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220 Cards in this Set
- Front
- Back
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What is blepharitis?
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-an infection of the eyelid that may sometimes be severe
-most commonly observed manifestation is the marginal form -almost any bacterium capable of causing skin infection can cause this disease |
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What are the typical etiologic agents responsible for causing blepharitis?
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bacterial=Staph (normal flora overgrowth)
viral=HSV (kids), Varicella zoster (older pts), Molluscum contagiosum (immunocompromised) |
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What are the typical etiologic agents responsible for orbital cellulitis?
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Staph aureus
S. pyogenes Haemophilus influenzae (kids under 3) fungal agents in immunocompromised |
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What are the chief signs of orbital cellulitis?
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obvious edema of the eyelids and surrounding tissue
-restricted globe movement -this disease may be severe and lead to corneal involvement, usually this condition reveals the presence of another infection due to trauma, septicemia, sinus infection |
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What is conjunctivitis?
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-infection of conjunctival membranes with itching, burning, discharge
-discharge may be quite thick, but vision clears with blinking -NO significant vision impairment -papillary hyperplasia -U/L involvement initially, but ultimately spreads to both eyes |
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What are the possible causes of conjunctivitis?
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1)infection
2)allergy 3)inflammation from contact with noxious substances 4)diminished production of tears |
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What are the usual causes of bacterial conjunctivitis?
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1)S. aureus (mostly in adults)
2)S. pneumonia and Haemophilus influenzae -conjunctivitis of children, pink eye, epidemics |
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What is the treatment for bacterial conjunctivitis?
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S. aureus disease-topical antibiotics required
-disease is typically self-limited for others but abx may shorten the course |
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What is inclusion conjunctivitis?
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-eye disease caused by Chlamydia trachomatis
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Describe adult inclusion conjunctivitis.
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-there is mild discomfort and little/no discharge
-observe numerous papillae on the lower conjunctival membrane -rarely associated with corneal scarring |
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What is trachoma?
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-it is keratoconjunctivitis caused by C. trachomatis
-may eventually lead to complete loss of vision -the leading cause of preventable blindness in the world |
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Describe the progression of trachoma.
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-has a slow evolution
-begins as acute inflammatory conjunctivitis -lymphoid follicles and papillae develop on the conjunctiva of the superior lid -follicles eventually undergo necrosis -resolution results in scarring, inversion of eyelids and eyelashes -repeat infections/exposures are probably required to get to end stage blindness -constant abrasion of the cornea by malpositioned eyelids and eyelashes -secondary bacterial infections frequent -dry eyeball from reduced mucous production and development of a superior limbic pannus -fibrovascular membrane derived from CT leads to complete blindness |
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Describe the epidemiology of trachoma eye infection.
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-this disease is associated with poverty and unsanitary conditions
-infection probability and severity correlated with family situation -transmitted by mechanical vectors (flies) and infected fomites -having clean water for hand washing will reduce incidence of IC and trachoma |
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Describe diagnosis/treatment of IC and trachoma eye infections.
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-diagnosed based on clinical findings
-exam of conjunctival scrapings/impressions with Giemsa, iodine or FA (fluor. ab) tests -look for inclusion bodies -iodine stains glycogen accumulating in inclusions -iodine does NOT stain C. pneumonia or C. psittaci inclusion bodies -inclusion bodies are NOT prevalent in adults -tx:erythromycin,tetracyclines |
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What is ophthalmia neonatorum?
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-conjunctivitis in the first 28 days of life is typically result of inoculation of infant's eye during passage through birth canal
-prophylactic tx is mandated after delivery to prevent purulent conjunctivitis -1% silver nitrate plus erythromycin or tetracycline |
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What are the bacterial agents that cause ophthalmia neonaturom?
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1)neisseria gonorrhoeae-affects about half of all infants born to mothers with gonorrhea, manifest in day 2-5, frequently B/L, rapidly destructive, tx with abx
2)C. trachomatis-est. rate of infection in infants born to women with endocervical chlamydiosis is 70%, appears 5-10 days postpartum, U/L, erythematous conjunctivae, NO follicle formation evident |
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Describe the diagnosis and treatment of conjunctivitis of the newborn.
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-screen pregnant women in the 3rd trimester to complete tx before birth
-tx with erythromycin -tx newborn with oral and topical erythromycin -disease is sometimes observed in prophylactically treated populations |
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Describe viral conjunctivitis.
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-more common than bacterial etiology
-transmission by secretions (hand to eye) -hand washing vital for control - |
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What is follicular conjunctivitis?
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-viral infection w/o ocular complications
-ex. adenovirus conjunctivitis/pharyngeal conjunctival fever (PCF) -adenovirus PCF is often associated with multiple pt. outbreaks from inadequate chlorination of pools and eyedrops in physician's offices -ex:primary herpes simplex and varicella zoster infection |
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What is epidemic keratoconjunctivitis (EKC)?
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a viral eye infection also called "shipyard eye"
-adenovirus causes it -PCF with complication of corneal ulcer 10-14 days after initial sx -may persist for months |
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What is acute epidemic hemorrhagic conjunctivitis?
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a viral eye infection
-typical causes are coxsackie, enterovirus, adenovirus -acute onset, subconjunctival hemorrhages prominent -associated with crowding and poor hygiene |
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Describe the general features of keratitis.
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-corneal scarring from infection is a major cause of reduced vision and blindness
-correlated with common use of immunosuppresesant agents in eye disease tx -in less developed countries pneumococcus is the most common etiology of bacterial corneal ulcers -in developed countries it is non-pneumococcal bacteria and fungi -U/L infection -moderate to severe pain, photophobia -decreased/impaired vision are key feature |
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Describe viral keratitis caused by Herpes simplex virus.
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-typically seen in adults, rare in infants and children
-leading cause of infectious blindness in developed countries -HSV is characterized by establishment of latent infections -primary infection is typically early in life and subclinical -virus remains latent in the trigeminal or cervical ganglia -HSV keratitis may be epithelial, stromal, or both but stromal is more serious, epithelial is more common -2 forms of stromal disease are non-necrotizing and necrotizing -with epithelial form dendritic figures are seen on the corneal surface with staining -these pts. typically experience little pain/photophobia, but irritation and tearing are common |
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Describe varicella-zoster recrudescence (viral keratitis).
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-a potential complication of an outbreak of shingles from trigeminal ganglion
-shingles outbreaks tend to have sharp lines of demarcation and only affect only one side |
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Describe adenovirus keratitis.
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-a viral keratitis
-punctiform lesions in the cornea are characteristic |
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Describe the diagnosis and tx of viral keratitis.
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-scrapings from the cornea are examined by culture and direct microscopic exam (gram/giemsa stain)
-in HSV infection scrapings will reveal multinucleated giant cells -FA tests -acyclovir is the DOC for HSV-VZV infections -treat shingles pts. within 3 days of lesions appearance |
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Describe keratitis caused by bacteria.
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S. pneumoniae is the only true bacterial corneal pathogen, all the others require an overwhelming inoculum or ommunosuppressed cornea to cause infection
-P. aeruginosa is the most common bacterial infection and is associated with soft contact lens use, these bacterial are able to live in some disinfectants |
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Describe keratitis caused by fungal agents.
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-immunocompromised pts. mainly
-topical use of glucosteroids in eye may have severe consequences -aspergillus, candida, fusarium solani |
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Describe the tx/prevention of nonviral keratitis.
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-central corneal ulcer not clearly due to HSV is an emergency
-bacterial infections are a rare finding unless the corneal epithelium is breached such as in surgery is with abrasions |
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Describe retinitis.
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-U/L involvement at initiation, progresses to B/L due to viremia
-visual field loss or decreased visual acuity is often first complaint -CMV, VZV, HSV all causes |
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Describe CMV retinitis.
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an opportunistic infection of the immunocompromised
-most frequent viral cause of life and sight threatening infections in AIDS pts. -late in course of disease, prognosis for long-term survival is poor -will see patches of red and white on large fraction of retina -vitreous humor remains clear and free of inflammation -tx with ganciclovir or foscarnet |
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What is endophthalmitis?
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-infection typically involving several tissue layers and present in humor
-can arise via complication of intraocular (cataract) surgery, accounts for most cases and due to normal flora invasion -can be post traumatic from penetrating injuries to eye -can be endogenous from blood borne metastatic infection typically caused by candida -R. eye is 2X more frequently involved than left eye -B. cereus seen in drug users -can also be from uncontrolled infections of the cornea or orbital cellulitis |
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Describe the general characteristics of poliovirus infection.
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-it is a disease due to the destruction of motor neurons in the spinal cord caused by infection with polio virus
-results in flaccid, asymmetric paralysis -"infantile paralysis" -may be caused by agents other than polio virus -widespread outbreaks were a consequence of public health improvements |
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How is the diagnosis of poliomyelitis made?
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-fever and asymmetric flaccid paralysis
-isolation of virus from fecal matter or respiratory secretions by tissue culture are suggestive, but not definitive -serology coupled with virus isolation is best |
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Describe the characteristics of the poliovirus agent itself.
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-it is a picorna virus
-ssRNA genome -nonenveloped -rather acid stable -3 antigenic types of the disease causing wildtype virus are recognized, these type cross react somewhat but not enough to result in complete immunity to all the types after an infection with any one type |
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Describe polio epidemiology.
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-humans are the sole natural host
-eradication is theoretically possible -infection by direct or indirect fecal-oral route or by direct contact with infected respiratory secretion -summer autumn peak in temperate zones -no seasonal peaks in tropical regions -transmission facilitated b/c virions can remain infectious for long periods in food, water, milk -virus is easily inactivated by pasteurization -incubation period averages 1-2 weeks -the patient is maximally infectious during first wk of illness -there is pharyngeal and fecal excretion of virus |
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Describe the pathogenesis of poliovirus.
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-virus enters via GI tract, may penetrate via M cells
-virus multiplies in pharynx and small intestine, infected cell bursts in 6-8 hours, viremia by spreading to draining lymph nodes -virus seeds to many sites and spreads to CNS -infection of anterior horn cells of spinal cord, the brain stem with resp. paralysis and motor cortex of the brain -there is death of neural cells which results in paralysis of mm. innervated by those neurons -paralysis in NOT due to infection or death of mm. tissue -paralysis is usually asymmetric with maximum extent evident 2-3 days after onset of paralytic sx -the bulbar form of the disease affects involuntary mm. of resp. system |
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Describe the polio virus genome expression.
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-the virus is positive sense and functions directly as mRNA and is translated into a single giant polypeptide
-the polio virus genome encodes an internal ribosome entry site (IRES) that allows it to mimic host mRNA even though it does not have the guanosine cap structure -the virus antagonizes host mRNA translation by cleaving all guanosine caps from host mRNA ensuring that ONLY VIRA RNA will be translated -new RNA is covalently linked to a small viral protein VPg -some of the new + RNA will have VPg cleaved off and used as mRNA in the infection -other mRNAs will remain covalently linked to viral protein VPg and are immediately encapsidated |
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What percentage of polio virus infections are clinically evident?
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probably only around 1%
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What are the possible clinical syndromes caused by poliovirus?
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1)inapparent infection-most common 95%, will be asx to minor malaise
2)abortive illness-fever, malaise, HA, N/V, 3)nonparalytic poliomyelitis-2-10 days duration, 1% of ppl, pt. will recover spontaneously 4)paralytic poliomyelitis-flaccid paralysis from LMN damage, <1% of ppl., probably the most feared manifestation but actually very rare outcome, damage to nerves is permanent but some degree of recovery does take place 5)post polio syndrome-mm. atrophy, appears 30-40 yrs after an acute case of paralytic polio, recurrent mm. weakness, pain, fatigue, and additional atrophy, has a gradual clinical course which seldom results in complete disability of affected areas |
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What is bulbar paralysis and what disease is it associated with?
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associated with poliovirus
-cranial nerve involvement, difficulty with speech, swallowing, eye movements, facial mm. movement, can lead to resp. paralysis, direct paralysis of diaphragm mm. can also result in resp. failure, -very high mortality rates for bulbar disease prior to modern resp. support techniques |
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Describe the course of paralytic disease of polio.
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1)initiated with minor disease-viremia with constitutional symptoms and specific resp. or GI sx,
2)major disease sx and signs 1-3 days later-HA, fever, mm. stiffness, and paralysis, recovery is extensive by compensatory hypertrophy of mm. tissue that has not lost innervation, improved with physiotherapy |
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How is poliomyelitis prevented?
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-poliovirus has 3 serotypes and pts. must have abs against all 3 to be protected from the disease
-several vaccines are available 1)inactivated polio vaccine (salk) 2)enhanced potency vaccine IPV 3)live polio vaccine (Sabin) |
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Describe the inactivated polio vaccine (IPV).
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-formalin inactivation of virus grown in monkey kidney cultures
-4 inoculations over 1-2 year period -IPV if properly manufactured is NOT associated with disease induction -not as effective as OPV in preventing the spread of natural polio virus among susceptible people |
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Describe the enhaned potency polio vaccine (e-IPV).
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the relative levels of the 3 virus types are altered to ensure a solid response to all of them
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Describe the live polio vaccine (sabin).
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-live attenuated virus grown in primary monkey or human diploid cell cultures
-infects and immunizes but does not cause disease -back mutation of vaccine strain to paralytic type is known (about 10 cases per year seen, no case naturally seen since 1979 so is it really worth using??) |
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What is the CDC vaccination recommendations?
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OPV now phased out in favor of IPV
-poliovirus is near extinction and the VAPP risk is far greater than the risk of natural paralytic disease |
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What are the properties of poliovirus that make it vulnerable to eradication?
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-humans are the only natural hosts
-the virus is tough but it cannot persist in the environment forever -vaccination results in lifelong immunity -in 94, the americas were declared "polio free" -now polio has been imported by travelers into 24 countries that were once polio free |
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What are the polio vaccine controversies?
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1)SV40 (simian virus) co-inoculation with polio vaccines
-thought that it could be inapparently replicating in monkey cells to produce attenuated polio viruses for vaccines -it is not as easily inactivated as polio, and viable SV40 virus was unknowingly injected into early IPV and ingested by early OPV recipients (possibly) -there is NO increased cancer evident in this population but studies do suggest that children of mothers receiving SV40 in vaccines while pregnant DID have higher rates of brain malignancies -SV40 mediated PML (progressive multifocal leukoencephalopathy) may be a concern for future 2)OPV/AIDS hypothesis -OPV was used in a vaccination campaign in teh Belgian congo was produced in chimpanzee kidney epithelial cells, not in monkey kidney cells as claimed -if this was the case, it would bolster the idea that AIDS entry was a result of OPV vaccination but analysis of early OPV revealed only monkey DNA, no chimp DNA |
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What are the 2 classifications of picorna viruses?
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1)enteroviruses-typically associated with intestinal infection, tissue tropism is BROAD and many cells are infectable
2)rhinoviruses-cause resp. diseases exclusively -CNS infection with enteroviruses is common in the US, although polio is controlled the other are ubiquitous and multiple serotypes circulate -significant cause of morbidity in kids and adults with newborns and immunocomp. pts. at greatest risk due to the immaturity or malfunction of the immune system |
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What are the 3 non-polio enteroviruses we talked about?
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1)ECHO
2)coxsackie A and B 3)enterovirus 70 (conjunctivitis) -they are very similar to polio except: they are spread fecal/oral or resp. droplet spread, maternal illness around time of delivery increases risk of transmission |
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Describe the ECHO viruses.
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enteric cytopathic human orphan-orphan referring to lack of disease state associated with virus presence
-accidentally discovered in human feces in the absence of any disease during epidemiologic studies of polio viruses |
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Describe Coxsackie viruses.
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-non-polio enteroviruses
-2 groups are defined based on differing pathology to suckling mice A:diffuse myositis with acute inflammation of and necrosis or voluntary mm. fibers B:focal areas of degeneration of brain, focal necrosis in sk. mm. |
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What are the clinical manifestations of ECHO/coxsackie CNS infection?
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-In newborn, sudden onset, fever, vomiting, anorexia, rash and URT infection, signs of meningeal inflammation, death by hemorrhage hepatitis syndrome (ECHO 11) or encephalomyocarditis (Cox B)
-In older kids and adults, fever, HA, nuchal rigidity, enteroviruses are common agents of US meningitis -enterovirus meningitis outside the immediate (2 wks) neonatal period is not usually as severe - |
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How is diagnosis and treatment of ECHO and coxsackie viruses made?
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-throat and fecal samples for culture
-tricky, no single cell line works for all viruses -nonsx shedding of enteroviruses is common during fall/summer -CSF samples yield virus with long delay -coxsackie A will NOT grow in culture -couple culture with specific IgM serology to confirm -RT-PCR assays, body site of isolation is important, feces is the most sensitive but least disease specific , nasopharynx is a better link to disease, CSF and blood reveals invasive disease with high probability -tx is supportive |
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Describe the epidemiology of enteroviruses.
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-infections most common in summer and fall in termperate zones
-yound kids primarily -disease probability and severity are inversely proportional to age -fecal-oral transmission -each enterovirus season in the world is dominated by only a few viral serotypes |
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How are enteroviruses cleared from the host and what implications does this have for immunocompromised pts?
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by antibodies instead of by cellular immune mechanisms
-in agammaglobulinemic pts., they are at risk for chronic meningitis or meningoencephalitis that may last for years, often fatal -these pts. may be stabilized by admin. of IV antibody -severity of disease in newborns is related to the presence or absence of maternal ab to the infecting virus |
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What is the prevention for non-polio enteroviruses?
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-vaccines are unlikely to be developed b/c there are just too many serotypes of these agents
-the best control method is to reduce transmission through hand washing after diaper changes and disinfection of the area and avoiding use of shared utensils and drinking containers |
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Describe enterovirus 70.
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-acute hemorrhagic conjunctivitis
-rapid onset and highly contagious |
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Describe LCM (lymphocytic choriomeningitis virus).
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-arenavirus group (prototype)
-genome is 2 ssRNA strand circles that are ambisense (half behaves as + sense, half as - sense) with portions capable of serving as mRNA prior to transcription -virion is enveloped -cause chronic infections of rodents and incidental human zoonoses |
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Describe the clinical manifestations of LCMV.
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-in persons of normal health, LCMV is asx or produces a mild flu-like illness
-can cause an aseptic meningitis uncommon-1 week duration and rarely fatal -infection during pregnancy can result in vertical transmission to fetus -infection during first or second trimester may result in severe fetal illness -have been transmitted through organ transplantation |
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How is LCMV diagnosed and treated?
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-suspected in cases of aseptic meningitis
-NOT usually cultured, do IgM ab ELISA test -history of exposure to rodents -supportive tx |
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Describe the epidemiology of LCMV.
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-it is found wherever mice exist
-distribution of this virus is determined by the range of rodent hosts -human infections occur after virus-laden secretions/excretions of mice and the usual source is infected house mice -tend to have a fall/winter predominance -all age groups are susceptible |
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What is one of the main differences in infection caused by Cryptococcus neoformans and C. gattii?
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C neoformans typically only causes disease in immunocompromised hosts
-C. gattii is a new emerging infection that is found in immunocompetent hosts -fatal in most cases |
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What is the reservoir for C. neoformans?
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soil, bird droppings
-STAY AWAY FROM PIGEONS! |
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How is C. neoformans transmitted and what is the typical course of infection?
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-cryptococcosis follows inhalation of dessicated yeast cells
-usually starts as a pulmonary or skin infection and then may progress to CNS=results in meningoencephalitis (all cases are fatal) -results in systemic infections following multiplication of yeast cells (yeast form prefers CSF) -these disease are NOT communicable |
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Describe the general characteristics of C. neoformans.
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-all species are encapsulated yeast
-appear as creamy, mucoid colonies on Saboroud's dextrose agar or potato dextrose agar |
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What are the pathogenicity factors of C. neoformans?
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-capsule evades phagocytosis
-diphenol oxidase (laccase)-can be seen on bird seed agar -ability to grow at 37 C |
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What are the 2 main clinical manifestations of C. neoformans?
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1)pulmonary -asx or flu like
2)disseminated-meningitis, cryptococcoma, skin lesions, C. gattii causes more extensive infections |
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How is diagnosis is Cryptococcus made?
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-samples from CSF, sputum, aspiration from skin lesion
-direct exam with india ink -culture on SDA or PDA, birdseed agar in mixed infections -growth on canavanine glycine bromothymol blue medium will differentiate C. gattii (blue) from neoformans (yellow) but this takes about 1.5 weeks to grow -serology--detection of capsule antigen in CSF and serum by latex agglutination test |
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Describe the general characteristics of Toxoplasma gondii.
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-agent of toxoplasmosis
-third leading cause of death (US) attributed to foodborne illness -asx in immunocompetent hosts -severe complications in immunocompromised hosts and women NEWLY infected in prenancy -present in 2 distinct forms-trophozoites and cysts |
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What are the 2 morphological forms of Toxoplasma gondii?
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1)trophozoites-tachyzoite causes acute disease and is the actively proliferating form
-more efficiently cleared by immune system -bradyzoite-chronic disease, slowly replicating 2)cysts-zoitocyst tissue cyst that contains bradyzoites (in cells) -cysts are the infective stage |
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Describe the pathophysiology of toxoplasmosis.
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1)congenital cases
-damage is more severe the earlier in prego the infection results -can result in blindness, epilepsy, other developmental concerns -triad: chorioretinitis, hydrocephalus, intracranial calcifications 2)postnatal cases -fever, myalgia, blurred vision -may appear like milk flu like sx in immunocompetent hosts |
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Describe the epidemiology of toxoplasmosis.
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-infection is highest in hot, humid climates
-transmission does NOT usually occur through person to person contact -infection can occur through foodborne transmission, zoonotic, congenital, rarely-blood transfusions/organ transplant, very easily spread! |
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How is identification of T. gondii made?
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-diagnostic stages are zoitocysts and trophozoites
-can do serology ELISA to measure parasite specific IgG or IgM in pregnant women -molecular: PCR can detect parasite DNA in amniotic fluid -parasites can be isolated from CSF |
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How is T. gondii controlled?
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-cook meat thoroughly
-wear gloves during and wash hands after gardening -keep outdoor sandboxes covered -pregnant women should not clean litter box, adopt new cats |
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Describe the general characteristics of Naegleria fowleri.
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-facultative environmental protozoan
-found in soil and fresh water -results in a rare brain infection -this is a very severe, deadly infection |
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Describe the 2 morphological forms of N. fowleri.
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1)cyst-single nucleate (protective in harsh conditions)
2)trophozoites- -flagellate form arises based on change in ionic environment or lack of nutrients, occurs in mins. -amoeboid form is the reproductive form, only form in tissue, only form that feeds on bacteria, arises from flagellate form when conditions improve, phagocytose RBC, WBC, destroy tissue |
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Describe the life cycle and the clinical course of disease of N. fowleri.
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-the flagellate form is the infective stage
-enters nasal passages then transforms into amoeboid form -migrates along olfactory nerve to the brain and causes significant necrosis in olfactory bulbs and brain tissue -through the use of a sucker apparatus is consumes the cells of the brain -results in primary acute meningoencephalitis (PAM) -can infect healthy persons, signs and sx mimic bacterial meningitis -infection results in destruction of tissue and is rapidly fatal (w/in 2 days) |
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Describe the epidemiology of N. fowleri.
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-free living in freshwater
-contracted during summer months in southern states -also from swimming pools, streams and ponds -disease is not spread person to person -cannot be contracted from drinking contaminated water |
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How is N. fowleri diagnosed and treated?
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-CSF findings
-wet mount for mobile amoeba -trophozoites in tissue sections -clearing zones on E. coli covered agar plates (plates coated with E. coli, drop of CSF on plate, look daily for clearing zones, pick up amoeba, place in distilled water and look for flagellated form) |
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How is N. fowleri controlled?
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-avoid swimming in stagnant ponds
-do not disturb sediment in freshwater -keep head above water -salination occasionally works as a decontaminant -chlorine is ineffective |
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Describe the general characteristics of Acanthamoeba species.
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-there are many causative organisms
-morphological forms are trophozoite (infective stage, has spiked pseudopodia), cyst (resistant to environmental conditions) |
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Describe the 3 clinical syndromes of acanthamoeba species.
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1)granulomatous amoebic menigoencephalitis (GAM or GAE)
-hematogenous route to the brain following inhalation of cysts or infection through wounds -incubation period is weeks, death occurs 7-120 days -sx include mental and neurological, along with flu like sx, edema -100% mortality 2)ocular acanthamoebiasis keratitis and uveitis -introduced by trauma to the eye followed by contamination with cysts -may resemble corneal herpes 3)disseminated disease |
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Describe the epidemiology of acanthamoeba.
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-serum abs found in 50-100% of otherwise healthy people
-more cases of keratitis seen than GAE -found as a contaminant in soil and contact lens solutions -mostly affects immunocompromised hosts -free living organism that feeds on bacteria in nature -to control wear gloves while gardening and properly clean lesions |
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How is the diagnosis and treatment of acanthamoeba made?
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-both cysts and trophozoites can be observed in tissue sections
-keratitis-corneal scrapings -GAE-post mortem brain biopsy -examining CSF for organisms is not efficient as a diagnostic |
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Describe the general characteristics of balamuthia mandrillaris.
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-very closely related to acanthamoeba
-agent of GAE (granulomatous amoebic encephalitis) |
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Describe the 2 morphologic forms of B. mandrillaris.
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-exists in 2 forms
1)trophozoite-no flagella, mostly binucleate, flat pseudopodia for locomotion 2)cyst-3 layered wall -both forms are infectious! |
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Describe the pathophysiology of B. mandrillaris.
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amoeba enter through inhalation of cysts or through wounds
-may form a skin lesion or migrate to the brain -sx include facial paralysis, difficulty swallowing, seizures, paralysis, double vision |
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Describe the epidemiology of B. mandrillaris.
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soil organism that preys on other amoeba
-can infect healthy people -mortality rate >98% -found mostly in southern states and latin america -allows legionella to replicate within the parasite -increases virulence of parasite -control is to wear gloves and avoid swimming in stagnant pools |
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How is diagnosis and ID of B. mandrillaris made?
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-cysts and trophozoites can be ID in tissue sections
-not easily cultured -does not feed on bacteria, only co-cultured with primate hepatic cells or human brain cells |
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Describe the general characteristics of the rabies virion.
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-it is a rhabdovirus
-enveloped virion with a unique bullet shape -genome is ss RNA |
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Describe the clinical manifestations of rabies.
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1)prodrome-mild fever, pharyngitis, abnormal sensations referred to bite site
2)excitatory phase-anxiety, apprehension, hydrophobia in humans 3)coma, HTN, death |
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Describe the pathogenesis of rabies.
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local virus replication occurs at the inoculation site
-virus enters CNS via peripheral nerves and localizes via retrograde transport to limbic region of the brain -institute therapy before virus enters the CNS -cytokines (NO) contribute to damage -negri bodies are diagnostic |
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Describe the epidemiology of rabies.
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-the host range is huge and includes all mammals
-human rabies is a reflection of disease in animals and the degree of human contact with these animals -human cases have now been associated with all the major US reservoir animals -wild animals are the most important source of infection for humans and domestic animals in US |
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Describe rabies transmission.
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-not only transmitted by bite-"cryptic cases" are seen
-requires only exposure of mucous membrane of saliva of animal, with bats posing exceptionally high risk of transmission -aerosol transmission was documented in bat caves |
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How is rabies controlled?
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there is NO standard therapy for clinically overt rabies
-this disease is virtually 100% fatal once in enters the CNS -the Milwaukee protocol is an experimental tx (amantadine) first used in 2004, this approach has failed in additional N. american cases -avoid exposure, prevent disease in companion animals and herds -pre-exposure prophylaxis based on exposure risks -vaccine baiting program has been successful in minimizing disease in wild animal reservoir populations and halting the spread of rabies across certain regions |
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How is the diagnosis of rabies made?
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-establish disease probability by considering the natural history of rabies
-animal spp. and location (bats are very problematic, rodents and rabbits rarely infected) -nature of encounter (was the bite provoked or unprovoked? was animal behaving abnormally? -if possible, kill and examine the animal immediately for evidence of rabies infection -demonstration of viral antigen in a tissue specimen -most often done by a fluorescent Ab test, presence of negri bodies -culture-animal inoculation test -RT-PCR methods allow for rapid and sensitive detection of viral nucleic acid -usually any bite or contact with typical reservoir animals such as a fox, skunk, raccoon or bat is sufficient to begin tx |
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What is the post-exposure prophylaxis for rabies?
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administer BOTH human rabies immunoglobulin and vaccine
-clean the wound -instill half of HRIG directly in wound site and the remainder in the gluteal region with first dose of the vaccine -admin. vaccine into deltoid region (5 shots over 4 wks) -several vaccines are available, the human diploid cell vaccine (HDCV) is superior -rabies is a medical urgency, if abroad advise the patient to return to the US to get treated if possible |
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Describe herpes simplex virus encephalitis epidemiology.
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-most common cause of sporadic fatal encephalitis in the US
-both HSV 1 and 2 cause encephalitis -HSV1 encephalitis is typically due to reactivation of latent virus and more frequent in adults -HSV can cross the placenta -neonatal encephalitis infections tend to be due to HSV2 -evidence of HSV infection in the neonate (skin lesions, conjunctivitis) are important clues |
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Describe the pathogenesis of HSV encephalitis.
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-focal encephalitis limited to the frontal and temporal regions with associated signs and symptoms
-spread to CNS can be the result of primary infection or reactivation of latent virus -mortality rates high and neurologic deficits in survivors are significant |
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How is HSV encephalitis diagnosed?
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-if EEG is suggestive of HSV encephalitis a brain biopsy is taken and therapy is begun immediately
-non invasive MRI is becoming popular for diagnosis -specimen is sent for culture and direct observation (Tzanck smear) via fluorescent ab test (cell syncytia with ballooning) -PCR is being used more frequently for detection |
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What is aseptic meningitis?
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-it is called aseptic due to a failure to isolate bacteria from the patient
-fever, HA, stiff neck -mild disease is the norm |
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Describe the general characteristics of the arboviruses.
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-they are the "arthropod borne viruses"
-vectors are usually mosquitoes and ticks -all contain RNA -all are enveloped and inactivated by solvents -these viruses productively infect an unusually wide range of animal reservoirs -in US primarily birds and small mammals but disease may not always be apparent in these infected hosts -humans are often DEAD END hosts in which there is insufficient viral replication to sustain the continued infection of new hosts -the arboviruses show great diversity in physical structure and strategies of genome expression and replication |
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Describe the outcome of arbovirus infections.
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-with arbovirus infections mortality and sequelae depend on the specific viral agent, the age of pt., the extent to which encephalitis develops
-infections are usually subclinical -many have flu like sx and are not recognized as CNS infections -severe cases have aprupt onset of fever, HA, vertigo, N/V, confusion and personality changes, seizures -recovery may be complete or pt. may have long term deficits -kids usually have deafness, learning disab. |
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How is arbovirus diagnosed and detected?
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-a specific viral diagnosis is made in only about 10-20% of nonepidemic cases of meningoencephalitis
-presence of epidemics and/or season of infection may result in a high index of suspicion -can do serological tests-comparison of clinical isolate with abs to viruses found in that region -do MAC-ELISA (IgM ab capture ELISA) -CSF sample easiest to interpret and link to encephalitis -sometimes combined with virus specific monoclonal abs (MAb) to increase specificity -some viruses may cross react serologically complicating the diagnosis -tests for virus specific ab using CSF or serum -obtain a serum sample early and store for future analysis -4X or higher increase in titer btwn acute and convalescent phase sera is significant -culture IS NOT typical -can also perform nucleic acid based tests (NAT), RT-PCR |
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How can we monitor arboviruses in any given geographical area?
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-mosquito samples by trapping
-bird population antibody prevalence -baiting with sentinel animals |
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What are the key arbovirus infection diagnostic clues?
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-these are often diseases of specific places and times
-time is usually summer/fall when vectors are active -place-endemic focus area or outbreak sites -pt. age |
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Describe the epidemiology of arboviruses.
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-the arboviral encephalitides are zoonoses with reservoirs and means of dispersal in animals other than humans
-infectino cycles involve biting arthropods and vertebrates often rodents and birds -the actual host range of these viruses is amazing (amphibians may be included in cycles) -the arthropod is a true biological vector -the virus infects and multiplies in gut, disseminates in the hemolymph and ultimately est. a persistent infection in the salivary glands where it may be transmitted -the infected vector often shows no signs of disease -the virus does multiply in the vector and a period of incubation is needed to enhance the capacity to transmit the virus by biting -individual arboviruses are adapted to specific vector hosts |
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What is virus amplification and what organism does it apply to?
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-hosts that produce a sustained viremia can act as a reservoir of infection to previously uninfected arthropods and increase the number of infected vectors (ie. a bird getting bit by an uninfected mosquito then becomes infected by the bird)
-increased vectors then increases # of infected hosts, this increases the likelihood of humans becoming infected -transmission to humans requires bridge vectors that will feed actively on both animal reservoir hosts and humans -the incidence each year CANNOT be predicted b/c it depends on the hosts, vector, and climate -this is associated with arboviruses |
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Describe the cycle of transmission for arboviruses.
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-humans are often "dead end" hosts
-viremia is weak or not sustained in humans and does not allow for efficient infection of new vectors -to assure contribution to further viral transmission, animals must have titers of about 10^4/mL that are sustained for several days -Sylvatic cycle-humans are tangential hosts accidentally entering a natural zoonotic transmission cycle -Urban cycle-situation of large human pop. coexisting with large vector pops. such as mosquitoes -humans do exhibit sufficient viremia to sustain a true urban cycle for St. Louis encephalitis, Yellow fever, and dengue |
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For which disease do humans exhibit sufficient viremia to sustain a true urban cycle?
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St. louis encephalitis, yellow fever, and dengue
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How are arbovirus infections prevented?
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-complete eradication is not feasible b/c they have hosts and cycles that do not normally involve humans
-the best means of control is to interrupt the fundamental chain of transmission 1)eradication/control of arthropod vectors- 2)avoidance of exposure 3)immunization of nonhuman amplifying hosts-horses and pigs |
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Describe the togaviridae.
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ssRNA + stranded, small
-enveloped (toga=cloak) -has hemagglutinin in envelope -cytoplasmic replication -cause host cell pathology by halting translation of host cell mRNA -genus alphavirus (EEE, WEE, VEE-equine encephalites) |
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What groups of diseases make up the flaviviridae?
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genus flavivirus
st. louis encephalitis West nile encephalitis |
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Describe the bunyaviridae group.
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-genus orthobunyavirus
-genome is 3 circular segments of ssRNA - sense -enveloped -virion carries its own transcriptase bound to RNA with replication in the cytoplasm -california encephalitis virus supergroup (LaCrosse) |
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Describe eastern equine encephalitis.
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-eastern half of US mostly
-summer fall seasonal predominance in North, but year round in FLorida -most cases are in the period of June-October -EEE has bird and horse reservoirs with mosquito vectors -enzootic cycle btwn birds and strictly ornithophilic mosquitoes in freshwater swamp regions -to carry infection to humans other mosquito spp must act as bridge vectors -primarily virus transmission will be concentrated in permanent swamps and at the edges of such swamps -clinically overt encephalitis in kids under 15 and adults over 55 mostly -horse ownership not associated with increased risk of illness -has HIGHEST fatality rate (80%) |
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Describe western equine encephalitis.
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-west of mississippi river primarily
-summer fall -bird, horse, small mammal reservoirs with mosquito vectors -most WEE cases are in infants and children under 10 years old -5-15% fatality rate -sequelae are uncommon in adults but frequent in kids surviving infection -recurrent convulsions, motor changes in over 50% of kids infected in first month of life -most years WEE is sporadic but disease outbreaks do occur -culex tarsalis mosquito vector feeds on bird reservoirs and humans -mosquito adapted to flooded grounds and irrigated pastures -epidemic risk increased by heavy winter snow, spring rains, flooding all of which expand viral larval habitat |
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Describe venezuelan equine encephalitis (VEE).
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-central and south america, US everglades, texas
-a mosquito borne true "disease of place"-ppl enter zoonotic foci and enter cycle -usually a benign disease but outbreaks can be very extensive with many sx cases -can spread rapidly and continue until horses are depleted or dry weather decreases mosquito levels -horses are very important amplifying hosts |
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Describe St. louis encephalitis.
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-flavivirus
-midwestern US -summer fall-peak in aug/sept -bird reservoir with mosquito vector -sparrows are a principal amplifying host but vectors vary with geographic location -adults over age 40 -attack rates and severity of illness increase with age -greatest risk is associated with place of residence and outdoor activity in the evening -most outbreaks urban areas, low socioeconomic status -permanent sequelae uncommon - |
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Describe West Nile virus.
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-flavivirus that cross reacts antigenically with StLE
-first isolated in the uganda west nile province and is an emerging disease in the Americas -about 1 million ppl in US now estimated to have undergone WNV infection -WNV is unusual in that in about 20% of total infections result in clinically apparent illness -febrile illness of sudden onset lasting 3-6 days -most serious manifestation is fatal encephalitis in humans, horses, and birds -about 1:150 total infections result in severe neurological disease -the most important predictive factors for severe disease/death is advanced age (>50) or immune dysfunction -the flaccid paralysis syndrome is less common that meningitis or encephalitis |
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How is the diagnosis of WNV made?
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-MAC ELISA on CSF or serum in first week-reveals anti-WNV IgM abs
-IgM does not cross BBB so CSF positivity most strongly suggests CNS infection -pts. who have been infected recently with or vaccinated against yellow fever, dengue, st. louis encephalitis may have a positive MAC-ELISA but vaccinations and infections not involving CNS will not yield IgM positive CSF |
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Describe the california encephalitis virus group.
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-bunyaviruses
-important cause of mild encephalitis in the US -endemic in midwest -most cases due to the LaCrosse serogroup -summer fall-July to sept -school aged kids (6 month-16 yrs, boys esp) -small mammal reservoir with mosquito vector, day time feeding mosquito that breeds in tree holes, small containers with water, old tires |
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Describe colorado tick fever.
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-reovirus in teh genus coltivirus
-dsRNA genome -vector is a wood tick, reservoirs are ground squirrels and chipmunks -natural hosts found in mountainous regions -March-october (most btwn may and sept) -most frequent in males 15-40 -most ppl have a hx of tick attachment or exposure -saddle backed fever pattern (2-3 days of fever, afebrile for several days and then 2-3 days of fever again) -most pts. recover w/o problems -CTF pts. should not donate blood for at least 6 mos -infects erythroid precursor cells and can persist for months in RBCs |
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Describe the california encephalitis virus group.
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-bunyaviruses
-important cause of mild encephalitis in the US -endemic in midwest -most cases due to the LaCrosse serogroup -summer fall-July to sept -school aged kids (6 month-16 yrs, boys esp) -small mammal reservoir with mosquito vector, day time feeding mosquito that breeds in tree holes, small containers with water, old tires |
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Describe colorado tick fever.
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-reovirus in teh genus coltivirus
-dsRNA genome -vector is a wood tick, reservoirs are ground squirrels and chipmunks -natural hosts found in mountainous regions -March-october (most btwn may and sept) -most frequent in males 15-40 -most ppl have a hx of tick attachment or exposure -saddle backed fever pattern (2-3 days of fever, afebrile for several days and then 2-3 days of fever again) -most pts. recover w/o problems -CTF pts. should not donate blood for at least 6 mos -infects erythroid precursor cells and can persist for months in RBCs |
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Describe new variant CJD.
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-differs from classic CJD in pt. age and observable pathology and location
-younger pts. -core amyloid like deposition with an intense halo of spongiform degeneration -these novel alterations have NOT been observed at all or frequently in CJD cases in the US, australia, or Japan -vCJD cases have been homozygous for a methionine residue at position 129 of Prp |
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What is the vCJD origin hypothesis?
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-the restricted and chronology of vCJD have raised the possibility that bovine spongiform encephalopathy (BSE) or mad cow disease prions were transmitted to humans by food products
-BSE is a massive common source epidemic possibly caused by feeding meat bone meal to livestock -commonly known as mad cow disease, most cows were slaughtered and consumed before disease was manifest -hypothesis is that BSE prions have been passed to humans causing the appearance of vCJD |
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How is prion disease prevented?
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-tests are under development to detect and quantify BSE in cattle entering the human food chain
-destruction of infected food animals -banning certain animal husbandry practices such as MBM feeding and repeated parts recycling in ruminant feed stocks -prohibition of human consumption of CNS and lymphoid tissue from cattle over 6 mos of age |
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What is predicted in the future for vCJD?
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-an incubation period of up to 50 years is postulated based on experience with Kuru
-others posit the existence of asx vCJD "carriers" with surveys of tissue samples from hospital pts. suggesting the ultimate level of vCJD could be high and that blood transfusions from an unknown # of asx donor might perpetuate the epidemic even though dietary sources were eliminated years ago |
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Describe subacute sclerosing panencephalitis (SSPE).
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a chronic inflammatory and demyelinating disease
-rare, slowly progresssive dementing illness affecting primarily kids and young adults -evident 2-10 years after infection with measles virus -intracellular inclusions in neuronal cells, lymphocytic infiltration and destruction of nerve cells -continuous response to persistent measles infection of CNS, virus may exist in latent or defective form |
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Describe progressive multifocal leukoencephalopathy (PML).
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-subacute, progressive demyelinating disease
-association with underlying immune system disorder -reactivation of latent JC virus infection (human papovavirus including SV40 and papilloma viruses) -virus reactivation induces lysis of oligodendrocytes at multiple sites -with advent of AIDS more PML cases are manifest |
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Describe multiple sclerosis.
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-demyelinating disease that produces patchy lesions in white matter with a usual onset in young adulthood
-chronic progression -a viral etiology has been proposed but not proven -HHV-6 has been implicated in this and encephalitis of immune compromised pts. |
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Describe the HIV CNS pathologic mechanisms.
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-HIV-1 productive infection is primarily confined to nonneuronal cells
-perivascular and macrophages and microglial cells mostly -destruction of neural cells is probably indirect and due to a complex cascade of rxns involving both viral and host proteins -viral proteins provoke a host response -viral envelope proteins are structurally diverse and force release of neurotoxic molecules (NO) from infected macrophages -viral protein gp120 may also be neurotoxic |
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What are the portals of entry for CNS disease?
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-secondary invasion from the bloodstream
-penetrating injuries, congenital defects, shunts -contiguous spread from nasal sinus, middle ear, or a nearby infection -intra-axonal transport |
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What are the predisposing factors for meningitis?
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1)community acquired-colonization of the resp. tract,(ex. Neisseria meningitidis, S. pneumoniae, H, influenzae)
2)hospital acquired-iatrogenic procedures, altered immune status (ex: gram neg. rods, S. aureus, other strep and staph) |
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Describe the pathogenesis of bacterial meningitis.
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mucosal colonization-->entry into bloodstream-->penetration of BBB-->release of inflammatory cytokines-->WBC diapedesis into the CSF-->increased permeability of BBB-->exudation of serum-->edema, increased intracranial pressure, altered blood flow
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What are the signs/sx of CNS disease?
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fever, HA, ocular pain, N/V, stiff neck, previous history of URI
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Describe the CSF findings in CNS disease of bacterial meningitis.
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-presence of PMNs or >5 WBCs/mm3
-direct exam via wet mount, gram stain, acid fast stain -indirect exam via imaging methods |
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What properties must drugs have in order to be effective in treating CNS disease?
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-must penetrate the BBB
-must be bactericidal -synergistic combos are used empirically -final choice based on susceptibility data |
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Describe the general characteristics of purulent meningitis.
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-occurrence in kids >2 years old and adults
-irritability, lethargy, severe HA, fever, vomiting, nuchal rigidity, photophobia, convulsions, coma -aggressive tx is essential -fulminant course...death in hrs -neurologic sequelae in 30-50% of survivors |
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What are predisposing factors for neonatal meningitis?
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-immaturity of host defense mechanisms
-immaturity of organ systems, low birth wt -maternal factors such as PROM, urogenital infection during late term, intrauterine infection during early term, invasion of the uterine space |
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What are the signs/sx of neonatal meningitis?
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-different from that seen in adults
-characterized by hyperthermia or hypothermia, CNS manifestations, GI disturbance, resp. abnormalities (apnea, cyanosis) |
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What is the prognosis for neonatal meningitis?
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-generally poor
-survivors generally have permanent defects |
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What are the predominant agents of neonatal meningitis?
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Strep agalactiae
E. coli listeria monocytogenes |
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Describe the characteristics of Strep agalactiae.
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-Group B strep (most are beta hemolytic)
-has capsular polysaccharide, hyaluronidase, collagenase -encapsulated, normal flora of the vagina |
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Describe the difference btwn. early vs. late onset neonatal group B strep infections.
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early onset: maternal OB complications are common, sx develop during first 5 days of life, major clinical manifestations are bacteremia, pneumonia, and meningitis
late onset: maternal OB complications uncommon, sx develop 7 days-3 mos of age, major clinical manifestations are bone/jt infections, bacteremia with concomitant/fulminant meningitis |
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How is diagnosis of Strep agalactiae made?
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-organism isolated from normally sterile areas
-presumptive lab tests include detection of CAMP factor (accentuation of hemolysis due to interaction with staph Beta lysin) -definitive diagnosis requires isolation from blood, CSF, and the site of suppuration, DNA probes, Ag detection |
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Describe the general characteristics of E. coli which causes meningitis.
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-gram neg. enteric bacillus
-encapsulated strains are associated with meningitis -source is rectal colonization of mother's vagina (not endogenous infection) -leading cause of neonatal meningitis |
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Describe the seasonality and incidence of meningitis caused by HIB.
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late winter, early spring
infants 7-18 months |
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Describe the seasonality and incidence of meningitis caused by N. meningitidis.
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winter
infants and kids (1 month-19 yo) |
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Describe the seasonality and incidence of meningitis caused by S. pneumoniae.
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winter
infants kids adults (esp. elderly) |
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Describe the seasonality and incidence of meningitis caused by S. agalactiae.
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winter
neonates adults |
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Describe the seasonality and incidence of meningitis caused by L. monocytogenes.
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summer
newborns predisposed adults |
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Describe the general characteristics of Listeria monocytogenes.
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-gram postive motile coccobacillus
-requires reduced O2 tension for in vitro growth -is non-fastidious and grows at temps from 0-50 C -is a facultative intracell. pathogen in epithelial cells, macrophages, monocytes |
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What are the virulence factors of L. monocytogenes?
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-LPS like surface component which is antiphagocytic, responsible for induction of C-dependent hemolytic abs
-listeriolysin O is excreted which disrupts the phagolysosome membrane, inhibits ag processing |
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Describe the epidemiology of L. monocytogenes.
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-has a worldwide distribution
-found in living and nonliving matter-food and veggies, animal origin (raw hot dogs, chicken) -presence of animal and human carriers |
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Describe the pathogenesis of listeriosis.
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ingestion with raw, contaminated food-->penetration of epithelial cells-->in normal host it is eliminated by immune system
-in immune compromised hosts there is intra and extra cellular multiplication causing systemic disease |
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Describe the clinical manifestations of listeriosis.
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-in neonatal infections: acquired in utero results in stillbirth, abortion, death or pneumonia, seizures, skin lesions with high mortality if undiagnosed early
-acquired from mom's genital tract results in meningitis -adult infections: leading cause of meningitis in cancer and renal transplant pts., brain stem encephalitis classic feature |
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Describe the immunology of listeriosis.
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-immunity is T cell mediated, activated macrophages will kill stationary phase organisms only
-ab is only partially protective |
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How is diagnosis is listeriosis made?
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-alert the lab to your suspicion!
-gram stain of appropriate clinical material -organisms are pleomorphic -culture -"tumbling" motility in hanging drop preparation -DNA probe |
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Describe the general characteristics of HIB.
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-gram neg. non motile, pleomorphic CB
-fastidious |
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Describe the epidemiology of HIB disease.
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-colonizes the nasopharynx of healthy kids and adults
-spread by direct contact, secretions, or aerosols -socioeconomic risk factors are day cares, siblings, crowded household, parental smoking, lack of breast feeding -at risk populations are native alaskans, native americans, persons with humoral immunodef. |
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What are the virulence factors of HIB?
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-capsule composed of polyribose phosphate (virtually all invasive strains are type b, resistance to C in absence of specific ab)
-cell envelope contains LOS, similar to LPS |
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Describe the pathogenesis of HIB meningitis.
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colonization of nasopharynx-->penetration of epithelium-->presence in blood or lymph-->seeding of choroid plexus-->meningitis
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Describe the clinical manifestations of HIB meningitis.
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-antecedent URI and associated and preceding otitis media are common
-usual pattern is several days of mild antecedent infection followed by deteriorating signs and sx of meningitis -onset is insidious |
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How is diagnosis of HIB meningitis made?
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-gram stain of CSF is positive in about 70% of cases
-detection of capsular antigen in CSF, serum, or concentrated urine is positive in 90% of cases and determines prognosis -culture is diagnostic; bacteremia common -susceptibility tests are essential -conjugate vaccines are effective, given prophylactically in contacts |
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Describe the general characteristics of S. pneumoniae.
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-gram pos. non-motile, non-fastidious diplococcus
-capsule in antiphagocytic |
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Describe the epidemiology of pneumococcal infections.
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-acute purulent meningitis may follow pneumococcal pneumonia, infection at another site, or appear with no antecedent infection
-all ages are affected, but most common in elderly -most common agent in pts. with recurrent meningeal infections -vaccine effective |
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What are the clinical manifestations of Pneumococcal meningitis?
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-purulent, similar to signs of other bacterial infections
-acute onset and progression -marked, acute inflammatory exudate, involvement of underlying CNS tissue and often the ventricles |
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How is diagnosis is pneumococcal disease made?
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-gram stain reveals lancet shaped gram pos. cocci in pairs
-colonies are mucoid and alpha-hemolytic -differentiation from the viridans strep. by demonstration of optochin sens., bile solubility, quellung rxn |
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Describe the general characteristics of Neisseria meningitidis.
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-fastidious, gram neg. kidney bean shaped diplococcus
-encapsulated -asx or slightly sx nasopharyngeal carriers -transient bacteremia with fever and spontaneous resolution in 1-2 days -acute meningococcemia develops to meningitis |
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Describe the epidemiology of meningococcus caused by N. meningitidis.
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-humans are the only reservoir
-nasopharynx is colonized -presence of chronic carriers -infection requires close contact -determinants for susceptibility are ill-defined (integrity of mucosa, genetic predisposition, fatigue, crowding,etc) |
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Describe the characteristics of meningococcemia.
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-may evolve into meningitis
-presence of a skin rash, petechiae and pink macules, widespread eruption w/in hours -DIC and gram neg shock can occur -waterhouse-freiderichsen syndrome in children(hemorrhage into adrenal tissue) -similar signs as other forms of acute meningitis (incubation <1 wk) -hematogenous dissemination |
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Describe the sx seen in each of the affected age groups infected with N. meningitidis (meningococcus).
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infants: lack of signs of meningeal irritation early, presence of apnea, seizures, coma, etc
adults and kids: usual presence of specific signs, severe HA, vomiting, neurologic signs |
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How is diagnosis of meningococcal meningitis made?
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-characteristic petechial lesions=meningococcemia
-gram stain of CSF -cultivation of blood, CSF -detection of capsular polysaccharide in CSF -can use chemoprophylaxis of contacts with various drugs -a polysaccharide protein conjugate quadrivalent vaccine is used for children, teens, and high risk persons |
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Describe the general characteristics of parameningeal infections.
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-infection is usually secondary to adjacent infection of ear, sinuses, or skull bones
-infection can be related to metastasis from elsewhere in the body -nervous tissue is highly resistant to bacterial invasion -bacterial invasion of the brain is not a likely occurrence -usually a trauma or preceding predisoposing event that leads to spread of bacteria to brain -bacteroides fragilis is the most common obligate anaerobe -pyogenic brain abscesses are often mixed infections (anaerobic mostly) |
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What are some predisposing conditions associated with abscess sites?
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-trauma to cranium or face
-contiguous site of primary infection (otitis media/mastoiditis-->temporal lobe/cerebellar hemisphere abscess or dental sepsis can lead to frontal lobe abscess) -distant site of primary infection (congenital heart disease, bacterial endocarditis, lung abscess-->multiple abscess cavities) |
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What are the virulence factors of Bacteroides fragilis?
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-neuraminidase alters neuraminic acid containing glycoproteins
-hyaluronidase hydrolyzes hyaluronic acid of connective tissue --LPS activates Hageman factor, thereby initiating the intrinsic coag. pthwy. -polysaccharide capsule may interfere with chemotaxis, phagocytosis, and killing |
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Describe the pathogenesis of brain abscess.
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bacterial entry to the brain-->inflammatory response-->histologic progression: early cerebritis-->late cerebritis-->early capsule formation-->late capsule formation-->abscess
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Describe the clinical manifestations of brain abscesses.
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-it almost never occurs as a consequence of bacterial meningitis
-clinical manifestations reflect 3 separate processes: systemic reaction to infection may occur as a low grade fever, increased intracranial pressure produces HA of progressive severity and occasional localization, damage or destruction of brain tissue results in localizing signs (aphasia, nystagmus, etc) |
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Describe how diagnosis of brain abscess is made.
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-high index of suspicion
-lumbar puncture not recommended -CT or MRI scans generally useful |
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Describe the general characteristics of subdural empyema.
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-intracranial collection of pus between dura and arachnoid
-anaerobic strep are usual pathogens, but staph and enteric bacilli are also important -usual cause is infection of paranasal sinuses or otitis media, other causes include rupture of intracerebral abscess, penetrating skull wound, cranial osteomyelitis, septicemia, etc -mechanism varies: direct extension via bone erosion with otitis media, or indirect extension via venous drainage with paranasal sinus infection -usual clinical onset is acute, and progression varies from hrs to days with high mortality -diagnosis via CT and cerebral angiography -CSF exam for bacteria is usually negative |
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Describe the characteristics of a spinal epidural abscess.
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-a mass of pus located in the epidural space
-staph aureus is the usual pathogen but enteric bacilli and strep are also important -infections occur via direct extension from infection in adjacent tissues, by mets via bloodstream or by a perforating wound -acute cases present with purulent necrosis of the epidural fat that can be local or general -chronic cases present with a thickened, gray dura and replacement of fat with granulation tissue -severe back pain related to affected area -paralysis can occur, mortality rate high -irritation of nerve roots leads to radicular pain in trunk or extremities -diagnosis via myelography or CT scan |
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Describe malignant external otitis.
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-external aud. canal infection that progresses to adjacent tissues and the temporal lobe
-p. aeruginosa is the usual agent -infection spreads from the outer ear to the soft tissues below the temporal bone -rapidly evolving pain, with or w/o discharge is accompanied by swelling of parotid gland and paralysis of nerves VI-XII -cause of death usually meningitis -diagnosis via MRI and CT scans |
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What are the "big 3" granulomatous diseases?
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TB
syphilis leprosy |
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Describe the etiology of leprosy.
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-it is a chronic bacteriosis due to M. leprae
-acid-fast bacillus -obligate intracell. pathogen -grow in histiocytes, macrophages, and Schwann cells but NOT in cell-free media in vitro |
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Describe the epidemiology of leprosy.
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-poorly understood
-humans, monkeys, and armadillos may be infected -disease is more commonly seen in teens and young adults, but can appear at any age -route of infection is most likely the skin, but respiratory and other routes may be possible -incubation period of about 5 yrs |
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Describe the pathogenesis of leprosy.
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contact with m. leprae-->presence of genetic and other factors (adequacy of CMI)-->bacillary infection of mononuclear phagocytes and Schwann cells-->granuloma formation and nerve destruction
-there is a predilection of lesions for cooler parts of the body |
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Describe the clinical characteristics of leprosy.
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-earliest sign of infection is often only a hypopigmented macule, anesthesia may be present
-type of disease and progression dependent of the adequacy of CMI response -Tuberculoid leprosy (TL) -lepromatous leprosy (LL) -borderline leprosy (BB) -progression from TT to LL demonstrates increased # of bacilli in tissues and progression from predominately CMI response to a predom. AMI response (although the abs don't help in protection against the organism) -sx may not appear until 20 yrs after contact |
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Describe the clinical progression of leprosy.
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TL-->BB-->LL
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Describe the clinical characteristics of tuberculoid leprosy.
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-skin lesions are granulomatous and hypopigmented with raised edges and a flattened dry center
-peripheral nerve invasion results in anesthesia at the involved areas |
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Describe the clinical characteristics of lepromatous leprosy.
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-skin lesions are raised, and the histiocytes and macrophages contain many bacilli
-peripheral nerve destruction with anesthesia and eventual trauma, secondary infection, paralysis, ischemia, and distortion of hands and feet -in untreated cases, there is multiple organ involvement and death -many bacilli in skin and nasal secretions |
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Describe borderline leprosy.
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presence of many and varied lesions
-there are various forms with both types of lesions present (raised and flat) -progression toward LL or TL can occur |
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How is diagnosis of leprosy made?
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-residence in an endemic area and/or prolonged contact with pts. increases the likelihood of disease
-skin smear or biopsy is stained fro presence of acid fast bacilli and low or high numbers determined -scarcity of bacilli in TL pts. but abundance in LL -lepromin skin tests useful for prognosis but not diagnosis |
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What are the general characteristics of the clostridia?
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-bacteria found in soil and as normal intestinal flora
-important pathogenic spp are gram-pos. bacilli -environmentally resistant spores produced -exotoxins are responsible for the disease process -various spp. have medical importance |
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Describe the etiology of tetanus.
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-disease is due to clostridium tetani
-only one serotype -spores occur terminally in the bacillus -toxin production is plasmid-mediated |
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Describe the epidemiology of tetanus.
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-bacteria are commonly found in soils and are members of the intestinal flora of humans, horses, other spp
-risk groups are newborns and iv drug users -disease is rare in US but common in less developed countries |
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Describe the pathogenesis of tetanus.
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traumatic event-->establishment of anaerobic conditions-->bacterial multiplication/death with release of tetanospasmin-->binding to nerve endings, intra-axonal transport to inhib. interneurons-->inhibition of NT release-->spasmodic mm. contractions due to toxin effects on central motor control, autonomic function and NM junctions
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What are the clinical characteristics of tetanus?
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-a severe disease characterized by mm. spasms
-different clinical forms of disease are described, but generalized tetanus is the most common form -presence of risus sardonicus, opisthotonos, rigid limbs -resp. complications are common -cardiac complications include hypo and hypertension, tachycardia -death is due to resp. or cardiac complications |
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What are the different clinical forms of tetanus?
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1)generalized
2)neonatal-bacteria colonize the umbilicus, has high mortality in developing countries, rare in US 3)localized tetanus-disease only affects the limbs, rare form that resolves spontaneously 4)cephalic tetanus-disease occurs following head trauma, only facial mm. affected, rare form |
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How is diagnosis of tetanus made?
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-based on clinical findings
-false negs as well as false pos results are reported |
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Describe the prevention and tx of tetanus.
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-active immunization with tetanus toxoid has resulted in this becoming a rare disease in US
-DTap is 4 doses starting at 2 mos old, booster every 10 yrs -passive immunization with human tetanus immune globulin is given to suspected cases - |
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Describe the etiology of botulism.
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-disease is due to C. botulinum an anaerobic bacillus with subterminal heat resistant spores
-8 distinct toxins produced, all neurotoxic, the most potent exotoxin known -toxin production depends on bacteriophage infection |
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Describe the epidemiology of botulism.
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-spores are widespread in soils and sediments and in the GI tracts of various birds, fish, and mammals
-most common sources are foodborne cases occurring in outbreaks due to home-canned foods -honey with contam. spores by infants -wound botulism or GI colonization -in all cases of infection regardless of port of entry, the intracellular toxin is released via bacterial autolysis and produces paralytic illness (blocks Ach release leads to GI sx and paralytic illness) |
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What is the mechanism of the botulinum toxin?
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-NM conduction is blocked as a result of the binding of toxin to receptor sites on motor nerve terminals, with the inhibition of Ach release
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Describe the clinical characteristics of botulism.
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-incubation period varies with amount of systemic toxin
-some minor differences are related to toxin serotype: type E has a shorter incubation period -mortality rates are variable -cranial nerve palsies are typical-diplopia, dysphagia,etc -infant botulism results in flaccid paralysis and eventual involvement of the trunk and extremities -fixed, dilated pupil and dry, furrowed tongue |
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How is diagnosis of botulism made?
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-usually very difficult
-cardinal features include absence of fever, symmetric neurologic manifestations, pt. remains responsive, HR normal or slow in absence of hypotension, sensory deficits are absent (except for blurred vision) -confirmatory diagnosis depends on demonstration of toxin in feces or culture of bacteria |
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How is botulism treated?
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-elimination of the bacillary source
-removal of unabsorbed toxin -neutralization of toxin with antitoxin -supportive therapy -antitoxin from hyperimmunized adults administered IM (previously used equine origin had some risks ) |
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What is toxin production in tetanus governed by?
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a plasmid gene
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What is toxin production in botulism governed by?
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a bacteriophage
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What is more fatal: botulism or tetanus?
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tetanus usually
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Describe how prions are propagated.
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-a post translational conformation induction process occurs in which PrP (prion) forces the conversion of the normal cell protein PrPc to the diseased state
-no unique post-translational chemical modifications have yet been identified that differentiate PrPc from PrPsc -PrPsc accumulates in the brain even though levels of PrPc mRNA remain unchanged |
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Describe the prion disease mechanism and manifestations.
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-the exact mechanism of disease production remains uncertain
-substantial spongiform degeneration and astrocytic gliosis -pts lack any detectable immune response to the infection -the pts. brain is destroyed in 60 days w/o febrile response, leukocytosis, or humoral immune response -caused by teh accumulation of PrPsc that interferes with an undefined cellular process |
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How is diagnosis of prion disease made?
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-on clinical grounds
-consider in any pt developing a progressive subacute or chronic decline in cognitive or motor function -pt is usually an adult btwn 40 and 70 yrs old -confirmation with autopsy or brain biopsy -definitive diagnosis can be made if PrPsc is detected by ab after sample is exposed to limited proteolysis -genetic screens are of no value for sporadic or infectious disease diagnosis, the PrPc gene sequence will be entirely normal - |
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Describe prion disease epidemiology.
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-the rate of appearance of spontaneous CJD is stable across the world: 1 case /million ppl/year
-prion diseases appear in 3 ways: 1)genetic form: inherited pt. mutations that appear to destabilize the native structure of PrPc 2)sporadic form:comprise most cases of disease, may represent horizontal transfer of prions for infected animals or simply a spontaneous conversion of PrPc to PrPsc (mutations to the PrP gene are not found in these pts.) 3)infectious form-direct inoculation with PrPsc agent through corneal transplants, dura mater grafts, etc.. |
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Describe new variant CJD (vCJD).
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-differs from classic CJD in pt. age and observable pathology and location
-substantially younger pts -core amyloid like deposition with an intense halo of spongiform degeneration -vCJD cases have been homozygous for a methionine residue at position 129 of PrP |
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What is the vCJD origin hypothesis?
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the restricted distribution and chronology of vCJD have raised the possibility that bovine spongiform encepthalopathy or "mad cow disease" prions where transmitted to humans by food products
-BSE is a massive common source epidemic possibly caused by feeding meat bone meal to livestock -most cows were slaughtered and consumed before disease was manifest -transmission of BSE was by oral conssumption of prions, hypothesis is that BSE prions have been passed to humans causing the appearance of vCJD |
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How is prion infection prevented?
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-tranmission through blood is possible-steps have been taken to limit blood donation based on residence
-best means of control are destruction of infected food animals, banning certain animal hubandry practices such as MBM feeding and repeated parts recylcing in ruminant feed stocks, prohibition of human consumption of CNS and lymphoid tissue from cattle over 6 months of age (prions may enter through the M cells of the intestine and course through the lymph system) |
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What is the predicted future for vCJD?
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-an incubation period of up to 50 years is postulated for vCJD based on experience from Kuru
-some think that the existence of asx vCJD carriers might perpetuate the epidemic even though dietary sources were eliminated years ago |
