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RICKETTSIACEAE
Part-1
Family Rickettsiaceae
Genus Species
Rickettsia R.prowazekii
R.typhi R.rickettsii R.conorii R.australis R.sibirica R.akari
Orientia O.tsutsugamushi
Ehrilichia (Family: Anaplasmataceae) E.sennetsu E.chaffeensis
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• Howard Taylor ricketts- 1906
Genus Rickettsia
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• Small obligate Intracellular parasites
• Gram-Negative bacteria
– Stain poorly with Gram stain (Giemsa, Giemenez and machiavello stains used)
• Reservoirs - Animals, insects and humans
• Arthropod vectors (except Coxiella)
• Multiply by binary fission
• Possess a trilaminar cytoplasmic membrane and a cell wall of bacterial type.
• Possess both DNA and RNA
• Respond to Tetracycline (and chloramphenicol)
• Do not grow on ordinary culture media
General Features
• Obligate intracellular parasite
• Gram negative pleomorphic rods
• Parasite of arthropods – fleas, lice, ticks and mites.
• No Human to human transmission.
Rickettsia inside the host cell
0.25 u in diameter
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Rickettsial infections- classification
• Typhus fever group
- Epidemic typhus
(Louse born typhus/ classical typhus): R. prowazekii- Brill-Zinsser typhus
(Recrudescent typhus): ………..,,- Endemic typhus
(Murine typhus/ flea born typhus): R. typhi• Spotted fever group
- Rocky mountain spotted fever- RMSF:
R. Rickettsiae- Rickettsial pox:
R. akarii- Indian Tick Typhus :
R. Conorii-
Siberian tick typhus - Australian tick typhus
• Scrub typhus
-Orientia tsutsugamushi
Antigenic structure
• Group specific soluble Antigen
• Species specific Antigen
• Alkali stable polysaccharide
• Endotoxin
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General Features
The rickettsia are bacteria which are obligate intracellular
parasites. They are considered a separate group of bacteria
because they have the common feature of being spread by
arthropod vectors (lice, fleas, mites and ticks). The cells are
extremely small (0.25 u in diameter) rod-shaped, coccoid and
often pleomorphic microorganisms which have typical
bacterial cell walls, no flagella, are gram-negative and
multiply via binary fission only inside host cells. They occur
singly, in pairs, or in strands.
PATHOGENESIS
• Rickettsia are transmitted to humans by the faeces/bite of infected arthropod vector.
• Multiply at the site of entry and enter the blood stream.
• Localise in the vascular endothelial cells and multiply to cause thrombosis lead to rupture & necrosis.
RICKETTSIA INSIDE THE ENDOTHELIAL CELLS
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Replication of Rickettsia
• Infect endothelial cells in small blood vessels - Induced phagocytosis
• Lysis of phagosome and entry into cytoplasm - produce phospholipase
• Replication
• Release
A] EPIDEMIC TYPHUS (CLASSICAL TYPHUS)
Louse Born Typhus
Cause: Rickettsia prowazekii
Vector: Human body louse ( Pediculus humanus corporis) Human head louse ( Pediculus humanus capitis) Incubation period – 5-21 days
Mortality rate is 20-30% in untreated cases.
1] Typhus Fevers
LICE
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SYMPTOMS
• Severe headache
• Chills
• Generalised myalgia
• High fever ( 39-410C)
• Vomiting
• Macular rash after 4-7 days – first on trunk and spreads to limb.(Not on Palms & Soles)
• Lacks conciousness.
• This occur after the person recoveres from epidemic typhus and reactivation of the Rickettsia prowazekii which remained latent for years.
• Mild illness and low mortality rate.
B] Brill –Zinsser/ Recrudescent typhus
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C] ENDEMIC TYPHUS (MURINE TYPHUS)
• R. typhi
• Vector: Rat flea (Xenopsylla cheopis)
• Reservoir: Rat
• Infection occurs after rat flea bite
• Presentation
• pathogenesis
Rickettsial infections- classification
• Typhus fever group
- Epidemic typhus
(Louse born typhus/ classical typhus): R. prowazekii- Brill-Zinsser typhus
(Recrudescent typhus): ………..,,- Endemic typhus
(Murine typhus/ flea born typhus): R.`typhi• Spotted fever group
- Rocky Mountain Spotted Fever- RMSF:
R. Rickettsiae- Rickettsial pox:
R. akarii- Indian Tick Typhus : R. Conorii - Siberian tick typhus
- Australian tick typhus
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Rocky mountain spotted fever R. ricketsii Ixodid Tick
Rickettsial-pox R. akari Mite
Australian tick typhus R. australis Ixodid Tick
indian Tick Typhus R. conorii Ixodid Tick
Siberian tick typhus R.sibirica Ixodid Tick
DISEASE SPECIES VECTOR
Cont...
2] Spotted Fever Group
A] Rocky mountain spotted fever
• Most serious form
• Cause – R. rickettsii
• Infection occurs after tick bite
• Incubation period – 1 week
• More similar to typhus fever but the rash appears earlier and is more prominent (Palms & Soles involved)
Rocky mountain spotted fever R. ricketsii Ixodid Tick
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• The clinical symptoms of other spotted fevers are very similar to Rocky mountain spotted fever
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The rash in a case of Rocky Mountain spotted fever
Figure 21.3
Rocky Mountain Spotted Fever
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B] Rickettsial pox
• Patients develops a papulovesicular lesion at the site of the bite and the enlargement of lymph nodes.
• Followed by fever, chills, headache, malaise and myalgia.
• After 3-4 days, generalised papulovesicular rash appears.
• Recovery after 10-14 days.
Rickettsial-pox R. akari Mite
3] Scrub typhus
Scrub typhus
Orientia
tsutsugamushi
Trombiculid mite (chigger)
Rodents Asia-Pacific region from
maritime Russia and China to Indonesia and North Australia to Afghanistan
DISEASE SPECIES VECTOR RESERVOIR(S) GEOGRAPHIC
DISTRIBUTION
Japanese “tsutsuga” = small and dangerous and “mushi” = creature
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Scrub typhus
• 2-3 weeks after chigger bite abrupt severe headache, chills,
fever, conjunctivitis, deafness and a characteristic eschar at the site of chigger bite.
• Spleen & lymph nodes proximal to eschar enlarge
• One week after fever, a maculopapular rash appears on the trunk which later becomes generalised.
• Case fatality rate 10-60%
Complications of rickettsial diseases
• Bronchopneumonia
• Congestive heart failure
• Multi-organ failure
• Deafness
• Disseminated intravascular coagulopathy (DIC)
• Myocarditis (inflammation of heart muscle)
• Endocarditis (inflammation of heart lining)
• Glomerulonephritis (inflammation of kidney)
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Different Methods of LabDiagnosis
Specimen?
Biopsy PCR
“Does not grow on ordinary culture media”
Laboratory Diagnosis
Presumptive laboratory diagnosis is based on the finding of
rickettsial-like organisms in tissue or blood. Although the organisms are gram-negative, they only weakly take the counter stain, safranin.
Therefore, special staining procedures are used. Infected tissue may be stained with:
• 1. Macchiavello stain--organisms are bright red against the blue background of the tissue.
• 2. Castaneda stain--blue organisms against a red background.
• 3. Giemsa stain--bluish purple organisms.
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Gimenez stain of tissue culture cells infected with Rickettsia rickettsii
A Giemsa stain for visualizing Rickettsia rickettsii
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IMMUNOFLUORESCENT ANTIBODY TECHNIQUE – UTILISES FLUORESCENT ANTIBODY TO DETECT RICKETTSIAL
ANTIGEN IN INFECTED TISSUES
Serological tests
• Weil-Felix reaction
• Complement fixation test
• Latex agglutination test
• Enzyme immunoassay
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• Weil-Felix reaction
–To diagnose rickettsial infections by the demonstration of agglutinins to proteus strains• P.vulgaris ( OX 19, OX 2)
• P.mrabilis (OX K)
Basis of the reaction is the sharing of antigens between Rickettsia and proteus
DISEASE WEIL-FELIX
OX19 OX2 OXK
Epidemic typhus ++ +/- -
Endemic typhus ++ - -
Scrub typhus - - ++
RMSF + + -
Rickettsial pox - - -
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4. Enzyme-linked Immuno-Sorbant Assay (ELISA)
Ag-coated well
Ag-Ab complex
Optical Density
(OD)
ELISA test is a technique for detecting & measuring antigen or antibody.
:-It is one of the most reliable techniques to detect antibody against scrub typhus infection.
:-Its procedure is the principal for development of recent rapid diagnostic kits.
:-This technique is widely used in laboratories & hospitals.
Immunological Assays
Newer Techniques
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• Male guinea pig inoculated intra
peritioneally with blood of patients –
• Fever, scrotal swelling, Enlarged testis, and
cannot be pushed back.-due inflammation and adhesions between layers of Tunica vaginalis
• Test Positive for R.typhi (Endemic typhus ) and Negative for R. prowazekii (Epidemic typhus)
Neill-Mooser Reaction
ISOLATION - culture
• Blood is inoculated in guinea pigs/mice.
• Observed on 3rd – 4th week.
• Animal responds to different rickettsial species can vary
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Treatment
• Treatment should be started early in the first week of illness.
• Doxycycline (first choice)
• Tetracycline (alternate)