Towards Rabies Elimination In India ESCMID eLibrary © by ...

Dr. Reeta S. ManiAdditional Professor, Department of Neurovirology

WHO Collaborating Centre for Reference and Research in RabiesNational Institute of Mental Health & Neurosciences (NIMHANS)

Bangalore, India

Towards Rabies Elimination In India

28th ECCMID, Madrid, Spain; April 21, 2018 ESCMID eLibrary

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THE DEATH SENTENCE

RABIES

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100% PREVENTABLE!

RABIES

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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

CASE-1

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Dept of Neuropathology, NIMHANS, Bangalore ESCMID eLibrary

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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

CASE-2

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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

CASE-3

Goswami U et al. Psychiatric presentations of rabies. Trop Geogr Med 1984;36:77-81 ESCMID eLibrary

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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-4

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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

CASE-5

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Rabies: Challenges Diagnostic

Treatment/Management

Palliative care

Social

Medico-legal

Infection control

Case closure & grief counseling ESCMID eLibrary

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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 ESCMID eLibrary

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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%)

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The Lyssavirus Genus

Fooks et al. Rabies. Nat Rev Dis Primers.2017;3:17091 ESCMID eLibrary

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Transmission

The Bullet that Never Fails!

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Human Rabies: Clinical Course

Fooks et al. Rabies. Nat Rev Dis Primers.2017;3:17091 ESCMID eLibrary

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Rabies: Post Exposure Prophylaxis (PEP)

WOUND MANAGEMENT

PASSIVE IMMUNIZATION (RIG)

ACTIVE IMMUNIZATION (ARV)

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Highest burden of global human rabies

Rabies in India: Facts & Figures

>95% of human cases canine mediated; 60% victims children

Endemic in all states except the Islands of Andaman, Nicobar and Lakshadweep

Estimated stray dogs: 25-30 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 ESCMID eLibrary

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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 ESCMID eLibrary

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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 ESCMID eLibrary

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Human Rabies: Antemortem DiagnosisNIMHANS, Bangalore; 2012-2014 (n=128)

Test Sample Number Tested

Number Positive

RFFIT (Antibodies) CSF 89 20 (22.4%)

Real Time PCRCSF 81 10 (12.3%)

Nuchal Skin 59 11 (18.6%)

Saliva 77 18 (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):556-63. ESCMID eLibrary

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Human Rabies Survivors

Worldwide

Fooks et al. Rabies. Nat Rev Dis Primers. 2017; 3:17091 ESCMID eLibrary

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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):e0004774. ESCMID eLibrary

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Vaccines & Biologics: IndiaIndia 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 ESCMID eLibrary

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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) ESCMID eLibrary

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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

Rabies PEP in India-Reality

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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

Rabies PEP in India-Reality

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PEP failures extremely rare

Serious deviations in PEP protocolsIncorrect advice/regimenWound care Inadequate/Not doneSuturing of wounds without RIG administrationDelay in initiating PEPInadequate dosage of vaccineUnsuitable site of vaccine administrationInappropriate administration of RIG (only IM)Omission of RIG even in category III exposures

ERIG manufactured indigenously; fear of anaphylaxis

PEP Failures?

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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

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Way Forward using “One Health” approachRabies Control and Elimination: Ideal candidate for operationalization of“One Health” as it affects humans, domestic animals and wildlifeDemands 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 ESCMID eLibrary

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The Way ForwardHuman/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 pre-exposure 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 ESCMID eLibrary

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The Way ForwardVeterinary/Public Health

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) ESCMID eLibrary

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The National Rabies Control Programme- India

12th Five year plan

Nodal agency:

Human component (NCDC, Delhi)

Veterinary component (AWBI, Chennai)

NRCP

Human Health

to reduce mortality due

to rabies

Maintaining rabies free

areas as “rabies free”

Animal Health

To cut down transmission of

disease

Strengthening Inter-sectoralcoordination

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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? ESCMID eLibrary

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Goa State, India

Data Source-Mission Rabies, Goa

Population: 1,817,000Area: 3,702 km2

Density: 490/km2 or 1,300/ mi2

Estimated dog population: 1,30,000

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Year Number of human deaths

2014 17

2015 5

2016 1

2017 2

2018 0 (till date)

Human Rabies Cases: Goa, India

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

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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

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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

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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 operationalizationof One Health

Elimination of Human Rabies is Achievable!

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Partners in Rabies Control

APCRI

And several other public and private partners!

IMA, IVA, IAP

Several NGOs

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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

Acknowledgements

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Towards Rabies Elimination In India ESCMID eLibrary © by ...

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