RICKETTSIA

ORIENTIA

EHRLICHIA

ANAPLASMA

COXIELLA

BARTONELLAJialin Jin

Fudan university huashan hospital

Department of infectious diseases

2014 Nov

General introduction

Gram-negative, obligate intracellular coccobacilli bacteria that infect mammaols and arthropods

Rickettsiae are transmitted in the arthropods,which serves as both vector and reservior

Both DNA and RNA

Is sensitive to antibiotic

Culture：in animate media

Anthropods:

ticks, mites, lice, and fleas

Tick 扁虱Mite 螨虫

Louse 虱子

Live louse

Flea 跳蚤

Category of rickettsia

Genus

Rickettsia, Coxiella ,Orientia,Ehrlichia,Bartonella

Species

Rickettsia prowazekii (epidemic typhus),

Rickettsia typhi (endemic typhus), Rickettsia

rickettsii (spotted fever), Rochalimaea quintana

(trench fever), Coxiella burnetii (Q fever)

Biological features

Variable shape, coccobacilli

Gram negative

Microcapsule and slime layer

Culture : in york sacs of embryonated eggs

Antigenic structure

LPS

Rickettsia tsutsugamushi

Coxiella burnetii (Q fever)

LPSⅠ smooth

LPSⅡ rough

Weil-Felix reaction

Surface protein(SPA)

Transmission

Typhus, spotted fever and trench fever are

transmitted via arthropod vectors;

Q fever is acquired via inhalation or

ingestion of contaminated milk or food.

Pathogenesis：vasculitis

Virulence factors: endotoxin,

phospholipase A, and slime layer

Sites: vascular system producing vasculitis

血管炎

Characteristic triad of symptoms:

fever, headache and rash (no rash with Q

fever).

Replication cycle of Rickettsia and

Orientia

rickettsial family of diseases

Four groups

The spotted fever group

The typhus group

The Ehrlichia group

Q fever

spotted fever group typhus group Ehrlichia group Q fever

R. rickettsii

(Rocky Mountain

spotted fever)

R. prowazekii

(louseborne

or epidemic

typhus and

Brill–Zinsser

disease)

E. chaffeensis

[human monocytotropic

ehrlichiosis (HME)]

Q fever

(Coxiella

Burnetii)

R. Conorii

(Boutonneuse fever)

R. Typhi

(murine typhus)

Anaplasma

phagocytophilum

[human

granulocytotropic

anaplasma (HGA)]

R. australis

(Queensland tick

typhus)

Orienta

tsutsugamushi

(scrub typhus)

pathogens E. ewingii

R. Sibirica

(North Asian tick typhus)

E. muris

R. akari

(rickettsial pox)

Neorickettsia

sennetsu

Rocky Mountain spotted fever

Most severe disease in the spotted fever

group

Motality 22% in untreated

Motality 6% with treatment.

occurs throughout the United States,

Mexico,and Central and South America

late spring and summer

Dog tick or wood tick

Pathogenesis

Injected into the skin by ticks

Proliferates in the skin, disseminates via the

bloodstream.

Survives in the host cell cytoplasm

spreads cell-to–cell

producing necrotic cells

hemorrhage in heart, lung, CNS, skin, intestine,

pancreas,liver, skeletal muscle, and kidneys.

Clinical presentation : RMSF

Incubation period is 2 to 14 days.

Acute onset of nonspecific symptoms:

fever,headache, malaise, myalgias, and

nausea.

Abdominal pain may mimic cholecystitis or

appendicitis.

Clinical presentation: RMSF

Macular, petechial rash begins on ankles

and wrists and spreads to trunk 5 days after

symptoms begin

“Spotless” infection occurs in 10%—usually

elderly and dark skinned individuals.

Urticaria or pruritic rash makes the diagnosis

unlikely.

Macular rash in

the early stage

of RMSF

Necrosis in

the toes in

the late stage

of RMSF

Clinical presentation : RMSF

Other symptoms include aseptic

meningitis, conjunctivitis, fundoscopic

hemorrhages, and ARDS in severe

disease.

Death within 8 to 15 days if treatment is

not initiated within 5 days.

Diagnosis

epidemiology and clinical manifestations.

Culture not recommended.

Skin biopsy with immunofluorescence staining

has high specificity. Not recommended if

antibiotics has been given

Serology provides a retrospective diagnosis

Can be mistaken for viral syndrome, drug

allergy, and meningococcemia.

Treatment

infection drug doseRelative

efficacycomments

Rocky

Mountain

Spotted

Fever

doxycycline

100mg PO or IV q12h for

3-5 days after afebrile

Children <45 kg:

2.2 mg/kg per dose q12h

for 3 days after afebrile

First line

Short-course

doxycycline

causes

minimal harm

to developing

teeth

Chloramphenicol500mg PO or IV q6h for

3-5 days after afebrile Alternative

For pregnant

women

Typhus

pathogen diseases severity motality vector

R.

prowazekii

louse-borne typhus

epidemic typhusMost serious form 30-70% Body lice

Reactivation

of R.

prowazekii

Brill–Zinsser

disease

Mild, similar to

primary disease<5% Body lice

R. typhi

Flea-borne typhus

murine

or endemic typhus Milder form <5% Flea

R.

tsutsugamu

shi

Scrub typhus More gradual

onset;

Black eschar

mite larvae

(chiggers 恙螨)

Rickettsia prowazekii

普氏立克次体

epidemic typhus

average incubation periods : 1 week

the louse, sometimes fleas from flying squirrels

Respiratory tract and conjunctiva

Latent period: 2 weeks

Abrupt onset, fever, chills, headache,

myalgia, arthralgia

Rickettsia prowazekii

普氏立克次体 small-vessel vasculitis - tissue necrosis -

multiple organs involves

Lungs

Liver

gastrointestinal tract

Central nervous system

Skin: 60%, trunk-spreading outward, macular to

maculopapular to petechiae to peripheral

gangrene(occlusion)

30%-70% motality

Rickettsia typhi

地方性斑疹伤寒立克次体

endemic typhus

7-14 days

Mice

the louse & flea

Mouth,nose and conjunctiva

Gradual onset, fever, headache, myalgia,

cough

Rickettsia tsutsugamushi

恙虫病立克次体

Tsutsugamushi disease (scrub typhus)

Epidemiology：Asia Pacific rim（mite island）

Incubation time: 6 to 21 days

the onset is usually gradual

high fever, chills, and anorexia

Diffuse lymphadenopathy,

splenomegaly, conjunctivitis, and pharyngitis

Black eachar 焦痂 (~50%)

Diagnosis

based on clinical and epidemiologic findings

Acute and convalescent antibody titers

Immunofluorescence staining of the primary

eschar: rapid

Cross reaction to antigen of Bacillus proteus ,

Not recommended now for poor sensitivity and lack of specifity

Treatment

infection drug doseRelative

efficacy

typhus doxycycline

100mg PO or IV q12h for 3-5

days after afebrile

Children: Same as RMSF

First line

Chloramphenicol500mg PO or IV q6h for 3-5

days after afebrile Alternative

Add rifampin in

areas with resistant

strains

600-900mg PO q24h for 3-5

days after afebrile

EHRLICHIA

HME HGA

pathogen Ehrlichia chaffeensis Anaplasma phagocytophilum

disease human monocytic

ehrlichia

human granulocyte anaplasma

anthropods Lone Star tick found on

the whitetail deer

Ixodes, the same tick that

transmits Lyme disease and

babesiosis

Epidemic

region

southeast United States California, Minnesota, Wisconsin,

Massachusetts, Connecticut, New

York, and Florida.

Proposed life cycle for the agent of Human

Granulocytic Ehrlichiosis埃里希体病

Replication of Ehrlichia埃里希体

Clinical manifestation of

ehrichiosisHME HGA

Incubation time 7 days

Targeted cell monocytes granulocytes

motality 5% (mainly elderly and immunocompromised)

symptoms Gradual onset of fever, chills,headache,myalgias,

anorexia, and malaise.

Severe form respiratory insufficiency,

renal insufficiency, and

meningoencephalitis

(with lymphocytosis noted

in the cerebrospinal fluid)

respiratory insufficiency,

rhabdomyolysis, and

neutropenia resulting in

gram-negative sepsis

rash Macular, petechial rash

Rash incidence 30% to 40% 2% to 11%

Diagnosis: presumptive

Thrombocytopenia and leukopenia are

common (neutropenia in granulocytic form).

Moderate transaminase elevations

Morulae are rare in peripheral blood smears

in the monocytic form, common in the

granulocytic form.

Retrospective serology makes the diagnosis.

Morulae

Morulae found in human granulocytotropic

ehrlichiosis caused by Anaplasma phagocytophilum.

Coxiella burnetti贝纳柯斯体

Q fever

Resevoir: Cow and sheep

Vector: tick

High resistance

changes its outer LPS:

Phase II outer antigens in the environment.

Phase I outer antigens when infecting the host.

Replication of C. burnetii

Clinical manifestation of Q fever

Incubation period is 3 weeks

abrupt flu-like illness with cough.

maculopapular rash (<10%)

ARDS

Hepatitis

myocarditis and pericarditis;

Meningitis

chronic endocarditis (negative echo early

in the disease, high mortality).

Diagnosis (culture negative)

IgG (titer above 1:200) and IgM (titer above 1:50)

anti-phase II antigens indicate acute disease.

IgG (titer above 1:800) and IgA (titer above 1:100)

anti-phase I antigens indicate chronic disease.

PCR is sensitive and specific (available in some

locations).

treatment

not as effective as for rickettsial infections.

Treat with doxycycline for 2 weeks for

acute disease; fluoroquinolones may also

be helpful.

Treat with doxycycline and

hydroxychloroquine for 18 months to 4

years or life for chronic endocarditis.

Treatment

infection drug dose comments

Ehrlichiosis

and

anaplasmaDoxycycline

100 mg PO or IV q12h for

3–5 days after afebrile

Children: Same as Rocky

Mountain Spotted Fever

Also preferred

for children

Q fever Doxycycline, plus

hydroxycholoroquine

100 mg PO or IV q12h

200 mg PO q8h

Add hydroxy-

chloroquine for

endocarditis

Cat scratch disease and bacillary

angiomatosis

Caused by bartonella

Usually localized disease and seldom

cause serious illness

Epidemiology

Found worldwide, more common in warm

humid climates and young people

Cat as the primary vector

Fleas, also responsible for spread from cat to cat

pathogen disease

B. henselae CSD and bacillary angiomatosis

B. quintata Angiomatosis and trench fever

B. bacilliformis Oroya fever and Verruga peruana

Pathogen: Bartonella

Pleomorphic gram-negative bacilli

Take up Gram stain poorly

Binds silver and can be identified by

Warthin-Starry stain

pathogenesis

Enter the host through the break in the skin

Multiply at the site and spread to local lymphatic

system and adjacent lymph nodes

Flagellar and other surface protein mediate

attachment to red blood cells and endothelial cells

Multiply in vacuoles

Forming intracellular clusters similar to the

morulae of Ehrlichia.

Induce the formation of new vessels

Reason why not dissemination

Grow in both intracellular and extracelluar

environments

Induce both

Granulomatous reaction consisting of

macrophages and histiocytes

Acute inflammatory response consisting

primarily of PMNs

Bacteremia and dissemination in HIV

Clinical manifestation

Presents with a warm, tender, swollen lymph

node 2 weeks after the scratch.

Axillary node is most common (depend on the site

of innoculation)

The primary scratch can often be identified.

Low-grade fever is common.

Rarer manifestations

conjunctivitis, encephalopathy, and granulomas in

the liver and spleen，Parinaud’s oculoglanduar

syndrome (conjunctivitis and preauricular

lymphadenopathy )

Bacillary angiomatosis

AIDS with body lice

B. quintana primarily , B. henselae sometimes

Skin lesion: cluster of small reddish papules

that can enlarge to form nodules

Appear vascular and bleed when traumatized

Biopsy: multiple small blood vessels, enlarged

endothelial cells and polymorphonuclear

leukocyte infiltration

Treatment

infection drug dose comments

Bartonella

Lymphatic

disease

Azithromycin, or

clarithromycin, or

doxycycline, or

ciprofloxacin

500 mg PO once,then 250

mg

500mg PO q12h

100mg PO q12h

500mg PO q12h

All equally

effective

Severe

disease

Azithromycin, plus

rifampin

500mg PO q24h

600mg PO or IV q24h

Efficacy not

proven

Epidemiology summary

Organism disease vector reservior Incubation

R. rickettsii HMSF tick tick 2-14

R. prowazekii Epidemic

typus

Louse human 8

R. typhi Endimic

typus

Louse and

Flea

mice 7-14

R. tsutsugamushi Scrub typus Mite larva Wide mice 10-12

E. chaffeensis ehrlichiosis tick tick 12

C. burnetii Q fever tick Wild animal

Cow, sheep

20

B. hanselae CSD Cat, dog 14

Control

Sanitary: Arthropod and rodent control

Immunological: No vaccines are

currently available.

Chemotherapeutic: Tetracycline or

chloramphenicol are drugs of choice.

Thank u