Questions and Answers on Pandemic (H1N1) 2009 Influenza: The illness and Antiviral Drugs

Information on the Pandemic Illness

• How is it possible to prevent Pandemic (H1N1) 2009 infection and disease in newborn infants and in the nursery? (Added December 11, 2009)
• Can a mother transmit Pandemic (H1N1) 2009 infection to her newborn at the time of delivery? (Added December 11, 2009)
• How should the infant of a Pandemic (H1N1) 2009 infected mother be cared for at the time of and immediately after delivery? (Added December 11, 2009)
• What precautions should be followed for ongoing, continued care of mother and the infant? (Added December 11, 2009)
• What are the symptoms of seasonal influenza and the Pandemic (H1N1) 2009 influenza?
• What are some of the more important, yet rare complications of Pandemic (H1N1) 2009?
• When should clinicians suspect myocarditis?
• What underlying conditions place children and youth at higher risk of a serious outcome from Pandemic (H1N1) 2009 influenza?
• How is Pandemic (H1N1) 2009 virus different from seasonal influenza virus?
• Which children should be tested for influenza?

Information on Antiviral Drugs

• What influenza antiviral drugs are available?
• How effective are antiviral drugs at preventing influenza?
• Can children take antiviral drugs?
• Which anti-viral drugs are useful for Pandemic (H1N1) 2009?
• What are the recommendations for the use of antiviral drugs in young children?
• What are the side effects of antiviral drugs in children?
• Who doesn’t generally need treatment with influenza antiviral drugs?
• When should treatment with antiviral drugs be started?
• What can be done to reduce delays in antiviral treatment?
• What is the usual duration of treatment with antiviral drugs?
• Which children should be receiving an antiviral if they are exposed to suspected or proven Pandemic (H1N1) 2009?
• Can antiviral drugs be helpful for people unable to take the flu vaccine?
• What is the treatment of choice for pregnant women with suspected or confirmed Pandemic (H1N1) 2009 infection?
• What should we use for treatment if there is co-circulation of Pandemic (H1N1) 2009 and seasonal influenza A?
• What is the role of antibacterial therapy in patients with Pandemic (H1N1) 2009?
• Table 1. Dosage guidelines for oseltamivir (Tamiflu®) in infants, children and youth
• What if there is no oral suspension (liquid formulation) and there are no pediatric doses of oseltamivir (Tamiflu®) capsules available?
• Table 2. Dosage guidelines for zanamivir (Relenza®) in children and youth

Additional Reading and Useful Links

• General Information about Influenza
• Influenza Antiviral Information
• Influenza Vaccine Information

Appreciation

How is it possible to prevent Pandemic (H1N1) 2009 infection and disease in newborn infants and in the nursery? (Added December 11, 2009)
Note: At this time there is limited information on risk of transmission of H1N1 2009 to an infant. However, the Centers for Disease Control and Prevention (CDC) in the United States recently published guidelines on what they considered best practice for the US. A summary of this information and practical points from Canadian experts is provided below. The Public Health Agency of Canada (PHAC) plans to publish guidelines regarding management of neonates and pregnant woman during labor, and delivery. Other professional groups may also publish guidelines. The CPS Questions and Answers on this topic will be updated as additional information becomes available.

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Can a mother transmit Pandemic (H1N1) 2009 infection to her newborn at the time of delivery? (Added December 11, 2009)
There is a possibility of postpartum transmission from a mother with H1N1 2009 infection to her newborn via small particle aerosols or droplet exposure to newborn mucosal surfaces. Inoculation of newborn mucosal surfaces can also occur from caregivers, healthcare providers, or siblings.

Risk to the newborn is increased because of their immature immune system and need of constant close contact.

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How should the infant of a Pandemic (H1N1) 2009 infected mother be cared for at the time of and immediately after delivery? (Added December 11, 2009)
The priority is to minimize the infant's risk of exposure to droplets. The infant is considered to be exposed rather than infected after delivery.

 Intrapartum (Labor/Delivery/Recovery): Health Care workers should follow standard infection control practices for H1N1 2009 infection for confirmed cases or Influenza-like illness. Place a surgical mask on the ill mother during labor and delivery, if tolerated. Treat the mother with antiviral medication (Oseltamavir or Zanamavir) as soon as possible. Bathe the infant early, and consider the infant exposed, not infected, unless otherwise clinically indicated.
 
Postpartum: Manage the mother in the acute care setting according to your hospital’s or PHAC’s pandemic H1N1 2009 infection control guidance for the acute care setting. http://www.phac-aspc.gc.ca/alert-alerte/h1n1/hp-ps/ig_acf-ld_esa-eng.php. The infant may be cared for in the same room as the mother in an isolette, if available. Other options include placing the infant behind a curtain and in a bassinette at more than 2 meters from the mother.  While still in hospital, the infant will need to be managed as being “exposed” to H1N1 2009 for the first 96 hours of life. Over this time, precautions as outlined by PHAC (see above) will be needed, thus care in a normal full-term nursery may not be feasible. If the infant is suspected of having H1N1 2009 infection, the infant should be isolated.

The infant should only be fed by a healthy mother or caregiver. Since use of oseltamivir by the mother is not a contraindication to breast milk feeding, she should be encouraged and supported to breastfeed. This may include assistance to express breast milk if it is not safe for direct contact with the baby.

The mother can initiate contact and direct feeding of her baby if her symptoms have abated and her cough and secretions can be covered and controlled. In order to further minimize the risk of transmission of infection to the baby, some clinicians prefer to limit direct feeding by the mother for the first 72 hours of her antiviral therapy.

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 What precautions should be followed for ongoing, continued care of mother and the infant? (Added December 11, 2009)
The mother (and other symptomatic family members) should adhere to strict hand hygiene, wear a face mask, and use respiratory hygiene and cough etiquette for 7 days after symptom onset and symptom-free for 24 hours, whichever is longer. Limit visitors to healthy persons necessary for the family's emotional well-being and care.

Newborn care: Consider the infant exposed, not infected, unless otherwise clinically indicated.  Prophylactic use of antivirals in infants <3 months is not recommended. Antiviral treatment in cases of suspected infection with H1N1 2009 is authorized under Emergency use authorization for infants <1 year of age. (See Table 1. Dosage guidelines for oseltamivir, CPS Q and A on antivirals)

Discharge planning: The family needs to be instructed on newborn care at home, including strict hand hygiene, cough etiquette, limiting ill contacts to the newborn. Caregivers, including family members, daycare providers and siblings over 6 months of age should be instructed to receive H1N1 2009 vaccine. Caregivers need to be educated on the signs and symptoms of infant infection and steps to take if any are observed.

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What are the symptoms of seasonal influenza and the Pandemic (H1N1) 2009 influenza?
The symptoms of seasonal and H1N1 2009 influenza include fever, cough, sore throat, runny or stuffy nose, body aches, headache, chills and fatigue. Some people may also have vomiting and diarrhea. Some people may be infected with the flu, including H1N1 2009, and have respiratory symptoms without a fever.

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What are some of the more important, yet rare complications of Pandemic (H1N1) 2009?
The complications of H1N1 2009 can be classified as pulmonary and non-pulmonary.

Pulmonary Complications:

• Severe hemorrhagic viral pneumonia.
• Secondary bacterial pneumonia (due to group A streptococcus, Staphylococcus aureus, and Streptococcus pneumoniae).
• Mixed viral and bacterial pneumonia.
• Localized viral pneumonia.
• Severe laryngotracheobronchitis (croup).
• Exacerbation of chronic pulmonary disease.

Non-pulmonary Complications

• Acute myositis.
• Myocarditis or pericarditis.
• Toxic shock-like picture (due to invasive secondary bacterial sepsis).
• Encephalitis / encephalopathy.
• Reye’s syndrome.
• Gullain  Barré syndrome.

All of the above complications should be considered by front line clinicians in patients presenting with the appropriate clinical findings. Clinicians should pay particular attention to clinical deterioration during the course of illness, or after initial recovery as evidenced by:

• New onset of fever.
• Shortness of breath.
• Unexplained chest or abdominal pain.
• Lethargy or a change in level of consciousness.

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When should clinicians suspect myocarditis?
Some conditions require special consideration since the initial management may be different. (e.g., fluid resuscititation of patients with myocarditis).

In order to distinguish patients with myocarditis from other conditions, clinicians should look for the following:

• Tachycardia and hypotension disproportionate to the underlying illness.
• Presentation with a shock like picture, particularly fluid refractory shock – defined in the literature as the requirement for > 60 mls/kg to achieve haemodynamic stability.
• Cardiomegaly on chest x-ray.
• Unexplained metabolic acidosis or lactic acidosis.

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What underlying conditions place children and youth at higher risk of a serious outcome from Pandemic (H1N1) 2009 influenza?

• Neurological disorders, such as:
  • Epilepsy or cerebral palsy, especially when accompanied by neurodevelopmental disabilities (eg. moderate to profound intellectual disability [mental retardation] or developmental delay).
  • Neuromuscular disorders (eg, muscular dystrophy), when associated with impairment in respiratory functioning.

• Chronic respiratory diseases associated with impaired pulmonary function and/or difficulty handling lung secretions; moderate and especially severe persistent asthma; technology-dependent children (eg, those requiring oxygen, tracheostomy, or a ventilator).
  
  
• Moderate to profound intellectual disability (mental retardation) or developmental delay, especially when associated with other specific conditions (see above).

• Deficiencies in immune function or conditions that require medications or treatments (eg, certain cancer treatments) that result in significant immune deficiencies.

• Congenital heart disease or significant metabolic or endocrine disorders, especially if a child has specific respiratory conditions (see above).
  
  
• Renal, hepatic, hematological (including sickle cell disease) disorders.
  
  
• Receiving chronic aspirin therapy.
  
  
• Pregnancy or up to 2 weeks post-partum regardless of how the pregnancy ended.

(Adapted from the AAP website ‘Novel Influenza A (H1N1) Virus and Children with Underlying Medical Conditions - AAP Work Group Clarifies Children at Highest Risk – October 1, 2009)

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How is Pandemic (H1N1) 2009 virus different from seasonal influenza virus?
Seasonal influenza viruses in circulation since 1977 have been A H3N2, A H1N1 and B. Although the H1N1 2009 strain shares H and N antigens with the seasonal H1N1 strain, these are sufficiently different in that seasonal H1N1 does not induce immunity to the H1N1 2009 strain.  The H1N1 2009 strain has new antigenic components derived from swine and avian influenza as well as human influenza virus.  An important difference is that while H1N1 2009 influenza is sensitive to oseltamivir, seasonal H1N1 is not. On the other hand, seasonal H1N1 is sensitive to amantadine while the H1N1 2009 strain is not. Both are sensitive to zanamivir.

Which children should be tested for influenza?
In the early stages of the outbreak, children who warrant treatment with an antiviral drug, either because of severe influenza or an underlying health condition, should be tested. This is to avoid extensive use of antivirals for children with viral infections other than influenza, as widespread use may induce resistance. If results are not available within 24 hours, empiric treatment could be started and discontinued if another virus is identified. If or when it becomes clear that in the region the vast majority of viruses isolated from children with febrile respiratory illness are H1N1 2009, testing is no longer warranted. In general, testing is not indicated if the child is not to be treated, although there may be exceptional circumstances where the information will be required. Sending all children with febrile respiratory illnesses for testing will provide further opportunities for transmission and overwhelm the capacities of the diagnostic laboratories.

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What influenza antiviral drugs are available?
Influenza antiviral medications are prescription drugs (pills, liquid or oral inhalation powder) that decrease the ability of influenza viruses to reproduce and spread from cell to cell. While getting an influenza vaccine each year is the first and most important step in protecting against influenza, antiviral drugs are a second line of defense in the treatment and prevention of influenza. This document focuses on the commonly used agents, oseltamivir and zanamivir. A third agent, peramivir-intravenous, has recently received emergency use authorization in the USA. It can only be made available through 'special access' programs in the US. Reference is made to peramvir-intravenous for completeness sake. An intravenous form of zanamivir may be available through the special access program in Canada (tel. 613-941-2108).

How effective are antiviral drugs at preventing influenza?
It’s important to remember that influenza antiviral drugs are not a substitute for getting an influenza vaccine or for using infection control measures including proper hand hygiene. However, when used to prevent influenza, antiviral drugs are about 70% to 90% effective against susceptible viruses (i.e., viruses that are not resistant to the antiviral medication).

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Can children take antiviral drugs?
Yes. The two drugs recommended for use against influenza this season can be used in children. (See Table 1)

• Oseltamivir (Tamiflu®) comes in an oral suspension (liquid) for children and in capsules for older children and adults.
• Zanamivir (Relenza®) is an inhaled powder that comes with a disk inhaler and is only recommended for older children and adults.

Which antiviral drugs are useful for Pandemic (H1N1) 2009?
Almost all isolates are susceptible to the oral drug oseltamivir. All isolates are susceptible to zanamvir, but this drug is available only as a diskhaler so it is difficult to administer to children under age 10 years. There are shortages of zanamivir and of pediatric preparations of oseltamivir in some parts of Canada.

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What are the recommendations for the use of antiviral drugs in young children?
Treatment is recommended for all children who are hospitalized with suspected or confirmed H1N1 2009 infection.

For ambulatory patients, most experts advise that early empiric treatment should be considered for children < 2 years of age and those with chronic medical conditions (http://www.phac-aspc.gc.ca/alert-alerte/h1n1/guidance-orientation-amb-07-16-eng.php).

Children aged 2 years to 4 years without high risk conditions and with mild illness do not necessarily require antiviral treatment. While children 2 years to 4 years old are more likely to require hospitalization or urgent medical evaluation for influenza compared with older children and adults, the risk is much lower than for children younger than 2 years old.

The reason for not treating all infected children is that most children who are otherwise healthy recover without the need for antiviral treatment. In addition, there is the concern that widespread use of antiviral agents could increase the risk of the virus becoming resistant to the only two effective antivirals that are available. Providers should use clinical judgment to guide treatment decisions for healthy children.

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What are the side effects of antiviral drugs in children?
Reported side effects of oseltamivir are nausea and vomiting. Among children treated with oseltamivir in clinical studies, 14% had vomiting, compared with 8.5% of children getting a “placebo.” Nausea and vomiting might be less severe if oseltamivir is taken with food. In addition, there have been reports of self-injury or delirium among persons with influenza who take oseltamivir. However it has not been established if the drug was responsible for these events. Most of these reports have been in teenagers from Japan. The U.S. Food and Drug Administration advises that people taking either of the two medications recommended for influenza (oseltamivir and zanamivir) be monitored closely for abnormal behavior.

Side effects from zanamivir have been reported in fewer than 5% of people participating in clinical trials and have been reported at the same rate in people receiving zanamivir as those being given a “placebo.”

As zanamivir is given by inhalation, the major side-effect is that it can induce bronchospasm. Zanamivir should not be used in people with underlying respiratory disease, including asthma. Allergic reactions have also been reported.

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Who doesn’t generally need treatment with influenza antiviral drugs?
Treatment with influenza antiviral drugs is generally not needed for people who are not at high risk for complications or do not have severe influenza. However, any suspected influenza patient who presents with emergency warning signs (for example, difficulty breathing or shortness of breath) or signs of lower respiratory tract illness or worsening illness should seek medical care promptly to receive antiviral therapy when indicated.

Doctors may treat some people who are not in a high risk group based on their clinical judgment. In addition, doctors also may decide that treatment is not needed for some who are in a high risk group based on their clinical judgment.

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When should treatment with antiviral drugs be started?
Once the decision to administer antiviral treatment is made, treatment with zanamivir or oseltamivir should be initiated as soon as possible after the onset of symptoms. Evidence for benefits from antiviral treatment in studies of seasonal influenza is strongest when treatment is started within 48 hours of illness onset. However, some studies of oseltamivir treatment of hospitalized patients with seasonal influenza have indicated benefit, including reductions in mortality or duration of hospitalization even for patients whose treatment was started more than 48 hours after illness onset. Thus, individuals with severe influenza illness should receive antiviral treatment even if they present to hospital at > 48 hours after the onset of their illness.

When treatment is indicated, health care providers generally should not wait for laboratory confirmation of influenza to begin because laboratory testing can delay treatment and because a negative rapid test for influenza does not rule out influenza. The sensitivity of rapid influenza diagnostic tests (DFA) can range from 10-70% for H1N1 2009 virus.

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What can be done to reduce delays in antiviral treatment?
Clinicians can take several actions to reduce delays in antiviral treatment initiation. These include:

1. Informing people at higher risk for influenza about complications of the signs and symptoms of influenza and the need for them to get treated early.
2. Ensuring quick access to telephone consultation and clinical evaluation for these patients as well as patients who report severe illness.
3. Considering empiric treatment of patients at higher risk for influenza complications based on telephone contact if hospitalization is not indicated and if this will substantially reduce delay before treatment is initiated.

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What is the usual duration of treatment with antiviral drugs?
The recommended duration of treatment is five days. However, hospitalized patients with severe infections might require longer treatment courses.

Which children should be receiving an antiviral if they are exposed to suspected or proven Pandemic (H1N1) 2009?
Most experts recommend early therapy rather than prophylaxis because of the risk of precipitating viral resistance. Systems should be in place to enable exposed high-risk children to contact their health care provider and receive therapy on an urgent basis at the onset of symptoms. However, it would be reasonable to offer prophylaxis to the very high risk children who have had close contact with H1N1 2009, especially if provisions for early therapy presents logistical problems.

For children, close contact is defined as having lived with a person with H1N1 2009. Close contact usually does not include activities such as walking by an infected person or sitting across from a symptomatic person in a waiting room or office.

Post-exposure prophylaxis is discouraged for prevention of illness in healthy children or adults after potential exposure in community, school, camp or other settings. In addition to concerns about resistance, there are no safety data regarding long term or frequent use of antiviral agents in children, and limited data for healthy adults.

Pre-exposure antiviral chemoprophylaxis should only be used in limited circumstances, such as outbreak control in a closed setting, and in consultation with local medical or public health authorities.

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Can antiviral drugs be helpful for people unable to take the flu vaccine?
Yes. Experts recommend use of antiviral drugs for people allergic to eggs (which can cause them to have an allergic reaction to the vaccine) or for people who previously have encountered complications from Guillain-Barré syndrome (GBS) associated with influenza vaccination. In addition, taking antiviral drugs may be recommended among persons that may not have a good immune response to the flu vaccine.

What is the treatment of choice for pregnant women with suspected or confirmed Pandemic (H1N1) 2009 infection?
Oseltamivir and zanamivir are "Pregnancy Category C" medications, indicating that no clinical studies have been conducted to assess the safety of these medications for pregnant women. Pregnancy should not be considered a contraindication to oseltamivir or zanamivir use. Because of its systemic activity, oseltamivir is preferred for treatment of pregnant women.

What should we use for treatment if there is co-circulation of Pandemic (H1N1) 2009 and seasonal influenza A?
Further guidance will be provided depending on the nature of co-circulating seasonal influenza A. Seasonal H1N1 was largely resistant to oseltamivir but sensitive to amantadine and zanamivir.

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What is the role of antibacterial therapy in patients with Pandemic (H1N1) 2009?
Secondary bacterial infections may complicate H1N1 2009 infection. Clinicians should be aware of this possibility. Routine antibiotics are not needed. However, in the case of a secondary fever or secondary deterioration, thought must be given to a secondary bacterial infection and treatment with anti pneumococcal and anti staphylococcal antibiotics may be warranted.

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Table 1. Dosage guidelines for oseltamivir (Tamiflu®) in infants, children and youth

References:

1. United States (FDA). http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafety
   InformationforPatientsandProviders/ucm183870.htm
2. Europe (EMEA),  http://www.emea.europa.eu/humandocs/PDFs/EPAR/tamiflu/Tamiflu_PI_clean_en.pdf
3. United States (CDC), http://www.cdc.gov/h1n1flu/recommendations_pediatric_supplement.htm
4. Canada (PHAC), www.phac-aspc.gc.ca/alert-alerte/h1n1/guidance-orientation-07-20-eng.php
   

Footnotes:
*  CAUTION: Dosage adjustment required in renal failure if creatinine clearance < 30 mL/min
# CAUTION: oral solution is prescribed in milligrams (mg) of solution (not milliliters, mL). Errors have been made when parents interpreted mg as mL. The dosing dispenser packaged with oseltamivir (Tamiflu®) has markings only in 30, 45 and 60 mg. This works well for those over 15 kg and over 1 year. If under 1 year or less than 15 kg, a ml dropper or ml oral syringe needs to replace the prepackaged dosing dispenser with clear instructions to the parent on mls prescribed. 

Note: Dosage recommendations may be changed as new information becomes available. Please refer to reference sources for updates on dose recommendations. Current weight-based dosing recommendations are not intended for premature infants. Please seek consultation from an infectious disease clinician if treatment is being considered for such infants.

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What if there is no oral suspension (liquid formulation) and there are no pediatric doses of oseltamivir (Tamiflu®) capsules available?
In the absence of both oral suspension and pediatric capsules of oseltamivir (Tamiflu®), there is another option to meet the need for a pediatric prescription of oseltamivir (Tamiflu®). Adult dose (75 mg) capsules can be compounded by a pharmacist to create a pediatric formulation. Compounding is the mixing of drugs by a health care professional to fit the unique needs of a patient. The FDA in the US has a statement on their website at /www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm100228.htm to remind health care providers and pharmacists of the FDA-approved instructions for the emergency compounding of an oral suspension from oseltamivir (Tamiflu®) 75mg capsules as described in the FDA approved manufacturer package insert for oseltamivir (Tamiflu ®). Compounding an oral suspension from oseltamivir (Tamiflu®) 75mg capsules provides an alternative oral suspension when commercially manufactured oral suspension formulation is not readily available.

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Table 2. Dosage guidelines for zanamivir (Relenza®) in children and youth

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Additional Reading and Useful Links

General Information about Influenza

Canadian Paediatric Society (CPS), Infection control in paediatric office settings. www.cps.ca/english/statements/ID/id08-03.htm (Version current at May 4, 2009).

Canadian Paediatric Society (CPS). The New Influenza A Virus: A/Mexico/2009 (H1N1) Practice Point for Caregivers of Children and Youth. http://www.cps.ca/english/statements/ID/H1N1Mexico2009.htm

Public Health Agency of Canada (PHAC). www.fightflu.ca and 1-800 O-Canada (1-800-622-6232)  

US Center for Disease Control and Prevention (CDC), http://cdc.gov/h1n1flu/recommendations_pediatric_supplement.htm.

American Academy of Pediatrics (AAP), http://www.aap.org/new/AAP-Work-Group-CSHCN-H1N1-FINAL-10-1-09.pdf

US Centers for Disease Control and Prevention (CDC). Influenza-Associated Pediatric Mortality.  http://www.cdc.gov/flu/weekly/index.htm#MS  (Version current at October 15, 2009).

The ANZIC Influenza Investigators. Critical Care Services and 2009 H1N1 Influenza in Australia and New Zealand. N Engl J Med. 2009 [Epub ahead of print]

Bhat N, Wright JG, Broder KR, et al. Influenza-associated deaths among children in the United States, 2003-2004. N Engl J Med 2005;353:2559-67.

Chowell G, et al. Severe Respiratory Disease Concurrent with the Circulation with H1N1 Influenza. NRJM 2009;361:674-679.

Dodds L, McNeil SA, Fell DB, et al. Impact of influenza exposure on rates of hospital admissions and physician visits because of respiratory illness among pregnant women. CMAJ 2007;176:463-8.

ECDC Technical Emergency Team. Initial epidemiological findings in the European Union following the declaration of pandemic alert level 5 due to influenza A (H1N1). Euro Surveill. 2009;14(18):pii=19204

Izurieta HS, Thompson WW, Kramarz P, et al. Influenza and the rates of hospitalization for respiratory disease among infants and young children. N Engl J Med 2000;342:232-9.

Kumar A, Zarychanski R, Pinto R, et al. Critically Ill Patients With 2009 Influenza A(H1N1) Infection in Canada. JAMA. 2009 Oct 12. [Epub ahead of print]

Moore DL, Vaudry W, Scheifele DW, et al. Surveillance for influenza admissions among children hospitalized in Canadian Immunization Monitoring Program Active Centers. Pediatrics 2006;118:e610-19.

Rasmussen SA, Jamieson DJ, Bresee JS. Pandemic influenza and pregnant women. Emerg Infect Dis 2008;14:95-100.

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Influenza Antiviral Information

Canadian Paediatric Society (CPS), The use of antiviral drugs for influenza: Recommended guidelines for practitioners
http://www.cps.ca/english/statements/ID/ID06-04.htm

Public Health Agency of Canada (PHAC). Interim Guidance for emergency use of oseltamivir (Tamiflu in children under one year of age in the context of 2009 (H1N1) pandemic. http://www.phac-aspc.gc.ca/alert-alerte/h1n1/guidance-orientation-07-20-eng.php

Public Health Agency of Canada (PHAC). Guidance for Ambulatory Care of Influenza-Like Illness in the context of H1N1 influenza virus.
http://www.phac-aspc.gc.ca/alert-alerte/h1n1/guidance-orientation-amb-07-16-eng.php

US Center for Disease Control and Prevention (CDC), http://www.cdc.gov/h1n1flu/eua/peramivir.htm

US Centers for Disease Control and Prevention (CDC).
http://www.cdc.gov/h1n1flu/recommendations_pediatric_supplement.htm

US Food and Drug Administration (FDA), Public Health Alert: Potential Medication Errors with Tamiflu for Oral Suspension. http://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm183649.htm

American Academy of Pediatrics (AAP). Committee on Infectious Diseases.  Antiviral therapy and prophylaxis in influenza in children. Pediatrics 2007;119:852-860.

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Influenza Vaccine Information

Public Health Agency of Canada. Canadian Immunization Guide Seventh Edition – 2006. Part 4. Active Immunizing Agents. Influenza Vaccine.  http://www.phac-aspc.gc.ca/publicat/cig-gci/p04-inf-eng.php (Version current at October 15, 2009).

Institute of Medicine. Immunization safety review: influenza vaccines and neurological complications. http://books.nap.edu/openbook.php?record_id=10822 (Version current at October 15, 2009).

Carman WF, Elder AG, Wallace LA, et al. Effects of influenza vaccination of health-care workers on mortality of elderly people in long-term care: a randomized controlled trial. Lancet 2000;355:93-7.

Eisenberg  KA, Szilagyi PG, Fairbrother G, et al.Vaccine Effectiveness Against
Laboratory-Confirmed Influenza in Children 6 to 59 Months of Age During the 2003–2004 and 2004–2005 Influenza Seasons. Pediatrics 2008; 122 :911- 19.

Halasa NB, Gerber MA, Chen Q, Wright PF, Edwards KM. Safety and immunogenicity of trivalent inactivated influenza vaccine in infants. J Infect Dis 2008;197:1448-54.

Hviid A, Stellfeld M, Wohlfahrt J, Melbye M. Association between thimerosal-containing vaccine and autism. JAMA 2003;290:1763-6.

MacDonald NE. Riley LE, Steinhoff MC. Influenza immunization in pregnancy. Obstet Gynecol 2009;114:365-8.

Neuzil KM, Zhu Y, Griffin MR, et al. Burden of interpandemic influenza in children younger than 5 years: a 25-year prospective study. J Infect Dis 2002;185:147-52.

Nichol KL. Efficacy and effectiveness of influenza vaccination. Vaccine 2008;26 Suppl 4:D17-22.

Zaman K, Roy E, Arifeen SE, et al. Effectiveness of Maternal Influenza Immunization in Mothers and Infants. N Engl J Med 2008;359:1555-64.

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Appreciation

Portions of these question and answer materials have been adapted from internet sources. American Academy of Pediatrics (AAP). Public Health Agency of Canada (PHAC). US Centers for Disease Control and Prevention (CDC).

We also acknowledge and appreciate the following individuals for contributing valuable information: Anna Taddio (Toronto), Mary Appleton (Halifax), and Francoise Bayles (Halifax).

INFECTIOUS DISEASES AND IMMUNIZATION COMMITTEE
Members: Drs. Robert Bortolussi, Halifax, Nova Scotia (chair); Jane Finlay, Richmond, British Columbia; Jane McDonald, Montreal, Quebec; Heather Onyett, Kingston, Ontario; Joan Robinson, Edmonton, Alberta; Elisabeth Rousseau-Harsany, Montreal, Quebec (board representative)
Liaison: Drs. Upton Allen, Toronto, Ontario (Canadian Pediatric AIDS Research Group); Charles Hui, Ottawa, Ontario (Committee to Advise on Tropical Medicine and Travel); Nicole Le Saux, Ottawa, Ontario (Immunization Monitoring Program, ACTive); Larry Pickering, Atlanta, Georgia (American Academy of Pediatrics); Marina Salvadori, London, Ontario (National Advisory Committee on Immunization)
Consultant: Drs. James Kellner, Calgary, Alberta; Noni MacDonald, Halifax, Nova Scotia; Dorothy Moore, Montreal, Quebec
Principal authors:  Drs. Upton Allen, Toronto, Ontario, Heather Onyett, Kingston, Ontario; Noni MacDonald, Halifax, Nova Scotia; and Dorothy Moore, Montreal, Quebec.  

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Updated: December 11, 2009