Rikettsial diseases

1. RICKETTSIACEAERICKETTSIACEAE

2. TaxonomyTaxonomy

3. RickettsiaeRickettsiae
 DefinitionDefinition
 A genus of small, rod-shaped, round toA genus of small, rod-shaped, round to
pleomorphic microorganisms in the orderpleomorphic microorganisms in the order
Rickettsiales. They are true bacteria, gram-Rickettsiales. They are true bacteria, gram-
negative, and cultivable only in living tissues.negative, and cultivable only in living tissues.
Transmitted by lice and ticks, they causeTransmitted by lice and ticks, they cause
disease in humans and domestic animals butdisease in humans and domestic animals but
are also found in the cytoplasm of tissue cellsare also found in the cytoplasm of tissue cells
of lice, fleas, ticks and mites, which may act asof lice, fleas, ticks and mites, which may act as
reservoirs and vectorsreservoirs and vectors

4. RickettsiaeRickettsiae
 Group of bacteria that are fastidious,
 obligate intracellular pathogens
 They are pleomorphic & coccobacillary
 The organisms will not show up on
 Gram stain, but can be seen when either
 Gimenez or Giemsa stains are used

5.  Classification:Classification: 3 genera3 genera
Rickettsia sppRickettsia spp
Orientia tsutsugamushiOrientia tsutsugamushi evolved fromevolved from common ancestorcommon ancestor
Ehrlichia sppEhrlichia spp
Bartonella (Rochalimaea) quintanaBartonella (Rochalimaea) quintana - trench fever- trench fever
&&
Coxiella burnetiiCoxiella burnetii – Q fever – are no longer– Q fever – are no longer
considered to the members of the family.considered to the members of the family.

6. The name rickettsia has been given in honour of Howard
Ricketts who first identified the organism, its vector, and
route of transmission of Rocky Mountain Spotted Fever.

7. General characteristics
 They are very short, pleomorphic bacilli, non-motile,
non-capsulated.
 They are Gram negative, though they do not take the
stain well.
 They are obligate intracellular parasites.
 Multiplication is by binary fission within the host cell.

8.  Giemsa [bluish purple]Giemsa [bluish purple]
 Gimenez and Machiavello [deep red]Gimenez and Machiavello [deep red]

9. Cultural characters:
Do not grow on cell-free media.
They can be cultivated in the yolk sacs of
embryonated eggs.
Can be cultivated on cell cultures –HeLa, HEp2, Detroit 6
etc.
Laboratory animal like mice is used for primary isolation

10. Antigenic Structure
It possess 3 types of antigens
 Group specific soluble antigens
 Species specific antigen
 Alkali stable polysaccharide antigen

11. Alkali stable polysaccharide:
Found in many rickettsiae and is shared by certain strains
of Proteus vulgaris.
Weil-Felix test is based on cross reaction of the rickettsial
antigen with the O antigen polysaccharide found in Proteus
vulgaris OX-19, OX-2 and OX-K.
The test measures the antiricketssial Ab in patient’s
serum
It is no longer used in United States.

12. Pathogenesis
Organisms are maintained in nature and in arthropods –
ticks, lice, fleas & mites.
Mode of Transmission: To humans is by bite of vectors or
through faeces of infected arthropod vector.

15. On entry to human body
Organism multiplies locally & enters the blood stream
Invades the vascular endothelial cells.
Leading to proliferation of cells, and perivascular infiltration
Resulting in thrombosis of vessels
Rupture and necrosis

16. Rickettsial infection of endothelial cells.

17. Typical lesion caused is a vasculitis.
 Damage to vessels of skin results in rash, edema &
hemorrhage is due to increased capillary permeability.
 Rickettsiae produce endotoxin. Role of endotoxin in
human disease remains unclear.

18. RickettsiaRickettsia
speciesspecies DiseaseDisease
Natural cycleNatural cycle
GeographicGeographic
distributiondistribution
VectorsVectors HostsHosts
Typhus group:Typhus group:
RickettsiaRickettsia
prowazekiiprowazekii
Epidemic typhusEpidemic typhus HumanHuman
body licebody lice
HumansHumans WorldwideWorldwide
Recrudescent typhus (Brill-Recrudescent typhus (Brill-
ZinsserZinsser disease)
NoneNone HumansHumans WorldwideWorldwide
R. typhiR. typhi
(mooseri(mooseri ))
Murine typhusMurine typhus Rat FleasRat Fleas RodentsRodents WorldwideWorldwide
(Endemic typhus)(Endemic typhus) FleasFleas OpossumsOpossums USAUSA
R. felisR. felis Murine typhus likeMurine typhus like Cat FleasCat Fleas OpossumsOpossums USAUSA
Spotted Fever group:Spotted Fever group:
R. rickettsiiR. rickettsii Rocky Mountain spottedRocky Mountain spotted
feverfever
TicksTicks Small mammals,Small mammals,
dogs, rabbits, birdsdogs, rabbits, birds
North & SouthNorth & South
AmericaAmerica
R. conoriiR. conorii Boutonneuse feverBoutonneuse fever TicksTicks Rodents, dogsRodents, dogs Africa, SouthernAfrica, Southern
Europe, IndiaEurope, India
R. sibiricaR. sibirica North Asia tick typhusNorth Asia tick typhus TicksTicks RodentsRodents Eurasia, AsiaEurasia, Asia
R. japonicaR. japonica Japanese spotted feverJapanese spotted fever TicksTicks Rodents, dogsRodents, dogs JapanJapan
R. australisR. australis Queensland tick typhusQueensland tick typhus TicksTicks RodentsRodents AustraliaAustralia
R. akariR. akari RickettsialpoxRickettsialpox MitesMites House mice, ratsHouse mice, rats WorldwideWorldwide

19. Classification of Rickettsia
 Spotted Fever Group
 Typhus Group
 The Others

20. Spotted Fever Group
 Rocky Mountain
spotted fever
 – Rickettsia rickettsii
 • Rickettsial pox
 – Rickettsia akari
 • Canadian typhus
 – Rickettsia canada
 Mediterranean
spotted fever
 – Rickettsia conorii
 • Siberian tick typhus
 – Rickettsia siberica
 • Queensland tick
 typhus
 – Rickettsia australis

21. Typhus Group
 Murine typhus (also known as endemic
 typhus and fleaborne typhus)
Rickettsia mooseri (typhi)
 Epidemic typhus (also known as Brill-
 Brill-Zinsser disease and louseborne
typhus).Recrudescent typhus.
 – Rickettsia prowazekii
 • Scrub typhus (or Chigger fever)
 – Rickettsia tsutsugamushi

22. Arthropod Vectors
 Rickettsia are usually introduced into human
skin by the bite of an insect (flea or louse) or an
arachnid (tick or mite)
 These arthropods serve as both host and vector
to the rickettsia and reside on the reservoir
animals (dogs, mice, rats, and flying squirrels)

23. Example of Arthropod Vector
 Amblyomma
hebraeum
 Typical tick vector
of the rickettsial
spotted fever group

24. 12 tick-borne rickettsioses12 tick-borne rickettsioses
R. rickettsii
R. africae
R. conorii
R. conorii
R. slovaca
R. conorii Astrakhan
R. conorii Israël
R. australis
R. honeiR. honei
Indian tick typhus Rickettsia
R. japonica
R. mongolotimonae
R. helvetica
R. mongolotimonae
R. sibirica
R. conorii
R. conorii Israël
« R. heilongjiangii »
R. helvetica

25. Q- Ticks are vectors for the transmission of each of theQ- Ticks are vectors for the transmission of each of the
following diseasesfollowing diseases EXCEPT:EXCEPT:
A) Rocky Mountain Spotted FeverA) Rocky Mountain Spotted Fever
B) Epidemic TyphusB) Epidemic Typhus
C) Japanese spotted feverC) Japanese spotted fever
D) Boutonneuse feverD) Boutonneuse fever

26. Spotted fever group:
Disease of this group includes –
Rocky mountain spotted fever (RMSF)
R. rickettsii
Other tick borne diseases
R. siberica, R. conori, R. australis
Rickettsial pox
R. akari

27. Rocky mountain spotted fever (RMSF):
Causative organism: R. rickettsii
Vectors: Dermacentor variabilis (dog tick)
Reservoirs: Dogs & rodents
Transmission: is via tick bite
The organism is passed by the transovarian route from tick
to tick.
Humans are accidental hosts.
Incubation Period: 3-14 days

28.  Mainly seen inMainly seen in childrenchildren duringduring spring & early summerspring & early summer ––
ticks are active.ticks are active.
 Symptoms:Symptoms: Sudden onset of fever, severe headache,Sudden onset of fever, severe headache,
mayalgia.mayalgia.
 In 2-6 days, a typical rash is seen. It begins with maculesIn 2-6 days, a typical rash is seen. It begins with macules
and progress to petechiae.and progress to petechiae.
 The rash appears on theThe rash appears on the hand and feethand and feet && spreadsspreads
inwards to the trunkinwards to the trunk..
 It can be fatal if untreated.It can be fatal if untreated.

29. Early RashEarly Rash
Late Stage Petechial Rash
Early (macular) rash on sole of foot.

30. Other tick borne diseases:
Causative organisms: R. siberica, R. conori, R. australis
Vectors: Ixodid ticks
Disease resemble RMSF
Milder form
A black spot having a necrotic centre (eschar) is present
at the site of tick bite.
 Humans accidentally enter the natural cycle.

31. tick-bite eschartick-bite eschar
3 weeks after
removing the tick

32. Typical Eschar at Tick Bite Site

33. Skin rash during infection with
Rickettsia conori.
Tick bite fever, Rickettsia conori. Notice the
inoculation chancre

34. Rickettsial Pox:
Causative organism: R. akari
Vector: Liponyssoides sanguineus (Mites)
It’s a benign febrile disease
Carried by mouse to man by mite
Produces a vesicular rash
Mildest form, self limiting
Non fatal, resembles chicken pox

35.  Rash during rickettsial pox infectionRash during rickettsial pox infection

36. Typhus fever Group:
Consists of –
Epidemic typhus (Classical typhus)
R.prowazekii
Recrudescent infection (Brill–Zinsser)
R.prowazekii
Endemic typhus (murine typhus)
R. mooseri (R.typhi)

37. Epidemic typhus:
Causative organism: R.prowazekii
Vector: Pediculus humanus corporis
(human body louse)
Pediculus humanus capitis
Transmission: Autoinoculation by the person while
scratching the bite of infected body louse –produce
abrasion- which is portal of entry for the organisms.
Incubation Period: 6-15 days

38.  It is associated with wars & poverty.It is associated with wars & poverty.
 It is found in Africa & South America but not in UnitedIt is found in Africa & South America but not in United
States.States.
 Symptoms:Symptoms: Chills, fever, headache, pain, stupor andChills, fever, headache, pain, stupor and
delerium.delerium.
 Signs of severe meningoencephalitis, begin with rash.Signs of severe meningoencephalitis, begin with rash.
 If untreated - death occurs due to peripheral vascularIf untreated - death occurs due to peripheral vascular
collapsecollapse oror due to bacterial pneumonia.due to bacterial pneumonia.

39. Epidemic Typhus:Epidemic Typhus: Petechial RashPetechial Rash
Macular rash appears 4 – 7 days after the onset of illness.Macular rash appears 4 – 7 days after the onset of illness.
-firstfirst on theon the trunktrunk andand then to limbsthen to limbs..
-The rash becomes petechial and spreads over the entireThe rash becomes petechial and spreads over the entire
bodybody except face, palms and soles.except face, palms and soles.

40. Some develop a milder reactivity of latent infection afterSome develop a milder reactivity of latent infection after
many years.many years.
This isThis is Recrudescent typhus / Brill-Zinsser DiseaseRecrudescent typhus / Brill-Zinsser Disease
Signs and symptoms:Signs and symptoms: like epidemic typhus but are lesslike epidemic typhus but are less
severe.severe.
In United States it is seen in older people who hadIn United States it is seen in older people who had
epidemic typhus during World War II.epidemic typhus during World War II.

41. Q- Each of the following statements concerning epidemicQ- Each of the following statements concerning epidemic
typhus is correcttyphus is correct EXCEPT:EXCEPT:
A) The disease is characterized by a rashA) The disease is characterized by a rash
B) The Weil – Felix test can aid in diagnosis of the disease.B) The Weil – Felix test can aid in diagnosis of the disease.
C) The disease is caused by a rickettsiaC) The disease is caused by a rickettsia
D) The causative organism is transmitted from rodents toD) The causative organism is transmitted from rodents to
human by a tickhuman by a tick

42. Endemic typhus (Murine typhus):
Causative organism: R. mooseri (R.typhi)
Vector: Xenopsylla cheopis (rat flea)
Reservoir: Rats
Mode of infection: flea bite, or through contaminated food
with infected flea feces & rat urine.
Incubation Period: 1-2 weeks

43.  RickettsiaRickettsia typhityphi hostshosts

44.  Symptoms:Symptoms: Gradual onset of fever with severe headache,Gradual onset of fever with severe headache,
chills, generalized painschills, generalized pains
 A macular rash appears by about 5 days, first appearingA macular rash appears by about 5 days, first appearing
on the trunk.on the trunk.

45. Scrub Typhus :
Causative organism: Orientia tsutsugamushi
Geographic appearance: Far east, especially Myanmar
(Burma), India, Sri Lanka, New Guiena, Japan & Taiwan.
Vector & Reservoir: Chigger (Larval stage of mites)
The true reservoir is in mites that infest rodents.
Mites transmit the infection transovarially.
Man gets infected by bite of mite.

46. Clinical findings:Clinical findings:
 The disease resembles epidemic typhus clinically.The disease resembles epidemic typhus clinically.
 Eschar – the punched – out ulcer with a blackened scabEschar – the punched – out ulcer with a blackened scab
which indicates the location of mite bite is characteristicwhich indicates the location of mite bite is characteristic
feature.feature.
 Generalized lymphadenopathy & lymphocytosis areGeneralized lymphadenopathy & lymphocytosis are
common.common.
 Cardiac & cerebral involvement may be severe.Cardiac & cerebral involvement may be severe.

47. Laboratory diagnosis:Laboratory diagnosis:
Isolation of organism-Isolation of organism- is hazardousis hazardous
Serological test –Serological test –
Indirect immunofluorescenceIndirect immunofluorescence
ELISAELISA
Weil – Felix test: is of historic interest.Weil – Felix test: is of historic interest.

48.  R. rickettsii in skin section of a pink macule taken on about theR. rickettsii in skin section of a pink macule taken on about the
fourth day of R.M.S.F.fourth day of R.M.S.F.
 Preparation by Immune FluorescensePreparation by Immune Fluorescense

49.  Rickettsia rickettsii - Rocky Mountain Spotted FeverRickettsia rickettsii - Rocky Mountain Spotted Fever
Immunofluoresence reveals intracellular bacteriaImmunofluoresence reveals intracellular bacteria

50. TREATMENT:
Tetracycline, Chloramphenicol.
PREVENTION:
Wearing protective clothing
Using insect repellant
Delousing with insecticide
Use of rat-proofing buildings and using rat poisons.
Clearing jungle vegetation in which rats and mites live.

51. Vaccination:Vaccination:
A typhus vaccine containing formalin- killedA typhus vaccine containing formalin- killed R.R.
prowazekiiprowazekii organisms is effective and useful in theorganisms is effective and useful in the
military during the war time but available tomilitary during the war time but available to
civilians in United States.civilians in United States.
There is no vaccine against Rocky mountainThere is no vaccine against Rocky mountain
spotted fever.spotted fever.

52. Rickettsia and the origin of
mitochondria
 NATURE
12 November 1998
 Complete genome of typhus
agent
 NATURE NEWS SERVICE
 NATURE NEWS SERVICE
 ©M J Larkin Biological Sciences.
The Queen’s University of Belfast
 The publication in this week's Nature of the
complete sequence of the genome from
Rickettsia prowazekii, is not only of
considerable medical importance -
Rickettsia causes epidemic typhus - but
may also shed further light on the evolution
of mitochondria. Mitochondria are the
energy- Complete genome of typhus agent
generating organelles of most 'higher'
organisms and their origin has been much
debated. It is generally thought that they
arose from a bacterium living symbiotically
within a primitive eukaryote cell. Rickettsia
prowazekii appears to be very much like
this hypothesised ancestor. Alongside the
latest research we here re-present a
hypothesis, published earlier this year,
which sought to explain what drove a
Rickettsia-like bacterium to become the
ancestral mitochondria.

53. Rickettsia and the origin of
mitochondria
 The genome sequence of Rickettsia prowazekii and the origin of
Mitochondria SIV G. E. ANDERSSON, ALIREZA
ZOMORODIPOUR,JAN O. ANDERSSON, THOMAS
SICHERITZ-PONTÉN, U. CECILIA M. ALSMARK, RAF M.
PODOWSKI,
A. KRISTINA NÄSLUND, ANN-SOFIE ERIKSSON,
HERBERT H. WINKLER & CHARLES G. KURLAND ©M J
Larkin Biological Sciences. The Queen’s University of Belfast.
 Rickettsia, typhus and the mitochondrial connection MICHAEL
W. GRAY
The genome sequence of Rickettsia prowazekii, the agent that
causes typhus, has been determined. What emerges is a snapshot
of genome re-tailoring in a parasitic bacterium, and a new look at
the evolutionary connection between Rickettsia and mitochondria.

54. Rickettsia and the origin of
mitochondria
 The hydrogen hypothesis for the first eukaryote
WILLIAM MARTIN AND MIKLÓS MÜLLER
W. FORD DOOLITTLE The prevailing view of
the origin of complex eukaryotic cells presumes a
symbiosis, based on respiration, between a
bacterium ©M J Larkin Biological Sciences. The
Queen’s University of Belfast. and a primitive
eukaryotic 'host'. But could the symbiosis have
been based instead on hydrogen metabolism, with
the host being an archaean?

60.  Reference:Reference:
 MIMS: chapter 21MIMS: chapter 21
 Levinson: chapter 26Levinson: chapter 26
 Jawetz: chapter 27Jawetz: chapter 27