University of Wisconsin–Madison

MAP IN MANY HUMANS

2020-12-23 16:50:58

BY MICHAEL T. COLLINS

Dr. J. Todd Kuenstner, Pathology and Laboratory Medicine, Lewis Katz School of Medicine, Philadelphia, PA, and colleagues from seven other institutions have reported on the detection of MAP in the blood of people with and without Crohn’s Disease by multiple laboratory assays. Their article appears in the most recent issue of Microorganisms [Open Access, 14 pages with 51 references].

Abstract

Mycobacterium avium subspecies paratuberculosis (MAP) has long been suspected to be involved in the etiology of Crohn’s disease (CD). An obligate intracellular pathogen, MAP persists and influences host macrophages. The primary goals of this study were to test new rapid culture methods for MAP in human subjects and to assess the degree of viable culturable MAP bacteremia in CD patients compared to controls. A secondary goal was to compare the efficacy of three culture methods plus a phage assay and four antibody assays performed in separate laboratories, to detect MAP from the parallel samples. Culture and serological MAP testing was performed blind on whole blood samples obtained from 201 subjects including 61 CD patients (two of the patients with CD had concurrent ulcerative colitis (UC)) and 140 non-CD controls (14 patients in this group had UC only).

Viable MAP bacteremia was detected in a significant number of study subjects across all groups. This included Pozzato culture (124/201 or 62% of all subjects, 35/61 or 57% of CD patients), Phage assay (113/201 or 56% of all subjects, 28/61 or 46% of CD patients), TiKa culture (64/201 or 32% of all subjects, 22/61 or 36% of CD patients) and MGIT culture (36/201 or 18% of all subjects, 15/61 or 25% of CD patients). A link between MAP detection and CD was observed with MGIT culture and one of the antibody methods (Hsp65) confirming previous studies. Other detection methods showed
no association between any of the groups tested. Nine subjects with a positive Phage assay (4/9) or MAP culture (5/9) were again positive with the Phage assay one year later. This study highlights viable MAP bacteremia is widespread in the study population including CD patients, those with other autoimmune conditions and asymptomatic healthy subjects.

Comment

While the high rate of MAP detection in human blood samples is shocking, it is not surprising. MAP has been proven capable of infecting a wide array of animal species, including nonhuman primates. The majority of MAP-infected animals, e.g., cattle, goats and sheep, are used for food. Since food safety regulatory agencies have not declared MAP to be a zoonotic pathogen, those MAP-infected animals, and their products such as milk, legally enter the food supply daily. Multiple studies have detected live MAP in retail pasteurized milk, cheese, and meat. Thus, humans are being exposed every day.

As the concluding sentence of this Dr. Kuenstner’s publication states: “as a minimum measure of best practice, the possibility that MAP is a zoonotic pathogen should prompt public health measures to better control JD and MAP spread into food and the environment by governments worldwide."

For more on MAP as a human pathogen visit the website of the Human Para Foundation, the organization who funded this study.

Read this for more evidence that MAP is a zoonotic pathogen.

Read this for more on MAP in food and water.


 

WHY I DO THIS

2020-12-18 01:06:40

BY MICHAEL T. COLLINS

Once upon a time, about 17 years ago, there was a young Wisconsin girl named Lizi who was in 4H, a U.S. organization that provides experiences where young people learn by doing. Lizi decided to do a project to learn more about Johne's disease, something she had seen on her family's farm. She searched the web and found Johnes.org. Lizi used the information and images she found there to create a poster which she exhibited at the Lodi Agricultural Fair and Dane County Fair in Wisconsin, winning a blue ribbon for her efforts. Here is a picture of Lizi's poster.

This story came to light when Lizi was in my Veterinary Bacteriology & Mycology class, Fall semester in 2017, learning (again) about Johne's disease. Lizi shared this picture of her poster and granted me permission to tell her story.

The adjacent photo shows Lizi with a newborn calf on her family's farm. She graduated with her DVM degree from the University of Wisconsin School of Veterinary Medicine, May, 2020. She is pursuing a career in food animal medicine.

You never know what kind of impact knowledge sharing will have.

That is why I do this.

Michael T. Collins, DVM, PhD, DACVM

Comment: 4‑H is delivered by Cooperative Extension—a community of more than 100 public universities across the nation that provides experiences where young people learn by doing. For more than 100 years, 4‑H has welcomed young people of all beliefs and backgrounds, giving kids a voice to express who they are and how they make their lives and communities better.

If you feel you have seen this news posting before, you are not losing your mind. I originally posted this after Lizi was in my class and made me aware of our connection. In these tough times I feel that some heart-warming news like this is worth re-posting.


 

HAPPY BIRTHDAY DR. JOHNE!

2020-12-10 01:00:50

BY MICHAEL T. COLLINS

Johne

One-hundred eighty-one years ago, on December 10, 1839, Heinrich Albert Johne was born in Dresden, Germany. It seems fitting that Johnes.org celebrate, on this date, his lasting contribution to veterinary medicine.

Below you will find the story of his discovery, a brief biography, a little about the pathogen name, and the story of how I found this photo.

 

 

 

How it all started.

Dr. F. Harmes, a veterinarian in the Oldenburg region of Germany in 1895, had a client with a Guernsey cow that was doing poorly.  Dr. Harmes’ preliminary diagnosis was intestinal tuberculosis (TB).  TB in cattle was quite common in Germany then.  But when he did the tuberculin skin test to confirm his diagnosis, the cow tested negative.  So, the reason for the cow’s condition remained a mystery.

A few months later, the cow died.  Curious as to what killed the cow, Dr. Harmes sent intestines and other tissues to the Pathology Unit at the veterinary school in Dresden.  There the tissues were examined by Dr. Heinrich A. Johne, Professor of Pathology, and Dr. Langdon Frothingham, a visiting scientist from the Pathology Unit in Boston, Massachusetts.

They observed that the small intestine was quite a bit thicker than expected and that lymph nodes near this thick intestine were enlarged.  The photo at the right shows a normal intestine at the top and the intestine thickened due to Johne’s disease at the bottom.  Lymphoid tissue, called Peyer’s Patches, are also quite prominent (the raised and slightly red tissue running long-ways down the center of the thickened intestine).   Interestingly, Dalziel in 1913 saw the same kind of pathology when he removed a section of intestine from a person with Crohn’s disease remarking in his report that it resembled the cattle problem Dr. Johne had described.

Using what at the time were newly developed histopathology techniques, parts of the intestine were “fixed” (pickled in formaldehyde), sliced into very thin sections, placed on a microscope slide, and stained with special dyes – known as an acid-fast stain - designed to help visualize bacteria of the type causing TB. Under the microscope, Drs. Johne and Frothingham saw that the intestinal wall was filled with inflammatory cells of the kind to be expected in TB (macrophages and lymphocytes – the blue-colored stuff in the photo).  In addition, they saw abundant red-staining bacteria (which microbiologists call acid-fast bacteria) throughout the inflamed tissues.  Basically, it looked just like intestinal TB.  But, when a sample of the fresh infected tissue containing the red-staining bacteria was injected into guinea pigs, it didn’t cause TB.  This took place shortly after Louis Pasteur had devised the “germ theory” of disease and before techniques for growing bacteria in the laboratory were widely available.  Inoculating animals, therefore, was a routine way of detecting infectious microbes such as those that cause TB, and guinea pigs are quite susceptible to tuberculosis.  So, the diagnosis on this cow remained a mystery.

Drs. Johne and Frothingham concluded that the disease seen in the very sick Guernsey cow was caused by a bacterium other than the one normally causing TB in cattle, namely Mycobacterium bovis.  They speculated that perhaps the pathology was due to a related bacterial pathogen such as the one causing TB in birds, aptly named Mycobacterium avium.  Considering their subject’s gross pathology, microscopic pathology (histopathology) and animal inoculation findings, they proposed the name "pseudotuberculous enteritis" for the disease; a designation meaning inflammation of the intestine resembling intestinal TB but not actually the same as intestinal TB – somehow different.  Soon after publication of their report, veterinarians began reporting outbreaks of this curious intestinal malady among dairy cows in Denmark, The Netherlands and elsewhere in continental Europe.

More on Dr. Johne.

H.A. Johne was the son of a veterinarian. Twenty years later, he became a veterinarian himself and held a practice for the next seven years. From 1866-1876, he acted as district veterinary inspector. He was then appointed to a lectureship at the veterinary school in Dresden. For a teacher of veterinary medicine, he lectured in an unusually wide range of subjects: embryology, histology, obstetrics, exterior, physical diagnostics. In 1879, he was appointed professor of pathological anatomy and of general pathology. Later he also lectured on parasitology and methodical zoology, and he also started classes in such a new branch of research as bacteriology.

As a scientist, he concerned himself with tuberculosis, anthrax, rabies, glanders, actinomycosis, bothryomycosis among others. As a writer he left a wide literary production. His books were printed in a dozen editions. For many years he also edited “Zeitschrift tor Tiermedizin”, and acted as co-editor of “Rundschau auf dem Gebiet der Fleischbeschau”. In 1887, he visited Denmark, where he was nominated honorary member of the Danish Association of Veterinarians and decorated with the Order of Knight of the Dannebrog.

He was often guest of Professor B. Bang and his family, the flat of Bangs' is today the Veterinary History Museum, established in 1973 at the Royal Veterinary and Agricultural University in Copenhagen. His motto was: Duty Above All. With the distinguished array of titles: Geheim-Medizinalrat, Professor, Dr. med., Dr. med.vet.h.c. and Dr. phil., Heinrich Albert Johne retired in 1904, respected and honored by his many students and by foreign veterinary schools and societies. He died in 1910.

MAP

 In 1912, in one of those curious discoveries by serendipity, Twort and Ingram discovered how to grow the cause of Johne’s disease in the laboratory and named this bacterial pathogen Mycobacterium enteritidis chronicae pseudotuberculosae bovis johne.  Time and technology led to name changes and the cause of Johne’s disease is today known as Mycobacterium avium subspecies paratuberculosis or simply MAP. Johne’s disease, also called paratuberculosis, is now a disease of major global importance.

Dr. Johne photo credit

I found the photo of Dr. Johne was hanging in halls of the State Veterinary Serum Institute when I was on sabbatical working with Dr. J.B. Jørgensen at the State Veterinary Serum Laboratory, Copenhagen, Denmark. Together we were comparing new methods for culturing MAP from clinical samples. On my departure, Dr. Jørgensen gifted me a copy of this photo which hangs in my office and also appears on the Wikipedia page about Dr. Johne.

PS

For more historical events and people visit our history timeline.


 

POTENTIAL COST OF MAP IN MILK

2020-11-29 15:44:06

BY MICHAEL T. COLLINS

L. Chiu and colleagues from Cornell University and the University of Illinois published a research article exploring the societal costs of MAP in the milk supply and a link of MAP to Crohn’s disease. Their work was published in the International Journal of Food System Dynamics [Open Access].

ABSTRACT

Welfare costs of a potential food shock were estimated by disseminating information to milk drinkers on the prevalence of Mycobacterium avium sub. paratuberculosis (MAP) in the U.S. milk supply, its potential linkage to Crohn’s disease in humans, and subsequent government intervention to minimize MAP in the milk supply. We found that 19.6% of milk consumers exposed to MAP information would stop milk consumption at current market prices, and that only 5% of those would return to their original milk consumption levels after the government intervention. Societal costs of the food shock after the intervention were estimated at $18.2 billion.

RELATED STUDY

A similar study by H. Groenendaal and Zagmutt was published in the Journal of Dairy Science in 2008. This article, not cited by Chiu, explored three scenarios developed based on the effectiveness of possible risk-mitigation strategies. As reported in their publication, “in the first scenario, it was assumed that an effective strategy exists; therefore, a negligible demand decrease in the consumption of dairy products was expected. In the second scenario, it was assumed that new risk mitigation would need to be implemented to minimize the health hazard for humans. In this case, a small milk demand decrease was expected, but larger demand decreases were also possible. The third scenario assumed that no fully effective risk mitigation was available, and this resulted in a considerable demand decrease and a potential reduction in milk supply as a result of regulatory measures. A milk demand reduction of 1 or 5% resulted in a reduction in consumer surplus of $600 million and $2.9 billion, and a reduction in dairy farm income of $270 million and $1.3 billion, respectively. A decrease in milk supply would cause a slight increase in total losses, but would cause the greatest losses to test-positive dairy farms. Given the current scientific knowledge about MAP and CD, we conclude that if a link were established, it is most likely that the first or second scenario would occur. Thus, consumer response and economic consequences to the discovery of such a link are expected to be limited, but could be large if the consumer's perception of risk is large or if risk-mitigation strategies were ineffective.

COMMENT

Prevention pays! Dairy producers and processors should work to limit the potential impact of MAP on consumer acceptance of dairy products. The necessary diagnostic tools and knowledge on how to control MAP infections in dairy cattle are available. Some countries have implemented national control programs to help avert negative consumer reactions should medial science accept that MAP is a zoonotic pathogen. Actions to control MAP in dairy cattle can protect consumer confidence while also improving farm profitability and animal health and welfare.


 

JD CAUSES FALSE-POSITIVE TB TESTS IN CATTLE

2020-11-23 14:05:38

BY MICHAEL T. COLLINS

Mariana Assunção de Souza and 6 other Brazilian colleagues reported on the occurrence of Johne’s disease (paratuberculosis) in cattle that were necropsied based on a positive comparative cervical skin test for bovine tuberculosis (bTB). Their research article appears in the current issue of Acta Scientiae Veterinariae.

Abstract

Background: Bovine tuberculosis control programs are based on a standard diagnostic method, the intradermal test with purified protein derivatives, which is used to identify and eliminate diseased animals. Currently none of the tests available allow complete differentiation between infected and uninfected animals. The main limitations of the tests available are related to diagnostic sensitivity and specificity, which results in false-positive reactions due to the existence of cross infections, and also false-negative, inherent to the state of energy of some animals. The aim of this work was to study the intercurrence of paratuberculosis in tuberculosis reactive cattle by the comparative cervical test.

Materials, Methods & Results: Three hundred and thirty-four cattle were evaluated using the comparative cervical test (CCT) and serology for tuberculosis (TB) and paratuberculosis (PTB) ELISA IDEXX®. All of the animals testing positive by CCT were euthanized and necropsied. Fragments of lymph node, lung and intestine were collected and analyzed using histopathological techniques, with staining by Hematoxylin-Eosin (HE). Samples of lung and lymph nodes (retropharyngeal, submandibular, cervical and mediastinal) of the animals testing positive by CCT were evaluated using qPRC for M. bovis, and intestinal and mesenteric lymph nodes using PCR for PTB. Of the 334 cattle evaluated using the comparative cervical test, 16 were considered positive. No lesions suggestive of tuberculosis were found in the macroscopic inspection of the carcasses. The most evident anatomical and pathological finding was a thickening of intestinal mucosa, found in 12 of the 16 cattle submitted to necropsy. No microscopic lesions suggestive of TB were identified nor was the presence of M. bovis detected by qPCR. The main histopathological findings were observed in the small intestine and mesenteric lymph nodes and identified as enteritis, lymphangitis, lymphangiectasia and granulomatous lymphadenitis. In the intestine the changes are characterized by dilated and inflamed lymphatic vessels and intense inflammatory infiltrate on the mucosa and submucosa. Of the 334 serum samples evaluated, the M. bovis ELISA Antibody Test (IDEXX®) identified 17 positive animals. All the cattle considered positive by M. bovis ELISA were considered negative by CCT. In the samples from nine animals (9/16), DNA from M. avium subsp. paratuberculosis (MAP) was identified and in twelve carcasses (12/16) lesions characteristic of PTB were found, which were subsequently confirmed by histopathological techniques. In another nine animals of the herd anti-MAP antibodies were detected. None of those that tested positive by PTB ELISA were reactive by CCT.

Discussion: Animals considered positive by TB ELISA that were not positive in the intradermal test does not mischaracterize the clinical picture of the disease. Considering the inverse relationship between cell-mediated and humoral responses to M. bovis, the intradermal test and the serological tests are designed to measure different immunological responses, which develop during different stages of infection. The progress of the cellular immunological response to humoral immunity occurs in the most advanced stages of tuberculosis. Of the 16 cattle considered positive by CCT, 12 animals presented macroscopic and histological lesions suggestive of PTB and DNA from MAP was detected in nine. Although it is the official test for the control of TB in different countries, the intradermal test with PPD has presented limitations, primarily related to specificity. M. avium subsp. Paratuberculosis is considered the main cause of false positive reactions in the intradermal test. The PPD bacterial extract is a complex mixture of proteins, lipids, sugars and nucleic acids, and many of these components are also shared by numerous species of mycobacteria (tuberculous or not).

The Brazilian study illustrates the interaction of MAP and M. bovis, the cause of bovine tuberculosis (bTB), as a confounder when trying to use standard immune-diagnostic tests for bTB. Other authors have found similar results. Out October 30 news posting on this site discussed the need to wait at least 60 days after skin testing cattle for bTB before using serological tests (ELISA) for Johne’s disease (JD) in order to avoid false-positive JD blood tests.

In a different but related context, other authors have likewise noted this interaction between mycobacterial diseases such as TB, leprosy and those caused by non-tuberculosis mycobacteria (NTM). The most common NTM infections are due to bacteria in the Mycobacterium Avium Complex (MAC) which includes the cause of JD, i.e. MAP.

In a letter published in the journal Inflammatory Bowel Diseases in 2008, Dr. Marcel Behr from McGill University Health Centre, Montreal, Canada highlighted instances where one mycobacterial infection interferes with another. One example he cited is that TB and leprosy (caused by Mycobacterium leprae) behaved as antagonistic epidemics – one infection blocks the other. When human TB is controlled, as it has in most developed countries, and when BCG vaccination of humans stops, other mycobacterial infections rise in prevalence. The theory is that the absence of one mycobacterial infection, e.g. TB, causes an “immunological void”, i.e. an increased susceptibility of humans to other mycobacteria that now find more susceptible, immunologically naïve, hosts. Note: BCG is a live non-virulent vaccine used to control TB in humans in countries where the disease is endemic. This vaccine was originally derived from M. bovis.

Because MAP is strongly associated with Crohn’s disease, Dr. Behr noted that Crohn’s disease (CD) was more common in countries where TB was less common. Below is the graphic he published illustrating inverse association between TB incidence and CD incidence. This is yet another piece of evidence for mycobacterial, e.g. MAP, involvement in CD.

Related to this is the review article by Dr. Dow (15 pages with 173 references) published in February 2020 on the influence of BCG vaccination on a variety of autoimmune diseases. In that article he states: "MAP has been associated with an increasingly long list of inflammatory/autoimmune diseases: Crohn's disease, sarcoidosis, Blau syndrome, Hashimoto’s thyroiditis, autoimmune diabetes (T1D), multiple sclerosis (MS), rheumatoid arthritis, lupus and Parkinson’s disease. Epidemiologic evidence points to BCG providing a “heterologous” protective effect on assorted autoimmune diseases; studies using BCG vaccination for T1D and MS have shown benefit in these diseases." His article proposes that the positive response to BCG in T1D and MS is due to a mitigating action of BCG upon MAP infections.

For more on the potential of MAP to cause Crohn’s disease visit this page of our site. Or listen to a 10-minute presentation titled: MAP is a zoonotic pathogen.


 

15-ICP POSTPONED AGAIN

2020-11-20 16:09:49

BY MICHAEL T. COLLINS

In March 2020, in response to the global pandemic brought about by the COVID-19 virus the Committee of the 15th International Association for Paratuberculosis Colloquium 2020 made the hard decision to postpone ICP 2020 until 2021. The event was originally scheduled for 14th -18th June, 2020 in Dublin Castle. The 15th International Colloquium for Paratuberculosis was then re-scheduled for the 6th – 9th April 2021.

Last month the Local Organizing Committee (LOC) was faced with the decision of having to postpone again or to have a virtual conference next April. It was decided by the LOC to go for a live conference in June 2022. The committee was delighted that the organizers of the 16th ICP in Jaipur, India agreed to this and have postponed their Colloquium until 2024.

The ICP Committee invites you to the 15th IAP Colloquium in Dublin, Ireland in June 2022. Delegates attending the conference can be assured of a productive and memorable colloquium, discover Irish heritage, culture and music and of course, experience the world-renowned hospitality of Ireland.

Follow this website to stay informed about the 15-ICP being held in 2022.


 

OJD REVISITED – AUSTRALIA

2020-11-13 17:54:34

BY MICHAEL T. COLLINS

Dr. Peter Windsor and Dr. Richard Whittington published a review article on ovine Johne’s disease (OJD) control in Australia. This excellent review article appears in the journal Animals and is Open Access. It nicely reviews the pathogenesis and control of paratuberculosis in sheep, but the most interesting part of the article addresses the top 10 subjects of misinformation about OJD in Australia.

Abstract

OJD is no longer the serious animal health issue that it was for many Australian rural communities a decade and a half ago. Despite declining OJD prevalence as determined by abattoir surveillance, the disease continues to spread, with OJD extension programs required to continually address the  misinformation promulgated by some disaffected producers as new areas have become affected. Improved regional and on-farm biosecurity, including the introduction of a risk-based trading system, may have contributed to improved attitudes to OJD control, although attitudinal differences between OJD endemic areas and where the disease is not well established remain. Declines in on-farm OJD prevalence are almost certainly attributable to the widespread uptake of vaccination programs, although encouraging the ongoing use of vaccination to prevent recrudescence and improved biosecurity when mortalities disappear, remains challenging. Vaccination has provided a robust strategy for managing OJD and contributed significantly to the health of Australian sheep and the lives of producers with affected properties. As vaccination offers a pathway to reduce the risk of MAP infection entering the human food chain from small ruminant products, it should be more widely adopted globally, accompanied by research efforts to improve efficacy and importantly, the safety of vaccination to both operators and livestock.

Comment: Not all countries, such as the U.S., have access to the vaccine for paratuberculosis that is used in Australia. For pictures of sheep before and after developing clinical Johne’s disease can be found here.


 

JD IN SCIMITAR ORYX

2020-11-06 17:13:38

BY MICHAEL T. COLLINS

Claudio Pigoli and colleagues report on multiple cases of Johne’s disease in captive scimitar-horned oryx at a zoo in Italy. Their research article was published in the journal Animals and is Open Access. Genomic analysis shows that the MAP strains recovered from the Oryx are closely related to those isolated from cattle in Italy: evidence of ongoing spillover from domestic livestock to wildlife and animals in zoos.

Abstract

Paratuberculosis, a chronic disease caused by Mycobacterium avium subsp. paratuberculosis (MAP), in ten scimitar-horned oryxes (SHOs) hosted in an Italian zoological park and originating from a Slovakian flock, was documented by pathology, molecular, cultural, and serological testing. The infection origin in this threatened species was also investigated by genomic analyses. Following the death of six of the 10 SHOs, serial investigations of dead and alive animals were performed. Necropsy, carried out on five out of six animals, identified intestinal thickening and mesenteric lymphadenomegaly in one of the animals. Histopathology (5/6) revealed lepromatous (2/5) and tuberculoid (2/5) intestinal forms or lack of lesions (1/5). Ziehl-Neelsen and immunohistochemistry stains identified two multibacillary, two paucibacillary forms, and one negative case. MAP was identified by quantitative PCR (qPCR) in tissue samples in five out of five SHOs and was microbiologically isolated from two of the three animals whose fresh tissue samples were available. Fecal samples were collected in four of the six dead animals: all four resulted positive to qPCR and in MAP was isolated in three. ELISA identified MAP-specific antibodies in three of the five dead animals whose serum was available. qPCR identified MAP in the freshly deposited feces of two out of the four alive animals. From the feces of these two animals, MAP was microbiologically isolated in one case. All isolates were classified as MAP type C and profiled as INMV2 and MVS27 by molecular analysis. Genomic analysis of a field isolate revealed clustering with a European clade but was more similar to Italian than East European isolates. Our findings underline that paratuberculosis should always be considered in zoological parks in which endangered species are hosted. Infection can be subclinical, and multiple combined testing techniques may be necessary.

Author’s Conclusions

Our results underline the importance of considering paratuberculosis in zoological parks, where endangered species are often hosted. Paratuberculosis could represent a risk for the conservation of rare animals, and it is essential to include it in the panel of diagnostic tests to be performed on hosted animals. We also suggest testing dead animals, in which different diagnostic approaches are combined, with the final aim of fully elucidating the causes of death and defining their health status regarding paratuberculosis. WGA can help to trace the origin of infections, particularly in the case of moved animals. This study reports the first genome of an MAP strain isolated from SHOs and shows that the strain likely derived from the Italian cattle livestock, in which MAP is endemic.

For more on Johne’s disease in zoo animals check out this page of our website.


 

MILK ELISA & DAIRY CATTLE HERDS

2020-10-30 19:53:25

BY MICHAEL T. COLLINS

Two Related Research Publications

Two excellent articles about use of the ELISA diagnostic test on milk samples (milk ELISA) appeared in the past few weeks. The first, by Ozsvari and colleagues uses the milk ELISA to evaluate the impact of paratuberculosis on milk production, fertility, and culling in large commercial dairy herds in Hungary.  This article published in Frontiers in Veterinary Science is Open Access.

 

Abstract

Paratuberculosis (PTBC) is a chronic disease caused by Mycobacterium avium subsp. paratuberculosis (MAP), which is common in dairy herds worldwide, although the scale of its impact on herd productivity is unclear. The aim of our study was to determine the differences between MAP ELISA positive vs. negative cows in terms of milk production and quality, reproductive parameters, and culling. The data of five large dairy herds that participated in the voluntary PTBC testing program in Hungary were analyzed. Cows were tested by ELISA (IDEXX Paratuberculosis Screening Ab Test, IDEXX Laboratories, Inc., Westbrook, ME, USA) using milk samples collected during official performance testing. The outcome of the initial screening test involving all milking cows in the herds was used for the classification of the cows. The 305-day milk production, reproduction and culling data of 4,341 dairy cows, and their monthly performance testing results (n = 87,818) were analyzed. Multivariate linear and logistic models, and right censored tobit model were used for the statistical analysis. Test-day and 305-day milk production of ELISA positive cows decreased by 4.6 kg [95% CI: 3.5–5.6 kg, P < 0.0001 (−13.2%)] and 1,030 kg [95% CI: 708–1,352 kg, P < 0.0001 (−9.4%)], compared to their ELISA negative herdmates, respectively. Milk ELISA positive cows had 35.8% higher [95% CI: 17.9–56.4%, P < 0.0001] somatic cell count, on average. Test positive cows conceived 23.2 days later [95% CI: 9.2–37.3 days, P = 0.0012 (+16.5%)] and their calving interval was 33.8 days longer [95% CI: 13.2–54.4 days, P = 0.0013, (+9.7%)], compared to the negative cows, on average. Milk ELISA positive cows were less likely to conceive to first insemination (odds ratio: 0.49, 95% CI: 0.31–0.75, P = 0.0013), and required 0.42 more inseminations to conceive [95% CI: 0.07–0.77, P = 0.0192 (+13.7%)], on average. Milk ELISA positive cows were culled 160.5 days earlier after testing compared to their ELISA negative herdmates (95% CI: 117.5–203.5 days, P < 0.0001). Our results suggest that MAP ELISA positive cows experience decreased milk production, milk quality, fertility, and longevity, which supports the need to control the prevalence of PTBC in dairy herds.

______________

The second publication is by Barden and colleagues from the U.K. describes the effect of skin testing for bovine tuberculosis (TB) on milk ELISA results.  This article published in the journal Preventive Veterinary Medicine is available online only until November 29.

 

 

Abstract

Background: In the UK, quarterly Johne’s disease milk antibody ELISAs (JD-mELISAs) are commonly used to classify animals which are likely to be infectious, termed “red cows”. “Red cows” are classified following two positive results from the previous four tests (e.g. + - - +). All cattle are also regularly screened for bovine tuberculosis using intradermal avian and bovine tuberculin, and it is advised to maintain a 60 day interval between a tuberculosis test and JD-mELISA. Aims: To evaluate the impact of bovine tuberculosis testing on JD-mELISAs, and to quantify the impact of test specificity and “red cow” classification test pattern on the probability of infection.

Methods: Four years of individual cow milk records with JD-mELISA results were collated from 735 dairy farms and matched to tuberculosis testing records. A two-level multivariable logistic regression model quantified the effect of tuberculosis testing on JD-mELISA result. The specificity and age-dependent sensitivity of a single JD-mELISA were estimated and used to calculate likelihood ratios following each test. Using Bayes’ theorem, the posterior probability of infection with Johne’s disease was calculated for different specificities, ages of cow, and patterns of test results.

Results: There were increased odds of a positive JD-mELISA if it was ≤30 days (OR: 2.1) or 31− 60 days (OR: 1.2) after a tuberculosis test, compared to >90 days. A larger avian skin reaction at the tuberculosis test was also associated with increased odds of a positive JD-mELISA. The proportion of cows which tested exclusively negative after their first positive JD-mELISA was higher if that JD-mELISA was ≤30 days after a tuberculosis test compared to >90 days. The posterior probability of infection reduced substantially when the test specificity was slightly reduced. In “red cows” classified following two consecutive positive tests, if the test specificity was reduced to 0.95, then the posterior probability of infection was only >95 % if the prior probability was >13 %. If the “red cow” classification was due to two non-consecutive positive tests (+ - - +), the posterior probability of infection was only >95 % if the prior probability was >43 %.

Conclusions: Testing for Johne’s disease within 60 days of a tuberculosis test is associated with a higher chance of a positive JD-mELISA and this may reflect a reduction in the ELISA specificity. Relatively small reductions in JD-mELISA specificity can markedly reduce the posterior probability of infection which also depends on the pattern of test results which classifies “red cows”. [Red cows are those with 2 consecutive positive milk ELISA tests.]

____________

Comment: The milk ELISA is the most affordable testing option for commercial dairy cattle herds. It primarily identifies cows in the more advanced stages of a MAP infection. As the Ozsvari study shows, milk ELISA-positive cows are those that are less productive and likely to be culled sooner (160.5 days earlier) that their milk ELISA-negative herdmates. In countries with endemic bovine TB, where TB testing of cattle happens regularly, it is important to avoid use of the milk ELISA for at least 60 days after a whole herd TB skin test. TB skin testing seems to increase the rate of false-positive test results (decreases assay specificity).

Milk ELISA testing importantly makes JD control more affordable and thus increases producer participation in national programs like the one in the U.K. However, limitations in diagnostic sensitivity mean that while it is a useful tool for controlling MAP-infections in dairy cattle herds it is not sufficiently sensitive to drive eradication of the infection from herds. For that purpose, more sensitive tests, such as the fecal PCR, are required.


 

CAN MAP CAUSE CROHN’S DISEASE?

2020-10-23 20:02:56

BY MICHAEL T. COLLINS

Medical gastroenterologists commonly raise five concerns that seem to argue against a role for MAP in Crohn’s disease.

They are:

  1. Why is there variability in studies which aim to detect MAP in Crohn’s patients?
  2. Has MAP fulfilled Koch’s postulates?
  3. Why does immunosuppressive therapy not worsen Crohn’s Disease if it is caused by MAP, as is seen with MTB (the cause of tuberculosis)?
  4. Why is the incidence of Crohn’s not higher in at‑risk subgroups, such as veterinarians or farmers?
  5. If MAP causes Crohn’s, why doesn’t atypical mycobacterial antibiotic therapy (AMAT) cure Crohn’s, and related to that, have RCTs (randomized controlled clinical trials) shown that AMAT is ineffective?

Dr. Gurav Agrawal and colleagues (myself included) published and invited review in the journal Digestive Diseases and Sciences addressing these 5 questions. The article is Open Access (11 pages with 86 references).

Abstract

For decades, Mycobacterium avium subspecies paratuberculosis (MAP) has been linked to the pathogenesis of Crohn’s disease. Despite many investigations and research efforts, there remains no clear unifying explanation of its pathogenicity to humans. Proponents argue Crohn’s disease shares many identical features with a granulomatous infection in ruminants termed Johne’s disease and similarities with ileocecal tuberculosis. Both are caused by species within the Mycobacterium genus. Sceptics assert that since MAP is found in individuals diagnosed with Crohn’s disease as well as in healthy population controls, any association with CD is coincidental. This view is supported by the uncertain response of patients to antimicrobial therapy. This report aims to address the controversial aspects of this proposition with information and knowledge gathered from several disciplines, including microbiology and veterinary medicine. The authors hope that this discussion will stimulate further research aimed at confirming or refuting the contribution of MAP to the pathogenesis of Crohn’s disease and ultimately lead to advanced targeted clinical therapies.

Worth noting:

As evidence that some gastroenterologists think MAP is a cause of Crohn's disease, in the UK, a phase I clinical trial has started to investigate the safety and efficacy of two candidate MAP vaccines in patients with active Crohn's disease (ISRCTN - ISRCTN36126048).


 


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