SCRUB TYPHUS PRESENTIG AS EMERGENCY

DR.SURINDER THAKURPROFESSOR OF MEDICINE,

I.G.M.C., SHIMLA

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

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

BIOCHEMICAL PARAMETERSBLOOD 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

-CONJUGATED

2.1

0.7

0.3

NIL

SGOT/SGPT 206 / 151 85 / 97

Alkaline Phosphatase 219 123

S.PROTIENS – TOTAL

ALBUMIN

5.8

2.1

IgM, ELISA for scrub positive

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

CXR

18-08-2010 23-08-2010

ABGBLOOD - ABG 18-08-10

pH 7.409

pO2 41

pCO2 24

sO2 79 %

HCO3 15

PaO2/FiO2 <200

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

SCRUB TYPHUS

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]

EPIDEMIOLOGY 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.

TSUTSUGAMUSHI TRIANGLE

TSUTSUGAMUSHI

TRIANGLE

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.

ASIA AND WEST PACIFIC ISLANDS

ETIOPATHOGENESIS 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.

S 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.

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.

CLINICAL FEATURES 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.

CLINICAL SIGNS 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.

PROFILE OF SCRUB TYPHUS-IGMC 2010(IGM ELISA POSITIVE CASES)AGE WISE DISTRIBUTION OF CASES

Age grp(years)

Male Female Total % age

0-18 5 7 12 5.4319-35 20 80 100 45.2536-55 12 61 73 33.03>55 11 25 36 16.29Total 48 173 221 100

0-18 19-35 36-55 >55 Total0

50

100

150

200

250

MaleFemaleTotal

SEX DISTRIBUTION

78%

22%

Chart Title

FEMALE

MALE

SEX

FEMALE 173(78%)

MALE 48(22%)

OCCUPATION

FARMER96%

OTHER4%

Chart Title

OCCUPATION

FARMER 213(96%)

OTHER 8(4%)

MONTH WISE DISTRIBUTION

MONTH CASES(N=221)

JUNE 1

JULY 1

AUGUST 51

SEPT 106

OCTOBER 62

DISTRICT WISE DISTRIBUTION OF CASES

DISTRICT No. Of casesSHIMLA 90MANDI 47BILASPUR 26SOLAN 24 KULLU 13 SIRMOUR 13 HAMIRPUR 04

KANGRA 02KINNAUR 01UNA 01

SHIM

LA

MAN

DI

BILA

SPUR

SOLA

N

KULL

U

SIRM

OUR

HAMIR

PUR

KANGRA

KINNAU

RUNA

0102030405060708090

100

District wise distribution

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

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%)

LAB PARAMETERSParameter 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(lakh /cu mm)

1.5-4.5 21(10%)

RESPIRATORY FINDINGS N(%)

CREPITATIONS 56(25.3%) UNILATERAL PLEURAL EFFUSION 4(1.8%)BILATERAL PLEURAL EFFUSION 1(0.5%) CREPITATIONS + PLEURAL EFFUSION 8(3.6%)

Total 69(31.2%)

NORMAL69%

CREPITATIONS25%

U/L PLEF2%

B/L PLEF0%

CREPITATIONS + PLEF4%

Chart Title

CHEST XRAY FINDINGS N(%)

NORMAL172(77.8%)

PLEURAL EFFUSION 14(6.3%)

INHOMOGENOUS OPACITY /RETICULONODULAR SHADOWS

21(9.5%)

HOMOGENOUS OPACITY 3(1.4%)

PLEF+ HOMOGENOUS OPACITY11(5.0%)

CHEST X-RAY

ESCHAR- RIGHT FOREARM NEAR WRIST

ESCHAR;ANTERIOR ASPECT OF RIGHT THIGH

ESCHAR;LEFT ARM MEDIAL ASPECT JUST ABOVE ELBOW

ESCHAR; OVER SHAFT OF PENIS

OVER MEDIAL ASPECT OF THIGH

OVER THE ANTERIOR ABDOMINAL WALL

OVER THE SCROTUM

OVER THE AREA LATERAL TO RIGHT BREAST

HISTOPATHOLOGY OF ESCHAR

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

DIFFERENTIAL DIAGNOSIS TYPHUS FEVER DENGUE LEPTOSPIROSIS TYPHOID MALARIA INFECTIOUS MONONUCLEOSIS VIRAL H F

DIAGNOSISDISEASE OF RURAL AND SUBURBAN

AREAS. DIAGNOSIS DIFFICULT IN ACUTE

STAGE OF DISEASE.APPLICATION OF EPIDEMIOLOGICAL,

CLINICAL AND LAB PRINCIPLES.

EPIDEMIOLOGICAL Exposure to vector & animal reservoir Travel to endemic regionCLINICAL- ESCHAR & RASHLABORATORY Low wbc count Thrombocytopenia Elevated transaminasesDEFINITIVE DIAGNOSIS Serology -paired sera

LAB DIAGNOSIS Isolation of 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

SEROLOGY 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.

SEROLOGYSEROLOGY

Acutesensitivity

Specificity

Cost/sample

Time Ease

Setting Comments

IFA ++ +++

++++

2hours

++

Reference lab/hospital

• Serology gold standard, Requires propagation & purification of BSL3 agentsas antigen for assay, Requires fluorescence microscope, Standardization problems & Requires paired samples(retrospective diagnosis)

IIP ++ +++

+++

2hours

++++

Reference lab/hospital

-do- except requires light microscope only

Weil- Felix OXK2

+ ++ + 6-18hours

++++

Primary hospital

•Poor sensitivity for acutedisease• Requires paired samples(retrospective diagnosis)

DIP-STICK

++ +++

+++

<30mins

+++++

Primary hospital

• Does not require specializedequipment• Rapid and simple

AM. J. TROP. MED. HYG., 82(3), 2010, PP. 368–370

WEIL FELIX ELISA

PRINCIPLE HETEROPHILE AGGLUTINATION WITH PROTEUS ANTIGEN

RECOMBINANT ANTIGEN OF ORIENTIA

TIME OVERNIGHT 2 HRS

EASE OF PERFORMING

SIMPLE BUT TIME CONSUMING EASY BUT TECHNICALLY DEMANDING

COST CHEAP COST EFFECTIVE

NO OF SAMPLES REQUIRED

PAIRED SERA ;FOUR FOLD RISE SINGLE SERA ;> CUT OFF

RESULT INTERPRETATION

SUBJECTIVE; NO CONSENSUS ON SINGLE SIGNIFICANT TITRE

OBJECTIVE; CUT OFF BASED 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

ISOLATION ASSAYS BSL3 = BIOSAFETY LEVEL 3; + = LOW/POOR; +++++ = HIGH/EXCELLENT ON A FIVE-POINT QUALITATIVE SCALE.

ISOLATION

Acutesensitivity

Specificity

Cost/sample

Time Ease

Setting Comments

IN VITRO ISOLATION

+ +++++

+++++

7-60 days

+ BSL3 Reference lab

• Isolation of BSL3 agent• Requires infrastructure• Biocontainment issues• Retrospective diagnosis

MOUSE INOCULATION

+ +++++

+++++

5-30 days

+ BSL3 Reference lab

• Technically demanding• Isolation of BSL3 agent• Requires animal facilities• Biocontainment issues• Retrospective diagnosis

AM. J. TROP. MED. HYG., 82(3), 2010, PP. 368–370

GENETIC ASSAYSBSL3 = BIOSAFETY LEVEL 3; + = LOW/POOR; +++++ = HIGH/EXCELLENT ON A FIVE-POINT QUALITATIVE SCALE.

GENETIC TEST

Acutesensitivity

Specificity

Cost/sample

Time Ease

Setting Comments

REAL TIME PCR

+++

+++++

+++

3 hours

+++

Reference lab/hospital

• Expensive equipment• Requires infrastructure• Sensitivity dependent onsample type and timing• Possible contaminationissues

LOOP AMPLICATION

+++

+++++

++ 2 hours

++++

Primary hospital

• Simple• Inexpensive• Possible contaminationissues

AM. J. TROP. MED. HYG., 82(3), 2010, PP. 368–370

TREATMENT 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.

PROGNOSIS MORTALITY 7-30%.

POOR PROGNOSIS Missed diagnosis Late presentation Drug resistance MODS ARDS

PREVENTION 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.

PROPHYLAXIS 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.

Thanks