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  1. Rabies: Scientific Basis of the Disease and Its Management?
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However, these alternative transmission routes have been rarely documented [ 5 - 8 ]. In animals, hyperexcitability, autonomic dysfunction, and aerophobia are characteristic of encephalitic rabies.

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The paralytic form is characterized by flaccid paralysis in the bitten limb, which ascends symmetrically or asymmetrically. In humans, the first symptoms of rabies include listlessness, general weakness, bodily discomfort, fever, pains, or headache. These symptoms may last for a couple of days. Later, there may be a prickling or itching sensation at the site of bite, progressing within days to symptoms of cerebral dysfunction, agitation, anxiety, and confusion.

As the disease progresses, the person may experience abnormal behavior, delirium, hallucinations, insomnia, and respiratory failure. Once symptoms develop, the disease is often fatal. In fact, rabies remains one of the most ancient and deadly of human infectious diseases [ 2 , 5 , 8 ].

The virus incubation period in dogs may vary from one week to several months and may be influenced by the site of infection and the virus dose and strain. Diagnosis by clinical signs alone is inadequate since many rabid dogs develop dumb rabies which can easily be overlooked and others die without showing signs of rabies.

Rabies virus may be excreted in the saliva before clinical signs appear and may lead to infection of an unsuspecting and untreated bite victim. Dogs may recover from clinical rabies and may then intermittently excrete virus in the saliva [ 1 , 3 ].

Rabies - Scientific Basis of the Disease and Its Management

Rabies virus has been isolated from the saliva a female dog that had been inoculated with a rabies isolate from the saliva of an apparently healthy Ethiopian dog developed rabies but later recovered without supportive treatment collected at 42, , and days after recovery [ 4 , 6 ]. Rabies is considered a fulminating disease given that once the first clinical signs appear, there is no effective treatment.

However, a ray of hope emerged in with the report of a single patient recovering from rabies after aggressive, innovative treatment. Regrettably, this case was not clearly reproduced and the identification of targets for antiviral treatment in cases of rabies infection remains a major challenge [ 9 ]. Post-exposure prophylaxis consists of prompt and thorough wound cleansing and immunization with modern cell culture vaccines, together with administration of rabies immunoglobulin to those individuals who have not previously received pre-exposure prophylaxis [ 7 , 10 ].

On this specific topic, it is worth noting that historical reviews on the treatments and prevention of human rabies from ancient times up to the present have been undertaken [ 11 , 12 ]. After years of vaccination, rabies is still both a neglected disease and reemerging zoonosis [ 13 - 15 ]. It is now widely acknowledged that emerging and reemerging zoonotic disease events have heightened worldwide public awareness of the multidimensional linkages between domestic and wild animals, livestock production, and global public health [ 16 , 17 ].

There are many factors contributing to the emergence, reemergence, and intensification of zoonotic diseases. These include economic factors i.

Rabies : Scientific Basis of the Disease and Its Management

That most of the historical emerging diseases are intricately associated with very unique patterns of common determinants i. Indeed, for centuries, emerging and remerging infections have remained among the principal challenges to human survival and a fundamental challenge to the existence and wellbeing of societies all around the world [ 21 , 22 ].

It would be wrong, however, to pin down diseases only to seemingly verifiable facts.

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  • Even if capable of infecting a different host species, pathogens are usually, although not always, significantly less infectious to them. This is referred to as the species barrier, and it can be substantial, implying that much higher doses are required to infect the new host. For example, the dose of rabies virus from foxes required to infect dogs and cats has been shown experimentally to be up to a million times greater than that required to infect other foxes [ 23 , 24 ].

    A significant anthropogenic-dependent variable is dog care, disease knowledge, and leisurely practices. To give one example, a study to assess the knowledge and perceptions of dog-associated zoonoses in Brazos County, Texas, USA, demonstrated that many of the people surveyed lacked knowledge about dog-associated zoonotic diseases, which could seriously impact their health and the health of their families. Only 85 percent of respondents stated that they would seek emergency treatment if they believed that they may have been exposed to rabies, and only 59 percent of respondents were aware that exposure to rabies without treatment could lead to death [ 25 ].

    These anthropogenic-dependent variables are critically important given that exposures at the animal-human interface are a key risk factor in canine rabies. On this subject, researchers at the U. National Center for Injury Prevention and Control argue that the dog bite problem should be re-conceptualized as a preventable epidemic. They claim that breed-specific approaches to the control of dog bites do not necessarily address the issue that many breeds are involved in the problem not only dog breeds perceived as aggressive and that most of the factors contributing to dog bites are related to the level of responsibility exercised by dog owners.

    To this end, in an effort to prevent dog bite-related deaths and injuries, recommendations advanced include stronger animal control laws, better resources for enforcement of these laws, better reporting of dog bites, and public education about responsible dog ownership and dog bite prevention [ 26 , 27 ]. In relation to public communication and education about disease prevention and control, an important development aiding to raise awareness on zoonotic diseases is fast communication technologies, leading to a growing number of independent health information brokers. For instance, internet search engines provide a wealth of information on rabies and other diseases, as well as incorporating features to detect onsets of seasonal flu epidemics—which not only matched official surveillance data but did so in advance.

    Today there is a widening range of outlets discussing health and diseases, and the internet, it appears, is democratizing health information; but its unverifiable character facilitates misleading others and being misled, thus warranting caution [ 20 , 28 ]. One of these associated processes is urbanization. Rising urbanization is increasing the presence of traditional pets in households [ 31 , 32 ]. Many of these residences are in multi-building apartment complexes or condominiums where contact rates between people and dogs are increased, especially in playgrounds, leisure areas, and dog parks.

    Dogs are not only part of our daily lives and our immediate surroundings, but also have become substitutes for childbearing and child care to the point that owners allow dogs access to all rooms in an apartment or a house [ 33 ]. The rise in pet ownership is reflected in the amount of pet dogs in developed and developing nations.

    For example, the estimated pet dog population in the People's Republic of China is to million [ 34 ], in France is 8 million [ 32 ], in Taiwan is 2. Overall, according to one estimate, the current world population of domestic dogs may be as high as million, of which a substantial proportion is poorly supervised or free-roaming [ 37 ]. Rabies remains a looming threat to public health in developing and transitioning countries, and the indigenous threat of rabies continues in developed countries because of wildlife reservoirs [ 38 ].

    Both intergovernmental organizations and individual researchers estimate that rabies causes the deaths of over 55, persons every year, and this is known to be a conservative estimate. Most countries do not have the capacity for laboratory confirmation of rabies cases, and most suspected rabies victims do not die in hospital, so rabies is underreported [ 39 , 40 ].

    In addition to human death tolls and mounting healthcare costs related to rabies, there are numerous other linkages between diseases, health, socioeconomics, and international affairs that should also be considered [ 41 , 42 ]. Because of the broad geographic spread of rabies in the world, the following subsections will focus on canine rabies in specific continents or regions. The purpose of this is to disaggregate the data and information into recognizable categories, and also to ease the exposition and explanation of content.

    African countries are considered to be at particular risks of rabies infections.

    Rabies, Second Edition Scientific Basis of the Disease and Its Management

    Rabies has been, and continues to be, a public health threat in Angola [ 43 , 44 ], Southern Africa [ 44 ], Tanzania [ 45 ], and Zambia [ 46 ], among other countries. Here are a couple of examples: In South Africa, canine rabies has commonly been associated with the Eastern and Southern border areas in Mpumalanga Province, and, within this province, the Nkomazi District in the East has been most affected [ 47 ], as well as in the Limpopo Province [ 48 ]. Frequent outbreak reports throughout the country are probably an indication of inadequacy in the control of the disease at local levels.

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    • Moreover, the success and opportunism of rabies in Southern Africa is a reflection of the emergence and radiation of rabies in new host species and locales throughout the larger continent as a whole [ 49 ]. In Kenya, ever since rabies was first confirmed in , the disease has largely existed in varying degrees of occurrence with dogs being the principal reservoirs for rabies.

      Over the years an enzootic pattern covering most parts of Kenya emerged, thus posing threats to neighbors [ 50 , 51 ]. One of the most acute problems is that, for most African countries, rabies prevention and treatment are costly and the necessary resources often scarce or inadequate. Controlling rabies in dogs, the main agents of spread, will therefore emerge as an important part of any rabies eradication program.

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      At the moment, Australia is free of canine rabies. This is partly explained because all imported animals are subject to strict quarantine requirements, including vaccination for dogs and cats from all affected countries. It is believed that the country's poorly controlled canine population, its indigenous fauna, and the casual Australian lifestyle would make a rabies outbreak difficult to control. In the past, dogs played pivotal roles in rabies. Three decades ago, in a survey of animal bites in Canberra, out of a total of mammalian bites, 81 percent were due to dogs and cats [ 52 ]. In is interesting to note that until , Australia had recorded only one case of travel-acquired rabies.

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      Later, in , an extreme case of long-incubation rabies was diagnosed in a year-old girl of Vietnamese origin in whom rabies developed after she had lived continuously in Australia for almost five years [ 53 , 54 ]. While these cases are unusual, the evidence suggests that it can happen. While rabies in domestic animals and wild carnivores has become extremely rare in Western Europe [ 55 ], the world witnessed the reemergence of rabies in some regions of Europe Central and Eastern that were previously designated rabies-free, which demonstrates the need for continual vigilance and the adoption of strict control measures for extended time periods.

      Despite the significant advances that have been made during the 20th century in reducing the burden of rabies, especially in Central and Eastern Europe, the disease remains endemic in many countries, largely as a result of financial limitations and a poor veterinary infrastructure [ 56 , 57 ]. For example, rabies has been endemic in Lithuania for decades, with wildlife cases principally reported in red foxes and raccoons from to [ 58 ].

      Later, in the same country, a study from to reported that cases of rabies among foxes and raccoons had increased significantly [ 59 ]. In rabies situation reports, others have commented that an unfavorable situation remains mainly in the Baltic and nearby Southeastern countries [ 60 ], especially in Romania, Bulgaria, and Turkey [ 61 ]. In view of this situation, a number of Western European countries have voiced concerns on the threat of reintroduction of rabies virus.

      One of these is the United Kingdom, where risks from rabies exist on several levels. Based on assessments, scholars have positively commented on current UK government policy in light of a European call to harmonize rabies legislation across all Europe [ 62 ]. Without question, rabies in Eurasia is essentially a public health issue. Human rabies of canine origin has continued unabated for centuries in Eastern Eurasia, despite the Pasteur treatment and subsequent improvements of rabies post-exposure prophylaxis and novel biological products. In this sense, canine rabies, which is the main source of human contamination, remains practically uncontrolled.