This disease has been reported from centuries and many civilizations have been terrified by the symptoms present when one becomes a victim assuring him a horrible death.

The term “Rabies” seems to originate from the Latin “Rabere” (rage). Others associate the term to the Sanskrit “Rabhas” (To do violence). The disease was named “Lyssa” (violence or spirit of mad rage) by the ancient Greeks but nowadays the virus causing the disease is still classified in the genus Lissa virus.

In 3000 B.C., ceremonials of death were presided by a dog, considered as the emissary of death. Ironically, rabid dogs impose the disease in India and more than 20,000 people die each year from rabies. The first medical record describing death in human and dogs was found in the Mesopotamian Codex of Eshnunna in Babylon circa 2300-1930 B.C. A law was implemented stating that Babylonians must pay a fine if their dogs were to be found to transmit rabies to another dog or human being.

A Roman scholar Celsius was the first to suggest that Rabies can be transmitted through the saliva of an enraged animal but he incorrectly claimed that such patient with the disease would find a cure if he/she was kept under water. He certified that the one who did not draw would survive the disease. Others venture to report some barbaric cures like burning the wounds with a hot poker in which the hairs of the rabid dog were added.

In anyway, Rabies appears to have originated in the old world and one can trace the first epizootic infection in Boston in 1768 expanding to other states as well as the French West Indies and expanding to North America. There was a fear of Rabies in the 19th century in France and Belgium.  It was the recommended to apply the “St Hubert Key” on the wounds to help cauterize them, and then, by magical thinking, it will heal and protect from the virus.

The frenulum of the tongue was also considered as a reservoir for the virus of rabies. All these practices stopped when Louis Pasteur discovered the actual cause in 1885 and the emergence of the new vaccine. In modern times, the fear of rabies has also described it as the work of zombies or attached to fiction with possible widespread pandemic consequences.

Other interesting cure proposed for Rabies can be found over the years. “Mad stones” have been used in the 18th century. They consist in calcified hairballs found in the stomachs of ruminants like cows, goats, deer. It was believed that those mad stones had curative powers by extracting the madness out of the bile wound. They were highly prized and passed down through generations as family jewels. We can find examples of those stones sold at 2000 dollars by example in Essex County Virginia. President Abraham Lincoln has also used them to treat his sick son Robert after he was bitten by a rabid dog in 1849. He survived…

Edgard was a known alcoholic and was found with classic signs of Rabies as reported by his physician Joseph Morgan and when given water after he exhibited signs of rabies, but demonstrated a great difficulty in swallowing it.

In the 1880’s, Louis Pasteur was dealing with chicken cholera when he discovered a vaccine able to protect cattle against anthrax. He later wanted to refine the vaccine and try it on himself. In 1885, a young 9-year-old boy was mauled by a rabid dog and received the vaccine after a consultation with Louis Pasteur and 13 injections of the vaccine were given to him until his “complete recovery”. By the time, Louis Pasteur died and more than 20,000 people had received the Rabies vaccine in prophylaxis.

Today almost all pets are vaccinated against Rabies especially cats and dogs. Other wild animals like raccoons, skunks, foxes, bats are prone to carry the disease.

I am amazed when I read articles reporting so much stories about the way people were successfully treated with the vaccine of Rabies after contracting the disease. In a recent story, a child from San Antonio Texas, in Medina County was bitten by a bat and developed signs of Rabies. He was treated with the vaccines. I remember well in medical school, one of our teachers, Professor Adrien who taught us in Pre-Med (PCB) giving us an anecdotal story of a young gentleman who contracted rabies after being bitten by a rabid dog.

In Haiti, an ambulance will come to the home to pick up the victim and bring him/her to an unknown location. The grand-mother refused the idea of letting his grandson go and kept him enclosed in a chamber of the house where she used to store the seasoning spices like garlic, onion etc. After a week of extreme rage, she noted that the young man calmed down and ate all the garlic. It is reported that he healed from the disease.

The vaccine is really a post-exposure prophylaxis and people contacting the disease are given one dose of fast-acting rabies immune globulin which prevent them from becoming infectious, and 4 more vaccine shots will follow in the treatment over the next two weeks of the exposure. One or three cases of rabies are reported each year. In 2009, another case was found in Texas.

Rabies is due to a virus which attack the central nervous system and usually spreads through a deep bite or even a scratch from an infected animal. The disease is also found in the wild life among the coyotes, skunks, racoons’ populations but more often bats and foxes. Occasionally, some domesticated animals like the dogs and the cats can carry the disease. In any given year nearly hundreds of wild life animals have tested positive for rabies across the United States.

Usually, no symptoms are detected right away. A period of incubation may vary between one and three months with signs like fever, fatigue, pain and even tingling on the site of the wounds. The virus spreads to the nervous system leaving the individual with insomnia, confusion and anxiety. Soon a coma with subsequent heart and lung failures is observed until an ultimate death.

Rabies causes an inflammation of the brain in humans and animals. Early signs of fever and tingling at the wound site, will be followed by nausea, vomiting, uncontrolled excitement, fear of water (aquaphobia) and progressive inability to move part of the body. Rabies may present with vomiting, violent movements, confusion and/or loss of consciousness. Once those signs of meningeal irritation are observed, the outcome is virtually almost always fatal. These symptoms depend on the distance the virus took to travel along the peripheral nerves and reach the central nervous system.

As we stated it before, the virus is a lyssavirus which spread when an infected animal bites or scratches a human or another animal. The saliva is infected and can transmit the disease if it becomes in contact with a mucous surface like the eyes, the mouth or the nose. In many countries like India, Haiti etc, dogs are the most common animals transmitting the virus through their bites. Bats in general are the common sources of rabies in humans. Other rodents are rarely infected with the virus. You have to wait for the beginning of the symptoms prior to diagnose Rabies.

Extensive vaccination programs have decreased the incidence of the disease in dogs around the world. People at high risks may choose to get immunized especially the one working around bats. Once exposed, the rabies vaccine and sometimes the rabies immunoglobulins are effective in preventing the disease especially when taken prior to the beginning of the symptoms. It is recommended to wash the bites or the scratches areas for at least 15 minutes using soap and water, iodoform or povidone-iodine or any other detergent to reduce to number of viral particles. Only 16 people are known to have survived the disease as of 2016.

Less than 60,000 people died worldwide and less children below the age of 15 (40%). Most of the human deaths from Rabies occur in Asia and Africa. More than 150 countries have recorded cases of rabies while countries like Australia and Japan or Western Europe countries and the pacific islands do not have rabid dogs. This is why the disease is classified as a tropical disease.

The name Rabies or “madness” as we already discussed, is derived from the Latin language or from the Greek word “Lyssa” (Lud-Violent) to name the virus “Lyssavirus”.

You have generally to wait for between one and three months to see the apparition of symptoms related to rabies in human, once they were exposed through a bite from an infected animal or a scratch. Symptoms are seen when the brain and the meninges present signs of inflammation with partial paralysis, insomnia, confusion or agitation, abnormal behavior, terror, paranoia, hallucinations, fear of water (hydrophobia), difficulties in swallowing when any liquid is presented to the patient. leading to delirium and coma. Death is seen in 2 to ten days after the beginning of the symptoms. Once there are meningeal signs and meningitis, the death is almost always certain with an increase in saliva.

Other animals infected with the virus may also develop hydrophobia with an excessive saliva production at any attempt of drinking with painful spasms of the muscles of the throat and larynx. The virus accumulates in the salivary glands and is transmitted through a bite. In most of the cases of rabies, hydrophobia is present while in the remaining a paralytic form can also be seen with muscle weakness, loss of sensation and paralysis.

Rabies is caused by a number lyssavirus found especially among the Australian bats with their vibrions adding an enveloped RNA genome which encodes 5 genes in a nucleoprotein (N), a phosphoprotein (P) a matrix protein (M), a glycoprotein (G) and the viral RNA polymerase (L). The spikes on the exterior of the membrane of the virus interact with specific cell protectors like acetylcholine receptor to allow the entry of the virus (pinocytosis) through the cellular membrane and facilitate the virus penetration in the cell by way of an endosome. Then these five proteins will be released in an acidic environment.

Once within a muscle or nerve cell, the virus undergoes a replication and the 5 mRNA strands are translated into their corresponding proteins (P, L, N, G and M) to be transported to the Golgi apparatus for glycosylation. When there are enough viral proteins, the viral polymerase will begin synthetize new negative strands of RNA. The virus is neurotropic while travelling along the neural pathway into the central nervous system to bind the acetylcholine receptors at the neuromuscular junction. The virus travels to through the nerve cell axon as the P protein interact with “dynein” a protein present in the central nervous system (CNS) allowing the replication. Once the brain is infected, the virus travels and eventually migrates to the salivary glands where it becomes ready to be transmitted to any host.

All warm-blooded species can become a victim infected by the rabies virus, even birds can become infected but remain asymptomatic and recover. Birds artificially infected can develop rabies antibodies especially upon feeding on rabies -infected animals. The virus can also be adapted to grow in cold-blooded vertebrates. In-fact, most animals can be infected with the virus but this is the domestic dog which transmits human rabies in 99% of the time worldwide.

In the early stages, Rabies may be difficult to diagnose because it may also be confused to other diseases. The reference method for diagnosing rabies is the fluorescent antibody test (FAT), an immunohistochemistry procedure, implemented by the World Health Organization (WHO) which rely on the ability of a detector molecule (Fluorescein) coupled with a rabies specific antibody, forming a conjugate able to bind the rabies antigen.

Then the microscopic analysis of the samples as a direct method to identify the virus of Rabies. The specimen can’t be autolyzed because of reduced sensibility and specificity. The RT PCR assays proved to be a sensitive and specific tool for routine diagnostic purposes. especially in decomposed samples, taken after death. The diagnosis can be certainly made from brain samples taken after death. The same diagnosis can be made from saliva, urine and cerebrospinal fluids. The search for cerebral inclusion bodies called “Negri bodies” are pathognomonic of the disease in any post-mortem examination of the brain tissue. Those Negri bodies are found in 80% of the cases. The animal who involved in the bite should also be examined for rabies.

Light microscopic techniques may also be used to diagnose Rabies and it is often used in underdeveloped countries because of the low cost. Another test for rabies, developed by the CDC in 2018 and known as “LN34” can be performed easily on a dead animal’s brain.

Many differential diagnoses need to be kept in mind when facing a case of Rabies. Any case of encephalitis to other viruses like herpes viruses especially the type one varicella zoster or the enteroviruses like the coxsackieviruses or polioviruses, arboviruses like the West Nile virus. New cases of encephalitis were discovered by example in 1999, an outbreak of encephalitis in Malaysia with a 40% mortality rate and involving 300 cases where the Nipah virus, a zoonotic paramyxovirus found in pigs and bats which was responsible for those sporadic cases in children especially with encephalitis. Often the patient’s age, the travel history and possibly the exposure to rodent bites, ticks or other animal bites can help to secure a diagnosis.

Grossly, all human exposures to rabies were fatal until the discovery of a vaccine in 1885 by Louis Pasteur and Emile Roux, harvested from infected rabbits. Other countries have used similarly nerve tissues to create a vaccine. In 1967 a human diploid cell rabies vaccine was introduced but now we used a less purified chicken embryo cell vaccine while a purified Vero cell vaccine is also available.

A recombinant vaccine called VRG is being used in Belgium, France, Germany and the United States to prevent outbreaks in undomesticated animals. All domesticated animals are required to be vaccinated. In Asia, Africa and most of the Americas, dogs remain the principal host but mandatory vaccination of animal is less effective in rural areas. Oral vaccines are distributed in baits, a practice that has successfully reduced Rabies in the wild animal population in Canada, France, and United states specially to control the racoon population.

Deaths due to rabies nowadays, from dogs and cats, have dropped to a low from 100 a year, to now only one or two cases a year due to the widespread domestic animal vaccination. With the development of human vaccine and immunoglobulin treatment, more deaths are now seen with bat bikes which unfortunately can remain untreated because they may go unnoticed.

Treatment after exposure can prevent the disease within ten days. The vaccines are 100% effective when given early after exposure. Yearly, more than 15 million people get vaccinated after exposure. It is recommended in the US to receive one dose of human rabies immunoglobulin (HRIG) and four (4) doses of rabies vaccine over a 14-day period. HRIG may be expensive but it is better injected around the bites or deep intramuscularly away from the vaccination site.

People who have previously vaccinated against rabies, do not need to receive the immunoglobulin but can receive only the post exposure vaccination on day 0 and 3. The old nerve tissue-based vaccination which required multiple injections to the abdomen, is now being phased out to be replaced by a more affordable vaccine implemented by the World Health Organization. It is given Intramuscularly in the deltoid muscle and not in the gluteal area.

Circumstances in which a bat may be found in the room of a child mentally challenged or an intoxicated person can become an indication for a post exposure prophylaxis (PEP). This has been supported by a 2002 study to be an indication of support to recommend PEP for prophylaxis, when an individual has been found alone with a bat in his/her sleeping areas with a possible exposure which the patient may be unaware.

The Milwaukee protocol and the Recife protocol were proposed in 2003 when tested on a symptomatic teenager” Jeanna Giese”. She became the first person to have survived Rabies without any preventive treatments. They discussed the basic idea to put a person into a chemically induced coma and to use antiviral medication to prevent fatal outcome. The protocol was criticized and found unethical but others found it ineffective with concerns to the costs and the ethics.

Vaccination after exposure (PEP) is highly successful in preventing rabies. In unvaccinated humans, rabies is almost always fatal after neurological symptoms have developed. In 1990, 54,000 people died from rabies especially in Asia and Africa.  In 2010, 26,000 people lost their life to the disease. In 2015, India followed by China (6000) and the democratic republic of Congo (5600)) were accounted. Global Alliance for Rabies has a goal to eliminate deaths from rabies by the year 2030. This goal is supported by the World Health Organization (WHO), the World Organization of Animal Health (OIE) and the Food and Agriculture Organization of the United Nation (FAO).

Why does India have the highest rate of human rabies in the world? Simply because of the stray of dogs which has increased since a 2001 law forbade their killing. There is a mass hysteria known as the puppy pregnancy syndrome (PPS) which make dog bite victims believe that once they are bitten by a dog, there is a puppy growing inside them forcing them to seek for a faith healer but not for medical advices.

Around 20,000 people die every year from Rabies. In Australia, all rabies cases were due to bat bites and all were fatal. Three cases were compiled. In United States, domesticated animals are all vaccinated and cases of rabies are common in wild animals like bats, raccoons, skunks, foxes, although 100 dogs were found infected in the wild life. The most recent rabies’ death in the United States was in Illinois mainly because the male victim chose to refuse treatment following a bat bite in the neck.

In Europe, few cases of rabies are reported in any given tear but any case can be contacted during travelling as well. In Switzerland, the disease is practically eliminated since scientists placed chicken heads laced with vaccine in the Swiss Alps. Italy was declared free of rabies until 2008 but a re-emergence of the disease in the wild following a reported epidemic in the Balkans. It also affected Austria where an extensive program of vaccination is on the way. The United Kingdom is free of disease but only one fatal case since 2000 has been reported. Being an island, the United Kingdom is protected by quarantine procedures. Mexico is free of rabies and since 2019, no human transmission has been recorded.

Rabies is infectious to mammals and three stages of the central system infection are recognized.  The first stage is the prodromal stage during the first 3 days and is characterized by behavior changes. The second stage is the excitative stage lasting 3 to 4 days. This stage is often known as “Furious Rabies” with often the animal to be hyperactive to external stimuli and has a tendency to bite. The third stage is the paralytic stage caused by the damages produced to the motor neurons bringing incoordination, limb paralysis and drooling with difficulty in swallowing and subsequent paralysis of the face and the throat muscles. Death will follow by respiratory arrest.

I would not like to conclude without extending a little on the seasonal problem with rabies in our country of Haiti. We do have the highest rate in human rabies deaths in the western hemisphere with around 2 deaths a week but only seven deaths were reported to the healthcare authorities surely because of a poor surveillance and a limitation in our diagnostic capabilities or simply by a lack of education in the population. In 2017, rabies was still considered as a national problem.

Although only a few cases of human rabies are reported to health authorities. In 2016, a woman who had been exposed to rabies three months prior to be seen showing symptoms. She was evaluated at a hospital where no treatment were administered to her. Even after being reported to both the CDC and the national Department of Epidemiology and Laboratory Research (DELR), as required by Haiti’s surveillance program, the woman died. There is obviously a lack of communication and effectiveness in caring for human subjects in Haiti. The continued focus remains on eliminating dog-mediated rabies altogether.

I have my own experience with a rabid case while I was an intern on the Internal Medicine service of Professor Medard at the HUEH and we correctly diagnosed a young male patient with rabies. During his hospital stay, he exhibited all the clinical symptoms of the disease with finally neurological complications. The case was reported to the authorities, He was given proper vaccinations for a period of 14 days as per the protocol of the late 70’s, with multiple injection through the abdominal wall. His mind remained cleared while he was begging us to help him in staying alive.

I remained for a while attached to him and supported him during his admission/hospitalization and through his last moments but it became difficult for me as an intern, to accept the way, we were unable to make a difference and save his life. Once his meninges got involved in the process, it appeared to me that all hope were lost. He became incoherent and aggressive. I did not see a door of exit. It was for me a great moment to manifest my deception. I realized that once the disease presents itself with neurological signs, there were no chances of survival.

Meanwhile, I have learned that of the existence of Human diploid cell culture rabies vaccine (HDCV) or the purified embryo cell culture vaccine (PCEC) are being used for post exposure immunization against any human rabies infection. Healthcare providers are encouraged to administer a regimen of four (4) one cc or 1-mL dose of HDCV or PCEC vaccines intramuscularly to persons who have not been vaccinated for the disease… For the one unvaccinated, the first of the 4 doses, is immediately given after exposure (to a rabid animal) and additional doses are given on day 3, 7 and 13.

Individually, a post exposure prophylaxis (PEP) will require local treatment of the wound, vaccination and Immunoglobulin therapy occasionally depending on a prompt recognition of the symptoms or an adequate follow-up of the PEP use.

Dog vaccination remains the most effective way to control rabies in the dog population. It is true for all countries in the Americas. In Haiti, the United States Centers for Disease Control (CDC) is helping us in focusing on dog mediated rabies. Technicians have been trained to diagnose rabies while some laboratories can perform the direct Fluorescent Antibody test (DFA) or the Direct Rapid Immunohistochemistry test (dRIT).

The surveillance system is based on the report of a bite event to the medical providers or the medical centers. Then a rabies assessment is conducted while rabies officers try to locate the rabid animals to euthanize or quarantine them for two weeks. People of my generation remember well the “Chalan vehicle” catching in the streets the rabid dogs like they will do for the humans.

The World Bank has identified many low-income countries in Africa, Asia and the Americas where dog-mediated rabies, a major problem, resulted in thousands of deaths annually. In Haiti, these organizations have helped the MSPP to improve public education on Rabies. I learned also by my reading that the CDC and an NGO, the Christian Veterinarian Mission are helping in reporting cases of rabies. More, a dog vaccination program is also implemented. Rabid dogs bring a huge risk to people. I know that I can expand further on the problems in our country with our meager means and a population with a poor income per-capita. Health is an issue on which nobody can compromise.

I want to dedicate this page to all our medical students, interns, residents and attending affiliated to our Haitian health facilities who helped making a difference in our country. The case I share with you made me understand that our system was more effective perhaps at exterminating the rabid animals than saving any human who contacted the disease. I must take this opportunity to thank my friend Nadim Salomon MD, infectious disease specialist in New-York for providing me the most recent documentations on Rabies in our country of Haiti.


Maxime Coles MD
Boca Raton FL
November 2021



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