Pathology of Neonatal Non-albicansCandidiasis: Autopsy Study and Literature Review

Abstract

Introduction/Objectives Non- albicans Candida species such as Candida parapsilosis and Candida glabrata have emerged as prevalent pathogens in premature infants. The aim of this study was to systematically delineate the histopathologic findings in neonatal non- albicans candidiasis. Methods We performed a retrospective clinicopathologic analysis of extremely premature (23-28 weeks' gestation) infants diagnosed with invasive candidiasis. Archival autopsy tissues were subjected to periodic acid-Schiff, methenamine-silver and anti- Candida (immuno)histochemical stains, as well as dual anti- Candida and anti-cytokeratin or anti-CD31 immunofluorescence assays. In addition, we studied the prevalence of intestinal Candida colonization in a consecutive autopsy series of extremely premature infants. Results Based on positive postmortem blood and/or lung cultures, invasive candidiasis (3 non- albicans and 11 Candida albicans) was diagnosed in 14 of the 187 extremely premature infants examined between 1995 and 2017. In contrast to the well-known inflammatory and tissue-destructive phenotype of congenital C. albicans infection, invasive non- albicans candidiasis/candidemia caused by C. parapsilosis and C. glabrata was inconspicuous by routine hematoxylin-eosin-based histopathologic analysis despite a heavy fungal presence detected in intestines, lungs, and blood by targeted (immuno)histochemical assays. Intestinal colonization by Candida species was identified in 16 of the 26 (61%) extremely premature neonates who had lived for at least 1 week, as assessed by anti- Candida immunostaining. Conclusion Invasive neonatal non- albicans candidiasis/candidemia appears to have no distinct histopathologic signature. Based on the notoriously low sensitivity of fungal blood cultures and the observed high frequency of Candida intestinal colonization (>50%), it is likely that non- albicans candidiasis/candidemia may be underdiagnosed in (deceased) preterm infants. Routine inclusion of targeted (immuno)histochemical fungal detection strategies in the perinatal autopsy may lead to deeper insight into the prevalence and clinical relevance of neonatal non- albicans candidiasis.

Candida parapsilosis: from Genes to the Bedside

“…The lower mortality rate seen with C. parapsilosis is consistent with its reduced virulence relative to C. albicans, as described above and as noted in animal models (339,377,378). A recent series of autopsy findings in premature infants with candidemia who died likewise supports the reduced virulence of this species (379). C. albicans infection is frequently widely disseminated in postmortem tissues and can also be associated with inflammatory and tissue-destructive features.…”

High Biofilm Formation of Non-Smooth Candida parapsilosis Correlates with Increased Incorporation of GPI-Modified Wall Adhesins

“…Candida parapsilosis is a frequent cause of nosocomial and bloodstream infections, especially in critically ill neonates and immunocompromised patients [1]. Premature infants with a low birth weight are a principal risk group for acquiring C. parapsilosis infections due to the requirement of parenteral nutrition using abiotic devices, such as indwelling catheters [2]. This increases the probability of biofilm formation by this yeast, either alone or in combination with other Candida species or nosocomial bacteria.…”

Invasive Candida Infections in Neonates after Major Surgery: Current Evidence and New Directions

“…Whereas specific inflammatory and tissue-destructive histopathologic features were found in most neonatal C. albicans cases, the mechanisms underlying cases of species other than C. albicans are still poorly understood. According to autopsy-based data, species other than C. albicans could involve both the gastrointestinal tract and pulmonary airways and their incidence is often underrated [ 73 ].…”