Towards Rabies Elimination In India. by author

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Collaborating Centre for Reference and Research in Rabies National

1 Towards Rabies Elimination In India Dr. Reeta S. Mani Additional Professor, Department of Neurovirology WHO Collaborating Centre for Reference and Research in Rabies National Institute of Mental Health & Neurosciences (NIMHANS) Bangalore, India 28 th ECCMID, Madrid, Spain; April 21, 2018

2 RABIES THE DEATH SENTENCE

3 RABIES 100% PREVENTABLE!

4 CASE-1 A young boy, adopted by a couple Sudden onset of ascending paralysis Progressed to respiratory failure requiring ventilatory support Clinical diagnosis considered Guillain Barre sydrome Treated with large volume plasmapheresis and IVIG Despite therapy, succumbed to illness The distraught parents sued hospital for medical negligence Medico-legal case-autopsy done

5 Dept of Neuropathology, NIMHANS, Bangalore

6 CASE-2 29 year old woman from a southern state in India Conceived by IVF after 6 years of marriage Bitten by a stray dog on her hand in 2nd trimester Advised not to take PEP in pregnancy Developed rabies in 9th month of pregnancy Baby delivered by LSCS-survived Mother succumbed to rabies

7 CASE-3 Unknown, middle-aged man seen as a wandering lunatic Wearing dirty clothes, talking in excess, dancing, singing and occasionally weeping on the road Made sexual advances and remarks to the ladies passing by When he tried to assault a lady on the road, he was severely beaten up by a mob Succumbed to his injuries-medico legal case Unsuspecting diagnosis of Rabies after autopsy Goswami U et al. Psychiatric presentations of rabies. Trop Geogr Med 1984;36:77-81

8 CASE-4 A 10-yr-old girl with bilateral congenital hereditary corneal dystrophy Donor cornea obtained, she underwent keratoplasty of Rt. eye Postoperative period uneventful and the graft took well After 2 weeks she became aggressive and irritable; developed hydrophobia and died -16 days after keratoplasty No past history of any animal exposure Rabies diagnosis confirmed on postmortem brain Donor cornea had been obtained from a 26 yr old male, who died of suspected myocardial infarction Masthi R et al. Rabies in a blind patient: confusion after corneal transplantation. Natl Med J India. 2012;25:83-4.

CASE-5 A 6-year-old boy from a village in western India Bitten by a stray dog on his back and right side of neck (cat III ) Parents immediately took him to nearest PHC-where he was given both ERIG

9 CASE-5 A 6-year-old boy from a village in western India Bitten by a stray dog on his back and right side of neck (cat III ) Parents immediately took him to nearest PHC-where he was given both ERIG and vaccine After 6 weeks child developed paralytic rabies-lab confirmed by rise in antibody titres in CSF Retrospectively identified that ERIG had not been infiltrated in all wounds; vaccine dosage was inadequate Discharged home in a semi-comatose state with nasogastric tube feeding after one month stay in ICU

10 Diagnostic Rabies: Challenges Treatment/Management Palliative care Social Medico-legal Infection control Case closure & grief counseling

Rabies: Global Disease Burden The disease Rabies is an acute fatal encephalomyelitis in mammals resulting from infection by any of the viruses in genus Lyssavirus Annual number of human rabies deaths

11 Rabies: Global Disease Burden The disease Rabies is an acute fatal encephalomyelitis in mammals resulting from infection by any of the viruses in genus Lyssavirus Annual number of human rabies deaths globally 61,000 Vast majority of deaths (84%) in rural areas Estimated annual cost of rabies is US$ 6 billion, US$ 2 billion due to lost productivity after premature deaths and US$ 1.6 billion spent on PEP Maximum burden of human rabies in Asia and Africa

12 Rabies: Global Disease Burden Global : 61,000 deaths annually ( 84% in rural area) Asia: >30,000 ( 50%) India : 20,000 deaths annually (Asia : 67%), (Global: 33%)

13 The Lyssavirus Genus Fooks et al. Rabies. Nat Rev Dis Primers.2017;3:17091

14 The Bullet that Never Fails! Transmission

15 Human Rabies: Clinical Course Fooks et al. Rabies. Nat Rev Dis Primers.2017;3:17091

16 Rabies: Post Exposure Prophylaxis (PEP) WOUND MANAGEMENT PASSIVE IMMUNIZATION (RIG) ACTIVE IMMUNIZATION (ARV)

Rabies in India: Facts & Figures Highest burden of global human rabies >95% of human cases canine mediated; 60% victims children Endemic in all states except the Islands of Andaman, Nicobar and

17 Rabies in India: Facts & Figures Highest burden of global human rabies >95% of human cases canine mediated; 60% victims children Endemic in all states except the Islands of Andaman, Nicobar and Lakshadweep Estimated stray dogs: million 17.4 million animal bites annually; A dog bites a human every 2 seconds and every 30 minutes a human dies of rabies Estimated number of people taking PEP: ~4 million Estimated number of livestock rabies: unknown but considered high

Human Rabies: Need for Lab Diagnosis Diagnosis/distinguish from GB syndrome in paralytic/atypical rabies Early diagnosis helps avoid unnecessary tests and treatment Patient management/barrier

18 Human Rabies: Need for Lab Diagnosis Diagnosis/distinguish from GB syndrome in paralytic/atypical rabies Early diagnosis helps avoid unnecessary tests and treatment Patient management/barrier Nursing/Disinfection of ICU facilities Case closure and grief counseling Prophylactic vaccination to relatives, clinical & nursing staff Characterization of causative agent/molecular epidemiology

19 Human Rabies: Diagnostic Challenges Gold standard -Antigen detection by DFA in brain tissue (post-mortem) Obtaining consent for autopsy is a challenge Lab facilities for antemortem diagnosis few Sensitivity of antemortem diagnosis low-multiple tests on several clinical samples required to confirm diagnosis Antemortem tests can rule in Rabies but cannot rule out Rabies

20 Human Rabies: Antemortem Diagnosis NIMHANS, Bangalore; (n=128) Test Sample Number Tested Number Positive RFFIT (Antibodies) CSF (22.4%) Real Time PCR CSF (12.3%) Nuchal Skin (18.6%) Saliva (23.4%) Antemortem Diagnosis in 52/128 (40.6%) Mani RS et al. Human rabies in India: an audit from a rabies diagnostic laboratory.trop Med Int Health. 2016;21(4):

21 Human Rabies Survivors Worldwide Fooks et al. Rabies. Nat Rev Dis Primers. 2017; 3:17091

22 Rabies Survivors in India: An Emerging Paradox? Access to advanced medical facilities: Excellent ICU care All had received at least partial vaccination Survival not synonymous with Recovery All rabies survivors in India: severe sequelae Long-term emotional, social and economic repercussions for family Need to explore newer therapeutic strategies Prevention should remain primary focus Mani RS. Human Rabies Survivors in India: An Emerging Paradox? PLoS Negl Trop Dis. 2016;10(7):e

Vaccines & Biologics: India India leads the campaign for use of modern human rabies vaccines in South Asia India phased out nervous tissue derived vaccines (NTV) in 2005 Purified chick embryo cell

23 Vaccines & Biologics: India India leads the campaign for use of modern human rabies vaccines in South Asia India phased out nervous tissue derived vaccines (NTV) in 2005 Purified chick embryo cell vaccine (PCECV) and purified vero cell vaccine (PVRV) Private sector production capacity ~30 million doses of human rabies vaccine and ~4 million vials of ERIG (DGHS 2015) Potential for doubling the production capacity in future Monoclonal antibodies for human PEP launched recently

24 Intradermal rabies vaccination in India-A paradigm shift Administering minute doses (0.1mL) of vaccine into the layers of skin Rational and Scientific Highly Immunogenic, Safe and Efficacious Reduction in volume and costs (60-80%) Approved by WHO since 1992 Used in Thailand, Philippines and Sri Lanka since 1993 Approved by DCGI since 2006 (India) Implemented successfully in several states (public sector)

Rabies PEP in India-Reality Wound washing practices Often overlooked (despite being a critical step) Few primary health centres have facilities for wound washing Vaccines: Low compliance

25 Rabies PEP in India-Reality Wound washing practices Often overlooked (despite being a critical step) Few primary health centres have facilities for wound washing Vaccines: Low compliance due to- Myths and traditional/alternative systems of health care Inadequate awareness among bite victims /doctors Irregular supply/stock outs Non-affordability Confusion with IM/ID regimens

26 Rabies PEP in India-Reality Rabies Immunoglobulin (RIG) Life saving, yet usage in <5% of cases ERIG manufactured indigenously; fear of anaphylaxis HRIG imported; expensive, shortage of supply Non-affordability of RIGs (HRIGs in particular) by majority of victims Lack of awareness about RIG in bite victims/health care workers Deficit of trained manpower: Time consuming procedure for doctors Unfounded fear of anaphylaxis- doctors reluctant to use Non-availability/stock-outs in many parts of the country

27 PEP failures extremely rare PEP Failures? Serious deviations in PEP protocols Incorrect advice/regimen Wound care Inadequate/Not done Suturing of wounds without RIG administration Delay in initiating PEP Inadequate dosage of vaccine Unsuitable site of vaccine administration Inappropriate administration of RIG (only IM) Omission of RIG even in category III exposures

28 Rabies control in India: Challenges Rabies not a notifiable disease No systematic surveillance for human and animal rabies Few diagnostic laboratories (human and veterinary sector) Lack of intersectoral co-ordination Lack of ownership and leadership for dog rabies control Lack of community participation in dog rabies control No clear cut guidelines for dog vaccination and population control

Way Forward using One Health approach Rabies Control and Elimination: Ideal candidate for operationalization of One Health as it affects humans, domestic animals and wildlife Demands

30 Way Forward using One Health approach Rabies Control and Elimination: Ideal candidate for operationalization of One Health as it affects humans, domestic animals and wildlife Demands multi-dimensional approach: Socio-cultural dimension Technical dimension Organizational dimension Political dimension Resources Needs multidisciplinary approach and expertise involving different administrative levels and players Central government/local government/civic society, NGOs and international partners

31 The Way Forward ONE HEALTH APPROACH

32 The Way Forward Human/Medical/Public Health Reassessing the burden of rabies Make human rabies a notifiable disease Improving the availability, affordability and accessibility to life saving rabies vaccines & RIGs. Promotion of cost effective intradermal rabies vaccination for PEP and preexposure prophylaxis (PrEP) in vulnerable populations Advocacy on need to provide life saving RIGs to all cases with category III exposures visiting government hospitals free of cost Continuing Medical Education (CME) and Hands on training for professionals

33 Veterinary/Public Health The Way Forward Compulsory licensing of pet dogs with annual vaccination Expanding the network of rabies diagnostic laboratories in the country and enhancing real-time reporting through coordination between the medical and veterinary sectors. Setting up vaccine banks and launching planned mass dog vaccination campaigns (at least 70% coverage) in urban and rural areas Canine population Control The MOST COST EFFECTIVE STRATEGY for preventing rabies in humans is to eliminate rabies in dogs through vaccination (WHO, 2010)

34 The National Rabies Control Programme- India 12th Five year plan Nodal agency: Human component (NCDC, Delhi) Veterinary component (AWBI, Chennai) Strengthening Inter-sectoral coordination Human Health to reduce mortality due to rabies NRCP Animal Health To cut down transmission of disease Maintaining rabies free areas as rabies free

state) Few urban areas in the states of Rajasthan and Jharkhand

35 Success Stories in India: Towards Rabies Elimination No human rabies cases in Nilgiris (South India) and Sikkim (North-eastern state) Few urban areas in the states of Rajasthan and Jharkhand Mass dog vaccination in short period of time, Goa to be rabies free by 2020?

36 Population: 1,817,000 Area: 3,702 km 2 Density: 490/km 2 or 1,300/ mi 2 Estimated dog population: 1,30,000 Goa State, India Data Source-Mission Rabies, Goa

Year Human Rabies Cases: Goa, India Number of human deaths 2014 17 2015 5 2016 1 2017 2 2018 0 (till date) Availability and administration of PEP in Goa Government hospitals for free

37 Year Human Rabies Cases: Goa, India Number of human deaths (till date) Availability and administration of PEP in Goa Government hospitals for free Increased awareness in public and children to seek medical advice after a dog bite Mass anti rabies vaccination of dogs (owner and stray) Catching and removing a rabies suspected dog from a locality

38 Towards Rabies Elimination in India STRENGTHS OPPORTUNITIES WEAKNESS THREATS

Strategies known Dedicated community of rabies experts Weakness

39 Towards Rabies Elimination in India Strengths Totally preventable disease Basic tools are available. Strategies known Dedicated community of rabies experts Weakness Fund constraints-nrcp Less intersectoral collaboration No surveillance mechanisms, less data

regional and international organizations Threats Increasing canine

40 Towards Rabies Elimination in India Opportunities Children-most affected group Increasing focus on one health Partnership with regional and international organizations Threats Increasing canine population Animal welfare activism Animal and Human health experts work in isolation

41 Elimination of Human Rabies is Achievable! There is a proof of concept for controlling rabies in dog population A comprehensive rabies control programme includes mass dog vaccination, population control, accessibility and availability of PEP and public awareness The roadmap for rabies elimination should define a strategic approach, timeline and indicators Rabies elimination may serve as a model for operationalization of One Health

42 Partners in Rabies Control Several NGOs And several other public and private partners! APCRI IMA, IVA, IAP

43 Acknowledgements Director, NIMHANS, Bangalore Departments of Neurovirology and Neuropathology, NIMHANS Dr. Gyanendra Gongal, WHO Regional Office for South-East Asia, New Delhi Dr. Ashwathnarayana, Kempegowda Institute of Medical Sciences (KIMS), Bangalore

Towards Sustainable Prevention of Rabies at Source: Case Report India

Towards Sustainable Prevention of Rabies at Source: Case Report India S. Abdul Rahman Secretary Commonwealth Veterinary Association President, Association for Prevention and Control of Rabies in India