Cats in Latvia Reveal Hidden Fungal Disease Beyond Known Endemic Zones

Veterinarians in Latvia have documented three cases of feline histoplasmosis in a region where the disease had never before been reported, and molecular testing has now confirmed the culprit as Histoplasma capsulatum, a dimorphic soil fungus classically associated with the Americas and parts of Asia and Africa. The case series, published in Acta Veterinaria Scandinavica, describes three domestic shorthaired cats treated at two referral clinics between 2019 and 2020, all presenting with ulcerative or erosive skin lesions and all sharing the same small town of Tukums as their home. One case yielded the first molecular confirmation of the fungus in the entire Baltic region, and the phylogenetic analysis placed the Latvian isolate firmly within the Eurasian lineage of the species.

The significance of the finding lies less in the individual illnesses than in what they imply about the geographic range of a pathogen long considered absent from northern Europe. Histoplasmosis is classically endemic in the United States, Latin America, parts of Africa, India and Southeast Asia, but recent reports suggest it may be more widespread, with suspected endemicity in Central Europe, Turkey and Japan. Feline cases have previously been documented in Germany, France, Switzerland, Italy and the Netherlands, yet no cases had ever been reported from the Baltic States or Northern Europe. The Latvian cluster, occurring within two consecutive years and in one locality, suggests the fungus may be established in the environment there, raising the possibility that the disease is underrecognized rather than genuinely absent.

All three cats presented with cutaneous disease rather than the systemic forms more commonly described. The first was an adult male of unknown age, transferred from a shelter in Tukums to a Riga referral clinic in May 2019, carrying a feline immunodeficiency virus infection and sporting multiple ulcerative lesions on the head, back and forelimbs. Fine-needle aspiration cytology strongly suggested histoplasmosis, and the cat was started on oral itraconazole. Histopathology identified a fungal infection with differential diagnoses of Sporothrix and Histoplasma species based on organism morphology. After two weeks of therapy the shelter reported partial improvement in the back and leg lesions while head lesions remained unchanged; the cat stayed clinically stable, ate and drank normally, and was ultimately lost to follow-up, so treatment efficacy could not be assessed.

The second case arrived at the same clinic in August 2019, a three-year-old male from Tukums with a single erosive lesion on the left cheek. Cytology of a fine-needle aspirate was consistent with histoplasmosis, and the cat received the same itraconazole protocol. Follow-up showed complete resolution of the lesion, with marked clinical improvement and hair regrowth evident eight weeks after treatment began. This was the only patient whose outcome could be fully evaluated, and it stands as the sole confirmed treatment success in the series.

The third cat, a six-year-old castrated male with indoor-outdoor access, appeared in autumn 2020 with multiple erosive and pustular lesions on the ears, head and distal limbs. The owner reported the lesions emerged roughly two weeks after a cat fight. Initial wound cleaning and topical streptomycin ointment from a local veterinarian produced no improvement, prompting referral. On presentation the cat weighed five kilograms with a body condition score of three out of five and normal vital parameters. Cytology of fine-needle aspirates and impression smears was again consistent with histoplasmosis, but the owners declined further antemortem diagnostics, including retroviral testing and bloodwork. The cat was humanely euthanized, and with the owners’ consent, post-mortem skin biopsies, serum and urine were collected at the authors’ own expense for extended testing.

Cytology proved the workhorse diagnostic across all three cases. Smears stained with a modified Romanowsky stain revealed moderate to severe granulomatous inflammation populated by numerous intra- and extracellular yeast-like organisms roughly three to five micrometers in diameter, each with a central basophilic nucleus and a thin perinuclear halo, features the authors describe as morphologically consistent with H. capsulatum. Notably, the organisms were readily visible on routine stains, contradicting suggestions in some literature that special stains are required. The authors attribute the ease of detection to the heavy organism burden in the samples and caution that the experience might differ with other tissues. They argue that cytology’s speed, accessibility and low cost make it an invaluable first-line tool, potentially delivering a timely diagnosis rather than a posthumous one.

Histopathology of skin biopsies from the first and third cases showed granulomatous to pyogranulomatous dermatitis teeming with yeast organisms, and a Periodic acid-Schiff stain on the third case confirmed PAS-positive oval fungi surrounded by clear capsules. Yet morphology alone could not distinguish Histoplasma from Sporothrix, a fungus that produces strikingly similar cutaneous lesions. Immunohistochemistry performed at Michigan State University Veterinary Diagnostic Laboratory on tissue from the first and third cases showed positive staining for H. capsulatum antigen and negative staining for Blastomyces species, but the authors emphasize that limited validation of the antibody against other fungal species left open the possibility of cross-reactivity with Sporothrix, so the IHC result was not considered definitive.

Serology added another layer of nuance. Serum antibody concentrations measured at MiraVista Diagnostics in Indianapolis fell into the intermediate gray zone in all three cats, with values of 8.5, 8.2 and 8.5 against a reference scale where values below 8.0 are negative, 8.0 to 9.9 intermediate and above 10.0 positive. The authors interpret these equivocal results as likely reflecting early infection or variable immune response, and they note that antibody testing has been questioned in prior publications. Antigen testing proved more informative: in the third case, H. capsulatum antigen was detected in both serum at 5.21 nanograms per milliliter and urine at 14.32 nanograms per milliliter, both within the diagnostic positive range, though the authors caution that a more pronounced disease burden or higher antigen concentration in that cat cannot be excluded as an explanation for the difference.

The decisive confirmation came from molecular work on formalin-fixed, paraffin-embedded tissue from the third cat. Real-time PCR targeting the internal transcribed spacer 1 region of the ribosomal DNA and nested PCR targeting the Hcp100 gene both returned positive results for H. capsulatum DNA, and Sanger sequencing of the 210-base-pair Hcp100 fragment showed 100 percent identity with multiple reference isolates. Multilocus sequence typing of three additional loci, the Tub1, Arf and anti-H genes, yielded concatenated sequences of 571 base pairs that were aligned and analyzed by neighbor-joining phylogeny against 182 worldwide H. capsulatum strains. The Latvian cat isolate clustered with eleven feline and badger isolates from Germany and France and with three equine isolates from Poland and Egypt, including the reference strain ATCC58332 of the variety farciminosum, with 89 percent bootstrap support, placing it within the Eurasia geographic clade. Sequences were deposited in GenBank under accession numbers PV256415 through PV256418.

The authors acknowledge meaningful limitations. The exact environmental source of infection was never located, though two of the cats lived near the same broken shed where bats had been observed; the shed was not examined and bat droppings were not collected. Paraffin-embedded tissue likely limited the length of recoverable DNA, and frozen tissue would have better served phylogenetic resolution. Only one case was molecularly confirmed, biopsy material from another cat was lost in transit from the United States to Latvia, and one cat was lost to follow-up, precluding any assessment of treatment efficacy across the series. None of the cats had a travel history, all had outdoor access, and all three were ginger, though the authors note that any role for coat color or length in susceptibility is unknown. No autochthonous human cases are known in Latvia, and while zoonotic potential exists, no direct transmission from infected animals to humans has been described. The authors argue the clustering of cases, the local acquisition and the Eurasian phylogenetic placement together support a local source of infection and warrant surveillance, since fungi might also arrive with fertilizers or migrating animals, and climate change is suspected to be pushing infections into more northern areas.

Subject of Research: Autochthonous feline cutaneous histoplasmosis in Latvia confirmed by cytology, serology and molecular phylogenetic analysis

Article Title: Feline cutaneous histoplasmosis in a non-endemic region: diagnostic challenges and molecular confirmation of Histoplasma capsulatum in Latvia

Article References: Berzina, I., Nikolajenko, M., Matise-VanHoutana, I., Ulanova, V., Kivrāne, A., & Ranka, R. (2026). Feline cutaneous histoplasmosis in a non-endemic region: diagnostic challenges and molecular confirmation of Histoplasma capsulatum in Latvia. Acta Veterinaria Scandinavica, 68(1), Article 33. https://doi.org/10.1186/s13028-026-00883-4

Image Credits: AI Generated

DOI: 10.1186/s13028-026-00883-4

Keywords: feline histoplasmosis, Histoplasma capsulatum, Latvia, Baltic region, veterinary diagnostics, cytology, PCR, phylogenetics, emerging fungal disease, non-endemic region, skin lesions, cats