Chlamydia, Ricksettia & Other Intracellular Bacterial Pathogenss Flashcards
1
Q
Intracellular Bacterial Pathogens
A
- Chlamydia, Rickettsia, Anaplasma, Ehrlichia, Bartonella and Coxiella
- These organisms all have an intracellular life-cycle and are fastidious in their growth requirements
- some have an obligate intracellular life-cycle with an extracellular spore
-Chlamydia
• some have a completely obligate intracellular life-cycle and are arthropod (tick)-borne
- Rickettsia
- Ehrlichia
- Anaplasma
•and others are free-living or intracellular
- Bartonella
- Coxiella
2
Q
Chlamydia
A
• Obligate intracellular organisms
- cell wall similar to gram-negative bacilli
- lack peptidoglycan
- small genome
• Two developmental forms
- Elementary body (EB)
- spore-like with rigid envelope
- allows survival in the environment - Reticulate body (RB)
- resembles a typical gram-negative bacterium but … - must acquire many nutrients from the host
3
Q
Chlamydia Biphasic Life Cycle
A
• Biphasic developmental cycle
- EB binds to cell membrane of host cell
- Enters a vacuole and converts to RB
- Divides by binary fission
- Lyses the cell, releasing EB
4
Q
There are three Chlamydia species that infect humans
A
- Chlamydia trachomatis
- Chlamydophila psittaci
- Chlamydophila pneumoniae
- C. trachomatis is further divided into:
- biovars and serovars
5
Q
C. trachamatis Pathogenesis and Immunity
A
• Serovars have tropism
- A-K: squamocolumnar epithelium
- L1-L3: lymphoid tissue
• Tissue injury
- occurs due to cell death related to chlamydial replication
- host inflammatory response to Chlamydia and to necrotic debrís
• Immunity is slow and incomplete
- CD4 T lymphocytes
- Evasion
- persistence avoids IFN-γ tryptophan depletion
- doesn’t induce PMN trapping
- antiphagocytic
6
Q
C. trachamatis Epidemiology
A
- Humans are the only reservoir
- Trachoma is the most common cause of blindness in the world
- contracted in infancy
- from hands or secretions
- reinfection common
• 5% of sexually active adults have had genitourinary infection
- One-third of male sexual contacts of women with infection will develop urethritis
- Pharyngitis, proctitis common among MSM
7
Q
C. trachomatis 3 Clinical Syndromes
A
1.Ocular
- serovars A-C
- keratoconjunctivitis (trachoma)
- Genitourinary
- serovars D-K
- non-gonococcal urethritis
- epididymitis
- mucopurulent cervicitis
- pelvic inflammatory disease
- occasional pharyngitis and proctitis
- Rectocolitis
- serovars L1-L3
- lymphogranuloma venereum (LGV)
8
Q
C. trachomatis Trachoma
A
- Chronic inflammation of the conjunctiva caused by infection with Chlamydia trachomatis
- It is the world’s leading cause of blindness
- Prevalent in large regions of Africa, the Middle East, Asia, and Aboriginal communities of Australia - Associated with poor hygiene, youth, poor access to water and sanitation, and close contact between people
- Blindness occurs due to corneal scarring from multiple causes including trichiasis (inward turning of the eye lashes)
- Can be managed by
- Surgery
- Antibiotics (azithromycin)
- Facial cleanliness
- Sanitation
9
Q
C. trachomatis Neonatal inclusion conjunctivitis
A
- Acute watery followed by mucopurulent conjunctival discharge 5-14 days after birth
- Occurs by infection through the birth canal from mother with cervicitis
- Conjunctival scrapings show cytoplasmic inclusions
- Topical therapy is ineffective
- Oral therapy with erythromycin is recommended
10
Q
C. trachomatis Non-gonococcal urethritis/cervicitis
A
- Presents similarly to gonococcal infection but the discharge is less purulent
- Gram stain of the discharge reveals some inflammatory cells but no organisms
- Asymptomatic infections are common, especially in women
- Diagnosis:
- urine nucleic acid amplification test (NAAT)
• Treatment:
- 1000 mg azithromycin po once
11
Q
C. trachomatis Lymphogranuloma venereum (LGV)
A
- Serovars L1, L2, L3 of C. trachomatis are more tissue invasive than serovars D-K
- A primary lesion develops at the site of infection
- Followed days to weeks later by lymphadenopathy, fever, malaise followed by fibrosis, drainage
- Proctocolitis in MSM
- Diagnosis: clinical, NAATs of exudate, serology
- Treatment: doxycycline 100 mg bid x 3 weeks
- “Groove sign”
- separation of femoral and inguinal lymph nodes by the inguinal ligament
12
Q
C. trachomatis Reactive Arthritis
A
- Occurs in 1-2% of patients with C. trachomatis urethritis or cervicitis
- Immune-mediated inflammatory response to bacterial antigens associated with HLA-B27
- Oligoarthritis
- lower extremity large joints
- sacroiliitis
• Ocular findings
- conjunctivitis
- uveitis
• Skin
- circinate balanitis
- keratoderma blenorrhagicum (palm & sole papules) - aphthous ulcers
• Usually resolves over 2-6 months
13
Q
C. psittaci
A
- Psittacosis (parrot fever)
- A zoonosis due to C. psittaci
- Psittacine birds (parrots, parakeets, macaws, cockatiels) and poultry (turkeys, ducks) are the common sources
- usually as asymptomatic carriers
- Spread predominantly by respiratory route
- Fewer than 50 cases annually in the United States
- Presents with fever, chills, headache, hepatitis
- “Horder spots” maculopapular facial eruption
- Diagnosis is based on serology
- Doxycycline 100 mg BID for 10-21 days
14
Q
C. pneumoniae
A
- Initially isolated in the 1960’s from the respiratory tract
- Associated with “atypical” pneumonia - generally mild
- doxycycline appears effective
- diagnosis not generally available
• May reach a viable but culture negative state
- “persistence”
• Linked to other illnesses
- atherosclerosis
15
Q
Ricksettia
A
• Small (~0.5 x 1.0 µM), obligate intracellular gram-negative coccobacilli
- live within the cytosol
- divide by binary fission
- small reductive genomes (1.1-1.5 mB)
- First isolated by Howard Ricketts in 1906 from the blood of patients living in the Bitterroot Valley, MT
- There are at least 27 species
- Divided based on lipopolysaccharide
- Spotted fever group
- Typhus group
• Most are transmitted by ticks
- exceptions:
- epidemic typhus - lice
- murine typhus - fleas
- rickettsialpox - mites
16
Q
Ricksettia Pathogenesis
A
- Introduced into the skin
- Spread rapidly through lymphatics
- Phagocytosed by vascular endothelial cells
- Escape from phagolysosome into cytosol
- Cell-to-cell spread
- Results in small blood vessel endothelial inflammation
- ↑ vascular permeability, hemorrhage, and thrombosis
- petechial rash
- edema, hypovolemia, hypotension
- sepsis, shock
17
Q
Ricksettia Clinical Syndromes
A
• Although presentation varies with the different species, the syndrome produced by Rickettsia usually consists of :
- Headache
- Fever
- Myalgia
- Rash
- In some cases (not RMSF), there may be an eschar at the site of inoculation
- Doxycycline is the therapy
18
Q
Ricksettia Spotted Fever Group - RMSF
A
- Caused by R. rickettseii
- Untreated fatality rate of 23%
- 4% with treatment
- In the U.S., transmitted by Dermacentor and Rhipicephalus dog ticks
- Most prevalent in the Southeast and South-central U.S.
- but epidemic area in eastern AZ
• Peak incidence late spring and summer
19
Q
Ricksettia Spotted Fever Group - RMSF Clinical Presentation
A
- History of tick bite in 70%
- 2-14 days later
- fever, headache, myalgias, nausea, vomiting
• Petechial rash occurs after more several days
- wrists and ankles, spreads proximately
• Subsequently
- skin necrosis with digital gangrene
- renal failure
- acute respiratory distress syndrome
20
Q
Ricksettia Spotted Fever Group - RMSF Diagnosis
A
• Most diagnoses are made clinically
- Fever, headache, rash
- Appropriate exposure history
- tick exposure in endemic area
- Laboratory tools
- Time consuming, not generally available
• skin biopsy
- immunohistochemical stains
- PCR
• serology
- useful only 10-20 days after onset
21
Q
Ricksettia Spotted Fever Group - RMS Treatment and Prevention
A
• Therapy should not be delayed waiting specific laboratory tests
- high mortality if untreated
• Doxycycline
- 100 mg twice daily
- 7 days
- at least 3 days after abatement of fever
• Prevention
- Avoid tick-infested areas
- Protective clothing and repellents
- Remove ticks frequently
• ticks must feed ≥6 hr to transmit
22
Q
Other Spotted Fever Group (SFG) rickettsiosis
A
• Mediterranean spotted fever
- also called Boutonneuse fever
- “tache noire” eschar at bite
- R. connorii
- Rhipicephalus tick
- Siberian tick typhus
- Japanese spotted fever
- African tick bite fever
- Flea-borne spotted fever
23
Q
Rickettsialpox
A
- Caused by R. akari
- Transmitted by the bite of mouse mites
- Biphasic illness with two rashes
- an eschar at the site of the bite
- later followed by malaise, headache, fever and a papular-vesicular rash that leaves a black crust
- First seen in New York City but found in other urban areas
- Often resolves after one week but doxycycline may be helpful
24
Q
Ricksettia Typhus
A
- Caused by R. prowazekii
- Occurs at times of crowding and poor hygiene
- Transmitted by the feces of the human body louse - inoculation by scratching - causes latent infection that serves as reservoir and recrudescence
- Brill-Zinsser disease
- Sylvatic typhus
- fleas from flying squirrels in SE U.S.
• Treatment
- doxycycline
- washing clothes in hot water Epidemic (louse-borne) typhus
- Caused by R. typhi
- Transmitted by the feces of infected fleas - rat fleas (Xenopsylla cheops)
- cat fleas (Ctenocephalides felis)
- Texas, southern California
- Treatment
- Doxycycline
- Flea control Endemic (flea-b
25
Ricksettia Typhus - Scrub Typhus
* Seen in South Asia, China, and Indonesia - “tsutsugamushi triangle”
* Caused by Orientia tsutsugamushi
* Trombiculid mite larvae (chiggers) transmit through bite
- vectors and reservoir
* Humans are dead-end hosts
* Necrotic eschar develops at the site of the bite
* Followed by evanescent maculopapular rash
* 30% mortality if untreated
* Doxycycline effective
26
Ehrlichia and Anaplasma
* Recently discovered obligate intracellular small (0.5 µM) gram-negative bacilli
* Lack both lipopolysaccharide and peptidoglycan
* Infect white blood cells
- Ehrlichia chafeensis: human monocytes
- Anaplasma phagocytophilum: granulocytes
• Dense-cored cells (DCs) infect host cell
- Become reticulate cells (RCs) within cytoplasmic vacuoles
- Replicate inside vacuole (morula)
- Release DCs to infect other cells
* Vertebrate host (white-tailed deer)
* Transmitted by ticks
* Syndrome similar to rickettsial illness but rash less common
* Man is an incidental host
27
Human monocytotrophic ehrlichiosis (HME)
* Caused by Ehrlichia chaffeensis
* South central, southeast, mid-Atlantic U.S.
* Transmitted by the lone-star tick (Amblyomma americanum)
* Headache, fever, chills, myalgias, nausea, vomiting, diarrhea - 5-15 days after tick bite
* Anemia, leukopenia, thrombocytopenia, elevated aminotransferases (liver enzymes)
* Morulae seen inside monocytes
* Diagnosis clinical, PCR of blood, 4-fold rise in antibody
* Doxycyline is the treatment
28
Human granulocytic anaplasmosis (HGA)
* Caused by Anaplasma phagocytophilum
* Transmitted by the wood tick (Ixodes scapularis)
* New England and upper Midwest U.S.
* Headache, fever, chills, myalgias, nausea, vomiting, diarrhea
* Anemia, leukopenia, thrombocytopenia, elevated aminotransferases (liver enzymes)
* Morulae seen inside granulocytes
* Diagnosis clinical, PCR of blood, 4-fold rise in antibody
* Doxycyline is the treatment
29
Bartonella
* Facultative intracellular bacteria
* Propensity to infect vascular endothelium and erythrocytes
* Hemotrophic parasitism
- inoculation from infected arthropod
- residence in primary niche
- seeded to blood stream
- infect erythrocytes
- immune evasion and active immune modulation
30
Bartonella 3 Species Associated with Human Disease
• Three species associated with human disease
1. B. bacilliformis
- Carríon’s disease (Oroya fever, verruga peruana)
2. B. henselae
- Cat-scratch disease
3. B. quintana
- Trench fever
31
B. bacilliformis
* Occurs in the Andes mountain valleys of Peru, Ecuador, and Colombia
* Transmitted by the sand fly
* Oroya fever
- fever, headache, myalgia
- severe hemolytic anemia
• Verruga peruana
- chronic stage
- blood-filled skin nodules
32
B. henselae
* Caused by B. henselae
* Scratch from kitten or feral cat
- infested with fleas
* Papule develops at the site of the scratch
* Followed by lymphadenitis distal and ipsilateral to the scratch
* Rare complications
- Perinaud occuloglandular syndrome
- Neuroretinitis
* Diagnosis: PCR on lymph drainage
* Treatment: doxycycline
33
B. quintana
* Trench fever
* Also called “five-day fever” or “quintan fever”
* Caused by B. quintana
* Transmitted by feces of the human louse
* Original seen in World War I, now mostly in homeless persons
* Generally self-limited recurrent headache, fever, myalgia
34
Bacillary angiomatosis and peliosis hepatis
* Seen in severely immunocompromised patients - patients with AIDS
* Caused by both B. henselae and B. quintana
* Neovascular tumors of the skin and solid organs
* Bacteria can be seen on special stains within these tumors
35
Coxiella burnetti
* Q fever
* Caused by Coxiella burnetti
- facultative intracellular and free-living pleomorphic gram-negative coccobacillus
• Taken into phagolysosome vacuoles of alveolar macrophages
- can survive in the acidic environment and persist
• Zoonosis with cattle, goats, sheep and other animals as reservoirs
- Organisms are inoculated into the soil during parturition and inhaled by susceptible hosts
* Acute Q fever
* fever, headache, malaise
* pneumonia, myocarditis, hepatitis
* Chronic Q fever
* Stroke, heart failure, endocarditis
* Diagnosis: PCR of blood, serology
* Treatment: doxycycline ± hydroxychloroquine
36
Culture-negative endocarditis
* Bartonella henselae, B. quintana, and Coxiella burnetti may cause endocarditis
* Routine blood cultures are negative but echocardiogram reveals valvular vegetations
* Hence, these organisms are a cause of “culture negative endocarditis”
* Doxycycline + hydroxychloroquine has been used for treatment
