Publications by authors named "Dennis Tappe"

143 Publications

Multispecies Q Fever Outbreak in a Mixed Dairy Goat and Cattle Farm Based on a New Bovine-Associated Genotype of .

Vet Sci 2021 Oct 26;8(11). Epub 2021 Oct 26.

Clinic for Swine and Small Ruminants, Forensic Medicine and Ambulatory Service, University of Veterinary Medicine Hannover, Foundation, Bischofsholer Damm 15, 30173 Hannover, Germany.

A Q fever outbreak on a dairy goat and cattle farm was investigated with regard to the One Health concept. Serum samples and vaginal swabs from goats with different reproductive statuses were collected. Cows, cats, and a dog were investigated with the same sample matrix. The farmer's family was examined by serum samples. Ruminant sera were analyzed with two phase-specific enzyme-linked immunoassays (ELISAs). Dominant immunoglobulin G (IgG) phase II levels reflected current infections in goats. The cows had high IgG phase I and II levels indicating ongoing infections. Feline, canine, and human sera tested positive by indirect fluorescent antibody test (IFAT). Animal vaginal swabs were analyzed by qPCR to detect , and almost all tested positive. A new cattle-associated genotype C16 was identified by the Multiple-Locus Variable-number tandem repeat Analysis (MLVA/VNTR) from ruminant samples. Additionally, a possible influence of 17ß-estradiol on antibody response was evaluated in goat sera. Goats in early/mid-pregnancy had significantly lower levels of phase-specific IgGs and 17ß-estradiol than goats in late pregnancy. We conclude that the cattle herd may have transmitted to the pregnant goat herd, resulting in a Q fever outbreak with one acute human case. The influence of placentation and maternal pregnancy hormones during pregnancy on the immune response is discussed.
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http://dx.doi.org/10.3390/vetsci8110252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8626049PMC
October 2021

Emerging Microbes & Infections - Original Article: Human Borna disease virus 1 (BoDV-1) encephalitis cases in the north and east of Germany.

Emerg Microbes Infect 2021 Nov 16:1-19. Epub 2021 Nov 16.

Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.

In 2021, three encephalitis cases due to the Borna disease virus 1 (BoDV-1) were diagnosed in the north and east of Germany. The patients were from the states of Thuringia, Saxony-Anhalt, and Lower Saxony. All were residents of known endemic areas for animal Borna disease but without prior diagnosed human cases. Except for one recently detected case in the state of Brandenburg, all >30 notified cases had occurred in, or were linked to, the southern state of Bavaria. Of the three detected cases described here, two infections were acute, while one infection was diagnosed retrospectively from archived brain autopsy tissue samples. One of the acute cases survived, but is permanently disabled. The cases were diagnosed by various techniques (serology, molecular assays, and immunohistology) following a validated testing scheme and adhering to a proposed case definition. Two cases were classified as confirmed BoDV-1 encephalitis, while one case was a probable infection with positive serology and typical brain magnetic resonance imaging, but without molecular confirmation. Of the three cases, one full virus genome sequence could be recovered. Our report highlights the need for awareness of a BoDV-1 etiology in cryptic encephalitis cases in all areas with known animal Borna disease endemicity in Europe, including virus-endemic regions in Austria, Liechtenstein, and Switzerland. BoDV-1 should be actively tested for in acute encephalitis cases with residence or rural exposure history in known Borna disease-endemic areas.
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http://dx.doi.org/10.1080/22221751.2021.2007737DOI Listing
November 2021

No Metagenomic Evidence of Causative Viral Pathogens in Postencephalitic Parkinsonism Following Encephalitis Lethargica.

Microorganisms 2021 Aug 12;9(8). Epub 2021 Aug 12.

Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany.

Postencephalitic parkinsonism (PEP) is a disease of unknown etiology and pathophysiology following encephalitis lethargica (EL), an acute-onset polioencephalitis of cryptic cause in the 1920s. PEP is a tauopathy with multisystem neuronal loss and gliosis, clinically characterized by bradykinesia, rigidity, rest tremor, and oculogyric crises. Though a viral cause of EL is likely, past polymerase chain reaction-based investigations in the etiology of both PEP and EL were negative. PEP might be caused directly by an unknown viral pathogen or the consequence of a post-infectious immunopathology. The development of metagenomic next-generation sequencing in conjunction with bioinformatic techniques has generated a broad-range tool for the detection of unknown pathogens in the recent past. Retrospective identification and characterization of pathogens responsible for past infectious diseases can be successfully performed with formalin-fixed paraffin-embedded (FFPE) tissue samples. In this study, we analyzed 24 FFPE brain samples from six patients with PEP by unbiased metagenomic next-generation sequencing. Our results show that no evidence for the presence of a specific or putative (novel) viral pathogen was found, suggesting a likely post-infectious immune-mediated etiology of PEP.
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http://dx.doi.org/10.3390/microorganisms9081716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8398509PMC
August 2021

Investigation of fatal human Borna disease virus 1 encephalitis outside the previously known area for human cases, Brandenburg, Germany - a case report.

BMC Infect Dis 2021 Aug 10;21(1):787. Epub 2021 Aug 10.

Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Riems, Germany.

Background: The true burden and geographical distribution of human Borna disease virus 1 (BoDV-1) encephalitis is unknown. All detected cases so far have been recorded in Bavaria, southern Germany.

Case Presentation: A retrospective laboratory and epidemiological investigation of a 2017 case of fatal encephalitis in a farmer in Brandenburg, northeast Germany, demonstrated BoDV-1 as causative agent by polymerase chain reaction, immunohistochemistry and in situ hybridization. Next-generation sequencing showed that the virus belonged to a cluster not known to be endemic in Brandenburg. The investigation was triggered by a recent outbreak of animal Borna disease in the region. Multiple possible exposures were identified. The next-of-kin were seronegative.

Conclusions: The investigation highlights clinical awareness for human BoDV-1 encephalitis which should be extended to all areas endemic for animal Borna disease. All previously diagnosed human cases had occurred > 350 km further south. Further testing of shrews and livestock with Borna disease may show whether this BoDV-1 cluster is additionally endemic in the northwest of Brandenburg.
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http://dx.doi.org/10.1186/s12879-021-06439-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353434PMC
August 2021

GroEL is an immunodominant surface-exposed antigen of Rickettsia typhi.

PLoS One 2021 10;16(6):e0253084. Epub 2021 Jun 10.

Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.

Rickettsioses are neglected and emerging potentially fatal febrile diseases that are caused by obligate intracellular bacteria, rickettsiae. Rickettsia (R.) typhi and R. prowazekii constitute the typhus group (TG) of rickettsiae and are the causative agents of endemic and epidemic typhus, respectively. We recently generated a monoclonal antibody (BNI52) against R. typhi. Characterization of BNI52 revealed that it specifically recognizes TG rickettsiae but not the members of the spotted fever group (SFG) rickettsiae. We further show that BNI52 binds to protein fragments of ±30 kDa that are exposed on the bacterial surface and also present in the periplasmic space. These protein fragments apparently derive from the cytosolic GroEL protein of R. typhi and are also recognized by antibodies in the sera from patients and infected mice. Furthermore, BNI52 opsonizes the bacteria for the uptake by antigen presenting cells (APC), indicating a contribution of GroEL-specific antibodies to protective immunity. Finally, it is interesting that the GroEL protein belongs to 32 proteins that are differentially downregulated by R. typhi after passage through immunodeficient BALB/c CB17 SCID mice. This could be a hint that the rickettsia GroEL protein may have immunomodulatory properties as shown for the homologous protein from several other bacteria, too. Overall, the results of this study provide evidence that GroEL represents an immunodominant antigen of TG rickettsiae that is recognized by the humoral immune response against these pathogens and that may be interesting as a vaccine candidate. Apart from that, the BNI52 antibody represents a new tool for specific detection of TG rickettsiae in various diagnostic and experimental setups.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253084PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191997PMC
November 2021

Genomic and Micro-Evolutionary Features of (Variegated Squirrel Bornavirus 1, VSBV-1).

Microorganisms 2021 May 25;9(6). Epub 2021 May 25.

WHO Collaborating Centre for Arbovirus and Haemorrhagic Fever Reference and Research, Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany.

(VSBV-1) is an emerging zoonotic pathogen discovered in several exotic squirrel species and associated with fatal human encephalitis. The dynamics of VSBV-1 spread and evolution in its presumed natural hosts are unknown. Here, we present the phylogeny, micro-evolution, cross-species transmission and spread of VSBV-1 at a temporal and spatial resolution within the limits of animal husbandry. The results showed that VSBV-1 can be classified into six distinct groups and that the most recent common ancestor of the known German strains emerged at least 20 years ago. We here demonstrate that the genetic diversity of the VSBV-1 groups is shaped primarily by in situ evolution and most of the amino acid changes are deleterious polymorphisms removed by purifying selection. Evidence of adaptive evolution has been found in the G and L genes which might have an influence on transmission fitness. Furthermore, there was also evidence for some form of adaptive changes in the glycoprotein which suggests that many sites might be subjected to positive pressure evolving under episodic directional selection, indicating past occurrence of positive selection. Host switching events were detected as dominant evolutionary mechanisms driving the virus-host associations. Virus spread by animal trade followed by subsequent local micro-evolution in zoos and holdings is responsible for diversifying strains. Time-resolved phylogeny indicated that Prevost's squirrels might be the original squirrel species carrying and seeding the virus in Germany. This study provides the first insight into the ecology and micro-evolutionary dynamics of this novel viral pathogen in the captive exotic squirrel population under artificial ecological conditions (zoos and animal husbandry) and co-housing of different squirrel species.
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http://dx.doi.org/10.3390/microorganisms9061141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227138PMC
May 2021

Recurrent Swelling and Microfilaremia Caused by Dirofilaria repens Infection after Travel to India.

Emerg Infect Dis 2021 06;27(6):1701-1704

Human subcutaneous dirofilariasis is an emerging mosquitoborne zoonosis. A traveler returning to Germany from India experienced Dirofilaria infection with concomitant microfilaremia. Molecular analysis indicated Dirofilaria repens nematodes of an Asian genotype. Microfilaremia showed no clear periodicity. Presence of Wolbachia endosymbionts enabled successful treatment with doxycycline.
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http://dx.doi.org/10.3201/eid2706.210592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153875PMC
June 2021

Active Case Finding of Current Bornavirus Infections in Human Encephalitis Cases of Unknown Etiology, Germany, 2018-2020.

Emerg Infect Dis 2021 05;27(5):1371-1379

Human bornavirus encephalitis is a severe and often fatal infection caused by variegated squirrel bornavirus 1 (VSBV-1) and Borna disease virus 1 (BoDV-1). We conducted a prospective study of bornavirus etiology of encephalitis cases in Germany during 2018-2020 by using a serologic testing scheme applied along proposed graded case definitions for VSBV-1, BoDV-1, and unspecified bornavirus encephalitis. Of 103 encephalitis cases of unknown etiology, 4 bornavirus infections were detected serologically. One chronic case was caused by VSBV-1 after occupational-related contact of a person with exotic squirrels, and 3 acute cases were caused by BoDV-1 in virus-endemic areas. All 4 case-patients died. Bornavirus etiology could be confirmed by molecular methods. Serologic testing for these cases was virus specific, discriminatory, and a practical diagnostic option for living patients if no brain tissue samples are available. This testing should be guided by clinical and epidemiologic suspicions, such as residence in virus-endemic areas and animal exposure.
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http://dx.doi.org/10.3201/eid2705.204490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084505PMC
May 2021

[West-Nile-Virus Infection acquired in Germany in a Kidney Transplant Recipient].

Dtsch Med Wochenschr 2021 04 29;146(7):482-486. Epub 2021 Mar 29.

Bernhard-Nocht-Institut für Tropenmedizin, Hamburg.

Background: West-Nile-Virus (WNV) is a widely distributed flavivirus that is mainly transmitted between birds through different mosquito species (e. g. Culex, Aedes), but may also be transmitted to mammals including humans. WNV causes a spectrum of disease, ranging from asymptomatic infection to encephalitis in a minority of cases. Risk factors for severe disease are older age, cardiovascular disease and an immunocompromised state.

Medical History And Clinical Examination: Here we report about a 60-year-old male patient who was referred to the University Hospital of Halle (Saale) with severe fever two years after kidney transplantation due to hypertensive nephropathy. No infection focus could be found and by day 6 in the course of his illness the patient developed neurologic symptoms and viral encephalitis was suspected.

Treatment And Course: The patient was initially treated with aciclovir. After initial reduction of immunosuppression, coincident graft dysfunction was treated with methylprednisolon. WNV-infection was suspected due to recent emerging human cases in the nearby area of the city of Leipzig. WNV lineage 2 was detected in the patient's urine by RT-PCR and seroconversion with presence of anti WNV IgM and IgG could be demonstrated. Consecutively, aciclovir treatment was stopped. The patient fully recovered and the transplanted kidney regained adequate function. Kidney biopsy did not reveal gross rejection of the transplant.

Conclusion: This case highlights the need to consider rarer causes of illness like WNV-infection particularly in risk groups for more severe outcomes of infectious disease. WNV may be detected by PCR in the blood and cerebrospinal fluid early in the course of infection but it is also excreted for a prolonged period of time in the urine. Seroconversion to anti WNV IgG and IgM may be shown but serologic cross-reactivity among members of the flaviviridae family must be considered.
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http://dx.doi.org/10.1055/a-1218-9096DOI Listing
April 2021

Introduction and spread of variegated squirrel bornavirus 1 (VSBV-1) between exotic squirrels and spill-over infections to humans in Germany.

Emerg Microbes Infect 2021 Dec;10(1):602-611

Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.

The variegated squirrel bornavirus 1 (VSBV-1) is a recently discovered emerging viral pathogen which causes severe and eventually fatal encephalitis in humans after contact to exotic squirrels in private holdings and zoological gardens. Understanding the VSBV-1 epidemiology is crucial to develop, implement, and maintain surveillance strategies for the detection and control of animal and human infections. Based on a newly detected human encephalitis case in a zoological garden, epidemiological squirrel trade investigations and molecular phylogeny analyses of VSBV-1 with temporal and spatial resolution were conducted. Phylogenetic analyses indicated a recent emergence of VSBV-1 in European squirrel holdings and several animal-animal and animal-human spill-over infections. Virus phylogeny linked to squirrel trade analysis showed the introduction of a common ancestor of the known current VSBV-1 isolates into captive exotic squirrels in Germany, most likely by Prevost's squirrels (). The links of the animal trade between private breeders and zoos, the likely introduction pathway of VSBV-1 into Germany, and the role of a primary animal distributor were elucidated. In addition, a seroprevalence study was performed among zoo animal caretakers from VSBV-1 affected zoos. No seropositive healthy zoo animal caretakers were found, underlining a probable high-case fatality rate of human VSBV-1 infections. This study illustrates the network and health consequences of uncontrolled wild pet trading as well as the benefits of molecular epidemiology for elucidation and future prevention of infection chains by zoonotic viruses. To respond to emerging zoonotic diseases rapidly, improved regulation and control strategies are urgently needed.
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http://dx.doi.org/10.1080/22221751.2021.1902752DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018504PMC
December 2021

Establishing and evaluation of a polymerase chain reaction for the detection of Echinococcus multilocularis in human tissue.

PLoS Negl Trop Dis 2021 02 25;15(2):e0009155. Epub 2021 Feb 25.

Consultant Laboratory for Echinococcosis, Institute for Hygiene and Microbiology, University of Wuerzburg, Wuerzburg, Germany.

Background: Alveolar echinococcosis (AE) is caused by metacestode larva of the tapeworm Echinococcus multilocularis. AE diagnostics currently rely on imaging techniques supported by serology, but unequivocal detection of AE is difficult. Although polymerase chain reaction (PCR)-based methods to detect tapeworm DNA in biopsies have been suggested for several species, no validated protocol adhering to accepted guidelines has so far been presented for AE diagnostics. We herein established a PCR protocol for metacestode biopsies and technically evaluated the method using isolated parasite DNA and cells, biopsies of clinically relevant material, and formalin fixed paraffin-embedded (FFPE) human tissue blocks. We compared the results with an immunochemical (IHC) approach using the monoclonal antibody Em2G11 specific for the antigen Em2 of E. mulitlocularis.

Methodology/principal Findings: Based on tapeworm 12S rDNA sequences we established and validated a PCR protocol for robust detection of as little as 50 parasite cells per specimen and report 127 cases of positive identification of Echinococcus species in samples from humans and animals. For further validation, we analyzed 45 liver, heart, brain, and soft tissue samples as well as cytological probes of aspirates of FFPE-material from 18 patients with clinically confirmed AE. Of each patient we analyzed (i) fully viable lesions with laminated layer; (ii) tissue with mAbEm2G11-positive small particles of E. multilocularis (spems); (iii) mAbEm2G11-negative tissue adjacent to the main lesion; and (iv) lymph node tissue with mAbEm2G11-positive spems. To identify the areas for the PCR-based approach, we performed IHC-staining with the monoclonal antibody Em2G11. Micro-dissected tissue of these areas was then used for PCR-analysis. 9 of 15 analyzed samples with viable E. multilocularis lesions with laminated layer were positive by PCR. Of this group, all samples preserved for less than 6 years (6/6) were tested positive. 11 of 15 samples of spems and 7 of 9 samples of the control group mAbEm2G11-negative tissue were negative by PCR. We further show that all probes from lymph nodes with spems are PCR negative.

Conclusions/significance: We present a sensitive PCR method for the detection of E. multilocularis in human tissue, particularly in fresh biopsy material and tissue blocks stored for less than 5 years. While the diagnostic sensitivity of material containing only spems was higher using IHC, PCR detection was possible in IHC negative liver tissue and in patients with negative serology. Our results support the view that spems do not contain parasitic DNA or viable cells of the parasite. spems thus most probably do not directly contribute to metastasis formation during AE.
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http://dx.doi.org/10.1371/journal.pntd.0009155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906421PMC
February 2021

The complete mitochondrial genome of the pentastomid (Pentastomida) from reindeer () in Northern Norway.

Mitochondrial DNA B Resour 2020 Oct 15;5(3):3456-3457. Epub 2020 Oct 15.

Faculty of Veterinary Medicine, Department of Food Safety and Infection Biology, Norwegian University of Life Sciences, Sentrum, Oslo, Norway.

Here, we present the first complete mitochondrial genome of the pentastomid collected from the nasal passages of a reindeer () in Norway. The full length mitochondrial genome of , which measures 14,789 bp in length, contains 13 protein-coding genes, 2 ribosomal RNA genes and 22 transfer RNA genes. A clear A + T bias is observed in the mitogenome of with an overall base composition of 32.6% A, 27.5% T, 32.8% C, and 7,1% G., and a GC content of 39.9%. The gene arrangement is identical to that of previously described pentastomid mitogenomes.
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http://dx.doi.org/10.1080/23802359.2020.1823255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594850PMC
October 2020

Outbreak of Tularemia in a Group of Hunters in Germany in 2018-Kinetics of Antibody and Cytokine Responses.

Microorganisms 2020 Oct 23;8(11). Epub 2020 Oct 23.

Robert Koch Institute, 13353 Berlin, Germany.

In November 2018, an outbreak of tularemia occurred among hare hunters in Bavaria, Germany. At least one infected hare was confirmed as the source of infection. A number of hunting dogs showed elevated antibody titers to , but the absence of titer increases in subsequent samples did not point to acute infections in dogs. Altogether, 12 persons associated with this hare hunt could be diagnosed with acute tularemia by detection of specific antibodies. In nine patients, the antibody and cytokine responses could be monitored over time. Eight out of these nine patients had developed detectable antibodies three weeks after exposure; in one individual the antibody response was delayed. All patients showed an increase in various cytokines and chemokines with a peak for most mediators in the first week after exposure. Cytokine levels showed individual variations, with high and low responders. The kinetics of seroconversion has implications on serological diagnoses of tularemia.
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http://dx.doi.org/10.3390/microorganisms8111645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690809PMC
October 2020

Case Report: Molecular Identification of Larval Infection in the Pouch of Douglas.

Am J Trop Med Hyg 2020 12 17;103(6):2315-2317. Epub 2020 Sep 17.

National Reference Center for Tropical Pathogens, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.

is a tapeworm dwelling in the intestine of mustelids and a rare zoonotic cysticercosis pathogen in its larval stage. The metacestode is morphologically very similar to more prevalent cysticercosis parasites, such as the larvae of and , and may be indistinguishable from other metacestodes on histological sections. However, the epidemiology of human . infections is different, and for prognosis, prevention, and detection of natural parasite reservoirs, the species should be identified. We here report the molecular identification of a larva located in the pouch of Douglas in a female German patient who underwent surgery for endometriosis. This case represents the fifth human infection described worldwide; all previous cases were also in European women, involving the eye, brain, and the peritoneum.
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http://dx.doi.org/10.4269/ajtmh.20-0782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695056PMC
December 2020

Update on immunopathology of bornavirus infections in humans and animals.

Adv Virus Res 2020 30;107:159-222. Epub 2020 Jun 30.

Institute of Veterinary Pathology, Justus-Liebig-University Giessen, Giessen, Germany; Center for Brain, Mind and Behavior, Justus-Liebig-University Giessen, Giessen, Germany. Electronic address:

Knowledge on bornaviruses has expanded tremendously during the last decade through detection of novel bornaviruses and endogenous bornavirus-like elements in many eukaryote genomes, as well as by confirmation of insectivores as reservoir species for classical Borna disease virus 1 (BoDV-1). The most intriguing finding was the demonstration of the zoonotic potential of lethal human bornavirus infections caused by a novel bornavirus of different squirrel species (variegated squirrel 1 bornavirus, VSBV-1) and by BoDV-1 known as the causative agent for the classical Borna disease in horses and sheep. Whereas a T cell-mediated immunopathology has already been confirmed as key disease mechanism for infection with BoDV-1 by experimental studies in rodents, the underlying pathomechanisms remain less clear for human bornavirus infections, infection with other bornaviruses or infection of reservoir species. Thus, an overview of current knowledge on the pathogenesis of bornavirus infections focusing on immunopathology is given.
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http://dx.doi.org/10.1016/bs.aivir.2020.06.004DOI Listing
April 2021

Dirofilaria repens infection of the eye with concomitant microfilaremia in a traveller.

J Travel Med 2021 01;28(1)

Center for Infectious Diseases, Travel and Tropical Medicine, Municipal Hospital of Dresden, Saxony, Germany.

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http://dx.doi.org/10.1093/jtm/taaa119DOI Listing
January 2021

Ticks and tick-borne pathogens in animals and humans in the island nations of Southeast Asia: A review.

Acta Trop 2020 Sep 22;209:105527. Epub 2020 May 22.

Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.

Ticks are blood-feeding ectoparasites and major vectors of pathogens that cause infectious diseases in humans and animals worldwide including mammals, birds and reptiles. Despite the growing scientific effort in the 20th century, there is still limited information on ticks and tick-borne pathogens in Southeast Asia, especially concerning medical, veterinary, socioeconomic and agricultural aspects in the island nations. This review provides an overview of the current state of knowledge of ticks and their pathogens in the island nations of Southeast Asia and peninsular Malaysia. We aim to stimulate further research studies on ticks and tick-borne pathogens of human and veterinary importance in this geographical region.
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http://dx.doi.org/10.1016/j.actatropica.2020.105527DOI Listing
September 2020

Borna disease outbreak with high mortality in an alpaca herd in a previously unreported endemic area in Germany.

Transbound Emerg Dis 2020 Mar 29. Epub 2020 Mar 29.

Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany.

Borna disease virus 1 (BoDV-1) is the causative agent of Borna disease, an often fatal neurologic condition of domestic mammals, including New World camelids, in endemic areas in Central Europe. Recently, BoDV-1 gained further attention by the confirmation of fatal zoonotic infections in humans. Although Borna disease and BoDV-1 have been described already over the past decades, comprehensive reports of Borna disease outbreaks in domestic animals employing state-of-the-art diagnostic methods are missing. Here, we report a series of BoDV-1 infections in a herd of 27 alpacas (Vicugna pacos) in the federal state of Brandenburg, Germany, which resulted in eleven fatalities (41%) within ten months. Clinical courses ranged from sudden death without previous clinical signs to acute or chronic neurologic disease with death occurring after up to six months. All animals that underwent necropsy exhibited a non-suppurative encephalitis. In addition, six apparently healthy seropositive individuals were identified within the herd, suggesting subclinical BoDV-1 infections. In infected animals, BoDV-1 RNA and antigen were mainly restricted to the central nervous system and the eye, and sporadically detectable in large peripheral nerves and neuronal structures in other tissues. Pest control measures on the farm resulted in the collection of a BoDV-1-positive bicoloured white-toothed shrew (Crocidura leucodon), while all other trapped small mammals were negative. A phylogeographic analysis of BoDV-1 sequences from the alpacas, the shrew and BoDV-1-positive equine cases from the same region in Brandenburg revealed a previously unreported endemic area of BoDV-1 cluster 4 in North-Western Brandenburg. In conclusion, alpacas appear to be highly susceptible to BoDV-1 infection and display a highly variable clinical picture ranging from peracute death to subclinical forms. In addition to horses and sheep, they can serve as sensitive sentinels used for the identification of endemic areas.
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http://dx.doi.org/10.1111/tbed.13556DOI Listing
March 2020

Strongyloides stercoralis hyperinfection syndrome presenting as mechanical ileus after short-course oral steroids for chronic obstructive pulmonary disease (COPD) exacerbation.

Parasitol Int 2020 Jun 20;76:102087. Epub 2020 Feb 20.

Institute of Pathology, Technical University Munich, Munich, Germany.

We report a case of a fatal Strongyloides stercoralis hyperinfection syndrome (SHS) in a migrant from Kenya, who had been living in Germany for three decades. A short-course oral steroid treatment for Chronic Obstructive Pulmonary Disease (COPD) exacerbation had been administered four weeks prior to the presentation. The initial clinical and radiological findings suggested a mechanical small bowel obstruction as a cause of ileus. Our case highlights the importance of maintaining a high index of suspicion for strongyloidiasis in patients from endemic areas even years after they left the country of origin. It demonstrates that even a five-day course of prednisolone is able to trigger SHS in patients with underlying strongyloidiasis. History of frequent previous administration of oral prednisolone for COPD exacerbations in our case raises the question why and how the last steroid regimen provoked SHS. SHS can present with multiple gastrointestinal symptoms including ileus and the absence of eosinophilia during the whole course of the disease should not lower the level of suspicion in the appropriate clinical setting.
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http://dx.doi.org/10.1016/j.parint.2020.102087DOI Listing
June 2020

Travel-associated neurological disease terminated in a postmortem diagnosed atypical HSV-1 encephalitis after high-dose steroid therapy - a case report.

BMC Infect Dis 2020 Feb 18;20(1):150. Epub 2020 Feb 18.

Max von Pettenkofer Institute, Virology, Faculty of Medicine, LMU Munich, Pettenkoferstraße 9a, D-80336, Munich, Germany.

Background: Human encephalitis can originate from a variety of different aetiologies, of which infection is the most common one. The diagnostic work-up is specifically challenging in patients with travel history since a broader spectrum of unfamiliar additional infectious agents, e. g. tropical disease pathogens, needs to be considered. Here we present a case of encephalitis of unclear aetiology in a female traveller returning from Africa, who in addition developed an atypical herpes simplex virus (HSV) encephalitis in close temporal relation with high-dose steroid treatment.

Case Presentation: A previously healthy 48-year-old female presented with confusion syndrome and impaired vigilance which had developed during a six-day trip to The Gambia. The condition rapidly worsened to a comatose state. Extensive search for infectious agents including a variety of tropical disease pathogens was unsuccessful. As encephalitic signs persisted despite of calculated antimicrobial and antiviral therapy, high-dose corticosteroids were applied intravenously based on the working diagnosis of an autoimmune encephalitis. The treatment did, however, not improve the patient's condition. Four days later, bihemispheric signal amplification in the insular and frontobasal cortex was observed on magnetic resonance imaging (MRI). The intracranial pressure rapidly increased and could not be controlled by conservative treatment. The patient died due to tonsillar herniation 21 days after onset of symptoms. Histological examination of postmortem brain tissue demonstrated a generalized lymphocytic meningoencephalitis. Immunohistochemical reactions against HSV-1/2 indicated an atypical manifestation of herpesviral encephalitis in brain tissue. Moreover, HSV-1 DNA was detected by a next-generation sequencing (NGS) metagenomics approach. Retrospective analysis of cerebrospinal fluid (CSF) and serum samples revealed HSV-1 DNA only in specimens one day ante mortem.

Conclusions: This case shows that standard high-dose steroid therapy can contribute to or possibly even trigger fulminant cerebral HSV reactivation in a critically ill patient. Thus, even if extensive laboratory diagnostics including wide-ranging search for infectious pathogens has been performed before and remained without results, continuous re-evaluation of potential differential diagnoses especially regarding opportunistic infections or reactivation of latent infections is of utmost importance, particularly if new symptoms occur.
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http://dx.doi.org/10.1186/s12879-020-4859-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029604PMC
February 2020

Case Report: Successful Treatment of a Patient with Microfilaremic Dirofilariasis Using Doxycycline.

Am J Trop Med Hyg 2020 04;102(4):844-846

Nationales Referenzzentrum für Tropische Infektionserreger, Bernhard-Nocht-Institut für Tropenmedizin, Hamburg, Germany.

We report the case of a 56-year-old woman with microfilaremic dirofilariasis due to , which is a very rare condition in humans. Of note, just one of six large-volume blood samples of this patient was positive for microfilariae. Polymerase chain reaction (PCR) and sequencing of the parasite gene determined the geographic origin of the causative helminth. The patient was treated successfully with doxycycline. This drug was chosen because of the patient's reluctance to the use of ivermectin and to provide an anthelmintic effect by targeting the bacterial endosymbiont present in most filarial species.
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http://dx.doi.org/10.4269/ajtmh.19-0744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7124902PMC
April 2020

Molecular detection of Rickettsia spp., Borrelia spp., Bartonella spp. and Yersinia pestis in ectoparasites of endemic and domestic animals in southwest Madagascar.

Acta Trop 2020 May 11;205:105339. Epub 2020 Jan 11.

Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.

Little is known about the presence of vector-borne bacteria in southwest Madagascar. Anthropogenic alteration of natural habitats represents an important driver for the emergence of new diseases. Especially the involvement of livestock and the involuntary maintaining of invasive synanthropic animals (particularly rats) facilitate disease transmission from wildlife to humans and associated animals and vice versa. The dissemination or acquisition of ectoparasites is most likely in regions where human/wildlife contact is increasing. Little is known about the presence of vector-borne bacteria in southwest Madagascar. In 2016 and 2017, ectoparasites were collected from various introduced (cattle and goats, cats, dogs and chicken, rats and mice) and native animal species (mouse lemurs [Microcebus griseorufus], Grandidier's mongooses [Galidictis grandidieri], bastard big-footed mice [Macrotarsomys bastardi], greater hedgehog tenrecs [Setifer setosus] and lesser hedgehog tenrecs [Echinops telfairi]) in the northern portion of Tsimanampetsotsa National Park and the adjacent littoral region. Thirteen species of blood-feeding ectoparasites (235 individuals of ticks [5 species], 414 lice [4 spp.] and 389 fleas [4 spp.]) were investigated for the presence and identity of rickettsiae, borreliae, bartonellae and Yersinia pestis using PCR techniques. Rickettsia spp. were detected in every single ectoparasite species (Amblyomma variegatum, A. chabaudi, Rhipicephalus microplus, Haemaphysalis simplex, Argas echinops, Ctenocephalides felis, Echidnophaga gallinacea, Pulex irritans, Xenopsylla cheopis, Haematopinus quadripertusus, Linognathus africanus, L. vituli, Lemurpediculus verruculosus). Lice and ticks were found harboring rickettsiae identified as Rickettsia africae, while Rickettsia felis-like bacteria were associated with fleas. Borrelia spp. were detected in 5% of H. simplex and 1% of R. microplus ticks. Bartonella spp. were detected in 40% of H. quadripertusus pools and in 5% of L. verruculosus pools. Y. pestis was detected in X. cheopis and E. gallinacea fleas collected from a rat. This study presents the detection of a broad spectrum of vector-borne bacteria including potential pathogens, and an unexpected finding of Y. pestis far off the known plague foci in Madagascar.
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http://dx.doi.org/10.1016/j.actatropica.2020.105339DOI Listing
May 2020

Zoonotic spillover infections with Borna disease virus 1 leading to fatal human encephalitis, 1999-2019: an epidemiological investigation.

Lancet Infect Dis 2020 04 7;20(4):467-477. Epub 2020 Jan 7.

Department of Neuropathology, Technical University of Munich, Munich, Germany.

Background: In 2018-19, Borna disease virus 1 (BoDV-1), the causative agent of Borna disease in horses, sheep, and other domestic mammals, was reported in five human patients with severe to fatal encephalitis in Germany. However, information on case frequencies, clinical courses, and detailed epidemiological analyses are still lacking. We report the occurrence of BoDV-1-associated encephalitis in cases submitted to the Institute of Clinical Microbiology and Hygiene, Regensburg University Hospital, Regensburg, Germany, and provide a detailed description of newly identified cases of BoDV-1-induced encephalitis.

Methods: All brain tissues from 56 encephalitis cases from Bavaria, Germany, of putative viral origin (1999-2019), which had been submitted for virological testing upon request of the attending clinician and stored for stepwise diagnostic procedure, were systematically screened for BoDV-1 RNA. Two additional BoDV-1-positive cases were contributed by other diagnostic centres. Positive results were confirmed by deep sequencing, antigen detection, and determination of BoDV-1-reactive antibodies in serum and cerebrospinal fluid. Clinical and epidemiological data from infected patients were collected and analysed.

Findings: BoDV-1 RNA and bornavirus-reactive antibodies were detected in eight newly analysed encephalitis cases and the first human BoDV-1 isolate was obtained from an unequivocally confirmed human BoDV-1 infection from the endemic area. Six of the eight BoDV-1-positive patients had no record of immunosuppression before the onset of fatal disease, whereas two were immunocompromised after solid organ transplantation. Typical initial symptoms were headache, fever, and confusion, followed by various neurological signs, deep coma, and severe brainstem involvement. Seven of nine patients with fatal encephalitis of unclear cause were BoDV-1 positive within one diagnostic centre. BoDV-1 sequence information and epidemiological analyses indicated independent spillover transmissions most likely from the local wild animal reservoir.

Interpretation: BoDV-1 infection has to be considered as a potentially lethal zoonosis in endemic regions with reported spillover infections in horses and sheep. BoDV-1 infection can result in fatal encephalitis in immunocompromised and apparently healthy people. Consequently, all severe encephalitis cases of unclear cause should be tested for bornaviruses especially in endemic regions.

Funding: German Federal Ministry of Education and Research.
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http://dx.doi.org/10.1016/S1473-3099(19)30546-8DOI Listing
April 2020

Case Report: Eye Infection: The First Human Case in Germany.

Am J Trop Med Hyg 2020 02;102(2):350-351

Department of Ophthalmology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.

eye worm is a nematode transmitted by drosophilid flies not only primarily to carnivores and lagomorphs but also to humans. Only a few cases have been reported in Europe (Italy, France, and Portugal). Here, we report the first eye infection in a German patient.
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http://dx.doi.org/10.4269/ajtmh.19-0483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7008349PMC
February 2020

Low prevalence of Borna disease virus 1 (BoDV-1) IgG antibodies in humans from areas endemic for animal Borna disease of Southern Germany.

Sci Rep 2019 12 27;9(1):20154. Epub 2019 Dec 27.

Robert Koch-Institut, Berlin, Germany.

Borna disease virus-1 (BoDV-1) was recently discovered as cause of severe and often fatal encephalitis in humans. BoDV-1 is known to cause neurological disease in horses and sheep mainly in South and Central Germany. The virus is maintained in bicolored white-toothed shrews (Crocidura leucodon). The incidence of infection and risk factors in humans are completely unresolved. Veterinarians may be disproportionally BoDV-1-exposed through contact to animals not recognized to be BoDV-1 infected. We conducted three serosurveys predominantly in endemic areas of South Germany for the presence of BoDV-1-reactive antibodies. Anonymized residual samples from two serosurveys of veterinarians (n = 736) with interview data on exposures and one serosurvey among blood donors (n = 373) were screened with an indirect immunofluorescence antibody test, followed by a newly developed immunoblot as confirmatory assay. One serum from a 55-59-year-old veterinarian who worked in an animal practice and as a meat inspector but none from blood donors tested positive by the screening and confirmatory assays. We show that seropositive individuals are rare even in areas with highest zoonotic risk and in a group with potentially elevated exposure risk. In light of the low seroprevalence demonstrated here, the high case-fatality rate in clinically observed human BoDV-1 infections is even more impressive.
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http://dx.doi.org/10.1038/s41598-019-56839-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6934520PMC
December 2019

Two cases of airport-associated falciparum malaria in Frankfurt am Main, Germany, October 2019.

Euro Surveill 2019 Dec;24(49)

These authors contributed equally to this work and share last authorship.

Two cases of presumably airport-acquired falciparum malaria were diagnosed in Frankfurt in October 2019. They were associated with occupation at the airport, and parasites from their blood showed genetically identical microsatellite and allele patterns. Both had severe malaria. It took more than a week before the diagnosis was made. If symptoms are indicative and there is a plausible exposure, malaria should be considered even if patients have not travelled to an endemic area.
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http://dx.doi.org/10.2807/1560-7917.ES.2019.24.49.1900691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6905295PMC
December 2019

Complex Cytokine Responses in Imported Scrub Typhus Cases, Germany, 2010-2018.

Am J Trop Med Hyg 2020 01;102(1):63-68

National Reference Center for Tropical Pathogens, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.

Scrub typhus is a life-threatening zoonotic disease, which is caused by , an obligatory intracellular Gram-negative bacterium. It is transmitted by mites in endemic regions of Southeast Asia. So far, data on imported scrub typhus cases to non-endemic areas and immunological descriptions are rare. Eleven scrub typhus cases that had been diagnosed by the German National Reference Center for Tropical Pathogens between 2010 and 2018 were retrospectively reviewed for clinical symptoms, laboratory changes, and travel destinations. Patient sera were included if follow-up samples showed simultaneous seroconversion for IgM and IgG antibody responses by immunofluorescence assays or concurrence with the first serum sample. The median of seroconversion was week 2 after symptom onset. Cytokine levels were measured over time, demonstrating simultaneously upregulated major Th1, Th2, and Th17 cytokines in the acute phase of infection followed by normalization during convalescence. This study underlines the complex mixed cytokine response elicited by scrub typhus and highlights clinical and diagnostic aspects of imported infections with .
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http://dx.doi.org/10.4269/ajtmh.19-0498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947778PMC
January 2020

Immunopathology of Fatal Human Variegated Squirrel Bornavirus 1 Encephalitis, Germany, 2011-2013.

Emerg Infect Dis 2019 06;25(6):1058-1065

Variegated squirrel bornavirus 1 (VSBV-1) is a zoonotic virus that causes fatal encephalitis in humans who are infected after contact with exotic squirrels. We analyzed the brain lesions and the immune responses in all 4 known human cases that showed panencephalitis. Inflammatory infiltrates in areas positive for VSBV-1 RNA and antigen consisted of CD4+ and CD8+ T cells, with perivascular B-cell accumulation. Strong microglial response and bizarre astroglial expansion were present. Areas of malacia contained neutrophils and foamy microglia and macrophages. Immunopathologic examination during infection showed cleavage of caspase 3 in brain cells adjacent to CD8+ cells and widespread p53 expression, hallmarks of apoptosis. Cerebrospinal fluid analyses over time demonstrated increasing protein concentrations and cell counts, paralleled by pathologic lactate elevations in all patients. The most severe cerebrospinal fluid and histologic changes occurred in the patient with the highest viral load, shortest duration of disease, and most medical preconditions.
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http://dx.doi.org/10.3201/eid2506.181082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6537742PMC
June 2019

Ectoparasites of endemic and domestic animals in southwest Madagascar.

Acta Trop 2019 Aug 10;196:83-92. Epub 2019 May 10.

Bundeswehr Hospital Hamburg, Tropical Microbiology and Entomology Branch, Bernhard-Nocht-Strasse 74, 20359, Hamburg, Germany. Electronic address:

Human encroachment of natural habitats bears the threat of disease transmission between native and introduced species that had not come into contact before, thus promoting the spread of new diseases in both directions. This is a matter of concern especially in areas where human-wildlife contact has not been intense in the recent past. In southwest Madagascar, we collected ectoparasites from various mammalian hosts and chicken, and examined their host preferences and their prevalence in relation to season and habitat degradation. Field-work took place in the northern portion of Tsimanampetsotsa National Park and the adjacent coastal strip (littoral) in the dry and in the rainy season of 2016/2017. Endemic mammals were trapped with live traps placed in habitats of different degrees of degradation: 1) relatively pristine forest, 2) degraded forest, 3) cultivated and shrub land. Rats and mice were also trapped in 4) villages. We identified 17 species of ectoparasites (296 individuals of ticks [5 species], 535 lice [7 spp.], 389 fleas [4 spp.] and 13 mites [1 sp.]) collected from 15 host species. There was no indication for seasonal or habitat effects on parasite infection. A large portion of the parasites was host-specific. Some ectoparasite species were shared either by several endemic or by several introduced species, but apart from the introduced flea species Echidnophaga gallinacea (collected from six different hosts including the endemic carnivore Galidictis grandidieri) no other ectoparasite species was shared between endemic and introduced host species.
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http://dx.doi.org/10.1016/j.actatropica.2019.05.008DOI Listing
August 2019

Serum cytokine and chemokine changes during Toscana virus meningitis.

Med Microbiol Immunol 2019 Dec 11;208(6):727-730. Epub 2019 Apr 11.

Bernhard Nocht Institute for Tropical Medicine, Bernhard-Nocht-Str. 74, 20359, Hamburg, Germany.

Toscana virus is an important arbovirus causing meningitis and meningoencephalitis in countries around the Mediterranean Sea. While the clinical syndrome and laboratory diagnostic procedures have been well described, less is known about the immune response in Toscana virus meningitis and a possible use of cytokine and chemokine changes for the clinical follow-up of patients. We here characterized serum cytokine and chemokine profiles from 37 patients during the acute and convalescent phase of the infection. Only few serum cytokine/chemokine changes were detected during Toscana virus meningitis. Markedly increased concentrations of IP-10, interferon-α, IL-22, and eotaxin were found in the acute phase. Levels of interferon-α, IL-22, and eotaxin remained elevated in the convalescent phase, but decreased concentrations of GM-CSF were detected.
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http://dx.doi.org/10.1007/s00430-019-00611-yDOI Listing
December 2019
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