Mycobacterium paratuberculosis zoonosis is a One Health emergency.

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

Control of paratuberculosis: who, why and how. A review of 48 countries.

Paratuberculosis, a chronic disease affecting ruminant livestock, is caused by Mycobacterium avium subsp. paratuberculosis (MAP). It has direct and indirect economic costs, impacts animal welfare and arouses public health concerns. In a survey of 48 countries we found paratuberculosis to be very common in livestock. In about half the countries more than 20% of herds and flocks were infected with MAP. Most countries had large ruminant populations (millions), several types of farmed ruminants, multiple husbandry systems and tens of thousands of individual farms, creating challenges for disease control. In addition, numerous species of free-living wildlife were infected. Paratuberculosis was notifiable in most countries, but formal control programs were present in only 22 countries. Generally, these were the more highly developed countries with advanced veterinary services. Of the countries without a formal control program for paratuberculosis, 76% were in South and Central America, Asia and Africa while 20% were in Europe. Control programs were justified most commonly on animal health grounds, but protecting market access and public health were other factors. Prevalence reduction was the major objective in most countries, but Norway and Sweden aimed to eradicate the disease, so surveillance and response were their major objectives. Government funding was involved in about two thirds of countries, but operations tended to be funded by farmers and their organizations and not by government alone. The majority of countries (60%) had voluntary control programs. Generally, programs were supported by incentives for joining, financial compensation and/or penalties for non-participation. Performance indicators, structure, leadership, practices and tools used in control programs are also presented. Securing funding for long-term control activities was a widespread problem. Control programs were reported to be successful in 16 (73%) of the 22 countries. Recommendations are made for future control programs, including a primary goal of establishing an international code for paratuberculosis, leading to universal acknowledgment of the principles and methods of control in relation to endemic and transboundary disease. An holistic approach across all ruminant livestock industries and long-term commitment is required for control of paratuberculosis.

Relationship between selected perinatal paratuberculosis management interventions and passive transfer of immunity in dairy calves.

The objective of this cohort study was to assess the relationship between perinatal calf management practices relevant to the control of paratuberculosis and passive transfer of immunoglobulin in calves born in an endemically infected Irish dairy herd. Data from 176 calves were used to assess the effect of time spent in the calving area, individual versus non-designated calving and colostrum pasteurisation on serum total protein, zinc sulphate turbidity, globulin and γ-glutamyltransferase. In addition, the effects of colostrum quality, volume of colostrum fed, method of colostrum administration and calving season on passive transfer were quantified. Serum samples were collected as part of routine herd health monitoring from calves aged between one and seven days. Multivariate linear and logistic regression models were used to assess the effect of each variable on the test result and failure of passive transfer as determined using a cut-off point for each diagnostic test. Colostrum pasteurisation and calving area were not significantly associated with passive transfer, whereas increased time spent in the calving pen was consistently associated with a detrimental effect. In addition, a strong seasonal effect was apparent, which appeared to be unrelated to colostrum quality and calf management. The authors are unaware of published studies documenting such a significant seasonal effect on passive transfer.

Dam Mycobacterium avium subspecies paratuberculosis (MAP) infection status does not predetermine calves for future shedding when raised in a contaminated environment: a cohort study.

Uptake of Mycobacterium avium subsp. paratuberculosis (MAP) by calves in the first days of life from colostrum, milk and faeces is regarded an important moment of transmission. The objective of this study was to quantify the association between the MAP status of dams as determined by the presence of MAP DNA and antibody in colostrum and that of DNA in faeces and the environment with subsequent MAP shedding of their daughters. A cohort of 117 dam-daughter pairs giving birth/being born on eight commercial dairy farms with endemic paratuberculosis was followed where colostrum, faecal and environmental samples (dust) were analysed for the presence of MAP using an IS900 real-time PCR. Antibodies in colostrum were measured by ELISA. Analysis of dust samples showed that on all farms environmental MAP exposure occurred continuously. In significantly more colostrum samples (48%) MAP DNA was detected compared to faecal samples (37%). MAP specific antibodies were present in 34% of the colostrum samples. In total MAP DNA was present in faecal samples of 41% of the daughters at least once during the sampling period. The association between faecal shedding in the offspring and the dam MAP status defined by MAP PCR on colostrum, MAP PCR on faeces or ELISA on colostrum was determined by an exact cox regression analysis for discrete data. The model indicated that the hazard for faecal shedding in daughters born to MAP positive dams was not significantly different compared to daughters born to MAP negative dams. When born to a dam with DNA positive faeces the HR was 1.05 (CI 0.6; 1.8) and with DNA positive colostrum the HR was 1.17 (CI 0.6; 2.3). When dam status was defined by a combination of both PCR outcomes (faeces and colostrum) and the ELISA outcome the HR was 1.26 (CI 0.9; 1.9). Therefore, this study indicates that neither the presence of MAP DNA in colostrum, MAP DNA in faeces nor the presence of MAP antibodies in colostrum of the dam significantly influences the hazard of MAP shedding in their subsequent daughters up to the age of two years when raised in a contaminated environment.

Evaluation of the risk of paratuberculosis in adult cows fed Mycobacterium avium subsp paratuberculosis DNA-positive or -negative colostrum as calves.

OBJECTIVE: To estimate the risk of subclinical Mycobacterium avium subsp paratuberculosis (MAP) infection in cows that ingested MAP DNA-positive raw colostrum as calves, compared with risk in cows that ingested MAP DNA-negative raw colostrum as calves. ANIMALS: 205 calves born in 12 commercial dairy herds. PROCEDURES: Each calf was separated from its dam within 30 to 60 minutes after birth and fed raw colostrum. For each calf, samples of the colostrum fed were collected and tested for the presence of MAP DNA by use of a nested PCR assay for the target gene ISMAP02. Calves fed colostrum positive or negative for MAP DNA were classified into exposed (n = 69) and unexposed (136) groups, respectively. Each calf was tested for MAP infection at 30, 42, and 54 months of age by use of a serum ELISA and bacterial culture of feces. Weibull hazard regression models were used to evaluate the association between exposure to MAP DNA-positive colostrum and time to testing positive for MAP infection. RESULTS: Hazard of MAP infection was not different between groups (exposed vs unexposed) when serum ELISA, bacterial culture of feces, or both diagnostic tests (parallel interpretation) were positive. CONCLUSIONS AND CLINICAL RELEVANCE: Heifer calves fed MAP DNA-positive colostrum were at no greater risk of MAP infection, compared with heifer calves fed MAP DNA-negative colostrum. This result contradicts findings from other studies and should be interpreted with caution.

Predicting fadeout versus persistence of paratuberculosis in a dairy cattle herd for management and control purposes: a modelling study.

Epidemiological models enable to better understand the dynamics of infectious diseases and to assess ex-ante control strategies. For Mycobacterium avium subsp. paratuberculosis (Map), possible transmission routes have been described, but Map spread in a herd and the relative importance of the routes are currently insufficiently understood to prioritize control measures. We aim to predict early after Map introduction in a dairy cattle herd whether infection is likely to fade out or persist, when no control measures are implemented, using a modelling approach. Both vertical transmission and horizontal transmission via the ingestion of colostrum, milk, or faeces present in the contaminated environment were modelled. Calf-to-calf indirect transmission was possible. Six health states were represented: susceptible, transiently infectious, latently infected, subclinically infected, clinically affected, and resistant. The model was partially validated by comparing the simulated prevalence with field data. Housing facilities and contacts between animals were specifically considered for calves and heifers. After the introduction of one infected animal in a naive herd, fadeout occurred in 66% of the runs. When Map persisted, the prevalence of infected animals increased to 88% in 25 years. The two main transmission routes were via the farm's environment and in utero transmission. Calf-to-calf transmission was minor. Fadeout versus Map persistence could be differentiated with the number of clinically affected animals, which was rarely above one when fadeout occurred. Therefore, early detection of affected animals is crucial in preventing Map persistence in dairy herds.

Efficacy of feeding plasma-derived commercial colostrum replacer for the prevention of transmission of Mycobacterium avium subsp paratuberculosis in Holstein calves.

OBJECTIVE: To estimate the relative risk of paratuberculosis (Johne's disease [JD]) in calves fed a plasma-derived colostrum-replacement (CR) product versus raw bovine maternal colostrum (MC). STUDY DESIGN: Randomized controlled clinical trial. ANIMALS: 497 heifer calves born in 12 JD-endemic commercial Holstein dairy farms located in Minnesota and Wisconsin. PROCEDURES: Every calf was separated from its dam within 30 to 60 minutes after birth and systematically assigned to be fed raw bovine MC (control group, n = 261 calves) or CR (treatment group, 236 calves). The calves were monitored to adulthood and tested for Mycobacterium avium subsp paratuberculosis (MAP) infection by use of an ELISA to detect serum antibodies against MAP and bacterial culture for MAP in feces at approximately 30, 42, and 54 months of age. Weibull regression models were used to evaluate the effect of feeding CR (vs raw bovine MC) on the risk of developing JD infection. RESULTS: Calves fed CR at birth were less likely (hazard ratio = 0.559) to become infected with MAP (as determined by use of an ELISA, bacterial culture, or both diagnostic tests), compared with the likelihood for calves fed MC at birth. CONCLUSIONS AND CLINICAL RELEVANCE: This study revealed that feeding CR reduced the risk of developing MAP infection in Holstein calves born in JD-endemic herds, which implied that feeding raw bovine MC may be a source of MAP for calves. Plasma colostrum-replacement products may be an effective management tool for use in dairy herds attempting to reduce the prevalence of JD.

Johne's disease in a free-ranging white-tailed deer from Virginia and subsequent surveillance for Mycobacterium avium subspecies paratuberculosis.

Johne's disease (paratuberculosis) was diagnosed in a 2-yr-old, male, free-ranging white-tailed deer (Odocoileus virginianus) from Fauquier County, Virginia, USA, based on histopathology and culture for Mycobacterium avium subspecies paratuberculosis. Clinical and pathologic findings included emaciation; loss of body fat; chronic diarrhea; severe, chronic, diffuse granulomatous colitis with intrahistiocytic acid-fast bacilli; moderate, chronic granulomatous lymphadenitis with intrahistiocytic acid-fast bacilli; as well as moderate chronic, multifocal, lymphoplasmacytic hepatitis. These findings are consistent with previous reports of Johne's disease in cervids. Subsequent targeted surveillance of 10 emaciated deer with diarrhea, as well as sampling of 72 asymptomatic deer for M. avium subsp. paratuberculosis using culture of multiple tissue types, as well as serology using an enzyme-linked immunosorbent assay (ELISA) optimized for cervid antibody detection, did not reveal any additional cases of infection in this geographic region. To date, this appears to be an isolated case of Johne's disease in a free-ranging white-tailed deer, and infection with the causative agent for Johne's disease appears to be an infrequent occurrence in deer from this region. The origin of infection was most likely domestic ruminants. This is the first report of clinical Johne's disease in a free-ranging white-tailed deer outside of the Florida Keys, USA. Stressors, such as high deer population density and low selenium levels, may have contributed to the development of clinical disease in this case and warrant further investigation.

Pasteurization of colostrum reduces the incidence of paratuberculosis in neonatal dairy calves.

In the present study, the potential benefits of feeding pasteurized colostrum were demonstrated in calves born to dams naturally infected with Mycobacterium avium ssp. paratuberculosis. Calves were separated at birth from their dams and randomly allocated into a group fed either the colostrum of their dam (DC; n = 6), followed by feeding the milk of the dam for 3 wk and then milk replacer, or into a group fed pooled pasteurized colostrum (PC; n = 5) from healthy noninfected dams, followed by milk replacer. At 6 wk of age, calves were weaned onto calf starter, housed together, and fed in a similar manner throughout the rest of the 12-mo study. Calves were necropsied at the end of the study, and 25 tissue sites were sampled from each animal and cultured for M. avium ssp. paratuberculosis. Sixteen of the 25 tissue sites were positive for calves across both treatment groups, with 14 of the 16 tissue sites positive for DC calves and 9 of the 16 tissue sites positive for PC calves. The degree of colonization within a tissue was low and variable for calves within treatment groups, and fecal shedding of M. avium ssp. paratuberculosis was minimal during the 12-mo study. As a measure of the early immune response to infection, blood obtained from calves was stimulated in vitro with M. avium ssp. paratuberculosis antigen preparations, and IFN-Upsilon secretion was measured. Antigen-specific IFN-Upsilon was consistently greater throughout the study in DC calves (0.95 +/- 0.19) compared with PC calves (0.43 +/- 0.10). Although long-term benefits are unknown, these results indicate that feeding a source of colostrum from paratuberculosis-free dams may decrease the initial exposure of neonates to M. avium ssp. paratuberculosis, perhaps decreasing dissemination of infection over time.

Progress in national control and assurance programs for ovine Johne's disease in Australia.

Since the detection of ovine Johne's disease in Australia in 1980, 578 flocks have been diagnosed as infected, with 442 of these still infected. The disease was initially believed to be confined to the central tablelands area of NSW, but has subsequently been shown to be more widely distributed. Sheep strains of M. paratuberculosis are known to infect sheep and goats in south-eastern Australia. Although sheep strains have recently been identified in some cattle in Australia, epidemiological evidence to date supports the distinction between ovine Johne's disease, caused by sheep strains in sheep and goats, and bovine Johne's disease, caused by cattle strains in cattle, goats and alpaca, as a basis for control and eradication strategies. Four national initiatives to control and better understand OJD are outlined. The Australian Johne's Disease Market Assurance Program for sheep was launched in May 1997. By December 1998, 548 flocks had achieved an assessed negative status. Three flocks assigned a flock status have subsequently been found to be infected. National standards for State control of Johne's disease through zoning, movement controls and procedures in infected and suspect flocks have also been developed. In addition, a $40.1 m National Ovine Johne's Disease Control and Evaluation Program was agreed to in August 1998, and is currently being implemented. It is jointly funded by National and State industries, and Commonwealth and State governments. Its objectives are to deliver, through research and surveillance, a solid basis for a future decision on the most appropriate course for dealing with OJD and to maintain control of OJD nationally.

Herd testing to control bovine Johne's disease.

In 1996, the cattle industries and government in the Australian state of Victoria established a Johne's disease (JD) test and control program under which participating farmers are provided with an annual ELISA test of their adult herd and advice on disease control that is tailored to their farm. The program is delivered through private veterinarians under contract with the government. There are over 600 herds enrolled in the program and about one third of these have had three or more whole herd tests. This paper provides a review of the program to date. It describes changes in ELISA reactor rates and numbers of clinical cases, and provides evidence for progress in the program.

Progress in national control and assurance programs for bovine Johne's disease in Australia.

Cattle strains of Mycobacterium paratuberculosis are known to infect cattle, goats and alpaca in southeastern Australia, where there are also significant numbers of farmed deer. Although sheep strains have recently been identified in some cattle in Australia, epidemiological evidence to date supports the distinction (between bovine Johne's disease (JD), caused by cattle strains in cattle, goats and alpaca, and ovine JD, caused by sheep strains in sheep and goats) for the purposes of control and assurance programs. The National Johne's Disease Control Program is coordinated by the Australian Animal Health Council, working with the livestock industries and with the Commonwealth, state and territory governments. The council also brokers industry and government funding for the program. The National Johne's Disease Market Assurance Program for Cattle was launched in 1996 as the first of a suite of voluntary national market assurance programs (MAPs) to assess and certify herds as negative for JD. By December 1998, over 550 herds had achieved an assessed negative status. A MAP was also launched for alpaca in 1998 and a program for goats should be finalized in early 1999. National standards for state control of JD through zoning, movement controls and procedures in infected and suspect herds have also been developed. The paper covers factors affecting development and implementation, uptake of and improvements to national control and assurance programs for bovine JD in Australia.

Accidental self-inoculation with Mycobacterium paratuberculosis bacterin (Johne's bacterin) by veterinarians in Wisconsin.

We surveyed Wisconsin veterinarians to assess the frequency and severity of accidental self- and other human exposure to Mycobacterium paratuberculosis bacterin (Johne's bacterin). Of 199 veterinarians administering the bacterin to cattle, 22 reported one or more exposures, including 19 needle-stick exposures, 8 skin surface exposures, and 2 oral mucosa exposures. The mean incidence of needle sticks was 5.5/100 veterinarians/year of bacterin use or 1/1,000 doses administered. The mean total doses given in the needle-stick exposure group was 276 +/- 318 vs 80 +/- 268 in the group without needle-stick exposure, and the mean number of months administering the bacterin was 21.7 and 16.1, respectively; 63% of needle-stick exposures took place during the injection process. Five adverse reactions were reported, and each resulted from needle-stick exposure. The only systemic reaction followed an exposure to the original bacterin formulation of sonically ruptured M paratuberculosis in Freund incomplete adjuvant. The remaining reactions were to the current formulation of whole killed M paratuberculosis in mineral oil and ranged from a small nodule persisting for 4 to 6 months to painful inflammation of a finger persisting for 24 months. We anticipate an increase in incidence of these minimally debilitating injuries as the use and distribution of the bacterin expands. For hand wounds, we recommend conservative management. Surgical intervention should be considered if a granuloma persists and causes the patient functional difficulty.