Rickettsial diseases are caused by intracellular bacteria that are transmitted through arthropod vectors like ticks, mites and fleas. There are over 20 rickettsial pathogens that cause diseases in humans. Diagnosis can be difficult as symptoms are often non-specific. New genetic tools have led to the discovery of many new rickettsial diseases in the past 20 years. Prevention involves avoiding areas with infected vectors and using personal protective measures like insect repellents and protective clothing.

1. Rickettsial Diseases
Amita Kashyap

2. Rickettsial Diseases
 Emerging or re – emerging pathogens in
many places of the world
 Definitive diagnosis is difficult hence
occurrence often goes unrecognized
 New genetic tools – lead to discovery of
many new rickettsial diseases over the
past 20 years.
 Of the 14 currently recognized
rickettsioses, six have been described
within the last15 years

3. Rickettsial Diseases
 Require living cells for growth, yet are true
bacteria as they have metabolic enzymes and
cell walls, and are susceptible to antibiotics.
 Mammalian reservoirs and invertebrate
vactors (ticks, mites, fleas, and lice).
 Some invertebrate vectors can also serve as
reservoirs.
 Humans are usually accidental hosts and
play little role in natural disease
transmission.
 Four Groups:
◦ 1) Spotted fever group; 2) Typhus group; 3) Scrub

4. Global :
 The geographic as well as temporal
distribution is largely determined by their
vectors.
 Louse borne rickettsial diseases are
reported from across the world.
 Common flea species like the dog, cat,
and rat flea are also global in distribution.
 Ticks are more restricted in their
distribution. Tick borne diseases are,
therefore, more localized in their

5. India :
 Large number of documented outbreaks
of rickettsial diseases, particularly Scrub
typhus among Indian Armed Forces
personnel from different parts of the
country
 Occurrence of Rickettsioses, including
scrub typhus as well as spotted fevers
have been reported from H. P.,
Maharashtra, Assam, West Bengal,
Kerala and Tamil Nadu

6. Epidemiologic Features of Rickettsial
Dis. Diseases
Dis. Agent Vector Animal Geographical
Group Reservoir Distribution
Typhu Epide Rickett Human Humans Mountainous
s mic sia body louse regions of Africa,
Group typhu prowaz Asia, and Central
s ekii and South America.
India - J&K,
Himachal,
Uttarakhand,
W Bengal,
Arunachal Pradesh.
Murin Rickett Rat flea Rats, Worldwide
e sia (Xenopsylla mice
typhu typhi cheopis)
s
Indian Rickett Tick (Ixodes Dogs, Africa, India,
Tick sia sp Boophilus rodents Europe, East,
Typhu conorii sp Mediterranean, India
s Haemophysal - Uttaranchal

7. Epidemiologic Features of Rickettsial
Dis. Diseases Agent
Dis. Vector Animal Geographical
Group Reserv Distribution
oir
Spotted Rickettsia Rickettsi Mite House Russia, South
Fever l a mite Africa, Korea,
Group pox akari Turkey, Balkan
countries
Rocky Rickettsia Tick Rodent Mexico, Central and
Mountain rickettsii s South America
S. Fever
Orientia Scrub Orientia Mite (L Asia and Australia
typhus tsutsugam deliense) India - J&K,
ushi Himachal,
Uttarakhand,
W Bengal,
Arunachal Pradesh
Others Q fever Coxiella Inhalation Goats, Worldwide
burnetii of infectious sheep,
aerosols; cattle,
tick cats

8. Agent
 Rickettsiae are a diverse collection
of organisms with several
differences.
 The common threads that hold the
rickettsiae into a group are their
epidemiology and being obligate
intracellular
 Rickettsia are small (0.3 X 2 μm)
aerobic, obligate intracellular

9. Agent continued…
 Theorder Rickettsiales has two
families
◦ Rickettsiacese – has two genera :
 Rickettsia and Orientia.
◦ Anaplasmataceae - has five
genera.
 At least 26 agents from the order
Rickettsiales have been recognized
as human pathogens.
 Host : Travellers, wood cutters,

10. Transmission
 Transmission: by the
◦ bite of infected ticks and mites and
◦ contamination of the bite or other skin wounds with
the faeces of infected lice and fleas.
◦ The rickettsiae present in the dried excreta of
insects may also enter through the conjunctivae or
even through inhalation.
 In ticks and mites transovarial and trans -
stadial transmission of rickettsia frequently
occurs.
 Spread through the bloodstream to infect
vascular endothelium in the skin, brain,
lungs, heart, kidneys, liver,
gastrointestinal tract and other organs.

11. Clinical Features and Treatment of Rickettsial
Disease Diseases Clinical Features
IP Weil Felix Treatment
Reaction
Epidemic 6-15 Headache, chills, fever, OX - 19 Doxycycline
typhus Days prostration, 100mg BD for
confusion, photophobia, 7 – 10 days or
vomiting, till person is
rash (generally starting afebrile.
on trunk) Pregnant
women-
Chlorampheni
col 60 - 75mg/
kg/day in 4
divided doses
Murine 8-16 As above, generally less OX - 19 As above
typhus Days severe
Indian Tick 5 - 10 Fever, eschar, regional OX - 19 Same as
Typhus days adenopathy, Or OX - 2 above
maculopapular rash on Alternative -
extremities Ciprofloxacin

12. Clinical Features and Treatment of Rickettsial
Disease Diseases Clinical Features
IP Weil Felix Treatment
Reaction
Rocky 2-14 Headache, fever, OX – 19 Same as
Mountain Days abdominal pain, macular Or OX - 2 above
spotted rash progressing into
fever opular or petechial
(starting on extremities)
Scrub 6-21 Fever, headache, OX - K Doxycycline
typhus Days sweating, 100mg BD.
conjunctival injection, Rifampicin 600 -
adenopathy, 900mg/day,
eschar, rash, respiratory Azithromycin and
distress Ciprofloxacin
are other
alternatives
Q fever 3 - 30 Fever, headache, chills, None Doxycycline.
days sweating, Rifampicin,
pneumonia, hepatitis, Ciprofloxacin
endocarditis as other

13. Diagnosis
 Serology Titres of specific antibodies rise
to diagnostic levels usually by the second
week of illness.
 Indirect Fluorescent Antibody (IFA) and
ELISA tests are available for serology.
 The Weil – Felix test, which uses the OX
and K strains of Proteus vulgaris and P.
mirabilis, respectively is still the most
widely used diagnostic test in India. (not
very sensitive/ specific )
 PCR is also being increasingly used to
confirm the diagnosis

14. Prevention and Control
 The essential method of prevention is
avoidance of potentially vector infected
areas and
 Use of personal protective measures.
 Use of insect repellents such as DEET
(N,N-Diethyl-meta-toluamide) in
combination with appropriate clothing
such as long sleeves and anklets may
be useful in avoiding contact with
vectors.

15. Scrub Typhus: A dreaded disease of pre-
antibiotic era
 An acute, febrile, infectious illness, caused by
Orientia tsutsugamushi (zoonotic disease)
 First described from Japan in 1899.
 Humans are accidental hosts
 Disease of Military importance- 36,000 soldiers were
either incapacitated or died during World War II
 The first known vaccine actually used to
inoculate human subjects was dispatched to
India by the Allied Land Forces, South-East
Asia Command, in June 1945
 Scrub typhus is essentially an occupational
disease among rural residents in the Asia-
Pacific region.

16. World/ Asia
 Endemic to a part of the world known as
the “tsutsugamushi triangle”, which extends
from northern Japan and far-eastern
Russia in the north, to northern Australia in
the south, and to Pakistan in the west
 An estimated one billion people are at risk
for scrub typhus and
 An estimated one million cases occur
annually.
 Mortality rates in untreated patients range
from 0-30%.

17. Epidemiology • North: northern
Japan and far-
eastern Russia
• South: to
northern
Australia
• West: to
Pakistan and
Afghanistan
Infected vector live
in jungle, scrub
& grassland

18. The vector is present in most countries of the SEA
Endemic in certain geographical regions of India,
Indonesia, Maldives, Myanmar, Nepal, Sri Lanka and Thai
Scrub typhus-affected countries of Asia

19. India
 Scrub typhus is a reemerging infectious
disease in India
 Prevalent in many parts of India but lack
specific data
 Outbreaks reported from areas located in
the sub-Himalayan belt, from Jammu to
Nagaland.
 Himachal Pradesh, Sikkim and Darjeeling
(West Bengal) during 2003-2004 and
2007.
 From southern India during the cooler

20. India
 S/S are often non-specific (Fever, Eschar,
Regional lyphadenopathy, Maculopapule
rash, leukopenia).
 The non-specific presentation and lack of
the characteristic eschar in 40% patients
makes the misdiagnosis and
underreporting
 Non availability of diagnostic facilities leads
to lack of precise incidence of the disease
 An estimated one billion people are at risk
for scrub typhus and
 An estimated one million cases occur
annually.

21. The characteristic feature of
an outbreak of scrub typhus:
(i) the obvious association with certain
types of terrain;
(ii) the large percentage of susceptible
people, who may be infected
simultaneously following exposure
over relatively short periods;
(iii) the absence of a history of bites or
attack by arthropods

22. Agent
It is an obligate
intracellular gram-ve
bacterium that has a large
number of serotypes.
Does not have a vacuolar
membrane; thus, it grows
Orientia - freely in the cytoplasm of
tsutsugamushi under
microscope infected cells.
[Courtesy: Department
of Entomology, Armed O. tsutsugamushi has a
Forces Research different cellwall structure
Institute of Medical
Sciences (AFRIMS)] and genetic composition
than that of the rickettsiae.

23. Agent
 The mite is very small (0.2 – 0.4mm) and
can only be seen through a microscope or
magnifying glass.
 O. tsutsugamushi includes heterogeneous
strains classified in five major serotypes:
Boryon, Gilliam, Karp, Kato and
Kawazaki.
 Differentiation of serotypes is important for
laboratory diagnosis. Orientia
tsutsugamushi can be cultivated on L929

24. Disease transmission
Transmitted to humans and
rodents by the bite of infected
larvae of the trombiculid mite
Leptotrombidium deliense
(“chiggers”), which feeds on lymph
and tissue fluid rather than blood.
The bite of the mite leaves a
characteristic black eschar that is
useful to the doctor for making the
diagnosis.

26. Mode of Transmission

Rats & Mice
Mite
Mite
 Humans
(Accidental host
No direct person to person transmission
Mite Islands

27. Transmission
 The adult mites have a four-stage:
◦ egg, larva, nymph and adult.
 The larva is the only stage (chigger)
that can transmit the disease to
humans and other vertebrates
 Chigger mites act as the primary
reservoirs for O.tsutsugamushi
 They get infected by feeding on the
body fluid of small mammals,
including the rodents (rattus),

28. Transmission
 They maintain the infection
throughout their life stages and has
transovarial transmission.
 The infection passes from the egg to
the larva or adult - transtadial
transmission.
 Thus, chigger mite populations
can autonomously maintain their
infectivity over long periods of
time.

29. Earlier it was thought
that rodents were the
natural reservoir of
infection, but it is now
believed that mites
are both the vector
and the reservoir
Chigger mites fed on the
inner’s
ear lobe of wild-caught rat
This mite is fastidious in matters of
temperature, humidity and food,

30. Clinical Presentation
 The I.P.- 5 to 20 days (mean, 10-12
days)
 The chigger bite is painless or as a
transient localized itch.
 Bites are often found on the groin,
axillae, genetalia or neck.
 The illness begins rather suddenly with
shaking chills, fever, severe headache,
infection of the mucous membrane lining
the eyes (the conjunctiva), and swelling
of the lymph nodes.
 A spotted rash on the trunk may be

31. Clinical Presentation
 Eschars are rare in patients in countries of
South-East Asia
 Indigenous persons of typhus-endemic
areas commonly have less severe illness,
often without rash or eschar
 Whether this is due to past exposure to the
organism, or to other factors, is unknown.
 Symptoms may include muscle and
gastrointestinal pains.
 More virulent strains of O. tsutsugamushi can
cause haemorrhaging and intravascular

32. Clinical Presentation
 Complications may include atypical
pneumonia, overwhelming pneumonia
with adult respiratory distress syndrome
(ARDS)–like presentation, myocarditis,
and disseminated intravascular
coagulation (DIC).
 Often exhibit leucopenia.
 Acute scrub typhus appears to improve
viral loads in patients with HIV. (This
interaction is currently unexplained).

33. Specifc features
Maculopapular rashes
Onset: Appear at the end
of the 1st week, lasts
3~7days.
Location: Chest,
abdomen, whole trunk,
or upper and lower
limbs. rarely involves
the face, palms and
soles. .

34. Specifc features
Regional lymphadenopathy:
occur at the end of the 1st week.
localize: the draining lymph node around the
primary eschar
characterized by tenderness and enlargement
Generalized lymphadenopathy: appears 2-3
days later.

35. Differential Diagnosis
 Serology -
◦ Weil-Felix test,- Cheapest and most easily
available, 50% of patients have a +ve test
result during the second week.
◦ Complement-fixation test
 Each patient’s serum is systematically tested
against five O. tsutsugamushi serotypes. ( An
IgM titer > 1:32 and/or a four-fold increase
of titers between two sera confirm a recent
infection).
 However, due to cross-reactions among
serotypes, it is difficult to identify accurately a

36. Differential Diagnosis
 The gold standard is indirect
immunofluorescence antibody (IFA).
 Indirect immunoperoxidase (IIP) is a
modification of the standard IFA method that
can be used with a light microscope, results
are comparable to IFA.
 Commercial rapid diagnostic kits provide
reliable and well-accepted preliminary results
within one hour, but the availability of these
tests is severely limited by their cost.
 ELISA provides more sensitivity and equal
specificity when compared to commercial test

37. Differential Diagnosis
 The organism can be grown in tissue
culture or mice from the blood of
patients but results are not available in
time to guide clinical management.
 Molecular detection using polymerase
chain reaction (PCR) is possible from
◦ Skin rash biopsies, L. N. biopsies or
Ethylene Diamine Tetra Acetic acid (EDTA)
blood.
 Realtime PCR assays are as sensitive
as standard PCR but are more rapid

38. Specimen for laboratory and
Dispatch
 Depends on diagnostic method to be
used. And are preserved and shipped as
follows:
◦ Skin or lymph node biopsy
 If frozen at - 80°C after sampling, ship
in dry ice for culture.
 At room temperature for PCR.
 If formalin-treated or paraffin-
embedded, ship at room temperature
for immunohistochemistry.

39. Continued…
Heparinized blood
• Conserve at -80°C and then ship in
dry ice for culture.
EDTA blood
• Conserve at +4°C and then ship at
room temperature for PCR.
Serum
• Conserve at +4°C, then ship at
room temperature. Collect two
serum specimens 10 days apart.

40. Treatment
 Antibiotic therapy brings Rapid
defervescence- doxycycline,/
chloramphenicol
 Doxycycline and rifampicin combination-
where there is poor response to doxycycline
 Azithromycin or chloramphenicol -In
children or pregnant women
 Relapses if the antibiotic treatment is
discontinued too quickly, especially in patients
treated within the first few days
 No significant morbidity or mortality
occurs in patients who receive appropriate

41. Prophylactic treatment
 Single oral dose of chloramphenicol or
tetracycline given every five days for a
total of 35 days, with 5-day non-
treatment intervals, actually
produces active immunity to scrub
typhus.
 This procedure is recommended
under special circumstances in certain
areas where the disease is endemic.

42. Vaccine against scrub typhus?
 There is enormous antigenic variation
in Orientia tsutsugamushi strains, and
immunity to one strain does not confer
immunity to another
 A vaccine developed for one locality
may not be protective in another
locality, because of antigenic variation.
 This complexity continues to hamper
efforts to produce a viable vaccine

43. Precautions to
protect you from scrub
typhus?
 Protective clothing.
 Insect repellents containing dibutyl
phthalate, benzyl benzoate, diethyl
toluamide,etc applied to the skin and
clothing to prevent chigger bites.
 Do not sit or lie on bare ground or grass
 Clearing of vegetation and chemical
treatment of the soil may help to break
up the cycle of transmission from
chiggers to humans to other chiggers.

44. Control strategy
 Case identification - early diagnosis of
acute scrub typhus can greatly reduce
the chance of life-threatening
complications
 Public education -Advocacy, awareness
and education activities should be
targeted at schoolchildren, teachers and
women groups in endemic areas
involving community-based
organizations

45. Institution for research and training on
scrub typhus in the SEA Region
 The Armed Forces Research Institute of
Medical Sciences (AFRIMS) Bangkok, Thailand
is the WHO Collaborating Centre (CC) for
Emerging Diseases that is providing technical
support for outbreak investigation and
capacity building for diagnosis and control
of scrub typhus.
 The Department of Entomology,
AFRIMS is the only laboratory in the
world that has the ability to rear and
colonize scrub typhus-infected
Leptotrombidium mites, the vector of

46. MCQs
1. Limited area of intensive transmission of rickettsiae
called as
(a) Typhus Island (b) Mite islands (c) Rickettsiae Island
(d) None of the above
2. Agent for Indian Tick Typhus is (a) Rickettsia typhi
(b) Rickettsia conorii (c) Rickettsia akari (d) Rickettsia
prowazekii
3. Most commonly reported rickettsial infection in India
is (a) Scrub typhus (b) Indian Tick Typhus (c)
Epidemic typhus (d) Rickettsial pox
4. Epidemic Typhus is transmitted by (a) Tick (b) Mite
(c) Human louse (d) Rat flea
5. The infection is transmitted to man through the bite of
which form of infective mite (a) Larvae (b) Pupa (c)
Male adult (d) Female adult