The impact of lymph node ratio on disease recurrence in papillary thyroid microcarcinoma.

INTRODUCTION: Lymph node (LN) metastases in papillary thyroid microcarcinomas (microPTCs) are common. The lymph node ratio (LNR) has been proposed as a risk factor for recurrence in papillary thyroid cancer. However, its relevance in microPTC is undetermined. METHODS: Patients who underwent resection of their microPTC with concomitant LN clearance between 2005 and 2018 were identified. The LNR was calculated as the ratio of positive LNs to the total number of LNs. RESULTS: Data on 50 patients (36 female [72%]; median age 47 years [range: 19-84]) who underwent LN clearance (28 central [56%] vs 22 central + lateral [44%]) were analysed. Positive LNs were found in over two-thirds of the patients (n = 34; 68%). After a median follow-up of 61 months, 14 patients (28%) had developed recurrence. Positive LNs were not found to impact recurrence-free survival; extranodal extension and an LNR ≥ 0.26 were found to significantly increase the risk of recurrence on unadjusted analyses (p < 0.05). CONCLUSIONS: LN metastases are frequent among patients with microPTC. A higher LNR seems to be associated with recurrence. Additional studies are needed to further clarify these findings and to assess the possible role of LNR in treatment and surveillance.

Risk of malignancy in thyroid nodules with indeterminate (THY3f) cytology.

BACKGROUND: Fine-needle aspiration cytology (FNAC) is an integral part of thyroid nodule assessment. Nodules with an indeterminate cytology (THY3a-f) require formal histological assessment to confirm benign or malignant pathology. This study aimed to provide data for an evidence-based approach for management of patients with THY3f nodules. METHODS: Retrospective review of patients who had a thyroid FNAC reported as suspicious of follicular neoplasm (THY3f) or showing atypia (THY3a) were identified, and clinical, operative and outcomes data were analysed. RESULTS: Between 2018 and 2020, 200 patients (167F:33M, median age 51 years (range:18-86 years)) had a THY3f cytology. Most presented with a palpable nodule (n=104; 68.4%). Overall, 152 (76.0%;130F:23M) underwent surgery and 31 (20.4%) were found to have a thyroid carcinoma (22 follicular carcinomas, 7 papillary carcinomas, 1 medullary thyroid carcinoma and 1 metastatic renal carcinoma). An additional incidental carcinoma (size: 0.7-13mm) was found in seven (4.6%). Among those with cancer, a completion thyroidectomy and radioactive iodine treatment was indicated in nine (<6% of the entire cohort). Previously suggested risk factors for malignancy, eg male gender, large tumour size (>4cm) or age, were not found to be associated with increased risk. During the same period, THY3a cytology was reported in 53 patients, of whom 29 underwent diagnostic surgery and 4 patients were found to have a thyroid cancer (follicular, n=3 and medullary, n=1). CONCLUSION: One in five patients with features suspicious of a follicular neoplasm (THY3f) has a thyroid carcinoma. This risk is much lower for THY3a. This study reinforces the current recommendation for thyroid surgery in all patients with a reliable THY3f cytology, as no further stratifying risk factors could be identified.

Comparative performances of nomograms and conditional survival after resection of adrenocortical cancer.

BACKGROUND: Adrenocortical carcinomas (ACCs) carry a poor prognosis. This study assessed the comparative performance of existing nomograms in estimating the likelihood of survival, along with the value of conditional survival estimation for patients who had already survived for a given length of time after surgery. METHODS: This was an observational study based on a prospectively developed departmental database that recorded details of patients operated for ACC in a UK tertiary referral centre. RESULTS: Of 74 patients with ACC managed between 2001 and 2020, data were analysed for 62 patients (32 women and 30 men, mean(s.d.) age 51(17) years) who had primary surgical treatment in this unit. Laparoscopic (9) or open adrenalectomies (53) were performed alone or in association with a multivisceral resection (27). Most of the tumours were left-sided (40) and 18 were cortisol-secreting.Overall median survival was 33 months, with 1-, 3- and 5-year survival rates of 79, 49, and 41 per cent respectively. Age over 55 years, higher European Network for Study of Adrenal Tumours stage, and cortisol secretion were associated with poorer survival in univariable analyses. Four published nomograms suggested widely variable outcomes that did not correlate with observed overall survival at 1, 3 or 5 years after operation. The 3-year conditional survival at 2 years (probability of surviving to postoperative year 5) was 65 per cent, compared with a 5-year actuarial survival rate of 41 per cent calculated from the time of surgery. CONCLUSION: Survival of patients with ACC correlates with clinical parameters but not with published nomograms. Conditional survival might provide a more accurate estimate of survival for patients who have already survived for a certain amount of time after resection.

Influence of common clinical variables on intraoperative parathyroid hormone monitoring during surgery for primary hyperparathyroidism.

BACKGROUND: Intraoperative monitoring of parathyroid hormone (IOPTH) is a reliable method of predicting the cure of primary hyperparathyroidism (PHPT). The aim of this study is to assess whether common clinical variables (CCV) frequently encountered in patients with PHPT may affect the magnitude of PTH drop or the likelihood of patients meeting the intraoperative cure criterion. DESIGN: Patients who were surgically cured from PHPT caused by single gland disease (SGD) and had full IOPTH protocol (4 measurements) were stratified according to age, gland weight, renal function, vitamin D status and severity of hypercalcemia. The percentage of IOPTH drop and the frequency of patients who had true positive IOPTH test results were compared among groups. RESULTS: 762 patients had surgery for PHPT, of whom 746 were (98%) cured. Of these 746 patients, 511 who had SGD and a full IOPTH protocol were included in this study. The median IOPTH drop was significantly higher among younger patients, those with severe hypercalcaemia at 5, 10, 15 min after gland excision, giant glands (at 5-min only), patients with vitamin D deficiency (at 10, 15 min), and those with normal renal function (at 15 min only). The likelihood of the patients meeting the intraoperative cure criterion was not significantly affected among the groups except in patients with mild hypercalcaemia, who were significantly less likely to have 50% IOPTH drop than those with severe hypercalcaemia at all time points. The frequency of mildly hypercalcaemic patients who met cure criterion was significantly improved by extending measurement to 15 min. CONCLUSIONS: IOPTH monitoring has the ability to mitigate the variability of IOPTH kinetics associated with most clinical variables. Mildly hypercalcemic patients in particular may benefit from waiting for 15-min measurement before any surgical decision is made.

Safety and efficacy of transarterial embolization of hepatocellular adenomas.

BACKGROUND: Hepatocellular adenoma (HCA) larger than 5 cm in diameter has an increased risk of haemorrhage and malignant transformation, and is considered an indication for resection. As an alternative to resection, transarterial embolization (TAE) may play a role in prevention of complications of HCA, but its safety and efficacy are largely unknown. The aim of this study was to assess outcomes and postembolization effects of selective TAE in the management of HCA. METHODS: This retrospective, multicentre cohort study included patients aged at least 18 years, diagnosed with HCA and treated with TAE. Patient characteristics, 30-day complications, tumour size before and after TAE, symptoms before and after TAE, and need for secondary interventions were analysed. RESULTS: Overall, 59 patients with a median age of 33.5 years were included from six centres; 57 of the 59 patients were women. Median tumour size at time of TAE was 76 mm. Six of 59 patients (10 per cent) had a major complication (cyst formation or sepsis), which could be resolved with minimal therapy, but prolonged hospital stay. Thirty-four patients (58 per cent) were symptomatic at presentation. There were no significant differences in symptoms before TAE and symptoms evaluated in the short term (within 3 months) after TAE (P = 0·134). First follow-up imaging was performed a median of 5·5 months after TAE and showed a reduction in size to a median of 48 mm (P < 0·001). CONCLUSION: TAE is safe, can lead to adequate size reduction of HCA and, offers an alternative to resection in selected patients.

A genome-wide association study for susceptibility and infectivity of Holstein Friesian dairy cattle to digital dermatitis.

Selection and breeding can be used to fight transmission of infectious diseases in livestock. The prevalence in a population depends on the susceptibility and infectivity of the animals. Knowledge on the genetic background of those traits would facilitate efficient selection for lower disease prevalence. We investigated the genetic background of host susceptibility and infectivity for digital dermatitis (DD), an endemic infectious claw disease in dairy cattle, with a genome-wide association study (GWAS), using either a simple linear mixed model or a generalized linear mixed model based on epidemiological theory. In total, 1,513 Holstein-Friesian cows of 12 Dutch dairy farms were scored for DD infection status and class (M0 to M4.1) every 2 wk for 11 times; 1,401 of these cows were genotyped with a 75k SNP chip. We performed a GWAS with a linear mixed model on 10 host disease status traits, and with a generalized linear mixed model with a complementary log-log link function (GLMM) on the probability that a cow would get infected between 2 scorings. With the GLMM, we fitted SNP effects for host susceptibility and host infectivity, while taking the variation in exposure of the susceptible cow to infectious herd mates into account. With the linear model we detected 4 suggestive SNP (false discovery rate < 0.20), 2 for the fraction of observations a cow had an active lesion on chromosomes 1 and 14, one for the fraction of observations a cow had an M2 lesion on at least one claw on chromosome 1 (the same SNP as for the fraction of observations with an active lesion), and one for the fraction of observations a cow had an M4.1 lesion on at least one claw on chromosome 10. Heritability estimates ranged from 0.09 to 0.37. With the GLMM we did not detect significant nor suggestive SNP. The SNP effects on disease status analyzed with the linear model had a correlation coefficient of only 0.70 with SNP effects on susceptibility of the GLMM, indicating that both models capture partly different effects. Because the GLMM better accounts for the epidemiological mechanisms determining individual disease status and for the distribution of the y-variable, results of the GLMM may be more reliable, despite the absence of suggestive associations. We expect that with an extended GLMM that better accounts for the full genetic variation in infectivity via the environment, the accuracy of SNP effects may increase.

Quantification of Mycobacterium bovis transmission in a badger vaccine field trial.

In the UK and Ireland, Bacille Calmette-Guérin (BCG) vaccination of badgers has been suggested as one of a number of strategies to control or even eradicate Mycobacterium bovis infection in badgers. In this manuscript, we present the results of a badger field trial conducted in Ireland and discuss how the novel trial design and analytical methods allowed the effects of vaccination on protection against infection and, more importantly, on transmission to be estimated. The trial area was divided into three zones North to South (A, B and C) where vaccination coverages of 0, 50 and 100%, respectively, were applied. Badgers were trapped over a 4year period. Badgers were assigned to either placebo or vaccine treatment, with treatment allocation occurring randomly in zone B. Blood samples were collected at each capture, and serology was performed in these samples using a chemiluminescent multiplex ELISA system (Enfer test). The analysis aimed to compare new infections occurring in non-infected non-vaccinated badgers to those in non-infected vaccinated ones, while accounting for the zone in which the badger was trapped and the infection pressure to which this individual badger was exposed. In total, 440 records on subsequent trappings of individual non-infected badgers were available for analysis. Over the study period, 55 new infections occurred in non-vaccinated (out of 239=23.0%) and 40 in vaccinated (out of 201=19.9%) badgers. A Generalized Linear Model (GLM) with a cloglog link function was used for analysis. Statistical analysis showed that susceptibility to natural exposure with M. bovis was reduced in vaccinated compared to placebo treated badgers: vaccine efficacy for susceptibility, VES, was 59% (95% CI=6.5%-82%). However, a complete lack of effect from BCG vaccination on the infectivity of vaccinated badgers was observed, i.e. vaccine efficacy for infectiousness (VEI) was 0%. Further, the basic reproduction ratio as a function of vaccination coverage (p) (i.e. R(p)) was estimated. Given that the prevalence of M. bovis infection in badgers in endemic areas in Ireland is approximately 18%, we estimated the reproduction ratio in the unvaccinated population as R(0)=1.22. Because VES was now known, the reproduction ratio for a fully vaccinated population was estimated as R(1)=0.50. These results imply that with vaccination coverage in badgers exceeding 30%, eradication of M. bovis in badgers in Ireland is feasible, provided that the current control measures also remain in place.

Temporal and spatial distribution of lumpy skin disease outbreaks in Ethiopia in the period 2000 to 2015.

BACKGROUND: Lumpy skin disease (LSD) is an infectious viral disease of cattle caused by a virus of the genus Capripoxvirus. LSD was reported for the first time in Ethiopia in 1981 and subsequently became endemic. This time series study was undertaken with the aims of identifying the spatial and temporal distribution of LSD outbreaks and to forecast the future pattern of LSD outbreaks in Ethiopia. RESULTS: A total of 3811 LSD outbreaks were reported in Ethiopia between 2000 and 2015. In this period, LSD was reported at least once in 82% of the districts (n = 683), 88% of the administrative zones (n = 77), and all of the regional states or city administrations (n = 9 and n = 2) in the country. The average incidence of LSD outbreaks at district level was 5.58 per 16 years (0.35 year-1). The incidence differed between areas, being the lowest in hot dry lowlands and highest in warm moist highland. The occurrence of LSD outbreaks was found to be seasonal. LSD outbreaks generally have a peak in October and a low in May. The trend of LSD outbreaks indicates a slight, but statistically significant increase over the study period. The monthly precipitation pattern is the reverse of LSD outbreak pattern and they are negatively but non-significantly correlated at lag 0 (r = -0.05, p = 0.49, Spearman rank correlation) but the correlation becomes positive and significant when the series are lagged by 1 to 6 months, being the highest at lag 3 (r = 0.55, p < 0.001). The forecast for the period 2016-2018 revealed that the highest number of LSD outbreaks will occur in October for all the 3 years and the lowest in April for the year 2016 and in May for 2017 and 2018. CONCLUSION: LSD occurred in all major parts of the country. Outbreaks were high at the end of the long rainy season. Understanding temporal and spatial patterns of LSD and forecasting future occurrences are useful for indicating periods when particular attention should be paid to prevent and control the disease.

Transmission dynamics of lumpy skin disease in Ethiopia.

Lumpy skin disease (LSD) is a severe disease of cattle caused by a Capripoxvirus and often caused epidemics in Ethiopia and many other countries. This study was undertaken to quantify the transmission between animals and to estimate the infection reproduction ratio in a predominantly mixed crop-livestock system and in intensive commercial herd types. The transmission parameters were based on a susceptible-infectious-recovered (SIR) epidemic model with environmental transmission and estimated using generalized linear models. The transmission parameters were estimated using a survival rate of infectious virus in the environment equal to 0·325 per day, a value based on the best-fitting statistical model. The transmission rate parameter between animals was 0·072 (95% CI 0·068-0·076) per day in the crop-livestock production system, whereas this transmission rate in intensive production system was 0·076 (95% CI 0·068-0·085) per day. The reproduction ratio (R) of LSD between animals in the crop-livestock production system was 1·07, whereas it was 1·09 between animals in the intensive production system. The calculated R provides a baseline against which various control options can be assessed for efficacy.

Modelling the Innate Immune Response against Avian Influenza Virus in Chicken.

At present there is limited understanding of the host immune response to (low pathogenic) avian influenza virus infections in poultry. Here we develop a mathematical model for the innate immune response to avian influenza virus in chicken lung, describing the dynamics of viral load, interferon-α, -ß and -γ, lung (i.e. pulmonary) cells and Natural Killer cells. We use recent results from experimentally infected chickens to validate some of the model predictions. The model includes an initial exponential increase of the viral load, which we show to be consistent with experimental data. Using this exponential growth model we show that the duration until a given viral load is reached in experiments with different inoculation doses is consistent with a model assuming a linear relationship between initial viral load and inoculation dose. Subsequent to the exponential-growth phase, the model results show a decline in viral load caused by both target-cell limitation as well as the innate immune response. The model results suggest that the temporal viral load pattern in the lungs displayed in experimental data cannot be explained by target-cell limitation alone. For biologically plausible parameter values the model is able to qualitatively match to data on viral load in chicken lungs up until approximately 4 days post infection. Comparison of model predictions with data on CD107-mediated degranulation of Natural Killer cells yields some discrepancy also for earlier days post infection.

Efficacy of antibiotic treatment and test-based culling strategies for eradicating brucellosis in commercial swine herds.

Swine brucellosis caused by Brucella suis biovar 2 is an emerging disease in continental Europe. Without effective vaccines being available, the European Food Safety Authority (EFSA) recommends the full depopulation of infected herds as the only strategy to eradicate B. suis outbreaks. Using data collected from 8 herds suffering natural swine brucellosis outbreaks, we assessed the efficacy of four control strategies: (i) oxytetracycline treatment only, as a default scenario, (ii) oxytetracycline treatment combined with skin testing and removal of positive animals, (iii) oxytetracycline treatment combined with serological testing (Rose Bengal test-RBT-and indirect ELISA -iELISA-) and removal of seropositive animals and (iv) oxytetracycline treatment combined with both serological (RBT/iELISA) and skin testing and removal of positive animals. A Susceptible-Infectious-Removal model was used to estimate the reproduction ratio (R) for each strategy. According to this model, the oxytetracycline treatment alone was not effective enough to eradicate the infection. However, this antibiotic treatment combined with diagnostic testing at 4-monthly intervals plus immediate removal of positive animals showed to be effective to eradicate brucellosis independent of the diagnostic test strategy used in an acceptable time interval (1-2 years), depending on the initial number of infected animals.

Eight challenges in modelling infectious livestock diseases.

The transmission of infectious diseases of livestock does not differ in principle from disease transmission in any other animals, apart from that the aim of control is ultimately economic, with the influence of social, political and welfare constraints often poorly defined. Modelling of livestock diseases suffers simultaneously from a wealth and a lack of data. On the one hand, the ability to conduct transmission experiments, detailed within-host studies and track individual animals between geocoded locations make livestock diseases a particularly rich potential source of realistic data for illuminating biological mechanisms of transmission and conducting explicit analyses of contact networks. On the other hand, scarcity of funding, as compared to human diseases, often results in incomplete and partial data for many livestock diseases and regions of the world. In this overview of challenges in livestock disease modelling, we highlight eight areas unique to livestock that, if addressed, would mark major progress in the area.

Vaccination of cattle only is sufficient to stop FMDV transmission in mixed populations of sheep and cattle.

We quantified the transmission of foot-and-mouth disease virus in mixed cattle-sheep populations and the effect of different vaccination strategies. The (partial) reproduction ratios (R) in groups of non-vaccinated and vaccinated cattle and/or sheep were estimated from (published) transmission experiments. A 4 × 4 next-generation matrix (NGM) was constructed using these estimates. The dominant eigenvalue of the NGM, the R for a mixed population, was determined for populations with different proportions of cattle and sheep and for three different vaccination strategies. The higher the proportion of cattle in a mixed cattle-sheep population, the higher the R for the mixed population. Therefore the impact of vaccination of the cattle is higher. After vaccination of all animals R = 0·1 independent of population composition. In mixed cattle-sheep populations with at least 14% of cattle, vaccination of cattle only is sufficient to reduce R to < 1.

Detection of calcifications in retinoblastoma using gradient-echo MR imaging sequences: comparative study between in vivo MR imaging and ex vivo high-resolution CT.

BACKGROUND AND PURPOSE: Intratumoral calcifications are very important in the diagnosis of retinoblastoma. Although CT is considered superior in detecting calcification, its ionizing radiation, especially in patients with hereditary retinoblastoma, should be avoided. The purpose of our study was to validate T2*WI for the detection of calcification in retinoblastoma with ex vivo CT as the criterion standard. MATERIALS AND METHODS: Twenty-two consecutive patients with retinoblastoma (mean age, 21 months; range, 1-71 months) with enucleation as primary treatment were imaged at 1.5T by using a dedicated surface coil. Signal-intensity voids indicating calcification on T2*WI were compared with ex vivo high-resolution CT, and correlation was scored by 2 independent observers as poor, good, or excellent. Other parameters included the shape and location of the signal-intensity voids. In 5 tumors, susceptibility-weighted images were evaluated. RESULTS: All calcifications visible on high-resolution CT could be matched with signal-intensity voids on T2*WI, and correlation was scored as excellent in 17 (77%) and good in 5 (23%) eyes. In total, 93% (25/27) of the signal-intensity voids inside the tumor correlated with calcifications compared with none (0/8) of the signal-intensity voids outside the tumor. Areas of nodular signal-intensity voids correlated with calcifications in 92% (24/26), and linear signal-intensity voids correlated with hemorrhage in 67% (6/9) of cases. The correlation of signal-intensity voids on SWI was better in 4 of 5 tumors compared with T2*WI. CONCLUSIONS: Signal-intensity voids on in vivo T2*WI correlate well with calcifications on ex vivo high-resolution CT in retinoblastoma. Gradient-echo sequences may be helpful in the differential diagnosis of retinoblastoma. The combination of funduscopy, sonography, and high-resolution MR imaging with gradient-echo sequences should become the standard diagnostic approach for retinoblastoma.

Effects of postoperative morbidity on long-term outcome following surgery for colorectal liver metastases.

BACKGROUND: The impact of postoperative complications on long-term outcomes after surgery for colorectal liver metastases (CRLM) remains controversial. During the last decade, advances in surgical as well as non-surgical treatment have increased resectability and altered outcomes. We sought to determine the influence of postoperative morbidity on disease-free (DFS) and overall survival (OS). METHODS: All patients undergoing liver resection for CRLM for the first time between 2000 and 2011 were retrospectively identified from a prospective database. Postoperative morbidity was classified according to Dindo-Clavien grade. A Dindo-Clavien grade ≥ 3a was considered a major complication. Primary outcomes were DFS and OS depending on the presence or absence of postoperative morbidity. RESULTS: Of the 266 included patients, 97 patients (37 %) developed postoperative complications, of whom 61 (23 %) had major complications. Median DFS and OS (5-year) were 17 and 53 months (42 %). The occurrence of postoperative morbidity did not significantly shorten OS (p = 0.130) and DFS (p = 0.101). However, major morbidity reduced DFS significantly (p < 0.05). CONCLUSION: In the present study, the occurrence of major postoperative complications was associated with diminished DFS. However, the effect of (major) complications on OS did not reach statistical significance.

Horizontal transmission dynamics of White spot syndrome virus by cohabitation trials in juvenile Penaeus monodon and P. vannamei.

White spot syndrome virus (WSSV), a rod-shaped double-stranded DNA virus, is an infectious agent causing fatal disease in shrimp farming around the globe. Within shrimp populations WSSV is transmitted very fast, however, the modes and dynamics of transmission of this virus are not well understood. In the current study the dynamics of disease transmission of WSSV were investigated in small, closed populations of Penaeus monodon and Penaeus vannamei. Pair cohabitation experiments using PCR as a readout for virus infection were used to estimate transmission parameters for WSSV in these two species. The mortality rate of contact-infected shrimp in P. monodon was higher than the rate in P. vannamei. The transmission rate parameters for WSSV were not different between the two species. The relative contribution of direct and indirect transmission rates of WSSV differed between the two species. For P. vannamei the direct contact transmission rate of WSSV was significantly lower than the indirect environmental transmission rate, but for P. monodon, the opposite was found. The reproduction ratio R0 for WSSV for these two species of shrimp was estimated to be above one: 2.07 (95%CI 1.53, 2.79) for P. monodon and 1.51 (95%CI 1.12, 2.03) for P. vannamei. The difference in R0 between the two species is due to a lower host mortality and hence a longer infectious period of WSSV in P. monodon.

On the definition and utilization of heritable variation among hosts in reproduction ratio R0 for infectious diseases.

Infectious diseases have a major role in evolution by natural selection and pose a worldwide concern in livestock. Understanding quantitative genetics of infectious diseases, therefore, is essential both for understanding the consequences of natural selection and for designing artificial selection schemes in agriculture. The basic reproduction ratio, R0, is the key parameter determining risk and severity of infectious diseases. Genetic improvement for control of infectious diseases in host populations should therefore aim at reducing R0. This requires definitions of breeding value and heritable variation for R0, and understanding of mechanisms determining response to selection. This is challenging, as R0 is an emergent trait arising from interactions among individuals in the population. Here we show how to define breeding value and heritable variation for R0 for genetically heterogeneous host populations. Furthermore, we identify mechanisms determining utilization of heritable variation for R0. Using indirect genetic effects, next-generation matrices and a SIR (Susceptible, Infected and Recovered) model, we show that an individual's breeding value for R0 is a function of its own allele frequencies for susceptibility and infectivity and of population average susceptibility and infectivity. When interacting individuals are unrelated, selection for individual disease status captures heritable variation in susceptibility only, yielding limited response in R0. With related individuals, however, there is a secondary selection process, which also captures heritable variation in infectivity and additional variation in susceptibility, yielding substantially greater response. This shows that genetic variation in susceptibility represents an indirect genetic effect. As a consequence, response in R0 increased substantially when interacting individuals were genetically related.

Transmission of fish-borne zoonotic trematodes (Heterophyidae) to common carp (Cyprinus carpio) is independent of density of fish and trematodes.

Fish-borne zoonotic trematodes (FZTs) can cause major human health problems. The aim of this study was to quantify the transmission of parapleurolophocercous cercariae to common carp (Cyprinus carpio) and to study the effect of the density of cercariae and the density of fish on transmission with respect to the volume of water and surface area of the bottom. Fish were kept individually either as controls (n= 91) or were exposed to 250 cercariae in tubes with a volume of 25, 50, 100, 250 or 500 ml water (n= 190) with a surface area of 4, 12, 21, 30 or 49 cm2 (n= 195). The dose to which the fish were exposed was kept constant. Infection occurred in 94-100% of fish, with a mean of 15-18 metacercariae per fish and the proportion of FZTs established at 0.06-0.07 metacercariae per cercariae per fish. Neither the prevalence of infection with FZTs nor the number of metacercariae per fish nor the proportion of FZTs established were significantly associated with differences in the density of cercariae or the density of fish per ml water or per cm2 surface area. Thus, it was concluded that the transmission of cercariae to fish is independent of density.

Estimating the power of a Mycobacterium bovis vaccine trial in Irish badgers.

The aim of this study was to estimate the power, using simulation techniques, of a group randomized vaccine field trial designed to assess the effect of vaccination on Mycobacterium bovis transmission in badgers. The effects of sample size (recapture percentage), initial prevalence, sensitivity and specificity of the diagnostic test, transmission rate between unvaccinated badgers, Vaccine Efficacy for Susceptibility (VES) and Vaccine Efficacy for Infectiousness (VEI), on study power were determined. Sample size had a small effect on power. Study power increased with increasing transmission rate between non-vaccinated badgers. Changes in VES had a higher impact on power than changes in VEI. However, the largest effect on study power was associated with changes in the specificity of the diagnostic test, within the range of input values that were used for all other modelled parameters. Specificity values below 99.4% yielded a study power below 50% even when sensitivity was 100% and, VEI and VES were both equal to 80%. The effect of changes in sensitivity on study power was much lower. The results from our study are in line with previous studies, as study power was dependent not only on sample size but on many other variables. In this study, additional variables were studied, i.e. test sensitivity and specificity. In the current vaccine trial, power was highly dependent on the specificity of the diagnostic test. Therefore, it is critical that the diagnostic test used in the badger vaccine trial is optimized to maximize test specificity.