Pediatric Influenza Treatment & Management

As with other diseases, prevention of influenza is the most effective strategy. The Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) publishes recommendations for high-risk groups.

Selected patients may benefit from the use of antiviral agents. The ACIP also publishes recommendations on the use of antiviral agents for prevention and treatment of influenza.^[41] Early antiviral therapy must be considered among hospitalized children diagnosed with or suspected to have influenza, especially if they have risk factors such as asthma, cardiac problems, or other conditions, to prevent severe complications and prolonged hospitalization. Influenza vaccination also must be considered to prevent the infection.^[42]

One study analyzed the clinical data of adult patients with pandemic H1N1 2009 infection admitted to the ICU. Most of the 18 patients analyzed were obese and presented with severe respiratory distress and hypoxia in the summer months. A higher dose of oseltamivir (150 mg twice daily) and nonconventional modes of ventilation may have improved the outcome in these patients. The rapid influenza detection test (RIDT) had a 76% false-negative result; however, the infection was later confirmed with real-time reverse transcriptase polymerase chain reaction (rRT-PCR). These results suggest that early and aggressive treatment action should be taken in patients with a high clinical suspicion of severe influenza infection.^[43]

Influenza symptoms may last longer than 1 week. Caregivers can relieve and soothe children's aches and pains with basic supportive care. Acetaminophen may be administered for fever and relief of other symptomatology. (Caution: In children < 16 y who have symptoms of influenza infection or colds, aspirin is not recommended because of an association with Reye syndrome.)

Use cough suppressants and expectorants to treat the cough. Steam inhalations may also be useful. If dehydration occurs, administration of oral or intravenous fluids is indicated.

Two classes of antiviral agents are available for influenza: adamantanes (amantadine, rimantadine) and neuraminidase inhibitors (oseltamivir, zanamivir).^{[5, 44, 45]} Adamantanes are M2 ion channel inhibitors. Because of resistance among influenza A viruses, use of adamantanes has not been recommended since the 2005-2006 influenza season.^{[46, 47]}

Neuraminidase inhibitors inhibit the release of virus and its spread. Oseltamivir (Tamiflu) is approved by the U.S. Food and Drug Administration (FDA) for treatment and prophylaxis of influenza types A and B and is effective in treating avian influenza.^[45] Oseltamivir resistance has been rarely reported in pandemic H1N1 influenza virus and avian influenza A/H5N1 virus.^{[9, 48]}

Oseltamivir resistance emerged in the United States during the 2008-2009 influenza season. . Because of this, zanamivir (Relenza) was recommended as the initial choice for antiviral prophylaxis or treatment when influenza A infection or exposure was suspected. However, as of March 2011, all US seasonal influenza viruses tested for resistance by the CDC were susceptible to neuraminidase inhibitors.^[48]

Zanamivir and oseltamivir are approved for both prophylaxis and treatment of influenza A and B. When used for treatment, these agents can reduce the duration and severity of illness. They should be started as soon as possible after the onset of symptoms, but no later than 2 days after onset.

Treatment of avian influenza

Hospitalization is required in patients with avian influenza if respiratory distress results in subsequent ventilatory support. Oseltamivir is the primary drug of choice.^[39] Longer therapy may be needed to treat highly pathogenic (HP) avian influenza than seasonal influenza.

The WHO recommendations for HP avian influenza A/H5N1 are as follows^[49] :

• Patients with confirmed or suspected H5N1 infection should be treated with oseltamivir as soon as possible
• Zanamivir might also be considered as an alternative if the patient is capable of using an inhalers
• If neuraminidase inhibitors are available, amantadine and rimantadine should not be used as first-line therapies because of potential resistance
• If neuraminidase inhibitors are not available, amantadine can be used as a first-line therapy, provided the virus is susceptible
• If neuraminidase inhibitors are not available, rimantadine can be used if the virus is known to be susceptible because it has fewer side effects than amantadine
• If neuraminidase inhibitors are available, and if the virus is susceptible, then a combination of neuraminidase inhibitors and M2 inhibitors can be used in confirmed cases of H5N1 infection
• For prophylaxis in high-risk and moderate-risk exposures, give oseltamivir for 7-10 days from the day of exposure
• Prophylaxis is not recommended for low risk groups

For more information, see the World Health Organization Updated Guidelines for Avian Influenza Virus Management.

A combination of antiviral therapy (eg, oseltamivir and adamantanes if susceptibility is expected) and antibiotics is recommended if pneumonia and rapid progression is noted. If septic shock is present, corticosteroids and vasopressors may play a role.

Acute respiratory distress syndrome (ARDS) should be managed according to guidelines.

If the patient is hospitalized, an isolation room is required, with airborne precautions or a negative-pressure room. A particulate mask, such as N95, and goggles are recommended.

No special diet is indicated for influenza.

Adequate rest is recommended.

Handwashing with soap and water is the most appropriate way to prevent infection by an influenza virus. Other preventive measures are to avoid touching of eyes or nose before washing hands, and to avoid sharing personal items with another person during an influenza outbreak.

Patients with influenza who are clinically stable and are able to convalesce at home are instructed to stay at home to avoid spread in the community.

Influenza vaccination in targeted high-risk populations is the best means of preventing severe disease caused by influenza virus. Guidelines regarding the prevention and control of influenza have been established by the ACIP, and are regularly updated.^[50]

Vaccines made using inactivated influenza virus provide 60-90% protection against influenza when the vaccine matches the epidemic strain. The antigenic composition is reviewed annually so that the current vaccine contains the most recently circulating strains, usually one or more subtypes of influenza A virus and a subtype of influenza B virus.

Indications for influenza vaccine in the pediatric population include the following:

• Annual vaccination of all children aged 6 months to 18 years^[51]
• Annual vaccination of children and teenagers (6 mo to 18 y) with long-term use of aspirin or other conditions that place them at increased risk for complications from influenza^{[52, 50]}
• Patients with chronic pulmonary (eg, asthma) or cardiac disorders (except hypertension)
• Patients with chronic metabolic disease (eg, diabetes), renal dysfunction, hemoglobinopathies, or immunosuppression (eg, human immunodeficiency virus [HIV])
• Persons who have any condition (eg, cognitive dysfunction, spinal cord injuries, seizure disorders, or other neuromuscular disorders) that may compromise respiratory function or the handling of respiratory secretions or that can increase the risk for aspiration
• Pregnant women who will be in their second or third trimester during influenza season
• Household members (eg, children aged < 5 y) of persons at high risk
• Providers of essential community services (eg, police, fire)
• International travelers
• Students and dormitory residents
• Anyone wishing to reduce risk of influenza

The CDC recommends that the following pediatric groups receive priority for inactivated influenza vaccine:

• Residents of long-term care facilities
• Persons aged 2-64 years with comorbid conditions
• Children aged 6 months to 4 years (59 mo)^{[52, 50]}
• Women who will be pregnant during the influenza season
• Household contacts and out-of-home caregivers of children younger than 6 months

Recommendations regarding administration of influenza vaccine include the following:

• For adults and older children, the recommended site of vaccination is the deltoid muscle
• The preferred site for infants and young children is the anterolateral aspect of the thigh
• Influenza vaccine should be administered during the autumn season
• Two doses administered at least 1 month apart are recommended in children 6 months to 8 years who are receiving influenza vaccine for the first time; other children or adults may be vaccinated with one shot

Annual immunization is recommended because of declining immunity during the year after immunization and because, in most years, at least one of the antigens is changed in the vaccine to increase the antigenic similarity between the vaccine and circulating strains. The optimal time for influenza vaccination is usually between October and November.

Influenza vaccine should not be administered to persons known to have severe anaphylactic hypersensitivity to egg protein or to other components of the influenza vaccine. However, the presence of minor illnesses with or without fever is not a contraindication to the use of influenza vaccine. Influenza vaccine may be administered with pneumococcal vaccine and with other routine vaccinations of childhood.

Influenza vaccine is also available as a nasal spray (FluMist) for healthy children aged 2 years or older, adolescents, and adults aged 49 years or younger. Children aged 2-8 years who have not previously received influenza vaccine as a nasal spray require 2 doses at least 1 month apart. Those who only received 1 dose in their first year of vaccination should receive 2 doses in the following year. Children who take aspirin, have asthma, or have had a wheezing episode in the preceding 12 months should not receive the intranasal vaccine.

To curtail a potential pandemic situation, the major goals are early identification of sources of HP avian influenza virus A/H5N1 infection and limiting spread of the virus. Both the WHO and the CDC recommend a high degree of surveillance worldwide to identify outbreaks in poultry and death of migratory birds.^[53] Rapid containment processes, such as culling of infected birds, vaccinating nearby at-risk poultry, and vigilance for respiratory illness among personnel in contact with the affected poultry, are also needed.

Simple measures (eg, strict hand hygiene; standard, contact, droplet, and airborne precautions for 21 d) might reduce the spread of the virus.

Pneumococcal vaccination has been suggested as a prophylaxis option, to prevent secondary pneumonia from this pathogen. However, deaths due to avian influenza have been reported even without secondary bacterial infection.

An alert system has been developed for avian influenza depending on the incidence of human cases due to HP avian influenza virus A/H5N1. It ranges from level I-VI.^[53] Currently, the alert is set at level III because of a few cases of human-to-human transmission.

The United States and several other countries have developed a preparedness plan for a potential influenza pandemic.^[8] The US Secretary of Health and Human Services has developed a multiagency National Influenza Pandemic Preparedness and Response Task Group. This initiative jointly involves the CDC and several other agencies (international, national, state, local, and private) in preparing for a potential pandemic.^[54]

Travel recommendations

No recommendations have advocated carrying oseltamivir or zanamivir when traveling to countries where human avian influenza has been reported. However, consulting a local physician if illness develops has been recommended.^[54]

Sick or dying poultry should not be consumed because doing so increases the risk of acquiring the virus. Avoiding undercooked poultry and areas where the poultry is sold in the market is prudent. Also avoid raw or undercooked eggs. After exposure to poultry or eggs, wash hands, utensils, and exposed surfaces with soap and water.

If an illness develops with fever, cough, sore throat, or respiratory distress after exposure to poultry in areas where avian influenza has been identified, individuals must contact medical personnel. The history of travel and exposure to poultry must be disclosed prior to contact with the physician.

Avian influenza vaccination

The FDA approved the first vaccine for highly pathogenic (HP) avian influenza H5N1 (ie, avian or bird flu) in April 2007. The approval was based on one multicenter, randomized, double-blind, placebo-controlled, dose-ranging study in healthy adults aged 18-64 years.^[55] The trial investigated the safety and immunogenicity of the vaccine. In the study, 45% of 103 healthy adults who received two 90-mcg intramuscular doses of the vaccine 28 days apart had an improved immune response and produced antibody levels expected to reduce the risk of disease. In a subsequent study, a booster given 12 months after the second dose significantly boosted immune responses.^[56]

The H5N1 vaccine is not commercially available; it is stockpiled by the federal government to be distributed when necessary.^[55]

A vaccine against another avian influenza strain, H9N2, has also been developed. A study of live-attenuated H9N2 vaccine given intranasally to 50 adults (41 were seronegative) showed immunogenicity after 2 doses.^[57]

The Society of Hospital Epidemiology of America has published a document recommending universal vaccination of health care workers as a preparedness plan.^[58] By enhancing the vaccination rate, viral shedding and transmission can be reduced. This eventually decreases the risk of reassortment.

The challenges faced include manufacturing vaccines in a timely manner, finding appropriate substrates from which to isolate the virus, product safety, efficacy, and acceptance by the approving agency and the public. The HP avian influenza A virus vaccine poses a challenge because the contemporary method of growing the vaccine in the egg may not work because the HP avian influenza A virus can kill the embryonated egg.

Once an outbreak occurs, both the infected individual and contacts require neuraminidase inhibitors. This may necessitate mobilization of neuraminidase inhibitors from nations with stockpiles to regions where an avian outbreak is detected. Although this may not completely inhibit the transmission, the inhibitors may slow it down by decreasing viral shedding.

An effort should be made to enhance seasonal influenza immunization rates.

Avian influenza should prompt consultations with the following specialists:

• Infectious diseases specialist
• Pulmonologist
• Critical care specialist
• Infection control specialist