Первый слайд презентации: RABIES - HYDROPHOBIA, LYSSA
Identification. R abies is a cute, vir al illness of warm-blooded animals and man which transmited at stings or wet with saliva by the sick rabies animal s with the subsequent development of a lethal encephalitis. Annually from rabies in the world up to 5000 m a n died
Historical reference: 322 up to AD - Aristotle has connected disease of with stings by the sick rabies animal s 1 st century AD - K. Celsus has termed illness as " hydrophobia" 1804 – Zinke has successfully infected a healthy dog with a saliva of a rabi d dog 1885 L.Pastreur - has created an antirabic vaccine 1892. B. Babes and A. Negri (1903) - have detected at a rabies of specific inclusion in nervous cells ( inclusions Babes-Negry) 1903 – P. Remlinger - has proved a vir al nature of a rabies
Слайд 3: ETIOLOGY: F. Rabdoviridae ( bulletformal ) K. Lyssavirus, size from 80 up to 180 nm. RNA (-) It is have the form remind ing a bullet. It i s covered with the bilayer LIPIDE envelope, on which surface is glycoprotein (G) and protein М1 and М2
The rabies virus is a Lyssavirus. The virus has a bullet-like shape with a length of about 180 nm and a cross-sectional diameter of about 75 nm. One end is rounded or conical and the other end is planar or concave. The lipoprotein envelope carries knob like spikes, composed of Glycoprotein G. Spikes do not cover the planar end of the virion. Beneath the envelope is the membrane or matrix (M) protein layer which may be invaginated at the planar end. The core of the virion consists of helically arranged ribonucleoprotein. The genome is unsegmented linear antisense RNA. Also present in the nucleocapsid are RNA dependent RNA transcriptase and some structural proteins.
In the external environment is unstable: - a t pasteurization perish through 5 - 10 minutes - a t boiling perish instantly I t` s sensitive to disinfectants and fat-solvents There is only one antigenic variant, represented by 4 serotypes ( CVS - 24, Logos bat, Mokola, Duvenhage) Distinguish: "Wild" virus: - high pathogenic for the man and animal s - w ill derivate in cells of inclusion of the Babes-Negri - Is sec re ted with a saliva animal s and man - damage peripheral nerves - a t intracerebral infection of the rabbits results in their de ath through 12 - 28 days
The «fixed" virus - is obtained L. Pasteur by numerous reinfection of the laboratory animal s - t he death of the rabbits does not cause at infection - w ill not derivate inclusion Babes-Negri - i s not sec re ted with a saliva - not damage p eripheral nerves - a t intracerebral infection of mice causes their de ath in 7 days (fixed incubation) The antibodie s against of glycoprotein shape immunity against a rabies, but only in presence virion. Complement-fixing antibod ies against of a nucleocapsid - do not render protective of operation
EPIDEMIOLOGY To a rabies are sensitive all mammals therefore it wide-spreads everywhere, except for: of Australia and Antarctic Continent. In England, Iceland, Cyprus, Japan, New Zealand, Norway, Sweden, Finland, Spain, Portugal and Hawaii practically does not meet because of strict of quarantine at import animal s ! At a rabies exists 2 type of the epizootics : Wild rabies – main reservuoir - wild predatory animal sets: dog s, feiidae, the marten and civet-cat family, cheiroptera. In se veral locales of the world prevail: skunks ( USA ), wolves (Iran), fox es ( Europe and Northern America), vampire- bats -( islands of Caribbean Sea, Southern America, Africa)
Urban rabies – main reservuoir : dog s ( 60 % - 90 %), cat s (10 %), cattle and horse - is very rare! ! The modes of transmission - contact - aerogenic ( seldom) The factors of transmission: - saliva animal at a sting or wet with saliva (through microtraumas) - d ust or saliva - in caves with bats The virus is sec re ted with a saliva animal for some days before disease and all period of one!
On the average hazard of infection at one sting makes 15 % but it depends on localization of a sting: - at stings of a head (90 %), - at stings of the hand s (63 %), - at stings of the proximal portions of arms, legs - (23 %) The man of epidemiological danger does not represent! The rabies more often meets in spring – summer year's months - 70 % falling ill - from urban of the centers - t he men make 75 % from among falling ill 60 % falling ill at stings behind a medical care did not apply - 50 % falling ill in the age of from 20 till 59 years
PATHOGENY 1. The virus penetrate s through a injure skin or mucous and starts to be multiplied in a striated muscle s and connective tissue within many weeks or months (therefore such long-lived incubation ) 2. Antibodies, interferons and other factors of protection of an organism of the man perniciously operates on virus - descendants leaving cell and only at an inconsistency of this protection the viruses can penetrate into the nervous endings
3. Penetrated in nervous trunks the viruses advance centripetal with speed 3 mm / hours, easily overcome of synaptic connection - from this moment disease and de ath infectious man or animals are inevitable ! 4. The viruses migrate in basal ganglions and CNS, whence on centrifugal neurones get in various tissues: salivary glands, cornea of an eye s, hair follicles of a head. Sometimes it is capable to penetrate into salivary glands through basal ganglions, passing a CNS 5. The de ath of the patients occurs because of bulbar disorders. 3 cases of recovery are only described!!
PATHOMORPHOLOGY The viruses cause degenerative d amages of neurones in area hippocampus, thalamus, basal ganglions, but is especial in the field of the bridge and bottom of the IV ventricle. Damage respiratory and С VS of centres and appearance of a hydrophobia – there is spastic stricture of inspiratory muscles at view of water or attempt use of one. The hydrophobia does not meet at other encephalitises, as only at a rabies the brainstem is damage d, but survive uninjured the cerebral cortex and is saved consciousness!! In the struck cells hippocampus the eosinophilic inclusions ( Babes-Negry ) will be derivated, but the absence them does not ixclude a rabies !!
Слайд 18: Hematoxylin and eosin stain of Negri body in a rabies-infected neuron
Hematoxylin and eosin stain of Negri body in a rabies-infected neuron.
CLINIC ( rabies has of the next periods of illness) Incubation interval from 1 to 12 months (on the average 20 - 120 days) Minimum incubation - 6 days. Maximum to the 1 year At infection from bats - 3- 4 weeks. More shortly incubation are for children and for the persons vaccinated earlier from a rabies ( reason? ) Prodromal stage ( duration from 2 to 10 days ) - h eadache, fatig ue, nausea, vomiting - s tep-by-step moderate increase temperature of the body - excitement and fear of death, feeling of constraint in a breast and pharynx, frightening dreams and insomnia - p ain and paresthesia in the field of a sting
OBJECTIVE - r eddening and edema of area of cicatri ce from a sting - d ryness of a mucous oral cavity - p hotophobia, acousophobia, mydriasis with saving of light response of pupils 3. Acute neurologic stage (2 - 10 days) Main sign - attack of a hydrophobia : at view of water s ud den start by all body, shivering arms try to repel water, a head and trunk deviate back. T he face is cyanotic, with express ion of fear and suffering. The mydriatic pupils, exophthalmos, tachycardia. A dyspnea of an inspiratory type with involvement of auxiliary muscles, the inspiration make difficult because of a contraction of muscles of a pharynx and convulsive contraction s of a diaphragm, exhalation surface
Duration of an attack - some seconds - minutes, but result anyone effect on the patient ( bright light, touch, view of water, noise, motion of air) - its repetition. The patients are exited, fussy, implore about the help. After ending an attack - are rather quiet, but then the delirium and hallucinations joins : - a re attempted to run, to keep them in bed very difficultly, jump up, cry, rend one`s garments, garrulous ( children ) - v oice hoarse, respiration surface and intermittent - trembling of the tongue and arms, then to them joins: n ausea, vomiting, hiccup, accumulation of viscid slime in a mouth - i n 1-2 days the saliva plentiful also trickle down on a chin - h yperhidrosis, hyperthermia. If the patient has not perished, the illness passes in stage of paralyses
Слайд 23: T he plentiful saliva trickle down on a chin
4. Stage of paralyses (« a stage ominous of calm » ) - excitement and the cramps stop - s tarts to drink water and eat, the respiration becomes quiet - s ubjectively feel better, occurs belief in convalescence, but then in 1-2 days: - t he tachycardia accrues and is reduced BP - t he fever increases up to 42- 43 d.C. The paralyses of a various expressiveness and localizations are appeared ( in 20 % - uprising paralys i s Landry ) The mors of the patient occurs suddenly and without agony !
The se veral stages of illness can miss: the prodrome, violence, hydro or aerophobia, but it are found is very rare! Also the people have seldom cases of a " SILENT " rabies Thus all starts with paralyses more often uprising without hydro and an aerophobia (or they are weakly expressed) Current more long-lived, but is completed by bulbar violations and de ath of the patient - this form more often after stings of bats develops
DIFFERENTIAL DIAGNOSIS With other encephalitises, but if the brainstem is only d ama g ed at the saved consciousness and absence of sign s of the volumetric process of a brain - all versions are deflected !! By tetanus - there is no hydrophobia, but is constant of tonic tension of muscles and clonic cramps By botulism - general paralyses, there is no e xit ation and hydrophobias, touch violations and hyperthermia By hysteria - there are no changes of acid-base balance, absence of variations the eccentric behaviour of the patient also is not present a hyperthermia w ith a syndrome Guillain-Barre, polymyelitis, encephalomyelitis after antirabic vaccinations.
LABORATORY DIAGNOSIS At life of the patient: IFt of impressions of a cornea eye and sections of a skin in the field of a neck on boundary of growth of hair Selection of a virus with CSF, saliva, tears B iological test on mice de ath them in 7 days at intracerebral infection PCR ELISA - after escaping an acute neurologic stage After mors of the patient D etection inclusions Babes-Negry and usage IFt with biopsy material. Any positive test confirms the diagnosis even if others were negative!! All patients who have perished from an unknown encephalitis are subject to inspection on a rabies!!
TREATMENT - Bathing of the wound by water with soap through a catheter - Plotting on a wound of a bandage with viricidal by drugs (70 % ethanol, 1 % povidone - i odid e, 0,1% aqueus iodine ) Introduction around of a wound of an immunoglobulin of 20 IU / kg hetero or 10 IU/kg homologous Surgical treatment of a wound and the glucocorticoids will not be u s ed!!! - Active immunization by a vaccine КОКАВ or W 1-38 till 1 ml (2. 5 IU ) IM on 1, 3, 7, 14, 30, 90 days from a beginning of immunization - The preventive immunization - in the same dose, but the 3 th is aliquot: 1, 7, 21 days from a beginning of immunization
TREATMENT of the patients – large doses of interferons, immunoglobulin, long intensive care - but they are capable to save life only by separate patient!!! ANTIEPIDEMIC MEASURES - t he notice moves not later than 12 clocks - the quarantine is not put forth, DDD is not necessary. - t he search of the sick animal and contact persons will be carried out. T he sick animal are annihilated with research of their brain in vet- laboratory, T he patient is located in separate ward, the staff works in protective clothes, T he antirabic vaccinations are shown to the injureds - at stings of the patient or wet with saliva Veterinary of a measure – immunization animal s, the 6 th monthly quarantine for imported animal s, isolation of vagrant dogs and cats
TETANUS Identification. Acute infectious disease described by a se vere damages of the nervous system with appearance of tonic tension and clonic cramps striated muscles, resulting in asphyxias. Annually falling ill 1 million t he man ( lethality - 48 - 76 % ) ETIOLOGY Clostridium tetani – Gram (+) large rod by a size 4- 6 on 0.3-0.6 micron. A strict anaerobe. Has the vegetative forms and terminal spores, which in ground are saved till 10 years, but at boiling perish in 60 minutes. The vegetative forms at boiling perish in some minutes, but under operation disinfectans - only in 3-6 clocks Have O and Н - antigenes. (10 serovariants )
PATHOGENY In a place of implantation and colonization ( wound ) in anaerobic conditions starts production potent exotoxin ( l ethal dose for the man 130 microgr. ), consisting from a tetanospasmin and tetanolysin The tetanospasmin - operates remotely, is fixed on a surface of nervous cells, will penetrate in them and method of retrograde axonal transport gets in a spinal, oblong brain, reticular formation of a trunk and CNS. Contacting with synaptic regulate by protein synaptobrevin II and cellulebrevin, kills release brake neuromediators (glycine, the gamma - aminobutyric acid etc.) that results is to constant tonic tension of striated muscles
From this moment any external affect s on afferent nervous paths promote appearance of clonic cramps resulting in to an acidosis or even to a cardioplegia The tetanohemolysin - has hemolytic, cardiotoxic and lethal operation, but in clinic has auxiliary value. The processes of its derivation are not interlinked to synthesis of a tetanospasmin The exotoxin fast inactivates by warming, UVL, in an alkaline condition. In an intestine is not absorbe d, but also does not inactivate by enzymes GIT PATHOMORPHOLOGY The specific pathomorphologic changes miss, except for sign s of a degeneration and necros e s of tissues of a brain, basophilia of striated muscles. Characteristicly - fast cadaveric spasm!!!
EPIDEMIOLOGY The reservuoir and sources - herbivorous animal s, the birds, rodents, man (from 5 % up to 40 % of the people sec re t e of the infectious agent with feces ) In ground a population is supported by change of stages vegetation and sporulation The mechanism of transmission - contact Mode of transmission – traumatic, parenteral with infection through injure dermal integuments. The factors of transmission - anyone polluted stabing and cutting subjects (5 % -10 % - medical) Susceptibility high. 60 %- of the person of elderly age, 80 % - 86 % - from them - village inhabitants. After of recovery more often does not forms immunity.
CLINIC Incubation interval from 1 about 30 days (5 - 14 days) Tetanus distinguish under the following factors: 1. Place of invasion - t raumatic - i s inflammatory -d estructive - c ryptogenic 2. A generalization of the process - common - local 3. Degree of gravity - m ild (cramp 1 - 2 times per day) - moderate gravity (cramp more 2 times per day) - s e vere (cramp from 10 and more at one o'clock!!) 4. On periods of illness : a prodromal stage, Initial, height, convalescence
Prodromal stage - headache, sweating, irritability, tension and periodic contraction of muscles around of a wound (not for marks of the patients) Initial period - acute beginning, trismus ( spasm of masseters ) " risus sardonicus ", rigidity of muscles of a neck, imped ed swallowing (spastic stricture of muscles of a pharynx), hypertone of all striated muscles from the top to downward, but hands and stops save mobility Period of height - appearance of the first cramps on a background hypertone of sceletal muscles, opisthotonic, lordosis, a muscle pain at cramps, respiratory disorders and cyanosis of a skin and mucous, hyperthermia, sweating, dehydration, the loud cardiac sounds and rise B/P, are not capable to swallow and to drink. The duration of cramps about several minutes, between cramps hypertone of striated muscles is saved!!
Period of convalescence - 2 - 4 weeks The local tetanus - starts with a wound, but then passes in a common tetanus Cephalic tetanus Бруннера - "bulbar" - serious form with fast appearance of a paralysis of respiration and CVS The children's tetanus - is hypertone and clonic cramps, though other sign s of a tetanus can miss COMPLICATIONS Early - aspiration pneumonia, sepsis, tearing up m uscles and fracture of bones, asphyxia Late - tachycardia, hypotonia, common weakness, damage of the nucleicerebral nerves, d eformation of a backbone Differential diagnosis rabies, hysteria, e pilepsy, poisoning with s trychninum
Слайд 48: Neonatal Tetanus most commonly affects infants born to nonimmune mothers. Exotoxin produced by Clostridium tetanigains entry to the circulation when the infant's umbilical cord is cut or the umbilical stump is cleaned in a nonsterile fashion. Generalized rigidity and spasm affect the child in the first 2 weeks of life and may be fatal
LABORATORY DIAGNOSIS To frequent apply a clinico -epidemiological method, it is possible to u s e a biological method or PCR TREATMENT - t he introduction of an ATS ( antitanic serum ) 150, 000 IU hetero- or 3000 - 9000 IU homologous IV one time - p rocessing of a wound and use by an ATS 3000 IU - e limination of cramps (sedative and neuroleptics) - antibiotics - s ufficient hydration and normalization BMR ( basal metabolic rate) - artificial feeding ( IV or then with feeding tube ) - myelorelaxants and transition on artificial ventilation of the lungs Prophylaxis - compulsory vaccination since 3 rd month till 60 years.