Avian Influenza H5N1

Are We Ready for It?

There is evidence that we are in a "pre-pandemic" stage of avian influenza. Several articles have appeared in medical journals and the lay press, and we have fielded numerous calls regarding pandemic influenza risks. Impromptu question and answer sessions occur in every nursing station and hallway, and there has been great interest by physicians and health care workers in all specialties. We all have the same concerns: Are the risks real? And if so, what can we do to protect our patients and ourselves from becoming ill or dying from this infection?

Since 1997 there have been several small outbreaks of avian influenza causing disease in humans. The current avian influenza strain, H5N1, was first detected in humans in Hong Kong in 1997. Transmission occurred directly from poultry to humans, and the mortality in the first group was 33 percent (6 of 18 deaths). No further human cases of H5N1 were seen until 2003, when two additional infected patients were identified (one of whom died). Since 2004, however, there has been a major increase in H5N1 isolation from poultry flocks and humans. From January 2004 to October 10, 2005, 117 human N5H1 cases have been reported in Asia (Cambodia, Indonesia, Thailand, and Vietnam); of these, 60 (51 percent) were fatal (by comparison, the mortality rate for the 1918 H1N1 influenza pandemic was 2.5 percent). The vast majority of these recent cases have occurred from direct contact with infected poultry, uncooked poultry products, or contaminated surfaces. Although local governments have tried to contain the virus by mass slaughters of domesticated poultry, the virus has continued to spread through areas of Asia and Eastern Europe—possibly by migratory aquatic birds that become infected asymptomatically and shed large amounts of virus.

Fortunately, the current virus does not possess the genetic makeup required for human-to-human transmission. The concern, however, is that the virus could easily acquire the capability for rapid human-to-human transmission if genetic reassortment occurs in a secondary host that becomes infected with both H5N1 and a second influenza strain (such as the seasonal H3N2 influenza) that already possesses the capability for human-to-human transmission. Such a dual infection is possible in pigs and humans, and this scenario has been postulated as the genesis of the 1918 influenza pandemic.

Present thinking is that a pandemic likely will occur—we just do not know when. Unlike the usual seasonal influenza activity that occurs in a community for four to six weeks, pandemic influenza can occur in waves lasting a period of several months to two years.

With all the present advances in modern medicine, technology, information systems, and epidemiology, Are we better off now than in 1918 to successfully deal with a new pandemic? The answer is "maybe." The World Health Organization successfully dealt with SARS by aggressively isolating and quarantining local areas of activity. At the beginning of the pandemic they will attempt the same strategy. If, however, outbreaks of H5N1 occur in scattered locations simultaneously, this strategy will not be successful. Use of antiviral prophylaxis or treatment with the neuraminidase inhibitors oseltamivir (Tamiflu) or zanamivir (Relenza) might be effective in reducing transmission and reducing mortality. These drugs have in vitro activity against H5N1 and are effective against H5N1 in animal models, but thus far, there is no data on the clinical effect of these drugs on humans infected with H5N1.

Development of an effective H5N1 vaccine would be ideal, and there is currently a great deal of activity by industry and governments in this regard. Despite the potential effectiveness of a vaccine, there is no guarantee that a manufactured vaccine would be effective, and it is likely that the first investigational vaccines are still months to years away. In the event of a worldwide pandemic, the supply of vaccine and antivirals would not be sufficient. Governments around the world are stockpiling Tamiflu, but the available supply of medication will cover only a small percentage of the population, necessitating prioritization.

If we do not have vaccine available and there are insufficient antivirals, we will need to rely on those infection control strategies that have proved effective in preventing person-to-person spread:

First, we need to pay strict attention to "Respiratory Hygiene/Cough Etiquette" in all health care settings for individuals with signs and symptoms of a respiratory infection:

• cover nose/mouth when coughing and sneezing,

• use tissues to contain respiratory secretions and dispose of them in nearest waste receptacle after use,

• perform hand hygiene (soap and water or alcohol- based hand rub) after contact with respiratory secretions and contaminated objects/materials.

Health care facilities (including your offices) should be sure materials are available in waiting areas for patients and visitors:

• tissues and no-touch receptacles for used tissue disposal,

• conveniently located dispensers of alcohol-based hand rub; where sinks are available, ensure adequate supplies of soap and disposable towels are available.

Second, offer masks to persons who are coughing during periods of increased respiratory infection activity in the community. Procedure masks or surgical masks are sufficient in this setting. When space and chair availability permit, encourage coughing persons to sit at least three feet away from others in common waiting areas.

Third, when examining a patient with symptoms of respiratory infection, particularly when fever is present, observe Droplet Precautions (i.e., wearing a surgical or procedure mask for close contact) in addition to Standard Precautions (good handwashing; use of gloves, gowns, and eye protection if risk of secretions getting on hands, clothing, or being splashed in eyes). Maintain these precautions until it is determined that the cause of symptoms is not an infectious agent that requires Droplet Precautions (e.g., influenza).

"Cover Your Cough" posters should be posted in every office waiting room as well as hospital entrances to inform patients of the above. They are available in the Respiratory Hygiene link in either the influenza link or avian influenza link on the San Mateo County Web site (www.co.sanmateo.ca.us). Ask your medical supplier to provide you with adequate personal protective equipment: gloves, masks, gowns, and protective eyewear (goggles or face shields).

Fourth, if avian influenza is suspected or confirmed, more extensive precautions are taken, similar to those taken during the SARS outbreak (it may not be practical to do all of this in your office; as much as possible should be attempted prior to transfer to a hospital):

• Standard Precautions,

• Contact Precautions,

• Use gloves and gowns for all patient contact,

• Use dedicated equipment such as stethoscopes, disposable blood pressure cuffs, disposable thermom- eters, etc. If not available, disinfect the equipment with alcohol or alcohol pads or, preferably, your office EPA- approved disinfectant or disinfectant wipes,

• Eye Protection (i.e. goggles or face shields),

• Wear within three feet of patient,

• Airborne Precautions,

• Place patient in an airborne isolation room with monitored negative air pressure,

• Use a fit-tested N-95 respirator.

If the hospital is overwhelmed and Airborne Isolation rooms are not available, and /or supplies are limited, the use of at least any type of mask and the use of good handwashing and other personal protective equipment as available will at least afford some degree of protection.

Fifth, all health care workers should be vaccinated (this should be done even in the absence of avian influenza) with the most recent seasonal influenza vaccine. The vaccine offers protection against the predominant circulating influenza strain(s) and reduces the likelihood of dual infection with that strain and avian influenza, reducing the risk of genetic reassortment.

If an avian influenza pandemic occurs, the San Mateo Health Department, the California State Department of Health Services, and the CDC will provide additional guidance and direction including details on reporting, quarantine, and the availability and distribution of any vaccine or antivirals.

Even at present, if you encounter a patient from an area of the world with current avian influenza activity (see above) and suspect active H5N1 influenza, the San Mateo Health Department Disease Control should be notified and will coordinate appropriate testing (daytime: 650-573-2346; nightime and weekends: 650-363-4981). Our usual rapid influenza tests may or may not detect H5N1, depending on the kit used. Even with ordinary influenza, these kits only have sensitivities varying from 70 percent to 90 percent. Therefore additional testing (PCR, viral culture – but only to be done by the Health Department since positive cultures require higher levels of biosafety containment) will be required if H5N1 is suspected. Criteria for testing, according to the state of California enhanced surveillance protocol for H5N1, include the following:

For hospitalized patients:

• Radiographically confirmed pneumonia, acute respiratory distress syndrome, or other severe respira- tory illness for which an alternate diagnosis has not been established AND

• A history of travel within 10 days of symptom onset to a country with documented H5N1 avian influenza in poultry or humans.

Testing should be considered on a case-by-case basis in consultation with the San Mateo Health Department Disease Control for hospitalized or ambulatory patients with

• Documented temperature > 38°C (100.4° F), AND

• One or more of the following: cough, sore throat, shortness of breath AND

• History of contact with poultry (e.g. visited a poultry farm, a household raising poultry, or a bird market) or a known or suspected human case of influenza A/ H5N1 in an H5N1-affected country within 10 days of symptom onset.

Preparation is the key to preventing panic. If we take a proactive approach now and put it in place and start practicing the above recommendations, we will have a chance to prevent infection in ourselves and others and weather the storm, with or without sufficient antivirals or vaccine.