New Evidence for Person-to-Person Spread of Bovine TB

BIRMINGHAM, England, April 13 -- Six matching cases of tuberculosis here in 2005 originated from one person's exposure to bovine TB, strongly suggesting a rare cluster of human-to-human spread, researchers reported.

Despite a recent resurgence of bovine tuberculosis in British cattle herds, no associated increase in human cases had been noted until now, wrote Jason T. Evans, M.Sc., of Birmingham Heartlands Hospital, and colleagues, in the April 14 issue of the Lancet.

In the past, human mycobacterium bovis infection occurred in older patients after drinking unpasteurized milk, the researchers said.

In San Diego, from 1994 through 2000, 7% of human tuberculosis was caused by M bovis, and 90% of cases were in Mexican-born immigrants or U.S.-born Hispanic children. These cases wee associated with consumption of unpasteurized dairy products from Mexico, said Charles O.Thoen, D.V.M., Ph.D., of Iowa State University and Philip A. LoBue, M.D., of the University of California at San Diego, in an accompanying commentary.

More recently, in New York, M bovis was isolated from 35 patients with tuberculosis, also among Mexican-born immigrants or U.S.-born Hispanic children, also associated with consumption of unpasteurized dairy products from Mexico.

The new British cases came to light after identification of two epidemiologically linked cases of human M bovis infection through routine laboratory and surveillance activities.

Following this, 20 patients identified with M bovis infection in the Midlands from 2001 to 2005 were assessed by DNA fingerprinting (MIRU-VNTR and spoligotyping), with additional contact tracing and interviews for patients with the clustered strain. Contact tracing found no further cases.

Of these 20 cases, six genetically indistinguishable cases were identified. All these cases were young and British-born. Five patients had pulmonary disease, and one patient died due to M bovis meningitis, with four patients possessing factors predisposing to tuberculosis.

All patients lived within 10 miles of the center of Birmingham and had common social links through visits to bars and nightclubs in two different areas. Five of the six patients were male, with a mean age at diagnosis of 31.7 years. One patient was a household contact.

Four patients reported predisposing factors for tuberculosis, including steroid use, alcohol misuse, insulin-dependent diabetes, and HIV infection.

However, only one patient had a history of occupational contact with cattle and consumption of unpasteurized milk and cheese. But with the exception of this case, there was an absence of zoonotic links or consumption of unpasteurized dairy products.

The cluster occurred in an urban setting in a group of six relatively young patients. The data obtained by extensive conventional epidemiological investigations suggest that person-to-person transmission had occurred, the researchers said.

Transmission and subsequent disease were probably from a combination of host factors (heavy use of steroids and alcohol and HIV infection, for example) and environmental factors, such as prolonged and repeated contact in a confined, poorly ventilated, dark environment with noise and smoke resulting in coughing, the researchers said.

The outbreak reported here, the researchers said, shows that human cases of M bovis are not restricted to agricultural settings and can behave like M tuberculosis in the human population. Prospective surveillance and DNA fingerprinting identified this cluster, enabling health protection teams to set up control measures preventing further transmission, they said.

However, similar outbreaks of M tuberculosis and to a lesser extent M bovis are possible unless public-health control measures are instituted and maintained, they said. Additionally, the control program for bovine tuberculosis needs to continue.

In discussing the study limitations, the investigators wrote that the most likely explanation for the outbreak is that one person became infected with bovine tuberculosis from an environmental source and that a series of person-to-person transmissions occurred, However, they said, the direction of the transmission could not be confirmed, and additional cases and potential sources of infection might not have been identified.

Despite apparent transient social contacts between patients, there did not seem to have been any transmission to more immediate household contacts, they said.

Other limitations included the possibility of exposure recall bias, although it is unlikely that all these cases stemmed from an environmental source, they said.

It is reasonable to suggest that opportunities for human exposure exist as long as bovine tuberculosis remains endemic in cattle and wildlife reservoirs in parts of the Britain. In addition, they said, once transmitted, M bovis might be more likely to establish disease in people who are immunocompromised.

Referring to the successful public-health measures used in this investigation, the researchers emphasized the need to use all testing and surveillance systems, DNA fingerprinting, and inter-agency collaboration, rather than viewing each case as an individual zoonotic infection.

In the accompanying commentary, Drs. Thoen and LoBue wrote that reliable information is not generally available on the incidence of M bovis tuberculosis, especially in developing countries where the necessary diagnostic technology is not widely available.

The role of person-to-person airborne transmission in the spread of M bovis is controversial, they said. However, the report by Evans and colleagues is the "best documented" instance of multiple events of the probably person-to-person transmission, they wrote.

This information, they said, could have important implications in places such as sub-Saharan Africa, where HIV infection is prevalent, M bovis infection in cattle can be enzootic, and where pasteurization is not common.

In addition to measures to control infection in cattle, it is important, they wrote, to encourage pasteurization of dairy products, concentrate efforts in countries where HIV is endemic, and use standard public health measures to stop airborne human spread.

Finally, they said, measures should be developed to identify and control M bovis infection in wild animals, which might be an important source of infection for domesticated food-producing animals.