Study protocol for enhanced CJD surveillance in the 65+ years population group in Scotland: an observational neuropathological screening study of banked brain tissue donations for evidence of prion disease.

INTRODUCTION: Creutzfeldt-Jakob disease (CJD) is a human prion disease that occurs in sporadic, genetic and acquired forms. Variant CJD (vCJD) is an acquired form first identified in 1996 in the UK. To date, 178 cases of vCJD have been reported in the UK, most of which have been associated with dietary exposure to the bovine spongiform encephalopathy agent. Most vCJD cases have a young age of onset, with a median age at death of 28 years. In the UK, suspected cases of vCJD are reported to the UK National Creutzfeldt-Jakob Disease Research & Surveillance Unit (NCJDRSU). There is, however, a concern that the national surveillance system might be missing some cases of vCJD or other forms of human prion disease, particularly in the older population, perhaps because of atypical clinical presentation. This study aims to establish whether there is unrecognised prion disease in people aged 65 years and above in the Scottish population by screening banked brain tissue donated to the Edinburgh Brain Bank (EBB). METHODS: Neuropathological screening of prospective and retrospective brain tissue samples is performed. This involves histopathological and immunohistochemical analysis and prion protein biochemical analysis. During the study, descriptive statistics are used to describe the study population, including the demographics and clinical, pathological and referral characteristics. Controlling for confounders, univariate and multivariate analyses will be used to compare select characteristics of newly identified suspect cases with previously confirmed cases referred to the NCJDRSU. ETHICS AND DISSEMINATION: Brain tissue donations to EBB are made voluntarily by the relatives of patients, with consent for use in research. The EBB has ethical approval to provide tissue samples to research projects (REC reference 16/ES/0084). The findings of this study will be disseminated in meetings, conferences, workshops and as peer-reviewed publications. TRIAL REGISTRATION NUMBERS: 10/S1402/69 and 10/S1402/70.

Variant Creutzfeldt-Jakob disease in the United Kingdom: a countrywide or local risk?

BACKGROUND: The aim of this study was to identify factors that may have augmented local risks for variant Creutzfeldt-Jakob disease (vCJD). METHODS: A descriptive study was conducted of local investigations of UK cases of vCJD, who had lived close together at some point since 1980. The main outcome measures were domestic, educational, occupational, healthcare associated, social and recreational links between cases; common dietary, iatrogenic and other possible routes of exposure to vCJD infection; and locally elevated vCJD risk. RESULTS: A cluster of five cases of vCJD in a rural area in North Leicestershire was investigated in 2000 (p=0.004). A further 12 investigations of geographically associated cases of vCJD have been undertaken in the UK. In nine of the 12 locations, some or all of the local cases had consumed beef purchased from the same local retail outlets or provided by a common supplier of school meals, or had some aspect of their medical-dental care in common. In only three of these locations were circumstances identified where the local risk of transmission might have been elevated. In none of the locations was there strong evidence to exclude chance as a likely explanation for the local occurrence of these vCJD cases. CONCLUSION: Although it is possible that in some parts of the UK local factors may have increased the risk of acquiring vCJD, most cases that were geographically close to each other are most likely due to the same factors that gave rise to the large majority of other vCJD cases in the UK.

High accuracy of home-based community rapid HIV testing in rural Malawi.

OBJECTIVE: To assess the performance of rapid HIV antibody tests when used as part of a home-based community wide counseling and testing strategy in northern Malawi. DESIGN: A cross-sectional population survey of HIV infection, 2007 to 2008. METHODS: Adults aged 15 years or older in a demographic surveillance area were counseled and then offered an HIV test at their home by government-certified counselors. Two initial rapid tests (Determine and Uni-Gold) were performed on all samples and a third, tie-breaker test (SD Bioline) used to resolve discordant results. All people who wanted to know were posttest-counseled and informed of their results with referral to local clinical services if found to be HIV-positive. Laboratory quality control comprised retesting all positive and every tenth negative venous blood sample collected. RESULTS: A total of 10,819 adults provided venous blood samples for HIV testing, of whom 7.5% (813) were HIV-positive. The accuracy of the parallel testing strategy used was high with 99.6% sensitivity, 100.0% specificity, 99.9% positive predictive value, and 99.9% negative predictive value. CONCLUSION: Face-to-face rapid testing by health personnel with minimum training at the client's home performs well when used on a wide scale in the community setting.

Potential of environmental models to predict meningitis epidemics in Africa.

OBJECTIVES: Meningococcal meningitis is a major public health problem in Africa. This report explores the potential for climate/environmental models to predict the probability of occurrence of meningitis epidemics. METHODS: Time series of meningitis cases by month and district were obtained for Burkina Faso, Niger, Mali and Togo (536 district-years). Environmental information (1989-1999) for the continent [soil and land-cover type, aerosol index, vegetation greenness (NDVI), cold cloud duration (CCD) and rainfall] was used to develop models to predict the incidence of meningitis. Meningitis incidence, dust, rainfall, NDVI and CCD were analysed as anomalies (mean minus observed value). The models were developed using univariate and stepwise multi-variate linear regression. RESULTS: Anomalies in annual meningitis incidence at district level were related to monthly climate anomalies. Significant relationships were found for both estimates of rainfall and dust in the pre-, post- and epidemic season. While present in all land-cover classes these relationships were strongest in savannah areas. CONCLUSIONS: Predicting epidemics of meningitis could be feasible. To fully develop this potential, we require (a) a better understanding of the epidemiological and environmental phenomena underpinning epidemics and how satellite derived climate proxies reflect conditions on the ground and (b) more extensive epidemiological and environmental datasets. Climate forecasting tools capable of predicting climate variables 3-6 months in advance of an epidemic would increase the lead-time available for control strategies. Our increased capacity for data processing; the recent improvements in meningitis surveillance in preparation for the distribution of the impending conjugate vaccines and the development of other early warning systems for epidemic diseases in Africa, favours the creation of these models.

Geographic Information System mapping of snakebite incidence in northern Ghana and Nigeria using environmental indicators: a preliminary study.

Snakebite is an important health problem in many parts of rural West Africa where the carpet or sawscaled viper, Echis ocellatus, is responsible for most of the morbidity and mortality. Marked seasonal and geographical variation in the incidence of snakebite suggests an association with environmental factors that could potentially identify high-risk areas and inform health care decision making. This preliminary investigation describes a Geographic Information System (GIS) approach to risk mapping that identifies environmental variables potentially associated with variation in snakebite incidence rates at a number of health facilities in northern Ghana and Nigeria and which has been used to create a preliminary risk map of the potential probability of high snakebite incidence for West Africa. Detailed and extensive further studies will enable the more reliable estimation of snakebite incidence at a local level across the region.

Where is the meningitis belt? Defining an area at risk of epidemic meningitis in Africa.

Mapping an area at risk of epidemics of meningococcal meningitis in Africa has significant implications for their prevention and case treatment, through the targeted development of improved surveillance systems and control policies. Such an area was described using information obtained from published and unpublished reports of meningitis epidemics between 1980 and 1999 and cases of meningococcal disease reported by surveillance systems to WHO. The Sahel bore the greatest epidemic burden, with over two-thirds of documented outbreaks and high attack rates. In addition to those already in the Meningitis Belt, countries affected included Guinea-Bissau, Guinea, Côte d'Ivoire, Togo, the Central African Republic and Eritrea. Elsewhere epidemics were reported from a band of countries around the Rift Valley and Great Lakes regions extending as far south as Mozambique and from here west to Angola and Namibia in southern Africa. The cumulative pan-continental analysis provided evidence of an epidemic-susceptible area which extends beyond the region accepted as the Meningitis Belt and which, moreover, may be partially determined by the physical environment, as shown by a striking correspondence to the 300-1100-mm mean annual rainfall isohyets.