A Brazilian autopsy-based case series (2017 to 2019) of yellow fever patients reported pneumonia or haemorrhage in the respiratory tract as the immediate cause of death in 31 (42.4%) cases. Microscopy detected yeasts and hyphae in 27 (37%) and 9 (12%) cases, respectively. The yeasts were morphologically similar to Candida species, while the hyphae had morphology compatible with Aspergillus species. Hyphae resembling Mucorales species were also noted in one case. Surrounding the fungal forms were angioinvasion, tissue necrosis, cellular debris, and inflammatory reaction.
Further analysis using Sanger sequencing of tissue samples from 48 cases identified Candida species in 10 (47.6%) cases, Aspergillus in 4 (19%), and Trichosporon in 2 (9.5%). Others were Didymella glomerata, Debaryomyces hansenii, Cladosporium sphaerospermum and Apiotrichum domesticum in one case each.
Besides identifying associated fungal pathogens, the frequent finding of infectious necrotising tracheitis supported the fact that inhalation or aspiration were the main routes of respiratory infection in those cases. In contrast, few patients (7%) had clinical suspicion of pneumonia during their intensive care stay, which buttresses the significance of this study. Hence, although fungal pneumonia is seemingly unexpected in a patient with yellow fever, probably because of its hepatotrophic nature, the systemic immune dysfunction in severe yellow fever cases may predispose case-patients to invasive infections by opportunists. Screening such at-risk patients for invasive mycosis may improve clinical outcomes.
These observations further emphasise the need to consider fungal tracheobronchitis in ICU patients with severe viral infections. Yellow fever is added to the list of virus infections closely linked to fungal pneumonia, including influenza, Covid-19, severe fever with thrombocytopenia and cytomegalovirus in immunocompromised patients.
