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RickettsiaeRickettsiae

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RickettsiaeRickettsiae

StructureStructure Clinical ManifestationsClinical Manifestations PathogenesisPathogenesis EpidemiologyEpidemiology DiagnosisDiagnosis ControlControl

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RickettsiaeRickettsiae

bacteria which are obligate intracellular bacteria which are obligate intracellular parasitesparasites

spread by arthropod vectorsspread by arthropod vectors lice, fleas, mites and ticks lice, fleas, mites and ticks

The rickettsial diseases of man are usually The rickettsial diseases of man are usually broken down according to the arthropod broken down according to the arthropod vector vector

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GeneraGenera

RickettsiaRickettsia (11 species)- (11 species)- obligate intracellular parasites which do not multiply within obligate intracellular parasites which do not multiply within

vacuoles and do not parasitize white blood cells. vacuoles and do not parasitize white blood cells. OrientiaOrientia: spread by chiggers, parallel evolution: spread by chiggers, parallel evolution EhrlichiaEhrlichia (2 species) - (2 species) -

obligate intracellular parasites which do not multiply within obligate intracellular parasites which do not multiply within vacuoles but do parasitize white blood cells. vacuoles but do parasitize white blood cells.

CoxiellaCoxiella (1 species)-- (1 species)-- obligate intracellular parasite which grows in vacuoles of host obligate intracellular parasite which grows in vacuoles of host

cells.cells.

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TicksTicks

Soft TickSoft Tick EhrlichosisEhrlichosis E. chaffeensisE. chaffeensis

Hard TickHard Tick Rocky Mountain Rocky Mountain

spotted feverspotted fever Wild rodentsWild rodents R. rickettsiaR. rickettsia

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Lone Star TickLone Star Tick

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LouseLouse

Head Louse Body Louse

TyphusTyphus R prowazekiiR prowazekii Humans, squirrel fleas flying Humans, squirrel fleas flying

squirrelssquirrels Trench feverTrench fever

R quintanaR quintana HumansHumans

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FleaFlea

Vector for Murine Vector for Murine typhustyphus

caused by R typhicaused by R typhi Reservoir Reservoir Wild rodentsWild rodents

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C burnetiiC burnetii

C.burnetii differs from other rickettsia in that it C.burnetii differs from other rickettsia in that it is enclosed in a persistent vacuole during growth is enclosed in a persistent vacuole during growth and division. Six to ten daughter cells will form and division. Six to ten daughter cells will form within a host cell before the cell ruptures and within a host cell before the cell ruptures and releasesreleasesthem. them.

No arthropod vectorNo arthropod vector Q feverQ fever

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PreventionPrevention

Avoid tick - infested areasAvoid tick - infested areas wear protective clothing and use repellants. wear protective clothing and use repellants. Ticks are difficult to eradicate as they can Ticks are difficult to eradicate as they can

survive for 4 years without feedingsurvive for 4 years without feeding Remove ticks carefullyRemove ticks carefully

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Ehrlichia Intracellular growthEhrlichia Intracellular growth

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Ehrlichia Growth CycleEhrlichia Growth Cycle

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Rickettsia conorii GrowthRickettsia conorii Growth

Gram negative short rodsGram negative short rods Transverse Binary FissionTransverse Binary Fission Multiple in cytoplasmMultiple in cytoplasm Long filaments under poor Long filaments under poor

nutritional conditions, nutritional conditions, undergo rapid and multiple division undergo rapid and multiple division

into the typical short rod forms into the typical short rod forms when fresh nutrient is added. when fresh nutrient is added.

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Rickettsia conoriiRickettsia conorii

Immediately after division, the Immediately after division, the rickettsia engage in extensive rickettsia engage in extensive movements through the movements through the cytoplasm of the cell. cytoplasm of the cell.

Attach to “tail” of host actin Attach to “tail” of host actin filamentsfilaments

actin provides propulsion actin provides propulsion

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Metabolism Metabolism

In dilute buffered salt solutions, isolated rickettsia are unstable, losing both metabolic In dilute buffered salt solutions, isolated rickettsia are unstable, losing both metabolic activity andactivity andinfectivity for animal cells. If, the medium is enriched with potassium, serum albumin 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, 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 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 these cells is that they require the rich cytoplasm to stabilize an unusually permeable cell membrane. membrane.

The rickettsia have many of the metabolic capabilities of bacteria, but require an exogenousThe rickettsia have many of the metabolic capabilities of bacteria, but require an exogenoussupply of cofactors to express these capabilities. The response to exogenous cofactors supply of cofactors to express these capabilities. The response to exogenous cofactors implies animplies anunusually permeable cytoplasmic membrane. unusually permeable cytoplasmic membrane.

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Rickettsial Clinical ManifestationsRickettsial Clinical Manifestations

EntryEntry Ticks, fleas, lice, mitesTicks, fleas, lice, mites

SpreadSpread Blood stream & lymphaticsBlood stream & lymphatics

DiseaseDisease encephalitis, pneumonitis, rash, encephalitis, pneumonitis, rash,

nausea, vomiting, renal failurenausea, vomiting, renal failure ExitExit none none

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Rickettsia PathogenicityRickettsia Pathogenicity

Symptoms:Symptoms: Fever, chills, headache, Fever, chills, headache, myalgias, rashmyalgias, rash

Rash: Rash: hemorrhages in the skin. hemorrhages in the skin. Develops after 3 days Develops after 3 days

Not seen in 10% of casesNot seen in 10% of cases

Incubation Incubation 2-14 days after tick bite 2-14 days after tick bite [average 7days] Patient may not [average 7days] Patient may not recall painless tick bite.recall painless tick bite.

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Rash of Rocky Mountain Spotted Fever

Rash of Rocky Mountain Spotted Fever

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HyperplasiaHyperplasia

Hyperplasia of endothelial cells and localized Hyperplasia of endothelial cells and localized thrombus formation lead to obstruction of blood thrombus formation lead to obstruction of blood flow, with escape of RBC's into the surrounding flow, with escape of RBC's into the surrounding tissue. Inflammatory cells also accumulate about tissue. Inflammatory cells also accumulate about affected segments of blood vessels.affected segments of blood vessels.

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AngitisAngitis

Angitis appears to account for some of the Angitis appears to account for some of the more prominent clinical manifestations, more prominent clinical manifestations, such as petechial rash, stupor and terminal such as petechial rash, stupor and terminal shock. Death is ascribed to damage of shock. Death is ascribed to damage of endothelial cells, resulting in leakage of endothelial cells, resulting in leakage of plasma, decrease in blood volume, and plasma, decrease in blood volume, and shock. shock.

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ComplicationsComplications

Gastro-intestinal symptoms, respiratoryGastro-intestinal symptoms, respiratory

failure, encephalitis, renal failure.failure, encephalitis, renal failure.

Mortality is high when the disease progresses. Mortality is high when the disease progresses. This is usually due to the late development This is usually due to the late development of the rash and the difficulty of diagnosing of the rash and the difficulty of diagnosing the diseasethe disease

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Human Monocytic EhrelichiosisHuman Monocytic Ehrelichiosis

Since 1964, more than 400 Since 1964, more than 400 confirmed cases of HME, and confirmed cases of HME, and 170 cases of HGE have been 170 cases of HGE have been reported, including some from reported, including some from northern California. Many were northern California. Many were first thought to be Rocky first thought to be Rocky Mountain Spotted Fever.Mountain Spotted Fever.

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Clinical Manifestations: Q FeverClinical Manifestations: Q Fever

Entry:Entry: aerosol from infected aerosol from infected placenta of sheep goats cattleplacenta of sheep goats cattle

Spread:Spread: blood stream blood stream DiseaseDisease

Pneumonitis endocarditis, Pneumonitis endocarditis, granulomasgranulomas

no no ExitExit

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RickettsialpoxRickettsialpox

R. akariR. akari - Clinical infection is biphasic - Clinical infection is biphasic First phaseFirst phase

a vesicle develops at the mite bite site and the organisms a vesicle develops at the mite bite site and the organisms multiply ; within one week they have spread systemically.multiply ; within one week they have spread systemically.

Second phaseSecond phase fever, severe headache and chills, sweats, myalgias and fever, severe headache and chills, sweats, myalgias and

photophobiaphotophobia After 2-3 days a papulo-vesicular rash forms and spreads After 2-3 days a papulo-vesicular rash forms and spreads

over the body. over the body.

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Chemotherapy Chemotherapy

The drugs of choice for the treatment of The drugs of choice for the treatment of rickettsial diseases are chloramphenicol and rickettsial diseases are chloramphenicol and tetracycline.tetracycline.Each of these is highly toxic, especially in Each of these is highly toxic, especially in children, and must be used with care.children, and must be used with care.

The sulfonamides stimulate rickettsial growth The sulfonamides stimulate rickettsial growth and thus are contraindicated in the treatment of and thus are contraindicated in the treatment of these diseases. these diseases.

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Rocky Mountain Spotted Fever Incidence

Rocky Mountain Spotted Fever Incidence

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RMSF in USARMSF in USA

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Incidence of Epidemic TyphusIncidence of Epidemic Typhus

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Epidemic Typhus in USAEpidemic Typhus in USA

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Pathogenicity Pathogenicity

TransmissionTransmission to man, via the arthropod saliva, through a bite. to man, via the arthropod saliva, through a bite.

Arthropod vectorsArthropod vectors rickettsia multiply in the epithelium of the intestinal tract; rickettsia multiply in the epithelium of the intestinal tract; they are excreted in the feces, but occasionally gain access to they are excreted in the feces, but occasionally gain access to

the arthropods salivary glands. the arthropods salivary glands. Mammalian hostMammalian host

found in the endothelium of the small blood vessels, of the found in the endothelium of the small blood vessels, of the brain,skin and heart. brain,skin and heart.

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Transovarian CycleTransovarian Cycle

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EndotoxinEndotoxin

It is assumed that the observed clinical It is assumed that the observed clinical manifestations of a rickettsial infection are manifestations of a rickettsial infection are due to production of an endotoxin, although due to production of an endotoxin, although this endotoxin is quite different in this endotoxin is quite different in physiological effects from that produced by physiological effects from that produced by members of the members of the Enterobacteriaceae.Enterobacteriaceae.

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Evidence of EndotoxonEvidence of Endotoxon

IV-injected rickettsia cause rapid death in IV-injected rickettsia cause rapid death in experimental animals. experimental animals.

UV-irradiation of rickettsia diminishes UV-irradiation of rickettsia diminishes infectivity without reducing toxicity.infectivity without reducing toxicity.

anti-rickettsial drugs do not prevent rapid death in anti-rickettsial drugs do not prevent rapid death in experimental animals.experimental animals.

Antiserum specific for cell wall antigens of the Antiserum specific for cell wall antigens of the rickettsia prevents the toxic effect.rickettsia prevents the toxic effect.

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Lab DiagnosisLab Diagnosis

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Laboratory diagnosisLaboratory diagnosis

Presumptive of rickettsial-like organisms in tissue or Presumptive of rickettsial-like organisms in tissue or blood blood

Gram StainGram Stain Stain poorly with Gram’s stain Although the organisms are Stain poorly with Gram’s stain Although the organisms are

gram-negative, they only weakly take the counter stain, gram-negative, they only weakly take the counter stain, safranin. safranin.

Special StainsSpecial Stains Giemsa, Castaneda, Macchiavello stainsGiemsa, Castaneda, Macchiavello stains Fluorescent labelled antibody used to stain biopsy tissue.Fluorescent labelled antibody used to stain biopsy tissue.

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Special StainsSpecial Stains

Infected tissue may be stained with: Infected tissue may be stained with: Macchiavello stainMacchiavello stain--organisms are bright red --organisms are bright red

against the blue background of the tissue. against the blue background of the tissue. Castaneda stainCastaneda stain--blue organisms against a --blue organisms against a

red background. red background. Giemsa stainGiemsa stain--bluish purple organisms.--bluish purple organisms.

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ConfirmationConfirmation

serological reaction (Weil-Felix reaction) in serological reaction (Weil-Felix reaction) in which the titer of the agglutinins in the patient's which the titer of the agglutinins in the patient's serum against the Proteus strains OX-19, OX-2 serum against the Proteus strains OX-19, OX-2 and OX-K are determined. and OX-K are determined.

These Proteus strains have no etiological role in These Proteus strains have no etiological role in rickettsial infections, but appear to share rickettsial infections, but appear to share antigens in common with certain rickettsia. antigens in common with certain rickettsia.

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Proteus AntigensProteus Antigens

These antigens are alkali stable polysaccharide These antigens are alkali stable polysaccharide haptens haptens distinct from the group-specific and type-specific distinct from the group-specific and type-specific

antigens. antigens. Proteus infections are fairly common (especially in Proteus infections are fairly common (especially in

the urinary tract) and that they, too, may evoke the urinary tract) and that they, too, may evoke antibodies to the Proteus-OX strains. antibodies to the Proteus-OX strains.

This test is usually positive seven days after the This test is usually positive seven days after the initial infection. initial infection.

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Complement FixationComplement Fixation

A more specific complement fixation test is A more specific complement fixation test is available but does not show positive results available but does not show positive results until 14 days into the infection. until 14 days into the infection.

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FIAFIA

The indirect fluorescent antibody test is also The indirect fluorescent antibody test is also useful for the detection of IgM and IgG useful for the detection of IgM and IgG antibodies against rickettsia.antibodies against rickettsia.

Diagnostic test of choice for ehrlichiosis. Diagnostic test of choice for ehrlichiosis.

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Serology- Serology-

Indirect fluorescent antibody of patient’s serum Indirect fluorescent antibody of patient’s serum and latex agglutination.and latex agglutination.

In these tests, the antigen is known and the In these tests, the antigen is known and the unknown is the antibodies to Rickettsia in the unknown is the antibodies to Rickettsia in the patient’s serum.patient’s serum.

Antibodies are detected 2-3 weeks after onset of Antibodies are detected 2-3 weeks after onset of disease with FA.disease with FA.

Latex agg. can be positve earlier but will not be Latex agg. can be positve earlier but will not be sustained as long. sustained as long.

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Rickettsia rickettsiiRickettsia rickettsii

Disease/Bacterial FactorsDisease/Bacterial Factors Rocky Mountain Spotted FeverRocky Mountain Spotted Fever intracelluar parasite that intracelluar parasite that

multiples in host cytoplasmmultiples in host cytoplasm

TransmissionTransmission ticks are primay reservoir and ticks are primay reservoir and

vectorvector

Risk?Risk? Requires 24-48 hour exposure Requires 24-48 hour exposure

to feeding tickto feeding tick

Geography/SeasonGeography/Season Western Hemisphere, southeast Western Hemisphere, southeast

Atlantic and south central USAAtlantic and south central USA April-SeptApril-Sept

ControlControl tetracyclines & tetracyclines &

chloramphenicolchloramphenicol Avoid tick infested areasAvoid tick infested areas insect repellentinsect repellent remove ticksremove ticks

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Rickettsia prowazekiiRickettsia prowazekii

Disease/Bacterial FactorsDisease/Bacterial Factors Louse-borne typhus, Brill-Louse-borne typhus, Brill-

Zinsser DiseaseZinsser Disease

TransmissionTransmission humans are primary reservoirhumans are primary reservoir inoculation through break in inoculation through break in

skin via body louseskin via body louse

VectorVector human body louse, squirrel human body louse, squirrel

fleasfleas

Geography/ SeasonGeography/ Season central & south Americacentral & south America no seasonno season

Risk?Risk? Persons in crowded unsanitary Persons in crowded unsanitary

conditionsconditions close contact with infected personsclose contact with infected persons

ControlControl tetracyclines, chloramphenicoltetracyclines, chloramphenicol louse controllouse control

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Rickettsia typhiRickettsia typhi

Disease/Bacterial FactorsDisease/Bacterial Factors strict intracellular pathogenstrict intracellular pathogen

TransmissionTransmission break in skin via infected fleabreak in skin via infected flea

ReservoirReservoir rodents, cats, opossum, rodents, cats, opossum,

racoons & skunksracoons & skunks

VectorsVectors rat & cat fleasrat & cat fleas

Geography SeasonGeography Season Global, Southeast & gulf Global, Southeast & gulf

states of USAstates of USA

ControlControl tetracyclines, tetracyclines,

chloramphenicolchloramphenicol Control of rodent vectors Control of rodent vectors

Risk?Risk? People in crowded areas People in crowded areas

infested with rodentsinfested with rodents

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Coxiella burnetiiCoxiella burnetii

Disease/Bacterial FactorsDisease/Bacterial Factors strict intracellular pathogenstrict intracellular pathogen multiplies in cytoplasmic vacuolemultiplies in cytoplasmic vacuole stable in harsh envirnmentsstable in harsh envirnments

Reservoirs Reservoirs sheep goats, ticks, mammals birdssheep goats, ticks, mammals birds

TransmissionTransmission inhaled airborne particleinhaled airborne particle contaminated unpasteurized milkcontaminated unpasteurized milk

Geography /SeasonGeography /Season Global rare in Canada and Global rare in Canada and

USAUSA not seasonalnot seasonal

ControlControl tetracyclines tetracyclines

chloramphenicolchloramphenicol

Risk?Risk? Livestaock handlersLivestaock handlers patients with prosthetic or patients with prosthetic or

damaged heart valvesdamaged heart valves

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Ehrlichia chaffeensisEhrlichia chaffeensis

Disease/Bacterial FactorsDisease/Bacterial Factors EhrlichiosisEhrlichiosis Strict intracellular Strict intracellular

parasiteparasite vector lone star tick?vector lone star tick?

TransmissionTransmission break in skin via break in skin via

infected tickinfected tick

Geography/SeasonGeography/Season Common in Southeast, Common in Southeast,

Mid atlantic and South Mid atlantic and South Central USACentral USA

Most common May June Most common May June JulyJuly

ControlControl Tetracycline, Tetracycline,

chloramphenicolchloramphenicol Control of tick vectorControl of tick vector

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DONE!!!DONE!!!