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Transmission of sporadic Creutzfeldt-Jakob disease by blood transfusion: risk factor or possible biases

Posted Jan 07 2011 2:46pm
Transmission of sporadic Creutzfeldt-Jakob disease by blood transfusion: risk factor or possible biases

Maria Puopolo,
Anna Ladogana,
Vito Vetrugno,
Maurizio Pocchiari

Article first published online: 7 JAN 2011



DOI: 10.1111/j.1537-2995.2010.03004.x

© 2010 American Association of Blood Banks



BACKGROUND: The occurrence of transfusion transmissions of variant Creutzfeldt-Jakob disease (CJD) cases has reawakened attention to the possible similar risk posed by other forms of CJD.



STUDY DESIGN AND METHODS: CJD with a definite or probable diagnosis (sporadic CJD, n = 741; genetic CJD, n = 175) and no-CJD patients with definite alternative diagnosis (n = 482) with available blood transfusion history were included in the study. The risk of exposure to blood transfusion occurring more than 10 years before disease onset and for some possible confounding factors was evaluated by calculating crude odds ratios (ORs). Variables with significant ORs in univariate analyses were included in multivariate logistic regression analyses.



RESULTS: In the univariate model, blood transfusion occurring more than 10 years before clinical onset is 4.1-fold more frequent in sporadic CJD than in other neurologic disorders. This significance is lost when the 10-year lag time was not considered. Multivariate analyses show that the risk of developing sporadic CJD after transfusion increases (OR, 5.05) after adjusting for possible confounding factors. Analysis conducted on patients with genetic CJD did not reveal any significant risk factor associated with transfusion.



CONCLUSION: This is the first case-control study showing a significant risk of transfusion occurring more than 10 years before clinical onset in sporadic CJD patients. It remains questionable whether the significance of these data is biologically plausible or the consequence of biases in the design of the study, but they counterbalance previous epidemiologic negative reports that might have overestimated the assessment of blood safety in sporadic CJD.





http://onlinelibrary.wiley.com/doi/10.1111/j.1537-2995.2010.03004.x/abstract;jsessionid=656FB07EE4507FB2632BA3E691D3B824.d03t02






Eurosurveillance, Volume 12, Issue 3, 18 January 2007

Articles

Editorial team1


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Citation style for this article: Editorial team. Fourth case of transfusion-associated vCJD infection in the United Kingdom. Euro Surveill. 2007;12(3):pii=3117. Available online: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=3117
Date of submission

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Fourth case of transfusion-associated vCJD infection in the United Kingdom



Editorial team (eurosurveillance.weekly@hpa.org.uk), Eurosurveillance editorial office



A case of variant Creutzfeldt-Jakob disease (vCJD) has recently been diagnosed in a patient in the United Kingdom (UK), who received a blood transfusion from a donor who later developed vCJD [1]. This is the fourth case of probable transfusion transmission of vCJD infection in the UK. Three of the four recipients developed symptoms of vCJD.

The first symptomatic case of vCJD associated with blood transfusion was identified in December 2003. This individual developed vCJD six and a half years after transfusion of red cells donated by an individual who developed symptoms of vCJD three and a half years after donation.



A second case of vCJD 'infection' was identified a few months later in a person who had received red cells from a donor who developed symptoms of vCJD 18 months after donation. This patient (the second case) died from causes unrelated to vCJD five years after transfusion. Post-mortem investigations found abnormal prion protein in the spleen and a cervical lymph node., However, prion protein was not found in the brain, and no pathological features of vCJD were found.



A third case developed symptoms of vCJD six years after receiving a transfusion of red blood cells, and died two years and eight months later. The donor of the blood involved developed vCJD about 20 months after donating it.



These three cases have been published as case reports and in the findings of the ongoing collaborative study between the National Blood Services, the National CJD Surveillance Unit, and the Office for National Statistics. This study aims to collect evidence about transmission of CJD or vCJD via the blood supply [2,3,4,5].



The new, fourth case is in a patient who developed symptoms of vCJD eight and a half years after receiving a transfusion of red blood cells from a donor who developed vCJD about 17 months after this blood was donated [1]. The donor to this case also donated the vCJD-implicated blood transfused to the third case. As for all other reported clinical vCJD cases that have been tested for genotype, this patient is a methionine homozygote at codon 129 of the prion protein gene. The patient is currently alive.



All four cases had received transfusions of non-leucodepleted red blood cells between 1996 and 1999. Since October 1999, leucocytes have been removed from all blood used for transfusion in the UK. The effect of leucodepletion on the reduction of the risk of transmission of vCJD from an infective donation is uncertain.



This fourth case of vCJD infection associated with blood transfusion further increases the level of concern about the risk of vCJD transmission between humans by blood transfusion, although much remains unknown. This reinforces the importance of the existing precautions that have been introduced to reduce the risk of transmission of vCJD infection by blood and blood products [6]. No cases of vCJD have been associated with fractionated plasma products. The small group of living recipients of vCJD-implicated blood transfusion in the UK have been informed of their potential exposure to vCJD by blood transfusion, asked to take certain precautions to reduce the risk of onward person-to-person transmission of vCJD during health care, and offered specialist neurological evaluation and advice.



This article has been adapted from reference 1




References
Health Protection Agency. Fourth case of variant CJD associated with blood transfusion (press release). Press release, 18 January 2007. (http://www.hpa.org.uk/hpa/news/articles/press_releases/2007/070118_vCJD.htm)
Llewelyn CA, Hewitt PE, Knight RSG, Amar K, Cousens S, Mackenzie J, et al. Possible transmission of variant CJD disease by blood transfusion. Lancet 2004; 363:417-21.
Peden AH, Head MW, Ritchie DL, Bell JE, Ironside JW. Preclinical vCJD after blood transfusion in a PRNP codon 129 heterozygous patient. Lancet 2004 ; 364: 527-9.
Wroe SJ, Pal S, Siddique D, Hyare H, Macfarlane R, et al Clinical presentation and pre-mortem diagnosis of blood transfusion-associated variant CJD. Lancet 2006;368:2061-67.
Hewitt PE, Llewelyn CA, Mackenzie J, Will RG. Creutzfeldt-Jakob disease and blood transfusion: results of the UK Transfusion Medicine Epidemiology review study. Vox Sang. 2006;91(3):221-230.
Department of Health [London]. Further precautions to protect blood supply. Press release 2004/0104, 16 March 2004. (http://www.dh.gov.uk/PublicationsAndStatistics/PressReleases/PressReleasesNotices/fs/en?CONTENT_ID=4076608&chk=MTwE%2Bl)


http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=3117




Tuesday, September 28, 2010

Variant CJD: where has it gone, or has it?

Pract Neurol 2010; 10: 250–251


http://vcjdtransfusion.blogspot.com/2010/09/variant-cjd-where-has-it-gone-or-has-it.html




Tuesday, September 14, 2010

Transmissible Spongiform Encephalopathies Advisory Committee; Notice of Meeting October 28 and 29, 2010 (COMMENT SUBMISSION)

----- Original Message -----

From: Terry S. Singeltary Sr.

To: william.freas@fda.hhs.gov Cc: rosanna.harvey@fda.hhs.gov ; Emery, Bryan (CBER)

SEE FULL TEXT ;

http://tseac.blogspot.com/2010/09/transmissible-spongiform_14.html



Wednesday, September 08, 2010

Emerging Infectious Diseases: CJD, BSE, SCRAPIE, CWD, PRION, TSE Evaluation to Implementation for Transfusion and Transplantation September 2010

http://vcjdtransfusion.blogspot.com/2010/09/emerging-infectious-diseases-cjd-bse.html



Saturday, July 17, 2010

Variant Creutzfeldt-Jakob disease Ironside JW., Haemophilia.

2010 Jul;16 Suppl 5:175-80 REVIEW ARTICLE

http://vcjdtransfusion.blogspot.com/2010/07/variant-creutzfeldtjakob-disease.html



http://vcjdtransfusion.blogspot.com/




----- Original Message -----

From: Terry S. Singeltary Sr.

To: CJD-L@LISTS.AEGEE.ORG

Cc: BLOODCJD@YAHOOGROUPS.COM ; cjdvoice@yahoogroups.com

Sent: Friday, September 24, 2010 11:15 AM

Subject: [BLOODCJD] USA Blood products, collected from a donor who was at risk for vCJD, were distributed SEPTEMBER 2010

PRODUCT
Red Blood Cells. Recall # B-2300-10
CODE
Unit: W001607702825
RECALLING FIRM/MANUFACTURER
Recalling Firm: Department of the Air Force, Wright Patterson AFB, OH, by letter dated April 8, 2008.
Manufacturer: Depart of Air Force 88th Medical Group SGQC WPAFB, Wright Patterson AFB, OH. Firm initiated recall is complete.
REASON
Blood product, collected from a donor who was at risk for variant Creutzfeldt-Jakob Disease (vCJD), was distributed.
VOLUME OF PRODUCT IN COMMERCE
1 unit
DISTRIBUTION
Japan

___________________________________

PRODUCT
Recovered Plasma. Recall # B-2302-10
CODE
Units: R08951; P90041; P90041
RECALLING FIRM/MANUFACTURER
Blood Center of Northcentral Wisconsin, Inc., Wausau, WI, by fax on January 2, 2007. Firm initiated recall is complete.
REASON
Blood products, collected from a donor considered to be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE
3 units
DISTRIBUTION
NY

___________________________________

PRODUCT
1) Red Blood Cells Leukocytes Reduced. Recall # B-2338-10;
2) Plasma Frozen. Recall # B-2339-10
CODE
1) and 2) Unit: 5039861
RECALLING FIRM/MANUFACTURER
Community Blood Center, Inc., Appleton, WI, by letter dated September 21, 2007 or by electronic notification on September 21, 2007. Firm initiated recall is complete.
REASON
Blood products, collected from a donor who was at risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE
2 units
DISTRIBUTION
WI, Switzerland

___________________________________

END OF ENFORCEMENT REPORT FOR SEPTEMBER 22, 2010

http://www.fda.gov/Safety/Recalls/EnforcementReports/ucm227078.htm


PRODUCT

1) Cryoprecipitated AHF, Pooled. Recall # B-2155-10;

2) Recovered Plasma. Recall # B-2156-10

CODE

1) Unit: W036309907231;

2) Unit: W036309616077

RECALLING FIRM/MANUFACTURER

BloodCenter of Wisconsin, Inc., Milwaukee, WI, by fax and internet on May 5, 2010 and May 13, 2010. Firm initiated recall is complete.

REASON

Blood products, collected from a donor considered to be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.

VOLUME OF PRODUCT IN COMMERCE

2 units

DISTRIBUTION

TX, Switzerland

___________________________________

PRODUCT

Red Blood Cells Leukocytes Reduced. Recall # B-2157-10

CODE

Unit: 6371718

RECALLING FIRM/MANUFACTURER

South Texas Blood & Tissue Center, San Antonio, TX, by telephone on January 23, 2010 and by fax on January 25, 2010. Firm initiated recall is complete.

REASON

Blood product, collected from a donor who failed to answer questions regarding risk for vCJD, was distributed.

VOLUME OF PRODUCT IN COMMERCE

1 unit

DISTRIBUTION

TX

___________________________________

PRODUCT

Source Plasma. Recall # B-2212-10

CODE

Units: 09FMOG6851; 09FMOG3410; 09FMOG2756; 09FMOG1418; 09FMOF6640; 09FMOF2642; 09FMOF1554; 09FMOD7746; 09FMOF0063; 09FMOF7599

RECALLING FIRM/MANUFACTURER

BioLife Plasma Service LP, Springfield, MO, by fax on April 1, 2010. Firm initiated recall is complete.

REASON

Blood products, collected from a donor considered to be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.

VOLUME OF PRODUCT IN COMMERCE

10 units

DISTRIBUTION

CA

___________________________________

PRODUCT

1) Red Blood Cells Leukocytes Reduced. Recall # B-2213-10;

2) Recovered Plasma. Recall # B-2214

CODE

1) and 2) Unit: 6325245

RECALLING FIRM/MANUFACTURER

South Texas Blood and Tissue Center, San Antonio, TX, by facsimile on February 8, 2010. Firm initiated recall is complete.

REASON

Blood products, collected from a donor considered to be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.

VOLUME OF PRODUCT IN COMMERCE

2 units

DISTRIBUTION

FL, TX

___________________________________

END OF ENFORCEMENT REPORT FOR SEPTEMBER 15, 2010

http://www.fda.gov/Safety/Recalls/EnforcementReports/ucm225990.htm


PRODUCT
Source Plasma. Recall # B-2056-10
CODE
Units: FD0500537, FD0502880, FD0503259, FD0509894, FD0515518, FD0516063, FD0517957, FD0518606, FD0522255, FD0523346, FD0523544, FD0524204, FD0524698, FD0525142, FD0525845, FD0526653, FD0526878, FD0527579, FD0527845, FD0528519, FD0528827, FD0529544, FD0529761, FD0530471, FD0530712, FD0531425, FD0531801, FD0532483, FD0532869, FD0537501, FD0537687, FD0538370, FD0543210, FD0546250, FD0546632, FD0547328, FD0547832, FD0548286, FD0548743, FD0549325, FD0549840, FD0550427, FD0551448, FD0551572, FD0552307, FD0553173, FD0553418, FD0554063, FD0554834, FD0555041, FD0559685, FD0560235, FD0560592, FD0561168, FD0561786, FD0562212, FD0562883, FD0563248, FD0564435, FD0564723, FD0565467, FD0565880, FD0566540, FD0567053, FD0567723, FD0567965, FD0568941, FD0569180, FD0570057, FD0571177, FD0571477, FD0572411, FD0572818, FD0573582, FD0573871, FD0574531, FD0576955, FD0577140, FD0579983, FD0580403, FD0581156, FD0581623, FD0582680, FD0583090, FD0584073, FD0584500, FD0585410, FD0586089, FD0586790, FD0587500, FD0588791, FD0589023, FD0590248, FD0590600, FD0591592, FD0592445, FD0593277, FD0593712, FD0594626, FD0595049, FD0596132, FD0596519, FD0597701, FD0598681, FD0599198, FD0600210, FD0600690, FD0601755, FD0602401, FD0603415, FD0603985, FD0605122, FD0608608, FD0609074, FD0609979, FD0610508, FD0611469, FD0612006, FD0612905
RECALLING FIRM/MANUFACTURER
DCI Biologicals LLC, Farmington, NM, by facsimile on September 26, 2009 and electronic mail dated January 15, 2010. Firm initiated recall is complete.
REASON
Blood products, collected from a donor who was at risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE
119 units
DISTRIBUTION
NY, UK

___________________________________

END OF ENFORCEMENT REPORT FOR SEPTEMBER 8, 2010

http://www.fda.gov/Safety/Recalls/EnforcementReports/ucm225223.htm


PRODUCT
Source Plasma. Recall # B-2134-10
CODE
Units: 3910020431, 3910019695, 3910018715, 3910018227, 3910017100, 3910016675, 3910015596, 3910015120, 3910014175, 3910013575, 3910012934, 3910012281, 3910010102, 3910009899, 3910007715, 3910007430
RECALLING FIRM/MANUFACTURER
Talecris Plasma Resources, Inc., N Las Vegas, NV, by fax on July 17, 2009. Firm initiated recall is complete.
REASON
Blood products, collected from a donor considered to be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE
16 units
DISTRIBUTION
NC

___________________________________

PRODUCT
1) Red Blood Cells. Recall # B-2215-10;
2) Fresh Frozen Plasma. Recall # B-2216-10
CODE
1) and 2) Unit: 0951592
RECALLING FIRM/MANUFACTURER
Memorial Blood Centers, Saint Paul, MN, by letter on November 5, 2008. Firm initiated recall is complete.
REASON
Blood products, collected from a donor considered to be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE
2 units
DISTRIBUTION
MN

___________________________________

PRODUCT
Recovered Plasma. Recall # B-2217-10
CODE
Unit: 0951592
RECALLING FIRM/MANUFACTURER
Memorial Blood Centers, Saint Paul, MN, by letter on November 5, 2008. Firm initiated recall is complete.
REASON
Blood product, collected from a donor considered to be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), was distributed.
VOLUME OF PRODUCT IN COMMERCE
1 unit
DISTRIBUTION
MN

___________________________________

END OF ENFORCEMENT REPORT FOR SEPTEMBER 1, 2010

http://www.fda.gov/Safety/Recalls/EnforcementReports/ucm224723.htm



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