Rabies is neglected disease with 100% case fatality. Rabies kills more than 55,000 people each year in which 99% of the deaths are from developing countries. Rabies has been recognized in Ethiopia for centuries, and the disease has become endemic since the early 17th century. By estimation, 2771 to 10,000 people die of rabies each year in Ethiopia. The only vaccine available for human rabies post-exposure prophylaxis is the obsolete sheep brain-based Nervous Tissue vaccine (Fermi vaccine) and has been manufactured since early 1950s in Ethiopia. According to Ethiopian Ministry of Health, the annual performance report, the maximum manufacturing capacity for the Nervous Tissue Vaccine (NTV) of the country is about 32,000 doses, which is far below demand. The NTV is immunogenic, more reactogenic, life threatening and caused neurological adverse reactions in vaccinated people.

1. July, 2022
Addis Ababa, Ethiopia
Birhanu Hurisa (MSc, MA, PhD
Candidate)
Ethiopian Public Health Institute
Overview of Rabies and Anti-Rabies
Vaccine administration

2. o Rabies vaccine
o Immunizations schedule followed in Ethiopia for sheep
brain anti-rabies vaccine (Nervous Tissue Vaccine)
o Categories of rabies exposure and recommended post-
exposure
o PEP
o Vaccination schedule
o PEP in immunosuppressed individuals
o PEP in previously vaccinated persons
o Pre-exposure rabies prophylaxis
Outline

3. Rabies is widely distributed
across globe.
100% fatal
>55000 people die of rabies each
year
95% occur in Asia and Africa
1 death due to rabies every 10
minutes in the two continents
Most human death follow a bite
from infected dog
30% to 60% victims of dog bites
are children under age of 15
Rabies Epidemiology

4. In Ethiopia, it is estimated that up to 2,700 human
deaths occur annually due to rabies.
The first rabies epidemic of which we have record occurred
in Addis Ababa in August 1903, the outbreak lasted for a
few months and then disappeared‘ (Pankrust)
Traditional Medicine (Imperial cure)

6. All infections with rabid virus
resulted in death until louis pasteur
developed first rabies vaccine in
1885
Spinal cords of rabbit infected
with fixed virus
Joseph Meister 9 year old boy
vaccinated 13 injection were given
Patient saved
1st Vaccine for rabies

7. Categories of rabies exposure and recommended post-
exposure
Categor
y
Type of contact Type of
exposure
Recommended post-exposure
prophylaxis
I  Touching or feeding of animals
 Licks on intact skin
None None, if reliable case history is
available
II  Nibbling of uncovered skin
 Minor scratches or abrasions
without bleeding
Minor Wound Management + anti-
rabies
III  Single or multiple transdermal
bite or scratches licks on broken
skin
 Contamination of mucous
membrane with saliva (licks)
Severe Wound management + RIG +
Anti-rabies
NB. Bites from unidentified animal is classified as category III

8. PEP
PEP consists of:
(i) thorough washing and flushing of the
wound;
(ii) a series of rabies vaccine administrations
promptly started after an exposure, and if
indicated
(iii)RIG infiltration into and around the wound,
promptly after exposure

9. Immunization Schedules Followed In Ethiopia
for Sheep Brain Anti-rabies Vaccine (WHO,
1984)

10. The vaccine is 5% aqueous suspension of rabies virus-
infected sheep brain,
oTreated with 5% phenol at 22°C,
oContains a live and inactivated virus
oThis vaccine preparation is still used in a few under
developed countries
• Only used for PEP
• Around 32k doses are annually produced by EPHI

11. Type of exposure
 Extent or severity of the exposure
Type of animal species involved
Circumstances (i.e., provoked vs. unprovoked) leading to the bite or
other exposure
 Availability of the animal for confinement and observation or testing
The following factors should always assessed
before initiating PEP

12. i. If the bites are not severe, treatment should not be
given unless the veterinary surgeon gives a contrary
opinion upon observation of the animal.
ii. If the bites are severe/Multiple bites/ bites to the
face, head, neck, hands and genitals, immediate PEP
should be considered, treatment should be started as
soon as possible, but may be stopped if the animal is
seen to be healthy ten days after the bite.
Possibilities:

13. Contd..
iii. If for any reason the SUSPECTED ANIMAL is disappears
during the observation period, before the 10th day of the
observation, treatment must be start immediately.
iv. If the SUSPECTED ANIMAL is killed and laboratory tests
of brain material from the suspected or rabid animal is rabies
positive, the person should start the treatment immediately.

14. Initiate PEP regardless of the vaccination status, discontinue after result of
quarantine because there is possibility of vaccine or technical failure
Provoked vs. Unprovoked
Provoked animal: Unprovoked: more likely than a provoked attack to indicate that
the animal is rabid
PEP should not be initiated unless the risk level is identified to be very high as
indicated on the algorism
10 days of animal quarantine or laboratory test result will be waited to initiate
vaccination
Availability of the Animal for Confinement and Observation or Testing
PEP could be initiated if the animal suspected of rabies AT THE TIME of
exposure and discontinued at the fifth day if the status of the animal was
confirmed to be healthy.

15. S.no Vaccine Patient Vaccine dose Booster
dose
Route
1 Phenoli
zed NTV
Children two years of
age
2 ml X 14 (Daily) 10th, 20th &
30th days
following the
last injection
Sub-cutaneous
(around
umbilicus)
2 Children Three years of
age
3 ml X 14 (Daily) 10th, 20th &
30th days
following the
last injection
Sub-cutaneous
3 Children four years of
age
4 ml X 14 (Daily) 10th, 20th &
30th days
following the
last injection
Sub-cutaneous
4 Five years of age and
above
5 ml X 14 (Daily) 10th, 20th &
30th days
following the
last injection
Sub-cutaneous

16. o Storage and shelf life: - Five months (2 -8 oC)
o Do not freeze! Freezing destroys the antigenicity of
phenolized vaccine and the vaccine should not be used
if frozen.
o Do not use nerve tissue anti-rabies vaccine for pre-
exposure prophylaxis!

17. For individuals RE-EXPOSED within 3-6 months following
completion of full course of vaccination, only the three booster doses
with 10 days interval will be given to boost immune response.
 Individuals RE-EXPOSED after 6 months following complete
vaccination, full course of vaccination (17 injections) recommended
considering the presence of protective antibody titer not guaranteed.
Duration of Immunity

18. Shift in the vaccine type
A Shift from Nervous Tissue Vaccine (NTV) to Cell Culture
Full dose is required

19. Recommendation For Special Groups
 Immunosuppressed: The number of doses recommended will not be
changed for persons with altered immune status
-Cell Culture based vaccines are recommended
o Infants and Pregnancy: No contraindication
-Cell Culture based vaccines are recommended

20. Nervous Tissue Vaccine (NTV) Adverse effects
• NTV may cause pain, swelling, tenderness, itching, erythematous
patches after the beginning of the anti-rabies treatment,
• Fading in 6-8 hours and reappearing after the next dose
oSevere adverse events may occur with nerve tissue anti-rabies vaccines
o The magnitude of NTV side adverse effects is undocumented in Ethiopia
(rarely reported)
oBenefit outweigh the side effects

21. Modern Rabies vaccine

22. Rabies Vaccines
Purified chick embryo cell vaccines
Purified vero cell rabies vaccine Ag Content 2.5 IU/dose
Purified duck embryo vaccine
Human Diploid cell vaccine and Nervous Tissue Vaccine (NTV)
is not recommended
Cell culture Vaccines

23. o Lyophilised: dilute with sterile water
Storage 2-8⁰C-----3 years
Use in 6 hrs. of reconstitutions
o All vaccines have - equal efficacy in all varieties
o 99% sero-conversion
o Long lasting protection-----5-21 years
•Good anamnestic response after booster

24. PEP
PEP Should be given IMMEDIATELY and one should not await the results of the
LABORATORY DIAGNOSIS OR BE DELAYED BY DOG OBSERVATION when
rabies is suspected irrespective of vaccination status
Vaccination ≠Non rabid
No rodent rabies reported
No human to human transmission
Patients presenting for rabies PEP even months after having bitten should be treated as if
the contact has recently occurred

25. Adverse Reaction
oLocal- pain, red, swelling
• Usually local irritation … ID>IM
oSystemic – fever, headache, Dizziness
oNo contraindication
• Breastfeeding women, pregnant women, infants, toddlers

26. Vaccination Schedule
Two routes
I. Intramuscular
 vaccines should be injected into the
DELTOID MUSCLE for adults and children
aged 2 years and more.
 The ANTEROLATERAL THIGH is
recommended for younger children
 Vaccines should never be injected into the
GLUTEAL REGION
II. Intradermal

27. Intramuscular regimens
Intramuscular schedules for category II
and III exposures
1. The 5 dose Protocol (1-1-1-1-1 on
days 0,3,7, 14 and 28)
2. The 4 dose protocol: 1-1-1-1 on
days 0,3,7,14-28 days (New
Preferred)

28. Intradermal regimens-PEP
oRequires a reduced volume (0.1 ml per intradermal site) of
vaccine to be utilised thus reducing vaccine cost by 60-80%
oThis method is appropriate where vaccine or/and money are in
short supply, particularly in rural areas with high-flow clinics

29. Intradermal regimens-PEP (0.1 ml)
0-3-7
2—2—2 (two doses, two site)
 New WHO regimen
Trained staff is required
Large number of patients

30. PEP-Immunosuppressed
individuals
• Thorough wound treatment should be further stressed for
immunosuppressed individuals
• RIG should be administered deeply into the wound for both category
II and III exposures
• Vaccine should always be administered and no modification of the
recommended number of doses is advisable
• When possible, the rabies virus neutralizing antibody response should
be determined 2-4 weeks after vaccination to assess whether an
additional dose of vaccine is required

31. PEP (previously Vaccinated Persons) + Bite
oPeople who have received rabies vaccines
oTwo active immunization schedules (IM & ID) are available
1. 1-1 schedule on days 0 and 3 (last injection more than three
months) and PEP is not necessary if the last injection is within three
months
2. Intradermal: Day 0=4 site single dose schedule with 4 injections of
0.1ml equally distributed over left and right deltoids, thigh or
suprascapular areas during single visit

32. PEP (Previously vaccinated) cont.
oNo RIG should be applied
oHowever full PEP (vaccine + RIG) should be given to person:
oWho have received pre- or post exposure prophylaxis with
vaccines of unproven potency
oWhere immunological memory is no longer assured as a result
of HIV/AIDS or other immunosuppressive causes

33. Pre-exposure Rabies Prophylaxis (Prep)
oPeople at risk
o Recommended for anyone who is at continual (lab research, vaccine
production), frequent (docs treating rabies patient, zoo person) or increased
risk for exposure to the rabies virus, as a result of their occupation
(policemen)
1. Groups of persons at high risks of exposure to live rabies virus (laboratory
staff, veterinarians, animal handlers and wildlife officers)
2. Children living in or visiting rabies affected areas may be immunized
preventively on a voluntary individual basis or in mass campaign when
there are no economic, programmatic or logistical obstacles
3. Travellers to rabies-affected areas according to the level of risk in that area

34. PrEP Regimens
Intramuscular
• One Intramuscular dose is given on each of days 0 and 7 day
(NEW WHO)
Intradermal
o two doses of 0.1 ml is given on 0 and 7 (2-2) (NEW WHO)
oNB- there is no need to restart the series of the doses are
not given on the exact schedule

35. Booster dose
Required for patients having continuous exposure
 Ab titre every 6 month
Ab titre is less than 0.5 IU/ML, need booster
Ab Titre estimation Level not applicable, booster every five years

36. References
1. Rabies vaccines: WHO position paper – April 2018
2. Reduction in the dosage schedule of BPL-inactivated neural tissue
vaccine for rabies prophylaxis in man. K K Tripathi 1, S N
Madhusudana, A Sahu, Indian J Med Res 1990 Sep;91:334-9.
3. The WHO position on rabies immunization – 2018 updates
Katherine L. O’Brien a, , Terry Nolan b , on behalf of the SAGE WG
on Rabies
4. Laboratory techniques in rabies edited by F -X Mes in V h; Kapdri H
Koprnwsk - 4th ed 1996.