DOENAS CAUSADAS POR

PRONS

DOENAS POR PRONS

Doenas com caractersticas comuns:
- Causadas por agentes no convencionais (prons)
- Longo perodo de incubao (anos)

- Doena fatal, progressiva

- Leses no encfalo: vacuolizao de neurnios
- Sem resposta imune ou inflamatria

O QUE SO PRONS ?
So protenas normalmente encontradas nas clulas.
No tem genoma.
Os prons que causam doenas so alterados em sua conformao
Os prons normais so chamados PrPcel
Prons anormais so chamados PrPsc, em aluso a scrapie,
uma forma da doena em ovinos
Os PrPsc so altamente resistentes a:
calor, formol, nucleases
Os PrPsc so sensveis a disruptores de gorduras, como:
fenol, soda, ter, hipoclorito Na, fluorocarbonos

ENCEFALOPATIAS ESPONGIFORMES TRANSMISSVEIS

- Existem h

muito tempo
- Scrapie: h > 2 sculos
- CJD: desde 1920
- BSE: desde 1986
- Desfecho fatal uma vez verificados sinais
- Longo perodo de incubao
-No h resposta imune convencional

-Caracterstica comum: degenerao do crebro e medula

envolvendo uma protena normal do hospedeiro (PrP)
- PrP depositada em forma anormal e em excesso no crebro,
medula espinhal e muitos nervos e tecidos perifricos

PRIONS : o AGENTE
* PrPSc diferente do PrPc normal
- conformao diferente
- contm hlices (comparada com hlice em PrPc)
- menos solvel, muito resistente, inclusive a
proteases

PrPC

PrPSc

Infeco com PrPSc

PrPC do
Hospedeiro

Converso

Pron anormal altera conformao da

protena normal
E
segue

COMO PRONS CAUSAM DOENA?

OU:
PrPSc entra no encfalo e induz a troca de conformao
das proteinas normais
OU
Mutao no gene que codifica o pron normal
conformao anormal (PrPc => PrPSc)

A seguir , as molculas anormais (PrPSc) agragam-se e

formam depsitos

Como PRONS causam doena?

Os agregados de prions anormais (PrPSc)
formam depsitos amilides e fibrilas
levam a perturbao do funcionamento do encfalo

Fibrilas no microscpio eletrnico

- scrapie-

Doenas causadas por PRONS

(Encefalopatias espongiformes)

Histologia encfalo de vaca com BSE

SCRAPIE
* Doena neurolgica progressiva: incoordenao,
tremores, coeira, paralisia, morte
* Perodo de incubao 1 a 5 anos (logo afeta animais
usualmente de > 2 anos)

Sheep with scrapie

Scrapie

AGENTES NO CONVENCIONAIS (NO VIRAIS)

Neuroencefalopatias espongiformes:
- Scrapie (ovinos)
- Encefalopatia espongiforme bovina (BSE)
ou sndrome da vaca louca (bovinos)
-Encefalopatia transmissvel do mink
- Outras formas de encefalopatias animais

- Insnia familiar fatal (humanos)

- Kuru (humanos)
- Creutzfeld-Jacob Disease (CJD) (humanos)
- Gerstman-Strausler-Schenker (GSS) (humanos)
outras

ENCEFALOPATIAS ESPONGIFORMES TRANSMISSVEIS

NA ESPCIE HUMANA
Doena
Sinais
Via de aquisio Distribuio
Durao
_________________________________________________________________________
Kuru
Perda coordenao
Canibalismo
Nova Guin
3 meses a 1 ano
e demncia
_________________________________________________________________________
CJD
idem
Desconhecida na
Espordica:
1 a 10 anos;
forma espordica 1 em 1 milho usualmente 1 ano
Mutao herdada
do gene PrP

100 famlias
identificadas

Iatrognica
~80 casos
________________________________________________________________________
CJD variante
ingesto de alimentos
GB
contaminados c/ BSE ?
_________________________________________________________________________
GSS
Incoordenao,
Mutao herdada
50 famlias
2-6 anos
demncia
do gene PrP
identificadas
_________________________________________________________________________
Insonia
Distrbios do sono
Mutao herdada
9 famlias
1 ano
familiar
e SNA, incoord
do gene PrP
identificadas
fatal
e demncia
_________________________________________________________________________

Kuru

ENCEFALOPATIAS ESPONGIFORMES TRANSMISSVEIS

NOS ANIMAIS
Doena
Espcie
Transmisso
____________________________________________________
Scrapie
Ovinos
herdada
BSE

Bovinos

ingesto de protena
PrP de ovinos com scrapie;

FSE

Felinos

ingesto de protena
bovina /ovina contaminada
idem

MTE

Chronic Wasting
Disease

EEU

Marta
(mink, vison)

alce, mula,
cervo

Kudu, Niala,
Oryx

idem

____________________________________________________

ENCEFALOPATIA ESPONGIFORME BOVINA

SNDROME DA VACA LOUCA

ENCEFALOPATIA ESPONGIFORME BOVINA (BSE)

SINAIS CLNICOS

- durao 1- 2 semanas at 1 ano

- cerca de 2% dos animais do rebanho com sinais
- sinais neurolgicos:
- alteraes de comportamento
- hipersensibilidade ao toque

a rudos
- ataxia

BOVINE SPONGIFORM ENCEPHALOPATHY

Resultou da troca no processamento de raes com
carne na GB retiraram fluorocarbonos e diminuiram
temperatura de coco =>
Prons presentes em carcaas 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 (e.g.Switzerland, France, Germany, Italy,
Spain) and recently in Japan.

BSE NA GR-BRETANHA

VARIANT CREUTZFELDT-JAKOB DISEASE

CURRENT DATA (NOVEMBER 2011)
TOTAL
NUMBER OF
PRIMARY
CASES (NUM
BER ALIVE)

TOTAL NUMBER OF
SECONDARY CASES:
BLOOD
TRANSFUSION (NUMB
ER ALIVE)

CUMULATIVE
RESIDENCE IN UK
> 6 MONTHS
DURING PERIOD
1980-1996

UK

173 (0)

3 (0)

176

France

25 (0)

Republic of
Ireland

4 (0)

Italy

2 (0)

USA

3 (0)

Canada

2 (1)

Saudi
Arabia

1 (0)

Japan

1* (0)

Netherlands

3 (0)

Portugal

2 (0)

Spain

5 (0)

Taiwan

1 (0)

COUNTRY

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 alteraes
marcadas de comportameno e sem prurido

Primeiro relato de BSE (Veterinary

ENCEFALOPATIA ESPONGIFORME BOVINA (BSE)

RISCOS
O MAIOR RISCO A POSSIBILIDADE DE
TRANSMISSO A HUMANOS
CUIDADOS COM A CARNE E RESTOS DE
MATADOURO
PESSOAS QUE ESTIVERAM NO REINO UNIDO:
TRANSFUSES PROIBIDAS
PROIBIO DE VACINAS IMPORTADAS

ENCEFALOPATIA ESPONGIFORME BOVINA (BSE)

DIAGNSTICO

EXAME: POST MORTEM EM TECIDO NERVOSO:

Nestes, busca-se:
PRESENA DE DEGENERAO ESPONGIFORME

COLORAO POR IMUNO-HISTOQUMICA COM

ANTICORPOS ESPECFICOS
TESTE NA TERCEIRA PLPEBRA: PROPOSTO
P/DIAGNSTICO IN VIVO

TRATAMENTO/PREVENO
NO H TRATAMENTO
PREVENO:

EVITAR ADQUIRIR ANIMAIS DE REAS DE RISCO

EVITAS LINHAGENS GENETICAMENTE COMPROMETIDAS
NO ADMINISTRAR ALIMENTOS CRNEOS A NO CARNVOROS
NO CONSUMIR CARNE DE ANIMAIS INFECTADOS

Vaca louca?

Servio de utilidade pblica

Como identificar se o gado est com a sndrome da vaca louca...

Se a vaca mugir assim:

Se a vaca mugir assim

Ento pode preparar

o churrasco

melhor voc optar por

comer peixe

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.
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.

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 Australias bovine spongiform encephalopathy (BSE)-free
status to ensure Australian meat and meat products continue to have
strong access to domestic and international markets.
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 1950s
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:
- symptoms (psychiatric disorders e.g. depression, anxiety)
- pathology (lesions more florid),
- age (19-45 yrs, mean = 27 years)

* experiments show nvCJD prion is similar to BSE prion

* thus, nvCJD likely to be associated with consumption of
BSE-affected tissues removal of certain bovine
tissues from human food chain in the UK

Variant CJD may be more infectious than sporadic CJD

- ---------------------------------------------------Britain's Department of Health is greatly concerned that the prion
responsible for variant Creutzfeldt-Jakob disease may be more infectious
than the prion responsible for sporadic CJD.
Tests had shown that tonsils, spleen, lymph nodes, and appendix of
vCJD patients were all positive, whereas similar tests on patients with
sporadic disease were all negative. Therefore, there could be a greater
risk of secondary transmission from blood or surgical instruments.
He presented a list of common surgical procedures carried out in 41
cases of vCJD before the onset of clinical signs. In none of these
procedures had any precautions been taken apart from normal
sterilisation procedures.
He pointed out that prion proteins are remarkably resistant to sterilisation.
The Health Department announced in January 2001 it would spend GBP
200 million modernising National Health Service sterilisation equipment
and buying disposable surgical tools.

3. A Sndrome Gerstmann-Strussler-Scheinker
(GSS)
e Insonia Familiar Fatal
(FFI)
C
* Mutaes no gene PrP gene PrP espontaneamente
converte para PrPSc anormal
* Condies herdadas (autossomal dominante)

Os 230 amino acidos da

human PrP humana mostrando
stios de mutao associados com
GSS
(cdons 102, 105, 117, 198, 217)

CHRONIC WASTING DISEASE OF DEER AND ELK

* occurs in the US and Canada in many cervid species

* first seen in captive deer, but found in ~ 1-6% animals
shot by hunters
* epidemiology unknown: using land/facilities previously
grazed by sheep (scrapie-infected)?

Date: Thu, 25 Oct 2001 10:05:09 -0400 (EDT)

CHRONIC WASTING DISEASE, CERVIDS - USA (COLORADO)
*************************************************
The state has confirmed 6 cases of chronic wasting disease (CWD), the elk
and deer equivalent of mad cow disease. State officials here fear that some
elk infected with the fatal illness, CWD, were sold to private ranches in as
many as 15 states and could spread the disease to wild elk and deer
throughout the nation.
"We're trying to figure out the extent of the exposure," said a state
veterinarian with the Colorado Department of Agriculture. The state has
quarantined 1300 elk. On Friday, 9 were killed to be tested. There is no live
test.
CWD is similar to mad cow disease in beef cattle and variant CreutzfeldtJakob Disease (vCJD) in people. It is not known if CWD disease can be
transmitted to people who eat deer or elk meat or come in contact with
animal fluids. Nor is it known how animals become infected, though it is
believed that soil can be contaminated by the remains of an infected animal
for decades.

SCRAPIE
transmisso: gentica
Diagnstico baseado na histopatologia do enceflo
Ocorre na Europa, Amrica do Norte h casos no
Brasil originrios de animais importados e sua prole

BSE- CLNICA
Perodo de incubao: 2-8 anos; pico: 5 anos,
independente de raa;
Histologia: vacuolao neuronal no cerebelo/cortex;
fibrilas de placas amilides, infiltrao de astrcitos .
Sinais clnicos:apreenso, hiperestesia, o animal se
lambe frequentemente; paralisia progressiva e ataxia.
No h cegueira ou andar em crculos.