Lecture 39: Influenza and Other Viral Respiratory Tract Infections

Common cold

• Acute rhinitis with variable degrees of pharyngitis

• Fever is "low grade"

• Most common acute illness in industrialized world

6

OTC cough & cold medicine not

recommended for children < ______ years old

Zinc

-alternative therapy for common cold

-esp lozenges can reduce severity and duration of cold

-may lead to permanent anosmia intranasally

-Zinc

-Vitamin C

-Echinacea

-Nasal Saline

alternative therapies for common cold

Pharyngitis

-sore throat, particularly when swallowing

-fever, headache, or malaise

-swollen glands, or anterior neck pain

-nasal congestion, coryza, hoarseness, sinus discomfort or tenderness, ear pain, or cough

Pharyngitis

Physcial Exam:

-pharyngeal erythema

-tonsillar hypertrophy

-possibly purulent exudate

-anterior cervical lymph nodes are typically tender and enlarged

-palatal petechiae

-NSAIDs/Acetaminophen, Lozenges,

• Steroids (controversial)

treatment for Pharyngitis

• Coxsackie A virus (CAV)

• Herpes simplex virus (HSV)

• Epstein Barr Virus (EBV)

viruses that can cause exudative pharyngitis

• GAS

• Mixed anaerobic

• Corynebacterium diptheriae

bacteria that can cause exudative pharyngitis

Corynebacterium diptheriae

bacteria associated with a gray pseudomembrane

• Adenovirus (AdV)

• Influenza

• Rhinovirus (HRV)

• Coronavirus (CoV)

viruses assoc with non-exudative pharyngitis

Acute Bronchitis

acute respiratory disease with severe and prolonged cough that continues after other signs and symptoms of the acute infection have subsided

Acute Bronchitis

-sputum, fatigue, chest discomfort, sore throat, mild myalgoa, NO (or low grade) fever

-Cough often lasts 14-21 days

-Adenovirus (AdV)

-Rhinoviruses (HRV)

-Coronaviruses (CoV)

-Metapneumovirus

-Parainfluenza virus

-Respiratory syncytial virus (RSV)

-Influenza

common causes of acute bronchitis

• Direct damage to the respiratory mucosa

• Release of inflammatory substances

• Increased production and/or decreased clearance of respiratory secretions

• Stimulation of airway irritant receptors

why do we cough?

Pertussis

______________ is the only indication for antibacterial agents in the treatment of acute bronchitis.

-Dectromethorphan

-Guaifenesin

-Bromhexine

-Dexbrompheniramine/Pseudoephedrine

non prescription oral medicines that may improve acute cough

Reye's Syndrome

why do you NOT give aspirin to children with a viral infection?

Reye's Syndrome

• Acute noninflammatory encephalopathy and fatty degenerative liver failure

-mitochondrial injury resulting in dysfunction that inhibits oxidative phosphorylation and fatty acid beta-oxidation in a virus-infected, sensitized host

Influenza-like Illness (ILI)

• Fever, chills, severe fatigue, myalgia, respiratory symptoms

• Systemic symptoms appear first & then respiratory symptoms predominate over the next week

Influenza, Adenovirus, Parainfluenza, RSV

causative agents of influenze-like illness

Viral Pneumonia

• Vary from a mild and self-limited

illness to a life-threatening disease

• Worse in extremes of age

• Presentation overlaps with bacterial pneumonia & distinction on clinical history alone is not always possible

-may also be followed by a secondary bacterial

pneumonia

Influenza

what is responsible for over 50% of viral pneumonia cases?

Viral Pneumonia

-virus multiplies in the epithelium of the upper airway and secondarily infects the lung by means of airway secreations or hematogenous spread

Viruses (RSV)

most common agent of pneumonia in children

Viruses (e.g. influenza)

most common agent of pneumonia in adults

Influenza

most common agent of pneumonia in elderly

adenovirus, enterovirus, rhinovirus

viruses that spread by environmental factors

VZV

virus that spreads via direct contact with contaminated objects

CMV

virus that spreads via tranplantation of contaminated organs

CMV and HSV

viruses that spread via lower respiratory aspiration

CMV and HSV

viruses that spread via reactivation of a laten infection

CMV

viruse that spreads hematogenously

SARS, Measles, Adenovirus, Parainfluenza, RSV

viruses assoc with spread by healthcare personnel

Influenza

-Orthomyxoviridae

• Enveloped, 8 segments of negative sense single stranded RNA

• Envelope glycoproteins are hemagglutinins (HA) and neuraminidases (NA)

Influenza

• Transmission: virus-containing respiratory secretions (droplets).

-Epidemics in winter months.

• High frequency of antigenic variation

• Death highest among <2 y & >65 y and those with medical conditions

Drift

Antigenic _____________ of influenza:

small antigenic changes

Shift

Antigenic ______________ of influenza:

-large change with replacement of HA or NA

-H and N variability

-virus mutates often

-Flu RNA pilymerase does not have proofreading ability

-virus can undergo reassortment

Why is it difficult ot make influenza vaccines?

Influenza

-incubation period 1-4 days

-abrupt onset of fever, chills, headache, myalgia, malaise, anorexia, nonproductive cough, sore throat, nasal discharge

• Diagnosis: Immunologic detection of antigens via secretion sample or cultured

Supportive Care

treatment fo influenza

M2 Inhibitors

-Amantadine and Rimantadine

-active against Influenza A

-recommeded these not be used in US due to resistance

Neuraminidase Inhibitors

• Oseltamivir, Zanamivir, Peramivir

-active against influenza A and B

Influenza

Complications of _________________:

-myocarditis, pericarditis, myositis, rhabdomyolysis, encephalitis, aseptic meningitis, transverse myelitis, and Guillain-Barre syndorme

Secondary Bacterial Pneumonia

-influenze complicaiton

• At approximately day 5-10 after onset, patients will typically show improvement and then resurgence of fever, cough, sputum production & consolidation on CXR

• Typical organisms: S. pneumoniae, S. aureus, H. influenzae

Primary Viral Pneumonia

-complication of influenza

-severe dyspnea and may note retrosternal chest pain

-Ill-appearing patient in respiratory distress

-Rales, rhonchi, wheezes, and a prolonged expiratory phase may be found on lung exam.

Influenza

-fever, dry cough, myalgias, headache, and malaise

-nasal congestion and scratchy throat

-disease lasts 3-7 days but cough and fatigue may persist

-ill-appearing patient in respiratory distress. Rales, rhonchi, wheezes, and a prolonged expiratory phase may be found on lung exam. Acute respiratory failure is common.

Immunosuppressed Patients

Intranasal is always live, so can't give to ______________________

Adenovirus

• Non-enveloped; double-stranded DNA viruses (dsDNA)

• Causes: respiratory, GI & conjunctivitis

• Highly contagious

• Responsible for outbreaks with sequestered groups of people

-occur year-round but

account for a higher proportion of

pneumonias in the summer months

3 and 7; 4

For Adenovirus, Types ____________ are associated with more severe disease, and type _____ is associated with outbreaks among military recruits

Adenovirus

-self limiting upper respiratory tract disease with GI and conjunctivitis

-diagnosed via PCR

-with pneumonia, may present with cough and fever for up to 7 dayse followed by severe dyspnea

Adenovirus

-transmitted via direct contact with infectious secretions, fecal-oral, adn fomites

-flu-like illness

-epidemics in close groups such as military recruits, hospital wards, psych units

__________________ can stay viable for prolonged periods on environmental surfaces such as sinks and hand towels

-not susceptible to some commonly used disinfectants such as alcohol and ether.

-decontamination of environmental surfaces and instruments may be difficult and requires specific agents such as chlorine, formaldehyde, or heat. (UTD)

•Parainfluenza

•RSV

•Measles, Mumps

Paramyxoviruses

Human Metapneumovirus

-Paramyxoviridae

• negative single stranded RNA virus

• Cause upper and lower respiratory tract infections in people

of all ages

• Closely resembles RSV & often have co-infection

• Can also impact the elderly & ill adults severely

• Peak age 11 months

• Season: winter

• Diagnosis: nucleic acid amplification from NP wash

• Treatment: Supportive

Parainfluenza

• Family Paramyxoviridae - negative sense single-stranded RNA

• Human parainfluenza viruses (HPIVs)

•common virus that infects most persons during childhood.

• Type 3 is endemic year round

• Types 1 & 2 peak during the fall season.

Parainfluenza

• Transmission: direct contact w/ respiratory secretions & aerosols

• Incubation period - 3-6 days

• Can cause croup (seal-like bark), bronchiolitis in children

• Can cause common cold, pneumonia, exacerbation of COPD in adults

• Clinical features: fever, rhinitis, pharyngitis, laryngitis, bronchitis

• Diagnosis: PCR or cell culture from nasopharyngeal wash

• Treatment: supportive

Respiratory Syncytial Virus (RSV)

• Family paramyxoviridae - negative sense single-stranded RNA

• Transmission: fomites & aerosols

• Infects the very young & very old.

• Most common cause of LRTI in children < 1 yo

• Adult clinical features: coryza, pharyngitis, cough, fever, bronchitis, ILI, pneumonia, exacerbations of asthma & COPD

• There's no vaccine

Palivizumab

-may prevent RSV infections and protect high risk babies from serious complications

-may give a monthly shot during RSV season

Ribavarin + immune globulin

Treatment of RSV in immunosuppressed

Chemopropylaxis

passive transfer of antibody with palivizumab (Synagis) in high risk infants

Supportive Care and Chemopropylaxis

treatment of RSV

-Rhinovirus

-Enterovirus

-Poliovirus

-Coxsackie

Picornaviruses

Rhinovirus

• Family: Picornaviruses

• positive sense single-stranded RNA

• Season: early fall and late spring

• Reservoir: schoolchildren

• Transmission: aerosol & fomite

• Incubation period: 2 days

Rhinovirus

-Duration ~1 week.

• Mild illness: rhinorrhea, cough

• Moderate: Rhinorrhea, pharyngitis, bronchitis

• Exacerbations of cystic fibrosis, chronic obstructive pulmonary

disease (COPD), asthma, viral pneumonia

-treatment is supportive

Rhinovirus

half of all viruses recovered from middle ear effusions with acute otitis media

HSV-1, HSV-2, VZV, CMV, EBV, KSHV, HHV-6, HHV-7

Herpesviridae

Cytomegalovirus (CMV)

• Herpesviridae - enveloped, linear double-stranded DNA

• Pathophysiology: down-regulation of HLA on cell surface and interference with antigen processing, to evade recognition by the host.

• Prolonged virus shedding in urine, saliva, stool, tears, breast milk

• Transmission: direct contact

• Season: no seasonality

megalovirus (CMV)

• Perinatal - one of the TORCH infections

• Immunocompetent: mostly subclinical or acute pharyngitis similar to

mononucleosis

• Immunocompromised (esp. organ transplant, BMT)

• Can involve multiple organ systems

• Commonly interstitial pneumonia: fever, cough, dyspnea, crackles, tachypnea, hypoxemia. CXR - bilateral with diffuse or focal haziness involving the middle and lower lung fields

Ganciclovir and immune globulin

treatment for CMV

Hantavirus

• Family Bunyaviridae - virus infects the pulmonary capillary endothelium after inhalation

• Enveloped, 3 segmented negative sense single stranded RNA genome

• Transmission: acquired via direct contact with or inhalation of rodent urine (& feces)

Hanatavirus Pulmonary Syndrome (HPS)

• Abrupt fever, myalgias, malaise, and gastrointestinal symptoms.

• Then cough, dyspnea, and hypotension (noncardiogenic pulmonary edema_

• Rapid decompensation associated with pulmonary capillary leak syndrome, hypoxemia, and myocardial dysfunction is common.

-Disseminated intravascular coagulation & frank hemorrhage have been reported.

• Most deaths occur within 48 h of admission and are related to cardiogenic

shock

Coronaviruses

• Enveloped virus containing single-stranded, positive-sense RNA

-Typical coryzal illness.

• Can cause common cold, AOM, asthma, pneumonia, bronchitis

• Season: Predominate in winter/spring.

• Transmission: inoculation of the respiratory tract with infectious secretions via large droplets and close contact

SARS-CoV-1

• First recognized in Guangdong Province, China in late 2002

• Caused widespread pandemic in southern China in 2003

• Originated in bats, likely jumped to civets (weasel-like

mammals) in Chinese wet markets and then to humans

• Civets and raccoon dogs are intermediate hosts

SARS-CoV-1

-Severe respiratory symptoms with fever

-autopsy on lungs shows ARDS and organizing phase of alveolar damage without viral inclusions

• Incubation period after contact varies from 2 to 16 days (median 6 days).

• Symptoms: chills, rigors, and myalgias.

-Cough and headache, and crackles

. Sore throat, nausea and vomiting, and diarrhea

SARS-CoV-1

• Disease is more severe than diseases associated with most respiratory viruses

• About 25% of patients will require admission to the intensive care unit and will progress to ARDS and/or require mechanical ventilation

MERS-CoV

• Novel coronavirus is related to severe acute respiratory syndrome (SARS)

• Middle East Respiratory Syndrome (MERS)

• Found in Saudi Arabia in 2012. (Cont in clusters mainly in Middle East)

• Novel coronavirus is related to severe acute

respiratory syndrome (SARS)

• Middle East Respiratory Syndrome (MERS)

• Found in Saudi Arabia in 2012. (Cont in

clusters mainly in Middle East)

• Bats are suspected to be the original host

• Camels serve as intermediate hosts. Human to human transmission can occur.

• Symptoms: Fever, chills, cough, SOB, Pneumonia, ARDS, GI symptoms

• Diagnosis: qRT-PCR to respiratory secretions

-no vaccine and antivirals are ineffective

SARS-CoV-2

• Novel coronavirus related to severe acute respiratory syndrome

• COVID-19 is the disease NOT the virus! It is an abbreviation of coronavirus disease 2019.

• WHO was informed of unknown pneumonia in Wuhan City, China on Dec. 31, 2019

SARS-CoV-2

• Bats are suspected to be the origin

• Pangolins are suspected to be intermediate host; these are sold illegally at some wet markets

• Symptoms: Fever, chills, cough, shortness of breath, Pneumonia, ARDS, GI symptoms

• Diagnosis: qRT-PCR to respiratory secretions

-vaccines available

SARS-CoV-2

-fever or chills, cough, shortness of breath, fatigue, muscle or body aches, headache, loss of taste or smell, sore throat,

congestion or runny nose, nausea or vomiting, diarrhea

SARS-CoV-2

-Transmission: inhalation, deposition of droplets, touching mucous membranes

-larges droplets settle out of air rapidly

-greated risk of transmission is within 3-6 ft of an infectious source

-enters nose or throat

-targets ACE2 receptor

-replicates shedding virus

-infects alveoli tissue

-viral replication triggers immune response

-increased inflammation and infiltrates target and kill cells leaving debri and pus, causing pneumonia

how does SARS-CoV-2 kill you?

Variants of Concern

variant for which there is evidence of an increase in transmissibility, more severe disease, significant reduction in neutralization by antibodies generated during previous infection or vaccination, reduced effectiveness of treatments or vaccines, or diagnostic detection failures.

DNA or RNA

what kind of vaccine:

once delivered, DNA plasmid or mRNA expresses coronarviruse protein to provoke immune response

Viral Vectors

what kind of vaccine:

-uses a different virus to deliver coronavirus genes into cells to provoke an immune response

Protein Subunit

what kind of vaccine:

direct delivery of a coronavirus protein or protein fragment to provoke an immune response

Whole Virus

what kind of vaccine:

weakened or inactivated version of the corona virus delivered to provoke an immune response