The Role of Adenovirus in Hepatitis of Unknown Etiology Among Children in Turkey, July 2022 to January 2023.

BACKGROUND: In the first half of 2022, the increase in cases of severe acute hepatitis in children with no epidemiological link and unknown cause has aroused concern worldwide. In this study, we aimed to determine the frequency of adenovirus in children with hepatitis of unknown origin in Turkey. METHODS: In this study, which was conducted with the participation of 16 centers from Turkey, between July 2022 and January 2023, 36 pediatric patients under the age of 18 who met the definition of acute hepatitis were included. RESULTS: Twenty (55,6%) of patients were female and 16 (44,4%) were male, with a mean age of 41.55 ± 39.22 (3-192) months. The most common symptoms were fever (66.7%), weakness (66.7%), loss of appetite (66.7%), fatigue (61.1%), vomiting (61.1%), and diarrhea (47.2%). Six (16 %) children had acute hepatic failure. Eight of the 15 children (46%) had respiratory viral infections (rhinovirus/enterovirus, n = 4; rhinovirus + parainfluenza, n = 1; parainfluenza, n = 1, SARS-CoV-2 n = 2). Adenovirus was detected in 16 (44%) patients. Adenovirus and coinfections were detected in 7 patients. History of diarrhea and fatigue in the last month was significantly higher in the adenovirus group ( P = 0.023 and 0.018). One child who had both adenovirus and rhinovirus infection required liver transplantation; all others recovered with supportive care. CONCLUSION: There were no deaths in our series; however, the number of cases, etiology, and severity of the clinical course may have differed between countries owing to differences in case definitions, laboratory facilities, or regional genetic differences.

Immunomodulatory effects of voriconazole and caspofungin on human peripheral blood mononuclear cells stimulated by Candida albicans and Candida krusei.

BACKGROUND: Candida infections are frequently associated with high morbidity and mortality rates in immunosuppressed patients. T cell-mediated and phagocytic immunity are the primary protective immune responses against fungal infections. Antifungal agents such as voriconazole and caspofungin enter phagocytic cells and lead to various intracellular activities. In this study, the authors aimed to investigate the immunomodulatory effects of voriconazole and caspofungin on human peripheral blood mononuclear cells (PBMC) stimulated by Candida albicans and Candida krusei. METHODS: Human PBMC isolation was performed by Ficoll-hypaque density-gradient centrifugation method. Cell proliferation was assessed by colorimetric method using MTT. The cytokine levels in the human PBMC culture supernatants stimulated by C. albicans and C. krusei were determined by enzyme-linked immunosorbent assay. RESULTS: The addition of voriconazole and caspofungin lead to proliferation of PBMC. In the presence of voriconazole and caspofungin, the levels of IL-2, IFN-γ and IL-6 remarkably increased in PBMC stimulated by C. albicans and C. krusei. However, the combination of antifungal drugs and PBMC stimulated by Candida species did not increase the levels of TGF-ß and IL-10. CONCLUSIONS: The results indicate that voriconazole and caspofungin have immunomodulatory effects on human PBMC stimulated by Candida species. The interaction between antifungal drugs and PBMC stimulates Th1-type cytokine secretion. Cytokine stimulation from immune cells can assist in the elimination of fungal pathogens. Therefore, during the treatment of fungal infection, putative immunomodulatory effects of antifungal agents should be taken into account.