Abstract
Rabies remains a pressing public health issue, particularly in countries like India, where it inflicts a significant toll on marginalised communities. With approximately 20,000 deaths annually due to rabies, the disease underscores the urgency for effective prevention strategies. Despite the existence of post-exposure prophylaxis (PEP), rabies continues to claim lives, highlighting the importance of understanding and addressing the challenges in its implementation. This study aims to conduct a comprehensive analysis of strengths, weaknesses, opportunities and threats (SWOT) of India’s rabies PEP programme, emphasising the urgent need for enhanced strategies to combat this preventable yet incurable disease. A thorough review of scientific literature, governmental guidelines, programme documents and media reports related to rabies and PEP was undertaken. The SWOT matrix was employed to categorise the identified factors influencing PEP administration. The analysis revealed both strengths and weaknesses inherent in the current PEP programme. Despite the availability of effective biological products and political commitment, challenges such as inadequate inventory management, delayed dissemination of guidelines, poor awareness, inadequate infrastructure and budgetary constraints persist. However, opportunities for improvement, including information dissemination and technological innovations, were identified. Threats such as pandemics and misleading media reports pose additional challenges to rabies control efforts. By emphasising the preventable yet incurable nature of rabies and highlighting the annual toll it exacts on human lives, this study underscores the urgency for effective and coordinated public health interventions to achieve the goal of dog-mediated rabies elimination by 2030. The findings underscore the critical importance of addressing weaknesses and capitalising on opportunities to strengthen rabies control strategies in India. Proactive measures are essential to enhance inventory management, ensure guidelines’ dissemination, improve awareness levels, strengthen infrastructure and leverage technological advancements. Additionally, addressing threats such as pandemics and media misinformation requires collaborative efforts and proactive risk communication strategies. Through a targeted approach focused on enhancing rabies PEP implementation along with other measures such as community engagement to build awareness about rabies, and canine vaccination, including mass dog vaccination, India can significantly reduce the burden of rabies-related mortality.
Introduction
Rabies is one of the neglected tropical diseases (NTD) that predominantly affects already marginalised, poor and vulnerable populations. It is present on all the continents barring Antarctica. Globally, around 59,000 deaths per year are estimated to occur due to rabies, though actual numbers may differ due to underreporting. The estimated annual cost of rabies is about US $8.6 billion globally, which includes not only the medical care and associated costs but lost lives and livelihoods, and uncalculated psychological trauma. 1
Rabies is different from other infectious diseases as timely and adequate immunisation even after exposure to infectious agent can prevent clinical disease development in rabies. The emergency response to rabies exposure is post-exposure prophylaxis (PEP), which prevents virus entry to the central nervous system. It consists of extensive wound washing with soap and water for at least 15 min immediately after an exposure, anti-rabies vaccination and rabies immunoglobulin or monoclonal antibodies administration into the wound, wherever indicated. 2 Every year, more than 29 million people worldwide receive PEP against rabies. This is estimated to prevent thousands of rabies deaths annually. 1
Despite availability of life-saving PEP, the disease claims an estimated 59,000 deaths annually across the world, 1 with about one-third burden contributed by India (20,000 deaths). 3 India has its National Rabies Control Programme (NRCP), 4 National Action Plan for Dog Mediated Rabies Elimination by 2030 (NAPRE), 5 and guidelines for prophylaxis against rabies, 6 under which PEP is recommended for animal bites but gaps still exist in their enactment. Therefore, it is important to appraise and analyse the existing PEP under the national programme and guidelines to find out the strengths and weaknesses and potential opportunities and threats which might affect PEP implementation in totality.
Methods
This was a descriptive qualitative study. We reviewed the scientific literature, government guidelines and programme and press statements, and media reports related to rabies, animal bites and post-exposure prophylaxis for rabies to identify key internal as well as external attributes of the medical and existing health care system that can affect the PEP administration. Literature search was done using Google, Google Scholar, and PubMed. Websites of Ministry of Health and Family Welfare, National Centre for Disease Control, Indian Council of Medical Research, Government of India, States’ Governments and World Health Organization were accessed for programme guidelines. National Council of Educational Research & Training and United Nations Development Program, India websites were also accessed for relevant information. Press releases were obtained through Press Information Bureau of Government of India website. Various news reports were accessed through online sites for media reports related to rabies.
We categorised the points according to the SWOT matrix, that is, internal factors which facilitate (Strengths) or hinder (Weaknesses) the PEP implementation as per recommended guidelines and external factors that can help (Opportunities) or impede (Threats) the PEP implementation in future in India (Table 1).
SWOT Analysis of Rabies Post-Exposure Prophylaxis in India.
Results and discussion
Strengths
Availability of effective biological products: Rabies PEP requires administration of anti-rabies vaccine (ARV) and rabies immunoglobulins (RIGs) depending on the category of bite. 6 Safe and highly efficacious vaccines and immunoglobulins are available for the same. Nerve tissue vaccines, which were used previously have now been replaced with modern cell culture vaccines in India as per recommendations of WHO. 2 These vaccines are safer, and more efficacious than nerve tissue vaccines. However, the intramuscular route of administration of cell culture vaccines was costly and a limiting factor in its widespread use. Therefore, more economical intradermal route for cell culture vaccine administration was approved in India in 2006. 7
Efficient use of available biologicals: The schedule, route and site of vaccine and immunoglobulin have been revised, which has resulted in improved efficiency. Two-site intradermal schedule is followed for vaccine in place of intramuscular schedule since the last 18 years in India, which has been found to be most advantageous owing to its safety, immunogenicity and incurred the least direct costs compared to other schedules.2,8 Similarly, rabies immunoglobulin is now administered at the site of wound only, reducing its wastage without compromising the efficacy.9,10
Indigenous production of biologicals: India has made tremendous progress in pharmaceutical production and is rightly being called as the pharmacy of the world. The story for rabies is similar. Vaccines and equine-immunoglobulins for PEP are produced indigenously at the sites mentioned in Table 2. 6 There is substantial scope for increasing the production in the future if required as installed capacity for production is much greater than the current production levels. 11 For instance, in year 2021, 81.47 lakh (8.147 million) doses of tissue culture ARV were produced in India against the installed capacity of 180 lakh (18 million) doses per annum. 12
Inclusion of biologicals in the list of essential medicines: The rabies biologicals have been included in the national list of essential medicines, which acknowledges rabies biologicals being a priority health care need of our population. 13 However, there are interstate variations as health is a state subject in our country and availability of ARVs and RIGs depends upon the decisions of respective state governments. For example, states like Gujarat and Maharashtra have only included Human Rabies Immunoglobulin (HRIG),14,15 while Tamil Nadu and Kerala have included only Equine Rabies Immunoglobulin (ERIG)16,17 in their list of essential medicines. Inclusion in this list ensures availability of safe, efficacious and cost-effective rabies biologicals in adequate amounts, appropriate dosage forms and strengths, and assured quality to improve the health care delivery and management.13,18
Prioritisation for elimination: About 99% of all rabies transmission to humans is through dogs, which are the main source of human deaths due to rabies.1,3 Human vaccination can avert deaths but elimination of rabies is not possible with this intervention alone and the escalating costs further aggravate the challenges. The most cost-effective measure for rabies elimination is investment in rabies risk elimination at source. Thus, vaccination of dogs, dog population management and prevention of dog bites are an important strategies for rabies control as they interrupt the chain of transmission which is not done by PEP. Vaccinating at least 70% of dogs in at risk areas is the most effective strategy to prevent human rabies deaths. 19 The Government of India (GoI) has taken a huge step in this direction and prioritised the dog-mediated rabies for elimination, probably the first zoonotic disease that has been taken up for elimination and has also launched an action plan for the same. 5
Renewed political commitment: The rabies control efforts in India began as a pilot project in the 11th five-year plan followed by a nationwide National Rabies Control programme in the 12th five-year plan. 4 In 2021, the NAPRE was rolled out. 5 As a result of these policy-level initiatives, the states are now including the budget for rabies control in their programme implementation plans. For example, the Maharashtra budget under the National Disease Control Programme flexi-pool of the National Health Mission includes the budget requirement of USD 0.17 million (Rs 145 lakhs) for opening new anti-rabies clinics, maintenance of existing anti-rabies clinics, training, printing information, education and communication (IEC) material and reporting formats, for monitoring visits, and strengthening animal bite surveillance. 20
Evidence-based guidelines with frequent updates: Comprehensive guidelines have been published by World Health Organization (WHO) and the GoI, including frequently asked questions, which have been updated from time to time. 21 Updates in guidelines help the stakeholders for informed decision-making based on latest available evidence and current understanding of the subject to achieve optimal outcomes. For India, National Centre for Disease Control (NCDC) published the rabies prophylaxis guidelines in 2019. 6 It included topics on bite wound categorisation, regimen, route of administration, schedule, PEP in special circumstances and populations along with newer advancements and pre-exposure prophylaxis. 6 However, the national guidelines did not incorporate the WHO Expert Consultation (2017) recommendations, that is, a 1-week ID vaccination schedule for PEP and use of rabies monoclonal antibodies for passive immunisation, which are produced, licensed and used in India by private practitioners.
International commitment: In 2019, GAVI, the Vaccine Alliance included human rabies vaccines in its Vaccine Investment Strategy (VIS) 2021–2025, which would support scaling up rabies PEP in GAVI-eligible countries, leading to the start of planning the rollout of human rabies vaccines. Rabies is also included in the One Health concept, and an ambitious target has been set for its elimination, popularised as ‘Zero by 30’, in collaboration with WHO, Food and Agriculture Organization of the United Nations, World Organisation for Animal Health (WOAH), and the Global Alliance for Rabies Control. One Health collaboration and active involvement of various sectors along with community education, awareness generation activities and vaccination campaigns are crucial for rabies elimination. 22 Such an integrated One Health approach has been successfully implemented in Goa, India, to achieve rabies elimination at the state level. 23 However, sporadic cases have been reported in the state since 2023, mostly in border areas, highlighting the need for continuous vigil, surveillance and ongoing activities required to sustain disease under control.24,25
Institutional mechanisms for rabies diagnostics: One of the most challenging aspect in rabies epidemiology is the diagnosis of human and animal rabies because of high virulence of the virus and difficulty in sample collection for laboratory confirmation. Under NAPRE, a tiered structure of laboratory facilities at national, regional, state and district levels is envisaged for the diagnosis of rabies. 5 A WHO collaborating centre for reference and research on Rabies at National Institute of Mental Health and Neurosciences, Bengaluru is playing a vital role in the diagnosis of rabies cases in India. 26 At Karnataka Veterinary, Animal and Fisheries Sciences University (KFAFSU), a World Organisation for Animal Health (WOAH) Reference Laboratory for rabies is established in Bengaluru with collaboration of KVAFSU and Commonwealth Veterinary Association. 27
Emphasis on animal component: For efficient management of stray dog population, the Government of India has notified Animal Birth Control Rules, 2023. Various measures are being taken by Animal Welfare Board of India (AWBI) including financial assistance to animal welfare organisations, collaboration with local bodies for animal birth control programmes and mass dog vaccination, issue of advisories and guidelines for stray dog management, and collaboration with National Commission for Protection of Child Rights to address safety concerns related to stray animals. 28 Under the central schemes of Assistance to States for Control of Animal Diseases (ASCAD) and Rashtriya Krishi Vikash Yojana (RKVY), there is a provision for providing grants-in-aid to states for surveillance of animal diseases, capacity building, strengthening of biological production centres and diagnostic labs, awareness activities, anti-rabies vaccination and cold chain maintenance. Under NAPRE, the funding for vaccination will be provided by ASCAD, RKVY, state animal husbandry department, local governing bodies, urban municipalities and Panchayati Raj institutions in rural areas while funding for dog population management will be provided by AWBI, local governing bodies, urban municipalities, Panchayati Raj institutions in rural areas, non-government organisations and through corporate social responsibility. 5 A paradigm shift is required in policymaking and rational use of resources with more focus on proactive (mass vaccination of dogs) approach rather than reactive approach (PEP in animals).
Sites for production of rabies biologicals in India. 6
Weaknesses
Inadequate inventory management: The forecasting and procurement of rabies biologicals have been a weakness. As a result, the centres providing PEP experience stock-outs of vaccines and immunoglobulins frequently. A nationwide survey in the year 2019 showed that 18.5% and 40.7% government facilities reported ARV and RIG stock-outs respectively, while 50% of private facilities reported RIG stock-outs only. 29 The possible reason for RIG stock-outs at private facilities could be high cost of RIG, or time constraints to perform skin sensitivity testing before administering ERIG. Another plausible explanation could be inadequate availability of RIG at private facilities as evident from a recent nationwide survey, which showed availability of RIG in surveyed private facilities ranged from 0% in North-East Zone to 50% in North Zone. 30 There is dearth of recent data regarding the frequency of ARV and RIG stock-outs but various news reports have mentioned stock-out incidents at public hospitals.31–34 ARV stock-out incidents are rare at private hospitals. The possible reason for same could be, in the private sector, if one brand of ARV is not available in the market, other available brands are used as a substitution as reported in a nationwide survey. 35 However, the cost of PEP at private facilities adds to the out-of-pocket expenditure of patients. This can affect the compliance to PEP. 29 Considering the complex process of manufacturing and testing of rabies biologicals, the NCDC has put forth guidelines for their procurement. The lead time from order placement to actual delivery of 3–4 months should be taken into account for maintaining buffer stocks and placing orders in advance for which regular stock monitoring is required. The procurement agencies at the state and district levels should be sensitised to these aspects of procurement to prevent shortages. 36
Insufficient budgetary allocation: Under NRCP, funds are only provided for training, surveillance, laboratory strengthening and advocacy etc. and not provided for procurement of ARV as the state governments provide budget for procurement of medicines in the respective states. However, all the states and union territories (UTs) have been communicated to include ARV and anti-rabies serum (ARS) in their essential drug list and undertake the procurement of ARV and ARS under the National Free Drug Service initiative of National Health Mission to reduce the cost-burden on states and improving the availability of ARV and ARS. 37 But this will take time for successful implementation. As per a multi-centric survey in 2019, RIG was given free of cost in only 40% of anti-rabies clinics, which can lead to poor compliance to PEP. 29 A recent nationwide survey by Indian Council of Medical Research highlighted inadequate availability of ARV and RIG in public health facilities. Availability of ARV ranged from 0% at Urban Primary Health Centre in North zone to 100% in Medical College and Hospitals in North, North-East and South zone. Similarly, RIG availability ranged from 0% at Primary Health Centre to 100% in Medical College and Hospital in West zone. 30 There is a paucity of recent data regarding number of healthcare facilities providing free of cost RIG.
Delayed and inadequate dissemination and implementation of guidelines: Though guidelines are published frequently, their dissemination and implementation is a major weakness. NCDC guidelines have mentioned the format of the PEP treatment card. 21 However, each centre administering PEP has its own format printed on paper and to further worsen the situation, in the peripheral health institutes mostly due to time constraints, the entries are made manually on an outpatient department paper mentioning dates and other details of vaccination. These details are entered and maintained in record registers later, which leads to duplication of work. In addition, the format for keeping records has also been shared by NCDC. 21 Yet, each centre has its own format of line listing of patients in the registers. The formats for filling up the details can be simplified and should be uniformly used in all the centres. Even when the WHO updates its guidelines there are delays in its incorporation into the National Guidelines. For example, WHO endorsed the replacement of the intramuscular route with the intradermal route for WHO pre-qualified vaccines in 1992 and it was put forth in India after more than a decade in 2006. This delay in implementation was because Nerve Tissue Vaccine (NTV) production was stopped in India in 2004, and modern cell culture vaccines (CCV) were recommended for PEP. However, intramuscular administration of CCV was not economical for our country. Thus, GoI conducted a feasibility, efficacy and safety study through Indian Council of Medical Research on intradermal administration of CCV using available CCVs in the country. Thereafter, the Drug Controller General of India approved intradermal route for CCV administration based on WHO recommendations as well as results of trials on safety, efficacy and feasibility in 2006. 7 Similarly, WHO endorsed the 1-week intradermal regimen for PEP in 2018 but India still continues with the 4-week schedule. GoI seeks evidence on 1-week schedule for intra-dermal route among its citizens before accepting WHO guidelines and endorsing its use in our country. A prescription audit of PEP by checking how many patients come back for the last dose of ID vaccination on the 28th day should be considered as it is a matter of compliance with the internationally recommended vaccination schedule, which should not be ignored. Previous studies have shown variable compliance to 28th Day ID vaccination (54.4%–78%)38–40 Interestingly, the state of Himachal Pradesh implemented the 1-week ID schedule in 2018 due to prolonged shortage of rabies vaccine in the state, and it was considered prudent to implement dose saving 1-week ID schedule as recommended by WHO. In January, 2019, Government of India, Delhi (NCDC meeting of rabies experts) recommended that a national multi-centric study should be conducted to test the efficacy of this new WHO recommended 1-week regimen using Indian vaccines. Therefore, Himachal Pradesh reverted back to 1 month/4 dose ID schedule in 2019. 41 However, under pooling strategy in Himachal Pradesh, three visit (1-week) ID schedule is still being followed for dog bite PEP at pooling centres. 42 Inoculation of RIG only at the bite wound site was recommended by WHO based on a study in Himachal Pradesh, which was fortunately implemented in the same year in India too. 43
Mis-classification of animal bites: Minor scratches or abrasions without bleeding are categorised as type II animal bite and are given rabies vaccine only with no immunoglobulin. 6 However, there might be a confusion among treating doctors in identifying scratches with or without bleeding leading to mis-classification of bite category and inadequate PEP. Patients might also undermine the severity of wound and not seek PEP. This has resulted in deaths in animal bite victims. 44 Proper training of doctors and health staff involved in the care of animal bite victims and awareness generation activities among communities is the need of the hour to prevent such instances.
Inadequate awareness among health care workers: Poor knowledge about animal bite categorisation, inability to differentiate between intramuscular and intradermal regimens, indications, route, dose, schedule in case of previously immunised and unimmunised individuals (especially in special populations like people infected with human immunodeficiency virus (HIV)), insufficient awareness about immunoglobulin administration, lack of knowledge regarding pre-exposure prophylaxis (PrEP) and rescheduling among individuals who have received PrEP resulting in the allocation of two sites ID schedule instead of one (in case of exposed/re-exposed individuals who can document previous complete PrEP or PEP, one site ID administration on day 0 and 3 or one site IM administration of an entire vaccine vial on days 0 and 3 is recommended, 45 administering the vaccine to individuals already fully vaccinated within 3 months, are some of the knowledge gaps identified among healthcare workers including doctors in the studies conducted in India and other countries.46–49 Lack of awareness is leading to vaccine wastage in resource-limited developing countries like India. Furthermore, inadequate PEP might result in failure and preventable rabies death. This highlights the need for routine and re-trainings for healthcare providers engaged in rabies management and control at facility level.
Myths, misconceptions and misbeliefs among patients: Previous Indian studies have reported various harmful customs and practices among patients with animal bite due to insufficient knowledge and unfavourable attitude towards animal bite leading to not seeking treatment or delay in seeking treatment. Application of irritants like chili powder, salt, lime etc., inadequate or no wound washing practices including poor compliance with the methods and duration of washing by patients have been reported in literature. 50
Poor compliance to PEP: The compliance to PEP has been unsatisfactory in India. Studies from various parts of the country have reported variable compliance to ARV ranging from 52.3% to 78%, while compliance to RIG has ranged from 49.4% to 88%.38–40,48 Common reasons for non-compliance are misconceptions, the distance of the hospital, the timing of the clinic, loss of wages, lack of time, forgotten dates, non-availability, cost of the vaccine and immunoglobulin.38,48 Though the vaccines are provided free of cost in the government setup, there are indirect and opportunity costs for the visits to be made to complete the regimen, thereby affecting the overall compliance to PEP.
Inadequate infrastructure for PEP: A nation-wide multi-centric survey in 2019 showed glaring deficiencies in anti-rabies clinics of India for PEP. The first and foremost step in rabies PEP is immediate, thorough flushing of all wounds with soap and water for up to 15 min followed by application of antiseptic with virucidal activity. However, as per the survey, more than half of the surveyed facilities (54.3%) didn’t have adequate wound washing facilities and use of antiseptics to animal bite wounds. 29 This can lead to disastrous consequences among patients with animal bite and decreased PEP effectiveness. It is recommended to have wound wash facilities at all animal bite treatment centres. Along with the infrastructure, it is important to create public awareness about wound washing and media can play a huge role in creating the awareness.
Private sector dominance and increased demand for PEP: The vaccines and ERIGs are mainly manufactured in the private sector in India. Only 23% of ARV and 3% ERIG are produced by public sector and 77% of ARV and 97% ERIG is produced by private sector in our country as per WHO-APCRI Indian Rabies Survey Report 2017. 51 The demand for anti-rabies vaccine and serum is high due to the global campaign to eradicate rabies by 2030. Neighbouring nations including the Philippines, Malaysia and Myanmar are importing vaccine from India. The profitability of the export market could lead to neglect of domestic needs. Many states and stakeholders have pointed out that Indian manufacturers are not responding and not participating in domestic tenders due to the preferential export of ARV by Indian Manufactures at escalated prices to the neighbouring countries. In 2019, all ARV manufacturers were instructed by the GoI to ensure that the manufacturing should accord the first preference to meet domestic requirements including government institution supplies in the country. 37 There is adequate capacity in the private sector for manufacturing ARV, so the domestic market should not be neglected.
Vaccine wastage: ARV is an inactivated vaccine with multiple dose vial requiring reconstitution, and it should be used within 6 h of reconstitution. 6 However, as animal bites cannot be predicted in advance, and rabies PEP has to be administered as soon as possible after exposure, the reconstituted vaccine vial for one patient with animal bite has to be discarded if no other patient comes to the health facility within 6 h of vaccine reconstitution. Facilities to test anti-rabies antibodies in patients’ serum are limited and costly leading to reluctance and low utilisation among patients. Therefore, a fully immunised person, if again gets exposure after 2–3 years, is re-vaccinated with ARV which is accessible and available free of cost. But as per guidelines, in case of exposed/re-exposed individuals who can document previous complete PrEP or PEP, one site ID administration on day 0 and 3 or one site IM administration of an entire vaccine vial on days 0 and 3 is recommended. One of the study conducted in Delhi showed that about 22.3% animal bite victims reporting to a secondary care hospital had history of animal bite within the last 5 years. 52 These factors along with insufficient awareness among healthcare providers and patients and delay in update and dissemination of national guidelines lead to vaccine wastage. This was evident from the findings of Batish R et al who reported that about 82.5% cases of animal bite re-exposure were administered full course of treatment due to lack of documentation. 53
Inadequate surveillance system: The success of any intervention programme against rabies can be measured through robust surveillance system for recording and reporting animal bites, human deaths due to rabies and PEP. However, such system is grossly inadequate in our country. In India, the data on human rabies deaths are captured by Central Bureau of Health Intelligence and animal bites are reported on Integrated Disease Surveillance Program Portal in P form. 54 Standard definitions, recording and reporting formats have been finalised for uniform and streamlined reporting. But the recording and reporting system is fragmented and incomplete. There is a mismatch between actual number of human cases and estimated and reported cases. This results in underestimation of impact of rabies hindering effective policymaking. To address this challenge and strengthen the surveillance system, Ministry of Health and Family Welfare is advocating for declaration of rabies a notifiable disease by the states, and 20 states have already declared it as a notifiable disease. 55 Under NAPRE, provision of development of dedicated portal and geographic information system enabled surveillance system is made to improve surveillance and data sharing between various stakeholders. 5
Opportunities
Information, Education and Communication: Repeated health education about the importance of wound washing, early initiation and completion of the vaccine schedule can be conducted through the mass media, posters and field-level health care workers like accredited social health activists (ASHAs). School curriculum can also be modified to include the key messages about rabies being serious but preventable, avoiding dog bites, wound washing, vaccination and compliance, in the textbooks using simple vocabulary. One such example is the tenth standard textbook of National Council of Educational Research & Training (NCERT), which included a section on rabies describing the agent, mode of transmission, symptoms, and concept of One Health, which mentioned vaccination in 2018–19. In 2022–23, the 11th standard textbook had review plan for local authority to control rabies. 56 The institute and teacher have the responsibility to carry out this field-level activity for the students. Goa has demonstrated how effective risk communication can be enhanced by including the rabies topic in the school textbooks. 23 Social media is another important tool for creating awareness regarding rabies and PEP through online games, videos and images, and its potential should be fully harnessed. Increased use of mobiles and social media (like YouTube, WhatsApp, Facebook, Twitter) in LMICs is a great opportunity for rabies elimination. 57 It is also important to note that effective risk communication results in improvement in the reporting of animal bites to the health centres, which should be prepared with sufficient stocks and manpower to cater to these needs.
Information Technology (IT) solutions: At present, the vaccination entries are made manually on paper, which is not standardised across the country. Lack of documentation regarding full vaccination in an individual may lead to repeat administration of RIG after next animal bite and no rescheduling of the ARV. This results in ARV and RIG wastage and also diminishes patient compliance and exacerbates patient discomfort and suffering. The GoI have partnered with United Nations Development Program (UNDP) for the digitalisation of rabies vaccination. This will include tracking of beneficiaries, real-time monitoring of vaccine stocks and ensuring that all doses of PEP are administered to the animal bite victims. 58 Such platform if developed on the successful example of Co-Win for COVID-19 and U-Win for Universal Immunization Program in India can be used to improve the reporting, monitoring, and surveillance of animal bites and rabies.59,60 IT can also be used to monitor ARV and RIG stocks, to provide digital certificates for vaccination mentioning all relevant information for improving compliance and management of referrals and re-exposures, to maintain a central repository of cases, and for training of healthcare personnel. A helpline with chatbots can be created to provide information about the availability of first aid, RIG and ARV at nearest health facility. Although there are nodal officers for each state under NRCP, there can be institutional nodal officers with a common social media platform to address queries in real time for further improvement in implementation of guidelines at the level of institutions. Reminder text or social media messages can further improve the PEP compliance. An NRCP website is already launched to provide insights, resources and updates on rabies. The website will be a digital platform for states to enter animal bite and rabies-related information and will help community to find out nearby anti-rabies clinic and infectious disease hospital. It will also help in sending the SMS for follow-up vaccination. 61 Nonetheless, it requires lots of efforts to maintain uniformity across the country, and animal bites are not a priority at many places.
Newer biologicals: RIGs are blood-derived products and have many issues with quality, safety and availability. Monoclonal antibodies have advantages over RIGs like large-scale production with standardised quality, greater effectiveness, elimination of the use of animals in the production process and reduction in the risk of adverse events. 62 A proposal has already been put up in place to apply for inclusion of Anti-Rabies Virus Monoclonal Antibodies to the WHO’s Model Lists of Essential Medicines and Essential Medicines for Children. 63 Two anti-rabies monoclonal antibodies are already licensed in India, and three other candidates have reached clinical trials stage. 64 Recently, a study based on active post-marketing surveillance has reported a favourable safety profile of monoclonal antibodies. 65 However, NCDC has not included them in the national guidelines and requires more evidence about their efficacy and safety through multi-centric trials.
Interchangeability of vaccine product and route: Currently, it is not encouraged to interchange the vaccine product and/or route of vaccine administration until and unless the situation is unavoidable. But recent evidence suggests that changes in the rabies vaccine product and/or the route of administration during PEP are possible.8,66,67 WHO recommends if the switch is absolutely required, PEP need not be restarted, and the regimen should be continued/resumed as per the new vaccine/route of administration and the same is mentioned in the National Rabies Propylaxis Guidelines of India, 2019. 6 This will help in combating the vaccine shortage, improve the compliance and thereby reducing the fatality.
Advocacy for universal pre-exposure prophylaxis (PrEP): Implementation of present strategies of providing PEP, and sterilisation and immunisation of canine population seems challenging in India. Although some Indian cities have successful sterilisation and immunisation programmes against rabies, but it requires continued efforts and intensive resources to sustain gains made and prevent reversal of the situation. The cost and availability (especially in endemic areas) of ARV and RIG are the main problems with PEP which can pose threat to receipt of appropriate therapy. PrEP doesn’t eliminate the need for PEP but it simplifies the PEP schedule by eliminating need for RIG and reducing ARV doses as individuals with completed PrEP schedule (three ID/IM doses on days 0, 7 and a booster on day 21 or 28) require only two booster doses of ARV.6,68 A recent review elicited that a single-visit PrEP schedule in healthy non-immunocompromised individuals provides sufficient protection if booster PEP (irrespective of the vaccination schedule used for PEP) is given after a suspected rabies exposure. The studies analysed in this review had used two to four dose schedule of PEP. 69 In developing countries like India, an enormous population of free roaming dogs, inadequate awareness among pet owners, lack of sufficient data on dog population dynamics, devoting significant efforts on expensive animal birth control measures in place of canine vaccination, relying only on parenteral vaccines for canine population are some of the problems, which makes sterilisation and immunisation of canine population challenging.70–73 On the other hand, PrEP is safe and immunogenic against rabies with rare chances of failure. A recent study showed that primary immunisation with PrEP provides long-lasting immunity, and adequate immunological response can be elicited with a single IM booster dose after initial vaccination for several years. 74 There is now increasing advocacy to include PrEP in National Immunization Schedule in endemic regions. 75 But there are challenges regarding cost and logistics to this inclusion. The concerns related to shortage of vaccine if allocated for PrEP can be dealt by having a clear vaccination strategy, increasing the production and generating a dedicated PrEP stockpile. 75 It is important to ensure sufficient stocks for PEP along with monitoring its accessibility and availability before focussing on PrEP. However, PrEP can lead to complacency, and patients, especially children, may ignore the need for vaccination after an exposure and every effort should be made to make people aware about the role of PrEP and need of PEP post-exposure despite receiving PrEP. Additionally, disease control in reservoir through canine vaccination and sterilisation is equally important strategy for rabies elimination along with PEP and PrEP. A thorough review of current situation, available logistics and evidence and expert opinions is required to consider possibility of universal PrEP.
Oral rabies vaccine for dogs: Over the past four decades, iterative efforts to develop Oral Rabies Vaccines (ORV) have produced vaccinations with high safety profiles and a reliable protective immune response against the rabies virus in dogs. These can be considered for use along with parenteral rabies vaccines to boost herd immunity in rabies-endemic countries. The huge and often elusive population of stray dogs makes it difficult to efficiently access a large section of the canine population by parenteral approaches. In order to reach these dogs, existing parenteral techniques need large, highly competent dog-catching teams. This presents logistical, organisational and financial challenges for quickly reaching 70% dog vaccination coverage in urban environments. With ORV as a complementary tool to parenteral rabies vaccine for dogs, strategies to eliminate rabies in a significant portion of South Asia could be developed more quickly. 76
Intradermal vaccine delivery device: A variety of novel intradermal vaccine delivery systems are being developed by different organisations. PATH (Program for Appropriate Technology in Health) is actively engaged in trial and development of such devices and delivery systems. Microneedles and jet injectors are being evaluated for ID vaccine delivery as an alternate to traditional needles and syringes. 77 These devices can help calibrate the recommended vaccine dose for ID route and will reduce vaccine wastage and inadequate vaccine dose administration.
Threats
Pandemics: Pandemics like COVID-19 has the potential to disrupt the routine healthcare services delivery including vaccination. A sharp increase in rabies cases and deaths has been reported worldwide during and post-pandemic, which can be attributed to multiple factors. Stray dog menace increased due to abandonment of pet dogs, starvation of street dogs and reduced human–dog contact. Lockdowns affected the accessibility to PEP due to closure of dedicated bite centres. International vaccine shortages resulted in delayed vaccine procurement causing issues with availability. Financial constraints led to compromised rabies control activities like animal birth control and mass dog vaccination. For example, in Bhutan, due to the COVID-19 lockdown, annual mass dog vaccination was interrupted which reduced the herd immunity among local dog population. 78 Therefore, it is vital to improve the emergency preparedness for human rabies prophylaxis based on lessons learnt from COVID-19. Hospital medical emergency should include PEP, and it should be placed under emergency medical services. 79
Misleading media reports: Recently, increased number of rabies cases and deaths among vaccinated and unvaccinated individuals, majorly in the state of Kerala, have raised concern among general population. Several media report published news articles with headlines like ‘Girl dies of rabies in Kerala despite 3 jabs’. 80 However, detailed investigations into the cause of death due to rabies among vaccinated individuals showed severe nature of wounds and failure to seek immediate care as cause of mortality and not dubious effectiveness or potency of the biologicals nor the emergence of new and resistant rabies virus strains. 81 Erroneous interpretations of health information, which become more prevalent during epidemics and emergencies, can cause delays in the delivery of medical care, have a detrimental effect on people’s mental health, and raise vaccine hesitancy. 82
Dog vaccination: Current recommendations suggest vaccinating the dogs after 3 months of age against rabies. However, there have been reports of human rabies deaths due to transmission from <3-month-old dog. 83 Additionally, it is not recommended to take rabies vaccination following bite from a vaccinated dog, provided the dog is properly vaccinated against rabies and efficacy of vaccine is confirmed by laboratory evidence. 84 The protective antibody titres among dogs depend on various factors. 85 Also, the dog vaccination can lead to misconceptions about the need for human vaccination. Messages to prevent such misconceptions should be included in the IEC material.
Canine vaccine hesitancy: It is possible to conceptualise canine vaccine hesitancy (CVH) as dog owners’ doubts regarding the effectiveness and safety of regularly immunising their pets. CVH is linked to both resistances to evidence-based vaccination programmes and rabies non-vaccination. 86 In a study among veterinarians, the most frequent objections voiced by clients who were reluctant or resistant to vaccinate their dogs or cats were that the shots are expensive, needless, or could result in a serious or chronic illness. Furthermore, human anti-vaxx movement was found to be associated with CVH. 87
Conclusion
Through a targeted approach focused on enhancing rabies PEP implementation along with other measures such as community engagement to build awareness about rabies, and canine vaccination including mass dog vaccination, India can significantly reduce the burden of rabies-related mortality. By emphasising the preventable yet incurable nature of rabies and highlighting the annual toll it exacts on human lives, this study underscores the urgency for effective and coordinated public health interventions to achieve the goal of rabies elimination by 2030. The findings highlight the critical importance of addressing weaknesses and capitalising on opportunities to strengthen rabies control strategies in India. With an emphasis on the preventable nature of rabies-related deaths, proactive measures are essential to enhance inventory management, ensure guideline dissemination and leverage technological advancements. Some of the actionable measures can be procurement of ARV and ARS under the National Free Drug Service initiative of National Health Mission, following the guidelines by NCDC for procurement and regular stock monitoring to avoid stock-outs, training of doctors and health staff involved in the care of animal bite victims and awareness generation activities among communities harnessing the potential of social media through videos, games, etc. strengthening the infrastructure to ensure wound wash facilities at all animal bite treatment centres, and improving the coverage of canine vaccination. Additionally, addressing threats such as pandemics and media misinformation requires collaborative efforts and proactive risk communication strategies. All these measures require whole of government and whole of society approach through Jan Bhagidari.
