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.

0.00

0.01

0.02

0.03

0.04

0.05

0.06

0.07

0.08

0.09

0-4 5-9 10-14 15-24 25-34 35-44 45-54 55-64 65+

0.03

0.07

0.02

0.03

0.05 0.05

0.04

0.02

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