Surveillance and simulation of bovine spongiform encephalopathy and scrapie in small ruminants in Switzerland

BACKGROUND: After bovine spongiform encephalopathy (BSE) emerged in European cattle livestock in 1986 a fundamental question was whether the agent established also in the small ruminants' population. In Switzerland transmissible spongiform encephalopathies (TSEs) in small ruminants have been monitored since 1990. While in the most recent TSE cases a BSE infection could be excluded, for historical cases techniques to discriminate scrapie from BSE had not been available at the time of diagnosis and thus their status remained unclear. We herein applied state-of-the-art techniques to retrospectively classify these animals and to re-analyze the affected flocks for secondary cases. These results were the basis for models, simulating the course of TSEs over a period of 70 years. The aim was to come to a statistically based overall assessment of the TSE situation in the domestic small ruminant population in Switzerland. RESULTS: In sum 16 TSE cases were identified in small ruminants in Switzerland since 1981, of which eight were atypical and six were classical scrapie. In two animals retrospective analysis did not allow any further classification due to the lack of appropriate tissue samples. We found no evidence for an infection with the BSE agent in the cases under investigation. In none of the affected flocks, secondary cases were identified. A Bayesian prevalence calculation resulted in most likely estimates of one case of BSE, five cases of classical scrapie and 21 cases of atypical scrapie per 100'000 small ruminants. According to our models none of the TSEs is considered to cause a broader epidemic in Switzerland. In a closed population, they are rather expected to fade out in the next decades or, in case of a sporadic origin, may remain at a very low level. CONCLUSIONS: In summary, these data indicate that despite a significant epidemic of BSE in cattle, there is no evidence that BSE established in the small ruminant population in Switzerland. Classical and atypical scrapie both occur at a very low level and are not expected to escalate into an epidemic. In this situation the extent of TSE surveillance in small ruminants requires reevaluation based on cost-benefit analysis.

Comparing the demonstration of freedom from Trichinella infection of domestic pigs by traditional and risk-based surveillance

Traditionally, the routine artificial digestion test is applied to assess the presence of Trichinella larvae in pigs. However, this diagnostic method has a low sensitivity compared to serological tests. The results from artificial digestion tests in Switzerland were evaluated over a time period of 15 years to determine by when freedom from infection based on these data could be confirmed. Freedom was defined as a 95% probability that the prevalence of infection was below 0.0001%. Freedom was demonstrated after 12 years at the latest. A new risk-based surveillance approach was then developed based on serology. Risk-based surveillance was also assessed over 15 years, starting in 2010. It was shown that by using this design, the sample size could be reduced by at least a factor of 4 when compared with the traditional testing regimen, without lowering the level of confidence in the Trichinella-free status of the pig population.

Protocol for a population-based study of rheumatic heart disease prevalence and cardiovascular outcomes among schoolchildren in Nepal

Rheumatic heart disease (RHD) remains a major contributor to morbidity and mortality in developing countries. The reported prevalence rates of RHD are highly variable and mainly attributable to differences in the sensitivity of either clinical screening to detect advanced heart disease or echocardiographic evaluation where disease is diagnosed earlier across a continuous spectrum. The clinical significance of diagnosis of subclinical RHD by echocardiographic screening and early implementation of secondary prevention has not been clearly established. METHODS AND ANALYSIS: The authors designed a cross-sectional survey to determine the prevalence of RHD in children from private and public schools between the age of 5 and 15 years in urban and rural areas of Eastern Nepal using both cardiac auscultation and echocardiographic evaluation. Children with RHD will be treated with secondary prevention and enrolled in a prospective cohort study. The authors will compare the prevalence rates by cardiac auscultation and echocardiography, determine risk factors associated with diagnosis and progression of RHD, investigate social and economic barriers for receiving adequate cardiac care and assess clinical outcomes with regular medical surveillance as a function of stage of disease at the time of diagnosis. Prospective clinical studies investigating the impact of secondary prevention for subclinical RHD on long-term clinical outcome will be of central relevance for future health resource utilisation in developing countries. ETHICS AND DISSEMINATION: The study was considered ethically uncritical and was given an exempt status by the ethics committee at University of Bern, Switzerland. The study has been submitted to the National Nepal Health Research Council and was registered with http://www.ClinicalTrials.gov (NCT01550068). The study findings will be reported in peer-reviewed publications. CLINICALTRIALS.GOV IDENTIFIER: NCT01550068.

TSE surveillance in small ruminants and pigs: a pilot study

Switzerland is controlling Transmissible Spongiform Encephalopathies (TSE) in cattle (BSE) and small ruminants (scrapie). Since BSE is potentially transmissible to sheep, goats or pigs through feeding of contaminated meat and bone meal, implementation of an active surveillance programme for TSE in these species is discussed. The aim of this pilot study was to obtain preliminary data on the prevalence ofTSE and other neurological disorders in these populations. For that purpose, a total of 398 perished and 825 slaughtered adult small ruminants and pigs was examined for the presence of neuropathological changes. None of these animals revealed positive for TSE. However, the investigations demonstrated that perished sheep and goats exhibited a higher prevalence of relevant neuropathological changes when compared with slaughtered animals. From these results, it is concluded that perished small ruminants are probably a risk population for TSE and should be considered as target populations for an active surveillance programme.

Autofluorescence endoscopy in surveillance of Barrett's esophagus: a multicenter randomized trial on diagnostic efficacy

BACKGROUND AND STUDY AIMS: The reference surveillance method in patients with Barrett's esophagus is careful endoscopic observation, with targeted as well as random four-quadrant biopsies. Autofluorescence endoscopy (AFE) may make it easier to locate neoplasia. The aim of this study was to elucidate the diagnostic accuracy of surveillance with AFE-guided plus four-quadrant biopsies in comparison with the conventional approach. PATIENTS AND METHODS: A total of 187 of 200 consecutive Barrett's esophagus patients who were initially enrolled (73 % male, mean age 67 years, mean Barrett's segment length 4.6 cm), who underwent endoscopy for Barrett's esophagus in four study centers, were randomly assigned to undergo either AFE-targeted biopsy followed by four-quadrant biopsies or conventional endoscopic surveillance, also including four-quadrant biopsies (study phase 1). After exclusion of patients with early cancer or high-grade dysplasia, who underwent endoscopic or surgical treatment, as well as those who declined to participate in phase 2 of the study, 130 patients remained. These patients were examined again with the alternative method after a mean of 10 weeks, using the same methods described. The main study parameter was the detection of early cancer/adenocarcinoma or high-grade dysplasia (HGD), comparing both approaches in study phase 1; the secondary study aim in phase 2 was to assess the additional value of the AFE-guided approach after conventional surveillance, and vice versa. Test accuracy measures were derived from study phase 1. RESULTS: In study phase 1, the AFE and conventional approaches yielded adenocarcinoma/HGD rates of 12 % and 5.3 %, respectively, on a per-patient basis. With AFE, four previously unrecognized adenocarcinoma/HGD lesions were identified (4.3 % of the patients); with the conventional approach, one new lesion (1.1 %) was identified. Of the 19 adenocarcinoma/HGD lesions detected during AFE endoscopy in study phase 1, eight were visualized, while 11 were only detected using untargeted four-quadrant biopsies (sensitivity 42 %). Of the 766 biopsies classified at histology as being nonneoplastic, 58 appeared suspicious (specificity 92 %, positive predictive value 12 %, negative predictive value 98.5 %). In study phase 2, AFE detected two further lesions in addition to the initial alternative approach in 3.2 % of cases, in comparison with one lesion with conventional endoscopy (1.7 %). CONCLUSIONS: In this referral Barrett's esophagus population with a higher prevalence of neoplastic lesions, the AFE-guided approach improved the diagnostic yield for neoplasia in comparison with the conventional approach using four-quadrant biopsies. However, AFE alone was not suitable for replacing the standard four-quadrant biopsy protocol.

Prevalence of classical swine fever, Aujeszky's disease and brucellosis in a population of wild boar in Switzerland

During two survey rounds of a national surveillance system for infectious diseases in wild boar in Switzerland, each lasting four months from November to February, between 2001 and 2003, 1949 blood samples and 62 tissue samples from the spleen and 50 from the reproductive organs were collected from hunted wild boar. The survey was designed so that freedom from infection could be detected with a probability of 95 per cent at a threshold prevalence of less than 1 per cent for classical swine fever and Aujeszky's disease and less than 1.5 per cent for brucellosis. There was no serological evidence of classical swine fever or Aujeszky's disease, but brucellosis due to Brucella suis biovar 2 was confirmed serologically and by bacterial isolation.

Surveillance systems for sexually transmitted diseases in Switzerland

BACKGROUND: In Switzerland (population 7.4 million), 3 different systems contribute to surveillance for sexually transmitted infections. GOAL: The goal of this study was to compare time trends from surveillance systems for chlamydia, gonorrhea, and syphilis. STUDY DESIGN: We studied surveillance data (1997-2003) from laboratory reports in women and men, men attending dermatology clinics, and women attending gynecologists. RESULTS: Laboratory reports of episodes of Chlamydia trachomatis and Neisseria gonorrhoeae increased by 31% (from 2573 to 3449 cases) and 104% (from 259 to 528 cases), respectively. Over the same period, chlamydia reports from men attending dermatology clinics and women attending gynecologists did not change and dermatology clinic-based reports of gonorrhea in men increased only slightly. Syphilis reports from dermatology clinics increased by 127% (from 22 to 50 cases). CONCLUSIONS: Increases in laboratory reports of chlamydia and gonorrhea were not consistently detected in sentinel populations. Numbers of cases reported to all 3 systems were low. The performance of surveillance systems for sexually transmitted infections should be evaluated regularly.

Neuropathological survey of fallen stock: Active surveillance reveals high prevalence of encephalitic listeriosis in small ruminants

This paper describes the prevalence of brain lesions in the Swiss fallen stock population of small ruminants. 3075 whole brains (75% sheep, 25% goats) were collected as part of a year-long active survey of transmissible spongiform encephalopathies (TSEs) in small ruminants conducted by the Swiss authorities between July 2004 and July 2005. All fallen stock brains were systematically examined by histopathology to obtain reliable data on histologically identifiable brain lesions. Lesions were found in an unexpectedly high number of animals (8.1% of all examined brains). A wide spectrum of diseases was detected showing that this approach provides an excellent opportunity to screen for the prevalence of neurological diseases. Encephalitic listeriosis was by far the most frequent cause of CNS lesions in both species and its prevalence was unexpectedly high when compared to notified confirmed cases. In conclusion, the prevalence of listeriosis as estimated by passive surveillance based on the notification of clinical suspects has been underestimated in the past.

An analysis of the spatial and temporal patterns of highly pathogenic avian influenza occurrence in Vietnam using national surveillance data

The objectives of this study were to describe the spatio-temporal pattern of an epidemic of highly pathogenic avian influenza (HPAI) in Vietnam and to identify potential risk factors for the introduction and maintenance of infection within the poultry population. The results indicate that during the time period 2004–early 2006 a sequence of three epidemic waves occurred in Vietnam as distinct spatial and temporal clusters. The risk of outbreak occurrence increased with a greater percentage of rice paddy fields, increasing domestic water bird and chicken density. It increased with reducing distance to higher population density aggregations, and in the third epidemic wave with increasing percentage of aquaculture. The findings indicate that agri-livestock farming systems involving domestic water birds and rice production in river delta areas are important for the maintenance and spread of infection. While the government’s control measures appear to have been effective in the South and Central parts of Vietnam, it is likely that in the North of Vietnam the vaccination campaign led to transmission of infection which was subsequently brought under control.

Surveillance of bovine tuberculosis and risk estimation of a future reservoir formation in wildlife in Switzerland and Liechtenstein.

Bovine tuberculosis (bTB) caused by Mycobacterium bovis or M. caprae has recently (re-) emerged in livestock and wildlife in all countries bordering Switzerland (CH) and the Principality of Liechtenstein (FL). Comprehensive data for Swiss and Liechtenstein wildlife are not available so far, although two native species, wild boar (Sus scrofa) and red deer (Cervus elaphus elaphus), act as bTB reservoirs elsewhere in continental Europe. Our aims were (1) to assess the occurrence of bTB in these wild ungulates in CH/FL and to reinforce scanning surveillance in all wild mammals; (2) to evaluate the risk of a future bTB reservoir formation in wild boar and red deer in CH/FL. Tissue samples collected from 2009 to 2011 from 434 hunted red deer and wild boar and from eight diseased ungulates with tuberculosis-like lesions were tested by direct real-time PCR and culture to detect mycobacteria of the Mycobacterium tuberculosis complex (MTBC). Identification of suspicious colonies was attempted by real-time PCR, genotyping and spoligotyping. Information on risk factors for bTB maintenance within wildlife populations was retrieved from the literature and the situation regarding identified factors was assessed for our study areas. Mycobacteria of the MTBC were detected in six out of 165 wild boar (3.6%; 95% CI: 1.4-7.8) but none of the 269 red deer (0%; 0-1.4). M. microti was identified in two MTBC-positive wild boar, while species identification remained unsuccessful in four cases. Main risk factors for bTB maintenance worldwide, including different causes of aggregation often resulting from intensive wildlife management, are largely absent in CH and FL. In conclusion, M. bovis and M. caprae were not detected but we report for the first time MTBC mycobacteria in Swiss wild boar. Present conditions seem unfavorable for a reservoir emergence, nevertheless increasing population numbers of wild ungulates and offal consumption may represent a risk.

Inventory of veterinary syndromic surveillance initiatives in Europe (Triple-S project): current situation and perspectives.

Within the current context that favours the emergence of new diseases, syndromic surveillance (SyS) appears increasingly more relevant tool for the early detection of unexpected health events. The Triple-S project (Syndromic Surveillance Systems in Europe), co-financed by the European Commission, was launched in September 2010 for a three year period to promote both human and animal health SyS in European countries. Objectives of the project included performing an inventory of current and planned European animal health SyS systems and promoting knowledge transfer between SyS experts. This study presents and discusses the results of the Triple-S inventory of European veterinary SyS initiatives. European SyS systems were identified through an active process based on a questionnaire sent to animal health experts involved in SyS in Europe. Results were analyzed through a descriptive analysis and a multiple factor analysis (MFA) in order to establish a typology of the European SyS initiatives. Twenty seven European SyS systems were identified from twelve countries, at different levels of development, from project phase to active systems. Results of this inventory showed a real interest of European countries for SyS but also highlighted the novelty of this field. This survey highlighted the diversity of SyS systems in Europe in terms of objectives, population targeted, data providers, indicators monitored. For most SyS initiatives, statistical analysis of surveillance results was identified as a limitation in using the data. MFA results distinguished two types of systems. The first one belonged to the private sector, focused on companion animals and had reached a higher degree of achievement. The second one was based on mandatory collected data, targeted livestock species and is still in an early project phase. The exchange of knowledge between human and animal health sectors was considered useful to enhance SyS. In the same way that SyS is complementary to traditional surveillance, synergies between human and animal health SyS could be an added value, most notably to enhance timeliness, sensitivity and help interpreting non-specific signals.

Discrete Improvement in Racial Disparity in Survival among Patients with Stage IV Colorectal Cancer: a 21-Year Population-Based Analysis

Purpose Recently, multiple clinical trials have demonstrated improved outcomes in patients with metastatic colorectal cancer. This study investigated if the improved survival is race dependent. Patients and Methods Overall and cancer-specific survival of 77,490 White and Black patients with metastatic colorectal cancer from the 1988–2008 Surveillance Epidemiology and End Results registry were compared using unadjusted and multivariable adjusted Cox proportional hazard regression as well as competing risk analyses. Results Median age was 69 years, 47.4 % were female and 86.0 % White. Median survival was 11 months overall, with an overall increase from 8 to 14 months between 1988 and 2008. Overall survival increased from 8 to 14 months for White, and from 6 to 13 months for Black patients. After multivariable adjustment, the following parameters were associated with better survival: White, female, younger, better educated and married patients, patients with higher income and living in urban areas, patients with rectosigmoid junction and rectal cancer, undergoing cancer-directed surgery, having well/moderately differentiated, and N0 tumors (p<0.05 for all covariates). Discrepancies in overall survival based on race did not change significantly over time; however, there was a significant decrease of cancer-specific survival discrepancies over time between White and Black patients with a hazard ratio of 0.995 (95 % confidence interval 0.991–1.000) per year (p=0.03). Conclusion A clinically relevant overall survival increase was found from 1988 to 2008 in this population-based analysis for both White and Black patients with metastatic colorectal cancer. Although both White and Black patients benefitted from this improvement, a slight discrepancy between the two groups remained.

Serotype epidemiology of invasive pneumococcal disease in Swiss adults: A nationwide population-based study.

BACKGROUND In Switzerland, the heptavalent (PCV7) and 13-valent pneumococcal conjugate vaccine (PCV13) were recommended for all infants aged <2 years in 2007 and 2011, respectively. Due to herd effects, a protective impact on the invasive pneumococcal disease (IPD) rates in adults had been expected. METHODS Within this study, data from the nationwide mandatory surveillance was analyzed for all adult patients ≥16 years with IPD of known serotype/serogroup during 2003-2012. Trend (for IPD cases from 2003 to 2012) and logistic regression analyses (2007-2010) were performed to identify changes in serotype distribution and to identify the association of serotypes with age, clinical manifestations, comorbidities and case fatality, respectively. FINDINGS The proportion of PCV7 serotypes among all IPD cases (n=7678) significantly declined in adults from 44.7% (2003) before to 16.7% (2012) after the recommendation of PCV7 (P<0.001). In contrast, the proportion of non-PCV7 serogroup/serotypes increased for non-PCV13 but also PCV13 serotypes (not included in PCV7) at the same time. Serotype distribution varied significantly across ages, clinical manifestations and comorbidities. Serotype was furthermore associated with case fatality (P=0.001). In a multivariable logistic regression model, analyzing single serotypes showed that case-fatality was increased for the serotypes 3 (P=0.008), 19A (P=0.03) and 19F (P=0.005), compared to serotype 1 and 7F. CONCLUSION There was a significant decline in PCV7 serotypes among adults with IPD in Switzerland after introduction of childhood vaccination with PCV7. Pneumococcal serotypes were associated with case fatality, age, clinical manifestation and comorbidities of IPD in adults. These results may prove useful for future vaccine recommendations for adults in Switzerland.

Active surveillance for rheumatic heart disease in endemic regions: a systematic review and meta-analysis of prevalence among children and adolescents

BACKGROUND Rheumatic heart disease accounts for up to 250 000 premature deaths every year worldwide and can be regarded as a physical manifestation of poverty and social inequality. We aimed to estimate the prevalence of rheumatic heart disease in endemic countries as assessed by different screening modalities and as a function of age. METHODS We searched Medline, Embase, the Latin American and Caribbean System on Health Sciences Information, African Journals Online, and the Cochrane Database of Systematic Reviews for population-based studies published between Jan 1, 1993, and June 30, 2014, that reported on prevalence of rheumatic heart disease among children and adolescents (≥5 years to <18 years). We assessed prevalence of clinically silent and clinically manifest rheumatic heart disease in random effects meta-analyses according to screening modality and geographical region. We assessed the association between social inequality and rheumatic heart disease with the Gini coefficient. We used Poisson regression to analyse the effect of age on prevalence of rheumatic heart disease and estimated the incidence of rheumatic heart disease from prevalence data. FINDINGS We included 37 populations in the systematic review and meta-analysis. The pooled prevalence of rheumatic heart disease detected by cardiac auscultation was 2·9 per 1000 people (95% CI 1·7-5·0) and by echocardiography it was 12·9 per 1000 people (8·9-18·6), with substantial heterogeneity between individual reports for both screening modalities (I(2)=99·0% and 94·9%, respectively). We noted an association between social inequality expressed by the Gini coefficient and prevalence of rheumatic heart disease (p=0·0002). The prevalence of clinically silent rheumatic heart disease (21·1 per 1000 people, 95% CI 14·1-31·4) was about seven to eight times higher than that of clinically manifest disease (2·7 per 1000 people, 1·6-4·4). Prevalence progressively increased with advancing age, from 4·7 per 1000 people (95% CI 0·0-11·2) at age 5 years to 21·0 per 1000 people (6·8-35·1) at 16 years. The estimated incidence was 1·6 per 1000 people (0·8-2·3) and remained constant across age categories (range 2·5, 95% CI 1·3-3·7 in 5-year-old children to 1·7, 0·0-5·1 in 15-year-old adolescents). We noted no sex-related differences in prevalence (p=0·829). INTERPRETATION We found a high prevalence of rheumatic heart disease in endemic countries. Although a reduction in social inequalities represents the cornerstone of community-based prevention, the importance of early detection of silent rheumatic heart disease remains to be further assessed. FUNDING UBS Optimus Foundation.

A pilot study for targeted surveillance of bovine spongiform encephalopathy in Nigeria.

Bovine spongiform encephalopathy (BSE), popularly known as 'mad cow disease', led to an epidemic in Europe that peaked in the mid-1990s. Its impact on developing countries, such as Nigeria, has not been fully established as information on livestock and surveillance has eluded those in charge of this task. The BSE risk to Nigeria's cattle population currently remains undetermined, which has resulted in international trade restrictions on commodities from the cattle population. This is mainly because of a lack of updated BSE risk assessments and disease surveillance data. To evaluate the feasibility of BSE surveillance in Nigeria, we carried out a pilot study targeting cattle that were presented for emergency or casualty slaughter. In total, 1551 cattle of local breeds, aged 24 months and above were clinically examined. Ataxia, recumbency and other neurological signs were topmost on our list of criteria. A total of 96 cattle, which correspond to 6.2%, presented clinical signs that supported a suspect of BSE. The caudal brainstem tissues of these animals were collected post-mortem and analysed for the disease-specific form of the prion protein using a rapid test approved by the International Animal Health Organization (OIE). None of the samples were positive for BSE. Although our findings do not exclude the presence of BSE in Nigeria, they do demonstrate that targeted sampling of clinically suspected cases of BSE is feasible in developing countries. In addition, these findings point to the possibility of implementing clinical monitoring schemes for BSE and potentially other diseases with grave economic and public health consequences.