Rickettsiae
Rickettsiae
Rickettsiae
- bacteria which are obligate intracellular parasites
- spread by arthropod vectors
- lice, fleas, mites and ticks
- The rickettsial diseases of man are usually broken down according to the arthropod vector
Genera
- Rickettsia (11 species)-
- obligate intracellular parasites which do not multiply within vacuoles and do not parasitize white blood cells.
- Orientia: spread by chiggers, parallel evolution
- Ehrlichia (2 species) -
- obligate intracellular parasites which do not multiply within vacuoles but do parasitize white blood cells.
- Coxiella (1 species)--
- obligate intracellular parasite which grows in vacuoles of host cells.
Ticks
- Soft Tick
- Ehrlichosis
- E. chaffeensis
- Hard Tick
- Rocky Mountain spotted fever
- Wild rodents
- R. rickettsia
Lone Star Tick
Louse
- Typhus
- R prowazekii
- Humans, squirrel fleas flying squirrels
Flea
C burnetii
- C.burnetii differs from other rickettsia in that it is enclosed in a persistent vacuole during growth and division. Six to ten daughter cells will form within a host cell before the cell ruptures and releases them.
Prevention
- Avoid tick - infested areas
- wear protective clothing and use repellants.
- Ticks are difficult to eradicate as they can survive for 4 years without feeding
Ehrlichia Intracellular growth
Ehrlichia Growth Cycle
Rickettsia conorii Growth
- Transverse Binary Fission
- Long filaments under poor nutritional conditions,
- undergo rapid and multiple division into the typical short rod forms when fresh nutrient is added.
Rickettsia conorii
- Immediately after division, the rickettsia engage in extensive movements through the cytoplasm of the cell.
- Attach to “tail” of host actin filaments
- actin provides propulsion
Metabolism
- In dilute buffered salt solutions, isolated rickettsia are unstable, losing both metabolic activity and infectivity for animal cells. If, 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.
Rickettsial Clinical Manifestations
- Entry
- Ticks, fleas, lice, mites
- Spread
- Blood stream & lymphatics
- Disease
- encephalitis, pneumonitis, rash, nausea, vomiting, renal failure
Rickettsia Pathogenicity
Symptoms: Fever, chills, headache, myalgias, rash
Rash: hemorrhages in the skin.
Develops after 3 days
Not seen in 10% of cases
Incubation 2-14 days after tick bite [average 7days] Patient may not recall painless tick bite.
Rash of Rocky Mountain Spotted Fever
Hyperplasia
- Hyperplasia of endothelial cells and localized thrombus formation lead to obstruction of blood flow, with escape of RBC's into the surrounding tissue. Inflammatory cells also accumulate about affected segments of blood vessels.
Angitis
- Angitis appears to account for some of the more prominent clinical manifestations, such as petechial rash, stupor and terminal shock. Death is ascribed to damage of endothelial cells, resulting in leakage of plasma, decrease in blood volume, and shock.
Complications
Gastro-intestinal symptoms, respiratory
failure, encephalitis, renal failure.
Mortality is high when the disease progresses. This is usually due to the late development of the rash and the difficulty of diagnosing the disease
Human Monocytic Ehrelichiosis
- Since 1964, more than 400 confirmed cases of HME, and 170 cases of HGE have been reported, including some from northern California. Many were first thought to be Rocky Mountain Spotted Fever.
Clinical Manifestations: Q Fever
- Entry: aerosol from infected placenta of sheep goats cattle
- Disease
- Pneumonitis endocarditis, granulomas
Rickettsialpox
- R. akari - Clinical infection is biphasic
- First phase
- a vesicle develops at the mite bite site and the organisms multiply ; within one week they have spread systemically.
- Second phase
- fever, severe headache and chills, sweats, myalgias and photophobia
- After 2-3 days a papulo-vesicular rash forms and spreads over the body.
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.
Rocky Mountain Spotted Fever Incidence
RMSF in USA
Incidence of Epidemic Typhus
Epidemic Typhus in USA
Pathogenicity
- Transmission
- to man, via the arthropod saliva, through a bite.
- Arthropod vectors
- rickettsia multiply in the epithelium of the intestinal tract;
- they are excreted in the feces, but occasionally gain access to the arthropods salivary glands.
- Mammalian host
- found in the endothelium of the small blood vessels, of the brain,skin and heart.
Transovarian Cycle
Endotoxin
- It is assumed that the observed clinical manifestations of a rickettsial infection are due to production of an endotoxin, although this endotoxin is quite different in physiological effects from that produced by members of the Enterobacteriaceae.
Evidence of Endotoxon
- IV-injected rickettsia cause rapid death in experimental animals.
- UV-irradiation of rickettsia diminishes infectivity without reducing toxicity.
- anti-rickettsial drugs do not prevent rapid death in experimental animals.
- Antiserum specific for cell wall antigens of the rickettsia prevents the toxic effect.
Lab Diagnosis
Laboratory diagnosis
- Presumptive of rickettsial-like organisms in tissue or blood
- Gram Stain
- Stain poorly with Gram’s stain Although the organisms are gram-negative, they only weakly take the counter stain, safranin.
- Special Stains
- Giemsa, Castaneda, Macchiavello stains
- Fluorescent labelled antibody used to stain biopsy tissue.
Special Stains
- Infected tissue may be stained with:
- Macchiavello stain--organisms are bright red against the blue background of the tissue.
- Castaneda stain--blue organisms against a red background.
- Giemsa stain--bluish purple organisms.
Confirmation
- 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.
Proteus Antigens
- These antigens are alkali stable polysaccharide haptens
- distinct from the group-specific and type-specific antigens.
- Proteus infections are fairly common (especially in the urinary tract) and that they, too, may evoke antibodies to the Proteus-OX strains.
- This test is usually positive seven days after the initial infection.
Complement Fixation
- A more specific complement fixation test is available but does not show positive results until 14 days into the infection.
FIA
- The indirect fluorescent antibody test is also useful for the detection of IgM and IgG antibodies against rickettsia.
- Diagnostic test of choice for ehrlichiosis.
Serology-
- Indirect fluorescent antibody of patient’s serum and latex agglutination.
- In these tests, the antigen is known and the unknown is the antibodies to Rickettsia in the patient’s serum.
- Antibodies are detected 2-3 weeks after onset of disease with FA.
- Latex agg. can be positve earlier but will not be sustained as long.
Rickettsia rickettsii
- Disease/Bacterial Factors
- Rocky Mountain Spotted Fever
- intracelluar parasite that multiples in host cytoplasm
- Transmission
- ticks are primay reservoir and vector
- Risk?
- Requires 24-48 hour exposure to feeding tick
- Geography/Season
- Western Hemisphere, southeast Atlantic and south central USA
- April-Sept
- Control
- tetracyclines & chloramphenicol
- Avoid tick infested areas
- insect repellent
- remove ticks
Rickettsia prowazekii
- Disease/Bacterial Factors
- Louse-borne typhus, Brill-Zinsser Disease
- Transmission
- humans are primary reservoir
- inoculation through break in skin via body louse
- Vector
- human body louse, squirrel fleas
- Geography/ Season
- central & south America
- no season
- Risk?
- Persons in crowded unsanitary conditions
- close contact with infected persons
- Control
- tetracyclines, chloramphenicol
- louse control
Rickettsia typhi
- Disease/Bacterial Factors
- strict intracellular pathogen
- Transmission
- break in skin via infected flea
- Reservoir
- rodents, cats, opossum, racoons & skunks
- Geography Season
- Global, Southeast & gulf states of USA
- Control
- tetracyclines, chloramphenicol
- Control of rodent vectors
- Risk?
- People in crowded areas infested with rodents
Coxiella burnetii
- Disease/Bacterial Factors
- strict intracellular pathogen
- multiplies in cytoplasmic vacuole
- stable in harsh envirnments
- Reservoirs
- sheep goats, ticks, mammals birds
- Transmission
- inhaled airborne particle
- contaminated unpasteurized milk
- Geography /Season
- Global rare in Canada and USA
- not seasonal
- Control
- tetracyclines chloramphenicol
- Risk?
- Livestaock handlers
- patients with prosthetic or damaged heart valves
Ehrlichia chaffeensis
- Disease/Bacterial Factors
- Ehrlichiosis
- Strict intracellular parasite
- vector lone star tick?
- Transmission
- break in skin via infected tick
- Geography/Season
- Common in Southeast, Mid atlantic and South Central USA
- Most common May June July
- Control
- Tetracycline, chloramphenicol
- Control of tick vector
DONE!!!