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SCRUB TYPHUS
Presenter:
Dr. Madhu Gaikwad
Post Graduate Student
1
Guided by:
Dr. Shubhra A. Gupta
Associate Professor
Department of Community Medicine
Pt. J.N.M. Medical College, Raipur (C.G.)
Contents
 History
 Introduction
 Epidemiology
 Mode of transmission
 Life cycle
 Clinical features
 Complications
 Investigations & Diagnosis
 Management
2
Scrub Typhus
• Rickettsial infection caused by Orientia
tsutsugamushi, a gram negative obligate
intracellular coccobacillus bacteria of
Rickketsiaceae family.
tsutsuga = small and dangerous ; mushi = mite
• It was first described from Japan in 1899.
• In India first case was reported from Himanchal
Pradesh.
3
• Epidemic in India was first reported from
Kumaon region, in soldiers during the second
world war in Assam.
• Scrub typhus is the commonest occuring
rickettsial infection in India.
4
• There is an estimated one million new scrub
typhus infections every year and over one billion
people around the world are at risk.
• More during rainy and winter seasons.
5
AFTER RAINY SEASON
INCREASED HUMIDITY
HATCHING OF MITES EGG INTO
CHIGGERS LEADS TO TRANSMISSION
• It is generally seen in people whose
occupational or recreational activities bring them
into contact with ecotypes favorable with vector
chiggers.
• It occurs in area where scrub vegetation
– Consisting of low lying trees and bushes
– Banks of rivers
– Rice fields
– Poorly maintained kitchen garden
– Grassy lawns
6
Disease
Ricketssial
Agent
Insect Vector
Mammalian
Reserviors
Typhus Group
a. Epidemic Typhus
b. Murine Typhus
c. Scrub Typhus
R. Prowazekki
R. Typhi
O. tsutsugamushi
Louse
Flea
Mite
Human
Rodent
Rodent
Spotted Fever
Group
a. Indian Tick
Typhus
b. Rocky Mountain
Spotted fever
c. Rickettsial Pox
R. Conorii
R. Rickettsii
R. akari
Tick
Tick
Mite
Rodent, Dog
Rodent, Dog
Mice
Others
a. Q Fever
b. Trench Fever
C. Brunetti
Rochalimaea
Nil
Louse
Cattle, sheep, goat
Human 7
Classification of Rickettsial Diseases
Epidemiology
• Causative organism is Orientia tsutsugamushi
• Human acquires the disease from the bite
of an infected trombiculid mite larva (Chigger).
• Humans are accidental and dead end host.
• The larva is the only stage that can transmit
the disease to humans.
8
• Other life stages (nymph and adult) do not
feed on vertebrate animals. Both are free living
in the soil.
• Once infected, they maintain the transmission
through out their life cycle
• Transovarial and transstadial transmission of
infection occurs.
• Mites are both reservoir and vector of disease.
9
Transmission cycle
10
Endemic in the part of World known as
tsutsugamushi triangle extends from northern
Japan and far eastern Russia in the north, to
northern Australia in the south and to Pakistan in
the west.
11
• O. tsutsugamushi expresses a type specific
protein 56kDa protein which is unique and have
cross reacting epitopes resulting in genetic
diversity.
• 5 Serotypes:
Kato, Karp, Kawazaki, Boryong, Gilliam
12
Life cycle of Trombiculid mite
13
1 WEEK
1- 2 WEEKS
1-3 WEEKS
6 MONTHS
Clinical Features
• Incubation period: 5-20 days after the initial bite
• Clinical spectrum: self limiting disease to multi organ
dysfunction resulting in death.
• Untreated cases have high CFR 30-45%
• Chigger bite painless, noticed by transient localized
itch.
• First sign of disease is vesicular lesion at the site of
bite
14
• Bites are found on groin, axillae, genitalia,
perianal area or neck.
• Eschar may develop at the site of bite. (7-97%)
Rare in South East Asia
15
16
ESCHAR Chigger bite on the axilla
Chigger bite on the neck Spotted rashes over the trunk
• Fever with shaking chills
• Headache
• Myalgia
• Malaise
• Infection of conjunctiva
• Spotted Rash (3-5 days after onset of
symptoms, rare)
• Lymphadenopathy
17
Complications
• Develops after 1st week of illness:
– Atypical pneumonia with ARDS like
presentation
– Renal failure
– Encephalopathy
– Myocarditis
– Disseminated Intravascular Coagulation (DIC)
– Multiple organ dysfunction syndrome (MODS)
– Septic Shock
18
• Definition of Suspected/clinical case:
– Acute undifferentiated febrile illness of 5 days
or more with or without eschar should be
suspected as a case of Rickettsial infection.
– Fever of less than 5 days and eschar present,
should be considered as scrub typhus.
– Other features may be headache and rash
(fair persons), lymphadenopathy, multi-organ
involvement.
– Differential diagnosis- dengue, malaria,
pneumonia, leptospirosis and typhoid
Source: Guidelines for Diagnosis and management of rickettsial Disease in India, DHR-ICMR,
2015 19
• Definition of Probable case:
– A suspected clinical case showing titres of
1:80 or above in OX2, OX19 and OXK
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.
Source: Guidelines for Diagnosis and
management of rickettsial Disease in India,
DHR-ICMR, 2015
20
• Definition of Confirmed case:
A Confirmed case is the one 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)
Source: Guidelines for Diagnosis and management of rickettsial Disease
in India, DHR-ICMR, 2015
21
Supportive investigations
• TLC: >11,000 / microliter
• Mild thrombocytopenia
• Deranged LFT
• Albuminuria
• Chest X-ray- B/L infiltrates
22
• Specimens:
– Serum
– Blood collected in tubes with EDTA or
Sodium citrate
– Eschar, whole blood, buffy coat fraction and
tissue specimen.
– (Samples to be dispatched to laboratory at 2-
8 degree Celsius with label)
23
Specific investigations
Serology
• Weil Felix
test
• IgM and
IgG ELISA
• Immunofluo
roscence
assay (IFA)
Molecular
diagnosis
• PCR
Isolation of
Organism
24
Weil Felix test
• Sharing of antigen between rickettsia and
proteus is the basis.
• Carried out 5-7 days after onset of fever
• Titre of 1:80 is to be considered as possible
infection
25
26
• IgM and IgG ELISA
Most sensitive
IgM Antibody titre is observed at the end of
1st week, IgG appears at the end of 2nd
week.
Immunofluoroscence assay (IFA):
• Gold standard
• Fourfold rise in antibody titre is considered
diagnostic of scrub typhus.
• High cost and requirement of technical expertise
limit its wide use.
27
Polymerase Chain Reaction
• Rapid and specific test for diagnosis.
• Best within first week (7-10 days)
• Detects rickketsial DNA in whole blood and
eschar.
• Targeted at 56kDa and/or 47kDa surface antigen
gene.
• Rapid Diagnostic test for diagnosis of scrub
typhus is not recommended.
28
Isolation of organism
• Isolation should be done in laboratories
equipped with appropriate safety i.e. biosafety
level-3.
• Isolated by animal inoculation, embryonated
eggs and various cell lines
29
Treatment
1 Drug of choice Doxycycline 100 mg BD
2 Alternatives
Azithromycin 500 mg OD
Chloramphenicol 500 mg
QID
3
Children and
Pregnant
women
Azithromycin 500 mg OD
4
Drug resistant
serotype
Azithromycin + Rifampicin
Doxycycline + Rifampicin
Source: Ramasubramanian V, Senthur Nambi P. Scrub typhus. Medicine Update. India: Association of
Physicians of India. 2013:19-22.
30
• The recommended treatment duration is 7-14
days.
• Treatment < 7 days is initially curative but may
be followed by relapse.
31
Side effects of Tetracyclines:
• Should not be given to children under 8 years of
age and to the pregnant women as it is C/I in
pregnancy.
Source: Scrub typhus, CD Alert, National Center for Disease Control, DHS, GOI, May
2018
32
Discoloration of teeth (directly related to
no. of tetracycline therapy received)
Depression of skeletal growth in Children
• Should not wait for laboratory confirmation,
antibiotic therapy should be instituted when
rickettsial disease is suspected.
• At Primary level: The Health Care provider
needs to do the following:
– Recognition of disease severity: if
complications present- treatment with
doxycycline should be initiated before
referring the patient.
– In fever cases of duration of 5 days or more
where malaria, dengue and typhoid have been
ruled out treatment to be continued as per the
guidelines 33
At secondary and tertiary care:
• a) The treatment as specified above in
uncomplicated cases.
• b) In complicated cases the following
treatment is to be initiated –
I/V Doxycycline100mg twice daily in 100 ml
normal saline to be administered as infusion
over half an hour followed by oral therapy
Or
I/V Azithromycin in the dose of 500mg IV in
250 ml normal saline over 1 hour once daily
for 1-2 days followed by oral therapy
Or
34
• I/V chloramphenicol 50-100 mg/kg/d 6 hourly
doses to be administered as infusion over 1 hour
initially followed by oral therapy to complete 7-15
days of therapy.
• Management of the individual complications
should be done as per the existing practices.
Without appropriate treatment the case fatality
rate is 30%.
35
• Chigger Index: Average number of chiggers
infesting a single host.
• If >0.69 (critical value), it is an indicator for
implementation of vector control measures.
36
Preventive and control measures
37
1
Persons who cannot avoid infested terrain should wear
protective clothing, impregnate their clothing and bedding
with a miticide.
2
People should wash themselves and their clothes after
every potential exposure.
3
Insect repellents containing dimethyl phthalate (DMP),
benzyl benzoate and diethyl toluamide (DEET) can be
applied to the skin and clothing to prevent chigger bites.
4
Do not sit or lie on bare ground or grass; use a suitable
ground sheet or other ground cover.
5
Clearing of vegetation and chemical treatment of the
vegetation/ soil may help to break up the cycle of
transmission from chiggers to humans.
Chemoprophylaxis
• A single oral dose of chloramphenicol or
tetracycline given every 5 days for a total
of 35 days, with 5-day non-treatment
intervals. This is recommended under
special circumstances incertain areas
where the disease is endemic.
38
Vaccine
• There is no effective vaccine against scrub
typhus.
• There is enormous antigenic variation in O.
tsutsugamushi strain and immunity to one strain
does not confer immunity against another.
39
References
1. Guidelines for Diagnosis and management of rickettsial Disease in
India, DHR-ICMR, 2015
2. Ramasubramanian V, Senthur Nambi P. Scrub typhus. Medicine
Update. India: Association of Physicians of India. 2013:19-22.
3. Scrub typhus in India- An Impending Threat!, Sneha K Chuchanur,
Annals of clinical Immunology and Microbiology, 3 July 2018
4. CD Alert, National Centre for disease Control, Directorate General of
Health Services, Government of India, May 2018.
5. Park’s Textbook of Preventive and Social Medicine, 24TH Edition.
40
41

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Scrub typhus

  • 1. SCRUB TYPHUS Presenter: Dr. Madhu Gaikwad Post Graduate Student 1 Guided by: Dr. Shubhra A. Gupta Associate Professor Department of Community Medicine Pt. J.N.M. Medical College, Raipur (C.G.)
  • 2. Contents  History  Introduction  Epidemiology  Mode of transmission  Life cycle  Clinical features  Complications  Investigations & Diagnosis  Management 2
  • 3. Scrub Typhus • Rickettsial infection caused by Orientia tsutsugamushi, a gram negative obligate intracellular coccobacillus bacteria of Rickketsiaceae family. tsutsuga = small and dangerous ; mushi = mite • It was first described from Japan in 1899. • In India first case was reported from Himanchal Pradesh. 3
  • 4. • Epidemic in India was first reported from Kumaon region, in soldiers during the second world war in Assam. • Scrub typhus is the commonest occuring rickettsial infection in India. 4
  • 5. • There is an estimated one million new scrub typhus infections every year and over one billion people around the world are at risk. • More during rainy and winter seasons. 5 AFTER RAINY SEASON INCREASED HUMIDITY HATCHING OF MITES EGG INTO CHIGGERS LEADS TO TRANSMISSION
  • 6. • It is generally seen in people whose occupational or recreational activities bring them into contact with ecotypes favorable with vector chiggers. • It occurs in area where scrub vegetation – Consisting of low lying trees and bushes – Banks of rivers – Rice fields – Poorly maintained kitchen garden – Grassy lawns 6
  • 7. Disease Ricketssial Agent Insect Vector Mammalian Reserviors Typhus Group a. Epidemic Typhus b. Murine Typhus c. Scrub Typhus R. Prowazekki R. Typhi O. tsutsugamushi Louse Flea Mite Human Rodent Rodent Spotted Fever Group a. Indian Tick Typhus b. Rocky Mountain Spotted fever c. Rickettsial Pox R. Conorii R. Rickettsii R. akari Tick Tick Mite Rodent, Dog Rodent, Dog Mice Others a. Q Fever b. Trench Fever C. Brunetti Rochalimaea Nil Louse Cattle, sheep, goat Human 7 Classification of Rickettsial Diseases
  • 8. Epidemiology • Causative organism is Orientia tsutsugamushi • Human acquires the disease from the bite of an infected trombiculid mite larva (Chigger). • Humans are accidental and dead end host. • The larva is the only stage that can transmit the disease to humans. 8
  • 9. • Other life stages (nymph and adult) do not feed on vertebrate animals. Both are free living in the soil. • Once infected, they maintain the transmission through out their life cycle • Transovarial and transstadial transmission of infection occurs. • Mites are both reservoir and vector of disease. 9
  • 11. Endemic in the part of World known as tsutsugamushi triangle extends from northern Japan and far eastern Russia in the north, to northern Australia in the south and to Pakistan in the west. 11
  • 12. • O. tsutsugamushi expresses a type specific protein 56kDa protein which is unique and have cross reacting epitopes resulting in genetic diversity. • 5 Serotypes: Kato, Karp, Kawazaki, Boryong, Gilliam 12
  • 13. Life cycle of Trombiculid mite 13 1 WEEK 1- 2 WEEKS 1-3 WEEKS 6 MONTHS
  • 14. Clinical Features • Incubation period: 5-20 days after the initial bite • Clinical spectrum: self limiting disease to multi organ dysfunction resulting in death. • Untreated cases have high CFR 30-45% • Chigger bite painless, noticed by transient localized itch. • First sign of disease is vesicular lesion at the site of bite 14
  • 15. • Bites are found on groin, axillae, genitalia, perianal area or neck. • Eschar may develop at the site of bite. (7-97%) Rare in South East Asia 15
  • 16. 16 ESCHAR Chigger bite on the axilla Chigger bite on the neck Spotted rashes over the trunk
  • 17. • Fever with shaking chills • Headache • Myalgia • Malaise • Infection of conjunctiva • Spotted Rash (3-5 days after onset of symptoms, rare) • Lymphadenopathy 17
  • 18. Complications • Develops after 1st week of illness: – Atypical pneumonia with ARDS like presentation – Renal failure – Encephalopathy – Myocarditis – Disseminated Intravascular Coagulation (DIC) – Multiple organ dysfunction syndrome (MODS) – Septic Shock 18
  • 19. • Definition of Suspected/clinical case: – Acute undifferentiated febrile illness of 5 days or more with or without eschar should be suspected as a case of Rickettsial infection. – Fever of less than 5 days and eschar present, should be considered as scrub typhus. – Other features may be headache and rash (fair persons), lymphadenopathy, multi-organ involvement. – Differential diagnosis- dengue, malaria, pneumonia, leptospirosis and typhoid Source: Guidelines for Diagnosis and management of rickettsial Disease in India, DHR-ICMR, 2015 19
  • 20. • Definition of Probable case: – A suspected clinical case showing titres of 1:80 or above in OX2, OX19 and OXK 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. Source: Guidelines for Diagnosis and management of rickettsial Disease in India, DHR-ICMR, 2015 20
  • 21. • Definition of Confirmed case: A Confirmed case is the one 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) Source: Guidelines for Diagnosis and management of rickettsial Disease in India, DHR-ICMR, 2015 21
  • 22. Supportive investigations • TLC: >11,000 / microliter • Mild thrombocytopenia • Deranged LFT • Albuminuria • Chest X-ray- B/L infiltrates 22
  • 23. • Specimens: – Serum – Blood collected in tubes with EDTA or Sodium citrate – Eschar, whole blood, buffy coat fraction and tissue specimen. – (Samples to be dispatched to laboratory at 2- 8 degree Celsius with label) 23
  • 24. Specific investigations Serology • Weil Felix test • IgM and IgG ELISA • Immunofluo roscence assay (IFA) Molecular diagnosis • PCR Isolation of Organism 24
  • 25. Weil Felix test • Sharing of antigen between rickettsia and proteus is the basis. • Carried out 5-7 days after onset of fever • Titre of 1:80 is to be considered as possible infection 25
  • 26. 26 • IgM and IgG ELISA Most sensitive IgM Antibody titre is observed at the end of 1st week, IgG appears at the end of 2nd week.
  • 27. Immunofluoroscence assay (IFA): • Gold standard • Fourfold rise in antibody titre is considered diagnostic of scrub typhus. • High cost and requirement of technical expertise limit its wide use. 27
  • 28. Polymerase Chain Reaction • Rapid and specific test for diagnosis. • Best within first week (7-10 days) • Detects rickketsial DNA in whole blood and eschar. • Targeted at 56kDa and/or 47kDa surface antigen gene. • Rapid Diagnostic test for diagnosis of scrub typhus is not recommended. 28
  • 29. Isolation of organism • Isolation should be done in laboratories equipped with appropriate safety i.e. biosafety level-3. • Isolated by animal inoculation, embryonated eggs and various cell lines 29
  • 30. Treatment 1 Drug of choice Doxycycline 100 mg BD 2 Alternatives Azithromycin 500 mg OD Chloramphenicol 500 mg QID 3 Children and Pregnant women Azithromycin 500 mg OD 4 Drug resistant serotype Azithromycin + Rifampicin Doxycycline + Rifampicin Source: Ramasubramanian V, Senthur Nambi P. Scrub typhus. Medicine Update. India: Association of Physicians of India. 2013:19-22. 30
  • 31. • The recommended treatment duration is 7-14 days. • Treatment < 7 days is initially curative but may be followed by relapse. 31
  • 32. Side effects of Tetracyclines: • Should not be given to children under 8 years of age and to the pregnant women as it is C/I in pregnancy. Source: Scrub typhus, CD Alert, National Center for Disease Control, DHS, GOI, May 2018 32 Discoloration of teeth (directly related to no. of tetracycline therapy received) Depression of skeletal growth in Children
  • 33. • Should not wait for laboratory confirmation, antibiotic therapy should be instituted when rickettsial disease is suspected. • At Primary level: The Health Care provider needs to do the following: – Recognition of disease severity: if complications present- treatment with doxycycline should be initiated before referring the patient. – In fever cases of duration of 5 days or more where malaria, dengue and typhoid have been ruled out treatment to be continued as per the guidelines 33
  • 34. At secondary and tertiary care: • a) The treatment as specified above in uncomplicated cases. • b) In complicated cases the following treatment is to be initiated – I/V Doxycycline100mg twice daily in 100 ml normal saline to be administered as infusion over half an hour followed by oral therapy Or I/V Azithromycin in the dose of 500mg IV in 250 ml normal saline over 1 hour once daily for 1-2 days followed by oral therapy Or 34
  • 35. • I/V chloramphenicol 50-100 mg/kg/d 6 hourly doses to be administered as infusion over 1 hour initially followed by oral therapy to complete 7-15 days of therapy. • Management of the individual complications should be done as per the existing practices. Without appropriate treatment the case fatality rate is 30%. 35
  • 36. • Chigger Index: Average number of chiggers infesting a single host. • If >0.69 (critical value), it is an indicator for implementation of vector control measures. 36
  • 37. Preventive and control measures 37 1 Persons who cannot avoid infested terrain should wear protective clothing, impregnate their clothing and bedding with a miticide. 2 People should wash themselves and their clothes after every potential exposure. 3 Insect repellents containing dimethyl phthalate (DMP), benzyl benzoate and diethyl toluamide (DEET) can be applied to the skin and clothing to prevent chigger bites. 4 Do not sit or lie on bare ground or grass; use a suitable ground sheet or other ground cover. 5 Clearing of vegetation and chemical treatment of the vegetation/ soil may help to break up the cycle of transmission from chiggers to humans.
  • 38. Chemoprophylaxis • A single oral dose of chloramphenicol or tetracycline given every 5 days for a total of 35 days, with 5-day non-treatment intervals. This is recommended under special circumstances incertain areas where the disease is endemic. 38
  • 39. Vaccine • There is no effective vaccine against scrub typhus. • There is enormous antigenic variation in O. tsutsugamushi strain and immunity to one strain does not confer immunity against another. 39
  • 40. References 1. Guidelines for Diagnosis and management of rickettsial Disease in India, DHR-ICMR, 2015 2. Ramasubramanian V, Senthur Nambi P. Scrub typhus. Medicine Update. India: Association of Physicians of India. 2013:19-22. 3. Scrub typhus in India- An Impending Threat!, Sneha K Chuchanur, Annals of clinical Immunology and Microbiology, 3 July 2018 4. CD Alert, National Centre for disease Control, Directorate General of Health Services, Government of India, May 2018. 5. Park’s Textbook of Preventive and Social Medicine, 24TH Edition. 40
  • 41. 41