Copyright 2006 (updated Nov. 29, 2006)
This tip sheet was compiled by Maryn McKenna for fellow members of the Association of Health Care Journalists. McKenna is a journalist and author who covered the CDC for nine years at The Atlanta Journal-Constitution and is currently a Kaiser Family Foundation Media Fellow. She has been writing about avian and pandemic flu since 1997. Reach her at mmckenna@mindspring.com.
1 – Bird flu and birds
- What is “bird flu”?
- I’ve heard this bird flu being called “high path.” What does that mean?
- Ducks and other waterfowl migrate all over the world. Has there really never been an H5N1 in the United States?
- So does that mean wild birds are responsible for spreading the virus?
- Who keeps track of the bird side of the story?
Learn MoreAHCJ has compiled extensive resources for members who are covering avian flu and pandemic issues. We offer tips for smaller news organizations and dozens of links to information about preparedness plans, understanding the science, public health and more. |
2 – Bird flu and pandemic flu in humans
- So why is all this significant for humans?
- Why does flu go pandemic?
- So why is the Asian avian flu considered a pandemic risk?
- Does the virulence of the Asian avian flu mean that it is a pandemic strain?
- I’ve heard that pigs play a role in reassortment. How does that work?
- If the Asian avian flu were to become a pandemic strain, how fast would it spread?
- Who keeps track of the current human cases?
3 – Controlling pandemic flu
- Is vaccination an option for controlling pandemic flu?
- If vaccination is not an option, can antiviral drugs be deployed?
- What control options exist other than vaccines and anti-virals?
4 — Preparing for pandemic flu
- Who is in charge of preparing for pandemic flu’s arrival?
- Who pays for pandemic planning?
- How can I tell whether my state is doing a good job of pandemic planning?
5 — Quick links and notes on sources
- Are there sites that are good basic resources?
- Are there nonofficial sites I should pay attention to — or be wary of?
1 – Bird flu and birds
What is “bird flu”?
It’s the popular but imprecise term for the Asian avian flu, influenza A/H5N1, that has leapfrogged across the globe since late 2003.
There are three main types of influenza: A, B and C. A is the most common, causes the most serious disease, results in the largest epidemics, and has the most genetic variation. Influenza B and C infect only humans, but influenza A infects humans, animals and birds.
Science distinguishes among the multiple strains of influenza A by means of two proteins on the surface of the virus, hemagglutinin (which allows the virus to bind to cells and is designated H for short) and neuraminidase (which allows the reproduced virus to escape from cells and is designated N for short). To date, 16 Hs and 9 Ns have been recognized, meaning there are theoretically 144 influenza A’s, though not all have been observed in nature. Each of the H-N combinations is called a subtype.
The main host for all influenza As is wild aquatic birds — ducks and other waterfowl — which until recently were thought to carry a wide variety of influenza A strains around the globe without being made sick by them. Beyond birds, subtypes tend to cluster in species: H1, H2 and H3 infect humans, while H5, H7 and H9 tend to infect poultry. Generally, the flus that have adapted to one species do not cause disease in other species.
The term “bird flu” that we toss around so casually actually indicates an influenza A of a particular subtype that historically infected only wild birds and poultry but in 1997 began to sicken and kill humans. (NB: The A in “influenza A” does not stand for “avian.”)
Here are some basic influenza primers:
http://virology-online.com/viruses/Influenza.htm
I’ve heard this bird flu being called “high path.” What does that mean?
In their natural hosts, waterfowl, flu viruses are “low pathogenic” — they don’t cause significant disease. When some of those viruses, usually the H5, H7 and H9 subtypes, get passed to domesticated chicken and turkeys, they usually continue to be “low path”– they don’t cause disease and are not easily detected. However, as the virus adapts to its new host it can become “highly pathogenic” — capable of causing rapidly progressing fatal illness — in domesticated fowl. It can rip through a flock in hours to days; one expert once called it “chicken Ebola.”
Avian flu H5N1 is a high-path virus. The last major high-path outbreak in the United States resulted in the destruction of 17 million domesticated fowl and cost more than $60 million.
Here is a primer on highly pathogenic avian influenza (HPAI).
Ducks and other waterfowl migrate all over the world. Has there really never been an H5N1 in the United States?
There are two separate lineages of avian influenzas, Eurasian and North American. The H5N1 that everyone is so concerned about is a Eurasian subtype. Eurasian subtypes have not been recorded on this continent. The event that would ring alarm bells is the detection of the Asian lineage HPAI H5N1 subtype on this continent. Multiple government surveillance networks are looking for it.
LPAI North American H5s, including H5N1s, were rarely recorded in the United States in the 1980s and 1990s and were found in Canada in 2005. In summer 2006, the U.S. Department of Agriculture and Department of the Interior began a joint project to surveil thousands of wild birds; it has since isolated LPAI H5s, including H5N1, in dozens of wild birds. There is a table of findings (pdf), including bird species and locations.
So does that mean wild birds are responsible for spreading the virus?
Scientific opinion on the likelihood of the Asian-lineage virus traveling (and arriving in the Americas) via wild bird is mixed. The understanding of whether wild birds can be infected by, carry and transmit high-path viruses has undergone rapid change in the past five years, thanks largely to H5N1. It was originally thought that the viruses went one way, from wild birds to poultry, changing from low path to high path as they went, but not transmitting beyond poultry; now it appears that poultry can pass HPAI back to wild birds. The first wild-bird deaths from HPAI H5N1 were recorded in Hong Kong in 2002, and the first major die-offs of wild birds from HPAI H5N1 in 2005. This year, Chinese and American researchers reported finding Asian HPAI H5N1 in healthy-appearing birds, suggesting the birds can carry the virus long distances, though the infection rate was very low.
The cite for that paper:
Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2845-50. Epub 2006 Feb 10. Establishment of multiple sublineages of H5N1 influenza virus in Asia: implications for pandemic control. Chen H, et al.
Subsequently the “wild v. domesticated: who’s to blame” discussion has become very contentious. It has been thoroughly covered in the news section of Science (available through EurekAlert). Here are papers from a recent conference exploring the issue. The UK-based organizations BirdLife International and Grain have written briefs covering the controversy from the other side — defending wild birds and blaming poultry agriculture.
Who keeps track of the bird side of the story?
Internationally, the Food and Agriculture Organization of the United Nations and the Office International des Epizooties (OIE) of the World Animal Health Organization. The OIE maintains a list of countries reporting the appearance of Asian-strain H5N1.
In the United States, avian flu is the joint territory of the Department of the Interior (wild birds) and the Department of Agriculture (domestic/commercial). Both have lab networks that will work together to detect the strain’s arrival.
For most reporters the significance of the Asian avian flu lies in its possible threat to humans — but it is important not to dismiss the bird side of the story too quickly. Even if the Asian avian flu never becomes a widespread human infection, it will still have accounted for the deaths or preventive slaughter of hundreds of millions of domesticated birds, along with an unknown number of deaths among 89 species of wild birds to date. Those deaths are likely to have profound economic impacts in the developing world and may have significant ecological impacts if vulnerable wild-bird populations become infected.
Here is a list of the wild-bird species affected by H5N1 so far.
2 – Bird flu and pandemic flu in humans
So why is all this significant for humans?
|
CDC/Cynthia Goldsmith/Jackie Katz |
The most important reason is that H5N1 flu has crossed the species barrier from non-human to human. Other disease organisms that have made that leap — AIDS, measles, all the viral hemorrhagic fevers, for instance — have caused significant morbidity (illness) and mortality (death before the expected life span) as they adapted to their new hosts.
In normal years, influenza does not cause extraordinary morbidity and mortality — though it is a more serious disease, and causes more illness and death (36,000 deaths and more than 200,000 hospitalizations per year in the United States, according to the Centers for Disease Control and Prevention) than most laypeople realize. But several times a century, flu roars up into a pandemic — an epidemic that spreads rapidly over a wide geographic area, usually crossing national borders — in which there is both a higher attack rate and a higher mortality rate.
Here is a timeline of recorded pandemics (this article was written by someone promoting a somewhat contrarian book, but the historical information is reliable).
Why does flu go pandemic?
As it reproduces, the flu virus (which is an RNA virus and thus lacks DNA’s self-correcting ability) makes many small errors, slight changes in its genetic code. Those changes are the reason that flu vaccines must be reformulated each year: There is enough difference in the prevailing strain, year to year, that the immunity produced by the previous year’s vaccine formula will not protect against it. This accrual of small differences is called genetic drift.
Once in a while, however, the circulating flu virus undergoes a marked change in its makeup, known as genetic shift — usually, a change to a different subtype. When this happens, higher amounts of illness and early death occur, because the population — which has some low-level immunity to the circulating strain after years of exposure to its drifted variants — has no immunological experience with the new strain.
The 1918 pandemic, which killed 675,000 Americans and at least 50 million people around the world, arose after the circulating virus shifted to HIN1. The 1957 pandemic, which killed 70,000 Americans and 2 million worldwide, followed a shift from H1N1 to H2N2. The 1968 pandemic was caused by a shift from H2N2 to H3N2. It was much milder, killing 34,000 Americans and 1 million worldwide. One hypothesis holds that it had a lesser effect because the population was not truly naïve to the new strain: It had already been primed by exposure to the N2 portion of the 1957 strain. In addition, those who were elderly in 1968 retained some H3 immunity from that subtype’s last appearance in an H3N8 in 1881.
Here is an explanation of drift vs. shift by a prominent American flu-vaccine researcher.
So why is the Asian avian flu considered a pandemic risk?
Once you realize that the prime condition for the occurrence of a pandemic is the appearance of a flu virus against which humans have little immunity, it’s easy to see why Asian H5N1 would be considered threatening. A virus that normally circulates only in a non-human species would, by definition, be a virus with which human immune systems have no experience (and therefore no prior immunity).
Asian H5N1 first jumped to humans in summer 1997, starting with the illness and death of a 3-year-old child in Hong Kong. The outbreak was cut short by the rapid slaughter of the 1.4 million chickens in the city, but not before demonstrating that the H5N1 strain could cause significant mortality: of the 18 people sickened, six died — a case-fatality rate of 33 percent.
Here is the CDC’s summation of that outbreak.
Subsequently, H5N1 has maintained that high rate. After the 1997 episode, it vanished for several years, then reappeared in a drifted form; in early 2003, it sickened a Hong Kong father and son who had been visiting the mainland, killing the father (and possibly also a daughter who died during the mainland visit). In late 2003, the strain arose in Vietnam and Thailand; in January 2004, Vietnam informed the WHO that 11 children in Hanoi had been hospitalized with severe respiratory infections and seven had died.
Since then, the H5N1 strain has infected more than 250 known victims and killed more than 150 (as of November 2006), keeping the case-fatality rate consistently above 50 percent. There has been abundant speculation during the past few years over whether that 50 percent represents a true CFR or has been distorted by poor surveillance in the affected countries. That argument holds that there must be uncounted subclinical or asymptomatic infections that, if they were counted, would change the denominator of the case-fatality ratio and thus lower the CFR. Recently, though, researchers in Southeast Asia have failed to find evidence of asymptomatic cases, despite broad application of antibody tests in villages where residents would have been exposed to H5N1 flu.
Here is an explainer and cautionary note on case-fatality rates.
Does the virulence of the Asian avian flu mean that it is a pandemic strain?
Not yet, though it is considered a troublesome candidate. A pandemic strain must be able to cause serious illness and death, which the Asian H5N1 does — but it also must be highly contagious, which the Asian H5N1 is not, yet. So far, the vast majority of people sickened by that strain have apparently been infected by poultry, though in a few cases the virus appears to have been passed from person to person in small family clusters.
Health planners’ concern is that the virus will become more contagious. Until recently, it was thought that could occur only through reassortment, a process in which different flu strains that have infected the same individual swap segments of genetic material, resulting in a third strain. The 1957 and 1968 pandemic viruses were both reassortants of human and avian flu strains.
But pathbreaking work by Jeffery Taubenberger (originally of the Armed Forces Institute of Pathology, now at NIH) and his colleagues — the group who reassembled and sequenced the 1918 viral strain — has shown that reassortment is not necessary for a virus to become easily transmissible among humans. Taubenberger’s analysis of the 1918 viral sequence revealed it to be completely avian, not a mix of avian and human. That suggested the virus had jumped entire from birds to humans and then developed contagiousness as it adapted to its new host — an obvious and troubling parallel to H5N1’s cross-species leap.
Here is the paper that announced the completion of the 1918 analysis.
And here is an explanation of the role that reassortment and adaptation have played in pandemic-strain emergence.
I’ve heard that pigs play a role in reassortment. How does that work?
It’s a long-standing theory that pigs can serve as a “mixing vessel” for flus from different species, because pigs possess cellular receptors that permit infection by both avian-adapted (H5, H7) and human-adapted (H1, H2, H3) flu strains. This analysis provided the first evidence:
- Genetic Reassortment between Avian and Human Influenza A Viruses in Italian Pigs.
Virology, Volume 193, Issue 1, March 1993, 503-506. Maria R. Castrucci et al.
According to the WHO, there is no evidence that pig co-infection has produced any pandemic strains of flu, but the possibility remains a significant concern because of the intermingling of humans, pigs and domesticated birds in rural households in Asia.
Here is a WHO discussion of the issue, prompted by a report of H5N1 being recovered from pigs in 2005.
And here’s a longer discussion of the issue, from the veterinary school of University of Wisconsin.
If the Asian avian flu were to become a pandemic strain, how fast would it spread?
Very fast. The 1918 flu went around the world in 11 months, at a time when the fastest modes of travel were steamship and railroad. SARS took approximately a month to circle the globe. Pandemic flu is expected to spread as fast. Unlike many other diseases, people with flu can transmit the disease to others before they develop the symptoms that let them know they are infected, making it difficult to implement control strategies in time.
Since the Asian H5N1 became a concern, a number of teams of scientists have attempted to estimate how fast pandemic flu might spread, a process called modeling. Here are cites of some of the most important modeling papers:
- Cooper BS, Pitman RJ, Edmunds WJ, Gay NJ. Delaying the international spread of pandemic influenza. PLoS Med. 2006 Jun;3(6):e212
- Germann TC, Kadau K, Longini IM Jr, Macken CA. Mitigation strategies for pandemic influenza in the United States. Proc Natl Acad Sci U S A. 2006 Apr 11;103(15):5935-40. Epub 2006 Apr 3.
- Viboud C, Bjornstad ON, Smith DL, Simonsen L, Miller MA, Grenfell BT. Synchrony, waves, and spatial hierarchies in the spread of influenza. Science. 2006 Apr 21;312(5772):447-51. Epub 2006 Mar 30.
- Ferguson NM, Cummings DA, Cauchemez S, Fraser C, Riley S, Meeyai A, Iamsirithaworn S, Burke DS. Strategies for containing an emerging influenza pandemic in Southeast Asia. Nature. 2005 Sep 8;437(7056):209-14.
- Longini IM Jr, Nizam A, Xu S, Ungchusak K, Hanshaoworakul W, Cummings DA, Halloran ME. Containing pandemic influenza at the source. Science. 2005 Aug 12;309(5737):1083-7.
All discussions of flu’s potential spread depend on predictions of the pandemic strain’s reproductive number, or the average number of cases caused by any single case while that individual was infectious. If the reproductive number is less than 1, the outbreak peters out; if it is more than 1, it continues. The higher the number, the more rapid the spread.
Here is an explanation of influenza’s likely reproductive number.
Who keeps track of the current human cases?
The World Health Organization updates its tally at least once a week (look in the middle of the shaded box for the link to the latest tally — the WHO changes the URL with every update so making a static link to it is challenging.).
If human cases of avian flu, or a pandemic strain, were to begin spreading in the United States, the CDC would track them, using data from state health departments.
The CDC put up a page a while ago discussing all recent cases in which avian flu moved into humans, both high-path and low-path.
3 – Controlling pandemic flu
Is vaccination an option for controlling pandemic flu?
The basic control strategies are: prevent people from becoming infected, by using a vaccine, or treat them after infection, with antiviral drugs, to reduce the chance they will pass the infection to others. For pandemic flu, both are problematic.
Developing an influenza vaccine is a clumsy and time-consuming process that in most years taken up to six months and that depends on technology fundamentally unchanged since the 1950s. Vaccine virus is usually grown in embryonated chicken eggs. That step will not succeed if the pandemic strain is a high-path avian virus (because the virus will kill the chicken embryos). If a pandemic arrives in the next few years — before expected advances in vaccine-manufacturing technology permit a switch from chicken eggs to cell culture — the only option will be to engineer the lethality out of the virus using a process called reverse genetics, a step that will add months to vaccine production.
As a result, planners have accepted that there will be no vaccine available for the first six months of a pandemic. It is debatable how much there will ever be, since the entire worldwide flu-vaccine manufacturing capacity tops out at about 300 million doses per year, against a world population of more than 6 billion.
Here is a vaccine industry position paper on pandemic vaccine supply issues.
Here is an annotated timeline of pandemic vaccine research grants, with researchers’ names and institutions, maintained by the main U.S. funder, the National Institute for Allergy and Infectious Diseases.
|
CDC/James Gathany |
If vaccination is not an option, can antiviral drugs be deployed?
Hypothetically, yes: There are antiviral drugs that can diminish an attack of influenza and make it less likely the infection will be passed on. Practically, though, deploying antivirals faces a host of difficulties: There are a limited number of drugs; only a few of that limited number work against H5N1; flu viruses develop drug resistance rapidly; and stockpiling supplies and transporting them rapidly to the site of the first pandemic outbreaks will be extremely difficult.
There are currently only four drugs that can prevent or diminish a flu infection: two adamantanes, amantadine and rimantadine; and two neuraminidase inhibitors, oseltamivir (Tamiflu) and zanimivir (Relenza): Amantadine and rimantadine have little effect on H5N1 and are rapidly becoming useless against the current seasonal H3N2.
Here is a CDC brief on flu viruses’ rapidly increasing resistance to the adamantanes.
Tamiflu currently works against the Asian H5N1 strain — though some resistance has been recorded among human H5N1 cases in Southeast Asia — but it is in extremely short supply because it is made by only one manufacturer, Roche Pharmaceuticals Inc. (a division of Hoffman-La Roche). The U.S. government has vowed to stockpile the drug, but because numerous other national governments placed their orders first, the U.S. Tamiflu stockpile is unlikely to be filled before 2007.
The WHO’s page on vaccines and anti-virals.
What control options exist other than vaccines and anti-virals?
Lacking the pharmaceutical option, the most efficient way to keep the flu from spreading is to keep people who are infected from transmitting it to the uninfected. The mildest form of this practice is voluntary social distancing, which government planners liken to snow days: closing children’s schools and day cares, having adults stay home when sick, and discouraging large public gatherings.
The imposed forms of control to which government can resort are isolation and quarantine, which people often confuse. Isolation restricts the movement of those known to be ill; quarantine restricts the movement of those who are believed to have been exposed to an illness and are therefore at risk of becoming ill.
Here is a CDC fact sheet on the difference.
In the United States, most public health powers are reserved to the states — but in 2005, the White House added pandemic flu to a list of diseases over which the federal government can exercise direct authority. The addition was made by amendment to an existing Executive Order, 13295, that was last added to during the SARS outbreak when a suspected exposed person landed in California and refused a state quarantine order.
Here is the text of the amendment and here is a CDC fact sheet explaining the federal authority.
4 — Preparing for pandemic flu
Who is in charge of preparing for pandemic flu’s arrival?
As a national government and WHO member, the U.S. government’s planning makes reference to the WHO international guidance. Remember that the WHO has influence but little power, and can advise but not compel.
In the United States, responsibility for planning is shared jointly by the federal government and the states. In 2005 the federal government released the Department of Health and Human Services plan, which covers the actions of all the major health agencies and provides guidance to state health departments.
In 2006 the government released the National Pandemic Strategy, which goes beyond the HHS portion of planning to draw in other agencies such as Homeland Security. It also discusses vaccine research, antiviral stockpiling, international relationships and a number of other key topics.
http://www.whitehouse.gov/homeland/pandemic-influenza.html
In addition, each state must prepare a pandemic plan as a condition of receiving federal preparedness funds. Some states are very prepared; others are way behind. In addition, some states have balked at making their plans public. An easy way to find details on state plans and funds is through a federal site called www.pandemicflu.gov where you can find the page with all the state plans.
Who pays for pandemic planning?
Mostly the federal government, though states are being asked to come up with some of the money they need. Each state must hold a pandemic planning summit.
At the summits, HHS Secretary Michael Leavitt usually announces the Phase 1 allocation to each state.
Afterward, states are eligible for a second bolus of money, provided they conduct more distributed planning in their counties/cities/health districts. For details, contact each state health department.
How can I tell whether my state is doing a good job of pandemic planning?
The federal government has set benchmarks for state governments and issues checklists and guidances for social sectors (businesses, schools, health care, etc.).
It’s also useful to talk to the professional organizations that represent segments of the public health infrastructure, because they are hearing from their members in each state about what is and is not working.
- American Public Health Association
- Association of State and Territorial Health Officials
- Council of State and Territorial Epidemiologists
- National Association of County and City Health Officials
- National Association of Local Boards of Health
- Association of Public Health Laboratories
5 — Quick links and notes on sources
Are there sites that are good basic resources?
Are there nonofficial sites I should pay attention to — or be wary of?
There are many untrustworthy sites and few truly trustworthy ones. The avian flu/pandemic flu story has gotten into the echo chamber of the Internet: Most of the blogs and boards that are discussing this have great self-assurance and little reliable information. Approach them with great caution and always check out their claims independently.
That said, some sites worth monitoring are:
- CIDRAP News, the original-reporting arm of the Center for Infectious Disease Research and Policy at University of Minnesota
- Effect Measure, the pseudonymous blog of a public-health insider
- Connotea, which hosts an aggregator maintained by Nature writer Declan Butler
- The business site of Peter Sandman, a risk-communication expert
- The personal site of Crawford Kilian, a college professor and author who has taken a personal interest in flu.
- Flu Wiki, a collaborative effort; treat it with the same care you would any Wikipedia entries.
In addition, AHCJ has compiled extensive resources for members who are covering avian flu and pandemic issues. We offer tips for smaller news organizations and dozens of links to information about preparedness plans, understanding the science, public health and more.
