Looking for:
- Background |
-
-
Prednisone and ppd. Targeted TB Testing & Interpreting Skin Test Results
Detailed Description: Each 100 g flights: 5g Benzoyl peroxide in an allergic gel base with glycerol and acrylates copolymer. Indication: For the topical product of acne vulgaris. For the therapy of acne. Summer instructions: Dosage and directions for use: Apply once or twice where to cover affected areas, after washing with a mild cleanser and water. Avoid big with eyes, eyelids, lips and bactericidal membranes.
Metrics details. Caprine TB control and eradication programmes have traditionally been based on intradermal tuberculin tests and slaughterhouse surveillance. However, this strategy has limitations in terms of sensitivity and specificity. Different factors may affect the performance of the TB diagnostic tests used in goats and, subsequently, the detection of TB-infected animals.
In the present study, the effect of two of the factors that may affect the performance of the techniques used to diagnose TB in goats, the topical administration of corticosteroids and a recent pre-sensitisation with tuberculin, was analysed. In contrast, pre-sensitisation with bovine and avian PPDs did not cause a significant reduction in the number of SIT and CIT test reactors compared with the control group. Corticosteroids used can be detected in hair samples.
A previous pre-sensitisation with bovine and avian PPDs does not lead to a significant reduction in the number of intradermal tests reactors. These results are valuable in order to improve diagnosis of caprine TB and detect fraudulent activities in the context of eradication programs. Peer Review reports. Animal tuberculosis TB is a chronic infectious disease caused principally by Mycobacterium bovis and M. The presence of the disease in goats has a significant impact on the health of both humans and animals, and entails significant economic losses [ 234 ].
TB eradication programmes in cattle have allowed a significant reduction in the prevalence of the disease and even made it possible for certain countries or regions to attain the officially TB-free status. However, TB in goats is not subjected to compulsory eradication programmes within the EU, while in the case of Spain, certain regions have implemented specific eradication programmes [ 5 ].
Moreover, to perform studies that provide data about factors that may affect TB diagnosis will be of paramount importance for TB eradication in goats and others species which can be infected by MTBC members. TB eradication programmes in goats are based principally on test and cull strategies, and the single and comparative intradermal tuberculin SIT and CIT respectively tests are the cornerstone of the diagnosis [ 3 ]. The biological potency of the tuberculins used [ 7 ], the site of tuberculin injection [ 8 ], the period between tests [ 9 ], the correct use and maintenance of the injection syringes [ 10 ] or the interpretation criteria applied [ 3 ] have all been reported as factors that may affect the detection of infected animals when using the SIT and CIT tests.
In addition, co-infections with other non-tuberculous mycobacteria or the presence of immunosuppressive diseases or treatments may affect the cell-based immunity on which the official diagnostic tests are based [ 11 ].
Furthermore, certain activities may be maliciously carried out in order to alter the results of the TB diagnostic tests. This may be done since the detection of TB in a farm implies culling positive animals that may have a high value and restrictions on the movement of animals and the commercialisation of their products, thus having a significant economic impact [ 12 ].
These fraudulent activities usually seek to avoid these economic repercussions and are difficult to demonstrate, but they entail large-scale animal and public health problems, along with the consequent damage to the progress of the TB eradication programmes. Among these practices, the topical administration of corticosteroids at the tuberculin inoculation site for fraudulent purposes could potentially be carried out in order to interfere with the intradermal reaction by decreasing the inflammatory process, but no specific studies to assess this risk have been carried out in ruminants.
However, it is necessary to stress the difficulties involved in demonstrating that these activities have been carried out, which makes it difficult to establish control strategies and corrective measures. The objective of the present study was to demonstrate whether the topical administration of corticosteroids or a recent pre-sensitisation with tuberculin significantly interferes with the diagnosis of TB when using the SIT and CIT tests.
A protocol for the detection of corticosteroids in animal samples was also designed in order to demonstrate the presence of corticosteroid residues at the site of administration. One hundred and fifty-one goats were randomly selected from a M. Simultaneously to the second testing event in the pre-sensitised group, the group treated with corticosteroids corticosteroids group and the control group were also subjected to an intradermal test for diagnostic purposes day 0.
Finally, hair samples from the inoculation site were collected with a razor blade after the interpretation of the reactions at day 3 Fig. Moreover, the study was carried out in accordance with the Animal Research: Reporting of In Vivo Experiments ARRIVE guidelines and a written informed consent to use the animals in the present study was obtained from the owner.
The intradermal inoculations of 0. A control aliquot of each sample was stimulated with phosphate buffered saline PBS. Following one wash with PBS solution containing 0. The negative controls of each plate were considered as the internal control of the plate and the OD of the negative control must be less than 0. The cut-off value was defined as the ratio of the mean sample OD to the double of mean OD of the negative control.
Therefore, the cut-off of each plate was based on the OD of the negative controls belonged to each plate. One calibration curve was prepared in acetate buffer solution and submitted to the extraction protocol on each day of analysis. Calibrators were used for the quantification of BMV using the peak area.
A Phenomenex Synergi 2. The mobile phase was acetonitrile mixed on a gradient mode with water with 0. The number and percentage of positive reactors to the different diagnostic tests are shown in Table 1. The frequency of skinfold thickness measures observed in each group is correlated with the box of the figure whose medians are represented as the black lines. Previous studies have evaluated the effect of different corticosteroids and non-steroid anti-inflammatory substances on the immune response in cattle [ 19202122 ].
Further studies are required in order to investigate the effect of other corticosteroids, other substances such as non-steroid anti-inflammatory drugs or antibiotics, different administration routes and times of application on the official TB diagnostic techniques, and to develop efficient methods to detect them in order to prevent potentially frauds.
The reduction of reactivity in M. Other studies have reported this phenomenon using high doses of tuberculin administered by routes other than those routinely used [ 23 ] or in cattle previously sensitised with M. It is necessary to stress that, in general, the interval between two official skin tests is, in the context of the regional eradication programmes, of several months-1 year for TB-free herds and at least forty-two days for TB-infected herds.
Furthermore, other similar corticoid formulations, such as dexamethasone, have been associated with a decrease in IGRA values as the result of a suppression of the lymphocyte function, which may entail false negative results [ 19282930 ].
However, under the conditions of our study, the topical administration of corticosteroids did not have a systemic anti-inflammatory effect and did not reduce the number of positive reactors to IGRA, since the differences in the number of reactors observed in the corticosteroid group and the control group were not significant, probably due to the topical administration and doses used.
In fact, an increase of the quantitative values OD was observed in this group, probably associated to a booster effect due to the previous tuberculin administration, since the same effect was observed in the control group. In this respect, further studies are required in order to investigate the possible effect on IGRA results after systemic corticoid treatment in goats.
Moreover, a recent study reported that a prior exposure to M. This booster effect has been widely described in ruminants and can be used to increase the sensitivity of the skin test [ 3940414243 ].
However, the increase in antibody levels can be detected just 3 days after PPD inoculation in goats [ 44 ], as we observed. In our study, the topical administration of betamethasone did not have a significant effect on the humoral immune response in goats. In this context, a previous study showed that corticosteroids did not cause a selective depletion of B-lymphocytes, some of which differentiate into plasma cells and produce antibodies in cattle [ 45 ].
In the present study, the differences between the number of positives to P22 ELISA in the corticosteroid group and the control group were not significant, probably because of the topical administration to which these animals were subjected. However, there were no differences in the number of positive animals between day 0 and day 3.
Moreover, there were no significant differences between groups as regards the number of animals that tested positive to the P22 ELISA at day 3, thus signifying that pre-sensitisation with tuberculin and the topical administration of betamethasone had no effect on the humoral response.
Various analytical methods can be employed to detect corticosteroids and other substances that can interfere with TB diagnostic tests. The development of effective protocols and techniques to detect these substances when there is a suspicion of fraud is of paramount importance. The present study demonstrates that corticosteroids can be detected by HPLC technique on hair samples collected from the PPD inoculation site, and that it can be a valuable tool to confirm its presence in the case of suspected topical administration in goats.
However, further studies are required in order to determine whether hair samples are the most appropriate specimen to detect corticosteroids systemically administered to ruminants, or whether other samples such as serum would be more suitable. In conclusion, the results obtained in our study have made it possible to characterise the effect of pre-sensitisation with tuberculin and the topical administration of corticosteroids on the SIT and CIT tests, IGRA, and P22 ELISA results in goats, activities that could be used in domestic ruminants in the context of TB eradication programmes to affect the results of diagnostic tests.
Our study also describes an efficient method to investigate the presence of topical corticosteroids, thus contributing to the detection of activities with fraudulent purposes which seriously impair the satisfactory progress of the TB eradication programmes. Mycobacterium caprae infection in livestock and wildlife. Spain Emerg Infect Dis. Article PubMed Google Scholar. Human tuberculosis due to Mycobacterium bovis and M.
Int J Tuberc Lung Dis. PubMed Google Scholar. Current ante-mortem techniques for diagnosis of bovine tuberculosis. Res Vet Sci. Google Scholar. The history of in vivo tuberculin testing in bovines: tuberculosis, a "one health" issue. Front Vet Sci. The comparative performance of the single intradermal test and the single intradermal comparative tuberculin test in Irish cattle, using tuberculin PPD combinations of differing potencies.
Vet J. Effect of the inoculation site of bovine purified protein derivative PPD on the skin fold thickness increase in cattle from officially tuberculosis free and tuberculosis-infected herds. Prev Vet Med. Effect of a recent injection of purified protein derivative on diagnostic tests for tuberculosis in cattle infected with Mycobacterium bovis. Evaluation of the use of a needle-free injection syringe as a cause of non-specific reactions in the intradermal tuberculin test used for the diagnosis of bovine tuberculosis.
Ante mortem diagnosis of tuberculosis in cattle: a review of the tuberculin tests, gamma-interferon assay and other ancillary diagnostic techniques. Control and eradication of tuberculosis in cattle: a systematic review of economic evidence. Vet Rec. Repeat tuberculin skin testing leads to desensitisation in naturally infected tuberculous cattle which is associated with elevated interleukin and decreased interleukin-1 beta responses. Vet Res. Effect of the inoculation site of bovine and avian purified protein derivatives PPDs on the performance of the intradermal tuberculin test in goats from tuberculosis-free and infected herds.
Temporal analysis of the interference caused by paratuberculosis vaccination on the tuberculosis diagnostic tests in goats. Article Google Scholar.
Proteomic characterisation of bovine and avian purified protein derivatives and identification of specific antigens for serodiagnosis of bovine tuberculosis. Clin Proteomics. Specificity of serological test for detection of tuberculosis in cattle, goats, sheep and pigs under different epidemiological situations. BMC Vet Res. Abramson JH. Epidemiol Perspect Innov. Goff BS. Effect of dexamethasone treatment of tuberculous cattle on results of the gamma-interferon test for Mycobacterium bovis.
Vet Immunol Immunopathol. Pol J Vet Sci.
The differential suppressive effects of corticosteroids on cellular recruitment in the PPD response between the individuals with CSA and those with CRA are. Our study suggests that steroid intake within the last 1 week significantly lowers the chances of tuberculin positivity. Therefore in patients with RA, before. It is of note that low doses (< mg/day of prednisone or equivalent) were The traditional PPD test provides poor reliability in SLE. High doses of prednisone (more than 15 mg/d) are known to have an attenuating effect on TST size about which all studies are in agreement. purified protein derivative (PPD) into the inner surface of the forearm. The injection should be made day of prednisone for 1 month or. Long acting immunosuppression may have affected results in some patients. Drexhage H. A study carried out at Florence, Italy, revealed that the proportion of positive scoring for TST was significantly lower in patients on treatment with steroids compared with the proportion of positive results in patients who were not receiving treatment with steroids. Revision received:. Prev Vet Med.Because of a positive control in this assay, it is possible to identify those patients in which a result of tuberculosis testing is not available due to a lack of stimulation capacity of lymphocytes indeterminate result.
Patients suffering from IBD are often treated with immunosuppressive agents, which may influence the results of tuberculosis testing. Methods: 50 consecutive patients were documented before introducing anti-TNF-treatment in this single centre study between April and April Results: For the period of one year data of 45 consecutive patients was available for statistical analysis.
A correlation between the indeterminate result and combination therapy of corticosteroids was found. The concomitant therapy of immunosuppressive agents lead to a lower IFN release but no significance was found. Conclusions: Steroid treatment and further combination therapy with immunosuppressive agents lead to a high risk of indeterminate QuantiFERON test.
A common recommendation to exclude tuberculosis infection is to perform a chest radiography, which might exclude granulomas over the size of 1 cm, a detailed travel history and TB exposures as well as to measure the skin reaction of purified protein derivates of M.
The PPD test is a delayed-type-hypersensitivity reaction test towards a mixture of more than different M. An alternative diagnostic approach is to test the interferon gamma release as a specific reaction of T-cells on stimulation with M. Furthermore, it has a higher sensitivity and the possibility to detect an indeterminate result via a positive reaction control. The therapeutic strategy in Crohn's disease and ulcerative colitis is the use of corticosteroids in the acute phase of inflammation and immunosuppressive agents like azathioprine and 6-mercaptopurine or methotrexate for maintenance of the remission phase.
The immunosuppressive therapy may influence also the test of latent tuberculosis. In the performance of the tuberculin skin test a positive control is not implicated, whereas a false indeterminate result cannot be detected. We assessed the rate of indeterminate results of QuantiFERON test and its association with corticosteroid and immunosuppressive treatment. Consequently, we excluded these patients from all statistical analysis. This study was approved by the ethical committee of Lower Saxony, Hanover, Germany and was performed in concordance to Helsinki declaration.
Laboratory parameters including liver enzymes, CRP, white blood cell count, haemoglobin, thrombocytes etc. In short: one ml of whole venous blood was added to each of the three assay kit-tubes nil, mitogen, antigen.
The tubes were transferred via courier to the performing laboratory for assay. Indeterminate results were defined as increase less than 0. The primary point was to determine the influence of indeterminate results of the QuantiFERON test by immunosuppressive agents. Based on Kolmogorov—Smirmov tests normal distribution could not be assumed. Therefore we used median and quartile values box-whisker plots for data description.
The probability for a valuable test was predicted by a logistic regression model. For the logistic regression we included corticoid therapy immunosuppression, blood cell count of erythrocytes, leucocytes, thrombocytes, C-reactive protein, iron serum level, sex and the diagnosis of Crohn's disease or ulcerative colitis.
The dose depending curve Fig. Further patient data is presented in Table 1. One patient out of 45 corresponding to 2. To describe the difference between the patient group receiving corticosteroid, corticosteroids and immunosuppression in combination or no concomitant medication we used the Mann—Whitney- U -test. The indeterminate results were associated with corticosteroid treatment and stronger association was found in patients with combined immunosuppressive therapy and corticosteroid treatment.
These findings depend upon the dose. A daily dose of 15 mg or more showed a high risk for indeterminate results. We analysed the stimulation capacity in dependence of immunosuppressive therapy. The presented study shows the effect of anti-inflammatory agents on the outcome of testing the latent tuberculosis infection. Corticosteroid treatment increases the risk for indeterminate results.
Moreover, the combination of immunosuppressive medication with corticosteroids further increases the risk for an indeterminate result of the QuantiFERON test. Until now it is unclear, if this is due to the general immunologic situation of patients suffering from Crohn's disease or ulcerative colitis or not.
In the past the suspicion of modified immunologic reactions against tuberculosis agents in inflammatory bowel disease was discussed Fig. The therapeutic strategy against Crohn's disease and ulcerative colitis is the use of corticosteroids in the acute phase of inflammation and immunosuppressive agents like azathioprine and 6-mercaptopurine or methotrexate for maintenance of remission phase.
In patients with fistula disease and severe inflammation or failure to corticoid and or immunosuppressive therapy the treatment with anti-TNF-antibodies like Infliximab, Adalimuab or Certolizumab will be induced. In the presented patient group, However, in the presented patient population there was only one patient tested positively for latent tuberculosis infection.
We cannot comment on the risk for undiagnosed latent tuberculosis reaction because of the low number of patients with latent tuberculosis. We performed risk factors for the development of an indeterminate result and found that the corticosteroid therapy is the main risk factor for false negative results. The risk increases with higher doses of corticosteroids and is supported by immunosuppressive agents.
This is related to the reduced stimulation capacity of lymphocytes when patients receive corticoid treatment and is further reduced in case of concomitant therapy with immunosuppressive agents. The stimulation capacity is significantly higher in patients under immunosuppressive therapy when the daily corticoid dose is less than 15 mg prednisolone equivalent. However, the presented study population might show a low rate of latent tuberculosis infections compared to other studies, 14,15,22 but, nonetheless, our data represents the low incidence of tuberculosis infection in the northwest of Germany.
In the presented study a high rate of an indeterminate results occurred compared to the studies of Schoepfer at al. This might be due to the German recommendation of use of anti-TNF-therapy in patients with refractory disease to immunosuppressive agents or corticosteroids.
A couple of months ago Papay et al. However, in the IBD-cohort no data on the combined therapy with immunosuppressive agents and corticosteroids was available whereas in the second cohort data on corticosteroids is available and leads to similar results as the main risk factor for indeterminate results of the IFN-gamma release assay.
Moreover we could show in the presented study an influence depending on the dose of corticosteroids on the results of QuantiFERON-test.
In conclusion, we can confirm the data of Papay et al. Moreover, we found a high correlation between the combination of immunosuppressive agents and corticosteroids in the presented study. Therefore, we recommend reducing the corticosteroid treatment to less than 15 mg prednisolone per day if corticosteroid treatment is combined with immunosuppressive agents before starting the QuantiFERON-test.
If the clinical situation of the patient requires a high dose of corticosteroid treatment and does not allow a dose reduction of corticosteroids, we recommend excluding latent tuberculosis infection by chest-x-ray and detailed medical history.
The study-setup and the low patient number do not allow a comment on the risk for false negative results and no comparison to the tuberculin skin test. Travis S. Stange E. Lemann M. Oresland T. Chowers Y. Forbes A. European evidence based consensus on the diagnosis and management of Crohn's disease: current management Gut 55 Suppl. Google Scholar. Lin J. Ziring D. Desai S. Kim S. Wong M. Korin Y. TNFalpha blockade in human diseases: an overview of efficacy and safety Clin Immunol 13 — Furst D.
Problems encountered during anti-tumour necrosis factor therapy Best Pract Res Clin Rheumatol 20 — Keane J. Gershon S. Wise R. Mirabile-Levens E. Kasznica J. Schwieterman W. Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent N Engl J Med — Malipeddi A. Rajendran R. Kallarackal G. Disseminated tuberculosis after anti-TNFalpha treatment Lancet Hoffmann J. Preiss J. Autschbach F. Buhr H. Hauser W. Herrlinger K. Clinical practice guideline on diagnosis and treatment of Crohn's disease Z Gastroenterol 46 — Zeitz M.
Bischoff S. Brambs H. Bruch H. Diagnosis and therapy of ulcerative colitis: results of an evidence based consensus conference by the German society of Digestive and Metabolic Diseases and the competence network on inflammatory bowel disease Z Gastroenterol 42 —
No comments:
Post a Comment