Pulmonology Flashcards
Streptococcus pneuomoniae Virulence Factors
Encapsulated gram-positive coccus that are oval or lancet-shaped and are arranged in pairs or short chains.
They are alpha hemolytic due to pneumolysin (degrades hemoglobin; creates pores in host cell membranes and suppresses oxididated burst)
Lacks catalase
Virulent strains are covered with polysaccharide capsule (allows survival following phagocytosis; used for vaccine) and have surface protein adhesins that allow binding to oropharynx. They also secrete IgA proteases (avoid binding to mucus) and pneumolysin
Has two types of techoic acid-linked polysaccharides, C polysaccharide (precipitates CRP) and F antigen
Phosphocholine is unique to cell wall of S. pneumoniae and allows the cells bind to PAF receptors, get eaten, and be protected from host immune response.
Most damage to host is done by host defense, not by organism itself. This is augmented by amidase secreted by organism that facilitates shedding of its wall, increasing immune response.
First colonizes the oropharynx and then can spread to the lungs, paranasal sinuses, or middle ear.
Streptococcus pneumoniae Epidemiology
Common colonizer of throat and nasopharynx in healthy people, especially children. More common to see disease in cool months.
Disease is most common in young and elderly, both of which have less protective antibodies against the capsule.
Very often preceded by a viral disease like the flu as well as anything else that inhibits bacterial clearance.
Streptococcus pneumoniae Clinical Diseases
Pneumonia: develops when the bacteria multiply in alveolar spaces following aspiration. Erythrocytes, neutrophils, and macrophages follow organisms into alveolar spaces. Resolution occurs following anticapsular antibody development. Generally preceded by symptoms of a viral respiratory tract infection 1 to 3 days before onset of chills, chest pain, and productive blood tinged cough. Called lobar pneumonia because it normally is aspirated to lower lobes. Mortality is higher with S. pneuomoniae type 3, in elderly, and in those lacking a spleen. Pleural effusions are seen in 25 % of patients
Sinusitis and Otitis Media: normally preceded by a viral infection of the upper respiratory tract. Otitis media is more in children, the sinusitis is not age specific
Meningitis: leading cause of disease in children and adults. Mortality and severe neuro defects are 4 to 20 times higher with S. pneumo as compared to other organisms.
Bacteremia: occurs in 80% of patients with meningitis. Endocarditis may occus. Destruction of valve tissure also common.
Streptococcus pneumoniae Diagnosis and Treatment
Gram stain with quellung reaction (polyvalent anticapsular antibodies are mixed with bacteria then examined, leads to swelling of bacteria)
Pneumococcal C polysaccharide is excreted in urine and can be detected using a commercially prepared immunoassasy
Bile solubility test is also diagnostic (bile kills them) as is optochin (also kills them)
Treat with penicillin, fluoroquionolone, vancomycin combined with ceftriaxone
Also vaccinate susceptible populations with conjugated vaccine
Bacillus anthracis Immunology and Virulence
Gram-positive
large organism arranged as single or paired rods or as long, serpentine chains. Has a polypeptide (poly-D-glutamic acid) capsule which inhibits phagocytosis
Has three toxin protein components on a plasmid pXO1:
1) Protective antigen: forms a pore on the surface of the host cell that is capable of binding up to three EF or LF, leading to endocytosis. It is the most immunogenic of the three
2) edema factor: a calmodulin-dependent adenylate cyclase that increases cAMP resulting in edema
3) lethal factor: zinc-dependent protease that is capable of cleaving MAP kinase leading to cell death.
PA + EF = edema toxin. PA + LF = lethal toxin
Bacillus anthracis Epidemiology and Clinical Disease
Anthrax is a disease primarily of herbivores; we get it through contact with contaminated animals/animal products.
Acquired by inoculation (95%), ingestion, or inhalation (wool sorter’s disease, route of infection for bioterrorism).
Spores are weaponized by breaking them up into small, aerodynamic spores that can more easily reach the lower airways.
Cutaneous anthrax: starts with a painless papule at inoculation site that progresses to eschar. Massive edema may develop, mortality is 20% if untreated
Gastrointestinal anthrax: Nearly 100% fatal, symptoms depend on if it gets upper GI tract or lower
Inhalation anthrax: can be associated with prolonged latant period. Initial symptoms are nonspecific (flu-like). Second stage shows lots of edema, enlargement of mediastinal lymph nodes, respiratory failure, sepsis. Almost all cases proceed to shock and death within three days unless it is treated.
Bacillus anthracis Diagnosis and Treatment
One of few orgnanisms that can be seen when peripheral blood is Gram stained. They form long, thin strands that are nonmotile
It is difficult to tell apart from Bacillus cereus, but can do so by seeing if they colonies are hemolytic (cerues) or not (anthracis)
Capsule is not normally produced in culture
Forms “Medusa head” colonies (Uworld hits this a lot)
Treat with penicillin, doxycycline, or ciprofloxacin, not with sulfonamides or cephalosporins.
Vaccinate susceptible animals and burn the animals that die of anthrax, also vaccinate people that are likely to encounter the organism
Bacillus cereus
opportunistic pathogens that have relatively low capacities for virulence.
GI: Has two enterotoxins, one is heat stable and causes the emetic form of the disease (normally caused by eating contaminated rice; an intoxication), the other is heat-labile (similar action as V. cholerae) and causes the diarrheal form of disease (an actual infection, contaminated meat, vegetables or sauces). Treat symptoms
Ocular: three toxins implicated (necrotic toxin, cereolysin, phospholipase C) leads to rapid destruction of the eye. Normally follows a traumatic eye injury leading to soil in eye. Treat with vancomycin, clindamycin, ciprofloxacin, gentamicin
Don’t use penicillins and cephalosporins
Other: can cause IV catheter and CNS shunt infections. May be associated with ingestion of tea in immunocompromised.
It appears that the virulence pXO1 plasmid can be transferred from anthracis to cereus
Ubiquitous organisms found in soil, often found as insignificant contaminate in lab samples
Corynebacterium diptheriae Immunology and Virulence
Coryneform (“club shaped”) bacteria that is an irregularly staining, pleomorphic rod. Metachromatic granules have been pbserved following staining with methylene blue. Species is subdivided into four biotypes: belfanti, intermedius, gravis and mitis. The last two are associated with disease
Diptheria toxin: exotoxin produced at site of infection. It is introduced into orgnaism by a lysogenic bacteriophage (B-phage). Example of the classic A-B toxin. Receptor (heparin-binding epidermal growth factor receptor) binding and endocytosis are on B, catalytic component is on A. A inactivates elongation factor 2, halting host protein synthesis.
Found in poor areas where crowding and lack of vaccination is prevalent. Maintained in the population by asymptomatic carriage in the oropharynx. Humans are only known reservoir.
Corynebacterium diptheriae Clinical Disease
Respiratory Diphtheria: Onset is sudden iwth malaise, sore throat, exudative pharyngitis, and a low-grade fever. Exudate evolves into a pseudomembrane. This is eventually expectorated. This leads to myocarditis and neurotoxicity.
Cutaneous Diphtheria: Acquired through skin contact with infected persons. Leads to a papule that develops into a chronic, nonhealing ulcer.
Diagnosis is made clinically. ID is based on presence of cysteinase and absence of pyrazinamidase. All diphtheriae is tested for production of exotoxin via the Elek test.
Treat with diphtheria antitoxin, then with penicillin or erythromycin to eliminate the organism. Patients fail to develop protective antibodies following a natural infection.
Nocardia General Information
Strict aerobic rods that form branched filamentous form in tissues and culture. They resemble molds, and at one time Nocardia was thought to be a fungus. They are Gram positive, but most Gram stain poorly and appear to be gram-negative.
Similar cell wall to mycobacteria (tuberculostearic acid), but length of mycolic acids is shorter in Nocardia than in mycobacteria.
Described as “weakly acid-fast” which is used to distinguish from Actinomyces
Cord factor is an important virulence factor that facilitates intracellular survival.
Upon culture, presence of aerial hyphae and acid-fastness is unique to Nocardia
Nocardia Virulence, Immunity, and Clinical Disease
Protects itself from phagocytic killing by secreting catalase and superoxide dismutase. It can also use cord factor to prevent fusion of the phagosome-lysosome, prevent acidification of phagosome, and avoid acid phosphatase by using it as a carbon source.
The agent is exogenous (as opposed to actinomyces) orgnanism is not a part of the normal human flora, but is present in soil rich with organic matter
Bronchopulmonary disease in immunocompromised patients (especialy T-cells) with a high predilection for hematogenous spread to the CNS or skin. Develops after initial colonization of the upper respiratory tract by inhalation and then aspiration into lower airways. Causes cough, dyspnea, fever, and cavitation and spread to pleura are common.
Cutaneous Infections: Can be primary infections or spread from bronchopulmonary infections. Mycetoma has draining tracts with granules normally caused by N. brasiliensis. Lymphocutaneous infections mimic Sporothrix schenckii infections.
A third of all patients with Nocardia have dissemination to the brain that can form single or multiple brain abscesses
Can detect easily by microscopy, use acid fast test to distinguish from actinomyces. It is possible to grow the organism on BCYE agar.
Treat with antibiotics combined with surgical intervention. Trimethoprim-sulfamethoxazole is often used to treat local infections.
Prognosis is poor for immunocompromised patients with desseminated disease.
Actinomyces
Facultatively anaerobic or strictly anaerobi gram-positive rods that are not acid-fast. They develop delicate filamentous forms or hyphae and resemble fungi.
Produce chronic, slowly developing infections
Normally colonize the upper respiratory, GI, and female genital tracts but are not normally present on skin. They have a low virulence potential and cause diseaes only when the normal mucosal barriers are disrupted by trauma, surgery or infection.
Actinomycosis: characterized by development of chronic granulomatous lesions that become suppurative and form abscesses connected by sinus tracts. Macroscopically looks like “grains of sand”
Disease is endogenous (no person to person spread or outside inoculation)
Cervicofacial actinomycosis: most common infection. May occur as acute, pyogenic infection that can lead to draining sinus tracts along the jaw.
Can lead to a solitary brain abscess in CNS
Tough to confirm in lab because of cross contamination
Treat with penicillin and surgical debridement
Mycobacterium Tuberculosis
An intracellular pathogen that is able to establish lifelong infection. Infection begins in alveoli with phagocytosis by alveolar macrophages. M. tuberculosis prevents fusion of phagosome with lysosomes.
Upon infection, macrophages secrete IL-12 and TNF-alpha, driving a TH1 response and leading to increased macrophage killing. If this goes overboard it can lead to tissue necrosis. The organism does not directly damage host cells.
Alveolar macrophages, epitheliod cells, and Langhans giant cells with intracellular mycobacteria form a central core of a necrotic mass that is surrounded by a dense wall of CD4, CD8, and NK T cells and macrophages (granuloma). Organism can stay dormant for long periods of time in granulomas surrounded by fribrous material.
Humans are only natural reservoir
Initial focus is in middle or lower lung fields.
Tuberculosis
Disease can be insidious at onset. Patients have nonspecific complaints of weight loss, cough, night sweats, malaise, and bloody sputum.
Diagnosis is made by radiographic evidence, positive skin test and lab detection of mycobacteria through microscopy or in cultures.
Mycobacterium avium Complex
Can cause disease in immunocompetetent patients. Disease in HIV-infected patietns is primarily caused by M. avium.
Disease is often seen in middle-aged or older men with underlying pulmonary disease, which leads to a cavitary disease that resembles TB on chest X-ray.
Lady Windermere syndrome: Second form of MAC infection is observed in elderly female nonsmokers who may chronically suppress their cough reflex. They have lingular or middle lobe infiltrates. This is associated with significant morbitity and mortality.
Third form of disease is formation of a solitary pulmonary nodule
AIDS has made infection with MAC the most common mycobacterial infection in the US. In this case, the disease is disseminated with no organ spared.
Rapidly Growing Mycobacteria
low virulence potential,stain irregularly with traditional mycobacterial stains, and are more susceptible to conventional antibiotics.
Associated with disease occurring after bacteria are introduced into the deep subcutaneous tissues by trauma or iatrogenic infections.
Klebsiella
Have a prominent capsule that is responsible for the mucoid appearance of isolated colonies.
“Tenacious sputum” , lobar pneumonia, associated with alcoholism, a community-acquired pneumonia
Pneumonia caused by Kelbsiella species frequently involves the necrotic destruction of alveolar spaces, formation of cavities, and production of blood-tinged sputum.
Pseudomonas Virulence Factors
Usually motile, stright or slightly curved, gram-negative rods that are arranged in pairs. They are aerobic respirators and require very few nutrients to thrive.
Presence of cytochrome oxidase is used to distinguish them from enterobacteriaceae species. Some species produce diffusible pigments
Adhesins: adheres to host cells via its flagella, pili, LPS, and alginate. Alginate is a polysaccharide capsule that is present on mucoid pseudomonas and is especially prevalent in patients with cystic fibrosis.
Toxins: Exotoxin A is one of the most important virulence factors produced. It disrupts protein synthesis by blocking peptide chain elongation (less potent than diphtheriae toxin). Pyocyanin is a blue pigment that catalyzes the production of superoxide and hydrogen peroxide as well as stimulates IL-8 release. Pyoverdin is a yellow-green pigment that is a siderophore that regulates ETA secretion. LasA (serine protease) and LasB (zinc metalloprotease) act together to degrade elastin which damages the lung parenchyma. Phospholipase C is a heat-labile hemolysin that has an unclear association with disease. Exoenzymes S and T are ADP ribosyltransferases which are secreted into host cells via a type III secretion system.
Antibiotic Resistance: mutation of porin proteins is main means of resistance. Also produces many different beta-lactamases
Pseudomonas Epidemiology and Clinical Diseases
Associated with many different environments, particularly moist surfaces. It has minimal nutritional requirements, tolerates a wide range of temperatures, and is resistant to many antibiotics and disinfectants.
Can transiently colonize hospitalized patients (not nessecarily bad)
Pulmonary Infections: Infections of the lower respiratory tract can range from asymptomatic colonization to severe necrotizing bronchopneumonia. Colonization is seen in patients with cystic fibrosis or other chronic lung diseases. People at risk are those who have 1) recieved broad spectrum antibiotics killing off competitive flora, 2) recieved mechanical ventilation allowing access to lower respiratory tract
Primary Skin and Soft Tissue Infections: Well-known colonizer of burn wounds due to moist surface and inability of neutrophils to reach bacteria. Folliculitis can result from contaminated water. Osteochondritis of the foot can occur after a penetrating injury
Urinary Tract Infections: seen with long-term indwelling catheters
Ear Infections: External otitis (swimmer’s ear). Malignant external otitis is a virulent form of disease seen in person’s with diabetes and the elderly.
Eye Infections: Can lead to corneal ulcers
Bacteremia and Endocarditis: Bacteremia is clinicallly indistinguishable from that caused by other gram-negative bacteria. Happens a lot to immunocompromised. Endocarditis is seen primarily in IV drug users. The tricuspid valve is often involved.
Pseudomonas Identification and Treatment
Has simple culture requirements and is cultured on MacConkey agar on air-broth interface (it’s aerobic)
Positive oxidase test, flat colonies with spreading border, B-hemolysis, a green pigmentation, and a sweet, grapelike odor are all red flags.
Treat with a combination of antibiotics, and try to sterilize everything you can to avoid infection in the first place
Burkholderia
Opportunistic pathogens related to Pseudomonas species.
Pulmonary infections range from colonization to bronchopneumonia primarily in patients with cystic fibrosis or chronic granulomatous disease.
Colonization of the lungs of a cystic fibrosis patient with B. cepacia is such a poor prognosis that it contrindicates lung transplant.
Diabetics, and individuals with chonric renal or lung disease are susceptible.
Treat with trimethoprim-sulfamethoxazole
Stenotrophonmonas maltophilia
Originally classified as a Pseudomonas species.
Responsible for infections in debilitated patients with impaired host-defense mechanisms.
Causes bacteremia and pneumonia.
resistant to carbapenems
Trimethoprim-sulfamethoazole is treatment of choice
Actinobacter
Actinobacter: related to Pseudomonas, they are ubituitous saprophytes.
opportunistic pathogens
Moraxella: aerobic, oxidase-positive, gram negative diplococci that are resistant to penicillins.
Haemophilus
small, pleomorphic, gram-negative rods present on mucous membranes of humans. Grown on chocolate agar due to need for hemin and NAD. Has a polysaccharide capsule with six serotypes (a-f). Type b is the one that the conjugated polysaccharide vaccine is made for.
Non-encapsulated H.influenzae colonizes the upper respiratory tract in virtually all people within the first few months of life. They can spread to the ears (otitis media), sinuses (sinusitis), and lower respiratory tract (bonchitis, pneumonia).
Capsulated H.influenzae is uncommon in upper respiratory tract but is a common cause of disase in unvaccinated children (meningitis, epiglottitis). High grade bacteremia may develop in these cases. The capsule is the major virulence factor (called the PRP because it contains ribose, ribitol and phosphate). It produces IGA1 proteases. Can cause meningitis, cellulitis, arthritis, conjunctivitis, and chancroid, as well as :
Epiglottitis: characterized by cellulitis and swelling of supraglottic tissues. Can lead to obstruction of the airway and death.
Otitis, Sinusitis, and Lower Respiratory Tract Disease: nonencapsulated strains are opportunistic pathogens of the upper and lower airways.
Organism is easily seen if present in CSF
“satellite phenomenon” describes growth on unheated blood agar around S. aureus. Staph lyses the erythrocytes, then the organism can grow around it.
Treat with broad-spectrum cephalosporins
Bordetella Pertussis
Small, strictly aerobic, gram-negative coccobacillus. Often die in culture due to toxic substances and metabolites in growth media.
Infection leads to whooping cough. Requires exposure to organism, bacterial attachment to respiratory tract (carried out by pertactin and filamentous hemagglutinin), proliferation, and production of localized tissue damage and systemic toxicity.
Pertussis toxin is a classic A-B toxin. The A (or S1) portion of the toxin is an ADP-ribosyl transferase which inacticates the Gialpha pathway, leading to increased cAMP, leading to increased secretion and mucus production characterisitic of the paroxysmal stage of pertussis
Adenylate cyclase/hemolysin: a bifunctional toxin that is activated by calmodulin. It increases cAMP concentrations as well as inhibits leukocyte chemotaxis, phagocytosis, and killing
Dermonecrotic toxin: heat-labile toxin that at low doses causes vasoconstriction that may lead to localized tissue destruction
Tracheal cytotoxin: inhibits cilia movement at low concentrations, causes extrusion of ciliated cells at higher concentrations.
This is a human disease with no other recognized animal targets or reservoirs.
Disease proceeds through three stages:
1) Catarrhal stage (1-2 wks): resembles the common cold. Patients at this stage are the most contagious
2) Paroxysmal stage (2-4 wks): ciliated epithelial cells are extruded, clearance of mucus is impaired. This is when the whooping cough occurs (repetitive cough followed by inspiratory whoop).
3) Convalescent stage (3-4 wks): paroxysms diminish in number and severity, but secondary complications may occur.
Organism is identified based on its microscopic and colonial morphology and their reactivity with antiserum.
Treatment is primarily supportive
Vaccine is acellular
Legionella pneumophila
A ubiquitous aquatic saprophyte that is slender, pleomorphic, obligate aerobes, and gram-negative. They do not stain with common reagents but can be seen in tissues stained with Dieterle silver stain. They require L-cysteine and iron for primary isolation. Growth on supplemented media vs. none on conventional blood agar is used for preliminary identification. They metabolize amino acids
Legionella are intracellular parasites that multiply inside macrophages, monocytes, et c (including amoebaes). They are bound by C3b and endocytosed by CR3, then they prevent phagolysosome fusion. They aren’t killed until T-cells activate the macrophages. Cell mediated immunity is more important to fighting disease.
Pontiac Fever: A flu-like illness that may be a hypersensitivity reaction to bacterial toxin
Legionnaires Disease: more severe than Pontiac fever and if untreated causes considerable morbitity and mortality. Hits a lot of organs, but primary manifestation is pneumonia with multilobar consolidation, evident on X-ray, and inflammation and microabscesses in lung tissue.
Mycoplasma and Ureaplasma
Smallest free-living bacteria. They are unique in that they do not have a cell wall, and their cell membranes contain sterols. They are therefore resistant to antibiotics interfering with cell wall synthesis.
They form pleomorphic shapes and can fit through filtration pores, leading to the original thought that they were viruses.
They grow slowly
P1 adhesin is most important means of adherence to the respiratory epithelium. It interacts with sialated glycoprotein receptors at base of cilia. This kills the cilia then the cells, leading to inhibition of ciliary elevator.
M. pneumoniae functions as a superantigen that is a strict human pathogen. It sets up an easy infection by other organisms.
Exposure typically results in asymptomatic carriage. It can also result in tracheobronchitis and acute pharyngitis. Can lead to atypical pneumonia or walking pneumonia.
Mulberry shaped colonies
*Cold agglutinins: Mycoplasma makes IgM that can help with diagnosis; it also leads to a form of hemolysis- IgM binds to erythrocytes and lyses them at low temps (similar to autoimmune hemolytic anemia)
*Typically the radiographic images will appear much more severe than how the patient clinically presents
Blastomycosis
Systemic funal infection caused by Blastomyces dermatitidis
Endemic to the Mississippi River basin, around the Great Lakes, and in the Southeast region of the US in decaying organic matter
Thermal dimorph (yeast at body temp, mold at room temp)
Broad-based budding multinucleated yeasts (blastoconidia) that have distinctive “double-contoured” walls (microscopically diagnostic)
Infection is through inhalation of conidia, it is not transferred from person to person
Pulmonary disease: may be asymptomatic or present as a mild flulike illness. More severe infections resemble bacteria pneumonia and can progress to ARDS. A subacute or chronic form can resemble TB or lung cancer.
Extrapulmonary disease: chronic cutaneous infections can result, normally from hematogenous dissemination from the lungs. Lesions may be papular, pustular, or indolent. Normally painless, seen on face, scalp, neck, hands, and may be mistaken for squamous cell carcinoma.
Rare in AIDS patients
Amphotericin-B for life-threatening disease, itraconazole for mild disease (fluconazole as an alternative)
Dogs are the most susceptible animals (10x that of humans)
Coccidioidomycosis
An endemic mycosis caused by *Coccidioides immitis * (Calinfornia) or C.posadasii (outside California). Growth is enhanced by bat and bird droppings.
Caused by inhalation of arthroconidia, exposure to which is greatest in late summer and fall
(dusty conditions)
Dimorphic: grows as a mold in lab and a spherule in tissue that reproduces via “progressive cleavage”
Most virulent of all human mycotic pathogens. Can produce an asymptomatic pulmonary disease or a flu-like illness. Primary disease normally resolves on its own. If not, secondary disease consisting of nodules, cavitatioin, and progressive pulmonary disease occurs. Can get to extrapulmonary sites like skin, soft tissues, bones, joints, and meninges.
Has predilection for males (9:1), women in third trimester, AIDS patients, and people in extremes of age groups.
Diagnose via histo, isolation of fungus in culture, and serologic testing. Histo is preferrable because it is extremely infectious when cultured.
Treat with amphotericin B followed with an azole if nessecary.
Minimal treatment of 1 year
Histoplasmosis
Caused by two varieties of Histoplasma capsulatum.
Thermally dimorphic: hyaline mold in culture, yeast in tissue.
Endemic to Ohio and Mississippi River valleys in US (var capsulatum) and Africa (var dubosii). Natural habitat is soil with high nitrogen content (bird and bat feces).
Usual route of infection is inhlataion of microconidiea which can remain localized or disseminate hematogenously or by the lymphatic system. They are phagocytosed by macrophages and become parasites.
var Capsulati: asymptomatic infection in 90% of individuals. Self-limited flu-like infection in some. Most infections resolve with supportive care, but in heavy exposure ARDS is seen. Mediastinal fibrosis is a rare complication. Can show progressive pulmonary fibrosis, disseminated histoplasmosis (more common in children and AIDS), subacure disseminated histo (fever, weight loss, malaise), and acute disseminated histo (may present with septic shock, fatal within days to weeks)
High disease burden in patients with disseminated disease.
Treat with itraconazole if nessecary, amphotericin-B if extremely bad case.
Paracoccidioidomycosis
Caused by Paracoccidioides brasiliensis AKA South American blastomycosis
Major dimorphic endeic fungal infection in Latin America (more in South than Central). Especially found in places of high humidity, rich vegetation (forests)
Forms a “pilot wheel” of budding yeast
May be subclinical or progressive. The primary infections are often self-limited, but the organism becomes dormant for long periods of time. Progressive disease shows cough, purulent sputum, chest pain, weight loss, fever, and pulmonary lesions. Can also extend to skin and mucosa, leading to painful lesions of the mouth and gums (90% of these patients are male!!!).
Diagnose based on yeast form
Treat with itraconazole, amphotericin B if bad case
Adenoviruses
Linear, double-stranded DNA viruswith a covalently attached terminal protein. It is a non-enveloped icosadeltahedron.
Histologic hallmark is a dense, central intranuclear inclusion within infected epithelial cells.
Spread by aerosol, close contact, or fecal-oral means (farting on pillows = pink eye), can get from poorly chlorinated pools
Infects mucoepitherlial cells in respiratory, GI and conjunctiva. It can latently persist in lymphoid tissues.
Causes acute febrile pharyngitis and pharyngoconjunctival fever, acute respiratory disease (fever, cough, haryngitis, cervial adenitis), croup, laryngitis, and bronchiolitis
High prevalence of infection in military recruits
They are being considered for delivery of genes in gene therapy
Rhinoviruses
Picoraviruses that are labile at acidic pH (no GI tract for them) and grow best at 33C (which is why they like the nose)
naked icosahedral capsid structure that have pico (+) RNA and looks like a eukaryotic mRNA; encodes a polyprotein that is cleaved to viable proteins.
Receptor to gain entry to cell is a member of the immunoglobulin superfamily (ICAM-1); RNA is injected into cell
Most important cause of common cold. Lots of serotypes, so immunity is hard to establish
For the love of God, wash your hands
Coronaviruses
Second most prevalent cause of the common cold
Named after the the halo (crown) shape seen upon microscopy… and the beer (has crown on bottle)
Enveloped virions with the longest (+)RNA genome, which eventually splits to seven individual mRNAs
Optimum temperature is 33-35C, like the Rhinoviruses (nasal passages are this temperature). Unlike the rhinoviruses, they can apparently survive the GI tract
Infections occur most in slimey little chlidren
Also the causitive agent of SARS, treat with quaratine
Parainfluenzae Viruses
Paramyxovirus consisting of (-)ssRNA which is enveloped. Enters cells via sialic acid.
Usually cause mild cold-like symptoms but can also cause serious respiratory tract disease. Especially associated with laryngotracheobronchitis (croup)
Easily inactivated by dryness and acid. Hosts are humans
Causes giant cell formation in upper respiratory tract, where it stays 75 % of the time. The other 26% it goes to lower respiratory tract.
Only partial immunity develops
Primary infections happen at a young age
Respiratory Syncytial Virus
Paramyxovirus consisting of (-)ssRNA which is enveloped. Enters cells via sialic acid. Produces giant cells (syncytia)
Unlike other paramyxoviruses, it lacks hemagglutinin and neuraminidase activities.
Most common cause of fatal acute respiratory tract infection in infants and young children. Infects everyone by age 2 or so. Causes common cold and pneumonia, as well as bronchiolitis
Doesn’t seem like antibodies are very effective, reinfection occurs often. Infections occur in winter (white walkers) and epidemics occur every year.
Necrosis of the bronchi and bronchioles lead to “plugs” of mucus (mostly immune mediated)
Treat with Ribavirin and passive immunization with RSV antibodies
Human Metapneumovirus
Paramyxovirus consisting of (-)ssRNA which is enveloped. Enters cells via sialic acid.
Difficult to grow in culture. Infectoins can cause anything from common cold to pneumonia and bronchiolitis.
Associated with otitis media.
Hantavirus
A member of Bunyaviridae that is an enveloped, segmented, negative-stranded virus that does not have a matrix protein.
Maintained in rodents, spread by inhaling their urine (if you’re into that kind of thing)
Sin Nombre is a member of the hantaviruses
Hantavirus pulmonary syndrome can cause ARDS
Influenza Viruses
Orthomyxoviridae consists of influenza A, B, and C. They are enveloped, segmented, negative sense ssRNA viruses
Initially the virus targets and kills mucus-secreting, ciliated, and epithelial cells, inhibiting this primary defense. Can cause considerable shedding of epithelium of bronchi or alveoli. Also promotes bacterial adhesion. Most “flu” symptoms are from interferon induction
Bird flu: The H5N1 that is infective to humans is unique because it is not a reassortment and can pass directly from bird to man.
Human: H3N5
Swine: H1N1: caused a pandemic in 2009, when everyone was expecting a pandemic from avian flu.
Drift: small mutations, causes epidemics annually
Shift: rearrangement of genomes, causes pandemics periodically
Most drift and shift takes place with hemagglutinin; shift only occurs in influenza A. Packaging of virus occurs pretty much randomly, hence shift
The 2013-2014 trivalent influenza vaccine is made from the following three viruses:
- an A/California/7/2009 (H1N1)pdm09-like virus;
- an A(H3N2) virus antigenically like the cell-propagated prototype virus A/Victoria/361/2011;
- a B/Massachusetts/2/2012-like virus.
Cryptococcus neoformans
This fungus is worldwide in distribution and is found as a ubiquitous saprophyte of soil, especially that which is enriched iwth pigeon droppings
Spherical to oval encapsulated yeastlike organism; Upon staining with India ink spherical cells with “halos” (extracellular polysaccharide capsule) can be seen
Acquired via inhalation of C. neoformans from the environment
Subsequent dissemination from the lungs, usually to the CNS, produces clinical disease in susceptible individuals (opportunistic pathogen); Major opportunistic pathogen of patients with AIDS
Most common cause of fungal meningitis; clinical presentation -> fever, headache, meningismus, visual disturbances, abnormal mental status, and seizures
May present as pneumonic process or, more commonly, as a CNS infection secondary to lymphatic spread from a primary pulmonary focus
Universally fatal if left untreated (cryptococcal meningitis); treat with amphotericin B plus flucytosine acutely 2 wks then oral fluconazole 8 wks (Also want to treat CNS pressure)
CSF samples collected during follow-up must be cultured
Aspergillus sp.
Exposure to aspergillus in the environment may cause allergic reactions in hypersensitized hosts or destructive, invasive, pulmonary and disseminated disease in highly immunosuppressed individuals
Grow in culture as hyaline molds. Grow as branched, septate hyphae that produce conidial heads when exposed to air in culture and in tissue
The hyphae may be seen within blood vessels (angioinvasion), causing thrombosis
Common throughout the world and their conidia are ubiquitous in air, soil, and decaying matter
Respiratory tract is the most frequent, and most important, portal of entry
Both the paranasal sinuses and lower airways may become colonized wiht aspergillus resulting in obstructive bronchial aspergillosis and true aspergilloma (“fungus ball”). Treatment typically not warranted unless pulmonary hemorrhage occurs (then surgical excision)
Invasive pulmonary aspergillosis (IPA) and disseminated aspergillosis are devastating infections seen in severely neutropenic and immunodeficient patients
Symptoms: fever and pulmonary infiltrates, often accompanied by pleuritic chest pain and hemoptysis
Prevention of aspergillosis in high-risk patients is paramount (filter air). Treat with amphotericin B (voriconazole if A. terrus)
Zygomycetes sp.
Infections due to Zygomycetes are rare (1.7 per million in US). However, infections due to these agents are generally acute and rapidly progressive (70% - 100% mortality)
Molds with broad, hyaline, sparsely septate, coenocytic hyphae.
Typically angioinvasive
Sporadic disease that occurs worldwide with Rhizopus arrhizus being the most common cause of human zygomycosis. Ubiquitous in soil and decaying vegetation, and infection may be acquired by inhalation, ingestion, or contamination of wounds with sporangiospores form the environment. Nosocomial spread may occur by way of air-conditioning systems, particularly during construction
Invasive zygomycosis occurs in immunocompromised patients and may cause infection in 1% - 9% of solid organ transplants, especially those with diabetes mellitus
Pulmonary zygomycosis occurs as a primary infection in neutropenic patients and may be misdiagnosed as invasive aspergillosis. The pulmonary lesions are infarctive as a result of hyphal invasion and subsequent thrombosis of large pulmonary vessels
Histopathologic sections stained with H&E or PAS are most useful
Amphotericin B is first-line therapy often supplemented with surgical debridement and immune reconstitution. Posaconazole is the only triazole that’s useful (Voriconazole prophylaxis actual has lead to outbreaks)
Pneumocystosis jirovecci
Pneumocystosis jirovecci causes infection almost exclusively in debilitated and immunosuppressed patients, especially those with HIV infection. It is the most common opportunistic infection among individuals with AIDS.
Reservoir in nature is unknown
Respiratory tract is main portal of entry for P. jirovecci in humans. Pneumonia is the most common presentation of pneumocystosis.
Hallmark of P. jirovecci infetion is an interstitial pneumonitis with a mononuclear infiltrate composed predominantly of plasma cells
Clinical picture: Dyspnea, cyanosis, tachypnea, nonproductive cough, and fever
Diagnosis is almost entirely based upon microscopic examination of clinical material, mainly bronchoalveolar lavage (BAL) fluid (90% - 100% sensitivity)
Cornerstone for both prophylaxis and treatment is trimethoprim-sulfamethoxazole
