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Spread person-to-person as often as MTB
Mycobacterium bovis, the publicity-shy member of the M. tuberculosis complex linked to consumption of unpasteurized dairy products, is probably spread by person-to-person contact, a new study from San Diego shows.
The bug is often acquired by ingesting the unpasteurized dairy products widely available in Mexico. Person-to-person transmission has also long been suspected, but it’s been hard to prove, notes Philip LoBue, MD, medical epidemiologist with the San Diego County TB Control Division. "Often you’d have several cases in the same family, sometimes even linked by RFLP, but then you’d discover everyone has also eaten the same unpasteurized cheese, so you couldn’t conclude anything for certain," he says. That changed when LoBue did a study of close contacts of cases infected with the pulmonary form of M. bovis and found infection rates were virtually the same as for pulmonary TB.
San Diego, as M. bovis aficionados know, is a veritable hotbed of research on the low-profile critter. Counting LoBue’s work, which is not yet published, only two serious studies of the bug have been undertaken; both were done by researchers working in San Diego. No one knows whether that means San Diego has more M. bovis than other American cities along the Mexican border, adds LoBue. All that’s known for sure is that San Diego labs test for the bug more often than anyone else.
PZA resistance points to M. bovis
BACTEC and other mycobacterial laboratory assays only show whether an isolate is a member of the TB complex, but because the vast majority of cases of TB in the United States are M. tuberculosis, few labs bother looking much further, says LoBue. Should they wish to do so, though, there’s a way. Although most TB strains are sensitive
to pyrazinamide (PZA), M. bovis produces an enzyme that renders the drug ineffective. So even though though few labs routinely bother looking, the marker for M. bovis is resistance to PZA.
All San Diego-area public health labs test for PZA resistance, and they turn up a fair amount of the infection, including an occasional outbreak. Looking back at case totals between 1993 and 1999, LoBue located 107 cases of the bovine-dwelling pathogen. Still, all 107 amounted to less than 5% of the total TB caseload, LoBue notes — really, just a drop in the bucket. "It’s a curiosity more than anything else, I suppose," he says.
That 5% still gets plenty of respect from San Diego clinicians, LoBue points out. "Pediatricians, especially, are quite familiar with it," he says. Besides kids, those infected with HIV are frequent targets for the mycobacterium. This suggests the bug exists in latent form, just like its better-known sibling, and becomes active when immune systems are weak or impaired.
In kids, it’s the nodes or gut
In children, M. bovis most frequently lodges in the lymph nodes or abdomen, says LoBue. When pediatricians see a child with swollen lymph nodes or with abdominal symptoms — including fever, abdominal pain, and perhaps also diarrhea and/or constipation — "they immediately think M. bovis," says LoBue. The abdomen and lymph nodes account for about 52% of M. bovis cases, with the remainder of cases pulmonary in nature, resulting in symptoms virtually identical to those caused by M. tuberculosis, he adds.
The cases LoBue studied were evenly divided between U.S.-born and Mexican-born residents of the city. The two groups had in common the habit of driving south across the border to buy a chunk of unpasteurized cheese. "You’ll hear people say the unpasteurized cheese has a better taste, and they prefer it," LoBue adds. Worth noting is the fact that consumption of unpasteurized dairy products confers the risk not just for M. bovis, but also for brucellosis, campylobacter, and salmonella, he notes.
But does knowing whether you’ve got M. bovis or just garden-variety TB make any real difference? Among M. bovis-watchers, that’s a hotly debated question, LoBue says. San Diego clinicians typically give the bug the benefit of the doubt, treating it for an extra three months of isoniazid and rifampin (meaning for nine months). Their rationale is simple: When a culture comes back positive for TB, the patient is started on the usual four drugs. Once the isolate is shown to be sensitive to INH and RIF, the usual course is to drop the ethambutol. But if the bug turns out to be resistant to PZA, LoBue explains, you’ve been treating it with only two drugs, so why not treat a little longer, just to be safe?
Whether a longer duration of treatment is really necessary isn’t known for sure, though, and probably never will be. "Suppose you don’t extend the therapy," LoBue suggests. "A certain number of cases won’t be cured; and when that happens, even though they probably don’t know if it’s because you’ve got M. bovis or not, they go ahead and restart therapy." Either way, you’re cured. Plus, even though M. bovis is PZA-resistant in a test tube, no one’s certain the same thing applies in real life.
Finally (the argument goes), back in the days when short-course TB therapy was testing its wings in trials, there was no test for PZA resistance, so no one looked for M. bovis (though presumably some folks in the studies had M. bovis, not M. tuberculosis). "And people will point out that without any longer treatment, those people evidently did fine anyway," LoBue says sanguinely.
It’s doubtful that anyone will do a large comprehensive study to settle such questions, either. Even in San Diego, there’s simply not enough M. bovis to go around.
Only under one set of circumstances does it make sense to know whether the TB at hand is M. bovis or not, LoBue says. Because the bug is PZA-resistant, it probably wouldn’t do to treat it in latent form (assuming such a thing really exists) with short-course preventive therapy consisting of RIF and PZA. Imagine — well, LoBue says, clearly humoring his interrogator — imagine a patient who’s HIV-positive, lives close to the border, and has a passion for unpasteurized dairy products. If all that seems a bit much to digest, just remember the moral of M. bovis, says LoBue: When in Mexico, don’t eat the unpasteurized cheese.