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  • Implications of BSE infection screening data for the scale of the British BSE epidemic and current European infection levels.

    1 February 2019

    The incidence of confirmed clinical cases of bovine spongiform encephalopathy (BSE) in Great Britain continues to decline, but the recent discovery of cases in previously unaffected countries (including Israel, Japan, Poland, Slovenia and Spain) has heightened concerns that BSE transmission was more intense and widespread than previously thought. We use back-calculation methods to undertake an integrated analysis of data on infection prevalence in apparently healthy cattle and the incidence of confirmed clinical disease. The results indicate substantial underascertainment of clinical cases over the course of the British epidemic, and consequently that two- to fourfold more animals were infected than previously estimated. Upper bounds on the predicted size of the new variant Creutzfeldt-Jakob Disease (vCJD) epidemic are unaffected, as the prediction methods employed fit to observed vCJD mortality data, and are not sensitive to estimates of the absolute magnitude of past human exposure to BSE-infected cattle, only to relative changes in exposure through time. We also estimate the per-head incidence of infection in cattle born between 1993 and 1997 in other European Union countries, using data on the testing of apparently healthy cattle slaughtered for consumption. Infection incidence for cattle born after mid-1996 was highest in Greece, Italy and Belgium, with Spain and The Netherlands having intermediate levels, and estimates for Great Britain, Germany and France being comparably low.

  • Surrogate markers for disease progression in treated HIV infection.

    1 February 2019

    OBJECTIVE: To characterize the relationships among highly active antiretroviral therapy (HAART), HIV-1 RNA levels, immune system markers, and clinical outcome in a cohort of HIV-1-infected homosexual men. PATIENTS: A total of 123 men enrolled in the Amsterdam cohort study of HIV-1 infection and AIDS with a documented seroconversion for HIV-1 antibodies and known date of seroconversion were included in this study. METHODS: CD4 + /CD8 + T-cell counts and HIV-1 RNA levels in plasma were measured approximately every 6 months. Dates of starting and stopping antiretroviral therapy were also recorded. The relationship between HIV-1 RNA in plasma, CD4 + /CD8 + T-cell counts and HAART and their influence on clinical outcome were examined using a graphical chain modeling approach. Generalized estimating equations were used to examine correlations among the three disease markers. Hazards models with time-dependent covariates were used to examine the influence of HAART and the disease markers on progression to AIDS. RESULTS: HAART was significantly associated with reduced disease progression (relative hazard [RH] of AIDS, 0.20;, 95% confidence interval [CI], 0.05-0.85). The most recent HIV-1 RNA measurement and CD4 + T-cell count are independently associated with disease progression (adjusted RH for HIV-1 RNA 1.8 per log 10 increase; 95% CI, 1.2-2.6, p =.002; adjusted RH for CD4 + 0.48 per 100 x 10(6)/L increase; 95% CI, 0.40-0.58; p <.001). Depending on these measurements, HAART was no longer significantly associated with AIDS (adjusted RH, 0.81; 95% CI, 0.18-3.6; p =.78). CONCLUSIONS: HIV-1 RNA levels in plasma and CD4 + T-cell counts are currently considered as effective surrogate markers for the effect of HAART on disease progression in this cohort.

  • Vaccine design, evaluation, and community-based use for antigenically variable infectious agents.

    1 February 2019

    A major challenge for vaccine design and development, and for trials of new vaccines, is to tackle antigenically variable infectious agents. Here we outline a few general conceptual issues and then discuss new frameworks that are being developed to help understand how vaccination might change the distribution, abundance, and type of strains in a population. Herd Immunity is a key concept in population-based immunisation programmes and has to be considered in vaccine design and use even though it may cause a conflict between the needs of the individual versus those of the community. This issue is of increasing importance since once common infections are becoming rare due to effective vaccination. Concomitantly, adverse effects arising from immunisation are becoming more apparent as infection-induced morbidity declines to very low levels. Efficacy is widely regarded as a key criterion in vaccine design but duration of protection is of equal importance. Whether it is possible to produce effective vaccines to antigenically diverse pathogens remains uncertain but progress towards this goal will be enhanced by a better understanding of the population genetics of the target infectious agent facilitated by molecular epidemiological studies to assess the genetic constitution of pathogen populations and changes therein over time.

  • Analysis of dam-calf pairs of BSE cases: confirmation of a maternal risk enhancement.

    1 February 2019

    We investigate whether a calf born to a dam that develops bovine spongiform encephalopathy (BSE) (prior or subsequent to the birth) is itself at an enhanced risk of developing BSE. Analyses utilize the main database on reported BSE cases in the British cattle herd maintained by the Central Veterinary Laboratory in Weybridge to trace the dams of BSE-affected animals born following the ruminant feed ban in July 1988. The data reveal a significantly enhanced risk of disease in calves born to BSE-affected dams, with the risk being greatest when birth occurs after the onset of clinical signs of disease in the dam. The dependence of the maternally enhanced risk on the maternal incubation stage at birth argues for a significant component of direct maternal transmission of the aetiological agent of BSE, and offers little support for the hypothesis of genetic predisposition. Using a statistical likelihood model, we obtain estimates of the rate of direct maternal transmission by maternal incubation stage; however, biases in the available data make these values minimum estimates.

  • Some blood plasma constituents correlate with human cataract.

    1 February 2019

    AIMS: To look for differences between matched pairs of patients and controls in concentrations of various plasma constituents which might indicate dysfunctions associated with cataract. METHOD: One thousand patients were taken from the cataract waiting list of a specialist eye hospital. For each patient a matched control of the same sex and half-decade of age but without cataract was taken from the patient list of the family doctor of the patient; the control was the next alphabetically after the patient on the doctor's list. The patients and controls were visited in their homes by a team of nurses who performed venepunctures and collected information for a questionnaire. Eye examinations were performed by a team of ophthalmologists. RESULTS: Significant differences were found between the cataract and control groups in 10 of the 18 examined plasma constituents. A constellation of three--bilirubin, alkaline phosphatase, and gamma glutamyl transpeptidase--was significantly higher in the cataract group, suggesting subclinical liver dysfunction as a risk factor. Steroid treatment and diabetes increased cataract risk. Endogenous basal plasma cortisol levels were raised in the cataract group, irrespective of steroid use and diabetic status. Alkaline phosphatase, calcium, glucose, and sodium were all raised in the cataract group. Given the raised total protein and albumin also found in the cataract group, the lower albumin/(total protein-albumin) ratio (an approximation for albumin/globulin ratio) may imply an increase in globulin, suggestive of possible (chronic) infection. Total cholesterol was lower in the cataract group. CONCLUSION: Human cataract in older age groups seems to be due to an accumulation of risk factors, even if individual mean concentrations are well within normal limits but, of course, differing significantly from the corresponding means in the control population.

  • The spatial analysis of covariates in a study of environmental epidemiology.

    1 February 2019

    Kanawha County, West Virginia, includes a deep river valley with a large population living in close proximity to many chemical manufacturing centres. One study of this area combined an epidemiologic survey of children attending Kanawha County schools with the measurement of the concentrations of 15 volatile organic compounds at each of the 75 elementary schools. Results have been reported by Ware et al. This paper further examines the associations of the concentrations of the ten individual volatile organic compounds related to chemical manufacturing processes with observed lower respiratory symptoms, generalizing the model of spatial variability and measurement error proposed by Donnelly et al. and using semi-variograms to assess the validity of model assumptions.

  • Badgers prefer cattle pasture but avoid cattle: implications for bovine tuberculosis control.

    1 February 2019

    Effective management of infectious disease relies upon understanding mechanisms of pathogen transmission. In particular, while models of disease dynamics usually assume transmission through direct contact, transmission through environmental contamination can cause different dynamics. We used Global Positioning System (GPS) collars and proximity-sensing contact-collars to explore opportunities for transmission of Mycobacterium bovis [causal agent of bovine tuberculosis] between cattle and badgers (Meles meles). Cattle pasture was badgers' most preferred habitat. Nevertheless, although collared cattle spent 2914 collar-nights in the home ranges of contact-collared badgers, and 5380 collar-nights in the home ranges of GPS-collared badgers, we detected no direct contacts between the two species. Simultaneous GPS-tracking revealed that badgers preferred land > 50 m from cattle. Very infrequent direct contact indicates that badger-to-cattle and cattle-to-badger M. bovis transmission may typically occur through contamination of the two species' shared environment. This information should help to inform tuberculosis control by guiding both modelling and farm management.

  • Bovine Tuberculosis Risk Factors for British Herds Before and After the 2001 Foot-and-Mouth Epidemic: What have we Learned from the TB99 and CCS2005 Studies?

    1 February 2019

    Over the last couple of decades, the UK experienced a substantial increase in the incidence and geographical spread of bovine tuberculosis (TB), in particular since the epidemic of foot-and-mouth disease (FMD) in 2001. The initiation of the Randomized Badger Culling Trial (RBCT) in 1998 in south-west England provided an opportunity for an in-depth collection of questionnaire data (covering farming practices, herd management and husbandry, trading and wildlife activity) from herds having experienced a TB breakdown between 1998 and early 2006 and randomly selected control herds, both within and outside the RBCT (the so-called TB99 and CCS2005 case-control studies). The data collated were split into four separate and comparable substudies related to either the pre-FMD or post-FMD period, which are brought together and discussed here for the first time. The findings suggest that the risk factors associated with TB breakdowns may have changed. Higher Mycobacterium bovis prevalence in badgers following the FMD epidemic may have contributed to the identification of the presence of badgers on a farm as a prominent TB risk factor only post-FMD. The strong emergence of contact/trading TB risk factors post-FMD suggests that the purchasing and movement of cattle, which took place to restock FMD-affected areas after 2001, may have exacerbated the TB problem. Post-FMD analyses also highlighted the potential impact of environmental factors on TB risk. Although no unique and universal solution exists to reduce the transmission of TB to and among British cattle, there is an evidence to suggest that applying the broad principles of biosecurity on farms reduces the risk of infection. However, with trading remaining as an important route of local and long-distance TB transmission, improvements in the detection of infected animals during pre- and post-movement testing should further reduce the geographical spread of the disease.

  • Exploration of the power of routine surveillance data to assess the impacts of industry-led badger culling on bovine tuberculosis incidence in cattle herds.

    1 February 2019

    In the UK, badgers (Meles meles) are a well-known reservoir of infection, and there has been lively debate about whether badger culling should play a role within the British Government's strategy to control and eventually eradicate tuberculosis (TB) in cattle. The key source of information on the potential for badger culling to reduce cattle TB in high-cattle-TB-incidence areas remains the Randomised Badger Culling Trial (RBCT). In late 2013, two pilot areas were subjected to industry-led badger culls. These culls differed importantly from RBCT culling in that free-ranging as well as cage-trapped badgers were shot, and culling took place over a longer time period. Their impacts will be harder to evaluate because culling was not randomised between comparable areas for subsequent comparisons of culling versus no culling. However, the authors present calculations that explore the power of routine surveillance data to assess the impacts of industry-led badger culling on cattle TB incidence. The rollout of industry-led culling as a component of a national cattle TB control policy would be controversial. The best possible estimates of the effects of such culling on confirmed cattle TB incidence should be made available to inform all stakeholders and policy-makers.