| Editor's Note: The past week's news stories on H1N1 influenza focused on the waning second wave of 2009 H1N1 influenza, new data in regard to H1N1 vaccine safety, the report of the US Centers for Disease Control and Prevention (CDC) of 10,000 H1N1 deaths, and new evidence about the effectiveness of oseltamivir. 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. |
H1N1 Epidemic Update
From Thomas Friedan, MD, MPH, Director of the US Centers for Disease Control and Prevention (CDC).
Numbers for swine flu for April-November 14, 2009: 50 million people in the United States have been infected (15% of the US population), with 200,000 hospitalized and 10,000 deaths;
Vaccine supply: 85 million doses of H1N1 vaccine are available, and states are expanding access to the vaccine;
The second wave of H1N1 is resolving; it is not possible to predict whether there will be a third wave; and
A 12-state survey shows that American Indians and Alaskan natives are 4 times more likely to die from swine flu; the reason is unknown.
From CDC FluView Week 48.
The second wave is winding down as evidenced by low rate of positive tests for influenza (8.9% of samples tested); 2.7% of outpatient visits are for influenza-like illnesses; and only 14 states now report widespread influenza activity
Significance to practitioners: all indicators are significantly decreased
The second wave is coming to a close
The patient who presents with influenza-like illness symptoms is now more likely to have something else: paraflu; respiratory syncytial virus (adenovirus, coronavirus, rhinovirus, etc)
Patients probably do not have seasonal flu -- at least not yet (see below)
Influenza surveillance: Typing of influenza isolates from November 29 through December 3, 2009 found that 344 of 352 isolates (97.7%) were positive for swine flu. Significance to practitioners: If a patient has influenza-like illness, it is most likely 2009 H1N1 influenza because seasonal flu has not started yet
Antiviral resistance: Analysis of resistance test results since September 1, 2009 shows that 18 of 2043 strains (0.8%) were resistant to oseltamivir. Reviews of 19 cases with documented oseltamivir resistance in the United States showed that all but 2 patients had previous oseltamivir exposure. Significance to practitioners
If a patient tests positive for 2009 H1N1 influenza, there is a 99% chance that the influenza will be sensitive to oseltamivir
If there was no previous oseltamivir exposure, the probability of sensitivity to oseltamivir is 99.9%
All 2009 influenza A (H1N1) strains are sensitive to zanamivir
Pediatric deaths: for the period from August 30 to December 12, 2009, 204 pediatric deaths were attributed to 2009 H1N1 influenza. Typing was completed on 166 patients and 165 were positive for 2009 H1N1 influenza. The age breakdown for the 204 cases
Age < 2 years: 37 deaths
Ages 2-4 years: 21 deaths
Ages 5-11 years: 76 deaths
Ages 12-17 years: 70 deaths.
The 204 figure is the reported number of deaths, but the CDC estimates that the true number is more than 5-fold higher -- 1090 pediatric deaths caused by 2009 H1N1 influenza. For pediatric deaths, this is by far the worst flu season in 4 years, and seasonal flu has not yet started. Analysis of 96 of the 204 reported deaths indicates bacterial superinfection in 30 (31%) of the cases:
Significance to pediatric practitioners
The 2009 H1N1 influenza vaccine is a high priority in children over 6 months of age
Remember the concern for bacterial superinfection with 3 major pathogens: pneumococcus; Staphylococcus aureus; and group A streptococci. Clinical clues for these infections are lobar pneumonia or necrotizing pneumonia, a biphasic clinical course, and high white blood cell count and/or positive cultures, especially for the 3 major pathogens.
Safety of Influenza A (H1N1) 2009 Monovalent Vaccines: United States, October 1-November 24, 2009
Vaccine safety data reported to the Vaccine Adverse Event Reporting System (VAERS; the voluntary reporting system for consumers operated by the CDC and the US Food and Drug Administration [FDA]) are the basis for this summary. All serious reactions are evaluated by medical officers. Any "signals" from this analysis are pursued at the next step -- as assessment of the incidence of these events in the Vaccine Safety Data (VSD; a collaboration between the CDC and 8 large managed care organizations representing 9.5 million people). The VAERS data reported here are from the period October 5, 2009 (when the swine flu vaccine first became available) to November 24, 2009 when vaccine distribution reached 46.2 million doses of swine flu vaccine and 98.9 million doses of seasonal flu vaccine (Table 1).
Table 1. Number of Adverse Events
| Vaccine | Doses (million) |
Serious Adverse Events Total Rate Deaths |
||
|---|---|---|---|---|
| Swine • Live • Killed |
46.2 11.3 34.9 |
204 52 135 |
82 NS NS |
13 3 10 |
| Seasonal • Live • Killed |
98.9 NS NS |
283 35 232 |
47 NS NS |
16 0 15 |
Per million
Reports of Serious Adverse Events.
Guillain-Barré syndrome (GBS): 4 cases have been verified and 4 are under investigation; the number of expected cases of GBS (not associated with vaccination) for this period is 30-40;
Anaphylaxis: 13 cases;
Pregnancy complications: 13 cases of spontaneous abortion, stillbirth, or preterm delivery; and
Deaths: 13, including 9 associated with serious disease, 1 car crash after leaving vaccination clinic for vaccination, and 3 under investigation.
Conclusion: There are no concerning safety signals to date after 2009 H1N1 vaccination. For GBS, for example, there are 4 verified events and 4 under investigation, but the expected number in 8 weeks (the period of postvaccination follow-up for an association with GBS) is 30-40 unrelated cases. The VSD data for these adverse events show no cases of vaccine-associated GBS in 438,376 H1N1 vaccine recipients.
Significance to practitioners: Advocate for the 2009 H1N1 influenza vaccine, especially for the high-priority groups: pregnant women; people who care for children < 6 months of age; people who are 6 months to 24 years of age; healthcare workers; and people aged 25-64 years with chronic conditions, including immune deficiency. If patients express concern for vaccine safety, remind them that:
This vaccine is manufactured with the same methods that have been used to make every flu vaccine for the past 40 years;
Eleven different surveillance systems are monitoring the safety of this vaccine;
To date, 46 million doses have been given, and there is no clear evidence of serious safety concerns; and
Keep perspective. In the United States, 10,000 people have died as a result of infection with 2009 H1N1 influenza, and only 1 death was clearly related to being vaccinated -- a 56-year-old woman who was killed in a car crash after leaving the vaccination clinic.
CDC: H1N1 Flu 10,000 Deaths
The latest estimates from the CDC are that by mid-November, 2009 H1N1 influenza has killed 10,000 Americans, sent 213,000 to the hospital, and sickened a total of 50 million people -- one sixth of the US population.
Commentary. The US totals using midpoint estimates, as of mid-November 2009, are shown in Table 2.
Table 2. US Totals for Cases, Hospitalizations, and Deaths
| Age | Cases | Hospital | Deaths |
|---|---|---|---|
| 0-17 years 18-64 years 65 years |
16 million 27 million 4 million |
71,000 121,000 21,000 |
1090 7450 1280 |
| Total | 47 million | 213,000 | 9820 |
It is important to remember that these figures are for mid-October to mid-November, so that (1) the numbers are expected to rise with completion of the second wave; (2) the numbers are exceptionally high for the 1090 deaths in children and 7450 deaths in young adults; and (3) seasonal flu is still to come, and we may or may not have a third wave of 2009 influenza A (H1N1).
Oseltamivir Efficacy Questioned in Preventing Influenza Complications
The evidence for the efficacy of oseltamivir in reducing complications in otherwise healthy individuals with pandemic influenza is now uncertain, according to a recent Cochrane review.
Commentary. This report is a Cochrane Library review of neuraminidase inhibitors. As noted above, the conclusion is that neuraminidase inhibitors "have modest effectiveness against the symptoms of influenza in otherwise healthy adults." On the basis of meta-analysis of 20 trials, the effect of taking oseltamivir on an individual is an average reduction in symptoms of about 1 day. It should be emphasized that the CDC recommendations for oseltamivir use in this 2009 influenza A (H1N1) pandemic are restricted to those who are seriously ill or at high risk for influenza-associated complications. The details of the CDC recommendations are:
Persons with suspected or confirmed influenza with severe, complicated, or progressive illness or who are hospitalized; or
Persons with confirmed or suspected influenza who are at increased risk for serious morbidity or mortality, as with pregnancy, asthma, or other chronic underlying conditions.
H1N1 Flu Less Severe Than Feared
Harvard researcher Marc Lipsitch, DPhil, and colleagues from the UK Medical Research Council and the CDC predict that when the fall/winter wave of H1N1 swine flu is over, it will have been no more severe than an average flu season.
Commentary. The conclusions reported here are from a collaborative study by the UK Medical Research Council and the CDC. The investigators aimed to define the severity of 2009 H1N1 in the United States using the case hospitalization rate and the case-fatality rate. They used data from Milwaukee, Wisconsin, and New York City, plus a statistical approach known as Bayesian analysis. The conclusion is that during the first wave (April-July 2009), the rate of symptomatic cases was 1.4% (1/70); the rate of hospitalization in the intensive care unit was 0.25% (1/400); and the death rate was 0.05% (1/2000). These rates were highest for people > 18 years and lowest for children 5-17 years. On the basis of these numbers, the investigators speculated that the death toll is comparable to most influenza seasons, but there have been many more deaths in young adults.