From molecular advances to limited clinical impact: The persistent gap in chromoblastomycosis.

BACKGROUND: Chromoblastomycosis (CBM) is a chronic implantation mycosis of considerable morbidity, first described more than a century ago, predominantly affecting rural populations in tropical and subtropical regions. Although historically associated with impoverished settings, an increasing number of cases have been reported in both endemic and non-endemic areas, including high-income countries, reflecting an underrecognized epidemiological landscape. Despite its burden, key metrics such as disability-adjusted life years (DALYs) remain undefined, as highlighted by recent global health initiatives. While advances in diagnosing and treating patients with CBM have been made, new technologies have not been incorporated into broader clinical and public health interventions.

METHODOLOGY/PRINCIPAL FINDINGS: Herein, we synthesize recent advances in CBM, focusing on the expanding biodiversity of etiological agents driven by molecular taxonomy, the growing role of molecular diagnostics, and emerging therapeutic strategies. Novel genera and species have been identified, particularly among immunocompromised hosts, reshaping our understanding of host-pathogen interactions. Molecular tools, including PCR-based and genomic approaches, have improved species-level identification, although their availability remains largely restricted to reference centers. Therapeutically, extended-spectrum triazoles and terbinafine have shown the most consistent activity, while adjunctive immunomodulatory strategies, such as imiquimod, are emerging as promising alternatives. However, these advances sharply contrast with real-world clinical practice. In endemic settings, diagnosis continues to rely on low-cost conventional methods, which, given their sensitivity, should be more widely incorporated into public health screening and active case-finding strategies. Antifungal susceptibility testing lacks clear clinical correlation, and treatment decisions remain largely based on observational studies, in the absence of randomized controlled trials.

CONCLUSIONS AND SIGNIFICANCE: CBM exemplifies a neglected tropical disease in which substantial progress in basic science has not translated into improved patient outcomes. Strengthening public health strategies, expanding access to simple and effective diagnostic tools, and prioritizing implementation-focused research are urgently needed to bridge this persistent gap.