H1N1 (Swine) Flu Update

New estimates about the spread of H1N1 flu in the U.S. show that infection could possibly be much higher than originally thought. An Aug. 24 report1 released by the President’s Council of Advisors on Science and Technology estimates that “swine flu could infect half the U.S. population this fall and winter, hospitalizing up to 1.8 million people and causing as many as 90,000 deaths — more than double the number that occur in an average flu season.” The 86-page report also states that the virus could cause symptoms in 60 million to 120 million people, more than half of whom might seek medical attention.

And, while the U.S. federal government wasn’t initially armed with these numbers, steps to prepare the country for the worst have already been taken. For starters, the federal government has provided grants to cash-strapped states that are ill-prepared financially to handle this crisis due to the deep recession. In addition, federal agencies, drug manufacturers and local governments have been fiercely working to get healthcare providers the needed vaccines and to effectively roll out an immunization campaign to manage the pandemic.

Current Spread of H1N1

Worldwide, the H1N1 pandemic “has caused significant disruptions and economic damage in parts of the Southern Hemisphere,” contributing to the deaths of more than 1,799 people in at least 168 countries.¹ The Centers for Disease Control and Prevention (CDC) reported that the most recent individual statistics for the numbers of H1N1 flu cases in the U.S. between April 15, 2009, and July 24, 2009, were 43,771 confirmed and probable cases.² Of those, 5,011 people were hospitalized and 302 people died. However, the CDC recognizes that those numbers are likely far from the actual numbers. The more likely number was about one million people during that time frame.

Individual case counts, which are what the CDC was collecting since the first reported case of H1N1, are an inaccurate representation of the true burden of the disease, says the CDC, because many people likely became mildly ill with H1N1 flu but never sought treatment. In addition, many people who sought treatment were never officially tested or diagnosed. This is because testing was limited to hospitalized patients. Recognizing this, the CDC decided to stop tracking individual statistics and, instead, switch to the traditional surveillance system of aggregate national reports. The aggregate report, which can be viewed at www.cdc.gov/h1n1flu/update.htm#totalcases, shows the total number of hospitalizations and deaths weekly, as reported by individual states and territories.

As of the end of August, a total of 9,079 hospitalizations and 593 deaths associated with H1N1 flu were reported to the CDC. And, during the last two weeks of August, H1N1 influenza activity increased in Alabama, Florida, Georgia, Kentucky, Mississippi, North Carolina, South Carolina and Tennessee where outpatient visits to healthcare providers for influenza-like illness increased to a level usually seen only during peak winter periods. Also since the end of August, 33 of the 101 influenza-associated pediatric deaths in the U.S. were due to the H1N1 virus.

The Disease Burden in Populations

Aside from the novel strain of this flu, what makes H1N1 even more unusual is the age distribution it affects. Older adults who are typically most at risk of serious complications from seasonal flu appear to be least affected by H1N1. The hypothesis is that these individuals may have built up some immunity to H1N1 because they were previously exposed to a different strain of swine flu that appeared in 1976, either through inoculation or infection.

Looking at the individual statistical data collected April 15 through July 24, 2009, the CDC has categorized those groups that are at greatest risk of infection from the H1N1 flu.² Individuals at highest risk appear to be age 25 and younger. The data specifically show 26.7 cases of H1N1 per 100,000 people ages 5 through 24 years, 22.9 per 100,000 cases in people ages 0 through 4 years, and only 6.97 people per 100,000 in those ages 25 to 49 years. The rates were lowest for individuals ages 50 to 64 (3.9 per 100,000) and those ages 65 and older (1.3 per 100,000). The data also show that the hospitalization rate was highest among children ages 0 through 4 (4.5 per 100,000), followed by individuals 5 through 24 years (2.1 per 100,000) and individuals ages 65 and older (1.7 per 100,000).

Underlying medical conditions play a major role in the rate of hospitalization for those infected with the H1N1 virus, much as they do with the seasonal flu virus. However, unlike with the seasonal flu, the CDC has indicated obesity as an additional underlying health condition that places people at greater risk of serious H1N1 flu-related complications.

H1N1 Vaccine

Five manufacturers have been in production of the H1N1 vaccine for the U.S. — sanofipasteur, Novartis Vaccines, GlaxoSmithKline, MedImmune and CSL Biotherapies — all of which already produce U.S.-licensed seasonal vaccine.³ Having a license for the seasonal flu vaccine is key to getting the new H1N1 vaccine in circulation as soon as possible. Manufacturers with a seasonal flu license will not be required to apply for a new H1N1 license. Instead, they will follow recent recommendations by the FDA to evaluate the 2009 H1N1 vaccines using the same regulatory process to approve new viral strains contained in the annual seasonal influenza vaccines. These strain change supplements are not required to be supported by new clinical data, which is expected to expedite the licensure process for the pandemic vaccine.

Sanofi Pasteur was the first manufacturer to submit a supplemental application for licensure of its influenza A (H1N1) 2009 monovalent vaccine in mid-August.⁴ This supplemental process will likely be the process that all manufacturers will use for this year’s H1N1 vaccine for licensure, according to Luke Noll, a vaccine specialist for FFF Enterprises, Inc., Temecula, Calif. However, it should be noted that while clinical data are not required, manufacturers will make available immunogenicity and safety data through clinical studies. These clinical trials began in July by the National Institute of Allergy and Infectious Diseases (NIAID), and in mid-August by individual manufacturers under contract with Health and Human Services.

Why are additional trials needed by NIAID? These trials are “intended to generate data that are outside a [manufacturer’s] clinical development plan but that may be needed to support licensure or use of the vaccine under emergency use authorization (EUA).”⁵ EUAs are issued by the FDA to “permit either the use of an unapproved medical product or an unapproved use of an approved medical product during certain types of emergencies with specified agents.” As of this writing, all clinical trials by both the NIAID and manufacturers had produced positive results to protect against the H1N1 strain with no adverse effects. However, they are still ongoing.

The H1N1 influenza vaccine will be made using the same processes and facilities that are used to make the seasonal influenza vaccine. While the World Health Organization (WHO) recommended that countries use vaccines with adjuvants (an ingredient used to boost the body’s immune response), that is unlikely in the U.S. since there are no licensed flu vaccines with adjuvants in the U.S. “The adjuvanted vaccine was being considered,” explains Noll. “However, it would probably be the last resort because of the additional legal requirements of using an unlicensed product.” Instead of testing an adjuvanted vaccine, says Noll, manufacturers and the NIAID are testing two doses of vaccine at various potency levels in both adults (7.5 mcg, 15 mcg and 30 mcg) and children (7.5 mcg and 15 mcg), respectively. In addition, those who are worried about thimerosal (a preservative used in vaccines that is a form of mercury), needn’t be. There will be a thimerosal-free vaccine available for pregnant women and children.

As of this printing, the FDA has approved vaccines in production, and it is expected that they will be ready for distribution in mid-October. However, the WHO reported in July that the swine flu viruses being used to make the vaccine were not growing enough of a key ingredient, producing half as much “yield” as regular flu viruses.⁶ And, U.S. officials in mid-August slashed their estimate of how many swine flu vaccine doses will be available.⁷ The Department of Health and Human Services (HHS) had originally said that 120 million doses would be on hand in mid-October, but it changed that estimate to about 50 million doses, followed by another 20 million doses delivered each week after that.

Originally, it was thought that individuals would need two doses of the H1N1 vaccine spaced three weeks apart to protect them against the virus. However, recent findings by manufacturers and the NIAID have shown that a single dose of the vaccine triggers a protective immune response in more than 90 percent of the adults treated.8 In one study, reported on in the Sept. 10 issue of the New England Journal of Medicine, 240 healthy volunteers ages 19 to 64 who were broken into two groups (those younger than age 50 and those 50 and older) received an initial dose of the vaccine followed by a second dose 21 days later. The younger group received a 15 mcg dose (the standard dose used for a single strain in the seasonal influenza vaccine), and the older group received a 30 mcg dose. Data showed that three weeks after the first of the two scheduled vaccines, 96.7 percent of participants who received the lower dose and 93.3 percent of those treated with the higher dose achieved the desired immune response.

According to the NIAID, preliminary analyses of their trial data align with these findings, and studies are ongoing.⁹ It is anticipated, then, that only one dose of the H1N1 vaccine will be needed when it becomes available in October. In addition, because only one vaccine will be needed, more vaccine will be available than originally anticipated.

Anticipating a need for some protection against the H1N1 flu prior to the availability of the injectable vaccine, the CDC announced in late September that 3.4 million doses of inhalable H1N1 vaccines will be available the first week of October, with the initial influx of 195 million doses purchased by the U.S. government. The nasal spray vaccine, known as FluMist, is approved for healthy people between the ages of 2 and 49, but it is not approved for pregnant women because it contains a live virus.

The Government Plan

There is little doubt that the H1N1 flu will get a jump on the vaccine. Therefore, the CDC reported in August that approximately 159 million persons in the U.S. would be given priority. These include 5 million pregnant women, 4 million parents and caregivers of children younger than 6 months old, 14 million healthcare workers, 102 million people between ages 6 months and 24 years, and 34 million adults between ages 19 and 64 with chronic diseases. In addition, the CDC recommended that individuals ages 25 through 64 years only be vaccinated after these groups. Should there not be enough vaccine available for the priority populations, they have further prioritized the order of vaccine dispensing.

The plan is to ship the vaccine to “clinics, offices, health departments and other project area-designated sites which may include a mix of public health and private sector sites via centralized distribution” — the same process that is used to ship vaccines for the childhood immunization program to immunization providers.³ According to the CDC, the “key benefits of using a centralized, third-party distributor to support H1N1 vaccine distribution is that it allows distribution of doses to a much larger number of provider sites than would be feasible with direct manufacturer distribution.”

The amount of vaccine distributed to each project area will be in proportion to its population. And, in addition to the vaccine, the HHS will provide needles, syringes, Sharps containers and alcohol swabs.³

The Healthcare Provider Role

The main role of healthcare providers is to not only encourage H1N1 vaccination, but to ensure that those who are getting vaccinated do so safely. All individuals need to be screened for contraindications (such as egg allergy), and all need to be provided with information sheets describing the vaccine’s risks and benefits, signs and symptoms of adverse events to look for following vaccination, as well as how to report adverse events.¹⁰

Healthcare providers need to prepare for the worst and expect the best. Could the predictions for the spread of the H1N1 pandemic be worse? Yes. It could be as severe as the 1918 pandemic that killed 675,000 people in the U.S. and up to 50 million worldwide, said Homeland Security Secretary Janet Napolitano.¹¹ However, it’s more likely that this pandemic will mirror 1957 when flu killed about 70,000 people in the U.S. and one to two million worldwide.