Clinical insights into Candidatus Mycoplasma haemominutum-associated anaemia in naturally infected cats: flea-associated risk and paradoxical clinicopathological findings.

BACKGROUND: The specific pathophysiological drivers and host-pathogen-environment factors that dictate the pathogenicity of Candidatus Mycoplasma haemominutum (CMhm) remain poorly defined, hindering accurate clinical interpretation and effective disease control. This study provides detailed mechanistic insights into CMhm-associated anaemia in naturally infected cats by integrating analyses of concurrent diseases and comprehensive clinicopathological panels, alongside molecular characterisation in an under-represented region. Two groups of CMhm-infected cats (anaemic, n = 13; non-anaemic, n = 25) were systematically screened for 14 concurrent infectious, metabolic, or endocrine conditions, alongside extensive haematological, biochemical, and iron profile assessments. Multivariable logistic regression identified independent risk factors, while CMhm molecular diversity was assessed using 16S rRNA gene sequencing. RESULTS: Multivariable analysis identified flea infestation as the sole significant driver of anaemia (OR 7.77; P = 0.04), underscoring a key vector-trigger role and contributing evidence to the ongoing debate on CMhm's flea-borne transmission. Although specific conditions such as feline immunodeficiency virus, feline leukaemia virus, Mycoplasma haemofelis, Candidatus Mycoplasma turicensis, and hyperglycaemia were not statistically significant, they may still be biologically relevant. Notably, most cats in the non-anaemic group also had comorbidities, suggesting that disease stage or severity may be more critical than mere presence. Supporting this, the anaemic group showed significantly lower lymphocyte counts and a downward trend in other leucocytes. Anaemia appeared deceptively normocytic-normochromic and non-regenerative despite ongoing CMhm-induced haemolysis, indicating additional counteracting mechanisms. Detailed clinicopathological and concurrent disease investigations pointed to true iron deficiency (flea-related) and functional iron deficiency (inflammatory comorbidities) as contributors. The coexistence of these three opposing pathophysiological processes shaped the paradoxical haematological and iron profile. Molecular analysis identified three CMhm nucleotide sequence types (nSTs) new to the region. CONCLUSIONS: The results of this study suggest that CMhm-associated anaemia is likely a secondary condition, in which environmental triggers and host immune status shape disease manifestation. This study elucidates the complex pathophysiological mechanisms underlying anaemia, providing insights to enhance clinical diagnosis and inform control strategies.