Creutzfeldt-Jakob Disease Surveillance in Argentina, 1997–2008

Abstract

Background: Epidemiological data on Creutzfeldt-Jakob disease (CJD) from Latin America are limited. We present a comprehensive epidemiological survey on CJD patients in Argentina based on systematic surveillance between 1997 and 2008. Methods: A CJD Surveillance Referral Center (SRC) was established in Argentina in 1997; previously a Neuropathology Referral Center was used from 1983 to 1996. All suspected cases referred to the SRC were classified using established criteria on the basis of information derived from the following: clinical data form, EEG, MRI (both for central review), cerebrospinal fluid (CSF) for protein 14-3-3 Western blot (WB), autopsy or biopsy material for neuropathology, prion protein (PrP) immunohistochemistry and PrP WB, as well as blood for DNA studies (when brain tissue was not available). Results: Of the 517 patients referred to the SRC between 1997 and 2008, 211 (40.8%) had CJD or other transmissible spongiform encephalopathies (TSEs) (definite or probable). Possible cases totaled 14.5%, while cases with no WHO criteria accounted for 16.4%. Non-CJD cases excluded by biopsy/autopsy or during follow-up corresponded to 28.2% of the 517 referrals. Main differential diagnoses included neurodegenerative diseases such as Alzheimer’s disease, frontotemporal dementia, vascular, metabolic or viral encephalopathy, and Hashimoto’s disease. Five percent of referred patients ultimately recovered. Eighty-three percent of TSE cases were sporadic CJD; 17% were genetic, mainly E200K (15.6%); the remaining 1.4% included an octarepeat insertion and two Gerstmann-Sträussler-Scheinker cases (P102L). Seventy-four of 100 definite cases had frozen tissue available for molecular subtyping (PrP^Sc/codon 129). CSF protein 14-3-3 WB sensitivity was 72.3% and specificity was 92.1%. Clinical diagnostic criteria for probable CJD when compared to definite diagnosis by neuropathology showed 71.3% sensitivity, 86.2% specificity, 94.4% positive predictive value and 48% negative predictive value. Country incidence increased over time and reached 0.85 cases per million in 2008, with the highest rate detected in the city of Buenos Aires (1.8). Districts with 6% of the total population have never reported suspected cases. Conclusion: In spite of an increase in incidence observed over time, the difference between Buenos Aires city, where the incidence is comparable to that of smaller European countries with higher population density, and the incidence observed in the rest of the country suggests underreporting in nonmetropolitan areas, probably due to a lack of access to specialized medical facilities. CSF WB sensitivity results for protein 14-3-3 were probably linked to the fact that testing was not routinely repeated during the course of the disease, when earlier test results had been negative. The spectrum of molecular CJD subtypes observed did not differ from other countries in Europe. No iatrogenic or variant CJD cases were identified. The sensitivity and negative predictive value of clinical diagnostic criteria...

Scientific Opinion on a request for a review of a scientific publication concerning the zoonotic potential of ovine scrapie prions

“…Despite these considerations, mortality rates are remarkably similar in the majority of countries in Europe (Kovacs et al, 2007;Gubbels et al, 2012;Jansen et al, 2012;Brandel et al, 2013) and are consistent with recent national surveillance data from Argentina (Begue et al, 2011), Australia (Klug et al, 2013b) and Japan (Nozaki et al, 2010). It is of note that Australia has never reported a case of Classical scrapie.…”

The Features of Genetic Prion Diseases Based on Chinese Surveillance Program

“…The age at disease onset of the patients with genetic prion diseases is approximately 10 years younger than that of sCJD cases [ 7 ]. These data highlight that the pattern of Chinese genetic prion diseases possesses common features of genetic prion diseases worldwide [ 19 , 20 , 21 , 22 , 23 , 24 ], though subtle differences remain across disease sub-types.…”

“…The clear predominance of FFI (39%), T188K (23%) and E200K (13%) cases in Chinese genetic prion diseases may illustrate a unique pattern that differs from not only Caucasian but also North-east Asian (e.g., Japanese and Korean) disease trends [ 4 , 25 , 26 ]. The literature indicates that E200K is the most common mutation in many European countries [ 22 , 27 ], while FFI and various GSS mutations are also frequently observed [ 19 , 28 , 29 , 30 ]. In some special regions, such as the Italo-Greek villages of the southeast Calabria region in Italy [ 31 ], the Slovakian [ 32 ] and the Libyan Jews in Israel [ 33 ], the distributions of the E200K mutation, either in patients or in the health carriers, are extremely elevated.…”

PMCA Applications for Prion Detection in Peripheral Tissues of Patients with Variant Creutzfeldt-Jakob Disease

“…BSE, also known as mad cow disease, was first discovered in 1986 in the United Kingdom and reached an epidemic peak in 1992 [20]. This resulted in stricter controls on cattle-derived food and many national CJD surveillance systems have been established [22][23][24][25][26][27]. Few cases of vCJD transmission between humans have been described in patients subjected to blood transfusion [28].…”