“Stupid about STDs” update

On Monday, I mentioned a survey MSNBC and Zogby conducted regarding attitudes about sex and STDs. Today on MSNBC, they have another article on the rise of STDs in America, highlighting some depressing trends. Meanwhile, in what you’d think would be across-the-board good news, a vaccine has been tested against 2 types of human papilloma virus (HPV), an STD which is the most common cause of cervical cancer. Despite having a 100% effectiveness in preventing infection with these viruses (which together cause ~70% of all cervical cancers), there is organized resistance to the vaccine, on the grounds that it will increase promiscuity:

“Abstinence is the best way to prevent HPV,” says Bridget Maher of the Family Research Council, a leading Christian lobby group that has made much of the fact that, because it can spread by skin contact, condoms are not as effective against HPV as they are against other viruses such as HIV.

“Giving the HPV vaccine to young women could be potentially harmful, because they may see it as a licence to engage in premarital sex,” Maher claims, though it is arguable how many young women have even heard of the virus.

I’d say that attitudes like this in the 21st century are unbelievable, but having spent way too much time discussing biology with creationists, I’m well aware they’re all too common. Tragic.

Newsflash: people still stupid about STDs

Okay, so it’s just an MSNBC survey (aided by none other than Dr. Ruth), but geez, when will people ever wise up about sex?

MSNBC.com and Zogby International asked online readers to share some intimate details about their personal lives, and more than 56,000 adult men and women — one of the largest responses ever to a sex survey in the United States — revealed that many are playing a pretty risky game.

Just 39 percent of people who took the survey always ask whether a new partner is infected with HIV, the virus that causes AIDS, or other STDs. Nearly one-third said they never check on a prospective partner’s sexual health status, and among those with less than a high school education, almost 50 percent never discuss the issue of STDs with a new partner — troubling statistics given the deadliness of AIDS and rising rates of genital herpes and other diseases.

Depressing. Seems that many still equate the idea of an STD-positive partner with “dirtiness.” (“S/He’s cute–he can’t have AIDS/syphilis/herpes/etc.”) If nothing else, you’d think those annoying Valtrex commercials would advance the meme that good-looking people can have herpes and other nasty infections. It would be interesting to find out if there was any correlation between these kinds of attitudes and having abstinence-only sex education in school…

They also mention “fear of rejection” and other related concerns as playing a role in the low number of participants who discuss sexual history with their partners. I recognize that it can be embarrassing and awkward, but if you’re too embarrassed to ask the person you’re planning on getting naked with about their STD status, maybe it’s time to re-think the rendezvous? That’s just something I have a tough time wrapping my head around.

Pandemic influenza awareness week. Day 5: How ready are we, and what can YOU do?

Thus far this week, I’ve discussed the history of pandemic influenza in general, and avian flu in particular. I’ve discussed some issues that must be addressed to prepare us for a pandemic, and the groundbreaking resurrection of the Spanish influenza virus. Today I want to end the series with a look at how prepared we currently are as a nation, and highlight some personal preparedness steps you can take.

If you recall from Tuesday, the first outbreak of H5N1 was back in 1997. The anthrax attacks were in 2001. Surely by now we’re prepared for some kind of serious, large-scale, biological event, right?

The Feds: “um, er, the dog ate my homework?”

The U.S. is still working on finalizing its Pandemic Influenza plan, which it keeps promising will be done “soon.” But scientists are a bit skeptical…

“We need more than just a plan; we need the resources to actually activate it,” said Jeffrey Levi, a pandemic specialist at the Trust. “The real test of the plan will be whether it comes with dollars attached.”

The current draft of the administration’s plan fills several hundred pages. It describes the role of the federal government in coordinating the response to a flu pandemic and outlines steps to be taken at all levels of government before and during an outbreak.

In addition to production and stockpiling of vaccines and antivirals, the plan seeks to conduct research, prepare public education campaigns and develop ways for hospitals to handle large numbers of patients.

Recent events have at least gotten the politicians on both sides of the aisle to start speaking. (And reportedly, Bush even read The Great Influenza over his August vacation). Another Republican, Senate Majority leader Bill Frist has suggested a 21st Century “Manhattan Project” to deal with pandemic influenza:

I speak of substantial increases in support for fundamental research, medical education, emergency capacity, and public health infrastructure. I speak of an unleashing of the private sector and unprecedented collaboration between government and industry and academia. I speak of the creation of secure stores of treatments and vaccines and vast networks of distribution.

Above all, I speak not of the creation of a forest of bureaucratic organization charts and the repetition of a hundred million Latinate words in a hundred million meetings that substitute for action, but action itself — without excuses, without exceptions — with the goal of protecting every American and the capability to help protect the people of the world.

I call for the creation of the ability to detect, identify, and model any emerging or newly emerging infection, present or future, natural or otherwise — for the ability to engineer the immunization and cure, and to manufacture, distribute, and administer what we need to get it done and to get it done in time.

This is a bold vision. But it is the kind of thing that, once accomplished, is done. And it is the kind of thing that calls out to be done — and that, if not done, will indict us forever in the eyes of history.

Democratic Senate leader Harry Reid said:

Perhaps the only thing more troubling than contemplating the possible consequences of an avian flu pandemic is recognizing that neither this nation nor the world are prepared to deal with it.


Given the very real possibility of an outbreak, its potentially severe consequences, and our relative lack of preparedness, we need to take immediate action on several fronts to prepare this nation and the American people for a potential outbreak and to reduce its impact should it occur.

On September 29th, the Senate approved $4 billion to buy antivirals and to fund “other measures” (including surveillance, vaccine development, and state and local preparedness) to ready for a pandemic. However, it’s not certain this will pass through Congress, as Alaskan Senator Ted Stevens threatened to block the money, as the avian flu “has not yet become a threat to human beings.” With all due respect, Senator Stevens doesn’t get it. Whether the current H5N1 is the next pandemic, or whether that burns out and another virus comes along in 5 or 10 years, we need to be prepared. Preparedness takes money. You’d think some politicians would learn the benefits of an “all hazards approach” to disaster preparedness, but unfortunately, far too many are stuck with the “just in time” model. “Just in time” will be too late for an influenza pandemic.

Even if the money is provided, there are no guarantees that the U.S could even get a stockpile of Tamiflu, made by Swiss pharmaceutical company Roche. Roche has set up a first-come, first-serve waiting list for the drug, and sources have reported that the U.S. is nowhere near the top of the list. Currently, we have about 2 million doses in stock; ideally, they want 20 million doses or more. Secretary of Health and Human Services Michael Leavitt has said they should have ordered it earlier, and he “doesn’t know” why that wasn’t done.

Pandemic czar Stewart Simonson doesn’t seem to know, either. Simonson was brought on board by former HHS Secretary Tommy Thompson; Simonson was Thompson’s former legal counsel in Wisconsin. His official job is to “coordinate interagency activities between HHS, other federal departments, agencies, offices and state and local officials responsible for emergency preparedness and the protection of the civilian population from acts of bioterrorism and other public health emergencies.”

The scary part is that even if we have plenty of Tamiflu, we can’t be 100% sure it would work. A strain of H5N1 isolated from Vietnam earlier in the year was reportedly resistant to Tamiflu, although the accuracy of those reports remains in question.

So what about the vaccine?

There has been some progress with an H5N1 vaccine. Clinical trials are already underway for a vaccine produced by Sanofi Pasteur. Another vaccine by the same manufacturer was tested earlier in the year, but was made without an adjuvant (a chemical added to the vaccine preparation to further stimulate the immune system). For that vaccine, in order to be effective, 12 times as much vaccine was needed compared to the regular influenza vaccine. Additionally, MedImmune, the company which makes the nasal FluMist vaccine, has announced that it will work with the NIH to develop a library of vaccines for more than a dozen strains of H5N1. FluMist is a live attenuated vaccine; the avian flu vaccines by MedImmune will also be live. MedImmune’s Kathleen Coelingh suggests that even if the vaccine isn’t a perfect match to the circulating strains, having a live vaccine can elicit cross-protective immunity; enough to help in a pandemic situation. However, it will take years for this project to reach fruition.

Work has also been moving forward on a influenza vaccine targeted at other viral proteins, rather than the viral hemagglutinin and neuraminidase that are currently targeted. Again, while those are in the pipeline, it will take years of development until they are approved—if they work at all.

The Q word

President Bush has recently said that American troops may be used to enforce quarantines in areas suffering from influenza outbreaks. Such an action would require a change in law, and would be a shift in the way quarantines have been handled since the inception of the United States. It also brings to mind images of the movie “Outbreak.”

Would large-scale, forced quarantines even work in today’s world? Keep in mind that quarantines are for exposed, but still healthy, individuals. In this era of email, cell phones, and text messages, a “heads-up” notice could be sent in minutes, before officials had time to locate everyone who had potentially been exposed. The population is exceedingly mobile; most people could hop in a car, or on a bus, plane, or train in no time. If even a small proportion of them flee into an uninfected area, the net result could easily be to make the situation worse than it had been previously. This is yet another area where we need an evidence-based plan prior to proceeding.

What YOU can do

First and foremost, not be overly worried. Predicting outbreaks is an inexact science, to put it mildly. Anytime we deal with living targets, and especially with ones that can evolve as rapidly as influenza viruses, things get messy. We can’t simply appeal to the laws of physics in order to anticipate what trajectory the virus will proceed along. So, do what you can, educate others, but take the sage advice of the Hitchhiker’s Guide, and Don’t Panic.

Second, wash your hands. It’s not sexy advice, I admit. But ever since Semmelweis, it’s been the smartest thing a public health professional can advise. And really, many of us still don’t do it correctly. It is recommended to wash with soap and running water for at least 20 seconds. I know that when I’m in public restrooms (and I work within a hospital building!), I very rarely see people wash that long. So, be a bit more contientious when you wash. Teach your children to do this as well: have them count to 20 or sing their ABC’s while washing their hands. If you’re not around a faucet, hand sanitizers with 70% ethanol are also effective. (To my knowledge, Triclosan, the other common ingredient in hand sanitizers, has not been proven effective at killing viruses–so watch the ingredients and stick to alcohol).

If you’re sick, please, please, please stay home. Adults are contagious for ~5 days and children for up to 21 days after becoming sick. Don’t go and expose others when you’re coughing, sneezing and hacking all over the place.

Avoid touching your eyes, nose, and mouth. Again, think about how many times you do this every day. This is one way influenza can enter a body. Also, re-train yourself not to cover your mouth with your hands when you cough: use a tissue, or the crook of your arm—something that won’t come into contact as often with surfaces, or with other people.

Get a flu shot. No, it won’t protect you from “bird” flu, but should that virus spread, it will prevent you from being co-infected with both viruses and passing along any potential recombinant viruses. And remember, even garden-variety influenza kills 36,000 a year in the United States: that’s nothing to sneeze at. (Groan).

Get stocked up. You should always have a supply of food, water, medications, and basic household necessities on hand in the event of any kind of disaster–including ones caused by infectious agents. We’re all susceptible to either hurricanes, or earthquakes, or tornadoes, or blizzards, or floods, or [insert your favorite disaster here], so there’s no excuse to not be ready.

Additional steps to take should a pandemic occur

Avoid sick or dead birds, especially wild birds.

Avoid close contact and shaking hands.

Don’t share eating utensils, glasses, etc.

Disinfect surfaces with a 1:50 bleach or 70% alcohol solution. Solution must remain on surface for at least 2 minutes. (Use 1:5 bleach solution with 10-15 minutes contact time should be used for surfaces contaminated with body fluids).

More suggestions can be found here on the flu wiki.

A Closing Plea

Finally, in the long term, one thing you can do is make prudent use of your vote, and your voice. The public health infrastructure in the United States has been seriously underfunded for many, many years. In addition to the regular hot-button issues, investigate how public health-friendly your candidate is the next time you vote. Lobby your current legislators (Senators here, find and contact your Representative here) for more money for surveillance and vaccine development. Let them know this is an important issue to you. Write letters to the editor of your local paper to raise awareness in the general public. Even if this pandemic doesn’t emerge, improvements in our preparedness capability and vaccine manufacturing procedures will only put us ahead of the game the next time a deadly influenza virus—or any other infectious agent–emerges.

Thanks for reading!

Other posts in the series:

Day 1: History of Pandemic Influenza.

Day 2: Our adventures with avian flu.

Day 3: Challenges to pandemic preparedness

Day 4: 1918 influenza virus reconstructed

More resources on pandemic influenza:

  • CIDRAP Pandemic influenza news
  • Infectious Disease Society of America (IDSA) Pandemic/Avian flu
  • CDC’s site on Avian flu
  • Flu wiki
  • Pandemic Influenza awareness week Day 4: 1918 influenza virus reconstructed

    I know I said I was going to discuss a bit more about pandemic preparedness today, but I think I’ll hold off on that to discuss this story:

    It sounds like a sci-fi thriller. For the first time, scientists have made from scratch the Spanish flu virus that killed millions of people in 1918.

    Why? To help them understand how to better fend off a future global epidemic from the bird flu spreading in Southeast Asia.

    Researchers believe their work offers proof the 1918 flu originated in birds, and provides insights into how it attacked and multiplied in humans. On top of that, this marks the first time an infectious agent behind a historic pandemic has ever been reconstructed.

    This isn’t the first time parts of the 1918 flu virus have been “resurrected.” Other genes have already been spliced into “modern” influenza viruses, in order to test whether the presence of the 1918 gene increases the virulence potential of the virus. However, this is the first time the entire virus has been re-assembled.

    How’d they do it?

    Researchers led by Jeffrey Taubenberger have been working on sequencing the 1918 influenza virus for several years. To obtain the virus, they unearthed victims of the pandemic who’d died in a small town called Brevig Mission, Alaska. They obtained one sample from this location. Additionally, Taubenberger is employed at the Armed Forces Institute of Pathology, which houses an immense collection of tissue samples. 2 lung samples were found in that repository, fixed in formalin, from 1918 flu victims. These three samples have been sequenced and pieced together bit-by-bit, each gene being compared to those from other influenza isolates along the way. It was already known that the 1918 virus was most closely related to the mammalian isolates they examined, but it was the most “avian-like” of all of those. Therefore, they suspected it was an avian virus that had been adapting to mammals for awhile prior to the pandemic. The current research with the whole virus supports this claim.

    To get whole virus, the scientists used a process called “reverse genetics.” Normally, we have an organism first (bacteria, plant, human, etc.), and want to decipher certain portions of their DNA. In reverse genetics, we start from the nucleotide sequence first, and arrive at the gene products. In this case, plasmids carrying all of the genes to make up the 1918 flu virus were inserted into human kidney cells, which act as the virus factories. The plasmids replicated within the cells, producing the viral proteins. These proteins assembled within the cell, and voila–intact virus.

    These viruses were then injected into mice in order to determine the virulence of the virus–and it’s a doozy. According to Nature:

  • 50 times as many virus particles are released from human lung cells a day after infection with the 1918 virus as are released after exposure to a contemporary strain called the Texas virus.
  • 13% of body weight is lost by mice 2 days after infection with 1918 flu; weight loss is only transient in mice infected with the Texas strain.
  • 39,000 times more virus particles are found in mouse lung tissue 4 days after infection with 1918 flu than are found with the Texas virus.
  • All mice died within 6 days of infection with 1918 flu; none died from the Texas strain.
  • The concern

    Not surprisingly, many people are concerned about this revelation. They’ve pointed out that the group has made what is possibly the ideal bioterrorist agent: deadly and highly transmissible. Tumpey et al. counter back that significant precautions were taken, and remain in place regarding storage and handling of the virus. We also need to remember the old causation triangle:

    Though the agent may be the same, the host and the environment are much different. The population in 1918 may have been mostly naive to H1N1 serotype viruses, but the current population is not. Indeed, there’s an H1N1 serotype virus in the vaccine forumlation for 2005-6, and similar viruses have been used for years. Viruses of this serotype have been circulating for decades, so much of the population should have at least a partial immunity to the 1918 virus. Additionally, one change in the greater “environment” is the production of antiviral drugs. Tamiflu has already been shown to be effective against the 1918 virus. As I mentioned yesterday, the 2 influenza models published showed that Tamiflu could be used to halt the spread of a pandemic virus, if it’s given soon enough and if the R0 is low enough. If there is an intentional release by terrorists, or an accidental release due to a lab accident, there should be enough time to isolate cases and provide Tamiflu before it turns into an epidemic situation. Finally, as the 1918 virus isn’t out there circulating (and, therefore, evolving) in nature, a “just in case” vaccine could be made. Given the fact that we have a virus out there that is similar in many ways to the 1918 virus, I think the potential benefits outweigh the possible risks at this point in time. I just hope they don’t prove me wrong.

    Other posts in the series:

    Day 1: History of Pandemic Influenza.

    Day 2: Our adventures with avian flu.

    Day 3: Challenges to pandemic preparedness

    More resources on pandemic influenza:

  • CIDRAP Pandemic influenza news
  • Infectious Disease Society of America (IDSA) Pandemic/Avian flu
  • CDC’s site on Avian flu
  • Flu wiki
  • Pandemic influenza awareness week. Day 3: Challenges to pandemic preparedness

    The scientific community is all too familiar with the dangers an influenza pandemic could bring. The politicians and general public are starting to become aware of the issue as well; indeed, one can hardly open a newspaper or turn on the television without hearing about “bird flu.” So, what’s actually being done to prevent an influenza catastrophe? What are the issues? What can be done?

    These are the questions that keep public health officials awake at night, because the answer is always that we’re not doing enough. While we may be resigned to the fact that a future pandemic can’t be completely prevented, the damage can be minimized. Today, I’ll begin discuss the problems we face, and the proposed solutions to counter them, when it comes to pandemic influenza preparedness.

    The recognition of an influenza pandemic has the capacity to change the world overnight. It takes months to manufacture an influenza vaccine, and antivirals are in limited supply. In developing countries, they need not even worry about these: they will simply be out of their reach, due to the cost and limited availability that can be expected in the event of a pandemic. Foreign travel would be decreased, or halted. Domestic travel may be curtailed as well. And this is just for starters. A year-long (or, worst case scenario, multiple-year) pandemic could be a catastrophe like none we’ve seen in almost a century. Will it get to that? No one knows, but we need to prepare for that as one possibility.

    The Good, The Bad, and The Ugly

    Is this just more fear-mongering? The 2003 SARS experience is an instructive example. It showed how fast an infectious agent could globe-trot: once the virus emerged in China, it spread to five countries within 24 hours, and had reached every continent except Antarctica within a few months. Though the epidemic ended up being fairly small in terms of infections and fatalities (~8000 cases and 800 deaths), the financial impact was massive. In Canada, Toronto was the epicenter of the epidemic, as a traveler from Hong Kong began the wave of infection in that city that would go on to claim 43 lives and infect 438. The economic cost of this? An estimated $419 million to tourism alone; another $763 million on health care. The cost to the Asia-Pacific region has been tagged at the $40 billion mark; flights to the area decreased by 45% from the previous year. Keep in mind, these numbers are for a fairly small, fairly contained, 6-month epidemic. Influenza pandemics can last 12-36 months, and influenza is much more highly transmissible than the SARS coronavirus.

    Due to both international travel and international trade, an influenza pandemic is necessarily an international issue. This may seem obvious, but when influenza response plans are made, they are all too often drafted to be specific to the community, the state, or the nation. This is all well and good, but unrealistic. Comprehensive preparedness needs to involve and coordinate all different levels, and many different types of entities. Specifically, it needs to involve those in the private sector as well as the public sector; currently, many companies have no plans in place should a pandemic occur, and many government plans don’t go far enough in collaborating with various companies whose assistance they may need in the wake of a pandemic. There are a number of repercussions that may hit industry heavily. Manufacturing of non-necessities and other “trivial” activities may be scaled back in order to conserve scarce resources. At the same time, production of critical goods–food, medicines, everyday items such as soap, gasoline, etc.–would need to be preserved with a diminished workforce and crippled supply chain. Our medical, military, and service positions (police, firefighters) may be weakened, due to not only illness/death in the ranks, but also because some will refuse to put themselves at further risk.

    I mentioned developing countries earlier. In many areas, there are already governments in chaos, or on the verge of it. An influenza pandemic would serve to further de-stabilize these regions, as the government becomes increasingly helpless to assist their populace. This, in turn, can work to spread the pandemic further, as refugees flee into new areas, bringing their microbial stow-aways along with them.

    Insights from mathematical models

    They’re trite but true: “an ounce of prevention is worth a pound of cure;” and “knowledge is power.” Mathematical modelers work at the interface of math and biology in order to turn knowledge about infectious disease biology into targets for prevention. By tweaking the parameters and assumptions built into the model, they can see which variables have the greatest effect on outcome. 2 such analyses were published in the past 2 months, Strategies for containing an emerging influenza pandemic in Southeast Asia in September 8th’s Nature, and Containing pandemic influenza at the source in Science‘s August 12th issue. Both were focused on southeast Asia; both looked mainly at targeting antivirals to the at-risk population as a way to control the outbreak. They also looked at the effects of reducing the “social distance” between individuals (reducing their number of contacts), and the effect of quarantine. (See here for some cool supplemental movies that illustrate all this). Both determined that it should, in theory, be possible to contain a pandemic at its source, if the virus has a basic reproductive rate (R0) of below ~1.8; that is, each infected person infects less than an average of 1.8 others. These reports have led to an increased push by many world governments to stockpile one of these antiviral drugs, Tamiflu. I’ll discuss tomorrow the implications of and problems with this decision.

    What about vaccines?

    Clearly, an effective vaccine that could be produced well in advance of a potential or looming pandemic would be ideal. However, right now, that’s simply not possible. First, we don’t have the corporate backing. The number of companies willing and able to produce influenza vaccine has dropped off precipitously in the past 2 decades, from more than a dozen in 1980 to only a few in 2004. This is a pragmatic decision; the result of both mergers and a simple lack of profitability for the company. Vaccines are not big cash cows; indeed, they can potentially be drains. Vaccines are difficult to design and test, and with an increase in the anti-vaccine climate in the United States, it’s easy to see why some companies simply choose to avoid the issue. Flu vaccines are even more of a pain than other vaccines. Due to the frequent changes in the circulating influenza viruses, the vaccines must be made rapidly, increasing the risk of contamination or other mistakes. New batches need to be made every year, and can’t be banked for sale in subsequent years. Finally, the viruses need to be grown in live chicken eggs. This is particularly a problem with H5N1. I mentioned yesterday that this virus was nicknamed “chicken Ebola” due to the fact that it is highly lethal in chickens–and that includes chicken eggs. There have been some advances in growing the virus in eggs, but there’s no guarantee that, should we be facing a pandemic with this virus, the eggs could be cultivated fast enough to mass-produce a vaccine in time for it to have any effect on stemming the epidemic. What we need, badly, is 1) a cell culture-based method of vaccine production, getting rid of the eggs; and 2) a pan-influenza vaccine: one that works against all (or at least, most) strains of the virus. Work is being done on both of these, but it’s not something that’s going to ameliorate the situation for awhile yet.

    Another concern involves the group targeted for vaccination. In typical years, those who are designated “high risk” have first dibs at the influenza vaccine in most areas. According to the CDC guidelines, these include:

    1.) People at high risk for complications from the flu:
    • People 65 years and older;
    • People who live in nursing homes and other long-term care facilities that house those with long-term illnesses;
    • Adults and children 6 months and older with chronic heart or lung conditions, including asthma;
    • Adults and children 6 months and older who needed regular medical care or were in a hospital during the previous year because of a metabolic disease (like diabetes), chronic kidney disease, or weakened immune system (including immune system problems caused by medicines or by infection with human immunodeficiency virus [HIV/AIDS]);
    • Children 6 months to 18 years of age who are on long-term aspirin therapy. (Children given aspirin while they have influenza are at risk of Reye syndrome.);
    • Women who will be pregnant during the influenza season;
    • All children 6 to 23 months of age;
    • People with any condition that can compromise respiratory function or the handling of respiratory secretions (that is, a condition that makes it hard to breathe or swallow, such as brain injury or disease, spinal cord injuries, seizure disorders, or other nerve or muscle disorders.)

    2.) People 50 to 64 years of age. Because nearly one-third of people 50 to 64 years of age in the United States have one or more medical conditions that place them at increased risk for serious flu complications, vaccination is recommended for all persons aged 50 – 64 years.

    3.) People who can transmit flu to others at high risk for complications. Any person in close contact with someone in a high-risk group (see above) should get vaccinated. This includes all health-care workers, household contacts and out-of-home caregivers of children 0 to 23 months of age, and close contacts of people 65 years and older.

    However, would these be the wisest people to target during a pandemic year? In typical years, if we plot the mortality as a function of age, we see a “U-shaped” curve: the oldest and youngest die at the highest rates. However, in pandemic years (1918 being the most dramatic example), we may see a “W-shaped” curve: the old and young still die, but those between the ages of ~15-40–the “young and healthy” who normally don’t have to worry about dying from influenza–also experience high mortality rates (see below):

    Should we target this “middle” group for vaccination in the event of a pandemic? If so, and anticipating limited vaccine supplies, do we do it in addition to, or instead of, the other high-risk groups? These are questions that need to be addressed and ironed out long before a pandemic strikes.

    Another approach is to target vaccination to those most likely to spread the virus, rather than to those most likely to die from it. A recent paper in The American Journal of Epidemiology suggests that vaccinating 3 and 4-year-olds may be the way to stem influenza outbreaks. Currently, children over 2 aren’t a target group for the vaccine; increasing coverage in the 3-18 age population may indirectly reduce overall mortality by reducing spread of the virus through the community.

    What we need, like, yesterday

    Even the best planning can fall through when the completely unexpected happens. As hard as we try to incorporate all kinds of variables and possible outcomes, sometimes you just can’t see an issue until it slaps you in the face. Despite many years of study, there are still too many unanswered questions about influenza. We need surveillance, surveillance, surveillance. We need better numbers about who the viruses are infecting, and where. We need to capture those asymptomatic infections, and examine as many viruses as we can at a molecular level to see how the virus is evolving. We need to sample as many animals as we can, to get a better handle on the ecology of the virus. We need to do this not only in Asia and the United States, but worldwide. We need to have incentives for companies to sink time and money into influenza vaccination research programs. We need additional anti-influenza drugs. We need better response plans at all levels. We need to figure out what to do with the surge of patients and, inevitably, corpses that will be a result of an influenza pandemic. We’ve recently seen the effects of a localized disaster on a community (and the effect of poor planning/response afterwards); during a pandemic, many of the largest cities in the U.S. would experience a shortage in hospital and morgue space. Even our supply of respirators would be overwhelmed. In the U.S., 75-80,000 of the 105,000 mechanical ventilators are in use at any given time for ordinary medical care. During influenza season, typical use increases to 100,000. Were a pandemic to strike, we may fall short by as many as several hundred thousand ventilators–and the situation is similar in all developed countries, so we can’t count on our allies to bail us out.

    Depressed yet? All is not lost. There are some plans in place (whether they will be effective is another story…), and there are also steps you can take, as an individual, to prepare. More on that tomorrow.

    Other posts in the series:

    Day 1: History of Pandemic Influenza.

    Day 2: Our adventures with avian flu.

    More resources on pandemic influenza:

  • CIDRAP Pandemic influenza news
  • Infectious Disease Society of America (IDSA) Pandemic/Avian flu
  • CDC’s site on Avian flu
  • Flu wiki
  • Pandemic influenza awareness week. Day 2: Our adventures with avian flu

    Anyone working in the area of influenza virus epidemiology is familiar with the name Robert Webster. A virologist at St. Jude’s Children’s Hospital in Memphis, the native New Zealander has been leading the charge against influenza for well over 40 years. Barely out of graduate school, Webster hypothesized that something like genetic reassortment (which had not yet been discovered) occurred to cause the big changes that appeared among human influenza viruses, driving pandemics. He performed a simple experiment that cemented the course of his career: he found that serum from patients who had survived the 1957 influenza pandemic reacted with avian influenza viruses. Later genetic analyses showed that the “Asian flu” virus had indeed received 3 of its 8 gene segments from birds. It happened again in 1968: the pandemic virus was the result of a reassortment between human and avian influenza viruses. These observations led to more than 30 years of surveillance of waterfowl in many different countries, and the revelation that these waterfowl constitute a reservoir of all known subtypes of influenza virus.

    Webster’s worst fears seemed to be coming true in 1997. Hong Kong was experiencing an influenza outbreak in chickens so severe it had been nicknamed “chicken Ebola.” Humans were also affected. The first case was in a 3-year-old boy from Hong Kong. Though doctors knew he had died of the flu, they were uncertain of the strain, and sent samples off to several high-level laboratories for further testing. When it came back H5N1, the Centers for Disease Control and Prevention sent Keiji Fukuda to Hong Kong to investigate. After a month of searching, he and his team found no further evidence of infection with this avian virus in the human population–so they left, writing off the boy’s illness as a “freak occurrence.” They were premature. By the end of the year, 18 cases had been confirmed; 6 died. Clinical features often included a primary viral pneumonia and death quickly after onset of symptoms. The route of transmission in all cases appeared to be direct bird-to-human contact. Fearing a public health crisis, officials ordered the culling of Hong Kong’s entire poultry population. Analysis of the virus showed it to be a serotype H5N1 virus.

    Though H5N1 has gotten the lion’s share of the spotlight, other avian viruses have caused human disease in the past decade. In The Netherlands, an H7N7 virus caused 89 infections with 1 death in 2003. Human infections with avian H7N3 were reported in British Columbia in 2004, and with H7N1 and H7N3 in Italy between 1999 and 2003. Avian H9N2 viruses were in the spotlight in 1999, when they were found in 3 children in Hong Kong who were suffering from flu-like symptoms. All three recovered.

    The United States isn’t isolated from this type of outbreak, either. During 1983 in Pennsylvania, influenza burned through the poultry population, where health officials there resorted to the same drastic measure they took in Hong Kong: destruction of the entire poultry stock. In 2002, avian H7N2 caused an outbreak among poultry in Virginia, and at least one serologically-confirmed human case. This virus was seen again in the United States in 2003, when a patient showed up at a New York hospital with respiratory symptoms. It’s still unknown how he contracted the virus.

    Clearly, avian viruses infect humans periodically–quite likely, much more often than we know about. However, H5N1 seems to be different. It has infected, and killed, an incredibly diverse group of animals, including those who normally are unaffected by influenza: blue pheasants, black swans, turtledoves, leopards, mice, domestic cats, even tigers. And both laboratory and clinical analyses conclude that it seems to have gotten worse since 1997.

    H5N1 was back on the radar in 2003, when it caused 35 cases (24 of them fatal) in Vietnam and Thailand. In 2004, the virus caused 44 known cases in humans; 32 of them were fatal. Most of these cases were in previously-healthy children and adults. Poultry was again infected, and this time around seemed to be even more virulent. 120 million birds were killed between January and March of 2004. Additionally, pigs had been infected. This was particularly worrisome, as pigs had long been thought to act as a “mixing vessel” between human and avian strains. (Pig cells are able to bind both human and avian hemagglutinin; thus, viruses of both types can replicate within their cells, with the possibility of recombination and spread of a “humanized” avian virus). Animals normally resistant to influenza disease were again affected. Leopards and tigers died in a Thai zoo after consuming infected raw chicken. In the latter case, it seems that tiger-to-tiger transmission occurred as well.

    There is also evidence for at least one case of human-to-human transmission during this outbreak. In Thailand, a young girl died, followed shortly by her mother, who had served as her nursemaid. No contact between the mother and poultry could be found. Additionally, an aunt of the girl, who had also assisted in her care, complained of a sore throat, cough, and fever. She was later found to be infected with H5N1 as well. It was feared that this could be the beginning of The Big One. However, no other cases stemmed from these, and it seems likely that the transmission was due to the large amount of time spent in close contact with the girl and her secretions; the virus did not appear to be easily passed person to person–so far.

    As of October 2005, cases of avian H5N1 have been reported in Thailand, Cambodia, Indonesia, and Vietnam. Combined, there have been 72 cases and 28 deaths in these countries since the end of 2004, and a total of 116 confirmed cases and 60 deaths since 2003. These are likely underestimates. If anything can be said about H5N1, it’s that it is unpredictable. A case was written up in the February 2005 New England Journal of Medicine detailing a fatal case where a child presented with severe diarrhea, followed by seizures, coma, and death. A sibling had died of the same symptoms two weeks earlier, and neither child showed any respiratory symptoms characteristic of influenza. Nevertheless, H5N1 virus was isolated from several specimens isolated from the second patient. Therefore, we are likely missing even many symptomatic infections–because they are presenting with the wrong symptoms. It is worrisome to think that the virus may be adapting to humans during infections like these. Additionally, avian influenza has been shown to cause asyptomatic infections. A report in the October Journal of Infectious Diseases showed that in a group of workers exposed to avian H7N1 and H7N3 influenza viruses during the Italian outbreak of 1999-2003, 7 of 183 people tested were seropositive to at least one of the viruses, suggesting they had been infected during the epidemic. None reported a history of influenza-like illness following exposure to the avian viruses. It’s not known what the extent of sub-clinical infection with these viruses may be, either in Asia, or in the United States or Europe.

    An influenza pandemic is a kind of viral perfect storm. Three requirements must be met: 1) the human population must lack antibodies to the virus; 2) the virus must make humans ill; 3) the virus must be efficiently transmitted between humans. H5N1 certainly meets the first two requirements; the scientific community is holding its collective breath waiting for the third condition to be met. In tomorrow’s article, I’ll discuss more about surveillance efforts and models used to predict or control an outbreak, should one occur.

    Robert Webster is currently in his mid-seventies, and much of that life has been spent battling and studying influenza. With all he’s seen, it’s significant that he’s made the following comments regarding H5N1:

    This is the worst flu virus I have ever seen or worked with or read about. We have to prepare as if we were going to war–and the public needs to understand that clearly. This virus is playing its role as a natural bioterrorist. The politicians are going to say Chicken Little is at it again. And, if I’m wrong, then thank God. But if it does happen, and I fully expect that it will, there will be no place for any of us to hide. Not in the United States or in Europe or in a bunker somewhere. The virus is a very promiscuous and efficient killer.

    This is the “war on terrorism” that we really should be sinking money into. Even if H5N1 isn’t the next pandemic strain, or if it is but doesn’t come anywhere near the level of the 1918 outbreak, it has served to point out holes in our preparation procedures for a disaster of that magnitude. More on that tomorrow.

    Other posts in the series:
    Day 1: History of Pandemic Influenza.

    More resources on pandemic influenza:

  • CIDRAP Pandemic influenza news
  • Infectious Disease Society of America (IDSA) Pandemic/Avian flu
  • CDC’s site on Avian flu
  • Flu wiki
  • Pandemic influenza awareness week. Day 1: History of pandemic influenza

    It’s hard to avoid hearing about influenza virus these days. In all the noise, it’s tough to sort out the facts from the rumors and conspiracy theories. I’ve already discussed a bit about the basic biology of the virus in this post, so I’m not going to review that here (though a good overview can be found here for those of you who need to bone up on your influenza virus biology). So, this week, as a part of Pandemic influenza awareness week, I’ll be writing a 5-part series about various issues regarding influenza. Today, I’ll discuss the history of influenza, focusing on past pandemics. The rest of the week will address the following topics, with the goal of presenting a review of the facts without the scare-mongering:

  • “Avian flu” and H5N1, 1997-present
  • How do we prevent/control a pandemic? What models and surveillance can tell us
  • Where we are now–are we ready for a pandemic?
  • Other issues in influenza

  • So, without further ado, let’s dive into today’s topic:

    A quick trip through the history of pandemic influenza

    Influenza is an ancient disease. It is first described by Hippocrates in 412 BC, though the term “influenza” would not be coined until the 14th century. (“Influenza” is Italian for “influence,” as the prevailing idea of disease causation at that time was the influence of the stars). In 1580, a disease originating from Asia and thought to be influenza swept through Europe, Africa, and the Americas on trade routes. While these cannot be confirmed as influenza, a better handle on the symptoms of the disease makes it likely that several influenza pandemics occurred in the 1800s: in 1833, 1836, 1847 and 1889.

    The worst influenza pandemic in recorded history took place in 1918-1919. At least 40 million, and likely closer to 100 million deaths worldwide have been attributed to the virus, most of them occurring in the 16-week period between September-December 1918. In large U.S cities, more than 10,000 deaths per week were attributed to the virus. It is estimated that as many as 50% of the population was infected, and ~1% died. To compare, in “normal” (interpandemic) years, it is estimated that between 10-20% of the population is infected, with a .008% mortality.

    Despite its popular name of the “Spanish flu,” it’s uncertain where the pandemic originated. (During World War I, Spain was one of the few countries who did not censor media, so reports of the state of the epidemic in that country were widely circulated). Scientists and historians have put forth points of origin in China, Vietnam, India, France, Great Britain, and the U.S. (Kansas). Contemporary reports of the pandemic contain imagery that harkens back to the 14th century Black Plague. Morgues were overwhelmed; dead were buried in simple pine boxes, as the supply of caskets was quickly depleted; public activities were cancelled; spitting on the street was criminalized. The death toll made the casualties as a result of World War I pale by comparison. The virus struck hardest in the young and healthy, whose rapid immune response actually became their downfall. Enough young people died that it dramatically decreased the average life expectancy in that year (see figure below, from Nature Medicine 10, S82 – S87 (2004)).

    Typically, influenza causes death due to a secondary bacterial pneumonia. Bacteria are able to take advantage of the host’s compromised immune status and damaged lung cells, establishing a potentially deadly infection. However, during the 1918 pandemic, a greater percentage of the deaths in the 20-45 age group were due to primary pneumonia: pneumonia caused by a combination of the influenza virus and the host response, with no bacterial invaders involved. In some patients, this occurred within a matter of hours from the first symptoms. A Pennsylvania medical student documented the phenomenon:

    As their lungs filled, the patients became short of breath and increasingly cyanotic. After gasping for several hours, they became delirious and incontinent, and many died struggling to clear their airways of a blood-tinged froth that sometimes gushed from their nose and mouth. It was a dreadful business.

    Though serological studies carried out in the 1930s had already identified the virus as a serotype H1N1, it was long thought that was the end of the potential information that could be found about the virus. However, in the mid-1990s, a group of researchers led by Jeffrey Taubenberger at the Armed Forces Institute of Pathology found samples of lung tissue from soldiers who had died of the 1918 virus in the archive at that institute. Additionally, pathologist Johan Hultin provided an additional sample from the lungs of an Inuit woman in Alaska who had died during the pandemic. These samples have been sequenced in an effort to determine what it was that made the 1918 virus so virulent. Though these questions are still being investigated, the preliminary data suggests that the virus was a human-avian reassortant which had entered the human population a short time before the pandemic (likely 6-12 months).

    Though the 1918 pandemic has been the most dramatic example of the killing potential of influenza, there have been 2 other pandemics in the last 100 years. In 1957, a H2N2 virus appeared in China. This “Asian flu” quickly swept through the population, replacing the previously-circulating H1N1 virus and killing 70,000 in the U.S. Similarly, in 1968, an H3N2 virus emerged from Hong Kong to replace the H2N2 virus. This pandemic resulted in 34,000 American deaths. The H1N1 serotype re-surfaced in 1977, and currently, H3N2, H1N1, and reassortant H1N2 viruses circulate in the human population.

    The H1N1 caused an additional scare in 1976. In January of that year, a private at Fort Dix, New Jersey, collapsed and died following a march. It was determined that he died of “swine flu,” serotype H1N1. Although he was the only death at the fort, health officials were highly concerned. Secretary of health F. David Matthews stated that

    there is evidence there will be a major flu epidemic this coming fall. The indication is that we will see a return of the 1918 flu virus that is the most virulent form of flu. In 1918, half a million people died. The projections are that this virus will kill one million Americans in 1976.

    With hindsight, we can see that a proclamation with this level of certainty is folly, but at the time, it was thought that influenza cycled in a fairly regular pattern, varying between very high pathogenicity strains and lower pathogenicity strains. It was thought that the world was overdue for another high pathogenicity strain, and that the “swine flu” virus just might be the one. In March of 1976, President Ford announced that he would ask Congress for funds to produce enough vaccine “to inoculate every man, woman, and child in the United States.” Of course, this epidemic never materialized, and actually dealt a blow to the influenza vaccine campaign, as reported side effects of the vaccine included Guillain-Barré syndrome, a debilitating neurologic condition.

    Looking back, one can certainly draw parallels between the scare and build-up to vaccination in 1976 and today with H5N1. However, just because that pandemic never materialized does not mean that the same thing will happen with today’s “avian flu.” At this point, we just don’t know, but it behooves us to hope for the best, but prepare for the worst.

    Tomorrow: all about avian flu and H5N1, from its initial identification in 1997 to today.

    More resources on pandemic influenza:

  • CIDRAP Pandemic influenza news
  • Infectious Disease Society of America (IDSA) Pandemic/Avian flu
  • CDC’s site on Avian flu
  • Flu wiki
  • Marshall and Warren win prize for work on Helicobacter as cause of peptic ulcers

    But I thought biologists were too “close-minded?”

    Australians Barry J. Marshall and Robin Warren won the 2005 Nobel Prize in medicine Monday for showing that bacterial infection, not stress, was to blame for painful ulcers in the stomach and intestine.

    The Australians’ idea was “very much against prevailing knowledge and dogma because it was thought that peptic ulcer disease was the result of stress and lifestyle,” Staffan Normark, a member of the Nobel Assembly at the Karolinska institute, said at a news conference.

    This is a great example of how science works. These men proposed a hypothesis that was pretty far outside the mainstream at the time (even though there had been some antecdotal and published evidence regarding antibiotic treatment and resolution of ulcers). They tested it; they gathered evidence to support it; they published their results in the literature; and eventually, they overturned the prevailing notion that ulcers were caused by stress and diet based on the experimental evidence. They didn’t rely on think tanks, or mission statements, or pressure from supporters in high places in order to have their ideas accepted–they won over their audience on the merits of their research. Was it easy? From interviews I’ve read, hell no. But they perservered, others joined them in uncovering evidence that supported their hypothesis, and today, they’ve been rewarded with one of the highest honors that a scientist can receive. Congratulations, gentlemen, and let this serve as yet another example of scientists embracing new ideas when they’re backed by quality research.