Human Human RickettsiosesRickettsioses

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HistoryHistory• Epidemic typhus - 16th century• Associated with wars and famine• WW I and WW II - 100,000 people

affected• Ricketts identifies causative agent of

Rocky Mountain spotted fever - 20th century

• Arthropod vectors identified

RickettsiaRickettsia, Orientia, Ehrlichia , Orientia, Ehrlichia AnaplasmaAnaplasma and and CoxiellaCoxiella

• Small obligate intracellular parasites(bacteria) • Once considered to be viruses • Gram-negative bacteria

– Stain poorly with Gram stain (Giemsa)• “Energy parasites”

– Transport system for ATP • Reservoirs - animals, insects and humans• Arthropod vectors (except Coxiella)

Disease Organism Vector Reservoir

Rocky Mountain R. rickettsii Tick Ticks, rodentsspotted fever

Epidemic typhus R. prowazekii Louse Humans, squirrel

Flea Fleas, flyingsquirrels

Murine typhus R. typhi Flea Rodents

Rickettsialpox R. akari Mite Mites, rodents

Scrub typhus O. tsutsugamushi Mite Mites, rodents

Ehrlichiosis E. chaffeensis Tick Deer

Q fever C. burnetii None Cattle, sheep,goats, cats

TICK FLEA

LouseMite

Vectors

Replication of Replication of Rickettsia and OrientiaRickettsia and Orientia• Infect endothelial cells in small blood vessels • Lysis of phagosome and entry into cytoplasm • Replication• Release

Groups of Rickettsia Based on Antigenic StructureSpotted fever group: R. rickettsii Rocky Mountain spotted fever Western hemisphere R. akari Rickettsialpox USA, former Soviet Union R. conorii Boutonneuse fever Mediterranean countries,

Africa, India, Southwest AsiaTyphus group: R. prowazekii Epidemic typhus South America and Africa

Recrudescent typhus Worldwide Sporadic typhus United States

R. typhi Murine typhus Worldwide

Scrub typhus group: O. tsutsugamushi Scrub typhus Asia, northern Australia,

Pacific Islands

Pathogenesis and ImmunityPathogenesis and Immunity

• No known toxins or immunopathology• Destruction of cells

– Leakage of blood into tissues (rash)– Organ and tissue damage

• Humoral and cell mediated immunity important for recovery– Antibody-opsonized bacteria are killed– CMI develops

Epidemic TyphusEpidemic Typhus

• Etiology: Rickettsia prowazekii• Vector: Human body louse• Body louse – Human – body louse cycle• Most common in people living under

unhygienic conditions– Refugee camps– Famine– Poverty

TransmissionTransmission

• Human body louse– Pediculus humanus corporis– Infection acquired by feeding on infected person– Excrete R. prowazeki in feces at time of feeding– Lice die within 2 weeks – Louse feces rubbed into – bite or superficial abrasions– Inhalation of feces

TransmissionTransmission

• Humans required for life cycle – Organism dies with louse– No trans-ovarian transmission– Host responsible for maintaining infection

• No person-to-person transmission

Clinical SymptomsClinical Symptoms

• Incubation: 7-14 days• High fever, chills, headache,

cough, severe myalgia• Macular eruption

– 5-6 days after onset– Initially on upper trunk, spreads to entire body

• Except face, palms and soles of feet

Brill-Zinsser DiseaseBrill-Zinsser Disease(Recrudescent Typhus)(Recrudescent Typhus)

• Occurs years after primary attack– Person previously affected or lived in endemic

area– Reactivation of latent organisms in Reticulo

Endothelial Cells– Milder symptoms

• Febrile phase 7-10 days– Rash often absent– Low mortality rate

Endemic TyphusEndemic Typhus(Murine Typhus)(Murine Typhus)

• Etiology: Rickettsia tytphi• Vector: Rat flea• Rat – Rat flea – Human cycle• Zoonosis• Clinical symptoms :

– Similar to Epidemic typhus– Milder illness– Low mortality

Neil-Mooser reactionNeil-Mooser reaction(Tunica reaction)(Tunica reaction)

• Intraperitoneal inoculation of R.typhi into Male Guinea Pig

• Characteristic Scrotal inflammation• Scortum become enlarged and protruded

testes• Due to adhesion of layers of Tunica

vaginalis

Rocky Mountain Spotted FeverRocky Mountain Spotted Fever

• Etiology: Rickettsia rickettsii• Vector: Ticks• Tick – Tick (transoverian) -Human cycle• Most serious type of spotted fever

Epidemiology - Epidemiology - R. rickettsiiR. rickettsiiRocky Mountain Spotted FeverRocky Mountain Spotted Fever

• Most common from April - September• Vector - Ixodid (hard) tick via saliva

– Prolonged exposure to tick is necessary• Reservoirs - ticks (transovarian

passage) and rodents– Humans are accidentally infected

• Most common rickettsial infection in USA– 400 -700 cases annually– South Central USA

RMSFRMSF

• I.P 1 week• High grade fever• Severe headache, myalgia• Vomiting , abdominal pain, cough etc• Rash (Maculopapular) appears on 4th Day• Initially on Wrists, ankles, palms and soles• Rash becomes petechial / haemorrhagic• Eschar at the site of Bite• Hypovolemia, shock• Mortality : 6 – 70% in un treated

ESCHAR

RMSF - rashRMSF - rash

R. Akari R. Akari RickettsialpoxRickettsialpox- Epidemiology - - Epidemiology -

• Sporadic infection in USA• Vector - house mite• Reservoir - mites (transovarian

transmission) and mice• Humans accidentally infected

RickettsialpoxRickettsialpox

• Phase I (1 week incubation period)– papule at bite site– Eschar formation

• Phase II (1 -3 week later)– Sudden onset of fever, chills headache and

myaglia– Generalized rash - papulovessicular, crusts

• Mild disease; fatalities are rare

Scrub TyphusScrub Typhus

• Etiology: Orientia tsutsugamushi• Vector: Trombiculid mite larvae

(Chigger)• Mammals / birds – Chigger – Human cycle• Transoverian transmission

Orientsia (Rickettsia) Orientsia (Rickettsia) tsutsugamushitsutsugamushi

• Scrub typhus• Japanese “tsutsuga” = small and

dangerous and “mushi” = creature• “Scrub” - associated with terrain with scrub

vegetation

Scrub typhus - distributionScrub typhus - distribution

Scrub typhusScrub typhus

• I. P : 2-3 weeks• Headache, Chills, fever• Characteristic Eschar at the site of Mite

bite• Spleenomegaly, Lymphadenopathy• Maculopapular rash appears after a week• Case fatality : 10 – 60% if untreated

Scrub typhus - EscharScrub typhus - Eschar

EhrlichiaEhrlichia and and AnaplasmaAnaplasma

Replication of Replication of Ehrlichia Ehrlichia and and AnaplasmaAnaplasma

• Infection of leukocytes - Phagocytosis• Inhibition of phagosome-lysosome fusion• Growth within phagosome - Morula• Lysis of cell

Epidemiology - Ehrlichia Organism Disease Vector Reservoir Distribution

E. chaffeensis Human monocytic ehrlichiosis

Lone star tick

White-tailed deer

Southeastern, Mid-Atlantic and South Central United States

E. ewingii

Human granulocytic ehrlichiosis

Deer and dog ticks

White-tailed deer

Southeastern, Mid-Atlantic and South Central United States

A. phagocytophilium Human

granulocytic ehrlichiosis

Deer and dog ticks

Small mammals

Wisconsin, Minnesota and Connecticut

Ehrlichia chaffeensisEhrlichia chaffeensis

• Human monocytic ehrlichiosis

Vector - Tick

Human Monocytic EhrlichiosisHuman Monocytic EhrlichiosisE. chaffeensisE. chaffeensis

• Sudden onset of fever, chills, headache and myalgia

• No rash in most (80%) patients• Leukopenia, thrombocytopenia and

elevated serum transaminases • Mortality rates low (<5%)

Laboratory Diagnosis - Laboratory Diagnosis - E. E. chaffeensischaffeensis

• Morula in blood smears (rare)

• Culture is possible but rarely done

• Serology is most common

• DNA probes & PCR are available

Ehrlichia ewingiiEhrlichia ewingii and and Anaplasma phgocytophiliumAnaplasma phgocytophilium

• Human granulocytic ehrlichiosis

From: Koneman et al. Color Atlas and Textbook of Diagnostic Microbiology, Lippincott

Vector - Tick

Human Granulocytic EhrlichiosisHuman Granulocytic Ehrlichiosis

• Sudden onset of fever, chills, headache and myalgia

• No rash in most (80%) patients• Leukopenia , thrombocytopenia and

elevated serum transaminases • Mortality rates low (<5%)

Laboratory Diagnosis - Laboratory Diagnosis - E. ewingiiE. ewingii and and A. phagocytophiliumA. phagocytophilium

• Morula in blood smears (rare)

• Culture is possible but rarely done

• Serology is most common

• DNA probes & PCR are available

Q feverQ fever

• Disease of Animals

Q FeverQ Fever

• Etiology : Coxiella burnetii– Obligate intracellular parasite– Stable and resistant– May resist pasteurization

TransmissionTransmission

• Aerosol– Parturient fluids

• 109 bacteria per gram of placenta

– Urine, feces, milk• Direct contact• Fomites• Ingestion• Arthropods (ticks)

TransmissionTransmission

• Person-to-person (rare)– Transplacental (congenital)– Blood transfusions– Bone marrow transplants

EpidemiologyEpidemiology

• Worldwide– Except New Zealand

• Reservoirs– Domestic animals

• Sheep, cattle, goats• Dogs, cats

– Birds– Reptiles– Wildlife

EpidemiologyEpidemiology

• Occupational and environmental hazards– Farmers– Veterinarians and technicians– Meat processors, – Laboratory workers

Human DiseaseHuman Disease

• I P: 2-5 weeks• Highly infectious : Low infective dose• Humans are dead-end hosts• Disease

– Asymptomatic (50%)– Acute– Chronic

Acute InfectionAcute Infection

• Flu-like, self limiting • Atypical pneumonia (30-50%)

– Non-productive cough, chest pain– Acute respiratory distress possible

• Hepatitis• Skin rash (10%)• Other signs (< 1%)

– Myocarditis, pericarditis, meningoencephalitis• Death: 1-2%

Chronic DiseaseChronic Disease

• 1-5% of those infected– Prior heart disease, pregnant women,

immunocompromised• Endocarditis• Other

– Osteomyelitis– Granulomatous hepatitis– Cirrhosis

• 50% relapse rate after antibiotic therapy

Risk to Pregnant WomenRisk to Pregnant Women

• Mostly asymptomatic• Transplacental transmission• Reported complications

– In-utero death– Premature birth– Low birth weight– Placentitis

Laboratory DiagnosisLaboratory Diagnosis

• Isolation– Animal Inoculation– Tissue culture (HeLa cells, HEp-2 cells)

• Antigen detection - IFA• Antibody detection (Serology)

– Weil Felix Reaction– Rickettsial serology: IFA (Gold Standard)

• Molecular Diagnosis - PCR

BartonellaBartonella

Microbiology - Microbiology - BartonellaBartonella

• Small Gram-negative aerobic bacilli• Difficult to culture• Infect animals but do not cause disease in

animals• Insects are thought to be the vectors in

human disease• Some species infect erythrocytes

Bartonella Organism Disease

B. quintana (formerly Rochalimaea quintana)

Trench fever (shin-bone fever, 5 day fever), bacillary angiomatosis, bacillary peliosis endocarditis

B. henselae Cat-scratch disease, bacillary angiomatosis, bacillary peliosis endocarditis

B. bacilliformis Oroya fever (bartonellosis, Carrion’s disease)

B. elizabethae Endocarditis (rare)

Bartonella quintanaBartonella quintana

• Trench fever– Shin-bone fever– 5 day fever

Epidemiology - Epidemiology - B. quintanaB. quintanaTrench FeverTrench Fever

• Associated with war and famine• Vector - human body louse

– Organism found in feces• Reservoir - humans

– No transovarian transmission– Cycle - human to louse to human

Trench FeverTrench Fever

• Infection may be asymptomatic or severe• Sudden onset of fever, chills, headache and

myalgia• Severe pain in the tibia (shin-bone fever)• Symptoms may appear at 5 day intervals (5

day fever)• Maculopapular rash may or may not develop

on the trunk• Mortality rates very low.

Bartonella henselaeBartonella henselae

• Cat-scratch disease

Epidemiology - Epidemiology - B. henselaeB. henselaeCat-scratch DiseaseCat-scratch Disease

• Acquired from cat bite or scratch and possibly from cat fleas

Clinical SyndromeClinical SyndromeCat-scratch DiseaseCat-scratch Disease

• Benign disease• Chronic regional lymphadenopathy

Laboratory Diagnosis - Laboratory Diagnosis - B. henselaeB. henselae

• Serology

Weil Felix ReactionWeil Felix Reaction

• Heterophile agglutination test• Common alkali stable ploysaccharide

– Ricketsiae– Proteus spp. Starins : OX19, OX2, OXK

• Non specific test• All rickettsial diseases may not answer

Weil Felix ReactionWeil Felix Reaction

Disease Proteus OX19 Ag

Proteus OX2 Ag

Proteus OXK Ag

Epidemic Typhus +++ + -

B Z Disease - - -Endemic Typhus +++ + -

Spotted Fevers ++ ++ -RickettsialPox - - -Scrub Typhus - - +++Trench Fever - - -Q Fever - - -

TreatmentTreatment

• Tetracyclin• Doxycyclin• Chloramphenicol

RickettsiaeRickettsiae