Updated on Regimens for Post-Exposure Prophylaxis Rabies-Free... · Flury LP PM-strain b PM-strain...
Transcript of Updated on Regimens for Post-Exposure Prophylaxis Rabies-Free... · Flury LP PM-strain b PM-strain...
Prof. Terapong Tantawichien, MD.
President of Infectious Diseases
Association of Thailand
Head of Division of Infectious Diseases,
Department of Medicine,
Chulalongkorn University
Assistant Director of Queen Savabha
Memorial Institute, Thaialnd
Updated on Regimens for Post-Exposure Prophylaxis
Post-Exposure Prophylaxis ( PEP) for Possible Rabies Exposure
Any animal bite or scratch should receive prompt local first aid by
thorough cleansing of wound with soap and povidone iodine.
Non-immunized patient will need to obtain full PEP in the event of
a possible exposure to a proven or suspected rabid animal. RIG and a
series of vaccination for severe exposure.
Concern: - RIG or rabies vaccine may not be available in
the destination country.
- Different post-exposure vaccine schedules,
alternative routes of administration, and other
rabies vaccines may be used abroad.
Immunized patient (who have completed a pre-exposure or post-
exposure rabies immunization) received the only booster vaccination
and do not require RIG.
Regimen Day 0-Day 3-Day 7-Day 14-Day 28-Day 90
Essen IM
Zagreb
(2-1-1) IM
TRC-ID
Booster
Vaccination
For pre-immunized host WHO 2013
1-1-1-1-1-0 or
1-1-1-1-0-0
( US, alternative WHO - Healthy, fully immune
competent host-WHO (vial/site)
2-0-1-0-1-0 (vial/site)
2-2-2-0-2 (0.1 ml/site)-modified
WHO- not definite potency for ID dose
REGIMENS FOR POST-EXPOSURE TREATMENT
1-1 IM or ID 4-site ID on single day
WHO recommendation: two doses of intramuscular (IM) or intradermal
(ID) vaccination on days 0 and 3.
As an alternative regimen, the patient may be offered a single-visit 4-
site ID regimen consisting of 4 injections of 0.1 mL of CCV equally
distributed over deltoids or anterior thighs.
Time
Primary vaccination
(tissue-culture vaccines) day 0 day 3
4-site ID:
Detoid and
Thigh or suprascrapular area
1 site ID
IM
1 site ID
IM
WHO Position Paper : Wkly Epidemiol Rec 2010(August 6) WHO 2013
RABIES EXPOSURE
Conventional Booster
vaccination
Alternative Booster vaccination
Rabies Vaccines and Immunoglobulin for Humans
Vaccine name Virus strain Substrate Type
Cell-culture
Human diploid cell culture
(HDCV)
Purified chick embryo cell
(PCECV)
Purified Vero cell (PVRV)
VERORAB, ABHAYRAB
Chromatographic
Purified Vero cell (CPRV)
Purified duck embryo (PDEV)
PM-strain
Flury LP
PM-strain
PM-strain
PM-strain
Human culture
Fibroblasts
Chick embryo cell
Vero cell
Vero cell
Duck embryo
b-Propiolactone-
inactivated
b-Propiolactone-
inactivated
b-Propiolactone-
inactivated
b-Propiolactone-
inactivated
b-Propiolactone-
inactivated
Highly purified equine RIG (ERIG) are now being manufactured in
Europe, Thailand, India, China and South America. HRIG – local products ( The Thai Red Cross Society,….)
Future Regimens for Post-Exposure Prophylaxis ?
Shorten regimens Reduced cost of vaccine High immunogenicity
Less visits
Safe and less side effects
Day 0 3 7 14
A control group received 2-site intradermal injections on days 0, 3, and 7 and 1 injection on days 28 and 90 ( standard TRC-ID) with equine rabies immunoglobulin. Results. All subjects in all groups had NAb value 0.5 IU/mL on days 14 and 28. The percentages of subjects who had a NAb value 0.5 IU/mL from days 0 through 360 were not significantly different among the 3 groups. GMTs for subjects receiving the 4-site intradermal regimen, with or without ERIG, had significantly higher NAb values than did the control group on day 14 and 28 . Clin Infect Dis 2010
4-site intradermal injections of 0.1 mL of PVRV to the deltoids and thighs on days 0, 3, and 7, with and without equine rabies immunoglobulin (40 IU/kg).
4-site ID
Evaluation of a one week intradermal regimen for rabies post-
exposure prophylaxis: Results of a randomized, open label,
active-controlled trial in healthy adult volunteers in India Sudarshan MK ; Human Vaccine Immunotherapeutic 2012 80 adult volunteers were enrolled and randomly either to PCECV or PVRV,
Each subject received intradermally one of the vaccines, using the one week regimen (4–4-4). Blood samples were collected on Days 0, 7, 14, 28,180 and 365
Rabies virus neutralizing antibody response following “single visit – 4 sites” ID booster
vaccination with PCECV and PVRV
Days Vaccine No. of
subjects
Range
of
RVNA
conc.
GMC
95% Confidence
Interval for GMC
t-value
P-value
(two-
tailed) Lower
Bound
Upper
Bound
Day 7 PCECV 8 2.5–5.5 3.81 3.13 4.64
0.515 0.612 PVRV 14 2.5–5.7 3.60 3.11 4.17
Day 14 PCECV 8 7.5–10.5 8.93 7.92 10.08
0.495 0.626 PVRV 14 6.5–10.6 8.62 7.81 9.51
Comparison of safety and immunogenicity of 2 WHO
prequalified rabies vaccines administered by one week,
4 site intra dermal regimen (4-4-4-0-0) in animal bite cases Narayana A; Human Vaccine Immunotherapeutic 2015 Comparative, open label, phase III, randomized clinical trial conducted in India.
90 subjects with CAT II/III exposures: ERIG was administered to CAT III exposures.
0.1 mL of either PCECV or PVRV was administered intradermally into 4 sites on days 0, 3 and 7 to all subjects.
Day of
blood
sample
Vaccine No. of
subjects
Range
(IU/mL)
GMC
(IU/mL)
95% CI t-value P value
Lower
Bound
Upper
Bound
14 Rabipur 45 4.5–16.5 14.50 13.50 15.57 0.095 0.924
Verorab 44 4.5–16.5 14.43 13.41 15.53
90 Rabipur 42 6.5–14.5 11.78 11.27 12.31 0.432 0.667
Verorab 43 10.5–14.5 11.93 11.47 12.40
365 Rabipur 32 4.5–8.5 5.95 5.50 6.44 0.933 0.354
Verorab 38 4.5–7.5 5.67 5.29 6.08
Comparison of geometric mean RVNA concentration following administration of Rabipur or Verorab using one week, 4 site ID regimen in animal bite cases
WHO recommendation (2013):
- 1 dose of IM or intradermal (ID) vaccination on days 0 and 3.
- Alternative regimen, a single-visit 4-site ID regimen consisting of
4 injections of 0.1 mL of CCV equally distributed over deltoids
or anterior thighs.
Time
Primary vaccination
(cell-culture vaccines) day 0 day 3
4-site ID:
Detoid and
Thigh or suprascrapular area
1 site ID
IM
1 site ID
IM
WHO Position Paper : Wkly Epidemiol Rec 2010(August 6) WHO 2013
RABIES EXPOSURE
Conventional Booster
vaccination
Alternative Booster vaccination
Clin Infect Dis 2001
Clin Infect Dis 2010
The period from 1998 through 2008 at QSMI, 5116 patients who received the
4-site booster vaccinations. 3335 patients (65.2%) had WHO category III risk
253 (4.95%) of the 5116 patients were bitten by animals with proven rabies.
No treatment failure, reduced direct and indirect cost of treatment
We conducted a prospective study of neutralizing antibody (Nab)
response after single-visit booster regimens compared with
conventional IM booster vaccination for PEP.
New Single-Visit Booster Regimens:
Time
Primary vaccination
(cell--culture vaccines) day 0 day 3
1 site ID
IM
1 site ID
IM
RABIES EXPOSURE
Alternative booster vaccination ?
• 2-site ID booster regimen with CCV administered on day 0
(may reduce the volume of vaccine and adverse reaction).
• One intramuscular booster with CCV dissolved in aluminium-
adjuvanted tetanus toxoid on day 0 (Phanuphak P, et al. Immunoenhancement
with combined rabies and aluminium-adjuvanted tetanus vaccines. Vaccine 1989; 7:249-52).
Time
Pre-exposure vaccination
(PVRV) day 0 day 3
Single-visit booster Group A (n=22) - 0.1 mL x 2 ID injections (total= 0.2mL)
Group B (n=22) - 0.2 mL x 2 ID injections (total= 0.4mL)
Group C (n=20) - 0.5 mL x 1 IM injection (dissolved in adjuvented TT)
Conventional booster (control)
Group D(n=22) – conventional 2 doses IM
0.5 mL x 1 IM injection on days 0 and 3
1 site IM 1 site IM
1 year later and no rabies exposure
Materials and Methods
A group of 86 healthy subjects (age range 19-20 years) who had received an
intradermal pre-exposure vaccination with purified Vero cell rabies vaccine
(PVRV; Verorab®: Sanofi Pasteur, France; batch number E0316-; potency, 13.1
IU/0.5 mL) 1 year earlier were recruited and randomly divided into 4 groups:
PVRV (Verorab®; Sanofi Pasteur, France; batch E0316;potency of 13.1 IU per ampule
and contains 0.5 mL of the diluent volume (potency, 2.6 IU /0.1 mL, 5.2 IU/0.2 mL).
Table 1. GMTs and range of titers of rabies Nab following different
booster regimens ( gr. A, gr B, gr C ) and conventional intramuscular
booster vaccination ( gr. D )
Days after booster vaccination
Group,finding 0 5 14 30** 180 360
Group A: 2-site 0.1ml ID day 0(n=22):GMT 0.7 2.2 18.5* 21.3 12.9 9.3
Range of Nab .3-3.9 .3-26.1 4.6-118 5.3-136 2.7-218 1.8-80.5
Subjects Nab <0.5 IU/ml 6 1 0 0 0 0
Group B: 2-site 0.2ml ID day0(n=22):GMT 0.7 2.2 40.5 39.6 27.0 13.2
Range of Nab titers .2-2.3 .7-9.2 9.6-648 3.3-569 1.3-336 2.1-218
Subjects Nab <0.5 IU/ml 7 0 0 0 0 0
Group C: 0ne IM+TT days 0 (n=20): GMT 0.6 1.4 37.0 32.1 ND 6.15
Range of Nab titers .07-2.2 0.1-5.7 8.5-147 10.5-147 ND 1.4-29.7
Subjects Nab <0.5 IU/ml 2 0 0 0 ND 0
Group D: control IM days 0,3 (n=22): GMT 0.7 1.1 40.9 25.8 16.8 6.3
Range of Nab titers .2-2.2 .3-5.0 6.2-208 4.8-136 2.7-175 1.2-45.5
Subjects Nab <0.5 IU/ml 6 2 0 0 0 0
*p<.05 gr. A vs. gr. B, C and D(control), **P< .05 gr. B vs. gr. A and D(control)
GMT of Nab group A was sig. lower than group B, C and D on day 14 (P <.05).
GMTs of Nab in group B (0.2 mL/ID site) were significantly higher than group A
(0.1 mL/ID site) and D on days 30 (P<.05).
There was no significant diff. between group C and group D (p > .05).
THANK YOU