More attention needed to M. bovis detection
Study shows forgotten pathogen in border states
Several years ago, when physicians at San Diego Medical Center diagnosed two unrelated patients on the same day with Mycobacterium bovis, they wondered if this more obscure member of the Mycobacterium tuberculosis (MTB) complex had experienced an undetected resurgence with the help of the AIDS epidemic and increased immigration from Mexico. Two studies have shown that M. bovis, indeed, is more prevalent than expected in their city, and their authors urge border states to be more vigilant in its detection.
One of the studies, presented at the Fourth Conference on Retroviruses and Opportunistic Infections in Washington, DC, in January, found that 17 of 97 or 17% of HIV-positive TB patients hospitalized at the hospital were infected with M. bovis.1
"Although this is a very selective population of patients who were hospitalized, it is quite a big percentage," says Franchesca Torriani, MD, lead author and assistant professor of medicine at the University of California at San Diego. "An increased incidence of bovine tuberculosis has recently been reported in San Diego . . . but what we think is happening more is that it’s just not being diagnosed as M. bovis but as MTB. (For information about other infections occurring on the West Coast, see story, above.)
A review of 73 patients treated at the hospital from 1980 to 1991 and published in Medicine found a similar high rate 12 of 42 adults among HIV-positive patients. It also found that 80% were of Hispanic origin. Non-Hispanic patients had either traveled extensively outside the United States or had relatives exposed to M. bovis, the authors note.1
The Centers for Disease Control and Prevention in Atlanta has been tracking cases of bovine TB in border states, says Steve Oseroff, MD, associate director of the National Center for Infectious Diseases. However, there is no evidence of a significant increase in M. bovis nor a need to require regular testing for it, mainly because the species responds well to MTB treatment, he says.
M. bovis was first described in the mid 1800s with the observation that tuberculosis lymphadenitis was seen more often in infants who were fed cows’ milk than those who were breast fed. M. bovis was distinguished from MTB in 1898 but was initially deemed harmless to humans a mistake that was corrected a decade later.2
With development of tuberculin testing, health officials in Europe began segregating TB-positive cows and destroying those that were infected. An aggressive bovine eradication program undertaken in the United States reduced the prevalence from 3.5% in 1917 to .06% in 1960.2
M. bovis, which is primarily transmitted to humans through unpasteurized cows’ milk but also can be spread through air, makes up less than 1% of mycobacterial isolates in this country. In the 12-year study, M. bovis accounted for 3% of TB cases in San Diego. There are little data for rates of M. bovis in Mexico, but because milk in rural areas is often not pasteurized, rates in humans are higher than in the United States, says Diane Havlir, MD, Torriani’s colleague at San Diego Medical Center.
"We have patients with M. bovis just because they visit family in Mexico that have different beliefs about pasteurization," she says. "The prevalence is really unknown because their labs don’t distinguish it, and they don’t have the same controls in this country that we have for M. bovis."
Most cases are reactivated disease
Although M. bovis can be spread from human to human, most cases in San Diego appear to be a reactivated disease. The fact that M. bovis is correlated with lower CD4 counts in the HIV-positive patients also suggests that most of the cases are not the result of new infection, Torriani explains.
Unlike MTB, bovine TB most frequently is manifested in the organs rather than the lungs, says Havlir. More than half of the 16 patients in the study had miliary TB. M. bovis also has a higher propensity to show up in the gastrointestinal tract because it is ingested (through milk), she adds.
Bovine TB is somewhat similar enough to MTB in its clinical treatment, except for one important difference. Most cases of M. bovis are resistant to pyrazinamide (PZA), one of four drugs commonly used in initial treatment of MTB. If M. bovis is not detected, a patient could possibly remain uncured.
"The only clinical relevance is that it is intrinsically resistant to PZA, and PZA is used in treatment of TB," Torriani says. "The main risk is in the population treated with PZA who would receive subtherapeutic regimens."
All 17 patients with M. bovis were found resistant to PZA, while isoniazid and rifampin resistance were found in 11% of isolates, she adds.
Because the microbiology of M. bovis also is similar to MTB (some researchers believe the two have evolved from a single species), rapid assay or commercial PCR tests cannot distinguish between the two mycobacteria. That means the only way to detect it is to grow a culture and perform a variety of biochemical tests, says Oseroff, adding that the clinical benefit may not outweigh the added cost.
Importance of species diagnoses
M. bovis’ resistance to PZA, however, underscores the importance of obtaining sensitivity results in populations that could be at higher risk for the strain, particularly HIV-positive patients, Torriani says. In other border states, such as Texas, increases in M. bovis have not been reported, most likely because it has not been looked for, she adds.
"The PZA resistance of M. bovis re-emphasizes the importance of establishing the microbiologic diagnosis of TB to the species level," conclude the authors of the Medicine article. "We strongly recommend continued surveillance for this forgotten pathogen because of the importation of Mexican cattle, the migration of Hispanic immigrants, and the persistence of extrapulmonary disease in immunocompetent and HIV-infected U.S. citizens."
Oseroff, however, downplayed the clinical importance of needing to make a distinction between M. bovis and MTB.
"There probably are other cases, particularly in people from Mexico and other developing countries who are likely to have M. bovis as opposed to MTD," he says. "But the public health significance is more epidemiological than clinical. We haven’t seen any problem in terms of response to treatment because most of the M. bovis strains are highly sensitive to the other TB drugs."
References
1. Torriani F, Havlir D, Hwang J, et al. A ten year review of Mycobacterium tuberculosis and Mycobacterium bovis infections in adults co-infected with HIV in San Diego. Presented at 4th Conference on Retroviruses and Opportunistic Infection, Washington, DC, January 1997. Abstract # 646.
2. Danker W, Waecker N, Essey M, et al. Mycobacterium bovis infections in San Diego: A clinicoepidemilogic study of 73 patients and a historical review of a forgotten pathogen. Medicine 1993; 72:11-35.
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