Viral Respiratory Tract Infections Flashcards
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List upper respiratory tract infections
Upper resp tract
Common cold / Coryza ;Covid-19 Influenza / Flu Acute tonsillitis Acute pharyngitis ( Sore Throat ) Acute otitis media Acute sinusitis
Nasal cavity
Oral cavity
Pharynx
Larynx
Coryza/ Common cold causitive agents
Adults & Children - Rhinovirus ,
Coronavirus ( COVID -19 ) ,
R.S.V.- ( Respiratory Syncytial Virus ).
Clinical features of Coryza/ common cold
Surfactant - explain term
Type 1 pneumocyte function
SARS-CoV-2 Pathogenesis
Fatigue Feeling cold Nose burning , Obstruction , Running of nose Sneezing Fever
Increased surface tension increases cohesion within the alveoli, pulling the alveoli closed.
The alveolar cells produce a specialized liquid, surfactant, that decreases the surface tension in the airways reducing the amount of energy required to expand the lungs.
Gas exchange
Pathogenesis
Virus attaches to Type 2 pneumocytes (f’n to produce surfactants) in alveoli
Virus spike protein (S spike) binds to ACE2 on membrane
Virus enters cell and releases +sense ssRNA
Virus uses ribosomes to convert mRNA to proteins via translation
RNA dependent RNA polymerase makes more mRNA
Polyproteins formed which are then cleaved by proteinases to form essential viral protein components
(cleaves the precursor viral polyprotein to produce functional proteins and enzymes)
Virus copies exit cell
– Type 2 pneumocyte becomes damaged and releases IFN-gamma which stimulates macrophages to respond (DAMPs released from within cell)
– Macrophage secretes :
IL-1, IL-6, TNF-alpha
– These cytokines travel to capillary and act as inflammatory mediators
(Inflammatory mediators = vasodilation + increased capillary permeability)
– Fluid leaks to outside alveoli and compresses alveoli
(Water has high surface tension b/c of H+ bonding btw H2O
Surfactant lines alveoli to prevent collapse due to high surface tension
Fluid moves into alveoli and drowns out surfactant thereby increasing the surface tension inside alveoli)
– Alveoli collapse + fluid surrounding alveoli impairing gas exchange = Hypoxemia (low O2)
This can lead to Acute respiratory distress syndrome (ARDS) (rapid onset of widespread inflammation in the lungs)
– Neutrophils come to area and destroy pathogen via ROS (e.g. proteases) which causes cell damage (type 1 and 2 pneumocyte) as well = less surfactant production + alveoli collapse
– Alveoli will contain cell debris of type 1 and 2, macrophages, neutrophils, fluid = lung consolidation
( occurs when the air that usually fills the small airways in your lungs is replaced with something else )
– Gas exchange process altered = hypoxemia
Productive cough (from consolidation)
– IL-1, IL-6, TNF-alpha travel to brain if in high amts and go to hypothalmus causing fever
– Low partial pressure of O2 stimulates chemoreceptors which causes SNS to be stimulated which causes increased heart rate
chemoreceptor detects changes such as > in blood levels of CO2 (hypercapnia) or < in O2 (hypoxia), and transmits info to CNS which engages body responses to restore homeostasis.
– Inflammation can spread through entire circulatory system causing increased capillary permeability and fluid leakage into surrounding tissues = low blood volume
– Vasodilation occurs = Lowered total peripheral resistance
(resistance of the arteries to blood flow. As the arteries constrict, the resistance increases and as they dilate, resistance decreases)
– Low blood volume + low peripheral resistance = low bp
– Low bp leads to low perfusion i.e. less blood moving to organs = multi system organ failure
Syndrome - define
group of symptoms which consistently occur together
COV-19 caused by
severe acute respiratory syndrome coronavirus 2 ( SARS-CoV-2 )
COV-19 spread via
Via respiratory droplets ( coughing , sneezing ) during face-to-face exposure or by surface contamination.
Most common symptoms of Cov-19
fever ,
cough ,
shortness of breath - (weakness , fatigue , nausea vomiting , diarrhea)
Lab ID - COV-19
PCR / RT-PCR testing of nasopharyngeal swab
Treatment - COV-19
Supportive care . Recent trials – dexamethasone decreases mortality , supplemental oxygen / ventilator .
COV-19 prevention methods
Face masks , N95 respirators , Physical social distancing , Hand washing / sanitizer , Travel restrictions , Isolation of patients , Quarantine of exposed people , Avoiding personal contact with pts. , PPE – healthcare workers
Causative organisms for (influenza) flu in order of prevalence
Influenza virus 80 %
Parainfluenza 2-9 %
Adenovirus 4 %
Features of (influenza) flu
Causes Epidemics and Pandemics
Highly contagious - viral infection.
Myxoviruses are divided into two families
1 ) Orthomyxoviridae e.g. Influenza viruses ;
2 ) Paramyxoviridae e.g. Parainfluenza virus and ( Mumps virus , Measles virus , Respiratory syncytial virus ).
Flu (Influenza) features
Common cold symptoms - because of HA binding to mucin receptors on RBC + epithelial cells of resp tract
Sudden onset after 12 - 24 hrs incubation
General weakness & fatigue
Feeling cold , shivering , temp.- Up to 39-40 C
No sore throat or No running nose
Severe back , muscle and joint pain
Influenza viruses are a member of Orthomyxoviridae
Spherical,
80 – 120 nm,
Helical nucleocapsid symmetry and surrounded by an lipoprotein - envelope.
Nucleic acid – negative sense single stranded RNA.
Structural proteins:
- PB1, PB2, PA - RNA transcription and replication
- NP - nucleoprotein (gives rise to nucleocapsid with helical symmetry)
- Matrix proteins: M1 - shell, M2 - ion channel
- Hemagglutinin (HA) and Neuraminidase (helps virus to pass through cell layer) - glycoproteins inserted in lipid envelope
- Non-structural proteins NS1 - interferon antagonist + inhibits pre mRNA splicing ; NS2 - export of molecules across the nucleus
Transmission - influenza
– cough , sneeze, contacts , fomites
Target cells to enter
–alveolar cells
Influenza multiplies locally where?
–respiratory epithelial cells
Influenza spreads to where?
–lower respiratory tract
Incubation period - influenza
18-72 hrs
Symptoms - influenza
chills , headache ,dry cough ,fever ,anorexia.
Specimen - influenza
Nasophyryngeal swab , kept at 4 C
Isolation of virus
In embryonated eggs and primary monkey kidney cell lines
Growth is detected by hemadsorption , hemagglutination test .
Molecular methods
Real time RT PCR : detects viral RNA
Antibody detection
ELISA
Treatment of Influenza
Neuraminidase inhibitor ( Zanamivir , Oseltamivir –[ Tamiflu ] for influenza A and B and also for H1N1- 2009 flu , H5N1 avian flu ) MoA- Blocks NA from allowing escape of virus from host cell to infect other cells so virus components stick to cell surface.
Matrix protein M2 inhibitor ( Amantadine and Rimantadine – for influenza A infection )
Neuraminidase inhibitor - MoA
Block the function of viral neuraminidases of the influenza virus, by preventing its reproduction by budding from the host cell.
Matrix protein M2 inhibitor - MoA
During viral entry, the intake of a proton via an M2 protein induces unfolding of the HA protein such that the fusion peptide is activated.
Thus Matrix protein M2 inhibitor blocks viral entry
(Amantidine - very successful in influenza A)
Prevention - influenza
Strict hand hygiene , isolation , use mask , remain at home and Vaccination prophylaxis .
EBV is mostly asymptomatic (T/F)
The manifestation of symptoms in EBV is referred to as ?
EBV- [Epstein –Barr virus] - Kissing Disease signs and symptoms
True
Infectious mononucleosis
Fever, Headache, Pharyngitis, Cervical lymphadenopathy, exaggerated fatigue
Splenomegaly - Stores many B cells so infected B cells will go there and CD8 T cells will follow to destroy infected cells causing swelling of spleen
Another name for Infectious Mononucleosis
Glandular Fever
Prevalence for Infectious mononucleosis
Among adolescents & Young adult
Clinically useful Laboratory tests : For - Epstein-Barr Virus
Heterophilie antibody : ( Paul - Bunnel Test - sheep RBCs)
Monospot test –modified heterophile agglutination test –hourse RBCs
IgM antibody to Viral Capsid Antigen ( VCA )
Atypical Lymphocyte ( Abnormal )
Heterophile antibody test
Heterophil antibodies have the ability to agglutinate red blood cells of different animal species.
The Paul-Bunnell test uses sheep erythrocytes; the Monospot test, horse red cells.
Monospot test
Monospot test - form of the heterophile antibody test, is a rapid test for Epstein–Barr virus (EBV).
- It is an improvement on the Paul–Bunnell test
IgM antibody to viral capsid antigen (VCA)
Presence of VCA IgM antibodies indicates recent primary infection with Epstein-Barr virus (EBV).
The presence of VCA IgG antibodies indicates infection sometime in the past.
Atypical lymphocytes
EBV affects which cells?
EBV pathogenesis
Normal lymphocyte - Small nucleus + little cytoplasm
Atypical lymphocytes - Bigger nucleus + more cytoplasm
- Reactive CD8 T cells killing infected
B cells
A few atypical lymphocytes are probably of little clinical significance.
A large number of atypical lymphocytes are often found in viral infections like mononucleosis (many B cells need to be killed), cytomegalovirus infections and hepatitis B.
Epithelial cells, B cells, T cells
- Transmission via saliva
- Virus infects epithelial cells of mouth then replicates and goes to oral pharynx (back of throat)
- Virus moves to lymphoid tissues of oral pharynx i.e. tonsils where B cells and T cells are and infects them
- B cells spread through lymph to other lymphoid tissues and infect those B cells
- Infection is eventually controlled with antibodies binding free floating virus + CTLs killing infected B cells
Molecular methods for EBV
– Detects EBV DNA by PCR .
Transmission - EBV
transmitted through salivary contact
EBV is a member of?
Herpesviridae
Treatment of EBV
Supportive such as analgesics used in infectious mononucleosis . Acyclovir is antiviral drug used in treatment .
Prevention of EBV
Patient isolation
Sore throat/ Pharyngitis - causative organisms
Pharyngitis vs Tonsillitis
- Epstein-Barr virus
- Adenovirus
- Influenza A , B
- Respi .syncytial virus
- Parainfluenzae
Both cause inflammation.
If tonsils are affected - tonsillitis.
If the throat is affected - pharyngitis.
Signs and symptoms of pharyngitis/tonsillitis
Sore throat Fever > 38 C Difficulty in swallowing Enlargement of tonsils Congested tonsils and pharynx Headache , fatigue Muscle pain
Tonsillar hyperemia / exudates
Soft palate petechia
Absence of nose drip
Enlarged tonsillar lymph nodes
Middle Respiratory Tract Infections
Epiglotitis Laryngitis Croup Tracheatitis Bronchitis Bronchiolitis
Contributing factors to middle respiratory tract infections
Smoking , previous lung damage , atmospheric pollution & cold damp weather
Epiglotitis - organisms
H influenzae, S pneumoniae, C diptherae
Laryngitis (inflammation of larynx/voicebox), Croup - organisms
Parainfluenza virus, influenza virus, adenovirus, occasionally RSV
Tracheitis - organisms
Parainfluenza virus, influenza virus, adenovirus, occasionally RSV
Bronchitis, Bronchiolitis
Parainfluenza virus, influenza virus, resp syncitial virus, adenovirus
Bordetella pertussis, H influenzae, Mycoplasma pneumoniae, Chlamydia pneumoniae
Human parainfluenza viruses are one of the major causes of middle and lower respiratory tract infection in adults. (T/F)
Human parainfluenza viruses are one of the major causes of middle and lower respiratory tract infection in young children.
Parainfluenza virus morphology
Transmission of parainfluenza virus
Unsegmented, -ve sense, ssRNA, enveloped, helical
Transmission by respiratory route ( by direct salivary contact or by large- droplet aerosols ).
Incubation period - parainfluenza virus
The incubation period is 5 - 6 days
Parainfluenza virus - does it multiply locally? What kinds of manifestations appear?
Virus multiplies locally and causes various respiratory manifestations
Clinical manifestations of parainfluenza virus
a ) Mild common cold syndrome like rhinitis (inflammation + irritation inside mucus membranes of nose) and pharyngitis .
b ) Croup / Laryngotracheobronchitis – involves children between 1-4 yrs age .
c ) Pneumonia or Bronchiolitis – involve infants below 6 months of age.
Otitis media – it is most common complication of parainfluenza virus inf . (T/F)
True
Parainfluenza viruses are important cause of outbreaks in paediatric wards , day care centers and in schools . (T/F)
True
Lab Diagnosis - parainfluenza viruses
I] Antigen detection : Viral antigens from nasopharynx detected by direct IF –( ImmunoFluorescence ) test by specific monoclonal antibodies .
2] Viral isolation : Specimen – nasal washes ,lung tissue & bronchoalveolar lavage fluid can be used. Primary monkey kidney cell line is most sensitive .
3] Serum antibodies measured by ELISA – IgM Ab rise indicate active infection .
4] Reverse transcriptase PCR assays are highly specific and sensitive but available only in limited settings .
Laryngitis - define
Inflammation of the voice box, or larynx , often viral.
What can cause dangerous complications in children regarding laryngitis?
Several forms of laryngitis occur in children that can lead to dangerous complications
What are these forms of laryngitis?
These forms include:
Croup
Epiglottitis
What is Croup ?
What is Epiglottis?
Croup is breathing difficulty accompanied by a “barking” cough , swelling around the vocal cords
Epiglottis - Abnormal high pitched breathing, severe sore throat
In what age group is croup common?
Common in infants and children ( 1- 4 years ).
Most common parainfluenza viruses
Influenza viruses ,
Respiratory syncitial virus ( RSV ) ,
Adenovirus
Symptoms of Croup
A cough that sounds like a seal barking .
Later the child may have labored breathing or stridor ( a harsh , crowing noise made during inspiration ) .
Fever
Upper resp tract inf for few days - Low grade fever + coryza
Virus then infiltrates larynx and trachea
Infiltration causes release of WBCs to area = pain + edema
Swelling = airway obstruction + turbulent noisy air flow (stridor)
(Stridor occurs during inhalation due to the swollen area being lower in partial pressure compared to outside cause collapse of airway causing turbulent flow of air through airways)
How long does Croup last?
5 or 6 nights
What is Epiglottis?
Inflammation & oedema of epiglottis and soft tissue above vocal cords
Age group for Epiglottis
Children 2- 6 years
Clinical manifestations of Epiglottis
Fever
Difficulty in breathing because of respiratory obstruction , swelling ,
Reddening of epiglottis.
Causative organisms of Epiglottis
Haemophillus influenzae.
Corynebacterium diphtheria .
Strepto .pneumoniae / Diplococcus pneumoniae
Infections of trachea and bronchi
Bronchitis - Inflammation of the bronchial tubes
Bronchiolitis - Inflammation of bronchioles
Tracheobronchitis – Inflammation of tracheobronchial tree
Bronchitis - define
Inflammation of the bronchial tubes
Bronchiolitis - define
Inflammation of bronchioles
Tracheobronchitis - define
Inflammation of tracheobronchial tree
Bronchitis is characterized by ?
inflammation of bronchus
Viral causes of bronchitis
Rhinovirus , Parainfluenza virus , Respiratory Syncytial Virus - RSV , Influenza virus , Adenovirus
Sources of secondary bacterial overgrowth in bronchitis
Haemophilus influenzae
Streptococcus pneumoniae
Staphylococcus aureus
Symptoms of bronchitis
Fever
Dry & painful cough initially
Later cough becomes productive
Expectoration of yellow green sputum
Treatment for bronchitis is used to treat secondary bacterial overgrowth (T/F)
True
Respiratory Syncytial virus - causes what in children and infants?
Young children and bronchiolitis and pneumonia in infants
RSV - transmission
Direct contact/ droplets via inhalation
Incubation period - RSV
Incubation : 3-5 days
Symptoms - RSV
Begins with running nose , fever , wheezing , dyspnea and cough
- Beings in upper resp tract - with rhinorrhea (runny nose), congestion, sneezing
- Within 1-3 days it spreads to lower airways causing swelling of terminal bronchioles = cough
- Bronchioles swollen + plugged with mucus = harder to move air = Tachypnea (fast breathing)
- Retractions (area between the ribs and in the neck sinks in due to person working hard to breathe)
If virus gets to alveoli = pneumonia
Infections are not common in over-crowded communities for Respiratory Syncytial Virus. (T/F)
False, they are common in overcrowded areas.
Lab ID - RSV
Antigen detection - Direct IF immunofluorescence test
Virus isolation – HeLa and Hep-2 cell lines for RSV –[CPE] cytopathic effect , syncytium formation seen .
RT-PCR .
Antibody detection by ELISA .
Direct IF Immunofluorescence test
DIF involves the application of antibody–fluorophore conjugate molecules to biopsy sample.
Antibody–fluorophore conjugates target abnormal depositions of proteins in the patient’s tissue. When exposed to light, fluorophore emits its own frequency of light, seen with a microscope.
Staining pattern and abnormal protein deposition seen
HeLa cell line - define
HeLa cell line - cultivated from tumor cells obtained from cervical cancer patient
Hep-2 cell line - define
Human epithelial type 2 (HEp-2) cells, considered to originate from a human laryngeal carcinoma
What are cytopathic effects?
Cytopathic effects (CPEs) are distinct observable cell abnormalities due to viral infection.
CPEs can include:
Loss of adherence to the surface of the container, Changes in cell shape from flat to round,
Shrinkage of the nucleus,
Vacuoles in the cytoplasm,
Fusion of cytoplasmic membranes
Formation of multinucleated syncytia, inclusion bodies in the nucleus or cytoplasm,
Complete cell lysis
RT-PCR uses
RT-PCR differs from PCR in that the enzyme reverse transcriptase (RT) is used to make a cDNA from the small amount of viral RNA in the specimen. The cDNA can then be amplified by PCR.
ELISA - uses
used to measure antibodies, antigens, proteins and glycoproteins in biological samples
DoC - RSV
Ribavirin
Rhinovirus - transmission, causes what
Transmitted by respiratory route and cause common cold
Incubation period - rhinovirus
2-4 days
Symptoms - rhinovirus
sore throat , sneezing , nasal discharge , nasal obstruction but no fever
Lab ID - rhinovirus
Grown in human diploid cell lines
WI-38 is a diploid human cell line composed of fibroblasts derived from lung tissue of a 3-month-gestation female fetus.
MRC-5 is a diploid cell culture line composed of fibroblasts, originally developed from the lung tissue of a 14-week-old aborted Caucasian male fetus.
Treatment
Symptomatic
Adenovirus - viral characteristics/morphology
Space vehicle shaped . dsDNA - linear, non enveloped , icosahedral capsid symmetry.
Adenovirus - can cause
URI (upper respiratory infection/common cold) and pneumonia
Specimen - adenovirus
Throat swab
Virus isolation - adenovirus
Hep-2 ,HeLa , KB , A549 cell line –shows CPE –rounding and grape-like clustering of swollen cells .
Treatment
Only symptomatic, no antibviral
Lower respiratory tract infections include
Lower respiratory tract
Diseases of lungs including alveolar space & terminal bronchioles Acute pneumonia Chronic pneumonia Pleural effusion ( empyema ) Lung abscess
Bronchi
Bronchioles
Alveolus
Pneumonia
Inflammation of the alveoli of the parenchyma of the lung with - consolidation and exudation (leaking fluid)
Exudate - define
any fluid that filters from the circulatory system into lesions or areas of inflammation.
It can be a pus-like or clear fluid - it leaks out of the blood vessels and into nearby tissues.
– composed of serum, fibrin, and leukocytes.
Consolidation in pneumonia - define
Condition where lung tissue becomes firm and solid rather than elastic and air-filled because it has accumulated fluids and tissue debris.
Symptoms - Pneumonia
Fever & chills , head ache , malaise , generalised myalgia.
Pleuritic chest pain , Tachycardia & tachypnoea.
Shortness of breath , difficulty & pain on breathing.
Cough :- Initially non productive , subsequently productive , mucopurulent yellow or green sputum.
Bacterial causes of Pneumonia
Streptococcus pneumoniae Staphylococcus aureus , Haemophilus influenzae , Klebsiella pneumonia , Mycobacterium tuberculosis, , Mycoplasma pneumoniae.
Parasitic causes of Pneumonia
Pneumocystis carinii.
Strogyloides stercoralis.
Fungal causes of pneumonia
Histoplasma capsulatum
Coccioides immitis
Cryptococcus neoformans
Aspergillus species
Viral causes of pneumonia
Influenzae A & Influenzae B , Adenovirus , Parainfluenzae , Resp.Syn.Virus ( RSV ) & COVID-19
Collection of specimen - Pneumonia
Mucopurulent or purulent (containing pus) sputum in early morning.
Pleural fluid (build-up of excess fluid between the layers of the pleura outside the lungs)
Transtracheal aspirate ( collection of bronchial secretions – useful when standard sputum collection has not provided adequate material)
Blood culture
Resp. Specimens / Blood for viruses & mycoplasma
Skin test for Tuberculosis : Mantoux test .
Lab ID methods
Gram staining - Bacteria & Candida
Z-N stain- M tuberculosis & Auramine-rhodamine stain .
Giemsa stain - for Pneumocystic carinii
Culture- Blood agar , MacConkey’s agar & selective media.
Lowenstein–Jensen ( L.J. ) medium for M .tuberculosis
Sabouraud’s dextrose agar - for Fungi.
Tissue culture , Embryonated egg , Animal - for Viruses .
Automated lab ID methods
Automated Methods :- BACTEC ; SEPTICHEK ; BacT/ALERT ; VersaTek . Rapid Test :- PCR ; GeneXpert ( RT-PCR ) ; Interferon Gamma Release Assay ; ELISA –QuantiFERON –TB Gold assay .
Antigen detection methods
Antigen detection:
- Immunoelectrophoresis- H influenzae , Pnemococci( Str.pne.)
- Latex agglutination - H influenzae , Pnemococci /strepto.pne.
- PCR / RT- PCR = Rapid .
