Pediatrics

Influenza

Overview: What every practitioner needs to know

Are you sure your patient has influenza? What are the typical findings for this disease?

Influenza is a contagious airborne disease, initially affecting the upper respiratory system. It can impact healthy children as well as those at high risk of influenza complications (e.g., children with chronic medical conditions such as asthma, diabetes mellitus, immunosuppression, and neurologic disorders).

Seasonal influenza epidemics have been responsible for notable morbidity and mortality, with the severity of systemic symptoms from this acute viral infection ranging from fever and fatigue to respiratory failure and death.

Influenza is vaccine-preventable, so all people 6 months of age and older should receive trivalent seasonal influenza vaccine each year.

Influenza virus infection is commonly marked by an acute onset of fever accompanied by chills, rigors, malaise, headache, diffuse myalgia and nonproductive cough.

Notable subsequent signs and symptoms include nasal congestion, sore throat, rhinitis, and persistent cough.

Abdominal pain, nausea, vomiting, diarrhea, and conjunctival injection are also possible, but are noted much less often.

What other disease/condition shares some of these symptoms?

Upper respiratory tract infections caused by other infectious pathogens share the same host of symptoms. These non-influenza etiologies include, but are not limited to:

Rhinovirus

Adenovirus

Respiratory syncytial virus

Parainfluenza virus

Bocavirus

Human metapneumovirus

Bordetella pertussis

Mycoplasma pneumonia and

Chlamydia pneumonia

Influenza infection generally presents with a greater severity of symptoms (e.g., fever, chills, myalgia) than the more common upper respiratory tract infection (e.g., nasal congestion, rhinorrhea).

What caused this disease to develop at this time?

Peak influenza activity in the United States may be noted anytime from November to May, but most commonly occurs in January and February. Community outbreaks can last 4 to 8 weeks or longer. Circulation of 2 or 3 influenza virus strains in a community may be associated with a prolonged influenza season of 3 months or more and bimodal peaks in activity.

Seasonal epidemics occur secondary to unremitting antigenic drift, or continuous minor antigenic variations within a particular type A subtype. Antigenic drift is responsible for the production of new strains of influenza A and B viruses. In the past 25 years (since the 1986-1987 influenza season), there have been only 4 seasons in which there was no antigenic drift in at least one of the influenza vaccine strains.

Influenza pandemics may occur secondary to antigenic shift, or abrupt, major changes in the influenza A virus, which include the creation of new hemaglglutinin antigen (HA) or neuroaminidase antigen (NA) components of thisvirus.

The most recent (April 2009 through August 2010) influenza A (H1N1) virus pandemic declared by the World Health Organization occurred secondary to antigenic shift creating a strain which was efficiently transmitted in a sustained manner in the setting of poor preexisting immunity. There now have been four influenza pandemics caused by antigenic shift in the 20th and 21st centuries.

Influenza virus types or subtypes vary in virulence, affecting influenza-related hospitalizations and deaths. For example, seasons with influenza A (H3N2) as the predominant circulating strain have demonstrated mortality rates 2.7 times higher than average mortality rates in seasons with different predominant strains.

Humans, including children, occasionally are infected with influenza A viruses of swine or avian origin.

Rare but severe infections with influenza A subtype H5N1 viruses have been identified since 1997 in Asia, Africa, Europe and the Middle East, areas where these viruses are present in domestic or wild birds.

Other influenza subtypes of avian origin, including H7, also are identified occasionally in humans.

Infection with a novel influenza A virus should be reported to the Centers for Disease Control and Prevention (CDC) as a nationally reportable disease.

What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?

Influenza viruses are orthomyxoviruses of three types (A, B and C), with type C viruses merely causing sporadic mild influenza-like illness (ILI) in children. Hence, only influenza A and B virus antigens are included in influenza vaccines.

Influenza type A is subcategorized by the presence of 2 surface antigens, hemagglutinin antigen (HA) and neuraminidase antigen (NA). The type A subtypes currently include the H1N1, H1N2 and H3N2 viruses.

In contrast, influenza B viruses are not separated into subtypes, but further divided into different strains.

Specific antibodies to these various antigens, especially to hemagglutinin, are important determinants of immunity. Rates of communal immunity, in turn, influence the incidence rates of the influenza virus.

Most patients demonstrating clinical symptoms consistent with uncomplicated influenza disease, while residing in an area with known circulating cases of influenza, do not require influenza diagnostic testing for clinical management.

Other laboratory tests, such as a complete blood cell count, are not necessarily indicated in confirming the diagnosis of influenza disease. A complete blood cell count and/or blood culture, however, may prove helpful in cases where bacterial superinfection or concominant bacterial disease is suspected.

Patients who should be considered for influenza diagnostic testing include:

-Hospitalized patients with suspected influenza,

-Patients for whom a diagnosis of influenza will warrant changes in clinical care, infection control, or management of close contacts (See Figure 1), and/or

Figure 1.

Persons at higher risk for influenza complications

-Patients who died of an unspecified acute illness in which influenza was suspected.

Respiratory tract specimens should be collected shortly after illness onset, preferably within the first 72 hours of illness. Specimen collection after 5 days of illness onset my result in false-negative results due to a marked decrease in quantity of viral shedding over time. In addition, if antiviral therapy is to be prescribed, treatment should be started as soon after illness onset as possible and should not be delayed while waiting for a definitive influenza test result. Clinical benefit is greatest when treatment is initiated within 48 hours of onset of symptoms.

Optimal specimens in infants and young children include nasal aspirates and swabs. Nasopharyngeal aspirates and swabs are preferable in older children and adults. Oropharyngeal and sputum specimens result in a lower yield for influenza virus detection.

In patients undergoing mechanical ventilation, upper and lower respiratory tract samples should be obtained. Lower respiratory tract samples include endotracheal aspirates and bronchoalveolar lavage fluid. Upon collection, respiratory specimens should be refrigerated and then tested for influenza as soon as possible to ensure accuracy of results.

Various methods of influenza testing include: Viral culture, reverse transcriptase-polymerase chain reaction (RT-PCR), immunofluorescence and rapid influenza diagnostic testing. Each method of testing possesses its own advantages and disadvantages as outlined below.

Viral Culture:

-Moderately high sensitivity and highest specificity available

-Confirmatory test

-Useful in public health surveillance

-Not recommended for timely clinical management as results not available for 48-72 hours

Reverse transcriptase-polymerase chain reaction (RT-PCR):

-Most sensitive and specific test available for influenza testing

-Confirmatory test

-Useful for quick differentiation between influenza types and subtypes

-Results available within 4-6 hours of specimen collection

-Preferred test for specimens obtained from patients with a history of exposure to animals with possible influenza illness (eg. H5N1)

Immunofluorescence:

-Includes either direct or indirect fluorescent antibody staining for influenza antigen detection

-Lower sensitivity and specificity than viral cell culture

-Screening test

-Results available in 3-4 hours

-Distinguishes between Influenza A and B

-Assay reliability depends on quality of specimen and laboratory expertise

►Results must be interpreted with caution given that the accuracy of these screening tests depend on disease prevalence

Rapid Influenza Diagnostic Testing (RIDT):

-Compared with RT-PCR and viral culture testing, rapid testing has a sensitivity of 50-70% and a specificity of 90-95%

-Screening test

-Results available in 10-30 minutes depending on type of test used

-Depending on type of test, may or may not distinguish between influenza A and B

►Results must be interpreted with caution given that the accuracy of these tests vary depending on disease prevalence

Knowledge of local disease prevalence is critical to proper interpretation of influenza screening tests (immunofluorescence and RIDT).

It is imperative to use clinical judgment in deciding whether or not any patient with an influenza-like illness (ILI) should be treated regardless of test results, especially because of the poor sensitivity of RIDTs.

A false positive screening result is most likely to occur in the context of low local disease prevalence.

A false negative screening result is most likely to occur in the context of high local disease prevalence.

Confirmatory testing (viral culture or RT-PCR) should be considered in these instances in order to confirm accurate results. See influenza diagnostic testing table for summary (Figure 2).

Figure 2.

Influenza diagnostic tests

Would imaging studies be helpful? If so, which ones?

Radiologic studies such as plain film chest x-rays may be obtained if there is a question of bacterial coinfection which may impact clinical decision-making or need for expanding antimicrobial coverage.

Confirming the diagnosis

See the Centers for Disease Control and Prevention algorithm (See Figure 3).

Figure 3.

Guide for considering influenza virus diagnostic tests

Refer to the laboratory studies section for sensitivities and specificities.

If you are able to confirm that the patient has influenza, what treatment should be initiated?

Treatment should be considered for anyone with suspected or confirmed influenza who:

- Has severe, complicated, or progressive illness,

- Is hospitalized, or

- Is at higher risk for clinical complications secondary to the influenza virus (See Figure 1).

Anyone who stands to benefit from decreased duration of symptoms according to a clinician’s judgment.

Populations not listed above with suspected or confirmed influenza and uncomplicated febrile illness typically do not require treatment.

Treatment should never be delayed while waiting for definitive influenza test results.

Timely use of antiviral medication (within 48 hours from onset of symptoms) may reduce the severity and duration of symptomology, risk for hospitalization and subsequent complications.

In patients with moderate to severe disease, treatment initiated after 48 hours from the onset of symptoms may still prove beneficial.

Antiviral medications can be used to treat or prevent influenza and can help control influenza outbreaks in institutional settings.

As treatment, antivirals decrease the duration of symptoms and reduce the severity of illness.

As a chemoprophylaxis, antivirals can be 70% to 90% effective in preventing influenza, but should never be used as a replacement for influenza vaccine.

Early treatment following exposure should be considered as an alternative to chemoprophylaxis for persons not at higher risk for influenza complications. This approach should help minimize the development of resistance. Patients should always be advised of potential side effect profiles of prescribed medications.

There are two classes of antiviral medication available for treatment or prophylaxis of influenza infections:

-Neuraminidase inhibitors: oseltamivir and zanamivir

-Adamantanes: amantadine and rimantadine

►The 2009 pandemic influenza A (H1N1) virus, which subsequently has replaced the previous influenza A (H1N1) seasonal strain, is largely susceptible to the neuraminidase inhibitors and resistant to adamantanes.

Since 2005, all H3N2 strains in the United States have been resistant to adamantanes. Influenza A (H3N2) and B viruses remain susceptible to oseltamivir.

Influenza B viruses are intrinsically resistant to adamantanes.

The resistance patterns among circulating influenza A virus strains simplify antiviral treatment, as 2009 pandemic influenza A (H1N1), influenza A (H3N2), and influenza B all are susceptible to neuraminidase inhibitors and resistant to adamantanes.

In summary, options for treatment or chemoprophylaxis of influenza in the United States depend on influenza strain resistance patterns.

Health care personnel should remain aware of the predominant circulating strain and its susceptibility profile. Recommendations will depend on local activity and may change throughout the season (refer to http://www.cdc.gov/flu/weekly/ for weekly updates on antiviral resistance).

The influenza virus strains expected to circulate during the 2011-2012 season and their anticipated antiviral sensitivities are shown in Figure 4.

Figure 4.

Antiviral sensitivities

Current treatment guidelines given by the American Academy of Pediatrics and Centers for Disease Control are demonstrated in Figure 5.

Figure 5.

Antiviral Treatment Guidelines

What are the adverse effects associated with each treatment option?

Adamantanes:

Central nervous system side effects (more common with amantadine than rimatadine)

-Nervousness, anxiety, difficulty concentrating, lightheadedness.

Gastrointestinal side effects

-Nausea, loss of appetite.

Delirium, hallucinations, agitation, and seizures are more common among persons with long-term illnesses.

Zanamivir:

Decreased respiratory function and bronchospasm, especially among those with asthma or other chronic lung disease.

Diarrhea, nausea, sinusitis, nasal infections, bronchitis, cough, headache, and dizziness have occurred in less than 5% of persons who have received the drug.

This drug is not typically recommended for anyone with underlying lung disease.

Oseltamivir:

Gastrointestinal side effects

-Nausea, vomiting.

Neuropsychiatric events

-Rare cases of self-injury and delirium, mostly among pediatric patients, primarily in Japan.

-It is unknown what effect oseltamivir may have on behavior, but unusual patient behavior should be reported immediately to a health care professional.

Children and adolescents with influenza should never receive aspirin or any salicylate-containing products secondary to increased risk of developing Reye syndrome.

What are the possible outcomes of influenza?

Influenza causes significant morbidity and mortality every season. The 50 to 60 million cases each year in the United States result in approximately:

25 million physician visits;

117,000 to 816,000 hospitalizations; and

3,349 to 48,614 deaths.

Most cases of influenza resolve without serious complications for healthy persons between the ages of 2 and 65. However, these individuals can increase a community’s disease burden and put vulnerable populations in danger of complications from infection leading to hospitalization or even death.

Vulnerable populations include children with high-risk conditions such as hemoglobinopathies, bronchopulmonary dysplasia, asthma, cystic fibrosis, malignancy, diabetes mellitus, chronic renal disease and congenital heart disease (See Figure 1).

Influenza is an important cause of otitis media. Acute myositis characterized by calf tenderness and refusal to walk has been described. In infants, influenza can produce a sepsis-like picture and occasionally can cause croup, bronchiolitis, or pneumonia.

Neurologic complications associated with influenza range from febrile seizures to severe encephalopathy and encephalitis with status epilepticus, with resulting neurologic sequelae or death.

Mortality secondary to the influenza virus has been reported in both chronically ill and previously healthy children. Invasive secondary infections or coinfections with group A streptococcus, Staphylococcus aureus (including methicillin-resistant S aureus [MRSA]). Streptococcus pneumoniae, or other bacterial pathogens can result in severe disease and death.

Influenza-related pediatric deaths have been recorded nationally beginning with the 2003-3004 influenza and vary from year to year. Of 153 laboratory-confirmed influenza-related pediatric deaths reported from 40 states during the 2003-2004 influenza season, 96 (63%) were children younger than 5 years of age and 61 (40%) were children younger than 2 years of age.

Among the 149 children who died in the 2003-2004 season and for whom information on underlying health status was available, 100 (67%) did not have an underlying medical condition.

Of the 53 pediatric patients 6 years of age or older who died in 2006-2007 and for whom immunization status was known, 50 (94%) had not been immunized against influenza. These data served as tremendous impetus in promoting universal immunization in the pediatric population rather than the prior age and risk-based recommendations.

In the following 3 seasons, the number of deaths among children reported annually ranged from 46 to 71. During these seasons, 55% of influenza-related deaths occurred in previously healthy children.

In the 2009-2010 influenza season, the number of influenza-related deaths in the United States pediatric population rose to 279.

During the H1N1 pandemic period from April 2009 to August 2010, a total of 344 laboratory confirmed influenza-related pediatric deaths were reported.

Many of these complications, including deaths, may have been prevented by annual influenza immunization.

All influenza-associated pediatric deaths should be reported to the CDC through state health departments.

What causes this disease and how frequent is it?

The influenza virus is typically transmitted when a person comes in contact with infectious respiratory droplets created by coughing or sneezing. Spread of the disease may also occur with contact of respiratory droplet-contaminated surfaces. The incubation period for the influenza virus is usually 1 to 4 days, with a mean of 2 days.

Viral shedding in nasal secretions usually peaks during the first 3 days of illness and ends within 7 days. Viral shedding may be prolonged in young children and immunodeficient patients and is directly correlated with degree of fever.

Patients are considered infectious during the 24 hours prior to onset of symptoms. Disease is characterized by the sudden onset of symptoms which may last for 7 days or more.

In the Northern Hemisphere, seasonal epidemics of influenza generally occur late fall through early spring. Peak influenza activity in the United States typically occurs between November and May, but most often peaks in January or February.

School-aged children represent the demographic with highest attack rates and this often results in secondary spread to family members and other household contacts. Outbreaks of the disease are commonly reported in areas where there may be a high population density and frequent close contact amongst individuals (e.g., schools, day care facilities, chronic care facilities). Communal incidence primarily depends on natural or vaccine-induced immunity.

Communities generally experience outbreaks that last 1 to 2 months. This period may last 3 months or more and may demonstrate bimodal peaks in activity when multiple strains circulate within a community during a given season.

Incidence rates of the influenza virus among children in the United States have been found to range from 10% to 40% each season.

Rates of serious illness, hospitalization, and mortality are highest among children under 2 years of age, as well as children with medical conditions that place them at increased risk for complications from influenza.

Variable rates of hospitalization secondary to influenza virus infection have been reported between ranging from 190-480 per 100,000 children. Variable rates of hospitalization in the United states secondary to influenza virus infection have been reported.

In the 2009-2010 season, children under age 4 age were found to be hospitalized secondary to the influenza virus at a rate of 88 per 100,000 children/year. Children aged 5-17 were hospitalized at a rate of 31 per 100,000.

Rates of hospitalization are higher in children with high-risk conditions (e.g., hemoglobinopathies, bronchopulmonary dysplasia, asthma, cystic fibrosis, malignancy, diabetes mellitus, chronic renal disease, and congenital heart disease) given that rates of secondary complications and death are far greater in this patient population.

Influenza and its complications have been reported to result in a marked increase in ambulatory care and emergency room visits as well as a 10% to 30% increase in the number of courses of antimicrobial agents prescribed to children during the influenza season. This translates into a sustained increase in medical costs as well as what is likely an important cause of inappropriate antimicrobial use.

Mortality secondary to the influenza virus has been reported in both children with special health care needs and previously healthy children.

How do these pathogens/genes/exposures cause the disease?

Influenza pandemics are marked by the rapid and global spread of a new influenza A virus subtype to which the population has little or no immunity. During the 20th and 21st centuries, there have been four documented influenza pandemics: 1918 (H1N1), 1957 (H2N2), 1968 (H3N2), and 2009 (H1N1).

Pandemics generally lead to remarkably increased morbidity and mortality rates compared with seasonal influenza. The pandemic in 1918 killed at least 20 million people in the United States and perhaps as many as 50 million people worldwide. The 2009 Influenza A (H1N1) pandemic occurred from April 2009 through August 2010. A reported range of 8,870-18,300 influenza-related deaths has been documented.

Pandemics threaten a disruption in access to care and an exhaustion of clinical provider and medical resources.

It is crucial that pediatric health care professionals be familiar with national, state, and institutional pandemic plans, including recommendations for vaccine and antiviral drug use as well as health care surge capacity.

Current recommendations and information on pandemic influenza can be found at www.pandemicflu.gov.

What complications might you expect from the disease or treatment of the disease?

Complications of the influenza virus infection include:

Ear infections

Sinus infections

Secondary bacterial pneumonia

Dehydration

Worsening of chronic conditions

Myositis

Myocarditis

Neurologic complications (febrile seizures, encephalopathy, encephalits, status epilepticus)

Guillain-Barré syndrome

Reye syndrome

Certain populations are at higher risk for these complications, such as:

People with chronic medical conditions such as asthma, diabetes, morbid obesity, immunosuppression or neurological disorders (See Figure 1)

Healthy children younger than 5 years of age

Infants younger than 6 months of age (vaccine is not licensed for this age group)

Pregnant women

People over the age of 65

Invasive secondary infections or coinfections with group A streptococcus, Staphylococcus aureus, Streptococcus pneumoniae or other bacterial pathogens can result in severe disease and death.

Methicillin-resistant staphylococcal community-acquired pneumonia has been reported in previously healthy children with concomitant influenza infection. This coinfection results in a noticeably swift clinical progression and high fatality rate.

During the neonatal period, influenza infection has been associated with sepsis-like syndrome, apnea and lower respiratory tract disease. This is an important example of the advantages to "cocooning" - immunization of pregnant women to benefit their unborn infants because transplacentally acquired antibody should protect newborn infants from infection with influenza virus. In addition, immunization of people who are in close contact with children with high-risk conditions or with any child younger than 5 years of age is an important means of protection for these children.

How can influenza be prevented?

Proper hand washing, using cough etiquette, and regular cleaning of potentially contaminated surfaces are vital in preventing the spread of influenza.

Protection can be maximized in following the below hygiene recommendations:

-Cover your nose and mouth with a tissue when you cough/sneeze and throw the used tissue away immediately. If you can't cover the cough/sneeze, cover your mouth and nose by sneezing or coughing into your upper arm.

-Wash your hands often with soap and water and as soon as possible after you cough/sneeze. If you are not near water, use an alcohol-based hand sanitizer according to the manufacturer's instructions.

-Keep yourself and any babies or children in your care away from people who are coughing or sneezing as much as you can.

-Get into the habit of not touching your eyes, nose, or mouth since germs can spread this way.

Droplet precautions also are recommended for children hospitalized with influenza in order to prevent spread of the virus.

Seasonal influenza vaccination is the most effective method for the prevention of influenza virus infection and its associated morbidities. It is recommended that vaccine be administered in the autumn, prior to the expected annual influenza season; however, since the onset of influenza season is variable and unpredictable, immunization may be administered throughout the winter and even early spring.

There are two forms of the vaccine, trivalent inactivated influenza vaccine (TIV) and live-attenuated influenza vaccine (LAIV), both of which contain the same 3, annually-selected virus strains (A [H3N2], A [H1N1], and B).

Most years, one or more strains are altered in the vaccine. Annual vaccination is recommended for all persons ages 6 months and older who do not have any contraindications to administration of vaccination. Even when the composition of the influenza vaccine does not change from the previous season, antibody titers in children may be reduced by as much as 50% within 12 months after vaccination, highlighting the value of annual receipt of vaccine.

Annual trivalent influenza vaccine is also indicated for household members and care-providers of children at high risk for disease morbidity, healthy children under 5 years of age and infants under the age of 6 months. Cocooning or immunization of people who are in close contact with children with high-risk conditions or with any child younger than 5 years of age is an important means of protection for these children.

TIV is an intramuscular vaccination licensed for administration to those 6 months of age and older. Prior recommendations for immunization determined by age and risk factors were replaced with the promotion of universal immunization based on elevated morbidity and mortality rates from influenza in the unimmunized population. TIV may be administered concurrently with other live and inactivated vaccines.

LAIV is administered as a nasal spray and is licensed for use in healthy, nonpregnant persons 2 through 49 years of age. The safety and efficacy of LAIV has not been established in persons with underlying medical conditions which may lead to greater risk for influenza-related morbidity.

LAIV is contraindicated in patients with the following: history of asthma, metabolic disease, immunodeficiency or chronic pulmonary or cardiovascular disorders.

LAIV may be administered concomitantly with inactivated and live vaccines; however, the administration of another live vaccine should not take place until at least 4 weeks have passed.

Availability of the influenza vaccine should be publicized to patients as soon as it becomes available (typically, in early Fall). It is recommended that individuals receive the vaccine as early as possible, but vaccine can still be beneficial even into early spring.

Antiviral medications may serve as an adjunct to vaccination when used for chemoprophylaxis after an exposure to influenza virus.

There is no vaccine approved for infants less than 6 months of age, and children 9 years of age and older should receive one dose of vaccine each year. The current dosing recommendations for the influenza vaccine in children 6 months through 8 years of age is as follows:

-Children who have never received (or it is unclear if they have received) the influenza vaccine should receive 2 doses prior to the first season they are immunized. The doses should be spaced 4-6 weeks apart.

-1 dose of the vaccine should be administered prior to each subsequent season.

-Children who received only 1 dose of the influenza vaccine prior to the first season they are immunized should receive 2 doses of the influenza vaccine (spaced 4-6 weeks apart) during the subsequent season.

Similar recommendations apply during a season in which the same vaccine composition is retained from the previous year. However, children need only receive 1 dose of influenza vaccine following their first year of immunization in such circumstances. Antibody titers have demonstrated to be adequate in this scenario.

How effective is influenza vaccine?

The efficacy and effectiveness of the influenza vaccine depends on the match between the vaccine strains and circulating strain in the community as well as the individual’s age and ability to elicit a strong immune response.

Prevention of influenza illness following immunization with TIV in healthy children older than 2 years of age is approximately 70% to 80%.

Limited data suggest that TIV efficacy is lower in children 6 through 23 months of age than children older than 23 months.

In one clinical trial, LAIV’s efficacy in preventing influenza A H3N2 was shown to be 86% to 96%.

There is growing evidence that LAIV has 32 to 55% greater efficacy in younger children than TIV.

What is the evidence?

Fiore, AE, Uyeki, TM, Broder, K, Finelli, L, Euler, GL, Singleton, JA. "Prevention and Control of Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices". MMWR.. vol. 59. 2010. pp. 1-62.

Fiore, AE, Fry, A, Shay, D, Bresee, JS, Uyeki, TM. "Antiviral Agents for the Treatment and Chemoprophylaxis of Influenza: Recommendations of the Advisory Committee on Immunization Practices". MMWR. vol. 60. 2011. pp. 1-24.

Thompson, MG, Shay, DK, Zhou, H, Bridges, CB, Cheng, PY, Burns, E. "Estimates of Deaths Associated with Seasonal Influenza - United States, 1976-2007". MMWR.. vol. 59. 2010. pp. 1057-1062.

"Recommendations for prevention and control of influenza in children, 2010-2011". Pediatrics.. vol. 126. 2010. pp. 816-826.

Harper, SA, Bradley, JS, Englund, JA, File, TM, Gravenstein, S, Hayden, FG. "Seasonal Influenza in Adults and Children - Diagnosis, Treatment, Chemoprophylaxis, and Institutional Outbreak Management: Clinical Practice Guidelines of the Infectious Diseases Society of America". Clinical Infectious Diseases.. vol. 48. 2009. pp. 1003-1032.

Web pages:

"Guidance for Clinicians on the Use of Rapid Influenza Diagnostic Tests for the 2010-2011 Influenza Season". http://www.cdc.gov/flu/professionals/diagnosis/clinician_guidance_ridt.htm. June 7, 2012.

"Seasonal Influenza - Weekly Report: Influenza Summary Update". http://www.cdc.gov/flu/weekly/. June 7, 2012.

Ongoing controversies regarding etiology, diagnosis, treatment

If local or national influenza surveillance data indicate a predominance of a particular influenza strain with known antiviral susceptibility profile, then empiric treatment can be directed toward that strain.

Oseltamivir is available in capsule and oral suspension formulations. The manufactured liquid formulation has a concentration of 12 mg/mL. If the commercially manufactured oral suspension is not available, the capsule may be opened and the contents mixed with a sweetened liquid by retail pharmacies to a final concentration of 15 mg/mL.

Continuous monitoring of the epidemiology, change in severity, and resistance patterns of influenza strains may lead to new guidance.

Treatment should be considered for:

Any child hospitalized with presumed influenza.

Influenza infection of any severity in high-risk children, regardless of influenza immunization status.

Any otherwise healthy child with influenza infection for whom a decrease in duration of clinical symptoms is felt to be warranted by his or her provider.

Earlier treatment provides more optimal clinical responses, although treatment after 48 hours of symptoms in the child with moderate to severe disease or with progressive disease may still provide some benefit.

Clinical judgment is an important factor in treatment decisions for pediatric patients presenting with influenza-like illness. Antiviral treatment should be started as soon as possible after illness onset, and should not be delayed while waiting for a definitive influenza test result. Currently available rapid antigen tests have low sensitivity and should not be used to rule out influenza.

People with suspected influenza who present with an uncomplicated febrile illness typically do not require treatment unless they are at higher risk of influenza complications, especially in situations with limited antiviral medication availability. Should there be a shortage of antiviral medications, local public health authorities might provide additional guidance about diagnostic testing and prioritizing treatment.

These recommendations apply to routine circumstances, but it should be noted that guidance may change on the basis of updated recommendations from the CDC in concert with antiviral availability, local resources, and change in epidemiology or severity of influenza.

Chemoprophylaxis should not be considered a substitute for immunization. Antiviral medications currently licensed are important adjuncts to influenza immunization for control and prevention of influenza disease.

Febrile Seizures and the Flu vaccine

During the recent 2010 influenza seasons in the Southern and Northern Hemispheres, two different influenza vaccine products appear to have been associated with elevated rates of febrile seizures among young children.

There are speculations that reporting increased in part because of the febrile seizures noted in children vaccinated with Afluria in the Southern Hemisphere. Increases may also have been related to concomitant vaccination with the latest pneumococcal conjugate vaccine, PCV13.

To date, the ACIP and AAP recommendations have not changed. Further research is needed to determine what relationship, if any, exists between inactivated influenza vaccine in toddlers and febrile seizures.

Egg Allergic Patients and Influenza Vaccine

Uncertainty remains over whether or not to vaccinate egg allergic individuals with a history of severe reaction, such as anaphylaxis.

Skin testing is no longer necessary and consideration should be given to using the lowest ovalbumin content in the vaccine.

The American Academy of Allergy Asthma and Immunology released a statement in 2010 supporting the regular administration of influenza vaccine to most other egg allergic persons. This demographic can be vaccinated with a single age-appropriate dose followed by 30 minutes of observation in the office (with appropriate resuscitative equipment available) or using a more conservative two-step graded challenge (administer one-tenth of vaccine dose, allow 30 minutes observation, administer remaining nine-tenths, allow 30 minutes observation).

Influenza vaccines do not cause influenza

Two types of trivalent seasonal influenza vaccine are used to immunize both children and adults, but neither one causes influenza.

Injectable trivalent inactivated influenza vaccine (TIV) contains viral antigens but no live virus and, therefore, cannot produce an active virus infection. The most common adverse events after administration are local pain and tenderness. Fever is also seen within 24 hours after immunization in approximately 10% to 35% of children younger than 2 years of age, but rarely in older children and adults. Mild systemic symptoms, such as nausea, lethargy, headache, muscle aches, and chills, also can occur after administration of TIV.

Live-attenuated influenza vaccine (LAIV) is administered intranasally to healthy people age 2 through 49 years. It is not recommended in those with a history of wheezing or other high-risk medical conditions. LAIV has the potential to produce mild symptoms including runny nose, headache, wheezing, vomiting, muscle aches and fever.

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