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Rabies

Disease Details

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Description: Rabies is a viral disease that causes acute inflammation of the brain in humans and other mammals, typically transmitted through the bite of an infected animal.
Type: Rabies is a viral disease. It is typically spread through the saliva of infected animals via bites or scratches, not through genetic transmission.
Signs And Symptoms: The period between infection and the first symptoms (incubation period) is typically one to three months in humans. This period may be as short as four days or longer than six years, depending on the location and severity of the wound and the amount of virus introduced. Initial symptoms of rabies are often nonspecific such as fever and headache. As rabies progresses and causes inflammation of the brain and meninges, symptoms can include slight or partial paralysis, anxiety, insomnia, confusion, agitation, abnormal behavior, paranoia, terror, and hallucinations. The person may also have fear of water.The symptoms eventually progress to delirium, and coma. Death usually occurs two to ten days after first symptoms. Survival is almost unknown once symptoms have presented, even with intensive care.
Rabies has also occasionally been referred to as hydrophobia ("fear of water") throughout its history. It refers to a set of symptoms in the later stages of an infection in which the person has difficulty swallowing, shows panic when presented with liquids to drink, and cannot quench their thirst. Saliva production is greatly increased, and attempts to drink, or even the intention or suggestion of drinking, may cause excruciatingly painful spasms of the muscles in the throat and larynx. Since the infected individual cannot swallow saliva and water, the virus has a much higher chance of being transmitted, because it multiplies and accumulates in the salivary glands and is transmitted through biting.Hydrophobia is commonly associated with furious rabies, which affects 80% of rabies-infected people. This form of rabies causes irrational aggression in the host, which aids in the spreading of the virus through animal bites; a "foaming at the mouth" effect, caused by the accumulation of saliva, is also commonly associated with rabies in the public perception and in popular culture. The remaining 20% may experience a paralytic form of rabies that is marked by muscle weakness, loss of sensation, and paralysis; this form of rabies does not usually cause fear of water.
Prognosis: Vaccination after exposure, PEP, is highly successful in preventing rabies. In unvaccinated humans, rabies is almost certainly fatal after neurological symptoms have developed.
Onset: Rabies onset typically follows an incubation period that can range from a few days to several months, with most cases occurring within 1 to 3 months after exposure. Early symptoms may include fever, headache, and general weakness or discomfort. As the disease progresses, more specific symptoms such as insomnia, anxiety, confusion, paralysis, hallucinations, agitation, hypersalivation, difficulty swallowing, and hydrophobia (fear of water) can occur. Once clinical symptoms appear, rabies is almost invariably fatal.
Prevalence: Rabies is a viral disease that affects the central nervous system of mammals, leading to brain inflammation and, almost invariably, death once symptoms appear.

**Prevalence:**
Rabies is most prevalent in Asia and Africa, where it is a significant public health problem. Worldwide, it is estimated that rabies causes around 59,000 human deaths annually. Domestic dogs are the most common source of human rabies deaths, especially in areas where vaccination of dogs is not widespread. In contrast, in many developed countries, rabies cases are rare due to rigorous pet vaccination programs and animal control measures.

**Nan:**
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Epidemiology: In 2010, an estimated 26,000 people died from rabies, down from 54,000 in 1990. The majority of the deaths occurred in Asia and Africa. As of 2015, India (approximately 20,847), followed by China (approximately 6,000) and the Democratic Republic of the Congo (5,600), had the most cases. A 2015 collaboration between the World Health Organization, World Organization of Animal Health (OIE), Food and Agriculture Organization of the United Nation (FAO), and Global Alliance for Rabies Control has a goal of eliminating deaths from rabies by 2030.
Intractability: Rabies is considered intractable once clinical symptoms appear. It is almost universally fatal at this stage. However, if exposure is suspected, prompt administration of post-exposure prophylaxis (PEP) can prevent the onset of the disease, effectively making early intervention crucial.
Disease Severity: Rabies is a severe viral disease that affects the central nervous system. It is almost always fatal once symptoms appear, making it exceptionally severe. Early vaccination post-exposure can prevent the onset of symptoms and save lives.
Healthcare Professionals: Disease Ontology ID - DOID:11260
Pathophysiology: Rabies is a viral disease that primarily affects the central nervous system (CNS).

**Pathophysiology:**

1. **Entry and Initial Replication:** The rabies virus enters the body typically through a bite or scratch from an infected animal. The virus initially replicates in the muscle cells at the site of entry.

2. **Neuromuscular Junction:** The virus eventually reaches the neuromuscular junction and binds to nicotinic acetylcholine receptors.

3. **Peripheral Nervous System (PNS):** From there, the virus travels along peripheral nerves towards the central nervous system by retrograde axonal transport.

4. **Central Nervous System (CNS) Involvement:** Upon reaching the CNS, the virus rapidly replicates and spreads throughout the brain, causing encephalitis. This leads to the clinical symptoms associated with the disease, such as agitation, hydrophobia (fear of water), and confusion.

5. **CNS to Peripheral Spread:** The virus also spreads centrifugally through the nerves to various other tissues, including salivary glands, skin, and eyes, facilitating further transmission via saliva.

The disease progression is typically rapid once symptoms appear, and it is almost always fatal if not treated promptly with post-exposure prophylaxis before symptom onset.
Carrier Status: Rabies is a viral disease that affects the central nervous system of mammals. It is typically transmitted through the bite of an infected animal. The virus travels from the site of infection to the brain, causing inflammation and symptoms.

**Carrier Status:** Animals, especially mammals such as bats, raccoons, skunks, foxes, and domestic dogs and cats, can be carriers of the rabies virus. Infected animals can transmit the virus to humans and other animals through their saliva, primarily via bites. Humans are not typically carriers of the virus; they either clear the infection following post-exposure prophylaxis or develop symptomatic rabies, which is almost invariably fatal if untreated before symptom onset.
Mechanism: Rabies is a viral disease that primarily affects the central nervous system. The causative agent is the rabies virus, a member of the Lyssavirus genus within the Rhabdoviridae family.

### Mechanism:
1. **Transmission and Entry**: Rabies virus is typically transmitted through the saliva of an infected animal, most often via a bite. The virus enters the body through the wound.

2. **Initial Replication**: Once inside the host, the virus initially replicates in local tissues, such as muscle cells, near the site of entry.

3. **Neuronal Transport**: The virus then binds to nicotinic acetylcholine receptors at the neuromuscular junction. From there, it hijacks the host's retrograde axonal transport mechanisms to travel within peripheral nerves to the central nervous system (CNS).

4. **Central Nervous System Involvement**: Within the CNS, the virus undergoes extensive replication, particularly in the brain, leading to widespread neuronal dysfunction.

5. **Descending Spread**: The virus also spreads centrifugally from the CNS back to various body tissues, including salivary glands, facilitating transmission to new hosts.

### Molecular Mechanisms:
1. **Virus Structure**: The rabies virus is an enveloped, negative-sense, single-stranded RNA virus. The envelope contains glycoprotein spikes that are critical for viral entry into host cells.

2. **Glycoprotein Function**: The glycoprotein (G protein) on the viral envelope binds to nicotinic acetylcholine receptors and additional neural cell adhesion molecules (NCAMs), facilitating entry into neurons.

3. **RNA Transcription and Replication**: Inside the host cell, ribonucleoprotein complexes aid in the replication and transcription of viral RNA. The RNA-dependent RNA polymerase transcribes the viral RNA genome into mRNA, which is then translated into viral proteins.

4. **Immune Evasion**: The rabies virus employs several strategies to evade the host immune response, including fast transport within neurons, minimizing exposure to the immune system, and suppression of interferon signaling pathways. The phosphoprotein (P protein) of the virus can inhibit host immune responses by interfering with interferon signaling.

5. **Pathogenesis**: The accumulation of viral particles and alteration of host cell functions lead to neuronal apoptosis and dysfunction. This results in the classic symptoms of rabies, such as encephalitis, hyperactivity, hydrophobia, and ultimately, death if untreated.

Understanding these mechanisms is critical for developing effective treatments and preventive measures, such as rabies vaccines and post-exposure prophylaxis.
Treatment: Rabies treatment is immediate administration of post-exposure prophylaxis (PEP), which includes wound cleaning, a series of rabies vaccinations, and in some cases, rabies immunoglobulin (RIG) to provide immediate antibodies. There is no cure once symptoms appear, making PEP essential for preventing the disease after exposure.
Compassionate Use Treatment: Compassionate use treatments for rabies may include the Milwaukee Protocol, which is an experimental and aggressive treatment approach involving induced coma and antiviral medications. However, this method has had limited success and remains controversial. Off-label or other experimental treatments might involve the use of antiviral drugs and immunotherapies that are not yet standard care but show potential in research settings. It's crucial to remember that rabies, once symptomatic, is nearly always fatal, and these treatments are typically pursued in dire situations.
Lifestyle Recommendations: Rabies is a serious viral disease that affects the central nervous system of mammals, including humans. Here are lifestyle recommendations to help prevent rabies:

1. **Vaccinate Pets:** Ensure that your dogs, cats, and ferrets are vaccinated against rabies. Stay up-to-date with their vaccinations as recommended by your veterinarian.

2. **Avoid Wild Animals:** Do not approach or handle wild animals, particularly those that are known carriers of rabies, such as bats, raccoons, skunks, and foxes.

3. **Secure Garbage:** Keep your garbage securely covered to avoid attracting wild animals to your home.

4. **Supervise Pets:** Keep pets under direct supervision when they are outside to prevent them from interacting with potentially rabid animals.

5. **Report Stray Animals:** Notify local animal control authorities if you see stray animals or animals behaving unusually.

6. **Travel Precautions:** If traveling to areas where rabies is common, consider getting a pre-exposure rabies vaccination and avoid contact with animals.

7. **Wound Care:** If bitten or scratched by an animal, wash the wound thoroughly with soap and water and seek medical attention immediately.

8. **Educate:** Teach children about the dangers of approaching unfamiliar animals and the importance of reporting bites or scratches.

Adhering to these lifestyle recommendations can significantly reduce the risk of rabies exposure.
Medication: For rabies, the treatment typically involves a series of post-exposure prophylaxis (PEP) injections. This includes one dose of rabies immune globulin (RIG) and a series of rabies vaccines administered over a specific schedule, usually on days 0, 3, 7, and 14. If exposure is suspected or confirmed, it's crucial to clean the wound immediately and seek medical attention as soon as possible.
Repurposable Drugs: Repurposable drugs for rabies have been explored with limited success. Historically, the Milwaukee Protocol, which involved the use of drugs like ketamine, midazolam, and amantadine, is the most well-known experimental treatment. However, it has shown limited success and remains controversial. Other antiviral drugs like ribavirin and interferon-alpha have also been considered but have not demonstrated consistent efficacy. The primary prevention remains post-exposure prophylaxis with rabies vaccine and immunoglobulin.
Metabolites: Rabies does not typically involve a specific set of metabolites used for its diagnosis or monitoring. Instead, diagnosis is primarily based on detecting the rabies virus or its antigens in tissue samples, often using techniques like direct fluorescent antibody testing, PCR, or virus isolation. Metabolomics, which studies metabolites, is not a standard approach in the clinical handling of rabies.
Nutraceuticals: Nutraceuticals are not a recognized treatment or preventive measure for rabies. Rabies is a viral disease that affects the central nervous system and requires immediate medical attention. The most effective prevention method is vaccination, both pre-exposure for at-risk individuals and post-exposure following a potential rabies exposure. Post-exposure prophylaxis (PEP) includes thorough wound cleansing and administration of rabies immunoglobulin (if indicated) and a series of rabies vaccinations. Prompt PEP is crucial, as rabies is almost universally fatal once clinical symptoms appear.
Peptides: Rabies is a viral disease that affects the central nervous system, primarily causing encephalitis. When discussing peptides in the context of rabies, it usually pertains to the development of peptide-based vaccines or therapeutic agents that target the rabies virus, aiming to neutralize it or inhibit its replication.

Nan refers to nanotechnology, which plays a role in the advancement of rabies treatment and prevention. Nanoparticles can be used to enhance vaccine delivery, improve the stability of antigens, and target virus-infected cells more effectively. Nanotechnology can also help in the development of diagnostic tools for early detection of the rabies virus.