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
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.
