Abstract
BackgroundThe yeast Candida is one of the most frequent pathogens isolated from bloodstream infections and is associated with significant morbidity and mortality. Problems with clinical and microbiological diagnosis of invasive candidiasis (IC) have prompted the development of non-culture-based laboratory methods. Previous reports suggest that serological detection of antibodies might be useful for diagnosing systemic candidiasis.MethodsDiagnosis of IC using antibodies against recombinant Candida albicans enolase (Eno) and fructose-bisphosphate aldolase (Fba1) was evaluated. Using recombinant Eno and Fba1 as coating antigens, enzyme-linked immunosorbent assays (ELISAs) were used to analyze sera from patients with candidemia (n = 101), Candida colonization (n = 50), bacteremia (n = 84), invasive aspergillosis (n = 40); and from healthy controls (n = 200).ResultsThe results demonstrated that ELISA detection of anti-Eno and anti-Fba1 IgG distinguished IC from other pathogenic infections in patients and healthy individuals. The sensitivity, specificity, and positive and negative predictive values were 72.3%, 94.7%, 78.5% and 93% for anti-Eno, and 87.1%, 92.8%, 76.5% and 96.4% for anti-Fba1 antibodies, respectively. Combining these two tests improved sensitivity up to 90.1% and negative predictive value up to 97.1%, with specificity and positive predictive values of 90.6% and 72.2%. The tests were specific to the Candida genus and antibody titers were higher for candidemia patients than for controls. Positive antibody tests were obtained before blood culture results for 42.2% of patients for anti-Eno and 51.1% for anti-Fba1.ConclusionThese data suggest that tests that detect IgG antibodies against Candida enolase and fructose-bisphosphate aldolase, especially when used in combination, could be a powerful tool for diagnosing IC.
Highlights
The yeast Candida is one of the most frequent pathogens isolated from bloodstream infections and is associated with significant morbidity and mortality
We report the serodiagnosis of infection by invasive Candida species using enzyme-linked immunosorbent assays (ELISAs) to detect specific antibodies against recombinant Eno and Fba1
(2) Candida colonization was defined as the presence of a positive Candida species culture from sputum only, none of these patients had a positive blood culture for Candida species but positive for other organisms. (3) the bacteremia was microbiologically defined by positive culture of blood and (4) invasive aspergillosis (IA) was defined according to the EORTC-MSG criteria [29]
Summary
The yeast Candida is one of the most frequent pathogens isolated from bloodstream infections and is associated with significant morbidity and mortality. Candida species are among the pathogens most frequently isolated from bloodstream infections, and are associated with significant morbidity and mortality [1,2]. A positive blood culture is considered the gold standard for candidemia diagnosis. A relatively low sensitivity (less than 50% according to previous studies), especially in the early period of infection, dramatically hampers the value of blood culturing in clinical practice [5]. We observed that in some cases, a patient with a positive blood culture will test negative without antifungal treatment after removal of intravenous catheters. Positive blood cultures can be caused by fitted intravascular catheters rather than invasive infection (data not shown). Other standard techniques for IC diagnosis including microscopic visualization of the infecting fungus and histopathology, usually lack specificity or sensitivity or require invasive procedures that cannot be performed because of the patient’s condition [5]
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