AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Influenza virus infections rank as one of the most common infectious diseases in humankind. An estimated 20-50 million persons died worldwide from the 1918-1919 H1N1 type influenza pandemic, with 549,000 deaths in the United States. This acute febrile illness with variable degrees of systemic symptoms contributes to significant loss of workdays, human suffering, mortality, and excess morbidity.

Influenza is one of the most contagious airborne infectious diseases. Patients frequently present to physicians with symptoms of influenza, the common cold, or a confusing combination of symptoms of both. In the Northern and Southern Hemispheres, these symptoms are more common in the winter months and result in clinics or emergency department waiting rooms becoming filled with patients who have flu or upper respiratory tract infections (URTIs).

Accurately diagnosing influenza A or B solely on clinical criteria is difficult. In addition to overlapping symptoms caused by URTI-type viruses, more serious viruses, including adenoviruses, enteroviruses, and paramyxoviruses, may initially cause influenzalike symptoms. The early presentation of mild or moderate cases of flavivirus infections, such as dengue, may initially be diagnosed as influenza. For example, some of the people who acquired West Nile fever in New York in 1999 were clinically diagnosed initially as having influenza.

Pathophysiology

Influenza results from infection with 1 of 3 basic types of virus, A, B, or C, which are classified within the family Orthomyxoviridae. These single-stranded RNA viruses share structural and biological similarities but vary antigenically.

The RNA core consists of 8 gene segments surrounded by a coat of 10 (influenza A) or 11 (influenza B) proteins. From an immunologic viewpoint, the most significant surface proteins are hemagglutinin and neuraminidase. The viruses are typed based on these proteins. For example, influenza A subtype H3N2 expresses hemagglutinin 3 and neuraminidase 2.

The most common prevailing human influenza A subtypes are H1N1 and H3N2. Each year, the trivalent vaccine used worldwide contains A strains from H1N1 and H3N2, along with an influenza B strain.

Influenza A is generally more pathogenic than influenza B. Influenza A is a zoonotic infection, and more than 100 types of influenza A infect most species of birds, pigs, horses, dogs and seals. Indeed, the 1918 pandemic that resulted in millions of human deaths worldwide is believed to have originated from a virulent strain of H1N1 from pigs or birds. Recently, scientists obtained and sequenced the 1918 H1N1 strain from a frozen corpse found in Alaska. The virus was reconstructed at the Centers for Disease Control and Prevention (CDC) laboratory in Atlanta and was found to be highly lethal when tested in mice; the virus was also found to be lethal to chicken embryos. This unique N1 neuraminidase is being studied in order to provide better insight into the N1 found in H5N1 bird flu.

H5N1 bird flu

In 1997, an avian subtype, H5N1, was first described in Hong Kong. Infection was confirmed in only 18 individuals, but 6 died. Sporadic cases of H5N1 infection continued to be described in southern China since then. In January 2004, an epidemic occurred in domesticated birds in Southeast Asia, primarily Vietnam. The H5N1 flu, in nearly all cases, is transmitted to humans from birds. Because of the poultry outbreaks and bird-to-human transmission, more than 240 human cases have been documented and more than 140 persons have died. Most deaths have occurred in Vietnam and Indonesia. Sporadic outbreaks have continued to occur since the 2004 outbreak. Human illness has occurred outside Southeast Asia, including Turkey.

Experts are concerned that a slight mutation could convert H5N1 to a strain that would be easily transferred from human to human. Such a strain could potentially spread rapidly and precipitate a catastrophic worldwide pandemic. As a result of this concern, efforts are currently underway to develop an effective vaccine. In addition, studies to expand the number of drugs that are effective against influenza are underway. Ribavirin has shown activity when tested in animal models.

Other avian influenzas

In March 1999, another avian subtype, H9N2, was described in 2 young children. Despite concern, no further outbreak of H9N2 infection occurred. Similar to H5N1 flu, experts are also concerned that a virulent strain of H9N2 influenza may mutate to allow human-to-human infection and that such a strain may possess the triad of infectivity, lethality, and transmissibility.

Influenza virus infection occurs after transfer of respiratory secretions from an infected individual to a person who is immunologically susceptible. If not neutralized by secretory antibodies, the virus invades airway and respiratory tract cells. Once within host cells, cellular dysfunction and degeneration occur, along with viral replication and release of viral progeny. Systemic symptoms result from inflammatory mediators, similar to other viruses. The incubation period ranges from 18-72 hours.

Viral shedding

Viral shedding occurs at onset of symptoms or just before the onset of illness (0-24 h). Shedding continues for 5-10 days. Young children may shed virus longer, placing others at risk for contacting the virus.

Frequency

United States

Epidemics occur in winter months and vary in severity and attack rates depending on the virus subtype involved. Millions of people may develop infection during a given year. The pandemics of 1918-1919 and 1957, which resulted in higher infection rates and very significant morbidity and mortality, demonstrate the impact of the disease.

In the United States, significant influenza activity occurred during the winter season of 1999-2000, and 2003-2004. The major strain to surface in the 2003-2004 season was influenza A/Fujian/411/2002 (H3N2). During the 2000-2003 and 2004-2005 seasons, influenza activity was relatively low in the United States.

International

In tropical areas, influenza occurs throughout the year.

Mortality/Morbidity

The CDC estimates that in excess of 20,000 deaths occur annually as a result of influenza virus when all years are averaged.

Sex

Women in the third trimester of pregnancy are at higher risk for complications of influenza A and B.

Age

Elderly people are at higher risk for complications of influenza A and B.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

The presentation of influenza virus infection can vary; however, it usually includes many of the symptoms described below. Patients with preexisting immunity or those who have received vaccine may have mild and less severe symptoms.

• Abrupt onset of illness is common. Many patients are able to report the time when the illness began.
• Fever may vary widely among patients, with some having low fevers in the 100°F range and others developing fevers as high as 104°F. Patients may report feeling feverish and a feeling of chilliness.
• Sore throat may be severe and last 3-5 days. The sore throat may be a significant reason why patients seek medical attention.
• Myalgias are a common symptom and range from mild to severe.
• Frontal/retroorbital headache is common and is usually severe. Ocular symptoms develop in some patients and include photophobia, burning sensations, pain upon motion, or a combination thereof.
• Rhinitis of varying severity is present in some patients but is generally not the overriding symptom.
• Weakness and severe fatigue may prevent patients from performing their normal activities or work. In some cases, patients may find activity difficult and require bedrest.
• Cough and other respiratory symptoms may be initially minimal but frequently progress as the infection evolves. Patients may report nonproductive cough, cough-related pleuritic chest pain, and dyspnea. In children, diarrhea may be a feature.
• Acute encephalopathy has recently been described to be associated with influenza A virus. In a case series of 21 patients, Steininger et al described clinical, CSF, MRI, and EEG findings. Clinical features included altered mental status, coma, seizures, and ataxia. Of those who underwent further testing, most had abnormal CSF, MRI, and EEG findings.

Physical

The general appearance varies among patients who present with influenza. Some patients may appear acutely ill, with some weakness and respiratory findings, while others may appear only mildly ill. Upon examination, patients may have some or all of the following findings:

• Fever may range from 100-104°F. The fever in elderly patients is not generally as high as that seen in young adults.
• Tachycardia most likely results from hypoxia, fever, or both.
• Pharyngitis may be present. Even in patients who report a severely sore throat, findings vary from minimal infection to more severe inflammation.
• Eyes may be red and watery.
• Nasal discharge is absent in most patients.
• Skin may be warm-to-hot, as reflected by the temperature status. Patients who have been febrile with poor fluid intake may show signs of mild volume depletion with dry skin.
• Pulmonary findings during the physical examination may include active cough, wheezing, rhonchi, or a combination thereof.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Acute HIV infection

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Findings of standard laboratory studies such as a CBC count and electrolytes assessment are nonspecific.
• Viral culture
• • The criterion standard for diagnosing influenza A and B is a viral culture of nasal-pharyngeal samples, throat samples, or both.
  • Obtain samples with Dacron swabs and send the samples in appropriate viral transport media (eg, multimicrobe [M4] transport media) to the laboratory to be cultured in several lines of cells. Laboratory diagnosis of influenza is established once specific cytopathic effect is observed or hemadsorption testing findings are positive. Staining the infected cultured cell lines with fluorescent antibody confirms the diagnosis.
  • The process may require 3-7 days, long after the patient has left the clinic, office, or ED and well past the time when drug therapy could be efficacious.
• Direct immunofluorescent tests
• • Some laboratories offer direct immunofluorescent tests on fresh specimens, but these tests are labor-intensive and are less sensitive than culture methods.
  • These tests require specially trained laboratory personnel (people generally not available during all shifts, even in large medical centers) for interpretation.
• Serologic studies
• • In order to overcome the expensive and time-consuming obstacle of culturing, several serologic tests have become available. In reality, many of these are not bedside tests; generally, 30-60 minutes are required to perform the test's multiple steps.
  • Some rapid tests are performed best in a laboratory, not in the office or ED.
  • Disadvantages to performing these rapid diagnostic tests include the cost of the laboratory personnel, the cost of the test itself, and potential false-negative results for influenza A and B. Test sensitivities generally range from 60-70%.
• Office tests
• • Recently, the US Food and Drug Administration waived federal Clinical Laboratories Improvement Act (CLIA) requirements and approved 3 office tests for diagnosis.
  • Of these, the fastest is the 10-minute QuickVue bedside test, which has a sensitivity of 70-80%.
  • Because of cost, availability, and sensitivity issues, most physicians diagnose influenza based on clinical criteria alone.

Imaging Studies

• In elderly or high-risk patients with pulmonary symptoms, perform chest radiography (CXR) to exclude pneumonia.

Procedures

• Patients with physical examination findings compatible with meningitis should undergo lumbar puncture.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

• As with other diseases, prevention is the most effective strategy.
  • The CDC has published recommendations for high-risk groups, including all health care personnel, who should be vaccinated.
  • Amantadine and rimantadine have been approved for many years for use against influenza A. However, beginning with the 2005-2006 season, amantadine and rimantadine were no longer recommended by the CDC because significant resistance has evolved against these two drugs.
  • Many physicians in primary care offices or the ED have not used these medications widely.
  • Disadvantages of these drugs include lack of efficacy against influenza B, potential adverse effects, and rapid development of viral resistance.
• Two new drugs have been marketed recently for treatment of influenza A and B. These are the neuraminidase inhibitors oseltamivir and zanamivir.
  • Oseltamivir is taken orally (75 mg bid), and zanamivir is taken via an inhalation apparatus (10 mg bid for 5 d).
  • Multiple studies have demonstrated their efficacy. These agents work by inhibiting influenza virus neuraminidase, a glycoprotein spike that protrudes from the virus envelope; this spike is needed for successful cellular release of virus and transmission within the body. To be effective, these new agents must be administered within 40 hours of the onset of symptoms.
  • Recent studies also demonstrate the efficacy of these agents in preventing influenza A and B, an exciting expansion in their use. The prophylactic dose is one half the acute treatment dose.
• • Neuraminidase inhibitors have several advantages compared with amantadine, including less evolution of resistance, efficacy against influenza B, fewer adverse effects, and dramatic reduction in symptoms, even in patients who have a full course of flu.
  • In a study of 445 patients by the Management of Influenza in the Southern Hemisphere Trialists (MIST) group 1, zanamivir was administered to one half of patients and placebo to the others within 36 hours of symptom onset. Duration of the flu was reduced by 1.5 days in normal-risk groups and 2.5 days in high-risk groups. A significant decrease in the severity of illness in patients treated with zanamivir allowed them to resume normal activities much sooner.
  • A recent study by Treanor compared oseltamivir with placebo. This analysis included patients with laboratory-based diagnoses of influenza and those with clinical diagnosis based on symptoms. The 629 patients were enrolled and randomized into 1 of 3 treatment arms: (1) standard-dose oseltamivir, (2) high-dose oseltamivir, and (3) placebo. In both oseltamivir groups, the mean illness duration was reduced from 103 to 70 hours. The symptom severity decreased in the treated group by 40%.
  • Additional studies analyzed the effect of neuraminidase inhibitors both in acute disease and in prevention.
    • In one of these studies, 837 relatives of family members infected with influenza were treated prophylactically with either placebo or zanamivir. While 20% of the placebo group became ill, only 4% of the drug-treated group became ill. In addition, this study provided treatment to the index case family member, resulting in a 2.5-day reduction in illness over placebo. Recombinant DNA viral sequences were performed in this study, and no resistant influenza strains developed.
    • A novel study analyzed the effects of oseltamivir in experimentally induced influenza in humans. In a controlled laboratory environment, volunteers were Inoculated intranasally with influenza A/Texas/36/91 (H1N1). One group was administered oseltamivir 26 hours before virus inoculation and another group was administered 28 hours after inoculation. In the prophylactic group, 38% of patients developed influenza compared with 67% in the placebo group. In the posttreatment group, the duration of illness was reduced from 95 to 53 hours and the severity was reduced by 50% compared with placebo.
    • Another recent study by Hayden analyzed 1559 healthy nonimmunized patients who were treated with either placebo or oseltamivir for 6 weeks. At the end of the period, 4.8% of the placebo group had laboratory-confirmed influenza, compared with only 1.2% of the oseltamivir group.
    • Ongoing studies are analyzing both treatment efficacy and the preventive effects of neuraminidase inhibitors.
• For each patient, individualize a decision about whether to prescribe one of the newer neuraminidase inhibitors based on the patient, the likelihood of the patient actually having influenza A or B, and the potential benefit.
  • Advantages for prescribing these agents include significantly reducing illness severity and duration. Elderly and high-risk patients also have decreased secondary complications of influenza when treated with these agents.
  • Disadvantages include potential adverse effects and costs. Some patients may be willing to pay $100 to have a less severe episode of the flu. Adverse effects include potential bronchospasm with inhaled zanamivir and nausea, vomiting, and headache from oseltamivir. The bronchospasm associated with zanamivir has received attention from national media. Until more data are available, physicians should not prescribe zanamivir to patients prone to bronchospasm.
  • Although oseltamivir is approved for use up to 48 hours after the initiation of symptoms, one study suggested that the most significant effect occurs when taken within 6 hours of symptom onset, and only limited effects when therapy is begun more than 24 hours after symptom onset.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Drug Category: Antiviral agents

Drugs indicated for treatment of influenza include neuraminidase inhibitors (ie, oseltamivir and zanamivir) and amantadine and rimantadine.

Drug Name	Zanamivir (Relenza)
Description	Inhibitor of neuraminidase, which is a glycoprotein on the surface of the influenza virus that destroys the infected cell's receptor for viral hemagglutinin. By inhibiting viral neuraminidase, release of viruses from infected cells and viral spread are decreased. Effective against both influenza A and B. To be inhaled through Diskhaler oral inhalation device. Circular foil discs that contain 5-mg blisters of drug are inserted into supplied inhalation device.
Adult Dose	5-mg oral inhalation bid for 5 d
Pediatric Dose	<7 years: Not established >7 years: Administer as in adults
Contraindications	Documented hypersensitivity; obstructive airway disease
Interactions	None reported
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Monitor respiratory status; caution in breastfeeding

Drug Name	Rimantadine (Flumadine)
Description	Inhibits viral replication of influenza A virus (H1N1), (H2N2), and (H3N2). Prevents penetration of the virus into the host by inhibiting uncoating of influenza A. Indicated for both prophylaxis and acute treatments. Resistant virus strains may develop and be transmitted. Not recommended by the CDC for the 2005-2006 influenza season because of resistance. Laboratory testing by CDC on the predominant strain of influenza (H3N2) currently circulating in the United States shows that it is resistant to these drugs.
Adult Dose	Acute treatment: 100 mg PO bid Prophylaxis: 100 mg PO bid
Pediatric Dose	<10 years: 5 mg/kg PO qd; not to exceed 150 mg >10 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Acetaminophen and aspirin reduce levels when taken concurrently; cimetidine increases plasma levels when taken concomitantly
Pregnancy	C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions	Caution in hepatic impairment

Drug Name	Amantadine (Symmetrel)
Description	Prevents penetration of virus into host by inhibiting uncoating of influenza A. Indicated for both prophylaxis and acute treatments. Resistant virus strains may develop and be transmitted. Not recommended by the CDC for the 2005-2006 influenza season because of resistance. Laboratory testing by CDC on the predominant strain of influenza (H3N2) currently circulating in the United States shows that it is resistant to these drugs.
Adult Dose	<65 years: 200 mg/d PO qd or divided bid >65 years: 100 mg PO qd
Pediatric Dose	<1 year: Not established 1-9 years: 5-9 mg/kg/d PO qd or divided bid; not to exceed 150 mg 10-12 years: 100 mg PO bid >12 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Drugs with anticholinergic or CNS stimulant activity increase toxicity; concurrent administration of hydrochlorothiazide plus triamterene with amantadine may increase plasma concentrations of amantadine
Pregnancy	C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions	Caution in liver disease, uncontrolled psychosis, eczematoid dermatitis, seizures, and patients receiving CNS stimulant drugs; CNS effects, including agitation, exacerbation of seizures, blurred vision, muscle rigidity, and behavioral changes, may occur; reduce dose in renal disease when treating Parkinson disease; do not discontinue abruptly; suicide attempts associated with use; sporadic cases of neuroleptic malignant syndrome have been associated with amantadine

Drug Category: Vaccine

Influenza A vaccine is administered each year prior to flu season. The CDC analyzes the vaccine subtypes each year and makes any necessary changes based on worldwide trends.

In April 2007, the US Food and Drug Administration (FDA) approved the first vaccine for H5N1 influenza (ie, avian or bird flu). The approval was based on one multicenter, randomized, double-blinded, placebo-controlled, dose-ranging study in healthy adults aged 18-64 years. The trial investigated the safety and immunogenicity of the vaccine. A total of 103 healthy adults received a 90-mcg dose of the vaccine via IM injection, followed by another 90-mcg dose 28 days later. In addition, approximately another 300 healthy adults received the vaccine at doses lower than 90 mcg, and a total of 48 received placebo by injection. Of the various doses tested, the study showed that the 90-mcg 2-dose regimen provided the better immune response and produced levels of antibodies expected to reduce the risk of acquiring H5N1 influenza in 45% of those who received it.

Drug Name	Influenza virus vaccine, intranasal (FluMist)
Description	Indicated for active immunization to prevent influenza A and B viruses in healthy children, adolescents, and adults. Induces antibodies specific to virus strains contained in vaccine following administration. The US Public Health Service determines influenza vaccine contents annually. Typically, 3 live attenuated virus strains, which antigenically represent the influenza strains likely to circulate the next flu season, are included in the formulation each year.
Adult Dose	0.2 mL intranasally (ie, 1 mL in each nostril) once per season >49 years: Not established
Pediatric Dose	<2 years: Not established 2-8 years NOT previously vaccinated with intranasal influenza vaccine: 0.2 mL intranasally (ie, 1 mL in each nostril), then repeat dose in 46-74 d 2-8 years previously vaccinated with intranasal influenza vaccine: 0.2 mL intranasally (ie, 1 mL in each nostril) once per season >8 years: Administer as in adults
Contraindications	Documented hypersensitivity to vaccine contents, including egg or egg protein; children or adolescents receiving aspirin therapy; Guillain-Barré history; known or suspected immune deficiency conditions, including those secondary to immunosuppressive therapies; asthma or reactive airway diseases
Interactions	Do not administer to children or adolescents receiving aspirin (may increase Reye Syndrome); do not administer until 48 h following discontinuing antiviral agents, and do not initiate antiviral agents for 2 wk following vaccine administration; no data regarding coadministration with other intranasal drugs
Pregnancy	C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions	For nasal use only; thaw prior to use; may increase cough, rhinorrhea, and nasal congestion following second dose in children; may cause cough, runny nose, or sore throat in adults

Drug Name	Influenza virus vaccine, H5N1
Description	Inactivated virus vaccine. Induces antibodies against viral hemagglutinin in vaccine, thereby blocking viral attachment to human respiratory tract epithelial cells. Estimated to reduce risk of contracting avian influenza by 45%. Indicated for active immunization of adults at increased risk of exposure to H5N1 influenza virus subtype.
Adult Dose	18-64 years: Administered as 2-dose regimen; 1 mL (90 mcg) IM on day 1, then repeat dose once on day 28
Pediatric Dose	<18 years: Not established >18 years: Administer as in adults
Contraindications	None known
Interactions	Immunosuppressive therapies (eg, high-dose corticosteroids, transplant antirejection medication, antineoplastic agents) may reduce immune response to vaccine
Pregnancy	C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions	Data limited; common adverse effects include pain and tenderness at injection site, headache, malaise, and myalgia; do not mix with other vaccines in same syringe; avoid in pregnant or breastfeeding women because of insufficient data in these populations

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Hospitalization
• • Most frequently, exacerbation of underlying chronic diseases by influenza may result in hospitalization. Some patients, especially elderly individuals, may be too weak to care for themselves alone at home.
  • On occasion, the direct pathologic effects of influenza may require hospitalization. Most commonly, this is influenza pneumonia.

Further Outpatient Care

• Patients who do not improve should return for further evaluation. Patients diagnosed with influenza infection should be educated about potential complications and encouraged to return for evaluation if concerned. This is especially true of patients with underlying chronic disease or those who are immunocompromised.

Deterrence/Prevention

• Influenza vaccine provides good protection against immunized strains. The vaccination becomes effective 10-14 days after administration.
• Each year in the United States, a vaccine that contains antigens from the strains most likely to cause infection during the winter flu season is produced.
  • For example, during 2001-2003, 2 strains of influenza A virus, A/Panama/2007/99 (H3N2) and A/New Caledonia/20/99 (H1N1), and 1 strain of influenza B (B/Hong Kong 330/01) comprised the vaccine.
  • During the 2003-2004 season, the vaccine contained the same A-H1N1 and B strains. However, the A-H3N2 strain selected was Moscow 10/99, similar to A-H3N2 Panama/2007/99. Instead, the predominant strain that surfaced in the United States was A-H3N2 Fujian/2007/99. The CDC believes that partial protection was still provided to individuals who received the vaccine. For the 2004-2005 and 2005-2006 seasons, similar compositions were used (eg, A/H1N1-New Caledonia/20/99, A-H3N2-Fujian/411/2002, B-Shanghai/361/2002).
  • For the 2006-2007 season, the trivalent vaccine contains the following antigenic strains: influenza A - H1N1: New Caledonia/20/1999; influenza A - H3N2: Wisconcin/67/2005 or equivalent; and influenza B: Malaysia 2506/2004 or equivalent.
• Influenza vaccine is also available as a nasal spray (FluMist) for healthy children aged 5 years or older, adolescents, and adults aged 49 years or younger. Clinical trials are limited in scope regarding the protective effects of live vaccine. The live virus is attenuated by cold; therefore, only very limited viral replication occurs at temperatures of more than 95°F.
• Specific recommendations for individuals who should be immunized can be obtained from the CDC (see Prevention and Control of Influenza). People recommended for immunization include elderly individuals, those with certain chronic diseases, and health care workers.
• A vaccine designed to be effective against H5N1 is currently under development, and contracts to produce several million doses have been awarded.

Complications

• Primary influenza pneumonia is characterized by progressive cough, dyspnea, and cyanosis following the initial presentation on the infection. CXRs show diffuse infiltrative patterns bilaterally, without consolidation, which can progress to a presentation similar to acute respiratory distress syndrome. Risks for viral pneumonia involve a number of complex host immune responses and viral virulence. Although elderly individuals, especially nursing home patients, and those with cardiovascular disease constitute the highest risk groups, do not forget that in the 1918-1919 epidemic, many young adults died of a pneumonia that some experts believe was caused directly by the virus.
• Secondary bacterial pneumonia can occur from a number of bacteria (eg, Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae).
• • The most dreaded is staphylococcal pneumonia, which develops 2-3 days following the initial presentation of viral pneumonia. Patients appear severely ill, with hypoxemia, an elevated white blood cell count, productive bloody cough, and a CXR showing multiple infiltrates. These patients are at risk for hypotension.
  • S pneumoniae or H influenzae pneumonia, if occurring as a complication, usually develops 2-3 weeks after the initial symptoms of influenza and can be managed as a community-acquired pneumonia, following standard antibiotic and admission/discharge guidelines. Because of increasing numbers of antibiotic-resistant staphylococcus emerging from the community, methicillin-resistant S aureus (MRSA) must be considered in any patient who develops pneumonia following an episode of influenza.
• Myositis is a rare complication. This group of patients may develop frank rhabdomyolysis, with elevated creatine kinase levels and myoglobinuria.
• Myocarditis and pericarditis have been associated with influenza infections.

Prognosis

• In patients without comorbid disease, the prognosis is very good, although some patients have a prolonged recovery time and remain weak and fatigued for weeks.

Patient Education

• For excellent patient education resources, visit eMedicine's Cold and Flu Center. Also, see eMedicine's patient education article Flu in Adults.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Early presentations of more serious infections initially may be erroneously diagnosed as influenza.
• Physicians who diagnose influenza in residents of nursing homes should notify the nursing home medical director so that preventive measures can be taken to protect other residents.
• Postinfluenza pneumonia is a serious complication and needs to be treated aggressively.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Belshe RB, Mendelman PM, Treanor J, et al. The efficacy of live attenuated, cold-adapted, trivalent, intranasal influenzavirus vaccine in children. N Engl J Med. May 14 1998;338(20):1405-12. [Medline].
• Bridges CB, Fukuda K, Cox NJ, et al. Prevention and control of influenza. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. Apr 20 2001;50(RR-4):1-44. [Medline]. [Full Text].
• Centers for Disease Control and Prevention (CDC). Update: influenza activity--United States, March 5-11, 2006. MMWR Morb Mortal Wkly Rep. Mar 24 2006;55(11):311-3. [Medline].
• Gross PA, Hermogenes AW, Sacks HS, et al. The efficacy of influenza vaccine in elderly persons. A meta-analysis and review of the literature. Ann Intern Med. Oct 1 1995;123(7):518-27. [Medline].
• Gubareva LV, Kaiser L, Matrosovich MN, et al. Selection of influenza virus mutants in experimentally infected volunteers treated with oseltamivir. J Infect Dis. Feb 15 2001;183(4):523-31. [Medline].
• Hayden FG, Gubareva LV, Monto AS, et al. Inhaled zanamivir for the prevention of influenza in families. Zanamivir Family Study Group. N Engl J Med. Nov 2 2000;343(18):1282-9. [Medline].
• Hayden FG, Atmar RL, Schilling M, et al. Use of the selective oral neuraminidase inhibitor oseltamivir to prevent influenza. N Engl J Med. Oct 28 1999;341(18):1336-43. [Medline].
• Hayden FG, Treanor JJ, Fritz RS, et al. Use of the oral neuraminidase inhibitor oseltamivir in experimental human influenza: randomized controlled trials for prevention and treatment. JAMA. Oct 6 1999;282(13):1240-6. [Medline].
• Linder JA. Influenza-associated deaths among children. N Engl J Med. Mar 23 2006;354(12):1317-8; author reply 1317-8. [Medline].
• Medical Letter. Rapid diagnostic tests for influenza. Med Lett Drugs Ther. Dec 17 1999;41(1068):121-2. [Medline].
• Medical Letter. Two neuraminidase inhibitors for treatment of influenza. Med Lett Drugs Ther. Oct 8 1999;41(1063):91-3. [Medline].
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Article Last Updated: Sep 25, 2007