Rabies is a neglected but preventable disease and has a mortality rate of almost 100%. It is widely spread throughout the world, and the annual death toll is about 59,000 cases. Asia and Africa have higher prevalence rates than other continents. In these regions, 40% of cases occur in children younger than 15 years of age. In travelers, the mortality rate is much lower due to increased use of rabies shots. It is important not to consider rabies as a disease of the past, but as a pathological situation that must still be dealt with today. Europe has achieved rabies-free status in many areas, but the rabies vaccine, also called rabies vaccine, for pets or companion animals remains important for animal health and prevention of outbreaks. The main cases, about 80 percent, come from wild species. In Europe, the species at highest risk of rabies to humans is the red fox. About 30 years ago a form of oral anti-rabies for foxes was developed to espouse the theory that removing infection in wild species leads to the removal of rabies in domestic animals. This theory led to incredible results, in 1990 there were about 21 thousand cases in Europe, which dropped to 5400 in 2004In Italy it had been eradicated from 1997 to 2008. Subsequently, however, the Experimental Zooprophylactic Institute of the Venezie (IZSVe) released data that hundreds of cases between 2008 and 2010 were positive in Veneto, Trentino Alto-Adige, and Friuli Venezia-Giulia. The situation has been linked to the sylvatic rabies outbreak in Slovenia. However, the affected regions took precautions and managed to lower the number of infections with time.
The incubation period averages 1-2 months but is highly variable. The clinical manifestations of rabies can be distinguished into three successive stages that occur after an incubation period that varies on average from 1 week to 3 months, but in some cases more than 1 year. Latency can depend on several factors: the infectious load, the extent of the wound, the immune system of the infected person, and how far away the wound is from the central nervous system.
Generally, the incubation period is quite long, ranging from 20 to 90 days.
Rabies can occur in two forms: The furious form, which makes up about 75% of cases, can divide into three stages:
- Nonspecific prodromal syndrome, which can last from 1 to 4 days. During this phase, several symptoms such as fever, migraine, general malaise, nausea, vomiting, sore throat, nonproductive cough, and myalgias are present. A symptom present in 50-80% of patients is loss of sensation or fasciculation of the inoculated area.
- Acute encephalitic phase preceded by periods of motor hyperactivity and agitation, followed rapidly by symptoms such as confusion, aggression, hallucinations, muscle spasms, convulsions, and paralysis. The patient in this phase alternates between moments of mental alteration and moments of lucidity, which, however, become increasingly rare until the patient falls into coma. Hyperesthesia with excessive sensitivity to bright light, loud noises, and touch is very common. Paralysis of the vocal cords is common, and body temperature can reach 40°C.
- Encephalitic phase of the rabic type, causing severe alterations of the brainstem centers. This causes vision problems, such as inflammation of the optic nerve or double vision of an image, facial paralysis, and typical difficulty in swallowing. At this stage in 50% of cases there is hydrophobia with difficulty breathing, violent and painful contractions of the respiratory muscles, due to the ingestion of overproduced salivary fluids. This picture leads the patient to a comatose state.
The paralytic form (about 25% of cases) is characterized by ascending paralysis. It is common in those who have been bitten by a bat and in those undergoing treatment after exposure to the virus. In Southeast Asia it occurs in individuals bitten by dogs. The lethality rate for rabies virus is still very high if not treated promptly. Death occurs in most cases 2 to 10 days after the onset of symptoms. Cases of survival after the onset of symptoms are rare; in fact, the mortality rate in these clinical pictures is about 99%.
Clinical diagnosis maỳ present some difficulty in the prodromal phase; encephalitic manifestations should be differentiated from poliomyelitis and other viral neuraxitis (inflammation of the nervous system), while tetanus is easily distinguished by lockjaw and opisthotonos (contractures and stiffness of muscles), which are always absent in rabies. Diagnostic ascertainment is based on virus isolation from saliva, CSF, urine, and nasal and conjunctival secretions. Serologic diagnosis uses titration of neutralizing and complement-fixing antibodies: these appear either during natural infection or following vaccination, but at a higher titer in the former case. Direct microscopic examination of autopsy material allows microscopic detection of Negri bodies in brain tissue and identification of the virus by the direct immunofluorescence method.
There is no useful drug therapy for rabies infection; only very few patients are reported in the entire medical literature to have survived the disease, only as a result of the intensive medical care to which they were subjected. Therefore, certain prophylactic measures carried out following exposure to the virus, such as cleaning the lesion and treatment with immunoglobulins and vaccine, are essential. Immunoglobulins have no time limits for their administration. Most of them should be administered deep in the wound. A WHO recommendation is to keep the suspect animal under observation for about 10 days, since symptoms for pets such as dogs and cats are not very specific. Other nations such as France, England and Spain recommend observation for about 14 days.
Education of children by parents, teachers, and the pediatrician in order to avoid contact with stray or wild animals is always a paramount measure. Children should be warned not to provoke or attempt to catch animals they may have occasion to encounter, especially during a trip. The most widely used rabies prophylaxis measure in industrialized countries is vaccination of domestic animals, trapping of wild animals, and vaccination of wild animals. WHO guidelines have indicated three main types of exposure that should be avoided:
- Coming into contact with the skin surface, even intact, with animals, their mucous membranes or their food
- Small scratches, abrasions without blood spillage, animal licks on some wounds or small bites on already abraded skin (rabies vaccination is recommended in these cases)
- Single bite, multiple bites, scratches, contamination of the mucous membrane with saliva, or suspicious contact with bats.
Pre-exposure vaccination (PrEP)
Pre-exposure prophylaxis (PrEP) using rabies vaccine is an important part of rabies prevention, but used only exceptionally. Although administered well before exposure, PrEP simplifies post-exposure prophylaxis (PEP) because immunoglobulins are no longer needed and only 2 vaccinations are needed instead of 4. The new 2018 World Health Organization (WHO) guideline recommends PrEP with rabies vaccine for people at high risk of rabies exposure due to their occupation or travel to an endemic setting with limited access to timely and adequate PEP. Current WHO-recommended PrEP schedules include two administrations on days 0 and 7. Recommendations on rabies pre-exposure prophylaxis (PrEP) in travelers have long been based on data from populations living in endemic areas. This has led to a preference to recommend rabies vaccination for children or long-term travelers, assuming that the risk of exposure is related to the duration of stay in the rabies endemic area. Recent data have shown that the protection conferred by a primary course of vaccine is long-term. Preventive vaccination against rabies should therefore be considered a long-term investment and widely applicable to travelers. In case of suspected exposure:
The prophylactic measures to be taken in case of a suspected animal bite are as follows:
- immediate cleansing of the wound with plenty of soap and water in order to reduce the viral infectious load and subsequent application of 40- to 70% ethyl alcohol; suturing should be postponed, and if the wound is deep, antirabies serum inoculation and possibly tetanus prophylaxis is advisable;
- immunoprophylactic treatment if the attacking animal is certainly infected or in the case of deep or localized head and neck wounds. Prophylaxis should be as early as possible; in this case it is called post-exposure prophylaxis
Post-exposure vaccination (PEP).
Indications for post-exposure prophylaxis (following potential rabies risk) depend on the type of contact with the rabid animal. The World Health Organization (WHO) distinguishes the type of prophylaxis based on the type of risk or exposure. Evaluation is variable depending on the patient's history in addition to geographic risk and extent of injury.
New post-exposure treatments are structured on 4- or 5-dose schedules depending on the above variables.