Dirk U. Pfeiffer

Principles and practical application of the receiver-operating characteristic analysis for diagnostic tests.

We review the principles and practical application of receiver-operating characteristic (ROC) analysis for diagnostic tests. ROC analysis can be used for diagnostic tests with outcomes measured on ordinal, interval or ratio scales. The dependence of the diagnostic sensitivity and specificity on the selected cut-off value must be considered for a full test evaluation and for test comparison. All possible combinations of sensitivity and specificity that can be achieved by changing the tests cut-off value can be summarised using a single parameter; the area under the ROC curve. The ROC technique can also be used to optimise cut-off values with regard to a given prevalence in the target population and cost ratio of false-positive and false-negative results. However, plots of optimisation parameters against the selected cut-off value provide a more-direct method for cut-off selection. Candidates for such optimisation parameters are linear combinations of sensitivity and specificity (with weights selected to reflect the decision-making situation), odds ratio, chance-corrected measures of association (e. g. kappa) and likelihood ratios. We discuss some recent developments in ROC analysis, including meta-analysis of diagnostic tests, correlated ROC curves (paired-sample design) and chance- and prevalence-corrected ROC curves.

Spatial Analysis in Epidemiology

This book provides an overview of the use of spatial statistics in epidemiology - the study of the incidence and distribution of diseases. Used appropriately, spatial analytical methods in conjunction with GIS and remotely sensed data can provide significant insights into the biological patterns and processes that underlie disease transmission. In turn, these can be used to understand and predict disease prevalence. This book brings together the specialised and widely-dispersed literature on spatial analysis to make these methodological tools accessible to epidemiologists for the first time. With its focus on application rather than theory, this book includes examples taken from both medical (human) and veterinary (animal) disciplines, and describes both infectious diseases and non-infectious conditions. It also provides worked examples of methodologies using a single data set from the same disease example throughout, and is structured to follow the logical sequence of description of spatial data, visualisation, exploration, modelling, and decision support.

The epidemiology of Mycobacterium bovis infections

Mycobacterium bovis has an exceptionally wide host range, but until recent years there was little concern about infection in species other than cattle and man. Diversification of farming enterprises has led to cognizance of the need for control in other domestic animals, notably deer. There has also been recognition that self-maintaining infection is present in wildlife hosts in some countries--notably the European badger in the United Kingdom and Ireland, the Australian brush-tailed possum in New Zealand, and various species of ungulates in limited areas of a number of countries. Although transmission of M. bovis can occur by a number of different routes, control measures imposed on cattle and to a lesser extent on other species have reduced a number of the routes to insignificance. Hence the vast preponderance of transmission within host species is now by the airborne route, and predominantly between species as well. Transmission of infection from badgers to cattle may be an exception, with evidence remaining equivocal about the relative importance of pasture contamination by excretion in badger urine and airborne transmission. In general, contamination of feed and pasture appears to be unimportant in transmission of the disease, because survival times of infective doses of organisms on fomites are relatively short under realistic conditions and because animals are not commonly exposed to a dose high enough to be infective by the alimentary route. Infection through the oro-pharyngeal mucous membrane may be significant, although the infective dose for this route is not known. While many species of animals can become infected with M. bovis, only a few act as maintenance hosts and the rest are spillover hosts in which infection is not self-maintaining. With the exception of cattle and deer, other species have become maintenance hosts only within part of their ecological range. For both badgers and possums, maintenance of infection within a local population is due to pseudo-vertical transmission from mother to young, and horizontal transmission linked to breeding activity. Transmission from possums to domestic animals appears to occur mainly during atypical behavioural interactions between the species, and this may well be important for badgers as well. Difficulties in controlling the disease adequately in domestic animals generally result from administrative problems since the necessary technical procedures are available and have been shown to be effective. Where there is interplay between infection in wildlife and domestic animals, eradication of the disease becomes impractical.(ABSTRACT TRUNCATED AT 400 WORDS)

Mapping H5N1 highly pathogenic avian influenza risk in Southeast Asia

The highly pathogenic avian influenza (HPAI) H5N1 virus that emerged in southern China in the mid-1990s has in recent years evolved into the first HPAI panzootic. In many countries where the virus was detected, the virus was successfully controlled, whereas other countries face periodic reoccurrence despite significant control efforts. A central question is to understand the factors favoring the continuing reoccurrence of the virus. The abundance of domestic ducks, in particular free-grazing ducks feeding in intensive rice cropping areas, has been identified as one such risk factor based on separate studies carried out in Thailand and Vietnam. In addition, recent extensive progress was made in the spatial prediction of rice cropping intensity obtained through satellite imagery processing. This article analyses the statistical association between the recorded HPAI H5N1 virus presence and a set of five key environmental variables comprising elevation, human population, chicken numbers, duck numbers, and rice cropping intensity for three synchronous epidemic waves in Thailand and Vietnam. A consistent pattern emerges suggesting risk to be associated with duck abundance, human population, and rice cropping intensity in contrast to a relatively low association with chicken numbers. A statistical risk model based on the second epidemic wave data in Thailand is found to maintain its predictive power when extrapolated to Vietnam, which supports its application to other countries with similar agro-ecological conditions such as Laos or Cambodia. The models potential application to mapping HPAI H5N1 disease risk in Indonesia is discussed.

The risk of death: the Confidential Enquiry into Perioperative Small Animal Fatalities

OBJECTIVE To estimate the risks of anaesthetic and sedation-related mortality in companion animals in the UK. (The Confidential Enquiry into Perioperative Small Animal Fatalities, CEPSAF). STUDY DESIGN A prospective cohort study with nested case-control study. ANIMAL POPULATION All small animals anaesthetized and sedated at participating centres between June 2002 and June 2004. METHODS Patient outcomes at 48 hours (alive, dead and killed) were recorded. Anaesthetic and sedation-related death was defined as death where surgical or pre-existing medical causes did not solely cause death. Species-specific risks of anaesthetic-related death and 95% confidence intervals (95% CI) were calculated. Risks were also estimated in the sub-sets of dogs, cats and rabbits that were either healthy or sick (ASA 1-2 and 3-5, respectively). RESULTS One hundred and seventeen veterinary practices participated in the study and 98 036 dogs, 79 178 cats and 8209 rabbits were anaesthetized and sedated. Overall risks of anaesthetic and sedation-related death in dogs were 0.17% (1 in 601, 95% CI 0.14-0.19%), in cats 0.24% (1 in 419, 95% CI 0.20-0.27%) and in rabbits 1.39% (1 in 72, 95% CI 1.14-1.64%) within 48 hours of the procedure. In healthy dogs, cats and rabbits, the risks were estimated to be 0.05% (1 in 1849, 95% CI 0.04-0.07%), 0.11%, (1 in 895, 95% CI 0.09-0.14%) and 0.73% (1 in 137, 95% CI 0.54-0.93%), respectively. In sick dogs, cats and rabbits, the risks were 1.33%, (1 in 75, 95% CI 1.07-1.60%), 1.40% (1 in 71, 95% CI 1.12-1.68%) and 7.37% (1 in 14, 95% CI 5.20-9.54%), respectively. Postoperative deaths accounted for 47% of deaths in dogs, 61% in cats and 64% in rabbits. Most other small animal species had higher mortality risks. CONCLUSIONS AND CLINICAL RELEVANCE Small animal anaesthesia appears to be increasingly safe. Greater patient care in the postoperative period could reduce fatalities.

Zoonosis emergence linked to agricultural intensification and environmental change

A systematic review was conducted by a multidisciplinary team to analyze qualitatively best available scientific evidence on the effect of agricultural intensification and environmental changes on the risk of zoonoses for which there are epidemiological interactions between wildlife and livestock. The study found several examples in which agricultural intensification and/or environmental change were associated with an increased risk of zoonotic disease emergence, driven by the impact of an expanding human population and changing human behavior on the environment. We conclude that the rate of future zoonotic disease emergence or reemergence will be closely linked to the evolution of the agriculture–environment nexus. However, available research inadequately addresses the complexity and interrelatedness of environmental, biological, economic, and social dimensions of zoonotic pathogen emergence, which significantly limits our ability to predict, prevent, and respond to zoonotic disease emergence.

Survival of Cats with Naturally Occurring Chronic Renal Failure Is Related to Severity of Proteinuria

BACKGROUND Tubulointerstitial kidney disease is a common cause of illness and death in pet cats and is typically not associated with overt proteinuria. HYPOTHESIS Proteinuria would be independently related to survival in cats with renal failure, with or without hypertension. ANIMALS The study included 136 client-owned cats; 28 apparently normal, 14 hypertensive but not azotemic, 66 azotemic but not hypertensive, and 28 both hypertensive and azotemic. METHODS Coxs proportional hazards model was used to determine the influence of initial plasma creatinine concentration, proteinuria (urine protein-to-creatinine ratio or albumin-to-creatinine ratio), age, and systemic hypertension on the risk of death or euthanasia during the follow-up period. Multivariable linear regression was used to determine the relation between severity of proteinuria and predictive variables, including age, plasma creatinine concentration, systolic blood pressure, sex, and urine specific gravity. RESULTS Plasma creatinine concentration and proteinuria were very highly related to survival. The hazard ratio (95% confidence intervals) for death or euthanasia was 2.9 (1.4-6.3) and 4.0 (2.0-8.0) for urine protein-to-creatinine ratio 0.2-0.4 and >0.4, respectively, compared with the baseline group with a urine protein-to-creatinine ratio of <0.2 and were 2.4 (1.2-4.8) and 4.9 (2.3-10.2) for an albumin-to-creatinine ratio of 30-82 mg/g and <82 mg/g, respectively, compared with a baseline group with albumin-to-creatinine ratio of <30 mg/g. Treated hypertensive cats did not have reduced survival, although systolic blood pressure, together with plasma creatinine concentration was positively related to the magnitude of proteinuria. CONCLUSIONS AND CLINICAL IMPORTANCE Despite the relatively low concentrations of proteinuria typical of chronic renal disease in cats, this measurement is of prognostic significance.

African swine fever: how can global spread be prevented?

African swine fever (ASF) is a devastating haemorrhagic fever of pigs with mortality rates approaching 100 per cent. It causes major economic losses, threatens food security and limits pig production in affected countries. ASF is caused by a large DNA virus, African swine fever virus (ASFV). There is no vaccine against ASFV and this limits the options for disease control. ASF has been confined mainly to sub-Saharan Africa, where it is maintained in a sylvatic cycle and/or among domestic pigs. Wildlife hosts include wild suids and arthropod vectors. The relatively small numbers of incursions to other continents have proven to be very difficult to eradicate. Thus, ASF remained endemic in the Iberian peninsula until the mid-1990s following its introductions in 1957 and 1960 and the disease has remained endemic in Sardinia since its introduction in 1982. ASF has continued to spread within Africa to previously uninfected countries, including recently the Indian Ocean islands of Madagascar and Mauritius. Given the continued occurrence of ASF in sub-Saharan Africa and increasing global movements of people and products, it is not surprising that further transcontinental transmission has occurred. The introduction of ASF to Georgia in the Caucasus in 2007 and dissemination to neighbouring countries emphasizes the global threat posed by ASF and further increases the risks to other countries. We review the mechanisms by which ASFV is maintained within wildlife and domestic pig populations and how it can be transmitted. We then consider the risks for global spread of ASFV and discuss possibilities of how disease can be prevented.

Leg disorders in broiler chickens: prevalence, risk factors and prevention.

Broiler (meat) chickens have been subjected to intense genetic selection. In the past 50 years, broiler growth rates have increased by over 300% (from 25 g per day to 100 g per day). There is growing societal concern that many broiler chickens have impaired locomotion or are even unable to walk. Here we present the results of a comprehensive survey of commercial flocks which quantifies the risk factors for poor locomotion in broiler chickens. We assessed the walking ability of 51,000 birds, representing 4.8 million birds within 176 flocks. We also obtained information on approximately 150 different management factors associated with each flock. At a mean age of 40 days, over 27.6% of birds in our study showed poor locomotion and 3.3% were almost unable to walk. The high prevalence of poor locomotion occurred despite culling policies designed to remove severely lame birds from flocks. We show that the primary risk factors associated with impaired locomotion and poor leg health are those specifically associated with rate of growth. Factors significantly associated with high gait score included the age of the bird (older birds), visit (second visit to same flock), bird genotype, not feeding whole wheat, a shorter dark period during the day, higher stocking density at the time of assessment, no use of antibiotic, and the use of intact feed pellets. The welfare implications are profound. Worldwide approximately 2×1010 broilers are reared within similar husbandry systems. We identify a range of management factors that could be altered to reduce leg health problems, but implementation of these changes would be likely to reduce growth rate and production. A debate on the sustainability of current practice in the production of this important food source is required.

Social-network analysis of Mycobacterium bovis transmission among captive brushtail possums (Trichosurus vulpecula)

Wild brushtail possums (Trichosurus vulpecula) are the main source of Mycobacterium bovis infection for New Zealand livestock. The disease is spread principally by infectious aerosol; therefore, social interactions determine disease transmission. In captive possums, den-sharing behaviour provided the greatest risk of tuberculosis transmission between animals. Den sharing between individual possums was used as the basic measurement for quantifying close proximity between animals over extended periods. Social-network analysis (SNA) was used to model patterns of social behaviour and to predict tuberculosis transmission. There was great diversity between groups in their social behaviour-but there were consistent trends in the SNA measures (closeness and flow-betweenness). With time, the social distance between possums in the same group increased, the social network became more homogeneous and the possums less differentiated from each other. Alteration of the physical environment of the pens (such as changing the number of dens or relocating the group to a new pen) had an inconsistent effect on social structure when comparing different groups. During the infection-transmission study, the possums that became infected had greater closeness and flow-betweenness scores than those that remained free of infection. Although standard statistical descriptive measures (such as the number of partners and the frequency of den-sharing events) were greater for the infected than the infection-free possums, the SNA-specific measures were more precise and could be compared across time and between groups.