the evolving saga

The Challenge | The Response | The Questions | Pandemic Preparedness | The Blog

The Health Challenge

A “new” influenza A H1N1 virus that combines genetic material from swine, avian and human influenza viruses was initially reported in Mexico and in the southwestern United States in early April 2009. Subsequently, the new virus has continued to spread steadily around the globe.

Although this strain of influenza seems relatively mild, deaths are occurring, primarily among people with pre-existing illnesses. Within the United States, nearly 9,000 laboratory-confirmed H1N1 infections have been reported from all 50 states, the District of Columbia, Puerto Rico and the U.S. Virgin Islands as of June 25, with 127 confirmed deaths. CDC has estimated that more than a million H1N1 infections have occurred in the United States.

Global totals as of May 29 include more than 70,000 laboratory-confirmed cases in more than 100 countries and 311 deaths (including 116 deaths in Mexico). Given the large number of deaths in Mexico and the generally milder course of illness in every other country so far, it is now widely believed that the actual number of persons infected in Mexico has exceeded 300,000.

There is considerable uncertainty about the outcome of the influenza season now unfolding in the southern hemisphere and about the next northern hemisphere influenza season that begins in the fall of 2009. In “normal” influenza seasons, an estimated 35,000-40,000 flu deaths occur in the United States. Worldwide, the annual flu deaths are estimated at 250,000-500,000 but may be much higher.

A major outstanding unknown is whether the new H1N1 virus might repeat the pattern seen in the 1918-1919 flu pandemic, when that variant of H1N1 appeared mild initially but reappeared during the next “regular” winter flu season as a more severe illness that killed tens of millions of people. The dilemma for U.S. and global policymakers is how to respond to the threat of a pandemic disease threat when the true magnitude of that threat cannot be known in advance.

Even as a mild illness with a low overall mortality rate, this H1N1 strain could cause many deaths worldwide, especially among youth or those with underlying illness (e.g., HIV), if it becomes a widespread illness. A mortality rate of only 0.25%, for instance, among 1 billion H1N1-infected people, would result in 2.5 million deaths.

Today, as opposed to 1918-1919, the world can expect the availability of large quantities of antibiotics, anti-viral drugs, and, it is hoped, a new and effective vaccine. Since early in this decade, following 9/11, anthrax, SARS and the threat of avian influenza, efforts have accelerated to strengthen preparedness in the United States, with over $8 billion invested in state, local and federal capacities.

In this same period, the WHO-led global surveillance and response system has been strengthened, including new authorities under the International Health Regulations, and more extensive use of rapid information technology and non-governmental data sources.

The Influenza Disease Challenge for Individuals

After direct exposure, influenza has an incubation period of 24-72 hours, during which infected individuals have no symptoms. Although they cannot definitively be identified as infected (making impossible the effective screening of incubating travelers), they may be able to spread the infection to others for some hours before they develop their own symptoms.

Once flu symptoms begin, most individuals remain contagious for 3-5 days. Spread occurs through respiratory droplets in the air (e.g., coughing, sneezing) or on hands or other surfaces (e.g., kissing, handshakes).

For most people, during most winter influenza seasons, influenza is a generally mild illness. Exceptions include young infants, the very old, and individuals with compromised immune systems or chronic respiratory disease.

Either of the related anti-viral drugs oseltamivir (Tamiflu) and zanamivir (Relenza) can reduce the duration of symptoms (and can perhaps reduce the severity of symptoms for those at particularly high risk) if started within the first 24-48 hours of symptoms. These drugs probably do not reduce the risk of spreading flu to others.

The Response

The U.S. Response

• In the United States, the new H1N1 virus in San Diego was quickly identified as unusual. Its details were published rapidly in CDC’s weekly Morbidity and Mortality Weekly Report.
• The outbreak came within the U.S. neighborhood – concentrated in Mexico and at home – and not, as expected, from Asia. It abruptly ended a lull in recent years in the perceived pandemic influenza threat. Pandemic influenza suddenly came to be seen as a serious threat to individuals, especially youth and those with pre-existing conditions, communities, the national economy, and regional trade and commerce.
• The fact that the outbreak proved to be mild versus severe meant that it only partly tested the U.S. preparedness system that had been built up rapidly since 2001. If the outbreak had been severe, the federal government would likely have encountered serious problems in expediting drugs and supplies from the federal to the state and local levels and in confirming cases.
• The government response appeared measured and appropriate. The President took a lead direct role in his 100 day press briefing and thereafter. Homeland Security Secretary Napolitano, CDC Acting Director Besser and Dr. Fauci of NIH each played highly visible roles and voiced consistent messages. The unfolding flu crisis appears to have expedited the confirmation of HHS Secretary Sebelius.
• Despite the fact that the Obama administration was still in transition – no Surgeon General, no CDC Director, initially no HHS Secretary, no NIH director -- interagency cooperation appeared to work well within the federal government, at the state level and most state-local interfaces. A few state governments were slow to distribute information and resources to their local levels.
• While there was much debate in the U.S. press on the merits of school closings and reopening, available data from past flu outbreaks suggests that closings have helped slow (but not prevent entirely) the spread of H1N1.
• Some in Congress pressed unsuccessfully for screening of people crossing from Mexico, even though most Mexico-related U.S. flu cases entered the United States via airplane, even though asymptomatic persons in the 1-3 day influenza incubation period cannot be identified with current technology, and even though the staff necessary to do almost any kind of health screening at the border could be employed far more usefully in the tracking of actual U.S. cases and their contacts.
• Apparently due to U.S. importation regulations related to bio-defense concerns, the Mexican national laboratory was unable to quickly ship laboratory specimens of influenza virus to CDC for analysis. The Mexican specimens for strain identification were instead sent to a W.H.O. reference laboratory in Canada.
• Messaging from health authorities was at times inconsistent regarding: travel to Mexico, the closing of schools and businesses, access to hospitals and clinics, and the value of standard surgical face masks. This was compounded by round-the-clock media coverage that sometimes sensationalized the threat and at other times was inappropriately reassuring.
• An initial request from the administration for $1.5 billion in supplemental funds for vaccine and drug purchases and $2 billion in contingency funds received strong bipartisan support. In the end, Congress authorized $7.7 billion, including $1.5 billion for CDC/DHHS and $5.8 billion for contingencies, as part of the $105.9 billion supplemental bill.

New England Journal of Medicine, Spread of a Novel Influenza A (H1N1) Virus via Global Airline Transportation, Massachusetts: 2009.

The Mexican Response

• There have been criticisms of an apparent delay in Mexico’s notification of W.H.O. about the initial cluster of cases of H1N1 flu. However, in a federal health system responsible for responding to frequent disease reports from multiple state governments, it is not clear that any significant delay occurred once Mexico’s central government had collected and analyzed its initial outbreak data.
• Once the magnitude of the outbreak became clear to Mexican authorities and the new virus strain had been identified, Mexican authorities at the highest levels took concerted action to slow or stop the spread of disease, at the same time that additional data were collected and refined. Schools were closed in many places, businesses in Mexico City were closed for a 5 day weekend, and other social distancing steps were taken.

The W.H.O. and Global Response

• Although the W.H.O. pandemic alert system worked reasonably well to facilitate information flow between countries and other interested parties, it was heavily criticized for its focus on geographic spread of disease and lack of focus on disease severity. Work is already underway to modify the system to incorporate measures of disease severity.
• Beyond the alert system concern, W.H.O. and Dr. Chan received generally high marks for their leadership and their leveraging of the new International Health Regulation authorities that came into force in 2007. Dr. Chan’s performance benefitted from her prior experience as Director of Health in Hong Kong where, during her tenure, the first outbreaks of both avian (H5N1) flu and SARS occurred.

The Questions

H1N1 influenza – a ‘slippery’ disease with many unanswered questions

Influenza virus is both a clinical and public health conundrum. As we move forward, policymakers will struggle with multiple challenges that often defy easy resolution. Outstanding key questions include:

• What will be the clinical severity and the geographic spread of the H1N1 virus in the next influenza season here?
• Will sufficient amounts of the pandemic flu H1N1 vaccine and anti-viral medication be available in time? Does the global production capacity exist?
• How safe and how effective will a vaccine made from this season’s virus be against next season’s influenza strain? How would the population be convinced to accept a new pandemic H1N1 flu vaccine in addition to the normal seasonal flu vaccine that is already in production? And when and how will a decision be made about using the new H1N1 vaccine once it is available in the fall of 2009?

In 1976, during the last swine flu scare, President Ford made an early combined decision to produce and distribute the vaccine. There was no subsequent spread of swine influenza disease, and there were rare but severe vaccine side effects, causing at least 25 deaths. The vaccine program was abruptly halted after 40 million Americans had been vaccinated.

Today, the decision has been taken to develop and produce a new H1N1 flu vaccine. A decision on actual use of the vaccine will come later.

• How quickly will the influenza strains of this season and the next flu season develop significant resistance to the few anti-viral drugs that are now effective? In the event of additional spread of H1N1, what is the appropriate use of anti-viral drugs for high risk individuals, health workers and other public safety workers? Inappropriate and excessive use for others could lead to increasing levels of drug resistance.
• What is the “best” way to use social distancing (including closures of schools and businesses) as a public health tool?
• What is the most effective messaging strategy to prepare the public for the uncertainty to come about the virus and the vaccine, in the face of rising public anxiety and an overheated media?
• How can the effective coverage of the global influenza surveillance system be expanded when disease surveillance capacities in many developing countries remain very weak? How much assistance is the U.S. government prepared to offer?
• In preparing for pandemic influenza, how will the United States, W.H.O. and other major donors take coordinated action to assist developing countries in meeting their urgent needs for both vaccines and antiviral drugs? Action in this area will significantly influence virus sharing from developing countries.