2009-2010 H1N1: What's New This Week -- January 11, 2010

Editor's Note: The past few weeks' published studies and news stories on H1N1 influenza focused on the waning pandemic, a second vaccine recall, a new influenza vaccine for seniors, H1N1 mortality in pregnant women, household transmissibility of pandemic H1N1, vaccine supply and safety, the public's intent (or lack of intent) to get vaccinated, positive outcomes from influenza, avian flu, clinical characteristics of pandemic H1N1 vs influenza-like illness (ILI) in military families, and H1N1 in indigenous populations. We provide links to those stories and commentary by infectious diseases expert, John G. Bartlett, MD. For more information on 2009 H1N1, see our H1N1 Influenza A (Swine Flu) Alert Center, where you will find the latest news, expert commentaries, resources for clinicians, and peer-to-peer discussions.

 

Testing Group Data Shows Swine Flu Waning in US

An analysis of 170,000 flu tests obtained between May and December 2009 revealed 2 peaks in the H1N1 "swine flu" epidemic: one in April and one at the end of October 2009. H1N1 flu is definitely waning now, although tests are still positive in about 40% of children ages 5-14 years.

Commentary. What practitioners need to know:

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  All indicators are trending down -- rates of flulike illness in office practice, positive influenza tests, hospitalizations, and influenza-attributable deaths.
  
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  The second wave is nearly over.
  
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  Most flulike illness encountered now is related to other viruses, especially respiratory syncytial virus and rhinovirus, but not seasonal flu yet;
  
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  The big question now is: What will happen to "seasonal flu"? Will it be: (1) the third wave of swine flu; (2) seasonal flu with the usual flu viruses (the viruses in the seasonal flu vaccine); or (3) it is already over -- in other words, no big flu season will occur in January-March?
  
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  The safe ploy is to get vaccinated against both 2009 H1N1 and seasonal flu, especially now that the vaccines are available, convenient, and inexpensive.
  

Another Drugmaker Recalls Swine Flu Vaccine in U.S.

On December 23, 2009, the US Food and Drug Administration (FDA) announced a non-safety-related recall of 13 lots of AstraZeneca MedImmune's 2009 influenza (A) H1N1 vaccine, because during stability testing, antigen concentrations in these lots were found to be below prespecified levels. MedImmune, LLC recommends that all lots marked with an expiration date between January 19 and January 26, 2010 should not be used, and that they be returned to the manufacturer.

Commentary. What does this mean to practitioners? In response to questions about the recall, practitioners can inform their patients of the following:

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  The manufacturer notified the US Centers for Disease Control and Prevention (CDC) and the FDA of the recalled lots on December 16 and December 21, 2009;
  
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  The recall involves only the live virus nasal spray vaccine;
  
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  The recalled lots represent 4.7 million doses, or about 4% of the total doses distributed to date;
  
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  People who received this vaccine should not get revaccinated because the potency was only slightly reduced; the recalled vaccine would still stimulate an adequate protective response;
  
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  MedImmune, LLC is notifying providers who received these 13 lots so that they can return them;
  
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  There is no safety issue with the recalled vaccine; and
  
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  Another recall occurred earlier in December when Sanofi Pasteur recalled 4 lots of pediatric injectable vaccine.
  

FDA Approves High Dose Seasonal Flu Vaccine for Seniors

The FDA has granted Sanofi Pasteur accelerated approval for a high-dose seasonal influenza vaccine (Fluzone® High-Dose) to prevent influenza caused by virus subtypes A and B in people aged 65 years and older, a group that is historically more susceptible to influenza and its complications.

Commentary. Important facts for providers about this new vaccine:

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  Fluzone® High-Dose is simply composed of more antigen, but produces a stronger antigenic response in persons > 65 years of age, who often have a poor vaccine response due to "immunosenescence";
  
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  This vaccine is for seasonal influenza;
  
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  It will be available next season (2010-2011);
  
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  The United States has 70 million persons > 65 years of age, or 20% of the population;
  
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  The average US flu season has 36,000 deaths -- 90% are in persons > 65 years of age; and
  
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  The new vaccine will not protect against swine flu or the current flu season.
  

H1N1 Influenza May Increase Maternal Deaths

Commentary. The bottom line for practitioners is:

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  The 2009 influenza A (H1N1) pandemic has been particularly harsh for pregnant women in terms of morbidity and mortality.
  
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  The presumed reason is immune deficiency of pregnancy.
  
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  The risk is greatest in the third trimester, but is also elevated in earlier trimesters.
  
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  Pregnancy is a very high vaccine priority because: (1) vaccine safety is well established; (2) the mother gets protection; and (3) the newborn gets protection from maternal antibodies. Remember that newborns are at high risk but cannot get vaccinated until they are 6 months of age.
  
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  Pregnant women often refuse this vaccine due to concerns about safety for their unborn children. We need to emphasize that babies and pregnant women are the ones at greatest risk if there is a third wave of H1N1 influenza, and that the vaccine is safe.
  

Lower Household Transmission of H1N1 in US Than in Past Pandemics

A study reported in The New England Journal of Medicine found that household transmissibility of the H1N1 influenza virus in the United States was lower than that seen in previous pandemics. Only 13% of household contacts of an infected index household member subsequently developed an acute respiratory illness, and susceptibility decreased with age.

Commentary. Practitioners should be aware that:

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  Swine flu seems to select the immunologically naive, ie, the young people who have not had many years of exposure to either influenza or the flu vaccine;
  
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  We previously said that swine flu went to camp in the summer (first wave) and to school in the fall (second wave);
  
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  The results of this report seem to confirm the correlation of age and vulnerability; and
  
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  It is still a good idea for people to wash their hands and sneeze into their sleeves at home, because most people who have flulike illnesses at this time have other respiratory viruses that may have different rates of transmission.
  

Vaccine News

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  Promotion: The US Department of Health & Human Services and the Ad Council have launched a campaign, Together We Can All Fight the Flu. The campaign includes television, radio, online banners, and outdoor advertising.
  
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  Seasonal flu vaccine to prevent pandemic flu: A study in ferrets showed that vaccination with both seasonal flu and pandemic flu provided better protection than pandemic flu vaccine alone. Of note, the ferret model is standard for studies of influenza in humans; the seasonal flu vaccine was given before pandemic flu vaccine, so it "primed" the animals' responses; and results suggest that previously having seasonal flu or a seasonal flu vaccine offers protection against pandemic H1N1 -- a finding that might be relevant to the high rates of serious H1N1 disease that we have seen in pediatric patients.
  
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  Supply: The total vaccine available as of December 28, 2009 was 119 million doses. It is estimated that 60 million people in the United States have received the vaccine. Plenty of vaccine is now available. It is offered in many pharmacies and drugstores at $10-$16. At present, supply of vaccine exceeds demand, according to CVS, Walgreens, Rite Aid, and Walmart.
  
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  National Influenza Vaccination Week is January 10-16, 2010. The aim of this national initiative is to highlight the importance of influenza vaccination. Influenza Vaccination Week was originally scheduled for December 6-12, 2009, but has been rescheduled for January 2010. The schedule of selected days for targeted groups to get vaccinated is as follows
  
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    January 10: kickoff
    
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    January 11: healthcare workers
    
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    January 12: people with high-risk conditions
    
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    January 13: children; pregnant women; and caregivers for infants < 6 months of age
    
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    January 15: seniors
    
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    January 16: wrap-up
    
  
  
  
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  Safety: Updated analysis of data from the Vaccine Adverse Event Reporting System (VAERS) is now available for reports received through December 11, 2009. At that time, 73 million vaccine doses had been delivered, although the number of doses actually administered is unknown, and 333 "serious" reports had been filed. The following are the highlights
  
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    There were 21 deaths -- all have been reviewed or are under review. No clear pattern to host or geographic location has been identified
    
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    There were 21 cases of Guillain-Barré syndrome. Of note, 80-160 new cases of Guillain-Barré occur each week in the United States
    
  • 
    Rates of serious reactions are not different from VAERS reports with seasonal flu vaccine.
    
  
  
  

In conclusion, there is no evidence of any new or unusual vaccine-related events.

Intent to Receive Influenza A (H1N1) 2009 Monovalent and Seasonal Influenza Vaccines

A report from the CDC describes a 2-stage survey conducted in August 2009, with visits to 207 homes in 2 census tracts in North Carolina. Important results include the following:

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  Intention to vaccinate children ages 6 months to 18 years: 65%;
  
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  Main reason to decline vaccine: low likelihood of infection (19%) or concern for vaccine side effects (14%); and
  
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  Main source of H1N1 information was television: 85%.
  

Commentary. Of interest, the CDC began an extensive promotional campaign for 2009 influenza A (H1N1) vaccine that included advertising during the college bowl games.

Five Reasons That H1N1 Is Actually Good for Us

Dr. William Schaffner, president-elect of the National Foundation for Infectious Diseases, explains his reasons for claiming that our experience with H1N1 had a few positive outcomes. His 5 reasons that H1N1 is actually good for us are:

1. 
   We demonstrated the capacity to produce twice as much flu vaccine as is usually demanded;
   
2. 
   Public demand for flu vaccine is up, but we need to sustain this demand;
   
3. 
   Manufacturers made the switch from seasonal to pandemic vaccine production priority "virtually overnight"; and
   
4. 
   Increased flu awareness.
   

What Happened to Avian Influenza?

Avian influenza started spreading across Asia in 2003 and is now endemic in poultry in some parts of Asia. This disease can spread rapidly in poultry flocks, cause disease that affects multiple organs, and has a mortality rate that approaches 100%. Avian influenza has occasionally crossed the species barrier and caused highly lethal disease in humans (Table 1). Bird-to-human transmission could be efficient or sustained with viral reassortment or adaptive mutation, but this has not happened so far.

Table 1. Human Cases of Avian Influenza (H5N1)

Cases	2003	2004	2005	2006	2007	2008	2009	Total
	4	46	98	115	88	44	72	467
Egypt Indonesia Thailand China Cambodia Vietnam Other	0 0 0 1 0 3 0	0 0 17 0 0 29 0	0 20 5 8 4 61 0	18 55 3 13 2 0 24	25 42 0 5 1 8 7	8 24 0 4 1 6 1	39 20 0 7 1 5 0	90 161 25 38 9 112 32
Deaths	4	32	43	79	59	33	13	263

Other countries include Azerbaijan, Bangladesh, Djibouti, Iraq, Lao People's Democratic Republic, Myanmar, Nigeria, Pakistan, and Turkey.

Important points with regard to these data:

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  The H5N1 (avian flu) reached its zenith in 2006 with 115 cases;
  
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  Indonesia has the highest total, but no cases in 2009;
  
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  Currently, the major site of new cases is Egypt; and
  
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  The overall mortality rate (2003-2009) is an astonishing 56%, but the most recent data (2009) show a mortality rate of 13 of 52 (25%), and in Egypt mortality was 4 of 39 (10%).
  

World Health Organization Pandemic (H1N1) Update

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  Strain typing: A total of 9507 specimens from 28 countries were positive for influenza. Subtyping of 3.7% of the specimens yielded seasonal flu virus, including types A (1.1%) and B (1.6%). Pandemic 2009 influenza A (H1N1) accounted for 90.8% of the subtypes, and the rest (5.6%) were untyped A strains. The conclusion is that as of mid-December, more than 95% of fully typed stains were the pandemic strain.
  
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  Resistance: Testing of more than 15,000 clinical isolates of 2009 influenza A (H1N1) from 86 countries showed that 168 had the H275Y mutation for resistance to oseltamivir, but all were sensitive to zanamivir.
  
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  The epidemic in the United States and Canada reached its peak 6 weeks ago (third week of November), and rates of ILI are now back to baseline. Cases in Canada showed that 53% of hospitalized patients had underlying conditions. In Europe, most countries have reached their peak and low levels of seasonal flu continue. Most cases of ILI have been in children aged 0-4 years (15 countries) or 5-14 years (18 countries). Increasing rates of respiratory syncytial virus infections have occurred in the past 6 weeks. In western and central Asia, limited data reveal influenza activity throughout the region. The temperate region of the southern hemisphere shows only sporadic activity throughout the region.
  
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  World Health Organization Director General Margaret Chan noted that (1) it is too early to say that we have passed the peak of 2009 pandemic flu in the world; (2) the disease is reported in 200 countries, and > 12,000 confirmed cases have died; (3) this pandemic may not be conquered until 2011; and (4) we are clearly not ready for a separate H5N1 bird flu pandemic.
  

Clinical Epidemiologic Characteristics of an Outbreak of Novel H1N1 Influenza Among US Military Beneficiaries

Background. The structure of the military healthcare system permitted a unique opportunity to study influenza in a population of 96,258 military beneficiaries. In this setting, the gold standard diagnostic test, reverse-transcriptase polymerase chain reaction (RT-PCR), was routinely used.

Results. From April 21 to May 6, 2009, 761 patients were tested for ILI, and 97 (13%) had infection with the pandemic influenza strain. A comparison of patients with and without confirmed influenza is shown in Table 2.

Table 2. Comparison of Patients With/Without Confirmed H1N1 Influenza

Characteristic	Positive Flu	Negative Flu
	n = 91 (12%)	n = 641 (88%)
Mean age Age, 2-24 years Contact with H1N1 Asthma	21 years 70% 52% 18%	20 years 45% 6% 16%
Flu vaccine < 12 months	66%	40%
Symptoms and signs Fever Cough Runny nose Nausea Diarrhea	100% 96% 44% 25% 7%	77% 74% 43% 24% 19%
Median temperature	101°F	99.6°F

 

Commentary. A major reason to review this paper is that it shows that patients who seek medical care for influenza often have respiratory tract infections caused by other viruses. A contemporary challenge is that many people who had unconfirmed cases of ILI think that they had pandemic flu and do not need the vaccine, but the results here support the recommendation for patients in this category (unconfirmed pandemic influenza) to get the vaccine unless there was virologic confirmation.

Indigenous Populations and 2009 Influenza (H1N1)

A curious correlation of high morbidity and mortality in some indigenous populations has been noted, as evidenced by the following groups:

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  American Indians/Alaskan Natives: In a 12-state review in which American Indians/Alaskan Natives comprised at least 3% of the population, the mortality rate was 4 times higher compared with other racial/ethnic groups.
  
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  Maori and Pacific Islanders in New Zealand: A review of cases showed that the rate of population-adjusted hospitalization was 5- to 7-fold higher for Maori and Pacific Islanders compared with New Zealand Europeans. The study authors noted that the same association with severe disease was found in the 1918-1919 influenza pandemic.
  
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  Aboriginals in Australia and the Inuit in Canada also appear to have high rates of severe disease due to the current influenza pandemic.