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RICKETTSIACEAEDr.T.V.Rao MD
T
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Zinsser, Lice And History In 1935, Harvard Medical School physician and
researcher Hans Zinsser wrote the brilliantand original Rats, Lice and History in which hetraced the effects of vermin-borne disease onarmies, cities and populations. From hisextensive research on head and body lice,
Zinsser stated unequivocally that "the bodyand head louse carry the infection [typhus]from one human to another.
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Zinsser, Lice And History
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General Characteristics Small obligate intracellular coccobacilli Gram negative (poorly), better stained with
Giemsa (Blue) Have cell wall, bigger than virus but smaller
than bacteria Have DNA and RNA Have an ATP transport system that allows
them to use host ATP Arthropod reservoirs and vectors ( e.g. ,
ticks, mites, lice or fleas).
Sensitive to antibioticsDr.T.V.Rao MD 4
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Category of rickettsia Genus
Rickettsia, Coxiella ,Orientia,Ehrlichia
Bartonella Species
Rickettsia prowazekii (epidemic typhus),
Rickettsia typhi (endemic typhus), Rickettsiarickettsii (spotted fever), Rochalimaeaquintana (trench fever), Coxiella burnetii (Q fever)
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Dr.T.V.Rao MD
History 17 th -19 th century
Epidemics in Europe as aresult of war, disaster, or in prisoners
1909: Transmission by lice 1917-1925: Russia
Estimated 25 million cases End of WWII
DDT used for control Vaccine developed
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Historical Photograph onTyphus
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Structure: of BacteriaSimilar with Gram negative bacteria
Cell wall: outer membranepeptidoglycanlipopolysaccharide (LPS)
Microcapsule and polysaccharide
Two antigenically distinct groups:LPS : heat-stable, cross-reactive with
somatic antigens of non-motile Proteusspecies (Weil-Felix test)
Outer membrane protein: heat-unstable, species-specific
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Rickettsia Small gram negative Bacilli Obligate intracellular pathogens. Parasites on - Lice, Fleas, Ticks Mites
colonizes the Gut.
In vertebrates colonizes Vascularendothelium and Reticuloendothelial
system. Dr.T.V.Rao MD 9
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Five genera in this class causehuman diseases:
RickettsiaBartonellaCoxiella (does NOT cause skin rash )EhrlichiaOrientia
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Replication
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Five genera in this class causehuman diseases:
RickettsiaBartonellaCoxiella (does NOT cause skin rash)EhrlichiaOrientia
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Genera 1.Rikettsia, 2.Orientia 3.Ehrcichia
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Typhus Group Murine typhus (also known as endemic typhus and flea borne typhus)
Rickettsia mooseri (typhi) Epidemic typhus (also known as Brill - Zinsser disease and louse borne typhus) Rickettsia prowazekii Scrub typhus (or Chigger fever) Rickettsia tsutsugamushi
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The Others Q Fever Coxiella burnetii Ehrlichiosis Ehrlichia canis Ehrlichia equi Ehrlichia chafeensis Several others now identified
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RICKETTSIAL INFECTIONS
Fever, headache, malaise, prostration, skinrash & Hepatosplenomegaly Classified into groups:
1. Typhus Group Epidemic typhus ,Murine typhus , Scrub typhus
2. Spotted Fever Group RMSF, Rickettsiapox
3. Q Fever4. Trench fever5. Ehrlichiosis
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Disease Organism Vector Reservoir
Rocky Mountainspotted fever
R. Rickettsii Tick Tick, wild rodents
Scrub typhus R. Tsutsugamushi Laval Mite(chiggers)
Mites, wild rodents
Epidemic typhus R. Prowazekii Louse Humans, squirrel fleas,flying squirrels
Murine typhus R. Thphi Flea Wild rodents
Q fever Coxiella Burnetii None Cattle, sheep, goats, cats
Diseases Caused by the Rickettsia
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DISEASES RICKETTSIALAGENT
INSECTVECTOR
MAMMALIANRESERVOIR
TYPHUS GROUP
a) Epidemictyphus
R. prowazekii Louse Human
b) Murine
typhus(Endemic typhus)
R. typhi Flea Rodents
c) Scrubtyphus)
R.tsutsugamush
i
Mite Rodents
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Rickettsia Prowazekii( Von Prowazekii )
Humans natural vertebrate hosts Vector - Human body louse,( Pediculus
humans corporis ) Lice get infected from patients. Life cycle get multiplied in gut 1 week Person person contact.
Lice bite causes itching and scratching Enters through respiratory tract / Conjunctivae Incubation 5- 15 days
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Genus -Rickettsia Two groups Typhus fevers,
Spotted fever.Morphology Rickettsia pleomorphic
Coco bacillary,Size 0.3 to 0.6 micron
x 0.8 - 2 microns.
Gram negative, non motileNon capsulate not stained easilyGiemsa and Gimenez staining methods.
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Typhus Fever
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Typhus Fever group 1. Epidemic Typhus 2. Recrudescent typhus (
Brill Zinsser disease ) 3. Endemic typhus
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EPIDEMIC TYPHUS (LOUSEBORNE TYPHUS)
Etiology: R. prowazekii
severe systemic infection &prostration
more fatal
Brill-Zinsser Disease recrudescent disease
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Epidemic Typhus - 1 Also known as louse borne typhus because it is spread human-to-human via the body louse
(which dies of its infection with Rickettsia prowazekii after about three weeks) This is a serious disease consisting of fever, severe headache, myalgia, and central rash Untreated, the mortality ranges from 20 -
40% Major killer in concentration camps of WW II Dr.T.V.Rao MD 25
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Cultivation Needs cell culture lines Grows in the Cytoplasm
Grows at 32 to 35
0c
Grows in yolk sac of developingchick embryo
Grows in mouse fibroblasts,Hela,Hep2
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Cultivation Rickettsia can not be grown in
bacteriological media, Obligate
intracellular pathogens. In continuous cell lines, Guinea pig,
Mice Infect the endothelial cells of
vascular system. Can synthesize ATPDr.T.V.Rao MD 27
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Life Cycle of Rickettsia
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Replication
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Dr.T.V.Rao MD
Transmission Human body louse
Pediculus humanus corporis
Infective for 2-3 days Infection acquired by feeding on infected
person
Excrete R. prowazekii in feces attime of feeding
Lice die within 2 weeks
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Transmission Louse feces rubbed into bite or
superficial abrasions Inhalation of feces Sylvatic typhus
Flying squirrel
30 human cases in eastern and central U.S.
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PATHOLOGYMultiply in endothelial cells of small blood vessels
Vasculitis
(skin rashes;other organs DIC & vascular occlusion)
Swollen & necrotic
Thrombosis of the vessels
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Antigenic structure
Species differ with Group specific
antigens. Sharing of antigens between
Rickettsia and Proteus basis of Weil Felix Heterophile agglutination Test.
Used Proteus strains 0X 19, OX2 OXKDr.T.V.Rao MD 33
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Epidemic TyphusAlso called as Louse borne Typhus
Classical TyphusRussia Eastern Europe Devastating Epidemics
in wars
Napoleons retreat
Russia 3 million deaths 1917 1921India - Kashmir
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R. Prowazekii
Louse
Human Human
Louse
Epidemic typhusDr.T.V.Rao MD 35
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R. Typhi
Rodent
Flea Rat Tick Flea Human
Rodent
Murine typhus(much milder than epidemic
typhus)Dr.T.V.Rao MD 36
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Le sions in Epidemic Typhus
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Rickettsia Prowazekii( Von Prowazekii )
Humans - natural vertebrate hosts Vector - Human body louse,( Pediculus
humans corporis )
Lice get infected from patients. Life cycle get multiplied in gut 1 week Person person contact.
Lice bite causes itching and scratching Enters through respiratory tract / Conjunctivae Incubation 5- 15 days
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Pediculus humanus corporis is theVector
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Clinical Symptoms Incubation: 7-14 days High fever, chills, headache, cough, severe
myalgia May lead to coma
Macular eruption 5-6 days after onset Initially on upper trunk, spreads to entire body
Except face, palms and soles of feet
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Clinical Features Fever, chills Rash on 4 th day
Spread from Trunk to Limbs Not face palms,
sole. In 2 nd week may into stuporous,delirious
stateMay reach 40 % fatality
Bacteria remain latent in Lymphoid tissue,cloudy state. Because of called as Typhus
May cause Recrudescent Typhus
( Called as Brill Zinser Disease.)Dr.T.V.Rao MD 41
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Dr.T.V.Rao MD
Brill-Zinsser Disease Occurs years after primary attack
Person previously affected or lived inendemic area
Viable retained organisms reactivated Milder symptoms
Febrile phase 7-10 days Rash often absent Low mortality rate
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Brill- Zinser DiseaseRecrudescent typhus fever
Earlier recovery from typhus fever Latency of the organism in lymphoid
tissue Reactivation leads to recrudescence.
Even louse get infected frompatients. Clinically similar but mild.
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Pattern of Temperature chart inTyphus Fever
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Endemic Typhus
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Endemic TyphusR.mooseri
Also called as Murine or Flea borne typhus From Rats -Transmitted by Rat flea Rickettsia multiplies in Gut and shed in feces Humans bitten by infected Rat flees. Saliva or feces rubbed on bitten area, may
lead to infection. R.typhi R. Prowazekii similar, Biological and
Immunological tests.
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Clinical features Mild disease Rat act as reservoir. Vector Rat flea -Xenopsylla cheopsis Rat flea bites rat Multiplies in the gut of the rat
Fleas un affted. Man gets infected accidentally Mexico Kashmir - chinaT.V.Rao MD
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Experiments on AnimalsNeill-Mooser Reaction
Male guinea pig inoculatedintra peritioneally withblood of patients, orisolates of S.typhi produce
Fever, and scrotalswelling, enlarged tests,and cannot be pushedback.-due inflammationand adhesions between
layers of Tunica vagina Test positive in R.typhi
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Treatment Chloramphenicol Tetracycline
Doxycycline 200mg Response within 48 hrs. usually
Vaccine Developed after World War II Not commercially available
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Spotted Fever Group Rickets 1906 Rickettsia of this
group, multipliesin Nucleus andCytoplasm
Ticks transmit
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RICKETTSIA INSECT MAMMALIA
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DISEASES RICKETTSIAL AGENT
INSECTVECTOR
MAMMALIAN
RESERVOIR
SPOTTED FEVER GROUP
a) Indian tick typhus
R. conorii Tick Rodent, Dog
b) Rocky
mountainspotted fever
R. rickettsii Tick Rodents,
Dogs
c) Rickettsialpox
R. akari Mite Mice
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Tick Typhus R.rickettsii Rock mountain spotted
fever R.siberica R.conori
R.australis.Ticks transmits bite- Trans ovarianspread
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Rocky Mountain spotted fever
Ticks in North / South America Tick type R.conori. Rickettsial Pox
Resembles like chicken pox
R. akari by miteMouse reservoir host.
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Ti k d i
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Ticks acts as vectors and reservoirsof Infection
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Rocky Mountain spotted fever
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Rock mo ntain spotted fe er
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Rocky mountain spotted fever
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Rocky Mountain spotted fever
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Rocky Mountain spotted fever
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Genus - Ehrlichia Small Gram negative , obligate intracellular
pathogens, Can infected Phagocytic cells. Called as Glandular fever Ehrlichia sennetsu causative agent. Cause atypical lymphocytosis No arthropod vector, Eating fish infected with flukes infected by
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Monocytic Ehrlichiosis Caused by Ixodid ticks, E.chaffensis. Deer, cattle, Sheep reservoirs
Leucopenia Thrombocytopenia Liver is involved. Doxycycline effective in Ehrlichosis Human granulocytic Ehrlichosis E.equi.
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Laboratory Diagnosis of Rickettsial
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Laboratory Diagnosis of Rickettsialdiseases
Isolation Serology Isolations can be dangerous if not
well protected.
R.typhi R.conori, R.akari causestunica reaction R.prowazeki only fever
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Diagnosis and Prevention
MicroscopySerological Test (Weil-Felix reaction, ELISA, IF,PCR)
Breaking the infection chain ( controlling and
killing the intermediate hosts and reservoirhosts)Inactivated vaccine has protective effectChloromycetin, tetracycline are helpful for
therapy, Sulphonamides are not administered(increasing the penetrating of the vessel).
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Laboratory Diagnosis Tissue
cultures In Vero cells, MRC 5
cells.
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SerologyWeil Felix Test
Test based on principle of Hetrophileagglutination tests
Non motile strains of Proteus are selected. OX19,OX2,OXK
Sharing alkali stable carbohydrate antigen bysome Rickettsia X certain strains of Proteusvulgaris OX19,OX2, and Proteus mirabilis OXK.
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Laboratory Diagnosis Weil Felix is simple to perform but of
Historical importance Other tests
Complement fixation tests,
Agglutination,
Passive hem agglutination.PCR
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DISEASE WEIL-FELIX
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OX19 OX2 OXK
Epidemic typhus ++ +/- -
Endemic typhus ++ - -
Scrub typhus - - ++
RMSF + + -
Rickettsial pox - - -
Q fever - - -
Trench fever ? ? ?Dr.T.V.Rao MD 66
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Different Methods of Diagnosis
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Older Techniques
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1. Giemsa Staining Technique:- utilizes peritoneal scrapings of infected mice.
Older Techniques:to detect O. tsutsugamushi
2. Weil-Felix Proteus Agglutination Test:-is a test which relies on the fact that Rickettsia and Proteus OX strains have common
antigens.:-is a test for the presence & type of rickettsial disease based on the agglutination of X-strain Proteus vulgaris with suspected Rickettsia in a patients blood serum sample. :-is commonly used in hospitals & clinics:-This test is now being replaced by a complement-fixation test.
Weil-Felix Proteus Agglutination TestDr.T.V.Rao MD 68
Newer Techniques
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2. Indirect Immuno-Peroxidase(IIP)
Control Infected
IIP= is a modification of IFA technique thatreplaces the fluorochrome with peroxidase.
Slide is observed using a bright-field
microscope.
Staining reaction is positive when O.tsutsugamushi particles stain light brown.
Immunological Assays
Newer Techniques:to detect O. tsutsugamush i
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Newer Techniques
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4. Enzyme-linked Immuno-Sorbant Assay (ELISA)
1. Add antigens
Ag-coatedwell
3. Add anti-Ab 2. Add mouse serum
Ag-Ab
complex OpticalDensity
(OD)Reading
4. Add enzyme-
substrate mix
5.Let colorize
ELISA test is a technique for detecting & measuring antigen or antibody.:-It is one of the most reliable techniques to detect antibody
against scrub typhus infection.:-Its procedure is the principal for development of recent
rapid diagnostic kits.:-This technique is widely used in laboratories & hospitals.
Immunological Assays
Newer Techniques:to detect O. tsutsugamushi
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Prophylaxis Control of vectors. Destruction
animal reservoirs,Dr.T.V.Rao MD 71
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Scrub Typhus Scrub typhus caused by Mild to fatal 6-18 days after bite of Mite An Escher is formed at the site of bite With enlargement of Lymph nodes,
Interstitial pneumonitis,lymphadenopathy,spleenomegalyEncephalitis, Respiratory failure,circulatory failure
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SCRUB TYPHUSEtiology: Orientia tsutsugamushi resembles Epidemic typhus except for
the ESCHAR generalized lymphadenopathy &
lymphocytosis cardiac & cerebral involvement may be
severe
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Epidemiology Source of infection-------- Rat
Route of transmission----- Trombiculid mites Susceptible population---- All susceptible
Epidemic features---------- Tsutsugamushi
triangle
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Epidemiology
Infected
animal Eg
g
Larva
Eg
g
Larva
Nymph
Nymph Adul
t
Adul
t Human
Natural cycle-natural focalizationNatural focus disease-zoonosis-borne diseases
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Scrub Typhus
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An important vector-borne disease, firstdescribed in 1899 in Japan.
During World War II, this disease killedthousands of soldiers who were stationed
in rural or jungle areas of the Pacifictheatre.
Scrub Typhus
The disease occurred and threatened people throughoutAsia & Australia. The range stretches from the Far-eastto the Middle-east (from Japan and Korea, Southeast Asia, Pakistan,India, to Arab countries and Turkey ). There are approx. 1 millioncases each year world-wide, & over 1 billion people atrisk.
Dr.T.V.Rao MD 76
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R. TsutsugamushiEggs Adult stage Nymphal stage
Nymphal stage Adult stage Eggs
Rats Nymphal stage Nymphal stage Human
Scrub typhus
Chigger
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b h
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Scrub typhus
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Scrub Typhus : A Rickettsial Disease
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Pathogen: Orientia tsutsugamushi Rickettsial bacteria
Vector: Leptotrombidium Chigger-Mite
An acute febrile, rickettsial diseasecaused by a gram-negative, rod-shaped (cocco-bacillus) bacterium,known as Orientia (Rickettsia)
tsutsugamushi.
Scrub Typhus : A Rickettsial Disease
O. tsutsugamushi is transmitted to vertebratehosts (rodents-primary host & humans-secondary or accidental host) by the bite of larvalmites (chiggers) of the genus Leptotrombidium , e.g. L. deliense, L. dimphalum, etc.
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Pathogenesis and pathology
Inoculation Invade Locallymph node Spread byBlood stream
Invade Vascularendothelium
Papulemaculoppularescharulcer
Enlargementof locallymph node
Generalsymptoms of intoxication
General organhyperaemia.Systemiclyphadenopath
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R. Tsutsugamushi
Eggs Adult stage Nymphal stage
Nymphal stage Adult stage Eggs
Rats Nymphal stage Nymphal stage Human
Scrub typhus
Chigger
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Scrub typhus
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Clinical Manifestation
Incubation period is 4~21
Sudden onset with a fever 1st week, systemic toxic symptoms
2nd week, get worse, complication
3th week, conv alesceDr.T.V.Rao MD 83
Specific features
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Specific features
Eschar
Probability: Higher than 60%.
Location: Axillary fossa, inguinal region,
perianal region, scrotum, buttocks and thethigh.Appearance: an ulcer surrounded by a red
areola, is often covered by a dark scab.
The most specific manifestation of scrubtyphus .
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Ri k i i l
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Ricketisial pox Transmitted by mites, Similar other spotted fever Head ache ,fever Escher at the site of bite by mite.
Maculopapular rash, can bevesicular,
Fever lasts for 1 weekDr.T.V.Rao MD 85
Ski L i Mi
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Skin Lesion Mite
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Q F
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Q Fever Occurs in veterinarians, ranchers, and animal
researchers who are in contact with infectedplacenta from sheep, cattle, or goats (no
arthropod vector for C. burnetii) Incubation period is 10 -28 days Fever and headache are common; 50% will
develop pneumonia after inhaling theorganism; hepatitis & endocarditis are rare Specific serology establishes the diagnosis
Bioterrorist threat? Dr.T.V.Rao MD 87
C i ll B ii
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Coxiella Burnetii Q fever query fever Self-limiting flu-like syndrome with high
fever (40 ) Primary reservoirs are wild (cattle,
sheep, goat etc.) Non-cross reactive antigen with non-
motile Proteus (Weil-Felix reactionnegative)
Live in macrophages of vertebrate hostDr.T.V.Rao MD 88
Genus Coxiella
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Q Fever Etiological agent ? Small in size called Coxiella burnetti
Ixodid tick spread the disease Domestic live stock get infected. Coxiella abundant in Tick feces, Survive in dried feces, Milk too infective Cause Human infection.
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C i ll b i
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Coxiella burnetti
Q fever Cow and sheep tick High resistance
abruptonset ,fever,headache,chills,myalgia,granulomatoushepatitis
chronic diaease withsubacuteonset ,endocarditis,hepaticdysfunction
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Q F
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Q - Fever
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Q F
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Q Fever Wool hides, Meat, Milk Enters through abrasions System infection through Intestine,
pulmonary, All organs are involved Can cause serious infection,
Hepatitis and meningitis,May last for 2 3 years as chronic condition
Infects Monocytes and MacrophagesDr.T.V.Rao MD 92
Q Fever
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Q Fever
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Pasteurization of Milk Which method is better ?
Pasteurization byholders method noteffective
Flash methodeffective.
Phase variation
applicablePhase I and Phase II
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Cli i l f t
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Clinical features
Present with head ache, chills,Pneumonia
Endocarditis, Meningitis,Encephalitis
Can cause latent infections.
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Q Fever
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Q Fever
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L b t Di g i
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Laboratory Diagnosis
Indirect Immunofluorescencemethods
Polymerase chain reaction, Genus specific applications in
progress. Isolation of the organism is
dangerous Dr.T.V.Rao MD 97
Treatment
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Treatment Doxycycline is effective. Tetracycline are highly
effective Nursing care May need blood transfusion.
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Eh li hi i
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Ehrlichiosis Ehrlichia chaffeensis most common
Human monocytotropic ehrlichiosis (HME) E. ewingii has also been identified Transmitted by lone star tick ( Amblyomma
americanum) White-tailed deer major host for tick
species and natural reservoir for bacteria Infections in coyotes, dogs, and goats
have been documented
99
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Ehrlichiosis Clinical Information
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Ehrlichiosis Clinical Information
Onset occurs 5 10 days after tick bite Infects leukocytes
E. chaffeensis prefers monoctyes E. ewingii prefers granuloctyes Morulae can be identified
Rash observed ~33% of patients with HME Vary from petechial or maculopapular to diffuse
erythema Occurs later in disease
Rash rarely seen with E. ewingii infections
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E . Chaffeensis Laboratory
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yCriteria
Confirmed Fourfold change in IgG by IFA in paired serum samples Detection of DNA by PCR Demonstration of antigen by IHC in biopsy or autopys
sample Isolation of bacteria by cell culture
Supportive Elevated IgG or IgM by IFA, ELISA, dot-ELISA or other
formats Morulae identification by blood smear microscopicexamination
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Bartonella
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Bartonella Gram ve bacilli/Anthropoids B.bacilliform, B.quintana,B henselae Bartonella bacilliform Also called as Oroya fever, A Medical student Peruvian
Daniel Carrion Credited for isolation.Called as Carrions Disease
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Bacterial Morphology
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Bacterial Morphology
B.bacilliform Pleomorphic
gram negativebacteria Carries a tuft of
polar flagella.
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Clinical features Progressive Anemia, Bacterial invasion of
Erythrocytes
Carries high mortality
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Bartonella ( Rochalimia )
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Bartonella ( Rochalimia ) Bartonella Quintana Called as trench fever Called as five day fever. Grows in cell free culture media.
Chronic/Latent infections Infection may lost > 20 yearsT.V.Rao MD
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Bartonella Henselae
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Bartonella Henselae Cat scratch disease (CSD) Weil-Felix reaction negati ve
Infection by cats or dogs Parinaud Eye -Lymph node
syndrome
The eye looks red, irritated, andpainful,
similar to conjunctivitis .Dr.T.V.Rao MD 107
Bartonella henselae
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Bartonella henselae Also called s cat scratch disease Caused by B.henselae Needs lymph node biopsy Staining sections with Warthim
Starry sating Associated in AIDS patients.
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Prevention
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Prevention Use of repellents in endemic areas Protective clothing in endemic areas Careful inspection & quick removal of ticks Useful vaccine for RMSF is available for high
risk groups such as forest rangers that work inendemic areas
Weekly doxycycline may prevent scrubtyphus infection in field workers
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