DOENÇAS CAUSADAS POR PRÍONS - ufrgs.br

1 DOEN AS CAUSADAS POR PR ONS DOEN AS POR PR ONS Doen as com caracter sticas comuns: - CAUSADAS por agentes n o convencionais (pr ons) - Longo per odo de incuba o (anos) - Doen a fatal, progressiva - Les es no enc falo: vacuoliza o de neur nios - Sem resposta imune ou inflamat ria O QUE S O PR ONS ? S o prote nas normalmente encontradas nas c lulas. N o tem genoma. Os pr ons que causam doen as s o alterados em sua conforma o Os pr ons normais s o chamados PrPcel Pr ons anormais s o chamados PrPsc, em alus o a scrapie , uma forma da doen a em ovinos Os PrPsc s o altamente resistentes a: calor, formol, nucleases Os PrPsc s o sens veis a disruptores de gorduras, como: fenol, soda, ter, hipoclorito Na, fluorocarbonos ENCEFALOPATIAS ESPONGIFORMES TRANSMISS VEIS - Existem h muito tempo - Scrapie: h > 2 s culos - CJD: desde 1920 - BSE: desde 1986 - Desfecho fatal uma vez verificados sinais - Longo per odo de incuba o -N o h resposta imune convencional -Caracter stica comum.

2 Degenera o do c rebro e medula envolvendo uma prote na normal do hospedeiro (PrP) - PrP depositada em forma anormal e em excesso no c rebro, medula espinhal e muitos nervos e tecidos perif ricos PRIONS : o AGENTE * PrPSc diferente do PrPc normal - conforma o diferente - cont m h lices (comparada com h lice em PrPc) - menos sol vel, muito resistente, inclusive a proteases PrPC PrPSc Infec o com PrPSc PrPC do Hospedeiro Convers o Pr on anormal altera conforma o da prote na normal E segue COMO PR ONS CAUSAM DOEN A? OU: PrPSc entra no enc falo e induz a troca de conforma o das proteinas normais OU Muta o no gene que codifica o pr on normal conforma o anormal (PrPc => PrPSc) A seguir , as mol culas anormais (PrPSc) agragam-se e formam dep sitos Como PR ONS causam doen a?

3 Os agregados de prions anormais (PrPSc) formam dep sitos amil ides e fibrilas levam a perturba o do funcionamento do enc falo Fibrilas no microsc pio eletr nico - scrapie- Doen as CAUSADAS por PR ONS (Encefalopatias espongiformes) Histologia enc falo de vaca com BSE SCRAPIE * Doen a neurol gica progressiva: incoordena o, tremores, co eira, paralisia, morte * Per odo de incuba o 1 a 5 anos (logo afeta animais usualmente de > 2 anos) Sheep with scrapie Scrapie AGENTES N O CONVENCIONAIS (N O VIRAIS) Neuroencefalopatias espongiformes: - Scrapie (ovinos) - Encefalopatia espongiforme bovina (BSE) ou s ndrome da vaca louca (bovinos) -Encefalopatia transmiss vel do mink - Outras formas de encefalopatias animais - Ins nia familiar fatal (humanos) - Kuru (humanos) - Creutzfeld-Jacob Disease (CJD) (humanos) - Gerstman-Strausler-Schenker (GSS) (humanos) outras ENCEFALOPATIAS ESPONGIFORMES TRANSMISS VEIS NA ESP CIE HUMANA Doen a Sinais Via de aquisi o Distribui o Dura o _____ Kuru Perda coordena o Canibalismo Nova Guin 3 meses a 1 ano e dem ncia _____ CJD idem Desconhecida na Espor dica: 1 a 10 anos.

4 Forma espor dica 1 em 1 milh o usualmente 1 ano Muta o herdada 100 fam lias do gene PrP identificadas Iatrog nica ~80 casos _____ CJD variante ingest o de alimentos GB contaminados c/ BSE ? _____ GSS Incoordena o, Muta o herdada 50 fam lias 2-6 anos dem ncia do gene PrP identificadas _____ Insonia Dist rbios do sono Muta o herdada 9 fam lias 1 ano familiar e SNA, incoord do gene PrP identificadas fatal e dem ncia _____ Kuru ENCEFALOPATIAS ESPONGIFORMES TRANSMISS VEIS NOS ANIMAIS Doen a Esp cie Transmiss o _____ Scrapie Ovinos herdada BSE Bovinos ingest o de prote na PrP de ovinos com scrapie; FSE Felinos ingest o de prote na bovina /ovina contaminada MTE Marta idem (mink, vison) Chronic Wasting Disease alce, mula, ?

5 Cervo EEU Kudu, Niala, idem Oryx _____ ENCEFALOPATIA ESPONGIFORME BOVINA S NDROME DA VACA LOUCA ENCEFALOPATIA ESPONGIFORME BOVINA (BSE) SINAIS CL NICOS - dura o 1- 2 semanas at 1 ano - cerca de 2% dos animais do rebanho com sinais - sinais neurol gicos: - altera es de comportamento - hipersensibilidade ao toque - a ru dos - ataxia BOVINE SPONGIFORM ENCEPHALOPATHY Resultou da troca no processamento de ra es com carne na GB retiraram fluorocarbonos e diminuiram temperatura de coc o => Pr ons presentes em carca as infectadas BSE BOVINE SPONGIFORM ENCEPHALOPATHY * ban in UK on feeding ruminant protein to ruminants in 1988 decline in incidence of BSE in UK * Cases have now been seen in many other European countries ( , France, Germany, Italy, Spain) and recently in Japan.

6 BSE NA GR -BRETANHA COUNTRY TOTAL NUMBER OF PRIMARY CASES (NUMBER ALIVE) TOTAL NUMBER OF SECONDARY CASES: BLOOD TRANSFUSION (NUMBER ALIVE) CUMULATIVE RESIDENCE IN UK > 6 MONTHS DURING PERIOD 1980-1996 UK 173 (0) 3 (0) 176 France 25 (0) - 1 Republic of Ireland 4 (0) - 2 Italy 2 (0) - 0 USA 3 (0) - 2 Canada 2 (1) - 1 Saudi Arabia 1 (0) - 0 Japan 1* (0) - 0 Netherlands 3 (0) - 0 Portugal 2 (0) - 0 Spain 5 (0) - 0 Taiwan 1 (0) - 1 VARIANT CREUTZFELDT-JAKOB DISEASE CURRENT DATA (NOVEMBER 2011) BOVINE SPONGIFORM ENCEPHALOPATHY * Reconhecida na GB em 1986; em 1997, > 172,000 casos, com > 60% das granjas leiteiras afetadas. * Sinais similares ao scrapie, mas vadcas tem altera es marcadas de comportameno e sem prurido Primeiro relato de BSE (Veterinary Record) ENCEFALOPATIA ESPONGIFORME BOVINA (BSE) RISCOS O MAIOR RISCO A POSSIBILIDADE DE TRANSMISS O A HUMANOS CUIDADOS COM A CARNE E RESTOS DE MATADOURO PESSOAS QUE ESTIVERAM NO REINO UNIDO: TRANSFUS ES PROIBIDAS PROIBI O DE VACINAS IMPORTADAS ENCEFALOPATIA ESPONGIFORME BOVINA (BSE) DIAGN STICO EXAME: POST MORTEM EM TECIDO NERVOSO: Nestes, busca-se: PRESEN A DE DEGENERA O ESPONGIFORME COLORA O POR IMUNO-HISTOQU MICA COM ANTICORPOS ESPEC FICOS TESTE NA TERCEIRA P LPEBRA.

7 PROPOSTO P/DIAGN STICO IN VIVO TRATAMENTO/PREVEN O N O H TRATAMENTO PREVEN O: EVITAR ADQUIRIR ANIMAIS DE REAS DE RISCO EVITAS LINHAGENS GENETICAMENTE COMPROMETIDAS N O ADMINISTRAR ALIMENTOS C RNEOS A N O CARN VOROS N O CONSUMIR CARNE DE ANIMAIS INFECTADOS Vaca louca? Se a vaca mugir assim melhor voc optar por comer peixe Se a vaca mugir assim: Ent o pode preparar o churrasco Servi o de utilidade p blica Como identificar se o gado est com a s ndrome da vaca Mad cow outbreak confirmed in Japan British government veterinarians have confirmed that a Japanese dairy cow that was suspected of having contracted mad cow disease has been infected with the illness, the first case reported outside Europe, Japanese government officials said Saturday.

8 The infected cow, a 5-year-old Holstein, first showed symptoms of the disease on Aug. 6 when the owners found the animal could not stand on its own. In a hurriedly arranged news conference, ministry officials said the government has no idea how the cow was infected but ruled out an immediate ban on the use of meat and bone meal (MBM) as feed for cows. MBM feed has been blamed for the spread of mad cow disease in Europe. The ministry has declared domestic MBM feed to be safe but is considering a total ban on imports. BSE : AUSTRALIAN RESPONSE National transmissible spongiform encephalopathy (TSE) surveillance To satisfy international trading agreements, Australia is required to prove freedom from bovine spongiform encephalopathy (BSE) and scrapie.

9 BSE and scrapie can only be diagnosed by examining brain tissue collected at post-mortem. The APHS surveillance program involves sampling animals showing nervous symptoms. Cases must be over two years of age as BSE and scrapie have a long incubation period and do not occur in young animals. Queensland's sampling target is 156 cattle and 40 sheep cases per year. An incentive scheme is now in place in Queensland to encourage producers to submit suitable cases for testing. Private veterinarians who participate in the program can receive an incentive payment. BSE : AUSTRALIAN RESPONSE Feeding of animal meals and fish meal to beef and dairy cattle, sheep and all other ruminants is now totally banned in Queensland This action has been taken: * to maintain Australia s bovine spongiform encephalopathy (BSE)-free status to ensure Australian meat and meat products continue to have strong access to domestic and international markets.

10 Prior to 10 August 2001 rendered meals derived from a horse or other equine, pig, kangaroo and wallaby, fish and poultry as well as blood meal derived from any animal were exempt from the ruminant feeding ban. Amendments to the Stock Regulation that came into force on 10 August 2001 have removed these exemptions and extend the ruminant-feeding ban to include all rendered animal meals with no exemptions. HUMAN PRION DISEASES 1. KURU * occurred in the highlands of Papua New Guinea * consumption of human brains in cannibalistic rituals transmission of abnormal prion protein * cannibalism abandoned in late 1950 s decline in incidence of kuru 2. CREUTZFELDT-JAKOB DISEASE (CJD) (i) Sporadic CJD * occurs ~ 1-3 cases/million people/year, caused by: - mutation of PrPc gene OR - spontaneous conversion of PrPc to PrPSc * usually affects people > 50 years (mean = 63 yrs) * sensory disturbances, sleeping disorders, dementia, motor disturbances, coma, death (ii) New variant CJD (nvCJD or vCJD) * first described in 1996 in the UK, 106 cases by June 01 * different to sporadic CJD.