Diagnosis of Mycobacterium microti Infections among Humans by Using Novel Genetic Markers

Abstract

As a result of DNA typing of Mycobacterium microtiisolates from animals in the United Kingdom and The Netherlands, we diagnosed four human M. microti infections. These are the first M. microti infections among humans to be reported. Three of the patients were immunocompromised and suffered from generalized forms of tuberculosis. The fourth patient was a 34-year-old immunocompetent male with a persistent cough and undefined X-ray abnormalities. Two of the M. microti infections were recognized by their IS6110 restriction fragment length polymorphism (RFLP) patterns, which showed a high degree of similarity with those of M. microti strains isolated from a pig and a ferret in The Netherlands. The two other humanM. microti infections were recognized by using the recently developed DNA fingerprinting method, “spoligotyping,” directly on clinical material. All M. microti isolates from the United Kingdom and The Netherlands were found to contain an exceptionally short genomic direct repeat region, resulting in identical two-spacer sequence reactions in spoligotyping. In contrast, the highly similar IS6110 RFLP patterns of the vole strains from the United Kingdom differed considerably from the RFLPs of all M. microti strains isolated in The Netherlands, suggesting that geographic isolation led to divergent strains in the United Kingdom and on the continent.

Mycobacterium genavenseinfection in two aged ferrets with conjunctival lesions

“…A single case of granulomatous enteritis in a ferret due to M avium has been reported 23 and there is also a single report of a M microti infection, presumably acquired following ingestion of an infected vole. 24 Tuberculosis due to M bovis is well documented in feral ferrets in New Zealand. 25 Intestinal lesions are observed most commonly, probably because infection results from the ingestion of tuberculous feral brush-tailed possums.…”

Identification of genetic markers forMycobacterium pinnipediithrough genome analysis

“…The three M. pinnipedii isolates were recovered from Argentinean fur seals (Arctocephalus australis) [12]. The 10 M. microti isolates were from the RIVM (National Institute for Public Health and the Environment, Bithoven, The Netherlands) strain collection [13]. The three M. bovis isolates and the reference strain M. bovis AN5 were from the CICVyA (Centro de Investigaciones en Ciencias Veterinarias y Agrarias, Buenos Aires, Argentine) strain collection.…”

A novel multi SNP based method for the identification of subspecies and associated lineages and sub-lineages of theMycobacterium tuberculosiscomplex by whole genome sequencing

“…There were three clinical isolates of M. microti , all of which were also correctly identified by Mykrobe predictor but not KvarQ or TB-Profiler with their default reference libraries. There have been at least 26 cases of M. microti infection in humans reported in the literature both with and without close contact with relevant animals being a feature of the clinical history 22,[49][50][51][52][53] . In a case series from Scotland, three out of four M. microti infections occurred in individuals not known to be immunocompromised and two of these had no known contacts with relevant animals 51 .…”

“…M. bovis BCG can cause complications usually, but not always, in immunosuppressed patients following BCG vaccination or be isolated as a result of bladder carcinoma treatment and should not be misdiagnosed as M. tuberculosis 21,22 . M. microti is found in wild cats and rodents and causes human infection which is usually in association with rodent contact 23 . M. pinnipedii is a bacterium causing tuberculosis in seals which is 4 sometimes transmitted to humans during outbreaks in zoos or wildlife parks 24 .…”