E1 the rabies transmission diagnosis treatment and prevention by TANGRAM

The rabies: transmission, diagnosis, treatment and prevention. 1

2 LiraLuna Jaquelín , RodríguezVilchis Ricardo

2 Student of the Medicine career. FESIztacala. UNAM, Teacher of the Medicine career. FESIztacala. UNAM

Abstract The rabies is an acute viral infectious disease that affects the central nervous system, it is adapted to replicate in mammals encephalon including humans, affecting the limbic area producing changes in animals behavior. It can manifest itself in two ways the paralytic form and the furious form, making the last one the most dangerous for the risk of contagious by bites of the infected animals, although bites is not the only way to acquire rabies virus in humans.There are reports of infection after organs transplant and the exposure by aerosol sprays. The rabies is called hydrophobia, derriengue, tronchado, rabies and lyssa. In Mexico, sylvatic rabies it is enzootic in vampires hematofogos (Desmodus rotundus) and is responsible in the 74%of the sylvatic rabies cases and are natural reservoirs and principal vectors of rabies in cattle. Coyotes, foxes, skunks, raccoons and possibly other wild mammals are also reservoirs of rabies virus.

Exist vaccine preexposure and post exposure but the use of it is limited because it depends of many vaccines and the cost is high for use as a preventive measure. Keywords: Rabies virus, human infection, rabies vaccine, rabies treatment, diagnosis of rabies. The rabies is an acute viral infectious disease that affects the central nervous system, it is progressive and incurable, the rabies virus produces severe encephalitis with a hundred percent close mortality. This infection can be transmitted to persons of any age, with antecedents of 1 domestic or wild animal attacks

The causal agents are the RNA of the virus of Mononegavirales order, family: 2 Rhabdoviridae, gender: Lyssavirus, species: rabies virus (RABV) . It has a projectile

form, with a 180 nm longitude and a 75 nm diameter on average.The nucleocapsid is involved by the lipoprotein matrix membrane (M) from 7.5 to 10 nm thickness and in the superficial part, are the glycoprotein peplomer, except in the rome portion of the particle. Actually there have been recognised 7 genotypes, all adapted to be

replicated in mammals encephalon, but the most affected species are chiroptera or bats and the carnivores or dogs. The glycoproteins (GP) are micro protuberances or superficial spikes that work like receptor ligands of the cell, the variability of this antigen (Ag) would explain the differences between the known Lyssavirus genotypes and it induces the formation of neutralizing antibodies. When in a mutation it is substituted the glutamine or isoleucine by arginine in the 333 portion of the viral genome, the virulence of the strain is modified because the arginine waste is essential for the fusion of the viral envelope with the neuron of the host and some others physicochemical changes of the glycoprotein are used to increase virus immunogenicity. The selective union of the virion to the neuron membrane is realized by a ganglioside and other means, like the adhesion molecule CD56; but in a muscular level the virus joins to the receptor of nicotinic acetylcholine acid where is internalized by endocytosis and mixed with the lysosome and the nucleocapsid escapes to the cytosol. It is known that the lipoprotein envelope of the virion is from cell origin and in it has inserted the glycoproteins of the membrane. The virus don't tolerate a lower 3.0 pH and high 11.0 pH; it is inactivated for ultraviolet light, sunlight, drying or exposure to formaldehyde, to the trypsin, the β 3 propiolactone and detergents.

It is in the cytoplasm of the white cell (neuron) where the viral replication happens, nevertheless this cell doesn´t have any enzyme able to transcribe and replicate the RNA starting from a template strand, for this reason the virus has its own transcriptase and replicase, using from the cell host just the function of proteins 4 translation and the synthesis of amino acids, lipids and nucleotides.

The rabies is called hydrophobia, derriengue, tronchado, rabies and lyssa. In Mexico, sylvatic rabies it is enzootic in vampires hematofogos (Desmodus rotundus) and is responsible in the 74% of the sylvatic rabies cases and are natural reservoirs and principal vectors of rabies in cattle. Coyotes, foxes, skunks, raccoons and 3,6 possibly other wild mammals are also reservoirs of rabies virus.

Small rodents (rats, squirrels) and reptiles, rarely or never serve as a reservoir of rabies in nature or as vectors for man.

There are two epidemiologic ways of rabies: the urban, usually spread by dogs. It can be manifested in a furious or paralytic way. And the sylvan form, vulgarly called 5 “derriengue”.

The rabies virus is found in saliva and infected animals excretions and inoculates the men when the animal carrier attacks and produces him some injury for bite in any 1 part of the body. The virus can´t be transmitted by healthy skin.

There are reports of exceptionals cases of transmission by other ways. They have been registered some cases after organ transplant like corneas, pancreas, kidneys and liver. It is documented the transmission by aerosol sprays on special circumstances for example in labs or bat caves with high viral load aerosolized virus particles viable. Pasteurized milk and cooked meat should not pose a risk of infection because the virus is inactivated with high temperature,but it shouldn't suggest the 6 consumption if it comes from infected animals.

In the period of 19901995, in Mexico were reported cases of human rabies, the state of Mexico was the entity with more reported cases, followed by Puebla with 31 cases, Mexico City with 27, Oaxaca with 24, Guerrero with 19 and Jalisco with 9 7 cases.

In ancient times the violent and irritable conduct in dogs was observated in hot weather, for that reason this seasonal period was known as “canícula” by the action 8 of the Sirio star of the constellation Canis Major over the sun.

Pathogenicity After the bite by an infected animal, the rabies virus is inoculated in the tissues and subcutaneous muscle, the infection of the muscle fibers is a several pathogenic 2 phase to the access of the virus into de periferic nervous system.

The centripetal transport of the virion into the axonic flow to the central nervous 10 system (CNS) has 3 mm/hr speed (approximately 5 cm by day). The virus

dislocates to CNS in motor and sensory axons by retrograde fast axonal transport. Axonal transport of rabies virus occurs exclusively in the retrograde direction. In the affected neurons of the spinal cord, occurs a post dissemination neuron by neuron into the axon of the CNS; by the fast axonal transport

in neuroanatomic

connections. Many types of neurons are infested by the virus in a wide dissemination in the CNS; infection of nonneuronal cells occurs with a much lower frequency.

Brain infection causes behavioral changes due to infection of neurons in limbic areas, which facilitates transmission vectors bites in rabies. It is easy the transmission of rabies by bites because the brain infection produces alterations in neurons of limbic areas, producing changes in the behavior of the host. There is a distant spread of the virus of CNS (centripetal dissemination) for neural pathways, usually involving the parasympathetic nervous system, who is responsible of salivary glands infection. Neurons infected with rabies may not operate normally due to degenerative changes that affect neural processes, including dendrites and axons. Rabies can differentiate into stages or periods in human: The incubation period is long and variable depending on the site of inoculation of virus, lasting 20 to 90 days; however, in humans this period can in rare cases, 9 exceed one year.

In the prodromal period general symptoms appear, making it difficult to determine which pathology affects the host, such as fatigue, weakness, loss of appetite, headache, fever and other discomfort. This may suggest the condition of the respiratory tract, the gastrointestinal system or CNS. Paresthesia or itching at the site of the bite is common, acute nervous system dysfunction can lead to paralytic rabies or furious. The short and hectic clinical course is initially characterized by hydrophobia (in 80% of patients), aerofobia and extreme excitement periods, interspersed with intervals of lucidity and complete understanding, unconsciousness and complete paralysis that 10 is followed by death, often due to respiratory failure.

The patients with furious form generally die into the first 7 days after the start of initial signs, although the survival can be so long as 2 or 3 weeks in paralytic form. Neurotropic virus can cause brain death by necrosis or apoptosis process, the rabies caused by canine variants of rabies virus can produce worse results than the caused by variants of the bat. The therapeutic coma to treat patients with neurological problems caused by rabies 11 virus should not be taken as a routine therapy because it has not tasted succesful.

It is vital laboratory diagnosis of rabies that is fast and accurate in humans in order to timely administer prophylaxis for postexposure.Traditional methods of microscopy tissues were simple and fast but has low sensitivity and only made with fresh tissues. Serological methods such as fluorescent antibody technique (FAT) and immunoenzymatic are rapid diagnosis of rabies (RREID) techniques they are widely used for postmortem diagnosis and have high sensitivity close to 100%. The new molecular methods based in PCR in real time permit the diagnosis antemortem and postmortem with a high sensibility, it can be realized in saliva, skin biopsy, cerebrospinal fluid, brain tissue and head. This technique can be used to examine donors who are at high risk of rabies, and to analyze facilitating viral load monitoring of the disease and the effectiveness of the experimental therapy. Currently the technique of realtime PCR is the only recommended for antemortem diagnosis of 12 rabies human kind.

The rabies can be prevented by postexposure prophylaxis (PEP), intradermal vaccines with potent prophylactic immunoglobulins are supplied shortly after the animal bite. The problem with this vaccine is the high cost to use it like prevention way, also the victims do not conclude in adequate way the treatment, mainly for not complying parameter recommended doses. Initially it was considered the administration of 6 vaccines postexposition, in 2005 in order to reduce the dose recommended dose administered alone 5 after the bite on days 0, 3, 7, 14 and 28 or 30. However, recently based on a recommendation of an expert group of the Advisory Committee on Immunization Practices USA, can further reduce the rate of 5 to 4 doses, skipping doses of 28 since 2010. But according to the latest OMS recommendation, this shortened regimen should be administered only to healthy 13 people risk exposure to virus.

The intradermal regimen for preexposure rabies prophylaxis is more economical compared to conventional intramuscular regimen in terms of volume of vaccine and 14 medical expenses subsequent doses required.

To reduce costs vaccines suggests the possible development of a monoclonal antirabies recombinant human IgG1 (SII RMAB) to replace the immunoglobulin 15 derived from serum and make it cheaper.

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