​Kembara Xtra - Medicine - Rabies

​Kembara Xtra - Medicine - Rabies 
A quickly progressing RNA rhabdovirus infection of the central nervous system (CNS) that affects both humans and mammals may manifest with signs of encephalitis or paralysis. It is also preventable by vaccination.
 CNS system(s) impacted
An alternative term for hydrophobia is difficulty to drink water.

All continents, with the exception of Australia and Antarctica, have cases of rabies.
More than 95% of rabies-related fatalities in humans happen in Asia and Africa.
Dogs are the most prevalent reservoir worldwide, but bats are the most prevalent reservoir in the United States.
There are typically only one to three cases per year in the United States; approximately one-third of those exposures take place outside of the country. Annual mortality is estimated at 55,000 worldwide.


Pathophysiology and Etiology 

 Bullet-shaped encapsulated, negative-sense single-stranded RNA, neurotropic virus of the family Rhabdoviridae; genus Lyssavirus. Transmission happens when an infected animal bites a person or when its saliva comes into touch with a mucosal membrane or an open wound.
- In North America, 33% and 60% of bat-variant virus cases in humans do not mention previous bat encounter or bites or scratches.
- There have been isolated instances of transplanted organ infection and laboratory aerosolization.
The virus replicates in the muscle after being transmitted, and it binds to acetylcholine receptors at the neuromuscular junction. The virus enters the CNS retrogradely by neurons, where it infects the dorsal ganglia and causes pain. The salivary glands are one organ where viral replication in the brain might spread to after being shed.

Risk Elements 
Animal handlers, lab workers, vets, and cave explorers are examples of occupations or activities that may expose one to infected animals. Other risk factors include travel to regions where canine rabies is an endemic problem.
The majority of cases in the US are linked to bat exposure.
There have been reports of human-to-human transmission through cornea, solid organ, and other tissue transplants. Exposure occurs internationally through both domestic and feral dogs. 

Prevention 

Preexposure vaccination is recommended for high-risk groups, such as veterinarians, animal handlers, wildlife rangers, and some laboratory professionals, when visiting regions of the world where there is a higher chance of contracting rabies from domestic animals, such as North Africa.
Source reduction and avoidance - Since the 1950s, the United States has seen a remarkable drop in cases due to the immunization of dogs and cats.
- Avoid approaching or handling any wild (or domestic) animals displaying unusual behavior and call animal control instead.
Post-exposure prophylaxis: If you have been bitten, scratched, or come into touch with potentially infectious animal saliva, get medical attention right away.
- By receiving prompt post-exposure care, prevent infection.
- If someone comes into direct touch with bats, they should think about postexposure prophylaxis.
- Hospital contacts of rabies patients do not need postexposure prophylaxis unless they have been exposed to saliva, cerebrospinal fluid (CSF), or brain tissue from the infected patient through mucosal membranes or an open wound (including a bite).
- Patients in hospitals should be placed in contact isolation with gowns, gloves, masks, and protective eyewear.

Diagnoses 
Diagnoses can be made postmortem via brain biopsy or antemortem via isolation of the virus or antibodies in the serum, saliva, CSF, or nuchal biopsy.

The majority of patients do not remember being exposed to animals in their past. Five stages (may overlap):
- Incubation period: The interval between a bite and the development of symptoms is between: from a week to a year
- Prodrome: lasts for days to weeks and consists of generalized symptoms like fever, lethargy, and anorexia plus/minus pain and paresthesia at the infection site. Acute neurologic phase: 2 to 10 days long. CNS symptoms are predominant; typically one of two forms: Encephalitic (furious) rabies: hyperactivity with hydrophobia, aerophobia, hyperventilation, hypersalivation, and autonomic instability; develops to hallucinations, paralysis, and stupor (80% of cases).  Symmetric or asymmetric paresis in 20% of instances with paralytic (dumb) rabies, frequently beginning at the site of infection. Underreporting of paralytic rabies is a result of incorrect diagnoses,
Coma may develop over several days following an acute neurologic episode and remain for hours to days. It may also come on suddenly, accompanied by respiratory arrest. Death may occur days to weeks later as a result of diaphragmatic paralysis.

clinical assessment 
Depending on the stage of rabies at the time of presentation, symptoms might range from a normal physical to severe neurologic abnormalities, such as paralysis and coma.  Check the bite site for edema and excoriation.
Encephalitis causes varying levels of consciousness with hyperarousal and intervals of lucidity. Hydrophobia causes the diaphragm, pharyngeal muscles, and accessory neck muscles to spasm when the patient is asked to swallow water or is given a glass of water. Aerophobia causes the accessory muscles of the neck, pharyngeal muscles, and diaphragm to spasm when blowing or fanning air on the face. may display a terrified expression when these incidents occur.
 Hypersalivation, hyperhidrosis, anisocoria, mydriasis, piloerection, and priapism are symptoms of autonomic dysfunction. The nonspecific prodrome of fever, malaise, anorexia, and headache frequently occurs. Limb weakness may be the presenting symptom with paralytic rabies. Neuropathic and/or radicular pain, sensory impairments, and seizures may be the presenting symptoms with bat-variant rabies.

Differential diagnosis: Any encephalitis that is rapidly progressing; it's vital to exclude out treatable encephalitis causes such HSV encephalitis, Japanese encephalitis, West Nile virus, Eastern equine encephalitis, enterovirus, and Nipah virus. Transverse myelitis, Botulism, Tetanus, Substance Use Disorder with Intoxication, Guillain-Barré Syndrome, and

Laboratory Results 
Multiple types of samples are analyzed to improve the likelihood of a positive test: serum, saliva, CSF, and skin biopsy. The negative predictive value of laboratory testing is low due to a number of factors, including intermittent shedding, antibody generation, and phase of disease.

Caution 
In the case of suspected rabies testing, get in touch with the state or local health agency so that safe arrangements can be made for the collection and transportation of lab samples (skin biopsy, saliva, serum, and CSF) to the CDC.

Initial examinations (lab, imaging)
Lumbar puncture: normal white blood cell count or mild pleocytosis; normal or mildly increased protein; rabies antibody titer
Rabies antibody titer in serum
Reverse transcriptase and polymerase chain reaction (RT-PCR) on saliva or immunofluorescence virus isolation  Hair follicles must be included in a skin sample from the nape of the neck in order to detect rabies using RT-PCR and/or direct fluorescent antigen (DFA).
Hyponatremia is frequent, and 50% of patients have positive immunofluorescence results for corneal smear stains.
MRI can help rule out other types of encephalitis, while head CT exhibits normal or non-specific features associated with encephalitis.
Brain tissue examination using DFA or RT-PCR can be used to confirm postmortem diagnoses.
Tests in the Future & Special Considerations
examining/testing the alleged swift animal:
 Submit the brain tissue from at least two different locations, preferably the brainstem and the cerebellum of the suspected rabid animal for direct fluorescent antibody testing if possible. No case of human rabies in the United States has been linked to a dog, cat, or ferret that remained healthy throughout the standard 10-day period of confinement after an exposure.
Interpretation of Tests
Brain biopsies may reveal encephalitis. Other abnormalities are frequently discovered only after death, such as brainstem, midbrain, and cerebellum.
Negri bodies are round or oval eosinophilic inclusions that are present in the cytoplasm of the Purkinje cells in the cerebellum and the pyramidal cells of the Ammon horn.

Management 

Analgesia and sedation are used as palliative care once symptoms have manifested. Patients receiving postexposure prophylaxis after being exposed to rabies but before developing symptoms. People who are at risk for infection utilize preexposure prophylaxis.

General Actions 
The first line of treatment is thorough wound cleaning with soap and water. If virucidal agent is available, such as povidone-iodine, apply it to the wound.

Medication 

Caution 

 Based on the conditions of a potential exposure, determine the necessity for postexposure prophylaxis with local wound care, rabies vaccine, and rabies immunoglobulin (RIG), and seek advice from public health professionals.
Greater risk is associated with bites that penetrate the skin as opposed to scratches; saliva exposure only poses a threat when it comes in touch with open sores or mucous membranes.
- Lack of availability of wild or domestic animals for quarantine
- Bat exposure - Wild-domestic hybrid animals (like wolfdogs)
- An attack that was not provoked (feeding a wild animal is regarded as provoking an attack).
Management: Unless the animal exhibits symptoms of sickness, prophylaxis is not necessary for bites from cats, dogs, and ferrets that can be observed for 10 days.
- The majority of carnivores, including raccoons, foxes, bats, and skunks, provide a significant danger, so prophylaxis should start right away unless the animal can be caught and put to sleep for a pathologic examination.
- Before beginning prophylaxis for rodents or cattle, check with your local public health authorities.
Postexposure prophylaxis: RIG (HyperRAB) 20 IU/kg given once as a passive vaccine. If feasible, infiltrate RIG close to the wound. administer the rest of the RIG IM. Use a different syringe or avoid injecting RIG into the same area of the body as the immunization.
- Active immunization: injection in the deltoid with purified chick embryo cell vaccine, human diploid cell vaccine (HDCV), rabies vaccine adsorbed (RVA), or rabies vaccine.
As soon as possible after exposure, administer the initial dose of 1 mL. Day 0 is the day of the initial dose.
On days 3, 7, 14, and 28, provide additional 1-mL doses.
For children, avoid the gluteal region and use the anterolateral side of the thigh.
- Immunity following vaccination is changed by immunosuppression.
If at all feasible, avoid using immunosuppressive medications during postexposure prophylaxis. Check serum samples for the presence of rabies virus-neutralizing antibodies if postexposure prophylaxis is administered to an immunosuppressed patient to gauge response to vaccination.
Patients who have had the vaccination before should receive two 1-mL doses: one right away and the other three days later. In these patients, RIG is unnecessary.
Preexposure immunization is recommended for persons in high-risk occupations such veterinarians, animal handlers, wildlife rangers, specific laboratory professionals, and those traveling to nations where rabies is enzootic. - Primary preexposure: 3 intramuscular 1-mL injections of HDCV or RVA on days 0, 7, and 21, or 28 in the deltoid area
- Preexposure boosters: Perform serum tests on individuals at risk of rabies exposure every two years. If immunity is dwindling, administer a 1-mL IM preexposure booster.
A booster can be given in its place if titer cannot be acquired.
 Negative effects: 0.6% of patients who receive HDCV boosters experience minor serum sickness reaction.


Further Treatments 
A palliative strategy is required for treating symptomatic rabies, and analgesia, sedation, and seizure control should be the main priorities.
Milwaukee protocol: experimental therapy including ketamine, midazolam, and amantadine; ribavirin was initially used but is no longer advised.
In 2004, amantadine and a medically induced coma were used to treat a patient with clinical rabies who had not received pre- or postexposure prophylaxis.
 Manage cerebral artery vasospasm (with a substance like nimodipine).
 Fludrocortisone and hypertonic saline, if necessary, to keep the sodium level normal.


Rabies has the greatest case fatality rate of any infectious disease if left untreated; once symptoms appear, it is typically thought to be 100% fatal.
Less than 20 cases of clinical rabies survivors have been reported so far. Almost everyone received a pre- or postexposure vaccination.

Complications
Multiorgan failure develops in the later stages of the illness:
Arrhythmias of the heart, heart failure, cardiac arrest, and myocarditis. Hyperventilation, hypoxia, respiratory depression, aspiration pneumonia, and neurogenic pulmonary edema. - An intestinal bleeding
There are many accounts of neurologic damage in the extremely rare instances that patients survive.

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