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1. DR.SURINDER THAKUR
PROFESSOR OF MEDICINE,
I.G.M.C., SHIMLA

2.  A 38-year-old male, farmer admitted with
 Fever, bodyache -12 days,
 Shortness of breath -2 days
 Referred from peripheral health institution as no
response to beta-lactam antibiotics.
 On examination the patient was conscious, febrile
& in respiratory distress,
 BP-110/70 mm Hg, PR-110/min regular, RR-36/min
 JVP not raised, No-Cyanosis, No-Edema
 B/L Eschar in the axilla with tender
lymphaedenopathy.
 ABDOMEN- Liver palpable, no spleenomegaly
 CHEST –B/L crepitations
 CVS & CNS -Normal

3.  Showing two eschars in axillary region in a
patient of scrub typhus.

4. BLOOD 18 – 08 -10 19 -08-10 23-08-10
Hb 13 13
TLC 4300 6400
DLC P61 L36 M1 E2
ESR 38 PLATELETS-160000
Random Blood Sugar 117 85 97
B.UREA 50 25
S.CREATININE 1.4 0.6
Na/K/Cl 127 / 4.55 / 96 134/ 4.5 / 96 136 / 4.4 / 105
S.BILIRUBIN – TOTAL 2.1 0.3
-CONJUGATED 0.7 NIL
SGOT/SGPT 206 / 151 85 / 97
Alkaline Phosphatase 219 123
S.PROTIENS – TOTAL 5.8
ALBUMIN 2.1
IgM, ELISA for scrub positive

5.  ECG-Sinus Tachycardia.
 ECHO-Normal Study
 Blood C/S-Sterile
 H1N1-Negative

6. 18-08-2010 23-08-2010

7. 18-08-10
BLOOD - ABG
pH 7.409
pO2 41
pCO2 24
sO2 79 %
HCO3 15
PaO2/FiO2 <200

8.  Managed in ICU.
 I/V azithromycin 500 mg OD for 5 days.
 Discharged after 1 week.

9.  Scrub typhus is a form of typhus caused by
o.tsutsugamushi.
 First described in china 318 AD, isolated in Japan in 1930
 Disease of rural villages and suburban areas.
 Term scrub is used because of the vegetation (terrain
between woods and clearing) that harbours the vector.
 However certain endemic areas can be sandy semiaired
and mountain deserts.
 Range tropical and temperate upto 3200 metres
 Scrub typhus often acquired during occupational
/agricultural exposure.
 Scrub typhus is one of the underdiagnosed, underreported
febrile illness requiring hospitalisation in the region [WHO]

10.  Scrub typhus is endemic in tsutsugamushi
triangle which extends from northern Japan, far
eastern Russia in the north to the Northern
Australia in the south and pakistan in the west.
 It was linked to war and military operations
during the second world war, also important
cause of PUO in U.S. forces during Vietnam
conflict.
 Precise incidence of disease is unknown.
 Estimated 1 billion people are at risk of scrub
typhus and estimated 1 million cases occur
anually.

11. TSUTSUGAMUSHI TRIANGLE

12.  It is endemic in certain geographic regions of
India, Indonesia, Maldives, Mayanmar, Nepal,
Srilanka and Thailand.
 It has also been reported from various parts
of India but specific data is not available.
 Seasonal occurence varies with the climate
in different countries.
 Forrest clearing, river banks, grassy regions
provide optimal conditions for infected mites
to thrive.

14.  Family rickettsiae, genus orientiae,
 Small obligate gram negative, intracellular
bacteria.
 Cell wall lacks peptidoglycans and
lipopolysaccharides.
 Serotypes identified Karp, Gilliam, Kawasaki,
Boryon, Kato, Litchfield (in Australia).
 Primary reserviour, chigger/mite, larval
stage,trombiculid mite(Leptotrombium daliense
and others)
 Secondary reserviour rodents, humans.
 Incubation period 5-20 days, mean10-12 days.

15.  Orientia tsutsugamushi is the causative agent &
transmitted to humans through the bite of
thrombiculid mites.
 The mites have a four-stage lifecycle: egg, larva,
nymph and adult.
 The chigger (larval) phase is the only stage that is
parasitic on animals or humans.
 Infection is maintained in nature transovarially from
one generation of mite to the next.

17.  Organism divides and breeds within the phagocytes
and escape from the cell back into the circulation to
continue to proliferate on the endothelium of small
blood vessels releasing cytokines which damage
endothelial integrity, causing fluid leakage, platelet
aggregation, polymorphs and monocyte proliferation,
leading to focal occlusive end-angiitis causing
microinfarcts.
 It is now well established that a majority of sequelae
associated with human rickettsioses are the outcome
of‘Rickettsial vasculitis’.
 Especially affects skeletal muscles, skin, lungs,
kidneys, brain and cardiac muscles.

18.  Illness varies from mild and self limiting to fatal
disease.
 Symptoms and signs varies in individuals with
different strains.
 Commonest symptom high grade fever ,headache
muscle pain ,cough, and GI symptoms.
 Severe disease in 2ND week.
 Meningitis , meningo-encephalitis , deafness,
pneumonia, ARDS, MODS & myocarditis.
 Uncommon: dual infection with leptospira,
typhoid.
 Reinfection & Relapses are seen due to variable
immunity to different strains.

19.  Maculopapular rash on the trunk<40%,often
missed.
 Eschar in <50% in primary infection, <30% in
endemic area and in reinfection.
 Lymphadenopathy regional and/or
generalized.

20. Age Male Female Total % age
grp(years)
0-18 5 7 12 5.43
19-35 20 80 100 45.25
36-55 12 61 73 33.03
>55 11 25 36 16.29
Total 48 173 221 100
250
200
150 Male
100 Female
Total
50
0
0-18 19-35 36-55 >55 Total

21. SEX
FEMALE 173(78%)
MALE 48(22%)
22% FEMALE
MALE
78%

22. OCCUPATION
FARMER 213(96%)
OTHER 8(4%)
OTHER
4%
FARMER
96%

23. MONTH CASES(N=221)
JUNE 1
JULY 1
AUGUST 51
SEPT 106
OCTOBER 62

24. DISTRICT No. Of cases District wise distribution
SHIMLA 90 100
90
MANDI 47 80
BILASPUR 26 70
60
SOLAN 24 50
KULLU 13 40
30
SIRMOUR 13 20
HAMIRPU 10
04 0
R
KANGRA 02
KINNAUR 01
UNA 01

25. SYMPTOMS
FEVER 220 (99.5%)
HEADACHE 61(27.6%)
COUGH 39(17.6%)
VOMITING 39(17.6%)
ALTERED SENSORIUM 34(15.4%)
PAIN ABDOMEN 30(13.6%)
BODYACHES 30(13.6%)
DYSPNEA 21(9.5%)
DECREASED URINE OUTPUT 16(7.2%)
DIARRHOEA 12(5.4%)
CHEST PAIN 5(2.3%)
HEMOPTYSIS 0

26. SIGNS
LYMPHADENOPATHY 104(47.1%)
ESCHAR 71(32.1%)
PEDAL EDEMA 68(30.8%)
SPLENOMEGALY 65(29.4%)
PALLOR 45(20.4%)
ICTERUS 37(16.7%)
RASH 22(10.0%)
FACIAL PUFFINESS 20(9.0%)
CONJUNCTIVAL SUFFUSION 18(8.1%)
HEPATOSPLENOMEGALY 12(5.4%)
ASCITIS 10(4.5%)
HEPATOMEGALY 6(2.7%)
CYANOSIS 4(1.8%)

27. Parameter Normal Range No of patients(%)
Urea(mg%) 20-40 81(36.6%)
Creatinine(mg%) 0.5-1.2 51(23.08%)
Albumin(g%) 3-5.3 87(hypo-36.37%)
Biluribin(mg%) 0.5-1.5 29(13.12)
ALP 30-120 87(36.37%)
AST(IU/L) 10-40 149(67.42)
ALT(IU/L) 10-50 106(47.96)
Thrombocytopenia 1.5-4.5 21(10%)
(lakh /cu mm)

28. RESPIRATORY FINDINGS N(%)
CREPITATIONS 56(25.3%)
UNILATERAL PLEURAL EFFUSION 4(1.8%)
BILATERAL PLEURAL EFFUSION 1(0.5%)
CREPITATIONS + PLEURAL
8(3.6%)
EFFUSION
Total 69(31.2%)
U/L PLEF CREPITATIONS +
2% PLEF
B/L PLEF 4%
0%
CREPITATIONS
25%
NORMAL
69%

29. CHEST X-RAY
CHEST XRAY FINDINGS N(%)
NORMAL
172(77.8%)
PLEURAL EFFUSION
14(6.3%)
INHOMOGENOUS OPACITY /RETICULONODULAR
SHADOWS
21(9.5%)
HOMOGENOUS OPACITY
3(1.4%)
PLEF+ HOMOGENOUS OPACITY
11(5.0%)

38. High-power photomicrograph shows dermal vasculitis with perivascular
infiltrates that consist mostly of lymphocytes and macrophages.

39.  TYPHUS FEVER
 DENGUE
 LEPTOSPIROSIS
 TYPHOID
 MALARIA
 INFECTIOUS MONONUCLEOSIS
 VIRAL HF

40.  DISEASE OF RURAL AND SUBURBAN AREAS.
 DIAGNOSIS DIFFICULT IN ACUTE STAGE OF
DISEASE.
 APPLICATION OF EPIDEMIOLOGICAL,
CLINICAL AND LAB PRINCIPLES.

41.  EPIDEMIOLOGICAL
Exposure to vector & animal reservoir
Travel to endemic region
 CLINICAL- ESCHAR & RASH
 LABORATORY
Low wbc count
Thrombocytopenia
Elevated transaminases
 DEFINITIVE DIAGNOSIS
Serology -paired sera

42.  Isolationof organisms & Culture of organisms
 Serological tests for antibodies
Weil Felix
IFA
Micro-immunofluroscence
IIP
ELISA
Rapid Diagnostic reagent strips
 PCR-Blood, Buffy coat & Eschar.
 Genetic assays

43.  Currently available serological tests for scrub typhus
have limitations.
 Serological tests are more reliable when the titers
show 4 fold rise in antibody titres for paired sample.
 Non endemic areas diagnosis can be made from single
sample
 However cut of values used are identical irrespective
of endemic and non endemic regions.
 Most frequently used antigen in IFA-karp, kato, &
galliam.
 IN IgM ELISA antigen used is against outer membrane
56 kd protein from strains of karp, kato, galliam and
boryon.

44. SERO Acute Spe Cost/ Time Ea Setting Comments
LOG sensit cific samp se
Y ivity ity le
IFA ++ +++ ++++ 2hours ++ Reference • Serology gold standard, Requires propagation &
purification of BSL3 agents
lab/hospit as antigen for assay, Requires fluorescence
al microscope, Standardization problems &
Requires paired samples
(retrospective diagnosis)
IIP ++ +++ +++ 2hours ++ Reference -do- except requires light
++ lab/hospit microscope only
al
Weil- + ++ + 6-18 ++ Primary •Poor sensitivity for acute
Felix hours ++ hospital disease
OXK2 • Requires paired samples
(retrospective diagnosis)
DIP- ++ +++ +++ <30 ++ Primary • Does not require specialized
STIC mins ++ hospital equipment
K + • Rapid and simple
AM. J. TROP. MED. HYG., 82(3), 2010, PP. 368–370

45. WEIL FELIX ELISA
PRINCIPLE HETEROPHILE AGGLUTINATION WITH RECOMBINANT ANTIGEN OF
PROTEUS ANTIGEN ORIENTIA
TIME OVERNIGHT 2 HRS
EASE OF SIMPLE BUT TIME CONSUMING EASY BUT TECHNICALLY
PERFORMING DEMANDING
COST CHEAP COST EFFECTIVE
NO OF SAMPLES PAIRED SERA ;FOUR FOLD RISE SINGLE SERA ;> CUT OFF
REQUIRED
RESULT SUBJECTIVE; NO CONSENSUS ON OBJECTIVE; CUT OFF BASED
INTERPRETATION SINGLE SIGNIFICANT TITRE ON CALCULATION ON
NORMAL SERA
ANTIBODY TESTED MAINLY IgM SEPARATE ASSAYS FOR IgM
AND IgG
SENSITIVITY 30- 60 93-97
SPECIFICITY 60- 90 91-95

46. ISOLA Acu Spe Cost/ Time Ea Setting Comments
TION te cific samp se
sen ity le
sitiv
ity
IN + +++ ++++ 7-60 + BSL3 • Isolation of BSL3 agent
VITRO ++ + days Reference • Requires infrastructure
ISOLAT lab • Biocontainment issues
ION • Retrospective diagnosis
MOUSE + +++ ++++ 5-30 + BSL3 • Technically demanding
INOCU ++ + days Reference • Isolation of BSL3 agent
LATIO lab • Requires animal facilities
N • Biocontainment issues
• Retrospective diagnosis
AM. J. TROP. MED. HYG., 82(3), 2010, PP. 368–370

47. GENET Acu Spe Cost/ Time Ea Setting Comments
IC te cific samp se
TEST sen ity le
sitiv
ity
REAL +++ +++ +++ 3 ++ Reference • Expensive equipment
TIME ++ hours + lab/hospit • Requires infrastructure
PCR al • Sensitivity dependent on
sample type and timing
• Possible contamination
issues
LOOP +++ +++ ++ 2 ++ Primary • Simple
AMPLI ++ hours ++ hospital • Inexpensive
CATIO • Possible contamination
N issues
AM. J. TROP. MED. HYG., 82(3), 2010, PP. 368–370

48.  Doxycycline 100mg 1BD X 7-15 days.
 Tetracyclin 500mg Qid X 7-15 days.
 Chloromycetin 500mg Qid X 7-15 days.
 Azihromycin 500mg 1OD X 3 days.
 Pregnant mothers & childrens Azithromycin
for 3 days.
 Rifampicin 600/900mg X 1OD for 1 week in
resistant cases.

49.  MORTALITY 7-30%.
 POOR PROGNOSIS
 Missed diagnosis
 Late presentation
 Drug resistance
 MODS
 ARDS

50.  Avoidance of intrusion in areas infested with
reservoir and vector.
 Proper clothing-Miticide and mite
repellent, detection & removal.
 Rodent control-trapping, rodenticide, depriving
food.
 Vector control-Ground treatment of residual
vegetation with insecticide.
 No satisfactory vaccine-enormous antigenic
variation of strains.
 Immunity of one strain doesnt offer immunity to
other strains.

51.  Recommended under special circumstances
where disease is endemic.
 Oral chloramphenicol or tetracycline given once
every 5 days for thirty-five days or weekly doses
of doxycycline during and for 6 weeks after
exposure have both been shown to be effective
regimens.
 Resistance to antibiotics has been noted in
several areas, therefore prophylaxis with
antibiotics cannot be guaranteed.

52. Thanks