Volume XX, Issue II, January 2019 ISSN 0973-5038

APCRIAPCRI JOURNAL

Oĸ cial Journal of the AssociaƟ on for PrevenƟ on and Control of Rabies in (Regd.)

Volume XXI, Issue II, January 2020

Published by AssociaƟ on for PrevenƟ on and Control of Rabies in India (APCRI)

Also available at: www.apcrijournal.com 1

APCRI Journal

Offi ce Bearers of Associa on for Preven on and Control of Rabies in India

Founder President & Mentor Dr. M. K. Sudarshan 9481778364/[email protected]

President Dr. D. H. Ashwath Narayana 9341948189/[email protected]

Vice President Vice President Dr. Durga Madhab Sathpathy Dr. SriKrishna Isloor 9861084175/drdurgams@rediff mail.com 9449992287/[email protected]

Joint Secretary Secretary General Treasurer Dr. Krishna Kumar Dr. Sumit Poddar Dr. Ravish H. S. 9431102588/[email protected] 9830059468/[email protected] 9900562743/drravishhs@rediff mail.com

Editor Dr. Kajal Krishna Banik 9331048886/[email protected]

Zonal Representa ve (North) Zonal Representa ve (North) Dr. H. K. Gohil Dr. Omesh Kumar Bhar 99680977505/[email protected] 9418120302/bhar [email protected]

Zonal Representa ve (East) Zonal Representa ve (East) Dr. Gautam Prasad Sarkhel Dr. Tapas Ranjan Behera 9433381169/[email protected] 937183787/[email protected]

Zonal Representa ve (West) Zonal Representa ve (West) Dr. Govardhan Meena Dr. M. K. Jhala 9414042908/[email protected] 9824243564/[email protected]

Zonal Representa ve (Central) Zonal Representa ve (Central) Dr. M. N. Siddique Dr. Lakhan L Ahirwar 9838071127/[email protected] 942444259/[email protected]

Zonal Representa ve (South) Zonal Representa ve (South) Dr. Sunil Kumar K M Dr. Sheela P. Haveri 9740545615/[email protected] 8618629403/[email protected]

Advisory Board Dr. S. Abdul Rahman, Dr. B. J. Mahendra, Dr. Jyothi B Du a, Dr. Jugal Kishore, Dr. Muralidhar Thambe, Dr. Chi aranjan Roy, Dr. Reeta S. Mani, Dr. Thinly Bhu a

Editorial Board Dr. Reeta S. Mani, Dr. Shrikrishna Isloor, Dr. Jairaj Singh Hanspal, Dr. Durga Madhab Sathpathy, Dr. Baisakhi Maji, Dr. Sunit Mukhopadhayay, Dr. D.H. Ashwath Narayana, Dr. Sumit Poddar, Dr. Ravish H.S.

1 Volume XXI, Issue III, January 2020

ASSOCIATION FOR PREVENTION & CONTROL OF RABIES IN INDIA GENERAL INFORMATION THE JOURNAL The APCRI has become a prime and one of the most vibrant scientifi c organization in the fi eld of rabies elimination with strength of about 750 life members and 40 Founder Life Members. Now APCRI serves as a platform that brings together the best minds in the country comprising of medical professionals, veterinary doctors and others for Advocacy, Research & information dissemination about prevention & control of Rabies. APCRI led by an excellent team of rabies experts and dedicated people and is actively involved in conducting rabies related research, organizing conferences, Continuing Medical Education (CME) programmes, symposia, lectures, trainings, scientifi c publications, book release, etc. and has a pan India representation with global impact.

APCRI has its own offi cial indexed and peer reviewed journal on prevention and control of rabies which is published biannually. It is indexed in Index Copernicus International vide ISSN 0973-5038.

APCRI, with the technical and fi nancial assistance from World Health Organization (WHO) undertook the landmark national multi-centric rabies survey India during 2002-2004. In 2017, it conducted another Indian multi-centric rabies survey to assess programmatic experiences on rabies control with technical and operational support of WHO. INFORMATION OF AUTHORS There are no page charges for APCRI Journal submission. Please check

http://www. apcrijournal. com/Instructions. aspx for details.

All articles must be submitted online at http://www. apcrijournal. com/ArticleSubmission. aspx

Or

To the Editor Dr. Kajal Krishna Banik Email id- kajalbanik@gmail. com, Secretary General Dr. Sumit Poddar Email id- drsumitpoddar@gmail. com, President Dr. D. H. Ashwath Narayana Email Id- dhashwathnarayana@gmail. com, Treasurer Dr. Ravish H. S. Email Id- drravishhs@rediff mail. com POSTAL INFORMATION Transaction of the Association for Prevention and Control of Rabies in India (ISSN 0973-5038) is published two times in a year by APCRI. Annual subscription price is Rs. 300, in addition with postal charges.

Dr. Kajal Krishna Banik Editorial Offi ce Editor, APCRI Journal Dr. Sumit Poddar Mob : 9331048886 Secretary General, APCRI Email : kajalbanik@gmail. com H. P. PODDAR MEMORIAL CLINIC & NURSING HOME 56H, Beliaghata Main Road, Kolkata- 700010 Phone No. - 033 2370 6644,2353 9586 Email – drsumitpoddar@gmail. com

2 APCRI Journal

ASSOCIATION FOR PREVENTION & CONTROL OF RABIES IN INDIA

CONTENTS PAGES • General Information 02 Editorial 04 Dr. Kajal Krishna Banik, Hony Editor, APCRI

Special ArƟ cles • Rabies Prophylaxis: What is new in WHO, 2018 Recommendations & its implementation in India – A commentary 05 Dr. M. K. Sudarshan • Improving vaccination coverage of human as well as dogs – Two important steps towards elimination of rabies 09 Dr. Prasanna Deshpande, Dr. S. Sai Krishna, Dr. Devi Prasad Sahoo • Rabies in wildlife -a review in Indian context 13 S. K Mukhopadhyay, D. Borkotoky

Original Research ArƟ cles • Out of pocket expenditure for availing rabies post exposure prophylaxis 18 Ramya MP, Ravish HS, Nitu Kumari, Jithin Surendran • A Prospective Study on Psychological Impact in Children After Dog Bite Injuries in Bengaluru Urban 27 Dr Kishore SG, Dr Deepak Murthy HJ, Dr Ranganath TS, Dr Anil Kumar, Mr Vishwanatha V Neela • Seasonal Trend Of Animal Bite Victims Attending Anti Rabies Clinic Of A Tertiary Care Hospital, Berhampur, . 33 Prof. Durga Madhab Satapathy, Dr. Nivedita Karmeee, Dr. P. Narmada Reddy, Dr. Debasish Pandit

Case Report • Safety and immunogenicity of Rabies Human Monoclonal Antibody (Rabishield) in a category III rabid dog bite: A case report 40 Dr. Tapas Ranjan Behera, Dr. Swetaleena Ashe • Serum Sickness should not rule out Equine Rabies Immunoglobulin Administration - A Case Study 42 Dr. Santoshinee Rout, Dr. Tapas Ranjan Behera

Special Report • Street Dog Survey 46 Dr. Shrikrishna Isloor • APCRICON 2020 Announcement 60 • Guidelines for applying for “Young Scientist Award” 61 • Instruction to Author 62 • Achievements & Awards 69

3 Volume XXI, Issue III, January 2020

EDITORIAL

With the blessings and good wishes of the readers, doctors and researchers on Rabies in general and the members of the Associa on of Physicians for Preven on and Control of Rabies in India in par cular we are here with the new edi on of our pres gious journal. I would like to acknowledge the services of the editorial board members and the contribu ons of our dynamic Secretary General for his tremendous amount of help and coopera on to publish this issue of the journal. Since the new commi ee took over the charge of this journal, we are trying our best to reach out each and every corners of the country to collect, collate and encourage for ar cles on diff erent aspects of rabies control and its management. Unfortunately we are not receiving suffi cient number of papers from the respected teachers, researchers and scien sts. We appeal you all through this to submit your works for publica on. As you all know that it’s not easy in our country to go for hassle free rabies management of rabies, similarly it’sS not possible to manage the disease without proper knowledge and informa on among the prac oners at large. That’s why we have incorporated some important angles of rabies management through diff erent ar cles. You will be glad to know that we have included the current global scenario and the eff orts of the World Health Organisa on (WHO) in this issue along with the most neglected aspect of our health care, the psychological impact of animal bites par cularly in the children. We have included one ar cle to make people aware regarding the seasonality of animal bites in our country with a specifi c inten on to encourage our members to work further to document the epidemiological scenario, if any. We emphasize that a er the last Na onal level guidelines on Rabies provided in 2015 should be rewri en and a fresh and eff ec ve na onal guidelines be published by our na onal Government incorpora ng diff erent recommenda ons of the WHO and other agencies working in the fi eld of rabies control and management without further delay. Let us hope for the best to be able to achieve the goal of Rabies elimina on from our country by 2030.

Dr. Kajal Krishna Banik MBBS, DPH, MAE Hony Editor Journal of the Associa on for Preven on and Control of Rabies in India (APCRI)

4 APCRI Journal

SPECIAL ARTICLE

Rabies prophylaxis: What is new in WHO, 2018 recommendations & its implementation in India - A commentary1 Dr. M. K. Sudarshan* MD (BHU), FAMS, HON, FFPH (UK)

ABSTRACT The World Health Organiza on following expert reviews and consulta ons recently in 2018 released two documents i. e. Technical Report Series on rabies, no. 1012 and Posi on Paper on rabies vaccines in weekly epidemiological record, no. 16. In India, the last na onal guidelines on rabies prophylaxis were provided in 2015. Hence, following the WHO, 2018 guidelines in January, 2019, a Government of India expert group on rabies met in New Delhi, reviewed the recent WHO guidelines for adapta on and issuing revised na onal guidelines. In this context, a cri cal appraisal of the rabies prophylaxis in the current situa on is elaborated in this ar cle for the informa on of both private medical prac oner and service provider in government ins tu ons. Key words: Rabies prophylaxis, rabies vaccine, rabies immunoglobulin, rabies monoclonal an body. The World Health Organiza on was established in 1948 as a specialized agency of the United Na ons serving as the direc ng and coordina on authority for interna onal health ma ers and public health. One of WHO’s cons tu onal func ons is to provide objec ve and reliable informa on and advice in the fi eld of human health, a responsibility that it fulfi ls in part through its extensive programme of publica ons. The latest updated informa on on rabies is available mainly from two WHO publica ons - 1. WHO Technical Report Series (TRS), 1012, WHO expert consulta on on rabies, 2018 and 2. Weekly Epidemiological Record (WER), Rabies vaccines: WHO posi on paper (PP), 16,2018. The TRS makes available the fi nding of various interna onal groups of experts that provide WHO with the latest scien fi c and technical advice on a broad range of medical and public health subjects. Members of such expert groups serve without remunera on in their personal capaci es rather than as representa ves of governments or other bodies; their views do not necessarily refl ect the decisions or the stated policy of WHO1. The PP summarizes the essen al. It must be noted here that information provided by WHO through its publications are only recommendatory in nature and for consideration of the national governments, professionals and others and not binding on them. Hence, the national governments review these recommendations that are largely global in nature and mostly through expert consultation in the local context and then subsequently adapt and implement them. In this context, on 8th January, 2019 a Government of India (GoI) expert group met at National Centre for Disease Control, Delhi, and reviewed the national guidelines on rabies prophylaxis3. This paper provides an expert review and crisp summary of these three reports.

1A. L. Saha Memorial Ora on Lecture, 64th Founda on day programme, 27th September, 2019, Indian Public Health Associa on, Kolkata *Founder President and Mentor, Associa on for Preven on and Control of Rabies in India, Re red Dean / Principal and Professor of Community Medicine, Kempegowda Ins tute of Medical Sciences, Bangalore-560070. Email: mksudarshan@gmail. com Informa on on rabies and rabies vaccines and concludes with the current WHO posi on on the use of rabies vaccines worldwide. The PP is intended for use mainly by na onal public health offi cials2.

Submission Date : 04/11/2019 Acceptance Date : 30/11/2019 5 Volume XXI, Issue III, January 2020

1. Rabies prophylaxis 1.1. Post – Exposure ( PEP) Regimens WHO recommendations list of preferred PEP regimens and alternatives, all of which have been assessed for immunogenicity, clinical outcome, feasibility and cost eff ectiveness is given below1: Table – 1. WHO – recommended and alternative post-exposure prophylactic regimens

No. of injection sites per clinic visit PEP Regimen Duration of course (day 0,3,7,14,21-28) WHO recommended intradermal regimen 1 week, two sites 7 days 2-2-2-0-0 WHO recommended intramuscular regimens 2 weeks 14-28 days 1-1-1-1-0 3 weeks 21 days 2-0-1-0-1 Alternative immunogenic intradermal regimens 1 month, two sites ≤28 days 2-2-2-0-2 1 month, simplifi ed four sites ≤28 days 4-0-2-0-1 1 week, four sites 7 days 4-4-4-0-0 However, from the above list, only the one month, two sites (2-2-2-0-2) ID regimen was approved by Government of India in 2006 and is in use in the country since then. All other above listed regimens are not approved by Government of India and also the product inserts/labels of the manufacturers that accompany rabies vaccines do not specify these other regimens. Consequently, it is advised not to use these other regimens and if used will amount to “off label” use. In January, 2019, a Government of India expert group observed lack of evidence with respect to this WHO recommendation in Indian settings and recommended multi-centric studies to generate more evidence3. As a result, the Association for Prevention and Control of Rabies in India (APCRI) is planning to conduct an Indian multicentric randomized controlled trial (RCT) using indigenous rabies vaccines, equine rabies immunoglobulin (eRIG) and rabies monoclonal antibody (rmAb) to assess the immunogenicity and safety of new one week, Institute Pasteur, Cambodia, IPC- ID regimen (2-2-2-0-0) and only wound infi ltration of eRIG and rmAb without systemic injection. 4 1.2. Post-exposure prophylaxis (PEP) following re-exposure in previously vaccinated individuals 1.2.1. Re-exposure less than three months of previous full course PEP or PrEP (with documentary evidence) Only wound management and no PEP immunization1,2 The GoI, 2019 expert group endorsed this line of management. 1.2.2. Re-exposure more than three months of previous full course PEP or PrEP Wound management and PEP immunization1,2 The dosage is one vial by IM route or 0.1mL by ID route Regimens 1-site ID on days 0 and 3 (1-1-0-0-0); or at 4-sites ID on day 0(4-0-0-0-0); or at 1-site IM on days 0 and 3 (1-1-0-0-0) No RIG is needed, irrespective of category II or category III exposure. However, the GoI 2019, expert group recommended continuation of the currently approved regimens of ID or IM vaccinations given on days 0 & 3.

6 APCRI Journal

2. Pre-exposure prophylaxis (PrEP) regimens The following are the WHO-recommended PrEP regimens Table -2. WHO-recommended PrEP regimens

No. of injection sites per clinic visit PrEP Regimen Duration of course (day 0,3,7,14,21-28) WHO recommended intradermal regimen Two visits 7 days 2-0-2-0-0 WHO recommended intramuscular regimen Two visits 7 days 1-0-1-0-0 PrEP under specifi c circumstances Single visit, ID 1 day 2-0-0-0-0 Single visit, IM 1 day 1-0-0-0-0 In January, 2019, the GoI expert group however, recommended continuation of the currently approved three dose regimen (0.1mL ID at one site or 1 vial IM given on days 0,7 and 21 or 28). 3. Using rabies vaccines labelled for intramuscular (IM) use by intradermal (ID) route Rabies vaccines labelled for intramuscular use can be used safely via the intradermal route, even if this constitutes “off –label” use1. The GoI expert group recommendation is awaited. 4. Evidence suggests that a change in the route of administration or in vaccine product during a PEP or PrEP course is safe and immunogenic2. However, the GoI, 2019 expert group approved the change in vaccine product and approval for change in route of administration is awaited. 5. Prioritizing rabies exposures when limited amount of RIG is available1 If a limited amount of RIG is available, it should be prioritized for exposed patients on the basis of the following criteria: • Multiple bites • Deep wounds • Bites to highly innervated parts of the body, such as the head, neck and hands • Severe immunodefi ciency • Bites from an animal with confi rmed or probable rabies • A bite, scratch or exposure to mucous membranes from a bat RestricƟ ng RIG or vaccine to people with high-risk exposure to rabies may endanger those with lower – risk exposure and should be considered carefully before being implemented. In January, 2019, the Government of India expert group did not accept this recommendaƟ on and recommended conƟ nuaƟ on of the current pracƟ ce that in all paƟ ents with category III exposure RIG should be given3. 6. Using RIG for only wound infi ltration without systemic injection WHO no longer recommends injecting the remainder of the calculated RIG dose –IM at a distance from the wound. Instead, the calculated RIG dose can be fractionated in smaller, individual syringes to be used for several patients. This requires handling and storage in aseptic conditions. Unused fractionated doses and open vials of RIG should be discarded by the end of the day2. However, in January, 2019 a Government of India expert group recommended continuation of the existing practice of injecting the remaining RIG volume intramuscularly, as close as possible to the presumed exposure site, to the

7 Volume XXI, Issue III, January 2020

degree that is anatomically feasible3. 7. For mucosal exposure with no wound, rinsing with (diluted2) RIG can be considered1. The GOI expert group recommendation is awaited. 8. Consumption of meat or milk from a rabid animal is strongly discouraged and should be avoided but if it occurs, PEP is not indicated2. Milk that has been pasteurized presents no risk for rabies virus (RABV) transmission1. The GoI, 2019 expert group endorsed this recommendation3 (for milk only and about meat it is silent) 9. If any doses are delayed, vaccination should be resumed and not restarted2. The GoI, 2019 expert group has endorsed this recommendation3 10. People who have received at least two doses (intradermal or intramuscular) of a cell culture vaccine on an appropriate schedule before discontinuation should be considered as having received PrEP2. The GOI expert group recommendation is awaited. 11. If available, the use of mAb products instead of RIG is encouraged2. In October, 2017, Serum Institute of India Pvt. Ltd. Pune launched the world’s fi rst rabies monoclonal antibody (RMAb) and is now available in the market. The GoI expert group recommended that rmAb needs to be studied for its eff ectiveness, safety in multi-centric Indian settings3. 12. What is “off label “use? All medicines, including rabies vaccines and immunoglobulins/ rabies monoclonal antibody are accompanied by product inserts (or also known as labels or enclosures, etc. ) that provide guidance for their use in the patients. These labels or product inserts are approved by the Drug Controller General of India (DCGI). Any usage that involves deviation from the guidelines provided in these product inserts/labels is considered as “off label “use. The private medical practitioners in particular must avoid “off label “use as in the event of any mishap, as they are liable to be sued under consumer protection act. In conclusion, in government institutions and in private practice the recommendations of Government of India and the guidelines given in the product (rabies vaccines, RIG & RMAb) insert shall be followed. Any use of WHO recommendation that is not endorsed by GoI or in the product insert may be made only in exceptional circumstances and solely with the intention of saving the life of the patient and it shall be defendable in a court of law, if the need arises. Lastly, the GoI national guidelines on rabies prophylaxis are expected to be issued soon this year. REFERENCES 1. WHO, WHO expert consultation on rabies, Technical Report Series, 1012, 2018, Geneva, Switzerland. 2. WHO, Rabies vaccines: WHO position paper – April, 2018, Weekly epidemiological record, no. 16,93, Geneva, Switzerland. 3. Government of India. National Centre for Disease Control, expert group meeting to review the national guidelines on rabies prophylaxis, 8th January, 2019, minutes of the meeting, New Delhi. 4. Ashwath Narayana. D. H. Indian multicentric study to assess the safety & immunogenicity of indigenous rabies vaccines using one week Institute Pasteur, Cambodia, regimen (2-2-2-0-0) & indigenous equine rabies immunoglobulin infi ltration of wounds without systemic injection – A project proposal, 21st National conference of APCRI, 6th July, 2019, Abstract book/conference souvenir, Ranchi, .

8 APCRI Journal

SPECIAL ARTICLE

Improving Vaccination coverage of Humans as well as Dogs – Two important steps towards Elimination of Rabies Dr. Prasanna Deshpande1, Dr. S. Sai Krishna2, Dr. Devi Prasad Sahoo3

Rabies is being targeted for elimination from India by 2030. It requires combined eff orts of government agencies, medical and veterinary professionals, private and non-government organizations as well as industry bodies involved with manufacture and supply of biologicals used for prevention of Rabies both in humans as well as carrier animals. Vaccination of host animals is as important as timely prophylaxis of humans to get rid of the disease as rabid animals can keep infecting humans unless they are disease free. Human Biologicals Institute (HBI) has been playing a key role since its launch in 2000 by supplying increasing volume of modern purifi ed vero cell cultured anti-rabies vaccine Abhayrab® from its facility at Udhagamandalam, , for vaccination of humans and has commenced supply from its new facility at Karkapatla, Telangana. Its parent organization Indian Immunologicals Limited has been contributing to the eff ort since 1989 by consistently supplying modern BHK cell cultured anti-rabies vaccine Raksharab for vaccination of animals from its facility at Hyderabad. Rabies is a viral zoonotic disease which causes signifi cant number of mortality in humans, especially in impoverished countries. Rabies virus (RABV) can have diff erent reservoir host species of mammals. The most important of these reservoirs as a source of human disease is the domestic dog. Transmission of RABV most commonly occurs following a bite from an infected host resulting in the deposition of virus-laden saliva into the wound. RABV is highly neurotropic and after a highly variable period, from a few weeks to months, it gets into peripheral nerve and travels to the dorsal root ganglion. Once within the spinal cord, the virus ascends to the brain, resulting in encephalitis that manifests in clinical signs and symptoms that can be categorized as either furious type or paralytic type of rabies. The more common and classical form furious rabies is characterized by symptoms of hydrophobia (fear of swallowing), aerophobia (fear of air current), and aggressive behavior. The paralytic form, also known as silent rabies, presents with ascending fl accid paralysis and in most cases, without the classical symptoms of hydrophobia or aerophobia. While the furious form mostly results in death within one week, in silent/ paralytic form of rabies the patient survives for weeks before ultimately succumbing to paralysis of respiratory muscles [1,2]. Across the world, canine rabies kills tens of thousands of people every year despite being a disease that is preventable by timely and proper prophylaxis. Repeated and well planned eff orts of mass animal vaccination had led to the elimination of spread of rabies by domestic dogs in high-income countries. Rabies now remains as a disease mostly in low and middle-income countries in Asia and Africa, and common among people living in rural, underserved populations where dog vaccination is rare. Following a rabid dog bite, prompt post-exposure prophylaxis (PEP) is the only way to ensure that the invariably fatal onset of rabies is prevented. Statistical modeling suggests that unless eff orts for dog vaccination are scaled up and gross improvements made in the PEP access, over 1 million people are likely to die of dog mediated rabies

1 Managimng Director,IIL 2 DGM Medical & Veterinary Services, IIL 3 Senior Manager, Medical Services, IIL

Submission Date : 03/12/2019 Acceptance Date : 10/01/2020 9 Volume XXI, Issue III, January 2020

between 2020 and 2035 [3]. Anti-rabies vaccine (ARV) is the most important component of PEP against rabies. In India, ESSEN regimen (comprising of fi ve doses, one each on days 0,3,7,14 and 28) has been approved for intramuscular administration while Modifi ed Thai Red Cross regimen (intradermal administration on 2 sites each on days 0,3,7 and 28) is the approved schedule for intradermal administration. A rabies virus neutralizing antibody (RVNA) titer of ≥0.5 IU/ml on day 14 after completion of vaccination with ARV is the consensus surrogate parameter agreed upon globally as indicative of an adequate response to immunization. Rabies vaccines can be administered by the intra-dermal (ID) or intramuscular (IM) route and various schedules have been approved in diff erent countries. Intra-dermal rabies vaccination was promoted by the World Health Organization (WHO) since 1992 after it was recommended by an expert committee constituted by it in 1991. This alternate route of administration has been shown to reduce the cost and dose requirement of vaccine by 60–80%, especially when used at high-volume clinics manned with trained staff . In the world, it was fi rst used in Thailand in 1990 and introduced in India after WHO recommendation around 2006 [4,5,6, and 7]. Though ID regimens could cut down the cost, due to the long duration of the schedules, persons requiring PEP often would not complete the full course of vaccination. The high cost of rabies PEP and likelihood of loss of income due to time spent in frequent travel to the clinic also pose as further barriers to treatment, particularly in lower- income countries where rabies is common. Available evidence supported feasibility of having PEP schedules with reduced duration, and in some cases, also reduction in number of doses administered without signifi cantly aff ecting immunogenicity and eff ectiveness against rabies. Evidence in favor of the 1-week 2-site ID regimen was recently supported by good clinical eff ectiveness and immunogenicity data from Cambodia, a rabies-endemic country. Reducing the number of visits and the associated costs by using these abridged regimens is likely to improve patient compliance. Based on these, the 2018 update of the WHO position on rabies vaccines addressed the need for more programmatically feasible recommendations that can improve overall outcomes for rabies while maintaining the effi cacy at individual level. The update considered the most recent evidence available to improve access to PEP to meet the needs of underserved populations better through shorter, less costly and more feasible schedules. These new PEP schedules for immunologically naïve individuals (of all age groups) include (a) 2-site ID administration on days 0,3 and 7 or (b) 1-site IM administration on days 0,3,7 and a fi nal dose between days 14–28 [6,8, 9]. A multi-centric trial proposed by APCRI to evaluate the newly proposed abridged ARV administration schedule is a welcome step which will help in establishing whether these schedules can be followed in countries like India. In this schedule known as one week Institute Pasteur, Cambodia regimen (2-2-2-0-0), intra-dermal doses will be administered at two sites over one week, on day 0,3 and 7. If the results of the study show protective titers, it will help in reduction of cost and improving compliance and may help in a big way towards reducing the disease burden. The study will also help manufacturers of ARVs by providing guidance in taking steps to adopt the abridged regimens recommended in the current WHO expert consultation on rabies [10,11]. Human Biologicals Institute (HBI), a division of Indian Immunologicals Limited, Hyderabad, is one of the manufacturers of modern cell cultured ARV for use in humans. Abhayrab®, a purifi ed vero cell cultured rabies vaccine (PVRV) manufactured by HBI, is an inactivated ARV that contributes in a big way towards meeting the requirement of the vaccine in India as well as many other countries in Asia and other continents. This helps in ensuring PEP coverage to a great extent. Since the launch of Abhayrab in the year 2000 from its manufacturing facility at Udhagamandalam (Ooty), Tamil Nadu, the company has been striving hard to cater to the requirement for ARV. In the last 15 years HBI has ramped up its capacity successfully. The supply of Abhayrab® increased from >16 million doses in the period 2004-2009 to >32 million doses in the period 2009-2014. The supply was further increased to >52 million doses in the period 2014-2019. HBI has also commenced supply from its new and modern facility at Karkapatla, Telangana and is making all eff orts to meet the requirement of the country and the rest of the

10 APCRI Journal world. While providing PEP in time is essential in preventing rabies in humans exposed to suspect rabid animals, other means are equally important to reduce the transmission and incidence of the disease. The elimination of human rabies mediated by dogs is attainable through multipronged approach with use of existing safe and eff ective human and veterinary vaccines and application of diff erent preventive modalities with a sound understanding of the disease. Globally, all developed countries have achieved this goal whereas Asia and Africa have lagged behind. Mass dog vaccination is considered one of the important modalities for the elimination of canine rabies which will ultimately lead to reduction in transmission of the disease to humans. Current veterinary vaccines used in majority of countries are safe and effi cacious and provide economic benefi ts through large-scale campaigns. Despite longer durations of immunity, turnover of canine populations necessitates that vaccination campaigns are performed regularly to achieve sustainably high proportions of herd immunity. However, the frequency at which such campaigns are being carried out remains unsatisfactory [3,12, and 13]. Mass dog vaccination campaigns, with a target of approximately 70% coverage of the estimated population have been tried successfully at many places. Intensive, widely advertised, large-scale vaccination campaigns yield good results as opposed to protracted, independent, uncoordinated area-by-area approaches. Operative since the 1920s, such canine vaccination programs have been proven eff ective not only in the developed countries but also in some places in lower income countries. The incidence of reported rabies is now negligible as compared to that in the past in most parts of Americas and Europe after repeated and successful mass animal vaccination eff orts. One project in Goa, in India, vaccinates around 100,000 dogs annually. With additional eff orts of providing rabies related education to children and responding to reports of dog suspected of carrying rabies, the state has achieved good success in control of rabies in the period 2015 to 2017. Reported cases of human rabies mortality in the state has fallen from 17 in 2014 to two in 2017 [13]. Indian Immunologicals Limited, Hyderabad, is a major supplier of animal anti-rabies vaccine (ARV), brand named ‘Raksharab’. The company had started production of this inactivated BHK cell cultured ARV for use in animals in 1989 at its Hyderabad facility. Currently around 15 million doses of ‘Raksharab’ are supplied per year which caters to a signifi cant part of the requirement of vaccines for vaccination of animals against rabies. The company has been supporting rabies control measures sustainably by regularly arranging free animal vaccination camps and holding awareness campaigns among animal handlers, school going children and other people at high risk. It is hoped that eff orts towards elimination of rabies from India and elsewhere in the world will be enhanced in near future. Indian Immunologicals Limited and its division Human Biologicals Institute continue to cater to the needs for high quality modern cell cultured animal as well as human ARVs from the respective facilities. Continuous eff orts are being made to improve the accessibility of the vaccines and improve the vaccination coverage and support all eff orts towards eliminating rabies from India as early as possible. REFERENCES 1. Hicks D. J. , Fooks A. R. and Johnson N. ; Developments in rabies vaccines; Clinical and Experimental Immunology, 169: 199–204; doi:10.1111/j. 1365-2249.2012.04592.

2. Mahadevan A. , Suja M. S. , Mani R. S. and Shankar S. K. ; Perspectives in Diagnosis and Treatment of Rabies Viral Encephalitis: Insights from Pathogenesis; Neurotherapeutics (2016) 13:477–492; DOI 10.1007/ s13311-016-0452-4

3. Wentworth D. , Hampson K. , Thumbi S. M. , Mwatondo A. , Wambura G. , Chng N. R. ; A social justice perspective on access to human rabies vaccines; Vaccine 37 (2019) A3–A5; https://doi. org/10.1016/j. vaccine. 2019.01.065

11 Volume XXI, Issue III, January 2020

4. National Guidelines on Rabies Prophylaxis-2015, National Rabies Control Programme, National Centre for Disease Control, India

5. Minutes of the Meeting - Expert group meeting to review the National Guidelines on Rabies Prophylaxis; 8th January 2019, NRCP/55027/11/ 2018-NCDC; National Centre for Disease Control, India

6. Kessels J. , Tarantola A. , Salahuddin N. , Blumberg L. , Knopf L. ; Rabies post-exposure prophylaxis: A systematic review on abridged vaccination schedules and the eff ect of changing administration routes during a single course; Vaccine 37 (2019) A107–A117; https://doi. org/10.1016/j. vaccine. 2019.01.041

7. Gongal G. , Sampath G. ; Introduction of intradermal rabies vaccination – A paradigm shift in improving post- exposure prophylaxis in Asia; Vaccine 37 (2019) A94–A98; https://doi. org/10.1016/j. vaccine. 2018.08.034

8. Tarantola A. , Ly S. , Chan M. , In S. , Peng Y. , Hing C. et al; Intradermal rabies post-exposure prophylaxis can be abridged with no measurable impact on clinical outcome in Cambodia, 2003–2014; Vaccine 37 (2019) A118–A127; https://doi. org/10.1016/j. vaccine. 2018.10.054

9. O’Brien K. L. , Nolan T. , on behalf of the SAGE WG on Rabies; The WHO position on rabies immunization – 2018 updates; Vaccine 37 (2019) A85–A87; Vaccine 37 (2019) A85–A87; https://doi. org/10.1016/j. vaccine. 2018.10.014

10. http://apcri. org/pdf/APCRICON%202019_Scientifi c_schedule. pdf; p-4

11. WHO Expert Consultationon Rabies, Third Report; WHO Technical Report Series1012; https://apps. who. int/iris/bitstream/handle/10665/272364/9789241210218-eng. pdf

12. Rupprecht C. E. , Kuzmin b I. V. , Yale G. , Nagarajan T. , Meslin F. X. ; Priorities in applied research to ensure programmatic success in the global elimination of canine rabies; Vaccine 37 (2019) A77–A84; https:// doi. org/10.1016/j. vaccine. 2019.01.015

13. Rattanavipapong W. , Thavorncharoensap M. , Youngkong S. , Genuino A. J. , Anothaisintawee T. ,

12 APCRI Journal

SPECIAL ARTICLE

Rabies in wildlife -a review in Indian context S. K Mukhopadhyay1 & D. Borkotoky2

INTRODUCTION Rabies is a latin word that means ‘madness’. Rabies is one of the most important viral zoonotic diseases aff ecting man and warm blooded animal. The disease has been observed in free and captive carnivores more than any other mammalian species. Urban and sylvatic are two epidemiological cycles maintained independently with occasional spill over from sylvatic to urban foci. Human is an accidental and usually blind host. Rabies has been recognized in India since the Vedic period (1500–500 BC) and is described in the ancient Indian scripture Atharvaveda, wherein Yama, the mythical God of Death, has been depicted as attended by 2 dogs as his constant companions, the emissaries of death (Deshmukh, 2004). Most animal bites in India (91.5%) are by dogs, of which about 60% are strays and 40% pets. The incidence of animal bites is 17.4 per 1000 population. A person is bitten every 2 seconds, and someone dies from rabies every 30 minutes. The annual number of person-days lost because of animal bites is 38 million, and the cost of post-bite treatment is about $25 million (Sudarshan, 2004). The National Multicentric Rabies Survey 2003, carried out by the Association for Prevention and Control of Rabies in India(APCRI), reported about 133 wild animal rabies death in various Species viz. mongoose- 98, jackal- 13, deer- 11, bear- 1, wolf-1, lion- 3, fox-1, rhinoceros-1, panther-1 during the period of 1992-2001. Through this literature an attempt is being made to ascertain the incidence of sylvatic rabies in India. OCCURRENCES Wild carnivores: During the period of 1967 to 1990 Na onal Zoological Park New Delhi has encountered cases of rabies: 2 white gress, a brown bear and a racoon. The gress showed symptoms akin to dumb form of rabies. There was slight drooling of saliva and tachycardia. The animal was off fed and no rise of temperature. As the disease progressed, the animal was emaciated with was ng of muscle of hindquarter and remained recumbent ll death. No prominent gross lesions were observed on necropsy. Laboratory inves ga on confi rmed the case (Arora, 1990-91). Brain specimen from a lioness, which died after showing clinical signs of rabies at Zoological Garden, Chatbir, Chandigarh was subjected to immunofl ourescene test at Central Research Institute(CRI), Kasauli was found to be positive for rabies (Singh et al 1981). In the year 1987, a lion at Renuka Safari in Himachal Pradesh showed symptom of furious form, attacking other lions, biting & striking against wire fence(gums and teeth were injured in the process). The lion was hypersensitive to sound. Hoarse roaring and drooling of saliva was noted. Paralysis, loss of appetite and hydrophobia was also observed. Gradually the animal become cachectic with complete paralysis and had dilated pupils. The animal died on the fourth day after onset of symptoms. The case was confi rmed at CRI Kasauli (Singh et al. , 1991) Rao et al. 1980 confi rmed rabies in three lions at Botanical Park, Bhubaneswar, Orissa. In the same park, Rao and Nayak (1984) confi rmed the death of a tigress ‘Kheri’ by histopathological examination and Flourescene Antibody Test (FAT). Prior to her death the animal showed abnormal behaviour, frequent vomiting, incoordinated movement but was able to drink water. In National Park, Bannerghata, Bangalore a bear (Melursus ursinus) was diagnosed with

1 Department of Veterinary Pathology, F/O Veterinary and Animal Science, WBUAFS, K. B. Sarani, Kolkata-37, , Email id : skmpath@gmail. com 2KVK-ICAR NRC on Mithun, Porba, Phek, Nagaland

Submission Date : 03/09/2019 Acceptance Date : 10/01/2020 13 Volume XXI, Issue III, January 2020

rabies. The animal manifested typical symptoms of rabies. Brain tissue smear showed presence of nigri bodies and biological test proved positive for rabies infection (Vijayasarathi et al. , 1983). In free living carnivores, the fi rst report of the disease was in two royal Bengal tigers (Panther tigris). The fi rst case was recorded in 1943 in Nagoan district and the second in 1950 near Saikowaghat in . The tigers attacked human, cattle and dogs. In both the cases Histopathological studies of brain specimen conducted at Pasteur Institute, Shillong confi rmed rabies infection (Pandit 1950-51). Three cases of mongoose-bite in human were reported. The brain of one mongoose was positive for rabies. Hence death of untreated bitten case was ascribed to mongoose bite (Grewal, 1932-33). Besides mongoose the disease is also reported in squirrels (Grewal & Nicholas, 1940). The outbreak of rabies among jackals of Nilgiri hills in 1943 and 1956 and in Tamil Nadu in 1979 were responsible for decline in their population. The brain of jackals proved positive for rabies (Pandit, 1979). Rabies surveillance in free living wild animals was carried out during 1976-80 in Tarai area of Uttar Pradesh. A total of 10 wild cats, 1 civet cat, 16 mongooses, 4 jackals and 62 shrews were screened. Presence of Nigri bodies could only be detected in 2 mongoose & 2 shrewa conclusively, but in either case virus was not isolated (Sethi et al. , 1980). About 6 years old feral leopard (Panther pardus) manifested aberrant behaviour in Karnataka state attacking villagers. The brain specimens collected at necropsy subjected to laboratory investigations (i. e Seller’s staining method of impression smear and biological testing in mice) led to the diagnosis of rabies (Jayakumar et al. , 1989). A Small Indian Civet cats (Viverricula indica) was tranquillized by National Zoological Park, New Delhi in the year 1991. The animal was wandering aimlessly in the populated urban area and attacked passerby. Later the animal showed inappetance, excitement, restlessness, drooping head, lower jaw hanging fi xedly, drooling of saliva and bumping into objects. Gradually the animal manifested incoordination of movement and muscle tremors of the hind quarters. The necropsy examination revealed severe congestion of the vital organs. Stomach and intestine were empty. The brain samples were sent to IVRI Izatnagar for pathological and virological diagnosis. Brain smear preparation made from inoculated mice was found positive for intracytoplasmic inclusion bodies indistinguishable from negri bodies as seen in rabies infection. The case was diagnosed as Furious rabies based on the clinical signs and course of illness coupled with biological fi ndings (Arora, 1993). Between 2007 and 2017,20 rabies suspected brain samples from dead animals covering diff erent species of wild animals from diff erent states of India such as Delhi (sambar deer, Himalayan sloth bear, hyena, and mongoose), Gujarat (hyena), Karnataka (wolf and bear), Punjab (jackal), (hyena), and Uttar Pradesh (bear) were submitted to ICAR - National Institute of Veterinary Epidemiology and Disease Informatics for confi rmatory rabies diagnosis. The samples were subjected for direct fl uorescent antibody test (dFAT), reverse transcription polymerase chain reaction (RT-PCR), and quantitative reverse transcriptase real-time PCR (RT-qPCR). The phylogenetic analysis of partial nucleoprotein gene sequences was performed. Of 20 samples, 11,10, and 12 cases were found positive by dFAT, RT-PCR, and RT-qPCR, respectively. Phylogenetic analysis showed that all Indian wild RVs isolates belonged to classical genotype 1 of Lyssavirus and were closely related to Arctic/Arctic-like single cluster indicating the possibility of a spillover of rabies among diff erent species (Reddy et al. , 2019). Jayson and Govind, 2014 reported a case of rabies in a mongoose in Kannur, . Mongoose species are known to be vectors of the rabies virus (Rhabdoviridae) (Rabies Survey Report 2003). Proboscida: Based on history and clinical signs, perhaps the fi rst case of rabies in Indian elephant attributed to the bites of rabid dog was described by Evan (1910) in his book entitled ‘Diseases of Elephant’. An elephant was attacked and bitten by a rabid dog at night in Hyderabad. Symptoms of delirium supervened after one month of exposure. The animal gradually became anorexic but did not manifest the symptoms of hydrophobia. The elephant was furious, unruly and died suddenly. On the same occasion another elephant died after 15 days after the one alluded to, with the same symptoms. In an another instance, paralytic rabies was recorded in a 25 year old elephant cow owned by the police station,

14 APCRI Journal

Paravatipur, Madras(Ramiah, 1932-33). The animal was biten on the left limb, trunk and tail by a rabid dog. Anti rabies vaccines was administered on the 9th day and the wounds were treated accordingly. On 43rd day, the cow developed sudden lameness of her hind limbs. Gradually hemiplegia progressed to parasis. She took meagre amount of grass and drunk water. The temperature of the animal ranged from 98.4 to 99.8 F. On 7th day of onset of symptoms, oedema developed on her head, neck and abdomen. She showed rapid pulse (70 /minute, Normal 30-35/minute). On the following day she was unconscious, sunken eyes, cyanotic mucus memebrane, rapid but feeble pulse, slow respiration but stertorous. The animal died on the 9th day. Brain sample sent to Pasteur Institute, Coonnor was positive for rabies. A case of rabies was reported in an 8 years old male elephant calf belonging to Achhetty Village, Dharmpura district of Tamil Nadu. The calf was found lying in sternal recumbancy unable to get up. Hind limb and tail showed slight refl exes and there was diffi culty in feeding and drinking water. Involuntary defecation was marked. The animal died following treatment. The brain impression smears and biological test conducted at Pasteur Institute, Coonoor revealed rabies (Gopal & Rao, 1968). Aravind et al, 2006 confi rmed a case of rabies in Indian elephant in Chivara, Kollam district, Kerela. The elephant was in lateral decumbency, posterior paralysis, subnormal rectal temperation and slow respiratory rate. The animal was off fed, dehydrated and did not pass urine and faeces. On post-mortem, petechial haemorrhage was observed in the intestinal mucus membrane. Speenomegally and meningeal congestion were prominent. Both positive FAT & PCR test confi rmed rabies. Perissodactylids: The fi rst record of rabies in among Indian species of perissodactylids was clinically attributed to the death of an Indian One horned Rhinocerous(Rhinoceros Unicornis) in Kolkata(Das, 1968). In Zoological Garden Lucknow, an 8 years old female rhinoceros died after showing clinical manifestation such as off fed, restlessness, frothy salivation, staggering gait, partial paralysis of lower jaw, biting tendency and head pressing against hard objects. Hydrophobia was not observed in the course of the disease. The animal succumbed after 6th day of onset of symptoms. Frothy exudate in the trachea and bronchi and severe congestion of the meningeal vessels were noted on necropsy. Histopathological examination revealed engorgement of blood vessel, marked neuronal degeneration, satellitosis and perivascular cuffi ng. Stained sections revealed nigrei bodies mainly in the pukenjee cells of the cerebellum. Mice inculated intracerebrally with brain suspension died after 5th day post inoculation showing typical paralytic symptoms. Brain impression smear stained with seller’s stain revealed presence of negri bodies (Mukherjee et al. , 1984) In the year 1992, a 29 years male rhinoceros of Zoological Park kanpur, Uttar Pradesh showed the symptom of excitement, aggressiveness, aimless movement, falling and rolling on the ground. Panting, groaning and drooling of saliva were other clinical symptoms noted. Staggering gait and exhaustion was conspicuously marked. Brain specimen to IVRI, Izatnagar (UP) for laboratory diagnosis confi rmed rabies infestion(Arora, 1993 ). Selvam et at. , (2003) report a case of rabies at National Zoological Park, New Delhi. The rhino suddenly felt to the grown showing colic symptom with paddling movement of all four legs, conjunctivitis, panting, groaning and restlessness. The animal was off fed and died after 2 days. Typical symptoms of rabies were not observed in the case. Artiodactyla: The reports on rabies in pigs are scanty (Jiang et al. , 2008 and Pessoa et al. , 2011). It accounts for only 0.1-1.1 % of the incidence of animal rabies (Dhillon & Dhingra, 1973). Although wild animals are suspected to be reservoirs of animal viruses like rabies, leading to the spread of the disease to the adjoining forest areas, the reports of confi rmed rabies cases are few. A case of rabies in a wild pig was confi rmed by FAT by Daly et al. 2014. On post mortem examination grossly frothy exudates in bronchi and lungs, petechial hemorrhages on the liver and diff use hyperemia of the gastric mucosa were observed. Histologically pink staining protein rich exudates in the alveoli and bronchi were observed in the lungs, liver section revealed sinusoidal congestion and cloudy swelling of the hepatocytes and in the stomach necrosis of the superfi cial lining epithelial cells and infi ltration of

15 Volume XXI, Issue III, January 2020

polymorph nuclear leucocytes in the lamina propria were observed. These gross and histological fi ndings indicated haemodynamic changes like hemorrhage and edema. Primates: A case of meningoencephalitis in rhesus monkey with paralysis of ears and limbs was found positive for rabies (Gill & Singh, 1977). Rodents: Bandicoots(Bandicoota malabarica) were found inapparent reservoir of rabies according to D’souza et al. (1968) REFERENCES Arora, B. M(1993), Prowling of a rabid wild small Indian civet (viverricula indica) Indian Journal of Wild Health Management 1(12):7-9. Arora, B. M. (1989-90), Annual Scientifi c Report. Centre for wildlife conservation, management and disease surveillance, IVRI, Izatnagar, UP 243122 Arora, B. M. (1990-91), Annual report National Zoological Park, New Delhi-3. Aravind, B. , Animilkumar, M. , Raju S. & Saseendranath, MR. (2006) A case of rabies in an Indian elephant (Elephus maximus),. Zoos, Print. 21(2): 2173. Bhatia, H. M. (1949) rabies in mongoose. Indian Veterinary journal 19.364-365. Jiang Y, Wang L & Xuan H (2008). An outbreak of pig rabies in hunan province, China. Epidemiology and Infection, 136(4) 504-508. Daly, CD. , Indu, K. and Vijayan. A case of rabies in a wild pig. Ind. J. Sci. Res. and Tech. 2014 2(5):23-24 Dhillon SS & Dhingra PN (1973). A note on rabies in swine. Veterinary medicine, Small animal Clinician. PubMed 68 D’Sauza, T. W. , Rao, J. R. , Victor, D. A. and Khader, T. G. A. (1981) A preliminary investigation of the role of Bandicota malabarica in transmission of rabies among dogs in the city of madras. Indian Veterinary journal 45:633- 638 Das, M. S. (1968) A note on some aspect of viral zoonosis. National Seminar on Zoonosis in India. 9-16 October, 1968 held at National Institute Of Communicable Disease, New Delhi Deshmukh RA. Rabies. Pune (India): Yogaksema Department of Virology, Haff kine Institute; 2004. Evan, G. H. (1910) Elephants and their diseases. A treatise of elephant Chapter VII published by Rangoon Superintendent, Govt. Printing Press, Burma Gill, B. S and Singh, B. (1978) A note on bacterial meningo-encephalitis in a rabid rhesus monkey. Journal of research. 15(3):346-347. Grewal, S. D. S. and Nicholas, M. J. (1940) Rabies in low lier animals. Indian Medical Gazette 75:739. Grewal, S. D. S. (1932-33)Rabies in the mangoose Indian Veterinary journal 9:159-163. Jaykumar, S. R. , Babu, M. M, Gopal, T. and Keshavamurty, B. S. (1989) Rabies in a wild leopard(Panthera pardus). Indian Veterinary Journal. 66:1076-1077. Jayson E. A. and Govind Suresh K. 92014) Mongoose Rabies In Kannur, Kerala, India. Journal of the Bombay Natural History Society, 111(2):125-126. Pandit, S. R. . (1979) Two instances of proved rabies in the tiger. Indian veterinary journal 28:250-252. Pandit, V. (1979) Certain aspects of rabies in wildlife and in domestic animals, Proceedings of summer sinstitute of pathology of diseases of wildlife, ICAR-USA, Bangalore held on 16th -20th May, 1979. indian journal of comparative microbiology and immunology of infectious disease. 5(1):32.

16 APCRI Journal

Ramiah, B. (1932-33). paralytic rabies in an elephant. Indian Veterinary Journal. 9:142. Rao, A. T. , Achrjyo, L. N. , Tripathy, S. B. and Nayak, B. C. (1980). Rabies in lions of Nandankanan Biological Park, Orissa, Tamil Nadu Journal of Veterinary Science and Animal Husbandry 9:350-351. Reddy GBM, Singh R, Singh KP, Sharma AK, Vineetha S, Saminathan M, Sajjanar B (2019) Molecular epidemiological analysis of wild animal rabies isolates from India, Veterinary World, 12(3): 352-357. Selvam, NP. , Rawat, RS & Bonal, BS (2003) Rabies in rhino at National Zoological Park, New Delhi - a case report. Zoos Print 18 (10): 13-14. Sethi, M. S. and Coworkers(1980) Reservoirs of zoonotic diseases of Uttar Pradesh. Technical Report PL-480. Departmental of Microbioology and Public Health, College of veterinary Science. G. B. Pant University of Agriculture and Technology, Pantnagar, U. P. Shah, V and Jaswal, G. S. (1979). Victims of rabid wolfs in india. Eff ects of severity and location of bites on developments of rabies. Journal of Infectious Diseases. 134:25-30. Singh, B. , Singh, N. , Chandra, M. and Joshi, D. V. (1981)Cause of mortality of some zoo animals. Zbl. Vet. Med. 28:596-602. Singh, M. , Dhoble, R. L. and Singh D. (1991) Rabies outbreak in a lion safari. Indian Veterinary Journal. 68(4):370. Sudarshan MK. Assessing burden of rabies in India. WHO sponsored national multi-centric rabies survey (May 2004). Assoc Prev Control Rabies India J 2004;6:44-5. Rabies Survey Report (2003): Assessing burden of rabies in India. Association for Prevention and Control of Rabies in India (APCRI) and World Health Organisation (WHO). 104 pp Veeraraghavan, N(1956). Report of Director for 1954. Pasteur Institute of South India, Conoor, Madras Vijayasarathi, S. K. , Panduranga, G. L, Seshadari, S. J and Rama Chandra, R. N. (1983). Rabies in a bear, National Symposium on disease of dairy animals. Indian Association of Veterinary Pathologists.

17 Volume XXI, Issue III, January 2020

ORIGINAL RESEARCH ARTICLE

Out of pocket expenditure for availing rabies post exposure prophylaxis Ramya MP1, Ravish HS2, Nitu Kumari3, Jithin Surendran3

INTRODUCTION The out of pocket expenditure for rabies post exposure prophylaxis is substantial and is borne by those who can least aff ord it. This depends on route of vaccine administration and the type of rabies immunoglobulin used; in addition, there are indirect expenses such as travel, loss of wages, food and others. OBJECTIVES 1. To describe the type of exposures and the post exposure prophylaxis received. 2. To estimate the out of pocket expenditure for availing post exposure prophylaxis. METHODOLOGY The study was conducted at the anti-rabies clinic, KIMS Hospital and Research Centre, Bangalore from Jan - Dec 2018. The details regarding out of pocket expenditure for PEP i. e, direct cost which includes amount spent on drugs & hospital charges and indirect cost like loss of wages, travel of patient and their attenders were collected. The data was analyzed using descriptive statistics. RESULTS A total of 858 Category III animal bite victims had availed post exposure prophylaxis; among whom, 724 had taken vaccination through intramuscular route & 134 through intradermal route. The cost incurred for PEP by intramuscular rabies vaccination was Rs. 4943 (IQR Rs. 4530 – 5440), with direct cost of Rs. 3580 (IQR Rs. 3290 - 3815) and indirect cost of Rs. 1350 (IQR Rs. 1050 – 1750). The cost incurred for intradermal rabies vaccination was Rs. 2663 (IQR Rs. 2353 – 3065), with direct cost of Rs. 1741 (IQR Rs. 1580 - 2058) and indirect cost of Rs. 910 (IQR Rs. 590 - 1180). CONCLUSION The economic burden for receiving the post exposure prophylaxis is substanƟ al. INTRODUCTION Animal bites are a major public health problem in most of the developing countries. In World Health Organization (WHO)’s South East Asia Region, there are more animal exposures than in any other part of the World; by virtue of large human and dog populations living in congested habitable areas. 1 More than 1.4 billion people in this region are at risk of rabies infection. Therefore, it continues to be a major public health and economic problem throughout the region, in most of the countries. 2,3

Corresponding Author: Ravish HS; Professor, Department of Community Medicine, Kempegowda Institute of Medical Sciences (KIMS), Bangalore. Email: drravishhs@rediff mail. com 1Assistant Professor, Department of Community Medicine, Sri Siddhartha Institute of Medical Sciences & Research Centre (SSIMSRC), Nelamangala, Bangalore Rural; 2 Professor, 3Post-graduate student, Department of Community Medicine, Kempegowda Institute of Medical Sciences (KIMS), Bangalore

18 Submission Date : 28/08/2019 Acceptance Date : 18/10/2019 APCRI Journal

Timely and complete post exposure prophylaxis (PEP) for exposed individuals is necessary to prevent rabies; but, the fi nancial expenditure for PEP in any country is substantial; which has to be borne by those who can least aff ord it. Poor people are at a higher risk and the average cost of rabies PEP after contact with a suspected rabid animal is about US$ 45 in Asia, where the average daily income is about US$ 1–2 per person. 4 In developing countries, an estimated 3.8% of the GNP and 31 days wages of an average Asian is spent for full course of PEP. 3 The type of anti-rabies vaccine (ARV) and route of administration as well as the type of rabies immunoglobulin (RIG) used, all signifi cantly infl uences the cost of treatment. In addition to the expense of rabies biological, expenditures for the physician, hospital, loss of income and the emotional & psychological impact of PEP. Post exposure prophylaxis is provided both in government and private health care facilities. Even though PEP is provided free of cost in most of the government hospitals, the animal bite victims will incur expenditure in the form of hospital user fees, purchase of syringes & drugs, loss of wages and travelling cost. 4,5,6 OBJECTIVES 1. To describe the type of exposures and the post exposure prophylaxis received 2. To estimate the out of pocket expenditure for availing post exposure prophylaxis MATERIALS AND METHODS (a) Study Place: Anti rabies clinic, KIMS Hospital & research center, Bangalore. (b) Study subjects: Animal bite victims. (c) Study Period: 1 year. (d) Study design: Descriptive study. (e) Sampling design: Purposive sampling. (f) Sample Size: 858 (g) Inclusion Criteria: ¾ Animal bite victims willing to give informed consent. ¾ All category III animal exposures. ¾ Subjects available for follow-up. (h) Exclusion Criteria: ¾ Category II & category III animal exposures. ¾ Re-exposure cases visiting for post exposure prophylaxis. METHODOLOGY The study was conducted at the anti-rabies clinic, KIMS Hospital and Research Centre, Bangalore from January to December, 2018 after obtaining the clearance from institutional ethics committee. All animal bite victims willing to give consent were included in the study. All study subjects were provided with PEP according to WHO recommendations in the anti rabies clinic. The details regarding socio-demographic characteristics, characteristic of biting animal, details of animal exposure and out of pocket expenditure for PEP i. e, direct cost which includes amount spent on drugs & hospital charges and indirect cost like loss of wages, travel of patient and attenders were collected. The data was entered using MS-Excel and analyzed using descriptive statistics. RESULTS The study included 858 Category III animal bite victims; among them 724 (84.4%) had received PEP through IM route and 134 (15.6%) through ID route. Majority of animal bite victims were <18 years of age (48.9%) followed by 48.4% of age group 18-59 years and 2.7% of age > 60 years. 64.8% of animal bite victims were males and 35.2%

19 Volume XXI, Issue III, January 2020

were females. Most of them had completed schooling (54.0%), 23.5% were illiterates and 22.5% were graduate/post graduate. 36.5% of animal bite victims were students. Table 1: Characteristics of biting animal.

IDRV TOTAL Characteristics of biting animal IMRV (n=724) (n=134) (n=858) Dog 663(91.6) 129(96.3) 792(92.3) Cat 37(5.1) 3(2.2) 40(4.7) BiƟ ng Animal Monkey 21(2.9) 1(0.7) 22(2.6) Cow 3(0.4) 1(0.7) 4(0.5) Vaccinated 85(11.7) 10(7.5) 95(11.1) Vaccination Unvaccinated 260(35.9) 20(14.9) 280(32.6) Status of animal Don’t know 379(52.3) 70(52.2) 449(52.3) Healthy 401(55.4) 64(47.8) 465(54.2) Sick 68(9.4) 12(9.0) 80(9.3) Fate of biting Died 14(1.9) 16(11.9) 30(3.5) animal Killed 37(5.1) 16(11.9) 53(6.2) Not traceable/ Unknown 204(28.2) 26(19.4) 230(26.8) In 92.3% of cases the biting animal was dog, followed by cat, monkey and cow. But only 11.1% of biting animal were vaccinated against rabies, 32.6% were unvaccinated and in 52.3% the vaccination status of biting animal was not known. Among biting animals 54.2% were healthy, 26.8% were not traceable, 9.3% were sick, 6.2% were killed, and 3.5% died.

Table 2: Characteristics of Exposure.

IDRV TOTAL Characteristics of exposure IMRV (n=724) (n=134) (n=858) Home 118(16.3) 25(18.7) 227(26.5) Place of bite Outside of home 606(83.7) 109(81.3) 631(73.5) Abrasion 350(48.3) 59(44.0) 409(47.7) LaceraƟ on 151(20.9) 25(18.7) 176(20.5) Type of Exposure Puncture wound 115(15.9) 19(14.2) 134(15.6) MulƟ ple wounds 108(14.9) 31(23.1) 139(16.2) Lower limb 382(52.8) 59(44.0) 441(51.4) Upper limb 207(28.6) 47(35.1) 254(29.6) Site of Exposure Head, neck & face 57(7.9) 18(13.4) 75(8.7) Trunk/Genitals 36(5.0) 4(3.0) 40(4.7) MulƟ ple sites 42(5.8) 6(4.5) 48(5.6) Provoked 198(27.3) 35(26.1) 233(27.2) Circumstance of bite Unprovoked 526(72.7) 99(73.9) 625(72.8) Most of the animal exposure happened while victims were outside the home (73.5%) and majority of them were unprovoked bites (72.8%). Abrasion (47.7%) were the most common type of wound followed by lacerations

20 APCRI Journal

(20.5%), punctured wounds (15.6%) and multiple wounds (16.2%). Among the study subjects Lower limbs (51.4%) were aff ected the most followed by upper limbs (29.6%), head neck and face (8.7%), trunk/genitals (4.7%) and multiple sites(5.6%). All animal bite victims were provided with post exposure prophylaxis which included thorough wound wash, anti- rabies vaccine administration and rabies immunoglobulin infi ltration at the study centre as recommended by WHO. 6 The cost incurred for availing post exposure prophylaxis who had taken intramuscular anti-rabies vaccination in the anti-rabies clinic was assessed among 724 animal bite victims

Table 3: Cost incurred for post exposure prophylaxis by intramuscular route (n=724)

Day 0 Day3 Day7 Day14 Day28 Total Direct cost Median Median Median Median Median Median (Q1-Q3) (Q1-Q3) (Q1-Q3) (Q1-Q3) (Q1-Q3) (Q1-Q3) 350 350 350 350 350 1750 Cost of ARV (325-350) (325-350) (325-350) (325-350) (325-350) (1625-1750) 930 930 Cost of RIG 0000 (470-950) (470-950) Administration 3700000370 charges Cost of pre- 60 60 0000 medication (0-60) (0-60) Cost of TT 500000 50 vaccination Cost of antibiotics/ 290 290 0000 anti- infl ammatory (250-350) (250-350) 38 38 Cost of Disposables 0000 (35-45) (35-45) 50 50 50 50 50 225 Hospital Charges (25-100) (20-60) (20-60) (20-60) (20-60) (140-350) Direct Cost 2060 385 385 385 385 3580 Median (Q1-Q3) (1681-2190) (370-425) (370-425) (370-425) (370-425) (3290-3815) Indirect Cost 300 150 150 150 150 900 Travel Expenses (200-400) (100-200) (100-200) (100-200) (100-200) (750-1100) Loss of Wages 400 (0-750) 0000400 (0-750) Other Expenses 80 80 0000 (Food) (0-150) (0-150) Indirect Cost 750 150 150 150 150 1350 Median (Q1-Q3) (400-1150) (100-200) (100-200) (100-200) (100-200) (1050-1750) Total Cost 2710 550 550 550 550 4943 Median (Q1-Q3) (2385-3207) (500-600) (500-600) (500-600) (500-600) (4530-5440)

The present study showed that, the total median cost incurred to the animal bite victims for availing post exposure prophylaxis with intramuscular rabies vaccination was Rs. 4943 with inter-quartile range of Rs. 4530 - 5440. The direct cost incurred was Rs. 3580 with inter-quartile range of Rs. 3290 - 3815, which included cost of purchasing

21 Volume XXI, Issue III, January 2020

anti rabies vaccine, rabies immunoglobulin, hospital administration charges, and cost of tetanus toxoid injection, cost of pre-medication, cost of disposables and cost of antibiotics, anti-infl ammatory & antiseptics. The indirect cost incurred was Rs. 1350 with inter-quartile range of Rs. 1050 - 1750, which included travel expenses, loss of wages, food expenses and others for the animal bite victim and the accompaniments if any for the entire course of vaccination.

Graph 1: Cost incurred to the patients for PEP by intramuscular route. Majority of the cost incurred for availing post exposure prophylaxis by intramuscular route was for direct expenses in the form of purchasing rabies biologicals and antibiotics, anti-infl ammatory and anti-septics. Similarly, the cost incurred for availing post exposure prophylaxis in the anti-rabies clinic was assessed among 134 study subjects who have taken intradermal anti-rabies vaccination. Table 4: Cost incurred for post exposure prophylaxis by intradermal route (n=134)

Day 0 Day3 Day7 Day28 Total Direct cost Median Median Median Median Median (Q1-Q3) (Q1-Q3) (Q1-Q3) (Q1-Q3) (Q1-Q3) 100 100 100 100 450 Cost of ARV (100-150) (100-140) (100-140) (100-140) (400-520)

22 APCRI Journal

475 475 Cost of RIG 000 (465-950) (465-950) Administration charges 370 0 0 0 370 60 60 Cost of pre-medication 000 (0-60) (0-60) 20 20 Cost of TT vaccination 000 (20-50) (20-50) Cost of antibiotics/ anti- 130 130 000 infl ammatory (95-162) (95-162) 35 35 Cost of Disposables 000 (25-36) (25-36) 10 20 20 70 Hospital Charges 20 (10-20) (10-20) (10-30) (50-80) Direct Cost 1300 120 120 120 1741 Median (Q1-Q3) (1176-1670) (110-160) (110-160) (110-160) (1580-2058) Indirect Cost 200 85 85 85 480 Travel Expenses (120-300) (75-100) (75-100) (75-100) (415-610) 400 400 Loss of Wages 000 (0-500) (0-500) 90 90 Other Expenses (Food) 000 (0-100) (0-100) Indirect Cost 650 85 85 85 910 Median (Q1-Q3) (300-890) (75-100) (75-100) (75-100) (590-1180) Total Cost 1958 220 220 215 2663 Median (Q1-Q3) (1691-2395) (200-250) (200-260) (195-260) (2353-3065) The total median cost incurred to the animal bite victims for availing post exposure prophylaxis with intradermal rabies vaccination was Rs. 2663 with inter-quartile range of Rs. 2353 - 3065. The direct cost incurred was Rs. 1741 with inter-quartile range of Rs. 1580 - 2058, which included cost of purchasing anti rabies vaccine, rabies immunoglobulin, hospital administration charges, cost of tetanus toxoid injection, cost of pre-medication, cost of disposables and cost of antibiotics, anti-infl ammatory & antiseptics. The indirect cost incurred was Rs. 910 with inter-quartile range of Rs. 590 - 1180, which included travel expenses, loss of wages, food expenses and others for the animal bite victim and the accompaniments if any for the entire course of vaccination. Graph 2: Cost incurred to the patients for PEP by intradermal route Majority of the cost incurred for availing post exposure prophylaxis by intradermal route was for direct expenses in the form of purchasing rabies biologicals and antibiotics, anti-infl ammatory and anti-septics. DISCUSSION

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Rabies is a neglected zoonotic disease caused by the rabies virus; occurs in over 100 countries and poses a potential threat to >3.3 billion people worldwide. The neglected disease indicates that, it is insuffi ciently addressed by Governments and the International community, as they are best defi ned by people and communities they aff ect the most i. e. , poor people living in the remote rural areas and urban slums of the developing World. It is however, the disease most amenable to control, as the tools for prevention i. e. , PEP are available worldwide. 7 Therefore, it is the fi rst zoonosis on the list of neglected diseases targeted for regional and eventually global elimination. More than 15 million people worldwide receive PEP and are estimated to prevent hundreds of thousands of rabies deaths annually. The estimated global expenditure for prevention and control of rabies exceeds US$ 1.6 billion. . 8, 9 Post exposure prophylaxis should be availed as early as possible after exposure in these endemic areas. Proper wound management and simultaneous administration of rabies immunoglobulin (RIG) combined with anti-rabies vaccine (ARV) is almost invariably eff ective in preventing rabies, even after high-risk exposure. 10 But, the cost of rabies PEP is a major limiting factor, since the rabies immunobiologicals are highly expensive and increases the burden to the bite victims. Hence compliance to vaccination is also aff ected. 11,12,13 The present study showed that, the total median cost incurred to the animal bite victims for availing post exposure prophylaxis with intramuscular rabies vaccination was Rs. 4943 (IQR-Rs. 4530 – 5440); with direct cost of Rs. 3580 (IQR-Rs. 3290 – 3815) and the indirect expenses of Rs. 1350 (IQR-Rs. 1050 – 1750). Similarly, the total median cost incurred to the animal bite victims for availing post exposure prophylaxis with intradermal rabies vaccination was Rs. 2663 (IQR-Rs. 2353 – 3065); with direct expenses of Rs. 1741 (IQR-Rs. 1580 – 2058) and indirect expenses of Rs. 910 (IQR-Rs. 590 – 1180). The cost incurred for availing post exposure prophylaxis with intramuscular rabies vaccination is 1.8 times more than that of intradermal rabies vaccination. Similarly, a descriptive study on economic costs of rabies post exposure prophylaxis done at both Government Hospital (where PEP is provided free of cost by ID route) & Private Medical College hospital (where PEP is provided for a cost by IM route), in Bangalore showed that, the total median cost incurred by the bite victims in Government hospitals was INR. 585 with IQR of INR. 444-725; which included direct cost of INR. 300 and indirect cost of INR. 285; and the cost spent by the government for providing PEP free of cost was INR. 1031; whereas,

24 APCRI Journal the total cost incurred in private hospital was Rs. 5200 with IQR of Rs. 4900-5701 which included direct cost of Rs. 3865 with IQR Rs. 3662-4120, in which most of the cost incurred was for purchasing ARV & RIG. The study concluded that the economic burden to the bite victims as well as for the government in the developing world was more; expected to rise in future due to increased population and ineff ective dog population control. 14 Likewise, another study on cost evaluation of intradermal vaccination at the anti rabies clinic in tertiary care hospital Mumbai, for an year, showed that the vaccine cost for IDRV was Rs. 2,80,600 and the vaccine cost for the intramuscular (IM) assuming 84% compliance was estimated as Rs. 15,64,000. The study concluded that Intradermal regime was cost eff ective and reduced the cost of vaccination by about 82% (assuming 84% compliance) thus an appropriate option for middle and low income countries like ours. 15 Therefore, PEP by intradermal rabies vaccination is a cost eff ective strategy, as there is economic advantages i. e, only 0.8 ml of vaccine is needed for each patient resulting in use of less than 1 vial/ patient as opposed to 5 vials/ patient to receive PEP using IM route and also only four visits are needed to complete vaccination as compared to IM regimen. So by this, we are able to reduce the indirect cost involved in terms of man hour cost, travel time and expenses for that visit. Thus by reducing the cost of vaccination, intra dermal rabies vaccination clearly makes an attractive option for resource- starved countries like ours. 16 Considering the large number of animal bite cases in the country and subsequent increase in the demand for modern rabies vaccines, universal switch over from intramuscular to intradermal route of rabies vaccination may be recommended which reduces both the cost and number of doses needed for PEP. 17 It reduces the volume of vaccine and direct cost required for PEP by 60% when compared with standard intramuscular vaccination and therefore, largely benefi ts the poor & needy. Therefore, it is rationale to introduce intra dermal rabies vaccination in rabies endemic country like India. 18 REFERENCE 1. WHO South East Asia region: Strategic Framework for Elimination of Human Rabies Transmitted by Dogs in the South-East Asia Region: World Health Organization, Regional offi ce for South East Asia; 2012. 2. Knobel DL, Cleaveland S, Coleman PG, Fevre EM, Meltzer MI, et al. Re-evaluating the burden of rabies in Africa and Asia. Bulletin of the World Health Organization 2005;83:360-68. 3. Wilde H, Khawplod P, Khamoltham T, Hemachudha T, Tepsumethanon V, Lumlerdacha B, Mitmoonpitak C, Sitprija V. Rabies control in South and Southeast Asia. Vaccine. 2005 Mar 18;23(17-18):2284-89. 4. WHO Technical Report Series No. 982. WHO Expert Consultation on Rabies. Second report. World Health Organization, Geneva; 2013. 5. Shantavasinkul P, Tantawichien T, Wilde H, Sawangvaree A, Kumchat A, Ruksaket N, Lohsoonthorn V, Khawplod P, Tantawichien T. Post exposure rabies prophylaxis completed in 1 week: preliminary study. Clin Infect Dis. 2010 Jan 1;50(1):56-60. 6. Sittichanbuncha Y, Chairat C, Sawanyawisuth K, Senthong V. Cost diff erences between complete and incomplete post-exposure courses of rabies vaccination. South East Asian J Trop Med Public Health. 2014 Sep;45(5):1048-52. 7. Sudarshan MK, Narayana DH, Madhusudana SN, Holla R, Ashwin BY, Gangaboraiah B, et al. Evaluation of a one week intradermal regimen for rabies post-exposure prophylaxis: Results of a randomized, open label, active-controlled trial in healthy adult volunteers in India. Hum Vaccin Immunother 2012;8:1077-81. 8. Ashwath Narayana DH, Ravish HS, Ramesh Holla. Clinical evaluation of safety of equine rabies immunoglobulin. Journal of APCRI, 2011;12(2):12-15. 9. Sudarshan MK, Madhusudana SN, Mahendra BJ, Rao NS, Ashwath Narayana DH, Abdul R S, etal. Assessing the burden of human rabies in India: results of a national multi-center epidemiological survey. Int J Infect Dis. 2007 Jan;11(1):29-35. 10. World Health Organization. Rabies vaccines: WHO position paper, Weekly Epidemiological Record, No.

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32.2010;85:309-20. 11. Hampson K, Coudeville L, Lembo T, Sambo M, Kieff er A, Attlan M, etal. Global Alliance for Rabies Control Partners for Rabies Prevention. . Estimating the global burden of endemic canine rabies. PLoS Negl Trop Dis. 2015 Apr16;9(4):e0003709 12. WHO South East Asia region: Strategic Framework for Elimination of Human Rabies Transmitted by Dogs in the South-East Asia Region: World Health Organization, Regional offi ce for South East Asia; 2012. 13. Shankaraiah RH, Rajashekar RA, Veena V, Hanumanthaiah AN. Compliance to anti-rabies vaccination in post-exposure prophylaxis. Indian J Public Health. 2015 Jan-Mar;59(1):58-60. 14. Ravish H S, Rachana RA, Malathesh U, Veena V, Rupsa B, Ramya M P. Economic cost of rabies post exposure prophylaxis. Indian Journal of Community Health 2017; 29 (2): 156-161. 15. Mankeshwar R, Silvanus V, Akarte S. Evaluation of intradermal vaccination at the anti rabies vaccination OPD. Nepal Med Coll J 2014; 16(1): 68-71. 16. Rahim A, Kuppuswamy K, Thomas B, Raphael L. Intradermal Cell Culture Rabies Vaccine: A cost eff ective option in antirabies treatment. Indian J Community Med 2010; 35(3): 443-4. 17. World Health Organization WHO guide to identifying the economic consequences of disease and injury. Geneva;2009. 18. Sudarshan MK, Mahendra BJ, Ashwath Narayana DH. Introducing intra dermal rabies vaccination in India: Rationale and Action plan. Journal of APCRI 2005;7(1):20-5

26 APCRI Journal

ORIGINAL RESEARCH ARTICLE

“A PROSPECTIVE STUDY ON PSYCHOLOGICAL IMPACT IN CHILDREN AFTER DOG BITE INJURIES IN BENGALURU URBAN” Dr Kishore SG1, Dr Deepak Murthy HJ2, Dr Ranganath TS3, Dr Anil Kumar4, Mr Vishwanatha V Neela5

ABSTRACT Introduction: Dogs are important members of many families in many countries. However, posttraumatic stress disorder (PTSD) in children after animal attacks has always been underestimated, and a more detailed study of PTSD in children after animal attacks is needed. Methods: 57 children after animal induced injuries were reviewed. Family Apgar Scale assessment and PTSD screening were performed. On week after the visit to anti-rabies clinic, the patient underwent evaluation for acute stress disorder (ASD) diagnosis, by using the Child Acute Stress Questionnaire. PTSD screening and interim history-taking were performed 3 months after the emergency department admission, by telephone or in face-to-face interviews, by using the Clinician-Administered PTSD Scale for Children and Adolescents. P values of <. 05 were considered significant.

Results: A total of 3 (5.26%) pa ents developed PTSD, including 2 pa ents with severe injuries and 1 pa ent with moderate injuries (X 2 = 48.104; P<0.000). No significant diff erences in PTSD occurrence according to gender and age were observed. Family Apgar Scale scores were not significantly related to PTSD (P =0.781). ASD and PTSD symptom severity scores were significantly associated (r = 0.51; P =0.005). Conclusions: Child victims of severe animal attacks should be considered at risk for the development of PTSD, family support was not correlated with posttraumatic stress symptoms in school-aged children after animal attacks, and ASD seems to be an early predictive indicator of PTSD. Key words: Dog bite, Acute stress disorder, Post-traumatic stress disorder INTRODUCTION Dogs are important members of many families in many countries. Although the majority of dogs live peaceably with their adoptive families, a significant number of people are bitten by dogs every year. In India, about 15 million people are bitten by animals and need post exposure prophylaxis. Most bites are by dogs (91.5%), 60% are strays and 40% pets. Children, because they tend to underestimate the danger arising from dogs, are exposed frequently to bite accidents. A US study found that 46% of school children had been bitten by a dog by the time they reached grade 12.1 Children who go through this traumatic event may have temporary diffi culty adjusting and coping. With time and good self-care usually, they get better. Some children may experience Acute stress disorder (ASD) and post-traumatic stress disorder (PTSD). The aesthetic and psychological consequences of bite accidents may influence negatively the quality of life of children and their families.2,3

1 Assistant professor, 2 Post graduate, 3 Professor and HOD, 4 Medical offi cer, 5 Statistician Department of Community Medicine, BMCRI

Submission Date : 21/01/2020 Acceptance Date : 30/01/2020 27 Volume XXI, Issue III, January 2020

Posttraumatic stress disorder (PTSD) describes the clustering of symptoms that develop after exposure to traumatic events. Substantial evidence shows that exposure to traumatic experiences may aff ect brain function in several ways and may have long lasting consequences. 4 Rates of PTSD and PTSD symptoms may vary according to traumatic exposure. 60% of children exposed to a sniper attack met PTSD criteria 1 year after the incident5 and studies of urban youths exposed to community violence reported PTSD rates of 24% to 34.5%. 6 For most animal-induced injuries, children seem to be unharmed or only transiently aff ected. However, severe dog bites/scratches and multiple injuries may bring tremendous harm to children, both physically and psychologically. PTSD in children after animal induced injury is common but is a neglected condition for clinical paediatricians and Anti Rabies Clinic Physicians. Pediatric patients with PTSD are at risk for social, learning, and developmental disorders. 7 Therefore, there is urgency for PTSD screening for children after animal attacks, to reduce the psychological impact for children. This study was conducted to assess the proportion and predictive factors for post-traumatic stress symptoms among children after dog bite injuries. METHODOLOGY The Anti Rabies Clinic (ARC) in Victoria Hospital, Bangalore medical college and research institute is one of the few rabies prevention centers in Karnataka, treating nearly 300 pediatric patients with animal-induced injuries each year. This study included children who were 5 to 12 years of age, were willing to participate in the study, and sought medical attention after an animal injury between December 2018, and May, 2019. Subject enrolment began after obtaining assent and informed consent from the child and his or her parents. A longitudinal study design was used among children who sustained Dog bite injuries (Category 3). Sample Size was calculated from the study Xiaowei et al8 with OpenEpi software and arrived to number of 57. Consecutive sampling was used to select the cases. The exclusion criteria included cognitive impairments, psychotic diseases, speech disorders, retardation and children who have sustained other acute/chronic injuries or trauma. The standard medical treatment for animal injuries at the emergency department consisted of postexposure vaccine prophylaxis of intradermal schedule for rabies and/or rabies immunoglobulin treatment, meticulous wound cleaning, and closure of gaping wounds (if needed). For each patient, the following information was recorded: victim’s name, age, gender, contact information, date of injury, breed of dog, anatomic location of the injury, number of wounds, circumstances of the injury, Family Apgar Scale scores and PTSD screen results. Detailed medical, psychiatric, and social histories also were obtained. One week after the ARC visit (on 7th day of ARV), the patients underwent assessment for acute stress disorder (ASD) diagnosis, by using the Child Acute Stress Questionnaire. 9 PTSD screening and interim history-taking were performed 3 months after the emergency department admission, by telephone or in face-to-face interviews, by using the PTSD Scale for Children and Adolescents. 10 Interviewers who conducted assessments at month 3 were not aware of the children’s ASD status at 7th day. Other scales were not used in this study because animal attack wounds diff er from wounds attributable to traffic accidents, which mainly involve organ damage, cranial damage, and bone fractures. Therefore, to classify wound severity, we divided the cases into 3 groups on the basis of whether sutures and hospitalization were needed. Mild injuries required only simple medical treatment, moderate injuries required sutures in the emergency department, and severe injuries required hospitalization. The Family Apgar Scale was used to evaluate family support and function. 11 The Family Apgar Scale consists of 5 questions, each addressing one of the following constructs regarding family support and functioning: adaptability, partnership, growth, aff ection, and resolve.

28 APCRI Journal

Descriptive analyses summarized subject characteristics and the prevalence of ASD and PTSD, expressed as means and SDs. ASD or PTSD status was described separately for children in 2 age groups (5–8 years and 9–12 years). The x2 test was used to compare the prevalence of ASD and PTSD according to gender, age group, and injury severity. Data were coded and entered into Excel and analysis was done using SPSS v 20.0. P values of <. 05 were considered significant. RESULTS In this study, 52 pediatric patients were interviewed, accounting for 42.8% of all pediatric patients with animal injuries during the study period. There were 32 boys and 25 girls. The mean age of the subjects was 7.2±2.8 (5-12). Of the 52 patients, 6 were hospitalized (severe injuries), 13 received sutures in the emergency department (moderate injuries), and the other 38 received only simple treatment (mild injuries) (Table 1). The majority of victims were injured by a dog known to them, that is, their family pet (16 of 52 children [30.7%]) or a dog known to them but not owned by them (24 of 52 children [46.15%]). Table 1.0 Demographic Characteristics of Subjects

Child age Mean ± SD (range) in years 7.2±2.8 (5-12) 5–8 y, n (%) 36 (63.2%) 8–12 y, n (%) 21 (36.8%) Child gender Male, n (%) 32 (56.1%) Female, n (%) 25 (43.9%) Wound severity (Category 3) Mild, n (%) 38 (66.8%) Moderate, n (%) 13 (23.1%) Severe, n (%) 6 (10.1%) Family Apgar Scale score Mean ± SD (range) 8.2±2.23 (3-10) A total of 7 (12.88%) victims met the symptom criteria for ASD. ASD occurrence was significantly higher in the severe injury group than the other 2 groups (X 2 =62.458 P=. 000). There were no statistically significant association in the occurrence of ASD according to gender (X 2 =3.403 P=. 065). Children 5 to 8 years of age were more likely than those 9 to 12 years of age to have ASD (X 2 =7.665 P=. 006 odds ratio: 2.765 [95% CI: 1.300– 5.881]). (Table 2.0) Table 2.0 ASD among injured children (%)

ASD n (%) Symptoms Mild Injury (n=38) Moderate Injury (n=13) Severe Injury (n=6) Dissociation a 2 (5.26%) 2 (15.38%) 3 (50%) Reexperiencing b 3 (7.89%) 5 (38.46%) 4 (66.6%) Avoidance b 2 (5.26%) 6 (46.15%) 3 (50%) Arousal b 3 (7.89%) 3 (23.07%) 3 (50%) ASD diagnosis 4 (10.52%) 3 (23.07%) 3 (50%) a At least 3 moderate/severe symptoms. b At least 1 moderate/severe symptom.

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No child in any wound severity group had PTSD at the admission assessment. A total of 3 (5.26%) patients developed PTSD, including 2 patients with severe injuries and 1 patient with moderate injuries (X 2 = 48.104; P<. 000). No significant diff erence was observed on the basis of gender (X 2 =0.628 P=. 428) or age group (X 2 =1.966 P=. 161), odds ratio: 0.498 [95% CI: 0.185– 1.342]. Family Apgar Scale scores were not significantly related to PTSD (P =0.781). (Table 3.0) ASD and PTSD symptom severity scores were significantly associated (r = 0.51; P =. 005). Table 3.0 PTSD Among Injured Children (%)

PTSD n (%) Symptoms Mild Injury (n=38) Moderate Injury (n=13) Severe Injury (n=6) Reexperiencing a 1 (0.38%) 3 (23.07%) 3 (50%) Avoidance b 0 2 (15.3%) 2 (33.3%) Arousal c 0 2 (15.3%) 2 (33.3%) PTSD diagnosis 0 2 (15.3%) 2 (33.3%)

a At least 1 moderate/severe symptom. b At least 3 moderate/severe symptoms. c At least 2 moderate/severe symptoms. DISCUSSION Animal-induced injuries are very common, especially among children. With the development of rabies vaccines and antibiotics, rabies occurrence and wound infection rates have been reduced significantly. For animal induced injuries, however, children may need more care from physicians, not only medical/surgical interventions but also psychological interventions. Little is known about the normal range of acute psychological responses of children in the immediate aftermath of animal attacks, which makes the identification of adverse children responses extremely difficult. Peters et al12 demonstrated that 12 of 22 pediatric patients developed PTSD symptoms after dog bites, but no detailed data and analyses were provided. Some studies involving PTSD in children were related to acute physical injuries, 13–15 such as traffic accidents, which are generally diff erent from the trauma of animal attacks. This study investigated PTSD occurrence in children after animal attacks and indicated possible predictive indicators. The reason why PTSD developed in some children is not known. However, it could be related to the intensity and aggressive character of the animal attack. 16 Our study also leads to the conclusion that child victims of severe animal attacks should be considered to be at risk for PTSD and may need early psychological support. In the severe injury group, 26.3% of the children developed PTSD, compared with 9.9% and 0.4% in the moderate and mild injury groups, respectively. No significant diff erences in PTSD occurrence according to gender and age were observed, although girls seemed to be more vulnerable and younger children seemed to be more likely to develop PTSD. In this study, we included only patients who fully met the criteria for ASD/ PTSD, excluding patients who might have symptoms but did not meet the criteria for ASD/PTSD diagnosis. For example, 63.4% and 57.9% of the children in the severe injury group developed reexperiencing and avoidance symptoms, respectively, but only 44.7% of the children had confirmed ASD. The situation was similar for PTSD diagnosis. Additional study may be needed specifically for children with ASD/PTSD symptoms but without a specific diagnosis. We hypothesized that less family support would contribute to posttraumatic stress symptoms in children after animal attacks. However, the study results do not support this hypothesis. ASD symptoms seem to be possible predictive indicators of PTSD. There have been numerous studies on the relationship between ASD and PTSD in adults, which revealed that 63% to 83% of patients diagnosed as having ASD develop PTSD. 17-19 Kassam-Adams and Winston et al 20 examined the utility of ASD as a predictor of PTSD among 8- to 17-year-old youths after traffic accidents and found a positive relationship. Furthermore, PTSD severity was found to be strongly associated with self-reported ASD symptom severity among youths and young adults who were assessed within hours after a violent injury. 21

30 APCRI Journal

Our study findings regarding the ASD-PTSD relationship indicated that ASD symptoms may be used as possible predictive parameters for PTSD in children after animal attacks. However, further investigation of the sensitivity and specificity may be needed. Previous studies examined factors related to the development of PTSD in children, such as demographic variables (eg, age and gender), previous psychopathologic conditions, injury severity, and physiologic factors (eg, heart rate and physiologic arousal). One study of 401 adolescents 12 to 19 years of age demonstrated that female gender, perceived threat to life, and violence-related mechanisms of injury were predictive of ASD, as measured with the Impact of Events Scale Revised. 22 In addition, another study found that the acute heart rate near the time of injury might be related to the development of PTSD in children after traffic-related physical injuries. However, many possible predictive indicators were not included in that study. Additional studies may take in to account possible related parameters for an overall evaluation of PTSD risk factors. There are some limitations to this study. Firstly, we evaluated urban and suburban populations, and rural areas were not covered. Therefore, a bias might have been generated through population selection. Because dogs in rural areas are more ferocious and more-severe wounds may be more common, cases of children experiencing PTSD may be more prevalent. Therefore, similar studies among children in rural settings and in other ethnic populations would be useful. Secondly, because no existing appropriate instrument could be used for evaluation of animal attack wounds, we divided the cases into 3 groups on the basis of gross wound severity. This triage was based mainly on the judgment of the physicians in the emergency department, and systematic diff erences in grouping might have occurred. Future studies might adopt a wound evaluation instrument to achieve better wound severity grouping. Lastly, this study enrolled only patients >5 years of age. Future studies should develop a more patient-friendly, easier questionnaire for PTSD evaluation in younger patients. CONCLUSION Child victims of animal attacks with severe injury should be considered at risk for the development of PTSD. Family support was not correlated with posttraumatic stress symptoms in school-aged children after animal attacks. ASD seems to be an early predictive indicator of PTSD. ARC physicians dealing with pediatric patients after animal attacks should be encouraged to instruct the children’s parents to observe the children closely after the injury, for psychological eff ects. DECLARATIONS Funding: None Confl ict of interest: None REFERENCES 1. Voelker R. Dog bites recognized as public health problem. JAMA. 1997;277(4): 278–280

2. Overall KL, Love M. Dog bites to humans: demography, epidemiology, injury, and risk. J Am Vet Med Assoc. 2001;218(12): 1923–1934

3. Sacks JJ, Sinclair L, Gilchrist J, Breeds of dogs involved in fatal human attacks in the United States between 1979 and 1998. J Am Vet Med Assoc. 2000;217(6):836–840

4. Cohen JA, Mannarino AP. Addressing attributions in treating abused children. Child Maltreat. 2002;7(1):82– 86

5. Pynoos RS, Frederick C, Nader K, et al. Life threat and posttraumatic stress in schoolage children. Arch Gen Psychiatry. 1987; 44(12):1057–1063

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6. American Academy of Child and Adolescent Psychiatry. Practice parameters for the assessment and treatment of children and adolescents with depressive disorders. J Am Acad Child Adolesc Psychiatry. 1998;37(10 suppl):63S–83S

7. Giaconia RM, Reinherz HZ, Silverman AB, et al. Traumas and posttraumatic stress disorder in a community population of older adolescents. J Am Acad Child Adolesc Psychiatry. 1995;34(10):1369–1380

8. Injury in China Investigation of Posttraumatic Stress Disorder in Children After Animal-Induced, Li Ji, Zhang Xiaowei, Wang Chuanlin and Liu Wei pediatrics 2010;126;e320-e324; originally published online Jul 12, 2010; DOI: 10.1542/peds. 2009-3530

9. Winston FK, Kassam-Adams N, VivarelliO’Neill C, et al. Acute stress disorder symptoms in children and their parents after pediatric traffic injury. Pediatrics. 2002; 109(6). Available at: www. pediatrics. org/ cgi/ content/full/109/6/e90

10. Newman E, Ribbe D. Psychometric review of the clinician-administered PTSD scale for children. In: Stamm BH, ed. Measurement of Stress, Trauma and Adaptation. Lutherville, MD: Sidran Press; 1996:106–114

11. Smilkstein G. The Family Apgar: a proposal for a family function test and its use by physicians. J Fam Pract. 1978;6(6):1231–1239

12. Peters V. Posttraumatic stress disorder after dog bites in children. J Pediatr. 2004; 144(1):121–122

13. de Vries AP, Kassam-Adams N, Cnaan A, etal. Looking beyond the physical injury: post-traumatic stress disorder in children and parents after pediatric traffic injury. Pediatrics. 1999;104(6):1293–1299

14. Kassam A. Encounters with the North: psychiatric consultation with Inuit youth. JCan Acad Child Adolesc Psychiatry. 2006;15(4): 174–178

15. Saxe G, Stoddard F, Courtney D, et al. Relationship between acute morphine and the course of PTSD in children with burns. JAm Acad Child Adolesc Psychiatry. 2001;40(8): 915–921

16. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4thed. Arlington, VA:American Psychiatric Association; 2000:463–468

17 Bryant RA, Harvey AG. Relationship between acute stress disorder and posttraumatic stress disorder following mild traumatic brain injury. Am J Psychiatry. 1998;155(5): 625–629

18. Brewin CR, Andrews B, Rose S, et al. Acute stress disorder and posttraumatic stress disorder in victims of violent crime. Am J Psychiatry. 1999;156(3):360–366

19. Difede J, Ptacek JT, Roberts J, et al. Acute stress disorder after burn injury: a predictor of posttraumatic stress disorder? Psychosom Med. 2002;64(5):826–834

20. Kassam-Adams N, Winston FK. Predicting child PTSD: the relationship between acute stress disorder and PTSD in injured children. J Am Acad Child Adolesc Psychiatry. 2004;43(4):403–411

21. Fein JA, Kassam-Adams N, Gavin M, et al. Persistence of posttraumatic stress in violently injured youth seen in the emergency department. Arch Pediatr Adolesc Med. 2002;156(8):836–840

22. Holbrook TL, Hoyt DB, Coimbra R, et al. High rates of acute stress disorder impact quality-of-life outcomes in injured adolescents: mechanism and gender predict acute stress disorder risk. J Trauma. 2005;59(5):1126– 1130

32 APCRI Journal ORIGINAL RESEARCH ARTICLE

Seasonal Trend of Animal Bite Victims Attending Anti Rabies Clinic of A Tertiary Care Hospital, Berhampur, Odisha. Prof. Durga Madhab Satapathy1, Dr. Nivedita Karmeee2, Dr. P. Narmada Reddy3, Dr. Debasish Pandit4

ABSTRACT NEED OF THE STUDY Rabies is a fatal viral zoonosis and a serious public health problem. It is 100% fatal yet preventable disease. It is a disease of the central nervous system caused by the bites of warm-blooded animals and transmitted to humans through animal bites, most commonly by dogs. The cases for post~exposure prophylaxis are reported throughout the year in the ARC but cases of unprovoked bites or animals with a high suspicion of Rabies infection or more number of cases are reported in certain periods of the year. The knowledge on specifi c seasonal trend of animal bite cases will help the policy makers to formulate appropriate plans especially IEC activities and provision of logistic support for management of animal bite cases. The following study was therefore conducted in the ARC of MKCG Medical College Hospital, Berhampur with the following objectives. OBJECTIVE 1. To study the month and season wise trend of animal bite victims over last 5 years.

2. To assess the seasonal distribution, if any, of bite victims with regards to type and behaviour of animal METHODOLOGY This was a record based cross sectional study carried out at ARC OPD in Department of Community Medicine, M.K.C.G. Medical college, Berhampur, Odisha. The duration of study was of 3 months from January-2019 to March-2019. The retrospective data of number of animal bite cases was collected form ARC OPD Register for the period from January 2014 to December 2018. Analysis was done in “R” software version 3.6.1. The “dplyr”, “ggplot2”, “forecast” and “stats” packages were used for data munging and trend analysis. RESULTS The total number of animal bite cases from January 2014 to December 2018 was 50484. An average of 10097 cases of animal bite were reported per year for the last 5 years with SD = 717.17. Dogbite was most common (83.33%), followed by cat bite (9.52%), monkey bite (5.65%) and others (1.2%). About 64.87% animal bite cases were males. Timse series analysis showed a trend of minimal decline of cases of animal bite since 2014 to 2018. Seasonality was noticed with maximum cases were reported in the month of October followed by November and December in each year. With respect to seasonality, highest number of animal bite cases was more during winter season followed by spring season and summer season. CONCLUSION There was a decrease in the burden of animal bite cases. Necessary intervention strategies based on epidemiological triad has to be designed and implemented for prevention & control of rabies.

Corresponding Author : Dr. Nivedita Karmee, niveditakarmee@yahoo. com 1H. O. D & Professor, 2Assos. Professor, 3,4 Post Graduate student, Department of Community Medicine, M.K.C.G. Medical College, Berhampur, Odisha.

Submission Date : 14/09/2019 Acceptance Date : 15/12/2019 33 Volume XXI, Issue III, January 2020

KEY WORDS Rabies, Seasonal trend, Epidemiological triad, Intervention strategy. INTRODUCTION Rabies is a viral zoonotic disease of central nervous system. It is caused by Lyssavirus type -1 which belongs to the family Rhabdoviridae. The virus is excreted in the saliva of the aff ected animal. A number of carnivorous like dogs, cats, jackels, wolves and bat species serve as a natural reservoir. Rabies in dogs is a source of 99% human infections and a potential threat to more than 3.3 billion people. All the warm blooded animals including man are susceptible to rabies. It is transmitted to man by contact, bites and licks of rabid animals. It is the only communicable disease of man which is fatal but vaccine preventable [1]. Rabies is responsible for about 59, 000 human deaths annually in over 150 countries with 95% of cases occuring in Africa and Asia [2]. More than 99% of all human deaths from rabies occur in the developing world. India is endemic for rabies accounting for 36% of the world’s deaths. It causes 18,000-20,000 deaths every year. Most 91.5% animal bites in India are by dogs, out of which about 60% are stray and 40% pets. A person is bitten in every 2 seconds and someone dies from rabies in every 30 minutes. The annual number of person-days lost because of animal bites is 38 million [3]. Citing the burden of rabies on a global scale, the global partners announced a plan “Zero by 30”, in the year of 2017. So the present study was conducted in Anti Rabies Clinic of M. K. C. G. Medical College, Berhampur, Odisha to fi nd out the trend of animal bite victims over a period of last 5 years and to assess the seasonality of animal bite victims. METHODOLOGY It was a record based cross-sectional study carried out at the Anti-Rabies-Clinic (ARC) OPD of M. K. C. G. Medical college, Berhampur, Odisha. The study was conducted over the period of 3 months from January 2019 to March 2019. The nature of the data used in the analysis was secondary data gathered from the OPD register of Anti-Rabies Clinic. Information about the socio-demographic profi le and the types of animal bite were collected for the period of 5 years from January 2014 to December 2018. The total number of reported cases were calculated monthwise irrespective of new and re-exposure status. All the three categories of the animal bite cases were included in this study. All the cases of animal bite reported to ARC OPD for the last 5 years were plotted as time-series plot. It is a line graph which represent the measurements taken over regular time interval. Time series decompostion is a statistical method that decomposes a signal into several components i. e. a trend, a periodic and a random component. The time-series plot was decomposed to analyse the trend and seasonality about the victims of animal bite reported to ARC OPD, MKCG Medical College. Data was entered in excel and analysed in “R” software version 3.6.1. The “dplyr”, “ggplot2”, “forecast” and “stats” packages were used for data munging and trend analysis. RESULTS A total of 50484 cases of animal bite were repoerted to ARC OPD during the period from January 2014 to December 2018. An average of 10097 cases of animal bite were reported per year for the last 5 years with SD=717.17. Highest number of animal bite cases were reported in the year of 2014 i. e. 10903 while the lowest number of cases in the year of 2018 were 9077. It was found that there was slight decrease in trend in the number of animal bite cases from 2014 to 2018. (Table1)

34 APCRI Journal

Table 1: Year-wise Distribution of the cases

Mean Time No of Animal =10096.8 Total Period Bite Cases SD =717.17 Male(n, %) Female(n, %) Rural(n, %) Urban(n, %) Jan 2014- 6809(62.45%) 4094(37.54) 7828(71.79%) 3075(28.20%) 10903 Dec 2014 Jan 2015- 6242(59.61%) 4229(40.38%) 7894(75.38%) 2577(24.61%) 10471 Dec 2015 Jan 2016- 7138(69.0%) 3206(40%) 6875(66.46%) 3469(66.46%) 10344 Dec 2016 Jan 2017- 6429(66.35%) 3260(33.64%) 7132(73.60%) 2557(26.395) 9689 Dec-2017 Jan 2018- 6129(67.52%) 2948(32.47%) 7225(79.59%) 1852(20.40%) 9077 Dec 2018 Total 32747(64.87%) 17737(35.13%) 36954(73.20%) 13530(26.80%) 50484(N)

Among the cases, 64.87% animal bite victims were males and 35.13% were females. Based on locality, 73.20% belonged to rural areas and rest (26.80%) were from urban and semi-urban areas. (Table-1). Majority of the cases were of dog bite (88.30%) followed by cat (7.52%) and monkey bite (4.11%). Only 1.7% of the cases were bitten by other animals. (Figure-1)

5.65% 1.20%

9.52%

Dog Cat Monkey Others

83.33%

Figure 1: Types of Animal The average number of animal bite cases per month were highest in the year of 2014. (mean=908, SD=272.17) and was lowest in the year of 2018. (mean =756, SD=139.83). (Table-2)

35 Volume XXI, Issue III, January 2020

Table 2: Month-wise description of Animal Bite Cases from 2014-2018. (N=50484)

No. of Standard Year Mean Minimum Maximum Total Months Deviation 2014 12 908 272.17 607 1448 10903 2015 12 872.6 356.68 585 1730 10471 2016 12 862 318.06 543 1744 10344 2017 12 807.4 213.79 543 1396 9689 2018 12 756 139.83 543 1019 9077 2014-2018 60 841.4 267.33 2821 7337 50484 The time series plot indicate that the months of October, November and December show rise in the cases above the monthly average value for each year. For the year of 2014,2015,2016 and 2017, the maximum number of cases were reported in the month of October followed by November and December. In the year of 2018, maximum animal bite cases were reported in the month of January. Though there was a decline of cases after January 2018, again rise of cases were seen in the month of October. A sudden rise of the number of cases was also seen in the month of August 2014. (Figure-2)

Loess Smooth Line 1750-

1500-

1250-

1000-

Number of Annimal Bite Cases Number of Annimal Bite 750-

500- Apr,14 Oct, 14 Apr,15 Oct,15 Apr,16 Oct,16 Apr,17 Oct,17 Apr,18 Oct,18 Time

Figure 2: Time series plot of the Animal Bite Cases Attending to ARC-OPD. To analyse the trend and sesonality, the monthly variation time series data was decomposed into trend and seasonality components by “loess smoothing method”. The time-series data was decomosed into trend, seasonality and irregularity. A downward trend of the counts of the animal bite cases which fi rst manifest itself from February 2018 is depicted in the fi gure. However with increase number of cases in October 2018, the annual number of cases remained high and the corresponding burden cannot be simply ignored. The additive model was considered since the random fl uctuations in the data are roughly constant in size over time. The seasonal plot displayed the sub-series by year. It shows that the seasonal component constrained to remain the same across the year for the last 5 years. This implies that there is a seasonality among in the number of animal bite cases attending Anti-Rabies Clinic in each year. (Figure-3)

36 APCRI Journal

1750 1500 1250

1000 Data 750 500 900 800

700 Trend 600

500 250

0 Seasonal -250 600 400 200 0

-200 Remainder 2014 2015 2016 2017 2018 2019 Time Figure 3: Seasonal Decomposition of Time series data into Trend, Seasonal and Irregular Component. Table 3: Seasonality Index of the time series data

Jan Feb Mar April May June July Aug Sep Oct Nov Dec Seasonality 0.094 0.082 0.078 0.076 0.074 0.059 0.065 0.074 0.071 0.143 0.101 0.084 Index

The average number of animal bite cases reported for the last 5 years was 841.4 (SD=267.33). The seasonality index were calclulated and it was found that the month of October shows the highest seasonal index (0.143) and minimum for the month of June (0.059) (Table 3). This indicate that the month of October was the peak time where maximum number of cases were attended to OPD followed by November and December. This time represent the continuation of winter and beginning of spring season in India. However in 2018, the trend shows slight reverse order. More number of cases were reported at the beginning of the year and with a peak in Oc tober, a decline in trend was seen. (Fig-4)

2014 2015 2016 KĐƚ 900 KĐƚ KĐƚ ƵŐ 500

600 EŽǀ 500 250 300 Dec EŽǀ EŽǀ :ĂŶ FebDĂƌ :ĂŶ ^ĞƉ Dec :ĂŶ 0 0 ĞǀŝĂƟŽŶĨƌŽŵƚŚĞǀŐ͘EŽŽĨĂƐĞƐ ĞǀŝĂƟŽŶĨƌŽŵƚŚĞǀŐ͘EŽŽĨĂƐĞƐ 0 ĞǀŝĂƟŽŶĨƌŽŵƚŚĞǀŐ͘EŽŽĨĂƐĞƐ Ɖƌ Feb DĂLJ DĂƌ Ɖƌ Dec Ɖƌ DĂƌ DĂLJ Feb DĂLJ :ƵŶĞ :ƵůLJ :ƵůLJ ^ĞƉ ƵŐ -250 :ƵůLJ ^ĞƉ -300 :ƵŶĞ ƵŐ :ƵŶĞ džсDŽŶƚŚůLJǀŐ͘ŶŝŵĂůŝƚĞĂƐĞƐ džсDŽŶƚŚůLJǀŐ͘ŶŝŵĂůŝƚĞĂƐĞƐ džсDŽŶƚŚůLJǀŐ͘ŶŝŵĂůŝƚĞĂƐĞƐ

2017 2018 600 KĐƚ 200 :ĂŶ

KĐƚ 400 100 Feb

0 200 EŽǀ DĂƌ X-axis = Avg. Monthly Cases (Mean=814.4) -100 DĂLJ Y-axis = Cases Higher than mean 0 EŽǀ Dec Y-axis = Cases Lower than mean Ɖƌ :ƵůLJ :ĂŶ Feb ƉƌDĂLJ

ĞǀŝĂƟŽŶĨƌŽŵƚŚĞǀŐ͘EŽŽĨĂƐĞƐ ^ĞƉ ĞǀŝĂƟŽŶĨƌŽŵƚŚĞǀŐ͘EŽŽĨĂƐĞƐ -200 DĂƌ Dec :ƵůLJ -200 ƵŐ :ƵŶĞ ^ĞƉ -300 :ƵŶĞ ƵŐ džсDŽŶƚŚůLJǀŐ͘ŶŝŵĂůŝƚĞĂƐĞƐ džсDŽŶƚŚůLJǀŐ͘ŶŝŵĂůŝƚĞĂƐĞƐ

Figure 4: Month-wise variation of Number of Animal Bite Cases.

37 Volume XXI, Issue III, January 2020

DISCUSSION: Current cross sectional study is conducted to fi nd out the trend of animal bite victims over a period of last 5 years and to assess the seasonal distribution of animal bite victims. In our study, it was observed that average animal bite cases were more in the month of October, November and December and less in the months of April and May. It is similar to a study by Sinha et al (2015)[5] where more cases were found in the months of October, November and December and fewer cases found in the months of August, July and September respectively. In contrast to this study, a study conducted by Dr Kulkarni et al[6] found maximum number of cases in the month of March, April and February. Maximum number of animal bite cases were by dogs followed by cats and monkeys which is similar to the fi ndings of TR Behera et al[7 ], Singh et al[8], and Sudarshan et al [9] where dogs were the most common (95.8%) biting animal. Males were more aff ected than females which could be because males are more involved in outdoor activities than females. Similar fi ndings were reported by Mahd Junaid et al[10], Shelke et al[11], Jain et al [12]. However in a study by Gupta et al[13] more females were the victims. Like wise majority of animal bite cases were from rural areas. This could be because in rural areas people mainly work outdoors and are largely farmers, daily labourers, etc. It was similar to the fi nding by Modi et al [14] and Behera TR et al [7]. However, studies by Sampath et al [15], Kirti V Kinge et al [16] reported that most of the animal bite victims were from urban areas. The attendance of animal bite cases at ARC was high during winter season and spring season and less during rainy season and summer season. It could be because winter season is the breeding season for dogs. This is similar to the fi ndings by Hanspal et al[17] and A. K. Pratap et al [18]. Contrary to this some studies conducted by Agrawal et al [19] and Vinay M et al [20] in which maximum animal bite cases were found in summer season. CONCLUSION AND RECOMMENDATION: As the burden of animal bite case is high, in every health facility there should be availability of vaccines and immunoglobulin. Most bites were by dogs and more in winter and spring season. It is necessary to vaccinate all the domestic dogs. Furthermore, most animal bite cases were from rural areas. So, there should be proper IEC activities to increase the awareness regarding the rabies prevention, treatment and adequate precautions to be taken especially during the winter season. The programs like ABC (Animal Birth Control) and mass vaccination campaign should function well to bring down the magnitude of animal bite cases. Source of Support: Nil Confl ict of Interest: Nil REFERENCES: [1] Park K. Textbook of Preventive and Social Medicine. 24rd edn. Jabalpur: BanarsidasBhanot, 2017. pp396,395 [2] Hampson k. et al. Estimating the global burden of endemic canine rabies. Trop dis. 2015; 9 (5): e0003786. [3] World survey of rabies: No. 32 for the year 1996. Geneva, World Health Organization, 1998 (WHO/EMC/ ZDI/98.4;) [4] Manazee R, Rabies in India CMAJ. 2008, Feb 2,178(5), 564-8

38 APCRI Journal

[5] Arijit sinha et al(2015) a study of profi le of rabid animal injury in human in a tertiary care infectious disease hospital of eastern india. International Journal of Advances In Case Reports ;2(4):256-260 [6] Kulkarni SK. Trend of Animal Bite Victims Reported to Anti Rabies Vaccination Clinic At A Tertiary Care Hospital Nanded Maharashtra. 2016;15(11):36–9 [7] Behera TR, Satapathy DM, Tripathy RM, Sahu A. Profi le of animal bite cases attending the ARC of MKCG Medical College, Berhampur (Orissa). APCRI JOURNAL, Vol IX, Issue II, Jan 2008:19-23 [8] Singh J. Epidemiological Characteristics of Rabies in Delhi and Surrounding Areas, 1998. Indian Pediatrics. 2001;38:1354-60. [9]. Sudarshan M, Madhusudana S, Mahendra B, Rao N, Ashwath Narayana D, Abdul Rahman S, et al. Assessing the burden of human rabies in India: results of a national multi-center epidemiological survey. Int J Infectious Dis. 2007;11(1):29-35. [10] Hospital C, Junaid M, Ahmad T, Hazare S, Meshram P, August J. Research Journal of Pharmaceutical, Biological and Chemical Sciences Epidemiological Study of Dog Bite Victims in Anti Rabies Clinic of A Tertiary. 7(2125):2125–9 [11] Shelke SC, Kamble MS, Niwal A. Epidemiological determinants of animal bite cases attending the anti- rabies immunization (ARV)OPD in Sassoon hospital, Pune. Int J Basic Appl Sci. 2015;5(2):98-101. [12] Jain M, Prakash R, Garg K, Jain R, Choudhary M. Epidemiology of animal bite cases attending anti-rabies clinic of a Tertiary Care Centre in Southern Rajasthan. J Res Med Dent Sci. 2015;3(1):79. [13] Gupta H, Mazta RS, Goel S. Epidemiological profi le of bite cases admitted at 50 bedded Community Health Center of Himachal Pradesh, India. Internet J Health. 2004:1528-8315. [14] Modi BK. A review of attendance trend of animal bite cases in the private antirabies clinic, at Kukarwada town in North Gujarat. APCRI J 2009;10(2):27–8. [15] Sampath G. Post exposure treatment—patients and practices. APCRI J 2004–2005;1,2(7):30–3. [16] Kinge KV, Supe AC. Epidemiology of animal bite cases reported to anti-rabies vaccination OPD at a tertiary care hospital, Nagpur. Int J Med Sci Public Health 2016;5:1579-1582 [17] Hanspal JS, Bhanderi D, Nagar S. A review of attendance trend of animal bite cases in anti rabies clinic of G. G. S Hospital, Jamnagar (Gujarat). APCRI Journal Vol III, Issue II, January 2007:16-18 [18] A. K. Pratap et al. Seasonal trend of animal bite cases reporting at anti rabies clinic (ARC) of MK. C. G. Medical College, Berhampur, Orissa. APCRI Journal Vol XIII, Issue I, July 2011:24-29 [19] Agrawal N, Reddajah VP. Epidemiology of dog bites, a community based study in India. Trop Doct. 2004:34(2):76-8 [20] Vinay M, Mahendra BJ, Poornima S, Harish BR, Subhas, Babu P, Anil. Profi le of animal bite victims and compliance to the 4 dose IDRV schedule among children attending Anti Rabies Clinic, MIMS, Mandya, APCRI Journal, VolXI, Issue II, January 2010 :38-40

39 Volume XXI, Issue III, January 2020

CASE REPORT

Safety and immunogenicity of Rabies Human Monoclonal Antibody (Rabishield) in a category III rabid dog bite: A case report

Tapas Ranjan Behera1, Swetaleena Ashe2

ABSTRACT The purpose of this case study is to re-establish the safety and immunogenicity of Rabies Human Monoclonal Antibody in Category III dog bite. A 7 years male child presented with a lacerated wound over the left palm following bite from a suspected rabid dog. He was administered Purifi ed Vero cell Rabies Vaccine as intra muscular regimen with Rabies Monoclonal Antibody (RMab) as per body weight. The Anti-Rabies Antibody titre was measured following RMab administration which had no side eff ects and was found to have Antibody levels above protective level. KEYWORDS Rabies Monoclonal Antibody, Essen Regimen, Anti Rabies Treatment INTRODUCTION Modern day Vaccines and Immunoglobulin/ Monoclonal Antibody has made the highly fatal disease, Rabies completely preventable. The mainstay of Anti-Rabies treatment following animal bite comprises of local wound care, Rabies Immunoglobuin or Rabies Monoclonal Antibody (RMab) along with Rabies Vaccine administration. The Anti-Rabies Vaccine takes 10-14 days to produce protective antibody level in an individual. The window period of this 10-14 days is taken care by administration of RIG/RMab to prevent from a deadly disease, Rabies. The cost factor of Human Rabies Immunoglobulin (HRIG) prohibits many doctors to prescribe and also the patients to purchase the same. The fear of side eff ects following use of ERIG is also a factor for its low use among doctors for Category III animal bite treatment. 1Thus this case study on use of RMab in a Category III dog bite focuses on Safety and Immunogenicity of the newly marketed RMab named Rabishield. CASE PROFILE A male child of 7 years from Anandapur, Keonjhar reported to the physician at Cuttack with the chief complaint of being bitten by a stray dog of abnormal behavior at 8.00 pm on 15th May 2017. It was an unprovoked lacerated bite over left hand and left thigh with bleeding. It was a Category III exposure as classifi ed by WHO categorization of animal bite injury. 2 The wound was thoroughly washed with soap and water by the parent of the child. He was counselled and given an option to choose among the three diff erent rabies immunoglobulins (ERIG, HRIG, RMab) available with their cost, advantages and adverse eff ects. He was then treated with anti-rabies vaccines, Rabies monoclonal antibody and F Heal cream for local application. He was advised anti-rabies vaccine (Inj Zoonovac, Batch number 17GRAB016) 0.5 ml as per IM schedule on days 0,3,7,14 and 28. The child was also treated with Rabies monoclonal antibody (Inj Rabishield Batch number 1877700102) at the site of bite. The dose was calculated as per his body weight i. e 3.33 IU/KG. As the child weighed 27 Kg, a total of 89.91IU i. e 2.25 ml was administered. Out of the total required calculated RMab, 1.75 ml was infi ltrated over left palm locally and rest

Corresponding Author : Dr. Tapas Ranjan Behera 1Assiatant professor, 2Junior Resident Department of Community Medicine, SCB Medical College and Hospital, Cuttack, Odisha, India.

40 Submission Date : 22/01/2020 Acceptance Date : 29/01/2020 APCRI Journal

0.5 ml was infi ltrated over left thigh. He was also advised antibiotics (Tab. Amoxyclav 325 1 tab BD for 5 days and NSAIDS (Syp Paracetamol and Mefenamic acid 250 mg SOS) for further management. Along with the above drugs, he was asked to locally apply F Heal cream (Tritium vulgare extract and 2 penoxyethanol) at the site of bite for healing of the wound. On completion of vaccination as IM schedule on 12th January 2018, the patient was asked for anti-rabies antibody titre. The wound had completely healed with no scar marks. The tests were conducted a week later and the rabies IgG level was 17 (Normal <40 U/ml) and Rabies IgM level was 8 (Normal <40 U/ml). Hence, the reports suggested of adequate antibody production on complete treatment with anti-rabies vaccine and Rabies monoclonal antibody. DISCUSSION In developing countries like India, where Government spends only 1.5% of GDP on health expenditure, cost eff ectiveness is a major issue. Equine rabies immunoglobulin though easily available still is a cause of concern for physicians due to its adverse eff ects such as anaphylaxis and serum sickness as found in the WHO- APCRI Survey in India in 2003.1High cost of human RIG due to its production from human serum from immunized donors makes aff ordability a major issue. Alternatively, a monoclonal antibody produced from mammalian cell lines, resulted in lower cost, lesser volume and reliable source of passive antibody for rabies PEP. 3 However, the major challenge to its use and replacing ERIG/HRIG, was the adequate production of Rabies antibody and an equivalent level of protection which can be overcome by more of phase IV post marketing surveillance of the product in multi-centric studies. However, we found a protective level of antibody production after RMab administration in the present case. Hence, Monoclonal Rabies Antibody off ers a reliable solution to address the cost, supply and safety issues as compared to the blood derived RIG. 4 Our case had an unprovoked bite by dog on both upper and lower limb which was similar to the fi ndings of DM Satapathy et al and Kaware et al. 4,5 We followed up the case for day 0,3,7,14,28, 90 days and no adverse eff ect was reported which was contrary to the fi ndings of DM Satapathy among 53 patients at VIMSAR, Burla, Odisha. 4 CONCLUSION Rabies Monoclonal Antibody thus stands out to be a new arena of scope against the safety and cost issues of ERIG and HRIG respectively. Thus RMab has proven to be an apt alternative to the presently available blood derived immunoglobulins. ACKNOWLEDMENT We highly appreciate the cooperation of the child’s father to have understood well the purpose of the investigation and willfully accepting to carry out the tests for antibody level following Rabies Monoclonal Antibody administration. REFERENCES 1. Sudarshan MK, Mahendra BJ, Madhusudana SN, Ashwanath Narayana DH, Rahman A, Rao NSN et al. An EpidemiologicalSstudy of Animal Bites in India: Results of a WHO Sponsored National Multi-Centric Rabies Survey. J Commun Dis. 38(1) 2006:32-39 2. WHO expert consultation on rabies, third report. (WHO Technical Report Series, No 1012), WHO 2018. 3. Susan E. Sloan, Cathleen Hanlon, William Weldon, Michael Niezgoda, Jesse Blanton, Josh Self et al. Vaccine 25 (2007) 2800- 2810 4. Satapathy DM, Panda D, Pradhan S, Patro S. Clinical Safety of Rabies Monoclonal Antibodies: A Follow up study conducted at ARC, VIMSAR, Burla. APCRI Journal, Vol XX, Issue II, January 2019, p 26-29. 5. Kaware A, Rokade H, SK M. Epidemiological study of patients attending anti-rabies vaccination clinic of tertiary care hospital of Southern Maharastra, India. Int J Community Med Public Heal. 2016 Feb 2; 3(4):865-8.

41 Volume XXI, Issue III, January 2020

CASE REPORT

Serum Sickness should not rule out Equine Rabies Immunoglobulin AdministraƟ on - A Case Study

Santoshinee Rout1, Tapas Ranjan Behera2

ABSTRACT A forty years old Hindu male presented to the Anti-Rabies Clinic of a tertiary care hospital with rashes all over the body associated with myalgia and mild fever following treatment with Anti-Rabies vaccine and Equine Rabies Immunoglobulin (ERIG) for Category III dog bite injury. On seventh day of vaccination, the person developed generalized rashes all over the body. He was primarily given anti-histamines, antibiotics and analgesics for 5 days from the 1st day of vaccination in which period he didn’t develop these rashes. The rashes were present more on face, shoulders, arms and forearms, thighs and sparse over the back. He was then treated with Inj Pheniramine maleate (2 ml) 1 ampule and tab Hicope 25 mg (Hydroxizine Hydrochloride), Tab Paracetamol 500mg and was completely cured after three days. The adverse reaction following ERIG administration was diagnosed as a case of Serum Sickness and reported to the Adverse Drug Reaction Monitoring Centre of the College. The purpose of this case study is to create awareness about the adverse drug reactions following ERIG administration among the health care personnel, importance of prompt management of such Serum Sickness cases and timely reporting to the ADR Monitoring centres. Keywords: Serum Sickness, Equine Rabies Immunoglobulin, Adverse Drug Reaction Monitoring, Rabies, Anti- Rabies Vaccination INTRODUCTION Rabies is a zoono c disease caused by Lyssavirus. It mainly aff ects the CNS and cause fatal encephalomyeli s in humans and animals. It is a 100% fatal disease and hence deserves utmost importance in slightest of injury from animal bite/ scratch; else a small negligence could cost a human life. This deadly disease can be prevented with just mely and appropriate an rabies prophylaxis. 1 Modern medical science with its fast evolu on has gi ed mankind with products from animals which are life-saving for humans. One such is the Equine Rabies Immunoglobulin (ERIG) which is administered to humans upon any bite/ scratch from warm-blooded animal. Heterologous serum administra on is associated with a number of adverse eff ects. So, skin sensi vity test is performed in order to know the clinical safety of the immunoglobulin. Howsoever, as the sensi vity and specifi city of skin sensi vity is very low, so tes ng will be of li le help in predic ng anaphylaxis or serum sickness. 2 WHO even recommends that there is no scien fi c background for performing a skin test before administra on of ERIG in the present era as the current available ERIG are pure. Serum sickness in humans is a reac on to proteins in an serum derived from a non-human animal source, occurring 5-10 days a er exposure. It is a type III immune complex hypersensi vity disorder. It usually presents

Corresponding author: Dr. Santoshinee Rout, Dr. Tapas Ranjan Behera, Assistant Professor, Department of Community Medicine, SCB Medical College, Cu ack, Odisha. Email: tapas4behera@gmail. com. Phone: 9937183787 1 Post Graduate Trainee, 2 Assistant Professor Department of Community Medicine, SCB Medical College, CuƩ ack, Odisha

42 Submission Date : 17/09/2019 Acceptance Date : 26/11/2019 APCRI Journal with symptoms such as rashes, arthralgia, fever, malaise, headache and gastrointes nal symptoms. 3 The human immune system mistakenly treats the serum proteins as an gen and start producing an bodies, which form immune complexes and precipitate in the walls of the blood vessels. Proper treatment with an -histamines, analgesics and cor costeroids, would completely cure the pa ent else it could lead to as serious a condi on as shock to cause death of the pa ent. 3 CASE PROFILE A forty years old male from Cu ack district of Odisha presented to the An -Rabies Clinic (ARC) of SCB Medical College hospital Cu ack Odisha on 9th of Nov 2019 with the chief complaints of erup on of rashes all over the body for last one day. It was associated with mild degree of fever, malaise and generalized pruritus. The pa ent had a history of Category III dog bite over the le leg (Tibial shin) on 2nd of November 2019. He had washed the wound with soap and water and came to the ARC on 2nd November 2019, where he was administered with Inj. Tetanus Toxoid 0.5 mL Intramuscular, Injec on Purifi ed Vero Cell Rabies Vaccine (PVRV, Injec on Abhayrab, manufactured by Human Biologicals Ins tute, TamilNadu, India Batch No. - 18URAB089, Mfg date October 2018, Expiry Date September 2021 with a potency of ≥ 2.5I. U. per vial), 0.1 mL over both arms intra dermally. He weighed 88 Kg and hence was advised to be infi ltrated with Equine Rabies Immunoglobulin (ERIG, Inj Equirab manufactured by Bharat Serums and Vaccines Limited, Mumbai, India Batch No. A02719007, Mfg date February 2019 Expiry Date January 2021 with a potency of 300 IU/ml) i. e. 10 mL a er the skin sensi vity test. The intra dermal skin test was done using 0.1 ml of ERIG diluted with 0.9 ml(1:10) of normal saline provided by the manufacturer over le forearm and with 0.1ml normal saline on right forearm as control. A posi ve test result is not a formal contraindica on for the use of sero therapy, but it should be considered as a warning. In such cases Equirab should be administered only a er ensuring the facility to overcome the anaphylac c shock. A nega ve test is not an absolute guarantee for the absence of an immediate allergic type reac on4. He was observed for any indura on a er 15 minutes but only a wheal of 5 mm was seen on le forearm and 3mm was seen on right forearm. Hence the test was read as nega ve. He was infi ltrated 2mL of ERIG at the site of bite as that much of amount was possible to infi ltrate locally over the bite site and rest 8 ml was administered as 4 ml each over the antero lateral aspect of both thighs, intra muscularly. He was further advised to take Tablet ce rizine (10mg) 1 tablet for 5 days in empty stomach in evening and Tablet Paracetamol 500mg three mes for 3 days. He was advised to a end the ARC for comple on of rest PVRV doses as scheduled on 5th Nov, 9th Nov and 30th Nov 2019.

Figure: Rashes over face, Shoulder and Upper Limb

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The person was apparently alright from the ini a on of treatment but on 8th Nov (i. e. 7th day of treatment) he presented to the ARC with rashes all over the body. The rashes fi rst appeared on the bite site where ERIG was administered locally followed by both thighs, both upper limbs, shoulders and face. They gradually increased in size. It was associated with very mild degree of fever, malaise, and generalized pruritus, more over the rashes. He denied of having any previous allergy to any food items or drugs neither he took any unusual foods in the recent days. He was then diagnosed to be a case of Serum Sickness following ERIG administra on. On examina on, vitals were stable with pulse 78 /min and BP 122/78 mmHg. The person was administered inj Pheniramine Maleate (Avil) 1 amp IM to start, ce rizine 10 mg before food for 7 days. The person was then followed up over telephone and he reported decrease in the size of rashes by the next day. He was called a er 2 days for clinical evalua on and was found to be completely cured of the rashes. He was further advised to complete his last scheduled An -Rabies Vaccine (ARV) on 30th Nov without any fear which he had completed. This case was reported to the Adverse Drug Reac on monitoring Centre of the ins tu on. DISCUSSION In our study, the pa ent was a male of 40 years of age. He was working in a transport agency. Transport personnel are at more risk of animal bites probably due to their outdoor travelling and parcel delivery at costumer doorstep by their pet dogs and even by stray dogs. Cases a ending ARC with history of dog bites/ scratches are more in comparison to other animals. Dogs are a major cause of rabies as also assessed by a na onal mul center survey where dogs (96.2%) were mainly responsible for human rabies deaths. 5 We no ced a good prac ce in the case i. e. washing the wound immediately with soap and water. A study on “Eff ec veness of child to child method of educa on regarding Rabies and its preven on” by Shwetha et al6 showed only 21.5% of subjects knew of washing wound with soap and water prior to educa on which was followed by 100% of them knowing it a er educa on. Serum sickness is a rare complica on occurring in response to ERIG administra on. Among the local adverse eff ects cited in Tripathy RM et al2 ur caria, dizziness, redness, vomi ng, localized swelling and headache were common. However, in our case there was no such symptom on the day of ini a on of treatment. The person complained of various systemic adverse eff ects such as generalized pruritus, malaise, mild fever and rashes. He was diagnosed to have Serum Sickness as also found in other studies by Behera TR et al in Odisha and Wilde et al in Bangkok where the incidences were 3% and 1.6% respec vely. 7,8 Another study by Maharana S et al9 found rashes to be the most common symptom in 97.82% of cases following ERIG administra on in the same se ng which was similar to our case. Our case reported of rashes on seventh day a er administra on of ERIG which was a rare occurrence as only 12% of cases following ERIG infi ltra on reported symptoms of serum sickness on tenth day. 9 Only one case among 48 cases observed for serum sickness by Maharana S et al9 required cor costeroids, however this pa ent was being treated with only an histaminic and did not required cor costeroids for management. CONCLUSION Reactions following immunoglobulin such as Serum sickness though a rare adverse eff ect yet awareness regarding its symptoms among the patients and proper guidelines to manage such cases is of utmost importance. Adverse eff ects following immunization has been a hindrance for successful outcome of any immunization program. The fear of serum sickness following use of ERIG need to be addressed with timely management with simple antihistamines and keeping in hand with Anaphylaxis Kit among Doctors treating animal bite cases. So, it is very necessary to make people aware of diff erent adverse eff ects that could follow vaccination and create a sense of urgency to seek timely treatment. It is also recommended that all immunization centers to be fully equipped with Adverse Eff ects Following Immunization (AEFI) kits or anaphylaxis kits as well as protocols for management of such cases. The life-saving drugs should be properly labelled, its usage made very clear to all the staff dealing with vaccination. In this era, where immunization has been a great step in averting disease and deaths, AEFI must be properly managed and reported to ADRM Centers on regular basis. This can surely be a step, safe enough, towards achieving the goal of “Dog-mediated Human Rabies free India by 2030”.

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REFERENCES 1. National Guidelines for Rabies Prophylaxis and Intradermal Administration of Cell Culture Rabies Vaccines. National Institute of Communicable Diseases. 2007. 2. Tripathy RM, Satpathy SP, Das S. Outcome of skin sensitivity test for assessing adverse reactions to equine rabies immunoglobulin in a tertiary setup of South Odisha. APCRI Journal 2018; 19(2): 13-15. 3. Serum sickness. Available from: http://en. m. wikipedia. org/wiki/Serum_sickness. 4. Wilde H, Chomchey P, Punyaratabandhu P. Purifi ed equine rabies immune globulin: A safe and aff ordable alternative to human rabies immunoglobulin. BulleƟ n of the WHO 1989; 67(6): 731-736. 5. Sudarshan MK. Assessing burden of rabies in India: WHO sponsored National multicentric Rabies survey, 2003. Indian Journal of Community Medicine 2005; 30(3): 100-101. 6. Shwetha, Vinay M, Harish Br. Eff ectiveness of child to child method of Education regarding Rabies and its prevention. APCRI Journal 2018; 19(2): 28-29. 7. Behera TR, Satapathy DM, Pratap AK et al. Post-exposure prophylaxis for rabies with ERIG and IDRV in children. J Commun Dis 2011; 43(1): 31-37. 8. Wilde H, Chomchey P, Punyaratabandhu P. Purifi ed equine rabies immune globulin: A safe and aff ordable alternative to human rabies immunoglobulin. BulleƟ n of the WHO 1989; 67(6): 731-736. 9. Maharana S, Behera TR, Pattnaik N. Serum sickness in patients receiving equine rabies immunoglobulin. J Commun Dis. 2018; 50(2): 1-4.

45 Volume XXI, Issue III, January 2020 SPECIAL REPORT Street dog survey in Bengaluru, Karnataka, India SubmiƩ ed by Dr. Srikrishna Isloor (Team Member) Survey conducted: September 2019

Executive summary A survey of the roaming dog popula on of Bengaluru Municipality was implemented by Bruhat Bengaluru Mahanagara Palike (BBMP) in September 2019 with addi onal technical support donated by Bangalore Veterinary College and NGOs, WVS India and Mission Rabies. The total popula on es mate for roaming dogs in Bangalore City was 3.1 lakh dogs (95% CI: 2,30,851 – 4,12,794), giving an overall human: dog ra o of 27.2 (95% CI: 20.4 – 36.6). City-wide door-to-door mass vaccina on of the owned dog popula on should be conducted as a priority to immunise those dogs in closest contact with people against rabies and to gather informa on about con nement prac ces, preferences for reproduc ve control and iden ca on.

Corresponding Author : Dr Srikrishna isloor *Associate Professor and in-charge, OIE Twinned Rabies DiagnosƟ c laborratory, Dept. of Veterinay Microbiology, Veteninary College Hebbal, KVAFSU, Bangalore, Karnataka. Submission Date: 05 / 01/2020 Acceptance Date: 29/01/2020

46 APCRI Journal

Background Bengaluru city is the third most populous city in India, with a human populaƟon of over 84 lakh people1 and covering an area of 741 km2. Like many metropolis seƫngs in India, Bengaluru has seen a dramaƟc increase in the number of dogs roaming the streets, with rising public concern over inƟmidaƟon and the spread of zoonoƟcdiseases, speciĮcally rabies. EsƟmaƟon of the roaming dog populaƟon of the city is essenƟal for planning rabies control and dog populaƟon management acƟǀŝƟĞs. The previous esƟmated dog populaƟon of Bangalore City was approximately 2,00,000 roaming dogs in 20062.

Figure 1 – Map of Bangalore Wards, labelled by Ward Number

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Survey Method The science of dog populaƟon esƟmaƟon is evolving, with the increasing use of technology to enhance the scale and eĸciency of survey acƟǀŝƟĞs. Here we used smartphone technology and a combinaƟon of survey methods to maximise the available resources. Basic Single-Sight (SS) Surveys were used to survey a large proporƟon of the city, whilst Sight-Resight (SRS) Surveys were used to evaluate how accurate the basic SS surveys were at esƟmaƟŶg total populaƟon in a region. The combined analysis of data from these two methods was used to calculate the total dog populaƟon esƟmate for the city. Types of survey 1) Single-Sight (SS) survey The most eĸcient way of gathering informaƟon about the number of dogs in a parƟcular area is for surveyors to travel down every road recording informaƟon about every dog seen. This basic survey involves a pair of surveyors travelling on a 2-wheeler bike through all parts of an allocated zone and recording details of every dog they see. Whilst both people keep a look out for dogs, one is responsible for driving and the other records details of the dogs sighted in the mobile phone App.

These SS surveys provide a snap-shot of the abundance of dogs in a given area, however the total number of dogs seen does not equate to the total dog populaƟon of the area because many dogs will not be observed on a single-pass. The movement of dogs and the limitaƟons of visibility result in some dogs not being seen when the surveyors pass by.

The proporƟon of the total populaƟon that is typically sighted on a basic survey is known as ‘detectability’. We can esƟmate the detectability of a given survey method using more intensive survey methods, such as Sight-Resight (SRS) Surveys.

2) Intensive (resight) survey The resight method involves conducƟng surveys of the same region over two days. On the ĮƌƐt day all of the dogs seen are ‘marked’, either physically with a marker or as in the current survey, virtually using a photograph. All dogs seen on the second day are recorded and whether or not they were ‘marked’ as seen on the ĮƌƐt day. This proporƟon makes it possible to esƟmate the total dog populaƟon for the region using Lincoln–Peterse’s formula, given below. LiƩers of puppies were not included in the resight calculaƟon due to sighƟng of a single lŝƩer of puppies considerably inŇĂƟng the number of sighted dogs with an unequal likelihood of being resighted on Day 2 as compared to the general populaƟon and therefore the potenƟal to skew the esƟmaƟon of detectability.

Unlike the Single-Sight Survey method, the SRS Survey method provides an esƟmate of the total populaƟon in the surveyed area, however they require more stĂī͕ experƟse and Ɵme to implement, limiƟng the area which can be covered. Therefore a combinaƟon of both SS and SRS surveys makes it possible to ďĞŶĞĮt from both scale and intensity of method.

Lincoln–Peterse’s formula: ( +1)( +1) = െ 1 ( +1)

Where N is the total esƟmated populaƟon size, n1 is the number iniƟally vaccinated, n2 is the total number of dogs recorded on post vaccinaƟons survey and m2 is the number of vaccinated dogs recorded on post vaccinaƟon surveys.

48 APCRI Journal

Approximate 95% conĮdence intervals were calculated using the Seber’s formula:

( +1)( +1)( െ )( െ ) = ( +1) ( +2)

±1.965 ( )

Detectability was calculated as the proporƟon of the total esƟmated populaƟon that was sighted on Day 1 as follows:

=

Survey zone selection Each survey was expected to sight approximately 150 dogs, with a standard deviaƟon of 100 dogs per sample unit. A percentage relaƟǀe precision of 10% was used with 95% conĮdence limits to calculate the required number of sampling units3:

=(200Τ ) ( / ) Where Q is PRP (10), is the esƟmated mean number of dogs per sample (150), is the esƟmated sample standard deviaƟon (100). The esƟmated number of sampling units required was 178. The Sight-Resight method was more intensive and so could be performed in fewer areas. A target sample size of 30 resight surveys (15 pairs) was feasible with the Ɵme and resources available. Given the exisƟng division of the city into 198 administraƟve wards, with each having corresponding human data from the 2011 India Census1, it was decided to conduct a Single-Sight survey from a random area of every ward, thus providing the required number of sample areas. To select Single-Sight Survey Zones, Wards were divided into Zones by separaƟon along major roads in Open Street Map. Of these Zones, one was randomly selected within each ward. Zones adjacent to the selected Zone were aggregated based on appearance on Google satellite images and roads so that: The Įnal survey zone was of a size which would take a survey team approximately one day to complete. The aggregated zones appeared roughly representaƟǀe of the ward with regard to road and building density. Sight-Resight Survey Zones were randomly selected from the Survey Zones.

Figure 2 – Final Sample Zones for Single-Sight and Sight-Resight Surveys

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Team Direction The WVS App has been developed to support the management of large scale dog vaccinaƟon campaigns and dog populaƟon surveys, with the ability to direct teams to speciĮc geographic areas, and record the GPS and other informaƟon about dogs sighted/vaccinated. Open access publicaƟons described this tool in detail4. In brief, the Project Manager assigns each Surveyor their allocated Zone in a website interface, which then appears on a map in the Surveyor’s phone. The Surveyors travels down every road in their Zones, compleƟng a form for every dog they see. The forms are customised to the survey and include quesƟons about the sex, age and neuter status of the dog, as well as recording the GPS locaƟon and Ɵme. For Sight-Resight surveys a photo of each dog is also taken. The App funcƟonsŽŋine and data is uploaded to the secure server once a day when connecƟon is available.

Figure 3 – IllustraƟon of Zone allocaƟon to Users in the web interface and display in individual user maps Schedule and Training The schedule was created based on ten SS survey teams working for 20 days and Įve SRS survey teams working 20 days. Surveyors were allocated Survey Zones from close to the part of the city where they reside for pracƟcal logisƟcal reasons and to ensure surveys were started on Ɵme. Zones were assigned through the WVS app and teams navigated within these Zones displayed on their smart phone. IniƟal training took place between 22/08/2019 to26/08/2019, during which Ɵme training ĮĞůd surveys were conducted in the central Wards of Bangalore. AddiƟonal pilot surveys were conducted on 30th and 31st August to reĮne Įeld protocols, before the oĸcial survey launched on 03/09/2019.

50 APCRI Journal

Extrapolation It is not possible to survey all areas of a city and so the esƟmated dog populaƟon must be extrapolated un- surveyed regions of the city using a known covariate such as geographic area or human populaƟon. Figure 4 summarises the method of extrapolaƟon from basic dog sight surveys used in this study.

Figure 4 – IllustraƟon for how the dog populaƟon was extrapolated from surveyed to unsurveyed regions

Analysis Survey Zones and map Įgures were created in QGIS. All analysis was performed in R Studio. All conĮdence intervals refer to the 95% conĮdence interval throughout this report. Omissions Surveys were omiƩed from analysis if: - Surveys were part of the training phase. - All or most GPS points were clustered around a few focal points within the survey region or were spread along speciĮc roads only as this would indicate that the survey protocol was not followed and the resulƟng data is invalid - The surveyor did not adhere to the allocated zone such that the region surveyed was not representaƟve of the ward as a whole.

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Results Sight-Resight Surveys A total of 17 valid Sight-Resight Surveys were completed (34 pairs), with a mean sighƟng rate on Day 1 of 127 dogs (CI: 104 – 149) and 125 dogs (CI: 103 – 147) on Day 2. The mean proporƟon of ‘marked’ dogs resighted on Day 2 was 72.1% (CI: 61.6 – 82.6) and the mean detectability was 68.0% (CI: 50.9 – 91.2).

Figure 5 – Summary of the areas surveyed by the Sight-Resight method. A) Map of city with GPS points and Zones surveyed, red box indicates the zone magniĮed in (B). B) Map of GPS points from dogs sighted on Day 1 and Day 2 of the survey conducted in Ward 105 on 27/09/2019 and 28/09/2019

The density of sighƟngs on Day 1 and Day 2 surveys was strongly correlated indicaƟng consistency in the rate of sighƟng between the two days (Figure 6).

Figure 6 - Graph ploƫng dog density (dogs/km2) for Day 1 and Day 2 Sight-Resight Surveys

52 APCRI Journal

Single-Sight Surveys A total of 196 valid Single-Sight surveys were conducted between 03/09/2019 and 10/10/2019 by 18 survey teamson22days.Surveyorsrecorded34,024dogsighƟngs over a total surveyed area of 113km2, covering 15% of the area of Bangalore city. Thirty Įǀe surveys were removed due to being part of training exercises or because correct survey protocol was not adhered to as based on distribuƟon of GPS points. The mean area surveyed was 0.58 km2 (CI: 0.50 – 0.65), sighƟng an average of 174 dogs per survey (SD 70.8, CI: 164 – 184). The mean density of dog sighƟngs was 408 dogs/km2 (CI: 376 – 441).

Figure 7 – Summary of the areas surveyed by the Single-Sight method. A) Map of city with GPS points and Zones surveyed, red box indicates the zone magniĮed in (B). B) Map of GPS points from dogs sighted on the Single Sight survey conducted in Ward 69 on 09/10/2019

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Demographics Of dogs sighted on Single-Sight surveys, 65.3% of adult dogs were male. Of the 9,630 female dogs sighted, 10.1% were recorded as lactaƟng. Overall 51.9% of dogs sighted were reported to be neutered.

Figure 8 – Chart of total Single Sight Survey sighƟngs by dog type

Figure 9 – Map of Wards of the proporƟon of roaming dogs that were reported as sterilized

54 APCRI Journal

Population estimate The total dog populaƟon esƟmate for Bangalore City was 3,09,898 dogs (CI: 2,30,851 – 4,12,794). The overall human: dog raƟo for the city was 27.2 (CI: 20.4 – 36.6), giving a mean of 3.67 dogs per 100 people (CI: 2.73 – 4.90). However there was considerable variaƟon in the density of dogs and the proporƟon of dogs and people in wards with higher human densiƟĞs (Figure 10, 11, Table 1).

Figure 10 – Graph of esƟmated Ward dog densiƟes by Ward human density. Human density calculated from India 2011 Census data. Blue line is the regression line with 95% conĮdence interval

Figure 11 - Graph of the Ward esƟmated number of dogs per 100 people by the Ward human density

55 Volume XXI, Issue III, January 2020

Table 1 – Mean esƟmated human to dog raƟos and dog density according to straƟĮcaƟon of Wards by human density. Brackets show 95% conĮdence interval.

Human density Dogs per 100 Dog density (people/km-2) Human: dog raƟo people (dogs/km-2) <30,000 31.6 (42.4 - 23.7) 4.4 (3.3 - 5.9) 513 (382 - 685) 30,001 - 60,000 64 (86 - 48) 1.9 (1.4 - 2.5) 744 (554 - 994) >60,001 100 (134.2 - 74.9) 1.2 (0.9 - 1.6) 936 (698 - 1250)

Figure 12 – Map of esƟmated dog density (dogs/km2) by Ward

Figure 13 – map of total dog populaƟon esƟmate by ward

Conclusion This city-wide survey esƟmated the total dog populaƟon of Bangalore city to be in the region of 3 lakh dogs, represenƟng 3.67 dogs per 100 people. This is comparable, if a lŝƩle higher than recent dog populaƟon esƟmates in other metropolis seƫngs in India. The esƟmate must conƟnue to be reĮned as new data becomes available from the evaluaƟon of mass dog vaccinaƟon and dog populaƟon management intervenƟons. This landmark survey paves the way for comprehensive planning of mass dog vaccinaƟon and targeted use of intensive populaƟon management iniƟaƟǀĞƐ to control rabies and improve the welfare of dogs and people alike.

56 APCRI Journal

Recommendations It is clear that reducing the community complaints regarding roaming dogs should be a top priority for the government, however how to do this in an ethical, economical and broadly popular way is sƟll not clear. Complaints of barking, chasing and biƟng were most commonly reported in a Chennai community survey, as cited by 54%, 50% and 39% of people respecƟvely5. Rabies was only speciĮcally cited by 15% of respondents, however in contrast to the annoyance caused by more common complaints, rabies can result in loss of life, inŇicƟng horrifying deaths on children and extreme trauma to their families. Rabies control may also be considered a ‘quick win’ in rapidly reducing the most lethal potenƟal consequences of roaming dogs through periodic mass vaccinaƟon, whilst longer-term populaƟon management iniƟaƟǀĞƐ are established. Figure 14 – Word cloud of perceived problems relaƟng to dogs, words shown in red indicate issues relaƟng speciĮcally to rabies

Progressing towards rabies control: 1) Owned/friendly roaming dog survey and vaccinaƟon The ĮƌƐt priority is to develop methods for a combined survey-vaccinaƟon campaign of the owned roaming dog populaƟon, eĸciently vaccinaƟng friendly dogs roaming the streets. This acƟvity used vaccinaƟon teams of two people going house by house, engaging with dog owners and registering any unsterilized owned roaming dogs for subsequent sterilizaƟon. This pilot community focused campaign aims to vaccinate the dogs in closest contact with people and to engage with dog owners and feeders to build trust and good will. 2) ExpandĞīŽrts to include the immunizaƟon of inaccessible roaming dogs The more diĸcult to catch dogs must be targeted for vaccinaƟon to achieve herd immunity and eliminate rabies. This could be done as part of a pulse vaccinaƟon campaign through safe use of Oral Rabies Vaccine to individually vaccinate dogs which cannot be handled for injectable vaccinaƟon. Safe and eīecƟǀe oral rabies vaccines are currently available for dogs, but are not licenced for use in India at present. Rabies has been demonstrated to dramaƟcally reduce aŌer two years of comprehensive vaccinaƟon, with eliminaƟon depending on prevenƟon of re-introducƟon from surrounding areas. 3) Strengthen canine and human rabies surveillance Establishing systems for public reporƟng and invesƟgaƟon of suspect rabies cases is essenƟal in gaining insights into rabies virus incidence and distribuƟon to guide vaccinaƟon eīorts.

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Progressing towards dog population management: Addressing the more general concerns regarding roaming dogs is more challenging than rabies control and requires a more holisƟc approach encompassing dog ownership, garbage management and societal percepƟon towards dogs. There are three main areas sustaining the dog populaƟon, each of which must be considered as part of a dog populaƟon management programme. 1) Human behaviour People are the driving force behind the presence of dogs on the streets. A considerable number of dogs roaming on the streets are likely to be supported by humans, either through ownership in that they are conĮned for some of the Ɵme, or indirectly through being fed on a regular basis. The people supporƟng these dogs must be enlisted in helping to prevent the producƟon of unwanted puppies through sterilizaƟon eīŽƌts. Abandonment of puppies by dog owners is likely to be a major contributor to sustaining the roaming populaƟon, and measures to prohibit such behaviours and provide high-quality, accessible opƟons for sterilizaƟon to prevent the producƟon of unwanted puppies is essenƟal. RegistraƟon of dogs through idenƟĮcaƟon tags and microchips can help to assign responsibility for speciĮc dogs to speciĮc people. 2) Resource availability Good rouƟne garbage management is important in removing unmanaged food sources from the streets. Feeding of stray dogs needs to be conducted responsibly through enlisƟng the help of people feeding dogs to support sterilizaƟon eīorts. 3) ReproducƟve capacity High quality free dog sterilizaƟon needs to be made available throughout the city for local breed dogs either through speciĮc sterilizaƟon clinics or through private vets using voucher systems. Mass sterilizaƟon acƟǀŝƟĞs are expensive and labour intensive to implement, with few large scale examples of successful outcomes in India. Therefore pilot intensive sterilizaƟon campaigns should include comprehensive evaluaƟon through community and dog sight surveys to monitor outcomes. There is a need to focus resources in a speciĮc geographic area unƟl the desired impact is achieved as opposed to a dispersed scaƩer-gun approach (Figure 15). Tools such as the WVS App can facilitate geographic team direcƟon. Figure 15 – Comparison of two geographic approaches to catching dogs for sterilizaƟon: A – dispersed scaƩer-gun approach. B – focal targeted approach using the WVS App for team direcƟon

16

58 APCRI Journal

Contributors The following people directly contributed to the planning and implementaƟon of the survey, in addiƟon to the many surveyors in the ĮĞld.

Bruhat Bengaluru Mahanagara Palike (BBMP) - Shri. D Randeep, Special Commissioner - Dr. S. Shashi Kumar, Joint Director (AH) - Dr. S M.Manjunath Shinde, Assistant Director (AH) Bangalore Veterinary College - Dr Shrikrishna Isloor, Associate Professor, Department of Veterinary Microbiology Mission Rabies & Worldwide Veterinary Service (WVS) - Dr Andy Gibson, Director of Strategic Research - Dr Gowri Yale, ScienƟĮc and Technical Manager

Acknowledment Dr. Srikrishna Isloor a Member of the Survey Team

References 1 Government of India, Ministry of Home Aīairs, Oĸce of the Registrar General & Census Commissioner. Census of India. 2011 hƩps://www.census2011.co.in/. 2 Sudarshan MK, Mahendra BJ, Narayan DH. A community survey of dog bites, anƟ-rabies treatment, rabies and dog populaƟŽn management in Bangalore city. J Commun Dis 2001; 33: 245–51. 3 Sutherland W. Ecological Census Techniques. Cambridge University Press, 2006. 4 Gibson AD, Mazeri S, Lohr F, et al. One million dog vaccinaƟŽns recorded on mHealth innovaƟŽn used to direct teams in numerous rabies control campaigns. PLoS One 2018; 13. DOI:hƩps://doi.org/10.1371/journal.pone.0200942. 5 Srinivasan K, Kurz T, KuƩuva P, Pearson C. ReorienƟng rabies research and praĐƟĐe: Lessons from India. Palgrave Commun 2019; 5: 1–11.

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60 APCRI Journal

ASSOCIATION FOR PREVENTION & CONTROL OF RABIES IN INDIA Guidelines for applying for “Young Scientist Award” 1. The applicant can either be a Medical or Veterinary person with a post graduate degree or diploma. 2. Age of applicant should not be more than 40 years as on 1st July of the conference year. 3. Application with full details of the research work in the fi eld of Rabies should not be submitted to Secretary General, APCRI*(in a sealed cover) on or before 31st May through head of the institution where he / she has completed the research work. 4. Research work(s) carried out as a project or a scheme or departmental research or Post Graduation research are eligible for consideration. 5. The research should have been carried out during the preceding 5years. 6. The research should have been carried out in India. 7. Evidence of age (Date of Birth) should be enclosed along with the application. 8. Only life members of APCRI are eligible to apply for the award. 9. The Award committee of APCRI reserves the right to defer the award if suitable candidates are not available in the particular year and the decision of the committee will be fi nal. 10. The award carries a cash prize (paid by Demand Draft) of Rs. 5,000.00, a citation & a certifi cate which will be given during the conference. 11. One award will be given per year. 12. The young scientist who applies and gets the award shall make the presentation of his/her research work during the Annual National Conference of APCRI during the same year. He/ She will be given Travel (2 tier AC train) fare & an amount of Rs. 3000.00 towards accommodation & incidentals.

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INSTRUCTIONS to Author

ABOUT THE JOURNAL APCRI Journal is the offi cial Journal of Association for Prevention and Control of Rabies in India. It is a peer- reviewed international journal and published biannually. Its ISSN is 0973-5038. It is Indexed in Index Copernicus International. The journal allows free access (Open Access) to its contents and permits authors to self-archive fi nal accepted version of the articles. The journal’s full text is available online at www. apcrijournal. com SCOPE OF THE JOURNAL The Association for Prevention and Control of Rabies in India publishes articles of authors from India and abroad with special emphasis on original research fi ndings that are relevant for developing country perspectives including India. The journal considers publication of articles as Original Articles, Review Articles, Brief Reports, Case Reports, Letters to the Editor, Personal Viewpoint, Notes and News for APCRI Journal and News Letter etc. THE EDITORIAL PROCESS A manuscript will be reviewed for possible publication with the understanding that it is being submitted to APCRI Journal alone at that point in time and has not been published anywhere, simultaneously submitted, or already accepted for publication elsewhere. The journal expects that authors would authorize one of them (corresponding author) to correspond with the Journal for all matters related to the manuscript. All manuscripts received are duly acknowledged. On submission, editors review all submitted manuscripts initially for suitability for formal review. Manuscripts with insuffi cient originality, serious scientifi c or technical fl aws, lack of a signifi cant message, and lack of rabies expertise or not conforming to the journal norms are rejected before proceeding for formal peer-review. Manuscripts that are found suitable for formal review are sent to two or more expert reviewers. During submission, the contributor is requested to provide names of at least two qualifi ed reviewers who have experience in the subject of the submitted manuscript and are not associated as contributor/s, but this is not mandatory. However, the selection of the reviewers is at the sole discretion of the editor/ managing editor. The journal follows a double-blind review process, wherein the reviewers and authors are unaware of each other’s identity. Based on the comments from the reviewers the editorial team takes a fi nal decision on the manuscript. The comments and suggestions (acceptance/ rejection/ amendments in manuscript) received from reviewers are conveyed to the corresponding author. If required, the author is requested to provide a point by point response to reviewers’ comments and submit a revised version of the manuscript. This process is repeated till reviewers and editors are satisfi ed with the manuscript. Manuscripts accepted for publication are copy edited for grammar, punctuation, print style, and format. Page proofs are sent to the corresponding author. The corresponding author is expected to return the corrected proofs within three days. It may not be possible to incorporate corrections received after that period. The whole process of submission of the manuscript to fi nal decision and sending and receiving proofs is completed online. With a view to achieve faster and greater dissemination of knowledge and information the journal will try to publish articles online as ‘Ahead of Print’ after the articles have been accepted for publication.

62 APCRI Journal

AUTHORSHIP CRITERIA Authorship credit should be based only on substantial contributions to each of the three components mentioned below: 1. Concept and design of study or acquisition of data or analysis and interpretation of data. 2. Drafting the article or revising it critically for important intellectual content; and 3. Final approval of the version to be published. Each contributor should have participated suffi ciently in the work to take rabies as responsibility for appropriate portions of the content of the manuscript. Once submitted the order cannot be changed without written consent of all the contributors. The journal prescribes a maximum number of authors for manuscripts depending upon the type of manuscript, its scope and number of institutions involved (vide infra). The authors should provide a justifi cation, if the number of authors exceeds these limits, in exceptional cases. CONTRIBUTION DETAILS Contributors should provide a description of contributions made by each of them towards the manuscript. Description should be divided in following categories, as applicable: concept, design, defi nition of intellectual content, literature search, clinical studies, experimental studies, data acquisition, data analysis, statistical analysis, manuscript preparation, manuscript editing and manuscript review. One or more author should take responsibility for the integrity of the work as a whole from inception to published article and should be designated as ‘guarantor’. CONFLICTS OF INTEREST/ COMPETING INTERESTS All authors must disclose any and all confl icts of interest they may have with publication of the manuscript or an institution or product that is mentioned in the manuscript and/or is important to the outcome of the study presented. Authors should also disclose confl ict of interest with products that compete with those mentioned in their manuscript. CLINICAL TRIAL REGISTRY APCRI Journal favors registration of clinical trials and is a signatory to the Statement on publishing clinical trials in Indian biomedical journals. APCRI Journal would publish clinical trials that have been registered with a clinical trial registry that allows free online access to public. SUBMISSION OF MANUSCRIPTS All manuscripts must be submitted on-line through the website http://www. apcrijournal. com/ ArticleSubmission. aspx. First time users will have to register at this site. Registration is free but mandatory. Registered authors can keep track of their articles after logging into the site using their user name and password. If you experience any problems, please contact the editorial offi ce by e-mail at Admin@apcrijournal. com. The submitted manuscripts that are not as per the “Instructions to Authors” would be returned to the authors for technical correction, before they undergo editorial/ peer-review. Generally, the manuscript should be submitted in the form of two separate fi les:

[1] Title Page/First Page File/covering leƩ er: This fi le should provide a. The type of manuscript (original article, brief research article, case series report, review article, Letter to editor, Images, etc. ) title of the manuscript, running title, names of all authors/ contributors (with their highest academic degrees, designation and affi liations) and name(s) of department(s) and/ or institution(s) to which the work should be credited,. All information which can reveal your identity should be here. Use. doc/docx fi les. Do not zip the fi les. b. Source(s) of support in the form of grants, equipment, drugs, or all of these;

63 Volume XXI, Issue III, January 2020

c. Acknowledgement, if any. One or more statements should specify 1) contributions that need acknowledging but do not justify authorship, such as general support by a departmental chair; 2) acknowledgments of technical help; and 3) acknowledgments of fi nancial and material support, which should specify the nature of the support. This should be included in the title page of the manuscript and not in the main article fi le. d. Registration number in case of a clinical trial and where it is registered (name of the registry and its URL) e. Confl icts of Interest of each author/ contributor. A statement of fi nancial or other relationships that might lead to a confl ict of interest, if that information is not included in the manuscript itself or in an authors’ form f. A statement that the manuscript has been read and approved by all the authors, that the requirements for authorship as stated earlier in this document have been met, and that each author believes that the manuscript represents honest work, if that information is not provided in another form (see below); and g. The name, address, e-mail, and telephone number of the corresponding author, who is responsible for communicating with the other authors about revisions and fi nal approval of the proofs, if that information is not included on the manuscript itself. [2] Blinded Article fi le: The manuscript must not contain any mention of the authors› names or initials or the institution at which the study was done or acknowledgements. Page headers/running title can include the title but not the authors› names. Manuscripts not in compliance with The Journal›s blinding policy will be returned to the corresponding author. The main text of the article, beginning from Abstract till References (including tables) should be in this fi le. Use rtf/doc fi les. Do not zip the fi les. Limit the fi le size to 1024 kb (1 MB). Do not incorporate images in the fi le. The pages should be numbered consecutively, beginning with the fi rst page of the blinded article fi le. [3] Images: Submit good quality color images. Each image should be less than 4 MB in size. Size of the image can be reduced by decreasing the actual height and width of the images (keep up to 1800 x 1600 pixels or 5-6 inches). JPEG is the most preferred format to upload images. Images can be submitted as jpeg fi les. Do not zip the fi les. Legends for the fi gures/images should be included at the end of the article fi le. Maximum 5 images per document is allowed to be uploaded. [4] The contributors› / copyright transfer form (template provided below) has to be submitted in original with the signatures of all the contributors or email (Admin@apcrijournal. com, as a scanned image. The hard copies of the Contributors’ form / copyright transfer form may be submitted online from the authors’ area on http://www. apcrijournal. com/ArticleSubmission. aspx [5] Documents of clearance by Institutional Ethics Committee or equivalent should also be sent as scanned image with fi rst page fi le. PREPARATION OF MANUSCRIPTS Manuscripts must be prepared in accordance with “Uniform requirements for Manuscripts submitted to Biomedical Journals” developed by the International Committee of Medical Journal Editors (October 2006). The uniform requirements and specifi c requirement of Association for Prevention and Control of Rabies in India are summarized below. Before submitting a manuscript, contributors are requested to check for the latest instructions available. Instructions are also available from the offi cial website of the Association for Prevention and Control of Rabies in India (http://www. apcrijournal. com) and from the manuscript submission site (http://www. apcrijournal. com/ ArticleSubmission. aspx). COPIES OF ANY PERMISSIONΈSΉ It is the responsibility of authors/ contributors to obtain permissions for reproducing any copyrighted material. A

64 APCRI Journal copy of the permission obtained must accompany the manuscript. Copies of any and all published articles or other manuscripts in preparation or submitted elsewhere that are related to the manuscript must also accompany the manuscript. The material should be sent to the address as follows Editor / Secretary General, APCRI, 56H, Beliaghata Main Road Kolkata-700010, West Bengal, India ORIGINAL ARTICLES: These include population based surveys, program evaluations, impact assessment studies, randomized controlled trials, intervention studies, studies of screening and diagnostic test, outcome studies, cost eff ectiveness analyses, meta-analysis, systematic reviews, cohort studies and case-control studies,. The text of original articles amounting to up to 3000 words (excluding Abstract, references and Tables) should be divided into sections with the headings Abstract, Key-words, Introduction, Material and Methods, Results, Discussion, References, Tables and Figure legends. Abstract should be structured, not more than 250 words, briefl y mentioning background, objectives, methods, results and conclusion. INTRODUCTION: State the purpose and summarize the rationale for the study or observation. MATERIALS AND METHODS: It should include and describe the following aspects: Ethics: The journal will not consider any paper which is ethically unacceptable. A statement on ethics committee permission and ethical practices must be included in all research articles under the ‘Materials and Methods’ section When reporting studies on human beings, indicate whether the procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional or regional) and with the Helsinki Declaration of 1975, as revised in 2000 (available at http://www. wma. net/e/policy/17-c_e. html). For prospective studies involving human participants, authors are expected to mention about approval of (regional/ national/ institutional or independent) Ethics Committee or Review Board, obtaining informed consent from adult research participants and obtaining assent for children aged over 7 years participating in the trial. The age beyond which assent would be required could vary as per regional and/ or national guidelines. Ensure confi dentiality of subjects by desisting from mentioning participants’ names, initials or hospital numbers, especially in illustrative material. When reporting experiments on animals, indicate whether the institution’s or a national research council’s guide for, or any national law on the care and use of laboratory animals was followed. The ethical standards of experiments must be in accordance with the guidelines provided by the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA) and World Medical Association Declaration of Helsinki on Ethical Principles for Medical Research Involving Humans for studies involving experimental animals and human beings, respectively). These articles generally should not have more than six authors. REVIEW ARTICLES: It is expected that these articles would be by invitation, written by individuals who have done substantial work on the subject or are considered experts in the fi eld. Articles by other rabies experts can be accepted on the basis of merit of article. A short summary of the work done by the contributor(s) in the fi eld of review/their area of expertise should accompany the manuscript. The prescribed word count is up to 3000 words excluding tables, references and abstract. The manuscript may have about 90 references. The manuscript should have an unstructured summary (250 words) representing an accurate

65 Volume XXI, Issue III, January 2020

summary of the article. The section titles would depend upon the topic reviewed. Authors submitting review article should include a section describing the methods used for locating, selecting, extracting, and synthesizing data. These methods should also be summarized in the abstract. Restrict the maximum number of tables and or/fi gures to four. The journal expects the contributors to give post-publication updates on the subject of review. The update should be brief, covering the advances in the fi eld after the publication of the article and should be sent as a letter to editor, as and when major development occurs in the fi eld. Review articles could be authored by upto six authors. BRIEF RESEARCH ARTICLE Brief Research article should contain interesting observations/ brief reports of original studies presenting the authors’ views on a topic of current interest. The purpose of a brief research article in APCRI Journal is to provide additional insights into topics of current rabies concerns. It should be limited to 1,500 words with unstructured summary not exceeding 150 words, no more than two tables and/or fi gures, and no more than 10 references. It could be authored by up to six authors. Ethical consideration as per original article should be followed. CASE STUDIES/ CASE SERIES REPORT: New, interesting and intriguing case studies can be reported. They should be unique and have demonstrated methods to overcome any rabies challenge by use of novel tools and techniques and provide a learning point for the readers. Case studies with rabies signifi cance or implications will be given priority. These communications could be of up to 1000 words (excluding Abstract and references) and should have the following headings: Abstract (unstructured summary not exceeding 150 words), Key-words, Introduction, Case report, Discussion, Reference, Tables and Legends in that order. It must not have more than 10 references. Case Reports could be authored by up to four authors. LETTER TO THE EDITOR: These should be short and decisive observations. They should preferably be related to articles previously published in the Journal or views expressed in the journal. They should not be preliminary observations that need a later paper for validation. The letter could have up to 500 words and 5 references. It could be generally authored by not more than four authors. REFERENCES: References should be numbered consecutively in the order in which they are fi rst mentioned in the text (not in alphabetic order). Identify references in text, tables, and legends by Arabic numerals in superscript after the punctuation marks. References cited only in tables or fi gure legends should be numbered in accordance with the sequence established by the fi rst identifi cation in the text of the particular table or fi gure. Use the style of the examples below, which are based on the formats used by the NLM in Index Medicus. The titles of journals should be abbreviated according to the style used in Index Medicus. Use complete name of the journal for non-indexed journals. Avoid using abstracts as references. Information from manuscripts submitted but not accepted/ published should be cited in the text as “unpublished observations” with written permission from the source. Avoid citing a “personal communication” unless it provides essential information not available from a public source, in which case the name of the person and date of communication should be cited in parentheses in the text. SENDING A REVISED MANUSCRIPT The revised version of the manuscript should be submitted online in a manner similar to that used for submission of the manuscript for the fi rst time. However, there is no need to submit the “First Page” or “Covering Letter” fi le

66 APCRI Journal while submitting a revised version. When submitting a revised manuscript, contributors are requested to include, the ‘referees’ remarks along with point to point clarifi cation at the beginning in the revised fi le itself. In addition, they are expected to mark the changes as underlined or colored text in the article. REPRINTS AND PROOFS Journal provides no free reprints. Request for reprints may be made to the editorial offi ce after acceptance of the articles for publication. MANUSCRIPT SUBMISSION, PROCESSING AND PUBLICATION CHARGES Right now there are no processing and publication charges. Submission charge: Nil CHECKLIST Covering letter • Signed by all contributors • Previous publication / presentations mentioned • Source of funding mentioned • Confl icts of interest disclosed Authors • Last name and given name provided along with Middle name initials (where applicable) • Author for correspondence, with e-mail address and mobile number provided • Number of contributors restricted as per the instructions • Identity not revealed in paper except title page (e. g. name of the institute in Methods, citing previous study as ‘our study’, names on fi gure labels, name of institute in photographs, etc. ) Presentation and format • Double spacing • Margins 2.5 cm from all four sides • Page numbers included at bottom • Title page contains all the desired information • Running title provided (not more than 50 characters) • Abstract page contains the full title of the manuscript • Abstract provided (unstructured summary of 250 words for review articles, structured abstract of about 250 words for original articles, unstructured summary of about 150 words for brief research article and case series report ) • Key words provided (three or more) • Introduction of 75-100 words • Headings in title case (not ALL CAPITALS) • The references cited in the text should be after punctuation marks, in superscript.

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• References according to the journal’s instructions, punctuation marks checked • Send the article fi le without ‘Track Changes’ Language and grammar • Uniformly American English • Write the full term for each abbreviation at its fi rst use in the title, abstract, keywords and text separately unless it is a standard unit of measure. Numerals from 1 to 10 spelt out • Numerals at the beginning of the sentence spelt out • Check the manuscript for spelling, grammar and punctuation errors • If a brand name is cited, supply the manufacturer’s name and address (city and state/country). • Species names should be in italics Tables and fi gures • No repetition of data in tables and graphs and in text • Actual numbers from which graphs drawn, provided • Figures necessary and of good quality (colour) • Table and fi gure numbers in Arabic letters (not Roman) • Labels pasted on back of the photographs (no names written) • Figure legends provided (not more than 40 words) • Patients’ privacy maintained (if not permission taken) • Credit note for borrowed fi gures/tables provided • Write the full term for each abbreviation used in the table as a footnote

68 APCRI Journal

ASSOCIATION FOR PREVENTION & CONTROL OF RABIES IN INDIA (APCRI)

The Association for Prevention & Control of Rabies in India (APCRI) was founded on 17th April, 1998 and is registered as a scientifi c society under the Karnataka Societies Act S-No 439,2000-01. It is an association of professionals, scientists and others who are committed to the elimination of rabies from India. 1. Annual Conference on 6th July (World Zoonosis Day) or near about (on Saturday and Sunday only) : Kolkata (1999), Bangalore (2000), Amritsar (2001), Jaipur (2002), Bhubaneswar (2003), Kolkata (2004), Shimla (2005), Jammu (2006), Hyderabad (2007), Lucknow (2008), Thiruvananthapuram (2009), New Delhi (2010), Chennai (2011), Kolkata (2012), Pune (2013), Mysore (2014), Hyderabad (2015), Bangalore (2016), Goa (2017), New Delhi (2018) and Ranchi (2019). 2. Workshops, Seminars & Training Programmes: • National workshop for APCRI trainers in modern WHO approved rabies prophylaxis at NIMHANS, Bangalore (2001). • National seminar on “Intradermal Rabies Vaccination”, KIMS, Bangalore (2003). • National workshop on “Developing guidelines for Rabies Prophylaxis” at Hyderabad (2006). • National workshop on “Rabies Prophylaxis” at Alleppey, Kerala (2006). • National workshop on “Rabies Immunoglobin (RIG) Administration” at KIMS, Bangalore (2008) • National seminar on Rabies Vaccines: Important Issues, at Visakhapatnam (Vizag), (1st March 2009). • National workshop on Development of IEC Material on Prevention of Rabies for School Children and Public at Mysore, Karnataka (20th & 21st March 2010). • National Seminar on “Rabies Post Exposure Prophylaxis-Recommendations and Practices” at New Delhi (17th March 2013). • National Seminar on Rabies Prophylaxis (2014) at Delhi (26th April, 2014). 3. Publications: APCRI Journal (Biannual) & APCRI News Letter (Biannual). 4. WHO sponsored “National Multi-centric Indian rabies survey” (2004). 5. Award: APCRI was honoured with “Chiron vaccines award 2000” for its contributions to prevention and control of Rabies in India. 6. APCRI in association with Indian Academy of Paediatrics (IAP) and Rabies in Asia (RIA) Foundation, formulated the IAP Guidelines for Rabies Prophylaxis in Children (2008). 7. Slides on “Rabies Prophylaxis – Current Concepts & Recommendations” prepared by an expert consultation (2001), revised in 2006 and now available on www. apcri. org. 8. Observed “World Rabies Day” on 8th September 2007,28th September 2008, 28th September 2009,28th September 2010,28th September 2011,28th September 2012, 28th September 2013,28th September 2014,28th September 2015,28th September 2016,28th September 2017,28th September 2018 and 28th September, 2019 throughout the country. 9. WHO-APCRI survey on “Post Exposure Prophylaxis modialities in India (2007).

69 Volume XXI, Issue III, January 2020

10. APCRI is regularly organizing Zonal/ Regional Conference & CME Programmes. 11. APCRI played a major role in implementation of Intradermal Rabies Vaccination (IDRV) in the country. 12. Manual on Rabies Immunoglobulin (RIG) Administration published in February 2009. 13. APCRI Educational Portal in 2010. The Site can be visited at edu. apcri. org. 14. APCRI-TATA Project on Rabies Control in Jamshedpur. 15. Conducted CME’S, Workshops and Training Programmes throughout the country. 16. Conducted WHO-APCRI Survey Report 2017, sponsored by WHO 17. Observed World Rabies Day on 28th September, in Ranchi RIMS with posters, sit and draw in 2018. 18. Introduced Louis Pasteur Oration, Lifetime Achievement Award, Dr. SN Madhusudana Oration, Young Scientist Award and Certifi cate of Merit Award regularly in every conference.

70 APCRI Journal

ASSOCIATION FOR PREVENTION & CONTROL OF RABIES IN INDIA (APCRI)

The AssociaƟ on for PrevenƟ on & Control of Rabies in India (APCRI) was founded on 17th April, 1998 and is registered as a scienƟ fi c society under the Karnataka SocieƟ es Act S-No 439, 2000-01. It is an associaƟ on of professionals, scienƟ sts and others who are commiƩ ed to the eliminaƟ on of rabies from India. 1. Annual Conference on 6th July (World Zoonosis Day) or near about (on Saturday and Sunday only) : Kolkata (1999), Bangalore (2000), Amritsar (2001), Jaipur (2002), Bhubaneswar (2003), Kolkata (2004), Shimla (2005), Jammu (2006), Hyderabad (2007), Lucknow (2008), Thiruvananthapuram (2009), New Delhi (2010), Chennai(2011), Kolkata (2012), Pune (2013), Mysore (2014), Hyderabad (2015), Bangalore (2016), Goa (2017), New Delhi (2018) and Ranchi (2019). 2. Workshops, Seminars & Training Programmes: NaƟ onal workshop for APCRI trainers in modern WHO approved rabies prophylaxis at NIMHANS, Bangalore (2001). NaƟ onal seminar on “Intradermal Rabies VaccinaƟ on”, KIMS, Bangalore (2003). NaƟ onal workshop on “Developing guidelines for Rabies Prophylaxis” at Hyderabad (2006). NaƟ onal workshop on “Rabies Prophylaxis” at Alleppey, Kerala (2006). NaƟ onal workshop on “Rabies Immunoglobin (RIG) AdministraƟ on” at KIMS, Bangalore (2008) NaƟ onal seminar on Rabies Vaccines: Important Issues, at Visakhapatnam (Vizag), Andhra Pradesh (1st March 2009). NaƟ onal workshop on Development of IEC Material on PrevenƟ on of Rabies for School Children and Public at Mysore, Karnataka (20th & 21st March 2010). NaƟ onal Seminar on “Rabies Post Exposure Prophylaxis-RecommendaƟ ons and PracƟ ces” at New Delhi (17th March 2013). NaƟ onal Seminar on Rabies Prophylaxis (2014) at Delhi (26th April, 2014). Many CME’S + Seminars throughout the Countries 2017-2019. 3. PublicaƟ ons: APCRI Journal (Biannual) & APCRI News LeƩ er (Biannual). 4. WHO sponsored “NaƟ onal MulƟ -centric Indian rabies survey” (2004). 5. Award: APCRI was honoured with “Chiron vaccines award 2000” for its contribuƟ ons to prevenƟ on and control of Rabies in India. 6. APCRI in associaƟ on with Indian Academy of Paediatrics (IAP) and Rabies in Asia (RIA) FoundaƟ on, formulated the IAP Guidelines for Rabies Prophylaxis in Children (2008). 7. Slides on “Rabies Prophylaxis – Current Concepts & RecommendaƟ ons” prepared by an expert consultaƟ on (2001), revised in 2006 and now available on www.apcri.org. 8. Observed “World Rabies Day” on 8th September 2007, 28th September 2008, 28th September 2009, 28th September 2010, 28th September 2011, 28th September 2012, 28th September 2013, 28th September 2014, 28th September 2015, 28th September 2016, 28th September 2017, 28th September 2018 throughout the country. 9. WHO-APCRI survey on “Post Exposure Prophylaxis modialiƟ es in India (2007). 10. APCRI is regularly organizing Zonal/ Regional Conference & CME Programmes. 11. APCRI played a major role in implementaƟ on of Intradermal Rabies VaccinaƟ on (IDRV) in the country. 12. Manual on Rabies Immunoglobulin (RIG) AdministraƟ on published in February 2009. 13. APCRI EducaƟ onal Portal in 2010. The Site can be visited at edu.apcri.org. 14. APCRI-TATA Project on Rabies Control in Jamshedpur. 15. Conducted CME’S, Workshops and Training Programmes throughout the country. 16. Conducted WHO-APCRI Survey Report 2017, sponsored by WHO 17. Observed World Rabies Day on 28th September, in Ranchi RIMS with posters, sit and draw in 2018. 18. Introduced Louis Pasteur OraƟ on, LifeƟ me Achievement Award, Dr. SN Madhusudana OraƟ on, Young ScienƟ st Award and CerƟ fi cate of Merit Award regularly in every conference. 71 NOTES

ASSOCIATION FOR PREVENTION & CONTROL OF RABIES IN INDIA (APCRI)

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Edited by Published by DR. KAJAL KRISHNA BANIK DR. SUMIT PODDAR MBBS, DPH, MAE MBBS, MBA, Ph.D. (Lincoln University), Editor, APCRI Mobile: 9331048886 FRSTM & H (UK) MACCP, MIPHA Secretary General, APCRI WBHS (Ex) Senior CriƟ cal Care & AnƟ Rabies Consultant, Printed by Formerly AƩ ached to SNP Hospital, Govt. WB ANDERSON PRINTING HOUSE PVT. LTD. Mobile: 9830599468 EN 11 Sector V Salt Lake City Kolkata: 700091 Mobile: 9831778972