Sabine Diedrich

Robert Koch Institut, Berlín, Berlin, Germany

Are you Sabine Diedrich?

Claim your profile

Publications (45)109.5 Total impact

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Infectious and inflammatory diseases of the central nervous system are difficult to identify early. Case definitions for aseptic meningitis, encephalitis, myelitis, and acute disseminated encephalomyelitis (ADEM) are available, but rarely put to use. The VACC-Tool (Vienna Vaccine Safety Initiative Automated Case Classification-Tool) is a mobile application enabling immediate case ascertainment based on consensus criteria at the point-of-care. The VACC-Tool was validated in a quality management program in collaboration with the Robert-Koch-Institute. Results were compared to ICD-10 coding and retrospective analysis of electronic health records using the same case criteria. Of 68,921 patients attending the emergency room in 10/2010–06/2013, 11,575 were hospitalized, with 521 eligible patients (mean age: 7.6years) entering the quality management program. Using the VACC-Tool at the point-of-care, 180/521 cases were classified successfully and 194/521 ruled out with certainty. Of the 180 confirmed cases, 116 had been missed by ICD-10 coding, 38 misclassified. By retrospective application of the same case criteria, 33 cases were missed. Encephalitis and ADEM cases were most likely missed or misclassified. The VACC-Tool enables physicians to ask the right questions at the right time, thereby classifying cases consistently and accurately, facilitating translational research. Future applications will alert physicians when additional diagnostic procedures are required.
    Preview · Article · Jan 2016 · EBioMedicine
  • Source

    Preview · Article · Oct 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Abstract BACKGROUND: In August and September 2014, unexpected clusters of enterovirus-D68 (EV-D68) infections associated with severe respiratory disease emerged from North-America. In September, the European Centre for Disease Prevention and Control (ECDC) asked European countries to strengthen respiratory sample screening for enterovirus detection and typing in cases with severe respiratory presentations. OBJECTIVES: To provide a detailed picture of EV-D68 epidemiology in Europe by conducting a retrospective and prospective laboratory analysis of clinical specimens. STUDY DESIGN: An initiative supported by the European Society for Clinical Virology (ESCV) and ECDC was launched to screen for EV-D68 in respiratory specimens between July 1st and December 1st 2014 in Europe and to sequence the VP1 region of detected viruses for phylogenetic analytic purposes. RESULTS: Forty-two institutes, representing 51 laboratories from 17 European countries, analyzed 17,248 specimens yielding 389 EV-D68 positive samples (2.26%) in 14 countries. The proportion of positive samples ranged between 0 and 25% per country. These infections resulted primarily in mild respiratory disease, mainly detected in young children presenting with wheezing and in immuno-compromised adults. The viruses detected in Europe are genetically very similar to those of the North-American epidemic and the majority (83%) could be assigned to clade B. Except for 3 acute flaccid paralysis (AFP) cases, one death and limited ICU admissions, no severe cases were reported. CONCLUSIONS: The European study showed that EV-D68 circulated in Europe during summer and fall of 2014 with a moderate disease burden and different pathogenic profile compared to the North-American epidemic. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.
    Full-text · Article · Oct 2015 · Journal of Clinical Virology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Acute disseminated encephalomyelitis (ADEM) is an inflammatory, demyelinating disease occurring several weeks after viral infection. Enteroviruses have been described as potential triggers of ADEM, but the closely related parechoviruses have not. The objective of the study is to assess the prevalence and disease presentation of ADEM after parechovirus infection in a syndromic surveillance program for pediatric infection/inflammation of the central nervous system (CNS). Methods: The surveillance was conducted at the Charité Department of Pediatrics in Berlin, Germany, from November 2010 to November 2014. All hospitalized children meeting predefined case criteria underwent highly standardized prospective clinical assessments based on the published case definitions, including for ADEM. Stool samples were independently analyzed by enterovirus and parechovirus real-time polymerase chain reaction at the Robert Koch Institute. Results: Of 105,557 patients screened, 774 (0.7%) fulfilled entry criteria for CNS infection/inflammation, with 114 cases ascertained as ADEM. Parechoviruses were detected in 2.5% of patients with CNS infection/inflammation, including 1 case fulfilling ADEM case criteria with the highest level of diagnostic certainty. Conclusions: We report a first case of ADEM after parechovirus infection in a 5-year-old female presenting with acute hemiparesis 2 weeks after a respiratory illness. Parechovirus disease should be included in the differential diagnosis of ADEM.
    No preview · Article · Sep 2015 · The Pediatric Infectious Disease Journal
  • [Show abstract] [Hide abstract]
    ABSTRACT: Germany is a partner of the Global Polio Eradication Initiative. Assurance of polio free status is based on enterovirus surveillance, which focuses on patients with signs of acute flaccid paralysis or aseptic meningitis/encephalitis, representing the key symptoms of poliovirus infection. In response to the wild poliovirus outbreak in Syria 2013 and high number of refugees coming from Syria to Germany, stool samples from 629 Syrian refugees/asylum seekers aged <3 years were screened for wild poliovirus between November 2013 and April 2014. Ninety-three samples (14.8%) were positive in an enterovirus specific PCR. Of these, 12 contained Sabin-like polioviruses. The remaining 81 samples were characterized as non-polio enteroviruses representing several members of groups A-C as well as rhinovirus. Wild-type poliovirus was not detected via stool screening involving molecular and virological methods, indicating a very low risk for the importation by Syrian refugees and asylum seekers at that time. Copyright © 2015 Elsevier GmbH. All rights reserved.
    No preview · Article · Aug 2015 · International journal of medical microbiology: IJMM
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Enterovirus 71 (EV-71) is involved in epidemics of hand, foot, and mouth disease (HFMD) and has been reported to occur with severe neurological complications in eastern and south-east Asia. In other geographical areas, the transmission of this virus is poorly understood. We used large sequence datasets (of the gene encoding the viral protein 1, VP1) and a Bayesian phylogenetic approach to compare the molecular epidemiology and geographical spread patterns of EV-71 subgenogroups B4, B5, C1, C2, and C4 in Europe relative to other parts of the world. For the study, European countries considered were European Union (EU) Member States and Iceland, Norway and Switzerland. Viruses of the B4, B5, and C4 subgenogroups circulate mainly in eastern and south-east Asia. In Europe sporadic introductions of these subgenogroups are observed, however C1 and C2 viruses predominate. The phylogenies showed evidence of multiple events of spread involving C1 and C2 viruses within Europe since the mid-1990s. Two waves of sporadic C2 infections also occurred in 2010 and 2013. The 2007 Dutch outbreak caused by C2 and the occurrence of B5 and C4 infections in the EU between 2004 and 2013 arose while the circulation of C1 viruses was low. A transmission chain involving a C4 virus was traced from Japan to the EU and then further to Canada between 2001 and 2006. Recent events whereby spread of viruses have occurred from, to, and within Europe appear to be involved in the long term survival of EV-71, highlighting the need for enhanced surveillance of this virus. © 2015, European Centre for Disease Prevention and Control (ECDC). All Rights Reserved.
    Full-text · Article · Aug 2015 · European communicable disease bulletin
  • [Show abstract] [Hide abstract]
    ABSTRACT: Systematicinvestigations assessing the clinical impact of human parechovirus(HPeV) disease are sparse. Non-invasive stool samples may be useful for targeted hospital-based surveillance. In the context of a quality-management program, all hospitalized children fulfilling predefined case criteria for CNS infection/inflammation underwent standardized neurologic examinations. Stool samples were collected for human parechovirus(HPeV) and enterovirus (EV) PCR and molecular typing at the National Reference Center. From 10/2010 to 12/2012, stool samples of 284 patients with suspected CNS infection/inflammation were tested yielding 12 (4.2%) HPeV+ samples and 43 (15.1%) EV+ samples.HPeV positive samples included HPeV-1, HPeV-3, and HPeV-6. No additional pathogens were identified in routine care.HPeV-positive patients were significantly younger (p<0.001) and more likely to present with seizures (p=0.001) and rash (p<0.0001)when compared withHPeV negative patients. In hospitalized children <4yrs of age presenting with suspected CNS infection/inflammation, seizures and/or rash, HPeV should be considered in the differential diagnosis. Large-scale public health surveillance may be indicated.
    No preview · Article · Jul 2015 · The Pediatric Infectious Disease Journal
  • [Show abstract] [Hide abstract]
    ABSTRACT: We used physician sentinel surveillance to identify 25 (7.7%) mild to severe infections with enterovirus D68 (EV-D68) in children and adults among 325 outpatients with acute respiratory infections in Germany during August-October 2014. Results suggested low-level circulation of enterovirus D68 in Germany. Viruses were characterized by sequencing viral protein (VP) 1 and VP4/VP2 genomic regions.
    No preview · Article · May 2015 · Emerging Infectious Diseases
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In 2010, a large outbreak of poliomyelitis with unusual 47% lethality occurred in Pointe Noire, Republic of Congo. Vaccine-mediated immunity against the outbreak virus was never investigated. A wild poliovirus 1 (WPV1) isolated from a fatal case (termed PV1-RC2010) showed a previously unknown combination of amino acid exchanges in critical antigenic site 2 (AgS2, VP1 capsid protein positions 221SAAL→221PADL). These exchanges were also detected in an additional 11 WPV1 strains from fatal cases. PV1-RC2010 escaped neutralization by three different mAbs relevant for AgS2. Virus neutralization was tested in sera from fatal cases, who died before supplementary immunization (n = 24), Gabonese recipients of recent oral polio vaccination (n = 12), routinely vaccinated German medical students (n = 34), and German outpatients tested for antipoliovirus immunity (n = 17) on Vero, human rhabdomyosarcoma, and human epidermoid carcinoma 2 cells. Fatal poliomyelitis cases gave laboratory evidence of previous trivalent vaccination. Neutralizing antibody titers against PV1-RC2010 were significantly lower than those against the vaccine strain Sabin-1, two genetically distinct WPV1s isolated in 1965 and 2010 and two genetically distinct vaccine-derived PV strains. Of German vaccinees tested according to World Health Organization protocols, 15-29% were unprotected according to their neutralization titers (<1:8 serum dilution), even though all were protected against Sabin-1. Phylogenetic analysis of the WPV1 outbreak strains suggested a recent introduction of virus progenitors from Asia with formation of separate Angolan and Congolese lineages. Only the latter carried both critical AgS2 mutations. Antigenetically variant PVs may become relevant during the final phase of poliomyelitis eradication in populations with predominantly vaccine-derived immunity. Sustained vaccination coverage and clinical and environmental surveillance will be necessary.
    Full-text · Article · Aug 2014 · Proceedings of the National Academy of Sciences
  • Source
    L Kuryk · M Wieczorek · S Diedrich · S Böttcher · A Witek · B Litwińska
    [Show abstract] [Hide abstract]
    ABSTRACT: The study describes genetic characterization of poliovirus (PV) strains isolated from sewage samples in Poland. The analyses were performed for the detection of any putative polio revertants and recombinants in three genomic regions by sequencing analysis. Thirty-six strains were analyzed. The analyzed strains were identified by neutralization assay as 7 strains of serotype P1, 10 strains of serotype P2, and 19 strains of serotype P3. Sewage isolates were sequenced in 5'UTR, VP1, and 3D genomic regions. All detected PVs were classified as vaccine strains on the basis of VP1 sequence. Mutational differences in the VP1 sequences of isolated viruses ranged from 0.0% to 0.4%, indicating a limited replication period. The genetic analysis of the 3D region showed that some strains have recombinant genomes. Nine strains were found as dipartite recombinants (seven strains-S3/S2, one strain-S2/S1, one strain-S3/S1), while one strain was found as tripartite recombinant (S3/S2/S1). No recombinants with non-PV enteroviruses were identified. None of wild-type PVs or vaccine-derived polioviruses (VDPVs) were detected. This study showed the absence of wild or VDPV circulation in the country and demonstrated the usefulness of environmental surveillance in addition to acute flaccid paralysis (AFP) surveillance in support of polio eradication initiatives. J. Med. Virol. © 2013 Wiley Periodicals, Inc.
    Full-text · Article · Jul 2014 · Journal of Medical Virology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Introduction Enteroviruses commonly encounter babies and children and infections present in a wide variety of symptoms ranging from asymptomatic infection, benign illness, and aseptic meningitis, hand-foot-and-mouth disease to severe life-threatening disease. Some newborns develop severe disease in the first 2 weeks of life and long-term sequelae may occur among survivors. Case presentation We present a case report of a Caucasian newborn baby boy with severe encephalitis and systemic coxsackievirus B3 infection. The coincidence of maternal infection as well as previous mild respiratory illness in his sister suggests either prenatal or horizontal postnatal transmission. An electroencephalogram showed a severe pathologic pattern with theta-delta-rhythm and spike-wave complexes on both hemispheres. We also observed an unusual prolonged viremia for a period of 6 weeks. Due to the lack of specific antiviral treatment options, the supportive management included ventilation and medical treatment of seizures. Phylogenetic analysis revealed a genogroup D2 virus previously exclusively detected in China and now described in Europe for the first time. Conclusions Enteroviral infection is an important differential diagnosis in neonatal encephalitis. Prolonged viremia must be taken into account and might correlate with disease severity. The newly observed enterovirus genotype D2 is spreading from Asia to other continents.
    Full-text · Article · May 2014 · Journal of Medical Case Reports
  • [Show abstract] [Hide abstract]
    ABSTRACT: Source: http://espid2015.kenes.com/PublishingImages/scientific-information/espid-abstracts/ESPID%202014%20abstracts.pdf Background and Aims: Human Parechovirus (HPeV) infections may cause a variety of clinical symptoms in children, but syndromic surveillance data are currently lacking. This study aims to assess HPeV-associated disease burden in infants and children with CNS-infection.Methods : The study was conducted in the context of a Quality Management Program at the Charité Department of Paediatrics. For detection of HPeV and molecular typing, stool samples were analysed at the National Reference Centre for Poliomyelitis and enteroviruses at the Robert Koch Institute in Berlin, Germany. Results: A 5 year-old Caucasian female resented with fatigue, acute hemiparesis/hyporeflexia and central facial paresis, recent febrile illness and PeV-positive stool, but no recent immunisations. CSF-analysis revealed 7 leukocytes (98% lymphocytes), negative bacterial and viral cultures, and oligoclonal IgG-bands. Multiple demyelinising lesions consistent with ADEM were confirmed by MRI and brain biopsy. The patient received high-dose i.v. methylprednisolone ollowed by oral prednisolone for three months. The patient recovered clinically, but ADEM lesions persisted up to six months after disease onset. Syndromic surveillance from 10/2010-12/2012 resulted in 284 paediatric cases of CNS-infection/inflammation. Of these, twelve cases (4.2%) showed RT-PCR-confirmed HPeV-infection with no alternative pathogen detected in routine care. HPeV-infection was significantly associated with age 1-4 years, seizures and rash (RR (95% CI) = 2.12(1.26-3.54), 2.16(1.39-3.34) and 4.25(2.21-8.16), P = 0.004, 0.001 and <0.0001, respectively).Conclusions : In hospitalised children, HPeV- infection may be associated with significant CNS disease, including post-infectious ADEM. In children <4 ears presenting with acute seizures and rash, HPeV should be included in the differential diagnosis.
    No preview · Conference Paper · May 2014
  • Source

    Full-text · Dataset · Mar 2014
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to gain insights into the tempo and mode of the evolutionary processes that sustain genetic diversity in coxsackievirus B5 (CVB5) and into the interplay with virus transmission. We estimated phylodynamic patterns with a large sample of virus strains collected in Europe with Bayesian statistical methods, reconstructed ancestral states of genealogical nodes, and tested for selection. The genealogies estimated with the structural 1D(VP1) and nonstructural 3CD loci allowed a precise description of lineages over time and co-circulating virus populations within the two CVB5 clades, genogroups A and B. Strong negative selection shaped the evolution of both loci but compelling phylogenetic data suggested that immune selection pressure resulted in the emergence of the two genogroups with opposed evolutionary pathways. The genogroups also differed in the temporal occurrence of the amino acid changes. The virus strains of genogroup A were characterized by sequential acquisition of nonsynonymous changes in residues exposed at the virus 5-fold axis. The genogroup B viruses were marked by selection of three changes in a different domain (VP1 C-terminus) during its early emergence. These external changes resulted in a selective sweep, which was followed by an evolutionary stasis still ongoing after 50 years. The inferred virus population history of CVB5 showed an alternation of the prevailing genogroup during meningitis epidemics across Europe and is interpreted as a consequence of partial cross-immunity.
    Full-text · Article · Sep 2013 · Journal of Virology
  • Source

    Full-text · Article · Dec 2012 · Expert Review of Vaccines
  • K Neubauer · K Beyrer · S Böttcher · S Diedrich

    No preview · Article · Mar 2012 · Das Gesundheitswesen
  • [Show abstract] [Hide abstract]
    ABSTRACT: Benign acute childhood myositis (BACM) is a rare syndrome associated with various viral infections. Bilateral calve pain may lead to inability to walk. During winter 2007/2008, we investigated a nationwide outbreak of influenza-associated BACM (IA-BACM) to identify etiologic (sub)type, describe the course of disease, and explore how well the syndrome is known among physicians. We performed retrospective and prospective case finding in all German federal states. Physicians returned patient-based questionnaires containing information about sex, age, disease progression, patient-management, and number of BACM cases treated previously. We compared IA-BACM cases with influenza cases from the German virologic sentinel surveillance system for influenza. We investigated 219 children with IA-BACM. They coincided with the curve of influenza B of the German virologic sentinel surveillance system for influenza. Median age was 7 years, 74% (160/216) of cases were male, median time between the onset of fever and onset of BACM-symptoms was 3 days lasting for a median of 4 days. Almost half of the affected children had presented at hospitals. One case with beginning renal impairment occurred, but the patient recovered completely. Most reporting physicians had not seen BACM-patients previously. Multivariable analysis showed IA-BACM's strong association with influenza B, male sex, and age between 6 and 9 years. Influenza B caused a large BACM outbreak in Germany. Onset of BACM symptoms followed shortly after the onset of influenza symptoms. The course of this disease was almost exclusively mild and self-limiting. Diagnosis of this rare but distinct clinical entity by the alert physician can spare the patient potentially unneeded invasive testing and hospital admission.
    No preview · Article · Aug 2011 · The Pediatric Infectious Disease Journal
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: EuroRotaNet, a laboratory network, was established in order to determine the diversity of co-circulating rotavirus strains in Europe over three or more rotavirus seasons from 2006/2007 and currently includes 16 countries. This report highlights the tremendous diversity of rotavirus strains co-circulating in the European population during three years of surveillance since 2006/2007 and points to the possible origins of these strains including genetic reassortment and interspecies transmission. Furthermore, the ability of the network to identify strains circulating with an incidence of ≥1% allowed the identification of possible emerging strains such as G8 and G12 since the beginning of the study; analysis of recent data indicates their increased incidence. The introduction of universal rotavirus vaccination in at least two of the participating countries, and partial vaccine coverage in some others may provide data on diversity driven by vaccine introduction and possible strain replacement in Europe.
    Full-text · Article · Jun 2011 · Epidemiology and Infection
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In October 2007, the working group CEN/TC 216 of the European Committee for standardisation suggested that the Sabin oral poliovirus vaccine type 1 strain (LSc-2ab) presently used for virucidal tests should be replaced by another attenuated vaccine poliovirus type 1 strain, CHAT. Both strains were historically used as oral vaccines, but the Sabin type 1 strain was acknowledged to be more attenuated. In Germany, vaccination against poliomyelitis was introduced in 1962 using the oral polio vaccine (OPV) containing Sabin strain LSc-2ab. The vaccination schedule was changed from OPV to an inactivated polio vaccine (IPV) containing wild polio virus type 1 strain Mahoney in 1998. In the present study, we assessed potential differences in neutralising antibody titres to Sabin and CHAT in persons with a history of either OPV, IPV, or OPV with IPV booster. Neutralisation poliovirus antibodies against CHAT and Sabin 1 were measured in sera of 41 adults vaccinated with OPV. Additionally, sera from 28 children less than 10 years of age and immunised with IPV only were analysed. The neutralisation assay against poliovirus was performed according to WHO guidelines. The neutralisation activity against CHAT in adults with OPV vaccination history was significantly lower than against Sabin poliovirus type 1 strains (Wilcoxon signed-rank test P < 0.025). In eight sera, the antibody titres measured against CHAT were less than 8, although the titre against Sabin 1 varied between 8 and 64. Following IPV booster, anti-CHAT antibodies increased rapidly in sera of CHAT-negative adults with OPV history. Sera from children with IPV history neutralised CHAT and Sabin 1 strains equally. The lack of neutralising antibodies against the CHAT strain in persons vaccinated with OPV might be associated with an increased risk of reinfection with the CHAT polio virus type 1, and this implies a putative risk of transmission of the virus to polio-free communities. We strongly suggest that laboratory workers who were immunised with OPV receive a booster vaccination with IPV before handling CHAT in the laboratory.
    Full-text · Article · Dec 2010 · BMC Infectious Diseases
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Human enterovirus 71 (EV-71) is a cause of seasonal epidemics of hand, foot and mouth disease, and of less common but severe neurological manifestations. Uncertainty persists regarding the circulation of virus populations in several geographical areas and the timescale of their dissemination. We determined EV-71 sequences at loci 1D (VP1 capsid protein) and 3CD (non-structural proteins) in 86 strains recovered in Austria, France and Germany and performed an evolutionary genetic study of extant virus populations. Phylogenetic analyses positioned 78 of the 86 sequences within two clades among subgenogroups C1 and C2. A minor sequence cluster was assigned to subgenogroup C4. Analyses incorporating the available sequences estimated the substitution rate in genogroup C at 3.66 x 10(-3) and 4.46 x 10(-3) substitutions per site year(-1) for loci 1D and 3CD, respectively, assuming a relaxed molecular-clock model for sequence evolution. Most of the 'European' strains belonged to clades C1b and C2b, which originated in 1994 [95 % confidence interval (CI), 1992.7-1995.8] and 2002 (95 % CI, 2001.6-2003.8), respectively. Estimates of divergence times for locus 3CD were consistent with those measured for locus 1D. Intertwining between clades representing EV-71 subgenogroups and clades corresponding to other enterovirus types (notably early coxsackievirus A prototype strains) in the 3CD phylogeny is highly indicative of ancestral recombination events. Incongruent phylogenetic patterns estimated for loci 1D and 3CD show that a single tree cannot model the epidemic history of circulating EV-71 populations. The evolutionary timescale of genogroup C estimated for both loci was measured only in decades, indicating recent dissemination.
    Full-text · Article · Sep 2010 · Journal of General Virology