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
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
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
25
Q
Ricksettia Typhus - Scrub Typhus
A
- 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
Q
Ehrlichia and Anaplasma
A
- 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
Q
Human monocytotrophic ehrlichiosis (HME)
A
- 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
Q
Human granulocytic anaplasmosis (HGA)
A
- 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
Q
Bartonella
A
- 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
32
Q
B. henselae
A
- 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
34
Q
Bacillary angiomatosis and peliosis hepatis
A
- 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
