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PAPERS: Kumanan Wilson, Catherine Code, and Maura N Ricketts Risk of acquiring Creutzfeldt-Jakob disease from blood transfusions: systematic review of case-control studies BMJ 2000; 321: 17-19 [Abstract] [Full text]

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Methodological limitations of studies understated in review.

Phil Jopson   (6 July 2000)

Variant Creutzfeld-Jacob Disease and the importance of tracing patients with corneal grafts

Guy Smith   (7 October 2000)

Methodological limitations of studies understated in review. 6 July 2000
Phil Jopson, Stage 3 Medical Student Newcastle University Medical School Send response to journal: Re: Methodological limitations of studies understated in review.	Methodological Limitations of studies understated in Review Dear Sir, In the systematic review of case-control studies by Wilson et al (1st July, p17) the authors investigate the strength of association between history of blood transfusion and development of CJd. In this paper, the "spurious result", namely the protective effect of past transfusion, is attributed to methodological limitations of the studies used. These include the method of reporting transfusion status. The paper quotes that "25-40% of transfusion recipients do not recall having received transfusions" . We consider this to be potentially a huge source of error. How much more so then is the inaccuracy of relying on surrogate ("usually relatives") reports for this information? Although we agree that this error may apply equally to both case and control groups, such a flaw must lead us to question the validity of results. We would suggest that future studies in this field could use hospital records to provide a more reliable source of data. Another limitation identified is the inconsistency of the method of selection of controls between the studies. We would agree, but would question how suitable it is to include studies in which the control group were recruited from hospital. As mentioned in the paper, these patients are more likely to have received a transfusion than are the general population. It certainly seems inappropriate to us to compare such studies with those which do have population control. Although this review seeks to address a valid question, it should perhaps have more clearly emphasised its focus on the sporadic form of the disease. At a glance, it can easily be assumed that the subject is variant CJd, which currently generates more public concern. Indeed, a similar review focusing on variant CJd may would seem to be more pertinent to current medical interest. Yours faithfully, Kate Albaya, Phil Jopson, Andie Peckett We gratefully acknowledge the help of Dr Tanya Pless-Mulloli
Variant Creutzfeld-Jacob Disease and the importance of tracing patients with corneal grafts 7 October 2000
Guy Smith, SpR Ophthalmology Southend Hospital Send response to journal: Re: Variant Creutzfeld-Jacob Disease and the importance of tracing patients with corneal grafts	Dear Sir, In 1999 there were 2224 corneal grafts, almost as many as all other organ types combined (2445) [personal communication UKTSSA]. All doctors need to take into account the presence of a corneal graft when managing patients, as systemic illnesses and treatments may trigger graft rejection. A corneal graft recipient provided the first evidence of human to human transmission of a spongiform encephalopathy [1]. Therefore in addition to the prevention of graft rejection, there is the issue of Creutzfeld-Jacob Disease (CJD) transmission. To date there have been 67 cases of variant CJD (vCJD) diagnosed in the UK [2], but the potential for a human epidemic is unknown. The incubation period can only be estimated to lie between 10 and 30 years because the exact pathogenic mechanism of the prion protein is uncertain. During this long presymptomatic period an organ donor infected with vCJD may transmit prions to a recipient. Despite the protocols in place to minimize the transmission of infection to the recipient, organ donors are not routinely screened for vCJD [3]. Three patients have already received a cornea or sclera from a donor with CJD [4]. Therefore patients receiving ocular tissue have not only their own risk of vCJD but that of the donor as well. Major visceral organ transplants are unlikely to be overlooked, however this is not the case with corneal grafts. Many healthcare professionals, doctors included, are unaware that penetrating keratoplasty involves the transplantation of human tissue. As a group these patients are at higher risk of developing and transmitting vCJD [5] so it is important to know who and where they are. We recently surveyed the General Practices who refer to our Eye Unit with reference to their patients with corneal grafts. 55 out of 66 practices responded. 28 practices were able estimated how many patients with corneal grafts were under their care. The partners estimates did not vary by more than one patient at most practices, however at one practice the estimate varied from two to eight patients. We then compared the estimates for each practice with our department’s register of corneal graft patients. At 9 practices the estimated number of patients with corneal grafts was correct. Of the remaining 19, 15 underestimated the number of patients and 4 practices overestimated the number of patients. Only one of the general practitioners contacted was able to name their corneal graft patients. We were unable to trace 10 of our graft patients back to the general practitioner to whom they were registered and no forwarding address was available. Because general practitioners are at the hub of the health care system, they are well placed to keep a register of corneal graft patients and inform other doctors of the presence of a corneal graft in their referral letters. In addition ophthalmologists need to emphasize the significance of having a corneal graft to their patients, in particular that they cannot offer their organs or tissues for transplantation. Should we also be telling them that they should not donate blood? Authors: G. T. SMITH, R. M. SHEARD Institution: Department of Ophthalmology, Southend Hospital, Prittlewell Chase, Westcliff-on-sea, Essex, SS0 0RY England. Corresponding Author: Mr Guy T. Smith, FRCOphth, Specialist Registrar in Ophthalmology, Southend Hospital. References: 1 Duffy P, Wolf J, Collins J, Devoe AG, Streen B, Cowen D. Possible person-to-person transmission of Creutzfeld-Jacob disease. N Engl J Med 1974;290:692-693. 2 Lueck CJ, McIlwaine GG, Zeidler M. Creutzfeld-Jacob disease and the eye. I. Background and patient management. Eye 2000;14:263-290. 3 Guidance on the microbiological safety of human organs, tissues and cells used in transplantation. Department of Health Advisory committee on the microbiological safety of blood and tissues for transplantation. August 2000. 4 Allan B, Tuft S. Transmission of Creutzfeld-Jacob disease in corneal grafts. BMJ 1997;315:1553-1554. 5 Eastland T. Infectious disease transmission through cell, tissue, and organ transplantation: reducing the risk through donor selection. Cell transplantation 1995;4:455-477.