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Prof. Terapong Tantawichien,M.D. Division of Infectious Diseases Department of Medicine Chulalongkorn University And Queen Savabha Memorial Institute ( WHO Collaborating for Rabies Research)
Rabies : Epidemiology of Human Rabies
Human Rabies: Dx and Treatment
Prevention
Post-Exposure Treatment Pre-Exposure Prophylaxis
QSMI,
Bangkok, Thailand
WWW. Saovabha.com
Rabies •Zoonotic disease: RNA virus: Family Rhabdoviridae, Genus Lyssavirus •Acute, progressive encephalomyelitis •Clinical disease almost always fatal
Human Rabies • Human rabies is most common in people aged under
15,however, all aged groups are susceptible.
• Reported incidence of human rabies cases is often
incomplete and the estimated of 50,000 deaths per year
may be an underestimated.
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0-4 5-9 10-14 15-24 25-34 35-44 45-54 55-64 65+
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0.03
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0.08
Rate
per
100,0
00 P
op.
Fig. 4 Reported Cases of Rabies per 100,000 Population
by Age-Group, Thailand, 2006.
WHO 2013
In Asia, the main route of rabies virus transmission is through rabid dog bites ( 96–98% of human rabies cases) In Asia, more than 2.5 billion people are potentially exposed to rabies infection; each year, an estimated 8 million people receive treatment after being exposed to animals that are suspected of rabies. The economic burden has been estimated to be US$ 563 million (96.5% of the total burden of rabies worldwide). Preventing the incurable: Asian rabies experts advocate rabies control (Meeting report);Vaccine 2006
Estimated numbers of human deaths from rabies, post-exposure treatments and pre-exposure prophylaxis (2004): Vaccine 2006
Country Population (million Notifiable No.of deaths No.of deaths inhabitants diseases / 100,000 China 1,306 Yes 0.2 2,651
India 1,027 No 2-3 20,000
Thailand 63 Yes 0.03 19
Philippines 84 Yes 0.29 248
Sri Lanka 20 Yes 0.48 97
Indonesia 219 Yes 0.045 99
Vietnam 82 Yes 0.099 81
HUMAN RABIES PREVENTION
CONTROL
Eradication
Stelirization-surgery,chemical
IMMUNIZATION
Free animal vaccine
VECTORS BITE HUMAN Rabies
PREVENT IMMUNIZATION
BITE
Education Post-exposure vac.
Law of regulation
Bite report
Diagnosis/treatment
Pre-exposure vac.
Community education
Co-ordination - Funding - High biological products
Recognized Primary host Geographical range and species
(WHO2013)
Rabies virus (RABV) Carnivora and bats (Chiroptera) Terrestrial mammals worldwide
except in Australia, Antarctica
islands; bats New World only
Australian bat lyssavirus Pteropodid bats (at least 4 species Australia, nearby islands
(ABLV) of Pteropus genus) and insectivorous
bats (Saccolaimus albiventris)
European bat lyssavirus 1 Insectivorous bats (predominantly Most of Europe
(EBLV1) Eptesicus serotinus)
European bat lyssavirus 2 Insectivorous bats (predominantly North-western Europe
(EBLV2) Myotis daubentonii and M. dasycneme)
Khujand virus (KHUV) Insectivorous bat Myotis mystacinus Central Asia
Aravan virus (ARAV) Insectivorous bat Myotis blythi Central Asia
Bokeloh bat lyssavirus(BBLV)Insectivorous bat Myotis nattereri France, Germany
Irkut virus (IRKV) Insectivorous bat Murina leucogaster Eastern Asia
Duvenhage virus (DUVV) Insectivorous bats Sub-Saharan Africa
Lagos bat virus (LBV) Pteropodid bats of several genera Sub-Saharan Africa
Mokola virus (MOKV) Unknown Sub-Saharan Africa
Shimoni bat virus (SHIBV) Insectivorous bat Hipposideros commersoni Kenya
West Caucasian bat virus (WCBV) Insectivorous bats from genus Miniopterus South-east Europe
Ikoma lyssavirus (IKOV) Not known United Republic of Tanzania
Rabies Virus Transmission
Rabies is spread between mammals by bites, by
contamination of intact and abraded mucosal membranes with
virus-laden saliva, by inhalation of aerosal, by ingestion of
infected prey and transplacentally.
In man, rabies is nearly always
secondary to bites, however, human
infections caused by non-bite exposures
including scratch, lick, and inhalation of
aerosols and transplantation of infected
cornea and organs also occur.
Jackson AC; Can. J. Neurol. Sci. 2011; 38: 689-695
Charles E Rupprecht,Lancet 2004
Rupprecht, CE NEJM 2004
Bat Rabies in the US and Canada Serres GD;CID 2008:46
Although inexpensive veterinary rabies
vaccines are available, mass
vaccination of dogs is not effective in
most of Asia and Africa.
Visitors to countries where canine rabies is endemic must assume that most local dogs have not been vaccinated.
Street dogs represent the most frequent risk for bite exposure
to travelers, followed by cats, monkeys, especially those that live near temples in parts of Asia.
Puanghat A; J Med Assoc Thai 2005 40% owned animals 15% history of vaccination
Laboratory proven rabies cases in Thailand, 2009 Wilde H, et al, Current Topics in Microbiology and Immunology 2012
In Asia, the main route of rabies virus transmission is through rabid dog bites ( 96–98% of human rabies cases)
Jackson AC; Can. J. Neurol. Sci. 2011; 38: 689-695
Risk of Rabies Exposure
Estimated numbers of human deaths from rabies, post-exposure treatments and pre-exposure prophylaxis (2004)Vaccine 2006 Country Post-exposure treatment No.of deaths
No.PET % TCV PET with RIG China 2,500,000 100% 2.1% 2,651
(0.2%)
India 2,300,000 78% 1.3% 20,000
(0.2%)
Thailand 351,535 100% 9% 19
(0.6%)
Philippines 55,301 100% 10% 248
(0.5%)
Sri Lanka 200,000 100% 25% 97
(1%)
Indonesia 6,770 50% 22 99
(219m)
Vietnam 615,000 10% 3% 81
Rabies is an endemic disease in Asia which causes approximately
31 000 deaths and where more than 8 000 000 courses of PEP are given annually.
The population of the 15 Asian countries endemic for rabies is 3.11 billion.
Duration of Different Stages Rabies
Durations
(% of cases)
Under 30 day:25%
30-90 days: 50%
90 days to yr : 20%
More than 1 yr: 5%
2-10 days
2-7 days
2-7 days
0-14 days
Stage
Incubation period
Prodrome and early
symptoms
Acute neurologic
disease
Coma
Death*
Type
(% of cases)
Furious rabies
(80%)
Paralytic rabies
(20%)
Atypical rabies
Associated Findings
None
Paresthesiae ,itching or
pain at the wound
fever; malaise;
anorexia; nauses;
and vomiting.
Hallucination; bizarre
behavior, anxiety;
agitation;
hydrophobia;
autonomic
dysfunction
Ascending flaccid
paralysis
*Rare recoveries have been reported. (Data from Fishbein.)
Diagnosis of human rabies
Definite : Presence of definite bite exposure plus 3 major cardinal manifestations - Aerophobia/hydrophobia - Fluctuating consciousness - Autonomic stimulation signs And/or one or more of the followings 1. Presence of Nab to rabies virus in serum/CSF in non-vaccinated patient 2. Virus isolation from suspensions of biopsy (brain or saliva) 3. Antigen detection by direct IF method (skin biopsy/brain) 4. Detection of rabies virus RNA in saliva by RT-PCR,NASBA 5. Local prodrome at the site of bite (and progress to involve the entire bitten region) plus above criteria Probable - Viral encephalitis (+bite exposure) plus clinical features (except phobic spasm) - Atypical GBS (+bite exposure): Fever, percussion edema, SIADH, bladder incontinence
Potential Treatment Options in
the Management of Human Rabies Cases
Ribavirin
Interferon
Rabies vaccine
Rabies immunoglobulin
Monoclonal antibody
Ketamine
Corticosteroids
A.C. Jackson / Antiviral Research 2013
HUMAN RABIES PREVENTION
CONTROL
Eradication
Stelirization-surgery,chemical
IMMUNIZATION
Free animal vaccine
VECTORS BITE HUMAN Rabies
PREVENT IMMUNIZATION
BITE
Education Post-exposure vac.
Law of regulation
Bite report
Diagnosis/treatment
Pre-exposure vac.
Community education
Co-ordination - Funding - High biological products
Rabies Immunization
• Post-Exposure Treatment Guideline and Regimens for Post-Exposure
Treatment:
Important Issues of ID regimens in limited-
resource countries
Rabies Immunoglobulin:
Inappropriate RIG Treatment
Booster Vaccination for Pre-Immunized Patients:
How and What’s benefit ?
• Pre-Exposure Prophylaxis
Pre-Exposure Prophylaxis for Children:
Important Issues of ID regimens
Abbreviate schedule of Pre-Exposure Regimen
Post-exposure rabies treatment
Nab IU/ml
Day after treatment
0.5
3 7 14 28
RIG
(passive
immunization)
Vaccine
(Active immunization)
First aid treatment Cleansing wound (s)
Medical treatment
Factors that should be considered in deciding whether or not to initiate postexposure prophylaxis include: • nature of the contact or injury • presence of rabies in the area where the contact occurred or where the animal responsible originated • availability of the animal for laboratory examination or observation • species of the animal • clinical status of the animal responsible • vaccination history of the animal, and type and timing of vaccine used The decision to administer post-exposure prophylaxis after an
exposure to an apparently healthy animal should be based on a careful risk assessment by a qualified medical professional. WHO 2004
Rupprecht, CE; NEJM 2004
Bite exposure ( wound care )
Rabies post-exposure treatment
Consider exposure
Category I Category II, III
Animal examination (brain)
possible( 20% ) not possible( 80% )
negative positive dog/cat wildlife
no treatment start treatment observation
yes no start treatment
normal abnormal FAT
Consider: 1. animal receives good care/minimal exposure risk
2. reliable history of vaccination during past 2 years
3. provoke condition
Complete Not complete
close observe for 10 days start treatment
start treatment stop if animal remain normal for 10 days
once disease symptoms appear
Diagram for Post-Exposure Rabies Treatment in Thailand
+
Rabies Post-Exposure Treatment
Group 1 ) Non-immunized patients :
WHO II : ESSEN-IM ,Zagrab IM, TRC-ID(2-2-2-0-2) regimen
WHO III : ESSEN-IM ,Zagrab IM, TRC-ID(2-2-2-0-2) regimen
plus rabies immunoglobulin (ERIG or HRIG)
Group 2 ) Patients who have received pre-or post-exposure
rabies vaccination with cell-culture rabies vaccine :
WHO II or III : Booster vaccination
Regimen : IM or ID on days 0 and 3
Regimen : 4-site ID(0.1ml) on day 0 ( alternate )
Group 3 ) Patients who have received semple or
suckling mouse brain Vaccine :
Treatment as group 1
Important Rabies Vaccines 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
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
IM - HDCV, PCECV, PVRV (Verorab, Abhayrab), CPRV, PDEV
Interchangeable types of vaccine- IM regimens
HDCV-PCECV Briggs DJ, et al. Vaccine 2000
ID-TRC- PCECV, Verorab, CPRV( study at QSMI, Thailand)
No study of interchangeable type of vaccine on ID regimen
Regimen Day 0-Day 3-Day 7-Day 14-Day 28-Day 90
Essen IM
Zagreb
(2-1-1) IM
TRC-ID
Oxford-ID
8 site
1-1-1-1-1-0 (5 doses IM) or
1-1-1-1-0-0 ( 4 doses IM- US, alternative WHO
– Healthy, fully immune competent host-WHO
(vial/site)
2-0-1-0-1-0 (vial/site)-WHO
2-2-2-0-2 (0.1 ml/site)-modified
WHO- not definite potency for ID dose
8-0-4-0-1-1
(0.1 ml of HDCV or PCEC or PVRV/site)
REGIMENS FOR POST-EXPOSURE TREATMENT
Rabies
Post-Exposure
Treatment Standard WHO intramuscular regimen
(ESSEN)
Day 0 3 7 14 28 90
+RIG
Dose: one IM dose (1 vial) into deltoid muscle (>2.5 IU/vial)
Type of vaccine: all tissue culture vaccines, PDEV
5 vial: 5 visits
US-FDA-approved IM-regimen 0-3-7-14 for post-exposure treatment
Intramuscular regimen-US-FDA-CDC, Alternative regimen for fully
immunocompetent( WHO position Paper; 2010,WHO 2013 )
Mediatrice Uwanyiligira: Clin Infect Dis 2012
Rabies Post-Exposure Treatment
Multi-site intramuscular regimen (Zagreb 2-1-1)
Day 0 3 7 14 21 28 90
+RIG
Dose : one IM dose (1 vial) into deltoid muscle (>2.5 IU/vial)
Type of vaccine: all tissue culture vaccines, PDEV
4 vial : 3 visits
Use : only WHO category II ?
Rabies Post-Exposure Treatment
2 site intradermal regimen (TRC 2-2-2-0-1-1, 2-2-2-0-2)
Day 0 3 7 14 28 90
+RIG
Dose : intradermally on upper arm/ 0.1 ml
/ site ID ( potency HDCV,PCECV, PVRV >
0.5 or 0.7 IU/site ID)
Type of vaccine : PVRV, PCECV, HDCV
<2 vial : 5 visits
Rabies Immunization
• Post-Exposure Treatment Guideline and Regimens for Post-Exposure
Treatment:
Important Issues of ID regimens in limited-
resource countries
Rabies Immunoglobulin:
Inappropriate RIG Treatment
Booster Vaccination for Pre-Immunized Patients:
How and What’s benefit ?
• Pre-Exposure Prophylaxis
Pre-Exposure Prophylaxis for Children:
Important Issues of ID regimens
Abbreviate schedule of Pre-Exposure Regimen
Use of rabies immune globulin (RIG)
Group 1 ) Non-immunized patients :
WHO category III : TRC-ID,ESSEN-IM regimen plus RIG
• Type : Equine rabies immune globulin
(ERIG) = 40 IU/kg
ERIG (QSMI)
Intradermal skin test: ERIG 1:100
- 0.02 mL read 15 min
Positive - wheal > 10 mm
(CID 1995; Tantawichien T, et al.)
Other ERIGs in Thailand
Skin tests are not recommended before administration of ERIG, as such
tests poorly predict severe adverse events and should not be the basis
for not giving equine immunoglobulin if it is needed. ERIG should be
administered under conditions that would allow management of an
anaphylactic reaction. (WHO 2013)
• Human rabies immune globulin
(HRIG) = 20 IU/kg
RIG Administration : single dose at the same time
as the first dose of vaccine (site of
RIG injection distant from site of
vaccine injection)
: It should be infiltrated around
and into all wounds If it is insufficient
to infiltrate all wound, sterile saline
can be use to dilute it (2-3 fold)
: Any remaining of RIG should
be injected IM at anterior thigh or
gluteal muscle
Both L; Lancet Infect Dis 2012;12: 397–407
Rabies Immunization
• Post-Exposure Treatment Guideline and Regimens for Post-Exposure
Treatment:
Important Issues of ID regimens in limited-
resource countries
Rabies Immunoglobulin:
Inappropriate RIG Treatment
Booster Vaccination for Pre-Immunized Patients:
How and What’s benefit ?
• Pre-Exposure Prophylaxis
Pre-Exposure Prophylaxis for Children:
Important Issues of ID regimens
Abbreviate schedule of Pre-Exposure Regimen
Rabies Post-Exposure Treatment
Group 1 ) Non-immunized patients :
WHO II : ESSEN-IM ,Zagrab IM, TRC-ID(2-2-2-0-2) regimen
WHO III : ESSEN-IM ,Zagrab IM, TRC-ID(2-2-2-0-2) regimen
plus rabies immunoglobulin (ERIG or HRIG)
Group 2 ) Patients who have received pre-or post-exposure
rabies vaccination with cell-culture rabies vaccine :
WHO II or III : Booster vaccination
Regimen : IM or ID on days 0 and 3
Regimen : 4-site ID(0.1ml) on day 0 ( alternate )
Group 3 ) Patients who have received semple or
suckling mouse brain Vaccine :
Treatment as group 1
Post-exposure prophylaxis for previously vaccinated individuals • For rabies-exposed patients who can document previous
complete pre-exposure vaccination or complete post-exposure
prophylaxis with a CCV.
• People vaccinated against rabies who have demonstrated
rabies-virus neutralizing antibody titres of ≥0.5 IU/ml.
The WHO recommends booster vaccination if
there is an additional occurrence of potential
exposure. Vaccination cards recording previous immunizations are invaluable for making correct decisions.
RIG is not indicated in such cases. WHO Position Paper : Wkly Epidemiol Rec 2010(August 6)
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
Clin Infect Dis 2010
The period from 1998 through 2008 at QSMI,
5116 patients who received the 4-site booster vaccinations.
The single-visit 4-site ID booster vaccination consists of 0.1-mL ID injections,
one each at both deltoids and thighs, using PVRV or PCECV.
3335 patients (65.2%) had WHO category III risk .
Most of the patients (83.3%) had received PEPpreviously, and the remaining
patients had received PrEP. (median time was 6 years: range 1 month to 25
yrs). Most of the biting animals were stray animals and were not available
for observation or necropsy. However, 253 (4.95%) of the 5116 patients were
bitten by animals with proven rabies.
No treatment failure, reduced direct and indirect cost of treatment
The WHO recommends booster vaccination if there is an
additional occurrence of potential exposure.
QSMI since 1998 Booster 1: 2-visit ID booster regimen(24%)
2-visit IM booster regimen (18%)
Booster 2 : 4-site ID booster regimen (58%) – 67% for severe exposure
Time
Primary vaccination
(tissue-culture vaccines) day 0 day 3
Booster 2
4-site ID:
Detoid and
Thigh or suprascrapular area
Booster 1
1 site ID
IM
1 site ID
IM
WHO Position Paper : Wkly Epidemiol Rec 2010(August 6) WHO 2013
RABIES EXPOSURE
Suwansrinon K;QSMI Vaccine 2006
Special Hosts and Rabies Vaccination
Toovey S :Travel Medicine and Infectious
Disease (2007) 5, 327–348
NAME OF PRESENTATION | 64
PVRV experience in children : Demonstrated efficacy study in different regimen with 100% survival rate
Survival of patients (total n=376 ) with Cat III exposure to proven rabid animals, after PEP
Study reference Number of
subjects Vaccination schedule Follow-up period Survival rate
[Chutivongse, 1988] 309 Essen-IM (6-dose) +/- RIG or
TRC-ID +/- RIG 3 months 100%
[Chutivongse, 1991] 40 Zagreb-IM + RIG
1 year
(100% sc at D14) 100%
[Thongcharoen,
1989]
27 Essen-SC +HRIG 2 year (100% sc at D14)
100%
1.Chutivongse S, Supich C, Wilde H. Acceptability and efficacy of purified vero-cell rabies vaccine in Thai children exposed to rabies. Asia Pac J Public Health. 1988;2(3):179-84.
2. Chutivongse S, Wilde H, Fishbein DB, Baer GM, Hemachudha T. One-year study of the 2-1-1 intramuscular postexposure rabies vaccine regimen in 100 severely exposed Thai patients using rabies immune globulin and Vero cell rabies vaccine. Vaccine 1991;9(8):573–6. 3.Thongcharoen P, Wasi C, Sirikawin S, Chaiprasithikul P, Puthavathana P. Rabies and post-exposure prophylaxis in Thai children. Asian Pac J Allergy Immunol 1989;7(1):41–6.
Vaccination of immunocompromised individuals Several studies of patients with HIV/AIDS have shown that those with
very low CD4 counts mount a significantly lower or no detectable
neutralizing antibody response to rabies virus.
In these patients and others in whom the presence of immunological
memory is no longer assured, proper, thorough wound treatment
and antisepsis accompanied by local infiltration of human or equine
rabies immunoglobulin and a complete series of five intramuscular
doses of rabies CCEEV is required for category II and III exposures.
When feasible, the rabies virus neutralizing antibody response should
be determined 2–4 weeks after vaccination to assess whether an
additional dose of vaccine is required.
When in doubt, consult an infectious disease specialist with expert
knowledge of HIV/AIDS and rabies prevention.
WHO 2013
Rabies Immunization in Immunocompromised Hosts
HIV-infected persons with low CD4+ T lymphocyte counts (<300-400/ml) have
an impaired (primary) antibody response after receipt of tissue culture rabies vaccines
(intradermal;2-2-2-0-1-1:Tantawichien T;CID2000 and ESSEN IM:abstract).
AIDS persons with CD4+ T lymphocyte counts <200/ml have an impaired
(primary) antibody response after receipt of tissue culture rabies vaccines (intradermal;
4-4-4-0-2-2:Tantawichien T;CID2001)
7 AIDS patients with CD4+ cell counts of less than 100 cells/µL
(range, 1-99 cells/µL) had a poor or even undetectable Nab response to doubling the
doses of intramuscular rabies vaccination with aluminum hydroxide-absorbed tetanus
toxoid. ( Tantawichien T; Presented at ECCMID 2010, Austria)
Booster Vaccination in AIDS patient : Adequate response ?
“Immune Response After Booster Vaccination in HIV – Infected Patients Who
Ever Received Rabies Primary Vaccination” Suda Sibunruang, Wipaporn Jaijaroensub, Pakamatz Klawplod, Terapong Tantawichien( presented at ECCMID 2012, UK)
All subjects ( CD4 + < 200 /ul) would receive conventional intramuscular booster rabies
vaccination on day 0 and 3. Their blood would be drawn for rabies neutralizing antibody
on day 0,7,14,30,90,180,360
Year 1988 1989 1989 1990 1991 1993 1993 1993 1993 1993 1994 1994 1994
Age (years)
6 9 8 3
45
41 3 7
12
13 44
37 2 1/2
Exposure* face-single, face, head arm, 12 sites month 2 sites face 5 sites Rt. Finger 3 sites head, cheek, eyebrow, Lt. Hand cheek cheek, ear cheek, nose Lt. Let Rt. Thumb Rt. Leg cheek, ear nose, mouth 5 sites
IP/day
12
25
14 20
30
13
13 13
11 m
202 30
45 10
Vaccine PVRV x 3 ERIG 800 IU TCV x 4? PCEC x 3 PVRV ID 2x2 TCV x 4? PVRV x 3 PCEC x3 PCEC x 3 PCEC x 5 1st vac. 10 m SMBV x 16 PVRV x 4 1st vac, D4 PVRV x 4 PCECID 2x3 ERIG 400 IU
Rabies death after post-exposure treatment in Thailand, 1988-1994 *All cases were bitten by dogs, severe exposure
Post-Exposure Rabies Vaccination
after Bite
IS IT SAFE ?
Failure of Rabies Post-Exposure Treatment
1 : 20,000 – 1 : 80,000
Additional Report of Failure to Response to Treatment after Rabies Exposure in Thailand. Hemachudha T, Clin Infect Dis 1999;28:143-4.
Rabies Immunization
• Post-Exposure Treatment Guideline and Regimens for Post-Exposure
Treatment:
Important Issues of ID regimens in limited-
resource countries
Rabies Immunoglobulin:
Inappropriate RIG Treatment
Booster Vaccination for Pre-Immunized Patients:
How and What’s benefit ?
• Pre-Exposure Prophylaxis
Pre-Exposure Prophylaxis for Children:
Important Issues of ID regimens
Abbreviate schedule of Pre-Exposure Regimen
Pre-Exposure Rabies Vaccination
day
0 7 21/28
Dose : one IM dose (1 vial) into deltoid muscle
or 0.1 ml of IM dose intradermally
Type of vaccine : all tissue culture vaccine, PDEV
Booster injection : •People at high or continuing risk of infection check
rabies neutralizing antibody titer every 6 month- 2
years (require > 0.5 IU/ml for protection)
•Re-exposure rabies virus
What and Why Pre-exposure Prophylaxis?
• Prevent infection in uncertain exposure.
• More economical compared with post-exposure prophylaxis of selected population.
• Avoid risk and adverse effect of rabies immunoglobulin in post-exposure treatment
• No failures reported in patients who received
Post-exposure booster vaccination after pre-exposure
prophylaxis
(The only way to prevent PEP failure in the areas where rabies
is endemic and where RIG is not widely available would be to
pre-immunize the entire potentially exposed population.)
Pre-exposure immunization is recommended for
anyone at increased risk of exposure to the rabies virus.
Laboratory personnel, animal handlers, veterinarians, and others
at risk for contracting rabies
Travelers who are likely to have exposures to dogs or cats in
canine rabies – endemic countries are being advised.
Optional vaccine for children (adults?) who are at a higher risk of
exposure and live in the worst canine rabies – endemic regions.
WHO encourages further studies on the feasibility,
cost-effectiveness and long-term impact of incorporating CCVs
in the early immunization programmes of infants and children in
communities where surveillance has proven rabies to be a major
problem.
Advice to travellers and residents according to level of risk:
No risk: No need for pre-exposure prophylaxis.
Low risk and moderate risk: People involved in any activities that
might bring them into direct contact with non haematophagous bats
and other wild animals, especially carnivores (for example, wildlife
professionals, researchers, veterinarians and adventure travellers
visiting areas where bats and other wildlife are commonly found)
should receive pre-exposure prophylaxis.
High risk: People travelling to rural areas or involved in activities
such as running, bicycling, camping or hiking should receive pre-
exposure prophylaxis.
Prophylaxis is also recommended for people with significant
occupational risks. Children should be preventively immunized as
they are at higher risk.
WHO 2013
WHO 2013
Travellers to and residents of rabies-affected areas, and indications for PrEP
Results: Of 13,235 travelers, 2% reported previous rabies vaccination, and only 3%
received rabies vaccine at the consultation. Travelers with trip durations > 6 months
(adjusted OR = 4.9 and those traveling for ‘‘research/education’’ or to ‘‘provide medical
care’’ (adjusted OR= 5.1 were more likely to receive rabies vaccination.
VECTOR-BORNE AND ZOONOTIC DISEASES 2014; 14,2014
Standard IM Pre-exposure schedule are expensive and
time-consuming. To increase vaccination uptake in endemic countries
and by travelers , simplified, cost-effective schedules should be strived
for, implying fewer clinical visits.
Abbreviated schedule for pre-exposure prophylaxis - 3 doses of ID pre-exposure prophylaxis ( different route )
ID pre-exposure schedules and IM schedules are equally effective.
- Shortened or low-dose pre-exposure prophylaxis
IM 2 doses ( days 0 and 28 )
ID 2 doses ( days 0 and 28 )
IM 1 dose ( day 0 )
ID 2 doses ( day 0 )
IM or ID 3 doses ( days 0,3 and 7)
ID schedules induce lower booster responses than IM schedules
when a lower ID dose is used.
Abbreviated ID/IM schedules induce immunologic memory and elicit
effective booster responses. No differences were found between
antibody titers at these various intervals.
Acknowledgement
Thank you