Influenza


Article Author:
Sameh Boktor


Article Editor:
John Hafner


Editors In Chief:
Sherri Murrell


Managing Editors:
Avais Raja
Orawan Chaigasame
Khalid Alsayouri
Kyle Blair
Radia Jamil
Erin Hughes
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Navid Mahabadi
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beenish Sohail
Hajira Basit
Phillip Hynes
Sandeep Sekhon


Updated:
2/18/2019 10:42:24 PM

Introduction

Influenza is a communicable viral disease that affects the upper respiratory tract including upper and lower respiratory passages. It is caused by a wide spectrum of influenza viruses. Some of these viruses can infect humans, and some are specific to different species. These viruses are transmissible through respiratory droplets expelled from the mouth and respiratory system during coughing, talking, and sneezing. The influenza viruses can be transmitted by touching inanimate objects soiled with the virus and touching the nose or eye. Influenza can be transmitted before the patient is symptomatic and until 5 to 7 days after infection. After infection, it takes a few days for most of the healthy patients to recover fully, but complications that include pneumonia and death are common in certain high-risk groups. These groups include young children, elderly, immunocompromised, and pregnant females. Symptoms of influenza include a runny nose, high fever, cough, and sore throat. Influenza spreads rapidly and efficiently in seasonal epidemics. Flu epidemics occur every autumn and winter in temperate regions and affect a significant portion of adults and children, but seasons differently impact age groups and severity.[1][2][3][4]

Etiology

There are four types of influenza viruses, A, B, C and D. Influenza types A and B cause human infection annually during the epidemic season. Influenza A has several subtypes according to the combination of hemagglutinin (H) and the neuraminidase (N) proteins that are expressed on the surface of the viruses. There are 18 different hemagglutinin subtypes and 11 different neuraminidase subtypes (H1-18 and N1-11). Influenza A viruses can be characterized by the H and N types such as H1N1 and H3N2. Influenza B viruses are classified into lineages and strains. Influenza B viruses that have circulated in recent influenza seasons belong to one of two lineages, influenza B Yamagata and influenza B Victoria. Influenza viruses have receptors responsible for making them species specific. The animal influenza viruses can cause infections in humans if the antigenic characters of the virus change. When this happens, transmission from person-to-person is usually inefficient. Influenza pandemics like 1918 and 2009 can occur if the transmission from person-to-person becomes efficient. Avian influenza, or Bird Flu, is an infectious disease of birds caused by a variety of influenza A viruses including A(H5N1), A(H5N8), and H7N9 viruses. These viruses are worrisome as they can change to develop the ability for transmissibility from person-to-person and start a severe pandemic. A good example of animal origin influenza is the 2009 Pandemic influenza, which is an animal influenza virus that likely started in South America in early 2009 and developed the ability to spread from person-to-person and spread globally.[5][6]

Epidemiology

Researchers isolated Influenza A in 1933, seven years later, they isolated influenza B. Influenza viruses in certain geographic regions of the northern and southern hemispheres are called an influenza epidemic which occurs every year during the winter seasons. The severity, length of influenza, and age groups that are highly impacted and complication rates such as hospitalizations and deaths differ significantly during different influenza seasons. When H3N2 viruses predominate, the season tends to be more severe especially among children and elderly. World Health Organization (WHO) conducts global influenza virologic surveillance that indicates influenza viruses are isolated every month from humans in a geographic region. In temperate regions, influenza activity peaks during the winter months. In the Northern Hemisphere, influenza outbreaks and epidemics typically occur between October and March, whereas in the Southern Hemisphere, influenza activity occurs between April and August. In the tropical belt, influenza circulates year-round. 

Pathophysiology

Influenza is an acute disease that targets upper respiratory tract and causes inflammation of upper respiratory tree and trachea. The acute symptoms persist for seven to ten days, and the disease is self-limited in most healthy individuals. The immune reaction to the viral infection and the interferon response are responsible for the viral syndrome that includes high fever, coryza, and body aches. High-risk groups who have chronic lung diseases, cardiac disease and pregnancy are more prone to severe complications such as primary viral pneumonia, secondary bacterial pneumonia, hemorrhagic bronchitis, and death. These severe complications can develop in as little as 48 hours from the beginning of symptoms. The virus replicates in the upper and lower respiratory passages starting from the time of inoculation and peaking after 48 hours, on average.  

Histopathology

Influenza viruses replicate in the epithelial cell lining of the upper and lower respiratory tracts. The pathology does not differ between natural or experimental infection. Definitive diagnosis of influenza needs serologic, immunologic, and molecular testing through RT-PCR for upper or lower respiratory tract specimens. Mild cases show pathological changes in the respiratory tracts, but severe cases show clear evidence of pathologic changes of pneumonia. The tracheobronchial changes due to influenza infection can be summarized as redness and inflammation with mucous and purulent discharge macroscopically, and desquamation and destruction of the pseudostratified epithelium of the trachea and bronchi with only the basal layer remained viable but inflamed microscopically.        

History and Physical

The clinical presentation of influenza ranges between mild to severe depending on the age, co-morbidities, vaccination status, and natural immunity to the virus. Usually, patients who received the seasonal vaccine present with milder symptoms, and they are less likely to develop complications.

Signs and symptoms of influenza in mild cases include a cough, fever, sore throat, myalgia, headache, runny nose, and congested eyes. A frontal or retro-orbital headache is a common presentation with selected ocular symptoms that include photophobia and pain with different qualities. The cause of ocular pain is related to the viral tropism that is associated with certain types and subtypes. Severe cases may progress to shortness of breath, tachycardia, hypotension, and need for supportive respiratory interventions in as little as 48 hours.

Evaluation

Diagnosis of influenza can be reached clinically especially during the influenza season. Most of the cases will recover without medical treatment, and they would not need laboratory test for the diagnosis. In high-risk cases, initiation of treatment should not be delayed until test results are obtained. Influenza laboratory tests should be ordered for cases where testing would inform clinical action or public health interventions such as the outbreak situations where the diagnosis of the causative agent is necessary for therapeutic and prophylactic recommendations.

Laboratory tests available for diagnosis of influenza are rapid antigen detection, a rapid molecular assay for the detection of viral RNA, immunofluorescence direct and indirect antibody staining for detection of viral antigen, real-time PCR test, and cell culture.

Treatment / Management

Influenza infection is self-limited and mild in most healthy individuals who do not have other co-morbidities. No antiviral treatment is needed during mild infections in healthy individuals. Antiviral medications can be used to treat or prevent influenza infection especially during the outbreaks in healthcare settings such as hospitals and residential institutions. Oseltamivir, zanamivir, and peramivir belong to the neuraminidase inhibitors family and can be used for the treatment of influenza A and B. The adamantanes antiviral family has two medications, amantadine, and rimantadine. Amantadine and rimantadine are effective against influenza A, but not influenza B. During recent influenza seasons, high rates of resistance have been identified in influenza A for the adamantanes antivirals, and they are not recommended for treatment or prophylaxis against influenza A. Resistance to the neuraminidase inhibitors has been low in recent influenza seasons, but the virus may mutate and develop resistance at any time. Resistance can develop in some patients following treatment, especially in immunocompromised patients. Oseltamivir can be used for chemoprophylaxis for individuals one year and older in cases of outbreaks and exposure in high-risk groups. The side effects of oseltamivir include skin reactions that might be severe and sporadic transient neuropsychiatric events; these side effects form a barrier to the use of oseltamivir in elderly and individuals that are at higher risk of developing these side effects. The only contraindication to zanamivir is an allergy to eggs.[6][7][8][9]

Enhancing Healthcare Team Outcomes

The prevention and treatment of influenza is with an interprofessional team that includes a nurse practitioner, primary care provider, internist, an emergency department physician, and an infectious disease specialist. The key is patient educations. All patients should be encouraged to get the annual flu vaccine that is available in November of each year.  While the flu vaccine is not 100% effective, it can lower the intensity and duration of symptoms in most people. Individuals who have lung disease, diabetes, chronic illnesses, the elderly and children should get the flu vaccine as it can prevent admission to the hospital. Every year, hundreds of individuals are admitted to the hospital and tragically some do die from the flu.[10] (Level V)


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Influenza - Questions

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Which of the following complications can be seen with influenza?



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Influenza B viruses can be treated with which medication?



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It is winter in the United States when a 3-year-old previously healthy child is brought to the emergency department after the parents witness a 5- to 10-minute episode of shaking of the arms and legs. The shaking stopped while on route to the emergency department. The child is now sleepy and not responsive to questions but responds during the exam. His temperature is 103.1 F. There is minimal nasal congestion, the throat is erythematous, the neck is supple, and bilateral anterior cervical adenopathy is present. The spleen tip is palpable. Heart exam is normal, and lungs are clear. What is a rapid and sensitive method to make the diagnosis?



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What is the appropriate intervention in the case of a nursing home in which an outbreak of influenza has occurred, and the residents have not received vaccinations?



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Which of the following is a treatment for an influenza infection?



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Seasonal influenza can be treated with which of the following?



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Which of the following infections has the highest incidence in the United States?



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Which of the following patients is least likely to require empiric treatment with oseltamivir therapy for suspected influenza?



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What genetic event is implicated in seasonal influenza pandemics?



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It is early winter in the United States and a 78-year-old female complains of fever, dry cough, a runny nose, malaise, and achiness for 1 day. Her oxygen saturation is normal and her lungs are clear. What is the most appropriate next step in management?



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What is the most common cause of hospitalization for an adult lower respiratory tract infection?



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During influenza epidemics, the highest rates of infection are seen in which of the following groups?



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The highest rates of serious illness and death are seen in which of the following groups during influenza epidemics?



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Which of the following groups is not at an increased risk for complications from influenza?



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How long is influenza virus contagious after the onset of symptoms?



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What characteristic of the influenza A virus allows for genetic reassortment?



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What infection is associated with neuraminidase production?



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Which is the best treatment option for seasonal influenza?



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What yearly vaccination is recommended for healthcare workers?



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What is the youngest age that an influenza vaccination can be administered?



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According to the US Centers for Disease Control and Prevention guidelines, which of the following are at high risk for influenza?



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Influenza - References

References

Alguacil-Ramos AM,Portero-Alonso A,Pastor-Villalba E,Muelas-Tirado J,Díez-Domingo J,Sanchis-Ferrer A,Lluch-Rodrigo JA, Rapid assessment of enhanced safety surveillance for influenza vaccine. Public health. 2019 Feb 12;     [PubMed]
Tennant RK,Holzer B,Love J,Tchilian E,White HN, Higher levels of B-cell mutation in the early germinal centres of an inefficient secondary antibody response to a variant Influenza Haemagglutinin. Immunology. 2019 Feb 15;     [PubMed]
Marshall C,Williams K,Matchett E,Hobbs L, Sustained improvement in staff influenza vaccination rates over six years without a mandatory policy. Infection control and hospital epidemiology. 2019 Feb 15;     [PubMed]
Odun-Ayo F,Odaibo G,Olaleye D, Influenza virus A (H1 and H3) and B co-circulation among patient presenting with acute respiratory tract infection in Ibadan, Nigeria. African health sciences. 2018 Dec;     [PubMed]
Havlickova M,Druelles S,Jirincova H,Limberkova R,Nagy A,Rasuli A,Kyncl J, Circulation of influenza A and B in the Czech Republic from 2000-2001 to 2015-2016. BMC infectious diseases. 2019 Feb 14;     [PubMed]
Yang L,Chan KP,Wong CM,Chiu SSS,Magalhaes RJS,Thach TQ,Peiris JSM,Clements ACA,Hu W, Comparison of influenza disease burden in older populations of Hong Kong and Brisbane: the impact of influenza and pneumococcal vaccination. BMC infectious diseases. 2019 Feb 14;     [PubMed]
Blanton L,Dugan VG,Abd Elal AI,Alabi N,Barnes J,Brammer L,Budd AP,Burns E,Cummings CN,Garg S,Garten R,Gubareva L,Kniss K,Kramer N,O'Halloran A,Reed C,Rolfes M,Sessions W,Taylor C,Xu X,Fry AM,Wentworth DE,Katz J,Jernigan D, Update: Influenza Activity - United States, September 30, 2018-February 2, 2019. MMWR. Morbidity and mortality weekly report. 2019 Feb 15;     [PubMed]
Haber P,Moro PL,Ng C,Dores GM,Lewis P,Cano M, Post-licensure surveillance of trivalent adjuvanted influenza vaccine (aIIV3; Fluad), Vaccine Adverse Event Reporting System (VAERS), United States, July 2016-June 2018. Vaccine. 2019 Feb 7;     [PubMed]
Kenmoe S,Tcharnenwa C,Monamele GC,Kengne CN,Ripa MN,Whitaker B,Alroy KA,Balajee SA,Njouom R, Comparison of FTD® respiratory pathogens 33 and a singleplex CDC assay for the detection of respiratory viruses: A study from Cameroon. Diagnostic microbiology and infectious disease. 2019 Jan 16;     [PubMed]
Doyle JD,Chung JR,Kim SS,Gaglani M,Raiyani C,Zimmerman RK,Nowalk MP,Jackson ML,Jackson LA,Monto AS,Martin ET,Belongia EA,McLean HQ,Foust A,Sessions W,Berman L,Garten RJ,Barnes JR,Wentworth DE,Fry AM,Patel MM,Flannery B, Interim Estimates of 2018-19 Seasonal Influenza Vaccine Effectiveness - United States, February 2019. MMWR. Morbidity and mortality weekly report. 2019 Feb 15;     [PubMed]

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