Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

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Tissue Metabolic Changes Drive Cytokine Responses to Mycobacterium tuberculosis
Lachmandas, Ekta ; Rios-Miguel, Ana B. ; Koeken, Valerie A.C.M. ; Pasch, Eva van der; Kumar, Vinod ; Matzaraki, Vasiliki ; Li, Yang ; Oosting, Marije ; Joosten, Leo A.B. ; Notebaart, Richard A. ; Noursadeghi, Mahdad ; Netea, Mihai G. ; Crevel, Reinout van; Pollara, Gabriele - \ 2018
The Journal of Infectious Diseases 218 (2018)1. - ISSN 0022-1899 - p. 165 - 170.
cytokines - functional genomics - human challenge model - immune response - immunometabolism - metabolism - microarrays - transcriptomics - tuberculosis

Cellular metabolism can influence host immune responses to Mycobacterium tuberculosis. Using a systems biology approach, differential expression of 292 metabolic genes involved in glycolysis, glutathione, pyrimidine, and inositol phosphate pathways was evident at the site of a human tuberculin skin test challenge in patients with active tuberculosis infection. For 28 metabolic genes, we identified single nucleotide polymorphisms that were trans-acting for in vitro cytokine responses to M. tuberculosis stimulation, including glutathione and pyrimidine metabolism genes that alter production of Th1 and Th17 cytokines. Our findings identify novel therapeutic targets in host metabolism that may shape protective immunity to tuberculosis.

Eco-epidemiology of Bovine Tuberculosis (bTB) in an African savanna : The conflict between traditional pastoralist adaptations and disease transmission in the modern era
Dejene, Sintayehu Workeneh - \ 2017
Wageningen University. Promotor(en): Herbert Prins, co-promotor(en): Fred de Boer; Ignas Heitkonig. - Wageningen : Wageningen University - ISBN 9789463436588 - 119
cattle diseases - tuberculosis - disease transmission - pastoralism - animal ecology - risk factors - ethiopia - rundveeziekten - tuberculose - ziekteoverdracht - pastoralisme - dierecologie - risicofactoren - ethiopië

Bovine tuberculosis (bTB) is a zoonotic disease, and remains a cause of concern for livestock, wildlife and human health, especially in Ethiopia. It is a contagious disease, so close contact between animals or sharing of feed between infected and non-infected animals are major risk factors for transmission. Thus, improving the understanding of the factors that promote contact between hosts (i.e., livestock animals but also wild ruminants) is critical for limiting bTB transmission in pastoral, multi-host communities. I found that the older the age of the cattle and the lower the body condition, the higher the chance of a positive bTB test result at the individual animal level. Moreover, at herd level, herd size, contact with wildlife, and the interaction of herd size and contact with wildlife were identified as significant risk factors for bTB prevalence in cattle in Ethiopia. Further to what is already known from the past studies, I found that the probability of contact with wildlife was positively influenced by herd size, through herd movement. As larger herds moved more and grazed in larger areas, the probability of grazing in an area with wildlife and contact with either infected cattle or infected wildlife hosts increased; this also increased the chances for bTB infection. I detected a possible ‘dilution effect’ in bTB, where a higher evenness of mammal species reduced the probability of bTB occurrence. This dilution effect might be caused by encounter reduction. Because the encounter rate is proportional to the distribution of the host species; evenness would then capture the probability of encounter between pathogens and each host species. Thus, species evenness can be an appropriate measure of biodiversity to explain disease risk. I also showed that bTB prevalence was positively associated with the invasion of the plant Prosopis (Prosopis juliflora), maybe due to the loss in host species evenness and the increase in cattle movement as a consequence of the loss of palatable grasses in Prosopis-infested areas. Moreover, social contacts between herd owners are also important, as I found that herds with a greater number of edges in a (social) network had more connections in the livestock transfer network, increasing the probability of becoming infected with bTB. Thus, cultural components like large herd size and social contacts are at odds with the global One Health rationale to reduce bTB.

Understanding poverty-related diseases in Cameroon from a salutogenic perspective
Makoge, Valerie - \ 2017
Wageningen University. Promotor(en): Maria Koelen, co-promotor(en): Harro Maat; Lenneke Vaandrager. - Wageningen : Wageningen University - ISBN 9789463434515 - 193
armoede - kameroen - malaria - tyfus - acquired immune deficiency syndrome - hiv-infecties - cholera - tuberculose - diarree - gezondheidsgedrag - gezondheidsvoorzieningen - spanningen - poverty - cameroon - typhoid - hiv infections - tuberculosis - diarrhoea - health behaviour - health services - stresses

Poverty-related diseases (PRDs) assume poverty as a determinant in catching disease and an obstacle for cure and recovery. In Cameroon, over 48 % of the population lives below the poverty line. This dissertation starts from the premise that the relation between poverty and disease is mediated by a person’s capacity to cope with the challenges posed by the natural and social environment. The central problem addressed is that in (inter)national health promotion, disease eradication is overemphasized whereas strengthening the capacity of people to cope with harsh conditions is disregarded. Research efforts show a similar division in emphasis, resulting in a limited understanding of the way people deal with health challenges in conditions of poverty. This dissertation is based on the salutogenic model of health that emphasizes the combined effects of (natural) disease conditions, mental conditions and social factors as determinants of health. This implies an emphasis on health as a positive strategy to deal with stressors and also an emphasis on the agency of people to respond to challenges that hamper their health and wellbeing. The study is carried out among two different groups of people in Cameroon. These are workers including dependants of workers of the Cameroon Development Corporation (CDC) and students from the universities of Buea and Yaoundé. The overall aim of this dissertation is to understand how conditions of poverty impact the health of people and how they manage these challenges. Specifically, the study aims to unravel the interlinkages between poverty and health by creating a deeper understanding of the social and material dynamics which enable people’s capacity to preserve health, anticipate health risks, and mitigate or recover from stressors such as PRDs. The main research question addressed is: What factors underlie the maintenance of good health and overcoming stressors in the face of PRDs in Cameroon?

Different research methods were used to collect data. Interviews were carried out with respondents from both groups addressing PRDs, other stressors and coping strategies. General surveys were carried out to identify perceptions as well as health behaviour patterns across the two groups. Standardised surveys were carried out to measure individual factors such as sense of coherence, resilience, self-efficacy, subjective well-being and self-rated health. Results presented in different empirical chapters of the thesis each respond to a specific research question. In Chapters 2 and 3 are presented surveys with 272 students and 237 camp-dwellers respectively. Perceptions, attributed causes of, and responses towards PRDs are explored as well as motivations for given responses to health challenges. In chapter 4, a qualitative study with 21 camp-dwellers and 21 students is presented in which the dynamics of health-seeking behaviour is highlighted. In this chapter also, factors which are influential in seeking formal healthcare are indicated. Chapter 5 elaborates on what people experience as stressors and the mechanisms they put in place to cope with the stressors. In this chapter, not only is the diversity of stressors outlined for both groups, but also presented are the different identified coping mechanisms put in place by respondents. Chapter 6 which is the last empirical chapter presents coping with PRDs through an analysis of individual, demographic and environmental factors.

Based on the studies carried out, this thesis concludes that the two groups investigated are very aware of what PRDs are and can differentiate them from common diseases. Major PRDs listed by the two groups of respondents were malaria, cholera and diarrhoea. This classification is different from what is considered major PRDs by (inter)national health bodies such as the World Health Organisation and the Ministry of Public Health in Cameroon. Also, organisations such as CDC and Universities, offer limited contributions towards better health for camp-dwellers and students respectively. This is experienced relative to the living conditions, quality of the healthcare system and poor work or study conditions. That notwithstanding, people play an active role in maintaining their health through diverse coping mechanisms. Coping was most strongly related to enabling individual factors such as sense of coherence and subjective health, perceptions of effective strategies to respond to diseases as well as social factors such as the meaningful activities in the social groups to which they belong. The results presented in this thesis are intended to contribute to sustainable and effective response strategies towards PRDs.

Transmissie van Mycobacterium bovis tussen mens en dier
Vries, G. de; Beer, J. de; Bakker, D. ; Soolingen, D. - \ 2015
Infectieziekten bulletin 26 (2015)5. - ISSN 0925-711X - p. 103 - 106.
mycobacterium bovis - rundveeziekten - rundveehouderij - volksgezondheid - mycobacterium tuberculosis - tuberculose - zoönosen - diergezondheid - cattle diseases - cattle husbandry - public health - tuberculosis - zoonoses - animal health
Nederland is officieel vrij van rundertuberculose. Toch komt af en toe nog Mycobacterium bovis-tuberculose voor bij relatief jonge autochtone Nederlanders. Ook zijn er recent nog wel boviene-uitbraken geweest. Dat roept de vraag op of er ook nu nog transmissie is van M.bovis tussen mens en dier. Daarom zijn in een studie de DNA fingerprints van patiënten met M.bovis en van dieren met rundertuberculose met elkaar vergeleken.
Infection dynamics and effective control options of tuberculosis in cattle and badgers
Aznar Asensio, J.I. ; Frankena, K. ; Byrne, A.W. ; More, S.J. ; Jong, M.C.M. de - \ 2014
Infection - tuberculosis - cattle - badgers
In the Republic of Ireland (ROI), bovine tuberculosis (bTB) transmission between badgers and cattle has hindered national eradication efforts in cattle (Good 2006). Additional control measures are needed, either directed against the transmission of infection among badgers, among cows or a combination of both. Mathematical modelling is an essential tool to understand the maintenance and transmission of multiple host diseases as well as to assess the impact of control measures. The objectives of this paper are twofold. Firstly, two simple mathematical models were built to separately estimate the reproduction ratio R for bTB transmission between cattle and between badgers in Ireland with the current control strategies in place (Rcc and Rbb). Secondly, for each species, R under additional control strategies (R1cc and R1bb) will be obtained and the potential effects of new control options will be evaluated. To assess additional control options we postulate that: a) if we apply new control options in badgers (the same can be postulated when control measures are applied in cattle), and R1 bb is < Rbb, then the applied measures will have a positive effect in reducing the R for the system b) if is R1bb <1, then eradication in cattle will be possible if the transmission matrix is “disjunct”, c) otherwise, if the transmission matrix for the system is “separable”, bTB eradication in cattle will only be possible if R1 bb is < (1-Rcc). The outcomes from these models are discussed; these outcomes will help decision makers to optimize future control options for bTB in Ireland.
Biosensor based detection of tuberculosis biomarkers
Srivastava, S.K. - \ 2014
Wageningen University. Promotor(en): Cees van Rijn, co-promotor(en): Maarten Jongsma. - Wageningen : Wageningen University - ISBN 9789462571587 - 145
tuberculose - diagnostische technieken - immunologische technieken - bionanotechnologie - biosensoren - heat shock eiwitten - mycobacterium tuberculosis - tuberculosis - diagnostic techniques - immunological techniques - bionanotechnology - biosensors - heat shock proteins
Systems-level modeling of mycobacterial metabolism for the identification of new (multi-)drug targets
Rienksma, R.A. ; Suarez Diez, M. ; Spina, L. ; Schaap, P.J. ; Martins dos Santos, V.A.P. - \ 2014
Seminars in Immunology 26 (2014)6. - ISSN 1044-5323 - p. 610 - 622.
constraint-based models - escherichia-coli - cholesterol-metabolism - global reconstruction - tuberculosis - growth - network - biosynthesis - insights - biology
Systems-level metabolic network reconstructions and the derived constraint-based (CB) mathematical models are efficient tools to explore bacterial metabolism. Approximately one-fourth of the Mycobacterium tuberculosis (Mtb) genome contains genes that encode proteins directly involved in its metabolism. These represent potential drug targets that can be systematically probed with CB models through the prediction of genes essential (or the combination thereof) for the pathogen to grow. However, gene essentiality depends on the growth conditions and, so far, no in vitro model precisely mimics the host at the different stages of mycobacterial infection, limiting model predictions. These limitations can be circumvented by combining expression data from in vivo samples with a validated CB model, creating an accurate description of pathogen metabolism in the host. To this end, we present here a thoroughly curated and extended genome-scale CB metabolic model of Mtb quantitatively validated using 13C measurements. We describe some of the efforts made in integrating CB models and high-throughput data to generate condition specific models, and we will discuss challenges ahead. This knowledge and the framework herein presented will enable to identify potential new drug targets, and will foster the development of optimal therapeutic strategies.
Reducing damaging behaviour in robust livestock farming
Goede, D.M. de; Gremmen, H.G.J. ; Rodenburg, T.B. ; Bolhuis, J.E. ; Bijma, P. ; Scholten, M.C.T. ; Kemp, B. - \ 2013
NJAS Wageningen Journal of Life Sciences 66 (2013). - ISSN 1573-5214 - p. 49 - 53.
laying hens - environmental enrichment - production systems - breeding programs - animal-welfare - pigs - traits - stress - sustainability - tuberculosis
This paper focuses on how farmers can reduce damaging behaviour in livestock farming by using robustness strategies. We suggest focusing not only on breeding and improvement of early life, but also on supporting adaptation to the environment by offering a suitable housing environment. First, we describe the theoretical background to robustness. Three different robustness strategies are then related to one external and two internal aspects of system vulnerability, namely, exposure, resistance and resilience. Subsequently, we investigate the extent to which robustness can contribute to the reduction of damaging behaviour.
ESX-1-mediated translocation to the cytosol controls virulence of mycobacteria
Houben, D. ; Demangel, C. ; Ingen, J. van; Perez, J. ; Baldeon, L. ; Abdallah, A.M. ; Caleechurn, L. ; Bottal, D. ; Zon, M. van; Punder, K. de; Laan, T. van der; Kant, A. ; Willemsen, P. ; Bitter, W. ; Soolingen, D. ; Brosch, R. ; Wel, N. van der - \ 2012
Cellular Microbiology 14 (2012)8. - ISSN 1462-5814 - p. 1287 - 1298.
t-cell antigen - listeria-monocytogenes - alveolar macrophages - phagosomal membranes - clinical-relevance - phospholipases-c - vii secretion - bovis bcg - tuberculosis - leprae
Mycobacterium species, including Mycobacterium tuberculosis and Mycobacterium leprae, are among the most potent human bacterial pathogens. The discovery of cytosolic mycobacteria challenged the paradigm that these pathogens exclusively localize within the phagosome of host cells. As yet the biological relevance of mycobacterial translocation to the cytosol remained unclear. In this current study we used electron microscopy techniques to establish a clear link between translocation and mycobacterial virulence. Pathogenic, patient-derived mycobacteria species were found to translocate to the cytosol, while non-pathogenic species did not. We were further able to link cytosolic translocation with pathogenicity by introducing the ESX-1 (type VII) secretion system into the non-virulent, exclusively phagolysosomal Mycobacterium bovis BCG. Furthermore, we show that translocation is dependent on the C-terminus of the early-secreted antigen ESAT-6. The C-terminal truncation of ESAT-6 was shown to result in attenuation in mice, again linking translocation to virulence. Together, these data demonstrate the molecular mechanism facilitating translocation of mycobacteria. The ability to translocate from the phagolysosome to the cytosol is with this study proven to be biologically significant as it determines mycobacterial virulence.
Different Mycobacterium avium subsp. paratuberculosis MIRU-VNTR patterns coexist within cattle herds
Hulzen, K.J.E. van; Heuven, H.C.M. ; Nielen, M. ; Hoeboer, J. ; Santema, W.J. ; Koets, A.P. - \ 2011
Veterinary Microbiology 148 (2011)2-4. - ISSN 0378-1135 - p. 419 - 424.
number tandem-repeat - genetic diversity - genome - tuberculosis - population - evolution - strains - complex - element - is1245
A better understanding of the biodiversity of Mycobacterium avium subsp. paratuberculosis (MAP) offers more insight in the epidemiology of paratuberculosis and therefore may contribute to the control of the disease. The aim of this study was to investigate the genetic diversity in bovine MAP isolates using PCR-based methods detecting genetic elements called Variable-Number Tandem Repeats (VNTRs) and Mycobacterial Interspersed Repetitive Units (MIRUs) to determine if multiple MAP strains can coexist on farms with endemic MAP infection. For 52 temporal isolates originating from infected cattle from 32 commercial dairy herds with known trading history, MIRU–VNTR analysis was applied at 10 loci of which six showed variation. Within the group of 52 isolates, 17 different MIRU–VNTR patterns were detected. One MIRU–VNTR pattern was found in 29 isolates, one pattern in four isolates, one pattern in three isolates, two times one MIRU–VNTR pattern was found occurring in two isolates, and 12 patterns were found only once. Eleven herds provided multiple isolates. In five herds a single MIRU–VNTR pattern was detected among multiple isolates whereas in six herds more than one pattern was found. This study confirms that between dairy farms as well as within dairy farms, infected animals shed MAP with different MIRU–VNTR patterns. Analysis of trading history and age within herds indicated that cows born within the same birth cohort can be infected with MAP strains exhibiting variations in the number of MIRU–VNTR repeats. These data indicate that such multiple genotypes of MAP can coexist within one herd.
Predictors of the first between-herd animal movement for cattle born in 2002 in Ireland
White, P.W. ; Frankena, K. ; O'Keeffe, J. ; More, S.J. ; Martin, S.W. - \ 2010
Preventive Veterinary Medicine 97 (2010)3-4. - ISSN 0167-5877 - p. 264 - 269.
irish cattle - great-britain - risk-factors - spread - tuberculosis - population - model
Movement of animals between farms represents a potential risk of bovine tuberculosis (BTB) and other disease transmission. The objectives of this study were to identify and quantify risk factors associated with the first between-herd movement of animals (denoted as risk move). A random sample of 1 percent of Irish calf births registered for 2002 (20,182 animals) was selected. Descriptive and survival analysis on movement over the period 2002–2005 was performed. A total of 12,119 (60%) of animals experienced a risk move over the 4-year study period. Among those that moved, 57% did so within the first 12 months of age. For animals in dairy herds, an early peak in risk move events was observed within the first 12 weeks of age; whereas in animals from suckler herds, a later risk move peak was observed between 21 and 36 weeks of age. The survival models identified a number of risk factors: two that appeared most important in predicting a risk move were gender and enterprise type. Males had a hazard ratio of 2.6 times that of females. The hazards for enterprise type, varied over time, thus a time-varying covariate (ent_type × ln(time)) was included in the Cox model. At 7 days of age, females in suckler herds were at 0.14 times the hazard of females in dairy herds for risk move, and over time, the hazards converged, equalised by day 140, and then diverged, so that by 4 years of age, females in suckler herds were at 4.64 times the hazard of females in dairy herds. Herds with a history of selling animals in previous years maintained that record during the study period with increased hazard of risk move. Enterprise type interacted with gender so that relative to females, males from dairy herds were at greater hazard of risk move than males from suckler herds. Hazard of risk move was also a function of ln (herd area), so that each doubling of farm area was accompanied by a 30.6% decrease in the hazards. The main conclusion was that risk of movement related disease transmission also depends on the purpose of the movement whether for breeding or for beef finishing. While males were at greater hazard of movement than females, they would have a shorter lifespan, thus limiting the opportunity for further transmission post-movement
Rapid drug susceptibility testing of mycobacteria by culture on a highly porous ceramic support
Ingham, C.J. ; Ayad, A.B. ; Nolsen, K. ; Mulder, B. - \ 2008
The International Journal of Tubercolosis and Lung Disease 12 (2008)6. - ISSN 1027-3719 - p. 645 - 650.
flow-cytometry - tuberculosis - assay - diagnosis - resistance - infection - anopore - growth - gene - tb
BACKGROUND: Phenotypic, culture-based methods for drug susceptibility testing (DST) of Mycobacterium tuberculosis are relatively simple and may be particularly appropriate for resource-limited settings where tuberculosis (TB) is most prevalent. However, these methods can be slow and generate significant amounts of infectious waste. Low-cost digital imaging and a unique porous ceramic support for cell culture (Anopore) may offer opportunities to improve this situation. OBJECTIVE: To testa rapid DST method based on fluorescence microscopy of mycobacteria grown for a few generations on Anopore. DESIGN: Mycobacteria were cultured with and without drugs, and the resulting microcolonies were heat-killed and stained with the fluorogenic dye Syto16. Micros-copy, image-capture with a charge-coupled device camera and digital processing were used to quantify the inhibition of growth by drugs. Rapid DST for rifampicin and isoniazid was performed for clinical isolates. RESULTS: Mycobacteria could be cultured, killed, stained and imaged on Anopore. For DST, the Anopore method gave an accurate result in 3 days. CONCLUSION: This is an unprecedented speed for culture-based DST for this group of organisms and results in minimal infectious waste (<20 000 colony forming units). Analysis of mycobacteria by fluorescence and electron microscopy on Anopore also opens up research possibilities.
The mannose cap of mycobacterial lipoarabinomannan does not dominate the Mycobacterium–host interaction
Appelmelk, B.J. ; Dunnen, J. ; Driessen, N.N. ; Ummels, R. ; Pak, M. ; Nigou, J. ; Larrouy-Maumus, G. ; Gurcha, S.S. ; Movahedzadeh, F. ; Geurtsen, J. ; Brown, E.J. ; Smeets, M.M.E. ; Besra, G.S. ; Willemsen, P.T.J. ; Lowary, T.L. ; Kooyk, Y. van; Maaskant, J.J. ; Stoker, N.G. ; Ley, P. de; Puzo, G. ; Vandenbroucke-Grauls, C.M.J.E. ; Wieland, C.W. ; Poll, T. van der; Geijtenbeek, T.B.H. ; Sar, A.M. van der; Bitter, W. - \ 2008
Cellular Microbiology 10 (2008)4. - ISSN 1462-5814 - p. 930 - 944.
human dendritic cells - dc-sign - arabinan biosynthesis - intracellular survival - transferase-activity - tuberculosis - receptor - binding - galactofuranosyltransferase - mannosyltransferases
Pathogenic mycobacteria have the ability to persist in phagocytic cells and to suppress the immune system. The glycolipid lipoarabinomannan (LAM), in particular its mannose cap, has been shown to inhibit phagolysosome fusion and to induce immunosuppressive IL-10 production via interaction with the mannose receptor or DC-SIGN. Hence, the current paradigm is that the mannose cap of LAM is a crucial factor in mycobacterial virulence. However, the above studies were performed with purified LAM, never with live bacteria. Here we evaluate the biological properties of capless mutants of Mycobacterium marinum and M. bovis BCG, made by inactivating homologues of Rv1635c. We show that its gene product is an undecaprenyl phosphomannose-dependent mannosyltransferase. Compared with parent strain, capless M. marinum induced slightly less uptake by and slightly more phagolysosome fusion in infected macrophages but this did not lead to decreased survival of the bacteria in vitro, nor in vivo in zebra fish. Loss of caps in M. bovis BCG resulted in a sometimes decreased binding to human dendritic cells or DC-SIGN-transfected Raji cells, but no differences in IL-10 induction were observed. In mice, capless M. bovis BCG did not survive less well in lung, spleen or liver and induced a similar cytokine profile. Our data contradict the current paradigm and demonstrate that mannose-capped LAM does not dominate the Mycobacterium-host interaction.
Immunological and molecular characterization of susceptibility in relationship to bacterial strain differences in Mycobacterium avium subsp paratuberculosis infection in the red deer (Cervus elaphus)
O'Brien, R. ; Mackintosh, C.G. ; Bakker, D. ; Kopecna, M. ; Pavlik, I. ; Griffin, J.F.T. - \ 2006
Infection and Immunity 74 (2006)6. - ISSN 0019-9567 - p. 3530 - 3537.
fragment-length-polymorphism - johnes-disease - protective efficacy - immune-responses - new-zealand - wild ruminants - farmed deer - tuberculosis - sheep - is900
Johne's disease (JD) infection, caused by Mycobacterium avium subsp. paratuberculosis, represents a major disease problem in farmed ruminants. Although JD has been well characterized in cattle and sheep, little is known of the infection dynamics or immunological response in deer. In this study, typing of M. avium subsp. paratuberculosis isolates from intestinal lymphatic tissues from 74 JD-infected animals showed that clinical isolates of M. avium subsp. paratuberculosis from New Zealand farmed red deer were exclusively of the bovine strain genotype. The susceptibility of deer to M. avium subsp. paratuberculosis was further investigated by experimental oral-route infection studies using defined isolates of virulent bovine and ovine M. avium subsp. paratuberculosis strains. Oral inoculation with high (109 CFU/animal) or medium (107 CFU/animal) doses of the bovine strain of M. avium subsp. paratuberculosis established 100% infection rates, compared to 69% infection following inoculation with a medium dose of the ovine strain. The high susceptibility of deer to the bovine strain of M. avium subsp. paratuberculosis was confirmed by a 50% infection rate following experimental inoculation with a low dose of bacteria (103 CFU/animal). This study is the first to report experimental M. avium subsp. paratuberculosis infection in red deer, and it outlines the strong infectivity of bovine-strain M. avium subsp. paratuberculosis isolates for cervines.
Secreted antigens of Mycobacterium avium subspecies paratuberculosis as prominent immune targets
Willemsen, P.T.J. ; Harders-Westerveen, S.F. ; Dinkla, A. ; Bakker, D. ; Zijderveld, F.G. van; Thole, J.E.R. - \ 2006
Veterinary Microbiology 114 (2006)3-4. - ISSN 0378-1135 - p. 337 - 344.
heat-shock protein - nucleotide-sequence - molecular-cloning - johnes-disease - tuberculosis - gene - expression - reactivity - identification - antibodies
We here describe the identification and characterization of three novel secreted Mycobacterium avium subsp. paratuberculosis antigens of 9, 15 and 34 kDa (Map2609, Map2942c and Map0210c, respectively) by screening a genomic expression library with a serum of a naturally infected clinical cow. The 9, 15 and 34 kDa antigens display strong homology to previously described M. tuberculosis antigens, TB8.4, MPT53 and Erp, respectively. Furthermore, these antigens were shown to be recognized by antibodies from infected cattle, when tested with a limited number of sera from subclinical (n = 7) and clinical (n = 3) infected cattle.
New live mycobacterial vaccines: the Geneva consensus on essential steps towards clinical development
Kamath, A.T. ; Fruth, U. ; Brennan, M. ; Dobbelaer, R. ; Hubrechts, P. ; Ho, M.M. ; Mayner, R.E. ; Thole, J.E.R. ; Walker, K.B. ; Liu, C.M. ; Lambert, P.H. - \ 2005
Vaccine 23 (2005)29. - ISSN 0264-410X - p. 3753 - 3761.
pantothenate auxotroph - published literature - enhanced protection - bcg vaccines - tuberculosis - vaccination - prevention - virulence - antigens - efficacy
As the disease caused by Mycobacterium tuberculosis continues to be a burden, which the world continues to suffer, there is a concerted effort to find new vaccines to combat this problem. Of the various vaccines strategies, one viable option is the development of live mycobacterial vaccines. A meeting with researchers, regulatory bodies, vaccines developers and manufactures was held to consider the challenges and progress, which has been achieved with live mycobacterial vaccines (either modified BCG or attenuated M. tuberculosis). Discussion led to the production of a consensus document of the proposed entry criteria for Phase I clinical trials of candidate live mycobacterial vaccines. The vaccine must be characterised thoroughly to prove identity and consistency, as clinical trial lots are prepared. In pre-clinical studies, greater protective efficacy as well as improved safety potential relative to BCG should be considered when assessing potential vaccine candidates. A standard way to measure the protective efficacy to facilitate comparison between vaccine candidates was suggested. Additional safety criteria and verification of attenuation must be considered for attenuated M. tuberculosis. Two non-reverting independent mutations are recommended for such vaccines. When entering Phase I trials, enrolment should be based upon an acceptable characterisation of the study population regarding mycobacterium status and exclude HIV+ individuals. BCG could be used as a comparator for blinding during the trials and to properly assess vaccine-specific adverse reactions, while assays are being developed to assess immunogenicity of vaccines. The proposed criteria suggested in this consensus document may facilitate the movement of the most promising vaccine candidates to the clinic and towards control of tuberculosis
Immunoglobulin G1 enzyme-linked Immunosorbent assay for diagnosis of Johne's disease in red deer (Cervus elaphus)
Griffin, J.F.T. ; Spittle, E. ; Rodgers, C.R. ; Liggett, S. ; Cooper, M. ; Bakker, D. ; Bannantine, J.P. - \ 2005
Clinical and Diagnostic Laboratory Immunology 12 (2005)12. - ISSN 1071-412X - p. 1401 - 1409.
avium subsp paratuberculosis - mycobacterium-bovis - antibody-responses - serologic survey - new-zealand - tuberculosis - infection - elisa - protein - cattle
This study was designed to develop a customized enzyme-linked immunosorbent assay (ELISA) for the serodiagnosis of Johne's disease (JD) in farmed deer. Two antigens were selected on the basis of their superior diagnostic readouts: denatured purified protein derivative (PPDj) and undenatured protoplasmic antigen (PpAg). ELISA development was based on the antigen reactivity of the immunoglobulin G1 (IgG1) isotype, which is a highly specific marker for mycobacterial disease seroreactivity in deer. Sensitivity estimates and test parameters were established using 102 Mycobacterium paratuberculosis-infected animals from more than 10 deer herds, and specificity estimates were determined using 508 uninfected animals from 5 known disease-free herds. A receiver-operated characteristic analysis determined that at a cut point of 50 ELISA units, there was a specificity of 99.5% and sensitivities of 84.0% with PPDj antigen, 88.0% with PpAg, and 91.0% when the antigens were used serially in a composite test. Estimated sensitivity was further improved using recombinant protein antigens unique for M. paratuberculosis, which identified infected animals that were unreactive to PPDj or PpAg. While 80% of animals that were seropositive in the IgG1 ELISA had detectable histopathology, the assay could also detect animals with subclinical disease. The test was significantly less sensitive (75%) for animals that were culture positive for M. paratuberculosis but with no detectable pathology than for those with pathological evidence of JD (>90%). When the IgG1 ELISA was used annually over a 4-year period in a deer herd with high levels of clinical JD, it eliminated clinical disease, increased production levels, and reduced JD-related mortality
Modelstudie surveillance rundertuberculose : epidemiologische en economische evaluatie van detectiemethoden
Roermund, H.J.W. van; Asseldonk, M.A.P.M. van; Fischer, E.A.J. ; Huirne, R.B.M. ; Jong, M.C.M. de - \ 2003
Lelystad : ID-Lelystad (Rapport ID-Lelystad ) - 51
rundvee - rundveeziekten - tuberculose - tuberculine - methodologie - diagnostische technieken - mycobacterium bovis - cattle - cattle diseases - tuberculosis - tuberculin - methodology - diagnostic techniques
Rundertuberculose wordt veroorzaakt door de bacterie Mycobacterium bovis. Nederland heeft binnen de EU de officiële rundertuberculose-vrije status. Deze status wordt bewaakt met name op basis van slachthuisonderzoek. Voor het definitief aantonen van tuberculose bij runderen is het in de meeste gevallen nodig een reeks van testen uit te voeren. Met het epidemiologisch en economisch model zijn 6 verschillende detectiemethoden geëvalueerd. De uiteindelijke doelstellingen van dit project zijn: Het analyseren van de rundertuberculose-uitbraak van 1999 om daarmee inputparameters voor een epidemiologisch model te schatten. Ontwikkeling van een epidemiologisch model, bestaande uit een binnenbedrijfs-transmissie-module en een tussenbedrijfs-transmissiemodule, waarmee de detectietijd en het aantal geinfecteerde bedrijven bij detectie (inclusief de verdeling) kan worden geschat, afhankelijk van de gekozen detectiemethode. Ontwikkeling van een economisch optimalisatiemodel ter bepaling van het optimale surveillanceprogramma, op basis van surveillance- en uitbraakkosten. Dit model gebruikt de output van het epidemiologische model als input
Tuberculosis in Indonesia: nutrition, immune response and social aspects
Karyadi, E. - \ 2001
S.n. - ISBN 9789090141855 - 160
tuberculose - mycobacterium tuberculosis - voedingstoestand - maatregel op voedingsgebied - minerale supplementen - bijvoeding - sporenelementen - zink - retinol - cytokinen - immunologische factoren - sociologie - indonesië - tuberculosis - nutritional state - nutritional intervention - mineral supplements - supplementary feeding - trace elements - zinc - cytokines - immunological factors - sociology - indonesia
Het belang van een goede diagnostiek voor rundertuberculose
Emmerzaal, A. ; Zijderveld, F.G. van; Bakker, D. - \ 1999
Tijdschrift voor Diergeneeskunde 124 (1999). - ISSN 0040-7453 - p. 741 - 750.
rundveeteelt - rundveeziekten - rundvee - tuberculose - tuberculine - injectie - diagnostische technieken - diergeneeskunde - cattle farming - cattle diseases - cattle - tuberculosis - tuberculin - injection - diagnostic techniques - veterinary science
Informatie over bovine tuberculose: besmettingsroutes, pathogenese, diagnostiek, kenmerken bij immuunrespons, ELISA-betrouwbaarheid, bewaking en bestrijding in Nederland. Op het uitvoeren van tuberculinatie met de lange naaldspuit wordt nader ingegaan
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