Conserving large populations of lions - the argument for fences has holes.

Packer et al. reported that fenced lion populations attain densities closer to carrying capacity than unfenced populations. However, fenced populations are often maintained above carrying capacity, and most are small. Many more lions are conserved per dollar invested in unfenced ecosystems, which avoid the ecological and economic costs of fencing.

Herd-level risk factors of bovine tuberculosis in England and Wales after the 2001 foot-and-mouth disease epidemic.

OBJECTIVES: We present the results of a 2005 case-control study of bovine tuberculosis (bTB) breakdowns in English and Welsh herds. The herd management, farming practices, and environmental factors of 401 matched pairs of case and control herds were investigated to provide a picture of herd-level risk factors in areas of varying bTB incidence. METHODS: A global conditional logistic regression model, with region-specific variants, was used to compare case herds that had experienced a confirmed bTB breakdown to contemporaneous control herds matched on region, herd type, herd size, and parish testing interval. RESULTS: Contacts with cattle from contiguous herds and sourcing cattle from herds with a recent history of bTB were associated with an increased risk in both the global and regional analyses. Operating a farm over several premises, providing cattle feed inside the housing, and the presence of badgers were also identified as significantly associated with an increased bTB risk. CONCLUSIONS: Steps taken to minimize cattle contacts with neighboring herds and altering trading practices could have the potential to reduce the size of the bTB epidemic. In principle, limiting the interactions between cattle and wildlife may also be useful; however this study did not highlight any specific measures to implement.

The prevalence, distribution and severity of detectable pathological lesions in badgers naturally infected with Mycobacterium bovis.

The Randomized Badger Culling Trial (RBCT) began in 1998 to determine the impact of badger culling in controlling bovine tuberculosis in cattle. A total of 1166 badgers (14% of total) proactively culled during the RBCT were found to be tuberculous, offering a unique opportunity to study the pathology caused by Mycobacterium bovis in a large sample of badgers. Of these, 39% of adults (approximately 6% of all adults culled) had visible lesions (detectable at necropsy) of bovine tuberculosis; cubs had a lower prevalence of infection (9%) but a higher percentage of tuberculous cubs (55.5%) had visible lesions. Only approximately 1% of adult badgers had extensive, severe pathology. Tuberculous badgers with recorded bite wounds (approximately 5%) had a higher prevalence of visible lesions and a different distribution of lesions, suggesting transmission via bite wounds. However, the predominance of lesions in the respiratory tract indicates that most transmission occurs by the respiratory route.

Tacrolimus versus cyclosporin as primary immunosuppression for kidney transplant recipients.

BACKGROUND: Kidney transplantation is the treatment of choice for most patients with end-stage renal disease (ESRD). Standard protocols in use typically involve three drug groups each directed to a site in the T-cell activation or proliferation cascade which are central to the rejection process: calcineurin inhibitors (e.g. cyclosporin, tacrolimus), anti-proliferative agents (e.g. azathioprine, mycophenolate mofetil) and steroids (prednisolone). It remains unclear whether new regimens are more specific or simply more potent immunosuppressants. OBJECTIVES: To compare the effects of tacrolimus with cyclosporin as primary therapy for kidney transplant recipients. SEARCH STRATEGY: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Cochrane Renal Group's specialist register and conference proceedings were searched to identify relevant reports of randomised controlled trials (RCTs). Two reviewers assessed trials for eligibility, quality and extracted data independently. SELECTION CRITERIA: All RCTs where tacrolimus was compared with cyclosporin for the initial treatment of kidney transplant recipients DATA COLLECTION AND ANALYSIS: Data were synthesised (random effects model) and results expressed as relative risk (RR), values <1 favouring tacrolimus, with 95% confidence intervals (CI). Subgroup analysis and meta-regression were used to examine potential effect modification by differences in trial design and immunosuppressive co-interventions. MAIN RESULTS: 123 reports from 30 trials (4102 patients) were included. At six months graft loss was significantly reduced in tacrolimus-treated recipients (RR 0.56, 95% CI 0.36 to 0.86), and this effect was persistent up to three years. Meta-regression showed that this benefit diminished as higher trough levels of tacrolimus were targeted (P = 0.04), after allowing for differences in cyclosporin formulation (P = 0.97) and cyclosporin target trough level (P = 0.38). At one year, tacrolimus patients suffered less acute rejection (RR 0.69, 95% CI 0.60 to 0.79), and less steroid-resistant rejection (RR 0.49, 95% CI 0.37 to 0.64), but more insulin-requiring diabetes mellitus (RR 1.86, 1.11 to 3.09), tremor, headache, diarrhoea, dyspepsia and vomiting. Cyclosporin-treated recipients experienced significantly more constipation and cosmetic side-effects. We demonstrated no differences in infection or malignancy. AUTHORS' CONCLUSIONS: Tacrolimus is superior to cyclosporin in improving graft survival and preventing acute rejection after kidney transplantation, but increases post-transplant diabetes, neurological and gastrointestinal side effects. Treating 100 recipients with tacrolimus instead of cyclosporin would avoid 12 suffering acute rejection, two losing their graft but cause an extra five to become insulin-requiring diabetics.

Clinical and cost-effectiveness of newer immunosuppressive regimens in renal transplantation: a systematic review and modelling study.

OBJECTIVES: To examine the clinical effectiveness and cost-effectiveness of the newer immunosuppressive drugs for renal transplantation: basiliximab, daclizumab, tacrolimus, mycophenolate (mofetil and sodium) and sirolimus. DATA SOURCES: Electronic databases. Industry submissions. Current Clinical Trials register. Cochrane Collaboration Renal Disease Group. REVIEW METHODS: The review followed the InterTASC standards. Each of the five company submissions to the National Institute for Clinical Excellence (NICE) contained cost-effectiveness models, which were evaluated by using a critique covering (1) model checking, (2) a detailed model description and (3) model rerunning. RESULTS: For induction therapy, three randomised controlled trials (RCTs) found that daclizumab significantly reduced the incidence of biopsy-confirmed acute rejection and patient survival at 6 months/1 year compared with placebo, but not compared with the monoclonal antibody OKT3. There was no significant gain in patient survival or graft loss at 3 years. The incidence of side-effects with daclizumab reduced compared to OKT3. Eight RCTs found that basiliximab significantly improved 6-month/1-year biopsy-confirmed acute rejection compared to placebo, but not compared to either ATG or OKT3. There was no significant gain in either 1-year patient survival or graft loss. The incidence of side-effects with basiliximab was not significantly different compared to OKT3/ATG. For initial/maintenance therapy, 13 RCTs found that tacrolimus reduced the 6-month/1-year incidence of biopsy-proven acute rejection compared to ciclosporin. There was no significant improvement in either 1-year or long-term (up to 5 years) graft loss or patient survival. The acute rejection benefit of tacrolimus over ciclosporin appeared to be equivalent for Sandimmun and Neoral. There were important differences in the side-effect profile of tacrolimus and ciclosporin. Seven RCTs found that mycophenolate mofetil (MMF) reduced the incidence of acute rejection. There was no significant difference in patient survival or graft loss at 1-year or 3-year follow-up. There appeared to be differences in the side-effect profiles of MMF and azathioprine (AZA). No RCTs comparing MMF with AZA were identified. One RCT compared mycophenolate sodium (MPS) to MMF and reported no difference between the two drugs in 1-year acute rejection rate, graft survival, patient survival or side-effect profile. Two RCTs suggest that addition of sirolimus to a ciclosporin-based initial/maintenance therapy reduces 1-year acute rejections in comparison to a ciclosporin (Neoral) dual therapy alone and substituting azathioprine with sirolimus in initial/maintenance therapy reduces the incidence of acute rejection. Graft and patient survival were not significantly different with either sirolimus regimen. Adding sirolimus increases the incidence of side-effects. The side-effect profiles of azathioprine and sirolimus appear to be different. For the treatment of acute rejection, three RCTs suggested that both tacrolimus and MMF reduce the incidence of subsequent acute rejection and the need for additional drug therapy. Only one RCT and one subgroup analysis in children (<18 years) were identified comparing ciclosporin to tacrolimus and sirolimus, respectively. CONCLUSIONS: The newer immunosuppressant drugs (basiliximab, daclizumab, tacrolimus and MMF) consistently reduced the incidence of short-term (1-year) acute rejection compared with conventional immunosuppressive therapy. The independent use of basiliximab, daclizumab, tacrolimus and MMF was associated with a similar absolute reduction in 1-year acute rejection rate (approximately 15%). However, the effects of these drugs did not appear to be additive (e.g. benefit of tacrolimus with adjuvant MMF was 5% reduction in acute rejection rate compared with 15% reduction with adjuvant AZA). Thus, the addition of one of these drugs to a baseline immunosuppressant regimen was likely to affect adversely the incremental cost-effectiveness of the addition of another. The trials did not assess how the improvement in short-term outcomes (e.g. acute rejection rate or measures of graft function), together with the side-effect profile associated with each drug, translated into changes in patient-related quality of life. Moreover, given the relatively short duration of trials, the impact of the newer immunosuppressants on long-term graft loss and patient survival remains uncertain. The absence of both long-term outcome and quality of life from trial data makes assessment of the clinical and cost-effectiveness on the newer immunosuppressants contingent on modelling based on extrapolations from short-term trial outcomes. The choice of the most appropriate short-term outcome (e.g. acute rejection rate or measures of graft function) for such modelling remains a matter of clinical and scientific debate. The decision to use acute rejection in the meta-model in this report was based on the findings of a systematic review of the literature of predictors of long-term graft outcome. Only a very small proportion of the RCTs identified in this review assessed patient-focused outcomes such as quality of life. Since immunosuppressive drugs have both clinical benefits and specific side-effects, the balance of these harms and benefits could best be quantified through future trials using quality of life measures. The design of future trials should be considered with a view to the impact of drugs on particular renal transplant groups, particularly higher risk individuals and children. Finally, there is a need for improved reporting of methodological details of future trials, such as the method of randomisation and allocation concealment. A number of issues exist around registry data, for example the use of multiple drug regimens and the need to assess the long-term outcomes. An option is the use of observational registry data including, if possible, prospective data on all consecutive UK renal transplant patients. Data capture for each patient should include immunosuppressant regimens, clinical and patient-related outcomes and patient demographics.

Incidental lesions found on CT colonography: their nature and frequency.

CT colonography has been used to detect colonic polyps and cancers, but its effect in practice will also be influenced by the frequency with which extracolonic lesions of various types are detected. We performed a systematic review of the types of incidental lesions found on CT colonography. This is necessary to model the benefits and harms of detecting extracolonic lesions. Primary clinical studies of extracolonic findings on CT colonography were identified from electronic databases, scanning reference lists and hand searches of relevant journals and conference proceedings. A data collection proforma was used to collect information on extracolonic findings. 17 discreet studies were identified, involving 3488 patients. In total 40% of patients were recorded to have abnormalities and many had more than one abnormality. Nearly 14% of patients had further investigations and 0.8% were given immediate treatment. Extracolonic cancers were detected in 2.7% (0.9% had N0M0 cancers) and 0.9% had an aortic aneurysm. The number of extracolonic findings was high in all studies. While only a small population were judged "important", the prevalence of serious lesions outside the colon was nevertheless higher than in many other screening programs.

Herd-level risk factors associated with tuberculosis breakdowns among cattle herds in England before the 2001 foot-and-mouth disease epidemic.

A case-control study of the factors associated with the risk of a bovine tuberculosis (TB) breakdown in cattle herds was undertaken within the randomized badger culling trial (RBCT). TB breakdowns occurring prior to the 2001 foot-and-mouth disease epidemic in three RBCT triplets were eligible to be cases; controls were selected from the same RBCT area. Data from 151 case farms and 117 control farms were analysed using logistic regression. The strongest factors associated with an increased TB risk were movement of cattle onto the farm from markets or farm sales, operating a farm over multiple premises and the use of either covered yard or 'other' housing types. Spreading artificial fertilizers or farmyard manure on grazing land were both associated with decreased risk. These first case-control results from the RBCT will be followed by similar analyses as more data become available.

Potential use of vaccination in cattle or badgers to control bovine tuberculosis.

The application of regular herd testing to identify and remove infected animals has proved to be a highly successful method of controlling bovine tuberculosis (TB) in many parts of the world. However, in some countries, notably the United Kingdom, Ireland and New Zealand, the disease has continued to pose a significant problem, despite intensive herd testing. Persistence of disease in these countries is associated with the presence of wildlife reservoirs of infection. Attempts to control bovine TB by culling of wildlife have been, at best, only partially successful and have proved difficult to sustain. This has led to considering of vaccination either of wildlife or cattle as a potential control measure. However, there are a number of obstacles that need to be overcome before vaccination can be considered a practical option. Vaccine efficacy, methods used for vaccine delivery in wildlife, potential interference of vaccination with diagnostic tests for cattle and appropriate design of field trials are among the issues that need to be addressed.

Confirmation of low genetic diversity and multiple breeding females in a social group of Eurasian badgers from microsatellite and field data.

The Eurasian badger (Meles meles) is a facultatively social carnivore that shows only rudimentary co-operative behaviour and a poorly defined social hierarchy. Behavioural evidence and limited genetic data have suggested that more than one female may breed in a social group. We combine pregnancy detection by ultrasound and microsatellite locus scores from a well-studied badger population from Wytham Woods, Oxfordshire, UK, to demonstrate that multiple females reproduce within a social group. We found that at least three of seven potential mothers reproduced in a group that contained 11 reproductive age females and nine offspring. Twelve primers showed variability across the species range and only five of these were variable in Wytham. The microsatellites showed a reduced repeat number, a significantly higher number of nonperfect repeats, and moderate heterozygosity levels in Wytham. The high frequency of imperfect repeats and demographic phenomena might be responsible for the reduced levels of variability observed in the badger.

Bovine tuberculosis: towards a future control strategy.

The Independent Scientific Group on Cattle TB was appointed by the Government in 1998 to implement and develop the research recommendations of the 1997 Krebs report on bovine tuberculosis in cattle and badgers. In this article, members of the group discuss the approach they are adopting in attempting to ensure that future control strategies are scientifically based. In a second article, to be published in next week's Veterinary Record, the group will consider the extent to which efforts to control the disease in cattle may be constrained by limitations in current testing procedures.

Pathogenesis and diagnosis of infections with Mycobacterium bovis in cattle. Independent Scientific Group on Cattle TB.

In last week's Veterinary Record, members of the Independent Scientific Group on Cattle TB discussed the approach they are adopting in attempting to develop sustainable strategies for controlling bovine tuberculosis in cattle (VR, February 19, pp 207-210). In this second, complementary article, they consider the extent to which efforts to control the disease may be constrained by limitations in current testing procedures.

Reproductive Skew in Multimember Groups.

Cooperative societies vary in the extent to which reproduction is skewed toward one or a few socially dominant animals. Many recent models attempt to explain this variation on the basis that a dominant who benefits from the presence of subordinates may offer them incentives, in the form of reproductive opportunities, to remain in the group. While most societies contain multiple members, however, these models have considered only the relationship between a dominant and a single subordinate or have assumed that all subordinates are identical. We develop an incentive-based evolutionary stable strategy model of reproductive skew in three-member groups, in which subordinates may vary in their opportunities for independent reproduction, their contribution to group productivity, and in their relatedness both to the dominant and to one another. Our model demonstrates that the conclusions of two-member models cannot all be generalized to larger groups. For example, relatedness among group members can influence whether or not the dominant does best to offer staying incentives to subordinates in a three-member, but not a two-member, group. Both the degree of skew and group stability depend on the relatedness between subordinates as well as on the relatedness of each to the dominant, and the incentives that each individual subordinate receives are influenced by the traits of the other. Whether such effects increase or decrease skew and group stability depends crucially on whether a third group member increases group productivity to a greater or lesser extent than the first.

Edge effects and the extinction of populations inside protected areas

Theory predicts that small populations may be driven to extinction by random fluctuations in demography and loss of genetic diversity through drift. However, population size is a poor predictor of extinction in large carnivores inhabiting protected areas. Conflict with people on reserve borders is the major cause of mortality in such populations, so that border areas represent population sinks. The species most likely to disappear from small reserves are those that range widely-and are therefore most exposed to threats on reserve borders-irrespective of population size. Conservation efforts that combat only stochastic processes are therefore unlikely to avert extinction.

Mother's little helpers: Patterns of male care in mammals.

Over the past 20 years, long-term studies have shown that mammalian fathers, brothers and even unrelated males may contribute substantially to the care of the young. Recently, more field studies of mammals with male care have further expanded interest in male care potential. Male mammals can never be sole care-givers because offspring depend on maternal milk, but assistance provided by males may allow females to produce more energetically costly litters. The need for such male care contributes to the development of obligate social monogamy or communal breeding.