The public health investigation may identify animals especially livestock and captive wildlife with an epidemiological link to the infectious patient. In North Dakota and Wisconsin, the public health agency alerts their animal health partners and a One Health investigation may be deemed necessary. All information on the human cases contained in this paper was collected during the normal process that occurs in these states when humans with TB are detected.
Whole genome sequences were obtained from both animal health and public health investigations. Briefly in step one, sequences were aligned to a reference; those identified as M. The variant call format vcf files created in step one were then added to a database of vcf files and step two was initiated which filters or flags unreliable and low quality variant calls, as well as groups sequences into user defined clades according to relatedness by identifying common SNPs.
The annotated and position referenced SNP tables allow for quick error identification and correction. The trees were then manually compared to the SNP table to ensure accuracy of the model. Supplementary File 1 lists the accession numbers for the publicly available sequences from previous studies 17 , 43 , Three cases met the criteria for inclusion, two M. Those cases are described in detail below. The case-patient, a man born in Mexico, had been recently diagnosed with another medical condition that likely suppressed his immune system resulting in active TB disease.
The case-patient worked for the dairy for at least 3 years prior to his diagnosis. During this time, he worked for 9 consecutive months then returned to Mexico for the remaining 3 months each year. During his employment, the case-patient worked with all ages of dairy cattle.
NDDOH tested three household contacts to the case-patient. The North Dakota operation housed dairy cattle and beef cattle. Beef and dairy heifers were often commingled for a few months each year. While the operation had no record of TB skin testing in the dairy or beef herds in the recent past, cull dairy and beef cattle from this operation were slaughtered at abattoirs with high granuloma submission rates for TB surveillance. All cows and heifers 6 months of age and older were tested using standard protocol of the caudal fold tuberculin CFT test in series with the comparative cervical tuberculin CCT test.
Upon necropsy, multiple micro abscesses were identified in a normal appearing mediastinal lymph node that was culture-positive for M. Samples were collected from all 10 cows and although no gross lesions were identified, samples were submitted for culture at NVSL. Representative, normal appearing lymph nodes from the head and thorax were submitted from ND3; these tissues were histologically negative for evidence of mycobacterial infection, but M.
Tissue from the post-mortem exam and the ear tags were DNA tested to confirm they were from the same animal and no errors were made during sampling, labeling, or processing.
Over the course of testing, approximately 40 cattle were removed from the herd and no additional infected cattle identified. Whole genome sequencing was conducted and the infected pregnant heifer ND1 had the identical strain to the dairy employee with active TB disease Figure 1 ; see Supplementary File 1 for SNP table.
Mycobacterium bovis was not detected in the beef cattle. The infected dairy cattle were born and raised on the dairy operation. Two herds with fence line contact were tested and no infected animals were detected.
Additionally, surveillance was conducted on barn cats, wild rodents, and hunter harvested deer with no disease detected. North Dakota Game and Fish Department conducted surveillance in the fall of on hunter-harvested deer and no lesions were identified. After a thorough investigation, no other possible sources of M. Figure 1. Maximum likelihood phylogenetic tree illustrating the genetic relationship between M. The color key indicates the origin of the cattle from which M. The human isolate is shown in red.
The scale bar represents a branch length of 10 SNPs. The tree is rooted to the reference genome M. The case-patient reportedly became ill in March before seeking medical care in early April. The case-patient presented in the emergency room with night sweats, cough, and fever.
Culture revealed the case-patient was infected with M. The case-patient was placed in respiratory isolation and started on a standard four-drug regimen Due to severe cavitary disease, the case-patient was treated with TB medications for a full year, with directly observed therapy for the entire course.
The case-patient was released from isolation in July when determined to no longer be contagious. The individual is believed to have become infected while previously living in a Latin-American country where M. Public health conducted a routine contact investigation that included TB risk assessment and testing of close contacts to the patient. No additional cases of infectious TB were identified in household or farm employee contacts.
Like the ND herd, all cows and heifers 6 months of age and older were testing using the CFT test and CCT-test in series, with no infected animals detected. A single CCT-suspect cow from this first test was euthanized and necropsied with no lesions identified. In September , the herd was tested a second time and was again test negative for bTB with no CCT-positive animals detected. In September , slaughter plant surveillance detected tuberculosis in a carcass from a cow that traced back to this herd, and M.
Seven infected cows were identified during this initial test based on culture of M. Two additional infected cattle were detected during herd testing in March , one infected cow was identified at slaughter in April , and one cow was detected following herd testing in June Since the detection of the herd as infected, more than 1, cows have been examined for bTB by either necropsy or slaughter surveillance.
One of the infected cows was test-negative and detected at slaughter. At the time of this writing, the herd has had a total of 12 cows, including the slaughter case, detected as infected with M.
The public health follow-up with farm employees continues until the farm is released from quarantine. Testing of source herds for purchased cattle added to the Wisconsin herd were not conducted since the epidemiologic investigation and WGS supported the human case-patient as the source of introduction into the herd. Figure 2. The scale bar represents a branch length of 15 SNPs. In early , a 1-day-old heifer calf from a dairy in New Mexico was transported to Texas where import regulations require post-import TB testing of cattle younger than 2 months of age that move into the state.
The heifer was raised at a facility in Texas and was TB test positive in April at approximately 4 months of age. There were no gross or microscopic lesions suggestive of MTBC infection. Mycobacterium tuberculosis was cultured from the retropharyngeal lymph node collected at necropsy and results were reported in June The heifer calf isolate grouped with sublineage 4.
The Texas Department of State Health Services DSHS conducted a source case investigation to determine if an infectious TB suspect had been identified by public health; however, a source case was not identified. Personnel from DSHS discussed the situation with dairy management, and a dairy employee was identified who exhibited signs and symptoms of TB but was no longer employed at the dairy.
Whole genome sequencing of human cases was just being implemented by the Centers of Disease Control and Prevention, and consequently, the previous human cases in this area had not been sequenced. However, both the calf and three adults in the region that were diagnosed in and 46 had a matching, rather rare spoligotype for Texas, with an octal code No employees were tested, but DSHS conducted symptom screening and provided education for the current employees.
We were unable to retrospectively obtain WGS from any of the Texas human cases to include in this report. The three cases presented here are the first formal reports of MTBC transmission from humans to cattle in the United States since In both the North Dakota and Wisconsin cases, the human TB case-patients were exposed to cattle on the operation prior to or at the time bTB was discovered in the cattle.
In the North Dakota case, bTB was detected in three dairy cattle within 2 months after the human was diagnosed; in the Wisconsin herd, it was 3 years between the human TB detection and the herd detection.
When bTB-affected herds in the United States are identified, state, and federal animal health agencies conduct epidemiologic investigations to determine the probable source of disease and trace any animals that left the herd to control disease spread. Historically, in the United States the most common sources for bTB infection in cattle have been other infected cattle.
The exception to this is in several counties in Michigan where bTB is endemic in the wild white-tailed deer population. Investigations in Michigan have identified deer as the most common source of infection in cattle Animal health authorities conduct interviews with herd owners to determine all potential routes of exposure, including sources of all purchased cattle over a multiyear period and any contact with cattle from other operations, including fence-line contact.
These exposures are investigated, and all cattle contacts are tested to determine their bTB status per Bovine tuberculosis eradication uniform methods and rules Additionally, most adult cattle that leave dairies undergo inspection at slaughter for bTB, which is the method by which most infected herds are identified. Inspection of carcasses at slaughter, or slaughter surveillance has been an effective method of detecting bTB in cattle in the United States.
This is highlighted by the WI herd being detected by slaughter surveillance and subsequently, having a test-negative, infected cow that was detected at slaughter.
Both the ND and WI herds sent animals to slaughter prior to bTB detection and they continue to do so on a routine basis, providing additional surveillance for bTB. The results of the North Dakota investigation suggest it is highly unlikely that cattle in the herd could have transmitted M. The progression of disease in ND1 appeared to be relatively recent given the finding of M. In the Wisconsin case, the case-patient was diagnosed with TB within 2—3 months of employment.
Although M. Most of the knowledge of TB in humans is based on infection with M. If the cattle were the source of the human infection, one would expect the farm family members to be exposed and potentially infected. The housemates of the patient were exposed to the patient and so it was expected that some or all of them would be infected. None of the patient's housemates were actively shedding M.
The North Dakota dairy herd has been tested 9 times since , with only the three infected cows detected at the first herd test, despite this additional testing. Only one of those three infected cows ND1 had a small gross lesion associated with bTB infection.
The WGS of the M. Significant epidemiological evidence supports the transmission of M. Evidence includes the degree of illness in the employee with active TB disease e.
Based on the epidemiological and laboratory evidence, the human was considered the most likely source of disease in the cattle by both animal and public health officials investigating the case. The last cow, ND3, had normal appearing lymph nodes that were histologically negative but culture positive. While it is impossible to guarantee that a herd will remain clear of disease, it is possible to reduce the risk of disease by the following means:.
The following web pages may be useful for those interested in finding out more about Bovine Tuberculosis. What is Bovine Tuberculosis TB? Topics: Animal Health and Welfare. Bovine Tuberculosis. Farming industry providers. Meat processors. Information providers. Tag manufacturers. Accreditation for farming industry providers. NAIT user guides for farming industry providers. TB and pest control.
Pest control operations in the regions. Our programmes. The NAIT programme. The TBfree programme. Follow us. The disease is more prevalent in most of Africa, parts of Asia and the Americas. Many developed countries have reduced or eliminated bovine TB from their cattle population; however, significant pockets of infection remain in wildlife in Canada, the United Kingdom, the United States and New Zealand.
Until the s when control measures began in developed countries, TB was one of the major diseases of domestic animals throughout the world. Today it remains a major disease of cattle and wildlife.
For many years the control of bovine TB has focused on the control of bovine TB in domestic cattle herds. This has been through whole herd skin testing, slaughter surveillance and monitoring the movement of animals between herds. If the bcg vaccine is used then it is impossible to differentiate between cattle that have TB and cattle that have been vaccinated. In addition in there started to be a worldwide shortage of the bcg vaccine.
The pasteurization of milk and other dairy products has been important in preventing the spread of the disease to humans.
Pasteurization means heating the milk to a sufficient temperature that any bacteria in the milk will be killed. These are as varied as:. In these instances it has been assumed that livestock, usually cattle, served as the initial source of infection for different wildlife species. It has however been unclear when this may have happened. The wildlife were then able to maintain the disease in their free ranging populations until contact between livestock and infected wildlife allowed the disease to be transmitted back to the livestock.
So this allows the disease to continue whatever action is taken with infected cattle herds.
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