Influenza

Influenza viruses A and B cause acute respiratory infection. Influenza may present with symptoms similar to the common cold (see Upper Respiratory Infection chapter) but more often causes acute and severe systemic symptoms, such as abrupt-onset high fever, myalgia, weakness, and severe pulmonary involvement.

Symptoms typically begin abruptly after a 1- to 4-day incubation. An infected person can pass the virus to others for 24-48 hours before symptoms begin and for approximately 1 week after symptom onset; however, shedding of influenza can be prolonged in children and in elderly or immunocompromised individuals. Uncomplicated influenza is debilitating during acute illness, but self-limited. In high-risk populations, however, influenza can cause significant morbidity and mortality.

Influenza has become a matter of increasing concern due to outbreaks of H5N1 avian influenza and the confirmation that the pandemic of 1918, which killed up to 50 million people, was caused by an avian virus with properties similar to those of H5N1. [1],[2] Wild birds may carry influenza viruses in their digestive tracts and are believed to pass them to domesticated birds, typically in poultry farms, where viruses may replicate and be transmitted to humans. Out of the 861 human cases of H5N1 influenza reported to the World Health Organization between 2003 and September 27, 2019, 455 people have died.[3] Novel H7N9 avian influenza, presently circulating among poultry farms in China, has a similarly high case-fatality rate among humans.[4]

At present, however, the greatest threat is seasonal influenza, which can be severe and has annual fatality rates in the US ranging from about 3,000-49,000 people.[5] Latest estimates suggest that between 3% and 11% of Americans become sick with influenza each flu season.[5]

Risk Factors

Contact with infected individuals. Direct contact with persons who have signs of a respiratory infection permits viral transfer. Coughing or sneezing aerosolizes respiratory droplets containing influenza virus. The droplets can enter the mouths or noses of those in close proximity, or make contact with hands and household surfaces, and can be transmitted to uninfected persons.[5] They can also be directly inhaled. Saliva is not an effective mode of transmission.

Immunocompromise. Persons with compromised immune systems, including those with malnutrition, diabetes, and chronic respiratory disease, generally have a higher risk of mortality if they are infected by influenza. Additionally, pregnant women, children (especially under age 2), and people > 65 years of age are at higher risk of flu-related complications.[6] In North America, the same is true of indigenous populations.

Winter season. Influenza infections more commonly occur between October and May, with a peak in incidence between December and February.[7] However, influenza viruses circulate year-round in the tropics. Also, although May through October are warm months in the Northern Hemisphere, these months are colder in the Southern Hemisphere, and viruses can therefore be imported to the US at any time of year.

Contact with infected birds. Risk for H5N1 and H7N9 influenza is principally related to contact with infected domesticated birds or bird feces, secretions, and products.

Diagnosis

Influenza typically has physical findings consistent with upper and/or lower respiratory tract infection, as well as systemic symptoms such as myalgia, fever, and headache.

Patients with symptoms or signs of lower respiratory infection, such as dyspnea and rales, should be evaluated for pneumonia or exacerbation of chronic lung disease. Persons who appear seriously ill may require hospitalization and antibiotic treatment when bacterial pneumonia or systemic infection is suspected.

Rapid influenza tests that identify the presence of influenza A and B in respiratory samples are valuable diagnostic tools when influenza is suspected in the clinic and when antiviral therapy could shorten the course and reduce symptoms.[8] Rapid tests may not be useful or cost-effective during outbreaks, when the probability of flu is high. Most individuals who present with flu-like illnesses during an outbreak can be treated accordingly without further testing.[9]

Laboratory surveillance through diagnostic testing can help track the specific viral strains circulating in a certain region or during a particular season, as well as antiviral resistance, but it does not inform immediate clinical decision-making in the context of a seasonal influenza outbreak where pretest probability of influenza is high. Laboratory surveillance also informs selection of vaccine strains for inclusion in subsequent years.

Prevention

Covering the mouth and nose when coughing and sneezing, frequent hand-washing, and avoiding touching one’s eyes and nose are the most effective preventive strategies to avoid infection.

The influenza vaccine, when well matched to circulating strains, reduces the risk of a doctor’s visit for influenza by approximately 40-60%.[10] Data from recent influenza seasons demonstrate an overall reduction in flu-related hospitalizations and intensive care unit admissions by 40% and 82%, respectively, following the influenza vaccine in adults.[10] The influenza vaccine reduces hospitalization among flu-infected community-dwelling older adults and people with chronic lung disease, diabetes, or chronic hepatitis B infection.[10],[11],[12],[13] The influenza vaccine also reduces severity of illness among those infected and has been associated with reduced risk of major adverse cardiovascular events.[14],[15]

Exercise appears to improve vaccine response, particularly in the elderly. Moderate exercise (> 20 minutes, 3 times/week) significantly improved antibody response to the influenza vaccine in studies in this population.[16],[17] In women aged 55 to 75 years, an episode of moderate-intensity exercise immediately prior to the influenza vaccine led to significantly higher antibody responses against the H1N1 influenza component compared with men.[18]

In older individuals, levels of perceived stress have been shown to affect certain immune responses to the flu vaccine (e.g., production of antibodies and interleukin-2).[19],[20] A limited body of evidence suggests that stress-management interventions can produce significant increases in antibody titer after flu vaccination.[20] In a study of adults aged 65-85 years, positive mood on the day of flu immunization was correlated to seroprotection against the H1N1 strain of influenza at both 4 and 16 weeks following vaccination, irrespective of age and sex.[21]

Treatment

Influenza is a self-limited illness, except in high-risk individuals or when a highly pathogenic strain is involved. Early treatment with antivirals can shorten symptom duration and severity; their benefit is greatest if started within 48 hours of symptom onset. Because of its high cost, preventive drug therapy may be reserved for high-risk populations. Vaccination remains the most effective mode of prevention. The following antivirals may reduce symptoms and shorten the course of disease:

Oseltamivir (Tamiflu), zanamivir (Relenza), and peramivir (Rapivab). These neuraminidase inhibitors are generally effective for treatment of influenza A and B, but only oseltamivir and zanamivir are approved for prevention. Most avian H5N1 infections have been sensitive to oseltamivir, although resistance has been reported.[22],[23] Oseltamivir and peramivir are generally well-tolerated but may cause gastrointestinal symptoms such as nausea, vomiting, and diarrhea. Zanamivir may cause respiratory side effects, including bronchospasm, in those with respiratory problems. Oseltamivir has been shown to reduce duration of influenza symptoms by about 1 day.[24]

Baloxavir (Xofluza). This endonuclease inhibitor has a different mechanism of action than that of the 3 other antiviral medications approved by the Food and Drug Administration and recommended by the Centers for Disease Control and Prevention (CDC) to treat influenza, listed above. Baloxavir is given as a single oral tablet and is indicated for treatment of flu in those over age 12 years. In patients with flu aged 12 to 64 years, efficacy of Baloxavir is similar to that of oseltamivir: Symptoms of influenza are reduced by about 1 day compared with placebo.[25]

Amantadine and rimantadine (M2 ion channel blockers). These drugs are effective against only influenza A, and resistance is common. Due to the high levels of resistance, the CDC has recommended that these drugs not be used for the prevention or treatment of currently circulating influenza A.[26]

Acetaminophen and NSAIDs. These common medications may improve myalgia, fever, throat pain, or headache. Aspirin should be avoided, particularly in children with an acute viral illness, due to the risk of Reye syndrome. When cold symptoms occur, only symptomatic treatment is beneficial (see Upper Respiratory Infection chapter). Patients should be advised to stay hydrated and rest as needed.

The most common complication of influenza is viral and/or bacterial pneumonia. Extrapulmonary complications include myositis, rhabdomyolysis, pericarditis, myocarditis, Reye syndrome, central nervous system complications such as encephalitis and Guillain-Barré syndrome, and toxic shock syndrome due to coinfection with S. aureus. All of these require specialized treatment.

Nutritional Considerations

Obesity. Obesity increases both the risk for influenza and its severity.[27] A study of 274 US counties found a significantly higher rate of hospitalization for influenza in communities where obesity, low fruit and vegetable consumption, and physical inactivity were more prevalent, compared with those where these conditions were less prevalent. In their analysis of pandemic H1N1 influenza cases in California, researchers documented an overrepresentation of both total cases and fatal cases in individuals with a body mass index of 30 or greater.[28] In addition to having a higher risk of uncomplicated and severe influenza, obese individuals who have been vaccinated against influenza have double the risk of acquiring influenza or influenza-like illness compared to vaccinated non-obese adults, irrespective of serological response to vaccine.[29]

Green tea catechins. Studies have revealed that some of the active plant compounds (catechins) in green tea inhibit viral infectivity and proliferation in vitro through numerous mechanisms. Both observational and controlled clinical studies have revealed the ability of green tea consumption or green tea concentrates to significantly lower the incidence of influenza.[30],[31] Furthermore, a randomized placebo-controlled trial demonstrated that capsules containing green tea significantly reduced symptoms of influenza or an influenza-like illness in healthy adults followed for 3 months, compared with those randomized to the placebo group.[32] Finally, in their meta-analysis of randomized clinical trials and prospective cohort studies, researchers demonstrated that gargling tea or its ingredients significantly reduced the risk of influenza infection, compared with those who gargled a placebo solution or who did not gargle at all.[33]

Sulforaphanes. In smokers, ingestion of broccoli sprout homogenates has been demonstrated to reduce influenza virus-mediated inflammation of the nasal mucosa, and viral replication.[34] In healthy volunteers, broccoli sprout homogenates have been shown to modulate immune cell responses to an attenuated strain of influenza, an effect that may be important in host defenses against the virus.[35]

Zinc. Zinc is an important nutrient for immune function. Deficiency is rare, except in elderly individuals. A study randomly assigned 50 healthy elderly subjects (ages 55-87) to a zinc supplement (45 mg zinc per day) or placebo for 12 months. There were 0 incidents of the flu in the zinc group, but 12 cases in the placebo group. The zinc group also experienced significantly lower incidents of overall infections and had reduced markers of inflammation and oxidative stress, as well as higher levels of plasma Zn levels.[36] Plant-based sources of zinc include legumes (beans, lentils, peas, peanuts), soy foods, nuts, seeds, and oats.[37]

Vitamin D. In a randomized clinical trial, high-dose vitamin D (1200 IU/day) supplementation (via oral preparation) was superior to low-dose vitamin D (400 IU/day) at preventing influenza A infection in infants. In those infants who acquired influenza A, the high-dose group had a shorter duration of fever, cough, and wheezing.[38]

Other lifestyle factors. Stress (reference), inadequate sleep (reference) and exercise, excessive exercise, smoking, and alcohol (reference) intake may negatively affect the immune system making it more difficult to fight the flu.[19],[39],[40]

Orders

See Basic Diet Orders chapter.

What to Tell the Family

Influenza is easily transmitted within households or closed living environments, such as long-term care facilities. Covering one’s mouth and nose while coughing and sneezing and prompt hand-washing should be encouraged. Refraining from touching the eyes and nose may also help prevent respiratory infections. A flu vaccine is likely to be helpful for all people age 6 months and older, but particularly those over the age of 65; pregnant women; children aged 6 months to 5 years; people living in long-term care facilities; anyone with a chronic disease, such as diabetes, hepatitis B or HIV infection, or asthma; household contacts of persons at high risk; and health care workers. When flu occurs in the family, prescription medicines may be effective for treatment or prevention if received within 48 hours of symptom onset.

References

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