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Publications citing this author (476)

    • Furthermore, ORF4 has also been identified as a novel target protein for persistent VZV specific CD4 + T cells, which may be involved in the control of VZV reacti- vation [25]. ORF68 has already been described as highly immunogenic VZV protein, eliciting both, humoral and cellular immune responses [11,26]. Recently, recombinant ORF68 has been utilized for the development of serological herpesvirus microarray [27].
    [Show abstract] [Hide abstract] ABSTRACT: Varicella-Zoster virus causes chickenpox upon primary infection and shingles after reactivation. Currently available serological tests to detect VZV-specific antibodies are exclusively based on antigens derived from VZV-infected cells. We present a systematic approach for the identification of novel, serologically reactive VZV antigens. Therefore, all VZV open reading frames were cloned into a bacterial expression vector and checked for small scale recombinant protein expression. Serum profiling experiments using purified VZV proteins and clinically defined sera in a microarray revealed 5 putative antigens (ORFs 1, 4, 14, 49, and 68). These were rearranged in line format and validated with pre-characterized sera. The line assay confirmed the seroreactivity of the identified antigens and revealed its suitability for VZV serodiagnostics comparable to commercially available VZV-ELISA. Recombinant ORF68 (gE) proved to be an antigen for high-confidence determination of VZV serostatus. Furthermore, our data suggest that a serological differentiation between chickenpox and herpes zoster may be possible by analysis of the IgM-portfolio against individual viral antigens.
    Full-text · Article · Jul 2010
    • In concert with the fact that myocardial infections are frequently observed after common colds in patients that were physically active during their common cold, HBoV could be accused being a further player in this clinical scenario. Consequently, as the leaky gut syndrome could not be deduced to other factors such as diet, inherited diseases or simultaneous infections, further studies should investigate on the role of HBoV in this syndrome because it could also be linked to the HBoV infection as HBoV is widely detected in feces (Albuquerque et al., 2007; Lee et al., 2007; Campe et al., 2008; Cheng et al., 2008; Yu et al., 2008; Szomor et al., 2009). As previously discussed, the Th2 response in the lung is accompanied by increased expression levels of IL-4, IL-5, IL-10 and IL-13 and is followed by increased levels of, among others, TARC and RANTES (Berin et al., 2001; Culley et al., 2006).
    [Show abstract] [Hide abstract] ABSTRACT: Introduction The human bocavirus (HBoV) is a parvovirus and is associated with mild to life-threatening acute or persisting respiratory infections, frequently accompanied by further pathogens. So far, there is limited knowledge on the mechanisms of persistence, and no reports on chronic infections or latency have been published so far. Case presentation An immunocompetent male patient suffers from a chronic HBoV1 infection, i.e. viral DNA was detected in both serum and bronchoalveolar lavage (BAL) for >5 months without co-infections and with respiratory symptoms resolved spontaneously while receiving symptomatic treatment with montelukast and corticosteroids. Following the symptomatic medication of a chronic infection with HBoV1 viraemia indicating active viral replication lasting over 5 months, the patient cleared the viraemia and no further viral DNA was detectable in the BAL. However, by fluorescence in situ hybridization analyses of mucosal biopsies, it was shown that the virus genome still persisted in the absence of viral shedding but in a more compact manner possibly representing a supercoiled episomal form of this otherwise linear single-stranded DNA genome. This indicated the entry into a latency phase. Moreover, the cytokine profile and the IP-10/TARC ratio, a marker for fibrotization, seem to have been altered by HBoV1 replication. Although specific IgG antibodies were detectable during the whole observation period, they showed an apparently insufficient neutralising activity. Conclusion On the one hand, these findings suggest that the symptomatic medication may have led to clearance of the virus from blood and airways and, moreover, that the viral DNA persists in the tissue as an altered episomal form favoured by lacking neutralising antibodies. This appears to be important in order to reduce possible long-term effects such as lung fibrosis.
    Full-text · Article · Jul 2016
    • We believe that different results mainly existed because of different geographical regions and different characteristics of H1N1 infection. On the other hand, our findings agreed with those from a German study reporting that clinical symptoms could not predict influenza infection [25]. Interestingly, analogous to our study, abnormal CRP was the most sensitive screening tool for influenza in a recent study from an ambulatory stem-cell transplant center during an influenza outbreak [26].
    [Show abstract] [Hide abstract] ABSTRACT: Introduction: Influenza-like illness (ILI) and acute respiratory infection (ARI) are common presentations during winter and indiscriminate antibiotic use contributes significantly to the emerging post-antibiotic era. Methodology: Otherwise healthy 152 patients, presenting to outpatient clinics with ILI/ARI, were included. Patients had history & physical, CRP, hemogram and nasopharyngeal swabs for rhinovirus A/B, influenza A/B, adenovirus A/B/C/D/E, coronavirus 229E/NL63 and OC43, parainfluenza virus 1/2/3, respiratory syncytial virusA/B, metapneumovirus and Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella pneumophila and Bordetella pertussis by PCR and for ABHS culture. Results: Median (IR) age was 26.5 (16.5). Time to presentation was shorter in men (p = 0.027). Patients with rhinovirus had lower rates (20%) of myalgia (p = 0.043). Patients with influenza virus had higher rates (97%) of elevated CRP (p = 0.016). Logistic regression revealed that patients with ILI/ARI and CRP ≥ 5 mg/L were 60 times more likely to have influenza virus infection than other viral agents (OR = 60.0, 95% CI = 2.65 to 1,358.2, p = 0.010). Rhinovirus predominated in December (54%), March (36%), and April (33%). Influenza virus predominated in January (51%). Fever was most common with adenovirus (p = 0.198). All GABHS cultures were negative. Atypical organisms and Bordetella pertussis were negative in all but one patient. Conclusions: Influenza virus is the most likely pathogen in ILI/ARI when CRP ≥ 5 mg/L. This might be explained by tissue destruction. Myalgia is rare with rhinovirus probably due to absence of viremia. Negative bacteria by PCR and culture suggest unnecessary antibiotic use in ILI/ARI.
    Full-text · Article · Aug 2016
    • We observed that Cq values of multiplex could not show a significant difference from the value obtained in singleplex assays for each genotype. Our findings get support from previous reports that demonstrated an advantage of multiplex assay and its superiority over other available assays including the conventional PCR, RFLP and sequence analysis.[28,32,36]These studies report that real-time qPCR assay can detect HCV genotypes in all the samples reported negative by sequencing and RFLP.
    [Show abstract] [Hide abstract] ABSTRACT: The variable response of hepatitis C virus (HCV) genotypes towards anti-viral treatment requires prior information on the genotype status before planning a therapeutic strategy. Although assays for typing or subtyping of HCV are available, however, a fast and reliable assay system is still needed. The present study was planned to develop a single-step multiplex quantitative real time polymerase chain reaction (qPCR) assay to determine HCV genotypes in patients’ sera.
    Full-text · Article · Mar 2017
    • In 1980, the World Health Organization declared the global eradication of smallpox and recommended to stop further vaccination against smallpox, taking into account the postvaccination complications caused by classical live VACV vaccine. Thus, worldwide , almost all individuals below 33 years of age have no immunity against smallpox and other human orthopoxvirus infections, resulting in numerous reported outbreaks of the human diseases caused by the zoonotic OPVs, including MPXV and CPXV (Campe et al., 2009; Carletti et al., 2009; Ninove et al., 2009). Therefore, there is a need to develop a rapid and reliable method for CPXV detection (Gavrilova et al., 2010).
    [Show abstract] [Hide abstract] ABSTRACT: The species cowpox virus (CPXV), genus Orthopoxvirus (OPV), consists of isolates highly variable in their biological properties and their genotypes. A TaqMan PCR assay for the specific detection of CPXV DNA based on sequences of the ORF D11L has been developed recently. (Gavrilova et al., 2010; Shchelkunov et al., 2011); however, a rather limited panel of CPXV stains has been used. When a much larger panel of 47 CPXV DNAs has been tested, three strains could not be amplified at all because of large deletions in their respective ORF D11L. In addition, a deletion of 23 bp led to low-efficiency detection of five other CPXV strains. To solve this problem a new primer/probe combinations was selected based on sequences of ORF D8L, and a new real-time PCR method for (i) a genus-specific detection of OPVs and (ii) a simultaneous CPXV-specific differentiation is described in this study. The specificity and sensitivity were assessed by analyzing DNA of 67 strains belonging to human-pathogenic OPV species, including variola virus, as well as specimens of CPXV-infected mice.
    Full-text · Article · Jan 2015
    • Occult HBV infection is transmissible through blood transfusion from human to human [5] and human to chimpanzee [6]. In addition, C-HBV infection developed after a liver transplant from an O-HBV-infected donor [7] . Retrospective studies have also identified O- HBV infection in 16–68% of tumours in patients with hepatocellular carcinoma (HCC) [8,9].
    [Show abstract] [Hide abstract] ABSTRACT: Occult hepatitis B virus (O-HBV) infection is characterized by the presence of HBV DNA without detectable hepatitis B surface antigen (HBV DNA+/HBsAg-) in the serum. Although O-HBV is more prevalent during HBV/HIV co-infection, analysis of HBV mutations in co-infected patients is limited. In this preliminary study, HBV PreSurface (PreS) and surface (S) regions were amplified from 33 HIV-positive patient serum samples - 27 chronic HBV (C-HBV) and six O-HBV infections. HBV genotype was determined by phylogenetic analysis, while quasispecies diversity was quantified for the PreS, S and overlapping polymerase regions. C-HBV infections harboured genotypes A, D and G, compared to A, E, G and one mixed A/G infection for O-HBV. Interestingly, nonsynonymous-synonymous mutation values indicated positive immune selection in three regions for O-HBV vs one for C-HBV. Sequence analysis further identified new O-HBV mutations, in addition to several previously reported mutations within the HBsAg antigenic determinant. Several of these O-HBV mutations likely contribute to the lack of detectable HBsAg in O-HBV infection by interfering with detection in serologic assays, altering antigen secretion and/or decreasing replicative fitness.
    Full-text · Article · Nov 2009
    • Approximately 27 outbreaks of norovirus infections occurred on cruise ships each year (2005e2009) [15]. Norovirus is considered one of the causes of travellers' diarrhoea with a prevalence ranging from 3% to 17% of travellers returning with diarrhoea [32,33]. The virus is usually introduced on board by passengers or crew infected prior to embarkation and from food contaminated before loading or contaminated environmental surfaces from previous cruises.
    [Show abstract] [Hide abstract] ABSTRACT: Cruise ships carry a large number of people in confined spaces providing an environment for transmission of infections. The aim of this study is to estimate the incidence of and describe the spectrum of respiratory infections and gastrointestinal illness among passengers and crew of cruise Ship A. The study was carried out from January 2011 to December 2013 on cruise Ship A, including passengers and crew who presented with symptoms suggestive of acute respiratory infection (ARI), influenza-like illness (ILI) and gastrointestinal illness (GI). Advice about preventive measures of respiratory and gastrointestinal infections and influenza vaccination was given to passengers and crew. Data were collected by using one standardized form per patient. The most common destination was Northern Europe (90.7%). The mean duration of cruise was 10.6 days; 440 passengers and 421 crew members who sought medical attention were studied (mean age 72.6 ± 9.5 and 33 ± 7 years, respectively). ILI, ARI and GI were diagnosed in 32.7%, 15.9%, 17% and 10.9%, 80%, 0.2% of ill passengers and crew, respectively. The association of ARI, ILI and GI incidence in passengers was statistically significant with season, destination and duration of travel; the incidence for all illnesses was higher during winter, for travel to South America and for >14 days (p-value<0.001). ARI, ILI and GI continue to pose a burden on cruise travel; therefore pre-travel advice is crucial for passengers and crew regarding respiratory and gastrointestinal infections. Surveillance and implementation of control measures are important for outbreak prevention.
    Article · Jun 2016
    • Quantification of EBV DNA by polymerase chain reaction in saliva samples was performed at the Institute of Virology, University of Munich, Germany as previously described with the use of primers detecting a specific sequence in the EBV's DNA polymerase BALF5 gene (Campe et al., 2003; Moosmann et al., 2010 ). All specimens were batch analyzed and read blind-coded.
    [Show abstract] [Hide abstract] ABSTRACT: During interplanetary exploration, chronic stress caused by long term isolation and confinement in the spacecraft is one of the major concerns of physical and psychological health of space travelers. And for human on Earth, more and more people live in an isolated condition, which has become a common social problem in modern western society. Collective evidences have indicated prolonged chronic stress could bring big influence to human immune function, which may lead to a variety of health problems. However, to what extent long-term isolation can affect the immune system and immune response? It is still largely unknown. A simulated 520-d Mars mission provided an extraordinary chance to study the effect of prolonged isolation. Six healthy males participated in this mission and their active neuroendocrine and immune conditions were studied with saliva and blood samples from all participants on chosen time points during the isolation period. As a typical neuroendocrine parameter, stress hormone cortisol was measured in the morning saliva samples. Immune phenotype changes were monitored through peripheral leukocyte phenotype analysis. Using an ex-vivo viral infection simulation assay we assessed the immune response changes characterized by the ability to produce representative endogenous pro-inflammatory cytokines. The results of this study revealed elevated cortisol levels, increased lymphocyte amount, heightened immune responses, suggesting that prolonged isolation acting as chronic stressors are able to trigger leukocyte phenotype changes and poorly controlled immune responses.
    Full-text · Article · Aug 2014
    • Due to the large sample size we were able to assess subtype-specific VE even in different age-strata within the elderly population. In contrast, in observational studies using the TND estimation of strain-specific VE in the elderly is often not possible or limited by large CIs [17,35,36,42,54]. Furthermore, the assessment of VE against severe influenza using the TND is possible but would require additional study sites in hospitals and is often logistically challenging and resource-demanding.
    [Show abstract] [Hide abstract] ABSTRACT: Background: Elderly people are at increased risk for severe influenza illness and constitute therefore a major target-group for seasonal influenza vaccination in most industrialized countries. The aim of this study was to estimate influenza vaccine effectiveness (VE) among individuals aged 60+ years over three seasons and to assess if the screening method is a suitable tool to monitor influenza VE in this particular target-group in Germany. Methods: We identified laboratory-confirmed influenza cases aged 60+ years through the national communicable disease reporting system for seasons 2010/11, 2011/12 and 2012/13. Vaccination coverage (VC) data were retrieved from a database of health insurance claims representing ~85% of the total German population. We applied the screening method to calculate influenza subtype-specific VE and compared our results with VE estimates from other observational studies in Europe. Results: In total, 7,156 laboratory-confirmed influenza cases were included. VE against all influenza types ranged between 49% (95% confidence interval [CI]: 39-56) in 2011/12 and 80% (95% CI: 76-83%) in 2010/11. In 2010/11 subtype-specific VE against influenza A(H1N1)pdm and B was 76% and 84%, respectively. In the following seasons, VE against influenza A(H1N1)pdm, A(H3N2) and B was 87%, -9% , 74% (2011/12), and 74%, 39%, 73% (2012/13). VE was higher among hospitalized compared to non-hospitalized influenza A cases. Seventeen observational studies from Europe reporting subtype-specific VE among the elderly were identified for the respective seasons (all applying the test-negative design) and showed comparable subtype-specific VE estimates. Conclusions: According to our study, influenza vaccination provided moderate protection against laboratory-confirmed influenza A(H1N1)pdm and B in individuals aged 60+ but no or only little protection against A(H3N2). Higher VE among hospitalized cases might indicate higher protection against severe influenza disease. Based on the available data, the screening method allowed us to assess subtype-specific VE in hospitalized and non-hospitalized elderly persons. Since controlling for several important confounders was not possible, the applied method only provided crude VE estimates. However, given the precise VC-data and the large number of cases, the screening method provided results being in line with VE estimates from other observational studies in Europe that applied a different study design.
    Full-text · Article · Dec 2015
    • The sensitivity of a recently developed multiplex rtRT-PCR system for the detection of influenza type A and B viruses and subtype H1N1 by Huber el al. was found to be 3.5 ? 10 2 RNA copies per PCR reaction [31]. However, the detection limit of the present study was almost the same as that of the single rtRT- PCR assay for the detection of influenza A virus, studied earlier [32]. The CDC rtRT-PCR Swine Flu Panel has been shown to detect 5 copies of RNA per reaction [33].
    [Show abstract] [Hide abstract] ABSTRACT: Introduction Influenza A is known as a public health concern worldwide. In this study, a novel one-step real-time reverse transcription polymerase chain reaction (rtRT-PCR) assay was designed and optimized for the detection of influenza A viruses. Material and methods The primers and probe were designed based on the analysis of 90 matrix nucleotide sequence data of influenza type A subtypes from the GenBank database of the National Center for Biotechnology Information (NCBI). The influenza virus A/Tehran/5652/2010 (H1N1 pdm09) was used as a reference. The rtRT-PCR assay was optimized, compared with that of the World Health Organization (WHO), and its analytical sensitivity, specificity and reproducibility were evaluated. In total, 64 nasopharyngeal swabs from patients with influenza-like illness (ILI) and 41 samples without ILI symptoms were tested for the virus, using conventional cell culture, direct immunofluorescence antibody (DFA) methods, and one-step rtRT-PCR with the designed primer set and probe and the WHO’s. Results The optimized assay results were similar to the WHO’s. The optimized assay results were similar to WHO’s, with non-significant differences for 10–10³ copies of viral RNA/reaction (p > 0.05). It detected 10 copies of viral RNA/reaction with high reproducibility and no cross reactivity with other respiratory viruses. A specific cytopathic effect was observed in 6/64 (9.37%) of the ILI group using conventional culture and DFA staining methods; however, it was not seen in non-ILI. Also, the results of our assay and the WHO’s were similar to those of viral isolation and DFA staining. Conclusions Given the high specificity, sensitivity and reproducibility of this novel assay, it can serve as a reliable diagnostic tool for the detection of influenza A viruses in clinical specimens and lab experiments.
    Full-text · Article · Dec 2016
    • Overall pooled adjusted VE in children under 18 years was 76% (95% CI 48–89%, p = 0.0003, I 2 = 50%, studies = 7, n = 3994) [10,12,18,19,22,27,28]. Pooled VE was 88% for adjuvanted vaccines (95% CI 69–95%, p < 0.0001, I 2 = 34%, studies = 4, n = 932) [18,22,27,28], and 45% for unadjuvanted vaccines (95% CI À13– 73%, p = 0.83, I 2 = 0%, studies = 3, n = 3062;Fig. 3) [10,12,19].
    [Show abstract] [Hide abstract] ABSTRACT: Background: The clinical effectiveness of monovalent influenza A(H1N1)pdm09 vaccines has not been comprehensively summarised. We undertook a systematic review and meta-analysis to assess vaccine effectiveness (VE) for adjuvanted and unadjuvanted vaccines. Methods: We searched healthcare databases and grey literature from 11 June 2009 to 12 November 2014. Two researchers independently assessed titles and abstracts to identify studies for full review. Random effects meta-analyses estimated the pooled effect size of vaccination compared to placebo or no vaccination for crude and adjusted odds ratios (OR) to prevent laboratory confirmed influenza illness (LCI) and related hospitalization. VE was calculated as (1-pooled OR)∗100. Narrative synthesis was undertaken where meta-analysis was not possible. Results: We identified 9229 studies of which 38 at moderate risk of bias met protocol eligibility criteria; 23 were suitable for meta-analysis. Pooled adjusted VE against LCI with adjuvanted and unadjuvanted vaccines both reached statistical significance (adjuvanted: VE=80%; 95% confidence interval [CI] 59-90%; unadjuvanted: VE=66%; 95% CI 47-78%); in planned secondary analyses, VE in adults often failed to reach statistical significance and pooled point estimates were lower than observed in children. Overall pooled adjusted VE against hospitalization was 61% (95% CI 14-82%); in planned secondary analyses, adjusted VE attained statistical significance in adults aged 18-64years and children for adjuvanted vaccines. Adjuvanted vaccines were significantly more effective in children compared to adults for both outcomes. Conclusions: Adjuvanted and unadjuvanted monovalent influenza A(H1N1)pdm09 vaccines were both effective in preventing LCI. Overall, the vaccines were also effective against influenza-related hospitalization. For both outcomes adjuvanted vaccines were more effective in children than in adults.
    Full-text · Article · Mar 2017
    • Alemtuzumab consolidation therapy has been studied in CLL trials. In one with initial fludarabine or FC therapy, followed 2 months later by alemtuzumab consolidation, 7/11 patients developed grade 3/4 infections (4 CMV reactivation, aspergillosis, tuberculosis, HZ), resulting in study termination [13] . In another with alemtuzumab consolidation 5 months after induction therapy response, 9/41 (22%) patients had CMV reactivation [14] .
    [Show abstract] [Hide abstract] ABSTRACT: The introduction of novel agents to the therapeutic armamentarium for oncologic, rheumatologic, and neurologic disorders has resulted in major clinical advances. These agents impact immune function, resulting in a discrete spectrum of infectious complications. Purine analogues and alemtuzumab alter cell-mediated immunity, resulting in opportunistic viral/fungal infections. Herpes zoster incidence increases with bortezomib. Hepatitis B reactivation may occur with rituximab. Cases of progressive multifocal leukoencephalopathy have occurred following monoclonal antibody therapy. Tumor necrosis factor-α inhibitor therapy is complicated by tuberculosis reactivation and fungal infections. We summarize the impact of these therapies on pathogenesis and spectrum of infection complicating their usage.
    Article · Nov 2014