Rickettsial diseases are infectious illnesses caused by bacteria called Rickettsia. These bacteria are transmitted to humans through bites from infected arthropod vectors, such as ticks, fleas, and lice. Common symptoms include fever, headache, muscle aches, rash, and fatigue. Prompt diagnosis and treatment with antibiotics are crucial for managing these diseases. Prevention involves avoiding contact with the vectors and practicing good hygiene. Rickettsial diseases can vary in severity, with some cases being potentially life-threatening if left untreated.

1. Rickettsial Diseases
in India
Dr. S Kunal Tejus
Pediatric Resident

2. 1. Gram negative coccobacilli
2. Obligate intracellular.
3. Transmitted by arthropods except Coxiella.
4. Parasitize endothelial cells.
5. All form basophilic inclusion bodies.

3. Epidemiology
1. Scrub typhus is the most prevalent and
endemic in India. India is part of
Tsutsugamushi Triangle.
2. Indian tick typhus.
3. Murine endemic typhus.

4. Etoiology
Feature Indian tick typhus Scrub typhus Murine endemic typhus
Causative organism Rickettsia conorii Orientia tsutsugamushi Rickettsia typhi
Vector Hard tick
(Ixodes)
Trombiculid mite/ chiggers Rat flea
(Xenopsylla)
Mamalian host/
reservior
Dogs/ rodents
Man
Rodents
Man (accidental)
Rodents
Man (accidental)
Epidemiological
risk
Endemic in Maharashtra, Karnataka,
Tamil Nadu, Telengana and Kerala.
Woodlands, Large domestic animals in
vicinity
Endemic in India (Tsutsugamushi
Triangle)
Any terrain from sea levels to
himalayan foot hills Woods and
clearings
Warm and coastal parts of India.

5. Rash morphology >90% appearance on 3–4days. Begins
as faint macule and becomes petechial,
later to purpura. First appears on
extremities and spread centrally.
Involves palm and soles
40–50% appearance on day4–5.
Macular/maculopapular. Rarely
petechial. Starts on trunk and
spreads to peripheries.
<15% appearance. As macule and becomes
petechial on trunks, extremities, soles and palms
Eschar 3–5%(uncommon) 5–80%(pathognomonic)
Needs to be actively searched for
Uncommon
Other significant
findings
Gangrene of digits/earlobes leading to
autoamputation
GI symptoms (diarrhea/ abdominal
pain)
Peripheral edema & calf muscle
tenderness.
Regional lmphadenopathy
CNS involvement
(Typhus=clouding of sensorium)
Sensorineural hearing loss
CNS involvement (milder)
(Typhus=clouding of sensorium)

6. Entomology
Hard tick
• presence of scutum
• marginal grooves
Flea
• small, wingless insects
• characteristic jumping movement
Chiggers
• compact, microscopic, circular
with no differentiation body

7. Pathogenesis
Eschar ulcer
microvascular
leakage
petechial rash.
tissue infarction or
hemorrhagic necrosis.

8. Clinical Manifestations
Incubation period is 1 to 2 weeks.
Triad of fever, headache and rashes.
Fever:
• Fever of unknown origin.
• Abrupt onset, high grade with chills.
• Diagnosis considered in patients with acute febrile illness with headache and
myalgia, in endemic areas with history of tick exposure or contact with dogs.
• Scrub typhus (62.8%), Indian tick typhus spotted fever (32.6%) and endemic
typhus fever (4.7%).
Headache and Myalgia:
• Severe frontal headache and generalised myalgia (in muscles of the lumber
region, thigh and calf)

9. Rash:
• hallmark of Spotted fever.
• evolving (initially macular, becoming maculopapular,
petechial, purpuric or gangrenous)
• centripetal spread
• involve palms and soles.
i. in scrub typhus, uncommon than Spotted fever (30
to 43% cases).
ii. in endemic typhus, atypical, initially appears on
trunk, spread centrifugally and sparing palms and
soles.
petechial rashes
purpuric rashes

10. Eschar:
• pathagnomonic to Scrub typhus (7-97%).
• crusty necrotic lesion with or without surrounding erythematous halo
• At the location of the vector bite.
• painless, nonpruritic and about 1 cm in diameter.
• usually single, like ‘skin burn of cigarette butt’.
• associated with regional painful lymphadenopathy, it is a marker of hidden or
developing eschar.

11. Systemic presentations:
i. Consider Rickettsia in aseptic meningitis or meningoencephalitis with
epidemiological history.
ii. Cough associated with pulmonary infiltrates or pneumonias, recommended
to add empiric treatment in addition to management of pneumonia, in
endemic regions.
iii. Gastrointestinal and hepatic presentation in the form of nausea, vomiting,
diarrhea, abdominal pain, Hepatosplenomegaly and hepatitis.
iv. Acute renal failure (ARF), as bad prognosis. Suspect in fever presents with
varying degrees of renal insufficiency, particularly if eschar exists.

12. Severe complications:
• Fulminant course seen particularly with spotted fever group in patients with
glucose-6-phosphate dehydrogenase (G6PD) deficiency.
i. Noncardiogenic pulmonary edema secondary to pulmonary microvascular
leakage.
ii. Meningoencephalitic syndrome and Long-term neurologic sequelae in
children who have survived severe disease.
iii. Acute renal failure is associated with bad prognosis
iv. Disseminated intravascular coagulation like syndrome and gangrene.

13. Investigations
Suggestive Laboratory Features For Rickettsial Infections
• Normal to low total leukocyte count in early stages and leukocytosis in
severe.
• Thrombocytopenia
• Raised ESR and CRP
• Hyponatremia
• Hypoalbuminemia and
• Elevated hepatic transaminases (SGPT)

14. Scoring system
Total score of 35, Cut-off set at 14
with sensitivity of 96% and specificity of 99%
Rathi - Goodman - Aghai Scoring System

15. Geisma/ castaneda stain Demonstrate basophilic inclusion bodies inside endothelial cells.
Cultivation Using laboratory animals (guinea pig, known as Neil Mooser
reaction). Intraperitoneal inoculation of patients blood into
guinea pigs leads to scrotal inflammation (enlarged with
adhesions and testes cannot be pushed back into abdomen).
Spotted fever: Scrotal necrosis.
Others: Scrotal swelling
Serology test Four fold rise in two serum samples, 2–4 weeks apart.
Weil-Felix: Single titer > 1:80 suggest possible infection.
Immunoglobulin M (IgM) enzyme-linked immuno sorbent assay
(ELISA)- high sensitivity and high specificity.
Immunofluorescence antibody (IFA)- gold standard.

16. Polymerase chain reaction
(PCR)
In first week of diagnosis
Done on whole blood, eschar or skin biopsy and eschar
scrapings.
Immunoperoxidase assay (IPA) Not routinely available
Imaging Chest X-ray shows infiltrates, mostly bilateral.
Nonspecific “starry sky” appearance on brain MRI.
“starry sky” appearance on brain MRI.

17. WEIL-FELIX REACTION
Heterophile agglutination test.
Principle: Based on cross-reactions occur between antibodies produced in acute rickettsial infections
with antigens of OX (OX 19, OX 2, and OXK) strains of Proteus species.
Procedure: Done as either a slide or a tube test. Antigens necessary (OX2, OX19, and OXK) can be
obtained commercially.
i. Slide method- 50–100µl of patient serum on the slide, Add a drop of desired antigen (Proteus
OX19 or OX2 or OXK), Mix the suspension by rotating the slide for 1 minutes, Visible
agglutination indicates the positive test.
ii. Tube method- Using 0.25% phenol saline as a diluent, series of tubes containing two fold
dilutions of patient serum are made with a final volume of 1 mL. A drop of antigen suspension is
added to each tube, and the mixture is incubated at 50–55 °C for 4–6 hours. A positive tube would
show visible flocculation or granulation. Generally, a titer of ≥1:320 is considered diagnostic

18. RICKETTSIAL DISEASE OX- 19
P. VULGARIS
OX- 2
P. VULGARIS
OX- K
P. MIRABILIS
1. EPIDEMIC TYPHUS +++ + -
2. BRILL ZINSSER - - -
3. ENDEMIC TYPHUS +++ +/- -
4. SPOTTED FEVER
EXCEPT
RICKETTSIALPOX
++ ++ -
5. SCRUB TYPHUS - - +++

19. Limitation of Weil-Felix test: Poor sensitivity and specificity (overall sensitivity
as low as 33% and specificity of 46%)
i. Low sensitivity, i.e. it gives a high percentage of false-negative results,
common in scrub typhus.
ii. Low specificity, i.e. false-positive results are obtained in other diseases such
as leptospirosis, UTI, Proteus infections, brucellosis, and acute febrile
illness.

20. Case Definitions
1 Suspected/
clinical case
• Acute undifferentiated febrile illness of 5 days or more and compatible with
Boxes 1 and 2; in the absence of alternate diagnosis.
2 Probable case • Suspected case with/without eschar or having rapid (<48hours) defervescence
with anti-rickettsial therapy
• Or Having Weil Felix test positive with titer of 1:80 or more
• Or Positive IgM ELISA for rickettsia
3 Confirmed case • Rickettsial DNA is detected in eschar sample or whole blood by PCR
• Or Four fold rise in antibody titers on acute and convalescent sera by IFA or IPA

21. BOX 1
Compatible Clinical Scenario for Rickettsial Infection
One or more of the following:
1. Undifferentiated fever of more
than 5 days.
2. Sepsis of unclear etiology.
3. Fever with rash.
4. Fever with edema.
5. Dengue-like disease.
6. Fever with headache and myalgia.
7. Fever with hepatosplenomegaly
and / or lymphadenopathy.
8. Aseptic meningitis /
meningoencephalitis / acute
encephalitic syndrome.
9. Fever with cough and pulmonary
infiltrates or community acquired
pneumonia.
10. Fever with acute kidney injury.
11. Fever with acute gastrointestinal
or
hepatic involvement.

22. BOX 2
Suggestive Epidemiological Features for Rickettsial Infections
One or more of the following within 14 days of
illness onset:
• Tick bite.
• Ticks seen on clothes or in and around homes.
• Visit to areas which are common habitats of
vectors (where rodents share habitats with
animals).
• Animal sheds in proximity of homes.
• Exposure to rodents.
• Contact with pet or stray dog infested
with ticks.
• Living in or travel to areas endemic for
rickettsial diseases.
• Occurrence of similar clinical cases
simultaneously or sequentially in family
members, coworkers, neighbourhood or
pets.

24. Diagnosis
• No rapid laboratory tests are available to diagnose early in the course of
disease.
• Only crucial factor for early diagnosis is high index of suspicion.
• Following factors taken together for diagnosis, which can then be confirmed
with serology.
1. Compatible clinical presentations.
2. Tick bite or tick exposure.
3. Epidemiological data.
4. Suggestive laboratory features.
5. Rapid defervescence with appropriate antibiotics.

25. Treatment
• Start empiric treatment without waiting for laboratory confirmation. Do not
stop treatment on basis of negative test results.
• Doxycycline is the drug of choice: Oral or intravenous. Dose: <40 kg- 2.2-4
mg/kg twice daily, >40 kg- 100 mg twice daily.
• Therapy should be continued for a minimum of 5-7 days and until the patient
has been afebrile for at least 3 days.
• If fever do not subside in 48 hours, consider alternate diagnosis or
doxycycline resistant strains

26. Sr.No Name of drug Dose, route and duration Comments
1. Doxycycline 4 mg/kg/dose BD per oral or
IV(maximum200mg)
5–7days or for atleast 3 days until
the patient is afebrile
Drug of choice
Rapid defervesce within 48hours
IV formulation for sick patients
2. Tetracycline 25–50mg/kg/dose every 6hourly
per oral (maximum 2g/ day)
Rapid defervesce within 48hours
IV formulation for sick patients
3. Chloramphenicol 50–100mg/kg/day every 6hourly
(maximum3g/day)
Most common adverse effect is
agranulocytosis
4. Azithromycin 10mg/kg/dayoncedaily
(maximum 500mg)
Preferred drug in pregnancy
Recommended when doxycycline
resistance
5. Clarithromycin 15mg/kg/dayBD Doxycycline resistance.

27. Differential Diagnosis
Rickettsial diseases can be easily confused with a variety of
• Viral (measles, enteroviral exanthems, dengue, infectious mononucleosis),
• Protozoal (malaria),
• Bacterial (meningococcemia, typhoid, leptospirosis, toxic shock syndrome,
scarlet fever),
• Collagen vascular (Kawasaki disease, other vasculitis) diseases,
• Adverse drug reactions,
• Invasive meningococcal disease.

28. Poor Prognostic Factors
• Child with G6PD deficiency,
• Sulfanamide therapy.
• Younger age,
• Shorter incubation period,
• Absence of rash,
• Diabetes mellitus,
• Delayed initiation of anti-rickettsial drugs.

29. Prevention
Vaccine and post-exposure prophylaxis is not available for clinical use.
Vector control: controlling rodents and cutting, burning and bulldozing vegetations
with heavy spraying of insecticides such as lindane.
Preventing vector bite: most effective strategy.
• Avoid exposure to vector infested habitats. Regular tick checks should be performed
after spending time with tick infested animals or in tick infested habitats.
• Closed toe shoes and light coloured (for tick visibility) long pants and long sleeves
cloths with shirt tucked into pants and pants tucked into socks or boots.
• Permethrin based (on cloths) and 20-50% DEET (N, N-diethyl-m-toluamide) based
(on skin) insect repellants.
• Hot water washing and hot drying effectively kills ticks on cloths.
• Pets should be protected with medications or tick collars and periodic de-ticking.

30. Prompt removal of attached ticks:
• Ticks need minimum 4-6 hours of attachment before they transmit infection.
• Bathing soon after exposure is effective.
• proper technique of tick removal using tweezers, grasp ticks head as close to skin surface as
possible and gently pull upwards with constant pressure.
• Attachment area should be immediately cleaned with soap and water or alcohol or an iodine
scrub.
• Ticks should neither be removed nor be crushed with bare fingers.
• Gasoline, nail polish, kerosene, petroleum jelly or lit matchsticks should not be used.
• Incineration of ticks after removal, rather than flushing down the sewer system is
recommended.
Pre-exposure chemoprophylaxis: Weekly doxycycline started before and for 6 weeks after
exposure is recommended.

31. Future Prospects
Research and development should focus on
1. Vaccines for rickettsial diseases
2. Rapid diagnostic card test combining antigen and antibody
3. Robust surveillance and reporting system.

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