Rabies - presentation 2024 ims & SUM Hospital campus 2

Rabies

1. Rabies: ZERO by 2030 Dr. Sai Chandan Das Associate Professor Community Medicine, IMS & SH-II SOA University

2. Plan of Presentation Introduction Global & National Burden Pathogenesis Mode of transmission Prevention & Management of Rabies Newer advancement in PEP Milestones achieved so far Rabies prevention and control strategies 2

3. Introduction Comes from “ rabhas ” , violence in Sanskrit “Lyssavirus” comes from Lyssa, the Greek goddess of fury Oldest known disease to affect mankind 3

4. Introduction Fatal encephalomyelitis in warm-blooded animals including humans 100 % preventable disease : PEP/ PrEP are available World rabies day is celebrated on 28 th Sept to marks the death anniversary of Louis Pasteur 4

5. Global Burden Threat to more than 3.3 billion people in the world 59000 human deaths annually due to dog mediated rabies Most of the deaths are estimated to have occurred in Asia (59.6%) and Africa (36.4%). 5

6. Economic burden due to Rabies Out of pocket expenditure 6

7. Rabies deaths (Humans) are often underreported Currently underreported by a factor up to 20 times in Asia and 160 times in Africa Misdiagnosed as another viral encephalitis or cerebral malaria Many deaths occur at home Inadequate surveillance Affects underserved population 7

8. Burden in India WHO-APCRI Survey (2004 ) : 17.4 million animal bites/ year and 20,000 deaths /year Million deaths study (2012 )  12700 deaths IDSP : 593 deaths due to suspected rabies (2017); 74 lakh animal bites reported (2018) Annual bite incidence is 0.1-5% State wise Animal Bite prevalence Year 2021 8

9. Mode of Transmission Frequent Occasionally Not reported Dogs & Cats Monkeys Bears Bats* Mongoose, Shrew Pigs Rodents* Cows & buffaloes Donkey Birds Foxes, Wolves & Jackals Horses Squirrel Note: All exposures with wild animals are considered Category III exposures. * Bite by bats or rodents do not ordinarily necessitate rabies vaccination in India. However, bites by bats or rodents in unusual circumstances may be considered for vaccination in consultation with an expert in the field of rabies. Dog is the main reservoir and transmitting animal in India most of the countries 9

10. IP- 5days to several years (usually 2-3months, rarely 1yr) Pathogenesis 10

11. IP- 5days to several years (usually 2-3months, rarely 1yr) Pathogenesis 11

12. Pathogenesis Depends on : Proximity of the virus entry to the CNS (Site of bite) Severity of bite No of wounds Biting animal species Treatment taken or not Density of motor endplates at wound site 12

13. 13

14. Pre-exposure Prophylaxis Vaccination given prior to exposure High risk of coming in contact with saliva, body fluids or tissues of rabid animals PrEP will stimulate to produce antibodies within 7-14days 14

15. 15

16. Pre-exposure Prophylaxis V accine-induced immunological memory is life-long , if PEP is given after exposure It obviates administration of RIG after a bite IAP recommends PrEP for children having pets at home 16

17. 17 Schedule of PrEP Vaccination 1

18. Booster vaccination for occupational exposure Individuals having occupational exposure should be tested for antibodies every 1–2 years Booster vaccination would be recommended only if RABV neutralizing antibody titers fall to <0.5 IU/ mL . 18

19. Management of animal bite by PEP Steps of Post Exposure Prophylaxsis Wound Wash WHO categorization of Wounds Active Immunization (ARV) Passive immunization (RIG/ RMab ) NOTE :Due to wide range of incubation periods, PEP should be given as soon as possible, however, it should not be denied to persons reporting late 19

20. ( RmAb ) 20

21. Steps and rationale of wound management Steps in wound management Rationale Physical Wash wound with running water up to 15min Mechanical removal of Virus Chemical Clean wounds with Soap and Water + Antiseptics Inactivation of virus Biological Infiltrate with RIG the depth and around the wound in Category III exposures and immunocompromised patients with Cat II bite Neutralization of the virus 21

22. Active Immunisation Available Cell culture vaccine Route Dose Storage Contraindication Purified chick embryo cell vaccine / Purified Vero cell rabies vaccine IM/ID 0.5ml PVRV / 1ml PCEC Btwn 2 and 8 degree Celsius **ID route has an equal immunogenic response compared to the IM. Best for low resource setting 22 Egg allergy/ pregnancy & lactation/ Immunocompromised

23. PEP can be safely given to infants, pregnant women and immune-compromised individuals, including children with HIV/AIDS 23

24. Morden rabies vaccines in India Sl no Brand Product Company 1 Abhayrab Purified vero cell rabies vaccine (PVRV) 0.5ml Human biological institute 2 Chirorab Purified Chick Embryo cell vaccine (PCEC) 1ml Sanofi/ Aventis/ Bharat/ Novartis 3 Rabivax -s Purified vero cell rabies vaccine (PVRV) 1 ml Serum Institute of India 4 Vaxirab -N Purified Chick Embryo cell vaccine (PCEC) 1ml Zydus Cadila 5 Rabio Purified Vero cell rabies vaccine (PVRV) 0.5ml Prosper Channel Life Science's India 6 Rabirix Purified Vero cell rabies vaccine (PVRV) 0.5ml Bharat Biotech 24 Minimal acceptable potency -2.5 IU/IM dose (Both IM & ID) Note : A list of WHO prequalified vaccines is available online (https:// extranet.who.int/ gavi /PQ_Web/)

25. Updated THAI Red cross regimen This is the only regimen approved by the Drug Controller General of India (DCGI) for intradermal usage of an anti-rabies vaccine in the country 25

26. Essen regimen (1-1-1-1-1) 26

27. Summary of Vaccination schedule 27 1

28. Switching from ID to IM or Vice versa Not recommended No sufficient scientific evidence following changes in route of vaccine administration during PEP Regimen to be continued/ resumed as per new administration route ID IM * Training module for Medical Officers, NCDC, GOI 28

29. Passive Immunization 29

30. RIG should never be administered at the same anatomical site Administration of IM (RIG ) is of no use , if required should be given distant from the site of ARV Passive Immunization 30 Infiltrate as much as possible into and around the wounds

31. Short comings of ERIG/ HRIG Limited availability Short shelf life (Approx 2yrs) even with correct maintenance of cold chain High cost (HRIG) Skin sensitivity test required (ERIG) High risk for severe allergic reactions 31

32. Newer advancement in PEP Monoclonal Antibodies ( RmAb ) Approved by DCGI in 2016 Dosage is 3.33 IU/kg body wt. to be given at the time of first vaccine dose Not beyond seventh day of 1 st dose of ARV 32

33. Newer advancement in PEP TwinRab : “Cocktail” containing at least two antibodies against RABV Dose : 40IU/kg body wt. 2 murine mAbs which bind to different epitopes on the rabies glycoprotein Safe and effective alternative to hRIG 33

34. 34

35. Reduction in adverse events No skin sensitivity test required Cheaper than HRIG Long term storage so convenience of supply to rural areas 35

36. 36

37. 37

38. Managing special situation of rabies exposure Safe with other UIP vaccines & COVID -19  Only different site No vaccine required for consuming raw milk of rabid animal HIV/AIDS  CD4 count < 200 : Wound Mx + RIG/ RMAb +5 doses of vaccine by IM only Additional dose decision to be taken after RABV neutralizing antibody response is determined 2–4 weeks/after 14 days of the last dose of vaccination 38

39. Targeted for Global Elimination ZERO by 2030 39

40. 2002: National guidelines for rabies prophylaxis to bring out uniformity in PrEP, PEP 2004: Nerve tissue vaccine is replaced with CCV for PEP 2007 -12: Rabies as priority zoonotic disease in 11 th five year plan & National guidelines for ID route of CCR vaccine 2008-11: GOI has introduced the pilot project on rabies control programme in 5 cities 2015: GOI, NCDC released Revised National Guidelines on Rabies prophylaxis 2012- 2017 : 12 th Five yr. Plan National Rabies control Programme (NRCP) 2006: Approved ID route for vaccination 2021: National Action Plan for Rabies Elimination (NAPRE) launched Milestones achieved so far 40

41. National Rabies control Program (NRCP) Govt. Of India launched National Rabies control Programme (NRCP) in the 12 th Five year Plan Objective: Achieve global target for Rabies – Zero by 2030 Human component Animal Component Training health professionals - Population survey of Dogs Use of IDRV - Mass Dog vaccination Strengthening surveillance - Dog populn Mx Lab strengthening - Strengthening surveillance IEC 41

42. NRCP website launched on 12 th March 2024 42

43. India Marching towards rabies elimination India has made it a priority to stop this preventable disease One Health India action plan is a model of leadership in India – can serve as e.g. for other rabies endemic countries 43

44. National Action Plan for Rabies Elimination (NAPRE) NAPRE provides framework & guidance document for the states/ stakeholders to develop their action plans, specific to their needs and aims at systematic reduction of rabies risk through sustained mass drug vaccinations, Pre & post exposure prophylaxis and public education 44

45. 45

46. 46

47. THANK YOU…….. 47

48. References Training module on Rabies for MO- National Centre for Disease Control, DGHS, MOHFW GOI Nation Action Plan for Dog Mediated Rabies Elimination From India by 2030, GOI, NCDC Zero by 30- The Global Strategic Plan WHO Expert Consultation on Rabies- Third report Indian Consensus Guidelines on Adult Immunization 48

49. 49