Hester J.T. Ward

Risk factors for variant Creutzfeldt-Jakob disease: A case-control study

To investigate the potential risk factors for variant Creutzfeldt‐Jakob disease (VCJD) in the United Kingdom.

Deaths from variant Creutzfeldt-Jakob disease in the UK

In 2002, 17 people died from variant CJD (vCJD) in the UK, compared with 20 in 2001 and 28 in 2000. We analysed data for deaths from vCJD since 1995 and estimated the underlying trend in mortality. The trend had a quadratic component (p=0.005), suggesting that the increase was not exponential, and that the previously increasing trend is slowing down. The death rate peaked in 2000. These findings are encouraging, but mortality might increase again in the future.

Incidence of variant Creutzfeldt-Jakob disease in the UK

The number of deaths from variant CJD (vCJD) in the UK increased in the last quarter of 1998, although numbers were lower in subsequent quarters. We analysed the numbers of definite and probable (living and dead) vCJD cases since 1994 to assess trends in incidence. We estimated that the number of onsets increased by 23% per year for 1994-2000 (p=0.004), and that deaths increased by 33% for 1995-2000 (p=0.005). The absolute number of cases in the UK is still low, but such an increase should be a matter of concern.

Risk factors for sporadic Creutzfeldt–Jakob disease

Although surgical transmission of Creutzfeldt–Jakob disease (CJD) has been demonstrated, these iatrogenic cases account for only a small proportion of all CJD cases. The majority are sporadic CJD (sCJD) cases of unknown cause. This study investigated whether some cases classified as sCJD might have an unrecognized iatrogenic basis through surgical or other medical procedures

A case-control study of sporadic Creutzfeldt-Jakob disease in the United Kingdom: Analysis of clustering.

Background: The authors investigated whether cases of sporadic Creutzfeldt-Jakob disease (CJD) had lived closer to one another at some time in life than individuals without sporadic CJD. Such a phenomenon would be compatible with some cases resulting from transmission. Methods: UK sporadic CJD cases occurring from 1990 to 1998 were identified. Age-, sex- and hospital-matched controls were recruited. Lifetime residential histories were obtained by interview, usually with a proxy respondent. With use of Monte Carlo simulation, the residential proximity of cases during various time periods was compared with that expected in the absence of any clustering, using the information collected on the controls. Results: Two hundred twenty sporadic CJD disease cases and 220 controls were included. Cases lived closer together than might be expected in the absence of any disease-clustering mechanism. This evidence became stronger as the critical period during which residential proximity was required to have occurred extended further into the past. Conclusions: These findings are consistent with some sporadic Creutzfeldt-Jakob disease (CJD) cases resulting from exposure to a common external factor. The rarity of sporadic CJD suggests that repeated point-source outbreaks of infection are more likely to explain our observations than direct case-to-case transmission. Identifying sources of such outbreaks many years after the event will be extremely difficult.

Variant Creutzfeldt-Jakob disease

Variant Creutzfeldt-Jakob disease is caused by the transmission of bovine spongiform encephalopathy to humans. The clinical and investigative features of variant CJD are relatively distinct from sporadic CJD. The number of cases of vCJD are increasing with time in the UK, but the total future number of cases of vCJD is uncertain.

The Epidemiology of Variant Creutzfeldt-Jakob Disease

Variant Creutzfeldt-Jakob disease (vCJD) was identified as a new disease in 1996. It was linked to infection with the bovine spongiform encephalopathy (BSE) agent although the epidemiological evidence for this was not strong, but later strain typing studies confirmed the association. The disease has affected predominantly young adults whose dietary and other characteristics are unexceptional compared to control groups, other than that all patients to date have been methoinine homozygous at codon 129 of the prion protein gene and the incidence has been about two times higher in the North of the UK. The number of cases in the 7 years after first identification of the disease has been considerably lower than initially feared, given the likely widespread exposure of the UK population to the BSE agent through contaminated beef products. Predictions of the possible future course of the epidemic have many associated uncertainties, but current mathematical models suggest that more than a few thousand cases is unlikely. Such modelling is limited by the absence of a test for infection with the vCJD agent. The development of a test that could be used on easily accessible tissue to detect infection early in the incubation period would not only advance understanding of the epidemiology of infection with the agent but would also aid the implementation of control measures to prevent potential iatrogenic spread.

A retrospective case note review of deceased recipients of vCJD-implicated blood transfusions.

Background  To date, four instances of probable transfusion–transmission of variant Creutzfeldt–Jakob disease (vCJD) infection have been described, and surviving recipients of vCJD‐implicated blood components have been informed that they may be ‘at risk’ of vCJD. Nearly two‐thirds of all recipients of vCJD‐implicated blood components are deceased, and many died before the vCJD risk was known. The primary aim of this study was to determine retrospectively whether there was evidence that any of the other deceased recipients of vCJD‐implicated blood components had any clinical signs or symptoms suggestive of vCJD in life. In addition, pathological material from recipients, stored at the time of surgery or autopsy, was sought to allow testing for evidence of vCJD infection. A secondary aim of the study was to obtain information on invasive healthcare procedures undertaken on recipients following the transfusion to identify the potential for onward transmission of infection.

Factors determining the potential for onward transmission of variant Creutzfeldt–Jakob disease via surgical instruments

While the number of variant Creutzfeldt–Jakob disease (vCJD) cases continues to decline, concern has been raised that transmission could occur directly from one person to another through routes including the transfer of blood and shared use of surgical instruments. Here we firstly present data on the surgical procedures undertaken on vCJD patients prior to onset of clinical symptoms, which supports the hypothesis that cases via this route are possible. We then apply a mathematical framework to assess the potential for self-sustaining epidemics via surgical procedures. Data from hospital episode statistics on the rates of high- and medium-risk procedures in the UK were used to estimate model parameters, and sensitivity to other unknown parameters about surgically transmitted vCJD was assessed. Our results demonstrate that a key uncertainty determining the scale of an epidemic and whether it is self-sustaining is the number of times a single instrument is re-used, alongside the infectivity of contaminated instruments and the effectiveness of cleaning. A survey into the frequency of re-use of surgical instruments would help reduce these uncertainties.

Variant Creutzfeldt-Jakob disease and exposure to fractionated plasma products.

Background  The risk to public health of onward transmission of variant Creutzfeldt–Jakob disease (vCJD) via blood transfusion and plasma product administration is of on‐going concern, particularly with the recent reported detection of abnormal prion protein in a person with haemophilia.