Rabies is a fatal viral disease transmitted through animal bites that kills tens of thousands of people annually worldwide. In India, an estimated 17-20,000 people die from rabies each year, with dogs responsible for the vast majority of human rabies deaths. Post-exposure prophylaxis, consisting of wound cleansing along with a vaccine regimen and potentially rabies immunoglobulin, is highly effective but access issues exist. New developments include monoclonal antibody treatments that could help address challenges with conventional immunoglobulin. Proper animal vaccination programs and public health education are critical to control this almost entirely preventable disease.

1. Dr. Immanuel Joshua
Junior Resident
Department of Community Medicine
Banaras Hindu University
Email: immanuel2346@gmail.com
RABIES
Update on prevention and
control strategy

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3. INTRODUCTION
• Rabies is an ancient disease mentioned in the ancient scripts.
• Derived from the Latin word – “madness” also, Sanskrit word ‘Rabhas’ - “to do violence”.
• Acute fatal viral encephalitis caused by a single stranded RNA virus
100% fatal but 100% preventable

4. THE PROBLEM
Estimated to cause 59 000 human deaths annually in over 150 countries
Many deaths occur at home
Surveillance is inadequate
It can be misdiagnosed as another viral encephalitis or cerebral malaria
Underreported by a factor of up to 20 times in Asia and 160 times in Africa
SOURCE: https://www.who.int/health-topics/rabies#tab=tab_1

5. BURDEN OF RABIES IN INDIA
WHO-APCRI (2004)
17.4 million bites and
20000 deaths/year
MILLION DEATHS STUDY (2012)
12700 Deaths
IDSP (2018)
74,00,000 animal bites; 593
deaths (suspected rabies)
Source: National Action Plan for eliminating dog mediated Rabies from India, MoHFW, GOI
India is home to 36% of global rabies cases of the world

6. Agent
 Single Strand RNA Virus- Lyssa virus
 Family- Rhabdoviridae
 Bullet Shaped, enveloped
 Thermo labile- sensitive to pasteurization and boiling
 Inactivated by soap, alcohol, iodine, formaldehyde, phenol and betapropiolactone
 Preserved by freeze drying, at ultra low temperatures (≤ - 200C) and glycerin

7. Reservoirs of Infection:
Incidental Host: Livestock, Man
 Urban Rabies: Dogs, Cats, Monkeys
 Wild Life Rabies ( Sylvatic)
 Bat Rabies
Dogs are the source of 99% of human rabies deaths

8. FOX
HYENA,
MONGOOSE
BATS
SKUNK
Wildlife and Bat Rabies
JACKAL

9. Modes of Transmission:
Bites from infected animals
Licks on Broken Skin / Mucous Membrane
Scratches
Inhalation
Organ transplantation
In 2004, CDC confirmed the first reported cases of rabies
transmission through solid organ transplantation
https://www.cdc.gov/rabies/resources/countries-risk.html

10. https://www.who.int/news-room/fact-
sheets/detail/rabies#:~:text=not%20report%20bites.-
,Symptoms,virus%20entry%20and%20viral%20load.
Incubation Period (In Man)
• 1 week – 12 months
• Ranges between 4 days to years
• Shorter in children (vulnerable group)
• Depends on;
 Site of bite
 Severity of bite
 Richness of nerve supply
 Amount of saliva deposited
25 year incubation: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3424805/

11. Pathogenesis

12. Clinical Manifestation
• Tingling / numbness at bite site
• Non specific symptoms
• Hydrophobia, Aerophobia
• Hallucinations, hyperactivity
• Death (cardio - respiratory failure)
• Survival : 3 – 5 Days
• Tingling / numbness at bite site
• Non specific symptoms
• Ascending Paralysis
• Coma
• Death (cardio - respiratory failure)
• Survival : 7 – 21 Days
Furious Type ( 80%) Paralytic Type ( 20%)
SOURCE: https://www.who.int/news-room/fact-sheets/detail/rabies

16. Treatment
• Admit in a separate quiet & breeze free area.
• Sedation with Morphine / Barbiturates.
• Muscle relaxants, Intensive cardio respiratory support
• Invasive procedures should be avoided.
• Emotional support and physical comfort.
• Barrier nursing and universal precautions.
PALLIATIVE

17. There are only 29 reported cases of rabies survivors worldwide to date; the last case
was reported in India in 2017. Out of which 3 patients (10.35%) were survived by
using the Milwaukee protocol and other patients survived with intensive care
support. The major reason for survival was the highest level of critical care support
SOURCE:
Nadeem M, Panda PK. Survival in human rabies but left against medical advice and death followed –
Community education is the need of the hour. J Fam Med Prim Care. 2020 Mar 26;9(3):1736–40.
RABIES SURVIVORS???

18. Dutch philosopher Desiderius Erasmus in around 1500

19. RIG
RIG
POST EXPOSURE PROPHYLAXIS (PEP)
• Local treatment of Wounds
• Immunization
• Immunoglobulin (+/-)
• Advice and counselling

20. RIG
RIG
Bite category and treatment
CATEGORY-1
• Licks on unbroken skin
• Touching / feeding animals
CATEGORY-2
• Nibble, cuts, scratches
without oozing of blood
CATEGORY-3
• Licks on mucous membrane or
broken skin
• Bites with breach of skin, bleeding
+
+

21. Wash the site of the bite/scratch:
 immediately after exposure
 thoroughly
 for 15 minutes
 with copious amounts of water & soap
Local treatment of wounds
Never apply
substances like chili, salt, lemon, herbs, etc
• Wound washing is the first life-saving measure
• Apply an iodine-containing, or similarly viricidal, topical
preparation (if available)
• Suturing only if required & after RIG.
• Simple, Non-occlusive dressing can be done if required
• Tetanus toxoid and antibiotics to be given as appropriate

22. Post-Exposure Prophylaxis
(PEP)

24. History of Rabies vaccination
Semple’s NTV
(14-21 doses)
Duck embryo vaccine
(14-23 doses)
Cell culture vaccines
(5-6 doses)
90 days
Cell culture vaccines
(3-5 doses)
3-4 weeks
6th July 1885
Pasteur’s rabbit
spinal cord vaccine
(13 doses; 47ml)
1911-2000
1950-1970
1970-1980
1980-2000

25. WHO prequalified vaccines
Prequalified vaccines are safe, effective, and well tolerated
Type of vaccine Brand Producer Country
Purified Chick Embryo Cell VaxiRab-N Cadila Health Ltd India
Purified Vero Cell Verorab Sanofi Pasteur France
Purified Vero Cell Rabivax-S Serum Institute of India India
Purified Chick Embryo Cell Rabipur Chiron Behring Vaccines Private Ltd India
…Do not fear modern rabies vaccines…
WHO does not recommend the use of nerve tissue vaccines

26. PEP regimen

27. Intradermal Schedules
• Approved by the WHO & DCGI (Feb 2006)
• Cost effective
• DCGI presently has approved only Rabipur and Verorab / Abhayrab for
ID administration
Pre-requisites
• Trained staff for ID technique.
• Vaccine vials should be stored between +2o C to +8o C.
• After reconstitution the total content used within 6 - 8 hours.

28. Rabies Immunoglobulin
(RIG)
Human Rabies Immunoglobulin (HRIG)
20 IU/kg BW (Max of 1500 IU) 40 IU/kg BW (Max of 3000 IU)
Equine Rabies Immunoglobulin (HRIG)
Rabies immunoglobulin (RIG) is:
• recommended for severe exposure (category III)
• not recommended if you have ever received rabies vaccines
• not recommended if you have received your first PEP dose more than 7 days ago

29. • Inject 0.1 ml of 1:10 dilution of the ERIG in normal saline, ID over flexor aspect of forearm.
• Observe for wheal, erythema, induration, itching, tachycardia, fall in BP, feeble pulse.
• Positive test reaction: Induration >10mm
• If skin test is positive – HRIG is preferred
• If ERIG has to be administered then pre treat with
Adrenaline with Antihistamine before administering full dose.
Test dose (ERIG)

30. RIG Infiltration
• RIG is most effective when administered locally and early.
• Infiltrate as much as possible into and around the wounds
• If RIG is insufficient to infiltrate all the wounds dilute it with NS
SOURCE: https://pubmed.ncbi.nlm.nih.gov/34549787/
The mean (±SD) volume of RIG infiltrated in wounds per unit length was 0.75 (±0.21) ml/cm and
per unit area was 3.18 (±1.75) ml/cm2. Regression equations were calculated. Proposed equations
y = 0.6x + 0.3, where y is the volume of RIG (ml) and x is the length of the wound (cm) and y = 0.9x
+ 1.1, where y is the volume of RIG (ml) and x is the area of the wound (cm2)
Estimating the Volume of eRIG
RIG
RIG

31. Challenges exist to equitable access to PEP
 High cost of vaccines and Very high cost of RIG
 PEP failures due to deviations from recommended protocols:
• incorrect vaccine and/or RIG administration
• delays and interruptions in the PEP schedule
• use of substandard black-market vaccines
 Shortage of vaccines
 Unavailability of RIG
 People’s reliance on traditional healing

32. Pre-Exposure Prophylaxis
(PrEP)

33. • Veterinarians, Laboratory personnel working with rabies virus, personnel treating Rabies
patients, Dog catchers, Forest staff, Zoo keepers, Postmen, Policemen, Courier Boys.
• Children in Canine rabies endemic countries.
PrEP is recommended for at high-risk individuals:
Pre-Exposure Prophylaxis
Having already received ≥2 doses of rabies vaccine (as PEP) at some point in life counts as PrEP
Pre-exposure prophylaxis shortens, but does not replace, the post-exposure one
PrEP consists of vaccination on day 0 and day 7

34. How does PrEP work?
7-14 days
Exposure Re-exposure
Administration of Rabies vaccine
Stimulates immune system
Anti-bodies develop
Neutralize the rabies virus
Memory immune cells formed
Production of neutralizing antibodies in short time
PrEP obviates administration of RIG after a bite

35. Intra-muscular (IM) administration schedule
0
Day: 7 21 28
(or)
BOOSTER DOSE
3 Visits, with 1 site on each visit DOSE: One IM dose (entire vial) into Deltoid (or thigh)
SOURCE: https://ncdc.gov.in/WriteReadData/linkimages/NationalGuidelinesforRabiesprophylaxis2019.pdf

36. Intra-dermal (ID) administration schedule
3 Visits, with 1 site on each visit
0
Day: 7 21 28
(or)
BOOSTER DOSE
DOSE: One ID dose (0.1ml)
SOURCE: https://ncdc.gov.in/WriteReadData/linkimages/NationalGuidelinesforRabiesprophylaxis2019.pdf

37. WHO Intramuscular (IM) administration schedule
2 Visits, with 1 site on each visit
0
Day: 7
DOSE: One IM dose (entire vial) into Deltoid (or thigh)

38. WHO Intra-dermal (ID) administration schedule
2 Visits, with 2 sites on each visit
0
Day: 7
DOSE: One ID dose (0.1ml)

39. National Rabies Control Program strongly advocates
use of intra-dermal route of rabies vaccines.
Intra-dermal administration is not the preferred route
for rabies vaccine administration in;
 Immuno-compromised individuals
 Individuals receiving Chloroquine, hydroxy-chloroquine
 Individuals on long term cortico-steroid therapy
Source:
https://ncdc.gov.in/WriteReadData/linkimages/NationalGuidelinesforRabiesprophylaxis2019.pdf
2020 Mar 2;221(6):927-933 doi: 10.1093/infdis/jiz558. Effect of Antimalarial Drugs on the Immune Response to Intramuscular Rabies Vaccination Using a Postexposure Prophylaxis Regimen

40. Management of Re-exposure in previously vaccinated individuals
For exposed or re-exposed patients who can document previous
complete PrEP or PEP the following guidelines would be applicable:
 Proper wound management should be done
 There is no need for RIG administration
 One-site vaccine administration (IM/ID) on day 0 and day 3
Re-exposure
Only adequate wound washing
Documented proof of complete PrEP or PEP within last 3 months

41. RABIES VACCINATION
 Day 0 is the day when the first dose of vaccine is administered.
 Deltoid area is the only acceptable site of IM vaccination in adults.
 In children, anterolateral aspect of thigh can be used.
 Rabies vaccines should never be administered in the gluteal region.
 Vaccine dose and regimen is the same for any age group.
 No contraindications for rabies PEP.

42. FAQs on Rabies Prophylaxis
Q. What happens if any PrEP or PEP doses are delayed?
vaccination should be resumed, not restarted
Q. Do PrEP or PEP doses depend on age and weight?
No, doses do not depend on age and weight
Q. Is a change in the administration route or in vaccine product during PrEP or PEP acceptable?
Q. Can PEP be delayed if RIG is not available on day 0?
Yes, a change in the administration route or in vaccine product is acceptable, if unavoidable
No, PEP must never be delayed if RIG is not available

43. Rabies monoclonal Anti-bodies
(RmAB)

44. Challenges with conventional RIG
 Short shelf-life (approximately 2 years) even with correct maintenance of cold chain
 Hesitancy regarding administration of eRIG
 Short supply with large demand
 Affordability of rabies immunoglobulin in high burden rabies endemic countries

45. Rabies monoclonal Anti-bodies: Advantages
 Rapid industrial production (meets global demand)
 RmAb is much cheaper than hRIG
 Reduction in risk of adverse events
 Significantly lower infiltration volume
 No skin sensitivity test required
SOURCE:
Gyanendra G, Gadey S. Monoclonal antibodies for rabies post-exposure prophylaxis:
A paradigm shift in passive immunization. Arch Prev Med. 2020 Aug 8;035–8.

46. Rabies monoclonal Anti-body (RmAb)
 Neutralizes all known isolates of Rabies virus
 Recommended for use by WHO
 Licensed in India in 2016 and launched in 2017
 World’s 1st recombinant monoclonal antibody against rabies
 Developed along with Mass Biologics, UMMS, USA
 US patented product
 Manufactured by the Serum Institute of India

47. TwinRab
Combines 2 mAbs which bind to different epitopes on rabies glycoprotein
 Licensed in 2019 and Marketed in 2020 in India
 COCKTAIL RmAb produced by
 Found to be safe and effective alternative to hRIG
Recommended dose is 40 IU/Kg
DOCARAVIMAB MIROMAVIMAB
Binds to site I or III on g-protein Binds to site II on g-protein
SOURCE: https://twinrab.com/images/pdf/Product_Information_TwinRab.pdf

48. Guidance note for preventing shortage of rabies vaccine
1. Manufacturing of ARV is a complex biological process and requires 3-4 months for manufacture
and testing. So the States may be sensitized about the minimum lead time required for supply.
2. Annual requirement of Rabies Vaccine, Human & Anti Rabies serum must be calculated 4-6
months in advance. Requirement must include 10% Wastage factor & buffer stock for 3 months.
3. As per the Drugs and Cosmetics Rules, 1945, the batch of Rabies Vaccine has to be released by
the manufacturer after testing. It is also mandatory to submit the samples of Rabies Vaccine to
Central Drugs Laboratory (CDL), Kasauli for evaluation before it is supplied in the country.

49. 4. Tenders should be issued for fixed quantities rather than the rate contracts.
5. Rabies Vaccine & Anti Rabies serum stock must be monitored on regular basis (district/
institute wise) and accordingly, plan the supply based on consumption.
6. The States shall analyse average time required for completing tender process to actual
placement of order and accordingly, the procurement procedures to be started well in advance.
7. The State Authorities need to be sensitized to analyse their annual requirement and the lead
time required for completing all procedures well in advance.
SOURCE: https://ncdc.gov.in/showfile.php?lid=420

50. 8. Anti-rabies vaccine and Anti rabies serum is part of essential drug list of NHM. Budget for
Rabies Vaccine & Anti Rabies serum may be proposed under national free drug initiative.
9. As per national guidelines, the preferred route of administration for ARV is Intradermal. It is
cost effective and requires 0.2 ml/ Visit/patient for ID route vs. 1 ml/visit/patient for IM route.
10. In case of shortage of Rabies vaccine, Human, please inform to National Pharmaceutical
Pricing Authority (NPPA), Department of Pharmaceuticals (DoP) or Ministry of Health and
Family Welfare (MoHFW) for addressing the issue.
SOURCE: https://ncdc.gov.in/showfile.php?lid=420

51. 3 ways to increase the cost-effectiveness of PEP
 Adopting the intra-dermal regimen (up to 80% savings)
 Using PEP as a reactionary measure, while mass dog vaccination is the primary one
 Strengthening integrated bite case management

52. National Rabies Control Programme (NRCP)
National Rabies Control Programme was approved during 12th FYP
by Standing Finance Committee meeting held on 03.10.2013
2 components:
 for roll out in the all States and UTs
 through nodal agency NCDC
 with total budget of Rs 20 Crores
 for pilot testing in Haryana and Chennai
 through nodal agency AWBI
 with total budget of Rs 30 Crores
HUMAN COMPONENT ANIMAL COMPONENT
SOURCE: https://ncdc.gov.in/index1.php?lang=1&level=1&sublinkid=146&lid=150

53. 1. Training of health care professionals on appropriate bite management and PEP
2. Advocacy for states to adopt and implement Interdermal route of PEP for
animal bite victims and Pre exposure prophylaxis for high risk categories.
3. Strengthen human rabies surveillance system.
4. Strengthening of regional laboratories under NRCP for Rabies diagnosis.
5. Creating awareness in the community
The Human Health Component has been rolled out in 26 States and UTs
OBJECTIVES

54. Minimum essential data elements for human rabies exposure
Reporting format under NRCP

58. Case definition for Human Rabies
(To be reported in S Form by Health Worker)
Death of a human with history of dog bite
few weeks/months preceding death
SUSPECT CASE
LABORATORY CONFIRMED CASE
A suspect or a probable human case that is laboratory-confirmed
(To be reported in L-Form by laboratories having confirmatory test facilities for rabies)
PROBABLE CASE
A suspected human case plus history of
exposure to a (suspect / probable ) rabid animal
(To be reported in P form by Medical Officers/Doctors)
SOURCE: https://ncdc.gov.in/showfile.php?lid=419

59. Laboratory Confirmed case : (confirmation by one or more of the following)
 Detection of rabies viral antigens by direct fluorescent antibody test (FAT) or by
ELISA in clinical specimens, preferably brain tissue (collected post mortem)
 Detection by FAT on skin biopsy (ante mortem)
 Detectable antibody titre in the serum or the CSF of an unvaccinated person.
 Detection of viral nucleic acids by PCR on tissue collected post mortem or intra
vitam in a clinical specimen (brain tissue or skin, cornea, urine or saliva)

60. A suspect rabid animal (as defined above) with additional history of a bite by another
suspect / probable rabid animal and/or is a suspect rabid animal that is killed, died, or
disappeared within 4-5 days of observing illness signs.
Suspect rabid animal:
Rabies-susceptible animal (usually dogs) which presents with any of the following
signs at time of exposure or within 10 days following exposure: unprovoked
aggression (biting people or animals or inanimate objects), hypersalivation, paralysis,
lethargy, abnormal vocalization, or diurnal activity of nocturnal species.
Probable rabid animal:

61. The “Zero by 30”
Rabies elimination strategy

62. Eliminating dog-mediated human rabies is a global public good
If we do not do anything,
Over 1 million people will die of rabies before 2030
The demand for post-exposure prophylaxis will escalate
Inequality will grow
The cycle of neglect of rabies will continue

63. Eliminating rabies aligns with global goals
The control of Neglected Tropical Diseases, for ending the devastating
human, social, and economic burden that diseases of poverty impose
on the most vulnerable and marginalized populations
The Sustainable Development Goals, for a better and more sustainable future for all

64. Rabies elimination requires a One Health approach
The health and wellbeing
of humans, animals, and
the environment is
interdependent
Human and dog rabies
are correlated
Addressing rabies at its
source is the most efficient
and cost-effective way to
break transmission

65. A One Health-based investment model saves lives
prompt post-exposure prophylaxis + large-scale mass dog vaccination

66. Rabies Elimination: Real-world examples
In 2019, Mexico became the first country to obtain WHO validation for
eliminating dog-transmitted rabies as a public health problem
Dog vaccination stops rabies transmission from dogs to humans

67. Current spending on rabies underinvests in dog vaccination

68. Vaccinating a dog is much cheaper than providing care to the victim of its bite
Human vs Dog Vaccination
 In private clinics and hospitals, each dose costs ₹350-400, so five doses cost ₹1,700-2,000.
 If a patient also requires immunoglobulin, then it entails an additional cost of ₹2,400.

69. “Zero by 30”
A three-pronged approach
Post-exposure prophylaxis
Mass dog vaccination
Awareness

70. ORGANISATIONS
AGENCIES

71. Organisations / Agencies Involved In Rabies Control In India
• Ministry of Health -Central and State
• State Animal Husbandry Department
• Animal Welfare Board
• NIMHANS, Bangalore
• Government Veterinary Colleges
(Governmental)

72. NGOs involved in Rabies control in India
• Rabies in Asia Foundation (RIA)
• Association for the Prevention and Control of Rabies in India (APCRI)
• Commonwealth Veterinary Association (CVA)
• Global Alliance for Rabies Control (GRAC)

73. Greater Hyderabad Municipal Corporation (GHMC) along with Blue Cross Hyderabad and 23
other NGOs working for animal rights launched ‘Mission Rabies’.
A month-long drive, the programme aims at administering anti-rabies vaccination to the
pets, street dogs and cats to prevent the spread of the deadly rabies disease
‘Mission Rabies’ launched in Hyderabad (Aug 28_2021)
E
X
A
M
P
L
E

74. Rabies prophylaxis
Covid pandemic
-APCRI

75. Founder President and Mentor of Association for Prevention and Control of
Rabies in India (APCRI, 1998) and Rabies in Asia (RIA, 2006) Foundation
Dr.M.K.Sudarshan
MD (BHU), FAMS, Hon.FFPH (UK)

76. Advisory of Rabies prophylaxis during Covid -19 pandemic 5.6.2021
Q Should we give anti rabies vaccines and rabies immunoglobulin/ rabies monoclonal
antibodies to stray animal bite cases, if they have received COVID-19 vaccine recently?
Q Can post exposure prophylaxis (PEP) for animal exposures & COVID-19 vaccine be given
on same day; if circumstances necessitate?
Q What should be done if there is animal exposure to lactating mothers who have received
COVID-19 vaccine recently?
Q What will be the preferred route of rabies vaccination (ID/IM); if they have received
COVID-19 vaccine recently?

77. Q After receiving anti rabies vaccination, when can one take 1" dose of COVID Vaccine?
Q What should be done for antibodies patient who has taken rabies monoclonal
(Rabishield/ Twinrab) and later antibodies for requires COVID-19 monoclonal treatment
or vice-versa?
Q Can PrEP against rabies be given in risk individuals who have received COVID-19 vaccine
recently?
Q Can we give intradermal rabies vaccine (IDRV) for PEP in the same arm where COVID-19
Vaccine was given IM?
SOURCE: http://www.apcrijournal.com/MainPageArticles/VOL%20XXIII%20ISSUE%20IVolXXIII_Iss_I_Jun21_Article1.pdf

78. World Rabies Day 2021
National Action Plan for Dog Mediated Rabies Elimination by 2030
Source: https://pib.gov.in/PressReleseDetail.aspx?PRID=1758965
Vision: “To reduce human deaths due to dog mediated rabies to zero by 2030”
NOTIFIABLE
DISEASE
in India
Human Rabies is made a

79. The NAPRE is based on recommendations of various international agencies
such as WHO,OIE, and Global Alliance of Rabies Control (GARC).
The successful implementation of NAPRE in India is based on 5 major pillars:-
National Action Plan for Rabies Elimination in India
Political will
Sustained
funding
Uninterrupted
supply of logistic
requirement
Intersectoral
coordination
Joint
planning and
reviewing
Community
participation
Operational
research

80. The phrase can be kept
100% true with effective
Rabies prevention and
control strategy

81. https://openwho.org/courses/NTDs
-Rabies-and-one-health