Possible Airborne Person-to-Person Transmission of Mycobacterium bovis — Nebraska 2014–2015

Mycobacterium bovis, one of several mycobacteria of the M. tuberculosis complex, is a global zoonotic pathogen that primarily infects cattle. Humans become infected by consuming unpasteurized dairy products from infected cows (1,2); possible person-to-person airborne transmission has also been reported (3). In April 2014, a man in Nebraska who was born in Mexico was determined to have extensive pulmonary tuberculosis (TB) caused by M. bovis after experiencing approximately 3 months of cough and fever. Four months later, a U.S.-born Hispanic girl from a nearby town who had been ill for 4–5 months was also determined to have pulmonary TB caused by M. bovis. The only social connection between the two patients was attendance at the same church, and no common dietary exposure was identified. Both patients had pulmonary cavities on radiography and acid-fast bacilli (AFB) on sputum-smear microscopy, indicators of being contagious (4). Whole-genome sequencing results of the isolates were nearly indistinguishable. Initial examination of 181 contacts determined that 39 (22%) had latent infection: 10 (42%) of 24 who had close exposure to either patient, 28 (28%) of 100 who were exposed to one or both patients in church, and one (2%) of 57 exposed to the second patient at a school. Latent infection was diagnosed in six contacts on follow-up examination, 2 months after an initial negative test result (4), for an overall latent infection rate of 25%. No infected contacts recalled consuming unpasteurized dairy products, and none had active TB disease at the initial or secondary examination. Persons who have M. bovis TB should be asked about consumption of unpasteurized dairy products (2), and contact investigations should follow the same guidance as for M. tuberculosis TB (4).

In April 2014, patient A, a man aged 42 years who was born in Mexico sought care for cough, fever, weight loss, and progressive debilitation over approximately 3 months. He had arrived in Nebraska from Mexico in 2010, and initially he worked on a dairy farm* and later in construction. No information was collected regarding his prior employment in Mexico, but he did report frequent consumption of raw milk. Chest radiography was consistent with advanced TB with cavities; numerous AFB were reported from sputum-smear microscopy. The result from nucleic acid amplification testing of sputum was positive for M. tuberculosis complex. The isolate was resistant both to pyrazinamide (PZA), which suggested that the infection was caused by M. bovis, and to low-concentration isoniazid (INH) (5). His treatment regimen was adjusted in consultation with national experts in drug-resistant TB. He recovered slowly and remained isolated at home until results from sputum smears were negative for AFB in August.

In June 2014, patient B, a Hispanic girl aged 16 years, who was born in Nebraska to Mexican parents, sought medical care after 2–3 months of cough. She initially received treatment for presumed bronchitis and allergies, without chest radiography. She remained ill through late July, when radiography revealed a pulmonary cavity and her sputum smear had numerous AFB. M. bovis resistant to PZA was identified after culture confirmation. She had never traveled outside the United States and was unaware of having consumed any dairy products from Mexico. She recovered quickly and remained in isolation at home until late September. The only social connection between patients A and B was regular attendance at the same church. The patients knew one another but their interactions were reported to be minimal.

Contact investigations were conducted in accordance with published guidelines (4) focusing on household contacts of both patients, community contacts at both the church and patient B’s school, coworkers of patient A, and persons who spent extended periods in a vehicle with him. Potentially exposed health care workers were notified for follow-up at their respective facilities with a request to report infections to the health department if identified. Tuberculin skin tests (TST) and interferon gamma release assays (IGRA) were used for testing U.S.-born and foreign-born contacts, respectively; IGRA was used for all members of the church, where the majority of contacts were foreign born. Contacts whose initial results were negative, but whose exposure to either patient had ended <2 months before testing, were retested after 8–12 weeks, because immune sensitivity might not be detectable during this period after new infection (4). Persons who had positive test results indicating infection had chest radiographs to exclude active TB disease and thus establish latent infection (4).^† All contacts were asked about their country of birth except those at a school attended by patient B where all were assumed to have been born in the United States. Midway through the investigation, after M. bovis was recognized as the causative agent, contacts who had positive test results were also asked about travel abroad and consumption of unpasteurized dairy products from Mexico.

Twenty-four persons had extended close exposure to either patient and were regarded as high-priority contacts (4); among these, 10 (42%) had positive results at initial testing (Table 1). Two were non-Hispanic U.S.-born contacts of patient A who did not attend the church. Among 11 high-priority contacts of patient B, seven were family members who were also potentially exposed to patient A at the church. Among patient B’s five siblings, four were born in the United States, had never traveled abroad, and did not recall consuming dairy products from Mexico; three of these four siblings were infected. Patient B’s eldest sibling and mother, both of whom were born in Mexico, were also infected but neither had active TB disease and thus would not have been infectious. Among 100 church members (excluding patient B and high-priority contacts of either patient), 28 (28%) had latent infection, including five U.S.-born children. Among 57 school contacts, one U.S.-born child was infected. No infections among exposed health care workers were reported.

Among 77 persons for whom retesting was indicated, 56 (73%) were retested, and six (11%) were determined to have latent infection (Table 2). During the interval between the first and second tests, none had traveled abroad or recalled eating unpasteurized dairy products from Mexico. No school contacts were retested, because their exposure had ended the previous May. No infected contacts had active TB disease, and all were offered a 4-month rifampin preventive regimen.^§

Patient A’s bacterial isolate, grown at a private hospital laboratory from a sputum sample collected April 24, 2014, was sent to the Nebraska Public Health Laboratory to facilitate genotyping at the Michigan state laboratory and first-line drug susceptibility testing at Associated Regional and University Pathologists, Inc.; second-line drug susceptibility testing was conducted at CDC. Patient B’s isolate was cultured by Nebraska Public Health Laboratory from a sputum sample collected during early August, and it was similarly sent for first- and second-line drug susceptibility testing and genotyping. Routine genotyping results of both patients’ isolates were indistinguishable. In late September 2014, both patients’ isolates were sent to the United States Department of Agriculture National Veterinary Services Laboratories (NVSL) where whole-genome sequencing was performed. Results suggested that the two patients’ isolates were closely related; phylogenetic comparisons differed by only three single nucleotide polymorphisms (SNPs). The sequences did not match others in NVSL’s library, but the isolates shared a common ancestor with isolates from five cattle in Mexico.^¶

Corresponding author: Bryan F. Buss, feu7@cdc.gov, 402-471-8820.

¹Career Epidemiology Field Officer Program, Division of State and Local Readiness, Office of Public Health Preparedness and Response, CDC; ²Division of Public Health, Nebraska Department of Health and Human Services; ³Northeast Nebraska Public Health Department, Wayne, Nebraska; ⁴Elkhorn Logan Valley Public Health Department, Wisner, Nebraska; ⁵Field Services and Evaluation Branch, Division of Tuberculosis Elimination, National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention, CDC; ⁶Department of Pathology and Microbiology, University of Nebraska Medical Center; ⁷Nebraska Public Health Laboratory, University of Nebraska Medical Center; ⁸USDA National Veterinary Services Laboratories, Ames, Iowa.

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TABLE 1. Investigation setting and results of initial testing* of contacts (N = 181) exposed to one or both of two Mycobacterium bovis tuberculosis patients, by United States versus foreign birth — Nebraska, 2014

Abbreviation: NA = not available.
* Tuberculin skin tests and interferon gamma release assays (IGRA) were used for testing U.S.-born and foreign-born contacts, respectively; IGRA was used for all members of the church where the majority of contacts were foreign born.
^† The counts in the four categories of settings are mutually exclusive. Among the 13 high-priority contacts of patient A, 11 did not attend the church. Among the remaining two who were also potentially exposed to patient B at the church, one tested positive (patient B’s grandfather). Among the 11 high-priority contacts of patient B, all were also potentially exposed to patient A at the church. Patients A and B were not counted as contacts for any setting.
^§ Non-Hispanic U.S.-born adults exposed at patient A’s residence.
^¶ Three Hispanic siblings of patient B (aged 7, 9, and 10 years).
** Six U.S.-born children. Unknown travel and dietary history.
^†† Countries of birth are Mexico (n = 26), Guatemala (n = 1), and Philippines (n = 1).
^§§ All 39 persons testing positive reported no knowledge of a prior positive TB test result, but information was lacking to verify the accuracy of their recall.

TABLE 2. Investigation setting and results of follow-up testing* performed 8–12 weeks after last potential exposure and after an initial negative result for contacts (N = 56) of one or both of two Mycobacterium bovis tuberculosis patients — Nebraska, October 2014

* An interferon-gamma release assay was used for testing at the church where foreign-born persons predominated and for other foreign-born contacts. Tuberculin skin tests were used for U.S.-born contacts.
^† Follow-up testing was not necessary for contacts at patient B’s school because the end of their exposure was >2 months before the investigation.
^§ Non-Hispanic U.S.-born individual exposed at patient A’s residence who reported no international travel at any time and no consumption of Mexico-origin unpasteurized dairy products. This person had no affiliation with the church or the school and reported no contact with patient B, who resided in a different town.
^¶ All three were patient B’s family members who were also potentially exposed to patient A at the church.
** All six denied both international travel and consumption of Mexico-origin unpasteurized dairy products in the interim. Among these, three were foreign born (two high-priority contacts of patient B and one church member).