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365 Cards in this Set
- Front
- Back
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What are capsomeres of viruses?
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the small protein subunits typically composed of several small proteins that combine in groups to form the capsid
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What is a viral capsid?
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the protein covering surrounding core of nucleic acid and enzymes (sometimes, if that particular virus houses its own enzymes)
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What is a virion?
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the complete (infectious) virus particle
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What is the envelope of a virus?
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membrane like outer covering of certain viruses
-combo of host membrane with some virus proteins -host membrane is studded with viral proteins and progeny virions acquire during budding out process |
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What are spikes (peplomeres)?
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virus proteins embedded in envelope that project from surface
-enzymatic activities are often associated with the spikes |
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What are the 2 basic patterns in which the proteins can associate with the nucleic acid genome of a virus?
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1)extended nucleic acid form
2)condensed nucleic acid form |
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Describe the viral genome.
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is composed of nucleic acids, can be DNA or RNA (never both, this distinguishes them from some unusual prokaryotes)
-have seen single stranded, double stranded, segmented |
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Describe a positive stranded virus.
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refers to viral "polarity"
-can serve as mRNA directly -they may be directly translated by host ribosomes into proteins -happens more quickly than neg. strand |
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Describe a negative stranded virus.
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-refers to polarity of the virus
-cannot be directly translated, must first be transcribed by a virus-encoded RNA dependent RNA polymerase to get a strand of + polarity that can act as mRNA and be translated by ribosomes |
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What is the central goal of virtually all viruses?
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to replicate virus at the expense of the host cell
-they just don't care about you. Period. -may result in lysis and death of the cell -alternative viral replication strategies that do not always kill the host are known, however |
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What are stages of animal cell virus replication?
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1)attachment-a latent period during which virus is developing inside the cell but is not readily evident outside the cell
-specific receptors arrayed at cell surface, determines host and tissue specificity and mode of spread in host 2)penetration/entry (via several modes) 3)uncoating-release of virus genome by removal of capsid (host directed process) 4)synthesis-strict temporal control of biosynthesis is the key, build the virus literally from the inside to the outside 5)maturation/release-burst or budding |
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What are the various modes of penetration/entry of a virus into a host cell?
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1)surface eclipse-direct fusion of capsid with host membrane
2)membrane-membrane fusion 3)receptor-mediated endocytosis-uptake in clathrin coated pits, fusion with lysosomes, removal of capsid |
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Describe the strict temporal control that viruses have over their synthesis once they enter host cell.
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early genes-genome synthesis
late genes-virion maturation and capsid -this strict temporal control is the key to viral replication |
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Describe the 2 methods of viral maturation/release.
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1)burst-also called lysis, host cell dies
2)budding-through cytoplasmic membrane -the host cell may remain viable for long periods of time, chronic production is possible |
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In general, where does replication and maturation of DNA viruses occur once in the host cell?
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in the host nucleus
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What is an example of a virus that supplies its own host -cell independent DNA replication functions?
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the Pox virus which is a large genome virus
-it supplies ALL replication functions including those for DNA synthesis |
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In general, where do RNA viruses replicate and mature once in the host cell?
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in the cytoplasm
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What problem do all RNA genome viruses share with regards to replication?
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RNA is comparatively unstable and molecules must be copied rapidly in the infected cell to provide genomes for packaging and mRNAs
-the host has no enzymes capable of performing the needed RNA copying tasks for the RNA virus and these molecules are either transported into the host in the virion itself or synthesized from the virus genome |
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Describe negative stranded RNA viruses.
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they need an RNA dependent RNA polymerase to transcribe the genome into a + or mRNA that can be translated into protein
-they place the required polymerase in the capsid and transport it pre-formed into the host to initiate the infection |
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What is the hallmark of retrovirus replication?
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reverse transcription and integration
-they are RNA viruses that first convert their (pseudo-diploid) RNA genome to DNA -one double stranded DNA is substituted for the 2 molecules of ssRNA genome that originally entered the cell -the DNA copy of the RNA genome must then be integrated into the host cell genome (becoming a provirus) for expression -the virus encodes reverse transcriptase, an RNA dependent DNA polymerase to reverse the flow of genetic info. and allow DNA to be made from RNA -they violate central dogma and follow path of RNA-->DNA-->RNA instead of DNA-->RNA-->protein |
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What viruses are strong risk factors for cancer development in humans?
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HPV 16/18-cervical, oral
Hep B and C-liver cancer EBV-Burkitt's lymphoma, nasopharyngeal cancer Herpes virus type 8-Kaposi's sarcoma with HIV Human T cell lymphotropic virus type 1 |
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How does a virus replicate once inside a host cell if it infects a host cell that is not actively dividing and producing DNA?
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some viruses are only able to replicate in actively growing cells
-some DNA viruses disrupt the host cell cycle control functions of p53 and Rb and nudge the host into something similar to "S" phase to replicate |
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What is bacterial lysogeny?
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-a stable, quasi-permanent association of virus and bacteria
-this is a replicative strategy for the virus, the viral genome is replicated each time the host genome replicates -bacteria that can establish lysogeny are called "temperate" |
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How is lysogeny established?
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-the infecting virus asseses the ability of the host cell to support it's replication
ex: the phage lambda of E. coli infecting virus senses host cell cAMP levels: if high, cell is starved, lysogeny is elected, if cAMP low, cell is nutrient replete and the lytic cycle is elected |
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Describe lysogeny termination.
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-also called prophage induction
-the association of virus and host may remain stable for long periods, but certain conditions may terminate this -DNA damage to host results in prophage induction -virus is able to assess the well-being of the host and the damage to the DNA results in a signal that the quiescent virus intercepts and quickly switches to the lytic cycle to escape from a dying host |
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What are some strong prophage inducing agents?
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certain antibiotics such as quinolones (provokes DNA damage)
-this induction may provoke a severe intoxication reaction in the antibiotic-treated pt. |
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What is lysogenic conversion?
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when a bacteriophage establishes lysogeny in a host cell and alters the phenotype of the host cell
-the lysogenized cell obtains and expresses genes that are actually a part of the viral genome -can be toxin genes that lead to expression of new surface structures -medically significant, lysogenic conversion may produce a dangerous pathogen from an otherwise completely nonpathogenic organism |
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What are some ways that viruses can evade immune functions in animal hosts?
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1)avoidance-infect quiescent cells to store genome without lytic consequences or invade immunologically privileged sites such as neural tissue that lacks MHC markers
2)blockade antigen presentation mechanisms by interfering with MHC expression 3)interrupt cytokine synthesis or interfere with cytokine receptors 4)inhibit apoptosis induction 5)evade ab/complement killing |
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What are the 3 basic types of persistent infections that are recognized with viruses infecting animal cells?
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1)latent (hidden) infections-intermittent acute episodes of virus production btwn. which there may be an absence of virus particles and very limited viral macromolecular synthesis (Herpes simplex)
2)chronic infections-quasi-nonlytic production of virus, continued presence of virus during periods in which overt clinical disease is absent (hep B) 3)transforming-cells are immortalized and properties altered (transformed) to those of cancer cells (HPV) |
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What is viremia?
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viral dissemination throughout the blood
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Describe CPE (cytopathic effects) of viruses and how they can aid in identifying certain viral infections.
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-viruses will immediately modify infected host cells and some of these changes will be visible on the cell or tissue
1)inclusion body formation-sites of viral replication or product accum. within cell (ex. Rabies-negri bodies) 2)syncytia formation (cell fusion)-multinucleated giant cells which enables the virus to evade immune clearance for a long time -herpes virus, RSV, measles |
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How is diagnosis of viral infection made?
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1)direct exam. of clinical samples-electron microscopy, detection of viral ags by fluorescent ab, hemadsorption (RBC's stick to surface of infected cells that express the viral hemagglutinin), hemagglutination, detection of viral genetic material, etc
2)virus culture-get the virus to replicate in culture and look for CPE, plaque formation, pock formation in embyronated eggs, death or pathology (LD50 or ID50 assays) in a whole animal assay 3)pt. serology-test paired (acute and convalescent) sera, look for an ab titer increase of 4X or greater in the assay |
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What is hemagglutination?
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RBC's are crosslinked by virion hemagglutinin protein and form a network
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How are viral infections controlled in animal populations?
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-they are difficult to treat and most successful approach is AVOIDANCE!
1)quarantine 2)vaccination 3)passive immunization 4)antiviral agents-halt viral replication but many toxic to host as well |
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What are prions and what are they implicated in?
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-new class of infectious agent, they are proteins, not viruses
-have very long incubation periods and always lethal -most are slowly progressive CNS infections -ex: mad cow disease, scrapie in sheep, CJD in humans |
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Describe the general characteristics of Acute respiratory diseases.
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-describes multiple infections of the nasal cavity and pharynx predominately viruses
-generally referred to as upper resp. diseases -lab workup not typical but antigen detection polymerase chain rxn, serology, and sometimes virus isolation can be performed for some agents if needed -one or two agents account for most cases and must consider the age, season,and location (epidemiology) -named by the anatomic site and these infections are typically benign, transitory, and self-limited -see nasal discharge, sneezing, cough, malaise, throat discomfort with 2-4 days incubation -fever not typical |
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How is ARD treated?
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supportive sx relief
-antibiotics will not help |
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Describe the general characteristics of the Rhinovirus class.
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-picoRNA virus family, ss RNA + sense
-nonenveloped -over 130 ag types known so pts. will get repeated colds -most human forms use ICAM-1 as cell surface receptor (Canyon hypothesis states that binding site for ICAM is located in deep clefts in the virion capsomeres, the inaccessibility of binding sites partially explains why recovery from one cold virus does not guarantee immunity to the other types that use same receptor) |
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Describe the epidemiology of rhinovirus.
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-infections are hyperendemic in winter months (the virus prefers a temp. of 33 C)
-greatest incidence is in children and young adults -hands and direct contact are a major factor in person/person transmission -an ab response occurs with infection but solid immunity is only transient (18 mos) |
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How does the rhinovirus stimulate expression of ICAM?
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stimulated by interferon (a host repsonse to viral infection)
-rhinovirus uses ICAM molecule receptor to infect host cells |
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How is rhinovirus spread controlled?
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transmission by aerosol and fomites
-hands are a major vector so handwashing an disinfection of objects are best means of control -cold eeze and zicam employ zinc gluconate to antagonize infectivity but problems with Zicam is an important warning to pts. -can now give Picovir (pleconaril) |
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What is Picovir (pleconaril)?
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developed to treat colds caused by rhinovirus
-binds to virion in canyon pocket and prevents receptor binding and proper virion uncoating -enteroviruses and rhinoviruses using LDL receptors-only virion uncoating is inhibited -effective in several trials but NOT approved for general use yet |
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What are 3C protease inhibitors and BIRR4?
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-can be given to treat common cold
1)3C protease inhibitors-prevents maturation of virus by halting intracellular protease activity 2)BIRR4-binds viral receptor site, interferes with cell infection -soluble engineered form of ICAM-1 delivered by nasal spray |
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Describe the general characteristics of adenoviruses.
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-dsDNA genome, non-enveloped with a complex icosahedral capsid structure
-resistant to phys./chem. agents, survive well outside body -52 antigenic types known -types 4,7 cause most adenovirus ARD in US - |
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Describe Adenovirus infection.
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lytic, persistent, and latent infections known
-infection of epithelial cells of resp. and enteric organs -latency observed in lymphoid tissue with reactivation by immunosuppression possible |
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Describe adenovirus replication.
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-viral DNA replication and assembly occur in cell nucleus
-dense inclusions observed in infected cell nucleus -virus protein E1A inactivates cell tumor suppressor protein Rb to promote cell cycle progression and transcription of viral genes -virus produces additional proteins, E1B-55K and E4-ORF3 to antagonize host cell p53 protein, increase its destruction and prevent it from activating other genes |
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What illnesses does adenovirus cause?
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-primary targets are children and young adults
-the host immune response is key in the resolution and suppression of infections b/c the virus can evade host immune responses and establish permanent latency causes: 1)adult pharyngitis-most frequent cause of pharyngitis in adults, peaks in winter mos. 2)Pharyngoconjunctival fever (PCF)-one-sided conjunctivitis with pre-auricular adenopathy, often swimming pool associated 3)pertusses like syndrome of young adults (types 4, 7)-military, college dorms |
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Describe adenovirus epidemiology.
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human reservoir only
spread by aerosol, fomites, close contact, or fecal-oral routs -fingers may spread virus to eyes -primary targets kids, young adults |
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How is adenovirus detected?
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-antigen detection, rapid tests available
-PCR tests to detect virus genome -they may est. permanent infections, making it difficult to be sure virus detection is necessarily correlated to the pt. disease at time of the test |
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Describe the general characteristics of coronaviruses.
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-ssRNA, + sense strand
-enveloped capsid with helical symmetry -pleomorphic virions with unique crown-like projections -2 major antigenic types recognized -optimum temp 33-35 C -infect epithelial cells of resp. tract |
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What is thought to be the second most common cause of the cold after rhinoviruses?
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coronaviruses
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Who is mostly affected by coronaviruses?
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all ages, mostly in children and infants
-sx identical to common cold |
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How is coronavirus spread?
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by aerosols and droplets
-infection is sporadic or in winter-spring seasons -one strain typically predominates |
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Describe SARS.
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-high case fatality rate
-the cause was a newly emerged coronavirus now thought to be extinct -sequence analysis has revealed that it is unlike any known human or animal coronavirus -thought to be of animal origin, food animals most suspect -only about 50% of original cases were traceable to human pts. -is a highly infectious disease-most pts. transmit to relatively few persons, handful of ppl managed to infect many contacts -needs to be a test to detect pts. early in disease course, genome detection by PCR, pt. ab detection (low sens./spec) |
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Describe the general structure in influenza viruses.
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-segmented, ssRNA genome, capsid with helical symmetry
-virion is enveloped and its surface is covered with spikes -3 major serotypes, types A, B, and C (designated by nucleocapsid proteins) |
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For which type of influenza virus do a large number of subtypes exist and what is responsible for this variation?
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type A viruses
-contains differing envelope spike proteins -H(hemagglutinin)-virion attachment and entry -N(neuraminidase)-progeny virion release and spread from infected cells -therefore, a person with specific abs to subtype H and N spikes will be immune to infection with that particular virus |
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How are influenza viruses named?
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type/location of discovery/isolate number/year/antigenic subtype
ex: A/Hong Kong/68/H3N2 -note that type B viruses do NOT include an H/N subtype ex:B/Malaysia/2506/2004 |
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What are the 2 basic types of antigenic variation seen in influenza viruses?
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1)antigenic drift-RNA viruses are messy replicators which gives them an evolutionary advantage, there are point mutations of H or N proteins that result in minor variations which are sufficient to allow virus to infect human pops. at a constant level and may result in pandemics
2)antigenic shift-genome segment exchanges -recombination involving complete genome segments encoding H or N genes -shuffling of genome segments within the virion during a mixed infection -creates a change to which many ppl are NOT immune and result in epidemics or pandemics |
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Describe the clinical features of influenza (incubation period, mode of spread, etc).
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short incubation period (1-2 days)
very abrupt onset of sx resp. tract entry -virus can retain infectivity on hard surfaces for 1-2 days, fomite and hand transmission is possible -sx persist for about a week and include fever, aches, chills, cough -children have same sx PLUS GI sx, otitis media, and sometimes croup -a long convalescence is common (cough for 1-2 weeks) -rates of infection are highest in children, but complications and deaths more severe at extremes of age and those with underlying med. issues |
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What determines the sx and duration of disease by influenza?
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the extent of epithelial tissue loss, interferon production, and cytokine production levels
-ex:highly pathogenic avian flu induces very high levels of cytokines that create some of the life-threatening responses to infection with that flu type (the cytokine storm) |
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WHat is the single most important cause of medically attended acute respiratory illness?
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influenza
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What are the 4 main possible complications of influenza infection?
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1)severe pulmonary disease
2)Reyes syndrome 3)Guillain-Barre syndrome 4)nosocomial infections |
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Describe the complication of severe pulmonary disease as a complication of influenza illness.
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can have:
1)primary influenza viral pneumonia-most cases have involved underlying debillitation 2)secondary bacterial pneumonia-pts. most often die not due to the virus, but the follow-on bacterial infections, return of fever is an ominous sign, -influenza infection promotes bacterial adhesion by compromising the muco-ciliary escalator system activity and exposing binding sites on the epithelium (S. pneumoniae, S. aureus, HIB) |
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Describe Reyes syndrome as a complication of influenza infection.
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-associated with many viral infections, not just the flu
-acute, sometimes catastrophic systemic disorder -edematous encephalitis, fatty alteration of liver, primarily observed in children 6 mos. -15 years and correlated with flu A/B or chickenpox infections treated with aspirin -has a complex, multifactorial origin that is combo of micro, genetic, and environmental factors |
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Describe Guillain-Barre syndrome as a complication of influenza virus infection.
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-peripheral nervous tissue demyelination, cause unclear but often w/in 2 wks of vaccination
-studies suggest that the risk of GBS from vaccine is substantially lower than that posed by a natural infection with the virus |
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What group of people are disporportionately affected by influenza?
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nursing home residents
-underlying disease, lack of vaccine response -in 2010 a new high-antigen dose inactivated flu vaccine became available for pts. over 65 yo |
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How is the diagnosis of influenza made?
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-in lab, via direct isolation from throat nasopharyngeal swabs for culture, enzyme immnoassay, Hemagglut. inhibition tests, rapid tests now available but sens/spec. lower than viral culture and vary by test manufacturer
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What is the tx for influenza infection?
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-typically supportive and symptomatic relief
1)amantadine and rimantadine- 2)neuraminidase inhibitors |
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Describe amantidine and rimantidine.
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effective against type A virus only, stops uncoating/penetration by halting hemagglut. conformational changes
-used prophylatically in US b/c do not interfere with the immune reaction to the inactivated vaccine so are frequently given with immunizationn -forms of the virus resistant to the antivirals will develop in some cases, |
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What is the mechanism of amantidine.
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-the M2 matrix protein is the target (acts as an ion channel and allows H+ ion entry to acidify interior and allow for uncoating of genome
-hemagglut. makes a conformational changes to have full fusion ability to allow viral membranes to fuse with engulfing veicle of host |
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Describe neuraminidase inhibitors.
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-block the active site of Neuraminidase and leave uncleaved sialic acid residues on the surface of both the host cell and viral envelopes
-b/c viral hemagglut. binds uncleaved sialic acid residues which will lead to viral aggregation at the cell surface and inhibit the cell-to -cell spread of infection -effective against A and B, must be applied w/in 24 hours of sx |
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What is the US approach to preventing the spread of influenza?
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annual mass vaccination of all perons aged 6 mos and older
-multivalent vaccine is made available each season |
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What are the 2 main types of vaccine given across the world for the influenza virus?
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1)inactivated (trivalent) for pts. 6 mos. and older
-whole virus, split, or a subunit (purified surface antigen) given 2)live attenuated-cold-adapted viruses delivered by nasal spray (flumist) for non-pregnant pts. 2-49 yo |
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Describe the 2010 fluzone high dose vaccine for influenza.
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for pts. over 65 yo
-trivalent inactivated vaccine with 4-fold increased antigen dosage levels -it is hoped that this vaccine will induce a stronger immune response in elderly |
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Describe the 2011 Intradermal TIV vaccine for influenza.
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-decreased levels of antigen and injected dose volume
-viruses employed in all vaccines are grown in embryonated chicken eggs -pts. don't have permanent immunity to any flu virus after vaccination, reliable duration about 18 mos. -2 admin. of vaccine (4 weeks apart) are recommended for kids 6 mos-8 yrs |
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What are the flu vaccine target groups?
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persons age 65 +
-residents of nursing homes or other chronic care housing facilities -adults and kids with chronic pulmonary or CV disorders -those with chronic diseases such as asthma, diabetes, renal dysfunction, or immunosuppression, peds pts. on long term aspirin therapy (Reyes syndrome risk), health care workers |
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How is the flu vaccine formulated?
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-it is a guess based on the most prevalent viruses in circulation 6-9 months before the projected delivery date of vaccine
-in northern hemisphere goal is to admin. vaccine in October well before the normal start of flu season |
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What strains of flu are associated with epidemics?
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A and B
-C causes inapparent infections and mild disease (sometimes epidemics) in children - |
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When is the typical peak in influenza infection?
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during winter season
-typical peak about 2 weeks after initial outbreak appears |
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Who is at greatest risk for flu infection?
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seronegative ppl
-most cases are in children and young adults -school age children play key role in flu dissemination through the community >80%of fatalities occur in the >65 age group |
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What species does influenza A infect?
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birds, pigs, horses, and humans
-may be found in endemic, epidemic, or pandemic forms |
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What species does influenza B infect?
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humans and seals
-can create epidemics but does not have the potential to create pandemic outbreaks like the type A viruses (a limited host range may limit the capacity to undergo sudden antigenic shifts) |
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How was the 1918 flu exceptional as compared to other flu viruses?
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1)it appeared early (october) and departed quickly
2)had an exceptional lethality rate 3)frequently killed pts. rapidly and directly 4)highest death rate in young adults -think recombination may have occurred within the H gene of this flu strain |
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What is the significance of the H5 bird flu?
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-experts have worried that the spread of "bird flu" across Asian chicken flocks signaled an imminent human pandemic
-the H5 human infection case fatality rate is extraordinarily high leading to fears that we faced a new killer flu pandemic -we have been unable to stop spread of H5N1 in birds |
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Describe the novel May 2009 influenza strain.
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H1N1 emerged in Mexico and spread quickly
-emerged in May and was the herald wave for the 09/10 pandemic |
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Describe influenza surveillance and the shortcomings of them.
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-3-4 influenza strains are in wide circulation every year
-normally, these are already identified strains -WHO runs a flu monitoring program and recognition of a new strain in humans provokes an alert -several weak links exist in this program tho, global surveillance is inadequate -current vaccine production methods are limited in scope and far too slow -if killer strain emerges in late summer, the seasonal flu vaccine production will be well underway with little possibility that the vaccine could be changed -the flu strain could kill chickens could impact egg production (vaccines are made from embryonated chicken eggs) -stockpiles of antivirals are insufficient in scale (w/o the vaccine complete protection demands drug admin. for the duration of the epidemic normally 6-10 weeks) |
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Describe the general features of croup.
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-syndrome of fever, hoarseness, and a barking cough in kids 6-18 mos. of age resulting from laryngeal obstruction
-croup due to laryngotracheobronchitis is a complication of an URT infection inflammatory response that constricts the trachea below the vocal cords due to laryngeal edema -causative agents are PIV type 1>PIV type 2 >>RSV |
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Describe the general features of the parainfluenza viruses.
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-nonsegmented, negative sense ssRNA genome (structurally similar to but distinct from influenza virus in biological properties and pathogen.)
-enveloped with protein spikes -4 known serotypes -H and N activities are present on the same peplomer molecule -novel fusion (F) protein causes syncytia (multinuc. giant cells) formation - |
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How does parainfluenza virus spread from person to person?
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via droplets from infected people
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Describe the clinical manifestations of PIV.
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-replication in URT epithelial cells esp. nasal turbinates and ciliated epithelium of the resp. tract
-2-6 day incubation period -sx include harsh cough, rhinitis, sore throat, SOB, virus usually confined to URT tissues - |
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What is the signal illness for PIV?
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Croup (2-3% of total PIV infections)
-caused by PIV types 1 and 2 mostly |
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How does PIV manifest in adults vs. kids?
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as a nonspecific URT infection
-in kids may invade lower airways, too |
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What are some PIV infection complications?
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-otitis media-infection causes eustachian tube dysfunction producing a neg. pressure in the middle ear antagonizing the clearance of nasopharynx bacteria
-parotitis |
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Describe PIV epidemiology.
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-seasonal upsurge in cases with Fall-Winter having greatest incidence
-prevalent in kids -types 1 and 2 have a complex, alternating epidemic periodicity in autumn season -type 3 is endemic (most kids have ab in 1 year) which sporadic epidemic outbreaks emerging most frequently in late winter or spring seasons -type 4 is new -life long immunity after infection is NOT observed, virus somehow interferes with full immune memory establishment -repeat infections with homotypic viruses are seen, but are usually mild |
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How is PIV diagnosed and treated?
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-detection of viral isolation from nasal washings or throat swabs is preferred method
-virions are stable and may be maintained for several days in viral transport medium -direct FAB or RT-PCR tests on cells/syncytia in nasal washings -give supportive tx and no vaccines available currently |
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Describe the general features of RSV infection.
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-in the paramyxovirus family (same as PIV, mumps, measles)
-important cause of LRT illness in infants and kids and most frequent cause of fatal acute resp. tract infection in infants -has a marked tendency to create syncytia in tissue culture |
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Describe the general features of the RSV viruses.
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-similar structure to other paramyxoviruses but with a smaller nucleocapsid
-neg. sense ssRNA helical genome, enveloped -lacks H and N, viral G protein is responsible for attachment and the F protein for host cell fusion -2 strains (A and B) recognized based on G protein antigenic variations -A subtype usually predominate and cause more severe disease |
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Describe the clinical manifestations of RSV infection.
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it is a resp. tract disease that ranges from a cold to severe pneumonia
-in older kids and adults:URT infection, sx identical to common cold, subject to re-infection, sx usually mild -infants:bronchiolitis and/or pneumonia, sometimes croup, direct invasion of epithelium and spread (formation of syncytia and induction of immune responses), excess mucus production, narrowing and plugging of bronchi, sx include fever, cough, dyspnea with tachypnea, and cyanosis -damage to the epithelial cells is a direct result of viral invasion and the host's immune response to infection |
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What factors would make an infant more likely to be RSV infected?
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-infant born in April through September, the 6 mos. preceding RSV season
-is in a family with older children -attends day care -lives in crowded conditions -was not breast fed |
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How is RSV spread?
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through fomites, direct contact, and resp. route
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Describe RSV epidemiology.
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-prevalent in young kids, esp. day care centers
-1% of all pediatric infections are serious enough to be hospitalized -expect annual epidemics each winter -adults get re-infected and transmit RSV to newborns -most likely introducer of RSV is a preschool or school age sibling |
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How is the diagnosis of RSV made?
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1)clinical presentation and time of year
2)detection of viral antigen-immuno-fluorescence tests or ELISA on nasal washings -virus difficult to culture, must innoculate samples quickly 3)serology-look for 4 fold increase in ab titer in serum usually confirmatory -collect acute and convalescent stage sera spanning 2-3 wk interval |
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How is RSV treated and prevented?
|
-supportive care esp in mild cases
-Ribivirin option for more severe cases admin. by inhal. -passive immunization with anti-RSV immunoglobulin for premies (5 monthly doses commencing in Nov) -prevention difficult, virus is easily transmitted in hospital setting -no vaccine - |
|
|
What do hemagglutinating viruses bind to cause hemagluttination?
|
they bind to sialic acid and cause RBCs to agglutinate
|
|
|
What is a hemagglutination inhibition assay?
|
a method used to reveal the presence of specific influenza neutralizing abs in pt. serum
-these abs, if present, will prevent the hemagglutination of RBCs -they are performed so that the presence/absence of interfering abs can be readily recognized -to be indicative of infection with virus, a minimum 4 fold increase in HI ab titer must be observed (paired sera samples, acute and convalescent are subjected to HI titer) |
|
|
What are the most common bacterial causes of otitis externa?
|
1)P. aeruginosa
2)S. aureus |
|
|
What are the sx and tx of otitis externa?
|
typically present with otalgia and otorrhea
--often require use of systemic analgesics -topical antibacterial agents can be used if infection is localized -fever >38.3 C indicates more than localized involvement and may require use of oral abx |
|
|
Describe the characteristics of P. aeruginosa which causes otitis externa.
|
-gram neg. bacilli, encapsulated, pigment producer (pyocyanin, pyoverdin)
|
|
|
Describe the characteristics of S. aureus which causes otitis externa.
|
gram positive cocci in clusters
-encapsulated -coagulase positive -Beta-hemolytic |
|
|
What is the wood's lamp illumination test used for detection of?
|
Pseudomonas infections causing otitis exerna
-the organism will glow green under the illumination of Wood's lamp |
|
|
What is sinusitis?
|
inflammation within the paranasal sinuses, may or may not be purulent
-can be acute, subacute, or chronic |
|
|
What are the most common bacterial causes of otitis media and sinusitis?
|
1)S. pneumoniae
2)H. influenzae 3)moraxella catarrhalis |
|
|
Describe the characteristics of S. pneumoniae which causes otitis media.
|
gram pos. diplococci
-virulent strains are encapsulated -alpha hemolysis |
|
|
What is the gram stain of H. influenzae?
|
gram neg. coccobacilli
|
|
|
What is the gram reaction of moraxella catarrhalis?
|
gram neg. diplococci
-it is also oxidase positive |
|
|
How is otitis media treated?
|
if bacterial otitis media is suspected abx can be prescribed
-DOC:amoxicillin (w or w/o clavulanate), alternatives available as well such as azithromycin -in chronic cases tympanostomy tubes may be inserted |
|
|
How is sinusitis diagnosed?
|
usually by clinical presentation and history
-nasal cytology (biopsy) is an option along with CT scan and allergy testing |
|
|
What is the treatment for sinusitis?
|
varies depending on type and offending agent
-nasal irrigation, analgesics, OTC decongestants, abx, nasal steroids or surgery |
|
|
Describe the characteristics of corynebacterium diphtheriae.
|
gram pos. pleomorphic bacilli, often club-shaped
-has a "chinese letters" appearance -grows aerobically on blood agar -has a phage encoded exotoxin=diphtheria toxin -contain metachromatic granules, can see them in grain stain or stain specifically for them |
|
|
Describe the diphtheria toxin.
|
-AB exotoxin produced when Iron concentration is low
-the toxin binds a heparin-binding EGF receptor and is endocytosed into the cell, then dissociates into A and B fragments -the A subunit is translocated to cytosol where it inactivates EF-2 halting protein synthesis |
|
|
What are the 2 types of diphtheria?
|
1)cutaneous-inoculation into broken skin, papule develops into a non-healing ulcer
2)respiratory -pharyngeal colonization, sudden onset of malaise, exudative pharyngitis, low-grade fever, and lympadenitis -formation of pseudomembrane=network of fibrin + bacteria + WBCs +necrotic epithelial cells -systemic complications |
|
|
Describe the pathogenesis of diphtheria.
|
adherence and proliferation of the bacteria-->2-6 days later localized damage due to exotoxin, inhibition of protein synthesis and cell death-->local necrosis and edema (thick grayish to black pseudomembrane and bull neck)
-if exotoxin production is continual will lead to systemic toxicity and myocarditis and demyelination |
|
|
Describe the epidemiology of diphtheria.
|
-found worldwide
-person to person spread via resp. droplets or skin contact -it is uncommon in developed countries due to immunization -resp. diphtheria is a reportable disease in the US |
|
|
How is the diagnosis of diphtheria made?
|
1)clinical examination
2)gram stain 3)bacteriologic isolation in culture (on blood agar, cysteine-tellurite agar-black colonies, and Loeffler's medium) -blood agar used to rule out hemolytic strep. 4)test isolates for toxin production -Elek test-immunodiffusion assay to detect secretion of exotoxin -PCR-detect presence of TOX gene -ELISA-detect exotoxin -immunochromatographic strip assay-very sensitive assay to detect diphteria exotoxin |
|
|
How is diphtheria treated?
|
-neutralize the exotoxin by admin. of diphtheria antitoxin (from CDC)
-abx therapy, DOC: penicillin or erythromycin -isolation to minimize spread -admin. of vaccine once pt. recovers -formalin inactivated toxin |
|
|
Describe the general characteristics of the causative agent for pertussis: Bordetella pertussis.
|
-small, gram neg. coccobacilli
-grows aerobically on enriched agar -several virulence factors in addition to endotoxin (adhesins and exotoxins) |
|
|
Describe the adhesins that pertussis bacteria uses.
|
-uses 3 adhesins to mediate the attachment and colonization of Bordotella pertussis to cilliated resp. epithelium
1)Pertactin=P69 2)filamentous hemagglutinin (FHA) 3)fimbriae -P69 and FHA contain RGD sequences that mediate attachment to integrins on epithelial cells |
|
|
Describe the pathogenesis of pertussis.
|
-exposure leads to bacterial attachment to ciliated resp. epithelial cells via adhesins and pertussis toxin
-localized proliferation and phagocytosis by macrophages but bacteria inhibit intracellular killing and can survive and replicate inside cells -release of exotoxins causes local tissue damage, systemic toxicity, and lymphocytic leukocytosis by inhibiting extravasation of lymphocytes |
|
|
What is the normal incubation period of pertussis?
|
7-10 days
|
|
|
What are the 3 stages of disease by pertussis?
|
1)catarrhal stage
2)paroxysmal stage 3)convalescent stage |
|
|
Describe the Paroxysmal stage of pertussis.
|
attacks or spasms, paroxysmal coughing often followed by vomiting, characteristic whoop due to labored inspiration following coughing, each attack lasts 1-2 mins, pt. feels generally well btwn attacks, epithelial cells are extruded impeding mucus clearance which also contributes to airway constriction
-sx last 2-4 wks but can be longer -many complications can occur including dehydration, wt. loss, insomnia, subconjunctival hemorrhage, etc |
|
|
Describe the catarrhal stage of pertussis.
|
inflammation of mucus membranes, presents as a nonspecific URT syndrome with slow onset (nasal congestion, runny nose, sore throat, low grade fever, etc), last for 1-2 wks, pts. highly contagious in this stage
|
|
|
Describe the convalescent stage of pertussis.
|
recovery
-paroxysms decrease in # and severity with gradual recovery over 2-6 wks -secondary complications can occur including seizures, death, pneumonia, and encephalopathy |
|
|
Describe the epidemiology of pertussis.
|
-strictly a human disease, often considered a peds disease
-worldwide epidemics occur every 2-5 yrs |
|
|
How is the diagnosis of pertussis made?
|
definitive diagnosis includes culture and/or PCR
-culture on an enriched medium: Bordet-Gengou or Regan lowe agar from a saline nasal wash or a nasopharyngeal swab -PCR is highly sensitive |
|
|
How is pertussis treated?
|
-macrolide abx are DOC and prophylaxis for nonimmunized contacts
-erythromycin for pts. >1 month -azithromycin <1 month -can also give TMP-SMZ for pts. > 2mos. -give Tdap (booster) or dTap (series) immunization |
|
|
Describe general characteristics of pneumonia?
|
-inflammation and consolidation of lung tissue
-due to an infectious agent, bacteria, fungi, viruses, parasites -6th leading cause of death in US -most common infectious cause of death |
|
|
What are the 2 sources in which pneumonia infection is divided into?
|
1)hospital acquired-develops 72 hrs or more following admission
2)community acquired (CAP)-develops in ppl with limited or no contact with medical settings |
|
|
What are the 2 divisions of Community acquired pneumonia?
|
1)typical-S. pneumo, H. influenzae, S. aureus, some K. pneumo.
2)atypical-zoonotic, nonzoonotic, usually have extrapulmonary involvement (systemic) |
|
|
What is the most common bacterial cause of CAP?
|
S. pneumoniae
followed by H. influenzae |
|
|
Describe atypical pneumonia.
|
-often cause systemic infections and have extrapulmonary involvement
-difficult to diagnose -unresponsive to Beta-lactams -most common forms caused by 3 zoonotic (Chlamydia psittaci, Francisella tularensis, Coxiella burnetti) and 3 non-zoonotic organisms (Chlamydia pneumo., mycoplasma pneumoniae, legionella pneumo.) |
|
|
Which bacteria that causes pneumonia is sensitive to optochin?
|
S. pneumoniae
|
|
|
What is the epidemiology of pneumonia?
|
-occurs more in colder, wetter mos.
-viral infections increase risk of pneumococcal pneumonias -incidence of disease is greater in young children and adults >65 yo -asymptomatic pts. major reservoirs -approx. 90 serotypes -organism is aspirated and allowed to replicate |
|
|
What are the virulence factors of pneumococcus?
|
-capsule is a major virulence factor (basis for serotyping and vaccine), the capsule inhibits phagocytosis, interferes with complement activity and prevents C3b opsonization of the bacteria
-has pneumolysin which interacts with target cell membrane, forms transmembrane pores and results in cell lysis and activates complement -peptidoglycan-teichoic acid complex illicits a big immune response -IgA protease degrades host secretory IgA -hydrogen peroxide causes apoptosis in host cells and elminates competing bacteria -pili contribute to colonization of the URT and activate large quantities of TNF -surface proteins-choline binding proteins act as adhesins that interact with carbs on the surface of pulmonary epithelial cells -autolysin causes lysis of pneumococcus and results in release of pneumolysin along with host cell apoptosis, does this in response to abx therapy and stationary phase and is attempt by organism to dampen host immune response -contains Hyaluronidase and Neuraminidase |
|
|
What is the mechanism of pneumonia infection?
|
-enters resp. tract through aspiration or other infected site
-organism multiplies in tissue and stimulates immune response -multiplication results in disease from heightened immune response -pneumonia develops -pathology and eventually hope for resolution |
|
|
Describe the significant signs/sx of pneumonia.
|
-sudden onset of fever, chills, chest pain, productive cough with purulent sputum, bacteremia in many cases, CXR shows consolidation in lungs
pneumococcus is responsible for a number of diff. diseases including bacterial meningitis, otitis media, sinusitis following dissemination can see these diseases as well as arthritis and peritonitis |
|
|
How is diagnosis of pneumonia made?
|
-colonies are small, round and green-colored on blood agar
-exhibit alpha hemolysis -gram pos. lancet shaped diplococcus -non-staining capsules -presumptive ID is optochin sensitivity -confirmation by bile solubility test (bile will lyse S. pneumoniae and will have no other effect on alpha-hemolytic strep) -quellung rxn to observe capsules -agglutination tests for capsular polysaccharides -genetic probe test looks for S. pneumoniae specific rRNA |
|
|
How is pneumonia treated?
|
DOC: penicillin G
-used in empiric therapy and in children but resistance becoming more prevalent -if strains are resistant to B-lactams give fluoroquinolones and vancomycin still used in children (issues with absorption into lungs) |
|
|
How is pneumonia prevented?
|
-Vaccines: 23 valent capsular polysaccharide vaccine, recommended for persons >65 and with predisposing factors
-7 valent capsular polysacc. vaccine-80% of infections in kids 6 yrs and younger, conjugated to a carrier protein so more immunogenic -also accounts for 74% of strains of penicillin-resistant S. pneumo. |
|
|
Describe the characteristics of H. influenzae.
|
non motile, gram neg. coccobacillus
-contains lipooligosaccharide (similar to LPS) -encapsulated or non-encapsulated strains -colonies require factors from RBCs for growth but do not have hemolytic properties -ability to lose its capsule and still capable of causing disease -most strains classified as opportunistic pathogens (nontypeable H. influenzae is part of the normal flora in 80% of population) -HIB can cause pneumonia in infants and young kids, also in debilitated hosts |
|
|
What are the virulence factors of H. influenzae?
|
1)polyribosylribitol phosphate (PRP) capsule-renders resistant to phagocytosis by PMNs
2)all virulent strains produce neuraminidase and an IgA protease 3)fimbriae are required for successful colonization in the nasopharynx 4)LOS (similar to LPS) |
|
|
Describe the pathogenesis of H. influenzae non-encapsulated strains.
|
-they produce adhesins that bind to mucins on the ciliated epithelial cells of the resp. tract
-in all cases causes: loss of cilia, inflammation, and sloughing of damaged epithelial cells |
|
|
How is identification of H. influenzae CAP made?
|
-gram staining
-serological testing to determine if encapsulated -difficult to culture due to growth requirements, poor isolation rates in clinical samples and when isolated, morphology depends on medium -ID-latex particle agglutination test (LAT), easier to achieve definitive results than culture methods b/c relies on antigen not bacteria, can be used during or following abx tx |
|
|
Describe how culture of H. influenzae is best accomplished.
|
-preferably chocolate agar with added (X)hemin and (V) NAD at 37 C in enriched CO2 incubator
-blood agar growth only achieved as a satellite phenomenon around other bacteria, colonies appear convex smooth grey or transparent (hard to see) -can be further characterized using catalase and oxidase tests (should be positive) -must then do further serological testing to distinguish btwn. non-encapsulated and encapsulted spp. |
|
|
How is H. influenzae typically treated and prevented?
|
with Beta-lactams (amoxicillin/clavulanic acid)
-if resistance is encountered or in highly invasive infections 3rd gen. cephalosporins are reasonably effective -preventable through use of one of 3 different Hib conjugate vaccines |
|
|
Describe the characteristics of Klebsiella pneumoniae.
|
-can cause both CAP and NP
-non motile, gram neg. bacillus -coated by a thick, slimy capsule -found in normal flora of mouth, skin and intestines -causes pneumonia in alcoholics and person with DM, often seen in homeless pop. |
|
|
What are the virulence factors of Klebsiella pneumoniae?
|
1)primary virulence factor-polysaccharide capsule which is antiphagocytic and prevents MAC mediated lysis
2)LPS 3)adhesins-either fimbrial or non-fimbrial -causes aggressive necrotizing CAP with predilection for upper lobes after aspiration of the organism, severe illness with rapid onset -often fatal, even with tx |
|
|
How is klebsiella pneumonia spread?
|
through direct contact
-host aspirates microbes into LRT -there is necrotic destruction of alveolar spaces, inflammation and hemorrhage in lungs -pts. have an acute onset high fever and productive cough with thick, blood tinged sputum, infection usually leads to abscess formation, cavitation and chest pain - |
|
|
How is diagnosis of Klebsiella made and what is the tx?
|
-gram stain/culture-mucoid capsule
-currant jelly sputum -CXR often shows cavitation -empiric therapy used but with rapid progression of disease about 50% of pts. die anyways -susceptibility testing rqrd.-use combos of fluroquin., aminoglycosides, and 3rd gen.cephalosporins |
|
|
Describe the significant signs/sx of pneumonia.
|
-sudden onset of fever, chills, chest pain, productive cough with purulent sputum, bacteremia in many cases, CXR shows consolidation in lungs
pneumococcus is responsible for a number of diff. diseases including bacterial meningitis, otitis media, sinusitis following dissemination can see these diseases as well as arthritis and peritonitis |
|
|
How is diagnosis of pneumonia made?
|
-colonies are small, round and green-colored on blood agar
-exhibit alpha hemolysis -gram pos. lancet shaped diplococcus -non-staining capsules -presumptive ID is optochin sensitivity -confirmation by bile solubility test (bile will lyse S. pneumoniae and will have no other effect on alpha-hemolytic strep) -quellung rxn to observe capsules -agglutination tests for capsular polysaccharides -genetic probe test looks for S. pneumoniae specific rRNA |
|
|
How is pneumonia treated?
|
DOC: penicillin G
-used in empiric therapy and in children but resistance becoming more prevalent -if strains are resistant to B-lactams give fluoroquinolones and vancomycin still used in children (issues with absorption into lungs) |
|
|
How is pneumonia prevented?
|
-Vaccines: 23 valent capsular polysaccharide vaccine, recommended for persons >65 and with predisposing factors
-7 valent capsular polysacc. vaccine-80% of infections in kids 6 yrs and younger, conjugated to a carrier protein so more immunogenic -also accounts for 74% of strains of penicillin-resistant S. pneumo. |
|
|
Describe the characteristics of H. influenzae.
|
non motile, gram neg. coccobacillus
-contains lipooligosaccharide (similar to LPS) -encapsulated or non-encapsulated strains -colonies require factors from RBCs for growth but do not have hemolytic properties -ability to lose its capsule and still capable of causing disease -most strains classified as opportunistic pathogens (nontypeable H. influenzae is part of the normal flora in 80% of population) -HIB can cause pneumonia in infants and young kids, also in debilitated hosts |
|
|
What are the virulence factors of H. influenzae?
|
1)polyribosylribitol phosphate (PRP) capsule-renders resistant to phagocytosis by PMNs
2)all virulent strains produce neuraminidase and an IgA protease 3)fimbriae are required for successful colonization in the nasopharynx 4)LOS (similar to LPS) |
|
|
Describe the pathogenesis of H. influenzae non-encapsulated strains.
|
-they produce adhesins that bind to mucins on the ciliated epithelial cells of the resp. tract
-in all cases causes: loss of cilia, inflammation, and sloughing of damaged epithelial cells |
|
|
How is identification of H. influenzae CAP made?
|
-gram staining
-serological testing to determine if encapsulated -difficult to culture due to growth requirements, poor isolation rates in clinical samples and when isolated, morphology depends on medium -ID-latex particle agglutination test (LAT), easier to achieve definitive results than culture methods b/c relies on antigen not bacteria, can be used during or following abx tx |
|
|
Describe how culture of H. influenzae is best accomplished.
|
-preferably chocolate agar with added (X)hemin and (V) NAD at 37 C in enriched CO2 incubator
-blood agar growth only achieved as a satellite phenomenon around other bacteria, colonies appear convex smooth grey or transparent (hard to see) -can be further characterized using catalase and oxidase tests (should be positive) -must then do further serological testing to distinguish btwn. non-encapsulated and encapsulted spp. |
|
|
Describe general characteristics of pneumonia?
|
-inflammation and consolidation of lung tissue
-due to an infectious agent, bacteria, fungi, viruses, parasites -6th leading cause of death in US -most common infectious cause of death |
|
|
What are the 2 sources in which pneumonia infection is divided into?
|
1)hospital acquired-develops 72 hrs or more following admission
2)community acquired (CAP)-develops in ppl with limited or no contact with medical settings |
|
|
What are the 2 divisions of Community acquired pneumonia?
|
1)typical-S. pneumo, H. influenzae, S. aureus, some K. pneumo.
2)atypical-zoonotic, nonzoonotic, usually have extrapulmonary involvement (systemic) |
|
|
What is the most common bacterial cause of CAP?
|
S. pneumoniae
followed by H. influenzae |
|
|
Describe atypical pneumonia.
|
-often cause systemic infections and have extrapulmonary involvement
-difficult to diagnose -unresponsive to Beta-lactams -most common forms caused by 3 zoonotic (Chlamydia psittaci, Francisella tularensis, Coxiella burnetti) and 3 non-zoonotic organisms (Chlamydia pneumo., mycoplasma pneumoniae, legionella pneumo.) |
|
|
Which bacteria that causes pneumonia is sensitive to optochin?
|
S. pneumoniae
|
|
|
What is the epidemiology of pneumonia?
|
-occurs more in colder, wetter mos.
-viral infections increase risk of pneumococcal pneumonias -incidence of disease is greater in young children and adults >65 yo -asymptomatic pts. major reservoirs -approx. 90 serotypes -organism is aspirated and allowed to replicate |
|
|
What are the virulence factors of pneumococcus?
|
-capsule is a major virulence factor (basis for serotyping and vaccine), the capsule inhibits phagocytosis, interferes with complement activity and prevents C3b opsonization of the bacteria
-has pneumolysin which interacts with target cell membrane, forms transmembrane pores and results in cell lysis and activates complement -peptidoglycan-teichoic acid complex illicits a big immune response -IgA protease degrades host secretory IgA -hydrogen peroxide causes apoptosis in host cells and elminates competing bacteria -pili contribute to colonization of the URT and activate large quantities of TNF -surface proteins-choline binding proteins act as adhesins that interact with carbs on the surface of pulmonary epithelial cells -autolysin causes lysis of pneumococcus and results in release of pneumolysin along with host cell apoptosis, does this in response to abx therapy and stationary phase and is attempt by organism to dampen host immune response -contains Hyaluronidase and Neuraminidase |
|
|
What is the mechanism of pneumonia infection?
|
-enters resp. tract through aspiration or other infected site
-organism multiplies in tissue and stimulates immune response -multiplication results in disease from heightened immune response -pneumonia develops -pathology and eventually hope for resolution |
|
|
Describe the epidemiology of pertussis.
|
-strictly a human disease, often considered a peds disease
-worldwide epidemics occur every 2-5 yrs |
|
|
How is the diagnosis of pertussis made?
|
definitive diagnosis includes culture and/or PCR
-culture on an enriched medium: Bordet-Gengou or Regan lowe agar from a saline nasal wash or a nasopharyngeal swab -PCR is highly sensitive |
|
|
How is pertussis treated?
|
-macrolide abx are DOC and prophylaxis for nonimmunized contacts
-erythromycin for pts. >1 month -azithromycin <1 month -can also give TMP-SMZ for pts. > 2mos. -give Tdap (booster) or dTap (series) immunization |
|
|
How is diphtheria treated?
|
-neutralize the exotoxin by admin. of diphtheria antitoxin (from CDC)
-abx therapy, DOC: penicillin or erythromycin -isolation to minimize spread -admin. of vaccine once pt. recovers -formalin inactivated toxin |
|
|
Describe the general characteristics of the causative agent for pertussis: Bordetella pertussis.
|
-small, gram neg. coccobacilli
-grows aerobically on enriched agar -several virulence factors in addition to endotoxin (adhesins and exotoxins) |
|
|
Describe the adhesins that pertussis bacteria uses.
|
-uses 3 adhesins to mediate the attachment and colonization of Bordotella pertussis to cilliated resp. epithelium
1)Pertactin=P69 2)filamentous hemagglutinin (FHA) 3)fimbriae -P69 and FHA contain RGD sequences that mediate attachment to integrins on epithelial cells |
|
|
Describe the pathogenesis of pertussis.
|
-exposure leads to bacterial attachment to ciliated resp. epithelial cells via adhesins and pertussis toxin
-localized proliferation and phagocytosis by macrophages but bacteria inhibit intracellular killing and can survive and replicate inside cells -release of exotoxins causes local tissue damage, systemic toxicity, and lymphocytic leukocytosis by inhibiting extravasation of lymphocytes |
|
|
What is the normal incubation period of pertussis?
|
7-10 days
|
|
|
What are the 3 stages of disease by pertussis?
|
1)catarrhal stage
2)paroxysmal stage 3)convalescent stage |
|
|
Describe the Paroxysmal stage of pertussis.
|
attacks or spasms, paroxysmal coughing often followed by vomiting, characteristic whoop due to labored inspiration following coughing, each attack lasts 1-2 mins, pt. feels generally well btwn attacks, epithelial cells are extruded impeding mucus clearance which also contributes to airway constriction
-sx last 2-4 wks but can be longer -many complications can occur including dehydration, wt. loss, insomnia, subconjunctival hemorrhage, etc |
|
|
Describe the catarrhal stage of pertussis.
|
inflammation of mucus membranes, presents as a nonspecific URT syndrome with slow onset (nasal congestion, runny nose, sore throat, low grade fever, etc), last for 1-2 wks, pts. highly contagious in this stage
|
|
|
Describe the convalescent stage of pertussis.
|
recovery
-paroxysms decrease in # and severity with gradual recovery over 2-6 wks -secondary complications can occur including seizures, death, pneumonia, and encephalopathy |
|
|
How is otitis media treated?
|
if bacterial otitis media is suspected abx can be prescribed
-DOC:amoxicillin (w or w/o clavulanate), alternatives available as well such as azithromycin -in chronic cases tympanostomy tubes may be inserted |
|
|
How is sinusitis diagnosed?
|
usually by clinical presentation and history
-nasal cytology (biopsy) is an option along with CT scan and allergy testing |
|
|
What is the treatment for sinusitis?
|
varies depending on type and offending agent
-nasal irrigation, analgesics, OTC decongestants, abx, nasal steroids or surgery |
|
|
Describe the characteristics of corynebacterium diphtheriae.
|
gram pos. pleomorphic bacilli, often club-shaped
-has a "chinese letters" appearance -grows aerobically on blood agar -has a phage encoded exotoxin=diphtheria toxin -contain metachromatic granules, can see them in grain stain or stain specifically for them |
|
|
Describe the diphtheria toxin.
|
-AB exotoxin produced when Iron concentration is low
-the toxin binds a heparin-binding EGF receptor and is endocytosed into the cell, then dissociates into A and B fragments -the A subunit is translocated to cytosol where it inactivates EF-2 halting protein synthesis |
|
|
What are the 2 types of diphtheria?
|
1)cutaneous-inoculation into broken skin, papule develops into a non-healing ulcer
2)respiratory -pharyngeal colonization, sudden onset of malaise, exudative pharyngitis, low-grade fever, and lympadenitis -formation of pseudomembrane=network of fibrin + bacteria + WBCs +necrotic epithelial cells -systemic complications |
|
|
Describe the pathogenesis of diphtheria.
|
adherence and proliferation of the bacteria-->2-6 days later localized damage due to exotoxin, inhibition of protein synthesis and cell death-->local necrosis and edema (thick grayish to black pseudomembrane and bull neck)
-if exotoxin production is continual will lead to systemic toxicity and myocarditis and demyelination |
|
|
Describe the epidemiology of diphtheria.
|
-found worldwide
-person to person spread via resp. droplets or skin contact -it is uncommon in developed countries due to immunization -resp. diphtheria is a reportable disease in the US |
|
|
How is the diagnosis of diphtheria made?
|
1)clinical examination
2)gram stain 3)bacteriologic isolation in culture (on blood agar, cysteine-tellurite agar-black colonies, and Loeffler's medium) -blood agar used to rule out hemolytic strep. 4)test isolates for toxin production -Elek test-immunodiffusion assay to detect secretion of exotoxin -PCR-detect presence of TOX gene -ELISA-detect exotoxin -immunochromatographic strip assay-very sensitive assay to detect diphteria exotoxin |
|
|
What are the most common bacterial causes of otitis externa?
|
1)P. aeruginosa
2)S. aureus |
|
|
What are the sx and tx of otitis externa?
|
typically present with otalgia and otorrhea
--often require use of systemic analgesics -topical antibacterial agents can be used if infection is localized -fever >38.3 C indicates more than localized involvement and may require use of oral abx |
|
|
Describe the characteristics of P. aeruginosa which causes otitis externa.
|
-gram neg. bacilli, encapsulated, pigment producer (pyocyanin, pyoverdin)
|
|
|
Describe the characteristics of S. aureus which causes otitis externa.
|
gram positive cocci in clusters
-encapsulated -coagulase positive -Beta-hemolytic |
|
|
What is the wood's lamp illumination test used for detection of?
|
Pseudomonas infections causing otitis exerna
-the organism will glow green under the illumination of Wood's lamp |
|
|
What is sinusitis?
|
inflammation within the paranasal sinuses, may or may not be purulent
-can be acute, subacute, or chronic |
|
|
What are the most common bacterial causes of otitis media and sinusitis?
|
1)S. pneumoniae
2)H. influenzae 3)moraxella catarrhalis |
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Describe the characteristics of S. pneumoniae which causes otitis media.
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gram pos. diplococci
-virulent strains are encapsulated -alpha hemolysis |
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What is the gram stain of H. influenzae?
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gram neg. coccobacilli
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What is the gram reaction of moraxella catarrhalis?
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gram neg. diplococci
-it is also oxidase positive |
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What do hemagglutinating viruses bind to cause hemagluttination?
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they bind to sialic acid and cause RBCs to agglutinate
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What is a hemagglutination inhibition assay?
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a method used to reveal the presence of specific influenza neutralizing abs in pt. serum
-these abs, if present, will prevent the hemagglutination of RBCs -they are performed so that the presence/absence of interfering abs can be readily recognized -to be indicative of infection with virus, a minimum 4 fold increase in HI ab titer must be observed (paired sera samples, acute and convalescent are subjected to HI titer) |
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Describe the general features of RSV infection.
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-in the paramyxovirus family (same as PIV, mumps, measles)
-important cause of LRT illness in infants and kids and most frequent cause of fatal acute resp. tract infection in infants -has a marked tendency to create syncytia in tissue culture |
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Describe the general features of the RSV viruses.
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-similar structure to other paramyxoviruses but with a smaller nucleocapsid
-neg. sense ssRNA helical genome, enveloped -lacks H and N, viral G protein is responsible for attachment and the F protein for host cell fusion -2 strains (A and B) recognized based on G protein antigenic variations -A subtype usually predominate and cause more severe disease |
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Describe the clinical manifestations of RSV infection.
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it is a resp. tract disease that ranges from a cold to severe pneumonia
-in older kids and adults:URT infection, sx identical to common cold, subject to re-infection, sx usually mild -infants:bronchiolitis and/or pneumonia, sometimes croup, direct invasion of epithelium and spread (formation of syncytia and induction of immune responses), excess mucus production, narrowing and plugging of bronchi, sx include fever, cough, dyspnea with tachypnea, and cyanosis -damage to the epithelial cells is a direct result of viral invasion and the host's immune response to infection |
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What factors would make an infant more likely to be RSV infected?
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-infant born in April through September, the 6 mos. preceding RSV season
-is in a family with older children -attends day care -lives in crowded conditions -was not breast fed |
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How is RSV spread?
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through fomites, direct contact, and resp. route
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Describe RSV epidemiology.
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-prevalent in young kids, esp. day care centers
-1% of all pediatric infections are serious enough to be hospitalized -expect annual epidemics each winter -adults get re-infected and transmit RSV to newborns -most likely introducer of RSV is a preschool or school age sibling |
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How is the diagnosis of RSV made?
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1)clinical presentation and time of year
2)detection of viral antigen-immuno-fluorescence tests or ELISA on nasal washings -virus difficult to culture, must innoculate samples quickly 3)serology-look for 4 fold increase in ab titer in serum usually confirmatory -collect acute and convalescent stage sera spanning 2-3 wk interval |
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How is RSV treated and prevented?
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-supportive care esp in mild cases
-Ribivirin option for more severe cases admin. by inhal. -passive immunization with anti-RSV immunoglobulin for premies (5 monthly doses commencing in Nov) -prevention difficult, virus is easily transmitted in hospital setting -no vaccine - |
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What are the 3 risk categories for hospital acquired pneumonia?
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1)patient-severity of illness, length of stay, immunocompromised pt.
2)iatrogenic-pathogens on hands of medical personnel, invasive procedures, abx use 3)organizational-contaminated air and water systems, staffing, layout of facility |
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What organisms predominately cause hospital acquired pneumonia?
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gram neg. aerobes with S. aureus increasingly common
-includes Klebsiella pneumoniae and P. aeruginosa |
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How is diagnosis of a hospital acquired pneumonia made?
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1)identify infectious agent-CXR often helpful
2)tissue biopsy 3)gram stain and culture 4)approach will vary depending on probable pathogen, host factors, and severity of illness |
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How is hospital acquired pneumonia often treated?
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direct coverage of P.aeruginosa which covers other aerobic Gram neg. organisms
-adjust if necessary: do gram stain and culture, abx susceptibility testing, and consider condition of pt. -for P aeruginosa synergistic drug combos are often required such as a 4th gen. cephalosporin + fluoroquinolones -try to avoid broad spectrum abx b/c will suppress normal flora and multi-drug resistant strains are common |
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What are the virulence factors of P. aeruginosa?
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1)pyocyanin-catalyzes ROS production, tissue damage
2)exotoxin A (AB toxin)-inhibits protein synthesis, produced by most clinical isolates and causes ciliastasis and immunosuppression 3)elastases (LasA and LasB) 4)alginate-mucoid polysacc. slime layer functions in adherence to lungs, inhibits mucociliary escalator (important in CF), antiphagocytic glycocalyx inhibits complement and ab binding 5)pili for attachment to host cells 6)LPS endotoxin |
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Describe epidemiology of P. aeruginosa.
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-widespread in environment-inhabits plants, soil, and water
-frequent or transient carriage on skin or in feces -an opportunistic pathogen in the hospital environment -transmission occurs via fomites, plants, fruits, hands |
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What clinical diseases are caused by P. aeruginosa?
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-it is not extremely virulent and requires a significant break in normal defenses to infect
-disease generally in compromised host -can cause UTIs, pneumonia, eye/ear and skin infections from hot tubs and contact lenses, burn pts. Cystic fibrosis |
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What is primary pneumonia caused by P. aeruginosa? Secondary?
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primary-limited to pts. on inhalation therapy with nebulization
secondary-associated with immunosuppression and other types of host compromise -in most pts. see toxicity and progressive cyanosis, development of empyema-pus in body cavity -in CF pts. chronic and recurrent episodes are common, infection confined to resp. tract and infection is B/L and residual damage occurs |
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How is diagnosis of P. aeruginosa made?
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-many media support growth (BAP and MacConkey)
-production of a water soluble blue green pigment -fruity smell and may tinge sputum or pus -pt. may fluoresce |
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What are the cell associated virulence factors associated with S. aureus?
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1)capsule-microcapsule, polysaccharide serotypes 5 and 8
2)protein A-binds to Fc of IgG interferes with phagocytosis and complement activation 3)clumping factor-sometimes referred to as cell bound coagulase -a cell wall protein that binds fibrinogen converted to fibrin=bacterial aggregation 3) |
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What are the extracellular enzymes associated with S. aureus?
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1)coagulase-binds prothrombin=staphylothrombin, converts fibrinogen to fibrin and creates localized clotting (NOT THE SAME AS CLUMPING FACTOR)
2)hyaluronidase, nucleases, lipases, 3)catalase+-inhibits phagocytic killing, interferes with myeloperoxidase system 4)staphylokinase dissolves fibrin clots 5)penicillinase-hydrolyzes penicillin -not virulence factor but leads to survival with inappropriate therapy |
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What toxins are associated with S. aureus?
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1)exfoliative toxins-lyse epithelial junctions (desmosomes), upper layers epithelium so no scarring
2)TSS toxin (TSST-1)-causes major systemic effects, induces the release of cytokines, superantigen 3)enterotoxins-induce release of cytokines, act on neural receptors in upper GI tract and activate vomiting center, superantigen 4)cytotoxins-lyse a variety of cells 5)Panton-Valentine Leukocidin (PVL)-a bicomponent cytotoxin responsible for leukocyte destruction and tissue necrosis, associated with severe necrotic hemorrhagic pneumonia, targets immunocompetent children/young adults that have previously healthy lungs and predisposing viral infection |
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What type of infection is present when Panton-valentine Leukocidin is involved?
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community acquired, NOT nosocomial b/c it occurs in immunocompetent people
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Describe the epidemiology of S. aureus.
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occurs worldwide
-humans carry it in anterior nares and perineum -transmission via close contact, resp. droplets, ingestion from food, shedding of skin lesions, unwashed contaminated hands to fomites to.... |
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What are the respiratory infections caused by S. aureus?
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1) inhalation pneumonia-community acquired several days after onset of flu
2)aspiration pneumonia-hospital acquired via aspiration or intubation 3)hematogenous pneumonia-usually due to release of an infected thrombus from venous system or tricuspid vegetation -can lead to empyema usually due to pulmonary infection |
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What are predisposing factors for staphylococcal pneumonia?
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1)staphylocidal defects of PMNs (ex. CGD)
2)severe diabetic decompensation 3)presence of a foregin body (intravascular devices) |
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What type of hemolysis does S. aureus have on BAP?
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beta
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Will S. aureus grow on mannitol salt agar?
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yes it will grow and ferment the mannitol producing a color change
-it is a facultative halophile |
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What is the tx for Staphylococcal infections?
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-it is an emerging superbug and therefore susceptibility testing is mandatory (MIC, MBC)
--vancomycin not a good choice b/c doesn't penetrate lung tissues -can give linezolid for MRSA -add TMPSMZ to linezolid for VRSA -vaccines are under clincal trials |
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Describe the etiology of URT infections.
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viruses (40% of cases) most common agents
-bacteria (30%) of cases -primary agent is S. pyogenes GABHS |
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Describe epiglottitis.
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-a type of URT infection
-acute bacterial-potentially lethal disease -most common agent is HIB, since the HIB vaccine there has been a shift to adults -Strep. pneumoniae can also cause this -the clinical course is rapid and explosive from mild to severe over 6-12 hrs |
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Describe laryngitis.
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no agent, isolated 33% cases
-gradual and self-limiting course of disease unlike epiglottitis -can be caused by a variety of agents |
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Describe the general characteristics of the genus streptococcus.
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-arranged as chains or pairs
-gram positive -catalase negative -nonmotile -hemolysis (either alpha, beta, or gamma) -growth on enriched medium or BAP (fastidious) -mesophiles, optimal growth at 37 C, -enhanced growth in CO2, capnophiles |
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What is the Lancefield Scheme of classification for Strep?
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-it is based on antigenicity of the cell wall carbohydrate
-Lancefield groups are designated A-U and pathogens are found in 6 groups (ABCDFG) |
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Describe the M protein of S. pyogenes.
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virulence factor found on cell envelope
-protects cell from phagocytosis, inhibits activation of complement -specific antibodies-B cells, aids macrophages and neutrophils in destruction -sequencing emm gene for epidemiological classification Class I, M protein-antigenic Class II, M protein-not antigenic |
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Describe the purpose of Protein F and the capsule of S. pyogenes.
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1)protein F and LTA-tissue tropism, F binds fibronectin surface host cells and LTA attaches to pharyngeal epithelium
2)capsule-composed of hyaluronic acid, inhibits phagocytosis |
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Describe the role of hemolysins used by S. pyogenes.
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1)make streptolysin O-Oxygen labile which destroys RBCs and WBCs
-hemolysis on BAP and in situ -immunogenic and can find abs systemically or during pharyngeal infection 2)streptolysin S-serum induced which destroys RBCs and WBCs hemolysis on BAP and in situ |
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What organism has C5a peptidase and what is its purpose?
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S. pyogenes
-degrades C5a and distrupts mediation of inflammation from recruitment and activation of phagocytic cells |
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What is the function of streptodornase?
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Made by S. pyogenes
-degrades DNA, reduces viscosity of purulent exudates |
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What is the function of streptokinase/fibrinolysin?
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made by S. pyogenes
-generates plasmin, breaks down fibrin and other clot forming proteins -previously used IV to treat PE |
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Describe the streptococcal pyrogenic exotoxins.
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-there are 3 types (A, B, C)
SpeA-superantigen causes massive cytokine release, tissue damage, lysogenized strains -responsible for streptococcal TSS and scarlet fever |
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Describe the epidemiology of S. pyogenes.
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-most common bacterial infection of the throat
-humans are the only reservoir -colonizes both skin and nose -more prevalent winter and early spring -transmitted via resp. droplets (pharyngitis), contact through skin, crowded spaces enhance both -does not survive well in environment, low probability of fomite transmission |
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What are the 3 mechanisms of S. pyogenes pathogenesis?
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1)pyogenic inflammation (suppurative)-pharyngitis
2)toxin-mediated-scarlet fever 3)immunologic disease-rheumatic fever, poststrep. acute glomerulonephritis |
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Describe toxin mediated infection by S. pyogenes.
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-scarlet fever is associated with pharyngitis,skin, soft tissue infections
-more common in kids with repeated strep infections -requires lysogenized S. pyogenes which releases SpeA exotoxin -can superimpose on strep. pharyngitis -punctate, blanching erythematous rash that spreads to ears, axilla, chest to trunk and extremities -sandpaper skin and Pastia lines (thomson sign) which are petechial lesions in the flexor skin folds -will then see desquamation after rash, circumoral pallor, strawberry tongue |
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Describe acute Rheumatic fever as caused by S. pyogenes.
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-ab mediated cytotoxic type II HS rxn
-most serious sequelae and is associated with pharyngitis -protein M abs cross-react with host cell antigens (joints and heart affected) -presents 1-4 wks after untreated GABHS pharyngitis -more frequent in tropical countries and is the main cause of heart disease in young ppl in developing countries -diagnosed by Jones' criteria, must have 2 major or 1 major and 2 minor |
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What are the 5 major manifestations of acute rheumatic fever?
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1)pancarditis-heart inflammation of all parts
2)joint swelling-migratory polyarthritis (knees, elbows and other large jts) 3)chorea 4)subcutaneous nodules 5)rash-erythema marginatum, transient red rings with raised edges |
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What are the 4 minor manifestations of acute rheumatic fever?
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arthralgia
elevated ESR or C reactive protein fever prolonged PR interval |
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Describe what occurs during reactivated acute rheumatic fever.
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happens with recurrence of Group A strep
-damage left side heart valves, mitral and aortic stenosis -more susceptible to infections -protect with prophylactic penicillin -pathognomonic lesions include Achoff bodies |
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Describe poststreptococcal glomerulonephritis.
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type III (immune complex mediated) HS rxn
-occurs mostly in kids -preceded by cutaneous and pharyngeal infections -deposition of immune complexes in the basement membrane of glomeruli leads to activation of complement cascade, PMN recruitment which secrete proteolytic enzymes which results in the glomeruli being destroyed by proteolytic enzymes -children present with puffy face, hematuria, possible hypervolemia due to fluid retention -this has a good prognosis |
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How is diagnosis of S. pyogenes made?
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1)swab of post. pharynx and tonsils
-screening test has high specificity (no false pos), use Rapid antigen detection test to test for A antigen form of C carbohydrate, takes 10-30 mins in office, must confirm neg. with BAP -confirmatory has high sensitivity (no false neg), plate on BAP, anaerobic Beta hemolysis 2)bacitracin sensitivity with A disk-99% GAS inhibited, 95% non-GAS not 3)PYR positive test-presumptive ID of GAS from other Beta-hemo. strep 4)serological tests aid in diagnosis, check for ASO which signifies rheumatic fever or recent infections, can also check for anti-hyaluronidase, anti-Dnase B, Anti-streptokinase |
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How is S. pyogenes infection treated and prevented?
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-duration varies according to degree of invasiveness
-penicillin VK is DOC, 10 day duration -if beta lactam HS use 2nd or 3rd gen. cephalosporins which are less cross reactive, -use macrolides or clindamycin if regional macrolide resistant strain -ultimate goal is to eradicate S. pyogenes before day 9-10 of signs to prevent poststrep disease -no vaccines available |
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At what ages are most cases of S. pyogenes pharygitis seen?
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5-15 years old
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Describe the general characteristics of M. tuberculosis complex (M. africanum; M bovis).
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-high concentration of mycolic acids in cell wall, fungus like or waxy bacteria
-cells and colonies are hydrophobic and clump -high lipid concentration contributes to resistance to detergents and abx with lack of antigenicity -slow growth rate (doubling time 20-24 hrs) -resistance to killing by acidic/alkaline cmpds. (beneficial when preparing MTB sputum samples with NaOH) -obligate aerobes, facultative intracell. pathogens, non-motile, bacilli -acid fast and heat sensitive (killed by pasteurization) -no glycocalyx, no endotoxins, exotoxins, or necrotizing enzymes -damage to humans comes from numbers + CW/VF + immune system response |
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Describe the epidemiology of TB.
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-humans are the only reservoir
-transmission is person to person -spread by aerosol droplet nuclei -about 3 microbes/droplet in aerosol -the virulence of the strains varies -susceptibility to abx varies, MDR strains are multi-drug resistant, XDR strains are extensively drug resistant -bimodal age distribution-infants and older adults |
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Describe why TB is more likely to cause infection in older patients.
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-due to failure of immune system
-possible reactivation of latent infection |
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Describe why TB is more likely to cause infection in infants and immunocompromised.
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due to hematogenous dissemination
-results in meningitis and other sx |
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What are the risk factors for initial infection with TB?
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-close contact with TB case (many children become infected by caregivers)
-residence in long-term care facility -low income/inner city housing -alcoholism or IV drug use -malnutrition -diabetes (30% increase in risk over lifetime) -silicosis (inhalation of silica dust) -immunosuppression |
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What is the risk of progression from TB infection into Tuberculosis?
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-a healthy individual with NO risk factors has a 10% risk over their lifetime
-ppl with HIV have a 7-10% chance per YEAR |
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What are the 2 building blocks of TB?
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1) mycolic acids-ONLY found in Acid fast bacteria
-long chain fatty acids which assist in dehydration resistance 2)mycoside-a mycolic acid + a carbohydrate=glycolipid |
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What is the function of Cord factor in TB?
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it is a virulence factor found in virulent strains of MTB
-a mycoside (2 mycolic acids + 1 disaccharide, trehalose 6, 6'-dimycolate) -produces parallel growth of bacteria and forms cords of cells -inhibits neutrophil migration -damages host cell mitochondria -induces release of TNF and promotes phagocytosis by macrophages |
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Describe the function of sulfatides in TB.
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mycosides that resemble cord factor, with sulfates attached to trehalose
-inhibit phagolysosome production during facultative intracellular growth |
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What is the function of Wax D in TB.
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a complex mycoside that acts as an adjuvant (enhances ab formation to an antigen)
-may activate CMI and DTH |
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What can the combination of Wax D and cord factor cause in host organism invasion with TB?
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may induce granuloma formation
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What is the function of Lipoarabinomannan (LAM) in TB?
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-may suppress macrophage presentation of MHC class II molecules
-may suppress T cell proliferation -provides resistance to ROI -may interfere with macrophage activation (by gamma IFN) |
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What are the 3 potential outcomes of TB infection?
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1)the immune system may be able to entirely destroy the microbes so that NO active case of TB-this happens in 90% of individuals colonized
2)granulomas form and control the pathogen-infection Primary infection-granulomas form and MTB eliminated -Latent TB infection-granulomas form but MTB becomes persistent infection until immunosuppression occurs, age or other diseases contribute and this results in secondary or reactivation of TB 3)the immune system unable to form granulomas -HIV active or medical immunosuppression -macrophages quickly disseminate mycobacteria hematogenously which leads to miliary TB |
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Describe the signs and sx seen in TB primary infection.
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-previously seen in kids, now adolescents and adults too
-primary fever (low grade to 39C), physical exam normal, additional Signs/sx present in 1/4 of ppl including chest pain and pleuritic chest pain, radiographic abnormality-hilar adenopathy |
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Describe the progression phase of primary TB infection.
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the inspired droplet nuclei land in the middle to lower zones of the lungs
-initially creates pneumonitis with collection of neutrophils and edema -eventually enter inactivated alveolar macrophages and multiply, facultative intracellular growth, multiply in cytoplasm or phagosome of cell -although these macrophages are NOT activated they may successfully break down MTB, travel to hilar lymph node, present MTB ags to T helper cells -ESAT 6 is the early secretory antigen target 6 -CFP10 is the culture filtrate protein -sensitized Th cells then multiply and return to infection site, release cytokines to attract and activate macrophages (gamma IFN and TNF alpha), also stimultes Ab production which is not effective b/c TB is intracellular and has external mycolic acids -activated macrophages then destroy bacteria, generate local tissue destruction, promote formation of granulomas due to release of lytic enzymes (causes caseous necrosis) -formation of granulomas or tubercle-Wax D and cord factor, will see areas of necrosis and viable MTB cells surrounded by macrophages -these structures become evident 2-6 wks after infection -TST or Mantoux skin test = POSITIVE due to activation of cellular immunity -positive QuantiFERON TB test, T-spot TB |
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What is a Gohn complex?
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seen in TB and refers to a distinct pattern of gramuloma formation in the lungs
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What is miliary TB?
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results when granulomas unable to contain MTB
-can occur during primary or secondary TB -from necrotic center, tissue surrounding BV is lysed and bacteria is spread hematogenously -in the new site, millet seed structures of macrophages form -due to rapid proliferation of MTB all over body there is loss of organ and system function |
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What is Potts disease?
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when M. TB is present in vertebral bodies
-causes chronic back pain and when untreated results in destruction of vertebrae and permanent disability |
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What are the 4 components of TB diagnosis?
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1)Tuberculin skin test (TST or Mantoux or PPD)
-or IGRA-INF gamma release assay 2)medical history 3)chest X-ray 4)bacteriologic examination |
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Who would you want to perform the TST, Mantoux, or PPD skin test on?
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-concentrate on high risk ppl that are likely to be exposed or infected such as health care professionals
-also ppl likely to develop infection or disease after exposure - |
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How is the TST, Mantoux, or PPD test performed?
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1)step one-injection of PPD just under skin (purified protein derivative)
-use standardized amount in tuberculin units -test results read 48-72 hrs -the PPD activates memory T cells and initiates a DTH response type IV -cannot initiate primary immune response -will be positive if there is a current or previous MTB infection but does not imply active disease or immunity |
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When would there be a false positive PPD test?
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previous BCG vaccination
-since 1921 only available vaccine -infection with closely related microbe M bovis or M kansasii could also cause a false pos. |
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What would cause a false negative with the PPD test?
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-anergic immunocompromised individuals
-resolve with 2 other DTH antigens: tetanus toxoid; mumps; Candida antigen -recently infected individual, takes about 4 weeks for DTH response (do 2 step testing) |
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What is QuantiFERON TB?
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-requires a single pt. visit to draw a blood sample (checks for gamma IFN)
-results available within 24 hrs -does not boost responses measured by subsequent tests which can happen with tuberculin skin tests -is not subject to reader bias that can occur with TST -is not affected by prior BCG vaccination -test is based on presence of IFN-gamma and uses ESAT 6 and CFP 10 to stimulate isolated T cells to produce IFN-gamma |
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How is the chest x-ray used in the diagnosis of TB?
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-rules out the possibility of pulmonary TB in positive TST
-shows any lung abnormalities if sx present -not a confirmatory test |
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Briefly describe the bacteriologic examination techniques used to examine TB.
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1)look at the specimens in the sputum, do a biopsy of the granuloma
2)staining techniques-acid fast stain, turant fluorescent which is preferred by clinical labs 3)from concentrated cultures can use AccuProbe for MTB, rRNA + DNA probe (northern blot) |
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How is TB cultured?
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-must be cultured to determine abx sensitivity
-previously took 1-7 weeks but now have BACTEC system that only takes 6-10 days -test abx sensitivity to 4 first-line abx (RISE) rifampin, isoniazid, streptomycin, ethambutol -the media contains radiolabeled palmitate as the sole carbon source, as MTB multiplies it breaks down the palmitate and liberates radio-labeled CO2 |
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What is culture and growth of TB required for?
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-susceptibility testing throughout tx
-monitor abx tx -ex:rapid molecular detection of TB and rifampin resistance done with 2 mL of processed sputum sample and an automated analyzer -results in about 2 hrs identifies of MTB Rifampin resistance |
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When is tx of TB started?
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upon detection
-positive TST, sx, and X-ray -check close contacts for a positive TST test as well -if they are negative, retest in 3-4 wks which represents the window btwn. exposure and positive DTH -then monitor therapy after beginning with sputum cultures |
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What is single drug therapy used for in the tx of TB?
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used for latent MTB infections
-NOT active disease -low numbers of TB so resistance not likely |
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What is multiple drug therapy used for in the tx of TB?
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4 drugs used RIPE/S
-used for high numbers of TB-intrinsic high mutation rate -never add a single drug to failing tx, always reassess and begin new tx -monitor tx with sputum samples and cultures |
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What is the main objective in TB treatment?
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obtaining culture conversion which is the first negative sputum or biopsy culture in a series
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What is MDR TB?
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multi-drug resistant TB
-resistant to 2 of the first line drugs isoniazid and rifampin |
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What is XDR TB?
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extreme-drug resistant TB
-resistant to isoniazid and rifampin and certain second line drugs such as fluoroquinolones and 1 of 3 injectable drugs (kanamycin, amikacin, capreomycin) |
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What is the BCG vaccine for TB?
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Bacille Calmette Guerin
-developed in 1921 from M. bovis -used extensively to protect children <3 years old -not as effective in adults -loosing effectiveness due to genetic variation in M. bovis |
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Describe the genetically altered BCG vaccine.
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-used against TB
-has addition of gene from Listeria -breaks down membrane of phagosome after uptake in phagosome -released into system and ab-mediated immunity develops -successfully tested in mice against XDR strain, now in phase I clinical trials |
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Describe the general characteristics of the aerobic actinomycetales.
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gram positive aerobes, catalase positive bacilli, colonized humans and animals,
-variety of forms: delicate branched hyphae and coccobacilli -commonly found feeding on decaying vegetation, soil, and in water -have mycolic acid in cell wall (mycobacterium, nocardia, coryne) |
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What are the most common causes of infection by non-tuberculin mycobacterium?
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1)MAC-mycobacterium avium complex (includes M avium and M intracellulare)
2)mycobacterium kansasii |
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What is the most common cause of mycobacterial infection in people with AIDS?
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DMAC
disseminated MAC |
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Describe general characteristics of MAC.
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both are weakly gram positive aerobic bacilli
-strongly acid fast -MAC is a slow growing organism (10-12 hrs doubling time) -colonization does not always lead to disease, grows optimally at 41 C -capable of intracellular growth and disease is a result of host response to infections -has intrinsic resistance to disinfection and is not killed by drinking water chlorination |
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Describe epidemiology of MAC.
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-infection by inhalation or ingestion (this is unlike TB)
-NO person to person transmission -infections found worldwide-ubiquitous like microbe -both organisms cause disease in immunocompromised hosts |
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In what population is pulmonary MAC usually seen?
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immunocompromised NON HIV positive individuals
-people with preexisting infections (lung disease) or immunosuppressed |
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Describe the pathology of MAC.
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can have MAC pulmonary or DMAC
-primary/new not reactivation of latent infection -Initial infection=colonization of GI tract or resp. tract -organism then invades and translocates to mucosal epithelium -infects resting macrophages/inactivated in lamina propria -spread to submucosa and carried to lymphatics and lymph nodes -in immunocompromised hosts it is then spread by hematogenous routs to liver, spleen, bone marrow, etc |
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What are the 3 forms in which MAC usually presents in immunocompetent people?
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1)pulmonary MAC
2)lymphadenitis 3)DMAC |
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Describe fibrocavitary disease (pulmonary MAC) caused by MAC.
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-upper lobe disease
-elderly male smokers -chronic pulmonary sx due to lung disease and can be difficult to distinguish from underlying disease -MAC easily removed from sputum |
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Describe fibronodular disease (pulmonary MAC) caused by MAC.
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-fastidious, elderly, female nonsmokers
-age >50 yrs -lingular or middle lobe infiltrates that look patchy and nodular on Xray -occurs with bronchiectasis -chronically suppress cough reflex which leads to nonspecific inflammatory changes and predisposes to MAC superinfection -similar clinical characteristics and body type (scoliosis, pectus excavatum , MVP) -known as Lady Windermere's disease |
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Describe lymphadenitis caused by MAC in the immunocompetent.
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-seen in children 1-4 yrs old and primarily involves unilateral cervical nodes
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Describe DMAC.
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-most common mycobacterial infection (seen in advanced AIDS)
-CD4<50 cells/microliter and DMAC -signs are FUO, sweating, diarrhea, dyspnea, upper R quad. pain -granulomas not effective in containing MAC (IFN-gamma and TNF alpha important in defense) and disease disseminates hematogenously to any organ -infected organs enlarge and become dysfunctional |
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What are some of the less frequent signs/sx of DMAC?
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1)immune reconstitution sydrome (IRS)
-as HAART progresses there is a rebound in CD4 levels -sudden increase in inflammatory response and produces nonspecific sx |
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Is MAC/DMAC reportable?
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not unless an AIDS confirming illness (unlike TB which is reportable)
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How is diagnosis of MAC/DMAC made?
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1)isolation-non-sterile sputum or bronchial wash may confirm colonization
2)lymph nodes-low bacterial counts may require cultivation for confirmation 3)CXR-important diagnostic to reveal pulmonary lesions 4)mycobacterial cell wall lipids (diff. for each spp.) 5)molecular techniques-PCR, culture cells for DNA/RNA extracts |
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How is MAC/DMAC treated?
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patients are NOT infectious and isolation is NOT required
1)combo therapy used -both HIV and immunocompetent receive 3 drug therapy (macrolides plus ethambutol and rifabutin, E and R hepatotoxic) -tx lasts min. of 1 year or until 12 mos. after sputum conversion 2)surgical incision of affected lymph nodes or lung foci 3)chemoprophylactic tx for HIV -azithro. or clarithromycin with CD4<50 until CD4>100 cells/microliter |
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Describe the general characteristics of Nocardia.
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-strict aerobic bacilli
-form branched hyphae -strongly acid fast, weakly gram positive -catalase positive, gelatin liquefaction, growth on nonselective media -growth is slow -colonies are dry to waxy, white to orange color, have aerial hyphae and grow at 35 and 45 C |
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How is Nocardia identified?
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2 molecular methods/2 target sequences used
-16s rRNA based PCR then sequencing -Restriction fragment length polymorphism (RFLP) for analysis of 16s and rRNA genes |
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Describe the virulence of Nocardia.
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same as MAC
-intracellular growth -numbers disrupt the function of organs and the disease itself is from the host immune system reaction |
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Describe epidemiology of Nocardia.
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-exogenous infections from ubiquitous organisms from soil rich with organic matter
-increased cases-abundance immunocompromised pts. -infections seem to be highest in southwest, dry dusty windy conditions favor aerosol formation -NOT transmitted person to person, NOT acquired in hospital |
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In the study done at Banner Good Sam. on Nocardia, in what patient population was it most likely to occur in?
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in a review of 16 pts
-75% had a chronic pulmonary condition -majority of cases presented as pulmonary disease, many of the pts had underlying debilitating disease like chronic lung disease -other underlying factors were diabetes, hematologic/other malignancies, transplantation, AIDS ->10% had no underlying factors -bottom line is it is usually an opportunistic infection and commonly presents as pulmonary disease |
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How is does Nocardia enter the body?
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-colonization of oropharynx by inhalation
-aspiration of oral secretion which then goes to lower airways |
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Who is at greatest risk for getting Nocardia?
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1)T cell deficiencies-leukemia, AIDS< corticosteroids,
2)chronic pulmonary diseases-bronchitis, emphysema, asthma, |
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How is Nocardia diagnosed?
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examine multiple samples of sputum or pus
-do a gram stain and a modified acid fast stain -CXR and CT is useful in evaluating and monitoring course of infection but really NO characteristic findings seen -biopsies can be done if no definitive ID by sputum -culture-notify lab if nocardia b/c has slow growth over 1 wk, not 48hrs., obscured by fast growers can prevent with BCYE agar or Modified Thayer Martin medium |
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What are the signs of clinical disease by Nocardia?
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-bronchopulmonary infections
-hard to distinguish from other pyogenic organisms but this develops slowly -cavitation and spread to pleura common, fever, cough,etc -it is very uncommon in immunocompetent ppl -suspect Nocardia when you see immunocompromised pt. presenting with pneumonia with cavitation and spread to pleura AND dissemination to CNS or subcutaneous tissues, -may see brain abscess |
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How is Nocardia treated?
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TMPSMX is standard
-can use 2-3 antimicrobials for empiric therapy in severe infection-IV with TMP SMX and amikacin while waiting for susceptibility tests -do IV therapy 3-6 wks but depends on severity, CNS involvement, immune status, resistance to drugs |
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Decribe the general characteristics of Legionella pneumophila.
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-most are serogroup1
-gram neg. bacillus -fimbriae, single polar flagellum, beta lactamase producer, catalase and oxidase positive -grows aerobically but requires a special medium, usually use BCYE (buffered charcoal yeast extract) and supplemented with abx to make selective for Legionella -commonly associated with water |
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Describe the pathogenesis of Legionella pneumophila.
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humans are infected through inhalation of aerosols
-bacteria are opsonized with C3b facilitating their phagocytosis -they survive intracellularly by inhibiting phagolysosome fusion -they then replicated inside phagosome and host cell is killed with phagosome lyses and toxic enzymes released (bacteria also released upon lysis) |
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What 2 disease can result from infection with Legionella?
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1)pontiac fever-a self-limited illness, sx. last 2-5 days and resolve spontaneously w/o tx, causes fever, chills, malaise, myalgia, etc. (no sign of pneumonia)
2)Legionnaires' disease-a severe, acute atypical pneumonia with a high mortality rate -2-10 days incubation period with abrupt onset of sx, fever, chills, dry nonproductive cough, headache, GI and neurologic sx, death is due to shock or resp. failure |
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What is the pathogenesis of Legionnaires' Disease?
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bacilli enter macrophages and multiply-->macrophages die-->release of chemotactic factors causes influx of PMNs and monocytes-->transudation of serum proteins, deposition of fibrin in alveoli and release of cytokines and enzymes-->acute fibropurulent necrotizing pneumonia
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Describe epidemiology of Legionella.
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-widespread in nature and moist environments
-in nature, the bacteria survive and replicate within protozoans -transmitted through aerosols, no person to person transmission -most cases are sporadic -risk factors include presence of a large inoculum, any compromise in pulmonary or immune function (smoking, elderly, alcoholics, etc) -immunity appears to be long lasting (CMI) |
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How is the diagnosis of Legionella made?
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culture is gold standard which requires specialized growth medium
-can also do rapid test for antigen in the urine but only detects infections with serotype 1 -IFA measures serum abs to Legionella, titer of 128 or higher is indicative of infection, or paired sera showing 4 fold increase is diagnostic |
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What is the DOC for Legionella?
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levofloxacin
-severe disease requires careful management and supportive therapy -no tx necessary for pontiac fever |
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Describe basic characteristics of Mycobacterium pneumoniae.
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-smallest of the free living bacteria
-do not have cell walls, cells stain poorly and are pleomorphic in shape -PM contains sterols -have "fried egg" appearance - |
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What is the most common cause of bacterial atypical pneumonia?
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M. pneumoniae
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What are the signs/sx of infection with M. pneumoniae?
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non productive cough that can last 1-2 months, inspiratory crackles, fever, chills, headache, and chest pain
-relapses are common and infection does NOT provide long lasting immunity |
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What is the pathogenesis of M. pneumoniae?
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-bacterial cells adhere to ciliated epithelium by P1 adhesin protein
-release H2O2 adn O2 radical resulting in ciliostasis and epithelial damage which impedes clearance of airways and leads to colonization and irritation of airways - |
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Describe the epidemiology of M. pneumoniae.
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-worldwide distribution year round
-targets 5-20 age group -reservoir is humans |
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How is diagnosis of M. pneumoniae made?
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CXR-infiltration, patchy infiltration
-serology-ELISA (titer>32 or a four fold increase=disease), cold agglutinin assay is a non-specific test -culture from sputum sample is not routine, use Eaton's agar which contains serum and abx, cultures grow slowly over months and |
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What is the DOC for M. pneumoniae?
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azithromycin
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What are the general characteristics of Chlamydia?
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-very tiny, non-motile, coccoid shaped bacteria
-obligate intracellular parasites found within intracytoplasmic inclusions -gram neg., no Peptidoglycan, LPS, have major outer membrane proteins that are cross-linked by disulfide binds to provide structural integrity -are unique in that they exist in 2 different forms (have unique life cycle); elementary and reticulate bodies |
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Decribe the pathogenesis of chlamydial disease.
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-initially infect the epithelial cells of the resp. tract, but can spread
-direct cell destruction + inflammation -immunity is NOT long lasting and the primary defense is PMN activity |
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Describe infant pneumonia caused by C. trachomatis.
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-two biovars:trachoma and LGV divided into 19 serovars based on antigenic variation in MOMP
-spread from mother to infant during birth -incubation period variable, sx 2-12 weeks after infection and can last from weeks-months -signs are rhinitis, staccato cough, diffuse rales, tachypnea, FTT, afebrile, eosinophilia is common |
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Describe the pneumonia caused by C. pneumoniae (chlamydia family).
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causes bronchitis and atypical pneumonia
-humans are only reservoir and transmitted person to person through inhalation via resp. droplets -biphasic presentation common -most infections are asymptomatic or mild with persistent non-productive cough and malaise -in atypical pneumo., CXR interstitial infiltrates may be seen -in severe infections there is unilateral lobe involvement |
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What are the clincal manifestations and patient history that would lead to C. trachomatis infection.
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positive maternal vaginal infection
diffuse b/l interstitial infiltrates abnormal lung sounds infants often have inclusion conjunctivities |
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How are chlamydial pneumonias diagnosed?
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1)serology-microimmunofluorescent assay to detect IgM/IgG
-single IgM titer>16 or -single IgG titer>512 or -four fold increase in paired sera 2)cell culture/microscopy-see intracellular inclusions |
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What is the DOC for chlamydial pneumonias?
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doxycycline
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What does zoonotic mean?
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transmissible from animals to humans under natural conditions
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What are the organisms acquired from a zoonotic source that can cause an atypical pneumonia?
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1)Chlaymdophila psittaci-inhalation of dried bird poop or resp. secretions from birds
2)Francisella tularensis-acquired from inhalation of organisms from infected animal tissues 3)Coxiella burnetti-inhalation of organisms from infected animal tissues or by ingestion of contaminated dairy products |
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Describe infection by Chlamydophila psittaci.
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-infection results in Psittacosis
-there has been a decline in the number of infections probably due to increased differentiation btwn. this organism and C. pneumoniae, better control in avian pops., and education -<50 cases in US, usually in adults -can be asymptomatic -organisms spread from the lungs to RES causing HSM with jaundice and focal necrosis -dissemination and chronic inflammation -edema, alveolar thickening, necrosis, and hemorrhaging results in cyanosis and anoxia |
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What is Psittacosis?
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a result of infection by C. psittaci
-transmitted from birds to humans via inhalation of dried bird excrement or dried bird respiratory secretions -if symptomatic, signs/sx are high fever, chills, myalgia, fatique, non-productive cough, consolidation, SOB, and chest pain, etc.. -signs and sx fade within a few weeks in uncomplicated infection - |
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How is C. psittaci diagnosed?
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-clinical manifestations and pt. history
-occupation/hobbies with birds -CXR will show interstitial infiltrates -abnormal lung sounds -pre/post antibody titer-4 fold increase -CF test is presumptive -MIF is definitive -cell culture not routinely performed |
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What is the DOC and prevention for C. psittaci?
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Doxycycline
prevention includes controlling the infections in birds |
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Describe the general characteristics of F. tularensis.
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small, gram neg. aerobic coccobacilli
-thin, lipid capsule -fastidious, has LPS but weak activity, no flagella, no pili, Beta lactamase producer -facultative intracell. organism, survives and replicates within endosomes, inhibits phagolysosome formation |
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Describe the epidemiology of F. tularensis.
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-transmission of the organism primarily by inhalation
-a VERY LOW infectious dose can cause resp. disease -NO person to person transmission -found worldwide, disease confined to the N. hemisphere, -most cases in Midwest in summer/winter -has various hosts, most common are rabbits, ground squirrels, and muskrats, vectors are ticks and deer flies |
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Who is at high risk for contracting F. tularensis?
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hunters, campers, trappers, lab workers, etc.
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Describe the characteristics of Pneumonic tularemia.
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-mortality rate is 30% +
-organism is inhaled and causes multiple, necrotizing granulomas that destroy the alveolar septa -bronchopneumonia, bronchitis, or tracheitis, patchy infiltrates in 1+ lobes, lobar pneumonia can develop -hilar lymph node enlargement, non-productive cough, pleuritic type chest pain -bacteremia can occur, macrophages enter hilar lymphatics |
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How is the diagnosis of pneumonic tularemia made?
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-it is difficult and dangerous
-pt. history is helpful -do a CXR and look for bronchopneumonia -culture aspirate of lymph nodes, sputum and/or draining sinuses, positive culture in 3 or so days, requires specialized growth media -detection of a 4 fold increase in Ig titer OR a single titer >160 -abs cross react with other spp so serology alone is not definitive |
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What is the treatment for tularemia?
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streptomycin
-many other drugs associated with relapses so not first choice |
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How is tularemia prevented?
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-wear gloves, follow precautions, process specimens in a biohazard hood
-avoid ticks and/or remove them promptly -live, attenuated vaccine for high risk ppl -does not prevent disease but reduces bad outcomes |
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Describe the general characteristics of Coxiellaceae.
|
-one member that causes human disease is Coxiella burnettii (causes Q fever)
-small, aerobic, gram neg pleomorphic bacilli -non motile, no exotoxins, weak endotoxin activity -can exist in 2 forms |
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What are the 2 forms in which C. burnettii is found in?
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1)small cell variant
-long lived, extracell, infectious form, resistant to environment 2)large cell variant -vegetative form seen in infected cells -obligate IC parasite survives within phagolysosome |
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Describe phase variation of the O antigen by C burnettii.
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1)phase I antigen is the wild type
-more resistant to phagocytosis -more virulent (resist IC killing mechanisms) 2)Phase II antigen is a deletion mutant -more easily phagocytosed and killed intracellularly -abs to these antigens can be detected and is an indication of pt. status |
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Describe epidemiology of C. burnetii.
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-reservoir: many animals, ticks, and birds
-vector: ticks but DOES NOT REQUIRE a vector for transmission, it is considered zoonotic disease -transmitted in one of 3 ways: inhalation, ingestion of contam. milk, bite from a tick -at highest risk are farmers, vets, lab workers, etc |
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Describe acute disease caused by C. burnetii.
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-causes Q fever which is a variable disease and can be acute or chronic
-acute caused by inhalation of aerosol particles, proliferation in alveolar macrophages -3 weeks incubation, abrupt onset of high fever, chills, severe HA, and other non-specific sx for 1-2 wks -can mimic atypical pneumonia -causes granulomas in the liver and sx of hepatitis |
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Describe chronic disease caused by C. burnetii.
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-infection that lasts more than 6 mos and only occurs in about 1% of pts.
-most common complication is subacute endocarditis generally on an artificial or damaged valve |
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How is C. burnetii diagnosed?
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-pt history helpful
-CXR is lung involvement -culture can be done but not routinely performed -staining and DNA probes -do serology: IFA, Igs to phase II antigen appear within 2 weeks, Igs to phase I require longer time to appear -in acute Q fever: IgM to phase I and II ags and IgG to phase II antigen -chronic Q fever:increased IgG/IgA to phase I antigen with constant /decline titer to phase II antigen -granulomas on liver biopsy -see increase WBC in 30% of pts. |
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What is the treatment for C. burnetii?
|
doxycycline=acute
combo therapy for chronic |
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How is C. burnetii prevented?
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-avoid contact with infected animals and milk
-an inactive vaccine has been developed but not approved for use in US yet |
