ICL 2.23: Rickettsia & Coxiella Flashcards
what’s the microbiology of rickettsia?
gram (-) pleomorphic rods
obligate intracellular parasites = can’t make ATP!
what’s the microbiology of coxiella?
gram (-) pleomorphic = coccobacillus
obligate intracellular pathogen
do rickettsiaceae gram stain?
yes but not well because thin PG layer
giemsa is best for staining
how are rickettsiaceae transmitted?
arthropod vectors = ticks, mites, lice, and flease
most species are maintained in their arthropod hosts by transovarian transmission = don’t have to have a blood meal from humans to maintain bacteria
what disease does R. rickettsii cause? vector? host? location?
rocky mountain spotted fever
vector = ticks
hosts = small mammals, dogs, rabbits, birds
North & South America
what disease does R. akari cause? vector? host? location?
rickettsialpox
vector = mites
hosts = mice, rats
worldwide
what disease does R. prowazekii cause? vector? host? location?
epidemic typhus
vectors = human body lice –> hosts = humans
OR
vectors = lice, fleas –> hosts = flying squirrels
worldwide
what disease does R. typhi cause? vector? host? location?
endemic typhus
vector = fleas
hosts = opossums
USA
what disease does coxiella burnetii cause? vector? host? location?
Q fever
vector = ticks
hosts = small mammals, sheep, goats, cattle, dogs
worldwide
what disease does orientia tsutsugamushi cause? vector? host? location?
scrub typhus
vectors = mites
hosts = rodents
asia, india, australia
how do rickettsiae enter host cells?
they enter host cells by stimulating phagocytosis or endocytosis
after engulfment, these bacteria degrade the phagosomal membrane by using phospholipase
then the bacteria replicate in the cytoplasm or nucleus, and are continually released from the cell
how do rickettsiae move around in the host cell?
they have intracellular motility via actin polymerization!
**the exception is the typhus group
which of the following do NOT utilize actin polymerization to mediate intracellular motility within host cells?
A. typhus group rickettsia
B. spotted fever group ricettsia
C. burkholderia pseudomallei
D. listeria monocytogenes
E. shigella flexneri
A. typhus group rickettsia
which cells do rickettsiae invade? what happens?
endothelial cells
rickettsial diseases are model examples of vasculitis with localization in endothelial cells –> the bacteria then uses the actin “railroad” to punch through to the next cell without detection
the major pathophysiologic effect of endothelial cell injury is increased vascular permeability = edema, hypovolemia, hypotension, hypoalbuminemia
rickettsiae also routinely infect vascular smooth-muscle cells
which bacteria causes Rocky Mountain spotted fever?
rickettsia rickettsii
which cells does rickettsia rickettsii infect?
it infects the cells lining blood vessels throughout the body
damage causes the blood to leak via tiny holes into surrounding tissues = rash!!
because of this, severe manifestations of this disease may involve the respiratory system, central nervous system, gastrointestinal system, or renal system
what are some of the risk factors of R. rickettsii infection?
- age extremities (young or old)
- male
- AA and american indian race
- chronic alcohol abuse
- glucose 6-phosphate dehydrogenase deficiency (we don’t know why)
- frequent exposure to dogs and residing near wooded-high grass areas increases risk of infection
is the incidence of RMSF increasing or decreasing?
increasing….
we think it’s because people are living in areas with more ticks
what is the principal reservoir and vector for R. rickettsii?
infected hard ticks
- wood tick = west US
- dog tick = eastern US and california
just know that the ticks that cause RMSF in america are a different species than the ones in south america
how is R. rickettsii transmitted?
ticks transmit the organism to vertebrates primarily by their bite
but also, infection may occur after exposure to crushed tick tissues, fluids, or tick feces because it’s enough to get through your skin and infect you
however, the bite is more infectious
what are the stages of how a tick infects someone with R. rickettsii?
ticks can become infected from feeding on an infected host in either the larval, nymphal, or adult stage –>
the major mammalian reservoir is wild rodents
after developing into the next stage, R. rickettsii may be transmitted to a second host by either:
- during the subsequent feeding process
- male ticks may infect female ticks through body fluids or spermatozoa transfer
- female tick can also transmit R. rickettsii to her eggs = transovarial transmission
once infected, a tick can carry the pathogen for life
where are most cases of RMSF in the US?
the tick belt!!!
aka the south-Atlantic and south-central regions of the United States
recently, highest incidence rates were OK, NC, MO, TN, AR
where is RMSF in the world?
it’s a western hemisphere disease!
aka it’s only in the americas
what time of the year is RMSF most common?
the summer months!!
this is when people are out and about and tick exposure is higher
which age group has a higher incidence of RMSF?
elderly
are people hospitalized for RMSF?
hospitalization rates have decreased over the years due to out increased ability to identify the disease earlier
the number of U.S. cases has increased dramatically since 2000
in what populations is RMSF often fatal?
Increased risk of fatal outcome in ages 0-9 years, American Indians, and African-Americans
in which 5 states do most RMSF cases occur in the US?
- Arkansas
- Missouri
- NC
- oklahoma
- TN
what are the symptoms of RMSF?
DAYS 1-2
1. abrupt onset high fever
- headache
- myalgia
- malaise
DAYS 2-4
1. faint macular rash begins on wrists and ankles and spreads centrally
- abdominal pain, nausea/vomiting
- cough
- calf tenderness
- periorbital and peripheral edema (more common in kids)
DAYS 5-7
1. fever > 104
- worsening respiratory status
- worsening abdominal pain
- rash becomes petechial and widely spread; involves palms and soles of feet**
DAYS 7-9
1. rash becomes diffuse and forms purpura
- necrosis of digits (could need amputation)
- septic shock
- myocarditis and cardiac arrhythmias
- renal failure
what is the DOC to treat RMSF?
doxycycline
doxycycline is the most effective and preventing severe stages of illness and death if administered within the first 5 days of symptoms
fever usually subsides within 24-72 hours if treated within 4-5 days of symptoms
what kind of rash do you see with RMSF?
Most often begins as small, flat, pink, non-itchy spots (macules) on the wrists, forearms, and ankles
RASH STARTS ON THE EXTREMITIES AND MOVES TOWARDS TRUNK!!!
spots turn pale when pressure is applied and eventually can become raised on the skin
the characteristic petechial rash may not be obvious until the sixth day or later after onset of symptoms and it only occurs in 35-60% of people
**also the rash can involve the palms or soles which is not usual!
which of the following does NOT cause rashes on the palms of the hands?
A. coxsackie virus
B. primary syphilis
C. measles
D. staphylococcal toxic shock syndrome
E. neisseria meningitidis
C. measles
what are the symptoms of advanced/fatal cases of RMSF?
In advanced or fatal cases, purpura and skin necrosis or gangrene may develop
since the bacteria is infecting the blood vessels and causing damage, the tissues start dying because blood is leaking out of the vessels and causing the spots
could require amputation of necrotic tissue!!!
what is the magic day for when you need to treat RMSF by?
5th day!!!
the odds of dying from RMSF are ≥5x greater for patients who do not receive anti-rickettsial therapy by the fifth day of their illness
must start treatment before diagnosis
how do you diagnose RMSF?
so most of the following techniques are weak so it’s really more based on history and clinical symptoms because you need to act quick
- Weil-Felix test (crossreactive with proteus antigens)
- IFA to detect either IgM or IgG but the antibody would take a while to show up…
- PCR
- can’t really culture unless it’s in host cells since it’s a intracellular parasite
how do you prevent RMSF?
no vaccine
avoiding tick exposure is best protection
FLASHCARD: microbiology, pathology, epidemiology, clinical, diagnosis, and treatment of rickettsia rickettsii
MICROBIOLOGY: Gram – cocci, minimal peptidoglycan, will not Gram-stain, facultative anaerobe, actin-based motility, obligate intracellular growth, prefer endothelial cells
PATHOLOGY: After introduced into skin, stimulate endocytosis in endothelium. Replicate and use actin-polymerization to invade adjacent cells without exposure to extracellular immunity. Cause leakage from endothelium. Eventually spread all over body, causing leakage from endothelium in most organ systems
EPIDEMIOLOG: hosted and transmitted by Dermacenter ticks in North, Central, and South America. Transmitted transovarily from adult tick to egg (larvae). Major vertebrate hosts are rodents. Highest incidence in OK, NC, MO, TN, and AR, but seen throughout US. Most cases seen in Spring-Summer and increases with patient age. Severe outcome more common in young children, Native and African-American
CLINICAL: Become sick very quick. Initially develop high fever, severe headache, and general illness, but often do not associate tick-bite. Develop rash 2-6 days after fever begins, starting as macules on wrists, forearms, and ankles; includes palms and soles of feet. Eventually spread to other parts. If advances, see purpura, skin necrosis, and gangrene. Mortality rate from 20% to 70%. Treat quickly
DIAGNOSIS: Cannot culture on medium. Must diagnose quickly to start treatment. Initial diagnosis is on clinical symptoms and epidemiology. IFA detection of Rickettsial antibodies is the standard. Can also do IFA or PCR of skin tissues
TREATMENT: Rapid treatment with tetracyclines (doxycycline) is standard
what disease does rickettsia akari cause and how is it transmitted?
causes Rickettsialpox
transmitted by mites
describe the biphasic nature of rickettsia akari?
PHASE 1
red papule develops at site of mite bite –> after 1-2 weeks incubation papule develops an eschar (black wound) –> fever develops as bacteria spread systemically
PHASE 2
develop irregular fluctuating fever
headache, chills, rigors, profuse sweating, myalgias, and generalized rash
how do you treat rickettsia akari infections?
doxycycline
low morbidity and mortality
what is the causative agent of epidemic typhus?
rickettsia prowazekii
prowazekii = ePimedic
this is what killed most of Napolean’s army and soldiers in a bunch of other wars
how is R. prowazekii transmitted?
epidemic typhus is a disease of humans*
human body lice transmits the agent from human to human
a person infested with infected lice acquires the bacteria when the lice or louse feces are rubbed into bite wounds or other skin abrasions
R. prowazekii is also endemic in flying squirrels –> fleas from squirrels can then feel on humans and infect them
in what situations are you more likely to become infected with R. prowazekii?
epidemic typhus commonly occurs in cold climates where people live in overcrowded unsanitary conditions
ex. occur during war and natural disasters
typically facilitated by lice infestation
in what areas of the world are R. prowazekii infections common?
epidemic typhus is currently prevalent in mountainous regions of Africa, South America, and Asia
what are the symptoms of an R. prowazekii infection?
abrupt onset of symptoms
clinical manifestations of typhus include intense headache, chills, fever, and myalgia
characteristic rash develops on the fourth to seventh day of disease
if the disease progresses, you’ll see significant alterations of mental status like stupor or eventually coma
hypotension and renal failure are also common in severe disease
epidemic typhus is a life-threatening illness even for young, previously healthy persons: <40% fatal if untreated
describe the rash spread seen in R. prowazekii infections
characteristic rash develops on the fourth to seventh day of disease
it first appears on the TRUNK and then spreads to extremities!! this is the OPPOSITE of RMSF!!!!
the rash also does NOT involve the face, palms or soles
which cells does R. prowazekii infect?
endothelial cells (just like RMSF)
so it effects small venous, arterial, and capillary vessels
the organism proliferates and spreads to form multiorgan vasculitis
gangrene of the distal portions of the extremities may occur as a result of thrombosis of supplying blood vessels
where does R. prowazekii replicate in the host cell?
the Typhus group does NOT utilize actin-based motility
it accumulate in cytoplasm until cell ruptures
what is the causative agent of endemic typhus?
rickettsia typhi
how is rickettsia typhii transmitted?
causes endemic typhus
rodents are natural reservoir
oriental rat flea and rat lice are vectors for human transmission
where in the world are rickettsia typhii infections common?
occurs in most parts of the world, particularly in subtropical and temperate coastal regions
particularly common along coastal port regions
Temperate climates may have a rise in the flea vector and a subsequent rise in the incidence of murine typhus in the summer months
is rickettsia typhii or rickettsia prowazekii more severe?
rickettsia prowazekii is more severe
rickettsia typhii has the same pathophysiology as epidemic typhus but it’s a milder disease
what are the symptoms of a rickettsia typhi infection?
aka endemic typhus
after 1-2 weeks, see abrupt onset of fever and chills
rash spreading from trunk to extremities
the mortality rate for treated patients with murine typhus is 1-4%
severe disease in elderly/debilitated persons
what is the causitive agent of scrub typhus?
orientia tsutsugamushi
how is scrub typhus transmitted?
it’s caused by orientia tsutsugamushi bacteria
rodents and mites are the natural reservoirs
it’s transmitted to humans by larval mite bite
where in the world in scrub typhus common?
Tsutsugamushi Triangle in Southeast Asia
current reemergence in locations such as India, Micronesia, and the Maldives
incidence is growing in South Korea and China north of the Yangtze River, where was previously unknown
what are the symptoms of scrub typhus?
caused by orientia tsutsugamushi bacteria
black eschar forms at the site of chigger bite followed by spread through the lymphatics and blood
chills, fever, headache, abdominal pain, nausea and vomiting and muscle aches
can develop rash on trunk/axilla that spreads to rest of body but NOT on the palms or soles
what happens in severe cases of scrub fever?
caused by orientia tsutsugamushi bacteria
- interstitial pneumonia
- acute respiratory distress syndrome
- meningoencephalitis
- acute kidney injury
- DIC
how do you treat scrub fever?
doxycycline or azithromycin
what is the causitive agent of Q fever?
coxiella burnetii
what stain do you use for coxiella burnetii?
giemsa
it gram stains poorly
how is coxiella burnetii transmitted?
wild animals are the natural reservoir but it’s best known for infecting farm animals (livestock)
ticks are an important vector for transmission between animals
however, aerosols are the main route of infection for humans –> vets and farmers are at risk
chronically infected animals shed bacteria in feces and urine, placenta, wool, milk
so people can get Q fever by touching feces, urine, milk or blood from an infected animal, breathing in bacteria, touching placenta or drinking raw milk
it’s also believed to be spread by wind = biochemical warfare??
what are the two forms of the intracellular cycle of coxiella burnetii?
- small-cell variant (SCV) –> like the elementary body in chlamydia
- large-cell variant (LCV) –> like the reticulate body in chlamydia
what is the small cell variant of coxiella burnetii?
metabolically inactive but infectious form of coxiella burnetii
it’s the extracellular form –> spore-like and extremely resistant to most environmental conditions
it attachs to the host cell membrane to enter phagocytic cells
after phagolysosomal formation, the drop in pH cause SCV to become active
SCV then divdes to become large-cell variant
what is the large cell variant of coxiella burnetii?
metabolically active, replicating form of coxiella burnetii
intracellular form = protected from antibodies via location
it replicates until it receives the signal to begin forming SCVs
how does coxiella burnetii spread throughout the body?
aerosols are the main route of infection for humans from livestock
after the SCV enter the lungs, the resulting LCVs proliferate and disseminate from the lungs to multiple organ systems
the bacteria persist in macrophages and use these to disseminate throughout host
where in the US is Q fever common?
out west where there’s lots of livestock
which age group is more susceptible to Q fever?
elderly
what time of the year is Q fever common?
april-june
this is calf season!! and infected animals shed coxiella burnetii bacteria in their placenta!!!
does Q fever require hospialization?
kinda….hospitalization rates are very high for Q fever
what are the two types of Q fever that you can get?
- acute disease
2. chronic disease
what are the symptoms of acute Q fever?
only about 50% of all people infected with C. burnetii show signs of clinical illness
after a long incubation period, most acute cases of Q fever begin with sudden onset of one or more of the following:
high fevers (up to 104-105° F), severe headache, general malaise, myalgia, confusion, sore throat, chills, sweats, non-productive cough, nausea, vomiting, diarrhea, abdominal pain, and chest pain
fever usually lasts for 1 to 2 weeks
30-50% of patients will develop an “atypical pneumonia”
hepatitis is also a common manifestation
most patients will resolve the infection within several months without any treatment
what are the symptoms of chronic Q fever?
chronic Q fever is uncommon but is a much more serious disease –> characterized by infection that persists for more than 6 months
patients who had acute Q fever may develop the chronic form as soon as 1 year or as long as 20 years after initial infection
endocarditis is a serious complication of chronic Q fever
≥65% of persons with chronic Q fever may die of the disease
how do you diagnose Q fever?
the symptoms of Q fever are not specific, so it is difficult to make an accurate diagnosis without appropriate laboratory testing
confirming a diagnosis of Q fever requires serologic testing to detect the presence of antibodies to Coxiella burnetii antigens
how can you diagnose Q fever based on antigenic phases?
Phase I is the initial form found in infected animals, but LPS levels are low = highly infectious SCV form; smooth LPS
Phase II is expressed later after become less infectious, but at higher levels = LCV form; rough LPS
in acute Q fever, IgM levels to phase II is usually significantly higher than that to phase I
with chronic Q fever, antibodies to phase I antigens of C. burnetii generally require longer to appear and indicate continued exposure to the infectious form of bacteria
so during a chronic infections, high levels of IgG to phase I in later specimens in combination with constant or falling levels of phase II IgG antibodies indicate chronic Q fever
how do you treat Q fever?
DOC = doxyclycline for adults and children of all ages
antibiotic treatment is most effective when initiated within first 3 days of illness
chronic Q fever endocarditis is much more difficult to treat effectively and often requires the use of multiple drugs = doxycycline and hydroxychloroquine in Q fever endocarditis for 18 months for native valves and 24 months for prosthetic valves
how do you prevent Q fever?
vaccine exists but not available in america
since most outbreaks occur around livestock facilities, prevention and control efforts are usually directed primarily toward these environments. these include:
- appropriate disposal of placenta and other birth products
- release only pasteurized milk and milk products
- quarantine imported animals
what are the symptoms of Q fever in animals?
C. burnetii does not usually cause disease in infected reservoir animals
however you will often see aborted offspring in pregnant animals
how infectious is Q fever?
very….
the infectious dose of virulent Phase I organisms in laboratory animals has been calculated to be as small as a single organism
estimated human ID25-50 (inhalation) for Q fever is 10 organisms
it’s a BSL3 organism
FLASHCARD: microbiology, pathology, epidemiology, clinical, diagnosis, treatment of coxiella burnetii
MICROBIOLOGY: Gram – cocci, will not Gram-stain, obligate intracellular parasite. Has two-phase life cycle. Small-cell variant (SCV) is infectious, non-metabolically active stable particle. Large-cell variant (LCV) not stable outside host cell, but replicate intracellular until form EB, then released
PATHOLOGY: SCV are very stable in the environment and can be spread in aerosols over a wide area. Enter lungs of susceptible animals/humans, where infect tissues and macrophages. Then convert to LCVs and replicate or persist in host cells. Can disseminate in host within macrophages. Non-reservoir hosts develop inflammatory disease in tissues where bacteria persist, including lungs, liver, and heart (severe)
EPIDEMIOLOGY: C. burnetii are found in the birth products (i.e. placenta, amniotic fluid), urine, feces, and milk of infected animals. People can get infected by breathing in dust that has been contaminated by these infected animal materials. Often transmitted between animal hosts via tick-bite. Most cases in Spring-early Summer and more prevalent in elderly. Most associated with interaction with livestock, particularly in western US
CLINICAL: About 50% of exposed will develop acute disease, with general illness symptoms. Severe cases may develop inflammation of the lungs (pneumonia) or liver (hepatitis). A small percentage of these may eventually develop chronic disease, most commonly those with heart valve disease, blood vessel abnormalities, or are immunosuppressed. Usually develop severe endocarditis
DIAGNOSIS: Cannot culture on plates. Usually test for antibodies to Phase I (early LPS) and Phase II (late LPS). In acute cases, IgM to Phase II is much higher than Phase I. In chronic disease, high levels of IgG to Phase I combined with similar or falling levels to Phase II
TREATMENT: Many acute cases self-resolve, but treatable with doxycycline. If chronic disease, treat with doxycycline and hydroxychloroquine for 18-24 months
