Discovery and validation of serologic biomarkers for the diagnosis and prognosis of invasive candidiasis by computational immunomics

Abstract

Invasive candidiasis (IC) is an opportunistic systemic mycosis caused by Candida species (commonly Candida albicans) that continues to pose a significant public health problem worldwide. Despite great advances in antifungal therapy and changes in clinical practices, IC remains a major infectious cause of morbidity and mortality in severely immunocompromised or critically ill patients, and further accounts for substantial healthcare costs. Its impact on patient clinical outcome and economic burden could be ameliorated by timely initiation of appropriate antifungal therapy. However, early detection of IC is extremely difficult because of its unspecific clinical signs and symptoms, and the inadequate accuracy and time delay of the currently available diagnostic or risk stratification methods. In consequence, the diagnosis of IC is often attained in advanced stages of infection (leading to delayed therapeutic interventions and ensuing poor clinical outcomes) or, unfortunately, at autopsy. In addition to the difficulties encountered in diagnosing IC at an early stage, the initial therapeutic decision-making process is also hindered by the insufficient accuracy of the currently available tools for predicting clinical outcomes in individual IC patients at presentation. Therefore, it is not surprising that clinicians are generally unable to early detect IC, and identify those IC patients who are most likely to suffer fatal clinical outcomes and may benefit from more personalized therapeutic strategies at presentation. Better diagnostic and prognostic biomarkers for IC are thus needed to improve the clinical management of this life-threatening and costly opportunistic fungal infection...

Las candidiasis invasoras son unas micosis sistémicas oportunistas producidas por diversas especies incluidas en el género Candida (entre las que destaca Candida albicans). Éstas representan un problema de salud pública importante a nivel mundial. A pesar de los grandes avances en el campo de la terapia antifúngica y de los cambios introducidos en su manejo clínico, estas infecciones siguen causando una morbilidad y una mortalidad elevadas en pacientes inmunocomprometidos y enfermos críticos, así como un gran consumo de recursos económicos en el sistema sanitario. La repercusión clínica y el coste económico de estas micosis se podrían reducir mediante un tratamiento antifúngico adecuado al inicio de la infección. Sin embargo, la detección precoz de las candidiasis invasoras es difícil ya que sus signos y síntomas clínicos son inespecíficos y los métodos de diagnóstico y de estratificación de riesgo que existen en la actualidad no son precisos ni rápidos. En consecuencia, estas infecciones se suelen diagnosticar en estadios avanzados (obteniéndose pronósticos desfavorables debido a retrasos en la administración del tratamiento antifúngico) o, por desgracia, en la autopsia...