micro respiratory pathogens 1 Flashcards
Chlamydia psittaci disease
Atypical Pneumonia
Psittacosis (parrot fever): caused by Chlamydia psittaci; reservoir = birds
Chlamydia microbiology
Gram negative
two functionally and morphologically distinct forms.
The small inert extracellular elementary body (EB) enters the cell by endocytosis
Reorganizes into a larger, metabolically active reticulate body (RB). The RB undergoes repeated binary fission to form daughter Ebs, which are released from the cell. These obligate intracellular parasites do not synthesize many metabolites and are dependent on the host cell
Tx for chlamydia
Drug of choice
Doxycycline is the treatment of choice, except in children younger than 9 years and in pregnant women.
Alternative drugs
Alternative agents include erythromycin (500 mg PO/IV qid) and newer macrolides such as azithromycin and clarithromycin
Chlamydia trachomatis
most common sexually transmitted pathogen in industrialized countries (3-4 million cases/year in the U.S).
Also neonatal infections contracted from the mother during passage through the birth canal. Neonatal pneumonia and neonatal inclusion conjunctivitis, which is prevented by administering erythromycin eye drops at birth - like ophthalmia neonatorum caused by N. gonorrhoeae.
Legionella pneumophila.microbiology
aerobic gram-negative rods, nonencapsulated, difficult to stain - facultative intracellular parasites
An important virulence determinant of L. pneumophila is the avoidance of phagosome-lysosome fusion in phagocytic cells.
Legionella disease
Atypical pneumonia
More illness is usually found in the summer and early fall
Pontiac fever is a milder illness caused by L. pneumophil
People get Legionnaires’ disease when they breathe in a mist or vapor (small droplets of water in the air) that has been contaminated with the bacteria.
The bacteria are NOT spread from one person to another person.
Legionella treatment
The antibiotics used most frequently have been levofloxacin and azithromycin.
Macrolides are used in all age groups while tetracyclines are prescribed for children above the age of 12 and quinolones above the age of 18.
Boretella pertussis microbiology
Fastidious aerobic gram-negative coccobacilli
Pertussis disease
Pertussis is primarily a toxin-mediated disease.
The bacteria attach to the cilia of the respiratory epithelial cells, produce toxins that paralyze the cilia, and cause inflammation of the respiratory tract, which interferes with the clearing of pulmonary secretions.
The clinical illness is divided into three stages: catarrhal, paroxysmal, and convalescent.
if untreated, persistent coughing lasts for an average of 7 weeks.
Francisella tularensisis microbiology facts
aerobic, Gram-negative , non motile and non-sporing coccobacillus and is the causative agent of the disease Tularemia
LPS has a reduced immunostimulatory property
The bacterial capsule plays a role in resistance to complement
Tuleremia Disease
The disease may be transmitted through the bite of ticks (wood, dog and lone star types) and deer flies; through contact with contaminated water, blood or tissue while handling carcasses of infected animals (for example, skinning or dressing animals); through eating insufficiently cooked meat of infected animals; or through inhalation of dust from contaminated soil, hay or grain. The virulence of the organism lends itself to its potential use as a biological weapon, leading to its classification as a Caterory A biodefense agent
Tularemia doesn’t occur naturally in humans and isn’t known to pass from person to person.
Acinetobacter baumannii microbiology
pleomorphic aerobic gram-negative bacillus water organism and preferentially colonizes aquatic environments. This organism is often cultured from hospitalized patients’ sputum or respiratory secretions, wounds, and urine. In a hospital setting, Acinetobacter commonly colonizes irrigating solutions and intravenous solutions
Acinetobacter baumannii disease
A. baumannii can cause apoptosis or cell death in human laryngeal
epithelial cells via an outer membrane protein (OMP 38).
Medications to which Acinetobacter is usually sensitive include:
Meropenem
Colistin
Polymyxin B
Amikacin
Rifampin
Minocycline
Tigecycline
Yersinia Pestis micro
Chubby gram-negative rods with bipolar inclusion bodies, said to look like safety pins
Type three secretion system injects effectors into host cells
Paralyze phagocytes
F1 protein antigen capsule is unique to Yp among the Yersinia
Basis of rapid tests and confirmatory serological tests
Yersinia pestis transmission
Transmission is via the flea from ground rodents (and rabbits) in New Mexico and adjoining states and some Rocky Mountain States to the north
Yersinia pestis disease
Bubonic (~60% fatality if untreated)
•Initial infection from flea bite (1-8 days incubation)
•Swollen painful axial or inguinal, femoral lymph node (buboes, Fig. 2), with fever, chills, headache, possible nausea, vomiting, prostration.
Ulcerous or macular lesion may or may not be seen at site of flea bite
Site lesions usually not as prominent as in tularemia, anthrax
About 25% of cases will progress to severe septicemia
Pneumonic (~100% fatal if not treated)
Yersinia pestis disease - dx
Productive Sputum more bloody and watery than purulent.
Serological, based on Abs to F1 surface protein Ag (Confirmatory)
•Gram stains of buboes, sputum, blood may reveal “safety pin rods”
•Culture (growth seen in a day or two)
•IF test (rapid, IF Ag) to detect Yp in clinical specimens (special labs)
•New RADT (dipstick test on F1 Ag in urine)
Yersinia pestis treatment
Aminoglycosidases = treatment
Gentamicin (Streptomycin, if available), Doxy, Cipro
Immediate treatment imperative, if pneumonic, septicemic
Post-exposure (pneumonic): doxy for 7 days
No vaccine at present
Brucella microbiology
Small G- aerobic coccobacillus
Facultative intracellular parasite of the RES (liver, spleen, bone marrow)
Brucella disease, symptoms, transmission
Brucellosis (also called undulant fever) is usually a slow-moving, chronic infection
But initial infection can be acute (flu symptoms with high fever)
•Relapsing fever (nocturnal with night sweats)
-granuloma
Dry cough, pleuritic pain; Chest Xray may be negative
Transmission
By contact (through abrasions) with infectious materials
Consumption of raw milk, unpasteurized cheese
Rarely, inhalation of aerosols from infected animals
Coxiella burneti micro
Gram negative bacillus that is usually discussed with rickettsiae because it is an obligate intracellular parasite, but we now know it is most closely related to Legionella
Coxiella burneti disease & treatment
Q fever
•One-third to one-half asymptomatic
•Acute febrile illness, atypical pneumonia lasts 2-4 weeks
•Sometimes liver and heart involvement
Most infections will spontaneously resolve, but doxycycline treatment can shorten duration and reduce risk for chronic infection.
Mycoplasma pneumoniae micro
smallest free-living organisms and lack a cell wall
The nutritional requirement of many mycoplasmas for a sterol (cholesterol) is unique among prokaryotes
mycoplasma pneumoniae disease prevalence
M. pneumoniae is now recognized as one of the most common causes of community-acquired pneumonia in otherwise healthy patients younger than 40 years.
it is most common in the first 2 decades of life
large outbreaks tend to occur in the late summer and fall. In summer, this organism may cause as many as 50% of all pneumonias.
The incubation period of mycoplasmal pneumonia tends to be averages 3 weeks, in contrast to that of influenza and other viral pneumonias, which generally average a few days.
Mycobacterium tuberculosis micro
large nonmotile rod-shaped bacterium
M. tuberculosis is an obligate aerobe
.
found in the well-aerated upper lobes of the lungs.
The bacterium is a facultative intracellular parasite, usually of macrophage
slow generation time, 15-20 hours
Chains of cells in smears made from in vitro-grown colonies often form distinctive serpentine cords.
Over 60% of the mycobacterial cell wall is lipid. The lipid fraction of MTB’s cell wall consists of three major components, mycolic acids, cord factor, and wax-D.
Mycobacterium tuberculosis disease - prevalence, timing, stages
Humans are the only reservoir for the bacterium.
Tuberculosis (TB) is the leading cause of death in the world from a bacterial infectious disease. The disease affects 1.8 billion people/year, which is equal to one-third of the entire world population
3 major cell wall components of MTB
Mycolic acids are unique alpha-branched lipids found in cell walls of Mycobacterium and Corynebacterium. They make up 50% of the dry weight of the mycobacterial cell envelope. Mycolic acids are strong hydrophobic molecules that form a lipid shell around the organism and affect permeability properties at the cell surface.
Cord Factor is responsible for the serpentine cording mentioned above. Cord factor is toxic to mammalian cells and is also an inhibitor of PMN migration
Wax-D in the cell envelope is the major component of Freund’s complete adjuvant (CFA).
MTB disease
The immune system produces macrophages that surround the tubercle bacilli. The cells form a hard shell that keeps the bacilli contained and under control.
Most people with TB infection have a positive reaction to the tuberculin skin test.
People who have TB infection but not TB disease are NOT infectious
HIV infection is the #1 predisposing factor for MTB infection
5 stages of the disease
MTB tx
The most commonly used drugs are rifampin (RIF) isoniazid (INH), pyrazinamide (PZA ) and ethambutol (EMB) or streptomycin (SM).
R-I-P-E-S
When adherence with the regimen is assured, this four-drug regimen is highly effective.
A vaccine against MTB is available. It is called BCG (Bacillus of Calmette and Guerin, named after the two Frenchmen that developed it). BCG consists of a live attenuated strain derived from Mycobacterium bovis
Bacillus anthracis micro
Gram-positive aerobic spore-former that form large “boxcar” G+ chains (no spores can be seen in blood smears or CSF). The spore is important to the persistence of Ba in nature because it allows the organism to remain viable for years (possibly 100 yrs) in the soil
Bacillus anthracis virulence
An antiphagocytic, non-antigenic capsule, consisting of poly-d-glutamic acid
An AB-type toxin (Anthrax Exotoxin that contributes to many symptoms
B = Binding component and is called the Protective antigen (PA)
Allows binding to host receptor and facilitates endocytosis and entry of A into the cytoplasm after endocytosis
A = Active subunit. Anthrax toxin is unusual in that there are two A subunits
Edema factor (EF): a calmodulin-activated adenylate cyclase Increases cAMP in target cells and is responsible for the swelling in cutaneous anthrax and systemic effects including mediastinal edema
Lethal factor (LF): a metalloprotease that cleaves host cell MAP kinases
Actinomycosis isrelii micro
Gram-positive, pleomorphic non–spore-forming, non–acid-fast anaerobic or microaerophilic bacilli
Branching filament-like structures that resemble fungal hyphae
Actinomycosis isrelii disease & treatment
Infections of the oral and cervicofacial regions are the most commonly recognized infections; however, the thoracic region, abdominopelvic region, and the CNS also frequently can be involved
Form hard yellow granules (sulfur granules) which are bacterial filaments solidified with tissue exudates These granules drain outside through sinuses
A patient may need to receive penicillin intravenously for 4 - 6 weeks, followed by several months of penicillin by mouth OR
o tetracyclines
o macrolides
o clindamycin
Corynebacterium diphtheriae micro
Gram-positive, aerobic, nonmotile, rod-shaped bacteria classified as Actinobacteria
characteristic of forming irregular, club-shaped or V-shaped arrangements in normal growth. They undergo snapping movements just after cell division
Corynebacterium diphtheriae virulence
Diphtheria toxin: required for virulence.
Diphtheria toxin is encoded by the tox gene on a lysogenic bacteriophage called beta-prophage. Strains lacking this phage are nontoxigenic (and, therefore, avirulent) and can be converted to toxigenic (and virulent) by lysogenization with beta-phage, an example of lysogenic conversion.
Diphtheria toxin inactivates protein synthesis elongation factor 2 (EF-2) by ADP-ribosylation (the transfer of an ADP-ribose group from NAD). One molecule of this toxin is sufficient to kill a cell.
Organism colonizes pharyngeal area, causing a lesion termed a Pseudomembrane
Symptom: very sore throat; lymphadenitis
Toxin gets into blood (bug remains in throat)
Damage to many organs, particularly the heart.
Diptheria treatment
Diphtheria antitoxin:
Treatment of diphtheria involves the early administration of diphtheria antitoxin, which neutralizes the circulating diphtheria toxin and reduces the progression of the disease.
It is not effective against toxin that has already bound to body tissue.
Diphtheria antitoxin is derived from horses, and it is only available from the Centers for Disease Control and Prevention (CDC).
The prompt administration of either erythromycin or penicillin can eradicate the bacteria and halt the production of further diphtheria toxin.
The administration of antibiotics also assists in preventing the transmission of diphtheria to others.
Nocardia asteroides micro
gram-positive, bacillary, branching bacteria whose hyphae often fragment to coccobacillary forms.
Catalase and superoxide dismutase inactivate reactive oxygen species from neutrophils and macrophages, reducing their toxic effects on Nocardia.
shorter-chained (40- to 60-carbon) mycolic acids
Nocardia asteroides disease & treatment
pulmonary nocardiosis: blood in sputum fever night sweats weight loss chest pain accompanying ventilation. cerebral nocardiosis: headache confusion general lethargy dissipating neurological function seizures. cutaneous nocardiosis:
Nocardiosis cases are typically treated with trimethoprim-sulfamethoxazole
Antibiotic treatment for immunocompetent persons is recommended for no less than 6 months
In immunosuppressed populations antibiotic therapy is continued for no less than 12 months
Streptococcus pneumonia micro
non-typable, lancet-shaped Gram-positive diplococcus
Strep pneumoia disease
community acquired pneumonia, it also causes meningitis, sinusitis, otitis media, and sepsis. It is a less frequent cause of endocarditis and other diseases. S. pneumoniae is a member of the commensal microbiota, asymptomatically colonizing up to 60% of healthy children and 30% of healthy adults
Increased fremitus (palpable vibration) is a useful finding. Chest x-ray may be more important in determining pneumococcal pneumonia than any of these other signs. The patient will usually have rust-colored sputum and shaking chills.
Gram-staining of sputum samples containing a large number of PMN, very few epithelial cells, and Gram-positive lancet-shaped diplococci (or short chains) would be indicative of S. pneumoniae.
Only 25% of pneumococcal pneumonia patients will have bacteremia, so a negative blood culture isn’t particularly helpful.
Meningitis. S. pneumoniae is the most common cause of bacterial meningitis in adults, except during an epidemic of meningococcal infection (Neisseria meningitidis). Pneumococcal meningitis may be due to direct extension from middle ear infection or sinusitis, but more likely through hematogenous spread (bacteremia) from these or other regions.
Strep pneumonia virulence factors
Polysaccharide capsule is probably the most important virulence factor. Its value is in its antiphagocytic effects, except in the presence of anti-capsule antibodies which are opsonic. There are more than 80 capsular types that can be identified by something called the Quellung reaction
Pneumolysin belongs to the pore-forming toxins first described as hemolysins. It binds to cholesterol in host cell membranes leading to cell lysis, recruitment of neutrophils and T- and B-lymphocytes, increasing the level of inflammation. It also may directly interact with TLR4 to stimulate cytokine production. It also contributes to damage that occurs in meningitis
break down hemoglobin into a green pigment.
a green zone called -hemolysis
Coronaviruses micro
large enveloped viruses that exhibit “crown-like” morphology when observed under the electron microscope.
CoVs have a non-segmented, positive-sense RNA genome of 27- to 32-kb in size, the largest RNA viral genome known to date.
The CoV genome has a 5’ methylated cap and a 3’polyadenylated-A tail and functions directly as mRNA
SARS
Coronaviruses
SARS-CoV causes severe lower respiratory tract infections, with most progressed to pneumonia.
Infection of susceptible cells (type II pneumocytes) with SARS-CoV results in diffuse alveolar damage. In severe cases, the disease develops into respiratory failure and acute respiratory distress syndrome (ARDS).
SARS-CoV also causes systemic diseases, with evidence of infection of the GI tract, liver, kidney and brain, among other tissues.
SARS-CoV was introduced into the human population by cross-species transmission from bats, the animal reservoir for SARS-like CoVs
Hantavirus micro
Bunyaviridae
spherical, enveloped particles that have a trisegmented, negative-sense RNA genome
One segment encodes the nucleocapsid protein, one the polymerase and the other encodes the two envelope proteins (G1 and G2). Each hantavirus is adapted to a single host rodent species
Hantavirus disease
The mechanism responsible for HPS is increased pulmonary capillary permeability that leads to severe pulmonary edema
Individuals become infected primarily by breathing air containing aerosolized rodent saliva, urine or feces.
Patients with HPS have very high levels of viremia at the onset of pulmonary edema and then rapidly clear the virus from plasma
lymphoblasts and macrophages are recruited to pulmonary tissue by the high viral burden which then provokes a lymphokine-mediated activation of vascular endothelium, thereby increasing pulmonary capillary permeability.
HPS advances through two distinct stages and is a severe disease characterized by a rapid onset of pulmonary edema followed by respiratory failure and cardiogenic shock.
Influenza Micro
Orthomyxoviridae
enveloped viruses with segmented, single-stranded, negative-sense RNA genomes.
three types of influenza viruses: A, B, and C. Virus types were defined by the antigenic differences in nucleocapid (NP) and matrix (M1) proteins
Influenza A viruses are further divided into subtypes based on the surface glycoproteins – hemagglutinin(HA) and neuraminidase (NA).
NA inhibitors
NA – receptor-destroying enzyme: cleaves sialic acid residues from virion and cell surfaces, playing a role in release of virus from infected cells and spread within the respiratory tract and preventing virion aggregation. NA enzyme inhibitors prevent the release of virus from infected cells
amantadine
rimantadine
M2 protein is present only in influenza A viruses. The ion channel activity of M2 plays a role in uncoating of the virus and possibly in the regulation of virus assembly. M2 is the viral target
Respiratory syncytial virus (RSV) micro
enveloped, nonsegmented, negative-strand RNA viruses that belong to the Paramyxoviridae family.
RSV prevalence
RSV is the leading viral cause of serious lower respiratory tract infections in infants worldwide.
RSV outranks all other microbial pathogens as the cause of bronchiolitis and pneumonia in infants under 1 year old.
Tx for RSV
Synagis (palvizumab): A recombinant monoclonal antibody that neutralizes RSV infectivity
Aerosolized ribavirin (nucleoside analog) Only FDA approved drug for RSV; Used to reduce virus shedding and clinical illness by interfering with virus replication; Has teratogenic activity and requires aerosol scavenging system in patient’s room.
RSV pathogenesis
RSV virions contain two major envelope glycoproteins, F and G
The fusion protein is similar in structure for all three viruses and is called “F” (for fusion) protein.
RSV can also bind to glycosaminoglycans (GAGs) found on the surface of airway epithelium. The attachment protein of RSV is simply called “G” (glycoprotein) because it does not bind sialic acid
human metapneumovirus (hMPV)
enveloped, nonsegmented, negative-strand RNA viruses that belong to the Paramyxoviridae family
hMPV is the second most commonly identified cause of pediatric lower respiratory illness, behind only RSV
hMPV also causes acute respiratory disease (ARDs) in older children and adults
F protein is responsible for both virus entry and fusion of adjacent cells, which results in the formation of syncytia
hMPV and hPIVs have two envelope proteins called F and HN
human parainfluenza viruses 1, 2, 3 and 4 (hPIV1, hPIV2, hPIV3, and hPIV4
enveloped, nonsegmented, negative-strand RNA viruses that belong to the Paramyxoviridae family
he viral protein responsible for attachment of hMPV and the hPIVs is called HN (Hemagglutinin-Neuraminidase) because it binds to sialic acid, similar to the hemagglutinin (HA) protein of influenza virus. Sialic acid is a major component of the mucus membrane layer lining the respiratory tract
hPIV-3 is second only to RSV as a cause of pneumonia and bronchiolitis in infants and young children.
Rhinoviruses
microbiology, infections
Picornaviridae family, which are small, non-enveloped, positive-stranded RNA viruses. The lack of an envelope allows the virus to persist for long periods of time on surfaces and makes it relatively resistant to desiccation.
More than 100 different serotypes of rhinoviruses exist and these are divided into 3 major groups based on their receptor use specificity.
Rhinovirus infections are typically self-limiting and restricted to the upper respiratory tract, but they may also cause otitis media and sinusitis.
Adenovirus
double-strand, linear DNA genome packaged in an icosahedral capsid without an envelope
release is achieved by cell lysis.
AdV are exceptionally stable against detergents
resistant to the low pH environment of the GI tract
more than 100 serotypes are defined by the capsid’s penton protein, a spike-like protein found at each of the icosahedron’s corners. The pentons are the likely attachment proteins of the virus and also are responsible for a toxic effect on cells. The production of penton-specific antibodies leads to life-long immunity against that particular serotype, but the numerous serotypes allow for subsequent AdV infections.
AdV hexon proteins, also capsid components, produce complement-fixing antibodies that do not provide immunity but are useful in identifying an AdV infection.
Adenovirus prevention
An attenuated, live vaccine is administered to military personnel due to the high incidence of ARD during boot camp or similar drills. The vaccine encapsulates serotypes 4 and 7 which allows for their enteric release. The viruses then produce a subclinical infection in the GI tract to promote immunity. The vaccine is not available to the general public
Histoplasmosis
appearance, location
dimorphic fungus, growing in soil enriched by bird or bat excrement as a mold with distinct “tuberculate” (bumpy) conidia (Fig. 1). In tissues, the fungus assumes a small yeast form that resists killing in macrophages.
H. capsulatum is endemic to the Ohio and Mississippi River Valleys (Fig. 5), thriving on the bird excrement found in the soil as each valley is a major flyway for migratory birds
Blastomyces dermatitidis
disease
dimorphic fungus found as a mold in the soil. However, unlike H. capsulatum, the yeast form assumed in tissues does not appear to survive in macrophages.
flu-like illness. Some patients acquire an acute pneumonia with purulent, brown or bloody sputum.
The infection can disseminate despite lung resolution, with 20-40% of patients exhibiting warty skin lesions. Bone, the genitourinary tract and prostate are also targets of disseminated infection (5-25% of infections), and 5% of AIDS patients will contract meningitis.
endemic in the Mid-South, and also in the southeastern and mid-western parts of the US.
Observation of broad-based budding yeast in clinical specimens
Coccidioides immitis
a dimorphic fungus found as a mold in the soil and whose tissue form is not a yeast, but rather a spherule (Fig. 2), a multi-compartmental structure that harbors 200-300 endospores. It is believed that the release of the endospores leads to spread of the infection
Valley Fever
Coccidioidomycosis is commonly referred to as “valley fever” because of its prevalence in the San Joaquin Valley of California. Valley fever develops in 40% of infections and is characterized by fever, arthralgia, fatigue, and rash
Direct observation of spherules is diagnostic and are best seen in skin lesion biopsies. Serologic tests to measure IgM or IgG are also useful
Aspergillosis micro
growing molds with branching (45° angle) septate hyphae (Fig. 3), even in tissue samples. Fluffy colonies can grow in culture within 1-2 days and completely cover the agar plate within 5 days. Aspergillus spp. are ubiquitous in the environment,
Mucormycosis micro & disease
Zygomycosis
broad, nonseptate hyphae that branch at 90° angles. These fungi are found in the soil as molds and can be disturbed and more commonly encountered after environmental disturbances such as tornadoes.
Mucormycosis is very rare, mostly seen in acidosis (diabetes mellitus) patients or patients on corticosteroid treatment. Mucormycosis takes the form of a fungal pneumonia or an invasive rhinocerebral form that can result in death in as short as two weeks. T
Pneumocystis
exhibits both fungal and protozoan characteristics, forming thin-walled cysts that contain sporozoites. The sporozoites mature upon release to form trophozoites, consistent with a protozoan nature. No hyphae are observed in infected tissues, and cholesterol, instead of ergosterol, is the predominant sterol in the plasma membrane. Still, rRNA analysis places P. jerovici closer to fungi than protozoans.
