02 September 2009

Novel A (H1N1) Influenza Virus Medical and Clinical Issues for Epidemiologists

The following list of recommendations and resources was compiled by Larissa May, MD, MSPH, for the Global Outreach Committee's blog series on the Novel A (H1N1) influenza virus.

***All recommendations are based on CDC and WHO guidelines and are based on the current relatively mild disease noted in patients in the developed world. These recommendations are subject to ongoing review and change. In the event of increased virulence of the novel A (H1N1) strain, or changes in morbidity and mortality, or regional variations in pattern of disease, recommendations are likely to change.***

Clinical Features:

Novel Influenza A (H1N1) presents in a similar fashion to seasonal influenza. Symptoms include fever, cough, sore throat, nasal congestion, myalgias, headache, chills, and fatigue/malaise. 25% of persons, including adults, may have GI-related symptoms, including vomiting and diarrhea (CDC, 2009) (Dawood F et al, 2009).


Clinicians should consider testing persons with ILI who are severely ill or at risk of influenza-related complications. In the event of a pandemic, the diagnosis of influenza will typically be made clinically by the treating provider, and most information on viral strains will be available through laboratory-based surveillance mechanisms. CDC is no longer recommending testing of all persons with suspected influenza infection.


Seasonal Influenza:
This year, the CDC’s Advisory Committee on Immunization Practices (ACIP) has extended the recommendations for annual seasonal influenza vaccination to include those individuals 6 months to 18 years of age, in addition to the traditional target groups:
• Healthcare workers
• Individuals greater than 65 years of age
• Individuals with comorbidities such as asthma, cardiopulmonary disease, chronic neurological issues, and immune suppression.
(CDC ACIP, 2009)

Novel A (H1N1) Influenza:

While a novel Influenza A (H1N1) vaccine is currently undergoing clinical trials, the expected dates for distribution are unknown due to uncertainty in clinical trial completion dates and time required for manufacture. In the event of a pandemic due to the novel Influenza A (H1N1) strain, in the United States it is likely the vaccine will be distributed via public health authorities through special allocation. Requirements for vaccine administration are yet to be finalized regarding the possibility of concurrent administration of seasonal and H1N1 vaccines and number of doses required. The ACIP is expected to revise their recommendations before the 2009-2010 influenza season. Currently, in terms of prioritization, the focus is on schools grades K-12, pregnant women, children 6 months to age 4, household contacts of infants less than 6 months, those under 65 at risk for severe influenza, and health care workers and first responders (CDC, 2009).

Treatment Recommendations:
Persons at risk are:
• Children younger than 5
• Persons aged 65 or older
• Children and young adults under 18 on long term aspirin therapy
• Pregnant women, adults and children with asthma
• Chronic pulmonary, cardiovascular, hepatic, hematologic, neurologic/neuromusuclar or metabolic disorders including diabetes)
• Adults and children with immunosuppression (includes HIV and immune suppressive medications)
• Residents of nursing homes or other long term care facilities.

Antiviral Medications:

According to the CDC, antiviral medications with activity against influenza are useful adjuncts in the prevention and early treatment of influenza (CDC ACIP, 2009).

Four antiviral agents are currently FDA licensed: amantadine, rimantadine, zanamivir, and olsetamivir. During the 2007-2008 and 2008-2009 influenza seasons, influenza A (H1N1) viruses with a mutation conferring resistance to olsetamavir commonplace in United States (99% resistance rate) and other countries (Lackenby et al, 2008; Meijia et al, 2009; WHO, 2009, CDC, 2008). However, the novel A (H1N1) strain has shown susceptibility to olsetamivir (Dharan et al, 2009).

During the novel A (H1N1) outbreak in May 2009, CDC published interim guidelines for treatment and prophylaxis of influenza in patients diagnosed with the novel H1N1 virus (CDC H1N1 Recommentations).

These guidelines recommend that all hospitalized patients with confirmed, probable or suspected H1N1 and persons at high risk for complications be treated with antiviral agents. Clinical judgment should be reserved for others on a case by case basis. Either olsetamivir or zanamivir may be used for treatment or prophylaxis. Chemoprophylaxis is recommended for close contacts of influenza cases who are at high risk, including healthcare workers, first responders and public health workers. Post exposure prophylaxis should be continued for ten days beyond the date of last exposure. Pre-exposure prophylaxis can be considered for persons at high risk who cannot avoid contact with an individual with influenza, i.e. caregivers of persons with influenza who are in high-risk categories. For ongoing occupational risk, temporary reassignment for persons at risk is recommended, or the use of personal protective equipment where exposure cannot be avoided. Consultation with local public health and medical experts is recommended (CDC, 2009).

Infection Control in Healthcare Settings:

CDC guidelines for contact and droplet precautions should be followed. Routine cleaning and disinfection protocols should be followed. In the event that a high risk procedure is undertaken (i.e. elective intubation, aerosol generating procedures such as the administration of nebulized medications, etc), airborne isolation in a negative pressure room with 6 to 12 air changes per hour should be instituted. If patients must be transported outside the room, a surgical mask should be placed on the patient. Although there is little evidence that use of an N95 respirator provides improved protection over a surgical mask, CDC is recommending all healthcare workers entering the room of a patient with influenza wear an N95 or equivalent respirator and be fit tested. Isolation precautions should be continued for 7 days or until symptoms resolve, whichever is longer. Healthcare workers in high risk categories should consider temporary reassignment, or if this is not possible, the use of a respirator. If a healthcare worker shows signs and symptoms of ILI, they should self-isolate at home and not return to work for 7 days or until symptoms resolve, whichever is longer (CDC Infection Control Guidelines).

Self-Isolation of Ill Persons with ILI:
Persons with ILI suspected of having influenza should self-isolate at home. They should separate themselves from other members of the household, particularly those at risk of developing complications of influenza, such as: infants under 6 months of age, the elderly, and those with comorbidities such as cardiopulmonary disease, diabetes, or immunosuppression. They should not return to work or school until 24 hours after resolution of fever or symptoms, whichever is longer. This is a change from the initial recommendation to stay away from others for 7 days (CDC Home Care Guidance) (CDC Exclusion Guidelines).

Use of Masks in the Non-Healthcare Setting:

For persons ill with confirmed, probable or suspected novel A (H1N1) (in the event of a pandemic, anyone with ILI), self isolation at home is recommended. Ill persons should stay at least 6 feet away from healthy individuals. Where this is not possible and in common areas of the home, the person should wear a facemask if tolerable, or tissue to cover their cough and sneeze. Persons at increased risk of severe illness due to influenza should avoid being the caregiver to a person with ILI. If unavoidable, they should consider the use of a facemask or respirator. Otherwise, routine use of masks by household contacts is not recommended.

For non-healthcare occupational settings, facemasks and respirators are not generally recommended, although they can be considered in those at risk of severe influenza where temporary reassignment is not possible (CDC Mask Recommendations).

Preparedness for H1N1:

United States: pandemicflu.gov
International: WHO Pandemic Preparedness

• Updates:
CDC International Situation Update
CDC Situation Update
• Guidance: CDC H1N1 Guidance

H1N1 General Information

CDC Interim Guidance on Antiviral Recommendations for Patients with Novel Influenza A (H1N1) Virus Infection and Their Close Contacts

Dawood FS, Jain S, Finelli L, et al. Emergence of a Novel Swine-Origin Influenza A (H1N1) Virus in Humans. NEJM 2009; 361:1-10.

Fiore AE. Shay DK. Broder K, et al. Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices. MMWR 2009: (58 Early Release): 1-52.

Dharan NJ, Gubavera LV, Meyer JJ, et al. Olsetamivir Working Group. Infections with Olsetamivir-Resistant Influenza A (H1N1) Virus in the United States. JAMA 2009; 301 (10): 1034-41.

About the Author:

Larissa May, M.D., M.S.P.H.
Associate Director of Clinical Research
Assistant Professor, Emergency Medicine,Microbiology, and Epidemiology
Co-director, MS in Public Health Microbiology and Emerging Infectious Diseases
The George Washington University
Washington, D.C.

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