I E Bergmann

CEP America, Emeryville, California, United States

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Publications (39)87.38 Total impact

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    ABSTRACT: The widespread perception of the effectiveness of applying tests based on the detection of antibodies against foot-and-mouth disease (FMD) viral non-capsid proteins (NCPs) to assess virus circulation irrespective of vaccination triggered the demand for international standards to evaluate the comparative performance of the upcoming assays against the OIE Index test developed at the Pan American Foot-and-Mouth Disease Center, PAHO/WHO. To this end, a panel was developed composed of 34 cattle sera from animals with an unambiguous exposed/infected status, covering serotypes O, A and C, obtained either under experimental conditions or from the field in regions with different epidemiological situations. Reference values in the Index test and their reproducibility in other laboratories, data on stability as well as results in four other commercial kits and one in house test were obtained. The characteristics of the panel which comprise adequate preparation following international guidelines, a broad range of antibody reactivity, proper stability and the ability to assess comparative diagnostic sensitivity, make it suitable as a reference standard to evaluate if tests equivalent to the OIE Index method are used in support of FMD control programs and by trading partners, and also whether they maintain their standards of diagnostic performance.
    Journal of Virological Methods 08/2008; 151(1):15-23. · 1.90 Impact Factor
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    ABSTRACT: Six tests for detection of antibodies against the non-structural proteins of foot-and-mouth disease virus (FMDV) were compared at an international workshop in Brescia, Italy in 2004 on the basis of dichotomous test results. However, as results from all of these assays were also available on a continuous scale, validation was extended by calculating and subsequently analysing the receiver-operator characteristic (ROC) curves and likelihood ratios (LR) for each test method. For the purposes of these analyses, test results for a total of 1337 sera were selected from the Brescia workshop dataset, 237 sera that had been obtained from cattle exposed to FMDV and 1100 sera obtained from cattle that were not exposed to the virus; sera from "exposed" cattle were considered to be "true positives" and sera from "non-exposed" cattle were considered to be "true negatives". Analysis of ROC curves showed that at specificities of both 99 and 99.5%, the IZS-Brescia and the Ceditest ELISA had significantly better detection rates in exposed cattle than the other ELISAs. The ROC analysis confirms the previous finding that the IZS-Brescia and the Ceditest ELISAs have both better detection rates in exposed cattle combined with a high specificity. The analysis of likelihood ratios provides information that may be very useful in the interpretation of test results, and a working example is presented to show how these likelihood ratios might be used in an objective approach to deciding the true infection status of surveyed populations.
    Vaccine 06/2008; 26(22):2723-32. · 3.49 Impact Factor
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    ABSTRACT: To validate the use of serology in substantiating freedom from infection after foot-and-mouth disease (FMD) outbreaks have been controlled by measures that include vaccination, 3551 sera were tested with six assays that detect antibodies to the non-structural proteins of FMD virus. The sera came from naïve, vaccinated, infected and vaccinated-and-infected animals; two-thirds from cattle, the remainder from sheep and pigs. The assays were covariant for sensitivity, but not necessarily for specificity. A commercial kit from Cedi-diagnostics and an in-house assay from IZS-Brescia were comparable to the NCPanaftosa-screening index method described in the Diagnostic Manual of the World Animal Health Organisation. Using these three tests the specificity and sensitivity for the detection of carriers in vaccinated cattle approaches or exceeds 99% and 90%, respectively.
    Vaccine 12/2006; 24(47-48):6966-79. · 3.49 Impact Factor
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    ABSTRACT: There has been much debate about the use of the so-called "vaccinate-to-live" policy for the control of foot-and-mouth disease (FMD) in Europe, according to which, spread of the FMD virus (FMDV) from future outbreaks could be controlled by a short period of "emergency" vaccination of surrounding herds, reducing the need for large-scale preemptive culling of at-risk animals. Since vaccinated animals may become subclinically infected with FMDV following challenge exposure, it is necessary to either remove all vaccinates (vaccinate-to-kill) or to detect and remove vaccinates in which virus is circulating or has established persistent infections (vaccinate-to-live), in order to rapidly regain the most favoured trading status of FMD-free without vaccination. The latter approach can be supported by testing vaccinated animals for the presence of antibodies to certain non-structural proteins (NSP) of FMDV, which are induced by infection with the virus, but not by vaccination with purified FMD vaccines. Using test sensitivity and specificity data established at a recent workshop on NSP assays [Brocchi E, Bergmann I, Dekker A, Paton DJ, Sammin DJ, Greiner M, et al. Comparative performance of six ELISAs for antibodies to the non-structural proteins of foot-and-mouth disease. Vaccine, in press], this paper examines the ways in which serological testing with NSP ELISAs can be used and interpreted and the effect that this will have on the confidence with which freedom from infection can be demonstrated within guidelines specified by the World Animal Health Organisation and the European Commission.
    Vaccine 11/2006; 24(42-43):6503-12. · 3.49 Impact Factor
  • G Darsie, A J Falczuk, I E Bergmann
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    ABSTRACT: The threat of using biological material for ago-bioterrorist ends has risen in recent years, which means that research and diagnostic laboratories, biological agent banks and other institutions authorised to carry out scientific activities have had to implement biosafety and biosecurity measures to counter the threat, while carrying out activities to help prevent and monitor the accidental or intentional introduction of exotic animal diseases. This article briefly sets outthe basic components of biosafety and biosecurity, as well as recommendations on organisational strategies to consider in laboratories that support agro-bioterrorist surveillance and prevention programs.
    Revue scientifique et technique (International Office of Epizootics) 05/2006; 25(1):321-7. · 0.69 Impact Factor
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    ABSTRACT: The use during the last decade of immuno-enzymatic tests based on the detection of antibodies to the non-capsid proteins (NCPs) of foot-and-mouth disease virus (FMDV) to assess viral circulation, irrespective of vaccination, supported the incorporation into the OIE code of the 'free from FMDV with vaccination' category and opened the way to a 'vaccination to live' policy. Eradication programmes in South America include systematic vaccination accompanied by large serosurveys through NCP antibody testing to ensure the absence of residual viral activity. For correct interpretation of serosurveys, a major prerequisite is that vaccines made of semi-purified preparations of inactivated virions do not contain levels of NCPs, which upon proper presentation conditions, could induce an antibody response under the conditions for field immunization. This work describes the development of an inhibition ELISA to detect NCP polyprotein 3ABC in viral suspensions destined for vaccine production as an in-process control during vaccine manufacture. Antibody responses against NCP 3ABC in vaccinated and revaccinated cattle, induced by vaccines with different purification processes and formulations, are discussed.
    Developments in biologicals 02/2006; 126:241-50; discussion 327.
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    I E Bergmann, V Malirat, E Neitzert
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    ABSTRACT: The ability of foot-and-mouth disease virus (FMDV) to establish subclinical and even persistent infection, the so called carrier state, imposes the need to reliably demonstrate absence of viral circulation, to monitor the progress of control measures, either during eradication programs or after reintroduction of virus in free areas. This demonstration becomes critical in immunized populations, because of the concern that silent viral circulation could be hidden by immunization. This concern originates from the fact that vaccination against foot-and-mouth disease (FMD) protects against clinical disease, but not necessarily against subclinical infection or establishment of the carrier state in cattle. A novel approach, developed and validated at PANAFTOSA during the 1990s, based on an immunoenzymatic system for detection of antibodies against non-capsid proteins (NCP) has proven valuable for monitoring viral circulation within and between herds, irrespective of the vaccination status. Antibodies against NCP are induced during infection but, in principle, not upon vaccination. The validation of this system led to its international recognition as the OIE index test. The fitness of this serosurvey tool to assess viral circulation in systematically vaccinated populations was demonstrated through its extensive application in most regions in South America. The experience attained in these regions supported the incorporation of the "free of FMD with vaccination" provisions into the OIE code. Likewise, it opened the way to alternatives to the "stamping out" policy. The results gave input to an old controversy related to the real epidemiological significance, if any, of carrier animals under the vaccination conditions in South America, and supported the development of recommendations and guidelines that are being implemented for serosurveys that go with control measures in vaccinated populations.
    Biologicals 01/2006; 33(4):235-9. · 1.62 Impact Factor
  • G. Darsie, A. J. Falczuk, I. E. Bergmann
    01/2006;
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    ABSTRACT: Since the implementation in 1988 of the foot-and-mouth disease (FMD) eradication programme in South America (PHEFA), significant advances have been made in the control of the disease. Particularly relevant has been the progress attained in one of the three subregions, the Southern Cone, where during the late 1990s most areas were recognized as FMD-free by OIE, with or without vaccination. To achieve PHEFA goals, development and implementation of diagnostic tools to trace for potential sources of infection was of utmost importance. Accordingly, priority was given to the identification of genetic links among circulating strains and, in relevant areas, to the systematic sero-epidemiological monitoring of persistent viral activity, regardless of vaccination condition. A genetic database of representative strains from South America, constructed at the Pan American Foot-and-Mouth Disease Center, constituted the basis for the phylogenetic analysis of viruses types O and A recorded recently in endemic regions, and during the emergencies in FMD-free areas of the Southern Cone. The genetic data placed all variants from the Southern Cone in a single lineage, which clearly differed from the evolutionary nodes that included the isolates in the Andean subregion, reflecting two independent production systems and livestock trade circuits. To complement the search for potential sources of infection, serosurveillance became an important adjunct. To this end, new tools to infer viral circulation within and between herds, irrespective of vaccination, were developed and validated. The diagnostic approach, based on an immunoenzymatic system that detects antibodies against non-capsid proteins, was particularly useful in support of epidemiological investigations after episodes and to confirm absence of viral activity in regions to be recognized as FMD-free, being especially important prior to the suspension of vaccination. Results of samplings in the Southern Cone during the 1990s strongly suggested that emergencies in this subregion did not originate from residual persistent activity in the areas declared FMD-free, but most probably from trade activities involving “hot spots” within the subregion.
    12/2005: pages 335-342;
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    ABSTRACT: Vaccination against foot-and-mouth disease (FMD) constitutes an important component of the policy for its control and eradication in South America. Considering that immunization may not impair subclinical infection, it became advisable to ally to vaccination campaigns a surveillance instrument to monitor silent viral circulation. Novel approaches for the evaluation of antibodies to FMD non-capsid proteins (NCPs), developed and validated at PANAFTOSA proved valuable for assessing viral circulation in immunized populations. The extensive and coordinated application in South America of vaccination together with this serosurvey tool indicated the effectiveness of systematic vaccination to prevent FMD spread and to restrain silent viral circulation intra- and inter- herds, and gave input to an old controversy related to the real epidemiological significance, if any, of carrier animals under the vaccination conditions in South America. The fitness of NCP tests to assess viral circulation in a population supported the incorporation into the OIE code of the "free of FMD with vaccination" category as a step prior to the recognition of the "free of FMD without vaccination" category. Likewise it released the path to allow animals, vaccinated for protective purposes during emergencies, to live for the term of their productive lives.
    Developments in biologicals 02/2004; 119:273-82.
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    ABSTRACT: Frequency distribution of reactivity levels of foot-and-mouth disease infection-specific antibodies in livestock populations was analysed. Specific antibody responses against non-capsid polyprotein 3ABC were assessed through a highly sensitive indirect enzyme-linked immonosorbent assay (I-ELISA 3ABC). A graphic display of data was designed based on three negative and three positive categories to illustrate reactivity patterns. The resulting patterns were correlated to the epidemiological status. On this basis, results of over 100,000 sera derived from cattle populations in regions with various well-documented epidemiological situations were compiled and are exemplified in this paper.Distinct distributions of antibody reactivity patterns reflecting the various epidemiological situations were attained. Whereas non-affected areas presented a rather homogenous negative pattern with very limited test-positive reactions, affected regions revealed quite heterogeneous profiles, including positive and negative categories, with distributions that varied according to the region. The use of graphic prints encompassing I-ELISA 3ABC antibody profile responses constituted an adequate epidemiological indicator of the risk of foot-and-mouth disease viral activity, providing immediate visualization for a rapid inference of the epidemiological situation of a region. Moreover, such profiles allowed for convenient follow-up of infection after a focus as a function of time and geographical spread.
    Archives of Virology 06/2003; 148(5):891-901. · 2.03 Impact Factor
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    ABSTRACT: Vaccination constitutes an important control policy for foot-and-mouth disease (FMD) in affected areas with advanced eradication programmes, as well as in free regions that decide to use immunization as a control measure after a recent introduction of the disease. However, considering that vaccinated animals exposed to FMD virus can establish sub-clinical infection and eventually remain persistently infected, availability of tools to identify sub-clinical infection and its silent transmission within and between herds, regardless of their vaccination state, is of utmost importance. In response to the need for new diagnostic tools to support the eradication campaigns implemented in 1988 in South America, during the past decade we have developed, validated and applied a highly sensitive and specific immuno-enzymatic system for recognition of persistence at a herd level. The system is based on the detection of antibodies against non-capsid proteins required for viral replication. These proteins, in principle, are removed from the viral suspensions destined for production of BEI inactivated vaccines. Within the validation steps, evaluation of potential induction of antibodies to non-capsid proteins caused by traces of these proteins eventually remaining in the vaccines was a major concern. This report presents a review on the experience gathered through the application of the system to various experimental and field immunization conditions. It was concluded that vaccination is not expected to induce antibody responses to non-capsid proteins that could lead to misinterpretation of serological investigations. Progress on the development of approaches towards vaccine certification to guarantee absence of interference will be discussed.
    Developments in biologicals 02/2003; 114:59-65.
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    ABSTRACT: Auto-processing of the non-structural polypeptide 3ABC of foot and mouth disease virus (FMDV) expressed in Escherichia coli-BL21-DE3 was prevented by mutating either four glutamic acid residues at the 3A/3B1, 3B1/2, 3B2/3 and 3B3/3C junctions (3ABCtet) or a single cysteine residue at position 383 within the 3C domain (3ABCm). Independent expression of 3ABC and 3ABCtet genes induced expression of chaperone DnaK and degradation of ribosomal S1 protein in E. coli. They also induced cleavage of nucleosomal histone H3 when transiently expressed in BHK21 cells. 3ABCtet, 3ABCm, 3AB and 3A proteins concentrated in the perinuclear region suggesting that peptide sequences within the 3A domain specify intracellular targeting of 3ABC in BHK-21 cells. We propose that 3ABC molecules localized in the nuclear periphery are a source of protease 3C activity and are responsible for histone H3 processing during FMDV infections.
    Virus Research 01/2003; 90(1-2):91-9. · 2.75 Impact Factor
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    I. E. Bergmann
    01/2003;
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    ABSTRACT: Foot-and-mouth disease (FMD) recombinant non-capsideal viral antigens 3A, 3B, 2C, 3D and 3ABC were assessed individually in an indirect enzyme-linked immunosorbent assay (I-ELISA) for their ability to screen for persistent infection-specific antibodies in cattle, regardless of vaccination condition. Results of sequential serum samples from non-vaccinated animals with experimentally induced persistent infection, and their correlation with virus isolation, indicated that the polypeptides 3A, 3B and 3ABC showed the most adequate characteristics for further field studies. Reliable performance of the I-ELISA with the selected antigen 3ABC was indicated by the distinct patterns observed for the frequency distribution values of naive and true positive samples. For regularly vaccinated livestock, a clear negative profile was proved in samples from regions without recent history of FMD. In contrast, at 90 and 900 days post-outbreak, coexistence of a positive and a negative population was established. These findings indicated that, irrespective of vaccination, the test allowed a classification of the herd-disease status. A high degree of agreement was observed between I-ELISA-3ABC and EITB results for clearly reactive and non-reactive sera. For samples with reactivity values close to that of the cut-off, the EITB profiles upheld the definition of the infection condition. On this basis, screening by I-ELISA-3ABC, together with confirmation of suspect or positive samples by EITB is proposed as an adequate and accurate approach for large-scale epidemiological surveillance.
    Archives of Virology 02/2000; 145(3):473-89. · 2.03 Impact Factor
  • I E Bergmann, V Astudillo, V Malirat, E Neitzert
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    ABSTRACT: Antibody profile responses elicited against foot‐and‐mouth disease virus nonstructural proteins, under various experimental and field conditions, were detected by means of highly sensitive immunoenzymatic approaches. On the basis of the results obtained, useful inferences were made for proper interpretation of seroepidemiologic surveys in the determination of residual viral activity in an animal population, regardless of its vaccination condition, and for import/export testing. In this work several considerations on survey strategy and assay approaches are discussed.
    The Veterinary quarterly 02/1998; 20 Suppl 2:S6-9. · 0.85 Impact Factor
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    ABSTRACT: An indirect enzyme‐linked immunosorbent assay (I‐ELISA) capable of detecting foot‐and‐mouth disease virus (FMDV)‐specific antibodies in sera from animals with previous viral exposure was developed, as an alternative tool to the enzyme‐linked immunoelectrotransfer blot (EITB) test previously described (Bergmann et al., 1993). Out of the 5 recombinant DNA‐derived FMD nonstructural viral antigens used in the EITB assay, 3ABC was selected, as a serologic probe for the I‐ELISA. High sensitivity for detection of acute as well as of subclinical infection, even at late stages of the persistent status, was indicated by the results for sera from naive animals following experimental infection, or following exposure to the virus under natural conditions. The ability of the test to identify FMDV persistently infected animals subjected to systematic vaccination was also demonstrated. High specificity was revealed by evaluating sera from cattle in FMD‐free regions without vaccination, including samples from cattle infected with a variety of bovine viruses. Analysis of sera from animals in FMD‐free areas under regular vaccination campaigns, including cattle with multiple immunization cycles showed that, ocasionally, antibodies against 3ABC are elicited. The data presented herein indicate that, in agreement with results obtained with the EITB test, the I‐ELISA detected FMDV‐specific antibodies, also at late stages of the persistent infection, maintaining nonspecific reactions at low levels, even in regions under systematic vaccination. Use of the I‐ELISA is suitable as a sensitive, safe, rapid, reproducible and economic test for the detection of previous virus exposure. A combination of screening by the I‐ELISA together with confirmation of suspect serum samples by the more specific EITB assay is proposed for large scale epidemiological surveillance.
    The Veterinary quarterly 02/1998; 20 Suppl 2:S24-6. · 0.85 Impact Factor
  • I E Bergmann, V Malirat, L E Dias, R Dilandro
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    ABSTRACT: To assess the potential of a highly sensitive enzyme-linked immunoelectrotransfer blot (EITB) assay to monitor persistent foot-and-mouth disease (FMD) viral activity in a livestock population. Cattle sera were obtained in Uruguay in 1992, 2 years after the last outbreaks of FMD. Prevalence of antibodies, as assessed by the EITB assay and by the conventional immunodiffusion in agarose gel method (virus infection-associated antigen [VIAA] test), was correlated with occurrence of FMD. A total of 2,194 serum samples were acquired from animals at different farms and were separated according to age: animals < and > 2 years old. Specific antibodies to replicating virus were detected by use of the EITB assay that utilizes a set of 5 bioengineered nonstructural antigens as serologic probes. EITB-positive reaction was restricted to sera from cattle in areas with the last outbreaks of FMD during 1989-1990, and to animals > 2 years old. All cattle sera from regions that were free of clinical FMD since (or prior to) 1989 were EITB negative. In contrast, use of the VIAA test yielded a rather homogeneous distribution of positive results when regions without FMD during the last 4 years preceding sample collection were compared with those affected during 1989-1990. VIAA test-positive reaction was also found in sera from animals born after the last FMD outbreak. The EITB assay proved to be a sensitive, specific, safe, rapid, and economic tool for monitoring the progress of FMD eradication programs, mainly because it eliminated false-positive results form the VIAA test.
    American Journal of Veterinary Research 08/1996; 57(7):972-4. · 1.35 Impact Factor
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    ABSTRACT: To assess whether foot-and-mouth disease virus (FMDV)-specific sequences could be identified in tissues from persistently virus-infected animals. Cattle with experimentally induced persistent FMDV infections were slaughtered at 750 days after viral exposure. Experimentally infected pigs were slaughtered at 28 days after FMDV inoculation. Postmortem specimens were asceptically removed. Three bovids and 3 pigs were studied, as well as 1 control animal for each species. Various tissues were examined for the presence of FMDV-specific sequences by dot-blot hybridization assay, using a molecularly cloned FMDV cDNA corresponding to the polymerase coding region. The FMDV-specific genomic sequences were only detected in RNA from spleen, lung, larynx, tonsils, pancreas, liver, esophagus, and WBC of bovids. It was established that, at late stages of the persistent infection, when virus isolation was not possible, cattle may carry FMDV-specific sequences in different tissues. Retention of viral sequences could not be demonstrated in specimens from experimentally infected swine, 28 days after viral inoculation.
    American Journal of Veterinary Research 03/1996; 57(2):134-7. · 1.35 Impact Factor
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    X Cao, I E Bergmann, R Füllkrug, E Beck
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    ABSTRACT: The effect of deletion of each of the two authentic polyprotein translation initiation sites of foot-and-mouth disease virus on viral protein synthesis and replication was analyzed. Deletion of either the first or the second initiation site led to the expression of only one form of the leader protein, L or L', respectively, but in vitro processing of the viral polyprotein and cleavage of eIF-4 gamma were not affected by either deletion. Whereas RNA in which the first translation initiation site had been deleted led to the production of viruses in transfected BHK cells, deletion of the second translation initiation site abolished virus replication.
    Journal of Virology 02/1995; 69(1):560-3. · 5.08 Impact Factor

Publication Stats

617 Citations
87.38 Total Impact Points

Institutions

  • 2006
    • CEP America
      Emeryville, California, United States
  • 1995
    • Stony Brook University
      Stony Brook, New York, United States
  • 1990
    • Universität Heidelberg
      Heidelburg, Baden-Württemberg, Germany