Mycobacterium microti: Not Just a Coincidental Pathogen for Cats

Abstract

Public interest in animal tuberculosis is mainly focused on prevention and eradication of bovine tuberculosis in cattle and wildlife. In cattle, immunodiagnostic tests such as the tuberculin skin test or the interferon gamma (IFN-γ) assay have been established and are commercially available. Feline tuberculosis is rather unknown, and the available diagnostic tools are limited. However, infections with Mycobacterium tuberculosis complex members need to be considered an aetiological differential diagnosis in cats with granulomatous lymphadenopathy or skin nodules and, due to the zoonotic potential, a time-efficient and accurate diagnostic approach is required. The present study describes 11 independent cases of Mycobacterium microti infection in domestic cats in Switzerland. For three cases, clinical presentation, diagnostic imaging, bacteriological results, immunodiagnostic testing, and pathological features are reported. An adapted feline IFN-γ release assay was successfully applied in two cases and appears to be a promising tool for the ante mortem diagnosis of tuberculosis in cats. Direct contact with M. microti reservoir hosts was suspected to be the origin of infection in all three cases. However, there was no evidence of M. microti infection in 346 trapped wild mice from a presumptive endemic region. Therefore, the source and modalities of infection in cats in Switzerland remain to be further elucidated.

Keywords: Mycobacterium microti; Mycobacterium tuberculosis complex; interferon-gamma assay; nontuberculous mycobacteria; pyogranulomatous lymphadentitis; vole bacillus.

Figure 1

(A–C) Timeline chart presenting an overview of the clinical and therapeutic features of cases 1–3. The unspecific chronic symptoms and the diagnostic challenge of feline tuberculosis caused by Mycobacterium microti often result in a prolonged disease course.

Figure 2

Case 1, histopathological features. (A–G) Lungs. (A) The parenchyma exhibits nodular, partly coalescing, non-demarcated granulomatous infiltrates (*) and alveoli that are packed with macrophages (arrows). HE stain. Bar = 100 μm. (B) The infiltrates (*) are dominated by Iba-1⁺ macrophages/epithelioid cells, and Iba-1⁺ macrophages are also confirmed to fill alveolar lumina (inset: arrows). Capillaries generally contain abundant monocytes (Iba-1⁺; arrows), providing evidence of monocyte recruitment into the tissue. Bars = 50 μm. (C) The granulomatous infiltrates (*) contain moderate numbers of disseminated T cells (CD3⁺). Inset: HE stain of infiltrate. (D) Only scattered B cells (CD45R⁺) are present in the infiltrate (arrowheads). However, they form lymphocyte aggregates close to bronchi (*: bronchiolar lumen), representing part of the bronchus associated lymphatic tissue (inset; arrowhead: bronchiolar glands). Bars = 50 μm. (E) Closer view of alveoli granulomatous infiltrates resembling accumulations of alveolar macrophages that fill and expand the alveoli (arrow). Adjacent alveolar lumen with edema fluid and individual desquamed alveolar macrophages (arrowhead). Within granulomatous infiltrates, there are abundant large epithelioid cells (top inset: arrowheads) and occasional bi- or tri-nucleated macrophages (bottom inset: arrowheads), but no multinucleated giant cells. HE stains. Bars = 50 μm. (F) Macrophages cells are also found in the exudate that fills the lumen of a small bronchiole (*). HE stain. Bar = 50 μm. (G) Bronchus with granulomatous infiltrate that breaks into the bronchial lumen (*; arrowhead). Immunohistology for Iba-1. Bar = 50 μm. (H,I) Mandibular lymph node. (H) Cortex and paracortex with effacement of the architecture my granulomatous infiltrates, as shown by the extensive infiltration of Iba-1⁺ macrophages that appear to invade the lymphatic follicles (*). (I) Immunohistology for CD45R confirms the cortical structures as follicles with adjacent granulomatous infiltrates (*). Bars = 50 μm.

Figure 3

Case 2, diagnostic imaging. The thoracic radiographs in a ventrodorsal (A) and right-to-left lateral (B) projection reveal a generalized severe increase of pulmonary opacity with a heterogeneous distribution. The most severely affected areas show a broncho-interstitial toward an alveolar pattern. (C) Computed tomography of the thorax at the level of the cardiophrenic angle displayed in a lung window (Window level/Window width: −500/1,400 HU). There is a severe generalized increase in pulmonary attenuation with a mixed pattern, confluent to consolidated areas.

Figure 4

Case 2, histological features. (A–F) Lungs. (A) Gross picture of the lungs after exenteration. All lung lobes appear consolidated, with focal nodular thickening of the parenchyma (arrows). (B) Severe pneumonia with multiple granulomatous infiltrates (arrows) and focal areas of fibrosis (arrowhead). Alveoli often contain macrophages as well (*). HE stain. Bar = 50 μm. (C) Numerous macrophages and epithelioid cells contain individual or bundles of acid fast bacilli (AFB). Ziehl Neelsen (ZN) stain. Bar = 20 μm. (D) Closer view of granulomatous infiltrate (arrow) and alveoli that are filled with desquamed vacuolated alveolar macrophages/type II pneumocytes (arrowheads) that also contain AFB (inset; ZN stain). HE stain. Bars = 20 μm. (E) The granulomatous infiltrates (*) are dominated by Iba-1⁺ macrophages/epithelioid cells. Staining of cells in the alveolar lumina shows that the majority are macrophages (Iba-1⁺). Bar = 20 μm. (F) T cells (CD3⁺) are found intermingled in small numbers in the granulomatous infiltrates. (G,H) Mandibular lymph node. (G) Cortex with focal granulomatous infiltrates (arrows) and a larger infiltrate toward the medulla, with central necrosis (*). HE stain. Bar = 50 μm. (H) Numerous macrophages/epithelioid cells in the infiltrates contain AFB. ZN stain. Bar = 20 μm.

Figure 5

Case 3, diagnostic imaging. (A) Computed tomography of the head. The mandibular and retropharyngeal lymph nodes are markedly enlarged and show a heterogeneous and hypoattenuating center (up to 2 cm in long axis). (B) Computed tomography of the thorax. The pulmonary parenchyma shows a generalized miliary pattern with ground glass opacity and few soft tissue nodules (1–2 mm).

Figure 6

Case 3, histological features. Skin with focal extensive pyogranulomatous infiltration stretching from the superficial dermis (A). (B) The infiltrate is dominated by epithelioid macrophages, intermingled with neutrophils (arrowheads) and fewer lymphocytes (arrows). HE stains. Bars = 100 μm (A) and 20 μm (B).