Case Study 4: Influenza A, H2N2 Outbreak in a Laboratory Student Guide SITUATION In the late 1950s, the H2N2 strain of the influenza A virus was responsible for the deaths of between one and four million people worldwide during what is commonly referred to as the Asian influenza pandemic. H2N2 continued to circulate in humans until 1968, when it disappeared with the emergence of influenza A/H3N2, which sparked the Hong Kong influenza pandemic. In present day vaccinations, the H2N2 virus is not included as part of the FDA-approved trivalent influenza vaccine. As a result, individuals born post1968 exhibit little to no immunity against influenza A/H2N2 strains. Proficiency testing (PT) is used to test a laboratory’s competency in performing a particular diagnostic test. Laboratories participating in a PT exercise receive samples containing specified material with an identity and quantity known only to those orchestrating the PT exercise. The laboratory analyzes the samples according to a predetermined protocol or standard operating procedure and reports the results to the exercise organizers. The organizers then inform the participating laboratory how closely the results reported match the accepted values. If and when necessary, the laboratory can take appropriate actions to improve its performance and capabilities. UPDATE 1 You are the director of the State Public Health Laboratory. On April 8, 2005, the College of American Pathologists (CAP) sends a fax to various national and international public health laboratories, including your State Public Health Laboratory, regarding a recently disseminated PT exercise. The fax alerts you that one of the specimens included in this exercise has been identified by a local laboratory in Canada as influenza A subtype H2N2. Approximately 4,600 PT samples containing H2N2 have been disseminated to laboratories between October 2004 and March 2005. Your laboratory received the PT samples one week ago. Some of your laboratorians, unaware that the samples contain the dangerous H2N2 virus, have already begun performing analysis on the PT specimens. 1. How worrisome do you consider this error to be? 2. What modes of transmission are associated with influenza viruses? 3. What laboratory hazards might lead to the accidental transmission of an influenza virus from a specimen to a laboratory worker? 4. What are the four laboratory biosafety levels? What do you know about each one? 5. What laboratory biosafety level would be appropriate for conducting routine influenza testing? 6. Group Brainstorm: Have one member of the group write ideas on the flip chart. What pieces of personal protective equipment (PPE) should be used when conducting routine influenza testing in the public health laboratory setting? UPDATE 2 After reading the fax, you make your way to the microbiology/virology section of the laboratory where the PT exercise was being handled. You share the news with staff members there, and discuss how to proceed with the situation (i.e., safely dispose of the dangerous samples). 7. Who are the stakeholders? Is there a need to communicate with outside stakeholders in this situation? If so, which stakeholders? 8. Which, if any, laboratory staff members could have been exposed to the H2N2 virus? 9. What surveillance strategies will you use to identify people who have been exposed or infected with H2N2? 10. Is there a potential that anyone could have been exposed to the H2N2 virus prior to the H2N2 samples arriving to the laboratory? If so, how could this have happened? 11. How would a chain of custody help you easily determine who had contact with the samples until the shipment reached the laboratory? UPDATE 3 In your discussions with staff in the microbiology/virology section, you are surprised and concerned to discover that a laboratorian from the microbiology/virology section has been out on sick leave for the past 2 days. You make some follow-up phone calls to obtain additional information regarding the sick employee. After further inquiry, you learn that the sick employee, a 45-year-old microbiologist named Cathy Stevenson, has been hospitalized with several flu-like symptoms. Cathy was among the few laboratory staff who had direct contact with the PT specimens, since she was responsible for preparing the samples for analysis. Rapid influenza testing reveals that she is indeed infected with influenza A, the same general type of flu as H2N2. Confirmatory cultures required to determine the subtype of the strain will take another 5-10 days. 12. Is shelter-in-place (workplace lockdown) a necessary and/or feasible action to take in this situation? What measures are associated with sheltering-in-place? Who has the authority to initiate a shelter-in-place order? UPDATE 4 As you attempt to maintain control of the situation in your state public health laboratory, CAP has been in contact with the World Health Organization and the Centers for Disease Control and Prevention via a continuous series of conference calls and emergency meetings, and other communications. It has been decided that the best way to handle the issue of the dangerous H2N2 shipment is to mandate laboratories to destroy their PT samples via autoclaving or incineration as quickly as possible. All laboratories in possession of H2N2 samples are instructed to report back within 24 hours to ensure that all samples have been destroyed and properly disposed of. 13. Knowing that you are dealing with H2N2, how will this affect the biosafety level guidelines that should be followed for safe disposal of the samples? UPDATE 5 Confirmatory cultures from your ill laboratory employee, Cathy Stevenson, are finally available. To the great relief of many, though Cathy is suffering from a severe bout of Influenza A, it is not subtype H2N2. While it is promising to know that Cathy’s infection was not found to be of the H2N2 strain, you do not yet consider yourself “out of the woods.” As such, you continue to closely monitor other potentially-exposed laboratory staff members for any signs or symptoms of flu. Not surprisingly, given the widespread dissemination of the PT samples and the involvement of the CDC and WHO, news of the dangerous PT shipment has hit the media. Local and national newspapers and media outlets are covering the story. Given the widespread national and international dissemination of the samples, the public reaction is one of concern. As expected, phones at your laboratory begin to ring off the hook with callers anxiously awaiting answers. In addition, local hospitals, doctors’ offices, and emergency rooms are observing an influx of “worried well” as a result of the news coverage and a leaked report that a laboratory employee had been hospitalized with severe flu-like symptoms. 14. What communication mechanisms can be used to address the fears of the public and properly communicate public health risks? CONCLUSION You have managed, with the help of your highly trained laboratory staff, to safely and successfully dispose of all of the dangerous H2N2 samples. On April 22, authorities confirm that virtually all H2N2 samples have been accounted for and properly destroyed. In addition, there are no reports of illness among laboratory staff or the general population. For now, the crisis has been averted. However, this issue raises concerns about the administration of PT programs, biosafety procedures, and the ability of laboratories to respond to emergencies that involve potential exposure to infectious agents. NOTE: In April of 2005, the CAP administered a PT exercise to several public health laboratories located in the United States and abroad. In an accident still not well-understood, the PT exercise resulted in thousands of samples of improperly attenuated influenza A/H2N2 virus being mistakenly sent to laboratories in 18 different countries. The samples were included in kits used regularly to test the ability of laboratories to identify strains of the flu virus. Ninety percent of the laboratories that received test kits were located in North America. Fortunately, all of the samples were destroyed, and there were no cases of H2N2 reported in the affected populations References Centers for Disease Control and Prevention Advisory Committee on Immunization Practices. Infection Control Measures for Preventing and Controlling Influenza Transmission in Long-Term Care Facilities. 2007. Available at: http://0www.cdc.gov.mill1.sjlibrary.org/flu/professionals/infectioncontrol/ longtermcare.htm. American Red Cross. Fact Sheet on Shelter-in-Place. 2003. Available at: http://www.redcross.org/services/disaster/beprepared/shelterinplace.pdf.