Patient 1 was a 41-year-old woman in whom sputum smear–positive tuberculosis was diagnosed in 2001. She was treated with isoniazid, rifampin, ethambutol, and pyrazinamide for 2 months and for 4 months more with rifampin and isoniazid. She made good clinical progress, but sputum samples remained positive for acid-fast bacilli (AFB), although cultures were negative. She was re-treated with isoniazid, rifampin, ethambutol, and pyrazinamide for 6 months. She became sputum negative and remained clinically well at her 6-month follow-up visit. She was not immunocompromised. No other patients with tuberculosis were identified in contacts, and no relevant animal contact had occurred.

Patient 2 was a 39-year-old man for whom HIV was diagnosed in 2003, who had bilateral pulmonary consolidation. The patient lived on a farm. He was initially treated with co-trimoxazole for suspected Pneumocystis carinii infection, and rifampin, isoniazid, and pyrazinamide were added when AFB were seen in the sputum sample. The patient’s condition deteriorated, and he died despite this drug treatment and intensive therapy unit support. No other patients with tuberculosis were identified in connection with this case.

Patient 3 was a 76-year-old woman who had received a diagnosis of pulmonary tuberculosis in 2005. She made an uneventful recovery following standard therapy with isoniazid, rifampin, and ethambutol for 2 months, followed by rifampin and isoniazid for a further 4 months. She was not immunocompromised, and she reported no major animal contact. No cases of tuberculosis were identified in connection with this patient.

Patient 4 was a 45-year-old woman who was seen in 2005 for hemoptysis; a diagnosis of cavitating pulmonary tuberculosis was made. She received treatment with isoniazid, rifampin, ethambutol, and pyrazinamide for 2 months and rifampin and isoniazid for 4 months more. She remained unwell, with further hemoptysis, and a residual cavity was shown on chest x-ray. Chemotherapy was reintroduced. She was not known to be immunocompromised. She had a pet cat and a dog, both in good health. No cases of tuberculosis were identified in contacts.

Figure

Figure. Comparison of the restriction fragment length polymorphism patterns of Mycobacterium microti strains from Scotland. Spoligo, spoligotyping.

The laboratory characteristics of the isolates are shown in Table 2. Biochemical tests were not possible because of sparse growth. Isolates were identified as M. tuberculosis complex by using the Accuprobe culture confirmation assay (GenProbe, San Diego, CA, USA), and species identification as M. microti was confirmed by spoligotyping. Since we do not perform drug susceptibility testing using solid media, only the 3 strains that grew well in liquid subculture were tested. Genotyping data on our isolates are summarized in Table 2 and the Figure.

M. microti infection is widespread in wild small rodent populations in the United Kingdom (2). There are sporadic reports, all from the United Kingdom and Western Europe, of M. microti infection in other mammals. Certain animals, such as cats (4,5) and New World camelids domesticated in Europe (6), seem to be particularly susceptible. The reported animal cases have all been detected in clinical veterinary practice and are unlikely to reflect the true field incidence. Difficulties with laboratory diagnosis probably further contribute to the underestimation of the incidence. M. microti grows poorly on traditional solid egg media, and modern automated liquid culture techniques do not seem to yield better results. Moreover, even when a mycobacterial infection is diagnosed, routine veterinary diagnostic procedures often do not identify the mycobacterium to species level. It is likely also that known animal cases are not all formally reported in the literature.

The transmission of M. microti to pets, particularly cats, is of particular concern. Cats are assumed to acquire the M. microti infection from infected wild rodents, but this assumption is not supported by the genotyping evidence. Most of the strains isolated from cats are genotypically very distinct from wild rodent strains, as shown in our cases and in the literature (5). Very little is known about the incidence and ecology of M. microti infection in farm and domestic animals.

Many of the human patients with M. microti infection appear to have no immunologic deficits (3 of our 4 patients and 3 of the 8 published cases for which relevant clinical details were available). However, inherited defects of interleukin receptor function are known to specifically predispose to intracellular infections, particularly mycobacterial infection (15). Therefore, some persons with apparently normal immunity infected with M. microti may in fact have undetected specific immune defects.

Human-to-human transmission of M. microti infection seems rare. In the single instance in which this possibility is moot, the secondary cases all occurred in the same mice-infested household (10).

Extensive trials of M. microti as a vaccine suggest that it lacks virulence for humans with normal immunity. However, it remains a potential threat to the substantial pool of persons with compromised immunity, including the unknown number who may have genetic defects specifically predisposing to mycobacterial infections.