Recalls raise questions on safety practices for donated blood CJD TSE PRION
Posted Sep 29 2013 12:42pm
Recalls raise questions on safety practices for donated blood
September 29, 2013
In March 2012, someone at increased risk for the human form of mad cow disease walked into a Red Cross blood center in Michigan to donate for the fifth time in recent years.
The donor — unidentified in public records — filled out the questionnaire used to determine whether someone’s blood can safely flow into the Red Cross’ national network, which generated $2.2 billion in sales last year, and be transfused into human patients.
The donor provided the usual information. This time, however, the Lansing-based Great Lakes Region Blood Services employee reviewing the questionnaire realized the person’s blood should not be collected that day and shouldn’t have been drawn the four previous times. Under federal guidelines, disqualification was automatic.
The U.S. Food and Drug Administration was notified. Screening procedures were reviewed. The donor was permanently barred. And, belatedly, a recall was issued for one unit of the donor’s blood that had been collected a year earlier and sent from Lansing to California.
Interviews with Red Cross officials and a review of 10 pages of FDA records associated with the recall don’t reveal whether the potentially dangerous blood product was transfused or whether a transfused patient was ever notified — leading to questions about accountability in the U.S. blood trade.
“That data is not specifically tracked and compiled by the FDA,” said Morgan Liscinsky, spokeswoman for the agency.
The FDA requires blood banks to track products recalled for HIV and hepatitis C and to notify transfused patients. For other infectious diseases, such as the human form of mad cow disease, “look-back procedures” are encouraged but not required, Liscinsky said.
Oral.05: Contaminated blood products induce a highly atypical prion disease devoid of PrPres in primates
Emmanuel Corney,1 Nina Jaffre,1 Jacqueline Mikol,1 Valerie Durand,1 Christelle Jas-Duval,1,2 Sophie Luccantoni-Freire,1 Evelyne Correia,1 Nathalie Lescoutra-Etcheqaray,3 Nathalie Streichenberqer,4 Stephane Haik,5 Chryslain Sumian,3 Paul Brown1 and Jean-Philippe Deslys1
1Commissariat a l'Energie Atomique; Institute of Emerging Diseases and Innovative Therapies (iMETI); Division of Prions and Related Diseases (SEPIA); Fontenay-aux- Roses, France; 2EFS·Nord de France; Lille, France; 3MacoPharm; Tourcoing, France; 4Hospices Civils de Lyon; Prion Unit; Neurobiology Department; Bron, France; 5Inserm; U 975·CNRS; UMR 7225 - Universite Pierre et Marie Curie; Paris, France
Background, Concerns about the blood-borne risk of prion infection have been confirmed by the occurrence in the UK of four transfusion-related infections of vCJD and an apparently silent infection in an hemophiliac patient. Asymptomatic incubation periods in prion diseases can extend over decades in humans. We present here unexpected results of experiments evaluating blood transmission risk in a non-human primate model.
Material and Methods, Cynomolgus macaques were inoculated with brain or blood specimens from vCJD infected humans or monkeys. Neuropathological and biochemical findings were obtained using current methods used for human patients.
Results, Thirteen out of 23 primates exposed to various human or macaque blood products exhibited a previously undescribed myelopathic syndrome, devoid of the classical features of prion disease, notably abnormal prion protein (PrPres) deposition, whereas the 14 corresponding brain-inoculated donor animals and 1 transfused animal exhibited the classical vCJD pattern. In passage experiments, plasma transfusion induced the same atypical phenotype after two years (again, with no detectable PrPres), whereas the intracerebral inoculation of spinal cord led to a typical prion disease with cerebral spongiosis and PrPres accumulation in the brain of the primate recipient. Interestingly, passage experiments in transgenic mice were largely unsuccessful.
In another experiment designed to test the efficacy of antiprion filters, three recipients of filtered red blood cells suspended in plasma are still healthy 4.5 y after transfusion whereas the recipients of unfiltered inocula died after 2.5 y with the atypical neurological profile.
Conclusion. We describe a new fatal neurological myelopathic syndrome in monkeys exposed to various vCJD/BSE-infected blood components.
Secondary transmission in primates confirms
(I) the transmissibility of this myelopathy, and
(2) its prion origin which could not be diagnosed as such in the first recipients.
This myelopathy might be compared in some respects to certain forms of human lower motor neuron disease, including neuromyelitis optica, the flail arm syndrome of amyotrophic lateral sclerosis (ALS), and the recently described FOSMN (facial onset sensory and motor neuronopathy) syndrome.
National Institute of Animal Health; Tsukuba, Japan
H-type bovine spongiform encephalopathy (BSE) is an atypical form of BSE, and has been detected in several European countries, and North America. Transmission studies of H-type BSE led to the emergence of the classical BSE (C-BSE) phenotypes during passages in inbred wild type and bovinized PrP-overexpressing transgenic mice. In this study, we conducted serial passages of Canadian H-type BSE isolate in bovinized PrP-overexpressing transgenic mice (TgBoPrP). H-type BSE isolate was transmitted to TgBoPrP with incubation periods of 320 ± 12.2 d at primary passage. The incubation period of 2nd and 3rd passage were constant (~= 220 d), no clear differences were observed in their biological and biochemical properties. However, at the forth passage, 2 different BSE phenotypes were confirmed; one is shorter survival times (109 ± 4 d) and the other is longer survival times. TgBoPrP mice with longer incubation period showed the H-type phenotype of PrPsc profile and pathology. However, those of shorter incubation period were different phenotypes from previously existed BSE prions (C-BSE, L-type BSE, and H-type BSE).
*** This study imply the possibility that the novel BSE prions with high virulence in cattle will be emerged during intraspecies transmission.
Evaluation of the Zoonotic Potential of Transmissible Mink Encephalopathy
We previously described the biochemical similarities between PrPres derived from L-BSE infected macaque and cortical MM2 sporadic CJD: those observations suggest a link between these two uncommon prion phenotypes in a primate model (it is to note that such a link has not been observed in other models less relevant from the human situation as hamsters or transgenic mice overexpressing ovine PrP ). We speculate that a group of related animal prion strains (L-BSE, c-BSE and TME) would have a zoonotic potential and lead to prion diseases in humans with a type 2 PrPres molecular signature (and more specifically type 2B for vCJD)
Together with previous experiments performed in ovinized and bovinized transgenic mice and hamsters [8,9] indicating similarities between TME and L-BSE, the data support the hypothesis that L-BSE could be the origin of the TME outbreaks in North America and Europe during the mid-1900s.
To date the OIE/WAHO assumes that the human and animal health standards set out in the BSE chapter for classical BSE (C-Type) applies to all forms of BSE which include the H-type and L-type atypical forms. This assumption is scientifically not completely justified and accumulating evidence suggests that this may in fact not be the case. Molecular characterization and the spatial distribution pattern of histopathologic lesions and immunohistochemistry (IHC) signals are used to identify and characterize atypical BSE. Both the L-type and H-type atypical cases display significant differences in the conformation and spatial accumulation of the disease associated prion protein (PrPSc) in brains of afflicted cattle. Transmission studies in bovine transgenic and wild type mouse models support that the atypical BSE types might be unique strains because they have different incubation times and lesion profiles when compared to C-type BSE. When L-type BSE was inoculated into ovine transgenic mice and Syrian hamster the resulting molecular fingerprint had changed, either in the first or a subsequent passage, from L-type into C-type BSE. In addition, non-human primates are specifically susceptible for atypical BSE as demonstrated by an approximately 50% shortened incubation time for L-type BSE as compared to C-type. Considering the current scientific information available, it cannot be assumed that these different BSE types pose the same human health risks as C-type BSE or that these risks are mitigated by the same protective measures.
Seven main threats for the future linked to prions First threat The TSE road map defining the evolution of European policy for protection against prion diseases is based on a certain numbers of hypotheses some of which may turn out to be erroneous. In particular, a form of BSE (called atypical Bovine Spongiform Encephalopathy), recently identified by systematic testing in aged cattle without clinical signs, may be the origin of classical BSE and thus potentially constitute a reservoir, which may be impossible to eradicate if a sporadic origin is confirmed.
***Also, a link is suspected between atypical BSE and some apparently sporadic cases of Creutzfeldt-Jakob disease in humans. These atypical BSE cases constitute an unforeseen first threat that could sharply modify the European approach to prion diseases.