BRIEFING DOCUMENT FOR UWHC REGARDING POSSIBLE INCIPIENT PANDEMIC INFLUENZA

And Briefing document for UWHC REGARDING POSSIBLE INCIPIENT PANDEMIC INFLUENZA

April 27, 2009

Dennis G Maki, MD

THE FACTS: Between early March and mid-April 2009 there was an inexplicable upsurge in influenza-like illness in multiple locations throughout Mexico, with numerous reports of deaths in younger victims. Respiratory specimens were not sent to WHO or the CDC until mid-April, and tests have shown epidemic disease with a new H1N1 swine-like influenza A virus not previously identified in human infections, now referred to as the ”swine influenza virus.”

Like all influenza A viruses, the new virus is a human-animal recombinant, containing genes from previously recognized avian and human influenza viruses, however this virus is very unusual, containing genetic sequences from North American avian influenza viruses, human influenza viruses, and European and Asian swine influenza viruses.

Most notably, in terms of its potential capacity to cause global pandemic disease, the virus has shown the capacity to spread efficiently and rapidly human-to-human and, based on the fragmentary epidemiologic data available to date, may be considerably more virulent than the human influenza A viruses of the past 90 years. What is unknown at this time is whether there is any pre-existing natural immunity or, especially, vaccine immunity in the general population.

There is now evidence of spread of this virus to multiple locations within the continental United States, Canada, and New Zealand. The U.S. government has declared a National Emergency, to enable shipments of antiinfluenza drugs from the National Stockpile to individual states.

What is known to the present time:

· As of April 26, there have been 1614 cases of influenza-like illness in Mexico, with 103 related deaths, 22 confirmed as swine influenza. Disease has been reported from 17 states throughout Mexico.

If these figures are accurate or even close to accurate, this is a mortality considerably higher than the 1918 H1N1 strain which is estimated to have killed approximately 2.5% of its victims worldwide. The influenza A strains of the past 50 years have had a case-fatality in the range of 0.1%.

· There have been 20 confirmed U.S. cases, 8 in New York, 7 in California, 2 in Kansas, 2 in Texas and 1 in Ohio. Inexplicably, all of the disease in U.S. patients has been very mild, with only two hospitalized and no deaths to date. Most of these individuals had recently been in Mexico or had contact with in individual who had recently returned from Mexico.

· There are 13 confirmed cases in New Zealand, 7 suspected cases in Spain, and 1 each in France, Israel and Brazil. All of these individuals had recently been in Mexico.

· The strain is resistant to amantadine and rimantadine but susceptible to oseltamavir (Tamiflu) and zanamavir (Relenza).

· It is not yet known whether individuals who had the current 2008-9 U.S. influenza vaccine have any immunity against this strain, however, limited testing at CDC has reportedly shown very little cross-reactive activity of vaccine antibody against the new swine flu strain.

· The U.S. government has not yet decided whether to initiate the huge effort to manufacture a vaccine against this strain in time for the Fall 2009-10 influenza season but is growing stock strains of the strain in preparation for the possible eventuality.

Editorial comment: It is extremely unusual to see an upsurge in influenza activity in the northern hemisphere as late as April or, especially, May. The last time it happened was in 1918, inaugurating the Great Influenza Epidemic; there was clinical influenza throughout the spring and summer of 1918, which was also extremely unusual, and in October 1918, the world was engulfed by a devastating global pandemic of highly virulent influenza which, also atypically, had a disproportionately high case-fatality rate among young adults. The Great Epidemic lasted from March 1918 until June 1920, ultimately claiming 50 to 100 million lives worldwide, an estimated 500,000 in the United States.

In early 1976 an H1N1 swine-like Influenza A strain was implicated in an outbreak on a military base in New Jersey, causing illness in 13 young soldiers, two of whom died. It was later determined that approximately 217 additional young soldiers had also become infected but had no illness. The linkage of this new 1918-like strain in fatal disease in young adults prompted the U.S. government to rush to produce a new vaccine against the strain, “the swine flu vaccine,” which was ultimately given to more than 60 million Americans that fall, in anticipation of a global 1918-like pandemic. However, no further infections with that strain were identified during the 1976-77 influenza season but the vaccine was linked to a very low but measurable ~1:100,000 risk of Guillain-Barre syndrome (and the Director of the CDC lost his job).

It is highly likely that it will be possible to determine the pandemic potential of this new strain by its behavior over the next 4 to 6 weeks. If many more cases are identified across the U.S. and around the world, especially with a case fatality >1-2%, it will be very clear that accelerated production of a targeted vaccine will be imperative to prevent catastrophic loss of lives and an economic depression.

Recent CDC recommendations for management of suspected or proven swine flu: http://www.cdc.gov/swineflu/whatsnew.htm

Definitions of Respiratory Illness

Acute respiratory illness
Recent onset of at least two of the following:

rhinorrhea or nasal congestion
sore throat
cough
fever or feverishness

Influenza-like illness: fever >37.8°C (100°F) + cough or sore throat

Case Definitions for Infection with Swine Influenza A (H1N1) Virus

A Confirmed case of swine influenza A (H1N1) virus infection is defined as a person with an acute respiratory illness with laboratory-confirmed swine influenza A (H1N1) virus infection at CDC by one or more of the following tests:

real-time RT-PCR
viral culture
four-fold rise in swine influenza A (H1N1) virus specific neutralizing antibodies

A Probable case of swine influenza A (H1N1) virus infection is defined as a person with an acute respiratory illness with an influenza test that is positive for influenza A, but H1 and H3 negative.
A Suspected case of swine influenza A (H1N1) virus infection is defined as:

A person with an acute respiratory illness who was a close contact to a confirmed case of swine influenza A (H1N1) virus infection while the case was ill OR
A person with an acute respiratory illness with a recent history of contact with an animal with confirmed or suspected swine influenza A (H1N1) virus infection OR
A person with an acute respiratory illness who has traveled to an area where there are confirmed cases of swine influenza A (H1N1) within 7 days of suspect case's illness onset.

Infectious period = 1 day before to 7 days after onset of illness
            Day before onset = Day -1
            Onset day = Day 0
            Days after onset = Days 1-7

Precautions to prevent spread:

Cover your nose and mouth with a tissue when you cough or sneeze. Throw the tissue in the trash after you use it.
Wash your hands with soap and water, especially after you cough or sneeze. Alcohol-based hands cleaners are also effective.
Try to avoid close contact with sick people.
If you get sick, stay home from work or school and limit contact with others to keep from infecting them.
Avoid touching your eyes, nose or mouth.

Strongly Recommend Home Isolation of Cases:

Persons who develop influenza-like-illness (ILI) (fever with either cough or sore throat) should be strongly encouraged to self-isolate in their home for 7 days after the onset of illness or at least 24 hours after symptoms have resolved, whichever is longer. Persons who experience ILI and wish to seek medical care should contact their health care providers to report illness (by telephone or other remote means) before seeking care at a clinic, physician’s office, or hospital. Persons who have difficulty breathing or shortness of breath or are believed to be severely ill should seek immediate medical attention.
If ill persons must go into the community (e.g., to seek medical care) they should wear a face mask to reduce the risk of spreading the virus in the community when they cough, sneeze, talk or breathe. If a face mask is unavailable, ill persons needing to go into the community should use a handkerchief or tissues to cover any coughing.
Persons in home isolation and their household members should be given infection control instructions: including frequent hand washing with soap and water. Use alcohol-based hand gels (containing at least 60% alcohol) when soap and water are not available and hands are not visibly dirty. When the ill person is within 6 feet of others at home, the ill person should wear a face mask if one is available and the ill person is able to tolerate wearing it.

Clinicians evaluating patients with respiratory illness:

Should consider the possibility of swine influenza virus infection in patients presenting with febrile respiratory illness who:

Live in an area where human cases of swine influenza A (H1N1) has been identified or
Have traveled to an area where human cases of swine influenza A (H1N1) has been identified within 7 days of the onset of their illness OR
Have been in contact with ill persons from these areas in the 7 days prior to their illness onset.

If swine flu is suspected, clinicians should obtain a nasopharyngeal swab for swine influenza testing which will be immediately forwarded to the Wisconsin State Laboratory of Hygiene and CDC for testing.

Using Facemasks or Respirators

Avoid close contact (less than about 6 feet away) with the sick person as much as possible.
If you must have close contact with the sick person (for example, hold a sick infant), spend the least amount of time possible in close contact and try to wear a facemask (for example, surgical mask) or N95 disposable respirator.
An N95 respirator that fits snugly on your face can filter out small particles that can be inhaled around the edges of a facemask, but compared with a facemask it is harder to breathe through an N95 mask for long periods of time.
Wear an N95 respirator if you help a sick person with respiratory treatments using a nebulizer or inhaler, as directed by their doctor. Respiratory treatments should be performed in a separate room away from common areas of the house when at all possible.
Used facemasks and N95 respirators should be taken off and placed immediately in the regular trash so they don’t touch anything else.
Avoid re-using disposable facemasks and N95 respirators if possible. If a reusable fabric facemask is used, it should be laundered with normal laundry detergent and tumble-dried in a hot dryer.
After you take off a facemask or N95 respirator, clean your hands with soap and water or an alcohol-based hand sanitizer.

Treatment of suspected, probable or confirmed swine flu:

Empiric antiviral treatment is recommended for any ill person suspected to have swine influenza A (H1N1) virus infection. Antiviral treatment with either zanamivir alone or with a combination of oseltamivir and either amantadine or rimantadine should be initiated as soon as possible after the onset of symptoms and continued for 5 days.

For antiviral treatment of confirmed swine influenza A (H1N1) virus infection, either oseltamivir or zanamivir should be given for 5 days.

These same drugs should be considered for treatment of cases that test positive for influenza A but test negative for seasonal influenza viruses H3 and H1 by PCR (probable swine influenza).

Prophylaxis for swine flu:

Antiviral chemoprophylaxis (pre-exposure or post-exposure) with either oseltamivir or zanamivir is recommended for the following individuals:

Household close contacts who are at high-risk for complications of influenza (persons with certain chronic medical conditions, elderly) of a confirmed or suspected case.
School children who are at high-risk for complications of influenza (persons with certain chronic medical conditions) who had close contact (face-to-face) with a confirmed or suspected case.
Travelers to Mexico who are at high-risk for complications of influenza (persons with certain chronic medical conditions, elderly).
Border workers (Mexico) who are at high-risk for complications of influenza (persons with certain chronic medical conditions, elderly).
Health care workers or public health workers who had unprotected close contact with an ill confirmed case of swine influenza A (H1N1) virus infection during the case’s infectious period.

Antiviral chemoprophylaxis (pre-exposure or post-exposure) with either oseltamivir or zanamivir can be considered for the following:

Any health care worker who is at high-risk for complications of influenza (persons with certain chronic medical conditions, elderly) who is working in an area with confirmed swine influenza A (H1N1) cases, and who is caring for patients with any acute febrile respiratory illness.
Non-high risk persons who are travelers to Mexico, first responders, or border workers who are working in areas with confirmed cases of swine influenza A (H1N1) virus infection.

UWHC PREPARATIONS:

All ED personnel, primary care providers and infectious disease consultants should be in-serviced and fully apprised of CDC recommendations for the management of patients with possible swine influenza or who have been potentially exposed to infection.

The UWHC Biologic Event Plan (12.20, September 15, 2006) should be reviewed by all administrators, department heads, ED personnel, Infectious Disease staff and nurses and Infection Control personnel. Hopefully, it will not be necessary to activate the Plan emergently but that we will be prepared to handle a gradually increasing number of patients presenting with, many being admitted, with acute swine flu.

It will be essential to make institutional plans for the disposition of patients with suspected swine flu. In general, patients who are not critically ill and are not at high risk of complications will not need to be hospitalized but will be treated and need to be followed closely in the outpatient setting. On the other hand, fragile elderly or compromised patients may need to be admitted preemptively and, certainly, critically ill patients will need to be admitted expeditiously to the dedicated to the F6/5 Emerging Infections Unit.

Administration, Clinical Services, Critical Care Services, Plant Services and Pharmacy should review the existent plans for the implementation of the F6/5 dedicated Emerging Infectious Diseases Unit with ventilator support capacity.

Our current inventory of masks, particularly N95 respirators, and other protective apparel should be reviewed and efforts should be made to purchase as many masks as can be obtained. It is predictable that there will be unprecedented needs for masks if pandemic influenza occurs with a highly virulent strain.

Similarly, it will be essential to determine whether additional ventilators can be made available if we are presented with very large numbers of patients requiring mechanical ventilatory support.

The laboratory will need to be prepared to handle large numbers of rapid influenza DFA tests on a stat basis. If a PCR test becomes clinically available for individual hospitals, it would be desirable for the test to be available on a stat basis.

The Hospital would be well advised to undertake another tabletop practice exercise as soon as possible, given the shortcomings and vulnerabilities identified in the first two. The results of these two exercises should be immediately reviewed to target needed redress.

All hospital departments but especially Clinical and Nursing services will need to have plans in place to be able to deal with the exigencies of large numbers of ill staff and assure that adequate numbers of well-trained staff are available to care for critically ill patients with swine flu.

An ongoing liaison with the Madison/Dane County Department of Health, Wisconsin Division of Health and the other State agencies responsible for emergency preparedness must be established and maintained.

The hospital should be prepared to provide a hotline, both for our staff who will have innumerable questions on an ongoing basis, as well as for patients and families, and the lay public.

Information for the media at the present time:

UWHC has had comprehensive plans in place to deal with the possibility of biologic disaster, either bioterrorism or pandemic emerging infectious disease, for a number of years, and we have had hospital-wide practice exercises to try to improve our efficiency with emergency implementation of the plan, if needed. Institutional preparations have included retrofitting a 36-room patient care unit to be convertable within hours into a dedicated negative-pressure, self-contained isolation unit for the care of exposed or critically ill infected and highly contagious patients, a unit which has built-in capacity for full critical care support, including up to eight mechanically ventilated patients.

More than 20 board-certified critical care staff physicians and 12 infectious disease staff consultants are available to provide 24/7 patient care and leadership of the institutional efforts to deal with a global pandemic of highly virulent influenza. However, the Asian and Canadian SARS epidemic of 2006 showed that while preexistent planning is extremely important, implementation of such plans are invariably found to be a work in progress, and it is essential to have the capacity to quickly adapt, to revise and change, as the circumstances dictate.

No healthcare system can prepare in isolation for biologic disaster or, especially, pandemic disease that might last for many months or even years. Our planning has been carried out in conjunction with the preparations of the other Madison hospitals, the Madison/Dane County Department of Public Health, and the Wisconsin Division of Health, and throughout its implementation, the Centers for Disease Control and the Department of Health and Human Services.