (MVA)-based vaccine candidate that expresses the MERS-CoV spike glycoprotein, MVA-MERS-S, in healthy adults.

Methods: This open-label, phase 1 trial was done at the University Medical Center Hamburg-Eppendorf (Hamburg, Germany). Participants were healthy men and women aged 18-55 years with no clinically significant health problems as determined during medical history and physical examination, a body-mass index of 18·5-30·0 kg/m and weight of more than 50 kg at screening, and a negative pregnancy test for women. A key exclusion criterion was a previous MVA vaccination. For the prime immunisation, participants received doses of 1 × 10 plaque-forming unit (PFU; low-dose group) or 1 × 10 PFU (high-dose group) MVA-MERS-S intramuscularly. A second identical dose was administered intramuscularly as a booster immunisation 28 days after first injection. As a control group for immunogenicity analyses, blood samples were drawn at identical study timepoints from six healthy adults, who did not receive any injections. The primary objectives of the study were safety and tolerability of the two dosage levels and reactogenicity after administration. Immunogenicity was assessed as a secondary endpoint by ELISA and neutralisation tests. T-cell immunity was evaluated by interferon-γ-linked enzyme-linked immune absorbent spot assay. All participants who were vaccinated at least once were included in the safety analysis. Immunogenicity was analysed in the participants who completed 6 months of follow-up. This trial is registered with ClinicalTrials.gov, NCT03615911, and EudraCT, 2014-003195-23 FINDINGS: From Dec 17, 2017, to June 5, 2018, 26 participants (14 in the low-dose group and 12 in the high-dose group) were enrolled and received the first dose of the vaccine according to their group allocation. Of these, 23 participants (12 in the low-dose group and 11 in the high-dose group) received a second dose of MVA-MERS-S according to their group allocation after a 28-day interval and completed follow-up. Homologous prime-boost immunisation with MVA-MERS-S revealed a benign safety profile with only transient mild-to-moderate reactogenicity. Participants had no severe or serious adverse events. 67 vaccine-related adverse events were reported in ten (71%) of 14 participants in the low-dose group, and 111 were reported in ten (83%) of 12 participants in the high-dose group. Solicited local reactions were the most common adverse events: pain was observed in 17 (65%; seven in the low-dose group vs ten in the high-dose group) participants, swelling in ten (38%; two vs eight) participants, and induration in ten (38%; one vs nine) participants. Headaches (observed in seven participants in the low-dose group vs nine in the high-dose group) and fatigue or malaise (ten vs seven participants) were the most common solicited systemic adverse events. All adverse events resolved swiftly (within 1-3 days) and without sequelae. Following booster immunisation, nine (75%) of 12 participants in the low-dose group and 11 (100%) participants in the high-dose group showed seroconversion using a MERS-CoV S1 ELISA at any timepoint during the study. Binding antibody titres correlated with MERS-CoV-specific neutralising antibodies (Spearman's correlation r=0·86 [95% CI 0·6960-0·9427], p=0·0001). MERS-CoV spike-specific T-cell responses were detected in ten (83%) of 12 immunised participants in the low-dose group and ten (91%) of 11 immunised participants in the high-dose group.

Interpretation: Vaccination with MVA-MERS-S had a favourable safety profile without serious or severe adverse events. Homologous prime-boost immunisation induced humoral and cell-mediated responses against MERS-CoV. A dose-effect relationship was demonstrated for reactogenicity, but not for vaccine-induced immune responses. The data presented here support further clinical testing of MVA-MERS-S in larger cohorts to advance MERS vaccine development.

Funding: German Center for Infection Research.
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http://dx.doi.org/10.1016/S1473-3099(20)30248-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7172913PMC
July 2020

Wound infection with Vibrio harveyi following a traumatic leg amputation after a motorboat propeller injury in Mallorca, Spain: a case report and review of literature.

BMC Infect Dis 2020 Feb 4;20(1):104. Epub 2020 Feb 4.

Division of Infectious Diseases, I. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Background: Vibrio spp. are aquatic bacteria that are ubiquitous in warm estuarine and marine environments, of which 12 species are currently known to cause infections in humans. So far, only five human infections with V. harveyi have been reported.

Case Presentation: A 26-year old patient was transferred to our center by inter-hospital air transfer from Mallorca, Spain. Seven days before, he had suffered a complete amputation injury of his left lower leg combined with an open, multi-fragment, distal femur fracture after he had been struck by the propeller of a passing motorboat while snorkeling in the Mediterranean Sea. On admission he was febrile; laboratory studies showed markedly elevated inflammatory parameters and antibiotic treatment with ampicillin/sulbactam was initiated. Physical examination showed a tender and erythematous amputation stump, so surgical revision was performed and confirmed a putrid infection with necrosis of the subcutaneous tissue and the muscles. Tissue cultures subsequently grew V. harveyi with a minimal inhibitory concentration (MIC) of 16 mg/L for ampicillin, and antibiotic treatment was switched to ceftriaxone and ciprofloxacin. Throughout the following days, the patient repeatedly had to undergo surgical debridement but eventually the infection could be controlled, and he was discharged.

Conclusions: We report the first human infection with V. harveyi acquired in Spain and the second infection acquired in the Mediterranean Sea. This case suggests that physicians and microbiologists should be aware of the possibility of wound infections caused by Vibrio spp. acquired in the ocean environment, especially during hot summer months. Since Vibrio spp. preferentially grow at water temperatures above 18 °C, global warming is responsible for an abundance of these bacteria in coastal waters. This will likely lead to a worldwide increase in reports of Vibrio-associated diseases in the future.
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http://dx.doi.org/10.1186/s12879-020-4789-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7001194PMC
February 2020

Immediate versus deferred antiretroviral therapy in HIV-infected patients presenting with acute AIDS-defining events (toxoplasmosis, Pneumocystis jirovecii-pneumonia): a prospective, randomized, open-label multicenter study (IDEAL-study).

AIDS Res Ther 2019 11 15;16(1):34. Epub 2019 Nov 15.

Infectious Diseases Clinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Background: To evaluate clinical outcomes after either immediate or deferred initiation of antiretroviral therapy in HIV-1-infected patients, presenting late with pneumocystis pneumonia (PCP) or toxoplasma encephalitis (TE).

Methods: Phase IV, multicenter, prospective, randomized open-label clinical trial. Patients were randomized into an immediate therapy arm (starting antiretroviral therapy (ART) within 7 days after initiation of OI treatment) versus a deferred arm (starting ART after completing the OI-therapy). All patients were followed for 24 weeks. The rates of clinical progression (death, new or relapsing opportunistic infections (OI) and other grade 4 clinical endpoints) were compared, using a combined primary endpoint. Secondary endpoints were hospitalization rates after completion of OI treatment, incidence of immune reconstitution inflammatory syndrome (IRIS), virologic and immunological outcome, adherence to proteinase-inhibitor based antiretroviral therapy (ART) protocol and quality of life.

Results: 61 patients (11 patients suffering TE, 50 with PCP) were enrolled. No differences between the two therapy groups in all examined primary and secondary endpoints could be identified: immunological and virologic outcome was similar in both groups, there was no significant difference in the incidence of IRIS (11 and 10 cases), furthermore 9 events (combined endpoint of death, new/relapsing OI and grade 4 events) occurred in each group.

Conclusions: In summary, this study supports the notion that immediate initiation of ART with a ritonavir-boosted proteinase-inhibitor and two nucleoside reverse transcriptase inhibitors is safe and has no negative effects on incidence of disease progression or IRIS, nor on immunological and virologic outcomes or on quality of life.
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http://dx.doi.org/10.1186/s12981-019-0250-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6857475PMC
November 2019

Safety and efficacy of elvitegravir, dolutegravir, and raltegravir in a real-world cohort of treatment-naïve and -experienced patients.

Medicine (Baltimore) 2019 Aug;98(32):e16721

Division of Infectious Diseases, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg.

The aim of this retrospective cohort study was to compare safety, efficacy and rates and reasons of discontinuation of the 3 currently approved integrase strand transfer inhibitors (INSTIs) elvitegravir (EVG), dolutegravir (DTG), and raltegravir (RAL) in HIV-infected treatment-naïve and -experienced patients in a real-world cohort. One hundred four treatment-naïve patients were prescribed an INSTI-based combined antiretroviral therapy (cART)-regimen (first-line group) and 219 patients were switched to an INSTI-based cART-regimen from another treatment regimen (switch group) at our institution between May 2007 and December 2014. Twelve months after initiation of treatment, 92% of patients in the first-line group (EVG: 96%, n = 22/23; DTG: 92%, n = 34/37; RAL: 90%, n = 28/31) and 88% of patients in the switch group (EVG: 94%, n = 32/34; DTG: 90%, n = 69/77; RAL: 85%, n = 67/79) showed full virological suppression (viral load <50 copies/mL). Side effects of any kind occurred in 12% (n = 12/104) of patients in the first-line group, and 10% (n = 21/219) of patients in the switch group. In the switch group neuropsychiatric side effects (depression, vertigo, and sleep disturbances) occurred more frequently in patients treated with DTG (11%, n = 10) compared to the 2 other INSTI-based cART-regimen (EVG: 2%, n = 1; RAL: 1%, n = 1). Side effects only rarely led to discontinuation of treatment (first-line-group: 2%, n = 2/104; switch-group: 1%, n = 3/219). In this real-world setting, INSTI-based ART-regimens were highly efficacious with no significant differences between any of the 3 INSTIs. Overall, side effects were only rarely observed and generally mild in all subgroups. In light of a slightly higher incidence of vertigo and sleep disturbances in patients switched to DTG, awareness of the potential onset of psychiatric symptoms is warranted during follow-up in those patients.
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http://dx.doi.org/10.1097/MD.0000000000016721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6708907PMC
August 2019

[Management of seasonal influenza in 2017/2018 at a German tertiary-care hospital].

Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2019 Jul;62(7):870-880

I. Medizinische Klinik und Poliklinik, Sektionen Infektiologie und Tropenmedizin, Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, Postfach O10 (2. Etage), 20246, Hamburg, Deutschland.

Background: There are only few structured reports on inpatient management of a seasonal influenza epidemic.

Objectives: A systematic description of a seasonal influenza patient population at a German university hospital to improve risk stratification and clinical care.

Methods: In this monocentric, retrospective observational study of the 2017/2018 influenza season at the University Medical Center Hamburg-Eppendorf, patients with confirmed influenza infection were included.

Results: Of all influenza swabs performed in the emergency department, 24% (n = 162/676) were positive. A total of 255 patients (median age 66 years) had an influenza infection (influenza A n = 79, influenza B n = 176); 27 (15.3%) were nosocomial infections. Of the 179 (70.2%) patients that were hospitalized, 51 (20%) received intensive medical care. Patients with subsequent need for intensive care had an elevated CRP level (69.5 mg/dl [SD 62.8] vs. 141.7 [SD 127.2] mg/dl) at the time of influenza diagnosis and more frequent infiltrates in X‑ray/CT of the thorax (n = 43 [33.6%] vs. n = 43 [84.3%]). Antiviral therapy with oseltamivir was administered for 74 (29.0%) patients and 11 (6.1%) patients were treated with extracorporeal membrane oxygenation (ECMO). Of the 23 (9.0%) patients who died, only four of them had been vaccinated (trivalent). Those four had an influenza B infection.

Conclusion: The structured use of diagnostic tests (influenza PCR, X‑ray/CT chest and CRP) and antiviral therapy (oseltamivir) as well as targeted management of admission, intensive care capacities, and an increase in vaccination rates are important for improving patient care and optimizing the use of resources during seasonal influenza epidemics.
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http://dx.doi.org/10.1007/s00103-019-02976-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7096087PMC
July 2019

Transjugular Intrahepatic Portosystemic Shunt (TIPS) for primary and secondary prophylaxis of variceal bleeding in hepatic schistosomiasis.

Travel Med Infect Dis 2019 Jul - Aug;30:130-132. Epub 2019 Jan 11.

I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany.

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http://dx.doi.org/10.1016/j.tmaid.2019.01.006DOI Listing
February 2020

Detectable Vesicular Stomatitis Virus (VSV)-Specific Humoral and Cellular Immune Responses Following VSV-Ebola Virus Vaccination in Humans.

J Infect Dis 2019 01;219(4):556-561

First Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg.

In response to the Ebola virus (EBOV) crisis of 2013-2016, a recombinant vesicular stomatitis virus (VSV)-based EBOV vaccine was clinically tested (NCT02283099). A single-dose regimen of VSV-EBOV revealed a safe and immunogenic profile and demonstrated clinical efficacy. While EBOV-specific immune responses to this candidate vaccine have previously been investigated, limited human data on immunity to the VSV vector are available. Within the scope of a phase 1 study, we performed a comprehensive longitudinal analysis of adaptive immune responses to internal VSV proteins following VSV-EBOV immunization. While no preexisting immunity to the vector was observed, more than one-third of subjects developed VSV-specific cytotoxic T-lymphocyte responses and antibodies.
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http://dx.doi.org/10.1093/infdis/jiy565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350948PMC
January 2019

Epidemiology, clinical and laboratory features of 24 consecutive cases of leptospirosis at a German infectious disease center.

Infection 2018 Dec 17;46(6):847-853. Epub 2018 Jul 17.

I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

To determine epidemiological, clinical and laboratory characteristics of leptospirosis, 24 consecutive patients diagnosed with the infection between 2011 and 2017 at the University Medical Center Hamburg-Eppendorf were retrospectively analyzed. The majority of patients were male travelers who returned from Southeast Asia and had a history of freshwater-associated activities. Considering the lack of discriminatory clinical or clinical chemistry parameters, leptospirosis should be regarded as differential diagnosis in any patient with acute febrile illness, especially with a history of travel to tropical and subtropical regions or freshwater exposure.
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http://dx.doi.org/10.1007/s15010-018-1181-xDOI Listing
December 2018

Schistosomiasis detected during appendectomy.

Lancet 2018 06;391(10139):2546

Department of Tropical Medicine, Bernhard Nocht Institute for Tropical Medicine & I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Electronic address:

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http://dx.doi.org/10.1016/S0140-6736(18)31329-1DOI Listing
June 2018

Diagnosis and Management of Systemic Endemic Mycoses Causing Pulmonary Disease.

Respiration 2018;96(3):283-301. Epub 2018 Jun 28.

Division of Clinical Infectious Diseases, Research Center Borstel, Borstel, Germany.

Systemic endemic mycoses cause high rates of morbidity and mortality in certain regions of the world and the real impact on global health is not well understood. Diagnosis and management remain challenging, especially in low-prevalence settings, where disease awareness is lacking. The main challenges include the variability of clinical presentation, the fastidious and slow-growing nature of the fungal pathogens, the paucity of diagnostic tests, and the lack of options and toxicity of antifungal drugs. Coccidioidomycosis and paracoccidioidomycosis are restricted to the Americas only, and while histoplasmosis and blastomycosis also occur predominantly in the Americas, these mycoses have also been reported on other continents, especially in sub-Saharan Africa. Talaromycosis is endemic in tropical and subtropical regions in South-East Asia and southern China. Systemic endemic mycoses causing pulmonary disease are usually acquired via the airborne route by inhalation of fungal spores. Infections can range from asymptomatic or mild with flu-like illnesses to severe pulmonary or disseminated diseases. Skin involvement is frequent in patients with paracoccidioidomycosis, blastomycosis, sporotrichosis, and talaromycosis and manifests as localized lesions or diffuse nodules in disseminated disease, but can also occur with other endemic mycoses. Culture and/or characteristic histopathology from clinical samples is the diagnostic standard for endemic mycoses. Immunological assays are often not available for the diagnosis of most endemic mycoses and molecular amplification methods for the detection of fungal nucleic acids are not standardized at present. The first-line treatment for mild to moderate histoplasmosis, paracoccidioidomycosis, blastomycosis, sporotrichosis, and talaromycosis is itraconazole. Severe illness is treated with amphotericin B. Patients with severe coccidioidomycosis should receive fluconazole. Treatment duration depends on the specific endemic mycosis, the severity of disease, and the immune status of the patient, ranging between 6 weeks and lifelong treatment.
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http://dx.doi.org/10.1159/000489501DOI Listing
October 2019

CD32 Expression of Different Memory T Cell Subpopulations in the Blood and Lymph Nodal Tissue of HIV Patients and Healthy Controls Correlates With Immune Activation.

J Acquir Immune Defic Syndr 2018 04;77(4):345-349

I. Department of Medicine, Infectious Disease Unit, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Background: Recently, CD32 has been described to be a specific surface marker of latently HIV-infected CD4 T cells, but little is known about the frequency and distribution of CD32 expression on naive and memory CD8 and CD4 T cell populations in HIV patients and healthy individuals.

Methods: We studied peripheral blood samples of 36 HIV-1-infected patients [23 viremic patients / 13 antiretroviral therapy(ART)-treated] and healthy individuals (n = 14) as well as cells from lymph nodes (8 HIV infected, 5 controls) using a multiparametric flow cytometry panel determining surface expression of CD3, CD8, CD4, CD45RA, CCR7, CD27, CD25, CD127, CCR5, CCR6, CXCR4, CD38, HLA-DR, TIGIT, and PD-1.

Results: Overall, expression of CD32 on total peripheral CD4 T cells between viremic HIV patients, ART-treated and healthy individuals only slightly differed (mean values 1.501%, 0.2785%, and 0.2343%, respectively). However, the level of expression was significantly higher in peripheral and lymph nodal memory CD4 T cell subpopulations of viremic patients compared with ART-treated patients and healthy controls. CD32 CD4 T cells showed higher immune activation and higher expression of CXCR4 than their CD32 counterparts. Furthermore, expression of CD32 on total CD4 T cells and memory T cell populations correlated with general immune activation regardless of the infection status.

Conclusions: Follow-up studies will have to further evaluate CD32 as marker of latently HIV-infected CD4 T cells since other host-related variables such as immune activation seem to influence CD32 expression regardless of the infection status.
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http://dx.doi.org/10.1097/QAI.0000000000001622DOI Listing
April 2018

Histology and Serum Cytokine Responses in an Imported Infection, Germany.

Am J Trop Med Hyg 2018 01;98(1):248-251

Dermatologikum Hamburg, Hamburg, Germany.

, a spotted fever group rickettsial pathogen, causes a syndrome consisting of scalp eschar and neck lymphadenopathy following tick bite. We analyzed the histologic skin reaction in the eschar, showing a prominent eosinophilic infiltration, as well as the presence of B lymphocytes and CD4- and CD8-positive T cells. Examination of the serum cytokine responses over time demonstrated an initial proinflammatory cytokine elevation followed by normalization.
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http://dx.doi.org/10.4269/ajtmh.17-0392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5928713PMC
January 2018

Helminthic infections in returning travelers and migrants with eosinophilia: Diagnostic value of medical history, eosinophil count and IgE.

Travel Med Infect Dis 2017 Nov - Dec;20:49-55. Epub 2017 Sep 4.

Department of Clinical Research, Bernhard-Nocht-Institute for Tropical Medicine, Hamburg, Germany. Electronic address:

Objectives: Eosinophilia in travelers and migrants returning from the tropics is often associated with invasive helminthic infections. Total IgE is considered a useful additional diagnostic parameter; however, both parameters are also increased in various other non-helminthic diseases.

Methods: We retrospectively evaluated travelers and migrants seen at our department between September 2007 and May 2014. Patients with an absolute eosinophil count ≥500 cells/μl were considered for further analyses.

Results: Among 6618 returned travelers and migrants, 154 (2.3%) had a total eosinophil count ≥500 cells/μL. Of these, 71 patients (46%) were diagnosed with helminthic infection. In an additional 62 patients (40%) with eosinophilia a final diagnosis was found, including non-helminthic infections in 34 patients and non-infectious causes in 28 patients, while in 21 patients (14%) no diagnosis was made. Patients with helminthic infections had higher eosinophil counts than travelers and migrants with other diagnoses (median 981 vs. 710 cells/μl; p = 0.001), while total IgE levels (n = 70; 172 vs. 152 kU/l; p = 0.731) were similar in both groups.

Conclusion: Eosinophil count but not total IgE levels are associated with helminthic infections in returning travelers and migrants with eosinophilia. Our results do not support the use of total IgE to differentiate helminthic infections from other causes of eosinophilia in this population.
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http://dx.doi.org/10.1016/j.tmaid.2017.09.001DOI Listing
May 2018

Dose-dependent T-cell Dynamics and Cytokine Cascade Following rVSV-ZEBOV Immunization.

EBioMedicine 2017 May 5;19:107-118. Epub 2017 Apr 5.

University Medical Center Hamburg-Eppendorf (UKE), 1st Department of Medicine, Hamburg, Germany; German Center for Infection Research(DZIF), Standort Hamburg-Lübeck-Borstel-Riems, Germany. Electronic address:

Background: The recent West African Ebola epidemic led to accelerated efforts to test Ebola vaccine candidates. As part of the World Health Organisation-led VSV Ebola Consortium (VEBCON), we performed a phase I clinical trial investigating rVSV-ZEBOV (a recombinant vesicular stomatitis virus-vectored Ebola vaccine), which has recently demonstrated protection from Ebola virus disease (EVD) in phase III clinical trials and is currently in advanced stages of licensing. So far, correlates of immune protection are incompletely understood and the role of cell-mediated immune responses has not been comprehensively investigated to date.

Methods: We recruited 30 healthy subjects aged 18-55 into an open-label, dose-escalation phase I trial testing three doses of rVSV-ZEBOV (3×10 plaque-forming units (PFU), 3×10 PFU, 2×10 PFU) (ClinicalTrials.gov; NCT02283099). Main study objectives were safety and immunogenicity, while exploratory objectives included lymphocyte dynamics, cell-mediated immunity and cytokine networks, which were assessed using flow cytometry, ELISpot and LUMINEX assay.

Findings: Immunization with rVSV-ZEBOV was well tolerated without serious vaccine-related adverse events. Ebola virus-specific neutralizing antibodies were induced in nearly all individuals. Additionally, vaccinees, particularly within the highest dose cohort, generated Ebola glycoprotein (GP)-specific T cells and initiated a cascade of signaling molecules following stimulation of peripheral blood mononuclear cells with Ebola GP peptides.

Interpretation: In addition to a benign safety and robust humoral immunogenicity profile, subjects immunized with 2×10 PFU elicited higher cellular immune responses and stronger interlocked cytokine networks compared to lower dose groups. To our knowledge these data represent the first detailed cell-mediated immuneprofile of a clinical trial testing rVSV-ZEBOV, which is of particular interest in light of its potential upcoming licensure as the first Ebola vaccine. VEBCON trial Hamburg, Germany (NCT02283099).
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http://dx.doi.org/10.1016/j.ebiom.2017.03.045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5440606PMC
May 2017

Screening and contact precautions - A survey on infection control measures for multidrug-resistant bacteria in German university hospitals.

Antimicrob Resist Infect Control 2017 13;6:37. Epub 2017 Apr 13.

Department I of Internal Medicine, University Hospital of Cologne, Kerpener Strasse 62, 50937 Cologne, Germany.

To assess the scope of infection control measures for multidrug-resistant bacteria in high-risk settings, a survey among university hospitals was conducted. Fourteen professionals from 8 sites participated. Reported policies varied largely with respect to the types of wards conducting screening, sample types used for screening and implementation of contact precautions. This variability among sites highlights the need for an evidence-based consensus of current infection control policies.
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http://dx.doi.org/10.1186/s13756-017-0191-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5390437PMC
April 2017

High clinical manifestation rate in an imported outbreak of hepatitis E genotype 1 infection in a German group of travellers returning from India.

Ann Hepatol 2017 Jan-Feb;16(1):57-62

Medical Practice, Hoheluftchausse, Hamburg, Germany.

Background. There are only few reports about travel-associated, imported tropical hepatitis E virus (HEV) genotype 1 infections within Western travellers. We describe the clinical course of a single outbreak of hepatitis E in a German travellers group returning from India and compare the results of two commercial HEV-seroassays.

Material And Methods: After identifying hepatitis E in an index patient returning from a journey to India all 24 members of this journey were tested for anti-HEV-IgG and IgM using two commercial seroassays (Wantai and Mikrogen), for HEV-RNA by PCR and HEV-Ag by an antigen-assay (Wantai).

Results: 5/24 (21%) individuals were viraemic with viral loads between 580-4,800,000 IU/mL. Bilirubin and ALT levels in these patients ranged from 1.3-14.9 mg/dL (mean 7.3 mg/dL, SD 5.6 mg/dL) and 151-4,820 U/L (mean 1,832U/L, SD 1842U/L), respectively and showed significant correlations with viral loads (r = 0.863, p < 0.001; r = 0.890, p < 0.001). No risk factor for food-borne HEV-transmission was identified. All viraemic patients (5/5) tested positive for anti-HEV-IgG and IgM in the Wantai-assay but only 4/5 in the Mikrogen-assay. Wantai-HEV-antigen-assay was negative in all patients. Six months later all previously viraemic patients tested positive for anti-HEV-IgG and negative for IgM in both assays. However, two non-viremic individuals who initially tested Wantai-IgM-positive stayed positive indicating false positive results.

Conclusions: Despite the exact number of exposed individuals could not be determined HEV genotype 1 infections have a high manifestation rate of more than 20%.The Wantai-antigen-test failed, the Wantai-IgMrapid- test and the Mikrogen-IgM-recomblot showed a better performance but still they cannot replace real-time PCR for diagnosing ongoing HEV-infections.
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http://dx.doi.org/10.5604/16652681.1226815DOI Listing
February 2017