Spring 2015 exam 1
OMSII CLIs
Rickettsiae
•
Damage:
• Rickettsiae can cause several severe diseases:
•
Rocky Mountain spotted fever (Rickettsia rickettsii) - Most important in the USA, eastern and southern states
transmitted by the Dermacentor spp of tick (not ixodes), vasculitis - infection of the blood vessel endothelium
can lead to encephalitis, pneumonitis, cardiac arrhythmia, nausea, vomiting, and abdominal pain.
•
•
•
•
•
•
•
•
Rash on palms and soles of feet. Triad: Headache, Fever, rash (1st AID)**
Typhus (R. prowazekii) [From the human body louse feces on skin]
Murine typhus (R. typhi),
Scrub typhus (Orientia tsutsugamushi),
Q Fever, which manifests as pneumonia and chronic endocarditis*** [Coxiella burnetii ] - granulomas, no rash
Human monocytotropic ehrlichiosis and human granulocytotropic anaplasmosis both infect leukocytes and
cause thrombocytopenia.
Diagnosis:
• Depends on clinical suspicion and acumen, since laboratory studies are seldom helpful in
establishing a diagnosis during the acute stage.
• Laboratory confirmation is usually achieved in the convalescent stage by demonstrating a fourfold or
greater rise in the titer of antibodies to rickettsial antigens. (antibodies not present initially during
acute presentation)
Treatment and prevention:
• Rickettsial infections can be treated with antibiotics that penetrate into host cells.
• Doxycycline DOC.
• Sulfa drugs actually seem to exacerbate both spotted and typhus fevers. Penicillins, aminoglycosides
do not affect the course of rickettsial diseases.
Rickettsiae
• Pathogen:
• Obligate intracellular bacteria (i.e. Cannot be grown on artificial media) and are not resolved
by light microscopy. Note: Rickettisiae Giemsa stain (1st AID)
• Small gram negative rods, however not readily stainable by gram stain
• Encounter:
• Zoonoses
• The distribution of various rickettsiae tends to be geographically limited and dependent on
the distribution of suitable arthropod (ticks, mites, fleas, lice, and chiggers) vectors or animal
reservoirs.
• Entry:
• Humans usually acquire infection by arthropod bites
• Except: Coxiella burnetii may be acquired by inhalation (cattle/sheep birth products) and
other routes. Not arthropods.
• Symptoms of Rocky Mountain spotted fever begin about a week after inoculation
• Replication & spread:
• The organisms have a predilection for vascular endothelial cells, causing blood vessel damage
and bleeding in various organs. In the skin, vascular damage results in rashes.
• Coxiella burnetii grows in Macrophages
• Ehrlichiosis grow in leukocytes.
Rickettsiae
Table 28-1 Etiology and Epidemiology of Prinicpal Rickettsioses
Rickettsial Agent
Diseases
Reservoir in Nature
Transmissio
n
Geographic
Distribution
Rickettsia rickettsii
Rocky Mountain
spotted fever
Ticks (transovarian
transmission)
Tick bite
North and South
America
Rickettsia conorii
Boutonneuse fever
Ticks (transovarian
transmission)
Tick bite
Southern Europe, Africa
and Asia
Rickettsia
prowazekii
Epidemic typhus
Humans, flying squirrels
Louse feces
Potentially world wide
Recrudescent typhus
(Brill-Zinsser disease)
Humans
None caused
by reactivation
Potentially world wide
Rickettsia typhi
Murine typhus
Fleas and rats
Flea feces
Worldwide, especially in
the tropics and
subtropics
Orientia
tsutsugamushi
Scrub typhus
Chiggers (transovarian
transmission)
Chigger bite
Asia, Oceania, and
northern Australia
Ehrlichia chaffeensis
Human
monocytotropic
ehrlichiosis
Deer, goats, dogs
Tick bite
North America, Africa,
Asia
Anaplasma
phagocytophilum
Human
granulocytotropic
anaplasmosis
Deer, elk, wild rodents
Tick bite
North America and
Eurasia
Coxiella burnetii
Q fever
Cattle, sheep, goats,
other livestock, cats
Aerosol from
infected birth
products; ticks
Worldwide
Bartonella
• Slow growing, Gram negative bacteria, zoonotic
• B henseale:Causes cat-scratch disease (immunocompetent), peliosis hepatitis,
bacillary angiomatosis (immunocompromised)
• B quinata (trench fever/bacteremia)
• B Bacilliformis: Oroya fever, verruga peruana
Encounter and entry:
• B henselae: cat scratch/bite
• B quinata: body louse
• B bacilliformis: South American sandfly
Spread, Multiplication, Damage
• Determined by the adequacy of the host immune response
Diagnosis
• Prolonged cultivation required; special stains; specific antibodies in the blood; PCR
Treatment
• Susceptible to macrolides, probably unnecessary in the immunocompetent
Borrelia
•
Pathogen:
•
•
•
•
Encounter:
•
•
•
•
•
The host immune response to the B. burgdorferi infection causes injury to the host tissues.
Diagnosis:
•
•
•
Lyme disease is a multistage disease that spread from the tick bite site to infect the skin, joints (migratory polyarthritis), heart,
eyes, CNS, and other tissues. Signs and symptoms can be intermittent.
Can cause heart block (1st AID)
Some preference for attachment to brain gangliosides. Common symptom is facial nerve palsy, frequently bilateral (1st AID)
Damage:
•
•
The initial infection is characterized by the hallmark erythema migrans or bull’s eye rash that expands out from the tick bite site.
Spirochete transmission to the host typically does not occur until day 3 of feeding
Spread and multiplication:
•
•
Wild animal reservoir, transmitted to humans via tick bite. Deer tick = Ixodes sp.**
FA: Reservoir is the mouse, important to life cycle
Entry:
•
•
•
Lyme disease is caused by the spiral-shaped bacterium (spirochete) Borrelia burgdorferi.
Borrelia infection in North America is limited to B. burgdorferi. But all species are significant source of Lyme disease in Europe and
Asia.
Giemsa stain
Diagnosis is based on the presence of erythema migrans and antibodies against B. burgdorferi, along with a history that suggests
exposure to infected ticks.
Confirmation can be done with serology ELISA or immunoblot
Treatment and prevention:
•
•
Lyme disease is effectively treated with antibiotic therapy if detected early. 2-4 weeks of Doxycyline in adults and amoxicillin in
children. CNS involvement usually treated with 3rd generation cephalosporin drugs (e.g. Cefatrixone).
Currently no vaccines.
Corynebacterium Diptheriae
*Notcoveredinourbookmuchexplicitly,thisis almoststraightFA
• Gram-positive, “club shaped” Rod
• Diptheria Toxin: AB Toxin that ADP-ribosylates EF-2, just like
Pseudomonas exotoxin A! (Encoded by a B-prophage)
• Sx: Pseudomembraneous pharyngitis (gray-white
pseudomembranes), lymphadenopathy, myocarditis, arrhythmias
• Dx: Metachromic Red/Blue granules and +Elek test for toxin
• Black colonies on Tellurite Agar (resembles “Chinese lettering”)
• Vaccine: part of dTAP, a “toxoid” vaccine [Boards will usually ask
question about recent immigrant (non-vaccinated, endemic areas)]
• Tx: Erythromycin/Macrolides
Trichinella
• Pathogens:
• Helminths that invade tissues
• round worms
• Trichinella spiralis
• Encounter:
• Trichinosis is maintained by a “cycle of carnivorism” in which predators and scavengers feed
on each other and acquire larvae encysted in muscles. Humans usually acquire infection from
undercooked meat from pigs or carnivorous game animals (bear meat=boards buzzword).
• Entry:
• Ingesting encysted larvae contaminated food. Larvae hatch in intestine, mature to adults and
release larvae that invade the intestinal wall and enter the bloodstream. The larvae then
encyst in striated or cardiac muscle.
• Spread and damage:
• Trichinella larvae disseminate from the intestine and encyst in skeletal muscles; fever, severe
muscle pain and intense eosinophilia occur when larvae disseminate to human skeletal
muscles
• Mild infection produces malaise, mild diarrhea, and periorbital edema; severe infection may
be life threatening with CNS involvement.
• Larvae can be present in the heart, skeletal muscle, brain, or GI tract
• Most infected people are asymptomatic
• Larvae encyst in muscle and produce a marked initial inflammatory response. The cysts
usually calcify, although the worms can remain viable for up to 30 years.
• Incubation times depends on larvae load (2-3 days to 10 days)
Trichinella
• Diagnosis:
• visualizing from body fluids or tissues.
• Serologic assays cannot distinguish a new infection from a past one, but is
useful for diagnosis of visitors to an endemic region.
• Rise in antibody titer is diagnostic. Typically occurs 3-4 weeks after infection.
• In severely ill patients, muscle biopsy
• Treatment/Prevention:
• Treatment of trichinosis may shorten the course of illness by killing adult
worms in the intestine to prevent ongoing larval dissemination.
• Prevention of acquisition, treatment of carriers and blocking the return of
parasites to the environment are strategies for interrupting the cycles of
helminth transmission.
• Early stages of infection anthelmintic drugs Albendazole, mebendazole kill
adult parasites in intestine and may prevent ongoing production of invasive
larvae. However later, they are of little use against the encysted larval forms
and may actually provoke symptoms. Bed rest and anti-inflammatory agents
are useful for controlling symptoms. Corticosteroids have been used in
severely ill patients with myocarditis and/or encephalitis
Bordetella Pertussis (aka whooping
cough)
• Encounter: Respiratory tract, only human-human transmission (esp
older adolescents/adults-> susceptible infants)
• Entry: Contagious, direct contact/inhalation respiratory droplets
• Spread and Multiplication: Colonization of upper and lower airways;
do NOT invade deeper tissues
• Damage: Paroxysmal hacking, WHOOPING cough-can be so bad the
kid vomits; (can cause 100-day cough). Dz depends on several
virulence factors, including microbial adhesins and toxins*
• Dx: Bordet-Gengou, aka “Potato” Agar-> not terribly sensitive,
especially as dz progresses. Can also make dx w/ DFA or molecular
techniques, also FA: Regan-Lowe Agar (charcoal, blood, antibiotic)
• Tx: Macrolides, Tetracyclines (best if given early)
• Prevention: Immunize w/ DPT/DTaP (acellular pertussis now given
due to side effects of whole cell)
Treponema Pallidum (aka
Syphilis)
• Spirochete
Encounter and Entry: genital mucosa/skin-sexual contact; can
be congenital*
Spread and Multiplication
• Primary syphilis: painLESS chancre
• Secondary syphilis: dissemination-rash on palms and soles,
constitutive sx, condyloma lata
• Tertiary syphilis**: destruction of tissue
Damage: Unknown mechanism
Dx: VRDL/RPR screening, FTA-ABS to confirm (will stay positive
even after tx, is more specific but more expensive); not
cultivatable. Can visualize treponemes in dark field microscopy
Tx/Prevention: No vaccine, susceptible to penicillin
Treponema Pallidum (aka Syphilis)
Bacillus Anthracis (Anthrax)
•
•
•
•
Gram + Rod, spore forming (infectious form, does NOT spread person-person)
Encounters: Terrorism (category A), zoonotic (“wool-sorter’s disease”)
Only bacteria with a polypeptide (glutamate) capsule
Virulence factors: Exotoxins
• Edema factor (+cAMP)- FA: Responsible for the eschar of cutaneous anthrax
• Lethal factor- a zinc metalloproteinase that cleaves cytoplasmic proteins and inactivates
MAPKK
• Protective antigen-the binding subunit that mediates entry into host cells; main component
of anthrax vaccine
• Various manifestations of the disease:
• Cutaneous: mild, purplish vesicles and papules that progresses to a black eschar 3-5 days
after contact
• Gastrointestinal: rare, after ingestion of contaminated meat; causes fever, bowel changes,
ulcers in the GI tract and abdominal tenderness; high mortality
• Inhalational: most lethal; bacilli are NOT found in the lungs-> spores are transported to the
lymphatics and germinate en route
•
•
Early sx: fever, myalgia, malaise
Late: hemorrhagic mediastinitis, widening of the mediastinum; 50% get hemorrhagic
meningitis, which is always fatal
• Tx/Prevention: Susceptible to many abx, including fluoroquinolones and tetracyclines;
vaccine available for those at high risk
Bacillus Anthracis (Anthrax)
Norovirus
•
Pathogen:
•
•
•
•
•
•
•
Encounter:
•
CRUSE SHIPS
•
Are associated with disease in diverse settings, including schools and childcare centers, nursing homes, vacation settings (e.g. camps and cruise
ships), military ships and maneuvers, restaurants and catered meals, and hospitals.
Have a peak incidence in the winter months in the North America. Year round occurrence
Explosive outbreaks
CRUSE SHIPS
•
•
•
•
Entry:
•
•
GI tract, diarrhea and vomiting. Generally mild and self limited. Can last from 24-48 hours.
Small intestine. Villous blunting in ileum and proximal jejunum with intact intestinal mucosa has been seen on biopsy from volunteers.
Leading cause of viral gastroenteritis in adults and 2nd leading cause of severe disease in children (behind Rotavirus).
Diagnosis:
•
•
•
Susceptibility to norovirus infection and disease is based on histoblood group antigen expression (e.g. blood type and secretor status).
Nonsecretors are immune, and B blood group are less likely to become infected [past PBL question]or develop symptomatic infection.
Damage:
•
•
•
•
Usually do not invade the intestinal mucosa or spread to other organs.
Replication:
•
•
•
Transmitted by the fecal-oral route, usually by person-to-person contact but also by ingestion of food or water.
Spread:
•
•
Calicivirus
ssRNA (+)
No envelope
Caspid- icosahedral
Cannot be cultivated
Short-term immunity only (6-26 weeks)
ELISA of ddx outbreaks but not individuals. .
RT-PCR of vial RNA in stools.
Treatment:
•
Viral gastroenteritis is not treatable by any specific therapy; rather, treatment is supportive to provide and maintain hydration.
Poxvirus
*again, not covered in our book much, so taking from FA
Naked, DS, linear DNA virus w/ a “complex” shape; the largest
DNA virus
• Only DNA virus to replicate exclusively in the cytoplasm*
Carries its own DNA-dependent RNA polymerase
• Smallpox (Variola)-> Live, attenuated vaccine available [WHO
declared eradication in 1979, by 1986 most of world had
stopped vaccinating.]
• Molluscum contagiosum- nodular, “umbilicated” flesh-colored
papule
Oxidase Test
• Oxidase test: determines if a bacteria produces cytochrome C
oxidases; 0xidase + bacteria catalyze donation of NADH to an
electron acceptor (usually O2)-> aka reduction
• Shows up as indophenol blue if +
• End product of rxn: H20 or H202 (further broken down by
catalase, see below)
Oxidase – Organisms (examples): Enterobacteraciae,
Salmonella, Proteus, Yersinia, Shigella
Oxidase +: Pseudomonas, Neisseria, H pylori
Catalase Test
• Catalase degrades H202->H20 and O2->+ test= BUBBLES,
whee
• Clinically used to distinguish Staph (catalase +) from Strep
(catalase -) and Clostridia (-) from Bacillus (+)
• People w/ Chronic Granulomatous Dz frequently get
infections from catalase + organisms
• Examples: Nocardia, Pseudomonas, Listeria, Aspergillus, Candida,
E coli, Staph, Serratia, B. Cepacia
Coagulase Test
• Coagulase is an enzyme that acts w/ a plasma factor and
converts fibrinogen to fibrin
• Clinically, it is used to distinguish Staph Aureus (coag +) from
other staph organisms (S. epidermidis, S. Saprophyticus etc)
• Y. Pestis is also coagulase +