Micro - Respiratory Flashcards

1
Q

Virus persistence on dry inanimate surfaces

A

Adenovirus - 7 days – 3 months
Rhinovirus - 2 hours – 7 days
Coronavirus - 3 hours
RSV - Up to 6 hours

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2
Q

Upper RT sx’s

A
  • Sinusitis
  • Rhinitis
  • Otolaryngitis
  • Laryngitis
  • Pharyngitis
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3
Q

Lower RT sx’s

A
  • Bronchitis
  • Bronchiolitis
  • Pneuomnias - CAPs (acute or subacute/chronic), nosocomial
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4
Q

Viruses w/main pathology elsewhere besides RT

A

Measles, chickenpox, smallpox, coxsackievirus, norwalk virus

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5
Q

Adenovirus

A

Family: Adenoviridae Genus: Mastadenovirus
Replication = Class I (nucleus)
Clinical syndromes: pharyngitis, conjunctivitis

• Fiber protein: attachment to host cell rec
• Rec varies w/ viral serotype:
– Serotypes 2 & 5: rec = CAR (Coxsackie Adenovirus Receptor)
• Cell surface glycoprotein belonging to IgG superfamily.
• Penton base has toxic activity
– Inhibition of cellular mRNA synthesis
– Cell rounding
– Tissue damage

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6
Q

Rhinoviruses

A

Virus family: Picornaviridiae
Icosahedral, non-enveloped

Clinical syndrome: Common cold. Humans are sole reservoir. Young children: more severe. Single community: often contains simultaneously circulating serotypes
– Single individual may be co-infected.

Relatively stable in environment, optimum temperature for growth is 33-35C (URT ideal for infxn), Ag drift.

Cell receptor = ICAM-1, Viral shedding
via surface cleft/canyon

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7
Q

Coronaviruses

A

Family: Coronaviridiae
• HCoV-229E, HCoV-OC43, SARS-CoV
Clinical syndromes: Common cold, SARS

Enveloped, helical nucleocapsid, characteristic fringe = surface/spike glycoproteins. S protein. Peplomers - define tropism, attach to prots or carbs, site of main Ag epitopes: Abs are neutralizing.

Re-infection by the same serotype possible: neutralizing Abs are short-lived. Transmission via droplets: fecal-oral route also possible.

Replication optimal at 33-34C in ciliated nasal epithelium. Difficult to isolate & grow

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8
Q

Human parainfluenza viruses (HPIV)

A

Virus Family: Paramyxoviridae
Subfamily: Paramyxovirinae
Genera: Respirovirus: HPIV 1 & 3
Rubulavirus: HPIV 2 & 4. Also includes mumps

Clinical syndrome: laryngotracheobronchitis; bronchitis

Enveloped. Glycoprotein with HN activity
• Fusion Factor (F) – viral entry. Abs against F protein = neutralizing
• V proteins (fusion proteins): evasion of immune response.
• Functions: – Prevent apoptosis, alter cell cycle, inhib dsRNA signalling – Prevent IF biosynthesis

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9
Q

Pneumovirus

A

Family: Paramyxoviridae, Subfamily: Pneumovirinae, Genus: Pneumovirus

• Enveloped, helical nucleocapsid
• Virally-encoded surface proteins:
– Fusion factor (peplomer): main viral Ag
– G glycoprotein : involved in attachment – Two subgroups: A & B
• Lacks glycoprotein with HN activity

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10
Q

Croup aka laryngotracheobronchitis

A
  • HPIV, Pneumovirus, RSV
  • Mostly young children and infants
  • Swelling and narrowing of the airway
  • Cough sounds like barking of a seal
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11
Q

RSV

A

• Entry is via epithelia of nose and eye.
– Large droplets on contaminated hands or surfaces (self-
inoculation).
• F & G proteins mediate attachment; F mediates membrane fusion.
• Primary site of replication = nasopharyngeal epithelium.
– Direct cytopathic effect loss of function.
• Can spread into lower RT after 2-5 days via various suggested mechanisms
• CD8+ T cells: subsequent dz enhanced when children vaccinated using heat-killed vaccine

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12
Q

Influenza

A

Virus survives drying for ± 24 hours, depending on ambient humidity
• Epidemics rarely continue in a community for more than 4 to 6 weeks
– Most people recover spont and gain long- lasting (but weak) immunity to that strain.

– Patient is contagious from before sxs
appear (end of day 1) for next 7 days
– Risk of secondary infxnn highest in time
from 6 to 12 days after infxnn

Children: same as those in adults, plus
– Higher fever
– G.I symptoms: (Vomiting, Abdominal pain)
– Earache (Otitis Media)
– Muscle pain and sometimes swelling
– Croup often but not always
– Febrile Convulsions (Children under 3: Rare)

Complications:
• Rare Neurological syndromes: Guillain Barre, Encephalitis, Reye’s Syndrome in Children – aspirin and aspirin containing drugs.

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13
Q

Influenza A

A

Only influenza A further classified by subtype on the basis of HA and NA. Influenza A subtypes and B viruses are further classified by strains.

Influenza A: All 15 “H” and 9 “N” found in Birds, domestic Ducks most commonly. Chickens -> sweeping epidemics. Pig is mixing bowl. Man can get from pig or duck
Hemagglutinin: • Major Ag against which neutralizing antibodies are directed.
– Highly variable -> evolution of new strains.
• 4 HA subtypes described in humans: HA1-3, HA5
Requires cleavage to be active:
– Carried out by cellular proteases found only in RT.
– Proteases probably define tissue tropism

Neuraminidase = Sialidase enzyme:
• removes term sialic acid residues from glycoproteins and
glycolipids.
Two subtypes described in humans: N1 and N2.
NO stimulation of neutralizing antibodies

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14
Q

Influenza B

A

Influenza B viruses are usually found only in humans.
•Two lineages of influenza B: •Victoria-like •Yamagata-like
•Only 1 is covered by the trivalent seasonal flu vaccine.
SHORTER TIME TO DEATH THAN INFLUENZA A

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15
Q

Amantadine & Rimantadine

A

– Inhibit uncoating of Influenza A only Target is M2 Protein
– No effect on Influenza B or C

• Excessive use of antimicrobials virtually guarantees the development of drug- resistant infectious agents
– Amantidine Resistant Influenza A

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16
Q

Zanamivir & Oseltamvir (Tamiflu®)

A

– Inhibit Neuraminidase: Without this, virus binds to its own sialic acid and forms useless clumps – blocking release.
– Work on Influenza A and B, not on C

• Excessive use of antimicrobials virtually guarantees the development of drug- resistant infectious agents
– Tamiflu Resistance

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17
Q

STREPTOCOCCI General Characteristics

A

Metabolism - fermentative with lactic acid production
Oxygen requirements - facultative anaerobes, • growth enhanced by CO2
• Nutritionally fastidious
– Normal culture medium = Blood agar (BA) • Yeastextract+peptone+5%blood

Lancefield classification NOT useful for some streptococci, e.g., S. pneumoniae. Used with serology & hemolysis patterns for preliminary ID (before 16S rRNA sequencing avail).

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18
Q

Streptococcus pyogenes

A

Group A Streptococcus = sens to Bacitracin. Beta hemolytic. Pharyngitis. LEUKOCIDIN, Hyaluronic acid capsule, M protein, Streptolysin, Streptokinase, Hyaluronidase, Pyrogenic exotoxins

19
Q

Streptococcus pneumoniae

A

Clinical syndrome: pneumonia, sinusitis, otitis media. Alpha Hemolysis = sens to optochin

Part of nasopharyngeal flora – 5-40% of healthy individuals. No animal/env reservoir.

Transmission: exogenous: person to person: droplets. • Endogenous. Winter & early spring incidence.

Pathogenesis: • Capsule, IgA protease, Pneumolysin, Autolysin, Transformation. Bloodstream in 15-30% of cases. Pneumolysin - Inhibits ciliated epithelial cell activity
Cytotoxic for alveolar and endothelial cells
Causes inflammation
Decreases PMN effectiveness

“polyvalent”capsularpolysaccharidevaccine, e.g., Pneumovax, Pnu-immune.
• Immunizesagainst23ofthemostcommon serotypes. young and elderly and those with:
– Chronic disease – HIV
– Alcoholism
• Also:7-valentconjugatedvaccine:T-cell dependent response.

20
Q

Corynebacterium diphtheriae

A

• 4 biotypes:gravis, mitis, belfanti and Gram+ve intermedium. Other non-pathogenic Corynebacteria spp. are normal flora in pharynx, nasopharynx and on skin.

– C. jeikeium: associated with bacteraemia, IV catheter colonization.
– C. minutissimum: RTI’s, wound infections.

Endemic in some subtropical and tropical countries. outbreaks in countries with breakdown in health infrastructure

21
Q

Hemophilus influenzae

A

Clinical syndromes: Otitis media, pneumonia, epiglottitis most common cause of epiglottitis.
Also associated: S. pneumoniae, C. diphtheriae, N. meningitis.

Gram –ve; pleomorphic. Facultative anaerobe. Normal component of Upper RT flora
Serotyped according to capsule (a to f)

• Coagulase negative, catalase positive
Culture: requires chocolate agar with X and V growth factors.
– X factor = acts as hemin
– V factor = nicotinamide adenine dinucleotide (NAD). (both released from blood following gentle heating). Is the ONLY Haemophilus species that requires both.

22
Q

Bordetella pertussis

A

Clinical syndrome: whooping cough (chronic bronchitis). Gram –ve coccobacillus. Unvaccinated children. Adults important as reservoir. Highly communicable.

Sample: Nasopharyngeal swab or secretions.
**Not cotton swab ** Not throat swab
very susceptible to drying.
• Culture (100% specific) – nutritionally fastidious: charcoal blood agar + cephalosporin (E.g., Bordet-Gengou)

Types of vaccines:
a) Whole cell (formalin-inactivated)
b) Acellular components, e.g., Fha, PT
• Lower rate of side effects
• aP = acellular Pertussis
23
Q

Klebsiella pneumoniae

A

Clinical syndrome: bronchopneumonia, lung abscesses
Enterobacteriaeceae. Gram -ve bacillus. Large capsule (mucoid appearance).
• Part of microbial flora: ~5% of healthy individuals.
• Two high affinity iron uptake systems: aerobactin & enterochelin.
• Necrotization of lung tissue – due in part to response to endotoxin (LPS).
• Range of microorganisms in addition to K.
pneumoniae can include:
– S. aureus, Anaerobes and microaerophiles from normal mouth flora. Microaerophils on outside use up O2; anaerobes grow on inside.

24
Q

Legionella pneumophila

A

Clinical Syndromes: 1.Legionnaire’s disease (pneumonia) 2.Pontiac fever (self-limiting)

• Gram–verod.Motile.Non-sporeforming. Can be associated with epidemics

• Exposure=inhalationofcontaminatedaerosols.
– Person-person transmission = rare.
• Can survive~50C for >30 minutes
• Facultatively intracellular (alveolar macrophages).
• Uptake via phagocytosis; prevent fusion of phagosome-lysosome.
• Much dmg = host inflammatory response.
• Virulence factors
– Intracellular growth
– Role of endotoxin?
– Role of extracellular protease?

25
Q

Pseudomonas spp

A

• Weakly pathogenic to persons w/nml innate and acquired immunity
– Most common infxn is Otitis Externa: Swimmer’s ear
• Dangerous for persons w/struc defects in body defenses
– Burn victims
– Cystic Fibrosis

  • Gram Negative Rods, Strictly aerobic. Highly motile with multiple flagella. Versatile Metabolism.
  • Non-hemolytic. Produces very mucoid colonies on conventional agar
  • Some strains produce the two pigments: Pyocyanin and Fluorescein, giving a green color to colorless media
26
Q

Pseudomonas and Cystic Fibrosis

A

Clinical syndrome: Necrotizing Bronchial Pneumonia

  • Pseudomonas aeruginosa and Burkholderia cepacia considered bona fide CF Pathogens
  • Abnml CF mucus constitutes ready-made biofilm for these organisms
  • Chronic inflam causes accum of WBCs, which only makes things worse.
  • Permanent, highly drug-resistant infxns are the rule for both.
  • Often fatal.
27
Q

Mycobacterium sp.

A
• Grow in long parallel chains “cords”. Aerobic. Non-spore forming. Resist drying but still sensitive to heat. Grows slowly in lab: 2-8 weeks.
Important species:
• M. tuberculosis
• M. bovis
• M. avis
28
Q

Tuberculosis pathogenesis

A

• Intracellular survival in alveolar macrophages
• Mechs:
1) Prevent oxidative burst & inhibit phagosome-lysosome fusion -> sulfolipids
2) Resist lysosomal enzs, ROS -> Cell wall lipids, LAM, secretion of SOD
3) Escape phagosome -> cytoplasm
LAM & Mycolic acids
Secrete siderophores: Exochelins Very high affinity for ferric ions

Culture: require enriched or special medium
• Löwenstein-Jensen agar
• Oleic acid - albumin broth
• Antimicrobial susceptibility testing = increasingly important (MDR strains)

29
Q

Tuberculosis treatment

A
  • First-line: Isoniazid, Rifampin, Streptomycin, Ethambutol
  • Second-line: Para-aminosalicyclic acid, Cycloserine, Fluoroquinolones

Prevention: Prophylactic antimycotics, BCG (Bacillus Calmette-Guérin) vaccine, Attenuated M. bovis strain

  • MDR-TB: Resistant to both isoniazid (INH) and rifampin
  • XDR-TB: MDR + resistant to any fluoroquinolone + 1 of the three following injectable drugs: Amikacin, Capreomycin, kanamycin
  • TDR-TB: XDR-TB that is completely resistant to all tested drugs (preliminary definition)
30
Q

Subacute LRT Infections aka “Walking” Pneumonias or “Atypical” pneumonias

A
• Prokaryotes
– Mycoplasma sp. 
– Chlamydia sp.
– Legionella sp.
– Miscellaneous viruses

• Eukaryotes
– Usually fungi:
– Histoplasma sp.
– Blastomyces sp. – Coccididioides sp. – Candida sp.

31
Q

Mycoplasma sp. “Walking Pneumonia”

Chlamydophilia sp. “Walking Pneumonia”

A

• Most common in Children > 5 Years old through young adults
• Outbreaks lasting months occur in crowded institutional settings (Military, Colleges, etc.)
• No quick, simple or cheap etiologic lab diagnosis
– Organism can be cultured, slowly and on special media
– Quick PCR based tests are emerging, but they are not really “cheap” nor “simple”

  • CDC does not separate out Chlamydophilia sp. Pneumonias from the Mycoplasma sp. Ones
  • Common in “middle age” Children, but 50% of cases occur in adults. Reinfection seems to be common.
  • No special risk groups.
32
Q

Respiratory Fungal Infections

A

Clinical Symptoms
Mostly mild (fever and cough) or asx. More severe: chills, malaise, fever, chest pain.
Sputum production, weight loss. Granulomatous lesions on skin or mucous mems (may mimic TB)

Pathogenesis
Key stages 1. Reach alveoli
2. Convert to form capable of replication at 37C – Mycelial->yeast form.May enhance survival of the fungi since yeasts aren’t killed as easily by phagocytes.
3. Colonize respiratory mucosa.

Samples for identification of the dimorphic fungi: • Sputum, Bronchoalveolar lavage (BAL)
Transtracheal aspirate, Lung biopsy
Techniques used will include:
1. Direct microscopy
2. Fixed specimens: Giemsa stain, indirect FA stain
3. Culture
4. Nucleic acid probes: Ab detection: limited d/t false positives and cross-rxn.
• DTH skin tests useful for dx of Coccidiodiomycosis: Mycelial phase antigen: coccidioidin
• Spherule phase antigen: spherulin
Exoantigen test
• Basis:immunodiffusion
– Look for presence of specific cell free antigens produced by mycelial phase of the fungi.

33
Q

Histoplasma capsulatum

A
2 clinically significant varieties
i. H. capsulatum var capsulatum
– Pulmonary & disseminated infections
– Eastern US and Latin America
– Thinner cell walls; smaller size (2-4 

ii. H.capsulatum var duboisii
– Skin and bone lesions
– Tropical Africa (“African histoplasmosis”)
– Thicker walled; larger yeasts (8-15

34
Q

Blastomyces dermatitidis

A

• Found in decaying organic matter.
• Outbreaks assoc w/contact w/ soil
• Most infxnns: mid and eastern N. America.
2 presentations
1) pulmonary and 2) extrapulmonary disseminated.

35
Q

Coccidioides sp.

A

MOST VIRULENT OF ALL THE HUMAN MYCOTIC PATHOGENS.

• Inhalation of a few conidia

36
Q

Cryptococcus neoformans

A
  • Worldwide distribution
  • Grows well in soil enriched by pigeon droppings (NB: birds are not vectors).
  • Most common fungal infection seen in AIDS patients.
  • Inhalation triggers production of capsule – Composed of glucuronoxylomannan (GXM).
  • Cryptococci have strong affinity for CNS (neurotropic).
  • Capsule detectable in blood and fluids: seems to down regulate the immune response.
  • Can oxidize exogenous catecholamines -> melanin: prevents fungi from phagocytic oxidative damage.
37
Q

Pneumocystis jirovecii

A
Unusual fungus
• Lacks ergosterol in cell walls
• Difficult to grow in culture
Epidemiology:
• Worldwide Geographic distribution
• Mayormaynotbetransmissible.
38
Q

Aspergillus sp.

A

Clinical syndromes: varied
• Various Aspergillus: fumigatus, flavus, Niger

Epidemiology:
Worldwide. Decaying matter,air, and soil. Outcome of infxn is strongly dependent on
host factors

2 forms of aspergillosis:

  1. Allergic
  2. Invasive:hyphae invade tissue.

Can also cause acute pneumonia in severely immunocompromised individuals. e.g, Neutropenia.

Sxs:
– Deadly, invasive pneumonia
– Hemoptysis
– High mortality

39
Q

Chemotherapy

A

Aspergillus sp., Pneumocystis

40
Q

Assisted ventilation

A

Aspergillus sp.

41
Q

Malnutrition

A

C. neoformans, Pneumocystis

42
Q

HIV infxn, AIDS

A

C. neoformans, Pneumocystis

43
Q

Neutropenia (WBC <500/mm3)

A

Aspergillus, other moulds and yeast-like fungi