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RICKETTSIA
MUHAMMED MAHFUZUR RAHMAN
Lecturer
Department of PHARMACY
2. Introduction
Obligate intracellular parasite
Gram negative pleomorphic rods
Parasite of arthropods – fleas, lice, ticks and mites.
No Human to human transmission.
Despite the similar name, Rickettsia bacteria do not
cause rickets, which is a result of vitamin D
deficiency.
In the past, positioned somewhere between viruses
and true bacteria.
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Rickettsia inside the
host cell
TICK
FLEA
MITE
LICE
3. Naming
The genus Rickettsia is named after Howard
Taylor Ricketts (1871–1910), who studied
Rocky Mountain spotted fever in the
Bitterroot Valley of Montana.
Ricketts was devoted to his research and, on
several occasions, injected himself with
pathogens to study their effects.
In 1910, Ricketts became interested in a
strain of typhus known as tabardillo, due to a
major outbreak in Mexico City.
Days after isolating the organism that he
believed caused typhus, he himself died of
the disease.
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Howard Taylor Ricketts
(1871–1910)
4. General characteristics
Structurally similar to gram (-) bacilli
DNA & RNA
Enzymes for Kreb’s cycle
Ribosomes for protein synthesis
Inhibited by antibiotics Tetracycline & Chloramphenicol
Originally thought to be viruses
Small size
Stain poorly with gram stain
Grows only in cytoplasm of Eukaryotic cells
Obligate intracellular parasites EXCEPT Coxiella
Rickettsia survival depends on entry, growth, and replication within the
cytoplasm of eukaryotic host cells. That’s why, they cannot live in artificial
nutrient environments and is grown either in tissue or embryo cultures.
Reservoirs – animals & arthropods
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5. General characteristics
Humans are accidental hosts
Cell wall is composed of peptidoglycan & LPS (similar to gram negative
bacteria)
Consists of 3 genera
Rickettsia
Ehrlichia
Coxiella
Intracellular location
Typhus group – cytoplasm
Spotted fever group – nucleus
Coxiella & Ehrlichia – cytoplasmic vacuoles
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Rickettsia rickettsii
Engorged tick attached to back of toddler's
head. Adult thumb shown for scale.
7. Rickettsial species and its disease
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Species Disease Reservoir
R. prowazekii
Epidemic typhus, Brill-Zinsser
disease
Human body louse
R. typhi Endemic typhus Rat flea
R. rickettsii Rocky-Mountain spotted fever Ticks
R. conori
Boutonneuse fever Ticks
R. australis
Australian tick typhus Ticks
R. siberica
Siberian tick typhus Ticks
R. akari Rickettsial pox
Mites
8. Pathogenesis
During the first few days of incubation period
• local reaction caused by hypersensitivity to tick or vector products
Bacteria multiply at the site & later disseminate via lymphatic system
Bacteria is phagocytosed by macrophages (1st barrier to rickettsial
multiplication)
If not, after 7-10 days
• organisms disseminate
• replicate in the nucleus or cytoplasm
Infected cells show intracytoplasmic inclusions & intranuclear inclusions
Endothelial damage & vasculitis progress causing
• Development of maculopapular skin rashes
• Perivascular tissue necrosis
• Thrombosis & ischemia
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9. Pathogenesis
Disseminated endothelial lesion lead to increased capillary permeability,
edema, hemorrhage & hypotensive shock
Endothelial damage can lead to activation of clotting system --->
Disseminated intravascular coagulation (DIC)
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12. Epidemic typhus (classical typhus)
Cause: Rickettsia prowazekii
Vector:
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Human body louse
Human head louse
Incubation period – 5-21 days
Mortality rate is 20-30% in untreated cases.
Symptoms
Severe headache
Chills
Generalised myalgia
High fever (39-410C)
Vomiting
Macular rash after 4-7 days
Lacks conciousness.
LICE
13. Brill –Zinsser/ Recrudescent typhus
This occurs after the person is recovered from epidemic
typhus and reactivation of the Rickettsia prowazekii.
The rickettsia can remain latent and reactivate months or
years later, with symptoms similar to or even identical to the
original attack of typhus, including a maculopapular rash.
This reactivation event can then be transmitted to other
individuals through fecal matter of the louse vector, and form
the focus for a new epidemic of typhus.
Mild illness and low mortality rate.
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14. Endemic typhus (Murine typhus)
Cause: Rickettsia typhi
Vector:
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Rat flea
Infection occurs after rat flea bite
Murine typhus is an under-recognized
entity, as it is often confused with viral
illnesses.
Most people who are infected do not
realize that they have been bitten by fleas.
Scanning electron
microscope (SEM)
depiction of a flea
15. Endemic typhus (Murine typhus)
Symptoms
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Headache
Fever
Muscle pain
Joint pain
Nausea
Vomiting
40–50% of patients will develop a discrete rash six days
after the onset of signs.
Up to 45% will develop neurological signs such as
confusion, stupor, seizures or imbalance.
16. Rocky Mountain spotted fever
Cause: R. rickettsii
Infection occurs after tick bite
Incubation period: 1 week
Most serious form
More similar to typhus fever but the rash appears
earlier and is more prominent.
Initial symptoms:
Fever
Nausea
Emesis (vomiting)
Severe headache
Muscle pain
Lack of appetite
Parotitis
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Later signs and symptoms:
Maculopapular rash
Petechial rash
Abdominal pain
Joint pain
Forgetfulness
17. Rickettsial pox
Cause: R. akari
Vector: Mite
Benign febrile illness with vesicular rash resembling chickenpox.
Self-limiting, non-fatal.
The first symptom is a bump formed by the bite, eventually resulting in a black,
crusty scab.
Many of the symptoms are flu-like including
Fever
Chills
Weakness
Achy muscles
The most distinctive symptom is the rash that breaks out, spanning the infected
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person's entire body.
18. Other spotted fever
The clinical symptoms of other spotted fevers are very similar to Rocky mountain
spotted fever
Maculopapular rash
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Late petechial rashes on
palm and forearm
Early (macular) rash on
sole of foot
20. Laboratory Diagnosis
Culture & isolation
Serologic test
Culture & isolation
Blood is inoculated in guinea pigs/mice.
Observed on 3rd – 4th week.
Animal responds to different rickettsial species can vary.
Difficult & dangerous because of the highly infectious nature of rickettsiae.
Symptoms:
Rise in temperature – all species.
Scrotal inflammation,swelling,necrosis – R.typhi, R.conori, R.akari (
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except R.prowazekii)
21. Serologic test
Weil-Felix test
Antibody detection
Based on cross-reactivity between some strains of Proteus &
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Rickettsia
Complement fixation
Not very sensitive & time consuming
Indirect fluorescence (EIA)
More sensitive & specific
Allows discrimination between IgM & IgG antibodies which helps in
early diagnosis
Direct immunofluorescence
The only serologic test that is useful for clinical diagnosis
100% specific & 70% sensitive allowing diagnosis in 3-4 days into the
illness
22. Weil-felix test
Heterophile agglutination test
Using non motile Proteus vulgaris strains (OX 19, OX 2, OX K) to find
rickettsial antibodies in patient’s serum.
Procedure:
Serum is diluted in three separate series of tubes followed by the
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addition of equal amount of OX 19, OX 2, OX K in 3 separate series
of tubes.
Incubation at 370C for overnight.
Observe for agglutination.
Interpretation:
Strong Agglutination with OX 19 => epidemic & endemic typhus.
Strong agglutination with OX 19 & OX 2 => Spotted fever
Strong agglutination with OX K => Scrub typhus (Scrub typhus by
Orientia tsutsugamushi )
23. Immunofluorescent antibody technique
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Immunofluorescent Antibody Technique
(utilizes fluorescent antibody to detect rickettsial antigen in infected tissues)
24. Treatment
Adequate antibiotic therapy initiated early in the first week of illness is highly
effective and is associated with the best outcome.
Fever usually subsides within 24-72 hours after starting antibiotic therapy. If
fever fails to subside with the use of a suitable antibiotic, the diagnosis of
rickettsial disease should be reconsidered.
Doxycycline is the drug of choice; it is preferred over other tetracyclines for
treatment of rickettsial infections.
Chloramphenicol may be used as an alternative.
Recent data from Europe suggest that
fluoroquinolones, such as ciprofloxacin and
ofloxacin, may be effective in the treatment of
certain rickettsial disease.
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25. Can any1 xplain this(!!)
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A bacterium named Bill and his brother
Went out for a drink with each other
In the midst of their quaffing
They split their sides laughing
And each of them now is a mother(??)