Respiratory Tract Infections

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Normal Flora of Respiratory System

Staphylococcus, Corynebacterium, Moraxella, Maemophilus, Bacteroides, Streptococcus

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Staphylococcus

G+ cocci in clusters, can include pathogen S. aureus, inhabits notrils, facultative anaerobes

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Corneybacterium

pleomorphic G- rods, non-motile, no spores; aerobic; Diptheroids include anaerobic/aerotolerant organisms

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Moraxella

G- diplococci/diplobacilli; aerobic; resemble Neisseria sp (ex: N. meningitidis)

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Haemophilus

small G- rods; facultative anaerobes; usu includes pathogen H. influenzae

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Bacteroides

small pleomorphic G- rods; strict anaerobes

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Streptococcus

G+ cocci in chains; alpha (viridans), beta and gamma types; potential pathogen S. pneumoniae; aerotolerant

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Upper RTIs

rhinitis, pharyngitis/tonsilitis, stomatitis, peritonsilar and retropharyngeal abscess; 80% d/t viral infection

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Middle RTIs

epiglotitis, laryngitis/croup, laryngotracheitis, laryngotracheobronchitis, bronchitis

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Causes of Rhinitis

usu always VIRAL; rhinovirus, adenovirus, coronavirus, parainfluenza, influenza, RSV, coxsackie A

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Causes of Pharyngitis or Tonsilitis

either viral or bacterial; adeno, parainfluenza, influenza, rhinovirus, coxsackie A/B, HSV, EBV; GAS (S. pyogenes), C. diptheriae, N. gonorrheae

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Causes of Stomatitis

either viral or bacterial; HSV, some coxsackie A; Candida, Fusobacterium sp., spirochetes

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Causes of Peritonsillar or retropharyngeal abscess

usu Bacterial; GAS (mc), Fusobacterium sp, S. aureus, H. influenzae (infants)

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Legionnaires Disease

Legionella pneumophila; G- flagellar rod; BCYE charcoal media, *direct fluorescent Ab only*; smokers/immunosupp; resistant to Cl lives in water systems; no person-person transmission; non-specific symptoms

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Legionnaires Disease: Pathogenesis

contaminated aerosolized water; incubate 2-10d; infxn confined to lung; MQs phagocytize; porin ptns bind C3b & MQ invasion potentiator (Mip) aid entry into MQ to multiply/kill cell; inflam/tissue necrosis = pneumonia w/sm abscesses

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Legionnaires Disease: Diagnosis

direct fluorescent antibody of deep specimen (lung aspirate, BAL, Bx); culture on BCYE; PCR or ELISA of urine

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Legionnaires Disease: Prevention, Treatment, Immunity

control source of infected water; Erythromycin alone or w/rifampin (no PCN or cephalosporins b/c b-lactamase producers); cell-mediated (cytokine-activated MQs limit intracellular growth)

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Mycoplasma pneumonia

no cell wall, irregular shape, aerobic, fried egg on mycoplasma media; not visible by G stain or sputum smear; droplet spread; 5-15yo mild Sx - "walking pneumonia"

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Mycoplasma pneumonia: Pathogenesis

binds bronchial column. epithelium (cytadhesin-oligosacharride complex) = mucosal desquamation; inflam in peribronchial tissue --> thickens bronchioles & alveoli (lymphocytes, plasma cells, MQs); usu only one lobe; shed from URT for 2wks

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Mycoplasma pneumonia: Diagnosis, Prevention, Treatment, Immunity

serologic: IgM antibody; no need to compare titers; avoid crowded areas, appropriately use Abx; Erythromycin & Tetracyclin (also azithromycin & quinolones); local (IgA mucosal 2-4wks) & systemic (Compl-fix Ab titers 2-4wks gone in 6-12mo); reinfxn common

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Klebsiella pneumonia

non-motile G- enterobacterial rod; polysacch capsule inhibits phago & comp deposit; mucoid colony; ferments lactose; Macconkey agar; nosocomial alcoholics/immunocomp; colonize mouth; R-factor plasmid transposon = Abx resistance; *Red current jelly sputum*

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Klebsiella pneumonia: Pathogenesis

50-80% mortality w/oTx; enters lung from mouth by inhalation/aspiration of infected mucous; virulent capsule no phago, kills host cells, forms abscess; **permanent lung damage even w/Abx**; metastatic abscesses via blood spread; shock d/t endotoxin

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Klebsiella pneumonia: Diagnosis, Prevention, Treatment

diagnose by culture (macconkey agar - lactose fermentation = pink mucoid colony); prevent w/sterile environments; Ciprofloxacin or combo of cephalosporin+aminoglycosides (b-lactamase producers)

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Pseudomonas aeruginosa

P. aeruginosa; isolate in pure culture from good specimen; resistant to Abx (LPS/porin, plasmid mutations); aerobic, no spores, G- rod, flagella; grows in water/salt; fruity odor, green pigment/slime, hemolysis on blood, oxidase+ (not enterob)

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Pseudomonas aeruginosa: extracellular products

Exotoxin A, S, & Elastase are secreted into host cells to inhibit ptn synth, kill cells, cytoskeleton, & digest elastin in distant organs, respectively; Other enzymes (hemolytic, lecithinase, collagenase, elastase activity)

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Pseudomonas aeruginosa: Pathogenesis

nosocomial (fatal in leukemia, CF, burns), neonates, IVDA (bone/joint infxn); infxn thru wound/endotracheal tube/catheter; attaches to epithelium by pili, flagella, slime; exotoxin A, S and elastin are virulent; CMI response is important to prevent infxn

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Pseudomonas aeruginosa: Diagnosis

culture on blood agar (hemolytic, oxidase+, pyocyanin, grows at **42*C**; fruity odor); severe infxns (lungs, blood vessels, skin, tendon, ligaments, intestine) need to be treated by combo of b-lactam and aminoglycoside

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Pseudomonas aeruginosa: Treatment

Pathogen-directed based on sensitivity test: B-lactam Abx (3rd gen cephalosporins - ceftazidime, cefepime, cefoperazone), Carbapenem (imipenem, meropenem), Monobactams (aztreonam); New aminoglycosides (Gentamicin, Tobramycin, Amikacin); Quinolones (cipro)

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Pseudomonas aeruginosa: Prevention

*vaccine is available for special groups* - burn pts, CF pts, immunocomp pts (it has antigens to several P. aeruginosa serotypes, only some protection)

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Chlamydia pneumoniae

obligate intracellular bacteria, no cell wall; C. trachomatis (common, GU, conjunctivitis, trachoma --> preventable blindness; *glycogen-inclusion bodies & sulfonamide susceptable*); C. psittaci (resp infxn a/w infected birds); C. pneumoniae (resp infxn)

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Chlamydia pneumoniae: microscopy, culture, diagnosis

intracellular reticular, inclusion & highly condensed elementary bodies; must be grown in HEp2 cells; *Dx w/immunofluoresence for EB antigen*

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Chlamydia pneumoniae:

community & nosocomial; 50% of adults are seropositive; bronchitis, pneumonia, sinusitis; droplets w/no seasonal variation; "walking pneumonia" - mild sx; usu a single lobe of lung infected; *interstitial streaks on CXR*

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Chlamydia pneumoniae: Prevention & Treatment

no prevention b/c bacteria is everywhere; Macrolides (erythromycin, clarithromycin, azithromycin); Tetracycline (tetra, doxycycline), Levofloxacin for 10-14days

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Chlamydia pneumoniae and atherosclerosis

a/w growth in smooth muscle, endothelial cells of coronary artery and macrophages; has been isolated from plaques;

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Chlamydia psittaci

zoonotic, causes parrot fever or ornithosis (disease of birds); transmitted to humans thru guano dust (around livestock or cats); occupational hazard for bird workers; can be confused w/C. pneumoniae; take Hx

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Chlamydia psittaci: Pathogenesis

infxn of resp epithelium; spreads to RE cells of liver and spleen causes focal necrosis; disseminates via blood to lung/other organs; lymphocytic/MQ infiltration of alveoli & interstitium; thick, edema, necrosis, hemorrhage, mucus plugs, *hypoxia, anoxia*

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Chlamydia psittaci: clinical features

dry and hacking cough; systemic complications d/t hematogenous spread (myocarditis, endocarditis, encephalitis, hepatitis); Bilateral lung involvement; **Serology comparison of acute & convalescent titers**; immunofluorescent Ab stain

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Chlamydia psittaci: prevention & treatment

control infxns in domestic birds (Tx w/45days of chlortetracycline HCl); vaccine available; Macrolide and Tetracycline work for early phase of infection

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Bacillus anthracis

aerobic, facultative, spore-form G+ box-car rods; low virulence saprophytes spread via air; heat/boiling-resistant central endospores, catalase+; D-glutamic acid *capsule is antiphagocytic & mucoid in blood culture; hemolytic; *exotoxin

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Bacillus anthracis: details

acquired by farm animal workers, vets, meat handlers, wool spinners; *bacterial cells are lysed in culture by lytic gamma phage specific to this species*; capsule stands out on india ink (like cryptococcus neoformans)

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Bacillus anthracis: exotoxin complex

Factor 1 (edema factor, EF, andenylate cyclase toxin inc cAMP production (like pertussis toxin)); Factor II: (protective antigen, PA, the binding domain w/2 active domains for factors 1 and 3; *vaccine target*); Factor III (Lethal factor, LF, essential)

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Bacillus anthracis: clinical conditions

*wool sorters' disease" d/t inhalation/pulmonary infxn (acute onset, fever, chest pain, hemorrhage, can be fatal); also cutaneous (contact thru broken skin/mucous membranes), GI (ingestion; fatal) and meningitis (rare)

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Bacillus anthracis: Diagnosis and Immunity

isolate from sputum (rough, medusa head colony on blood agar; **not hemolytic, not motile**); blood cultures are positive if pulmonary infxn; possible humoral response to capsule and toxin

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Bacillus anthracis: Prevention and Treatment

vaccinate livestock or humans; 3 sc injections 2wks apart + 3 more at 6, 12, 18mo; annual boosters required for protective immunity; *PCN (doxycycline or cipro if resistant to PCN)

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Pneumonic Plague: Yersinia pestis

G- coccobacillus, facultative, macconkey agar; **outer membrane, Yop, is virulent factor (inhib phago cytoskeleton, inflam cytokines, platelet aggregation) & is susceptible to drying; LPS somatic O polysacc, core polysacch (common Ag), lipid A (endotoxin)

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Pneumonic Plague: Yersinia pestis - diagnosis

Wayson staining; safety pin appearance of bacteria; *"fried egg" appreance on *blood agar*;

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Pneumonic Plague: Yersinia pestis - transmission

sylvatic (rodents to flea to human) SW USA; urban (human to human droplet spread from lungs)

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Pneumonic Plague: Yersinia pestis - Virulence factors in human host

Yops, plasmid for secretion apparatus, PAI (iron scavenger); F1 capsular ptn (gel-like antiphagocytic capsule; replicates in mucosa); Plasminogen activating protease (degrades fibrin in clots); lymphatics --> blood --> lung (necrosis, hemorrhage, plague)

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Pneumonic Plague: Yersinia pestis - Clinical features

2-3 incubation for pneumonic (2-7 for bubo; 5% turn pneumonic); mucoid-->bloody sputum; pleural effusion; grave prognosis (90% pneum, 75% bubo); lasting immunity from bubo recovery

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Pneumonic Plague: Yersinia pestis - Prevention & Treatment

CMI for intracellular killing; prevent by killing fleas & rodent havens; **Streptomycin** (also: tetracycline, chloramphenicol, TSX)

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Nocardia sp

aerobic G+ rods, branching pattern; weak acid fast staining; white donut colonies on chocolate/blood agar (smells like wet dirt); pulm infxn via inhalation of dirt (skin via open skin); immunocomp susceptible w/Tcell def; *no person-person transmission*

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Nocardia sp: Pathogenesis

N. asteroides = pulmonary form (N. brasiliensis = cutaneous); disruptionof acidification of phagosomes & resistance of oxidative burst of phagocytes; lesions: acute inflam, suppuration/destruction (confluent abscesses); may spread to brain abscess

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Nocardia sp: Diagnosis and Treatment

CXR and multiple sputum samples (isolate G+ rods w/branches or beads; acid-fast, donut colony, PCR); **Sulfonamides (also: amikacin, imipenem & broad-spec cephalosporins) for 6wks to stop dissemination; surgery if necessary, poor prog w/immunocomp

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Rhodococcus

aerobic, facultative intracellular pathogen of MQs (like legionella/listeria) chocolate agar: mucoid/salmon-pink colonies, some are acid fast; opportunistic pulm nodules/consolidation/abscesses in immunocomp; dissemination (LN, meninges, pericardium, skin

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Rhodococcus: clinical features and treatment

CXR: bilateral cavitation (like TB and aspirigillus fungus ball); Disseminated (combo IV of: vancomycin, imipenem, aminoglycosides, cipro, rifampin, erythromycin); Localized (single or combo: erythromycin, rifampin, cipro)

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The Common Cold

primary viral infxn (many different strains); not life-threatening, but causes damage to resp system & makes host susceptibel to secondary bacterial infxns that could be dangerous

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Symptoms of common cold

<1wk unless complicated by secondary bacterial infxn; malais, runny nose (clear-->cloudy-->green); scratchy/mild sore throat w/o hoarseness; cough for >1wk

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Causative agents of common cold

rhinovirus, corona virus, adenovirus (may cause epidemic); (other upper resp tract infxns: RSV, influenza/parainfluneza, coxsackie A/B, EBV, HSV)

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Rhinovirus

small ssRNA non-enveloped human virus; likes lower temp (33C) & low pH (7 - 5.3); inhalation of droplets/touching eyes or nose w/contaminated hands; the stress of cold doubles chance of getting sick! *esp kids

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Rhinovirus: Pathogenesis

attaches via specific receptors to resp epithelium; multiplies in cells & spreads; loss of ciliary motion/slough; inflam mediators (actue sx in 1-2d-->7) vasodil/plasma lead/inflam cell recruit; **innate (inflam/interferon) + adaptive (cell-med, humoral)*

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Rhinovirus: Prevention and Treatment

avoid contact w/people in acute stage; hand wash frequently; Treat symptoms (headache, runny nose, fever, sore throat, cough); Pleconaril, an anti-picornavirus drug, shortens symptoms by preventing viral uncoating/attachment release of RNA

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Adenoviral pharyngitis

dsDNA non-enveloped virus; stable in environment, low pH, bile, proteolytic enzymes (good GI pathogen); *inactivated by heat, Cl, disinfectants; **not seasonal, transmitted by resp droplets during acute illness or fecal-oral for months

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Adenovirus symptoms

fever, runny nose, sore throat (w/gray-white pus on pharynx/tonsils can be confused w/strep pharyngitis); *enlarged cervical nodes (not pesent in common cold); possible laryngitis, croup, bronchiolitis, pneumonia; *pharyngoconjunctival fever is specific*

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Non-respiratory manifestations of adenovirus

actue hemorrhagic cystitis w/hematuria and dysuria; Gastroenteritis

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Adenovirus pathogenesis

as a DNA virus, it replicates in nucleus and as a non-enveloped virus its virions are released after cell death; mild to severe infxn depending on strain (Types 4, 7, 21 cause sore throat/large nodes; Type 8 causes eye infxn)

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Adenovirus Diagnosis

swabs (nasopharyngeal, conjunctival, rectal) or Bx transported in viral media; Culture: Types 1-39 (HeLa, human embryonic kidney & human fetal diploid cells, A549 cell lines); Serotype F 40, 41 culture (Graham-293 modified HEK cell line); cells cluster

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Diagnosis of Adenovirus: aside from culture

rapid detection of enteric types (serotypes 40, 41) by ELISA or immunofluorescence antibody; Immune EM, PCR, nucleic acid probes; serology for epidemiologica studies

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Gross and microscopic appearance of lungs in adenovirus infxn

massive congestion/focal necrosis; smudgy intranuclear inclusions in pneumocytes w/hemorrhagic change

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Adenovirus: Prevention and Treatment

Tx symptoms; vaccination for military personnel (live serotype 4 and 7 in enteric-coated capsule); self-limiting w/in 1-3wks, use appropriate antibx if secondary bacterial infxn occurs

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Adenovirus Immunity

serotype specific and long lasting after infxn; group-specific complement-fixing antibodies are also produced

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Coronavirus (HCV)

causes 5-10% of common colds in adult & LRT infxn in kids; lipid enveloped RNA virus; spike ptns induce cell-mediated response & production of neutralizing Ab

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Coronavirus: Pathogenesis

3 types characterized (common cold, enteric infxns, SARS - severe acute resp distress syndrome)

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SARS

1st case in China 2002; 10% death rate; sudden fever, pneumonia-like, resp distress, diarrhea; droplet spread of infected cells;

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SARS: specimen collection

URI: naso-/oropharyngeal swabs; LRI: sputum, BAL, aspirate; Blood: serum acute & convalescent, plasma; Stool; Tissue (fixed & frozen) from organs if fatal

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Influenza

orthomyxovirus family; unusual genome has 8 segments; **spike ptn neuraminidase & hemaglutinin are virulent factors**; epidemics worldwide; antigenic changes; 3 major strains (*A-most severe*, B, C)

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Hemaglutinin

binds to receptors on ciliated epithelial cells

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Neuraminidase

destroys the receptors which hemaglutinin binds

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Hemaglutinin Subtypes of Influenza A

characterizes pandemics of 20th century: H1N1 Spanish flu 1918; H2N2 Asian flu 1957; H3N2 Hong Kong 1968; H1N1 Russian flu 1977

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Influena nomenclature includes

influenza type, geographic source, isolate number, year of isolation, hemagglutinin subtype, neuraminidase subtype; (type B does not occur as subtypes)

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Possible mechanism of flu pandemic antigenic types

antigenic drifts of human viruses; antigenic shift (genetic recombination of human viruses w/animal viruses in mixing vessel; usu pigs)

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Pigs as mixing vessels for flu viruses?

HA binds species specific sialic acids to galactose on host cells; bird (alpha 2, 3) & human (alpha 2, 6) viruses, BUT swine viruses bind either; both can bind pig resp epithelium & coinfxn = recomb; (humans bind avian & human...??)

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Influenza epidemiolgy

10,000-40,000 deaths/yr; current strains are H1N1 & H3N2; H5N1 avian is more virulent; possibility for pandemic d/t antigenic changes

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Cultural influences on spread of influenza

China; domestic ducks, geese, chicken are reservoirs; domestic pig mixing vessel for bird/human flu;

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Influenza: Pathology

infects respiratory epithelium (inhib ptn/DNA synth, releases lysosomal hydrolytic enzymes, desquamates ciliated & mucus cells); apoptosis activates complement, local inflam, mononuclear cells; repair 2-10wks; viremia rare

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Influenza: more pathogenesis

virus is toxic to tissues by impaired chemotactic, phagocytic & intracellular killing of PMNs & alveolar MQs; susceptible to 2* superinfxn w/bacteria; *Recovery depends on: IFN prod to stop replication, rapid NK regen, specific CTLs, Ab production*

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Clinical manifestations of Influenza

2day incubation; acute symptoms 3-5days (headache, body ache, fever, shaking chills, worsening dry cough); 2-6wks of fatigue, weakness, cough; few die d/t bacterial infxn (S. aureus, S. pyogenes, H. influenzae)

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Unusual acute manifestations of influenza

CNS dysfxn, myositis, myocarditis, Ryes Syndrome (infants & children 2-12days after onset, severe fatty infiltration of liver & cerebral edema, may be a/w other viral illnes, risk inc w/exposure to salicylates)

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Three routes of death in influenza

1. Underlying disease w/compensation (pts w/chronic pulm & CV dx; elderly pts); 2. Superinfxn (2* bacterial infxn leads to bacterial pneumonia & disseminated dx); 3. Direct Rapid Progression (rare, progression of viral asphyxiating pneumonia)

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Diagnosis of Influenza

nasopharyngeal or throat swab cultured in monkey kidney cells by hemadsorption or hemagglutination; detection of viral antigen in epithelial cells or secretions by rapid immunofluorescence/immunoenzyme assays; serologic dx for epidemiology (4x titer inc)

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Prevention of Influenza

*killed viral Ag vaccine (annual, if matched - 80-90% effective* (post-vaccine complications: Guillain-Barre 1 in 1mill); elderly, at risk (chronic heart/lung dx); w/o vaccine amantadine & rimantadine antivirals may offer short-term prevention

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Influenza Treatment

Amantadine & Rimantadine (type A virus; 70-90% effective; blocks ion channel of M2 ptn preventing viral uncoating & viral assembly; BUT resistant w/single AA substitution in transmembrane portion of M2 ptn); more effective if given w/in 48hrs of onset of

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Influenza Treatment: Neuraminidase inhibitors

Zanamivir & Oseltamivir; effective against type A & B virus; blocks enzymatically active neuraminidase glycoptn to limit viral release from infected cells; **no resistance yet**; more effective if given w/in 48hrs of onset of symptoms

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Influenza Immunity

cell mediated & humoral; Ab directed towards 1. Group Nucleoprotein Ag (no protection against reinfection); 2. Hemagglutinin (neutralizes virus on reexposure; most protective); 3. Neuraminidase (stops viral spread); reinfection occurs by diff subtype

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Parainfluenza virus

paramyxovirus grp; non-segmented enveloped ssRNA (neg sense); Virions (Hemagglutinin & neuraminidase - attachment, hemadsorption, hemagglutination) & Fusion ptn (F) spike (promotes fusion of host & viral membranes); **RNA synth in cytoplasm**

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Parainfluenza virus: disease

4 serotypes (1 & 3 are more severe than 2 & 4); can cause serious diseases in infants/young kids; 15-20% of hopsitalized non-bacterial respiratory diseases; droplet cellular transmission

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Parainfluenza 1

major cause of acute croup (laryngotracheitis) in infants & young kids; **outbreak occurs in fall** ==> SEASONAL

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Parainfluenza 2

causes coup and mild URI, primarily in kids; less severe than types 1 and 3; SEASONAL fall outbreak

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Parainfluenza 3

major cause of severe respiratory disease in infants & young kids; bronchitis, pneumonia, croup in kids <1yo; URI & tracheobronchitis in older kids & adults; *NOT SEASONAL*; 50% of kids exposed by 1yr of age

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Parainfluenza 4

causes mild URI; least common subtype

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Parainfluenza virus: symptoms

starts like URTI; may involve LRT (trachobronchitis or pneumonia); onset can be abrupt, like spasmodic croup; duration of illness usu 7-10days but can last 3wks

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Parainfluenza Diagnosis

isolate virus in monkey kidney cells; serology w/hemagglutination inhibition, complement fixation or neutralization assays of paired sera (acute/convalescent w/rising titers); immunoenzyme or immunofluorescence for rapid detection of antigen in resp epith

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Parainfluenza Prevention & Contorl

no method of control or specific therapy of this type of infection

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Respiratory Syncytial Virus Infection

paramyxovirus family; non-segmented enveloped ssRNA (neg-sense); F-fusion ptn (fusion of virus to target cells; infected cells together forming syncytia); G-highly glycosylated ptn (imp for virall attachment); Antigenic variations in G ptn = subgrp A or B

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Syncytial Virus Infection: Epidemiology

mc in infants/young kids (also elderly nosocomial outbreaks); SEASONAL late fall-late spring w/mid-winter peak; recurrence common; healthy ambulant infected people spread infxn

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RSV: Symptoms

infants/yng kids (runny nose, cough, SOB, wheezing, dusky d/t low O2); worse Px w/heart dx, lung dx, immunodef or cancer; Older infants (croup); Healthy adults/older kids (common cold symptoms)

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RSV: Pathogenesis

infects epithelial cells (death & sloughing); mucus/clotted plasma plugs clog inflamed bronchioles causing SOB/wheezing; inflam extending to alveoli causes pneumonia; high risk of 2* bacterial pneumonia

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RSV: Diagnosis

nasal wash/aspirates/swabs transported on ice; Rapid Dx (DFA, IFA, ELISA); culture 2-5days in HeLa, Hep-2, monkey kidney (shell vial technique); Serology (neutralizing Ab by CF, IF not useful for young infants); CXR: bilat infiltrates w/hyperinflation

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RSV: Prevention

no vaccine available; Monoclonal Ab (Palivizumad) used in pts w/underlying illness; Prevent nosocomial epidemics w/strict isolation

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RSV: Management

usu subsides in 2-5days; most managed w/O2 & tube feeding; Antiviral used for heart/lung pts; Abx for bacterial complications

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Hantavirus Pulmonary Syndrome

d/t sin nombre virus & related hantaviruses; enveloped bunyavirus family; 3-segmented ssRNA (neg sense); rodents have lifetime infxn w/o illness

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Hantavirus pulmonary syndrome: epidemiology

emerging infectious dx; SW USA quick death after flu-like illness; a/w inc mouse populations & substandard housing; rare person-person transmission

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Hantavirus pulmonary syndrome: Pathogenesis

inhaled dust contaminated w/urine, feces or saliva of infected rodents; virus enters blood; massive Ag in lung capillaries (other organs have less); inflam response leaks plasma into lungs & suffocates pt; loss of ICF leads to hypotension, shock, death40%

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Hantavirus pulmonary syndrome: Symptoms

similar to influenza; Early (fever, muscle ache, nausea, vomiting, diarrhea); Later (unproductive cough, SOB, shock, death); Histology: interstitial pneumonitis & intraalveolar edema

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Hantavirus pulmonary syndrome: Prevention & Treatment

minimize exposure to rodents; secure storage of food; restrict access of mice to house; use disinfectants; trap/kill mice; No antiviral Tx is currently available!!

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Pneumocystis carinii/jejuni pneumonia (Pneumocystosis)

fungus; phylum ascomycota; lacks egosterol in cell wall; can be IDed as multi-nucleated cysts in MQ or clusters of trophozoites; transmission unknown; causes disease in immunodef hosts (latent or new infxn)

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Pneumocystosis: Symptoms

gradual onset in immunodef individuals; SOB, tachypnea; low grade fever; non-productive cough (50%); dusky skin/mucus in advanced stages; death usu d/t respiratory failure

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Pneumocystosis: Pathogenesis

presumed inhalation of spores; attach to alveolar walls; inflam response accumulates mononuclear cells/fluid/fungi in alveolar spaces; walls thicken, scar & prevent O2 exchange

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Pneumocystosis: Diagnosis

interstitial opacities w/ground glass on CXR; MUST do BAL & show cysts/trophozoites by Wright, Giemsa, Papanicolau stain; Confirm w/methenamine stain or direct fluorescent Ab or PCR

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Pneumocystosis: Prevention and Treatment

2nd largest cause of death to AIDS pts, despite Trimethoprim-sulphamethoxazole (TSX) & HAART therapy; TSX needed when CD4 coutn is <200

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Pneumocystosis: Immunity

cell mediated (MQ & CD4 Tlymphocytes are most protective against infxn); Ab produced against surface glycoprotein & other antigens also play roles

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Coccidioidomycosis

aka (San Joaquin) Valley Fever; d/t coccidiodes immitis *dimorphic fungi; mold from soil/infectious barrel-arthospores; in vivo fungus is thick-walled sphere w/hundreds of endospores

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Coccidioidomycosis: Epidemiology

endemic to desert climates w/high carbon/salt content in soil; dormant winter/spring & growth in summer/fall; growth & spread w/rain, drought & wind cycles; outbreaks in farms, archeological digs, & mining

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Coccidioidomycosis: Symptoms

Common (fever, cough, chest pain, loss of appetite/wt); Less common (tender nodules on shin; joint pain d/t hypersensitivity to fungal Ag; Dissemination & abscesses; Chronic progressive pulm dx w/nodular fungomas & cavities impairing respiration

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Coccidioidomycosis: Pathogenesis

arthospores enter lung & form thick walls that rupture to release endospores that repeat process; inflam response causes symptoms; if host cannot eliminate fungi, necrosis/cavitation of lung occurs; rare blood, skin, mucus, brain; dissemination usu w/AIDS

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Coccidioidomycosis: Prevention & Treatment

avoid dust by planging vegetation & watering ground; Amphotericin B & Flucanozole treat serious cases (long-term dosage; adverse side effects)

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Histoplasmosis; Ohio Valley Fever; Spelunker's Disease

dimorpthic histoplasma capsulatum; growth below 35*C (white/brown fuzzy mycelium); growth at 37*C on blood is creamy & white; Mississippi, Ohio and river drainage areas; cavers at risk

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Characteristics of H. capsulatum

grows in soil contaminated w/bat or bird droppings; In tissue specimens growth is a tiny, oval yeast w/in MQ; NO capsule; Mold form has large conidia w/projecting knobs

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Histoplasmosis: Symptoms

usu none; ranges: benign-sever/acute-chronic; Pulm, Systemic, or Skin lesions; Cough, chest pain, SOB (severe pts), fever; Kids (liver/sleenomegaly), anemia, circ collapse, death; Adult (brain, intestine, adrenal, heart, BM, spleen); COPD=TB-like symptoms

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Histoplasmosis: diagnosis

1. identify conidia & dimorphism in culture; 2. Mycelial Ag by Immunodiffusion (exoantigen test); 3. Intracellular demonstration of organism w/H&E of tissue/BM w/Wright stain; 5. If disseminated, detect polysac Ag in serum or urine by enzyme immunoassay

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Histoplasmosis: Prevention & Diagnosis

avoid areas where soils are contaminated by bird/bat droppings; Amphotericin B & Itraconazole (both have serious side effects)

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Histoplasmosis: Immunity

infxn causes long-lasting immunity; Cell mediated response is most protective (and immunodef, esp AIDS, suffer progressive, disseminated dx); Humoral responses are not influential

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Aspergillosis

rapidly growing mold; branching septate hyphae; conidia on conidiophore; Colonies in 1wk at 30*C are flat, spreading blue/green w/white margin; Inhalation transmission (ex: air ducts cause nosocominal infxn)

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Aspergillosis: Pathogenesis

can cause allergic or invasive disease of lung

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Allergic Asperigillosis

transient pulmonary infiltrates; eosinophilia; rising asperigillus-specific Ab

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Invasive Asperigillosis

a/w pre-existing pulmonary dx (ex: COPD, TB, asthma) or immunodef; Lung tissue invasion may include blood vessels/hemoptysis; Acute pneumonia in immunodef (if defective phagocytosis); Dissemination to distant organs has grave Px

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Radiologic presentation/evolution of Asperigillus Pneumonia

baseline halo is transitory for <5days as it increases its volume for a week (halo disappears); once stabilized it forms a *characteristic air cresent* sign of fungal ball or aspergilloma

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Aspergillosis: Diagnosis

ID rapidly growing mold w/branching septate hyphae & characteristic conidium; Difficult distignuishing colonization from invasion so BAL, biopsy or lung aspiration is preferred; Serology NOT helpful b/c Ab is present in healthy people

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Aspergillosis: Prevention & Treatment

not many preventive measures; filter air to dec exposure; Amphotericin B & Itraconazole (not very effective if infxn is invasive...~100% mortality despite Tx); Surgical excision may be helpful

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Aspergillosis: Immunity

Innate immunity is most important; Inhaled conidia are killed by MQ, but those that survive germinate & form hyphae that are attacked by neutrophils

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