There are four types of influenza viruses: A and B, which are most commonly associated with seasonal flu activity and epidemics; C, which is relatively rare and causes mild respiratory illness; and D, which primarily affects cattle.

Influenza A

There are many subtypes of influenza A viruses, based on two proteins — hemagglutinin (H) and neuraminidase (N) — found on the surface of the viruses. Two strains of influenza A found in human beings are the H1N1 strain and the H3N2 strain.

A novel strain of influenza A (H1N1) virus, known as swine flu because it’s typically spread among pigs, led to a flu pandemic in 2009. Between April 2009 and April 2010, the CDC estimates that there were 60.8 million swine flu cases in the United States, which led to more than 274,000 hospitalizations and nearly 12,500 deaths. (5)

The H3N2 virus usually causes more severe symptoms and can be particularly dangerous to the young and elderly. Flu seasons that have many cases of the H3N2, such as the 2017–2018 flu season, tend to have higher rates of hospitalizations and flu-related deaths. H3N2 is particularly resistant to the flu vaccine, and it mutates more rapidly than other strains.

Influenza B

Less common than influenza A, these viruses cause similar symptoms and can lead to outbreaks or pandemics. Influenza B is not categorized by subtypes, but there are two strains of the virus: Yamagata and Victoria.

A study published in Clinical Infectious Diseases in July 2014 challenged the perception that influenza B was milder than influenza A. (6)

Influenza C

Like influenza A and B, these viruses are found in humans. But influenza C viruses are milder and do not cause epidemics. Seasonal flu vaccines, which contain strains of influenza A and B, do not protect against influenza C viruses.

Influenza D

This strain of influenza is not known to cause illness in humans. It primarily affects cattle, though researchers note that it could eventually form a new strain that poses more of a threat to humans. (7)

 

 

 

 

 

    Influenza virus is transmitted through infected respiratory droplets that are aerosolized by coughing, sneezing, or talking.

    The virus that attacks the lungs, nose, and throat.

    Less commonly, contact with fomites may cause transmission. 

    The virus binds to and enters the tracheobronchial ciliated epithelium by utilizing the viral surface hemagglutinin (H antigen).

    Viral replication then occurs. Peak viral shedding occurs in the first 48 to 72 hours of exposure to the virus, then declines and becomes undetectable within 10 days.

    Children and immunocompromised people may shed virus for several weeks. [12]

     

 

 

 

Content 10

Content 11

Outbreaks of illness of variable extent and severity occur nearly every year. Such outbreaks result in significant morbidity rates in the general population and in increased mortality rates among certain high-risk patients, mainly as a result of pulmonary complications.

Influenza occurs in outbreaks and epidemics worldwide, mainly during the winter season. Although acutely debilitating, influenza is usually a self-limited infection.

 

 

 

 

 

The majority of patients will have a self-limited, uncomplicated illness requiring only symptomatic care.

Oral Fluids (Water. Jouice. etc

Acetaminophne for muscle aches and fever (dose)

Cough suppressant.

Patients with more severe influenza may benefit from IV fluids, respiratory support, and occasionally vasopressors.

Table 153–1

Risk Factors for Severe Influenza3

Risk Factors for Severe Influenza3

Children younger than age 2 years

Adults age 65 years and older

Patients with comorbid conditions

Immunosuppressed

Pregnant patients

Patients younger than 19 years receiving long-term aspirin

American Indians/Alaskan natives

Morbidly obese patients

Residents of nursing homes and long-term care facilities

Those with pneumonia should be treated with antibiotics, targeting methicillin-resistant S. aureus if severe pneumonia exists.Two classes of antiviral drugs are available for the treatment and prevention of influenza [1-4]:

●The neuraminidase inhibitors, zanamivir, oseltamivir, and peramivir, which are active against both influenza A and B

●The adamantanes, amantadine and rimantadine, which are only active against influenza A. Due to a marked increase in resistant isolates, the Advisory Committee on Immunization Practices (ACIP) recommends that adamantanes not be used in the United States for the treatment of influenza, except in selected circumstances [1].

 

BENEFITS OF THERAPY — When initiated promptly, antiviral therapy with a neuraminidase inhibitor can shorten the duration of influenza symptoms by approximately one-half to three days; in most studies, the benefit has been greatest when given within the first 24 to 30 hours and in patients with fever at presentation [5-11].

Most trials of oseltamivir in ambulatory patients have been limited to patients presenting within 48 hours of symptom onset [12].

The prevailing impression has been that there is little or no benefit when treatment is initiated two days or more after the onset of uncomplicated influenza. However, a patient survey found that only 13 percent of patients called their clinician within 48 hours of the onset of influenza-like symptoms [13]. In a study of outpatients at increased risk for influenza complications, only 30 percent presented for care within 48 hours of symptom onset and, among those who did, only 15 percent were prescribed an antiviral agent [14]. The proportion was higher among patients who presented early and who had laboratory-confirmed influenza (43 percent) or who presented during the peak week of influenza season (31 percent).

Some studies have suggested that antiviral therapy reduces the severity and incidence of complications of influenza [8,11,15-18], the length of stay in those hospitalized for influenza including older adults [19,20], and influenza-associated mortality [21-23]. However, other studies of immunocompetent patients have not shown a reduction in complications of influenza among patients who received antiviral therapy [9,10].

The efficacy and safety of antiviral agents for seasonal influenza are discussed in greater detail below. (See 'Neuraminidase inhibitors' below and 'Adamantanes' below.)

 

●The adamantanes, amantadine and rimantadine, which are only active against influenza A. Due to a marked increase in resistant isolates, the Advisory Committee on Immunization Practices (ACIP) recommends that adamantanes not be used in the United States for the treatment of influenza, except in selected circumstances [1].

(See 'Choice of antiviral drug' below.)

 

 

 

 

 

Specific antiviral therapy is available for influenza (Table 224-3): the neuraminidase inhibitors zanamivir and oseltamivir for both influenza A and influenza B and the adamantane agents amantadine and rimantadine for influenza A.

Antiviral medications Relenza or Tamiflu.

 

 

The epidemiologic patterns of resistance to the influenza antiviral drugs are crucial elements in the selection of treatment. Up-to-date information on patterns of resistance to influenza antiviral drugs is available through www.cdc.gov/flu.

A 5-day course of oseltamivir or zanamivir reduces the duration of signs and symptoms of uncomplicated influenza by 1–1.5 days if treatment is started within 2 days of the onset of illness and may be effective if started up to 5 days after onset of symptoms. Zanamivir is administered via an oral inhalation device and may exacerbate bronchospasm in asthmatic patients. Oseltamivir has been associated with nausea and vomiting, whose frequency can be reduced by administration of the drug with food. Oseltamivir has also been associated with neuropsychiatric side effects in children. Peramivir, an investigational neuraminidase inhibitor that can be administered intravenously, is being evaluated in clinical trials, as is an intravenous form of zanamivir.

Amantadine and rimantadine are active only against influenza A, and widespread resistance exists among influenza A/H1N1 and A/H3N2 viruses that are circulating currently; thus, the use of these drugs is not recommended unless influenza isolates are known to be sensitive. Amantadine or rimantadine treatment of illness caused by sensitive strains of influenza A virus reduces the duration of symptoms of uncomplicated influenza by ~50% if begun within 48 h after onset of illness—an effect similar to that of the neuraminidase inhibitors. Of amantadine recipients, 5–10% experience mild CNS side effects, primarily jitteriness, anxiety, insomnia, or difficulty concentrating. These side effects disappear promptly upon cessation of therapy. Rimantadine appears to be equally efficacious and is associated with less frequent CNS side effects than is amantadine.

Ribavirin is a nucleoside analogue with activity against influenza A and B viruses in vitro. Its efficacy against influenza when administered as an aerosol is reportedly variable, and it is ineffective when administered orally. Its efficacy in the treatment of influenza A or B has not been established.

The therapeutic efficacy of antiviral compounds in influenza has been demonstrated primarily in studies of young adults with uncomplicated disease. The effectiveness of these drugs in the treatment or prevention of complications of influenza is unclear. Pooled analyses of observational investigations and some efficacy studies have suggested that treatment with oseltamivir may reduce the frequency of lower respiratory complications and hospitalization. Therapy for primary influenza pneumonia is directed at maintaining oxygenation and is most appropriately undertaken in an intensive care unit, with aggressive respiratory and hemodynamic support as needed.

Antibacterial drugs should be reserved for the treatment of bacterial complications of acute influenza, such as secondary bacterial pneumonia. The choice of antibiotics should be guided by Gram’s staining and culture of appropriate specimens of respiratory secretions, such as sputum. If the etiology of a case of bacterial pneumonia is unclear from an examination of respiratory secretions, empirical antibiotics effective against the most common bacterial pathogens in this setting (S. pneumoniaeS. aureus, and H. influenzae) should be selected.ntiviral therapy may be considered. Acetaminophen or nonsteroidal anti-inflammatory agents can be used for relief of headache, myalgia, and fever, but salicylates should be avoided in children <18 years of age because of the possible association with Reye’s syndrome . Because cough is ordinarily self-limited, treatment with cough suppressants generally is not indicated; codeine-containing compounds may be used if the cough is particularly troublesome. Patients should be advised to rest and maintain hydration during acute illness and to return to full activity only gradually after illness has resolved, especially if it has been severe.

 

 

The flu can be mild to severe to life-threatening, but most cases can be treated at home with over-the-counter medication and lots of fluids and rest.

 

 

Antiviral drugs can be used to treat the flu and speed recovery by 1 or 2 days. (4) But the CDC stresses that these drugs are a second line of defense against the flu after

 

Efficacy — Oseltamivir or zanamivir is recommended for the prevention of influenza based on their demonstrated efficacy and lower rates of resistance compared with the adamantanes [3-5].

However, it is important to assess the risk of oseltamivir-resistant influenza before choosing an antiviral drug for influenza chemoprophylaxis. (See 'Neuraminidase inhibitor resistance' below and 'Influenza activity' below and 'Choice of antiviral drug' below.)

 

 

General — The neuraminidase inhibitors are effective for the prevention of influenza in healthy individuals [6-14], in community-dwelling persons at high risk for influenza complications [15], and in residents of long-term care facilities [6,16-19].

The efficacies of oseltamivir and zanamivir have not been directly compared. One study examined the efficacy of treating influenza with oseltamivir in preventing secondary influenza in household contacts [20]. The efficacy was modest, suggesting that treating exposed individuals is a more effective preventive strategy.

In a 2003 meta-analysis of seven prevention trials, prophylactic therapy with oseltamivir or zanamivir was associated with substantially reduced rates of influenza [6]. The incidence of laboratory-confirmed influenza was significantly reduced when oseltamivir was used as seasonal prophylaxis in a healthy population (odds ratio [OR] 0.26, 95% CI 0.08-0.84), as postexposure prophylaxis in the household setting (OR 0.10, 95% CI 0.04-0.29), or as seasonal prophylaxis in a long-term care facility that housed elderly individuals (OR 0.08, 95% CI 0.01-0.61). The incidence of laboratory-confirmed influenza was also significantly reduced when zanamivir was used as seasonal prophylaxis in a healthy population (OR 0.31, 95% CI 0.14-0.64) or as postexposure prophylaxis in the household setting (OR 0.19, 95% CI 0.09-0.38).

A 2006 meta-analysis that included only trials of healthy adults showed similar reductions in the incidence of influenza with oseltamivir or zanamivir prophylaxis (relative risk [RR] 0.39, 95% CI 0.18-0.85 and 0.38, 95% CI 0.17-0.85, respectively) [7].

In a 2014 systematic review of unpublished clinical study reports from three randomized prophylaxis trials obtained from the European Medicines Agency and the manufacturer of oseltamivir, oseltamivir reduced the rate of symptomatic influenza in individuals (risk ratio [RR] 0.45, 95% CI 0.30-0.67; risk difference 3.05%, 95% CI 1.83-3.88 percent) [21]. In an analysis of reports from one prophylaxis trial, oseltamivir reduced the rate of symptomatic influenza in households (RR 0.20, 95% CI 0.09-0.44; risk difference 13.6 percent, 95% CI 9.52-15.47 percent). However, there was no reduction in asymptomatic influenza (ie, increases in antibody titers in the absence of symptoms) and no evidence of a reduction in transmission.

In a related 2014 systematic review of unpublished clinical study reports from four randomized prophylaxis trials obtained from the European Medicines Agency and the manufacturer of zanamivir, zanamivir reduced the risk of symptomatic influenza in individuals (RR 0.39, 95% CI 0.22-0.70; risk difference 1.98 percent, 95% CI 0.98-2.54 percent) [22]. In an analysis of reports from five trials, it also reduced the risk of symptomatic influenza when used for postexposure prophylaxis of households (RR 0.33, 95% CI 0.18-0.58; risk difference 14.84 percent, 95% CI 12.18-16.55 percent). However, there was moderate heterogeneity between studies. Zanamivir reduced the risk of self-reported investigator-mediated unverified pneumonia in adults (RR 0.30, 95% CI 0.11-0.80). Zanamivir did not reduce the risk of asymptomatic influenza in prophylaxis of individuals or postexposure prophylaxis of households.

Laninamivir, a long-acting inhaled neuraminidase inhibitor, was reported to be effective for preventing influenza infection in the household contacts of patients with influenza. In a randomized trial conducted in Japan, family members living with a patient with influenza infection (most of whom had influenza A H3N2 infection) within 48 hours of symptom onset were randomly assigned to receive a single dose of 40 mg of laninamivir, two doses of 20 mg of laninamivir given daily for two days, or placebo [14]. The proportion of participants who developed clinical influenza that was confirmed by laboratory testing was significantly lower in the laninamivir groups than in the placebo group (4.5 percent in the laninamivir single-dose group, 4.5 percent in the laninamivir two-dose group, and 12.1 percent in the placebo group). Laninamivir is approved for use in Japan but remains investigational elsewhere.

High-risk contacts — A multicenter, randomized trial evaluated the efficacy of zanamivir in community-dwelling individuals ≥12 years of age (mean age 60 years) who were at high risk for developing complications of influenza and who were able to take the first dose within five days of laboratory-confirmed local influenza activity [15]. Subjects took the study drug (inhaled zanamivir 10 mg or placebo once daily) for 28 days. Those who received zanamivir were less likely to develop symptomatic, laboratory-confirmed influenza (RR 0.17, 95% CI 0.07-0.44) and complications of influenza (RR 0.12, 95% CI 0.02-0.73).

Long-term care facilities — Oseltamivir is effective for preventing influenza virus spread during outbreaks in long-term care facilities [16-18]. A randomized trial of oseltamivir prophylaxis in residents of long-term care facilities assessed its efficacy in 548 patients ≥65 years of age in 31 long-term care facilities in the United States and Europe during the 1998 to 1999 influenza season [16]. Individuals were randomly assigned to receive oseltamivir (75 mg once daily for six weeks) or placebo within seven days of the detection of local influenza activity (defined as laboratory-confirmed influenza in one individual in the residential home or two individuals in the immediate geographic community). Oseltamivir prophylaxis was associated with a significant reduction in the incidence of laboratory-confirmed clinical influenza (0.4 versus 4.4 percent in the placebo group).

In patients who had received the influenza vaccine, there was also a significant reduction in the incidence of laboratory-confirmed clinical influenza (0.5 versus 5.0 percent). Twelve of 13 patients who developed influenza had been vaccinated, despite the fact that there was good antigenic match between the influenza vaccine and circulating strains of influenza [23]. Oseltamivir use was also associated with a significant reduction in the incidence of secondary complications, including bronchitis, pneumonia, and sinusitis (0.4 versus 2.6 percent).

Zanamivir has been studied less extensively than oseltamivir among residents of long-term care facilities, but small studies have suggested efficacy in this setting [24,25]. The route of administration (inhalation) might present more difficulty in this population than an oral drug.

Hematopoietic cell transplant recipients — Although the use of antivirals for the prevention of influenza has not been studied extensively among severely immunocompromised patients, oseltamivir was safe and effective in controlling an outbreak of influenza among hematopoietic cell transplant candidates and recipients in an outpatient residential facility [19].

Neuraminidase inhibitor resistance — Compared with the adamantanes, neuraminidase inhibitors have been less likely to promote the onset of viral resistance [26]. However, the emergence of influenza H1N1 isolates resistant to oseltamivir during the 2007 to 2008 season, and the high rates of oseltamivir resistance during the 2008 to 2009 season worldwide, is concerning [27-29]. Most isolates that were resistant to oseltamivir remained susceptible to zanamivir. Since September 2009, 99 percent of influenza virus isolates tested in the United States have been susceptible to neuraminidase inhibitors [4,30,31]. Information regarding antiviral resistance that emerges during the influenza season is available through the United States Centers for Disease Control and Prevention. (See 'Adamantane resistance' below and "Antiviral drug resistance among seasonal influenza viruses".)

Adverse effects — Adverse effects of neuraminidase inhibitors are typically mild, although serious side effects have also been described [32]. Zanamivir can cause bronchospasm and a decline in respiratory function in patients with asthma and other chronic respiratory disorders. As a result, the manufacturer has issued a warning advising particular caution in patients with asthma or chronic obstructive pulmonary disease [33].

Oseltamivir can also cause nausea and vomiting but these side effects have not generally resulted in discontinuation of therapy. (See "Pharmacology of antiviral drugs for influenza", section on 'Adverse effects'.)

ADAMANTANES — The United States Centers for Disease Control and Prevention (CDC) issued a health alert in January 2006 recommending that adamantanes (M2 inhibitors) not be used for the treatment or prevention of influenza in the United States due to high rates of resistance [5]. Resistance to the adamantanes remains high in the United States, and this recommendation remains in effect indefinitely [4].

Efficacy — Amantadine and rimantadine are only effective against influenza A [34]. A systematic review that included trials of healthy adults from 1969 to 1990, prior to the emergence of substantial rates of resistance, showed that amantadine was effective at preventing influenza A infection (efficacy 61 percent, 95% CI 35-76) [7]. Rimantadine showed a nonsignificant trend toward being effective (relative risk [RR] 0.28, 95% CI 0.08-1.08).

However, later studies that evaluated the use of rimantadine or amantadine for the concurrent treatment of index cases and close contacts showed no protection against influenza in contacts and a substantial rate of development of drug resistance [35,36]. As a result of the emergence of high rates of adamantane resistance worldwide, the adamantanes are no longer effective against currently circulating influenza A.

Adamantane resistance — Resistance can develop as early as two to three days after adamantane initiation and is mediated by single nucleotide changes involving the transmembrane portion of the viral M2 protein that is the target of these drugs. Isolates resistant to rimantadine are also resistant to amantadine and vice versa. (See "Pharmacology of antiviral drugs for influenza" and "Antiviral drug resistance among seasonal influenza viruses".)

The rate of adamantane resistance has risen since the mid-1990s. The United States Advisory Committee on Immunization Practices (ACIP) therefore recommends against the use of amantadine or rimantadine for the prevention or treatment of influenza in the United States [4]. (See 'Choice of antiviral drug' below and "Antiviral drug resistance among seasonal influenza viruses", section on 'Adamantane resistance'.)

Side effects — Studies in young adults have reported a discontinuation rate of 13 to 17 percent with amantadine, largely attributable to central nervous system (CNS) toxicity [37,38]. CNS side effects of amantadine include anxiety, insomnia, impaired thinking, confusion, lightheadedness, and hallucinations and are more common in elderly patients. Rimantadine causes fewer CNS side effects than amantadine (13 versus 6 percent in a randomized comparative trial) [37] and has a discontinuation rate due to adverse effects that is similar to placebo [37,38]. (See "Pharmacology of antiviral drugs for influenza", section on 'Adverse effects'.)

ANTIVIRAL PROPHYLAXIS — Antiviral drugs should not be used as a substitute for influenza vaccination. Their adjunctive use is appropriate in certain targeted populations, particularly during outbreaks in nursing homes, hospitals, and other long-term care facilities. (See "Seasonal influenza vaccination in adults".)

Target populations for prevention — Antiviral prophylaxis should be considered in specified populations at high risk for complications of influenza in identified situations of exposure, as discussed below [4,39].

Definition of high risk — Adults at increased risk for influenza complications include (table 1) [4,39,40]:

●Residents of nursing homes and chronic care facilities

 

●Adults ≥65 years of age

 

●Pregnant women and women up to two weeks postpartum [41]. The risk of complicated influenza during pregnancy increases by trimester and with associated comorbidities [42,43]. (See 'Pregnancy' below.)

 

●Individuals with chronic medical conditions including:

 

•Pulmonary disease, including asthma (particularly if systemic glucocorticoids have been required during the past year)

 

•Cardiovascular disease, except isolated hypertension

 

•Active malignancy

 

•Chronic renal insufficiency

 

•Chronic liver disease

 

•Diabetes mellitus

 

•Hemoglobinopathies such as sickle cell disease

 

•Immunosuppression, including HIV infection (particularly if CD4 <200 cells/microL), organ or hematopoietic cell transplantation, inflammatory disorders treated with immunosuppressants

 

•Any neurologic condition that can compromise handling of respiratory secretions (eg, cognitive dysfunction, spinal cord injuries, seizure disorders, neuromuscular disorders)

 

●Native Americans and Alaska Natives

 

●Individuals who are morbidly obese (body mass index [BMI] ≥40)

 

In a large cohort study, obese individuals (including those who were not morbidly obese) were more likely than nonobese individuals to be hospitalized for a respiratory illness during influenza season (BMI 30 to 34.9: 1.45 [95% 1.03-2.05]; BMI ≥35: 2.12 [95% 1.45-3.10]) [44]. Among individuals with a BMI ≥35, the association was present both for those without previously identified risk factors for severe influenza (odds ratio [OR] 5.10, 95% 2.53-10.24) and for those with one previously identified risk factor (OR 2.11, 95% 1.10-4.06). Obesity was first identified as a risk factor for severe influenza during the 2009 to 2010 H1N1 influenza pandemic. (See "Epidemiology of pandemic H1N1 influenza ('swine influenza')", section on 'Obesity'.)

Of the groups described above, patients at highest risk for influenza complications may be those with underlying lung disease and/or severe immunosuppression (eg, lung transplant recipients, individuals with advanced HIV infection [CD4<200 cells/microL], hematopoietic stem cell transplant recipients).

Although there are no data regarding the risk for severe or complicated influenza among asplenic individuals, influenza is a risk factor for secondary bacterial infections that can cause severe disease among such patients [45].

Definition of close contact — A close contact is an individual who has cared for or lived with a person who has confirmed, probable, or suspected influenza infection, or who has been in a setting where there was a high likelihood of contact with respiratory droplets and/or body fluids of such a person, including having talked face to face with a person with suspected or confirmed influenza infection [41].

Indications for chemoprophylaxis — The United States Advisory Committee on Immunization Practices (ACIP) states that the decision of whom to offer chemoprophylaxis to should be made on a case-by-case basis and should be based on the patient's individual risk for influenza complications, the risk of influenza acquisition from the specific exposure, recommendations from local or public health authorities, and clinical judgment [4]. If supplies of antivirals are limited, preference should be given to those at highest risk for influenza complications (eg, lung transplant recipients, individuals with advanced HIV infection [CD4<200 cells/microL], hematopoietic stem cell transplant recipients) who have been exposed to someone with influenza.

With the exception of residents of long-term care facilities, individuals who have been vaccinated against influenza during a season in which there is a good match between the vaccine antigens and circulating viruses generally should not receive prophylaxis. Conversely, during seasons in which there is not a good match between the vaccine antigens and circulating viruses, vaccinated individuals should be managed as if they are unvaccinated and prophylaxis should be offered to those with indications.

Individuals receiving prophylaxis should be counseled that chemoprophylaxis reduces but does not eliminate the risk of influenza, that susceptibility to influenza infection returns once the antiviral medication is stopped, and that adjunctive influenza vaccination should be administered if available [4].

Postexposure prophylaxis — The ACIP states that individuals in whom postexposure prophylaxis can be considered are those who have had close contact with a confirmed or suspected case of influenza during that person's infectious period (one day before the onset of symptoms until 24 hours after the fever ends) and who are at high risk for complications of influenza (eg, individuals with certain chronic medical conditions, <5 years of age, ≥65 years of age, pregnant women) (table 1) [4]. An alternative approach for such individuals involves early treatment. (See 'Definition of close contact' above and 'Definition of high risk' above.)

Balancing the evidence for efficacy of influenza chemoprophylaxis and the importance of both preventing complications in patients at high risk and reducing the risk of promoting antiviral drug resistance, we favor the following approach:

●We recommend influenza prophylaxis during influenza outbreaks in long-term care facilities in elderly and chronically ill residents regardless of prior influenza vaccination. (See 'Outbreaks in long-term care facilities' below.)

 

●In unvaccinated individuals at high risk for influenza complications who have been exposed to an individual with influenza within the previous 48 hours, we recommend influenza prophylaxis (table 1) [39]. Such individuals should also be vaccinated against influenza. (See 'Definition of high risk' above.)

 

●We recommend influenza prophylaxis for vaccinated individuals at high risk for influenza complications who have been exposed to an individual with influenza within the previous 48 hours when there is a poor match between the vaccine and circulating viruses.

 

●In vaccinated individuals at high risk for both a poor response to the vaccine and influenza complications (eg, transplant recipients, patients who received rituximab recently), prophylaxis can be considered for exposures within the previous 48 hours, even when the match between the vaccine and circulating viruses is good, though data to support this practice are lacking.

 

●The use of chemoprophylaxis in pregnant women is discussed below. (See 'Pregnancy' below.)

 

●Regarding the other groups for whom antiviral prophylaxis should be considered, we suggest that the decision of whether to offer prophylaxis be made based upon both the individual's risk for complicated influenza and the degree of exposure (table 1).

 

Postexposure prophylaxis should be used only when antivirals can be started within 48 hours of the most recent exposure [4]. Recommendations regarding the duration of prophylaxis are presented below. (See 'Duration' below.)

The United States Advisory Committee on Immunization Practices recommends postexposure prophylaxis only for individuals at increased risk for influenza complications [4], whereas the Infectious Diseases Society of America states that prophylaxis may be considered for otherwise healthy unvaccinated adults, including healthcare workers, and children ≥1 year of age who are in close contact with individuals at high risk for influenza complications during periods of influenza activity [40]. We agree that it is reasonable to offer prophylaxis to such individuals following close contact with an individual with confirmed or suspected influenza. The use of prophylaxis in staff members of healthcare facilities is discussed in greater detail below. (See 'Outbreaks in long-term care facilities' below and 'Hospital staff' below.)

Individuals who do not have risk factors for influenza complications and who are not close contacts of individuals at high risk for influenza complications do not require postexposure prophylaxis.

Given the concerning trends of increasing resistance with both the adamantanes and the neuraminidase inhibitors, the risk of promoting antiviral drug resistance should be considered when deciding which patients to offer prophylaxis. Overuse of the neuraminidase inhibitors, which are the agents of choice for the prevention and treatment of influenza, will promote further development of resistance that could lead to these agents becoming ineffective. (See 'Neuraminidase inhibitor resistance' above.)

Preexposure prophylaxis — During widespread outbreaks when no vaccine is available (as occurred during much of the 2009 H1N1 influenza A pandemic), preexposure prophylaxis has a very limited role because of concerns about the supply of antivirals, need for long-term use, and the potential for adverse effects and promotion of antiviral resistance [4]. Under such circumstances, preexposure prophylaxis should be used only in individuals at very high risk for influenza complications (eg, severely immunocompromised hosts) who cannot be protected by other means and have a high risk of exposure. (See 'Duration' below.)

Certain individuals who have ongoing occupational risk for exposure (eg, healthcare workers, first responders) who are also at increased risk of influenza complications should follow guidelines for personal protective equipment stringently or consider temporary reassignment in order to reduce the need for postexposure prophylaxis. (See "Infection control measures to prevent seasonal influenza in healthcare settings".)

Outbreaks in long-term care facilities — Influenza vaccination does not provide complete protection to all individuals, particularly among elderly residents of long-term care facilities. As a result, outbreaks can occur in long-term care facilities even when 80 to 98 percent of residents are vaccinated [46].

Influenza testing should occur when two or more residents demonstrate signs of an influenza-like illness within 72 hours of each other during influenza season [40]. Rapid recognition of the outbreak (defined as at least two cases or one laboratory-confirmed case with other compatible illnesses on the same unit when influenza is circulating in the community) and early initiation of prophylaxis is an important determinant of efficacy [40,46,47]. In a study of outbreaks of influenza A in long-term care facilities in New York during 2001 to 2004, facilities that initiated amantadine >5 days after outbreak onset had significantly longer duration of outbreaks, higher incidence rates, and higher case fatality rates than facilities that initiated earlier chemoprophylaxis [47].

We agree with the United States Advisory Committee on Immunization Practices and Infectious Diseases Society of America recommendations that the administration of antiviral drugs for both treatment and prevention should be a central component of influenza outbreak control in nursing homes and other long-term care facilities [4,40]. Chemoprophylaxis is recommended for all residents of an institution during an outbreak, even if they were vaccinated during the same influenza season.

Employees of long-term care facilities who have not been vaccinated can also receive chemoprophylaxis; they can also receive chemoprophylaxis when the vaccine is expected to be ineffective.

Recommendations regarding the duration of prophylaxis are presented below. (See 'Duration' below.)

Other components of outbreak control include initiation of droplet and contact precautions, offering influenza vaccination to unvaccinated staff and residents, restricting contact between residents and ill staff or visitors, and restricting staff movement between sites [4]. (See "Causes of infection in long-term care facilities: An overview" and "Infection control measures to prevent seasonal influenza in healthcare settings".)

Although it may not be feasible to perform influenza testing in all residents who develop influenza-like symptoms following identification of an outbreak, individuals who develop symptoms more than 72 hours after implementation of prophylaxis and those residing in previously unaffected units should be tested [40].

Treatment of influenza is discussed separately. (See "Treatment of seasonal influenza in adults".)

Hospital staff — In acute care settings such as hospitals, unvaccinated staff members who provide care for patients at high risk for influenza complications can be offered prophylaxis during an outbreak within the institution [4]. Such individuals can also be offered prophylaxis when the vaccine is expected to be ineffective. Infection control policies vary by institution, so staff should consult with the infection control department at their institution.

Pregnancy — All pregnant women are at increased risk of complicated influenza, but the risk increases by trimester and with associated comorbidities [41-43]. Conversely, the risk of antiviral complications is probably greatest in the first trimester. All four drugs (oseltamivir, zanamivir, amantadine, rimantadine) are classified as FDA Pregnancy Category C, indicating that their effects in pregnant women and their fetuses have not been well defined. No adverse events have been shown to be caused by oseltamivir or zanamivir among women who received these agents during pregnancy or among infants who were exposed while in utero, although there are limited data [48]. (See "Pharmacology of antiviral drugs for influenza", section on 'Pregnancy'.)

The United States Advisory Committee on Immunization Practices states that antiviral chemoprophylaxis can be considered in pregnant women and women who are up to two weeks postpartum (including following pregnancy loss) who are close contacts of individuals with suspected or confirmed influenza A infection [41]. Early treatment is an alternative to prophylaxis for some pregnant and postpartum women who have been exposed to an individual with possible influenza infection.

We recommend prophylaxis for all unvaccinated women exposed to a patient with influenza during the third trimester of pregnancy, as well as all unvaccinated women with comorbidities who are exposed to an individual with influenza during the second trimester of pregnancy. Comorbidities that increase the risk of influenza complications in pregnant women include chronic cardiac or pulmonary disease, diabetes mellitus, chronic renal disease, malignancy, and immunosuppression [49]. (See 'Definition of high risk' above.)

Zanamivir is probably the drug of choice for prophylaxis given its limited systemic absorption (table 2). Oseltamivir is an alternative agent for women with a relative contraindication to zanamivir, such as asthma or chronic obstructive pulmonary disease.

Antiviral prophylaxis in pregnant women is discussed in greater detail separately. (See "Influenza and pregnancy", section on 'Antiviral prophylaxis'.)

Choice of antiviral drug — Our recommendations regarding the choice of antiviral drug are in accordance with the United States Advisory Committee on Immunization Practices (ACIP) and the Infectious Diseases Society of America (IDSA) [4,40].

It is important to assess the risk of oseltamivir-resistant influenza before choosing an antiviral drug for influenza prophylaxis. Clinicians should review local or state influenza surveillance data weekly to determine which types of influenza (A or B) and subtypes (pandemic or seasonal H1N1; H3N2) of influenza A are circulating, as well as resistance patterns. This information, which is updated weekly, is available via the CDC through its website.

We recommend either oseltamivir (75 mg once daily) or zanamivir (10 mg [2 inhalations] once daily) for targeted populations with likely exposure to patients with pandemic H1N1 influenza A, H3N2 influenza A, or influenza B (table 2) [4]. Zanamivir should be used when oseltamivir-resistant influenza is suspected. Since oseltamivir is primarily excreted by the kidneys, dosing must be modified in the setting of renal insufficiency. Zanamivir is the drug of choice during outbreaks that are suspected to be caused by oseltamivir-resistant influenza [4]. Zanamivir inhalation powder should not be reconstituted in any liquid formulation and is not recommended for use in nebulizers or mechanical ventilators [50]. (See 'Target populations for prevention' above and "Pharmacology of antiviral drugs for influenza", section on 'Adverse effects' and "Antiviral drug resistance among seasonal influenza viruses", section on 'Treatment' and "Treatment of seasonal influenza in adults", section on 'Oseltamivir resistance'.)

Because of high rates of adamantane drug resistance in viral isolates, we recommend against using amantadine or rimantadine for the prevention or treatment of influenza, except during outbreaks of suspected oseltamivir-resistant H1N1 influenza in patients who have a contraindication to zanamivir (eg, asthma or chronic obstructive pulmonary disease) [51,52].

Because oseltamivir-resistant H1N1 viruses may be susceptible to adamantanes, rimantadine (or amantadine) can be used in combination with oseltamivir when zanamivir is contraindicated [4,51]. The recommended dose of rimantadine for the prevention of influenza in adults is 100 mg twice daily in the absence of renal insufficiency. (See 'Adamantanes' above.)

Duration — The necessary duration of antiviral prophylaxis is unclear. The usual duration of antiviral prophylaxis for seasonal influenza varies with the indication:

●During outbreaks in long-term care facilities, prophylaxis should be continued for at least two weeks and for one week after the last known case was identified [39]. As noted above, prophylaxis is recommended for all residents, including those who have received the influenza vaccine. (See 'Outbreaks in long-term care facilities' above.)

 

●For unvaccinated persons who have an indication for postexposure prophylaxis following household or other close contact in the community, the influenza vaccine should be administered [40] and antiviral prophylaxis should be continued for two weeks following influenza vaccination [39]. (See "Seasonal influenza vaccination in adults".)

 

●For previously vaccinated persons who have an appropriate indication, postexposure prophylaxis should be given for one week after the last known exposure [39].

 

●During community outbreaks, preexposure prophylaxis in unvaccinated individuals who have an indication for prophylaxis, including those who are unable to mount an immune response to the vaccine, may be given throughout the period of peak influenza activity (usually six to eight weeks) [8,37,38,40]. During widespread outbreaks when no vaccine is available (as occurred during much of the 2009 H1N1 influenza A pandemic), preexposure prophylaxis has a very limited role. (See 'Preexposure prophylaxis' above.)

 

VACCINATION — Annual vaccination against seasonal influenza is an essential component of influenza prevention. Seasonal influenza vaccination is reviewed separately. (See "Seasonal influenza vaccination in adults".)

INFECTION CONTROL — Infection control measures for patients with influenza are discussed separately. (See "Infection control measures to prevent seasonal influenza in healthcare settings" and "Treatment of seasonal influenza in adults", section on 'Infection control'.)

INFLUENZA ACTIVITY — The United States Centers for Disease Control and Prevention (CDC), in collaboration with the World Health Organization (WHO) and its reporting network, tracks influenza virus isolates throughout the world to monitor disease activity and antiviral resistance patterns and to predict the appropriate components for the annual influenza vaccine. Surveillance information, which is updated weekly during influenza season, is available via the CDC through its website. In addition, FluNet, a database for global influenza virus surveillance, is available on the WHO website. The typical trends of influenza activity in the United States are shown in the following Figure (figure 1).

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Treatment and prevention of seasonal influenza with antivirals".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Beyond the Basics topic (see "Patient education: Influenza prevention (Beyond the Basics)")

 

SUMMARY AND RECOMMENDATIONS — Antiviral drugs should not be used as a substitute for influenza vaccination. Their adjunctive use is appropriate in certain targeted populations, particularly during outbreaks in long-term care facilities. (See "Seasonal influenza vaccination in adults".)

Target groups

●The decision of whom to offer chemoprophylaxis to should be made on a case-by-case basis and should be based on the patient's individual risk for influenza complications, the risk of influenza acquisition from the specific exposure, recommendations from local or public health authorities, and clinical judgment. If supplies of antivirals are limited, preference should be given to those at highest risk for influenza complications (eg, lung transplant recipients, individuals with advanced HIV infection [CD4<200 cells/microL], hematopoietic stem cell transplant recipients). (See 'Indications for chemoprophylaxis' above.)

 

●Given the concerning trends of increasing resistance with both the adamantanes and oseltamivir, the risk of promoting antiviral drug resistance should be considered when deciding whether to recommend prophylaxis to a patient. (See 'Indications for chemoprophylaxis' above.)

 

●We recommend influenza prophylaxis for all residents during outbreaks in long-term care facilities regardless of prior influenza vaccination (Grade 1A). (See 'Postexposure prophylaxis' above and 'Outbreaks in long-term care facilities' above.)

 

●With the exception of residents of long-term care facilities, individuals who have been vaccinated against influenza during a season in which there is a good match between the vaccine antigens and circulating viruses do not require prophylaxis. (See 'Indications for chemoprophylaxis' above.)

 

●In unvaccinated individuals at high risk for influenza complications who have been exposed to an individual with influenza within the previous 48 hours, we recommend influenza prophylaxis (table 1) (Grade 1A). Such individuals should also be vaccinated against influenza. (See 'Postexposure prophylaxis' above.)

 

●We recommend influenza prophylaxis for vaccinated individuals at high risk for complications who have been exposed to an individual with influenza within the previous 48 hours when there is a poor match between the vaccine and circulating viruses (Grade 1A). (See 'Postexposure prophylaxis' above.)

 

●We suggest prophylaxis for unimmunized pregnant women exposed to a patient with influenza during the third trimester, as well as all unimmunized pregnant women with comorbidities who are exposed to an individual with influenza during the second trimester, provided that prophylaxis can be started within 48 hours of exposure (Grade 2C). (See 'Pregnancy' above and "Influenza and pregnancy", section on 'Antiviral prophylaxis'.)

 

●We suggest prophylaxis for otherwise healthy unvaccinated adults, including healthcare workers, and children ≥1 year of age who have had close contact with an individual with confirmed or suspected influenza and who are in close contact with an individual or individuals at high risk for influenza complications (Grade 2B). (See 'Postexposure prophylaxis' above.)

 

●Regarding the other groups for whom antiviral prophylaxis should be considered, the decision of whether to offer prophylaxis should be made based upon both the individual's risk for complicated influenza and the degree of exposure (table 1). Postexposure prophylaxis should be used only when antivirals can be started within 48 hours of the most recent exposure. (See 'Postexposure prophylaxis' above.)

 

●Individuals who do not have risk factors for influenza complications and who are not close contacts of individuals at high risk for influenza complications do not require postexposure prophylaxis. (See 'Postexposure prophylaxis' above.)

 

●During widespread outbreaks when no vaccine is available (as occurred during much of the 2009 H1N1 influenza A pandemic), preexposure prophylaxis has a very limited role. Under such circumstances, preexposure prophylaxis should be used only in individuals at very high risk for influenza complications (eg, severely immunocompromised hosts) who cannot be protected by other means and have a high risk of exposure. (See 'Preexposure prophylaxis' above.)

 

Choice of antiviral agent

●We recommend use of a neuraminidase inhibitor (oseltamivir or zanamivir) as the first-line agent for the prevention of influenza, when indicated (Grade 1A). Zanamivir is the drug of choice during outbreaks that are suspected to be caused by oseltamivir-resistant influenza. Zanamivir is relatively contraindicated in patients with asthma and chronic obstructive pulmonary disease. (See 'Neuraminidase inhibitor resistance' above and 'Choice of antiviral drug' above.)

 

●The recommended prophylactic dose of oseltamivir is 75 mg daily and of zanamivir is 10 mg (two inhalations) daily (table 2). (See 'Choice of antiviral drug' above.)

 

●Due to high levels of adamantane resistance, amantadine and rimantadine are generally no longer useful for the prevention of influenza. (See 'Choice of antiviral drug' above.)

 

Duration — The duration of postexposure prophylaxis varies depending upon the clinical indication:

●During outbreaks in long-term care facilities, prophylaxis should be continued for at least two weeks and for one week after the onset of illness in the last affected patient.

 

●For unvaccinated persons who have an indication for postexposure prophylaxis following household or other close contact in the community, the influenza vaccine should be administered and antiviral prophylaxis should be continued for two weeks following influenza vaccination.

 

●For previously vaccinated persons who have an appropriate indication, postexposure prophylaxis should be given for one week after the last known exposure. (See 'Duration' above.)

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Topic 7017 Version 35.0

 

 

 

Flu vaccination yearly to prevent seasonal influenza

Content 3

It is associated with increased morbidity and mortality in the very young, the elderly, and people with chronic illnesses

The duration varies depending on the virus involved and the immune system’s ability to fight off infection.

The very young, the elderly, and people with chronic illnesses are most susceptible to viral infections and possible complications because of an immature or definiet immune system.

Cold symptoms typically subside within 7 to 10 days, while the flu may last up to two weeks. Even after most symptoms subside, some, like fatigue, can linger for several days more.

“The best weapon we have is our own immune system,” says Donald W. Novey, MD, a family and integrative medicine specialist in Poulsbo, Washington. Good nutrition, adequate sleep and exercise, and low levels of stress can bolster the immune system. “A failure on any one of these four points can weaken the immune system and either prolong an existing cold or lead to more frequent ones,” Dr. Novey says.

Content 11

 

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