The fox was first treated with ivermectin for the mange and with amoxicillin combined with clavulanic acid for the suspected urinary infection. Instead of recovering, the animal worsened, growing weaker and paler. Only a month after admission, in September 2024, did the clinical team suspect a blood parasite and run a complete blood count, serum biochemistry, urinalysis and faecal examinations. The haematology revealed a regenerative anaemia marked by anisocytosis, polychromasia, Howell-Jolly bodies, rouleaux formation and increased reticulocytes, alongside leukocytosis with neutrophilia, a left shift and lymphocytosis. Biochemistry showed elevated alanine aminotransferase and alkaline phosphatase, increased total bilirubin, reduced total proteins with hypoalbuminemia, raised cholesterol, amylase and lipase, and a reduced sodium-to-potassium ratio. Urinalysis detected haemoglobinuria at 50 micromoles per litre together with haematuria. A blood smear then delivered the decisive clue: intraerythrocytic inclusions morphologically consistent with small piroplasmids.

Molecular confirmation followed quickly. DNA extracted from whole blood was analysed by conventional PCR targeting the 18S ribosomal DNA gene, and sequencing of the roughly 510-base-pair amplicon, compared against GenBank using BLAST, showed 99.6 per cent nucleotide identity with Babesia banethi. Crucially, the fox screened negative for antibodies against Leishmania infantum, Ehrlichia canis and Anaplasma phagocytophilum/platys, negative for Dirofilaria immitis antigen and negative for Rickettsia species DNA, ruling out common co-infections. B. banethi is a recently described small Babesia species, genetically distinct from the dominant fox piroplasm Babesia vulpes. While B. vulpes belongs to clade I of the piroplasmids, within the B. microti-like group, phylogenetic analyses place B. banethi in clade III, the so-called Western group, well apart from the large Babesia sensu stricto species such as B. canis, B. vogeli and B. gibsoni that infect domestic and wild carnivores. The species had previously been detected in foxes from Israel and Iraq, and its competent tick vector remains unknown, although parasite DNA has been found in Ixodes kaiseri ticks collected from infected animals.

With no guidelines for managing babesiosis in wildlife, the veterinary team turned to standard canine practice. At the end of September 2024 the fox received imidocarb dipropionate at 6.6 milligrams per kilogram subcutaneously, in two doses spaced 28 days apart, the most routinely used regimen for canine babesiosis. Fifteen days after the first dose the fox showed genuine clinical and haematological improvement, with only a persistent lymphocytosis marring the blood picture. Yet the parasitological follow-up told a different story: blood smears and PCR both remained positive, indicating persistent parasitaemia. Two weeks after the second imidocarb dose the animal continued to improve clinically and the parasitaemia and lymphocytosis had disappeared on smear, but PCR was still positive for B. banethi DNA. The drug had suppressed the disease without eradicating the parasite.

The relapse came roughly three months after the second imidocarb dose, in February 2025. The fox began showing mild lethargy and pale mucous membranes again, and laboratory work confirmed the return of anaemia, lymphocytosis, thrombocytosis and microscopically visible parasitaemia. Subsequent examinations at follow-up points roughly 255 and 281 days after the initial treatment recorded a consistent decline in the animal’s condition, with B. banethi detectable by both blood smear and PCR. Almost a full year after the original diagnosis, the team switched strategy. They initiated a combination of atovaquone and proguanil hydrochloride, the antimalarial sold as Malarone, at 20 milligrams per kilogram twice daily by mouth, together with azithromycin at 10 milligrams per kilogram once daily subcutaneously, for ten days, following the general regimen used against small-form Babesia infections in dogs.

The response was striking. At follow-up examinations roughly 331 and 352 days after the initial diagnosis, the fox showed marked clinical and haematological recovery, with a negative blood smear, although PCR positivity persisted. About two months after the end of the Malarone course the animal remained parasitaemic by PCR but was clinically stable, albeit with lingering laboratory abnormalities including lymphocytosis and hypergammaglobulinemia; a repeat SNAP Leish 4Dx test again came back negative. In January 2026 the fox received a second course of the atovaquone-proguanil and azithromycin combination, and one month after that therapy ended the animal was clinically stable, with only persistent lymphocytosis and elevated liver enzymes remaining, and for the first time tested both cytologically and molecularly negative for B. banethi.

The longitudinal record offers several lessons about how small Babesia parasites behave in their hosts and how treatment should be judged. PCR positivity soon after drug administration, the authors note, should not be read as treatment failure, because it may reflect the temporary persistence of parasite DNA rather than active infection; molecular testing is generally recommended no earlier than two months after completing therapy for small Babesia species. When PCR positivity lingers beyond three months, however, clinicians must consider sequestration of the parasite in target organs such as the spleen and in circulating erythrocytes, with the potential for reactivation after immunosuppressive events. For rescued wildlife destined for release, the authors argue that the primary indicator of therapeutic success should be clinical stabilisation and cytological negativity rather than complete clearance of parasite DNA, since foxes should spend as little time as possible in rehabilitation facilities.

The haematological details also distinguish this infection from better-known canine babesiosis. The mild thrombocytosis observed during the acute and relapse phases likely reflects rebound stimulation of the bone marrow in response to haemolytic anaemia, a pattern that contrasts with the thrombocytopenia commonly described in dogs infected with B. vulpes. Most other abnormalities, including anaemia, elevated liver enzymes and increased total bilirubin, mirrored those reported in dogs with small Babesia infections. Recurrent lymphocytosis, hypergammaglobulinemia and hypoalbuminemia pointed to chronic immune stimulation, while the raised ALT and ALP activities with hyperbilirubinaemia and brown urine probably reflected hepatocellular lesions secondary to haemolysis, anoxia and systemic inflammation. No hepatoprotective or additional supportive therapy was given, a limitation the authors acknowledge when interpreting the persistent liver enzyme changes. The team also stresses the complementary value of blood smear examination and molecular testing: smears identify acute, chronic and relapsing phases, while PCR confirms the species and documents persistent infection.

Why did this fox become visibly ill at all, when foxes are generally regarded as asymptomatic reservoirs of piroplasm infections? The severe sarcoptic mange and poor nutritional state may have impaired the animal’s immune response and prolonged the clinical course, but the absence of co-infections with other vector-borne pathogens or gastrointestinal parasites, together with the repeated recurrence of signs and parasitaemia, supports a primary pathogenic role for B. banethi itself. That possibility carries a broader warning. If a parasite can establish a persistent, treatment-refractory infection in a species considered relatively resistant to vector-borne pathogens, the clinical impact on more susceptible hosts, particularly domestic dogs sharing the same environment and exposed to the same potentially competent ticks, could be considerable. The case also highlights practical realities of wildlife medicine: follow-up intervals were stretched to limit repeated handling of the animal, which may have delayed detection of parasitaemia recurrences, and an earlier switch to atovaquone-proguanil with azithromycin as a first-line protocol might have shortened the disease course. Given the off-label use of atovaquone, the authors add that efficacy must be balanced against the risk of fostering antimicrobial resistance, a concern already documented for B. gibsoni in dogs. All clinical assumptions, they caution, now require validation in a larger series of B. banethi cases.

Subject of Research: Clinical course and treatment of Babesia banethi infection in a red fox

Article Title: Clinical Case and Follow‐Up of Babesia banethi Infection in a Red Fox

Article References: Clinical Case and Follow‐Up of Babesia banethi Infection in a Red Fox. (n.d.). https://doi.org/10.1002/vms3.71184

Image Credits: AI Generated

DOI: 10.1002/vms3.71184

Keywords: Babesia banethi, babesiosis, red fox, Vulpes vulpes, tick-borne pathogens, piroplasmids, wildlife medicine, imidocarb dipropionate, atovaquone-proguanil, azithromycin, regenerative anaemia, Italy