Human Human RickettsiosesRickettsioses
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AIMSRCAIMSRC
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