Rabies.pptx

RABIES-A fatal but preventable viral disease is explained in detail (with exclusive pictures) in this PowerPoint presentation.
It also includes the "updates on prevention and control strategy" and "Zero by 2030-Rabies Elimination Strategy"
This was presented at seminar hall, Department of Community Medicine, IMS, Banaras Hindu University as a part of PG seminar.

(The video by Lancet included in this may not be played in this slideshare platform...one can access youtube for the same)

1. Dr. Immanuel Joshua Junior Resident Department of Community Medicine Banaras Hindu University Email: [email protected] RABIES Update on prevention and control strategy

2. …Refresh… …Update… …Recapitulate… … Upgrade… + +

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 ”. A cute fatal viral encephalitis caused by a single stranded RNA virus 100% fatal but 100% preventable

4. THE PROBLEM E stimated 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 UNDEREPORTED 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 (≤ - 20 C) 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

13. 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

14. 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???

15. Dutch philosopher Desiderius Erasmus in around 1500

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

17. 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 + +

18. 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, N on-occlusive dressing can be done if required Tetanus toxoid and antibiotics to be given as appropriate

19. Post-Exposure Prophylaxis (PEP)

20. 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 6 th July 1885 Pasteur’s rabbit spinal cord vaccine (13 doses; 47ml) 1911-2000 1950-1970 1970-1980 1980-2000

21. 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

22. PEP regimen

23. 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 +2 o C to +8 o C. After reconstitution the total content used within 6 - 8 hours.

24. 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

25. 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)

26. 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

27. 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

28. Pre-Exposure Prophylaxis ( PrEP )

29. 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

30. 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

31. Intra-muscular ( IM ) administration schedule 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

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

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

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

35. 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

36. 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

37. 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.

38. 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

39. Rabies monoclonal Anti-bodies ( RmAB )

40. 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

41. 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 .

42. 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 1 st recombinant monoclonal antibody against rabies Developed along with Mass Biologics, UMMS, USA US patented product Manufactured by the Serum Institute of India

43. 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 B inds 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

44. 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.

45. 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

46. 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

47. 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

48. 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

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

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

51. 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

52. 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 )

53. 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:

54. The “Zero by 30 ” Rabies elimination strategy

55. 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 continu e

56. 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

57. 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

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

59. 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

60. Current spending on rabies underinvests in dog vaccination

61. 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.

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

63. ORGANISATIONS AGENCIES

64. 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)

65. 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)

66. 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) EXAMPLE

67. Rabi es prophylaxis Covid pan demic -APCRI

68. 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)

69. Advisory of Rabies prophylaxis during Covid -19 pandemic 5.6.2021 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? Can post exposure prophylaxis (PEP) for animal exposures & COVID-19 vaccine be given on same day; if circumstances necessitate? What should be done if there is animal exposure to lactating mothers who have received COVID-19 vaccine recently? What will be the preferred route of rabies vaccination (ID/IM); if they have received COVID-19 vaccine recently?

70. After receiving anti rabies vaccination, when can one take 1" dose of COVID Vaccine? 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? Can PrEP against rabies be given in risk individuals who have received COVID-19 vaccine recently? 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%20I VolXXIII_Iss_I_Jun21_Article1.pdf

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

72. 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 N APRE 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

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

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