Each year, experts from the FDA, World Health Organization, CDC, and others in the public health community study virus samples and patterns collected worldwide to identify virus strains likely to cause the most illness during the upcoming influenza season. Currently, there are 136 national influenza centers in 106 countries that conduct year-round surveillance for influenza viruses and disease activity. Based on the information that’s been collected and the recommendations of the FDA’s Vaccines and Related Biological Products Advisory Committee, the strains selected for the Northern Hemisphere’s 2011-2012 influenza season are:

• A/California/7/2009 (H1N1)-like virus (pandemic (H1N1) 2009 influenza virus)
• A/Perth /16/2009 (H3N2)-like virus
• B/Brisbane/60/2008-like virus

Six manufacturers are licensed to produce and distribute flu vaccines in the U.S. this year (brand names in parenthesis): CSL Limited (Afluria); GlaxoSmithKline Biologicals (Fluarix); ID Biomedical Corporation (FluLaval); MedImmune Vaccines Inc. (FluMist); Novartis Vaccines and Diagnostics Limited (Fluvirin); and Sanofi Pasteur Inc. (Fluzone, Fluzone High-Dose and Fluzone Intradermal).

For 2011, a new vaccine is also available. Sanofi’s Fluzone Intradermal was approved by the FDA in May [2]. It’s a shot that, unlike traditional flu shots, is injected under the skin instead of into the muscle. The company says the needle is 90% shorter than the kind used for intramuscular injection.

Cold and flu germs hide everywhere and everyone is at risk. Early last year, the CDC’s Advisory Committee on Influenza Practices recommended that everyone 6 months of age and older receive an annual influenza vaccination [3].

Flu season runs from November to April — most cases occur between late December and early March. Every winter, approximately 10-20% of people get the flu [4]. In children, the odds are even worse, with up to 40% of children becoming clinically ill due to the influenza virus. The most effective method to prevent infection, reduce symptom severity if you do get sick, and prevent the spread of virus to others is annual vaccination. Besides vaccination, one of the easiest ways to avoid getting sick is to wash your hands.

References

1. FDA approves vaccines for the 2011-2012 influenza season. U.S. Food and Drug Administration News Release. 2011 Jul 18.
2. FDA Licenses Sanofi Pasteur’s New Influenza Vaccine Delivered by Intradermal Microinjection. Sanofi Pasteur. 201 May 10.
3. CDC’s Advisory Committee on Immunization Practices (ACIP) Recommends Universal Annual Influenza Vaccination. Centers for Disease Control and Prevention press release. 2010 Feb 24.
4. Evans M. Flu shot. Can Fam Physician. 2005 Nov;51:1511-2, 1515-6.
   View abstract

What is influenza?

Influenza is a respiratory infection caused by a number of airborne RNA viruses that enter the body through the nose or mouth. Influenza viruses bind to epithelial cells in the nose, throat and lungs. Cells than absorb the virus. Once inside, the virus replicates using a cellular enzyme called an RNA-dependent RNA polymerase. The polymerase enzyme lacks proofreading capability and makes a spontaneous mutation at a rate of 1 per genome per replication [2]. Thus, essentially every influenza virus replicated contains a mutation. This is the reason why influenza viruses continually change over time and are able to evade the host immune system.

Symptoms of the flu present quickly and are worse than the common cold. Flu symptoms include body or muscle aches, chills, cough, high fever lasting 3-4 days, headache, sore throat, stuffy nose, extreme tiredness and stomach symptoms (more common in children), including nausea, vomiting and diarrhea. The incubation period between acquiring the infection and becoming ill is 1-4 days. Most heathy adults are able to infect other people 1 day before symptoms develop and up to 5 days after becoming sick [3]. Viral shedding, the period during which a person can infect others, usually peaks on the second day of symptoms. Children can infect others for several days prior to developing symptoms and can be infectious for more than 10 days. Since children can shed the greatest amounts of virus, they pose the greatest risk for viral transmission.

The flu vaccine: your options

The best way to prevent seasonal flu is to get vaccinated. Hospitalization and death from flu complications pose real risks; every year, on average, more than 200,000 people are hospitalized from flu complications and approximately 36,000 people die from the flu [3]. Immunizing children against influenza is perhaps the best method to reduce the occurrence of the flu in the community. If children receive the flu shot but the rest of the family abstains, the influenza attack rate drops by 40%; if parents also get the flu shot, the influenza attack rate drops by 80% [4].

The flu vaccine is available in two forms, a shot and a nasal spray (FluMist). The flu shot, which is approved for use in children 6 months and older, contains an inactivated flu virus. Although you may develop a slight reaction to the shot, including soreness at the injection site, muscle ache or fever, you won’t get the flu because the viruses in the vaccine have been inactivated. The nasal spray flu vaccine (FluMist), which is approved for use in children 2 years and older, contains a low dose of live but weakened flu virus. Similar to the flu shot, the nasal spray doesn’t cause the flu, but prompts an immune response so that your body develops antibodies necessary to fight influenza infection. A review of 48 reports on influenza vaccine efficacy over the past four decades found that the flu shot was 80% efficacious against influenza in healthy adults when the vaccine matched the circulating strain and the circulation was high [5]. If the circulating strain didn’t match the vaccine, efficacy was reduced to 50%. The flu vaccine was 30% effective against influenza-like illness. FluMist efficacy has been reported to be higher in both children and adults [6-8].

What else can you do?

In addition to the flu vaccine, one of the best ways to avoid getting sick and stay healthy is to simply wash your hands. Even something as simple as coughing or sneezing can spread cold and flu germs; hand washing is the single most important thing you can do to prevent the spread of infection and to stay healthy. Some scientists estimate that as much as 80% of all infections are transmitted by unwashed hands [9]. Nevertheless, a dab of soap and a quick rinse isn’t effective. The key is to wash your hands for at least 20 seconds to ensure that you’ve removed the microbes (here’s a trick: sing the ABC’s to yourself). By rubbing your hands with soapy water, you pull dirt and oil from your skin. The soap lather suspends any germs trapped inside and are then washed away when rinsing. If soap and water aren’t available, use an alcohol-based hand sanitizer. However, while alcohol-based hand sanitizers reduce the number of germs on skin, they aren’t necessarily more effective at reducing the flu virus on human hands. Studies have found that hand washing with soap and water is superior to all alcohol-based treatments.

References

1. Evans M. Flu shot. Can Fam Physician. 2005 Nov;51:1511-2, 1515-6.
   View abstract
2. Drake JW. Rates of spontaneous mutation among RNA viruses. Proc Natl Acad Sci U S A. 1993 May 1;90(9):4171-5.
   View abstract
3. Key Facts About Seasonal Influenza (Flu). Centers for Disease Control and Prevention. Updated 2007, Sep 17.
4. Hurwitz et al. Effectiveness of influenza vaccination of day care children in reducing influenza-related morbidity among household contacts. JAMA. 2000 Oct 4;284(13):1677-82.
   View abstract
5. Jefferson et al. Vaccines for preventing influenza in healthy adults. Cochrane Database Syst Rev. 2007 Apr 18;(2):CD001269.
   View abstract
6. Belshe et al. The efficacy of live attenuated, cold-adapted, trivalent, intranasal influenzavirus vaccine in children. N Engl J Med. 1998 May 14;338(20):1405-12.
   View abstract
7. Belshe et al. Efficacy of vaccination with live attenuated, cold-adapted, trivalent, intranasal influenza virus vaccine against a variant (A/Sydney) not contained in the vaccine. J Pediatr. 2000 Feb;136(2):168-75.
   View abstract
8. Treanor et al. Evaluation of trivalent, live, cold-adapted (CAIV-T) and inactivated (TIV) influenza vaccines in prevention of virus infection and illness following challenge of adults with wild-type influenza A (H1N1), A (H3N2), and B viruses. Vaccine. 1999 Dec 10;18(9-10):899-906.
   View abstract
9. Put Your Hands Together. National Center for Preparedness, Detection, and Control of Infectious Diseases (NCPDCID) and National Center for Zoonotic, Vector-Borne, and Enteric Diseases (NCZVED). 2008 Oct 13.

In this edition, moderator Lark McCarthy discusses the level of testing prior to the H1N1 influenza A vaccine distribution and the subsequent monitoring that’s planned during and after the phases of distribution with Dr. Bruce Gellin, Director of the National Vaccine Program Office (NVPO) within the HHS, Dr. Jesse Goodman, acting chief scientist with the U.S. Food and Drug Administration (FDA), Dr. Harvey Fineberg, President of the Institute of Medicine (IOM) and Dr. Anne Schuchat, Director of the Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention (CDC).

This video was recorded on October 14, 2009.

H1N1 vaccine distribution

An article published earlier this week in the Washington Post questioned the shortage of H1N1 flu vaccine. Out of 80-120 million doses promised for mid-October by pharmaceutical companies, only ~16.5 millions doses have been delivered thus far [1]. According to the story, government officials relayed information on vaccine availability to the public as soon as manufacturers provided estimates. However, company representatives have said that the government was informed about production challenges are are on track for vaccine delivery.

Those production challenges included a slow growing vaccine. Flu vaccines are currently grown in eggs, a process that normally takes six months [2]. To reduce the production time, several biotech companies are working to develop large-scale cell culture methods that could potentially grow vaccines in several weeks as opposed to the six months required for egg-based production [2].

Nevertheless, according to a post earlier this week on The Patient Report (via the AP), 22 million more doses of H1N1 influenza vaccine are now available and the shortage should ease over the coming weeks. Per our list of what you need to know about the H1N1 vaccine, check with your doctor, you children’s school and/or your local health department regarding a list of locations where the H1N1 vaccine will be offered.

While you’re waiting for the vaccine to become available, remember to take these preventative measures against the H1N1 influenza virus:

• Wash your hands often or use alcohol-based hand cleaner.
• Cover your nose and mouth with a tissue when you cough or sneeze! Dispose of promptly.
• Avoid touching your eyes, nose or mouth — these are areas where the virus can enter your body.
• Make sure you’re getting enough sleep.
• Eat well and drink plenty of fluids.
• Avoid sick people.

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References

1. Why such a shortage of swine flu vaccine? The Washington Post. 2009 Oct 27.
2. Gerdil C. The annual production cycle for influenza vaccine. Vaccine. 2003 May 1;21(16):1776-9.
   View abstract
3. Singer E. Pandemic fears hatch new methods in flu vaccine industry. Nat Med. 2005 Jan;11(1):4.
   View abstract

Two studies, which are available online as early release articles and will be published in the November edition of the Journal of the American Medical Association (JAMA), detail the characteristics, treatment and outcomes of critically ill patients with H1N1 in Mexico and Canada [1-2].

Although the death rate in each of the studies is quite different, it nonetheless is as high or higher than that of seasonal flu. Furthermore, although seasonal flu typically affects people of older age — the average annual rate of influenza-associated hospitalizations over the last 20 years for people age 65 and older is 70% [3] — these studies show that H1N1 is striking many who are much younger. In both studies, the majority of critically ill patients with influenza A H1N1 had rapidly progressive respiratory failure and required mechanical ventilation.

Critically ill patients with influenza A H1N1 in Mexico

The first observational study was of 58 critically ill patients with H1N1 at 6 hospitals in Mexico [2]. These patients accounted for 6.5% of 899 admitted to the hospital with confirmed, probable or suspected influenza A H1N1 between the months of March 24, 2009 and June 1, 2009. The patients had a median age of 44, just over half were female (53%) and 2 were healthcare workers. Two patients were children (10 and 14 years old). Only two patients had received a seasonal influenza vaccination in 2008 or 2009.

Patients developed symptoms a median of 6 days prior to hospitalization. Symptoms included fever, respiratory issues (cough, shortness of breath or wheezing), generalized weakness, muscle pain, headache and gastrointestinal symptoms of nausea, vomiting, or diarrhea. Additional disorders the patients presented with included obesity (36.2%), a past history of smoking (34.5%), hypertension (25.9%), diabetes type 1 or 2 (17.2%) and gastrointestinal disease (10.3%). The time from hospitalization to intensive care unit (ICU) admission was between 0 and 3 days. Almost all patients were treated with antibiotics; 78% received antiviral drugs (neuraminidase inhibitors); 69% received corticosteroids. Fifty-four of the 58 patients (93%), including one child, required mechanical ventilation during the course of hospitalization.

After 60 days from the onset of critical illness, 24 of the 58 (41%) had died. Most died within the first 2 weeks. The median age of patients who died was 39. All deaths within 28 days were primarily related to respiratory failure, with only one late death primarily related to multisystem organ dysfunction. Both children survived.

Critically ill patients with influenza A H1N1 in Canada

The second observational study was of 215 critically ill patients with confirmed, probable or suspected influenza A H1N1 at 38 study intensive care units in Canada [3]. Since patients that had confirmed or probable H1N1 infection were significantly younger, had a longer duration of mechanical ventilation and ICU stay, and higher mortality than those with suspected disease, the analysis was restricted to the 168 patients that had confirmed or probable influenza A H1N1 infection. The patients had an average age of 32.3, 67.3% were female, and 30% were children. Only 10 of the 168 patients (6%) had received a seasonal influenza vaccination in the past two years.

Patients developed symptoms a median of 4 days prior to hospitalization. The most common symptoms included fever, respiratory issues, weakness and muscle pain. Possible bacterial pneumonia was present in just over 54 patients (30%). Additional disorders the patients presented with included chronic lung disease (including asthma, COPD and bronchopulmonary dysplasia; 41.1%), obesity (33.3%), hypertension (24.4%), a past history of smoking (22.6%) and diabetes type 1 or 2 (20.8%). The time from hospitalization to intensive care unit administration was between 0 and 2 days.

Almost all patients were treated with antibiotics; 90.5% received antiviral drugs (neuraminidase inhibitors); 50.6% received corticosteroids. Mechanical ventilation was used in 81% of patients on the first day of ICU admission. Clinical evidence for bacterial pneumonia following ICU admission was found in almost one-quarter of patients (41 of 168).

After 90 days from the onset of critical illness, 29 of the 168 (17.3%) had died. Eighteen patients died within the first 2 weeks and 24 died within 28 days from the onset of critical illness. The median age of patients who died was 42. The primary reported causes of death included severe respiratory failure, secondary infection and sepsis (generalized invasion of the body by pathogenic microorganisms or their toxins), and multiorgan dysfunction.

What to expect

An accompanying editorial in the JAMA issue said that although both studies have substantial epidemiological limitations, they nonetheless [4]:

… provide important signals about what clinicians and hospitals may confront in the coming months. H1N1 can produce a rapidly progressive respiratory failure that is refractory to conventional mechanical ventilation, often in young, healthy patients — a group who are not currently a priority group for H1N1 vaccination.

You can protect yourself from the H1N1 virus as well as the seasonal flu:

• Get the H1N1 vaccine and the seasonal flu vaccine.
• Wash your hands often or use alcohol-based hand cleaner.
• Don’t cover your nose and mouth with you hand when you cough or sneeze! Use a tissue instead and throw it in the trash after use.
• Avoid touching your eyes, nose or mouth — these are areas where the virus can enter your body.
• Avoid sick people.
• Get lost of rest, eat well and drink plenty of fluids.
• If you do get sick, stay home.

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References

1. Dominguez-Cherit et al. Critically Ill Patients With 2009 Influenza A(H1N1) in Mexico. JAMA. 2009 Oct 12. [Epub ahead of print]
   View abstract
2. Kumar et al. Critically Ill Patients With 2009 Influenza A(H1N1) Infection in Canada. JAMA. 2009 Oct 12. [Epub ahead of print]
   View abstract
3. Thompson et al. Influenza-associated hospitalizations in the United States. JAMA. 2004 Sep 15;292(11):1333-40.
   View abstract
4. White and Angus. Preparing for the Sickest Patients With 2009 Influenza A(H1N1). JAMA. 2009 Oct 12. [Epub ahead of print]
   View abstract

We’ve received a number of questions and concerns about the swine flu and the H1N1 vaccine. Indeed, a new survey by the Harvard School of Public Health finds that six in ten adults are not “absolutely certain” they will get the H1N1 vaccine, citing concerns over side effects, lack of perceived risk and belief that they could receive medication if they do get sick [1]. Just over half of parents surveyed report being “absolutely certain” they well get the vaccine for their children. To help disseminate credible information on the H1N1 vaccine and provide additional sources for review, we’ve put together a list of questions and answers addressing what you need to know about the H1N1 vaccine.

When will the H1N1 vaccine be available in the U.S.?
The H1N1 vaccine is expected to arrive this coming week. Indeed, National Public Radio (NPR) is reporting that the first doses of vaccine will start arriving at hospitals, doctors’ offices and clinics around the country tomorrow [2]. Vaccine makers are shipping the vaccine earlier than previously predicted to 21 states and the cities of Washington, New York, Chicago and Los Angeles [3].

Where can I find the H1N1 vaccine when it comes out?
Currently, there isn’t a list of locations where the H1N1 vaccine will be offered. Check with your doctor, your children’s school and/or your local health department. Additionally, once the information is available, the Department of Health and Human Services will post the information on Flu.gov.

How many shots will be required?
For adults, H1N1 vaccine studies show that a single dose will provide protection. Preliminary unpublished clinical trials on children ages 6 months to 9 years suggest that two doses will be required, separated by at least 21 days.

Will I get swine flu from the H1N1 vaccine shot?
No. The H1N1 vaccine shot contains an inactivated flu virus. Although you may develop a slight reaction to the shot, including soreness at the injection site, muscle ache or fever, you won’t get the flu because the H1N1 virus in the vaccine has been inactivated (killed).

What if I’m allergic to eggs? Can I still get the vaccine?
Individuals that have egg allergies should not get flu vaccines in the regular way, since the virus used to produce the vaccine is grown in eggs. You should consult with a physician or allergist prior to vaccination to determine the degree of egg sensitivity. For asthmatic children with severe disease and egg hypersensitivity, a regimen has been developed for the administration of influenza vaccine [4].

What is the FluMist and who can get it?
FluMist is a nasal spray flu vaccine, which contains a low dose of live but weakened flu virus. Similar to the flu shot, the nasal spray doesn’t cause the flu, but prompts an immune response so that your body develops antibodies necessary to fight influenza infection.

Should my children get the vaccine?
Children generally have a higher risk for contracting seasonal flu. The H1N1 flu is no exception. From April through July, the attack rate of laboratory-confirmed cases of H1N1 was highest among children aged 5-14 years — 14 times higher than for adults 60 years of age or older [5]. Younger children also appear to be getting more severe cases of H1N1; the median age of hospital-admitted cases was 16 years of age.

Are there side effects to the vaccine?
No vaccine is 100% safe since it’s designed to simulate the immune system to produce antibodies. That said, not all adverse reactions that happen after a vaccination are due to the vaccination. In clinical trials of the H1N1 vaccine thus far, there have been no serious side effects. The most common side effects reported were injection-site pain, headache, muscle pain, malaise and nausea. The Vaccine Adverse Event Reporting System (VAERS) is being used to monitor vaccine safety, and is being supplemented by surveillance in the military services, the Veterans Affairs system and a new “real time” health plan monitoring system covering 15% of the U.S. population [2].

The H1N1 vaccine was produced the same way using the same materials as seasonal flu vaccines. However, the new H1N1 vaccine has received a great deal more scientific scrutiny than seasonal flu vaccines. Clinical trials on the H1N1 vaccine, which were performed to determine the dose required to stimulate an immune response, aren’t performed on the seasonal flu vaccine.

There were a number of cases of Guillain-Barre syndrome with the 1976 National Influenza Vaccination Program for swine flu. Should I be concerned with the new H1N1 vaccine?
In 1976, an earlier type of swine flu vaccine was associated with cases of Guillain-Barre syndrome (GBS), a disorder that causes the body’s immune system to attack parts of the nervous syndrome. The rate of occurrence was 2 in 100,000 (the syndrome normally strikes 1 in 100,00) [6]. The CDC anticipates that the N1N1 vaccine will have a similar safety profile as that of the seasonal flu vaccine, which is very good and has not been consistently associated with GBS. There have been no reports of GBS in the current H1N1 vaccine clinical trials.

Will the H1N1 influenza vaccine contain thimerosal?
The H1N1 vaccine is being manufactured in several formulations. Multi-dose vials will contain thimerosal (a mercury-based preservative) to prevent potential contamination after the vial is opened [7]. Single dose units will not contain thimerosal. In addition, the FluMist will not contain thimerosal.

Will the H1N1 vaccine contain adjuvants?
No. Adjuvants (immune stimulating compounds) are not being used in the H1N1 vaccine being distributed in the United States.

Can I get the seasonal vaccine along with the H1N1 vaccine?
Although simultaneous and sequential administration of seasonal influenza vaccine and the H1N1 inactivated vaccine is currently being studied, existing recommendations are that two inactivated vaccines can be administered at any time before, after, or at the same visit as each other [8]. Note that this does not include the FluMist, since it is a live modified flu virus.

Do I need a flu shot if I’ve already had the flu this year?
If you’ve had the flu this year, you’re immune to that specific virus, but there’s no guarantee you won’t catch another seasonal strain. Additionally, if you’ve had a seasonal flu strain, you’re not immune to the H1N1 virus. Your best bet is to get vaccinated against both the seasonal flu and H1N1.

If I’ve had swine flu, do I need the H1N1 vaccine?
If you’ve had the swine flu this year, then you’re resistant to reinfection since your body has generated antibodies specific to the virus. However, you should still get the H1N1 vaccination, since most suspected H1N1 cases are diagnosed without laboratory confirmation. Additionally, if you’ve had H1N1, you’re not immune to any of the seasonal flu strains and should get vaccinated against the seasonal flu.

What if I don’t want to take the H1N1 vaccine?
For the public, H1N1 flu vaccination is voluntary. All military personnel will be vaccinated against the H1N1 flu virus and many medical centers are making vaccination mandatory. Remember, like any other flu, H1N1 is contagious. Scientific evidence suggests that the virus can live in some people for at least eight days [9]. If you get sick or think you’re sick, stay home!

In addition to vaccination, one of the best ways to avoid getting sick is to effectively wash your hands and limit the spread of infection. Remember that coughing and sneezing can spread cold and flu germs.

References

1. Survey Finds Just 40% of Adults “Absolutely Certain” They Will Get H1N1 Vaccine. Harvard School of Public Health. 2009 Oct 2.
2. What You Need To Know About Swine Flu Vaccine. National Public Radio. 2009 Oct 5.
3. H1N1 vaccine on schedule, official says. CNN. 2009 Oct 1.
4. Murphy and Strunk. Safe administration of influenza vaccine in asthmatic children hypersensitive to egg proteins. J Pediatr. 1985 Jun;106(6):931-3.
   View abstract
5. Centers for Disease Control and Prevention (CDC). 2009 pandemic influenza A (H1N1) virus infections – Chicago, Illinois, April-July 2009. MMWR Morb Mortal Wkly Rep. 2009 Aug 28;58(33):913-8.
   View abstract
6. CDC H1N1 Flu | General Questions and Answers on Guillain-Barre syndrome (GBS). Centers for Disease Control and Prevention (CDC). 2009 Sep 14.
7. CDC H1N1 Flu | General Questions and Answers on Thimerosal. Centers for Disease Control and Prevention (CDC). 2009 Sep 14.
8. Kroger et al. General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2006 Dec 1;55(RR-15):1-48.
   View abstract
9. Eggertson L. Pandemic (H1N1) 2009 lives in some people for at least eight days. CMAJ. 2009 Sep 28. [Epub ahead of print]
   View abstract

Preliminary results from two studies published online last week by the New England Journal of Medicine (NEJM) show that a single dose of the H1N1 vaccine will offer protection for most adults within three weeks of vaccination [1-2]. This is good news in the fight against H1N1, since the vaccine won’t be ready until the start of flu season. On Sunday, Health and Human Services Secretary Kathleen Sebelius said that some vaccine may be available as early as the first full week in October [3].

Both vaccines were generated from the same vaccine virus (New York Medical College [NYMC] X-179A), and formulated and produced by either CSL Biotherapies [1] or Novartis [2]. The Novartis vaccine is being tested both with and without the company’s proprietary immune-stimulating compound (called an adjuvant), MF59. The NEJM report described below is an interim analysis of subject responses to adjuvanted vaccine. The CSL vaccine does not contain an adjuvant. Adjuvanted flu vaccines have not been used previously in the U.S. and health officials hope to use a vaccine without an adjuvant because of the regulatory issues involved (more extensive human testing would be required before FDA approval). MF59 has been used extensively in Europe since 1997 with no excess reports of autoimmune conditions.

The CSL Biotherapies H1N1 vaccine

The CSL Biotherapies vaccine was tested in one locality in Australia during winter at two different doses on 240 people (120 for each dose). An equal number of subjects from 18–49 years of age (59% female, 86% white, 43% had previously received seasonal influenza vaccine) and 50–64 years of age (53% female, 98% white, 48% had previously received seasonal influenza vaccine) were evaluated using a 15 microgram dose.

The study also evaluated a double dose (30 micrograms) that many people assumed would be necessary in another group of 120 subjects.

Although a robust immune response to the H1N1 vaccine following a single dose was unanticipated, post vaccination titers of 1:40 or more on hemagglutination-inhibition assay (a quantification of virus by hemagglutination) was observed in 96.7% of the recipients that received the 15 microgram dose and 93.3% of the recipients that received the 30 microgram dose. Titers of 1:40 or greater are considered to be protective. Thus, the low dose actually worked better than the double dose.

Surprisingly, 31.7% of subjects had antibody titers before vaccination of 1:40 or more on hemagglutination-inhibition assay. For subjects who were 50 years of age or older, the researchers suggest that this could be due to the presence of preexisting antibodies from exposure to H1N1 viruses circulating prior to 1957. For younger subjects, there may be a degree of previous 2009 H1N1 infection despite stringent exclusion criteria. Additionally, cross-reactive antibodies may also have played a role.

An increase in detectable specific H1N1 antibodies in blood serum (called seroconversion) occurred in 74.2% of subjects.

No deaths or serious adverse events were reported. The most commonly reported local adverse events within 7 days after receiving one dose of the H1N1 vaccine were injection-site tenderness and pain. Systemic adverse events reported were headache, malaise and muscle pain.

The Novartis H1N1 vaccine

The Novartis vaccine was tested in one locality in the U.K. during summer on 100 people aged 18–50 (65% female, 82% white, 37% had previously received seasonal influenza vaccine). The vaccine is boosted with the Novartis adjuvant, MF59.

Subjects were randomly assigned in 5 blocks of 20 patients to receive two doses of 7.5 micrograms of MF59-adjuvanted vaccine either concurrently administered on day 0 or administered in two doses, the first at day 0 and the second at day 7, 14 or 21. Data were evaluated at day 21 for four groups of 25 subjects:

• one dose on day 0
• two doses on day 0
• one dose on day 0 and one dose on day 7
• one dose on day 0 and one dose on day 14

Similar to what was observed in the CSL vaccine study, 15% of subjects had detectable prevaccination levels of hemagglutination-inhibition antibody. The researchers suggest that, despite excluding subjects with previous respiratory illness, this may be due to asymptomatic H1N1 infection.

By day 21, post-vaccination titers exceeded 1:32 by hemagglutination-inhibition assay in 88% of subjects who had received one vaccine dose by this time and in 92–100% of subjects who had received both doses.

The development of detectable specific H1N1 antibodies in blood serum occurred in 76% of subjects that received only one dose to date and 88–92% that received both doses.

No deaths or serious adverse events were reported. The most commonly reported local adverse event within 7 days after receiving the first dose of the H1N1 vaccine was injection-site pain. Systemic adverse events reported were headache, muscle pain, malaise and nausea.

More data to come

The discrepancies observed between the two trials may be due to several factors: technical differences in measurement of antigen in the doses used, the limited number of samples evaluated and the early time point following immunization. Additional companies — Sanofi Pasteur, GlaxoSmithKline and AstraZeneca — should be announcing preliminary trial results shortly. H1N1 vaccine studies in children started after the adult studies and aren’t completed yet. Researchers anticipate those results in two weeks.

For more information on seasonal influenza (flu) and H1N1 swine flu, visit the following websites:

• CDC seasonal flu pages
• Flu.gov

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References

1. Greenberg et al. Response after One Dose of a Monovalent Influenza A (H1N1) 2009 Vaccine — Preliminary Report. N Engl J Med. 2009 Sep 10. [Epub ahead of print] DOI: 10.1056/NEJMoa0907413
   View abstract
2. Clark et al. Trial of Influenza A (H1N1) 2009 Monovalent MF59-Adjuvanted Vaccine — Preliminary Report. N Engl J Med. 2009 Sep 10. [Epub ahead of print] DOI: 10.1056/NEJMoa0907650
   View abstract
3. Exclusive: Sebelius Says H1N1 Vaccine To Be Released Earlier Than Expected. ABC News, George’s Bottom Line. 2009 Sep 13.

Kids learn early on in preschool that to truly prevent the spread of germs, you’ve got to wash your hands. Nevertheless, a dab of soap and a quick rinse isn’t effective. The key is to wash your hands for at least 20 seconds to ensure that you’ve removed the microbes. By rubbing your hands with soapy water, you pull dirt and oil from your skin. The soap lather suspends any germs trapped inside and are then washed away when rinsing.

The right way to wash your hands

When washing you hands with soap and water, follow these steps:

1. Wet your hands and wrists with warm running water and apply soap.
2. Rub your hands, including the fingers, palm to palm in a circular fashion.
3. With palms still together, intertwine the fingers and rub in between them.
4. In a circular fashion, rub the back of each hand with the opposite palm, making sure not to ignore the knuckles and fingers.
5. Rub each thumb by gripping it with the opposite hand.
6. Continue washing hands for 20 seconds. Here’s a trick: sing the ABC’s to yourself.
7. Rinse your hands and wrists thoroughly under warm running water. Keep your hands lower than your elbows to avoid water flowing up the arms and then back down onto the hands, contaminating them.
8. Don’t turn off the water! Dry your hands completely using a clean or disposable towel.
9. Using the towel, turn off the faucet. If in a public restroom, use the towel to grasp the door handle and open the door, then discard the towel.

If soap and water aren’t available, use an alcohol-based hand sanitizer.

While alcohol-based hand sanitizers reduce the number of germs on skin, they aren’t necessarily more effective at reducing influenza A H1N1 virus on human hands. A recent study evaluated the effectiveness of routine hand hygiene against live human influenza A virus H1N1 using soap and water hand washing or one of three different types of alcohol-based hand rubs (61.5% ethanol gel, 70% ethanol plus 0.5% chlorhexidine solution, or 70% isopropanol plus 0.5% chlorhexidine solution) [3]. Hand washing with soap and water was found to be statistically superior to all three alcohol-based treatments.

For a visual demonstration on the effectiveness of hand washing, check out the publication linked below from the University of Georgia College of Agriculture and Environmental Sciences. An experiment was performed to show the difference in the amount of bacteria on an unwashed hand, a rinsed hand, a washed hand and a sanitized hand. The experiment involved touching agar plates (special food used to grow bacteria in a laboratory) with or without hand hygiene and then incubating them for 24 hours. Food, Hands and Bacteria illustrates the importance not only of hand washing but washing for more than 20 seconds [4].

To promote the importance of proper handwashing, CDC-TV released a video late last year, “Put Your Hands Together,” in its “Health Matters” series, presented below.

References

1. Swine flu could come back in more virulent form after summer, European experts say. BMJ 338:b1792. 2009 Apr 29.
2. Put Your Hands Together. National Center for Preparedness, Detection, and Control of Infectious Diseases (NCPDCID) and National Center for Zoonotic, Vector-Borne, and Enteric Diseases (NCZVED). 2008 Oct 13.
3. Grayson et al. Efficacy of soap and water and alcohol-based hand-rub preparations against live H1N1 influenza virus on the hands of human volunteers. Clin Infect Dis. 2009 Feb 1;48(3):285-91.
   View abstract
4. Food, Hands and Bacteria. Prepared by Estes Reynolds. Accessed 2009 May 6th

While the Centers for Disease Control and Prevention (CDC) has determined that the swine flu is contagious and is spreading from human to human [2], the WHO has indicated that most people infected with swine flu make a full recovery without the need for medical attention or antiviral drugs [3].

As of today, the U.S. has reported 91 laboratory-confirmed cases of the swine flu and one death [4]. Mexico has reported 26 confirmed cases with seven deaths; Austria (1), Canada (13), Germany (3), Israel (2), New Zealand (3), Spain (4) and the United Kingdom (5) have all reported laboratory confirmed cases (number in parenthesis) with zero deaths [5]. Public health agencies around the world, including the CDC and the WHO, are monitoring the spread of the swine flu and focusing on mitigation measures. That means providing information on social distancing interventions, including case isolation, school dismissal and childcare facility closure [6]. In terms of preparations and informing the public, U.S. officials agencies are already treating the swine flu outbreak as a "phase 6" event to stay ahead of the WHO [1].

In a CDC briefing yesterday, acting CDC Director Richard Besser said the following [7].

What we see in the United States, or have been seeing so far, has been milder, has been less severe than what has been reported out of Mexico. And as we continue to look, we will continue to monitor that. So there are five hospitalized cases, three in California and two in Texas. The median age is 16 years to 64 years. We expect to see more cases and will continue to report on those. As we move forward, we may start to move away from specific case numbers and more on to describing states and clusters. The incubation period in the United States appears to be about two to seven days, which is typical for what you see with an influenza virus. I want to take a moment and put this into context with seasonal flu. Many of you are well schooled in influenza and have been covering seasonal flu. But what we see with seasonal flu is that it can be unpredictable. On average, in the United States, each year from seasonal flu, we see approximately 36,000 deaths. And so influenza is a severe infection. It affects different people differently based on their own immunity, their ability to fight infection and factors around the virus.
[ ... ]
As this moves forward, I fully expect that we will see deaths from this infection. They’re seeing many deaths in Mexico, and we’re trying to learn more about that and why the situation in Mexico is different from here. And as we continue to investigate cases here, I expect that we will see deaths in this country.

Indeed, seasonal flu in the U.S. hospitalizes over a quarter of a million people annually and kills 36,000 every year [8]. Scientists hope to someday develop a vaccine that provides lifetime immunity from the flu. Until then, annual vaccinations are important in the fight against the flu. Note however that none of the annual flu vaccines were specifically targeted toward swine flu.

In the midst of alarming reports on swine flu that are bombarding us from the media as well as all the misinformation circulating on the Web, some science-based information is in order.

What is swine flu?

The swine flu, or more generally the influenza virus, is a respiratory infection caused by a variety of RNA viruses. Influenza A is an RNA virus that causes influenza in birds and some mammals, including swine (pigs). The virus uses two cell surface proteins to mediate entry and exit from host cells and is subclassified according to the viral proteins used. The protein hemagglutinin (pronounced hem-a-gloot-nin) allows the virus to bind to the cell that is being infected: there are 16 different hemagglutinin subtypes (H1 — H16). The protein neuraminidase (pronounced neur-a-min-i-dase), an enzyme that cleaves sialic acid from host and viral proteins, facilitates viral exit from the host cell: there are 9 neuraminidase subtypes (N1 — N9). All known strains of influenza A are made up of combinations of hemagglutinin and neuraminidase subtypes. The swine influenza A virus subtype is H1N1.

Using hemagglutinin, influenza viruses bind to sialic acid sugars (essentially a carbohydrate widely distributed in animal tissues in and bacteria) located on the surface of epithelial cells in the nose, throat and lungs. The cell then absorbs the virus in a process called endocytosis. Once inside the cell, the virus replicates.

The presence of the influenza A virus isn’t a surprise. The most-recent U.S. virus surveillance found that influenza A accounted for over half (67.3%) of all influenza viruses identified; almost all influenza A viruses (89.9%) were the H1N1 subtype [9]. What’s surprising is how severe the cases have been in Mexico, and it’s something the CDC is looking into.

How is the swine flu transmitted?

Like any other flu virus, the swine flu is transmitted primarily by air. Simply coughing or sneezing, or through direct contact (shaking hands or kissing) can spread cold and flu germs. One of the most effective ways to prevent illness is to wash your hands. You cannot contract swine flu by eating pork or pork products. The virus is killed by cooking temperatures of 160 degrees F / 70 degrees C [3].

What are the symptoms of swine flu?

The symptoms of swine flu are similar to seasonal flu:

• Body or muscle aches
• Chills
• Cough
• High fever, lasting 3-4 days
• Headache
• Sore throat
• Stuffy nose
• Extreme tiredness

There appears to be a greater prevalence of stomach symptoms with the swine flu, including nausea, vomiting and diarrhea.

What if I get sick from the swine flu?

There are two types of antiviral medicines that make it difficult for viruses to grow in your body:

• Neuraminidase inhibitors, which include oseltamivir (Tamiflu) and zanamivir (Relenza)
• M2 inhibitors, which include amantadine (Symadine, Symmetrel) and rimantadine (Flumadine)

Since October 1, 2008, none of the influenza A viruses tested in the U.S. were resistant to both oseltamivir and the adamantanes, and all influenza viruses tested this season have been susceptible to zanamivir [9]. The swine flu virus is sensitive to both oseltamivir (Tamilfu) and zanamivir (Relenza) [10]. Antiviral drugs reduce the severity of illness, make you feel better faster and may prevent serious complications.

How can I protect myself from the swine flu?

Here are some tips on how you can protect yourself from catching the swine flu:

• Wash your hands frequently or use an alcohol-based hand antiseptic.
• Get plenty of rest, drink plenty of fluids and eat nutritious food.
• Cover your nose and mouth with a tissue when you cough or sneeze. Throw the tissue in the trash after use.
• Avoid touching your eyes, nose or mouth. These are areas where the flu can enter your body.
• Avoid people that are sick.
• If you get sick, stay home and limit contact with others.

Additional credible sources of information on the swine flu can be found below:

• CDC Swine Flu page
• WHO Swine Influenza web site
• PandemicFlu.gov

References

1. WHO Raises Swine Flu Alert; Virus Claims First Life in U.S. The Washington Post. 2009 Apr 29.
2. Swine Influenza and You. Centers for Disease Control and Prevention. Accessed 2009 Apr 28.
3. Swine influenza frequently asked questions World Health Organization. 2009 Apr 27.
4. Swine Influenza (Flu). Centers for Disease Control and Prevention. Accessed 2009, Apr 29.
5. Swine influenza – update 5. World Health Organization Disease Outbreak News. 2009 Apr 29.
6. Interim CDC Guidance for Nonpharmaceutical Community Mitigation in Response to Human Infections with Swine Influenza (H1N1) Virus. Centers for Disease Control and Prevention. 2009 Apr 28.
7. CDC Briefing on Public Health Investigation of Human Cases of Swine Influenza. Centers for Disease Control and Prevention press briefing transcript. 2009 Apr 28.
8. Fiore et al. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2008. MMWR Recomm Rep. 2008 Aug 8;57(RR-7):1-60.
   View abstract
9. Update: influenza activity–United States, September 28, 2008-April 4, 2009, and composition of the 2009-10 influenza vaccine. Centers for Disease Control and Prevention (CDC). MMWR Morb Mortal Wkly Rep. 2009 Apr 17;58(14):369-74.
   View abstract
10. Antiviral Drugs and Swine Influenza. Centers for Disease Control and Prevention. Accessed 2009 Apr 29.

Scientists report in the current issue of the journal Nature Structural and Molecular Biology the isolation of a group of high-affinity antibodies that are potent inhibitors of a wide range of influenza viruses, including the H5N1 avian flu, the 1918 Spanish flu and some seasonal strains [1]. The antibodies may someday be used to create a vaccine that provides lifetime immunity from the flu.

Seasonal flu hospitalizes an average of 226,000 people in the U.S. annually, killing 36,000 every year [2]. Influenza A viruses have been associated with an increasing number of deaths; from 1990 — 1999, the greatest mean number of flu deaths were associated with influenza A (H3N2) viruses [3]. Each season, between one quarter- and a half-million people die of influenza worldwide [4].

Influenza A is an RNA virus that causes influenza in birds and some mammals. It uses two cell surface proteins to mediate entry and exit from host cells; the virus is subclassified according to the viral protein subtypes used. The protein hemagglutinin (pronounced hem-a-gloot-nin) allows the virus to bind to the cell that is being infected: there are 16 different hemagglutinin subtypes (H1 — H16). The protein neuraminidase (pronounced neur-a-min-i-dase), an enzyme that cleaves sialic acid from host and viral proteins, facilitates viral exit from the host cell: there are 9 neuraminidase subtypes (N1 — N9). All known strains of influenza A are made up of combinations of hemagglutinin and neuraminidase subtypes. For example, the recent spread of avian influenza A (bird flu) is caused by the H5N1 strain, while the 1918 Spanish flu pandemic was caused by the H1N1 strain.

In the current study, researchers screened a panel of human immunoglobulins against the lineage of H5 hemagglutinin and identified 10 antibodies that recognized the protein. Surprisingly, they found that three of the antibodies they tested further also recognized eight of the 15 other hemagglutinin subtypes, including the versions used by the avian flu, the 1918 Spanish flu pandemic strain and the most common human influenza subtypes.

The antibodies were then tested in mice treated with lethal doses of avian flu (H5N1). Mice that were given the antibodies 1 hour before or up to 3 days after infection survived, remaining healthy and showing minimal body weight loss over a 2-week observation period. The ability of the antibodies to protect the mice demonstrated therapeutic value.

Hemagglutinin consists of a globular head region connected to a fibrous stem domain, the base of which is associated with the virus (imagine a small mushroom on the surface of a sphere; see the illustration above). Vaccines principally generate antibodies that target the globular head region of hemagglutinin [4]. However, the head region changes rapidly, giving rise to new flu strains that are no longer recognized by the generated antibodies. This is the reason why annual vaccination is so important — to provide continued immune protection.

Antibodies typically block the binding of hemagglutinin to its cellular receptor. However, high-resolution structure analysis revealed that the antibody interferred with the subsequent step of hemagglutinin-mediated virus-host membrane fusion, inserting into a ‘pocket’ in the stem of hemagglutinin.

Three hydrophobic pockets (meaning having little or no affinity for water) are located below the globular head region of hemagglutinin. In the complex analyzed by scientists, one antibody binds in each pocket. Many influenza subtypes have the same stem structure, providing an explanation not only for the ability of the antibodies to block virus-host membrane fusion but to inhibit other influenza subtypes.

According to the World Health Organization, as of February 2009 there has been a total of 408 confirmed human cases of avian influenza A and 256 deaths. The researchers are starting animal safety tests and hope to begin clinical trials of antibody treatments by the 2011 — 2012 flu season [5].

This study has profound implications for the generation of a universal influenza vaccine. However, development of a vaccine that can produce those antibodies will take longer, since the stem domain of hemagglutinin typically typically escapes immune surveillance.

References

1. Sui et al. Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses. Nat Struct Mol Biol. 2009 Feb 22. DOI: 10.1038/nsmb.1566
   View abstract
2. Fiore et al. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2008. MMWR Recomm Rep. 2008 Aug 8;57(RR-7):1-60.
   View abstract
3. Thompson et al. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA. 2003 Jan 8;289(2):179-86.
   View abstract
4. Influenza Fact Sheet. World Health Organization. Accessed 2008 Mar 1.
5. Leslie M. Immunology. Flu antibodies stir new hope for treatment, vaccine. Science. 2009 Feb 27;323(5918):1160.
   View abstract