CALL BACK STUDY118 VOLUNTEER SUBJECTS, PREVIOUS PEP OR PREP WITH ANY TISSUE CULTURE VACCINE 5 – 21 YEARS PREVIOUSLY

METHOD

COLLECT SERUM DAYS 0, 5, 7, 14 FOR NEUTRALIZING ANTIBODY

BOOSTERS VERORAB ID 0.1 mL DAYS 0 AND 3

RESULTS

VACCINE 5- 10 YEARS PREVIOUSLY (PEP,PREP) 65

VACCINE 10-21 YEARS PREVIOUSLY (PEP.PREP) 53

DETECTABLE TITERS ON DAY 0 118

ANAMNESTIC RESPONSE ON DAY 5 118

HIGH TITERS ON DAYS 7 AND 14 118

(Suwansrinon K, Wilde H, Benjavongkulchai M, et al. Vaccine 2006;24: 3878-80)

CALL BACK STUDY DATA (NABs done by RFFIT test at QSMI. Cut off: > 0.03 )

Group IU/mL Day 0 Day 5 Day 7 Day 14

PREP 5-10 Y GMT 0.64 0.92 3.72 23.48 Range 0.03-8.00 0.04-12.34 0.50-20.89 4.82-67.72

--------------------------------------------------------------------------------------------------------------PEP 5-10 Y GMT 1.22 1.77 5.42 15.67

Range 0.18-25.94 0.25-30.84 1.25-54.18 4.00-73.85--------------------------------------------------------------------------------------------------------------

PREP 10-21 Y GMT 1.64 2.40 6.39 20.76 Range 0.07-11.97 0.16-19.15 0.81-24.84 3.26-383.09

----------------------------------------------------------------------------------------------------------------PEP 10-20 Y GMT 1.30 2.30 6.57 21.29

Range 0.08-16.71 0.11-30.84 0.48-35.12 3.54-135.44---------------------------------------------------------------------------------------------------------------

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PEP FAILURE, MANAGEMENT ERROR1985

• DAY 0: THAI MALE 41 YEARS,

• DOG BITE UPPER LIP DEEP

• Day 0: WOUND CARE, HDCV IM gluteus

• DAY 2: HRIG IM INTO GLUTEAL REGION. WOUND NOT INFILTRATED HDCV 1 AMP IM DELTOID

• DAY 4: HDCV IM

• DAY 7: HDCV IM

• DAY 14 HEADACHE, FEVER, HDCV GIVEN AT 8 SITES 0.1 Ml ID

• DAY 15: PROGRESSION TO HYDROPHOBIA, AEROPHOBIA, SPASMS

• DAY 16: DEATH. NO AUTOPSY.•

ERRORS: CAT III, WOUND NOT INJECTED. HDCV GLUTEUS FROM QSMI COLLECTION

PEP FAILURE, MANAGEMENT ERROR 1987

• THAI MALE 53 Y (BANGKOK)

• DAY 0: BITTEN BY DOG WHICH DIED 4 DAYS LATER AND FAT • POSITIVE FOR RABIES. DEEP WOUNDS BOTH HANDS • AND FINGERS. APPROPRIATE WOUND CARE GIVEN.• DAY 6: DOG FAT POS. START PVRV ID. ERIG PASTEUR INTO WOUNDS• REST IM ( GLUTEUS)• DAY 9: PVRV ID 0.1 Ml x 2• Day 12: PVRV ID 0.1 Ml x 2• Day 26: FEVER, HEADACHE, NUMBNESS OF RT ARM AND • SHOULDER, LATER WEAKNESS OF HAND AND • DYSARTHRIA.• DAY 27: STILL COHERENT. NOW DYSEASTHESIA OF LT ARM.• ADMISSION TO CUH. START PHOBIC SPASMS,• AEROPHOBIA, SEIZURES, AND RAPID PROGRESSION.• DAY 28: DEATH. FAT POSITIVE ERROR: CAT III. DELAY 6 DAYS QSMI COLLECTION

PEP FAILURE, MANAGEMENT ERROR 1994

• THAI GIRL AGE 2.5 (BANGKOK )• DAY 0: BITTEN BY STREET DOG • MULTIPLE DEEP WOUNDS FACE.• APPROPRIAT WOUND CARE• SUTURES UNDER KETAMINE ANESTHESIA• PCEC VACCINE BY TRC ID REGIMEN • DAY 1: ERIG (BERNA) 40 IU/KG HALF INTO WOUNDS AND • REST IM ( GLUTEUS). NOT ALL WOUNDS INJECTED• DAY 3: PCEC ID 0.1 X 2• DAY 7: PCEC ID 0.1 X 2• DAY 10: ONSET OF TYPICAL FURIOUS RABIES WITH PHOBIC • SPASMA, AEROPHOBIA, HYDROPHOBIA.• HOSPITALIZED FOR COMFORT CARE.• DAY 17: DIED. NO AUTOPSY.• ERROR: CAT III, SUTURE OF WOUNDS BEFORE RIG• QSMI COLLECTION

PEP FAILURE, MANAGEMENT ERROR 1987

• THAI BOY AGE 9 Y (CHACHINGSAO)

• DAY 0: BITTEN BY STREET DOG. SEVERE WOUNDS AT 12 SITES OF FACE,

• HEAD, ARM. APPROPRIATE WOUND CARE

• NOT ALL WOUND INJECTED WITH 4.2 mL ERIG (BERNA) UNDILUTED

• PVRV ( PASTEUR MERIEUX) 1 mL IM DELTOID

• DAY 3: PVRV IM

• DAY 7: PVRV IM

• DAY 14: PVRV IM

• DAY 21: ONSET OF ENCEPHALITIC RABIES

• DAY 25: DEATH. AUTOPSY POSITIVE FOR RABIES

• ERROR: CAT III, NOT ALL WOUNDS INJECTED WITH ERIG

• QSMI COLLECTION

PEP FAILURE, MANAGEMENT ERROR

2000 2000 • Day 0: THAI GIRL 7 YR, CHACHINGSAO

• DOG BITE : FACE LEFT CHEEK, EYE BROW, ARM• WOUND CARE,• STARTED PET WITH 8-SITE ID REGIMEN (PCEC –CHIRON)• NO RIG AVAILABE

• DAY 7: 4-SITE ID GIVEN. CHILD WELL

• DAY 12: HEADACHE, FEVER, PAIN OVER LEFT EAR, HOSPITALIZED

• DAY 13: WORSE, CONFUSED, AEROPHOBIA, SPASMS, AGGITATED, • ENT NEG, CT NEG, ROUTINE LAB, SPINAL FLUID • UNREMARKABLE.

• DAY 14: COMATOUS, INTUBATED

• DAY 15: DIED, NO AUTOPSY .

• ERROR: CAT III, 8-SITE IN PLACE OF RIG• SRIAROON C. VACCINE 2003

PEP FAILURE, MANAGEMENT ERROR2005

DAY 0: BURMESE FEMALE AGE 44, NORMAL HOST, DOG BITE IN BURMA, LACERATIONS

FACE INCLUDING NOSE. WOUND CARE IN BURMA WITH SUTURE. TRANSFER

TO THAI SIDE SAME DAY. WOUND INJECTED WITH ERIG (THAI RED CROSS

PEPSIN DIGESTED). STARTED ON PCEC IM DELTOID

DAY 3: PCEC IM

DAY 7: PCEC IM

DAY 14:PCEC IM

DAY 15: ONSET OF FURIOUS RABIES SYMTOMS

DAY 17: DEATH

(Potencies of vaccine and ERIG checked at US-CDC, all meet standards)

ERROR: CAT III, SUTURE BEFORE RIG INJECTION

QSMI COLLECTION

PEP FAILURE1997

• THAI FEMALE 72 Y (BANGKOK)

• DAY 0: BITTEN BY UNKNOWN DOG. SMALL DEEP WOUND CHEEK• IMMEDIATE WOUND CARE.• WOUND INJECTED WITH ERIG (PASTEUR ) REST DELTOID• PVRV (PASTEUR-MERIEUX) IM DELTOID

• DAY 3: PCEC (CHIRON) IM DELTOID

• DAY 7: PCEC (CHIRON) IM

• DAY 14: PCEC (CHIRON) IM

• DAY 20: ONSET OF PARALYTIC RABIES. FULL ICU CARE • • DAY 29: (SERUM ANTIBODIES 27 IU SERUM AND DETECTABLE IN CNS

• DAY 31: DEATH. AUTOPSY POSITIVE FOR RABIES

• T. HEMACHUDHA ET AL. CID. 1999; 28: 143-44

PEP FAILURE1997

• THAI BOY 9 (BANGKOK )

• DAY 0: DOG BITE. SUPERFICIAL BLEEDING • SCRATCH OF NOSE AND CHEEK WITHOUT BLEEDING. • APPROPRIATE WOUND CARE .• WOUNDS INFILTRATED WITH ERIG PASTEUR REST IM. • PCEC CHIRON IM DELTOID.

• DAY 3: PCEC IM DELTOID

• DAY 7: PCEC IM DELTOID

• DAY 14: PCEC IM DELTOID

• DAY 30: ONSET OF FURIOUS RABIES

• DAY 37: DEATH. AUTOPSY POSITIVE FOR RABIES

T. HEMACHUDHA ET AL. CID. 1999; 28: 143-44

WHY PEP FAILURES?

POOR OR NO WOUND CARE

VACCINE OF POOR QUALITY

RIG OF POOR QUALITY

NO RIG GIVEN AT ALL

NOT ALL BITE WOUNDS INJECTED

EXCEPTIONALLY LARGE VIRAL LOAD

VIRUS CLOSE TO NERVE 0R RAPIDLY NVASIVE VIRUS STRAIN UNRELIABLE REPORTING

Child face

Hand bites

WHAT ARE WE MISSING?Old data indicate as much as 40% rabies infectionrate can be avoided by energetic wound cleaning [1].

Wound cleaning and antisepsis is enshrined in WHO guidelines [2]

3 rabies PEP centers in India and Pakistan were visitedEach treated over 100 animal bites daily. None had facility to clean wounds

We may many PEP failures by just washing wounds

• 1) Kaplan MM, Cohen D, Koprowski H, et al Studies on the local treatment of wounds for the prevention of rabies. Bull WHO 1962;26:765-75.

• 2) WHO. Expert Committee on Rabies, Technical Report Series 824. Geneva 1992.

AN ARGUMENT FOR PREP

• IN RABIES HYPERENDEMIC REGIONS WHERE DOG CONTROL IS FAILING

• FOR CHILDREN WHERE PEP NOT READILY AVAILABLE OR WHO LIKELY NOT REPORT EXPOSURES

• CAN BE DONE USING ID METHOD AND MULTIPLE DOSE VIALS.