الجمعة، 27 مارس 2009

Rickettsias



Rickesias

Scientific classification
Kingdom:
Bacteria
Phylum:
Proteobacteria
Class:
Alpha Proteobacteria
Order:
Rickettsiales
Family:
Rickettsiaceae
Genus:
Rickettsia
Species
Rickettsia felis , Rickettsia prowazekii , Rickettsia rickettsii , Rickettsia typhi Rickettsia conorii , Rickettsia africae




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). that may transmit the organism to mammalian hosts.
· 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 (except for Rickettsia prowazekii), gram-negative and multiply by binary fission only inside host cells, Coxiella replicate only in the phagolysosome.
· They occur singly, in pairs, or in strands.
· Most species are found only in the cytoplasm of host cells, but those which cause spotted fevers multiply in nuclei as well as in cytoplasm.
· In the laboratory, they may be cultivated in living tissues such as embryonated chicken eggs or vertebrate cell cultures.
· The rickettsiae have very small genomes of about 1.0-1.5 million bases.

· The family Rickettsiaceae is taxonomically divided into three genera:
1. Rickettsia (11 species):
obligate intracellular parasites which do not multiply in vacuoles and do not parasitize white blood cells.

2. Ehrlichia (2 species):
Obligate intracellular parasites which do not multiply in vacuoles but do parasitize white blood cells.
3. Coxiella (1 species):
Obligate intracellular parasite which grows preferentially in vacuoles of host cells.
4. Baartonella (3 species):
Intracellular parasite which attacks the red blood cells.


Structure:
· The structure of the typical rickettsia is very similar to that of Gram-negative bacteria.
· The typical envelope consists of three major layers:
ü An innermost cytoplasmic membrane.
ü Athin electron dense rigid cell wall and an outer layer.
· The outer layer resembles typical membranes in its chemical composition and its trilaminar appearance.
· The cell wall is chemically similar to that of Gram-negative bacteria in that it contains diamino pimelic acid and lacks teichoic acid.
· There are no discrete nuclear structures.
· The flagellum of R. prowazekii is similar to that of other bacteria.

Metabolism:

In dilute buffered salt solutions:
· isolated rickettsia are unstable, losing metabolic activity & infectivity for animal cells.
· If however, the medium is enriched with potassium, serum albumin and sucrose, the isolated organisms can survive for many hours.
· If ATP is added to the solution, the organisms metabolize and consume oxygen.
· The basis for the obligate parasitism of these cells is that they require the rich cytoplasm to stabilize an unusually permeable cell membrane.
· The rickettsia have many of the metabolic capabilities of bacteria, but require an exogenous supply of cofactors to express these capabilities. The response to exogenous cofactors implies an unusually permeable cytoplasmic membrane.
Growth and Multiplication:
· Rickettsia normally multiply by transverse binary fission.
· Under poor nutritional conditions:
v The rickettsia cease dividing and grow into long filamentous forms, which subsequently undergo rapid and multiple division into the typical short rod forms when fresh nutrient is added.
v Immediately after division, the rickettsia engage in extensive movements through the cytoplasm of the cell.
v Six to ten daughter cells will form in a host cell before the cell ruptures and releases them.
· C. burnetii differs from other rickettsia in that it is enclosed in a persistent vacuole during growth and division.
Pathogenicity:
· In their arthropod vectors, the rickettsia multiply in the epithelium of the intestinal tract so they are excreted in the feces, but occasionally gain access to the arthropods salivary glands.
· They are transmitted to man by the arthropod saliva, through a bite.
· In their mammalian host, they are found principally in the endothelium of the small blood vessels, particularly in those of the brain, skin and heart.
· Hyperplasia of endothelial cells and localized thrombus (تجلط دموى) formation lead to obstruction انسداد او اعاقه of blood flow, with escape of RBC's into the surrounding tissue.
· Inflammatory cells خلايا ملتهبه also accumulate about affected segments of blood vessels. This angiitis _التهاب وعائى _appears to account for some of the more prominent clinical manifestations مظاهر
· Death is ascribed to damage of endothelial cells, resulting in leakage of plasma, decrease in blood volume, and shock.
· It is assumed that the observed clinical manifestations of a rickettsial infection are due to production of an endotoxin, this endotoxin is quite different in physiological effects from that produced by members of the Enterobacteriaceae.
·
This is inferred, although the toxin has not been isolated, from these facts:
1. IV-injected rickettsia cause rapid death in experimental animals.
2. UV-irradiation of rickettsia diminished their infectivity without reducing toxicity.
3. The use of anti-rickettsial drugs does not prevent rapid death in experimental animals.
4. Antiserum specific for cell wall antigens of the rickettsia prevents the toxic effect.


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; so special staining procedures are used.

Infected tissue may be stained with:
ü Macchiavello stain:
organisms are bright red against the blue background of the tissue.
ü Castaneda stain:
blue organisms against a red background.
ü Giemsa stain:
bluish purple organisms.
· Confirmative diagnosis is based on a serological reaction (Weil-Felix reaction) in which the titer of the agglutinins in the patient's serum against the Proteus strains OX-19, OX-2 and OX-K are determined.
· These Proteus strains have no etiological role in rickettsial infections, but appear to share antigens in common with certain rickettsia.
· These antigens are alkali stable polysaccharide haptens which are distinct from the group-specific and type-specific antigens.
· In interpreting the results, it must be kept in mind that Proteus infections are fairly common (especially in the urinary tract) and that they, may evoke antibodies to the Proteus-OX strains.
· This test is usually positive seven days after the initial infection.
· A more specific complement fixation test is available but does not show positive results until 14 days into the infection.
· The indirect fluorescent antibody test is also useful for the detection of IgM and IgG antibodies against rickettsia. In fact, this is the diagnostic test of choice for ehrlichiosis.
Diseases:
The rickettsial diseases of man are usually broken down according to the arthropod vector as seen in table below.





Disease
Causal agent
Animal reservoir
Weil-Felix response
1. Louse-borne



European epidemic typhus
Rickettsia prowazekii
-------------------------------------------
OX-19
Brill's disease
Rickettsia prowazekii
-------------------------------------------
Negative
Trench fever
Bartonella quintana
-------------------------------------------
Negative
2. Flea-borne



Endemic murine typhus
Rickettsia typhi
Wild rodents
OX-19
Cat scratch fever/Bacilliary angiomatosis
Bartonella henselae
Domestic cat
Unknown
3. Mite-borne



Scrub typhus
Rickettsia tsutsugamushi
Wild rodents
OX-K
Rickettsialpox
Rickettsia akari
House mice
Negative
4. Tick-borne



Rocky Mountain Spottedfever
Rickettsia rickettsii
Dog, rodents
OX-19, OX-2
North Asian tick typhus
Rickettsia siberica
Wild rodents
OX-19, OX-2
Fievre boutonneuse
Rickettsia conorii
Dog, rodents
OX-19, OX-2
Queensland tick typhus
Rickettsia australis
Marsupials, rodents
OX-19, OX-2
Q-fever
Coxiella burnetii
Cattle, sheep, goats
Negative
Spotted fever
Rickettsia rhipicephali
Dogs
Unknown
Ehrlichiosis
Ehrlichia canis
Dogs
Negative
Ehrlichiosis
Ehrlichia chaffeensis
Dogs
Negative
5. Fly-borne



Oroyo fever/Verruga peruana
Bartonella bacilliformis

Unknown
Chemotherapy:
The drugs of choice for the treatment of rickettsial diseases are chloramphenicol and tetracycline. Each of these is highly toxic, especially in children, and must be used with care. The sulfonamides stimulate rickettsial growth and thus are contraindicated in the treatment of these diseases.

Taxonomy:
· The genus Rickettsia is included in the bacterial tribe Rickettsieae, family Rickettsiaceae, and order Rickettsiales.
· This genus includes many other species of bacteria associated with human disease, including those in the spotted fever group and the typhus group
:



Spotted Fever Group (SFG):
• Rickettsia rickettsii is the cause of Rocky Mountain spotted fever (RMSF)
• Rickettsia rickettsii is found in the Americas and is transmitted to humans through the bite of infected ticks.
• Other spotted fever group rickettsiae include:
R. akari (rickettsial pox), R. japonica (Japanese
spotted fever), R. sibirica (North Asian tick typhus), tick bite fever), R. helvetica (perimyocarditis), R. australis
(Queensland tick typhus) and R. honei (Flinders Island spotted fever).
• The spotted fever rickettsiae have been found on every continent except Antarctica.
Typhus Group (TG):
• Rickettsia prowazekii is the cause of epidemic or louse-borne typhus
• R. prowazekii infects human vascular endothelial cells, producing widespread vasculitis.
• Infection usually is transmitted from person to person by the body louse and, therefore, tends to manifest under conditions of crowding and poor hygiene.
• Other rickettsiae in the typhus group include R. typhi and R. felis.
• Murine typhus is caused by transmission of R. typhi from rats, cats and opossums to humans via a flea vector.
• Murine typhus is found worldwide and is endemic to areas of Texas and southern California in the United States.
Scrub Typhus Group (STG) :
• R. tsutsugamushi is the cause of scrub typhus.
• Originally called Rickettsia tsutsugamushi, this organism was given its own genus designation because it is phylogenetically distinct from the other rickettsiae, though closely related. Orientia tsutsugamushi is transmitted to humans by the bite of trombiculid mites (chiggers), which are the vector and host.
• Scrub typhus occurs throughout much of Asia and Australia.
Summary
1. The rickettsia are extremely small gram-negative rod-shaped, coccoid or pleomorphic bacteria with limited metabolic capabilities.
2. The Family Rickettsiaceae contains three genera: Rickettsia, Ehrlichia, and Coxiella.
3. All of the members of the Family Rickettsiaceae are obligate intracellular parasites due to a highly permeable cytoplasmic membrane.
4. Confirmative diagnosis of rickettsial diseases is accomplished via the Weil-Felix test, a complement fixation test and/or an indirect fluorescent antibody test.
5. The drugs of choice for the treatment of rickettsial diseases are chloramphenicol and tetracycline.
6. Louse-borne rickettsial diseases include European epidemic typhus, and Brill's disease. Man is the sole reservoir for louse-borne diseases.
7. The only flea-borne rickettsial disease is endemic murine typhus.
8. Mite-borne rickettsial diseases include scrub typhus and rickettsialpox.
9. Tick-borne rickettsial diseases include Rocky Mountain spotted fever, North Asian tick typhus, Fievre boutonneuse.10. The major target tissue of the rickettsia is vascular endothelium.

Best wishes
Prof. Dr. F. A. Mansour





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