• Amyloid arthropathy associated with multiple myeloma: polyarthritis without synovial infiltration of CD20+ or CD38+ cells.

      Pessler, Frank; Ogdie, Alexis R; Mayer, Christian T; Kretzschmar, Warren W; Dai, Lie; Elsaman, Ahmed M; Einhorn, Eugene; Krenn, Veit; Schumacher, H Ralph (2014-03)
      To describe histological, immunohistochemical and ultrastructural features of synovial biopsies of amyloid arthropathy associated with multiple myeloma (MM).
    • Analysis of contingency tables based on generalised median polish with power transformations and non-additive models

      Klawonn, Frank; Jayaram, Balasubramaniam; Crull, Katja; Kukita, Akiko; Pessler, Frank (2013-05-30)
      Abstract Contingency tables are a very common basis for the investigation of effects of different treatments or influences on a disease or the health state of patients. Many journals put a strong emphasis on p-values to support the validity of results. Therefore, even small contingency tables are analysed by techniques like t-test or ANOVA. Both these concepts are based on normality assumptions for the underlying data. For larger data sets, this assumption is not so critical, since the underlying statistics are based on sums of (independent) random variables which can be assumed to follow approximately a normal distribution, at least for a larger number of summands. But for smaller data sets, the normality assumption can often not be justified. Robust methods like the Wilcoxon-Mann-Whitney-U test or the Kruskal-Wallis test do not lead to statistically significant p-values for small samples. Median polish is a robust alternative to analyse contingency tables providing much more insight than just a p-value. Median polish is a technique that provides more information than just a p-value. It explains the contingency table in terms of an overall effect, row and columns effects and residuals. The underlying model for median polish is an additive model which is sometimes too restrictive. In this paper, we propose two related approach to generalise median polish. A power transformation can be applied to the values in the table, so that better results for median polish can be achieved. We propose a graphical method how to find a suitable power transformation. If the original data should be preserved, one can apply other transformations – based on so-called additive generators – that have an inverse transformation. In this way, median polish can be applied to the original data, but based on a non-additive model. The non-linearity of such a model can also be visualised to better understand the joint effects of rows and columns in a contingency table.
    • Anti-nuclear autoantibodies in the general German population: prevalence and lack of association with selected cardiovascular and metabolic disorders-findings of a multicenter population-based study.

      Akmatov, Manas K; Röber, Nadja; Ahrens, Wolfgang; Flesch-Janys, Dieter; Fricke, Julia; Greiser, Halina; Günther, Kathrin; Kaaks, Rudolf; Kemmling, Yvonne; Krone, Bastian; Linseisen, Jakob; Meisinger, Christa; Moebus, Susanne; Obi, Nadia; Guzman, Carlos A; Conrad, Karsten; Pessler, Frank; Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017-06-06)
      We determined the prevalence of anti-nuclear autoantibodies (ANAs) in the German adult population and examined the association between ANAs and cardiovascular and metabolic disorders.
    • Comparison of response patterns in different survey designs: a longitudinal panel with mixed-mode and online-only design.

      Rübsamen, Nicole; Akmatov, Manas K; Castell, Stefanie; Karch, André; Mikolajczyk, Rafael; Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017)
      Increasing availability of the Internet allows using only online data collection for more epidemiological studies. We compare response patterns in a population-based health survey using two survey designs: mixed-mode (choice between paper-and-pencil and online questionnaires) and online-only design (without choice).
    • Corticosteroid-induced spinal epidural lipomatosis in the pediatric age group: report of a new case and updated analysis of the literature

      Möller, Jana C; Cron, Randy Q; Young, Daniel W; Girschick, Hermann J; Levy, Deborah M; Sherry, David D; Kukita, Akiko; Saijo, Kaoru; Pessler, Frank (2011-02-01)
      Abstract Spinal epidural lipomatosis is a rare complication of chronic corticosteroid treatment. We report a new pediatric case and an analysis of this and 19 pediatric cases identified in the international literature. The youngest of these combined 20 patients was 5 years old when lipomatosis was diagnosed. Lipomatosis manifested after a mean of 1.3 (+/- 1.5) years (SD) (median, 0.8 years; range, 3 weeks - 6.5 years) of corticosteroid treatment. The corticosteroid dose at the time of presentation of the lipomatosis ranged widely, between 5 and 80 mg of prednisone/day. Back pain was the most common presenting symptom. Imaging revealed that lipomatosis almost always involved the thoracic spine, extending into the lumbosacral region in a subset of patients. Predominantly lumbosacral involvement was documented in only two cases. Although a neurological deficit at presentation was documented in about half of the cases, surgical decompression was not performed in the cases reported after 1996. Instead, reducing the corticosteroid dose (sometimes combined with dietary restriction to mobilize fat) sufficed to induce remission. In summary, pediatric spinal epidural lipomatosis remains a potentially serious untoward effect of corticosteroid treatment, which, if recognized in a timely manner, can have a good outcome with conservative treatment.
    • Corticosteroid-induced spinal epidural lipomatosis in the pediatric age group: report of a new case and updated analysis of the literature.

      Möller, Jana C; Cron, Randy Q; Young, Daniel W; Girschick, Hermann J; Levy, Deborah M; Sherry, David D; Kukita, Akiko; Saijo, Kaoru; Pessler, Frank; Helmholtz Centre for infection research, Inhoffenstr. 7, D-38124 Braunschweig, Germany. (2011)
      Spinal epidural lipomatosis is a rare complication of chronic corticosteroid treatment. We report a new pediatric case and an analysis of this and 19 pediatric cases identified in the international literature. The youngest of these combined 20 patients was 5 years old when lipomatosis was diagnosed. Lipomatosis manifested after a mean of 1.3 (+/- 1.5) years (SD) (median, 0.8 years; range, 3 weeks - 6.5 years) of corticosteroid treatment. The corticosteroid dose at the time of presentation of the lipomatosis ranged widely, between 5 and 80 mg of prednisone/day. Back pain was the most common presenting symptom. Imaging revealed that lipomatosis almost always involved the thoracic spine, extending into the lumbosacral region in a subset of patients. Predominantly lumbosacral involvement was documented in only two cases. Although a neurological deficit at presentation was documented in about half of the cases, surgical decompression was not performed in the cases reported after 1996. Instead, reducing the corticosteroid dose (sometimes combined with dietary restriction to mobilize fat) sufficed to induce remission. In summary, pediatric spinal epidural lipomatosis remains a potentially serious untoward effect of corticosteroid treatment, which, if recognized in a timely manner, can have a good outcome with conservative treatment.
    • Determination of nasal and oropharyngeal microbiomes in a multicenter population-based study - findings from Pretest 1 of the German National Cohort.

      Akmatov, Manas K; Koch, Nadine; Vital, Marius; Ahrens, Wolfgang; Flesch-Janys, Dieter; Fricke, Julia; Gatzemeier, Anja; Greiser, Halina; Günther, Kathrin; Illig, Thomas; Kaaks, Rudolf; Krone, Bastian; Kühn, Andrea; Linseisen, Jakob; Meisinger, Christine; Michels, Karin; Moebus, Susanne; Nieters, Alexandra; Obi, Nadia; Schultze, Anja; Six-Merker, Julia; Pieper, Dietmar H; Pessler, Frank; TWINCORE; Zentrum für experimentelle und klinische Infectionsforsching GmbH, Feodor-Lynen Str. 17, 30625 Hannover, Germany. (2017-05-12)
      We examined acceptability, preference and feasibility of collecting nasal and oropharyngeal swabs, followed by microbiome analysis, in a population-based study with 524 participants. Anterior nasal and oropharyngeal swabs were collected by certified personnel. In addition, participants self-collected nasal swabs at home four weeks later. Four swab types were compared regarding (1) participants' satisfaction and acceptance and (2) detection of microbial community structures based on deep sequencing of the 16 S rRNA gene V1-V2 variable regions. All swabbing methods were highly accepted. Microbial community structure analysis revealed 846 phylotypes, 46 of which were unique to oropharynx and 164 unique to nares. The calcium alginate tipped swab was found unsuitable for microbiome determinations. Among the remaining three swab types, there were no differences in oropharyngeal microbiomes detected and only marginal differences in nasal microbiomes. Microbial community structures did not differ between staff-collected and self-collected nasal swabs. These results suggest (1) that nasal and oropharyngeal swabbing are highly feasible methods for human population-based studies that include the characterization of microbial community structures in these important ecological niches, and (2) that self-collection of nasal swabs at home can be used to reduce cost and resources needed, particularly when serial measurements are to be taken.
    • Development of a Bead-Based Multiplex Assay for the Analysis of the Serological Response against the Six Pathogens HAV, HBV, HCV, CMV, T. gondii, and H. pylori.

      Filomena, Angela; Pessler, Frank; Akmatov, Manas K; Krause, Gérard; Duffy, Darragh; Gärtner, Barbara; Gerhard, Markus; Albert, Matthew L; Joos, Thomas O; Schneiderhan-Marra, Nicole; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017-10-30)
      The spread of infectious diseases and vaccination history are common subjects of epidemiological and immunological research studies. Multiplexed serological assays are useful tools for assessing both current and previous infections as well as vaccination efficacy. We developed a serological multi-pathogen assay for hepatitis A, B and C virus, cytomegalovirus (CMV),
    • Differentiation of Human Pluripotent Stem Cells into Functional Endothelial Cells in Scalable Suspension Culture.

      Olmer, Ruth; Engels, Lena; Usman, Abdulai; Menke, Sandra; Malik, Muhammad Nasir Hayat; Pessler, Frank; Göhring, Gudrun; Bornhorst, Dorothee; Bolten, Svenja; Abdelilah-Seyfried, Salim; Scheper, Thomas; Kempf, Henning; Zweigerdt, Robert; Martin, Ulrich; TWINCORE, Zentrum für experimentelle und klinischeInfektionsforschung GmbH, Feodor-Lynen-Str. 7, 30625 Hannover, Germany. (2018-05-08)
      Endothelial cells (ECs) are involved in a variety of cellular responses. As multifunctional components of vascular structures, endothelial (progenitor) cells have been utilized in cellular therapies and are required as an important cellular component of engineered tissue constructs and in vitro disease models. Although primary ECs from different sources are readily isolated and expanded, cell quantity and quality in terms of functionality and karyotype stability is limited. ECs derived from human induced pluripotent stem cells (hiPSCs) represent an alternative and potentially superior cell source, but traditional culture approaches and 2D differentiation protocols hardly allow for production of large cell numbers. Aiming at the production of ECs, we have developed a robust approach for efficient endothelial differentiation of hiPSCs in scalable suspension culture. The established protocol results in relevant numbers of ECs for regenerative approaches and industrial applications that show in vitro proliferation capacity and a high degree of chromosomal stability.
    • Discovery of Leptospira spp. seroreactive peptides using ORFeome phage display.

      Ramli, Siti Roszilawati; Moreira, Gustavo M S G; Zantow, Jonas; Goris, Marga G A; Nguyen, Van Kinh; Novoselova, Natalia; Pessler, Frank; Hust, Michael; TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany. (PLOS, 2019-01-01)
      Leptospirosis is the most common zoonotic disease worldwide. The diagnostic performance of a serological test for human leptospirosis is mainly influenced by the antigen used in the test assay. An ideal serological test should cover all serovars of pathogenic leptospires with high sensitivity and specificity and use reagents that are relatively inexpensive to produce and can be used in tropical climates. Peptide-based tests fulfil at least the latter two requirements, and ORFeome phage display has been successfully used to identify immunogenic peptides from other pathogens. Two ORFeome phage display libraries of the entire Leptospira spp. genomes from five local strains isolated in Malaysia and seven WHO reference strains were constructed. Subsequently, 18 unique Leptospira peptides were identified in a screen using a pool of sera from patients with acute leptospirosis. Five of these were validated by titration ELISA using different pools of patient or control sera. The diagnostic performance of these five peptides was then assessed against 16 individual sera from patients with acute leptospirosis and 16 healthy donors and was compared to that of two recombinant reference proteins from L. interrogans. This analysis revealed two peptides (SIR16-D1 and SIR16-H1) from the local isolates with good accuracy for the detection of acute leptospirosis (area under the ROC curve: 0.86 and 0.78, respectively; sensitivity: 0.88 and 0.94; specificity: 0.81 and 0.69), which was close to that of the reference proteins LipL32 and Loa22 (area under the ROC curve: 0.91 and 0.80; sensitivity: 0.94 and 0.81; specificity: 0.75 and 0.75). This analysis lends further support for using ORFeome phage display to identify pathogen-associated immunogenic peptides, and it suggests that this technique holds promise for the development of peptide-based diagnostics for leptospirosis and, possibly, of vaccines against this pathogen.
    • Early Lymphocyte Loss and Increased Granulocyte/Lymphocyte Ratio Predict Systemic Spread of in a Mouse Model of Acute Skin Infection.

      Loof, Torsten G; Sohail, Aaqib; Bahgat, Mahmoud M; Tallam, Aravind; Arshad, Haroon; Akmatov, Manas K; Pils, Marina C; Heise, Ulrike; Beineke, Andreas; Pessler, Frank; TWINCORE, Zentrum für experimentelle und klinischeInfektionsforschung GmbH, Feodor-Lynen-Str. 7, 30625 Hannover, Germany.
      Group A streptococci may induce lymphopenia, but the value of lymphocyte loss as early biomarkers for systemic spread and severe infection has not been examined systematically. We evaluated peripheral blood cell indices as biomarkers for severity and spread of infection in a mouse model of skin infection, using two isolates of greatly differing virulence. Internal organs were examined histologically. After subcutaneous inoculation, strain AP1 disseminated rapidly to peripheral blood and internal organs, causing frank sepsis. In contrast, seeding of internal organs by 5448 was mild, this strain could not be isolated from blood, and infection remained mostly localized to skin. Histopathologic examination of liver revealed microvesicular fatty change (steatosis) in AP1 infection, and examination of spleen showed elevated apoptosis and blurring of the white pulp/red pulp border late (40 h post infection) in AP1 infection. Both strains caused profound lymphopenia, but lymphocyte loss was more rapid early in AP1 infection, and lymphocyte count at 6 h post infection was the most accurate early marker for AP1 infection (area under the receiver operator curve [AUC] = 0.93), followed by the granulocyte/lymphocyte ratio (AUC = 0.89). The results suggest that virulence of correlates with the degree of early lymphopenia and underscore the value of peripheral blood indices to predict severity of bacterial infections in mice. Early lymphopenia and elevated granulocyte/lymphocyte ratio merit further investigation as biomarkers for systemic spread of skin infections in humans and, possibly, related pyogenic streptococci in humans and animals.
    • An Egyptian HPAI H5N1 isolate from clade 2.2.1.2 is highly pathogenic in an experimentally infected domestic duck breed (Sudani duck).

      Samir, M; Hamed, M; Abdallah, F; Kinh Nguyen, V; Hernandez-Vargas, E A; Seehusen, F; Baumgärtner, W; Hussein, A; Ali, A A H; Pessler,, F; TWINCORE, Zentrum für experimentelle uns klinische Ifektionsforschung GmbH, Feodor-Lynen-Str. 7, 30625 Hannover, Germany. (2018-01-24)
      The highly pathogenic avian influenza (HPAI) H5N1 viruses continue to cause major problems in poultry and can, although rarely, cause human infection. Being enzootic in domestic poultry, Egyptian isolates are continuously evolving, and novel clades vary in their pathogenicity in avian hosts. Considering the importance of domestic ducks as natural hosts of HPAI H5N1 viruses and their likelihood of physical contact with other avian hosts and humans, it is of utmost importance to characterize the pathogenicity of newly emerged HPAI strains in the domestic duck. The most recently identified Egyptian clade 2.2.1.2 HPAI H5N1 viruses have been isolated from naturally infected pigeons, turkeys and humans. However, essentially nothing is known about their pathogenicity in domestic ducks. We therefore characterized the pathogenicity of an Egyptian HPAI H5N1 isolate A/chicken/Faquos/amn12/2011 (clade 2.2.1.2) in Sudani duck, a domestic duck breed commonly reared in Egypt. While viral transcription (HA mRNA) was highest in lung, heart and kidney peaking between 40 and 48 hpi, lower levels were detected in brain. Weight loss of infected ducks started at 16 hpi and persisted until 120 hpi. The first severe clinical signs were noted by 32 hpi and peaked in severity at 72 and 96 hpi. Haematological analyses showed a decline in total leucocytes, granulocytes, platelets and granulocyte/lymphocyte ratio, but lymphocytosis. Upon necropsy, lesions were obvious in heart, liver, spleen and pancreas and consisted mainly of necrosis and petechial haemorrhage. Histologically, lungs were the most severely affected organs, whereas brain only showed mild neuronal degeneration and gliosis at 48 hpi despite obvious neurological clinical signs. Taken together, our results provide first evidence that this HPAI H5N1 isolate (clade 2.2.1.2) is highly pathogenic to Sudani ducks and highlight the importance of this breed as potential reservoir and disseminator of HPAI strains from this clade.
    • Exhaled breath analysis in childhood rheumatic disorders--a longitudinal study.

      Hendel, N; Akmatov, M K; Hamel, J; Vogelberg, C; Pessler, F; TWINCORE Centre for Experimental and Clinical Infection Research Feodor-Lynen-Str. 7 30625 Hannover, Germany. (2016-06)
      We aimed to evaluate the fraction of exhaled nitric oxide (FENO50) and deaerated exhaled breath condensate pH (dEBCpH) as non-invasive markers of subclinical airway inflammation in pediatric patients with rheumatologic disorders. We determined FENO50 and dEBCpH in a prospective study spanning at least 12 months, comprising 85 pediatric patients with rheumatologic disorders, including juvenile idiopathic arthritis (JIA, n  =  63), chronic recurrent multifocal osteomyelitis (CRMO, n  =  6), systemic lupus erythematosus (SLE, n  =  3), juvenile dermatomyositis (JDM, n  =  1) and other rheumatic disorders (n  =  12). dEBCpH was determined once in a group of children without evidence of rheumatologic or pulmonary disease (controls, n  =  90). Findings were correlated with results of pulmonary function tests. Atopic sensitization was assessed by RAST or skin prick test in 76 patients. Atopic sensitization was detected in 34% (26/76) of patients. Neither FENO50 nor dEBCpH correlated with disease activity, but intermediately (20-35 ppb) or highly elevated (>35 ppb) levels were observed at least once in 26 patients (31%), 19 of whom had atopic sensitization. Median dEBCpH did not differ between cases and controls (8.05 versus 8.02; p  =  0.48). Median dEBCpH decreased slightly over the study period (p  =  0.02), whereas FENO50 values did not change significantly (p  =  0.89). There were several patients with significantly abnormal dEBCpH values that could not be readily explained by diagnosis, higher disease activity, medications, or atopic sensitization. Thus, there were no consistent abnormalities in FENO50 or dEBCpH in this cohort of Caucasian patients with relatively stable rheumatologic disorders, but there were some patients with abnormal values of unknown significance.
    • Gene Regulatory Network Inference of Immunoresponsive Gene 1 (IRG1) Identifies Interferon Regulatory Factor 1 (IRF1) as Its Transcriptional Regulator in Mammalian Macrophages.

      Tallam, Aravind; Perumal, Thaneer M; Antony, Paul M; Jäger, Christian; Fritz, Joëlle V; Vallar, Laurent; Balling, Rudi; Del Sol, Antonio; Michelucci, Alessandro; Twincore Centre of Experimental and Clinical Infection Research; a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover 30625, Germany. (2016)
      Immunoresponsive gene 1 (IRG1) is one of the highest induced genes in macrophages under pro-inflammatory conditions. Its function has been recently described: it codes for immune-responsive gene 1 protein/cis-aconitic acid decarboxylase (IRG1/CAD), an enzyme catalysing the production of itaconic acid from cis-aconitic acid, a tricarboxylic acid (TCA) cycle intermediate. Itaconic acid possesses specific antimicrobial properties inhibiting isocitrate lyase, the first enzyme of the glyoxylate shunt, an anaplerotic pathway that bypasses the TCA cycle and enables bacteria to survive on limited carbon conditions. To elucidate the mechanisms underlying itaconic acid production through IRG1 induction in macrophages, we examined the transcriptional regulation of IRG1. To this end, we studied IRG1 expression in human immune cells under different inflammatory stimuli, such as TNFα and IFNγ, in addition to lipopolysaccharides. Under these conditions, as previously shown in mouse macrophages, IRG1/CAD accumulates in mitochondria. Furthermore, using literature information and transcription factor prediction models, we re-constructed raw gene regulatory networks (GRNs) for IRG1 in mouse and human macrophages. We further implemented a contextualization algorithm that relies on genome-wide gene expression data to infer putative cell type-specific gene regulatory interactions in mouse and human macrophages, which allowed us to predict potential transcriptional regulators of IRG1. Among the computationally identified regulators, siRNA-mediated gene silencing of interferon regulatory factor 1 (IRF1) in macrophages significantly decreased the expression of IRG1/CAD at the gene and protein level, which correlated with a reduced production of itaconic acid. Using a synergistic approach of both computational and experimental methods, we here shed more light on the transcriptional machinery of IRG1 expression and could pave the way to therapeutic approaches targeting itaconic acid levels.
    • Hematological parameters in the early phase of influenza A virus infection in differentially susceptible inbred mouse strains.

      Preusse, Matthias; Schughart, Klaus; Wilk, Esther; Klawonn, Frank; Pessler, Frank; Helmholz Centre for Infection Research (2015)
      Hematological parameters have not received much attention in small animal models of infection, particularly at very early time points. We therefore studied changes in leukocyte and thrombocyte numbers in a mouse model of influenza A virus (IAV) infection, including measurements within the first 24 h after infection, and also assessing effects, if any, of the infection/anesthesia procedure on these parameters.
    • Hepatitis B vaccination timing: results from demographic health surveys in 47 countries.

      Schweitzer, Aparna; Akmatov, Manas K; Krause, Gerard; BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56, 38106 Braunschweig, Germany. (2017-03-01)
      To examine the impact of hepatitis B vaccination schedules and types of vaccines on hepatitis B vaccination timing.
    • Host Genetic Background Strongly Affects Pulmonary microRNA Expression before and during Influenza A Virus Infection.

      Preusse, Matthias; Schughart, Klaus; Pessler, Frank (2017)
      Expression of host microRNAs (miRNAs) changes markedly during influenza A virus (IAV) infection of natural and adaptive hosts, but their role in genetically determined host susceptibility to IAV infection has not been explored. We, therefore, compared pulmonary miRNA expression during IAV infection in two inbred mouse strains with differential susceptibility to IAV infection.
    • Identification of Cerebrospinal Fluid Metabolites as Biomarkers for Enterovirus Meningitis.

      Ratuszny, Dominica; Sühs, Kurt-Wolfram; Novoselova, Natalia; Kuhn, Maike; Kaever, Volkhard; Skripuletz, Thomas; Pessler, Frank; Stangel, Martin; TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany. (MDPI, 2019-01-15)
      Enteroviruses are among the most common causes of viral meningitis. Enteroviral meningitis continues to represent diagnostic challenges, as cerebrospinal fluid (CSF) cell numbers (a well validated diagnostic screening tool) may be normal in up to 15% of patients. We aimed to identify potential CSF biomarkers for enteroviral meningitis, particularly for cases with normal CSF cell count. Using targeted liquid chromatography-mass spectrometry, we determined metabolite profiles from patients with enteroviral meningitis (n = 10), and subdivided them into those with elevated (n = 5) and normal (n = 5) CSF leukocyte counts. Non-inflamed CSF samples from patients with Bell’s palsy and normal pressure hydrocephalus (n = 19) were used as controls. Analysis of 91 metabolites revealed considerable metabolic reprogramming in the meningitis samples. It identified phosphatidylcholine PC.ae.C36.3, asparagine, and glycine as an accurate (AUC, 0.92) combined classifier for enterovirus meningitis overall, and kynurenine as a perfect biomarker for enteroviral meningitis with an increased CSF cell count (AUC, 1.0). Remarkably, PC.ae.C36.3 alone emerged as a single accurate (AUC, 0.87) biomarker for enteroviral meningitis with normal cell count, and a combined classifier comprising PC.ae.C36.3, PC.ae.C36.5, and PC.ae.C38.5 achieved nearly perfect classification (AUC, 0.99). Taken together, this analysis reveals the potential of CSF metabolites as additional diagnostic tools for enteroviral meningitis, and likely other central nervous system (CNS) infections.
    • Impact of rotavirus vaccination on coverage and timing of pentavalent vaccination - Experience from 2 Latin American countries.

      Schweitzer, A; Pessler, F.; Akmatov, M K; Twincore Centre of Experimental and Clinical Infection Research; a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover 30625, Germany. (2016-05-03)
      We examined the coverage and timing of rotavirus vaccination and the impact of rotavirus vaccine introduction on coverage and timing of the pentavalent vaccine. We used data from the Demographic and Health Surveys in Honduras (2011/2012) and Peru (2012). The samples were divided into 2 subcohorts: children born before and after the introduction of rotavirus vaccine. We compared coverage and timing of the pentavalent vaccine in the aforementioned subcohorts. Coverage with the first and second doses of rotavirus vaccination was 95% (95% confidence intervals: 93-97%) and 91% (89-95%) in Honduras and 79% (77-82%) and 72% (69-75%) in Peru, respectively. Coverage increased in both countries over the years. The proportion of children vaccinated according to age-appropriate vaccination schedules varied between 67% (second dose of rotavirus vaccinations in Peru) and 89% (first dose of rotavirus vaccination in Honduras). Coverage with the first and second doses of pentavalent vaccination remained constant over the years in Honduras, while in Peru there was a significant increase in coverage over the years (p for trend, <0.0001). In both countries, timing of pentavalent vaccination was better in post-rota-cohorts than in pre-rota-cohorts. Since its introduction, coverage of rotavirus vaccination has improved over time in both countries. An introduction of rotavirus vaccination in both countries appears to have improved the coverage and timing of other similarly scheduled vaccinations.
    • Improved coverage and timing of childhood vaccinations in two post-Soviet countries, Armenia and Kyrgyzstan.

      Schweitzer, A; Krause, G; Pessler, F; Akmatov, M K (2015)
      Timing of childhood vaccinations has received close attention in many countries. Little is known about the trends in correctly timed vaccination in former Soviet countries. We examined trends in vaccination coverage and correct timing of vaccination in two post-Soviet countries, Armenia and Kyrgyzstan, and analyzed factors associated with delayed vaccinations.