Cardiac allograft vasculopathy in Dutch heart transplant recipients.

BACKGROUND: Cardiac allograft vasculopathy (CAV) is a multifactorial disease and a major cause of graft failure after heart transplantation. However, the impact of CAV may vary according to the definition and the regional differences in transplantation settings. OBJECTIVES: We sought to assess CAV prevalence, predictors and prognosis in Dutch heart transplant recipients based on coronary angiography, following the 2010 standard nomenclature of the International Society for Heart and Lung Transplantation. METHODS: Patients ≥18 years who underwent heart transplantation at our centre with at least one coronary angiography during follow-up were included in the analysis. Clinical variables were collected prospectively. RESULTS: Among 495 analysed recipients, there were 238 (48 %) with CAV. The prevalence of CAV was 18, 47 and 70 % at 4, 12 and 20 years, respectively. In the multivariable proportional hazards regression analysis, only male donor gender and increasing donor age were significantly associated with the risk of CAV. The long-term prognosis of the patients with CAV at fourth-year angiography was significantly worse as compared with that of CAV-free patients, independently of the severity of CAV (p < 0.001). CONCLUSION: The prevalence of CAV increased gradually over time, with a similar trend as in other registries. Post-transplant survival is decreased in patients with any degree of early CAV, indicating that management strategies should start with donor selection and preventive measures immediately after transplantation.

Mechanisms of functional improvement through cognitive rehabilitation in schizophrenia.

Whereas the efficacy of cognitive rehabilitation in schizophrenia is widely known, studies examining mechanisms for functional improvement are still scarce. The aim of the study was to examine the mediational mechanisms through which cognitive rehabilitation improves functioning in schizophrenia. One hundred and eleven schizophrenia patients were randomly assigned to either a 4-month cognitive rehabilitation group or an active control group. Patients underwent a neurocognitive battery (including processing speed, verbal memory, working memory and executive functioning) and social cognition assessment (emotion perception, theory of mind and social perception). Functioning was assessed by the combined use of a performance-based instrument, the UCSD Performance-based Skills Assessment (UPSA) and an observer-rated instrument, the Global Assessment of Functioning (GAF). The trial was registered in clinicaltrials.gov (NCT02796417). Multiple mediational analyses revealed that the effect of cognitive rehabilitation on functional improvement was partially mediated by changes in processing speed and verbal memory, but not by the domains of social cognition and negative symptoms. More specifically, verbal memory partially mediated the treatment's effect on performance-based functioning (UPSA), whereas processing speed acted as a partial mediator for observer-rated functioning (GAF). The effect of rehabilitation on functioning did not take place through all the domains that showed significant improvement. Verbal memory and processing speed emerged as the most crucial factors. However, these complex interactions need further research.

Effect of nutritional status and fat reserves on the periparturient immune response to Haemonchus contortus infection in sheep.

A study was made of the effect of body fat stored by ewes in early pregnancy on the subsequent immune response to gastrointestinal parasites around parturition. Pregnant ewes were given access to a lucerne pelleted diet either ad libitum (H) or at approximately 0.70 of their maintenance requirements (L) from the 42nd day of pregnancy in order to achieve a clearly differentiated level of body reserves by the 90th day of pregnancy. Then, all animals were put on the same plane of nutrition till 3 weeks after parturition. All ewes in both groups received 7,000 infective larvae of Haemonchus contortus per week for 7 weeks prior to lambing. The dietary treatments led to large differences between both groups of ewes in back-fat thickness that had a high correlation with mean plasma concentrations of leptin. In spite of the fact that animals were on the same plane of nutrition at infection time, host resistance, as measured by faecal egg counts, was significantly affected by the nutritional treatment established during early pregnancy. This effect produced noticeable differences in worm size and in worm burden at lambing. The response was accompanied by a marked increase in circulating eosinophils in better-fed ewes than in those maintained on a restricted diet in early pregnancy. Serum pepsinogen concentration, however, was inversely affected by the nutritional treatment till lambing, showing a maximum difference as early as 2 weeks after infection. The results support the view that higher levels of nutrition during early pregnancy enhance the expression of immunity against gastrointestinal parasites around parturition. Furthermore, the differences in the immune response appeared associated with serum leptin levels suggesting that leptin may be a key link between nutritional status and the protective immune reactivity against GI nematode infection.

Efficiency of Duddingtonia flagrans against Trichostrongyle infections of sheep on mountain pastures.

The control of sheep nematode parasites in extensive mountain/transhumant management systems using the nematophagous fungus Duddingtonia flagrans was assessed in this study. Two groups of Churra Tensina ewes were allowed to graze for 8 weeks in autumn on two separate paddocks of infected pasture near their winter sheds in the valley. At lambing, ewes and their twin lambs were turned out into the same paddocks for the following 12 weeks. One group of ewes received a daily dose of 5 x 10(5) chlamydospores of Duddingtonia flagrans/kg live weight per day both in autumn and in spring, while the other group was used as a non-treated control. Daily dosing of grazing ewes with the fungus D. flagrans had a clear effect on reducing autumn pasture contamination. This had a subsequent effect on the over-wintering larvae population that was confirmed by a 20% lower worm burden of tracer lambs kept in early spring on the paddock previously grazed by fungus treated ewes. In spring, pasture contamination was also significantly reduced in the paddock grazed by fungi-treated ewes and their lambs showed a 61% lower worm burden and a better performance than the control lambs. Results herein show that fungal spores fed to sheep at critical times with regard to the epidemiology of parasite infection, can have a significant effect on the infective larvae present on pasture, which could further improve lambs performance. This novel approach to parasite control would be of interest amongst both organic and conventional sheep farmers operating in mountain regions.

STR data for 11 autosomal STR markers from Costa Rica, Central America.

Allele frequencies for 11 STR autosomal loci (F13A01, F13B, FESFPS, LPL, CSF1PO, TH01, TPOX, VWA, D16S539, D7S820 and D13S317) were obtained from a sample of 200 unrelated individuals from Costa Rica, Central America.

Fast pathway ablation in a patient with iterative atrioventricular nodal reentrant tachycardia and prolonged PR interval.

A safe approach to radiofrequency catheter ablation is still unclear and not well defined in patients with AV nodal reentrant tachycardia and prolonged PR interval. In our study, a patient with iterative AV nodal reentrant tachycardia and prolonged PR interval underwent fast pathway radiofrequency catheter ablation. By mapping Koch's triangle, the earliest retrograde atrial activation area was localized. Radiofrequency energy was delivered here with the interruption of tachycardia with no complications.

An epidemiological study of parasitic gastroenteritis in sheep under an intensive grazing system.

Romanov X Rasa Aragonesa ewes rearing twins and kept on pasture at a mean stocking density of 35 ewes ha-1 were used to study the epidemiology of parasitic gastro-enteritis under an intensive grazing system on irrigated land in the northeast of Spain. Measurements were made of the population of infective larvae on the pasture, level of serum pepsinogen, faecal worm eggs in ewes and lambs, and lamb growth rates. In addition, postmortem worm counts from "indicator" lambs were used to establish the level of infection at each rotational grazing cycle. Two generations of parasites were identified in the experiment. One of them, derived from the eggs deposited the previous autumn, gave rise to the first infection of the animals in March and April. This was responsible for the first outbreak of parasitism in the lambs. This was indicated by an increase in serum pepsinogen levels, the appearance of diarrhoea and a significant decrease in lamb growth rates. Ostertagia spp., Nematodirus spp. and Trichostrongylus spp. were present. The second generation, which appeared during May, was derived from the eggs of the previous generation and gave rise to an outbreak of parasitism in the lambs at the beginning of May and the middle of June. Haemonchus spp. and Chabertia ovina were present. Under the conditions of this experiment, the overwintering larvae have an important epidemiological significance as the gastro-intestinal nematodes are one of the main limiting factors for developing intensive sheep production systems.

Grazing management strategies for the control of parasitic diseases in intensive sheep production systems.

The effect of forward (F) and lateral (L) creep grazing, as two possible management alternatives of intensive production systems, on the gastro-intestinal nematode epidemiology of ewes and lambs was studied. Two groups of Romanov x Rasa Aragonesa ewes rearing twins and maintained on an autumn-contaminated pasture at a mean stocking density of 35 ewes ha-1, were used. Measurements were made of the population of infective larvae on the pasture, level of serum pepsinogen, worm eggs in faeces of ewes and lambs, and lambs' growth rate. In addition, post-mortem worm counts from 'indicator' lambs were used to establish the level of infection at each rotational grazing cycle. Two different waves of nematode infection were identified. In both treatments, the over-wintering larvae were responsible for the first outbreak of parasitism which was particularly important for lambs on Treatment F. The second wave of infection apparently came up with several overlapped L3 generations and had different effects on the animals of each group. While early pasture contamination was suffered by the lambs of Treatment F, lambs on Treatment L were not seriously affected until the end of the third grazing cycle (end of May). The different grazing behaviour of lambs in both treatments appeared to be related to the outbreak of parasitism in lambs. The general pattern of liveweight gains was similar for both groups of animals. However, during the first 90 days on pasture lamb growth rate under Treatment L (193 g day-1) was significantly higher than that under Treatment F (164 g day-1). The serum pepsinogen values, worm burdens and liveweight gains indicate that under intensive systems where lateral creep grazing is allowed for lambs, the level of parasite infection is maintained within acceptable limits for the first 90 days on pasture with lambs' growth rate close to their potential. However, the parasitic consequences of grazing under a forward creeping system indicate that anthelmintic drenchings should be used at lambing and at 3-week intervals thereafter during the first 42 days on pasture, after which the risk of contamination from the over-wintering population is over.

Dynamics of pasture contamination by gastrointestinal nematodes of cattle under extensive management systems: proposal for strategic control.

An epidemiological study of gastrointestinal nematode parasitism in beef cattle in mountainous areas of Spain was performed. The dynamics of contamination with gastrointestinal nematode larvae of Pyrenean pastures was studied over four years at five areas at different altitudes (900 m to 2100 m), grazed by animals according to traditional systems of beef cattle in mountainous areas. Grass samples were taken every two weeks and larval differentiation was performed. Worm egg counts of grazing animals were assessed in cows, heifers and calves. A consistent seasonal pattern of infective larvae on pasture through the study was observed. In hay meadows, located below 1000 m, infective larvae were found from the end of October until June of the following year. At higher altitudes (1200-2100 m), a bimodal pattern of pasture larvae contamination was observed with increases in late spring (March-June) and in late autumn (September-November). Ostertagia spp., Cooperia spp., Trichostrongylus spp., Oesophagostomum spp., and Nematodirus spp. were found, with Ostertagia spp. being the most frequently found, followed by Cooperia spp. The highest increase of larval contamination in autumn coincided with the grazing of animals in hay meadows. This elevated autumn larval population had a very important epidemiological role because these larvae remained as overwintered larvae until the following grazing season, starting the cycle of contamination of the animals.

Effect of level of feed intake on the development of gastrointestinal parasitism in growing lambs.

A study was conducted to examine the role of nutrition in the development of gastrointestinal (GI) parasitism, performance and pathophysiology of parasitism in female lambs. Forty-four months old ewe lambs received for 6 weeks 0, 1500 or 7000 L(3) larvae of Teladorsagia circumcincta in two doses per week. The animals were given access to a pelleted diet to meet energy requirements for gaining weight close to their potential (H) or approximately 50% of it (L). The level of protein in the diet was 20-30% above requirements for both planes of nutrition. Measurements of body weight, serum pepsinogen concentration and faecal egg counts were taken at weekly intervals. All animals were slaughtered 2 weeks after the last larval dosing for estimation of worm count, carcass composition and reproductive tract development. Voluntary intake of infected animals decreased by approximately 10%. Both nutrition and infection influenced lamb performance and carcass composition. However, no direct effects on reproductive tract parameters due to the presence of infection were observed. The level of L(3) infection showed a significant effect not only on faecal egg counts and on worm burden, as it could be expected, but also on the proportion of females to males, which increased significantly with the level of infection. While the plane of nutrition did not show a significant effect on faecal egg counts or on worm burden, surprisingly, both female worm size and their fecundity decreased significantly with the level of nutrition. This response was accompanied by a significant increase in the concentration of circulating eosinophils suggesting that the immune response of lambs consuming high levels of energy was enhanced compared to that of lambs kept on a restricted diet. Results herein show that in young female lambs fed on adequate levels of protein, an improvement in energy supply does not only improve carcass characteristics but clearly enhances the development of resistance to GI nematodes infection. This may have decisive management implications for the control of parasitic infections in sustainable production systems.

Monthly fluctuations of worm burdens and hypobiosis of gastrointestinal nematodes of calves in extensive management systems in the Pyrenees (Spain).

Monthly fluctuations of worm burdens and arrested development of gastrointestinal nematodes in cattle from a mountainous region of Spain were studied. Fourteen previously helminth-naive calves grazed together with a herd of 120 cattle from May to November following the traditional extensive grazing system used in mountainous regions of Spain (permanent calves). Each month, throughout the grazing season, two helminth-naive calves (tracer calves) were added to the herd and allowed to graze for 4 weeks. Every 2 weeks, throughout the grazing period, faecal and blood samples from the permanent calves, and pasture grass samples for larval recovery were collected. Every 4 weeks, throughout the grazing period, two tracer and two permanent calves were removed from the herd and housed on concrete for 2 weeks before being slaughtered. The nematode parasite species identified from the animals were: Ostertagia ostertagi, O. lyrata, Teladorsagia circumcincta, Trichostrongylus axei, Cooperia oncophora, Trichostrongylus longispicularis, Capillaria bovis, Nematodirus helvetianus, Oesophagostomum radiatum, Chabertia ovina and Trichuris spp. O. ostertagi was the predominant species, followed by C. oncophora and T. axei. The highest numbers of worms recovered from the tracer calves were observed in May, June, September and November with average worm burdens of 4050, 3775, 2775 and 2825, respectively. These dates corresponded with 2 months of spring grazing in areas below 1000 m (May-June), the last month of grazing in areas higher than 1000 m (September), and the last month of autumn grazing in areas below 1000 m (November), respectively. The highest total worm burden (8000 worms per animal) was observed in the permanent calves in June after 2 months of grazing below 1000 m. The average total worm burden in the permanent calves during the study was 5825 worms per animal. As in other cool temperate regions of the Northern hemisphere, the highest percentage of larval inhibition was observed in autumn, with maximum levels of 63.4% for Ostertagia spp. and 89.3% for Cooperia oncophora. Similar inhibition levels were observed in parasites from both tracer and permanent calves, indicating that previous exposure was not the primary cause of larval inhibition.

Efficacy of moxidectin against gastrointestinal nematode infections in sheep.

The efficacy of moxidectin against gastrointestinal nematode infections was studied in 30 Fleischschaf x Rasa Aragonesa male lambs aged 3 months at the beginning of the experiment. The lambs were distributed in three groups of 10 animals each and experimentally infected with a mixture of an equal number of infective (L3) larvae from each of the following species: Haemonchus contortus (2000), Ostertagia circumcincta (2000), Trichostrongylus colubriformis (2000) and Trichostrongylus vitrinus (2000). Two groups of lambs were drenched with 0.2 mg moxidectin per kg body weight at 6 (Group B) and 21 (Group C) days post challenge while the third group of animals (Group A) remained untreated. The efficacy of the treatment based on worm counts 4 weeks post infection was of 100% against 4th stage larvae of all species and 100%, 99.98%, 100% and 100% against adults of H. contortus, O. circumcincta, T. colubriformis and T. vitrinus, respectively. Significant differences were found in daily weight gain between treated (Group B+C, 157.9 g day-1) and untreated lambs (Group A, 116 g day-1). No differences in feeding behaviour or health condition between treated and untreated lambs were observed.

Seasonal changes of gastrointestinal nematode burden in sheep under an intensive grazing system.

A study was conducted of the monthly fluctuations of worm burdens and arrested development of gastrointestinal (GI) nematodes in sheep from a commercial farm of the Ebro valley (Spain). Twenty-four previously helminth-free female lambs (permanent lambs) grazed together with a flock of 500 resident ewes for 12 months following a three lambing/2-year reproductive management system. Two helminth-free lambs (tracer lambs) were added to the flock each month and allowed to graze for 4 weeks. Measurements were made of the population of infective larvae on the pasture, and of levels of serum pepsinogen and faecal worm eggs in ewes and lambs. Additionally, post-mortem worm counts from two tracer and two permanent lambs were used to establish the level of infection at monthly intervals. Three generations of parasites were identified in the experiment. The generation derived from eggs deposited the previous autumn gave rise to the first infection of the animals in January and May. This infection had low consequences for the animals, but it signified the initiation of infection and the resumption of the annual cycle of pasture contamination. The second generation, appearing between June and July, was the year's most important source of infection and gave rise to an outbreak of parasitism in permanent lambs. This was indicated by an increase in levels of serum pepsinogen, the appearance of diarrhoea, and an important decrease in lamb growth rates. The third wave of infection, occurring in October and November, there was less impact than the previous one with respect to the level of infection, but it was the origin of the future over-wintering population. Teladorsagia circumcincta was the predominant species, followed by Haemonchus contortus and Trichostrongylus colubriformis. The highest numbers of worm recovered from both the tracer and permanent lambs were observed in July, with average numbers of 7900 and 19,200, respectively. The inhibition phenomenon was more evident in permanent than in tracer lambs, and mainly affected H. contortus as evidenced by populations exhibiting arrested larvae values of over 70% in January and February. Results obtained in this study confirm the epidemiological importance of the over-wintering L(3) generation as the initial source of the animal's infection and the origin of the annual resumption of pasture contamination cycles.

Comparative susceptibility of Pyrenean and Brown Swiss calves to gastrointestinal nematodes in subclinical naturally acquired infections.

The susceptibility of two common breeds of cattle in the Pyrenees, Brown Swiss and Pyrenean breed, to parasitism by gastrointestinal nematodes was studied. Twenty-two female calves (13 Brown Swiss and 9 Pyrenean), 3 months old with a mean weight of 112.8 +/- 18.33 and 103.3 +/- 17.11 kg respectively at the start of the study, were used. The calves began their first grazing season grazing with 200 cattle following the traditional grazing system for mountainous areas: Stabling during winter (December-April), grazing on harvesting meadows at an elevation of 900 m in the spring (May-June) and autumn (October-November), and grazing areas between 1200-2100 m during the summer (July-September). Faeces, blood samples and calves growth rate were taken at 2-week intervals throughout the grazing season. Faecal egg counts of gastrointestinal nematodes, level of serum pepsinogen, total serum protein and blood parameters were measured. The worm egg counts and Cooperia sp. counts were significantly smaller in the calves of Pyrenean breed than in Brown Swiss throughout the experiment. Numbers of eggs of the other genera of parasites found were smaller in the calves of Pyrenean breed than in calves of Brown Swiss breed, but no statistical differences were found. Blood was compared during two periods: the prepatent and patent periods. During the first period, no differences were found between the breeds for any parameter studied. However, during the patent period, Pyrenean animals had significantly greater numbers of erythrocytes, haemoglobin values and packed cell volume (PCV) values, and smaller numbers of eosinophils than animals of the Brown Swiss breed. No differences were found in the level of serum pepsinogen, total serum protein and live weight gains between the two breeds.

Liver transplantation for hepatocellular carcinoma in cirrhotic patients.

A consecutive series of 88 patients underwent transplantation for hepatocellular carcinoma with cirrhosis over a 7-year period. Liver transplantation was indicated because of the tumor in 75 cases (85.2%); tumor was an incidental finding in 13 cases (14.8%). One patient was retransplanted due to primary nonfunction. The perioperative mortality was 4.5%. Tumor recurrence was observed in seven patients (7.95%) with incidental tumor recurrence in one case. As in patients with known primary liver tumors pretransplant, a thorough follow-up is advisable to establish an early diagnosis of recurrence. The actuarial survival for nonincidental hepatocellular carcinoma at 1, 3, and 5 year was 92%, 77%, and 75%, respectively. The differences in actuarial survival between hepatitis C negative and positive hepatocellular carcinoma were not significant (log-rank test P=.27), though there was a clear improvement in results (94%, 85%, and 78% vs 90%, 71%, and 71%), at 1, 3, and 5 years meaning that HCV infection is an important prognostic factor. Although transplantation for HCC has the advantages of removing the tumor and the cirrhotic liver, it remains a controversial topic. In our experience patients showing lesions less than 5 cm or three or fewer lesions experience an equivalent survival to transplanted patients who do not have cancer.

[Cardiac rhythm disturbances in hypertensive cardiopathy]. / Le alterazioni del ritmo cardiaco nella cardiopatia ipertensiva.

Patients with hypertensive heart disease are at a significantly increased risk for cardiovascular morbidity and mortality. Ultrastructural and gross anatomical cardiac changes, combined with hemodynamic and neurovegetative balance fluctuations, are frequently responsible for cardiac arrhythmias of atrial and/or ventricular origin. The prevalence, the pathophysiologic mechanism and the prognostic significance of cardiac rhythm disturbances occurring in hypertensive heart disease are discussed in this review.

Radiofrequency catheter ablation of atrioventricular nodal reentry tachycardia: selective approach to the slow pathway via the superior vena cava.

Selective radiofrequency catheter ablation of the slow atrioventricular nodal pathway is currently considered the first-line therapy for patients suffering from recurrent symptomatic atrioventricular nodal reentry tachycardia. In most cases slow pathway conduction may be selectively eliminated or modified by the application of radiofrequency current at the posterior portion of Koch's triangle. The ablation site is usually targeted by careful mapping of this area performed using an ablation catheter advanced via the inferior vena cava approach. In this report we describe 2 cases in which the conventional approach to the target site was either impossible owing to the presence of an atresic inferior vena cava (case 1), or contraindicated in view of a history of common femoral vein thrombosis, subsequently extended up to the inferior vena cava (case 2). In both patients a superior vena cava approach was utilized and the slow pathway was successfully ablated. In case of arrhythmias necessitating slow pathway mapping and ablation, such an approach may be considered as a feasible and safe alternative whenever, owing to the presence of anomalies and/or diseases of the inferior vena cava, the conventional approach cannot be employed.

Variability of the egg hatch assay to survey benzimidazole resistance in nematodes of small ruminants under field conditions.

The egg hatch assay (EHA) is one of the main in vitro methods for detection of benzimidazole resistance in nematode parasites of small ruminants. However, although the EHA has been standardised at the laboratory level, the diagnostic performance of this method has not been fully characterised for field screenings. In the present work, monthly variation of benzimidazole resistance estimated by EHA was surveyed over two years in three sheep flocks and in one goat and an additional sheep flock sharing the same pastures. Resistance was measured by calculating both the effective dose of thiabendazole (TBZ) that inhibited hatching of ≥50% of parasite eggs (ED50) and the proportion (Pdd) of eggs hatching at a discriminating dose of 0.1 µg/ml TBZ. Pdd exhibited higher variability than ED50, in agreement with the higher sensitivity of Pdd to changes in resistance levels. Both resistance parameters, however, were highly correlated, and their variation was similarly related to the same factors. Resistance levels differed among sheep flocks, and the resistance level of the goat flock was higher than that measured for the sheep flock sharing the same pasture. Moreover, monthly variation of resistance in goats did not mirror that recorded in sheep. Resistance levels varied seasonally, with the highest values recorded in the spring, and they were inversely related to the number of days that samples were stored under anaerobic conditions. In addition, they were directly associated with the relative abundance of Teladorsagia spp. but inversely related to the relative abundance of Haemonchus spp. After controlling for the effects of these identified factors for variation, inter-monthly sampling variation due to unknown factors was the main source of variability, accounting for more than 60-70% of variance for both resistance parameters and yielding absolute estimation errors higher than 0.06 for ED50 or 0.2 for Pdd when resistance was estimated from a single sampling. Optimum sample size, estimated from variance components, suggested that at least 4-5 samplings would be needed to halve this absolute error, whereas additional samplings would slightly increase precision but at the cost of substantially increasing sampling effort. More research is needed to identify the main factors involved in this inter-sampling variation to standardise the implementation of EHA under field conditions.

Management and environmental factors related to benzimidazole resistance in sheep nematodes in Northeast Spain.

A survey to determine the level of parasite resistance to benzimidazoles (BZ) under field conditions was performed on 107 commercial sheep farms located in the Aragon region of northeast Spain. Resistance was measured using the discriminant dose, a simplified form of the in vitro egg hatch assay (EHA). Taking into account the spatial structure of the data, a multivariate approach was applied to management and environmental variables as well as to their relationships with BZ resistance levels compiled from each flock. Results estimated that 11% of flocks had resistant parasite populations, although we suspected the presence of BZ-resistant parasite strains in 98% of the sample. Resistance levels were more similar among the nearest flocks, suggesting a contagious spatial distribution of resistance (i.e., resistance at neighbouring farms was not independent from one another). Management variables such as frequency of deworming, grazing in private pastures and underdosing were positively related to resistance levels, whereas only the use of BZ was negatively related to resistance levels, likely because BZ were replaced by other anthelmintics in flocks where reduced BZ efficacy was suspected. In addition to climatic conditions and seasonality, land use was an environmental variable associated with observed BZ resistance levels. Generally, resistance was highest in cooler and wetter areas but was lower in flocks sampled during January-March compared to flocks sampled in April-June or October-December. Variation partitioning procedures showed that the variation of resistance explained by the effect of environmental variables was higher than management variables. The effects of both variable groups, however, highly overlapped with the spatial structure of resistant levels, which suggests that a considerable amount of the effects attributable to both variable groups may be actually due to the spatial distribution of resistance. The resistance variation explained by the spatial component suggested that other uncontrolled factors acting at short spatial scale (e.g., common management and environmental variables; the importation of resistant strains and their posterior spread across neighbouring flocks; the selection history of the worms carried out by historical management events previous to this survey; and genetic, physiological or both types of parasite population variation) could yield this contagious spatial structure of BZ resistance. Although further research is needed, both seasonal variation and the dependence of resistance levels among neighbouring flocks should be taken into account in the design of future research or observational resistance programmes to minimise spatial and temporal pseudo-replication. Thus, research would avoid biased estimations of resistance prevalence or of its relationship with putative factors.