Mycobacterium bovis infected domestic cats in an officially bovine tuberculosis free country resulting in human infection

Abstract

Although the Netherlands is an officially bovine tuberculosis (bTB) free (OTF) country, sporadic infections with Mycobacterium bovis still cause tuberculosis (TB) in (non-bovine) mammals, including humans. We describe for the first time cases of M. bovis infection in domestic cats in the Netherlands with transmission between companion animals and humans. In January 2023, a domestic cat, euthanized due to severe respiratory clinical signs, was diagnosed with M. bovis. Subsequently, three other cats from the household were euthanized and also diagnosed with M. bovis. The remaining kitten and dog received antibiotic treatment. Human contacts were screened using Tuberculin Skin Test (TST) and Interferon-Gamma Release Assay (IGRA). Lung lesions were detected in a TST⁺/IGRA^- contact which tested positive for M. bovis DNA. This human lung-derived M. bovis DNA contained single nucleotide polymorphisms (SNPs) that were also identified in the DNA of M. bovis isolated from the cats in this household, strengthening the hypothesis of intra-species M. bovis transmission within the household. The four TST⁺ human contacts received antibiotic treatment. In the same period, another domestic cat from an unrelated household was euthanized due to respiratory clinical signs and diagnosed with M. bovis. This M. bovis strain differed 500 SNPs from the strains of the first household and was therefore genetically distinct. Commercially available, ready-to-use raw pet food was a suspected source in both households, however this could not be confirmed. These cases illustrate the need for one-health vigilance among both veterinarians and human physicians as essential to control outbreaks and prevent further spread to humans, companion animals, wildlife and livestock.

Keywords: Feline tuberculosis; Human transmission; Mycobacterium bovis; Officially bTB free (OTF) country; The Netherlands; Zoonosis.

Fig. 1

Timeline Case 1. Within the household the index case I (kitten A1) was one out of four kittens (kitten A1–4) from a litter of cat A. Cat B, cat C and dog D also lived in the same household. The onset of clinical signs is indicated with a blue arrow. Time of necropsy, X-ray, PCR and culture results are indicated on the timeline. Prophylactic antibiotic treatment is indicated with a brown arrow. Created in BioRender. https://BioRender.com/k47q463. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 2

Lung tissue of cat A. Multiple granulomas (arrows) are visible on the surface (A) and in the cross section of the lung (B). Granulomas are classified as stage IV granulomas consisting of a confluent core of necrotic lung tissue (arrowhead in C: microscopical hematoxylin-eosin (HE) stain overview of the lung). The central necrosis is surrounded by a band of epitheloid cells, lymphocytes and fibroblasts but no multinucleated giant cells. D: high magnification of the framed rectangle in C. Immunohistochemical staining for mycobacteria shows multiple clusters of positively stained (remnants of) bacteria in the necrotic lung tissue (E). Insert in E: Ziehl-Neehlsen staining of acid-fast bacteria in the necrotic lung tissue. Bar = 1000 μm (C) or 100 μm (D and E).

Fig. 3

Intestinal lymph nodes and small intestines of cat A. Cut surface (A. left) and microscopical HE stained overview (A. right) of the enlarged ileo-caecal lymph node which is composed almost entirely of necrotic tissue (arrow heads) with foci of mineralization (arrows).The necrotic tissue is surrounded by a thick fibrous capsule and some epitheloid cells and lymphocytes (B: high magnification of framed rectangle in A). Positive immunohistochemical staining for mycobacteria in serial section (C). Cross section (D. left) and microscopical HE stained overview of the ileum (D. right) showing multiple granulomas in the mucosa and submucosa (arrowheads). Granulomas consist of a central necrotic core surrounded by numerous epitheloid cells, lymphocytes and fibroblasts (E: high magnification of framed rectangle in D.) Positive immunohistochemical staining for mycobacteria in serial section (F). Bar = 5000 μm (A), 2500 μm (D) or 100 μm (B, C, E, F).

Fig. 4

Timeline Case 1I. Index case II was one out of four kittens from a litter. The four kittens were distributed over three households. The index case lived with another cat in the new household. The onset of clinical signs is indicated with a blue arrow. Time of necropsy, X-ray, PCR and culture are indicated on the timeline. Created in BioRender. https://BioRender.com/t08m346 (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 5

SNP based phylogenetic tree of M. bovis isolates. The sequences from the first household cluster together, while index case II falls in a separate cluster. M. bovis strain names are indicated in the first column. The host of M. bovis isolation is shown in the second column. Isolates from cats in this case report are indicated in the third column. The tree is midpoint-rooted, using M. tuberculosis H37Rv as outgroup. Numbers on tree nodes represent bootstrap values, the horizontal scale bar indicates nucleotide substitutions per site.