A Forgotten Episode of Marburg Virus Disease: Belgrade, Yugoslavia, 1967.

In 1967, several workers involved in poliomyelitis vaccine development and production fell ill at three different locations in Europe with a severe and often lethal novel disease associated with grivets (Chlorocebus aethiops) imported from Uganda. This disease was named Marburg virus disease (MVD) after the West German town of Marburg an der Lahn, where most human infections and deaths had been recorded. Consequently, the Marburg episode received the most scientific and media attention. Cases that occurred in Frankfurt am Main, West Germany, were also described in commonly accessible scientific literature, although they were less frequently cited than those pertaining to the Marburg infections. However, two infections occurring in a third location, in Belgrade, Yugoslavia, have seemingly been all but forgotten. Due in part to their absence in commonly used databases and in part to the fact that they were written in languages other than English, the important articles describing this part of the outbreak are very rarely cited. Here, we summarize this literature and correct published inaccuracies to remind a younger generation of scientists focusing on Marburg virus and its closest filoviral relatives of this important historical context. Importantly, and unfortunately, the three episodes of infection of 1967 still represent the best in-depth clinical look at MVD in general and in the context of "modern" medicine (fully resourced versus less-resourced capacity) in particular. Hence, each individual case of these episodes holds crucial information for health care providers who may be confronted with MVD today.

Working Safely with Vaccinia Virus: Laboratory Technique and Review of Published Cases of Accidental Laboratory Infections with Poxviruses.

Vaccinia virus, the prototype Orthopoxvirus, is widely used in the laboratory as a model system to study various aspects of viral biology and virus-host interactions, as a protein expression system, as a vaccine vector, and as an oncolytic agent. The ubiquitous use of vaccinia viruses in laboratories around the world raises certain safety concerns because the virus can be a pathogen in individuals with immunological and dermatological abnormalities, and on occasion can cause serious problems in normal hosts. This chapter reviews standard operating procedures when working with vaccinia virus and reviews published cases of accidental laboratory infections with poxviruses.

[Analysis on status and characteristics of laboratory-acquired vaccinia virus infections cases].

OBJECTIVE: By analyzing the status and characteristics of vaccinia virus laboratory-acquired infections in the bibliographical information, this paper provides relevant recommendations and measures for prevention and control of vaccinia virus laboratory-acquired infections in China. METHODS: Choosing PubMed, Embase, Biosis and SCIE, SSCI, CPCI-S as well as CPCI-SSH covered by Web of Science as the data source, indexing the bibliography of vaccinia virus laboratory-acquired infections, this paper analyzes the information on whether to vaccinate, the occurrence time of symptoms, diseasedparts, symptom characteristics and the disease-causing reasons. RESULTS: The outcome shows that 52. 9% of the cases never get vaccinated, 82.4% engaged in vaccinia virus related researches never get vaccinated in 10 years, 52. 9% get infected by the accidental needlestick in hands during the process of handling animal experiments, 70. 6% of infections occur in the hands and having symptoms after being exposed with an average of 5. 1 days. CONCLUSION: Although it is still controversial that whether or not to be vaccinated before carrying out vaccinia virus related works, it should be important aspects of prevention and control of vaccinia virus laboratory-acquired infections with the strict compliance with the operating requirements of the biosafety, by strengthening personal protection and timely taking emergency measures when unforeseen circumstances occur, as well as providing the research background information to doctors.

Working safely with vaccinia virus: laboratory technique and review of published cases of accidental laboratory infections.

Vaccinia virus (VACV), the prototype orthopoxvirus, is widely used in the laboratory as a model system to study various aspects of viral biology and virus-host interactions, as a protein expression system, as a vaccine vector, and as an oncolytic agent. The ubiquitous use of VACVs in the laboratory raises certain safety concerns because the virus can be a pathogen in individuals with immunological and dermatological abnormalities, and on occasion can cause serious problems in normal hosts. This chapter reviews standard operating procedures when working with VACV and reviews published cases on accidental laboratory infections.

Investigation of the first laboratory-acquired human cowpox virus infection in the United States.

BACKGROUND: Cowpox virus is an Orthopoxvirus that can cause infections in humans and a variety of animals. Infections occur in Eurasia; infections in humans and animals have not been reported in the United States. This report describes the occurrence of the first known human case of laboratory-acquired cowpox virus infection in the United States and the ensuing investigation. METHODS: The patient and laboratory personnel were interviewed, and laboratory activities were reviewed. Real-time polymerase chain reaction (PCR) and serologic assays were used to test the patient's specimens. PCR assays were used to test specimens obtained during the investigation. RESULTS: A specimen from the patient's lesion tested positive for cowpox virus DNA. Genome sequencing revealed a recombinant region consistent with a strain of cowpox virus stored in the research laboratory's freezer. Cowpox virus contamination was detected in 6 additional laboratory stocks of viruses. Orthopoxvirus DNA was present in 3 of 20 environmental swabs taken from laboratory surfaces. CONCLUSIONS: The handling of contaminated reagents or contact with contaminated surfaces was likely the mode of transmission. Delays in recognition and diagnosis of this infection in a laboratory researcher underscore the importance of a thorough patient history-including occupational information-and laboratory testing in facilitating a prompt investigation and application of control and remediation measures.

Viral infections in workers in hospital and research laboratory settings: a comparative review of infection modes and respective biosafety aspects.

OBJECTIVES: To compare modes and sources of infection and clinical and biosafety aspects of accidental viral infections in hospital workers and research laboratory staff reported in scientific articles. METHODS: PubMed, Google Scholar, ISI Web of Knowledge, Scirus, and Scielo were searched (to December 2008) for reports of accidental viral infections, written in English, Portuguese, Spanish, or German; the authors' personal file of scientific articles and references from the articles retrieved in the initial search were also used. Systematic review was carried out with inclusion criteria of presence of accidental viral infection's cases information, and exclusion criteria of absence of information about the viral etiology, and at least probable mode of infection. RESULTS: One hundred and forty-one scientific articles were obtained, 66 of which were included in the analysis. For arboviruses, 84% of the laboratory infections had aerosol as the source; for alphaviruses alone, aerosol exposure accounted for 94% of accidental infections. Of laboratory arboviral infections, 15.7% were acquired percutaneously, whereas 41.6% of hospital infections were percutaneous. For airborne viruses, 81% of the infections occurred in laboratories, with hantavirus the leading causative agent. Aerosol inhalation was implicated in 96% of lymphocytic choriomeningitis virus infections, 99% of hantavirus infections, and 50% of coxsackievirus infections, but infective droplet inhalation was the leading mode of infection for severe acute respiratory syndrome coronavirus and the mucocutaneous mode of infection was involved in the case of infection with influenza B. For blood-borne viruses, 92% of infections occurred in hospitals and 93% of these had percutaneous mode of infection, while among laboratory infections 77% were due to infective aerosol inhalation. Among blood-borne virus infections there were six cases of particular note: three cases of acute hepatitis following hepatitis C virus infection with a short period of incubation, one laboratory case of human immunodeficiency virus infection through aerosol inhalation, one case of hepatitis following hepatitis G virus infection, and one case of fulminant hepatitis with hepatitis B virus infection following exposure of the worker's conjunctiva to hepatitis B virus e antigen-negative patient saliva. Of the 12 infections with viruses with preferential mucocutaneous transmission, seven occurred percutaneously, aerosol was implicated as a possible source of infection in two cases, and one atypical infection with Macacine herpesvirus 1 with fatal encephalitis as the outcome occurred through a louse bite. One outbreak of norovirus infection among hospital staff had as its probable mode of infection the ingestion of inocula spread in the environment by fomites. CONCLUSIONS: The currently accepted and practiced risk analysis of accidental viral infections based on the conventional dynamics of infection of the etiological agents is insufficient to cope with accidental viral infections in laboratories and to a lesser extent in hospitals, where unconventional modes of infection are less frequently present but still have relevant clinical and potential epidemiological consequences. Unconventional modes of infection, atypical clinical development, or extremely severe cases are frequently present together with high viral loads and high virulence of the agents manipulated in laboratories. In hospitals by contrast, the only possible association of atypical cases is with the individual resistance of the worker. Current standard precaution practices are insufficient to prevent most of the unconventional infections in hospitals analyzed in this study; it is recommended that special attention be given to flaviviruses in these settings.

[Preliminary studies on pathogenic microorganisms laboratory-acquired infections cases in recent years and its control strategies].

OBJECTIVE: To analyze and study types, infections routes and causes of global pathogenic microorganisms laboratory-acquired infections cases reported in the literatures from 2000 to 2009 and to discuss prevention and control strategies. METHODS: (1) Pathological observation of hepatic specimens: hepatic tissue pathogenic microorganisms laboratory-acquired infections. Methods PubMed, Embase, Biosis and Webs of Science covering SCIE, SSCI, CPCI-S and CPCI-SSH are chosen as data sources, "laboratory-acquired (associated) infections" are searched as the key words to search laboratory-acquired infections literature published from 2000 to 2009, from which information and data are accessed to be collected, analyzed and researched. RESULTS: There are 19 species of pathogenic microorganisms causing laboratory-acquired infections in the last 10 years, including 15 species of bacteria, accounting for 78.9%; 4 species of virus, accounting for 21.1%. There are 83 cases reported, of which there are 60 bacterial cases, accounting for 72.3%; and 23 virus cases, accounting for 27.7%. Ingestion and inhalation are main routes of infections, respectively accounting for 32.5% and 31.3%, which are mainly due to accidents, accounting for 47.0%. CONCLUSION: In recent years, pathogenic microbiology laboratory-acquired infections continue to occur, and it is mainly due to accidental infections, which expose laboratory workers' low sense of safety and deficient operation methods. Laboratory staff should strengthen their senses of safety and comply with safe operation procedures, which are still the key to prevent laboratory-acquired infections.

Risks associated with vaccinia virus in the laboratory.

Vaccinia virus (VACV) is used commonly in research laboratories. Non-highly attenuated strains of VACV are potentially pathogenic in humans, and VACV vaccination and biosafety level 2 facilities and protocols are currently recommended for vaccinated laboratory workers in the United States who handle non-highly attenuated strains of the virus. Despite this, laboratory-related VACV exposures continue to occur and a number of recent instances of VACV infection in non-vaccinated laboratory workers have been documented. We provide a discussion of the usage and risks associated with VACV in laboratory research.

Managing potential laboratory exposure to ebola virus by using a patient biocontainment care unit.

In 2004, a scientist from the US Army Medical Research Institute of Infectious Diseases (USAMRIID) was potentially exposed to a mouse-adapted variant of the Zaire species of Ebola virus. The circumstances surrounding the case are presented, in addition to an update on historical admissions to the medical containment suite at USAMRIID. Research facilities contemplating work with pathogens requiring Biosafety Level 4 laboratory precautions should be mindful of the occupational health issues highlighted in this article.

Comparison of the sensitivity of in vivo antibody production tests with in vitro PCR-based methods to detect infectious contamination of biological materials.

Bacteria and viruses may be transmitted to laboratory rodents by contaminated biological materials such as transplantable tumours, cell lines, sera or other biological materials. Biological materials are currently being screened using the mouse or rat antibody production (MAP/RAP) test (serological testing). We decided to test and validate an alternative assay using polymerase chain reaction (PCR/realtime PCR) technology to detect viral contamination directly in biological material. The aim of this study therefore is the validation of our new PCR assays and the comparison of PCR and the MAP test. For 8/14 viruses, conventional PCR was more sensitive and more specific than the MAP test in detecting murine viruses. For 12/14 viruses, the realtime PCR was more sensitive than the MAP test. In 2/14 cases, all three detection methods had the same sensitivity. Furthermore, PCR screening clearly conforms to the principles of the 3Rs as a replacement technique because it eliminates the need for using animals to screen for murine viruses in biological material.

Accidental infection of laboratory worker with vaccinia virus.

We report the accidental needlestick inoculation of a laboratory worker with vaccinia virus. Although the patient had previously been vaccinated against smallpox, severe lesions appeared on the fingers. Western blot and polymerase chain reaction-restriction fragment length polymorphism were used to analyze the virus recovered from the lesions. The vaccinia virus-specific immunoglobulin G levels were measured by enzyme-linked immunosorbent assay. Our study supports the need for vaccination for laboratory workers that routinely handle orthopoxvirus.

Response of laboratory staff to vaccination with an inactivated Rift Valley fever vaccine--TSI-GSD 200.

Laboratory staff and students were vaccinated with a formalin-inactivated rift valley fever (RVF) vaccine. This study showed that the vaccine used (TSI-GSD 200) was able to bring about the production of antibodies in recipients. For the production of a high titered antibody response, three doses of the vaccine were required. One or two doses of the vaccine did not produce a greater than four-fold rise in antibody titre. A greater than four-fold rise in antibody titre following vaccination, is considered significant. The complete dose of the vaccine, that is, three doses, was necessary for protection. This study also showed that the haemagglutination inhibition (HI) test was capable of detecting antibodies, few weeks post vaccination. Though such HI antibodies broaden with time, it could be used for screening purposes and a more specific test, e.g., plaque reduction neutralisation (PRN) test used for confirmation of such results.

Sabia virus incident at Yale University.

An incident involving a human exposure to a newly isolated arenavirus, Sabia virus, in the Yale Arbovirus Research Unit occurred at Yale University on August 8, 1994. A senior-level visiting research scientist was exposed to Sabia virus while purifying the virus from a large volume of tissue culture fluid. The exposure resulted in development of a Sabia virus infection followed by recovery of the patient. The incident resulted in a comprehensive review by a Yale faculty committee and an external expert committee. As a result, a number of new practices and procedures were added to Yale's biosafety policy for investigating infectious agents in BL-3 facilities.

Experimental pneumonia virus of mice infection of guineapigs spontaneously infected with Bordetella bronchiseptica.

Guineapigs that were intranasally inoculated with pneumonia virus of mice (PVM) seroconverted to PVM by 11 days post-infection. During the course of study (2-60 days post-infection) no gross or histologic lesions were identified within the lungs that could be attributed to PVM infection. Mild rhinitis and tracheitis were found in most animals and acute purulent bronchopneumonia in two animals, which may have resulted from spontaneous subclinical Bordetella bronchiseptica infection. Viral and bacterial respiratory diseases of the guineapig are briefly reviewed.