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Miscellaneous Obligate
 Intracellular Bacteria
Rickettsia, Bartonella, Ehrlichia,
    Coxiella and Chlamydia
Obligate intracellular bacteria
• Only 2 orders of pathogenic bacteria are currently
  recognized (I think) as obligate intracellular parasites.
  They are obviously difficult to culture in a lab setting.
   – Rickettsiales: Rickettsia, Bartonella (not an OIP),
     Coxiella, Ehrlichia, and others not discussed
   – Chlamydiae: only 1 genus, Chlamydia…but wait…

• Why they are OIPs: a) they are incapable of some life
  processes (replication, metabolism, etc.), b) ???, c) like
  facultatives they can 1. avoid other immune
  cells/weapons and 2. easily disseminate
• Theories on how they are OIPs: a) they can evade
  reactive oxygen cell defenses, b) they can prevent
  phagosome formation or other cooperative immune
  mechanisms, c) ???
• You want more? See this link
  http://www.cvm.uiuc.edu/courses/vp631/Intracell_Bacteria/index.html
Rickettsiales & typhus
• At least 3 genera in this order (Rickettsia, Bartonella,
  Ehrlichia) cause some form of typhus. Typhus (also called
  typhus fever) means “stupor of fever.” Typhus symptoms
  include fever, headache, muscle and joint pain (arthralgia),
  abdominal pain & diarrhea, and a characteristic rash that
  starts (2-6 days following onset of other symptoms) on the
  wrists and ankles, and spreads to the trunk (or vice versa).
• Typhus pathogens (except Coxiella) are transmitted by
  insect vectors (lice, fleas and ticks). They disseminate via
  blood to cause multiple-organ pathology and symptoms, but
  circulatory system and the CNS is the major target.
• Typhus pathogens discussed here: Rickettsia rickettsii
  causes “tick typhus,” Rickettsia prowazekii causes “louse
  typhus,” Rickettsia typhi causes “murine typhus,” Bartonella
  henselae causes cat scratch fever, & then Ehrlichiosis
Typhus rash
Rickettsia
• Rickettsia are very small, so small that they are barely
  visible under oil immersion microscopy. They are
  structurally Gram negative but stain poorly.
• Being OIPs, they can not be cultured axenically. They can
  only be cultured in cell culture, embryonated eggs, or
  susceptible animals. They divide by standard prokaryotic
  binary fission within host cells.
• All of the medically significant Rickettsia except R. typhi (so
  that includes R. rickettsii and R. prowazeki in here) possess
  antigens that cross-react with antigens of Proteus vulgaris.
  This fact is used in the Weil-Felix agglutination serology
  test to detect anti-Rickettsial antibodies in patients serum
• All of the Rickettsia are transmitted by arthropod vectors
  (Coxiella is the exception) and all are zoonoses with the
  exception of R. prowazeki which is human to human.
Rickettsia rickettsii
• R. rickettsii causes 95% of all modern typhus cases and
  deaths in the US - ~1000 cases/year. This is a severe
  condition with an untreated mortality is ~20%.
• Most cases occur in children during the spring or summer.
• It causes “tick typhus”, also known as Rocky Mountain
  spotted fever. The wood tick or dog tick is the insect
  vector. Despite the name, most cases occur along the
  east coast where dog ticks are most prevalent. Ticks, dogs
  and rodents are the reservoir.
• Symptoms of typhus were mentioned previously. CNS
  symptoms include headache, delerium and coma.
  Circulatory damage includes coagulation, edema and
  venous destructin & collapse. Due to the potential severity,
  it is critical that diagnosis be made quickly on clinical
  grounds. Prompt treatment (broad-spectrum AB such as
  doxycycline or tetracycline) results in complete cure
RMSF cases – CDC survey 94’-98’
Distribution of the American
dog tick




Distribution of the “Rocky
Mountain” wood tick
Rickettsia prowazekii
• R. prowazeki causes louse typhus, ie. epidemic typhus, or
  Brill-Zinsser disease (or these days “jail fever” ).
• In terms of deaths, this is the #1 worst of the typhus
  organisms, especially during the European wars (Napolean
  at Waterloo, WW1 and WW2). This organism killed ~3
  million people in WW1 (mostly Russians) and defeated
  Napolean or you might be speaking French.
• The insect vector is body lice – poor hygiene, unclean.
  Transmission occurs human to human via lice vector, either
  directly in blood, or more likely as the contaminated louse
  feces is scratched into the bite wound. To clarify, this is the
  only one in the group that does NOT require an animal
  reservoir as a necessary part of the life cycle.
• Modern louse typhus is prevalent in refugee populations,
  prisons & jails, and in the otherwise poor & homeless.
• Symptoms can be acute and RMSF-like, or a milder
  sporadic / latent condition years after the initial infection
  when immunity wanes – this in known as Brill-Zinsser
  disease
Rickettsia typhi
• R. typhi causes Murine typhus or endemic typhus – as
  opposed to epidemic typhus, cases occur commonly and a
  few at a time in endemic areas: those where conditions
  favor the rodent (murine = rodent) reservoir and flea vector.
• It is most prevalent in depressed tropical port areas such
  as those in the Caribbean Islands. Like R. prowazeki,
  scratching contaminated flea feces into the bite wound is
  the primary means of transmission. The rash is backwards
  here: trunk  extremities. Murine typhus is milder, and will
  resolve untreated within 3 weeks.
• Diagnosis of all Rickettsial diseases is based upon clinical
  presentation and history with reservoirs and vectors, and
  speciation (confirmed) with serological techniques – anti-
  serum agglutination. Culturing of cells is not a feasible
  component of identification / diagnosis
Bartonella henselae
• Bartonella, originally thought to be a Rickettsia, are NOT
  OIPs – they can be cultured axenically. They are
  pleomorphic Gram negative rods.
• Bartonella (formerly Rochalimea) henselae causes
  angiomatosis (damaged vessels of skin = lesions
  resembling Karposi Sarcoma) in immunocompromised
  patients, especially in AIDS patients.
• In the immunocompetent, it causes “cat scratch fever.”
  Part of the normal cat flora, it can be transmitted to
  humans by cat scratch, bit, or flea vector. The primary
  symptom is self-limiting lymphodenopathy.
• Like R. prowazeki, B. quintana was transmitted by lice
  during WW1. It is thought to have killed ~ 1million
  French, Belgian and German soldiers on the western
  front and decimated the Serbian army to the east. The
  condition is typhus, with epidemic typhus-like symptoms.
Angiomatosis – B. henselae
Coxiella burnetti
• Coxiella (formerly Rickettsia) burnetti causes Q fever. It is
  unique in the group by NOT requiring an insect vector,
  however it is an OIP, is a zoonosis, and is considered a
  typhus organism.
• C. burnetti is transmitted by inhaled aerosol (1’ respiratory
  pathology) from urine, feces, placental tissue and amnion of
  cattle, sheep and goats. It is often transmitted during
  livestock birthing on farms.
• Along with typhus symptoms, pneumonia and hepatitis
  occur – diagnostic. The typhus rash is more rare here than
  in the other syndromes. The condition is usually self
  limiting
• Q = query or unknown: the cause of the disease was
  unknown when 1st described in Australia in 1937.
Ehrlichia
• 3 species of Ehrlichia (E chaffeensis, E. ewingii, E.
  phagocytophilia ) have emerged since 1986 as significant
  tick-borne human pathogens.
• All preferentially infect non-specific leukocytes (as OIPs).
  E. chaffeensis infects monocytes / macrophages, and E.
  phagocytophilia and E. ewingii infect granulocytes.
• All have been referred to as spotless Rocky Mountain
  spotted fever. Symptoms are similar as is severity. ~ 500
  cases occurred last year with a 10% mortality rate.
• Each is thought to be transmitted by a few tick species
  including the deer tick, with deer serving as reservoir.
  Areas of greatest prevalence coincide with Lyme disease
  and RMSF cases.
• Laboratory diagnosis by serology - immunofluorescence
Chlamydia
• Chlamydia are small OIPs that do not use insect vectors.
  They are incapable of ATP synthesis, and they replicate by
  a distinctive intracellular life style existing in two stages: 1.
  totally O.I. infectious “elementary bodies” and 2.
  reproductive forms called “reticulate bodies” which can
  survive extracellularly to infect other host cells. Due to their
  odd nature they were once thought to be viruses.
• C. trachomatis causes a highly contagious and common
  (#1 most common bacterial STD) urogenital STD,
  conjunctivitis leading to trachoma which is a leading cause
  of blindness in African & Asia, and lymphogranuloma
  venereum primarily in AIDS patients.
• Like the Rickettsias, as OIPs culture is impractical, and not
  a common means of diagnosis and ID.
• C. trachomatis diagnosis: 1. microscopic examination of
  scrapings for presence of inclusion bodies, 2. serology, 3.
  nucleic acid probes
continued
• C. pneumoniae is a common cause of atypical
  pneumonia, transmissible from person to person in
  respiratory aerosols.
• C. psittaci causes a pneumonia called psittacosis. Cells
  are transmitted airborne from birds or their droppings.
  Diagnosis of C. pneumoniae and C. psittaci are by
  serology.
• Recent data suggests that Chlamydia can be persistent,
  and cause cardiovascular disease, arthritis and other
  systemic conditions.
Chlamydia life cycle

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MDL 237 - Miscellaneous obligate intracellular bacteria

  • 1. Miscellaneous Obligate Intracellular Bacteria Rickettsia, Bartonella, Ehrlichia, Coxiella and Chlamydia
  • 2. Obligate intracellular bacteria • Only 2 orders of pathogenic bacteria are currently recognized (I think) as obligate intracellular parasites. They are obviously difficult to culture in a lab setting. – Rickettsiales: Rickettsia, Bartonella (not an OIP), Coxiella, Ehrlichia, and others not discussed – Chlamydiae: only 1 genus, Chlamydia…but wait… • Why they are OIPs: a) they are incapable of some life processes (replication, metabolism, etc.), b) ???, c) like facultatives they can 1. avoid other immune cells/weapons and 2. easily disseminate • Theories on how they are OIPs: a) they can evade reactive oxygen cell defenses, b) they can prevent phagosome formation or other cooperative immune mechanisms, c) ??? • You want more? See this link http://www.cvm.uiuc.edu/courses/vp631/Intracell_Bacteria/index.html
  • 3. Rickettsiales & typhus • At least 3 genera in this order (Rickettsia, Bartonella, Ehrlichia) cause some form of typhus. Typhus (also called typhus fever) means “stupor of fever.” Typhus symptoms include fever, headache, muscle and joint pain (arthralgia), abdominal pain & diarrhea, and a characteristic rash that starts (2-6 days following onset of other symptoms) on the wrists and ankles, and spreads to the trunk (or vice versa). • Typhus pathogens (except Coxiella) are transmitted by insect vectors (lice, fleas and ticks). They disseminate via blood to cause multiple-organ pathology and symptoms, but circulatory system and the CNS is the major target. • Typhus pathogens discussed here: Rickettsia rickettsii causes “tick typhus,” Rickettsia prowazekii causes “louse typhus,” Rickettsia typhi causes “murine typhus,” Bartonella henselae causes cat scratch fever, & then Ehrlichiosis
  • 5. Rickettsia • Rickettsia are very small, so small that they are barely visible under oil immersion microscopy. They are structurally Gram negative but stain poorly. • Being OIPs, they can not be cultured axenically. They can only be cultured in cell culture, embryonated eggs, or susceptible animals. They divide by standard prokaryotic binary fission within host cells. • All of the medically significant Rickettsia except R. typhi (so that includes R. rickettsii and R. prowazeki in here) possess antigens that cross-react with antigens of Proteus vulgaris. This fact is used in the Weil-Felix agglutination serology test to detect anti-Rickettsial antibodies in patients serum • All of the Rickettsia are transmitted by arthropod vectors (Coxiella is the exception) and all are zoonoses with the exception of R. prowazeki which is human to human.
  • 6. Rickettsia rickettsii • R. rickettsii causes 95% of all modern typhus cases and deaths in the US - ~1000 cases/year. This is a severe condition with an untreated mortality is ~20%. • Most cases occur in children during the spring or summer. • It causes “tick typhus”, also known as Rocky Mountain spotted fever. The wood tick or dog tick is the insect vector. Despite the name, most cases occur along the east coast where dog ticks are most prevalent. Ticks, dogs and rodents are the reservoir. • Symptoms of typhus were mentioned previously. CNS symptoms include headache, delerium and coma. Circulatory damage includes coagulation, edema and venous destructin & collapse. Due to the potential severity, it is critical that diagnosis be made quickly on clinical grounds. Prompt treatment (broad-spectrum AB such as doxycycline or tetracycline) results in complete cure
  • 7. RMSF cases – CDC survey 94’-98’
  • 8. Distribution of the American dog tick Distribution of the “Rocky Mountain” wood tick
  • 9. Rickettsia prowazekii • R. prowazeki causes louse typhus, ie. epidemic typhus, or Brill-Zinsser disease (or these days “jail fever” ). • In terms of deaths, this is the #1 worst of the typhus organisms, especially during the European wars (Napolean at Waterloo, WW1 and WW2). This organism killed ~3 million people in WW1 (mostly Russians) and defeated Napolean or you might be speaking French. • The insect vector is body lice – poor hygiene, unclean. Transmission occurs human to human via lice vector, either directly in blood, or more likely as the contaminated louse feces is scratched into the bite wound. To clarify, this is the only one in the group that does NOT require an animal reservoir as a necessary part of the life cycle. • Modern louse typhus is prevalent in refugee populations, prisons & jails, and in the otherwise poor & homeless. • Symptoms can be acute and RMSF-like, or a milder sporadic / latent condition years after the initial infection when immunity wanes – this in known as Brill-Zinsser disease
  • 10. Rickettsia typhi • R. typhi causes Murine typhus or endemic typhus – as opposed to epidemic typhus, cases occur commonly and a few at a time in endemic areas: those where conditions favor the rodent (murine = rodent) reservoir and flea vector. • It is most prevalent in depressed tropical port areas such as those in the Caribbean Islands. Like R. prowazeki, scratching contaminated flea feces into the bite wound is the primary means of transmission. The rash is backwards here: trunk  extremities. Murine typhus is milder, and will resolve untreated within 3 weeks. • Diagnosis of all Rickettsial diseases is based upon clinical presentation and history with reservoirs and vectors, and speciation (confirmed) with serological techniques – anti- serum agglutination. Culturing of cells is not a feasible component of identification / diagnosis
  • 11. Bartonella henselae • Bartonella, originally thought to be a Rickettsia, are NOT OIPs – they can be cultured axenically. They are pleomorphic Gram negative rods. • Bartonella (formerly Rochalimea) henselae causes angiomatosis (damaged vessels of skin = lesions resembling Karposi Sarcoma) in immunocompromised patients, especially in AIDS patients. • In the immunocompetent, it causes “cat scratch fever.” Part of the normal cat flora, it can be transmitted to humans by cat scratch, bit, or flea vector. The primary symptom is self-limiting lymphodenopathy. • Like R. prowazeki, B. quintana was transmitted by lice during WW1. It is thought to have killed ~ 1million French, Belgian and German soldiers on the western front and decimated the Serbian army to the east. The condition is typhus, with epidemic typhus-like symptoms.
  • 13. Coxiella burnetti • Coxiella (formerly Rickettsia) burnetti causes Q fever. It is unique in the group by NOT requiring an insect vector, however it is an OIP, is a zoonosis, and is considered a typhus organism. • C. burnetti is transmitted by inhaled aerosol (1’ respiratory pathology) from urine, feces, placental tissue and amnion of cattle, sheep and goats. It is often transmitted during livestock birthing on farms. • Along with typhus symptoms, pneumonia and hepatitis occur – diagnostic. The typhus rash is more rare here than in the other syndromes. The condition is usually self limiting • Q = query or unknown: the cause of the disease was unknown when 1st described in Australia in 1937.
  • 14. Ehrlichia • 3 species of Ehrlichia (E chaffeensis, E. ewingii, E. phagocytophilia ) have emerged since 1986 as significant tick-borne human pathogens. • All preferentially infect non-specific leukocytes (as OIPs). E. chaffeensis infects monocytes / macrophages, and E. phagocytophilia and E. ewingii infect granulocytes. • All have been referred to as spotless Rocky Mountain spotted fever. Symptoms are similar as is severity. ~ 500 cases occurred last year with a 10% mortality rate. • Each is thought to be transmitted by a few tick species including the deer tick, with deer serving as reservoir. Areas of greatest prevalence coincide with Lyme disease and RMSF cases. • Laboratory diagnosis by serology - immunofluorescence
  • 15. Chlamydia • Chlamydia are small OIPs that do not use insect vectors. They are incapable of ATP synthesis, and they replicate by a distinctive intracellular life style existing in two stages: 1. totally O.I. infectious “elementary bodies” and 2. reproductive forms called “reticulate bodies” which can survive extracellularly to infect other host cells. Due to their odd nature they were once thought to be viruses. • C. trachomatis causes a highly contagious and common (#1 most common bacterial STD) urogenital STD, conjunctivitis leading to trachoma which is a leading cause of blindness in African & Asia, and lymphogranuloma venereum primarily in AIDS patients. • Like the Rickettsias, as OIPs culture is impractical, and not a common means of diagnosis and ID. • C. trachomatis diagnosis: 1. microscopic examination of scrapings for presence of inclusion bodies, 2. serology, 3. nucleic acid probes
  • 16. continued • C. pneumoniae is a common cause of atypical pneumonia, transmissible from person to person in respiratory aerosols. • C. psittaci causes a pneumonia called psittacosis. Cells are transmitted airborne from birds or their droppings. Diagnosis of C. pneumoniae and C. psittaci are by serology. • Recent data suggests that Chlamydia can be persistent, and cause cardiovascular disease, arthritis and other systemic conditions.