A debate on elimination of dog-mediated human rabies in developing countries by 2030

Within the medical community, rabies is frequently described as the “low-hanging fruit” among infectious diseases, given its preventability and the practicality of eradicating dog-transmitted rabies [1]. However, rabies is responsible for approximately 59,000 deaths each year, meaning that rabies deaths occur as frequently as every nine minutes around the world [2]. Furthermore, rabies-associated deaths are estimated to be even higher due to the underreporting of cases [3,4]. Extensive eradication campaigns targeting both urban and sylvatic rabies have resulted in the elimination of dog-mediated rabies from North America, Western Europe, Japan, and some Latin American countries.

Despite such efforts, the persistence of dog-mediated rabies in the developing world raises questions regarding the reasons for the delay in its elimination while the frameworks and appropriate tools for its global eradication presently exist. Indeed, the practicality of eliminating even sylvatic rabies propagated through wildlife species is well-demonstrated through successful eradication programs in Western Europe and North America. As such, why has it been taking so long for the disease to be eliminated, especially when the elimination of wildlife related rabies due to foxes in Europe and raccoons and skunks in North America proves that it is possible? Interestingly, this is also where the problem lies.

Human rabies is a serious public health issue that affects 150 different countries [5]. However, most of the deaths due to dog-mediated rabies occur in Asia and Africa [6]. The majority of human rabies deaths, about 59.6%, happen in Asia, followed by Africa with 36.4%. In contrast, the Americas account for less than 0.05% of human rabies deaths [2]. According to the World Health Organization (WHO), India bears a substantial burden in the global context of rabies-related mortality, accounting for 36% of such deaths worldwide. Furthermore, within the South-East Asia region, India represents a notable majority, contributing to 65% of the rabies-related fatalities. The National Rabies Control Program documented 6,644 clinically suspected cases and associated human rabies deaths from 2012 to 2022. Concerns are rising about more people dying from rabies, especially in the State of Kerala. The number of sick dogs has doubled in the last five years there. Out of 300 samples taken from dogs, 56% were found to have rabies, which is way more than the 32% in a similar study in 2016 [7,8]. Furthermore, as of now, every country on the African mainland is recognized as having an ongoing issue with dog-mediated rabies, leading to an estimated 21,500 human deaths from rabies each year [9,10]. In addition, the problem of bat-mediated rabies remains significant in South America. A concentration of cases among dogs was noted in Bolivia. Among the 192 reported human cases during the research timeframe, 70% were transmitted by bats. The primary cause of infection, leading to numerous cases in Peru, Ecuador, Colombia, and Brazil, was the widespread prevalence of the aerial cycle, primarily associated with common vampire bats [11]. Globalization has long been stated as a culprit for aiding in the spread of infectious diseases [12]. The WHO has named world rabies day 2021 “Rabies: Facts, not Fear” as a reminder of the importance of rabies and its resemblance to COVID-19 in the aspect of vaccination hesitancy [13].

Although the WHO is doing a remarkable job at trying to keep all infectious diseases (such as rabies) under control by setting ambitious yet realistic goals for their elimination [14], higher levels of determination must be implemented on national and international levels [15]. Obtaining, increasing, and maintaining governmental engagement of different low-income countries greatly affected by dog-mediated rabies is crucial for reaching the WHO goal of eliminating all dog-mediated rabies deaths by 2030. Dog-mediated rabies must cease to be portrayed as a disease of the developing world, even if it only affects these areas. If globalization is able to bring awareness to infectious diseases such as HIV/AIDS which affect the entire world, it must also be used in a reverse perspective to show that the elimination of dog-mediated rabies is definitely a possibility, assuming that priorities are reassessed.

The main objective, as defined by the WHO, for the elimination of dog-mediated rabies is to break the transmission cycle which infects humans. Through preemptive measures, such as sustained canine vaccinations, countries may move from having endemic rabies to being rabies-free, if rabies vaccination is obligate. This situation is defined by a steep decrease in human rabies cases due to the aforementioned mass intervention. If rabies control measures are effective, then the next step would show a definitive interruption in dog-to-human rabies transmission presented in the form of zero human deaths. This step is followed by a verification that there indeed have been no further human rabies deaths and a final declaration of being rabies-free; which must be maintained through the continuation of confinement measures [16]. The major obstacles in Africa and Asia include free-ranging dog populations (Figure 1), limited accessible resources for dog owners, poor veterinary and human health infrastructure, low illness awareness, and lack of effective communication between the veterinary and the human health sectors [17,18]. Moreover, a more comprehensive strategy is still required to control rabies, and taking an ecological perspective seriously is crucial. Any zoonotic disease reservoirs, big data mining, open-access forecasts, and future outbreaks must be studied [19].

Figure 1.

The fatal anthropozoonotic infection, rabies, is an acute disease affecting the central nervous system and is impossible to cure when the symptoms emerge [20]. While there have been extensive studies into finding a cure after the occurrence of symptoms, it is now universally accepted that preemptive measures are not only the most effective in terms of treatment but are also financially cost-effective [21]. Many animal reservoirs have been considered for the rabies virus; however, bearing in mind that domestic dogs constitute the main source of infection for human rabies worldwide [21,22] (Figure 2), canine vaccinations are considered one of the most effective means of controlling rabies. It is believed that canine-transmitted rabies can be eliminated by the vaccination of at least 70% of at-risk dogs every year [23]. Different vaccination methods; such as door-to-door vaccination, oral vaccination, and capture vaccination, have been developed to produce the best seroconversion rate and limit the vaccination costs as much as possible. But evidently, a combination of all these methods concerning every region’s situation is required to reach this target vaccination coverage [24,25]. Some of commercial vaccines for dogs include a live attenuated vaccine produced locally by the Institut Pasteur Algerie (Vetera^®), a phenol-inactivated vaccine without adjuvant (Rabisyva^®, Syva, Spain), and an inactivated vaccine with adjuvant (Rabigen^®, Virbac, France) [26]. Injectable vaccines, especially intramuscular, are the most common, but oral and intranasal options offer alternatives [27]. Elevating vaccination rates in hard-to-reach dogs through oral vaccines has the potential to establish robust herd immunity. This, in turn, could lead to the eradication of canine rabies within the targeted dog population [28,29]. Furthermore, SAG2 vaccine represents the initial registration of an oral anti-rabies vaccine in India. Moreover, the outcomes of this safety and efficacy trial involving indigenous stray dogs played a pivotal role in the government of India’s decision to register the Rabidog-SAG2 oral rabies vaccine in March 2006 [30]. Moreover, it exhibits potential as a promising asset for orchestrating oral vaccination campaigns, particularly in nations where the coverage of parenteral vaccines for dogs remains insufficient to eradicate canine rabies. Subsequent field studies are imperative to compare diverse protocols of vaccine bait distribution and ascertain the optimal strategy for vaccinating Indian dogs. This research builds upon earlier assessments conducted in Tunisian dogs, contributing to a comprehensive understanding of the vaccine’s efficacy and the most effective deployment methods in distinct regional contexts [31].

Figure 2.

Even in presumably rabies-free countries there is always a risk of reemergence through other carrier animals, such as bats and foxes, and traveling to endemic areas; thus, maintaining preventive measures and vaccination should always be a public health priority [32]. However, canine vaccinations are rarely enforced in low-income countries, and old-fashioned preemptive control methods, such as mass culling of community dogs, are preferred in some areas [33]. Nevertheless, these outdated methods have been proven to be ineffective and even counterproductive [33]. While this method might seem to be effective at first, it creates an ecological vacuum, attracting more dogs into the area due to the newly found high biotic potential based upon local sources [33]. The initial financial burden of putting preemptive measures into place, and the ineffectiveness of those preemptive measures that are chosen generally due to lower costs, lead to the fact that rabies in the developing world is mainly treated on a post-exposure basis. However, studies conducted in Asia and Africa have proven that such an approach to rabies makes its economic burden much more substantial. Direct medical costs from post-exposure prophylaxis (PEP), costs of controlling rabies among dogs, livestock losses, and surveillance costs [34] are all to be considered if PEP is the only form in which a country tries to control rabies.

To prevent human rabies mortality and lessen the financial burden of the illness brought on by cases in animals, the management of rabies necessitates an integrated strategy and coordinated efforts by regional, national, and municipal governments. In South America, official livestock vaccination campaigns are often not included in the Veterinary Services’ control programs, despite the significance of rabies in animals and the existence of viable vaccinations [11]. Moreover, vaccination of livestock against rabies is also not included in the control programs in European countries [35]. Such approaches to avoiding rabies, however, demonstrate significant variation, and there are several obstacles hindering the efficacy of the control measures, including outdated legislation, a lack of international collaboration, and a lack of vaccination programs for animals [11].

It is essential to understand the circumstances of various nations and their rabies-related demands in order to develop tailor-made approaches for rabies elimination in low-income countries. Canine vaccinations in combination with post-exposure prophylaxis (PEP) in humans are shown to effectively reduce the incidence rate of rabies in regions where dog-mediated rabies is endemic. While this combination is cost-effective, rabies cannot be sustainably controlled without suitable long-term financial commitment. However, implementing development impact bonds [36], which are a form of sustainable investment-based funding used to address societal issues and can be applied as long-term financial aid [21], would be an effective solution to overcome this obstacle. This type of funding is believed to be especially effective in the case of rabies control in low-income countries as the funding is based on the success rate of the cause [37]. Since it is known that firstly, the elimination of rabies is an achievable possibility based on other successful cases from developed countries, and secondly, that the consistent and mandatory vaccination of dogs is definitely effective in reducing human rabies cases; it is highly likely for investors to be willing to invest funds due to the high economic return of their shares [38].

A stronger focus on the elimination of dog-mediated rabies in low-income countries by developed countries that have already eliminated this type of rabies, could also be achieved by more dedication to rabies education. For instance, few people in the developing world know that rabies is more likely to be transmitted to humans by pets rather than wildlife [39]. The WHO, a leading organization in the dissemination of information and awareness about rabies, has recently launched an online course with the collaboration of the Food and Agriculture Organization (FAO) about the prevention of this disease to reach the goal of “zero by 30” [40]. Spreading this type of knowledge could ensure that a relapse of rabies could be prevented. Especially in low-income countries, where animal husbandry is a main means of livelihood, this could be of utmost importance. This scenario can be observed in the case of Türkiye, where rabies incidence rates had been successfully controlled in the mainly urban west and sprung up again more recently in the poorer East Anatolia Region, where animal husbandry is largely practiced [41]. Coupled with the enforcement of dog vaccinations for pets or guard dogs, this could also prevent cross-switching and cross-border transmission of rabies, especially since dogs are the main transmitter of rabies to other species as well [42,43].

Another important aspect of sustainable rabies aid is assessment of its local threat and the shortcomings in an area that prevent adequate elimination of rabies. The Stepwise Approach towards Rabies Elimination (SARE) framework is a planning and evaluation tool designed by the FAO and the Global Alliance for Rabies Control (GARC) for countries to assess the suitableness of their rabies prevention, control, and elimination efforts [25,44]. The framework can not only serve as a means of classifying countries but also gives concrete steps and objectives required to develop on its scale, allowing the countries to develop on their own and also providing potential investors more insight into what type of aid is needed and where. This is believed to speed up the rabies elimination process while focusing on a “One-Health” approach [45]. This framework, however, also gives insight into whether the country requires external aid, or can finance vaccination programs itself; ensuring that more aid will go to countries that are not able to do so themselves. On the other hand, countries that can finance dog vaccination programs themselves would greatly benefit from rabies educational programs.

Region-specific networks have also been developed over the past few years to focus on achieving the “zero by 30” goal. The Middle East, Eastern Europe, Central Asia, and North Africa Rabies Control Network (MERACON) is one of these newly formed networks consisting of the at-risk stakeholder courtiers of these regions in order to eliminate dog-mediated rabies [25].

The interplay of sustainable investment strategies and rabies education through developed countries could also positively affect the cooperation of culturally diverse regions and help garner coordinated actions from different areas affected by dog-mediated rabies. All of this, however, depends on the amount of global publicity that rabies receives as an infectious disease. If the strategies are successfully applied, they could catapult rabies from the status of being a rotten apple to a low-hanging fruit.

The different approaches used in developing and low-income countries are summarized in Table 1.

Previous research suggests that rabies may be locally eradicated with mass dog vaccination campaigns, which would significantly improve the lives of both people and animals. Even with the clear benefits, dog immunization programs are noticeably lacking throughout the African continent [46]. Human rabies mortality can be avoided by promptly giving PEP to people bitten by dogs. However, many local healthcare systems do not have easy access to PEP, and there is frequently low adherence to PEP in addition to limitations on dog vaccination programs [47].

Because of the government’s “One Health” strategy, the number of human rabies cases in China has dropped steadily since 2007, with 200 deaths recorded in 2020. Thirteen provinces had fewer than ten cases apiece out of the total 21 provinces that reported cases. It is still difficult, for example, to get more than 75% of dogs vaccinated against rabies, particularly in developing nations. More than 15 times as many people are currently seeking outpatient treatment for rabies post-exposure prophylaxis than were first noted. Ensuring comprehensive control of rabies requires addressing these issues, which include enhancing dog vaccination and care [48]. In order to achieve the target of “Zero rabies deaths by 2030,” canines must develop a long-lasting immunity. This entails vaccinating a huge number of dogs, controlling dog populations, keeping a careful eye on the spread of rabies, and employing oral vaccines on a big scale to eradicate the virus in wild animals. In addition to these initiatives, we ought to inform communities about the significance of these precautions and offer reasonably priced treatments to those who have been exposed to rabies [48]. Wherever rabies is prevalent in the world, strengthening political commitment and advancing dog-mediated rabies control measures, such as dog vaccination, are crucial.

Understanding from Japan and other countries that have successfully eradicated the illness can be very helpful in the fight against dog-mediated rabies. Very few records of dog rabies epidemics occurred in Japan after World War II, and very little is known about the process that led to the eradication of rabies [49].

Moreover, the actual number of stray dogs that were unowned at the time the Rabies Prevention Act was passed was unknown, but it was a significant number. The act gave prefectural and city health centers the authority to hire dog catchers to pick up stray dogs. Leash use among dogs was encouraged by this campaign. The owners of the canines were alerted by the center officials if their tags were registered; if not, the chief officers of the relevant city, township, or village were notified. It was allowed for dog owners to search the centers for their lost pets. In compliance with the act’s requirements, dogs that were not owned were put to death [49,50]. Furthermore, registered dog owners received alerts about a vaccination campaign, in which shots were given every two years until 1985. Following immunization, a vaccination certificate was given to the owners by the local government. According to information from a retired government servant veterinarian, owners were urged to register their vaccinated pets through veterinarians if they were not already registered. Certain steps were legally required in case of a rabies outbreak [51].

Furthermore, widespread dog vaccination programs have been shown to dramatically reduce the incidence of rabies in both human and canine populations. Several studies confirm that the most economical approach to avoiding human rabies is to target the main source of rabies infection by canine vaccination [52,53,54,55]. According to Lugelo A. et al. [56], the use of Zeepots and the engagement of One Health advocates appeared to improve community awareness, vaccine accessibility, and campaign participation. Maintaining high levels of coverage over the course of the annual cycle can be facilitated by incorporating a variety of vaccination techniques into an approach for continuous delivery.

In conclusion, the global endeavor to eliminate dog-mediated human rabies by 2030 confronts a complex landscape, particularly in low-income countries across Asia and Africa. While successful strategies in developed regions showcase the potential for eradication, challenges such as socio-economic disparities, cultural nuances, and healthcare limitations impede progress in less affluent nations. The existing frameworks, though effective, encounter obstacles related to the mismanagement of funds and the need for tailored approaches. Sustainable investment strategies, region-specific assessments, and international collaborations emerge as essential components for achieving the WHO’s goal. Incorporating development impact bonds and targeted educational initiatives becomes crucial in addressing economic, cultural, and healthcare dimensions. It is imperative to redefine dog-mediated rabies not merely as a localized issue but as a global concern, prompting a shift in priorities, heightened awareness, and cross-border cooperation. The array of strategies deployed in different regions underscores the importance of tailoring approaches to local contexts, emphasizing the significance of a One-Health perspective and continuous evaluation through frameworks like SARE. The success of the initiative hinges on collective determination, sustained funding, and a united global front against this preventable yet persistently challenging disease, especially in low-income countries where the impact is most profound.