Influenza

Hemagglutinin and neuraminidase surface expression on type A and B influenza viruses are required for entry and exit, respectively from cells.

Type C influuenza virus express hemagglutinin-esterase-fusion protien in their surface (Lamb RA).

Type A is subtyped on the basis of HA and neuraminidase expressed on the surface of the virus: eg. H1N1.

A transmembrane protein ion channel, matrix 2, acidifies the internal aspect of the virus and allows its replication.

Each year approximately 20% of the world’s population develops an infection.

In the 2017-2018 season influenza resulted in an estimated 49 million illnesses, 960,000 hospitalizations and 79,000 influenza associated deaths.

Others estimate 290,000-650,000 respiratory deaths each year around the world due to influenza, along with an estimated 3-5,000,000 cases of severe illness.

Estimated 20-30% of children and 5-10% of adults worlwide each year.

Mostly occurs during the winter months and is an important cause of hospitalization and deaths during that season.

This is especially true in patients greater than 65 years and older and in patients with cardiac, pulmonary, or renal comorbidities.

Generally resolves without sequelae.

Increased risk of infection in children younger than one year, and adults older than 65 years, and in persons with comorbidities such as pregnancy, immunodeficiency, diabetes, dementia, stroke, and diseases of the heart, lungs, kidneys.

Influenza is particularly severe in infants and children.

Influenza related hospitalization rates and children younger than two years arrival hospitalization rates in those 65 years and older.

Annual rates vary from 100 to 500 per hundred thousand children.

Deaths from influenza are much rarer in children than an adult 65 years and older.

Predisposes to secondary bacterial infections such as pneumonia.

80% of childhood deaths are in unvaccinated patients.

Bacterial agents most commonly isolated in cases of secondary bacterial pneumonia are are Streptococcus pneumoniae and S aureus.

Presumed mechanism for secondary bacterial infection involves inflammation of the respiratory tree with local immunocompromise permitting bacterial invasion of the bronchial epithelium and penetration into the pulmonary lining.

Bacterial pneumonia complications caused by S aureus includes necrotizing and cavitary disease, including abscess and empyema.

Severe influenza requiring hospitalization is more prevalent in impoverished neighborhoods nationwide.

Obesity increases duration of virus shedding of influenza A virus.

Lung abscesses caused by S aureus have a mortality rate of approximately 50% compared with the overall death rate of approximately 20% across all lung abscesses.

Sporadic outbreaks can occur during any time of the year.

Influenza epidemiological patterns: seasonal local outbreaks known as epidemics and global outbreaks known as pandemics.

In recent years there have been 4-5 pandemics occurring with intervals of 9-39 years in between each outbreak.

Each year 17-50 million Americans are infected.

The probability of infection varies with the prevalence, the match between vaccination strain and the prevalent strain and vaccination status of an individual.

Pandemics occurs when a completely new genetic strain of the virus emerges and that is referred to as antigenic shift. and affects various countries at the same time.

The demography of effective groups may differ by the scale of the outbreak.

In pandemics the disease is more severe and widespread then in epidemics, the latter usually caused by continuous change of existing virus strain, antigenic drift.

Viruses influenza virus is transmitted usually by inhalation of the virus or by direct contact with respiratory secretions of an infected person via cough or sneezing.

The risk of viral transmission to others occurs while the virus is being shared from the respiratory tract, usually within 2-3 days of illness onset.

There is a strong correlation between viral replication , clinical symptoms, and disease severity.

Detection of viral new clinic acid by reverse transcriptase polymerase chain reaction from respiratory specimens is used as an approximation of the presence of actively replicating influenza virus.

Most viral shedding occurs during the first 2-3 days after the onset of illness

The short duration of viral shedding is consistent with a brief window of clinical benefit from neurminidase inhibitors.

Shedding of the virus can be more prolonged in children and immunocompromised hosts increasing the risk of infection in their household.

With exposure to a viral load a host’simmunity and inflammatory responses begin, leading to alveolar inflammation, airway hyperreactivity, broncoalveolar obstruction and impaired diffusion capacity, explaining the symptomatology of influenza.

Annually causes over 300,000 hospitalizations and 20,000-40,000 deaths.

New CDC study shows flu vaccine prevented more than 7 million flu illnesses, 109,000 flu hospitalizations, and 8,000 flu deaths during the 2017-2018 flu season.

Approximately 3-5 million cases of severe seasonal influenza and up to 500,000 influenza related deaths each year worlwide.

Average annual direct medical care costs are estimated $10 billion, with the total annual economic impact of approximately $87 billion.

The severity of influenza is unpredictable from 1 season to another and is dependent on factors such as the purulence the involved strain, the match of the flu vaccine relative to the circulating strain, how many population is vaccinated, and when the vaccine was made available.

Influenza is unique among respiratory viral agents in that effective intervention to prevent transmission is present, that is vaccination.

Rapid influenza diagnostic tests can detect influenza virus nucleoprotein (NP) in a simple test that provides results within 15 minutes.

The FDA found that rapid influenza diagnostic tests detect viral antigens and samples at the highest concentrations, but detection varied by test and viral type and subtype at low concentrations.

Sensitivity of rapid test are generally 40 to 70% of that of viral culture or reverse transcriptase-polymerase chain reaction.

Sensitivity ranges from 10 to 80% have been reported, which means that rapid sensitivity antigen test are commonly false negative.

Because of the variability in rapid influenza detection test performance, especially at lower viral concentrations, negative tests might not exclude influenza virus infection in patients with signs and symptoms, and therefore antiviral therapy should be not should not be withheld because of negative rapid viral testing.

Human influenza transmitted by inhalation of infectious droplets and droplet nuclei, direct contact and by indirect fomite contact with self-inoculation to the upper respiratory tract or conjunctival mucosa.

Associated mortality has increased over time, from 7-32,000 annual deaths in the late 70’s to 36-72,000 annual deaths in the late 1990’s (Thompson WW).

Increased mortality attributable to influenza related to increased number of elderly and immunosuppressed people as well as intrinsic viral virulence and increasing global spread of new viruses.

In oncology patients mortality can be a high as 5-10%.

Children and young adults with neurologic and neurodevelopmental illnesses have increased risk and complications, including death from seasonal influenza.

Transmission can occur by coughing or sneezing where infectious particles from 0.1 to 100 microm may be inhaled.

Seasonal illness in temperate zones that usually appears during cold weather months.

Most cases arise in children and younger adults.

Children aged <5 years and those with certain chronic medical illnesses are at increaed risk for the development of complications and death from influenza.

Risk of infection within the household is 20%.

Rates of infection highest among children but severe illness and deaths most common in patients with medical illnesses and among patients over the age of 65 years.

Hospitalization rate for young children with confirmed disease is similar to those among the elderly and outpatient visits by infants and young children are the most frequent by any other age group.

Hospitalization rates from severe illness as high as 3 per 1000 children age 6-23 months and as high as 9 per 1000 for children under the age of 6 months.

Increased susceptibility of pregnant women to influenza, and increased risk of adverse pregnancy outcomes and maternal death.

The adverse effects of antenatal influenza suggests a biological effect in the mother that compromises the mother and fetus, and it appears to be due to associated immunologic changes that inhibit the inflammatory response to the influenza virus.

Vaccination doing pregnancy reduces the risk of an influenza diagnosis.

Vaccination for influenza during pregnancy is not associated with increased fetal mortality and may reduce the risk of influenza related to fetal death.

Manifested by sudden onset of fever, myalgias, headache, cough, malaise, pharyngitis and rhinitis.

Typically adults challenged with influenza virus have an onset of symptoms within 24 hours of infection, with peak viral shedding and peak symptom severity occurring 2-3 days postinfection.

Symptoms and viral shedding generally abate by day eight postinfection.

Co-infections predominantly occur during periods of high influenza viral shedding, but may occur concurrently or shortly after influenza infection.

Can exacerbate preexisting medical problems of pulmonary or cardiac origin, cause a secondary bacterial pneumonia and evolve into influenza pneumonia.

One in 4 patients admitted to ICU with severe influenza have a bacterial coinfection.

Influenza-in children can be associated with otitis media and nausea and vomiting.

Those at high risk for complications are children 6-23 months of age, healthy individuals 65 years of age and older, children and adults with chronic illnesses, pregnant women and residents of nursing homes and other long-term care facilities.

Rates of hospitalization for young children comparable to those among elderly patients.

Children under the age of 2 years experience higher morbidity rates than any other group except those older than 65 years.

Average 92 deaths per year in children below the age of 5 years.

Typically resolves after a number of days but cough and malaise may persist for 2 or more weeks.

Can lead to bacterial pneumonia or primary influenzal viral pneumonia.

Estmated average 23,000 plus deaths with underlying respiratory and circulatory causes from 1976-2007 in the US associated with influenza (CDC).

Estimated average from 1976-2009 66324 deaths attributable annually to combined conditions of influenza and pneumonia (CDC).

Mortality from combined categories of influenza and pneumonia highest in patients 65 years or older.

Bacterial coinfection complicates 0.5% of all influenza cases in young healthy patients, 2.5% in older individuals and those with predisposing illnesses.

Individuals with high risk of developing influenza related complication including coinfection include adults over the age of 65, children younger than five years of age, pregnant women, morbidly obese individuals and people with pre-existing medical conditions such as COPD, cardiovascular, renal, hepatic, neurologic, metabolic, or immune suppressed individuals.

Individuals colonized with Streptococcus pneumoniae have an increased risk of ICU admissions or death in the setting of influenza.

Co-infection with staphylococcal aureus, which colonizes the nares of 30% of adults, is associated with increased risk of death in adults and children with influenza.

MRSA co-infection is associated with severe disease and death in adults and children with influenza.

Among children vomiting and otitis media occur commonly.

May be associated with neurological complications including seizures, encephalitis, Reye syndrome and other neurological disorders in association with types A or B seasonal influenza.

Neuraminidase inhibitors can protect families from getting influenza 72-84% of the time.

Influenza A predominant type accounting for 99.5% of cases.

In a pandemic high viral loads and high transmission rates occur.

Cornerstone of prevention is annual vaccination.

In a study of the effectiveness of surgical mask compared with the N95 respirator among nurses to protect against influenza resulted in non-inferior rates of laboratory confirmed influenza (Loeb M).

Surgical masks have an efficacy of preventing the transmission of influenza within 1% of N95 respirators (Loeb M).

Growing resistance to antiviral agents has made some influence of drugs less effective over time.

Resistance to antiviral drugs can emerge rapidly.

Osetamivir taken orally and zanamivir (Relenza) which is inhaled can be used for chemoprophylaxis and treatment of influenza.

Three antiviral meds: inhaled zanamivir (brand name Relenza), intravenous peramivir (Rapivab), or oral oseltamivir (Tamiflu).

A 2014 review by the Cochrane Collaboration found that Tamiflu does not reduce hospitalization rates for the flu, and only shortened the duration of people’s symptoms by 17 hours.

Tamiflu can also keep people from getting the flu.

It is not a substitute for early flu vaccination.

Approved to treat influenza in people whose symptoms have not lasted longer than two days.

Works best when taken 48 to 72 hours after the onset of flu symptoms.

Among circulating influenza viruses resistance to oseltamivir is currently low.

When used for prophylaxis after susceptible A or B strains of seasonal influenza are 70-90% effective.

The amantadines are no longer recommended for implemented treatment or prophylaxis because of viral resistance.