In the JournalsPerspective

Nebraskan cases suggest airborne person-to-person transmission of M. bovis

Contact investigations of two pulmonary tuberculosis cases resulting from Mycobacterium bovis infection suggest that multiple instances of potential airborne transmission may have contributed to the bacterium’s spread among Nebraskan residents.

M. bovis is a zoonotic pathogen responsible for pulmonary infection in cattle, but also is capable of spreading to deer, humans and other mammals, according to an MMWR study. Human M. bovis and M. tuberculosis are clinically indistinguishable, but require unique regimens due to inherent treatment resistances.

“Human M. bovis disease is typically attributed to consumption of unpasteurized milk (or dairy products made from unpasteurized milk) in or imported from countries with affected cattle herds,” researchers wrote. “Person-to-person airborne transmission of M. bovis has been reported infrequently, with uncertainty remaining about dietary exposures.”

Airborne transmission likely in some cases

In April 2014, a Nebraskan man aged 42 years who emigrated from Mexico in 2010 sought care for persistent cough, fever, weight loss and progressive debilitation. Nucleic acid amplification testing of sputum suggested pulmonary TB resulting from M. bovis. The man reported being currently employed on a dairy farm, as well as frequent consumption of raw milk.

Two months later, a girl aged 16 years who was born in Nebraska also sought medical care for persistent cough, which was eventually diagnosed as M. bovis TB. The patient reported no history of international travel and no memory of consuming Mexican dairy products.

Cultures grown from the patients’ sputum samples revealed the two isolates to be indistinguishable, with later whole-genome sequencing results suggesting that the two were closely related and shared a common ancestor with isolates collected from Mexican cattle. The only social connection identified between the patients was attendance at the same church, where their interactions were reported as minimal.

Contact investigations of household, community and work acquaintances found 24 individuals with extended close exposure, 10 of whom were determined to have latent infection. Another latent infection was detected among 57 school contacts of the second patient, while 28 of 100 individuals exposed to either patient at the church also showed infection. Two months after initial testing, follow-up examination of these contacts identified six more infections, resulting in an overall latent infection rate of 25%.

An investigation of possible transmission events suggested that airborne transmission was likely in approximately one-third of the identified infections, the researchers wrote, but unrecognized consumption of imported dairy products carrying the pathogen should not be ruled out.

“This report adds to the evidence for airborne person-to-person spread of M. bovis,” the researchers wrote. “Public health responses to M. bovis pulmonary TB should be the same as those for M. tuberculosis TB, with the additional inquiries about consumption of unpasteurized dairy products. The ongoing incidence of M. bovis TB in humans substantiates the need to control bovine tuberculosis globally and to pasteurize all milk and dairy products.”

M. bovis TB rises in California

M. bovis has gradually become a greater concern in other states such as California, where resulting TB cases appear to have increased, according to a retrospective review published last year in Emerging Infectious Diseases.

Using data from the state’s TB registry collected from 2003 to 2011, researchers identified culture-confirmed patients whose initial drug susceptibility results demonstrated resistances akin to M. bovis. They reviewed the registry for sociodemographic, clinical and treatment outcome information for all patients, and conducted bivariate analysis of these patient characteristics.

They found that the proportion of TB cases in California for all ages caused by M. bovis increased from 3.4% of 2,384 cases in 2003 to 5.4% of 1,808 cases in 2011 (P = .002), an increase over the 1% to 2% of TB cases in the U.S. reportedly attributable to M. bovis infection. In multivariate analysis, the researchers determined independent associations between M. bovis disease and Hispanic ethnicity, extrapulmonary disease, diabetes and immunosuppressive conditions. Also of note, all six cases of M. bovis disease in children during 2010 and 2011 had at least one parent or guardian who was born in Mexico, as opposed to 38% of child case-patients with disease attributable to M. tuberculosis (P = .005).

“In California, there are ongoing interventions designed to limit the demand for and distribution of unpasteurized and contaminated dairy products, which are associated with M. bovis disease and other foodborne diseases,” the researchers wrote. “Elimination of human M. bovis disease in California likely requires further implementation of programs to reduce M. bovis contamination.” – by Dave Muoio

Disclosure: The researchers report no relevant financial disclosures.

Contact investigations of two pulmonary tuberculosis cases resulting from Mycobacterium bovis infection suggest that multiple instances of potential airborne transmission may have contributed to the bacterium’s spread among Nebraskan residents.

M. bovis is a zoonotic pathogen responsible for pulmonary infection in cattle, but also is capable of spreading to deer, humans and other mammals, according to an MMWR study. Human M. bovis and M. tuberculosis are clinically indistinguishable, but require unique regimens due to inherent treatment resistances.

“Human M. bovis disease is typically attributed to consumption of unpasteurized milk (or dairy products made from unpasteurized milk) in or imported from countries with affected cattle herds,” researchers wrote. “Person-to-person airborne transmission of M. bovis has been reported infrequently, with uncertainty remaining about dietary exposures.”

Airborne transmission likely in some cases

In April 2014, a Nebraskan man aged 42 years who emigrated from Mexico in 2010 sought care for persistent cough, fever, weight loss and progressive debilitation. Nucleic acid amplification testing of sputum suggested pulmonary TB resulting from M. bovis. The man reported being currently employed on a dairy farm, as well as frequent consumption of raw milk.

Two months later, a girl aged 16 years who was born in Nebraska also sought medical care for persistent cough, which was eventually diagnosed as M. bovis TB. The patient reported no history of international travel and no memory of consuming Mexican dairy products.

Cultures grown from the patients’ sputum samples revealed the two isolates to be indistinguishable, with later whole-genome sequencing results suggesting that the two were closely related and shared a common ancestor with isolates collected from Mexican cattle. The only social connection identified between the patients was attendance at the same church, where their interactions were reported as minimal.

Contact investigations of household, community and work acquaintances found 24 individuals with extended close exposure, 10 of whom were determined to have latent infection. Another latent infection was detected among 57 school contacts of the second patient, while 28 of 100 individuals exposed to either patient at the church also showed infection. Two months after initial testing, follow-up examination of these contacts identified six more infections, resulting in an overall latent infection rate of 25%.

An investigation of possible transmission events suggested that airborne transmission was likely in approximately one-third of the identified infections, the researchers wrote, but unrecognized consumption of imported dairy products carrying the pathogen should not be ruled out.

“This report adds to the evidence for airborne person-to-person spread of M. bovis,” the researchers wrote. “Public health responses to M. bovis pulmonary TB should be the same as those for M. tuberculosis TB, with the additional inquiries about consumption of unpasteurized dairy products. The ongoing incidence of M. bovis TB in humans substantiates the need to control bovine tuberculosis globally and to pasteurize all milk and dairy products.”

M. bovis TB rises in California

M. bovis has gradually become a greater concern in other states such as California, where resulting TB cases appear to have increased, according to a retrospective review published last year in Emerging Infectious Diseases.

Using data from the state’s TB registry collected from 2003 to 2011, researchers identified culture-confirmed patients whose initial drug susceptibility results demonstrated resistances akin to M. bovis. They reviewed the registry for sociodemographic, clinical and treatment outcome information for all patients, and conducted bivariate analysis of these patient characteristics.

They found that the proportion of TB cases in California for all ages caused by M. bovis increased from 3.4% of 2,384 cases in 2003 to 5.4% of 1,808 cases in 2011 (P = .002), an increase over the 1% to 2% of TB cases in the U.S. reportedly attributable to M. bovis infection. In multivariate analysis, the researchers determined independent associations between M. bovis disease and Hispanic ethnicity, extrapulmonary disease, diabetes and immunosuppressive conditions. Also of note, all six cases of M. bovis disease in children during 2010 and 2011 had at least one parent or guardian who was born in Mexico, as opposed to 38% of child case-patients with disease attributable to M. tuberculosis (P = .005).

“In California, there are ongoing interventions designed to limit the demand for and distribution of unpasteurized and contaminated dairy products, which are associated with M. bovis disease and other foodborne diseases,” the researchers wrote. “Elimination of human M. bovis disease in California likely requires further implementation of programs to reduce M. bovis contamination.” – by Dave Muoio

Disclosure: The researchers report no relevant financial disclosures.

    Perspective
    Russell Kempker

    Russell Kempker

    While the predominant means of M. bovis transmission is through unpasteurized dairy products, the recent article by Buss and colleagues provides convincing evidence of the airborne person-to-person transmission of M. bovis between two persons. The multiple lines of evidence supporting this include the high infectiousness of the source patient — as indicated by cavitary pulmonary disease — and sputum microscopy positive for acid fast bacilli, which provide the epidemiological links between the two persons and the genetic relatedness of the two M. bovis isolates. The second patient also had no known exposure to unpasteurized dairy products and thus no other obvious source of acquiring M. bovis disease. The conversion of latent TB tests from negative to positive among six contacts also strengthens the claim for airborne transmission.

    While this report illustrates the potential for M. bovis airborne transmission, available data suggest that this is not a major mode of disease spread in the United States. The report is important in that it highlights the need to gather further prospective data on the mode of M. bovis transmission by utilizing new and advanced tools, including whole-genome sequencing.

    M. bovis accounts for approximately 1% of TB cases in the United States, but in some geographic areas, including those on the U.S.-Mexican border, the organism is responsible for a greater burden of TB cases. This was shown by Gallivan and colleagues in a retrospective study of all TB cases in California. They found that M. bovis accounted for 3.4% of all TB cases in 2003 and 5.4% of cases in 2011, and among children accounted for nearly 25% of TB disease. All the children with M. bovis disease had parents from Mexico, and most had spent significant time there. The authors cite these findings to suggest spread of M. bovis from unpasteurized dairy products. Additional surveillance studies incorporating more detailed risk-factor assessment, including dairy product consumption along with whole genome sequencing of all M. bovis isolates, will help elucidate the modes of M. bovis transmission and help direct targeted prevention efforts.

    Reference:

    Gallivan M, et al. Emerg Infect Dis. 2015;doi:10.3201/eid2103.141539.

    • Russell Kempker, MD
    • Assistant professor of infectious diseases Emory University School of Medicine

    Disclosures: Kempker reports no relevant financial disclosures.

    Perspective
    Arnon Shimshony

    Arnon Shimshony

    Bovine TB, caused by M. bovis, a member of the Mycobacterium tuberculosis complex, is a major infectious, zoonotic disease among cattle worldwide. Other domesticated animals, and certain wildlife populations, are susceptible as well. Transmission to humans is mostly caused by the consumption of unpasteurized bovine milk, but occasionally by airborne transmission from human patients with bovine TB such as the case described in the current report. Among cattle, aerosol exposure to M. bovis is considered to be the most frequent route of infection, but infection by ingestion of contaminated material also occurs.

    In cattle, after infection, nonvascular nodular granulomas (tubercles) may develop. Characteristic TB lesions occur most frequently in the lungs and the retropharyngeal, bronchial and mediastinal lymph nodes. Lesions can also be found in the mesenteric lymph nodes, liver, spleen, on serous membranes and in other organs. In countries with TB eradication programs in cattle, clinical evidence of TB is seldom encountered because the intradermal tuberculin test (a delayed hypersensitivity reaction) enables presumptive diagnosis and elimination of infected animals before signs appear (applying the “test and slaughter” policy). Prior to the national TB eradication campaigns, however, clinical signs associated with TB were commonly observed, including weakness, anorexia, emaciation, dyspnea, enlargement of lymph nodes and cough — particularly with advanced TB. After death, infection is diagnosed by necropsy and histopathological and bacteriological techniques.

    M. bovis has been identified in humans in most countries where isolates of mycobacteria from human patients have been fully characterized. The incidence of pulmonary TB caused by M. bovis is higher in farm and slaughterhouse workers than in urban inhabitants. The transmission of M. bovis to humans via milk and its products is eliminated by the pasteurization of milk. One of the results of bovine TB eradication programs has been a reduction in disease and death caused by bovine TB in the human population.

    The rigorous application of tuberculin testing and culling of reactor cattle has eliminated M. bovis infection from farmed bovine populations in some countries, but this strategy has not been universally successful. During 2015, M. bovis was identified in two U.S.-based dairy herds: in Texas (January) and Michigan (April). Two beef herds were found to be infected in Michigan: one in July 2015 and more recently in January.

    In such cases, the reactive animals are culled, followed by repeated tuberculin tests applied periodically in all animals in the herd to allow the regaining of TB-free status. There is also a nationwide surveillance program in slaughter plants. If lesions consistent with TB appear on a carcass, a sample is sent to the National Veterinary Services Laboratories of the Department of Agriculture’s Animal and Plant Health Inspection Service for confirmation. The state officials will likely trace the movements of animals into and out of this herd in an effort to find the source of infection.

    Investigations of sporadic M. bovis reoccurrence have shown that wildlife reservoirs exist in some countries and can act as a source of infection for cattle, deer and other livestock. The risk that these reservoirs of infection constitute for domestic animals and humans is quite variable depending on the specific epidemiological situation for the species and the environment. The detection of infection in a wildlife population requires bacteriological investigation or the use of a valid testing method for the species involved (the tuberculin test is not effective in all species) together with epidemiological analysis of information. The badger in the United Kingdom and the Republic of Ireland, wild boar in Spain, the brush-tail possum in New Zealand and several wild living species in Africa have been shown to be capable of maintaining M. bovis infection. Control of transmission from the wildlife population to farmed species is complex and, to date, has relied on the reduction or eradication of the infected wildlife population. The use of vaccination to control the disease in some species continues to be investigated.

    M. bovis has been isolated from farmed and free-living cervidae (deer) and buffalo in North America. The disease may be subacute or chronic, with a variable rate of progression. A small number of animals may become severely affected within a few months of infection, while others may take several years to develop clinical signs, which are related to lesions in the animal. M. bovis in North American cervidae has been engaging animal health authorities for decades and continues to do so, and particularly challenges grazing cattle. The tuberculin test can be used in farmed deer.

    Human infection caused by M. bovis has been mostly, but not completely, eradicated in the U.S. by pasteurization of milk and culling of herds shown positive on tuberculin skin testing. M. bovis human infection continues to be reported, primarily in immigrants from countries where bovine TB remains endemic, such as in Latin America and Mexico, where many presumably acquired their infection.

    M. bovis circulation among humans deserves the attention of both human and animal health agencies. Testing of personnel in cattle plants will be helpful to exclude cases in cattle from human origin, a possible — and known — scenario.

    • Arnon Shimshony, DVM
    • Infectious Disease News Editorial Board member Associate professor at the Koret School of Veterinary Medicine Hebrew University of Jerusalem, Rehovot

    Disclosures: Shimshony reports no relevant financial disclosures.