2. INTRODUCTION
Rickettsial diseases are considered some of the most covert emerging
and reemerging diseases and are being increasingly recognized in
India
3. • The family rickettsiaceae is named after Howard Taylor Ricketts who
discovered spotted fever rickettsia and died of typhus fever during his
studies.
4. RICKETTSIA
• It is a heterogeneous group of
small obligatory intracellular gram
negative coccobacilli
• The organisms will not show up on Gram stain, but can be seen when
Giemsa stain is used
5. TAXONOMY
• The family rickettsiaceae is named after Howard Taylor Ricketts
• ORDER- RICKETTSIALES
• FAMILY- RICKETTSIACEAE
• TRIBE- RICKETTSIEAE
• GENUS- RICKETTSIA
• GENERA- ANAPLASMA
EHRLICHIA
ORIENTIA
NEORICKETTSIA
RICKETTSIA
WOLBACHIA
CANDIDATUS NEOEHRLICHIA
6.
7. Properties of Rickettsiae
MORPHOLOGY-
• Nonmotile noncapsulated
• Under electron microscope rickettsia are seen to have three layered
cell wall, a trilaminar plasma membrane and outer slime layer
8. CULTIVATION
• Unable to grow in cell free medium
• Grow best in cells which are not metabolizing
• Optimum temperature is 32-35degreeC
• Readily cultivated in yolk cells of developing chick embryos. Also grow on mouse
fibroblast, HeLa, Hep 2,detroit 6 and other continuous cell lines
• Tissue culture is not satisfactory for primary isolation
• Laboratory animals such as guinea pigs and mice are useful for isolation of
rickettsia from patients
9. RESISTANCE-
• Rickettsia are readily inactivated by physical and chemical agents. Rapidly
destroyed at 56degreeC and at room temperature when separated from
host components
• Susceptible to tetracycline, chloramphenicol and ciprofloxacin
• Penicillin and sulphonamides are ineffective
• Sulphonamides actually enhance the growth of rickettsia and worsen the
condition if administered to patients
10. • ANTIGENIC STRUCTURE
• Rickettsia have species and group specific antigens
• Spotted fever rickettsia have dominant outer membrane proteins OMP A
and OMP B
• OMP A- species specific acting as an adhesion for host cells
• OMP B- contain species specific epitopes
• ALKALI STABLE POLYSACHHARIDE – 3rd surface antigen found in some
rickettsia and in some strain of typhus rickettsia
• Sharing of antigen between rickettsia and proteus is the basis for diagnosis
of rickettsial infections by demonstration of agglutinins to proteus strains
OX 19, OX 2, and OX K
11. TRANSMISSION
• Bite of infected ticks and mites
• Contamination of the skin wounds with the feces of infected lice and
fleas.
• The rickettsia present in the dried excreta of insects may also enter
through the conjunctiva or even through inhalation.
• In ticks and mites transovarial and transstadial transmission of
rickettsia occurs
• Spread through the blood stream to infect vascular endothelium in
the skin ,brain, lungs, heart, kidneys, liver, gastrointestinal tract and
other organs.
14. These arthropods serve as both host and vector to the rickettsia and
reside on the reservoir animals (dogs, mice, rats, and flying squirrels)
• Characteristic of rickettsia is that mammals and arthropods are
natural hosts
• Transmitted to humans by arthropods
• No human to human transmission
15. Other route of spread
• Two of the rickettsial diseases are unique in that humans may
acquire them by direct inhalation
–Q fever (Coxiella burnetii)
–Epidemic typhus (Rickettsia prowazekii)
16. RICKETTSIAL DISAESES
• Disease caused by rickettsia and orientia species are collectively
referred to as rickettsiosis
• Classically divided into the typhus group and spotted fever group
• Orientia spp makes up the scrub typhus group
18. EPIDEMIOLOGY
• NORTH- Northern Japan and far
eastern Russia
• SOUTH- to northern Australia
• WEST- to Pakistan and
Afghanistan
• Infected vector live in jungle,
scrub and grassland
19. • Rickettsial diseases have been documented in India since 1930s
• Scrub typhus from kumaon region, Assam in soldiers of second world
war
• Scrub and murine typhus from Jabalpur in Madhya Pradesh
• Murine typhus from Kashmir
• Rickettsiosis of which scrub is the commonest reported from several
states in India
• Jammu and kashmir, Himachal pradesh, Uttaranchal, Bihar, West
Bengal, Meghalya, Rajsthan, Maharashtra, Karnataka,Tamil Nadu,and
Kerela
22. WHEN TO SUSPECT RICKETTSIAL DISEASE?
1.EPIDEMIOLOGIC
2.CLINICAL FEATURES
3.LABORATORY
23. Epidemiological clue-
• Exposure to ticks, fleas and mite
• Travel to or residence in an endemic geographic region
• Exposure to parturient ruminants, cats, dogs and flying squirrels
• H/O of previous louse borne typhus
24. Clinical features-
• Prolonged fever, malaise & headache
• Macular or maculopapular rash
• An eschar at site of tick or mite bite
26. LABORATORY-
1. specific investigation-
• SEROLOGICAL TESTS
• Weil Felix Test-
• After 5-7 day of onset of fever
• Titre of 1:80 is considered to be positive
• IgG/IgM ELISA Test:
• Highly specific test
• Ig M at the end of 1 week
• Ig G at the end of 2 week
• Immunoflourescence assay (IFA) test- Gold standard but costly and not
available
27. PCR-
• Rapid and specific test
• Detect Reckettsial DNA from the blood of febrile patients
Direct detection of organism and its antigen from tissue
28. 2. Supportive laboratory Investigations
• Total Leucocytes Count during early course of the disease may be normal but
later in the course of the disease WBC count may become elevated to more
than 11,000 / cu. mm.
• Thrombocytopenia with hemorrhage
• Raised Transaminase levels
• Increase acute phase reactants-- c-reactive protein, fibrinogen, ferritin
• Increase serum creatine kinase
• Hyponatremia
29. • X-ray of chest- infiltrates, mostly bilateral
X-r
)
30. CASE DEFINITION
• SUSPECTED CLINICAL CASE- acute undifferentiated febrile illness of
5 or more days with or without eschar should be suspected as a case
of rickettsial infection.
• If eschar is present fever of less than 5 days duration should be
considered as a case of scrub typhus.
• PROBABLE CASE- a suspected clinical case showing titres of 1:80 or
above in OX2,OX 19 and OX K antigens by weil felix test and an
optical density OD >0.5 for IgM by ELISA are considered positive for
typhus and spotted fever groups of rickettsiae.
31. • CONFIRMED CASE- in which:
• Rickettsial DNA is detected in eschar samples or whole blood by PCR
Or
• Rising antibody titers on acute and convalescent sera detected by
Indirect Immune Fluorescence Assay (IFA) or Indirect
Immunoperoxidase Assay (IPA)
32. SCRUB TYPHUS
• The term scrub is used because of the type of vegetation (terrain
between woods and clearings) that harbours the vector
• Highly endemic in Thiruvananthapuram, kashmir, himachal pradesh,
hilly areas, forest regions, rajasthan.
• Most of the Scrub typhus are regularly seen during the period
November to March.
33. • Causative agent is O.tsutsugamushi.
• Found in areas where they harbour the infected chiggers particularly
areas of heavy scrub vegetations.
34.
35. • Reservoir and vector: Trombiculid mite which feeds on small mammals.
• MODE OF TRANSMISSION:- By bite of infected larval mites. Infection
occurs during wet season when the mites lay their eggs. It is the larva
(chigger) that feeds on vertebrate hosts.
TRANSMISSION CYCLE-
MITE------RATS AND MICE-----MITE----RATS AND MICE
!
MAN
36. Clinical Features
Incubation period -6-21 days
Fever, headache, myalgia, cough and GIT symptoms.
ESCHAR – A punched out ulcer covered with a blackened scab
which indicates the location of the mite bite.
• Eschar is found only in around 50% of patients.
• Eschar is painless and patient was not report of it.
• Often the patient was not notice it because of its presence in concealed sites.
37.
38. Rashes-40% on days of 4-6 of illness
Lymphadenopathy and may be associated with splenomegaly
In severe case, encephalitis and interstitial pneumonia due to vascular
injury
39. SEROLOGICAL TESTS
Indirect Flourescent antibody test (IFA) test ( Titer ≥ 1: 200 ),
Complement Fixation Test.
Weil Felix Test
Scrub IgM ELISA Test: Highly specific test
PCR – Amplification of O. tsutsugamushi DNA from the blood of
febrile patients.
Direct detection of organism and its antigen from tissue
40. WEIL-FELIX TEST
• Heterophile antibody test
• Agglutination test in which sera are tested for agglutinins to the O
antigens of certain non motile Proteus strains OX19, OX2 and OXK.
• The basis of the test is the sharing of an Alkali stable carbohydrate
antigen by rickettsiae and by certain strains of Proteus.
• A 4 fold rise in agglutinin titres in paired titres is diagnostic.
41. • Sera from Epidemic and Endemic typhus agglutinate OX19 and
sometimes OX2.
• In tick borne spotted fever, both OX19 and OX2 are agglutinated.
• OXK agglutinins are found only in scrub typhus.
42.
43. • Negative
• Rickettsial pox,
• Trench fever, and
• Q fever.
False positive reaction –
1.urinary or other infections by Proteus
2. liver diseases and
3.Typhoid fever.
44. • Isaac, et al.(28) have demonstrated that the sensitivity of Weil-Felix
was 30% at a breakpoint titre of 1:80, but the specificity and positive
predictive value 100%.
• However, with a single serum sample available, the test is suggestive
of infection only at a high cut off titer (≥1: 320) at which the positive
predictive value and the specificity is reliable.
45. • Poor sensitivity but good correlation between the results of the WF
test and detection of IgM antibodies by an indirect
immunofluorescence assay (IFA) is often observed.
46. TREATMENT
• Tetracycline is the DOC.
• Doxycycline 100mg Bid PO ×7-15 days.
• Chloramphenicol 500mg qid PO×7-15 days.
• IV Chloramphenicol 150 mg/ kg per day a
• Azithromycine 500 mg for 3 days
47.
48.
49. ROCKY MOUNTAIN SPOTTED FEVER(RMSF)
• First recognized in 1896 in the Snake River Valley
of Idaho
• was originally called "black measles“
• Howard T. Ricketts established the identity
of the infectious organism that causes this disease,
Rickettsia rickettsii.
51. Pathogenesis
• R. rickettsii organisms are released through saliva during a feeding
• Usually 12-24 hrs of attachment is required
• It spread lymphohematogenously
• Once organisms enter the body, they multiply within endothelial cell linings of
small blood vessels
52. • Increase vascular permeability, with resulting edema,hypovolemia and ischemia
• Activation of platalets, generation of thrombin and of the fibrolyic symtem all
appear to be homeostatic physiologic
53. Clinical features
• Incubation period-1weeks(2-14 days)
1.Common symptoms- fever, headache, malaise, myalgia,anorexia and
vomiting
2. Rash- 14% cases on 1st day
49% on the 3rd day
• Blanching, erythematous macules arouond ankles feet, later wrists and hands; palms
and soles often involved
• Petechiae on day 6
54.
55. 3.Others-
• Hypovolemia leads to prerenal azotaemia and hypotension
• Cardiac involvement manifests dysthymias
• Renal failure with dehydration causes acute tubular necrosis
• Jaundice and hepatic failure
• CNS manifestations- confusion ,ataxia ,seizure ,coma and encephalopalitis.
• Myositis, and multiple rhabdomyonecrosis are rare
• Ocular – conjunctivitis, retinal vein thrombosis and haemorrhage
56. DIAGNOSIS
Suspect if classic triad
Acute and convalescent titers
Immunofluorescence assay
PCR
Isolation of R rickettsii from clinical specimen
57. Clinical triad-Fever, Rash and H/O of exposure of tick
Indirect immunofluorescence IgG assay-
• Most common serologic test for confirm diagnosis.
• Sensitivity 89-100% and specificity 99-100%
• Diagnostic titre of >64
• It can be negative at time presentation of ds
58. PCR- detection of R.rickettsii DNA in blood
Cutaneous biopsy -sample from a rash lesion. 3 mm punch biopsy from such
lesion is 70% sensitivity and 100% specific.
59.
60. Q FEVER
• Q fever was so named by Derrick in 1937 as ‘query fever’
• Coxiella burnetii is causative agent of Q fever
• Obligate intracellular, gram negative
and pleomorphic coccobaacillus
63. Clinical feature
• Incubation: 2-5 weeks
• One organism may cause disease
• Humans are dead-end hosts
• Usually show clinical signs of illness
• Disease
• Asymptomatic (50%)
• Acute
• Chronic
67. Diagnosis
• Serology (rise in titer)-most commonly used
• IFA-is sensitive and specific and method of choice
• CF, ELISA, microagglutination
• Chronic infection,phase I is higher than phase II antigen and anti-
phase I IgG titre of >6400
• DNA detection methods
• PCR
• Isolation of organism
• Buffy-coat blood sample or tissue
69. Treatment
• Acute Q fever-
• Doxycycline 100mg BD for 14 days
• Trimethoprim-sulfamethoxazone in pregnancy
• Chronic Q fever
• Doxycycline 100mg BD and hydroxychloroquine 200 mg TDS for 18 days
• Doxycycline 100mg BD + Rifampin 300 mg or ciprofloxacin 750 mg once daily
70. Q Fever as a Biological Weapon
• Accessibility
• Low infectious dose
• Stable in the environment
• Aerosol transmission
• WHO estimate
• 5 kg agent released on 5 million persons
• 125,000 ill - 150 deaths
• Could travel downwind for over 20 km
71. Mediterranean spotted fever
• Regional name for the disease caused by organism-
• Boutonneuse fever
• African tick-bite fever
• Indian tick bite
• Kenya tick fever
• Causative agents-
• Mediterranean spotted fever-R.conorii
• African tick-bite fever-R.African
72. • Vector- brown dog tick
• Incubation period-4-10 days
• Clinical feature
• Fever
• Rash-vesicular, sparse or absent altogether
• Esher lesion at site the tick bite
• Painful regional lymphadenopathy
73. Rickettsial Pox
• Also called as vesicular ricketsiosis
• Mildest Rickettsial disease to human
• Self limited, nonfatal
• Causative agents- R.akari
• Vector-Mite
• Reservoir of infection- mice
74. • Clinical feature-
• Incubation period-10-17 days
• Faver, headahe,and malaise
• Nause, abdominal pain
• Eschar lesion
• Enlarged of the regional lymph node
• Macular rash
• 2-6 days
• into papules,vesicles, and crust
75. EPIDEMIC TYPHUS
• Typhus’is derived from tyfos, the ancient Greek word for ‘fever with stupor’ or
cognate with the Sanskrit word for ‘smoke’, dhupa.
• Epidemic typhus
(camp fever/ jail fever/ hospital fever/ ship feve/famine fever/epidemic louse-
borne typhus and "louse-borne typhus")
• is a form of typhus so named because the disease often
causes epidemics following wars and natural disasters.
77. Transmission
• Human body louse
• Pediculus humanus corporis
• Infective for 2-3 days
• Infection acquired by feeding on infected person
• Lice die within 2 weeks
78. Clinical feature
• 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
• Skin necrosis and interstitial pneumonia in severe case
79. Brill-Zinsser Disease(relapsing louse-borne typhus)
occurs as recrudescence of previous infection with Rickettsia
prowazekii.
• Person previously affected or lived in endemic area
• Viable retained organisms reactivated
• Milder symptoms
• Febrile phase 7-10 days
• Rash often absent
• Low mortality rate
81. NEW OR EMERGING RICKETTSIAL DISEASES
TIBOLA (TICK BORNE LYMPHADENOPATHY)-
• was first described in 1997 in France.
• The causative agent, Rickettsia slovaca,
• transmitted by Dermacentor ticks.
• In Spain, similar case called as DEBONEL.
DEBONEL ( DERMACENTOR-BORNE-NECROSIS-ESCHAR-
LYMPHADENOPATHY)
Related to Rickettsia slovaca and R.sibricia.
82.
83. • CLINCAL FEATURES
• Fever, malaise & headache
• At the site of the tick bite an
eschar with oedematous margins
• Painful lymph node in the region
of tick bite, characterically in the
region of occipital and behind of
SCM muscle
• Doxycycline (100 mg twice daily
for adults)-DOC
85. TRIAD OF - Fever, Headache And
Myalgia
with rash-
• Rubeola
• Rubella
• Meningococcemia
• Toxic shock syndrome
• Drug hypersensitivity
• Secondary syphilis
• IIP
• Disseminated gonococcal infection
without rash-
• Influenza,
• Infectious Mononucleosis,
• Enteroviral Infection.
• Viral Hepatitis,
• Leptospirosis,
• Typhoid Fever,
• Gram Neg And Positive Bacterial
Sepsis,
86. Differentiating Amongs Rickettsial Diseases
Rocky Mountain spotted fever (RMSF): The rash usually appears
on about the 4th febrile day as blanching macules on wrists,ankles the
extremities and gradually becomes petechial as it spreads to the trunk,
palms, and soles over several days.
87. Scrub typhus: Manifestations are similar to those of RMSF and
epidemic typhus. However, scrub typhus occurs in different
geographic areas, and frequently, an eschar develops with satellite
adenopathy.
88. Rickettsialpox: This disease is mild, and the rash, in the form of
vesicles with surrounding erythema, is sparse and may resemble
varicella.
Epidemic typhus: The rash usually appears initially in the axillary
folds and on the trunk. Later, it spreads peripherally, rarely involving
the palms, soles, and face.
Murine typhus: The rash is nonpurpuric, nonconfluent, and less
extensive.
89. TAKE TO HOME MASSAGE
• Rickettsial infections are prevalent in various parts of India.
•Fever, rash, headache, myalgia, lymphadenopathy and eschar are
various clinical features of these infections.
• Pts usually present with prolonged fever and rash
• History of exposure to vector are crucial for diagnosis.
•Therapy is easy and affordable with dramatic results and needs to be
started on clinical suspicion, as there is no specific test for early
diagnosis.
• Doxycycline is the drug of choice
90. • DHR-ICMR -GUIDELINES FOR DIAGNOSIS AND MANAGEMENT OF
RICKETTSIAL DISEASES IN INDIA
• Harrison `s Principle of Internal Medicine 19e
• Rickettsial Diseases- JAPI .july 2012 • VOL. 60
91.
92. Meningococcemia:
• Rash- develops rapidly, pink, macular, maculopapular, or petechial
• petechially confluent or ecchymotic
• ecchymotic tender when palpated.
93. Rubeola: The rash begins on the face, spreads to the
trunk and arms, and soon becomes confluent.
• Rubella: The rash usually remains discrete.
Post auricular lymph node enlargement
and lack of toxicity
