Chlamydia, Rickettsia and Related

Question 1

what genus of bacteria does this describe?
- obligate intracellular parasites
- cannot synthesize ATP without host cell
- extracellular form is spore-like
- multiply in cytoplasm of host by distinctive life cycle
- 3 species associated with human disease, one of which may cause infertility in women

Answer 1

Chlamydia

3 species: C. trachomatis, C. pneumoniae, C. psittaci

Question 2

what is the general life cycle of Chlamydia?

Answer 2

1. Elementary body (EB) —> phagocytosis into host cell
2. migration to perinuclear area —> reorganization to Reticulate body (RB)
3. RB multiply, reorganizing back into EBs
4. host cell ruptures, EB released

Question 3

this species of Chlamydia causes a variety of disease, including ocular trachoma, the most common cause of preventable blindness

what is?

Answer 3

Chlamydia trachomatis

ocular trachoma: chronic conjunctivitis that progresses into cornea scarring and blindness; in endemic areas, usually occurs early in life, reinfection common (natural infection does not confer protection against reinfection)

Question 4

what species of Chlamydia causes all of these:
- ocular trachoma
- inclusion conjunctivitis
- infant pneumonia
- genital tract infections
- lymphogranuloma venerum

briefly describe each of these

Answer 4

Chlamydia trachomatis - note that natural infection does not confer protection against reinfection

• ocular trachoma: most common cause of preventable blindness
• inclusion conjunctivitis: acute, adults with concurrent genital tract infections or infants during passage of infected birth canal
• infant pneumonia: moderately ill, no fever
• genital tract infections: most common cause of bacterial STD in US
• lymphogranuloma venerum

Question 5

what is done in the US to prevent neonatal inclusion conjunctivitis caused by passage through the birth canal of a mother infected with Chlamydia trachomatis?

Answer 5

newborns given erythromycin eye drops prophylactically (also protects against gonorrhea)

*note that adults with inclusion conjunctivitis usually have concurrent genital tract infections

Question 6

what is the most common cause of bacterial STD in the US

describe the illness

Answer 6

Chlamydia trachomatis - genital tract infections can be transmitted via vaginal, oral, anal sex

majority of infections M+F are asymptomatic (in contrast to N. gonorrhoeae, which causes acute symptoms)

women: can lead to cervicitis, urethritis, pelvic inflammatory disease (PID), possible infertility/ectopic pregnancy

men: can lead to nongonococcal urethritis, epididymitis

Question 7

what is the primary preventable cause of infertility in women?

Answer 7

Chlamydia trachomatis

women under 25 and older women with risk factors should be tested annually - PCR from vaginal swab (W) or urine (M)

Question 8

which species of Chlamydia is the most common cause of human infection? what illness does it cause?

Answer 8

Chlamydia pneumoniae: only recognized serovar is TWAR

most common among children (5-14)

—> mild upper respiratory tract infection but can also cause pneumonia or bronchitis

Question 9

what species of Chlamydia poses a particular risk to poultry workers, pet shop workers, veterinarians, or people owning birds as pets (esp. imported birds)?

Answer 9

Chlamydia psittaci: zoonosis contracted through inhalation of respiratory secretions or dust from droppings of infected animals or handling infected tissue

—> spectrum of clinical manifestations, hard to diagnose (most common symptoms are fever, headache, sore throat)

Question 10

What pathogens belong to the Spotter Fever Group (2) and Typhus Group (3), respectively, of Rickettsia and Orientia?

Answer 10

Spotted Fever Group: Rickettsia rickettsii, Rickettsia akari

Typhus Group: Rickettsia prowazekii, Rickettsia typhi, Orientia tsutsugamushi

*common symptoms: fever, headache, rash

Question 11

how are Rickettsia and Coxiella transmitted, respectively?

Answer 11

both groups are obligate intracelular organisms

Ricketssia: transmitted via arthropod vector (flea, lice, mites, ticks)

Coxiella burnetii: zoonosis - goats/sheep/cattle are primary reservoirs and shed organism in urine/feces/birth products/milk, air-borne transmission

Question 12

which cells do Chlamydia and Rickettsia target, respectively?

Answer 12

Chlamydia: targets columnar epithelial cells lining mucous membranes (—> conjunctivitis, cervicitis, pneumonia)

Rickettsia: most target endothelial cells lining blood vessels (—> vascular lesions produce hallmark rash)

Question 13

what is the most virulent species in the Spotted Fever Group of Rickettsia & Orientia? Why is diagnosis difficult?

Answer 13

Rickettsia rickettsii: causes Rocky Mountain spotted fever (RMSF)

early diagnosis difficult because hallmark rash appears 2-5 days after onset of illness

diagnosis based on clinical findings, antibiotic therapy (doxycycline) initiated immediately (serologic tests only to confirm diagnosis later)

Question 14

how does Rickettsia rickettsii propagate in host cells? (obligate intracellular pathogen)

Answer 14

1. attach to receptors on host vascular endothelial cells via outer membrane proteins OmpA or OmpB
2. induce phagocytosis, escape from phagosome, proliferate in cytosol
3. proliferation damages cell, leading to increased vascular permeability
4. spread via host cell actin-mediated propulsion
   —> characteristic petechial rash (wrist and ankles towards trunk)

Question 15

describe the clinical characteristics of Rocky Mountain spotted fever, caused by Rickettsia rickettsii (obligate intracellular)

Answer 15

incubation period 2-17 days

fever/headache/myalgia —> rash 3-5 days later, moves from wrist/ankle to trunk

damage to blood vessels (bacteria target endothelial cells) —> organ failure, neurological defects

*note that “spotless” fever may occur in older or black patients

Question 16

what is the drug of choice for treating Rocky Mountain spotted fever, caused by Rickettsia rickettsii? (obligate intracellular)

Answer 16

Doxycycline (begin before diagnosis confirmed, highly virulent and serology tests not reliable early in infection)

Question 17

how is Rickettsia akari (of the Spotted Fever Group) transmitted and what cells does it target? (obligate intracellular)

Answer 17

transmitted to humans via mouse mite

targets macrophages/monocytes (NOT endothelial cells, as other Rickettsia do)

Question 18

what are the clinical characteristics of infection by Rickettsia akari (of the Spotted Fever Group, obligate intracellular pathogen)

Answer 18

causes rickettsialpox

via mouse mite bite —> primary papule forms, ulcerates, and forms darker eschar (ALWAYS PRESENT)

AKARI causes ESCHARi

infection disseminates —> fever, generalized rash, many eshcars

Question 19

which Rickettsia is capable of causing devastating epidemics, and how is it transmitted?

Answer 19

Rickettsia prowazekii (of Typhus Group)

human body louse-borne typhus (recently, flying squirrels)

outbreaks have paralleled war, natural disasters, etc

Question 20

what are the clinical characteristics of infection caused by Rickettsia prowazekii (of Typhus Group)?

Answer 20

human body louse-borne typhus

severe headache, fever, myalgia, rash that spreads trunk to extremities (opposite of Rocky Mountain spotted fever!)

Question 21

What illnesses do Rickettsia typhi and Orientia tsutsugamushi (of Rickettsia Typhus Group) cause, respectively?

Answer 21

Rickettsia typhi —> murine typhus: tropical seaboard regions, rat or rat flea reservoir, causes systemic endothelial infection with fever

Orientia tsutsugamushi —> scrub typhus: chigger (type of mite) is reservoir, transmitted transovarally favoring females, disease of Far East

Question 22

Ehrlichia and Anaplasma are unlike most Rickettsia in that infection does not occur through endothelial cells. Rather, Ehrilcihia infects _______, while Anaplasma infects ____

Answer 22

Ehrlichia: infects monocytes and macrophages

Anaplasma: infects neutrophils

Question 23

Ehrlichia and Anaplasma are both _____ borne zoonoses

Answer 23

tick borne zoonoses

Question 24

Ehrlichia and Anaplasma are tick borne zoonoses that multiply intracellularly in monocytes/macrophages (Ehrlichia) and neutrophils (Anaplasma)

their multiplication within the cytoplasm looks like inclusion bodies and are referred to as ____

Answer 24

morula

Question 25

what illness does Ehrlichia chaffeensis (obligate intracellular bacteria) cause? how should it be treated?

Answer 25

Human Monocytic Ehrlichiosis (HME): mostly undiagnosed, fever/headache/myalgia, leukopenia is key feature

over half cause maculopapular or petechial rash

treat with Doxycycline

[recall that Ehrlichia infect monocytes/macrophages]

E. chaffeensis causes chaffing from rash

Question 26

what illness does Anaplasma phagocytophilum (obligate intracellular bacteria) cause?

Answer 26

Human Granulocytic Anaplasmosis (HGA): neutropenia is key finding (recall Anaplasma invades neutrophils)

disseminates to bone marrow and spleen

morulae are usually present and helpful for diagnosis (inclusions in cells where bacteria is dividing)

Question 27

contrast Human Monocytic Ehrlichiosis (HME) to Human Granulocytic Anaplasmosis (HGA): what species cause each, which usually presents with rash, which usually presents with morulae?

Answer 27

HME: Ehrlichia chaffeensis, leukopenia, maculopapular or petechial rash [morulae rare]

HGA: Anaplasma phagocytophilum, neutropenia, morulae present [rash is rare]
[note the species name has “phago” in it, and neutrophils are phagocytes]

Question 28

how is Coxiella burnetii (obligate intracellular bacteria) transmitted? what kind of illness does it cause?

Answer 28

ticks/arthropods propagation —> sheep/goats/cattle reservoir —> shed via urine/feces/milk

very resistant to destruction due to spore stage

transmission primarily via inhalation of aerosols - VERY infectious (single organism can cause infection)

Q fever: self-limited febrile illness (no rash)

Question 29

for each of these findings, indicate whether they are MOST LIKELY to be found with infection from Rickettsia rickettsii, Ehrlichia chaffeensis, or Anaplasma phagocytophilum:
a. rash
b. leukopenia
c. neutropenia
d. morulae
e. vasculitis

Answer 29

Rickettsia rickettsii —> RMSF (Rocky Mountain Spotted Fever)
Ehrlichia chaffeensis —> HME (Human Monocytic Ehrlichiosis)
Anaplasma phagocytophilum —> HGA (Human Granulocytic Anaplasmosis)

a. rash: RMSF (90%)
b. leukopenia: HME
c. neutropenia: HGA
d. morulae: HGA
e. vasculitis: RMSF (hallmark)