Miscellaneous Obligate Intracellular Bacteria

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Miscellaneous Obligate Intracellular Bacteria

• Rickettsia, Bartonella, Ehrlichia, Coxiella and
  Chlamydia

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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, Chlamydiabut 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

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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

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Typhus rash
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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.

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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

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RMSF cases CDC survey 94-98
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Distribution of the American dog tick
Distribution of the Rocky Mountain wood tick
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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

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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

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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.

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Angiomatosis B. henselae
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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.

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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

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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

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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.

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Chlamydia life cycle