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Mycobacterium Striction Fragment Length Polymorphism Method (IS6110 RFLP) (7) View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by PubMed Central DISPATCHES United Kingdom and Western Europe. Although there are Human and Animal no published reports of M. microti infections from the Unit- ed States, 3 of the strains in SpolDB4 are from this country. Infections with M. microti strains yield broadly similar, high–copy num- ber fi ngerprints by the insertion sequence 6110–based re- Mycobacterium striction fragment length polymorphism method (IS6110 RFLP) (7). microti, Scotland In the 12-year period from 1994 through 2005, we iso- Francis Xavier Emmanuel,* Amie-Louise Seagar,* lated M. microti from 4 humans and from 5 animals (2 cats, Christine Doig,* Alan Rayner,* Pauline Claxton,* a llama, a badger, and a ferret). No clinical details were and Ian Laurenson* available for the animal cases. The animal and human cases were from different locations in Scotland. No epidemio- During 1994–2005, we isolated Mycobacterium microti logic links were apparent. from 5 animals and 4 humans. Only 1 person was immuno- compromised. Spoligotyping showed 3 patterns: vole type, The Patients llama type, and a new variant llama type. Patient 1 was a 41-year-old woman in whom spu- tum smear–positive tuberculosis was diagnosed in 2001. aturally occurring mycobacteria that are part of the She was treated with isoniazid, rifampin, ethambutol, and NMycobacterium tuberculosis complex include M. tu- pyrazinamide for 2 months and for 4 months more with berculosis, M. bovis, M. caprae, M. africanum, M. microti, rifampin and isoniazid. She made good clinical progress, and M. pinnipedii. Although these species show remark- but sputum samples remained positive for acid-fast bacilli able genetic homology, there are notable phenotypic differ- (AFB), although cultures were negative. She was re-treated ences, particularly in their relative pathogenicity for differ- with isoniazid, rifampin, ethambutol, and pyrazinamide ent mammalian species. for 6 months. She became sputum negative and remained Tuberculosis in wild rodents was fi rst studied in 1937 clinically well at her 6-month follow-up visit. She was not as part of an investigation of cyclical changes in the popu- immunocompromised. No other patients with tuberculosis lation density of voles (1). Field voles, bank voles, wood were identifi ed in contacts, and no relevant animal contact mice, and shrews are particularly susceptible to infec- had occurred. tion with M. microti (2). However, other small mammals Patient 2 was a 39-year-old man for whom HIV was such as guinea pigs, rabbits, mice, and rats are resistant to diagnosed in 2003, who had bilateral pulmonary consolida- M.microti infection, even at high doses of infection. More tion. The patient lived on a farm. He was initially treated recently, sporadic cases have been described in larger with co-trimoxazole for suspected Pneumocystis carinii mammals (3–6). infection, and rifampin, isoniazid, and pyrazinamide were There have been only 6 published reports of human added when AFB were seen in the sputum sample. The pa- infections, comprising 13 patients in total (7–11). Salient tient’s condition deteriorated, and he died despite this drug information from these reports is summarized in Table 1. treatment and intensive therapy unit support. No other pa- M. microti has been used in extensive trials to assess tients with tuberculosis were identifi ed in connection with its effi cacy and safety as a vaccine. Percutaneously admin- this case. istered M. microti vaccine was found to be safe but no more Patient 3 was a 76-year-old woman who had received a effective than M. bovis BCG (12). The low virulence and diagnosis of pulmonary tuberculosis in 2005. She made an poor immunogenicity are due to several key genetic dele- uneventful recovery following standard therapy with iso- tions, resulting in the inability to produce the strongly im- niazid, rifampin, and ethambutol for 2 months, followed by munogenic T-cell antigens ESAT-6 and CFP-10 (13). rifampin and isoniazid for a further 4 months. She was not Several genotypes of M. microti have been recog- immunocompromised, and she reported no major animal nized by spacer oligotyping (spoligotyping). The llama- contact. No cases of tuberculosis were identifi ed in connec- type (presence of spacers 4–7, 23, 24, 26, 37, 38) and the tion with this patient. vole-type (only 2 spacers, 37 and 38) have been well de- Patient 4 was a 45-year-old woman who was seen scribed; both types are involved in human infections (5,7). in 2005 for hemoptysis; a diagnosis of cavitating pulmo- The international spoligotyping database (SpolDB4) (14) nary tuberculosis was made. She received treatment with includes 40 M. microti strains, 37 of which are from the isoniazid, rifampin, ethambutol, and pyrazinamide for 2 months and rifampin and isoniazid for 4 months more. She *Scottish Mycobacteria Reference Laboratory, Edinburgh, Scot- remained unwell, with further hemoptysis, and a residual land, United Kingdom cavity was shown on chest x-ray. Chemotherapy was rein- 1924 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 13, No. 12, December 2007 Infections with Mycobacterium microti, Scotland Table 1. Summary of all reported cases of human infections with Mycobacterium microti * Case- Age, sex, Immune Animal patient no. Ref country status Infection site contact Laboratory findings Outcome 1(8)48 y, M, HIV positive Lung None Llama type. Good growth in liquid Cured Germany medium. Poor on pyruvate. Drug susceptible. Curved bacilli. 2(7,10) 39 y, M, the HIV positive Lung; lymph House mice Cultures negative; curved bacilli Cured after Netherlands nodes in sputum. Vole type on direct prolonged spoligotyping. therapy† 3(7) 12 y, M, the Renal Lung None Vole type. Other details Cured Netherlands transplant meninges unavailable. 4(7) 41 y, M, the Renal Peritoneal Wild small Vole type. Other details Died despite Netherlands transplant rodents unavailable. therapy 5(7) 34 y, M, the Normal Lung Lived in Vole type. Other details Cured Netherlands mobile home unavailable. 6(9)53 y, M, Normal Lung None Llama type. AFB film negative. Cured Germany Liquid culture better than pyruvate agar. No growth on normal egg media. Fully drug susceptible. Noncurved bacilli. 7(9) 58 y, M, Diabetic Lung None Vole type. Growth on liquid Cured Germany culture only (poor). Susceptibility not done. Noncurved bacilli. 8(5) Not known; Not known Not known Not known Llama type. Not known England or Wales 9–12 (5) Not known; Not known Not known Not known Vole type. Not known England or Wales 13 (11) 69 y, sex not Normal Abdominal/ Not known Vole type. Primary culture in Died, despite known, miliary liquid. Subculture in solid agar. appropriate Germany therapy *Ref, reference; M, male; AFB, acid-fast bacilli. †Three household contacts were found to be tuberculin positive. troduced. She was not known to be immunocompromised. grows poorly on traditional solid egg media, and modern She had a pet cat and a dog, both in good health. No cases automated liquid culture techniques do not seem to yield of tuberculosis were identifi ed in contacts. better results. Moreover, even when a mycobacterial infec- The laboratory characteristics of the isolates are shown tion is diagnosed, routine veterinary diagnostic procedures in Table 2. Biochemical tests were not possible because of often do not identify the mycobacterium to species level. It sparse growth. Isolates were identifi ed as M. tuberculosis is likely also that known animal cases are not all formally complex by using the Accuprobe culture confi rmation as- reported in the literature. say (GenProbe, San Diego, CA, USA), and species identifi - The transmission of M. microti to pets, particularly cation as M. microti was confi rmed by spoligotyping. Since cats, is of particular concern. Cats are assumed to acquire we do not perform drug susceptibility testing using solid the M. microti infection from infected wild rodents, but this media, only the 3 strains that grew well in liquid subculture assumption is not supported by the genotyping evidence. were tested. Genotyping data on our isolates are summa- Most of the strains isolated from cats are genotypically rized in Table 2 and the Figure. very distinct from wild rodent strains, as shown in our cas- es and in the literature (5). Very little is known about the Conclusions incidence and ecology of M. microti infection in farm and M. microti infection is widespread in wild small rodent domestic animals. populations in the United Kingdom (2). There are sporadic Many of the human patients with M. microti infection reports, all from the United Kingdom and Western Europe, appear to have no immunologic defi cits (3 of our 4 patients of M. microti infection in other mammals. Certain animals, and 3 of the 8 published cases for which relevant clinical such as cats (4,5) and New World camelids domesticated in details were available). However, inherited defects of inter- Europe (6), seem to be particularly susceptible. The report- leukin receptor function are known to specifi cally predis- ed animal cases have all been detected in clinical veterinary pose to intracellular infections, particularly mycobacterial practice and are unlikely to refl ect the true fi eld incidence. infection (15). Therefore, some persons with apparently Diffi culties with laboratory diagnosis probably further con- normal immunity infected with M. microti may in fact have tribute to the underestimation of the incidence. M. microti undetected specifi c immune defects. Emerging
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