Friday, March 4, 2011

Outbreak: Biosafety Levels and Hemorrhagic Fever

Outbreak (Keepcase)
Outbreak (Keepcase) 1995 Starring
 Dustin Hoffman, Rene Russo,
Morgan Freeman, Kevin Spacey and
Donald Sutherland as Evil Army General
I love, with a capital L O V E, the suspense of Outbreak [1995], starring Dustin Hoffman and Rene Russo.  I couldn't help but narrate the scene when all the biosafety laboratory levels [BSL-1, 2, 3 and 4] were shown.  Our concept of hygiene on the grand screen [well, 17 inch television this last time].  The measures we take to protect ourselves from everything ranging from everyday dirt to Staphylococcus to HIV to TB to Ebola virus are different.  Even though the immunology science depicted is not completely correct, and that the fictionalized virus shown was really Ebola, and that the infected village scene dated 1967 matchs the date of first known Marburg virus outbreak [in Marburg, Frankfurt and Yugoslavia],   I can love it for its infectious drama.


The researchers and the steps they take to prepare, research, and investigate is extraordinary.  In Outbreak, the lives of the people in the US Army Medical Research Investigation of Infectious Diseases [USAMRIID] and the Centers for Disease Control [CDC] are highlighted...and in many places stretched to the ridiculous and conspiratorial.  Nonetheless, the investigation of infectious disease is fascinating.


When a research fellow, our Antiinfective Research Unit was initially a standard microbiology research lab, but we worked to incorporate additional safety measures to begin cell culture work with HIV infected cells.  Our addition was a class II biological safety cabinet, incubator, and additional equipment for cell culture.  All those late nights reading American Type Culture Collection [ATCC] and CDC manuals come alive for me when I watch this movie...except that the movie is infused with hyper-emotion and anabolic caffeine.  I only needed standard coffee on these late-night reading binges.

Das erste deutsche BSL-4-Hochsicherheitslabor ist in Marburg
BSL 4 photograph from farm3 on Flickr

The first, least cautious biosafety laboratory level [BSL-1] is basically bench-top work with organisms not thought to cause disease in immunocompetent humans.  It is separated from food, with safe handling of materials with gloves and eye protection.  Hygiene consists of good handwashing, use of disinfectants, and autoclaving of equipment.  BSL-2 is what most microbiology labs conform to unless dealing with animal research [BSL 3] or more dangerous microbiologics [BSL-4].  People that work in a BSL-2 lab are trained to handle pathogenic organisms, there is limited access to lab, and actions that may aerosolize materials is performed in a biological safety cabinet. BSL-3 labs have workers trained to handle serious or potentially lethal organisms in a specially designed room with enclosed biological safety cabinets.  BSL-4 requirements differ from level 3 in that the organisms are either incredibly dangerous without treatment availability, aerosolization is highly possible, or that the transmission of a dangerous organism is unknown.  A BSL-4 lab is depicted below.  BSL-3 and BSL-4 Laboratories require special approval and certification.


This illustration shows the typical process of entering and exiting a BSL-4 laboratory, though specifics might vary from facility to facility.
Biosafety Level 4 Laboratory: from NIAID.nih.gov


School children can learn how to plate skin flora on agar over standard benchtops at school [BSL-1].  Most microbiologic laboratories are BSL-2 format, and work on microorganisms not likely to aersolize including dengue fever, polio, HIV, Chlamydia, Hepatitis, Methicillin Resistant Staphylococcus [MRSA], some Salmonella and others.  If animal microbiologic research is done or organisms more likely to be aerosolized, like Yersinia pestis [plague bacteria] and anthrax, BSL-3 practices would be required.  SARS, Rift Valley Fever, typhoid [Salmonella typhi], and West Nile Virus are further examples of organisms studied in BSL-3 laboratories.  The organisms that require BSL-4 containment are many of the hemorrhagic fever viruses and smallpox. 


What is viral hemorrhagic fever? Viral hemorrhagic fever [VHF] is when a patient has an abrupt fever with chills and aches, debilitation, accompanied by coagulation and/or bleeding.  Blood vessels may become leaky, leading to shock and respiratory distress.  Often, other organs such as liver and kidneys may fail.  Treatment is mainly supportive--fluids, transfusions, comforting the patient.  


Ribavirin may be used for Lassa fever, Rift Valley fever, HFRS,  and perhaps Crimean-Congo HF.  Interferon may be helpful for Argentine or Bolivian HF  A special plasma may be used for Argentine hemorrhagic fever.  If hemorrhagic fever with renal syndrome develops [HFRS], such as can happen with Hantavirus, dialysis may be needed. Inhibitors of viral fusion to cells need to be developed to treat/prevent VHF. A vaccine for CCHF found in Bulgaria may help patients not infected with the strain from India.  A vaccine for dengue fever is in development.  A list of all the known hemorrhagic fever viruses are listed at the end of this post.


Maryn McKenna, in Beating Back the Devil:  On the Front Lines With the Disease Detectives of the Epidemic Intelligence Service [2004] gives real accounts of trained investigators for the CDC.  The Epidemic Intelligence Service [EIS] was formed during the Korean War, and the doctors receive extensive training, leave for missions  immediately when told to do so, and have lives much like the rest of us--except more interrupted.  Obviously their job takes a toll--family life is different from ideal, danger is imminent, hours are long.  However, the work, for two years, is captivating.  After following the first group trained after 9/11, she tells stories of the new trainees and others through the years.  Much like our protagonists in Outbreak, they are human, with issues too.

Ebola Plush Toy from
http://www.thinkgeek.com/geektoys/plush/6708/images/888/
Hemorrhagic Virues [in alphabetical order, with natural animal host]

  • Congo Crimean hemorrhagic fever [CCHF] [tick-borne]
  • Dengue HF [mosquito]
  • Ebola [not fully known, fruit bats]
  • Guanarito or Venezuelan HF [rodent]
  • Hantavirus [with renal syndrome] [rodent]
  • Junin or Argentine HF [rodents]
  • Kyasanur Forest HF [tick borne]
  • Lassa Fever [not always HF] [rodents]
  • Lujo virus [newly discovered]
  • Machupo or Bolivian HF [rodents]
  • Marburg [possible fruit bats]
  • Omsk HF [tick-borne]
  • Rift Valley Fever [mosquito]
  • Sabia or Brazlian HF [rodents]
  • Yellow Fever [mosquito]

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