Seroprevalence of reproductive and infectious diseases in cattle: the case of Madre de Dios in the Peruvian southeastern tropics.

OBJECTIVE: The objective of this study was to determine the seroprevalence of reproductive and infectious diseases in tropical cattle in the Tambopata and Tahuamanu Provinces in the department of Madre de Dios, Peru. SAMPLE: 156 bovines from 7 cattle farms were sampled. These farms used exclusive grazing for food and natural mating for reproduction and did not have sanitary or vaccination programs. METHODS: The serum of blood samples was subjected to ELISA with commercial kits for the detection of antibodies against Neospora caninum, Mycobacterium avium subsp paratuberculosis (MAP), Leptospira interrogans, pestivirus bovine viral diarrhea virus-1, retrovirus bovine leukemia virus (BLV), orbivirus bluetongue virus (BTV), and herpesvirus bovine herpes virus-1 (BHV). The data were analyzed by means of association tests with χ2 (P < .05) and Spearman rank correlation (P < .05) in the SPSS v.15.0 software (IBM Corp). RESULTS: A low prevalence of antibodies to L interrogans, N caninum, M avium subsp paratuberculosis, bovine viral diarrhea virus-1 was found, but it was high to BTV, BLV, and BHV (100%, 53.85%, and 72.44%, respectively). The presence of BLV and BHV was higher in the Las Piedras District, bovines less than 5 years old, and cattle with breed characteristics of zebu and crossbred (P < .01). In addition, there was a significant correlation between both infections, showing 83.3% of BLV positivity that were also BHV positive (P < .01). CLINICAL RELEVANCE: The high prevalence of antibodies to BTV, BHV, and BLV could be due to livestock management practices, direct contact with infected animals, and variation of the presence of vectors and natural reservoirs in the context of climate change in the tropics.

Prevalence of paratuberculosis in cattle based on gross and microscopic lesions in Ethiopia.

BACKGROUND: Paratuberculosis, caused by Mycobacterium avium subsp. paratuberculosis (MAP), is a chronic progressive granulomatous enteritis mainly affecting domestic and wild ruminants worldwide. Although paratuberculosis could be prevail in Ethiopia, there is a scarcity of epidemiological data on paratuberculosis in the country. Thus, this study was conducted to estimate the prevalence of paratuberculosis based on gross and microscopic lesions in cattle slaughtered at ELFORA Abattoir, central Ethiopia. Small intestines and associated lymph nodes of 400 apparently healthy cattle which were slaughtered at ELFORA export abattoir were examined for gross and microscopic lesions of paratuberculosis. The microscopic lesions were classified into four grades (I-IV) based on the type and number of cells infiltrated into the lesion. The prevalence of paratuberculosis was estimated on the basis of gross as well as microscopic lesion of paratuberculosis. RESULTS: The prevalence of paratuberculosis was 11.25% (95% Confidence interval, CI = 0.083-0.148) on the basis of gross lesion. However, relatively lower prevalence (2.0%, 95% CI = 0.01, 0.039) was recorded based on microscopic lesion. The gross lesions were characterized by intestinal thickening, mucosal corrugations and enlargement of associated mesenteric lymph nodes. On the other hand, the microscopic lesions were characterized by granuloma of different grades ranging from grade I to grade III lesions. CONCLUSIONS: The present study indicated the occurrence of paratuberculosis in cattle of Ethiopia based on the detection of gross and microscopic lesions consistent with the lesion of paratuberculosis. The result of this study could be used as baseline information for future studies on the epidemiology and economic significance of paratuberculosis.

Mycobacterium paratuberculosis zoonosis is a One Health emergency.

A singular pathogen has been killing animals, contaminating food and causing an array of human diseases. Mycobacterium avium subspecies paratuberculosis (MAP) is the cause of a fatal enteric infectious disease called Johne's (Yo'-nees), a disorder mostly studied in ruminant animals. MAP is globally impacting animal health and imparting significant economic burden to animal agriculture. Confounding the management of Johne's disease is that animals are typically infected as calves and while commonly not manifesting clinical disease for years, they shed MAP in their milk and feces in the interval. This has resulted in a "don't test, don't tell" scenario for the industry resulting in greater prevalence of Johne's disease; furthermore, because MAP survives pasteurization, the contaminated food supply provides a source of exposure to humans. Indeed, greater than 90% of dairy herds in the US have MAP-infected animals within the herd. The same bacterium, MAP, is the putative cause of Crohn's disease in humans. Countries historically isolated from importing/exporting ruminant animals and free of Johne's disease subsequently acquired the disease as a consequence of opening trade with what proved to be infected animals. Crohn's disease in those populations became a lagging indicator of MAP infection. Moreover, MAP is associated with an increasingly long list of human diseases. Despite MAP scientists entreating regulatory agencies to designate MAP a "zoonotic agent," it has not been forthcoming. One Health is a global endeavor applying an integrative health initiative that includes the environment, animals and humans; One Health asserts that stressors affecting one affects all three. Recognizing the impact MAP has on animal and human health as well as on the environment, it is time for One Health, as well as other global regulatory agencies, to recognize that MAP is causing an insidious slow-motion tsunami of zoonosis and implement public health mitigation.

Genome-wide association analysis for susceptibility to infection by Mycobacterium avium ssp. paratuberculosis in US Holsteins.

Paratuberculosis, or Johne's disease, is a chronic, granulomatous, gastrointestinal tract disease of cattle and other ruminants caused by the bacterium Mycobacterium avium subspecies paratuberculosis (MAP). Control of Johne's disease is based on programs of testing and culling animals positive for infection with MAP and concurrently modifying management to reduce the likelihood of infection. The current study was motivated by the hypothesis that genetic variation in host susceptibility to MAP infection can be dissected and quantifiable associations with genetic markers identified. Two separate GWAS analyses were conducted, the first using 897 genotyped Holstein artificial insemination sires with phenotypes derived from incidence of MAP infection among daughters based on milk ELISA testing records. The second GWAS analysis was a case-control design using US Holstein cows phenotyped for MAP infection by serum ELISA or fecal culture tests. Cases included cows positive for either serum ELISA, fecal culture, or both. Controls consisted of animals negative for all tests conducted. A total of 376 samples (70 cases and 306 controls) from a University of Minnesota Johne's management demonstration project and 184 samples (76 cases and 108 controls) from a Michigan State University study were used. Medium-density (sires) and high-density (cows) genotype data were imputed to full genome sequence for the analyses. Marker-trait associations were analyzed using the single-step (ss)GWAS procedure implemented in the BLUPF90 suite of programs. Evidence of significant genomic contributions for susceptibility to MAP infection were observed on multiple chromosomes. Results were combined across studies in a meta-analysis, and increased support for genomic regions on BTA7 and BTA21 were observed. Gene set enrichment analysis suggested pathways for antigen processing and presentation, antimicrobial peptides and natural killer cell-mediated cytotoxicity are relevant to variation in host susceptibility to MAP infection, among others. Genomic prediction was evaluated using a 5-fold cross-validation, and moderate correlations were observed between genomic breeding value predictions and daughter averages (∼0.43 to 0.53) for MAP infection in testing data sets. These results suggest that genomic selection against susceptibility to MAP infection is feasible in Holstein cattle.

Buyer beware! Disease testing newly arrived cattle to dairy farms in Ontario.

The objective of this cross-sectional study was to evaluate the presence of infectious disease in newly arrived cattle on dairy farms in Ontario. Cattle that were more than 2 years old and arrived at dairy farms within the previous year were tested. A total 321 cattle from 56 dairy farms were sampled and had blood submitted to a diagnostic laboratory. Of all sampled cattle, 0.0%, 39.6%, 2.2%, and 1.3% tested positive for Anaplasma, bovine leukemia virus, Mycobacterium avium subsp. paratuberculosis, and Salmonella Dublin, respectively. Based on these results, it is imperative that dairy producers are vigilant to ensure they do not purchase animals with these important and untreatable infectious diseases.

Acheteur prenez garde! Dépistage des maladies des bovins nouvellement arrivés dans les fermes laitières de l'Ontario. L'objectif de cette étude transversale était d'évaluer la présence de maladies infectieuses chez les bovins nouvellement arrivés dans les fermes laitières de l'Ontario. Les bovins âgés de plus de 2 ans et arrivés dans les fermes laitières au cours de l'année précédente ont été testés. Au total, 321 bovins provenant de 56 fermes laitières ont été échantillonnés et leur sang a été soumis à un laboratoire de diagnostic. De tous les bovins échantillonnés, 0,0 %, 39,6 %, 2,2 % et 1,3 % ont été testés positifs pour Anaplasma, le virus de la leucémie bovine, Mycobacterium avium subsp. paratuberculosis et Salmonella Dublin, respectivement. Sur la base de ces résultats, il est impératif que les producteurs laitiers soient vigilants pour s'assurer qu'ils n'achètent pas d'animaux atteints de ces maladies infectieuses importantes et incurables.(Traduit par Dr Serge Messier).

Estimating the burden of multiple endemic diseases and health conditions using Bayes' Theorem: A conditional probability model applied to UK dairy cattle.

The Global Burden of Animal Diseases (GBADs) is an international collaboration aiming, in part, to measure and improve societal outcomes from livestock. One GBADs objective is to estimate the economic impact of endemic diseases in livestock. However, if individual disease impact estimates are linearly aggregated without consideration for associations among diseases, there is the potential to double count impacts, overestimating the total burden. Accordingly, the authors propose a method to adjust an array of individual disease impact estimates so that they may be aggregated without overlap. Using Bayes' Theorem, conditional probabilities were derived from inter-disease odds ratios in the literature. These conditional probabilities were used to calculate the excess probability of disease among animals with associated conditions, or the probability of disease overlap given the odds of coinfection, which were then used to adjust disease impact estimates so that they may be aggregated. The aggregate impacts, or the yield, fertility, and mortality gaps due to disease, were then attributed and valued, generating disease-specific losses. The approach was illustrated using an example dairy cattle system with input values and supporting parameters from the UK, with 13 diseases and health conditions endemic to UK dairy cattle: cystic ovary, disease caused by gastrointestinal nematodes, displaced abomasum, dystocia, fasciolosis, lameness, mastitis, metritis, milk fever, neosporosis, paratuberculosis, retained placenta, and subclinical ketosis. The diseases and conditions modelled resulted in total adjusted losses of £ 404/cow/year, equivalent to herd-level losses of £ 60,000/year. Unadjusted aggregation methods suggested losses 14-61% greater. Although lameness was identified as the costliest condition (28% of total losses), variations in the prevalence of fasciolosis, neosporosis, and paratuberculosis (only a combined 22% of total losses) were nearly as impactful individually as variations in the prevalence of lameness. The results suggest that from a disease control policy perspective, the costliness of a disease may not always be the best indicator of the investment its control warrants; the costliness rankings varied across approaches and total losses were found to be surprisingly sensitive to variations in the prevalence of relatively uncostly diseases. This approach allows for disease impact estimates to be aggregated without double counting. It can be applied to any livestock system in any region with any set of endemic diseases, and can be updated as new prevalence, impact, and disease association data become available. This approach also provides researchers and policymakers an alternative tool to rank prevention priorities.

Bayesian estimation of prevalence of Johne's disease in dairy herds in Southern Italy.

Johne's disease (JD) is a chronic granulomatous disease caused by Mycobacterium avium subsp. paratuberculosis (MAP) causing important losses on dairy farms. In Italy, voluntary programs to control MAP infection in dairy cattle are implemented in the Northern part of the country, where several studies have been carried out. Conversely, the disease status has not been fully investigated in the Southern regions. The aims of this study were to (i) determine the herd-level true prevalence (HTP) and (ii) the conditional within herd animal-level prevalence (CWHP) of JD in selected dairy cattle herds in Southern Italy. Serum samples were taken from 27 farms and analysed using a commercial ELISA test. A Bayesian model was fitted to the data. The estimated posterior mean of HPT was 0.46 (89 % CI 0.25-0.67), while the mean CWHP was 0.03 (89 % CI: 0.012-0.045). The results presented in this study call for designing and implementing an effective JD control program at national level.

Infections and Multiple Sclerosis: From the World to Sardinia, From Sardinia to the World.

Multiple Sclerosis (MS) is an inflammatory disease of the central nervous system. Sardinia, an Italian island, is one of the areas with the highest global prevalence of MS. Genetic factors have been widely explored to explain this greater prevalence among some populations; the genetic makeup of the Sardinians appears to make them more likely to develop autoimmune diseases. A strong association between MS and some infections have been reported globally. The most robust evidence indicating the role of infections is MS development concerns the Epstein-Barr virus (EBV). Anti-EBV antibodies in patients once infected by EBV are associated with the development of MS years later. These features have also been noted in Sardinian patients with MS. Many groups have found an increased expression of the Human endogenous retroviruses (HERV) family in patients with MS. A role in pathogenesis, prognosis, and prediction of treatment response has been proposed for HERV. A European multi-centre study has shown that their presence was variable among populations, ranging from 59% to 100% of patients, with higher HERV expression noted in Sardinian patients with MS. The mycobacterium avium subspecies paratuberculosis (MAP) DNA and antibodies against MAP2694 protein were found to be associated with MS in Sardinian patients. More recently, this association has also been reported in Japanese patients with MS. In this study, we analysed the role of infectious factors in Sardinian patients with MS and compared it with the findings reported in other populations.

Comparison of Mycobacterium avium subsp. paratuberculosis infection in cattle, sheep and goats in the Khuzestan Province of Iran: Results of a preliminary survey.

BACKGROUND: Paratuberculosis or Johne's disease, the chronic infectious granulomatous enteritis of ruminants, is a worldwide infection, which is caused by Mycobacterium avium subsp. paratuberculosis (MAP). The most common symptoms of this disease in cattle are loss of milk production, weight loss and diarrhoea, whereas in sheep and goats, the symptoms are emaciation, anorexia and severe disability. OBJECTIVES: The aim of this study was to compare the seroprevalence of MAP in cattle, sheep and goats in the southwest of Iran. METHODS: Blood samples were randomly collected from 530 cattle, 568 sheep and 368 goats in southwest of Iran. Sera were tested by a commercial ELISA kit (ID vet; ID Screen® Paratuberculosis Indirect) for detection of antibodies of MAP. RESULTS: Overall apparent and true seroprevalence rate of MAP was 6.00% (95% CI: 4.90%-7.30%) and 13.25% (95% CI: 11.55%- 14.95%). Apparent and true seroprevalence of MAP, respectively, was 4.34% (95% CI: 3.88%-6.46%) and 9.19% (95% CI: 6.98%-11.98%) in cattle, 6.87% (95% CI: 5.05%-9.27%) and 15.37% (95% CI: 12.60%-16.60%) in sheep and 7.07% (95% CI: 4.82%-10.18%) and 15.86% (95% CI: 12.41%-20.01%) in goats, respectively. As a result, there was no significant relationship between animal species and MAP infection. Moreover, multivariate logistic regression showed that the infection rate is not associated with age, gender and geographical location in cattle, sheep and goats (P > 0.05). CONCLUSION: This study confirms that the seroprevalence of MAP is relatively considerable in the cattle, sheep and goats in the southwest of Iran, although in cattle, it is less than goats and sheep. Therefore, preventive and control measures should be considered by animal health authorities and meat and dairy processing units.

Is vaccination a viable method to control Johne's disease caused by Mycobacterium avium subsp. paratuberculosis? Data from 12 million ovine vaccinations and 7.6 million carcass examinations in New South Wales, Australia from 1999-2009.

BACKGROUND: Mycobacterium avium subsp. paratuberculosis (MAP) causes Johne's disease (or paratuberculosis), a chronic wasting disease of ruminants and other animals resulting from granulomatous enteritis. There are increasing concerns that MAP is zoonotic. The prevalence of Johne's disease is increasing worldwide. In an attempt to control an epidemic of ovine Johne's disease (OJD) in New South Wales (NSW), a government/industry sponsored voluntary vaccination/on-farm management program commenced in 2000. We report herein an observational study of changes in disease prevalence as vaccination progressed, based on abattoir surveillance data for OJD from 1999 to 2009. We also discuss the epidemiological, policy, regulatory, research, economic and sociological elements that contributed to the development of a mature control program, whose aim was to halt the epidemic spread of OJD in a naïve sheep population. METHODS: NSW was divided into areas of "High" (HPA), "Medium" (MPA) and "Low" (LPA) OJD prevalence. A killed whole cell vaccine (Gudair®) was administered to sheep from 2000 to 2009. Trained examiners evaluated the viscera of adult sheep carcasses at slaughter for gross evidence of OJD. MAP infection was confirmed by histopathology. PRINCIPAL FINDINGS: From 2000-2009, 12 million vaccine doses were administered in NSW (91%; 10.9 million in the HPA). Many of the vaccinated flocks were suffering > 5% annual mortality in adult sheep, with some individual flocks with 10-15% losses attributable to OJD. A total of 7.6 million carcasses were examined (38%; 2.9 million from the HPA). Overall, 16% of slaughter consignments (sheep consigned to the abattoir from a single vendor) were positive for OJD, of which 94% were from the HPA. In the HPA, the percentage of animals with lesions attributable to OJD at slaughter fell progressively from 2.4% (10,406/432,860) at commencement of vaccination in 2000 to 0.8% (1,573/189,564) by 2009. Herd immunity from vaccination in the HPA was estimated at 70% by 2009, the target commonly espoused for an effective control program based on vaccination. This coincided with a progressive decrease in reports of clinical disease and mortalities in vaccinated flocks. SIGNIFICANCE: We show a decrease in the prevalence of lesions attributable to OJD in NSW concomitant with initiation of voluntary vaccination, on-farm management plans, abattoir monitoring and feedback of animal prevalence data to sheep producers. We conclude that a target of ≤ 1% regional prevalence of OJD affected sheep at slaughter is achievable using these interventions.

SEROPREVALENCE OF ANTIBODIES AGAINST MYCOBACTERIUM AVIUM SUBSP. PARATUBERCULOSIS AND ITS RELATIONSHIP TO AGE AND SEX OF TEXAS WHITE-TAILED DEER (ODOCOILEUS VIRGINIANUS) IN COAHUILA, MEXICO.

Paratuberculosis (PTB) is a disease that affects cattle (Bos taurus), goats (Capra aegagrus hircus), sheep (Ovis aries), and wild animals, such as white-tailed deer (Odocoileus virginianus), since all ruminants are susceptible. The causal agent is Mycobacterium avium subsp. paratuberculosis (MAP). The disease is chronic, consumptive, and incurable; it causes chronic granulomatous gastroenteritis with lymphangiectasis and lymphangitis leading to a syndrome of malnutrition and eventually to death. Mycobacterium avium subsp. paratuberculosis is transmitted in feces mainly orally; however, it can also be transmitted vertically. Thus, the objective of this study was to determine the seroprevalence of MAP antibodies and its relationship to age and sex of Texas white-tailed deer in the subclinical stage of PTB in Coahuila, Mexico. The entire population (n=99) belonging to the Wildlife Management and Conservation Unit (WMCU) San Juan, Monclova, Coahuila, Mexico was captured. Mycobacterium avium subsp. paratuberculosis was diagnosed using an enzyme-linked immunosorbent assay by serologic test. Seroprevalence variables of adult vs. young females and males vs. females were compared. The treatments were assigned at random. For the analysis of data, the chi-square test was used. Total seroprevalence in an intensive WMCU was 16% (16/99). Total seroprevalence by sex was 5.0% (5/99) for males and 11% (11/99) for females, and total seroprevalence by age was 7% (7/99) for young and 9% (9/99) for adult. Within sex, the seroprevalence in males was 16% (5/31) and 16% (11/68) in females. There were no statistical differences for any of the comparisons. Total seroprevalence of the white-tailed deer population in the WMCU was 16%, and PTB seroprevalence was independent of sex or age of the sampled individuals of this population.

Mycobacterium avium subspecies paratuberculosis and bovine leukemia virus seroprevalence and associated risk factors in dairy herds in Minas Gerais state, Brazil / [Soroprevalência do Mycobacterium avium subespécie paratuberculosis e vírus da leucemia bovina e fatores de risco associados em rebanhos leiteiros de Minas Gerais, Brasil]

Mycobacterium avium subesp. paratuberculosis (MAP) e o vírus da leucemia bovina (BLV) são agentes que causam grandes perdas econômicas nos rebanhos. O objetivo deste estudo foi avaliar a situação epidemiológica da paratuberculose bovina (PTB) e leucose enzoótica bovina (EBL) em rebanhos leiteiros de Lagoa Formosa, Minas Gerais, Brasil. Foram coletadas 236 amostras de sangue de vacas, as quais foram submetidas aos testes ELISA e imunodifusão em gel de ágar para detecção de anticorpos contra MAP e BLV. A soroprevalência de anticorpos contra MAP e BVL foi de 20% para os rebanhos e 6% para os animais e de 85% para os rebanhos e 50,42% para os animais, respectivamente. A presença dessas enfermidades deve servir como um alerta para os produtores e veterinários, para que concentrem maior atenção na implementação de medidas higiênico-sanitárias, incorporando elementos de vigilância com base nos riscos identificados no estudo.(AU)

Short communication: Occurrence and differentiation of Mycobacterium avium ssp. paratuberculosis (MAP) strains from milk of cows from herd with low prevalence of MAP.

Mycobacterium avium ssp. paratuberculosis (MAP) is an important pathogen responsible for the chronic progressive granulomatous enteritis known as paratuberculosis. None of the detection methods of MAP infection based on isolation of the bacterium is 100% sensitive or specific. In this article, we describe the comparison of 2 MAP detection methods: direct isolation of genetic material and culture, in individual and pooled milk samples. The genetic types of MAP detected in the samples were also identified. The study was performed in a herd of 321 cows; apparent herd seroprevalence was 3.43%. Seven of 11 individual milk samples from seropositive cows were positive by culture (and confirmed by PCR), whereas all 11 were positive by direct PCR. Of the 62 milk pools from seronegative animals, 15 were positive by culture (and confirmed by PCR) and 13 were positive by direct PCR. Using multiplex PCR and PCR-restriction enzyme analysis (PCR-REA) methods, C (cattle) and S (sheep)-types of mycobacteria were identified. Most of the genetic material tested belonged to C-type. Detection of the MAP type occurring in an infected herd can help track the source of infection. We suggest using genetic material isolated directly from pooled milk samples for quick diagnosis, identification of MAP type, and tracking of infection, without the need to sequence the entire genome.

High prevalence of subclinical paratuberculosis in buffaloes (Bubalus bubalis) in Maranhão, Brazil.

Paratuberculosis is an infectious, chronic, and incurable disease that affects ruminants, causing enteritis and chronic granulomatous lymphadenitis, characterized by malabsorption syndrome, its agent is the Mycobacterium avium subsp. paratuberculosis (MAP). Thus, the objective of this work was to identify and characterize MAP in buffalo herds slaughtered in Baixada Maranhense region. Samples of intestines, mesenteric lymph nodes, and ileocecal valves were collected from 115 buffaloes slaughtered at Baixada Maranhense slaughterhouses to perform the diagnosis by histopathological examination using staining with Hematoxylin and Eosin (H&E) and Ziehl-Neelsen, bacterial isolation, and real-time PCR. In the histopathology by H&E staining, there was evidence suggestive of paratuberculosis in 30% (31/115) of the buffaloes. With Ziehl-Neelsen staining, acid-fast bacilli (AFB) were visualized in 27% (26/115) of the tissue samples analyzed. MAP was isolated in 4.3% (5/115) of the fecal samples subjected to bacterial culture. The samples inoculated in HEYM with mycobactin J produced colonies identified with MAP according to their own morphological characteristics such as round, white, smooth and slightly rough, alcohol-acid staining, and slow growth with 8 weeks of incubation and mycobactin dependence. The agent confirmation was performed in five bacterial isolates (4.3%) and 15 (13%) fragments of jejunum, ileum, and mesenteric lymph node by the IS900 real-time PCR technique. The results of the present study demonstrate the subclinical occurrence of paratuberculosis in flocks of buffalo slaughtered in slaughterhouses of Baixada Maranhense.

Characteristics and Epidemiological Investigation of Paratuberculosis in Dairy Cattle in Tai'an, China.

Paratuberculosis, a chronic and sometimes fatal disease of ruminants, is caused by Mycobacterium avium subsp. paratuberculosis (MAP). In this study, we examined paratuberculosis cases among 2-4-year-old dairy cows at farms in Shandong Province, China. Paratuberculosis cases were diagnosed based on clinical symptoms, pathological autopsy, and histopathological inspection. Characteristics of paratuberculosis in the affected dairy cattle included poor body condition, persistent diarrhea, subcutaneous edema, granulomatous ileitis (multibacillary), mesenteric lymphadenitis, and hepatitis. Acid-fast bacilli from fecal specimens and lymphocytes were putatively identified as MAP based on Ziehl-Neelsen staining, then confirmed using polymerase chain reaction-based testing and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analyses. Overall, only one MAP strain was isolated from a herd with symptomatic diarrhea. However, analysis of 586 serum samples from nine herds in Tai'an City revealed that 66.7% of herds and 14.2% of animals were seropositive for MAP. Our findings suggest that paratuberculosis is widely prevalent and therefore a significant threat to the dairy industry in Tai'an City, Shandong Province, China.

Baseballs, tennis balls, livestock farm manure, the IDH1 mutation, endothelial cell proliferation and hypoxic pseudopalisading (granulomatous) necrosis: Mycobacterium avium subspecies paratuberculosis and the epidemiology, cellular metabolism and histology of diffuse gliomas, including glioblastoma.

An increased rate of diffuse gliomas, including glioblastoma, has been noted in livestock farmers in Western countries. Some researchers have suggested that a zoonotic virus or bacteria present in the livestock animal's feces or manure may be a possible etiologic factor. Mycobacterium avium subspecies paratuberculosis (MAP), the cause of a chronic enteropathy in domestic livestock and a probable zoonosis, is heavily excreted in an infected animal's feces or manure, contaminating soil and ground on the animal's farm. Once excreted in an animal's feces, MAP lasts indefinitely in a dormant but viable form, and easily spreads outside farms to the surrounding environment. MAP's presence throughout the soil in countries where MAP infection of domestic livestock is extensive and long-standing may explain the increased rates of glioblastoma in tennis and baseball players who handle balls coated with MAP-contaminated dirt. MAP infection is consistent with glioblastoma's two defining histopathologic characteristics: endothelial cell proliferation and pseudopalisading necrosis. MAP is a non-tuberculous or atypical mycobacterium, which can cause hypoxic necrotizing granulomas, granulomas that resemble areas of pseudopalisading necrosis. There are known bacterial causes of endothelial cell proliferation. Almost unique amongst intracellular bacteria, MAP's variant isocitrate dehydrogenase 1 (IDH1) enzyme, a type 2-oxoglutarate ferredoxin oxidoreductase, can use a host cell's cytosolic α-ketoglutarate in its own Krebs or tricarboxylic acid cycle. MAP's ability to use a host cell's α-ketoglutarate may explain the survival advantage of the cytosolic IDH1 enzyme mutation for patients with diffuse gliomas including glioblastoma, astrocytoma, and oligdendroglioma, a mutation that results in a reduced supply of cytosolic α-ketoglutarate. MAP may therefore be one possible infectious cause of glioblastoma and the other histologic categories of diffuse glioma.

Prevalence of Mycobacterium avium subspecies paratuberculosis IS 900 DNA in biopsy tissues from patients with Crohn's disease: histopathological and molecular comparison with Johne's disease in Fars province of Iran.

BACKGROUND: Crohn's disease is a chronic enteritis of humans that affects the gastrointestinal tract, especially the terminal ileum, cecum and colon. The etiology of this disease is still unknown but seems to be multifactorial. There are reports about the potential link between Crohn's disease in humans and the causative agent of Johne's disease in ruminants. Because of the prevalence of Johne's disease in the Fars Province of Iran, the aim of this study was to investigate the prevalence of MAP in the biopsy tissues of patients affected by Crohn's disease in this area. METHODS: The study was performed from April 2015 to June 2017 at Namazi Hospital, Shiraz University of Medical Sciences, and School of Veterinary Medicine, Shiraz University, Shiraz, Iran. Intestinal biopsies of 30 patients (12 male and 18 female; mean age, 34 years; range 4-77 years) with the confirmed diagnosis of Crohn's disease and 30 patients diagnosed as non-inflammatory bowel disease (19 male and 11 female; mean age, 38 years; range 13-68 years) were studied by molecular, histopathological and histochemical methods. Also, similar numbers of adult goats affected by Johne's disease were studied, comparatively. DNA extractions of tissue specimens were subjected to PCR to amplify a 413-bp sequence of the IS900 gene. RESULTS: Using IS900-PCR, the overall prevalence of MAP in patients affected by Crohn's disease and non-inflammatory bowel disease were 47 and 13%, respectively. In addition, the prevalence of MAP in goats affected by Johne's disease was 70%. Using acid-fast histochemical staining, only 7% of Crohn's disease patients were weakly positive as paucibacillary and 43% of Johne's disease cases were moderate to strongly positive as multibacillary. Histopathologically, granulomatous enteritis (83 and 90%), lymphoplasmacytic enteritis (17 and 14%), edema and lymphangiectasia (67 and 96%), and vasculitis (20 and 73%) were common findings in Crohn's and Johne's diseases, respectively. CONCLUSION: Our findings demonstrate a remarkable association between MAP and CD in this population, and support an etiologic relationship between MAP infection in humans and the development of CD. MAP infection in human tissue may display species-specific pathologic findings, as occurs with other zoonotic pathogens.

Age-related distribution and dynamics of T-cells in blood and lymphoid tissues of goats.

Neonatal mammals have increased disease susceptibility and sub-optimal vaccine responses. This raises problems in both humans and farm animals. The high prevalence of paratuberculosis in goats and the lack of an effective vaccine against it have a strong impact on the dairy sector, and calls for vaccines optimized for the neonatal immune system. We characterized the composition of the T-cell pool in neonatal kids and adult goats and quantified their turnover rates using in vivo deuterium labelling. From birth to adulthood, CD4+ T-cells were the predominant subset in the thymus and lymph nodes, while spleen and bone marrow contained mainly CD8+ lymphocytes. In blood, CD4+ T-cells were the predominant subset during the neonatal period, while CD8+ T-cells predominated in adults. We observed that thymic mass and cellularity increased during the first 5 months after birth, but decreased later in life. Deuterium labelling revealed that T-cell turnover rates in neonatal kids are considerably higher than in adult animals.

Systematic review and meta-analysis on the association of tuberculosis in Crohn's disease patients treated with tumor necrosis factor-α inhibitors (Anti-TNFα).

AIM: To perform a meta-analysis on the risk of developing Mycobacterium tuberculosis (TB) infection in Crohn's disease (CD) patients treated with tumor necrosis factor-alpha (TNFα) inhibitors. METHODS: A meta-analysis of randomized, double-blind, placebo-controlled trials of TNFα inhibitors for treatment of CD in adults was conducted. Arcsine transformation of TB incidence was performed to estimate risk difference. A novel epidemiologically-based correction (EBC) enabling inclusions of studies reporting no TB infection cases in placebo and treatment groups was developed to estimate relative odds. RESULTS: Twenty-three clinical trial studies were identified, including 5669 patients. Six TB infection cases were reported across 5 studies, all from patients receiving TNFα inhibitors. Eighteen studies reported no TB infection cases in placebo and TNFα inhibitor treatment arms. TB infection risk was significantly increased among patients receiving TNFα inhibitors, with a risk difference of 0.028 (95%CI: 0.0011-0.055). The odds ratio was 4.85 (95%CI: 1.02-22.99) with EBC and 5.85 (95%CI: 1.13-30.38) without EBC. CONCLUSION: The risk of TB infection is higher among CD patients receiving TNFα inhibitors. Understanding the immunopathogenesis of CD is crucial, since using TNFα inhibitors in these patients could favor mycobacterial infections, particularly Mycobacterium avium subspecies paratuberculosis, which ultimately could worsen their clinical condition.

CLINICAL SIGNS, ANTEMORTEM DIAGNOSTICS, AND PATHOLOGICAL FINDINGS ASSOCIATED WITH MYCOBACTERIUM AVIUM SUBSPECIES PARATUBERCULOSIS INFECTION IN MISHMI TAKIN ( BUDORCAS TAXICOLOR TAXICOLOR).

Mycobacterium avium subspecies paratuberculosis (MAP) is a cause of contagious and typically fatal enteric disease, primarily affecting ruminant and pseudoruminant species. During a MAP outbreak in a captive collection, six of nine adult Mishmi takin ( Budorcas taxicolor taxicolor) showed marked weight loss over 1-3 mo, followed by an acute deterioration. Fecal culture and microscopy failed to identify MAP shedding. Necropsy findings included grossly normal intestines and marked enlargement of mesenteric lymph nodes. Histological findings included multibacillary granulomatous enteritis, mesenteric lymphadenitis, and periportal hepatitis. MAP was confirmed by culture of intestinal and lymph node tissues from the index case. Results of antemortem serological testing using an indirect ELISA (ID SCREEN® Paratuberculosis Indirect) were corroborated by findings at necropsy or survival of the outbreak. Mishmi takin appear to show high MAP susceptibility and a rapid disease course compared with domestic ruminant species.