Resp Viruses Flashcards
Resp Tract Broken Down
- _Upper Resp: _
- Nose (mouth)
- Throat
- Epiglottis
- Larynx
- Middle ear & paranasal sinus
- Lower resp:
- Trachea
- Brochi
- Bronchioles
- Alveoli
- Deaths by resp infections #1 among low income populations
Defense against infections
- Nose: Hair, cilia, turbinates or nasal concha/mucus filter dust & particles = Sneezing
- Change in direction: airway from sinuses to pharynx deposits particles @ **back of throat **
- Lymphoid tissue:
- Adenoid gland: Between nose & throat @ end of soft palate
- Tonsils: Both sides of pharynx
- Trachea: layer of mucus & ciliated cells=Coughing
- Resp secretions: Lysozyme (gram+ bacterial cell walls), IgA, lactoferrin, mucus
- Alveolar macrophages: Lower resp tract
- Normal flora: upper resp tract
How Pathogens avoid immune defense
- Avoid mucus = NOT being expelled out
- Avoid phagocytosis & multiply/divide in phagocytic cell
- Major virulence factors(mol secreted by pathogens):
- Bacterial adherence-surface structures
- Extracellular toxins-Cytoxins
- Growth in host tissue-intracellular
-
Evasion of hose defense:
- Capsules-multiple types
- Production of IgA proteases
- TB avoiding immune defense w/granuloma
- Multiple strains of strep (94)
Syndromes of Upper Resp
- Defense = Normal Flora
- Common cold
- Pharyngitis
- Influenza
- Diphtheria
- Sinusitis & Otitis Media
- Rhinocerebral mucrormyosis
- **Effects immunocomprimised **
- Epiglottis
- Croup/laryngitis
Syndromes of Lower Resp
- Defense: Macrophages
- Whooping cough
- Bronchitis/Brochiolitis
- Influenza
- Pneumonias
- Typical
- Atypical (walking) develops from bacteria, viruses, fungi not common typical (chlamydo, mycoplasma, legionella)
- Community/Nosocomial (hospital)
- Occupational-Bacillus anthracis/Chlamydophila psi
- Regional
- Opportunisitc-Aspergillus spp/pneumocystis Jiro
- Pulm TB = Myobacterium TB
Etiologic Agents of Resp Infections
- Microbal toxins that cause disease-Viruses, bacteria, fungi, Protozoan(unicellular), Helminthes
- Viruses more common
- Bacterial infection more serious=life threatening diseases
- Many of upper resp tract pathogens ALSO cause lower resp tract infections
- Influenza can effect BOTH lower/upper
- Vocal cords are a marker for upper & lower resp tract
- Bacteria:
- Staph aureus-major cause of pneumonias
- Francisella tularensis-gram(-) lethal cases of pneumonias
- Coxiella burnetti-Gram(-) bio weapon
Common Cold
- Acute viral infection of resp tract w/inflammation in some or ALL airways (nose, paranasal, throat, middle ear, larynx)
- Symptoms:
- Nasal discharge & obstruction
- Sneezing
- Sore/scratchy throat
- Cough
- Chilly sensation w/slight fever
- Etiology: Multiple agents 90% viral
- Rhinovirus (common)
- Coronavirus (SARS-10-15%)
- Influenza (25-30%)
- Adenovirus (5-10%)
- Also less common chlamydia
- Human Metapneumoviruses (influenza)
- Complications: Sinusitis & otitis media Both Viral/Bacteriral w/asthma
- Treat w/1st gen anti-histamines or NSAID
Pharyngitis
- Divided into Naso, Oro, Laryngo (top-bottom)
- More common in children & @ winter time
- Symptoms: “Sore throat”
- Dysphagia (pain w/swallowing)
- Fever & headache
- Enlarged lymphnodes(neck)
- Occasional runny nose/post nasal drip
- Pus or no pus
- Etioloic agents:
- Adenovirus
- Coxsackie
- Epstein Barr (mono)
- Strep pyogenes
- Corynebacterium Diph <u><strong>(mycobacterium)</strong></u>
Sinusitis & otits media
- Occurs after viral infections
- Sinusitis: Inflammation & obstruction of sinuses due to pus_(may follow tootch extraction due to normal flora)_
- Fever-headache
- Thick colored post nasal discharge
- Halitosis
- Otitis media: Inflammation & obstruction of middle ear due to pus behind tympanic(NOT present in viral)-sharp pain w/hearing loss, vomiting (anorexia)
- Pathogens:
- Strep pneumoniae (normal flora)
- Haemophilus influenzae (normal flora)
-
Moraxaella catarrhalis <strong>(common)</strong>
- gram(-) aerobic
-
Pseudomonas aeruginosa <strong>(common)</strong>
- Immunocomprimised
Croup: Laryngotracheobronchitis
- Area between pharynx/trachea contains vocal cords w/mucous membrane
- Symptoms: Resp obstruction swelling
- Follows upper resp infection
- Breathing diff, hoarseness w/Seal’s bark cough, Inspiratory stridor (high pitched-vibrating)
- Gets worse laying down
- High risk in 3 months-5 years
- Exam: Restrictions on breathing, PROLONGED inspiration/expiration, wheezing
- Sucking in of skin on inhalation-increased use of chest wall muscles
- X-ray-Steeple sign (narrowing of upper trachea)
- Etiology: Parainfluenza virus (80%), RSV, measles, adeno, influenza
Bronchitis/Bronchiolitis
- Inflammation of bronchial tubes-occurs after upper resp
- Symptoms:
- Fever, cough, & sputum production
- Sore throat
- Runny or stuffy nose
- Headache
- Muscle aches & extreme fatigue
- Etiology: Virus & bacteria
- RSV (syncytial-COMMON)
- Parainfluenza/Influenza
- Mycoplasma pneumon
- Chlamydophilia (community)
Pneumonias Classification
- Infection of alveoli or walls
- Could involve interstital (between alveoli)
- Classification:
- Location-Community or nosocomial
- Oset-typical (acute), atypical (gradual), Chronic
- Site affected- lobular, multilobular, broncho, interstitial
- Regional- found only certain areas
- Occupational-zoonotic <strong>(cross species)</strong>
- Aspiration-Normal flora from Upper
Symptoms of Pneumonia
-
Typical: rapid onset, high fever/chills, dyspnea, productive cough (blood), wheezes/cracks
- X-ray: Dense consolidation
-
Atypical: moderate onset, low fever/chills, sudden attack cough w/moderate sputum
- X-ray: Vague-patchy consolidation
- Chronic: Gradual onset, night sweats, low grade fever, weight loss w/productive cough
RNA virus Rhino (Non-enveloped-Picornav fam)
- ss(+) RNA & 100 types known
- Replication in cytoplasm RNA-dep/RNA poly
- Reservior: Humans/Chimpanzees
- Transmission: Worldwide, seasonal(summer-fall), Direct contact, resistant to drying/Detergents
- Pathogensis: receptor on host ICAM-1
- Low infectious dose/Nose, eye, mouth
- Infected cells make-histamine/bradykinin
- Replicates @ 33C better for upper resp
- Acid labile-Killed in stomach
- Diagnosis: Rarely done
- Viral isolation-swabs saliva, nasal, pharyngeal
- Serology-confirm virus as infection & assessment of immune status
- Treatment: Hand washing w/NO vaccine due to so many serotypes
RNA virus Corona (enveloped-Coronavir fam)
- Spikes on surface due to large glycoprotein=Looks like *corona/crown *
- (+) ssRNA virus replicated in cytoplasm w/RNA dependent RNA poly
- optimum temp 33-35C=Upper resp
- S protein for attachment coating itself resemmbling Fc-gamma receptors on immunoglobulins
- Reservior-Corona(Human)
- SARS-Cov(bats, cats, raccoon)
- MERS-NCOV(middle east bats, camels)-Immunocomprimised
- Transmission-Airborne droplets nasal or Oral-fecal (winter-spring)
- SARS-COV: kills alveolar cells w/diarrhea
- High fever, sore throat, ATYPICAL pneumonia, dyspnea
- RT-PCR w/ELISA Ab=Diagnosis
- Treat: Interferon-Ribavirin
DNA virus (non-enveloped) Adenovirus life cycle
- Icosahedral shape w/hexon capsid proteins
-
Peplomers: Pentons @ apices w/protuding fibers=attachment (HE)
- Purified fibers toxic to human cells
- Reservoir: Humans w/asymptomatic shedding
- Receptors on host cells:
- CAR-Coxsackie: Glycoproteins in Ig super family (CAR used by Coxsackie virus too)
- CD46 (membrane co-factor protein)
- MHC class 1
- Integrin (internalization)
- Sialic acid (RBC & Upper resp)
- Endocytosis-Repication in nucleus
- Early protein synthesis FOLLOWED by replication THEN late protein synthesis
DNA virus (non-enveloped) Adenovirus Pathogenesis
- Lytic: Permissive cells=host cell death
- Target cell-muco-epithelial cells in resp tract (upper & lower), GI, Urinary
- Latent: non-permissive cells=recurrence in immuno comprimised pts
- Target cell-Infections in lymphoid cells (tonsils, adenoid, peyer’s patches)
- Transforming infection: Cancer @ the site on incoculation <strong>(hamsters only)</strong>
- Transmission: Close contact, aerosol, fecal-oral
- Resists dryness, deteregents, mild Cl- (survive up to 90 days in pools)
- High Risk: Children, crowded areas, SWIMMING clubs
DNA virus (non-enveloped) Adenovirus Clinical
- Pharyngitis=1,2,3,5,7:
- Common cold symptoms
- Fever, Sore throat, Inflammed Pharynx
- Pharyngoconjunctival fever=3,7:
- Assoc w/pools
- Conjunctivitis, fever, vocal cord inflamm
- Acute resp disease=4,7,21:
- Military recruits
- 3rd week of training
- Fever, malaise, sore throat
- Sudden drop in O2 in blood
- Vaccine available (made of 4&7) oral & replicate in GI bypas resp
- Pneumonia=1,2,3,7:
- Mostly children and severe
- GI(diarrhea)=40,41
- Diagnosis: Immunoassay fluorescent Ab or ELISA or PCR
RNA virus Coxsackie (Non-eveloped Picornaviri)
- (+)ssRNA w/2 types A & B
- Reservoir: Humans
-
Transmission: P to P, fecal-oral, Airborne
- Ex. Diaper changing stations
- High risk: infants & young children in Summer/Fall seasons
- Treatment: COXA self-limiting (4-7days)
- No vaccines
- Prevention: Proper hygiene, boiling utensils
- Herpangina: Vesicular pharyngitis
- Sudden fever, headache, Sore throat, Dysphagia
- Ulceration/Rash in pharynx, tonsils, mouth
- Hand-foot-mouth: mild fever, vesicular lesion-hand, foot, mouth, tongue
- Caused by type COXA16
DNA virus Herpes (enveloped) General
- Large w/linear dsDNA
- Lytic, persistant or latent transforming infections
- Vesciles seen in HSV1/2
- HSV 1=Cold sores-latent in trigenminal
- Grouped on what cell types they infect
- Alpha herpes(infect epi cells):
- Simplex (HSV-1 & 2)-Upper resp
- Zoster-varicella (HHV 3)
- Gamma herpes(infect vareity cells):
- Epstein-Barr (HHV4)
- Kaposi sarcoma (HHV8)
- Beta herpes(infect lymphoid cells):
- Cytomegalovirus (HHV5)-Upper resp
DNA virus Herpes (enveloped) Epstein Barr
- ds linear DNA-Enveloped HHV4
- Asymptomatic shedding w/saliva w/lifelong infection
- Transmission-P to P saliva
- High risk-Young adults not infected <strong>(mono)</strong>
- Infections in infants (when maternal Ab stops) or early childhood life long immunity
- Cell infected = Epithelial (oro/Naso) & B-lymph
- Virual gp350 attaches to comp C3b receptor-CR2(CD-21)->Gp42->MHC2
- Permissive(productive): replicates/lysis of infected cells contain-
- Early Ag, Viral capsid Ag, Membrane Ag
- Non-permissive(latent):B cell mitogen (uncontrolled prolif) EBV DNA in nucleus, NOT integrated w/chromosome
- Epstein barr nuclear Ag & Latent membrane protein = Immortal growth
DNA virus Herpes (enveloped) Epstein Barr Clinical
- Acute: Infectious Mono=Heterophile Ab (+) sheep blood agar (paul-bunnel test)
- Fever, Sore throat, Lymphadenopathy, Splenomegaly & FATIGUE 1-4 weeks
- Chronic: Recurrent-Fatigue, low grade fever, sore throat
- Ampicillin<strong>(beta-lactam)</strong>rash seen in pts under treatment
- Additional diseases associated:
- Leukemia/Lymphoma-T-cell def or Immunosuppresed
- Burkitt’s-Tumor of Bcell, Jaw/face, Africa-malaria belt
- Nasopharyngeal carcinoma-Cancer of epi, Asia, genetic
- Oral Hairy leukopenia-AIDS pt, Wart like growth, multiplies in epi cells
DNA virus Herpes (enveloped) Epstein Barr Diagnosis
- Incubation time 2 months or more
- Hematologic:
- Atypical T lympho (Downey cells)
- T cells are larger w/vacuolated cytoplasm & basophilc inclusions
- Serology:
-
Heterophile Ab: non specific IgM Ab-Bind to paul-Bunnel Ag on horse, sheep RBC
- Monospot test(horse)-quick
-
EBV specific Ab test: IgM active infection against viral capsid Ag or Early Ag
- IgG & AntiEBNA for chronic
- Treatment: Self-limiting or Steroids for controlling swelling
RNA virus (enveloped) Paramyxoviridae
- (-) sense ssRNA & non-segemented
- Cytoplasmic replication
- Buds from plasma membrane
- 3 genera cause Resp tract infections
- Paramyxovirus: Parainfluenza/Mumps
- 2 spikes:
- F peplomer spike=fusion results in multinucleated cells (synctia)
- Posses spike=Hema & Neuraminidase
- Pneumovirus: Resp syncytial & Metapneumo
- Morbillivirus: Measles
RNA virus (enveloped) Parainfluenza Clinical
- Transmission: inhalation of large droplet
- High risk: Children 6mos-12yrs, short term immunity after disease
- Pathogenesis: Inside epi cells-form giant cell & lysis
- Adhesion mediated by Hemagglutnin-binds to sialic acid
- Neuraminidase clips sialic acid for virus release
- Clinical: Croup & Laryngotraceobronchitis
- Mild cold-like upper resp infection
- Can extend to larynx, trachea, & bronchial tree = CROUP or bronchiolitis & pneumonia
- Croup=cough is sharp like seal’s bark due to subglottal swelling=High pitch
- X-ray steeple sign
RNA virus (enveloped) Parainfluenza diagnosis
- Best specimens are nasopharyngeal secretions
- Ag detection: Immunofluorescence
- Serology: Hemagglutination inhibition test, ELISA
- Treatment:
- Hospitalization-Treat symptomatically & monitor airway continuosly
- Cold or warm mist (humidirfier)-Croup tent
- O2-may have intubated due to narrowing of trachea
- IM dexamethasone (corticosteroid) & inhaled epinephrine (pediatric)
- NO vaccine & re-infections common
RNA virus (enveloped) RSV General
- (-) ssRNA w/surface spikes only F protein (NO HG or Neuraminidases)
- F protein: fusion multinucleated (syncytia)
- Reservior: Humans everyone infected by age 3
- Subtype B: asymptomatic affect majority of population
- Subtype A: More severe & dominant in most outbreaks
- Transmission: Inhalation of large droplets-Peaks in winter
- High Risk: Premies-more severe w/lower resp=Brochiolitis
- Common cause of acute FATAL resp tract infections
- Adults: Mild symptoms, common-cold like. Very few infections are life threatening
RNA virus (enveloped) RSV Pathogenesis
- Cause of fatal acute resp tract infection in infants
- Infects epi cell & make giant cells & kills cells
- Immuno mediated (CD-8) cell injury-necrosis/sloughing of bronchiolar epi
- Formation of plugs-Mucus, fibrin, necrotic material obstructs airway=Bronchiolits
- More dangerous in infants due to smaller peripheral airways than adults
- Symptoms: Mild Upper resp infection progress to cough->wheeze->dyspnea
- Increased resp rate=Tachypnea
- Rales, fever->turns into Lower resp=Pneumonia
- RSV sign: intercostal/substernal retraction
- Long-term=Asthma & pulm deficits
RNA virus (enveloped) RSV Diagnosis
- Ag detection assays (immuno)-
- Cytophatic effect=Multinucleated cells w/basophilic cytoplasmic inclusion bodies
- Treatment:
- Symptomatic-Bronchodialators (metaproterenol/Albuterol) helps relieve chest congestion & wheezing
- Severe cases=O2 therapy, Aerolized Ribavirin (analogue of guanosine)
- Passive immunization: Hyperimmune globulin against RSV (Respigam)
- Prevention: Infection for re-infection
- Immuno-prophaylaxis-Children under 2 who have chronic lung disease
- Monoclonal Ab against F-protein(palivizumab)
RNA virus (enveloped) Metapneumovirus
- ss(-) RNA from family paramyxoviridae
- Recently recognized pathogen
- Could cause 15% of children’s colds
- Can cause:
- Bronchitis (mucous membranes)
- Bronchiolitis (small bronchioles)
- Pneumonia
- Very common-children by age 5 are seropositive
RNA virus (enveloped) Influenza-General
- ss(-)RNA & 8 Segmented RNA
- Replicates in nucleus<strong>(instead of cytoplasm)</strong>
- Has RNAdep-RNApoly
- Matrix proteins important in uncoating:
- HA (hemagglutinin)
- Initiate by binding to sialic acid on epi cells
- Agglutinates clumping-RBC
- NA (neuraminidase)
- Cuts sialic acid to release virus/dissolves mucus
- Vaccines target these proteins (no binding=no infection)
- 3 types based on variation of matrix proteins & nucleocaspid proteins (viral penetration into host nucleus)
RNA virus (enveloped) Influenza-Life Cycle
- HA sticks to sialic acid on host cell-Virus enters by fusion into endosome (storage b4 nucleus)
- Matrix proteins=uncoating
- Nucleocapsid to host cell nucleus, viral polymerases require methylated cap of RNA (Cap-mRNA-Poly A) of host cell. Cap region of RNA for binding to ribosomes.
- (+) RNA made from each segment=viral polymerase on each segment(-)sense RNA for viral progeny made=viral Shedding
- +mRNA proteins in cytoplasm.
- Early proteins (polymerases and NP) for transcription and replication go to nucleus and mix w/–ssRNA.
- HA and NA , M proteins transported to host cell membrane.
RNA virus (enveloped) Influenza-Types
-
Type A ONLY one w/sub-types based on variation on HA/NA Ag
- 16 HA sub = H1-H16
- 9 NA sub = N1-N9
- Found in many species_-Native host is duck_
- Type A assoc w/Pandemic <strong>(Spanish Flu)</strong>
- Reassortment Antigenic shift:
- Abrupt change when 2 strains infect one cell=RNAs mix giving rise to NEW strain
- ONLY A
- Type B ONLY humans
- Point mutation/Antigenic shift:
- Type A&B-Yearly epidemics occur
- RNA segments are altered affect major Ag sites for glycoproteins
- RNA virus prone to more mutations than DNA
- Peplomers mutation=Cross species infect
RNA virus (enveloped) Influenza-Clinical
- Incubation 1-4 days
- Fever, headache, sore throat, muscle pain, DRY cough
- Recovery 7-10 days
- Severity in young & elderly ALSO pts w/chronic cardio-pulm diseases
- Pneumonia caused by Influenza
- Pneumonia caused by secondary bacterial infection-MOST COMMON (Staph aureus, Staph pneumoniae, H. Influenzae)
- Reye’s syndrome-Acute encephalomyelitis(inflammation of CNS)in children-assoc w/aspirin use
- CNS issues-Seizures, weakness in periphery, hallucinations
RNA virus (enveloped) Influenza-Diagnosis
- Nasal/throat swabs, sputum
- Detection=Ag/genome DFA, ELIZA, RT-PCR specific ID for types or subtypes
- Fast results-used in screening during epidemics
- Viral isolation & ID-Cell/egg culture:
- Hemagglutination or Hemabsroption assay NOT specific
- Serology: measure Ab lvl (titer)-Acute hemagglutination inhibition assay, Comp fixation
-
Treatment: neuraminidase inhibitors stop viral release given 48 hrs of onset
- Oseltamivir(tamiflu)-oral
- Zanamivir(Relenza)-inhaled
- Stop uncoating-block martix proteins_ONLY A_
- Amantadine or Rimantadine
RNA virus (enveloped) Influenza-Vaccine
- Flu shot-Inactivated vaccine (killed virus)
- Composed of H1N1, H3N2 + type B
- Nasal spray vaccine:
- Live attenuated=Reconstructed from mutant strain & virulent strain (weak)=Reassortment
- Mutant strains does NOT grow well above 25C=Cold adapted mutant
- Will grow in upper BUT not Lower resp making it less virulent