1. 1918 influenza victims crowd an emergency hospital at Fort Riley, Kansas.

2. Influenza Update Best Practices
Jason Cohen, MD
Assistant Professor of Internal Medicine
Hospitalist Section
10/30/09

3. Goals of Presentation Review basic science of influenza.
Discuss status of current influenza outbreak and its historical context.
Propose referral, admission, treatment and discharge criteria for patients with influenza-like illness.

4. What is Influenza Virus of the Orthmyxoviridae family.
Genome consists of 8 single-stranded RNA segments.
Designation of influenza viruses as A, B or C based on characteristics of nucleoprotein and matrix protein antigens. The most severe and extensive outbreaks have been caused by influenza A viruses.
Influenza A further subdivided based on surface antigens - Hemagglutinin (H) and Neuraminidase (N).

5. H what, n what?
Three major antigenic subtypes of Hemagglutinin (H1, H2, H3) and two major subtypes of Neuraminidase (N1, N2)recognized in human infection.
Hemagglutinin allows virus to bind and enter the cell.
Neuraminidase allows virus to exit cell and spread infection.
Antibodies to Hemagglutinin determine immunity, while those to Neuraminidase limit viral spread and contribute to reduction of infection.
Minor changes in Hemagglutinin and Neuraminidase occur through antigenic drift, while major variations are the result of antigenic shift pandemic a result of antigenic shift from H1N1 to H2N2.

6. 16 subtypes of Hemagglutinin and 9 subtypes of Neuraminidase circulate in wild and domestic bird populations

7. Is this the same h1n1 that killed 30 million people in 1918?
Yes and No. It has the same Hemagglutinin and Neuraminidase proteins on its outside, but is a different strain. The strain that caused the 1918 pandemic was able to infect pigs but not kill them. The virus adapted to the pigs and is thought to have contributed to the current lineage of H1N1 “swine” influenza. The current virus has two genes from viruses that normally circulate in pigs, and avian and human genes (a “quadruple reassortant virus.”) The new H1N1 is missing a particular amino acid that is believed to increase the virulence of the virus.

8. Match the flu
1) Spanish Flu a) Pandemic of ) Avian Flu b) H3N2 3) Asian Flu c) Pandemic of ) Hong Kong Flu d) H5N1 5) Russian Flu e) Pandemic of 1957

9. The Typical Flu Season... Runs from November thru May.
Contributes to somewhere around 200,000 hospitalizations.
Is responsible for 36,000 deaths.
60% of hospitalization typically occur in those over 65.

10. Where are we now?
Between August 30th and October 17th, 8,204 laboratory-confirmed hospitalizations for H1N1 in the United States.
During same time period, 411 laboratory-confirmed H1N1 deaths.
Over half of hospitalizations (53%) for H1N1 have occurred in people under the age of 25.
One-third of deaths have been in people years old, and one-third in patients age In a typical flu season, 90% of deaths are in patients over age 65.
CDC reports that from 8/ /17 they received reports of 21,823 hospitalizations and 2,416 deaths, with 8,204 hospitalizations and 411 deaths laboratory-confirmed.

11. Percentage of Visits for Influenza-like Illness (ILI) Reported by the U.S. Outpatient Influenza-like Illness Surveillance Network (ILINet), National Summary and Previous Two Seasons (Posted October 23, 2009, 5:30 PM ET, for Week Ending October 17, 2009)

12. Where are we headed?
Latest CDC update showed a continued increase in the number of reported cases of H1N1 and visits to physicians and hospitals.
Number of visits, hospitalizations, and deaths all higher than what would be expected for this time of year.
At UNMH, 38 patients on expanded droplet precautions (17 with confirmed H1N1.)
Half of ICU beds taken up by H1N1 patients (almost all on ventilators.)
UNMH has seen a decrease over the last week in the number of visits to the flu clinic (peaked at 60 visits/day, currently at visits/day.)

13. Still can’t decide what to wear to the Halloween Party?

14. Vaccination Recommendations
The CDC recommends that the following groups be prioritized for receipt of the H1N1 vaccine as it becomes available:
pregnant women
people who live with or care for children younger than 6 months of age
health care and emergency medical services personnel with direct patient contact
children 6 months through 4 years of age
children 5 through 18 years of age who have chronic medical conditions
*As of October 16, 2009, the CDC predicts that there will not be a shortage of vaccine (though supply may be unpredictable.)

15. Diagnosis of H1N1
Symptoms: fever (95%), headache, cough (88%), sore throat, myalgias, chills, malaise, runny nose - and in the case of H1N1, diarrhea and vomiting (39%).
ILI is defined as fever (temperature of 100°F [37.8°C] or greater) and a cough and/or a sore throat in the absence of a known cause other than influenza.
Patients with symptoms of uncomplicated influenza do not require diagnostic testing for clinical management.
45% under 18, 5% over 65 (typically over 60% of hospital admissions in a typical year)
45% had elevation of AST/ALT
73% had an underlying chronic condition (asthma, neuromuscular disease, heart disease, pregnancy)
Prevalence of obesity in the study population comparable to U.S. population - but higher number of morbidly obese. Not enough data to make conclusion about obesity as independent risk factor for hospitalization or complication

16. Clinical Testing
Rapid influenza diagnostic tests are reactive with the nucleoprotein of H1N1, but lack sensitivity ( %)
Positive results of RIDTs may be used to guide therapy (high specificity) but negative results should be interpreted with caution.
The CDC recommends that rRT-PCR testing should be performed when definitive determination of influenza infection is necessary.
See for Interim Guidance for the Detection of Novel Influenza A Virus

17. When is PCR testing necessary?
Hospitalized patients with suspected influenza
Patients for whom a diagnosis of influenza will inform decisions regarding clinical care, infection control, or management of close contacts.
Patients who died of an acute illness in which influenza was suspected.
See further recommendations at

18. Who Requires Hospitalization?
No clear guidelines from the CDC.
NHS published an algorithm suggesting that the following criteria be met for discharge from the ER:
1) Absence of respiratory distress
2) Respiratory rate ≤ 30
3) SpO2 ≥ 92% on room air
4) No evidence of dehydration
5) Tolerating oral fluids

21. Cohorting of H1N1 patients
The CDC recommends single-patient rooms when available, prioritizing patients with excessive cough or sputum production.
If necessary, okay to cohort patients that are infected with the same organism.
If necessary to place a patient on droplet precautions with a patient who does not have the same infection, avoid placement with immunocompromised patients or patients at high risk for complications.
Assure patients are at least 3 feet apart and keep curtain pulled between patients.

22. Isolation of H1N1 patients
The CDC continues to recommend use of N95 masks despite recent studies that suggest the non-inferiority of surgical masks. UNMH has made the decision to use surgical masks.
Where there is a high risk for aerosolization of respiratory secretions (intubation, bronchoscopy,) N95 masks are appropriate.
Non-sterile gloves should be worn when contact with potentially infectious materials is anticipated.
Isolation precautions for patients who have influenza symptoms should be continued for the 7 days after illness onset or until 24 hours after the resolution of fever and respiratory symptoms, whichever is longer, while a patient is in a healthcare facility.

23. Treatment of hospitalized patients with H1N1
Oseltamivir 75mg po BID for 5 days
In patients who are persistently febrile, oseltamivir may be continued for a longer duration.
Patients with chest x-ray abnormalities should be treated with antibiotics for community-acquired or healthcare-associated pneumonia, as appropriate.
Peramivir available through clinical trial (Drs. Goade and Kellie) and emergency use authorization from FDA.

24. When to treat with oseltamivir
UNMH Infection Control has recommended treating all patients admitted with respiratory infections or exacerbations of chronic respiratory conditions.
Data suggests that earlier treatment improves outcomes - do not delay initiation of oseltamivir while awaiting rRT-PCR results.
Treat patients regardless of the duration of their symptoms. Hospitalized patients may benefit even if therapy is started more than 48 hours after onset of symptoms.

25. Still undecided? Consider the old standbys.

26. Proposed Admission Order Set

27. Proposed discharge criteria for H1N1
Afebrile for ≥ 24 hours.
Able to tolerate PO.
Stable or decreasing oxygen requirement of 4 liters or less with ambulation.

28. Follow-up Care
Patients with chronic medical conditions should be seen by a healthcare provider within 5-10 days following discharge.
Patients without significant comorbidities do not require routine follow-up.
Patient found to have abnormal chest x-ray findings during hospitalization should have repeat chest x-ray in 4-6 weeks following discharge to document resolution.

29. Treatment modalities are limited
Treatment modalities are limited. Hospitalization and complications are high. Defense is the best offense. Wash your hands. Get Vaccinated.

30. References
Faix DJ, Sherman SS, Waterman SH. Rapid-Test Sensitivity for Novel Swine-Origin Influenza A (H1N1) Virus in Humans. N Engl J Med Jun 29 Hurt AC et al. Performance of influenza rapid point-of-care tests in the detection of swine lineage A(H1N1) influenza viruses. Influenza and Other Respiratory Viruses 2009;3(4): Thompson WT et al. Influenza-Associated Hospitalizations in the United States. JAMA 2004;292: Loeb M et al. Surgical Mask vs N95 Respirator for Preventing Influenza Among Health Care Workers. JAMA. 2009;302(17):(doi: /jama ). Harrison’s Principles of Internal Medicine, 15th edition. Bar SA, Herrington JD, Busti AJ, et al. Is oseltamivir effective if administered greater than 48 hours after the onset of flu-like symptoms from the swine-origin influenza A (H1N1) viral infection? PW Pharmacother Newsl 2009;1(23):1-4. McGeer A, Green KA, Plevneshi A et al. Antiviral therapy and outcomes of influenza requiring hospitalization in Ontario, Canada. Clin Infect Dis 2007;45; Jain S et al. Hospitalized Patients with 2009 H1N1 Influenza in the United States, April-June NEJM. 2009;361(epub ahead of publication.) Interim Recommendations for Clinical Use of influenza Diagnostic Tests During the Influenza Season. Interim Guidance for the Detection of Novel Influenza A. Swine flu clinical package for use when there are exceptional demands on healthcare services. Department of Health, United Kingdom.