Describe Rickettsia, Ehrlichia, and Coxiella
short, obligate intracellular, gram negative rods (note that they express LPS similar to gram negs, but don't gram stain well)
Describe the pathogenesis of Rickettsia and related microbes
Upon cutaneous infection, vasculitis is typically produced in the endothelial layer of the infected blood vessel wall and progresses to skin rash caused by hemorrhage and edema resulting from damage.
No exotoxins or cytolytic enzymes have been produced but its believed endotoxin production is a main player in fever and petechia characteristic of these infections
What causes Rocky Mountain Spotted Fever?
How is Rickettsia transmitted to humans?
ticks mostly via dogs
When do most cases of RMSF occu?
Areas commonly impacted?
Most cases are pediatric with transmission occuring primarily in the spring and summer months and VASTLY in GA, NC, and VA.
How does RMSF present? Mortality?
-acute onset of flu-like symptoms that include fever, myalgias (especially in the calves), HA, and prostration.
Rash then develops within 2-6 days of acute symptoms, starting at the ankles and wrists, and progressing to the trunk, palms, and soles.
delirium and coma can occur, as well as DIC and edema.
Fatal if untreated about 25% of time
How is RMSF diagnosed?
Pt. history of potential exposure and confirmed by serology using the Weil-Felix test or IFA (below)
How is a Weil-Helix test performed?
On a solid surface (glass slide, tile, card), a small amount (50–100 μL) of the patient’s serum is placed. A single drop of the desired antigen is added, and the resulting suspension is mixed and then rotated for one minute. Visible agglutination is indicative of a positive result, and corresponds roughly to a titer of 1:20. Positive results can be further titrated using the tube method, which is more labour-intensive.
Using 0.25% phenol saline as a diluent, a series of tubes containing twofold dilutions of patient serum are made with a final volume of 1 mL. A drop of antigen suspension is added to each tube, and the mixture is incubated at 50–55 °C for 4–6 hours. A positive tube would show visible flocculation or granulation, which is accentuated when the tube is gently agitated. The titer corresponds to the most dilute tube in the series that still shows positivity. Generally, a titer of ≥1:320 is considered diagnostic.
How is RMSF treated?
Describe the epidemiology of Epidemic typhus (Richettsia prowazekii).
transmited to humans via lice (but not actually believed to be zonootic but may be in flying squirrel) and from human to human after being shed from the lice in feces as they feed on the host
How does Epidemic typhus present?
high morbidity/mortality disease that begins with sudden onset of flu-like symptoms lasting for 1-3 weeks and then rash development 5-9 days after that.
Severe cases can have cardiac or CNS involvement and if left untreated, the death rate is from 10-60%
How is the rash of Epidemic typhus different from that of RMSF?
it spreads from the trunk to the extremities and is not observed on the palm or soles.
How does death typically occur in Epidemic typhus?
bacterial pneumonia or vascular collapse
How is Epidemic typhus diagnosed?
IFA and ELISA to visualize bus in infected tissue or to measure increase in anti-R proazekii Abs (4 fold increase)
Weil-Felix not used
How is Epidemic typhus treated?
doxycycline or tetracycline DOC with chloramphenicol being the next choice
What causes Endemic typhus?
How is rickettsia typhi trasmitted to humans?
rat fleas (small mammals are reservoirs (rats, opossums))
How does endemic typhus present?
Similar to epidemic typhus except that the symptoms are significantly less severe and mortality is rare even when untreated
Diagnosis: via serology
What are the bugs of the Ehrlichia species?
Ehrlichia chaffeensis and Anaplasma phagocytophilia (formerly known as Ehrlichia phagocytophilia)
these bugs cause southern tick-borne disease
What tick transmits anaplasmosis? Ehrlichosis?
Anaplasmosis- blacklegged rick or Ixodes ticks
Ehrlichiosis- Lone Star deer tick
What disease does Ehrlichia chaffeensis cause?
human monocytic ehrlichiosis
What happens once Ehrlichia chaffeensis enters the body?
The obligate intracellular pathogen infects and replicates within monocytes
Dx: blood smear showing MORULAE (below) in monocytes is diagnostic- which is then confirmed via serology. NOTE: the Weil-Helix test does not work for this organism
Where is Ehrlichiosis common?
How does Ehrlichiosis present?
flu-like symptoms (fever, chills, malaise, and muscle pains) with additional symptoms such as GI problems, cough, and conjuctival injection.
Around 60% of children develop a skin rash, while only abut 30% of adults do.
How is Ehrlichiosis treated?
Describe anaplasmosis phagocytophilia.
What is it transmitted through?
Mortality rates? What are the main causes?
Disease caused by anaplasma phagocytophilia (aka rocky mountain spotless fever) trasmitted via Ixodes ticks that presents variably with symptoms ranging from fever and HA to muscle pains, cough, confusion, and malaise.
Although it is assoicated with high morbidity, it is very rarely fatal (due to hemorrhage, renal failure or neurological problems).
How is Anaplasmosis diagnosed? Tx?
Diagnosis depends on area of interest and morulae in NEUTROPHILS (below)
Rash is uncommon in anaplasmosis. What does rash development suggest?
co-infection with B. burgdorferi
Describe coxiella burnetii. Main reservoirs?
How does transmission occur?
obligate intracellular gram neg rod (considered one of the rickettsial diseases) that primarily inhabits cattle, sheep, and goat.
Transmission occurs via ingestion or contact with contaminated milk or dairy products or animal viscera (aka during birthing) OR via ticks
T or F. Humoral immune responses have very limit impact against Coxiella burnetii
T. Intracellular inside macrophages (expresses a number of gene products to survive)
How does Q-fever typically progress?
The typical course is an acute febrile (or commonly asymptomatic) illness that lasts 2-4 weeks and commonly resolves even without treatment.
What are two possible severe sequelae of Q-fever?
endocarditis or granulomatous hepatitis (mortality approaches 100% is untreated)
How is Q-fever dignosed? Tx?
serology for increasing titer of Cb-specific Ab
Tx: doxycycline (shorted disease duration and mitigates risk of chronic infection)
How do spirochetes look?
These are bacteria that are very flexible and highly motile, with a corkscrew-like appearance.
Borrelia spp. and Leptospira Interrogans (and Treponema pallidum- causes syphillis)
What disease does Borrellia burgdorferi cause?
How is B. burgdorferi usually detected?
Can be visualized using either darkfield microscopy or by staining (Giemsa or silver stain)
patient blood or spinal fluid samples are usually negative
How is Borrelia transmitted to humans? What time of year (why)?
What are the primary reservoirs for Ixodes ticks?
via ticks (Ixodes scapularis on the east coast and Midwest, and Ixodes pacificus on the west coast) primarily during the summer months because this is when nymphal stage ticks feed, and the nymphal stage ticks are the most efficiency vectors for transmission. (Efficient transmission of the bug requires between 24-48 hrs of feeding time by the tick)
The primary reservoirs are small mammals (especially the white footed mouse), but others can be involved.
Main states for lyme disease?
NY, NJ, Pennsylvania, and Connecticut are responsible for 80% of cases
What organs does lyme disease typically impact?
bug dissemination from original site to many organs, including the HEART, joints, and CNS.
No virulence factors have been ID'd, but it does use antigenic variation of its outer surface proteins (OSPs) to optimize living conditions
How does Stage 1 Lyme disease present? Describe the rash
painless, non-pruritic rash (bull's eye or erythema chronicum migrans) between 3-30 days after transmission that may be accompanied by fever, chills, or arthralgias.
Describe Stage 2 of Lyme disease. When does it start?
begins weeks to months later and is characterized by cardiac (myocarditis and various forms of heart block) and neurological symptoms such as Bell's palsy (below). Bilateral facial nerve palsy is highly suggestive of Lyme disease.
What is stage 3 of lyme disease?
can last for a long time and is characterized by development of arthritis, primarily in large joints like the knees and shoulders, and progressive CNS disease
How is lyme disease diagnosed?
serology using ELISAs to measure either IgM or IgG specific for Borrella with confirmatory Western blot (PCR now available as well)
hard to culture
How is Stage 1 lyme disese treated? Stage 2-3?
Stage 1: doxy, tetra, or amoxicillin
Stage 2-3: IV ceftriaxone or penicillin G
What causes Relapsing fever and what are their carriers?
two species of Borella, namely
B. hermsii via Ixodes ticks
B. recurrentis via body louse
What are the reservoirs of Borella?
rodents and other small animals primarily in Western U.S.
How does relapsing fever present? Why?
fever that lasts for about a week and then recurs around two weeks later that can continue up to 10 times due to the bugs ability to undergo antigenic variation of the outer surface proteins.
Skin rashes are rare
How is relapsing fever diagnosed? Tx?
visualization of spirochetes on blood smear (serology is of little value)
Tx: tetracycline or doxycycline
What are leptospira and how can they be seen?
do NOT stain well with dyes, but are sometimes visible via dark field mircoscopy
What are the main reservoirs of Leptospira interrogans?
rats, rodents, livestock, and household pets (dogs are primary)
How does Leptospira transmission occur?
via contamined water or soil that becomes contaminated when an animal urinates. Can be transmitted via drinking or SWIMMING (common in triathlons)
also common in farmers, miners, sewer workers, and those of lower SE status in urban areas
Describe the pathogenesis of Leptospira interrogans
dissemination to the liver, kidneys, lungs, and CNS.
The disease is typically biphasic, suggesting antigenic variation occurs
How does Leptospirosis present?
two distinct phases seperated by a period of quiescence.
Early phase: begins with flu-like symptoms including fever, chills, and commonly conjunctivitis that eventually wane
Late phase: variable but can see liver damage (jaundice), kidney dysfunction (Well's disease), lung hemorrhage, or aseptic meningitis
How is leptospirosis diagnosed?
Pt. Hx with clinical symptoms. Serology can sometimes detect a marked increase in anti-leptospira IgM titer, which is diagnostic.
How is leptospirosis treated? Prevention?
Tx: penicillin G
Prevention: vaccination of livestock and pets
What is the causative agent of cat scratch fever?
Describe Bartonella heneslae
-small gram neg rod
-pleomorphic under staining
-has polar flagellum
Epidemiology of Bartonella heneslae
transmitted from cats via bites and scratches (mostly kittens) and also rarely via cat fleas (cat feces or urine does not result in transmission)
human to human transmission is not significant
How does cat scratch fever present? Progression?
usually self-limiting infection primarily seen in children that begins with fever and tender, enlarged lymph nodes (below) near the bite. A papule may be observed prior to the development of nodes.
The disease typically has a long course but resolves without treatment in those who are immunocompetent.
What are the possible complications of SCF in immunocompetent patients?
endocarditis or encephalitis
How is SCF different in immunosuppressed patients?
bacillary angiomas can occur in the skin or visceral organs
How is SCF diagnosed?
serology OR via a specific staining procedures for Bartonella called a Warthin-Starry silver stain procedure (reveals pleomorphic rods)
How is SCF treated?
Tx is not typically recommended, but in cases with severe LAD, azithromycin is the best choice, along with doxy and erythromycin
What is the incubation period of anthrax?
How does anthrax present?
between 2-12 days and sometimes even faster.
At the infection site, a painless lesion develops that includes edema. Subsequently, the lesion becomes blistered and ultimately a painless necrotic center develops (called eschars).
Accompanying symptoms include dizziness, heart palpitations, lymphangitis, and sepsis without treatment