M Frosch

Publications of M Frosch

• Molecular typing methods for outbreak detection and surveillance of invasive disease caused by Neisseria meningitidis, Haemophilus influenzae and Streptococcus pneumoniae, a review.

  Authors: Odile B Harrison, Angela B Brueggemann, Dominique A Caugant, Arie van der Ende, Matthias Frosch, Stephen Gray, Sigrid Heuberger, Paula Krizova, Per Olcen, Mary Slack, Muhamed-Kheir Taha, Martin C J Maiden

  Microbiology (Reading, England). 05/2011; 157(Pt 8):2181-95.

  Invasive disease caused by the encapsulated bacteria Neisseria meningitidis, Haemophilus influenzae and Streptococcus pneumoniae remains an important cause of morbidity and mortality worldwide,Invasive disease caused by the encapsulated bacteria Neisseria meningitidis, Haemophilus influenzae and Streptococcus pneumoniae remains an important cause of morbidity and mortality worldwide, despite the introduction of successful conjugate polysaccharide vaccines that target disease-associated strains. In addition, resistance, or more accurately reduced susceptibility, to therapeutic antibiotics is spreading in populations of these organisms. There is therefore a continuing requirement for the surveillance of vaccine and non-vaccine antigens and antibiotic susceptibilities among isolates from invasive disease, which is only partially met by conventional methods. This need can be met with molecular and especially nucleotide sequence-based typing methods, which are fully developed in the case of N. meningitidis and which could be more widely deployed in clinical laboratories for S. pneumoniae and H. influenzae.

• Evaluation of the VITEK 2 AST-N111 card for detection of extended-spectrum beta-lactamases (ESBLs) in Escherichia coli, Klebsiella pneumoniae, and Klebsiella oxytoca compared to ESBL Etests and combination disk methods.

  Authors: G Valenza, S Müller, C Schmitt, D Turnwald, T-T Lam, M Frosch, M Abele-Horn, Y Pfeifer

  European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology. 01/2011; 30(7):869-72.

  The VITEK 2 AST-N111 card was evaluated for detection of extended-spectrum beta-lactamases (ESBLs) by testing 51 ESBL positive and 50 ESBL negative isolates of E. coli, K. pneumoniae, and K. oxytoca.The VITEK 2 AST-N111 card was evaluated for detection of extended-spectrum beta-lactamases (ESBLs) by testing 51 ESBL positive and 50 ESBL negative isolates of E. coli, K. pneumoniae, and K. oxytoca. The occurrence of beta-lactamase genes was confirmed by PCR and sequencing. The advanced expert system (AES) of the VITEK 2 system achieved sensitivity and specificity values of 100% and 96.0%, respectively. The ESBL test of the VITEK 2 AST-N111 card showed a sensitivity of 92.1% and a specificity of 90.0%. Contradictory results obtained with the two VITEK 2 tools could be clarified by combination disk tests in nine of 11 isolates. The combined use of AES and ESBL tests of the AST-N111 card in association with combination disk tests in case of contradictory results seems to be a reliable method for ESBL detection.

• New diagnostic PCR for Haemophilus influenzae serotype e based on the cap locus of strain ATCC 8142

  Authors: T.T. Lam, J. Elias, M. Frosch, U. VOGEL, H. Claus

  Int.J.Med.Microbiol. 10/2010;

  A new PCR protocol for molecular typing of Haemophilus influenzae serotype e (Hie) was developed. To this end, the sequence of the cap region II of Hie strain ATCC8142 was identified, which was >99%A new PCR protocol for molecular typing of Haemophilus influenzae serotype e (Hie) was developed. To this end, the sequence of the cap region II of Hie strain ATCC8142 was identified, which was >99% identical to the recently published sequence of Hie isolate 274. The PCR using primer pair TTL63/TTL64 amplifies an internal 592-bp fragment of ecs4, an e-specific capsule synthesis gene, in 40 of 40 Hie strains. Of all non-Hie strains, there were no false positives. False-negative results of the PCR proposed by Falla et al. (1994) are explained by single nucleotide insertions in the primer sequences

• Comparison of two interferon-gamma release assays and tuberculin skin test for detecting latent tuberculosis in patients with immune-mediated inflammatory diseases.

  Authors: S Kleinert, O Kurzai, J Elias, K Marten, C Engelke, M Feuchtenberger, J Sandstede, M Frosch, H-P Tony, C Kneitz

  Annals of the rheumatic diseases. 02/2010; 69(4):782-4.

• Banding pattern indicative of echinococcosis in a commercial cysticercosis Western blot.

  Authors: Dennis Tappe, B Grüner, P Kern, M Frosch

  European journal of medical research. 09/2009; 14(10):451-2.

  Objective: A commercial cysticercosis Western blot was evaluated for serological cross-reactivity of sera from patients with alveolar (AE) and cystic echinococcosis (CE). - Methods: A total of 161Objective: A commercial cysticercosis Western blot was evaluated for serological cross-reactivity of sera from patients with alveolar (AE) and cystic echinococcosis (CE). - Methods: A total of 161 sera were examined, including 31 sera from AE-patients, 11 sera from CE- patients, 9 sera from patients with other parasitic diseases and 109 sera from patients with unrelated medical conditions. All AE- and CE-sera were also examined by the echinococcosis Western blot. - Results: More sera from patients with AE than with CE showed cross-reactivity in the form of ladder-like patterns ("Mikado aspect") and untypical bands at 6-8 kDa (71% and 77.4% versus 27.3% and 45.5%, respectively). In contrast, triplets of bands in the area above 50 kDa and between 24 and 39-42 kDa were more frequent in CE than in AE sera. The fuzzy band at 50-55 kDa typical for cysticercosis was absent in all AE and CE sera. - Conclusions: Atypical banding patterns in the cysticercosis Western blot should raise the suspicion of a meta?cestode infection different from Taenia solium, i.e. Echinococcus multilocularis or E. granulosus, especially when the Mikado aspect and an altered 6-8 kDa band is visible in the absence of a fuzzy 50-55 kDa band.

• Limitations of amphotericin B and nitazoxanide in the treatment of alveolar echinococcosis.

  Authors: D Tappe, A Müller, M Frosch, A Stich

  Annals of tropical medicine and parasitology. 04/2009; 103(2):177-81.

• Curative Resection of Hepatic Alveolar Hydatids.

  Authors: D Tappe, R Melcher, M Maier, W Kenn, K Müller-Hermelink, M Frosch

  Infection. 12/2008;

• Whole-genome comparison of disease and carriage strains provides insights into virulence evolution in Neisseria meningitidis

  Authors: C. Schoen, J. Blom, H. Claus, A. Schramm-Gluck, P. Brandt, T. Muller, A. Goesmann, B. Joseph, S. Konietzny, O. Kurzai, C. Schmitt, T. Friedrich, B. Linke, U. Vogel, M. Frosch

  Proc.Natl.Acad.Sci.U.S.A. 03/2008; 105.

  Neisseria meningitidis is a leading cause of infectious childhood mortality worldwide. Most research efforts have hitherto focused on disease isolates belonging to only a few hypervirulent clonalNeisseria meningitidis is a leading cause of infectious childhood mortality worldwide. Most research efforts have hitherto focused on disease isolates belonging to only a few hypervirulent clonal lineages. However, up to 10% of the healthy human population is temporarily colonized by genetically diverse strains mostly with little or no pathogenic potential. Currently, little is known about the biology of carriage strains and their evolutionary relationship with disease isolates. The expression of a polysaccharide capsule is the only trait that has been convincingly linked to the pathogenic potential of N. meningitidis. To gain insight into the evolution of virulence traits in this species, whole-genome sequences of three meningococcal carriage isolates were obtained. Gene content comparisons with the available genome sequences from three disease isolates indicate that there is no core pathogenome in N. meningitidis. A comparison of the chromosome structure suggests that a filamentous prophage has mediated large chromosomal rearrangements and the translocation of some candidate virulence genes. Interspecific comparison of the available Neisseria genome sequences and dot blot hybridizations further indicate that the insertion sequence IS1655 is restricted only to N. meningitidis; its low sequence diversity is an indicator of an evolutionarily recent population bottleneck. A genome-based phylogenetic reconstruction provides evidence that N. meningitidis has emerged as an unencapsulated human commensal from a common ancestor with Neisseria gonorrhoeae and Neisseria lactamica and consecutively acquired the genes responsible for capsule synthesis via horizontal gene transfer

• Microbiological evaluation of the new VITEK 2 Neisseria-Haemophilus identification card

  Authors: G. Valenza, C. Ruoff, U. Vogel, M. Frosch, M. bele-Horn

  J.Clin.Microbiol. 11/2007; 45.

  VITEK 2 is an automated identification system for diverse bacterial and fungal species. A new card (the Neisseria-Haemophilus [NH] card) for the identification of Neisseria spp., Haemophilus spp.,VITEK 2 is an automated identification system for diverse bacterial and fungal species. A new card (the Neisseria-Haemophilus [NH] card) for the identification of Neisseria spp., Haemophilus spp., and other fastidious gram-negative or gram-variable microorganisms has been developed, but its performance in a routine clinical laboratory has not yet been evaluated. In this study, a total of 188 bacterial strains belonging to the genera Actinobacillus, Campylobacter, Capnocytophaga, Cardiobacterium, Eikenella, Gardnerella, Haemophilus, Kingella, Moraxella, and Neisseria were investigated. The NH card was able to identify 171 strains (91%) correctly without the need for extra tests; one strain (0.5%) was misidentified, and five strains (2.7%) could not be classified. Eleven strains (5.8%) were identified with a low level of discrimination, and simple additional tests were required to increase the correct-identification rate to 96.8%. The results were available within 6 h. Based on these results, the new VITEK 2 NH card appears to be a good method for the identification of diverse groups of fastidious organisms, which would otherwise require testing with multiple systems. However, more work is needed to evaluate the performance of VITEK 2 with regard to Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, and Kingella bacteria because of the insufficient number of strains tested in this study. Moreover, further reduction of the detection time would be desirable

• Target gene sequencing to characterize the penicillin G susceptibility of Neisseria meningitidis

  Authors: M.K. Taha, J.A. Vazquez, E. Hong, D.E. Bennett, S. Bertrand, S. Bukovski, M.T. Cafferkey, F. Carion, J.J. Christensen, M. Diggle [......] M. Musilek, M. Paragi, A. Saguer, A. Skoczynska, P. Stefanelli, S. Thulin, G. Tzanakaki, M. Unemo, U. Vogel, M.L. Zarantonelli

  Antimicrob.Agents Chemother. 08/2007; 51.

  Clinical isolates of Neisseria meningitidis with reduced susceptibility to penicillin G (intermediate isolates, Pen(I)) harbor alterations in the penA gene encoding the penicillin binding protein 2Clinical isolates of Neisseria meningitidis with reduced susceptibility to penicillin G (intermediate isolates, Pen(I)) harbor alterations in the penA gene encoding the penicillin binding protein 2 (PBP2). A 402-bp DNA fragment in the 3' half of penA was sequenced from a collection of 1,670 meningococcal clinical isolates from 22 countries that spanned 60 years. Phenotyping, genotyping, and the determination of MICs of penicillin G were also performed. A total of 139 different penA alleles were detected with 38 alleles that were highly related, clustered together in maximum-likelihood analysis and corresponded to the penicillin G-susceptible isolates. The remaining 101 penA alleles were highly diverse, corresponded to different genotypes or phenotypes, and accounted for 38% of isolates, but no clonal expansion was detected. Analysis of the altered alleles that were represented by at least five isolates showed high correlation with the Pen(I) phenotype. The deduced amino acid sequence of the corresponding PBP2 comprised five amino acid residues that were always altered. This correlation was not complete for rare alleles, suggesting that other mechanisms may also be involved in conferring reduced susceptibility to penicillin. Evidence of mosaic structures through events of interspecies recombination was also detected in altered alleles. A new website was created based on the data from this work (http://neisseria.org/nm/typing/penA). These data argue for the use of penA sequencing to identify isolates with reduced susceptibility to penicillin G and as a tool to improve typing of meningococcal isolates, as well as to analyze DNA exchange among Neisseria species

• [3rd Workshop on Epidemiology, Prevention and Treatment of Invasive Meningococcal Disease in Würzburg 2006]

  Authors: J Elias, M Reinhardt, W Hautmann, I Harms, H Oppermann, M Schröter, W Hellenbrand, P Oster, O Kurzai, M K Taha, R Nossal, M Frosch, M Vogel

  Gesundheitswesen (Bundesverband der Ärzte des Öffentlichen Gesundheitsdienstes (Germany)). 05/2007; 69(4):256-62.

  On October 5th, 2006, the German Reference Centre for Meningococci (NRZM) held the 3rd Workshop on Epidemiology, Prevention and Treatment of Invasive Meningococcal Disease, in collaboration with theOn October 5th, 2006, the German Reference Centre for Meningococci (NRZM) held the 3rd Workshop on Epidemiology, Prevention and Treatment of Invasive Meningococcal Disease, in collaboration with the German Society for Hygiene and Microbiology (DGHM). Given the recent recommendation of the German Standing Committee on Vaccination (STIKO) for conjugate meningococcal C vaccination of all children in the second year of life, observations from meningococcal C conjugate vaccination campaigns in other European countries were presented and compared to the German situation. Moreover, the newly implemented cluster detection routines employed at the NRZM and their integration into the interactive geographical information system EpiScanGIS were shown. Based on recent experiences from regional outbreaks in Oberallgäu, Sangerhausen, and Greater Aachen, examples for public health intervention were given at the conference. In addition, current developments in the area of meningococcal research, as well as trends in antimicrobial susceptibility were covered. Finally, the latest evidence concerning the clinical management and chemoprophylaxis of this invasive bacterial disease was discussed.

• [3rd Workshop on Epidemiology, Prevention and Treatment of Invasive Meningococcal Disease in Wurzburg 2006]

  Authors: J. Elias, M. Reinhardt, W. Hautmann, I. Harms, H. Oppermann, M. Schroter, W. Hellenbrand, P. Oster, O. Kurzai, M.K. Taha, R. Nossal, M. Frosch, M. Vogel

  Gesundheitswesen. 04/2007; 69.

  On October 5th, 2006, the German Reference Centre for Meningococci (NRZM) held the 3rd Workshop on Epidemiology, Prevention and Treatment of Invasive Meningococcal Disease, in collaboration with theOn October 5th, 2006, the German Reference Centre for Meningococci (NRZM) held the 3rd Workshop on Epidemiology, Prevention and Treatment of Invasive Meningococcal Disease, in collaboration with the German Society for Hygiene and Microbiology (DGHM). Given the recent recommendation of the German Standing Committee on Vaccination (STIKO) for conjugate meningococcal C vaccination of all children in the second year of life, observations from meningococcal C conjugate vaccination campaigns in other European countries were presented and compared to the German situation. Moreover, the newly implemented cluster detection routines employed at the NRZM and their integration into the interactive geographical information system EpiScanGIS were shown. Based on recent experiences from regional outbreaks in Oberallgau, Sangerhausen, and Greater Aachen, examples for public health intervention were given at the conference. In addition, current developments in the area of meningococcal research, as well as trends in antimicrobial susceptibility were covered. Finally, the latest evidence concerning the clinical management and chemoprophylaxis of this invasive bacterial disease was discussed

• First case of febrile bacteremia due to a wild type and small-colony variant of Escherichia coli.

  Authors: D Tappe, H Claus, J Kern, A Marzinzig, M Frosch, M Abele-Horn

  European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology. 02/2006; 25(1):31-4.

  Reported here is a case of a febrile illness caused by a wild type and small-colony variant of Escherichia coli in an anorectic patient. A review of the literature revealed that the formation ofReported here is a case of a febrile illness caused by a wild type and small-colony variant of Escherichia coli in an anorectic patient. A review of the literature revealed that the formation of small-colony variants in E. coli has been recognized since 1931. In recent years, an association has been established between those variants and chronic recurrent infections. This report describes for the first time the isolation of an E. coli small-colony variant from a blood culture of a patient who had suffered from chronic urinary tract infections in the past.

• Isolation of Brucella melitensis from a patient with hearing loss.

  Authors: G Valenza, B Kallmann, A Berend, R Mlynski, K Nöckler, O Kurzai, M Frosch, M Abele-Horn

  European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology. 02/2006; 25(1):67-8.

• Comparative evaluation of a new Vitek 2 system for identification and antimicrobial susceptibility testing of Streptococcus pneumoniae.

  Authors: M Abele-Horn, K Stoy, M Frosch, R R Reinert

  European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology. 02/2006; 25(1):55-7.

• Carbohydrate composition of meningococcal lipopolysaccharide modulates the interaction of Neisseria meningitidis with human dendritic cells

  Authors: O. Kurzai, C. Schmitt, H. Claus, U. Vogel, M. Frosch, A. Kolb-Maurer

  Cell Microbiol. 09/2005; 7.

  Meningococcal lipopolysaccharide (LPS) is of crucial importance for the pathogenesis of invasive infection. We show that sialylation and elongation of the alpha-chain effectively shields viableMeningococcal lipopolysaccharide (LPS) is of crucial importance for the pathogenesis of invasive infection. We show that sialylation and elongation of the alpha-chain effectively shields viable unencapsulated Neisseria meningitidis from recognition by human dendritic cells (DC). In contrast, beta- and gamma- chain of the LPS carbohydrate moiety play only a minor role in the interaction with DC. The protective function of the LPS for the bacteria can be counteracted in vivo by phase variation of the lgtA gene encoding LPS glycosyltransferase A. Capsule expression protects N. meningitidis efficiently from recognition and phagocytosis by DC independent of the LPS structure. Despite the significant impact of LPS composition on the adhesion and phagocytosis of N. meningitidis no differences were found in terms of cytokine levels secreted by DC for IL1-beta, IL-6, IL-8, TNF-alpha, IFN-gamma and GM-CSF. However, significantly lower levels of the regulatory mediator IL-10 were induced by encapsulated strains in comparison to isogenic unencapsulated derivatives. IL-10 secretion was shown to depend on phagocytosis because poly alpha-2,8 sialic acid did not influence IL-10 secretion. The use of truncated LPS isoforms in vaccine preparations can therefore not only result in attenuation but also in more efficient targeting of DC

• Interlaboratory comparison of PCR-based identification and genogrouping of Neisseria meningitidis

  Authors: M.K. Taha, J.M. Alonso, M. Cafferkey, D.A. Caugant, S.C. Clarke, M.A. Diggle, A. Fox, M. Frosch, S.J. Gray, M. Guiver [......] K. Kesanopoulos, A.M. Klem, P. Kriz, J. Marsh, P. Molling, K. Murphy, P. Olcen, O. Sanou, G. Tzanakaki, U. Vogel

  J.Clin.Microbiol. 01/2005; 43.

  Twenty clinical samples (18 cerebrospinal fluid samples and 2 articular fluid samples) were sent to 11 meningococcus reference centers located in 11 different countries. Ten of these laboratories areTwenty clinical samples (18 cerebrospinal fluid samples and 2 articular fluid samples) were sent to 11 meningococcus reference centers located in 11 different countries. Ten of these laboratories are participating in the EU-MenNet program (a European Union-funded program) and are members of the European Monitoring Group on Meningococci. The remaining laboratory was located in Burkina Faso. Neisseria meningitidis was sought by detecting several meningococcus-specific genes (crgA, ctrA, 16S rRNA, and porA). The PCR-based nonculture method for the detection of N. meningitidis gave similar results between participants with a mean sensitivity and specificity of 89.7 and 92.7%, respectively. Most of the laboratories also performed genogrouping assays (siaD and mynB/sacC). The performance of genogrouping was more variable between laboratories, with a mean sensitivity of 72.7%. Genogroup B gave the best correlation between participants, as all laboratories routinely perform this PCR. The results for genogroups A and W135 were less similar between the eight participating laboratories that performed these PCRs

• Combined surgical and antifungal treatment of a subcutaneous infection due to Paecilomyces lilacinus.

  Authors: O Kurzai, T Vaeth, W Hamelmann, F-M C Müller, H Klinker, P Langmann, M Frosch, F Mühlschlegel

  Medical mycology : official publication of the International Society for Human and Animal Mycology. 07/2003; 41(3):253-8.

  Paecilomyces lilacinus was the causal agent of a case of subcutaneous infection in a patient with liver cirrhosis. Surgical treatment in combination with systemic amphotericin B therapy led toPaecilomyces lilacinus was the causal agent of a case of subcutaneous infection in a patient with liver cirrhosis. Surgical treatment in combination with systemic amphotericin B therapy led to complete recovery. Retrospectively performed microdilution testing revealed dose dependent in vitro susceptibility of the isolate to voriconazole (MIC = 2 g/ml) and terbinafine (MIC = 1 microg/ml).

• Postmortem isolation of Pseudotaeniolina globosa from a patient with aortic aneurysm.

  Authors: O Kurzai, P Keith, S de Hoog, M Abele-Horn, M Frosch

  Mycoses. 05/2003; 46(3-4):141-4.

  We describe the isolation of the melanized meristematic fungus Pseudotaeniolina globosa from the aortic wall of a patient who died while undergoing surgery for aortic aneurysm and aortic valveWe describe the isolation of the melanized meristematic fungus Pseudotaeniolina globosa from the aortic wall of a patient who died while undergoing surgery for aortic aneurysm and aortic valve regurgitation as a result of dilated cardiomyopathy. Meristematic fungi related to P. globosa have until now been considered as environmental saprobes found predominantly in ecological niches with low water activity. The isolate was identified by phenotypic analyses and by sequencing of the rDNA internal-transcribed spacer domain. The clinical significance of this isolation remains unclear but isolation of meristematic fungi from clinical specimen should be thoroughly evaluated in terms of their significance in future.

• The genus Neisseria: population structure, genome plasticity, and evolution of pathogenicity.

  Authors: U Vogel, M Frosch

  Current topics in microbiology and immunology. 02/2002; 264(2):23-45.