NEWS

Chronic Wasting Disease (CWD) is in the news as experts raise concerns about its unchecked spread. Read here the Opinion/Hypothesis article in the July/August issue of mBio titled: Chronic Wasting Disease in Cervids: Implications for Prion Transmission to Humans and Other Animal Species. The authors of the article conclude: Available data indicate that the incidence of CWD in cervids is increasing and that the potential exists for transmission to humans and subsequent human disease. Given the long incubation period of prion-associated conditions, improving public health measures now to prevent human exposure to CWD prions and to further understand the potential risk to humans may reduce the likelihood of a BSE-like event in the years to come.

Today's Johnes.org news item contrasts CWD with a more common chronic wasting disease known as Johne’s disease (JD). I do this with the intention of questioning the relative importance of CWD and JD to society and urging science-based decisions on animal disease control investments. The evidence in the table below and the references that follow speak for themselves.

Footnotes:

• ¹ Crohn’s disease affects more than 1 in 800 people in North America, and while the incidence has plateaued in more industrialized countries, since 1990 the incidence has been rising in newly industrialized countries in Africa, Asia, and South America, including Brazil.
• ² Type 1 Diabetes Mellitus affects roughly 1 in 550 youth (<20 years old) in the U.S. and Canada, and the incidence is rising.
• ³ Multiple Sclerosis affects roughly 1 in 700 in the U.S., and the incidence is rising.

References and recommended reading:

• MAP as a zoonosis on this site: https://johnes.org/general-information/zoonotic-potential/
• Race, B. et al. 2014. Chronic wasting disease in nonhuman primates. Emerg Infect Dis 20(5): 833-837.
• Lombard, JE, et al. 2013. Herd-level prevalence of Mycobacterium avium subsp. paratuberculosis infection in United States dairy herds in 2007. Preventive Veterinary Medicine. 108:234-238.
• Nielsen, SS, and Toft, N. 2009. A review of prevalences of paratuberculosis in farmed animals in Europe. Prev Vet Med 88:1-14.
• Ellingson, JLE, et al. 2005. Detection of viable Mycobacterium avium subsp. paratuberculosis in retail pasteurized whole milk by two culture methods and PCR. J Food Protection 68(5):966-972.
• Chiodini, R. et al. 2012. Crohn’s disease and the mycobacterioses: A quarter century later. Causation or simple association? Critical Reviews in Microbiology 38(1):52-93.
• Ng, SC. 2017. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet. 390:2769-2778.
• Waddell, LA, et al. 2015. Review Article: The zoonotic potential of Mycobacterium avium ssp. paratuberculosis: a systematic review and meta-analyses of the evidence. Epidemiol Infect 143:3135-3157.
• National Advisory Committee on Microbiological Criteria for Foods. 2010. Review: Assessment of Food as a Source of Exposure to Mycobacterium avium subspecies paratuberculosis (MAP). J Food Protect 73(7):1357-1397.
• Sechi, L. et al. 2008. Humoral immune responses of Type 1 Diabetes patients to Mycobacterium avium subsp. paratuberculosis lend support to the infectious trigger hypothesis. Clinical and Vaccine Immunology Feb:320-326.
• SEARCH for Diabetes in Youth. 2006. The Burden of Diabetes Mellitus among US youth: Prevalence estimates. Pediatrics 118(4).
• Dilokthornsakul, P. et al. 2016. Multiple sclerosis prevalence in the United States commercially insured population. Neurology 86(11).
• Cossu, D. et al. 2011. Association of Mycobacterium avium subsp. paratuberculosis with Multiple Sclerosis in Sardinian patients. PLoS One 6(4):e18482.

Abstract submission for the 15th International Colloquium on Paratuberculosis to be held in Dublin, Ireland on June 14th to 18th has opened at https://www.icpdublin.com/abstract and will remain open until December 1st. Hope that you will submit an abstract!  Looking forward to a great conference next Summer.

Complete information about the upcoming 15-ICP can be found here.

Dr. Pamela Steur published a study regarding MAP transmission on Chilean dairy farms as part of her doctoral dissertation in the laboratory of Dr. Miguel Salgado, Instituto de Medicina Preventiva Veterinaria, Facultad de Ciencias Veterinarias, Universidad Austral de Chile, Valdivia, Chile. Her article appears in the journal Tropical Animal Health and Production.

This interesting study found an association between the seroprevalence of MAP infections in dairy herds based on ELISA (IDEXX) and the number of MAP in milk intended for feeding to calves. MAP detection in milk was enhanced by use of peptide-mediated magnetic separation (PMS) technology as developed and refined in the laboratory of Dr. Irene Grant, Queens University Belfast. Up to 1 million MAP per milliliter of milk were detected. This figure from their publication illustrates the association of herd seroprevalence and level of MAP in milk intended for feeding to calves.

Comments: This study highlights how a MAP infection epidemic gains momentum as the number of cows shedding MAP steadily rises and the rate of contamination of milk being fed to calves increases in parallel. Milk is perhaps the most efficient vehicle for transmission of MAP to the most susceptible animals in dairy herds, calves. Some of the MAP in milk is directly excreted from the udder but the majority probably come with fecal contamination of the milk. While dairy producers in some countries can afford to use on-farm pasteurizers or purchase calf milk replacer (pasteurized powdered milk) as a means of protecting calves from MAP, this is not always an option. Moreover, when bulk feeding of milk to calves is practiced (instead of milk from one cow to one calf) the infection rate accelerates quickly. Pictured here is an example of a “calfeteria” in use on a Chilean dairy farm.

This is the title of an August 15 blog posting by the Beef Cattle Research Council (BCRC) in Canada.  The author uses Johne’s disease as an example about the broader issues of farm biosecurity.

Here is an excerpt:

A well-run herd can introduce and spread Johne’s disease just by buying the wrong animal. Johne’s cannot be prevented by vaccination or effectively treated by antibiotics, and accurately identifying and culling infected animals is very difficult before they get visibly ill. Johne’s disease also can’t be prevented by high herd health, nutritional, grazing, or genetic management. Many beef producers may think they have closed herds, but realistically speaking hardly anyone does. Appropriate biosecurity is the best thing producers can do to help keep Johne’s from entering their herds.

The article goes on to describe the prevalence of Johne’s disease in Canadian beef cattle herds and much more.  So, check it out!

Management decisions to protect calves from infection such as separation of infected cows at calving and discard of calves, milk and colostrum from MAP positive cows, or pasteurization of their milk, are uncommon in seasonal, pastoral New Zealand (NZ) dairy farming. Pasture management is greatly complicated by any increase in the number of groups of grazing cows. The NZ Animal Compounds and Veterinary Medicines act (1987) prohibits the sale of milk for human consumption when that milk is contaminated with drug residues. Consequently, calves are commonly fed on milk from sick cows, those undergoing antimicrobial treatment or excluded from the main herd for other reasons.

Therefore, in NZ, there has been relatively little engagement from dairy farmers in the control of JD unless they have experienced a high clinical prevalence and there is evidence of increasing prevalence of JD especially in the South Island of the country.

Andrew Bates et al., Vetlife Centre for Dairy Excellence, Geraldine, NZ reported in BMC Veterinary Research (Open Access) the results of a single herd study where a high prevalence of clinical JD and MAP infection was reduced over a 4 year period using an annual test and cull approach. The strategy was based on a herd testing protocol using an initial herd screening using serological ELISA coupled with a quantitative fecal PCR (fPCR) test to confirm the status of ELISA-positive animals.

Over the 4 year period a total of 4,358 blood samples were submitted from 2,211 cows and of these 683 were submitted for fPCR. Culling decisions followed a decision tree approach shown below. To aid the removal of animals shedding large numbers of MAP, a priority was made to remove all animals with a high fPCR status, followed by those that were had high ELISA results.

For all age groups considered the apparent seroprevalence of cows testing positive decreased from 26% in 2013–2014, to 2.3% in 2016–2017. The reported proportion of calved cows culled annually from suspected clinical Johne’s disease fell from 5% in the year preceding the control program to 0.4% in the final year of the study.

On this farm, reduction in the prevalence of infection was achieved by reducing the infectious pressure through targeted culling of heavily shedding animals together with limited measures to protect calves at pasture from exposure to Mycobacterium avium subsp. paratuberculosis (MAP).

This study demonstrates that - with a combination of pre-calving diagnostic testing to identify and remove animals that are the major source of infectious spread, coupled with simple management changes to physically separate replacement calves from MAP infected adult cattle - effective reduction in the prevalence of JD is possible for NZ dairy farmers.

Comment: This important study validates that removing the most infectious animals from a herd significantly decreases the prevalence of the infection.  However, it ignores the economic utility of the program, i.e. the cost-benefit of this approach.  If the ELISA was valued at US$5.00 and the fPCR at US$30 (typical costs in U.S. labs), then the cost of this control program, in laboratory testing costs alone, was $42,280.  Most herd owners would question the return on investment without receiving some compensation from the processor buying his/her milk or from a governmental agency concerned with food safety. 

The study recently published in BMC Veterinary Research, which surveyed 48 countries around the world, highlighted the crucial need to secure funding and international support for implementing long-term veterinary control programs against paratuberculosis. BMC publishers asked Emeritus Professor Richard Whittington, who led and formed the network of international experts, more about the disease, how the survey was carried out and the implications of the survey findings. The blog title is: Q&A on Paratuberculosis in livestock: insights to a neglected disease and experts’ recommendations.

Read the BMC blog.

If you missed it, this takes you to the original survey publication.

Research Article

Nathalia M. Correa-Valencia and colleagues reported on the herd-level prevalence of paratuberculosis in Northern Antioquia, Columbia. Their study, titled: Prevalence of Mycobacterium avium subsp. paratuberculosis infection in dairy herds in Northern Antioquia (Colombia) and associated risk factors using environmental sampling, appears in the latest issue of Preventive Veterinary Medicine. In comparison to other countries, the prevalence of paratuberculosis in dairy herds in this region of Columbia is low.  This finding should increase efforts to protect the as yet non-infected herds.

Abstract

This cross-sectional study aimed to determine Mycobacterium avium subsp. paratuberculosis (MAP) herd-level prevalence using a quantitative real-time PCR method (qPCR), performed on environmental samples. Secondly, the study aimed to explore herd-level risk factors associated with the presence of MAP in dairy herds with in-paddock milking facilities of the Northern region of the Province of Antioquia (Colombia). Study herds (n = 292) located in 61 different districts from six municipalities were randomly selected amongst 7,794 dairies registered in the foot-and-mouth disease vaccination records from 2015. The sampling strategy considered a proportional allocation, both at municipality and district level. Participant herds were visited once between June and October 2016 to collect one composite environmental sample and to complete a risk assessment questionnaire. Each composite environmental sample contained material from six different sites of concentration of adult cattle and/or high traffic areas (e.g. areas surrounding waterers and feeders, areas surrounding the current mobile milking-unit places). Identification of MAP was achieved using a duplex qPCR (Bactotype MAP PCR Kit®, Qiagen). A herd was considered as MAP infected if the environmental sample was positive in the qPCR. Information about the general characteristics of the herd, management practices, and knowledge about the disease was collected using the risk-assessment questionnaire. The information on risk factors was analyzed using a multivariable logistic regression model. The apparent herd-level prevalence was 4.1% (12/292; 95% CI: 1.8-6.4). Herds with a history of mixed farming of cattle with other ruminants had higher odds of being MAP infected than herds without (OR = 3.9; 95% CI: 1.2-13.2). Our study demonstrates the MAP prevalence in dairy herds from Antioquia, Colombia and the possible relationship between MAP environmental positivity with the history of mixed farming of cattle with other susceptible ruminants.

This map from Wikipedia shows the location where the study was done.

Comment: Lombard et al. reported results from a survey of U.S. dairy herds using similar surveillance methods (Preventive Veterinary Medicine 108:234-238).  In that NAHMS Dairy 2007 study, the apparent herd-level prevalence of MAP was 70.4% (369/524 had ≥1 culture-positive composite fecal samples out of 6 tested).  Adjusting for the estimated herd sensitivity and herd specificity of the test method, the estimated TRUE herd-level prevalence of paratuberculosis in U.S. dairy herds was 91.0% (95% probability interval, 81.5 to 99.3%).

Research Article – Open Access

Luttikholt et al. from the Department of Small Ruminant Health, GD Animal Health, The Netherlands, reported on the accuracy of an ELISA (IDEXX) used on milk samples from goats in both MAP-vaccinated and non-vaccinated herds. The cut-off for a positive test was based on ROC analysis and set at 25 S/P%. The cut-off recommended by the kit manufacturer for bovine milk samples is ≥30 S/P%. This article appears in the July 2019 issue of Veterinary Sciences.

Abstract

The aims of our study were to calculate the most appropriate cut-off value for milk samples in a serum-validated Mycobacterium avium subsp. paratuberculosis (MAP) ELISA and to analyze MAP ELISA responses in milk samples from vaccinated and non-vaccinated dairy goats in the Netherlands. Analyzed herds were representative for location and herd size of dairy goat herds in the Netherlands. A significantly higher proportion of the analyzed 49 herds were organic as compared with the total Dutch dairy goat population. First, the MAP ELISA was optimized using 992 paired serum and milk samples. At a cut-off of 25 S/P%, the relative sensitivity (Se) was 58.4% (n = 992, 95% CI: 48.8%−67.6%) and relative specificity (Sp) was 98.5% (n = 992, 95% CI: 97.5%−99.2%), as compared to serum ELISA results. The percentage of positively tested herds was 78.2% (n = 49, 95% CI: 63.4%−88.1%). The percentage of positive milk samples per herd (n = 22) was on average 4.6% (median, min, and max of 4.7%, 0.0%, and 10.7%, respectively). Average age of ELISA-positive (3.2 years) and -negative goats (3.2 years) was not different. Significantly more vaccinated goats tested positive (6.7%) as compared with non-vaccinated goats (1.1%). This study shows that a high number of vaccinated and non-vaccinated commercial dairy goat herds in the Netherlands have MAP-ELISA-positive goats.

Comments

Clearly, MAP infections are common in Dutch dairy goat herds (78.1% had 1 or more milk ELISA-positive animals) which somewhat higher than MAP infection prevalence estimates among goat herds in other countries (see the discussion section of the paper and previous news items on this site). MAP vaccination increased the rate of animals testing positive by the milk ELISA but, as the authors acknowledge, this could be because vaccinating herds have a higher infection rate, i.e. the reason they started vaccinating for paratuberculosis.

This study compared an ELISA on milk samples to the same ELISA applied to serum samples as the reference test. Normally the reference test should be a more sensitive assay such as fecal culture or fecal PCR – sometimes called “gold standard” assays.  By using the serum ELISA as a reference test the reported sensitivity of the milk ELISA is somewhat inflated because the serum ELISA sensitivity in goats when compared to fecal culture has been reported as 74.3% using fecal culture as the reference test by traditional sensitivity estimate methods (Salgado et al., 2007) and 63% using Bayesian methods and including fecal culture results (Kostoulas et al, 2006). Thus, if we assume that the serum ELISA reference test in this study detected 68.6% of all truly MAP-infected animals (based on the mean sensitivity reported by two published studies I cited) and the present study found that only 58.4% of the serum ELISA-positive animals were also milk ELISA-positive, one could estimate that true sensitivity of the milk ELISA in goats for detecting MAP infected animals shedding MAP in feces was at most 40% (58.4% x 68.6%). Had the authors used the cut-off recommended for this ELISA when bovine milk samples, the sensitivity estimate would be lower still.

Use of low sensitivity tests works well for herds, regions or countries wanting to demonstrate that MAP is not a big problem and/or to lessen consumer concerns. However, it can misrepresent the true magnitude of the paratuberculosis problem and lead herd owners to under-estimate the significance of MAP infections to the health of their herd.

Research Article

F. Larussi and colleagues from the Experimental Zooprophylactic Institute of Apulia and Basilicata, Foggia, Italy and University of Barri, Italy reported a large study to investigate the prevalence of Johne’s disease in sheep and goat herds and the risk factors associated with being seropositive. This study was published in Small Ruminant Research August 2019.  It used serum samples and the ELISA kit sold by ID-Vet- Innovative Diagnostics, France.

Abstract: Paratuberculosis (PTB) is a well-documented chronic and sometimes fatal infection that affects the small intestine of ruminants both in captive and free-ranging living conditions. Although the infection has been detected on small ruminant farms worldwide, epidemiological and risk factor information regarding Mycobacterium avium subspecies paratuberculosis (MAP) infection on semi-extensive sheep and goat farms is generally still scarce, particularly in the Mediterranean area and in Italy. This paper reports the epidemiological findings and risk factors of the infection on semi-extensive sheep and goat farms in Apulia. It particularly focuses on the involvement of biological, structural and management factors, as well as the farmers’ socioeconomic data as predisposing causes of PTB, and investigates their possible connection with the survivability of the infection.

The true seroprevalence values of MAP on semi-extensive Apulian sheep and goat farms are reported and the risk factors causing the spread of infection analyzed. Data were collected through a two-year survey over the whole regional area, involving 419 farms, 16,903 sheep and 9369 goats. The epidemiological results showed a true seroprevalence of 66.2% for flocks and of 9.7% at the animal level. Analysis of the risk factors showed that the spread of infection occurs via several concomitant biological, managerial, and farmer-related factors.

The survey highlighted the need for urgent and suitable control plans providing guidelines to help Apulian farmers and their veterinarians contain and eliminate the disease, prevent biological risks for animal and humans as well as negative economic effects on the regional livestock sector.

Comment: This is a well-designed and executed study and one of the largest of its kind in sheep and goats. The study’s analysis of risk factors was particularly interesting and useful. The prevalence findings are similar to those of a survey if dairy sheep and dairy goats in Ontario Canada reported in The Canadian Veterinary Journal, February 2016. Unfortunately, neither the Italian study nor the Canadian study are open access article. Science Direct charges a fee of US$35.95 to purchase a PDF of the Italian article.

New thinking on Johne's and Getting the best from your JD review - AHDB Dairy

Dr. Peter Orpin offers a webinar (published June 27, 2019) discussing how veterinarians and farmers can work together effectively to reduce the prevalence of Johne’s disease in their dairy herds using structured risk assessments, farm walks and 100% engagement in Johne's disease control using UK’s National Johne's Management Plan.

During this webinar Dr. Orpin, a veterinary practitioner in Leicestershire and one of the key experts involved in developing the control strategies for Action Johne’s covers:

• a review of the risks of transmissions and new thinking on disease progression within infected herds,
• advice on how we can effectively manage and create a clear plan of action for infected cows and
• how to generate a “green calving line and green calf line” to produce healthy productive low-risk JD replacements.

The control of Johne's Disease is a real challenge but one that can be tackled. The majority of dairy farms in Great Britain are now part of the National Johne's Management Plan and have adopted one of the 6 strategies for dealing with Johne's disease recommended by the Action Group of Johne’s.

You can access this one hour long webinar on You Tube (the first 40 minutes are a presentation  and the remainder is Q&A).

Explanatory note: The UK program adopts the Danish system of classify cows based on ELISA testing of milk samples for antibody to MAP and the color code animals based on the results: “Red” cows are those that tested positive on the last 2 milk ELISAs, “Yellow” cows have fluctuating milk ELISA results, and “Green” cows are consistently negative by milk ELISA. The Red cows are considered in the most advanced stage of Johne’s disease and the most infectious, i.e. highest risk of spreading the infection on the farm.

Comment: The webinar is particularly good at describing why Johne’s disease control programs on dairy farms fail.