H?N?: Prepare Before it Arrives!

“For the first time in human history, we have a chance to prepare ourselves for a pandemic before it arrives …. It is incumbent upon the global community to act now.” Dr. Margaret Chan, Director-General, WHO

In the last century we had three flu pandemics: Spanish flu in 1918, Asian flu in 1957, and Hong Kong flu in 1968. In the United States, the Spanish flu killed more people than all the combat deaths of the 20th century, with more than 500,000 deaths in the United States and 20–40 million worldwide.

Only the influenza A strain causes pandemics in humans. Influenza A is characterized by two surface glycoproteins: hemagglutinin (H) and neuraminidase (N). Hemagglutinin has 15 subtypes and neuraminidase has nine. Birds can be infected by most of the H subtypes, but humans and pigs only with H1, H2, and H3, and, rarely, with subtypes H5, H7, and H9.

Despite the many H and N subtype combinations, only a few have caused human disease: H1N1 Spanish flu, H2N2 Asian flu, and H3N2 Hong Kong flu. Pandemics are caused by antigenic shift, a sudden, major change in combinations of H and/or N proteins on the virus surface leading to a new influenza A virus to which there is no pre-existing immunity. Small shifts cause minor pandemics, which occur every 30–40 years, and large shifts cause major pandemics, every 100 years.

A global pandemic is not like other standard health emergencies. It will have a longer duration than other emergency events with waves of activity separated by months. Large segments of the population will be affected, including the young and healthy. There will be simultaneous rapid spread of disease.

What will the potential impact be on our society and our places of work?

Everyday life will be disrupted because so many people in so many places will become seriously ill at the same time. The impact could range from school and business closings to the interruption of such basic services as public transportation and food delivery. We will likely see an increase in absenteeism to 40 percent due to illness, caring for the sick, and efforts at avoiding infection. Many schools will close, and parents will need to care for their children at home. People will avoid flu “hotspots,” which will severely impair the business continuity of service-based organizations.

How might an influenza pandemic affect the economy?

There will undoubtedly be immediate supply-and-demand side effects, as well as longer-term supply side effects. Disruption of transportation networks will limit the ability to receive and distribute goods. The labor supply will be restricted. The general slowdown in economic activity will reduce gross domestic product (GDP) and potentially cause a recession as business confidence will be dented. Arrears and default rates on consumer and business debt will probably rise. One example we can model the potential effect on the economy is the experience with the SARS epidemic. The outbreak in 2003 resulted in 770 deaths globally, and economic damages were estimated at $30–$50 billion. However, fear — spread in advance of the pathogen — did much greater damage than the disease itself.

Centers for Disease Control and Prevention (CDC) models predict an H5N1 (avian influenza) pandemic in the United States will have a clinical attack rate of 25–35 percent, leading to 300,000–750,000 hospitalizations at a cost of $3.2–$4.5 billion, and 20–40 million outpatient visits costing $9.5–$11.5 billion. The case fatality rate estimated to be 1–2 percent will result in 1–2 million U.S. deaths with an estimated cost to society of $10–$14 billion and 20–40 million deaths worldwide. The cost estimates for persons who become ill with no medical care are $7–$10 billion. The total U.S. economic impact of the next super bird flu pandemic is estimated at $70–200 billion. Many already feel the numbers are outdated as the data were based on a 1999 emerging infectious diseases article.

How might an influenza pandemic affect the U.S. healthcare system?

As we well know, coordination of care is challenging in the United States, as most healthcare systems and hospitals are private, financially stressed, often serve defined patient populations, operate with few excess beds, and have a “just-in-time” delivery system. Even a moderate pandemic could exceed surge capacity of U.S. hospitals and intensive care units. Healthcare facilities may be overwhelmed, straining staff and creating shortages of beds, ventilators, and supplies. Hospitals and overstressed ERs may require surge capacity; nontraditional patient triage sites such as schools may need to be created.

Healthcare workers will be the first responders, not traditional fire and law. As the threat of a pandemic becomes more likely, it is imperative that the public and especially healthcare professionals gain a basic understanding of pandemic influenza.

What are the requirements for a pandemic?

First, there must be isolation from humans with a new influenza virus. Second, there must be little or no immunity in the population. Third, there must be demonstrated ability of the virus to replicate and cause widespread infection — this usually means a greater than 20 percent clinical attack rate over a wide geographic area, with significant mortality. Fourth, and most important, there must be efficient person-to-person transmission.

We have all heard the reports predicting that the next “big one” will be triggered by H5N1, avian influenza. So what do we know about avian influenza (AI)? The natural reservoir is wild waterfowl. Infections do not cause disease and is shed in feces into the cold water, where it may last days and then be spread to other birds. This is how it survives seasons. Wild birds can transmit the disease globally to domestic fowl through migratory flyways. Since December 2003 there have been increasingly widespread outbreaks of H5N1 affecting domestic fowl from Asia to Eastern Europe, with over one billion deaths.

What do we know about instances of avian influenza in humans?

The first cases of H5N1 appeared in Hong Kong in 1997. Since then there have been 321 laboratory-confirmed cases worldwide with 194 deaths, a mortality of 60 percent, mostly in people with close contact with sick or dead poultry. A few suspected cases of human-to-human spread have been reported but none proven. The World Health Organization has characterized pandemics into six phases. We are in pandemic phase three, which acknowledges human infections but no human-to-human transmission. Progression to phase four will occur when groups of human infections appear, suggesting person-to-person spread. This is where vaccine and infection control will play the biggest role.

How will pandemic present?

Cases can present anywhere (clinics, wards, ICU, ER) with clusters of similar clinical symptoms, and may have high mortality. Cases may appear in health providers. The incubation period has been estimated at two to eight days (with a range of 2–17 days). The initial symptoms have been very high fever, cough, profound dyspnea, abdominal pain, watery diarrhea, nose bleeds, and conjunctivitis. Standard laboratory findings are nonspecific. Marked lymphopenia has been found. Patients develop worsening pneumonia and lung injury, eventual ARDS, and death (average 9–10 days after disease onset). No benefit has been demonstrated from antiviral or steroid treatment in late-stage disease. About half of deaths are due to secondary bacterial infections; early use of broad-spectrum antibiotics will save lives. Of the current antivirals, only Tamiflu and Relenza, which are neuraminidase inhibitors, may prevent or lessen the effects of avian influenza in healthcare workers when taken prophylacticlly. Physicians will face ethical dilemmas as to who will receive critical care and scarce resources such as ventilator support.

Why hasn’t avian influenza (H5N1), to which humans have no immunity, already become pandemic?

There are numerous possibilities such as increased surveillance, restriction of poultry movement, culling practices (the destruction of entire poultry populations) with compensation, better sanitation and market conditions, increased access to healthcare, antibiotics, ICUs, and vaccinations. One of the biggest reasons is the lack of viral reassortment, which may just be plain luck.

How will avian influenza H5N1 strain change into super bird flu?

We know that avian influenza viruses are very common in wild and domesticated birds. They rarely cause human infections because of inefficient replication and sporadic transmission. Swine are often the middle man, with infections from both avian and human viruses. The birth of pandemic influenza will likely occur here through genetic reassortment when the two viruses merge together in pig to form a new combination that now causes human infection and efficient human-to-human transmission. Even rarer, a true mutation of an avian virus can occur that is now able to cause infection and transmission directly in humans.

What can we do to prepare?

Individually, we can encourage healthcare providers and patients to practice appropriate hand hygiene, encourage seasonal influenza vaccine shots, assemble pandemic preparedness kits for providers and patients, and become involved in local response groups like CERT and MRC. Physicians, clinics, and hospitals must actively participate in pandemic preparedness efforts at the local level. Healthcare providers and public officials can also refer to the County of San Diego Health and Human Services Agency Pandemic Influenza Plan (223 pages) at www.modern-day.com/PanFlu/links.htm.

At the state level, efforts at surveillance, epidemiology, public health interventions, surge capacity, and communications are underway. On the national front, the National Strategy for Pandemic Influenza, which was developed on November 1, 2005, guides the nation’s preparedness and response to a flu pandemic (www.hhs.gov/pandemicflu/plan/). It is based on the strategy for early detection and surveillance of new influenza strains and vaccine development (production) and coverage (distribution to the population). In addition, attempts are underway to stockpile sufficient numbers of antiviral courses. The Strategy charges the U.S. Department of Health and Human Services (HHS) with leading the federal pandemic preparedness. The HHS Pandemic Influenza Plan is a blueprint for pandemic flu preparation and response. In particular, the HHS Plan provides guidance to national, state, and local policy makers and health departments.

Vaccination still remains one of the most effective ways for preventing influenza and reducing its health consequences. Current focus is on avian influenza H5N1. The FDA has recently approved a candidate vaccine; immunogenicity, however, has been poor. Due to antigenic shift and reassortment, the exact strain for the next pandemic will be unknown (H?N?), so we cannot predict. It will take months to develop a specific vaccine that works against any super-flu that causes a pandemic. With current world vaccine production capacity, only 100–250 million people worldwide will be vaccinated in the first waves of the pandemic. Vaccine and an adequate supply of antiviral drugs may not be available for months. Good-old-fashioned isolation, quarantine, and the use of personal protective equipment will be the most effective strategies to deploy.