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CASE REPORT article

Front. Immunol.

Sec. Microbial Immunology

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1648436

Intracranial Infections of Candida albicans and Mycobacterium intracellulare Associated with CARD9 Deficiency: Case Report and Review of Literature

Provisionally accepted
Congchen  TangCongchen Tang1Chao  ChenChao Chen2Xiaoju  LvXiaoju Lv1Xie  YiXie Yi3Xiong  LiXiong Li3Jiangchao  LongJiangchao Long4Hui  YeHui Ye1*
  • 1Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
  • 2The Second People's Hospital of Yibin City, Yibin, China
  • 3Sichuan University West China Hospital Department of Laboratory Medicine, Chengdu, China
  • 4People's Hospital of Dafang, Bijie, China

The final, formatted version of the article will be published soon.

Background: Invasive candidiasis, most commonly caused by Candida albicans, poses a significant mortality risk and is challenging to treat. Non-tuberculous mycobacterial infections are opportunistic and linked to immune impairment. Caspase recruitment domain-containing protein 9 (CARD9) represents a class of proteins that incorporates the caspase recruitment domain, and its deficiency follows a strict autosomal recessive inheritance pattern, resulting in an impaired immune response. Case Presentation: A 51-year-old male who was admitted to the hospital 3 years ago because of recurrent fever accompanied by headache. The causative factor remains elusive and symptomatic treatment yielded unsatisfactory results. Next-generation sequencing (NGS) of cerebrospinal fluid (CSF) identified the fungus as C. albicans. Following antifungal therapy, the patient experienced relief from fever and headache; however, he subsequently developed a hydrocephalus. CSF culture indicated NTM—Mycobacterium intracellulare, prompting the initiation of anti-NTM treatment. Given the recurrent infections, we collected peripheral blood for whole exome sequencing, which revealed a CARD9-deficient homozygote with a new mutation site identified as c.175C>T (p. Arg59Trp). The patient was hospitalized on 8 occasions for diagnostic assessment and treatment. Presently, antifungal treatment has been discontinued after 9 months of therapy, while anti-NTM therapy is being maintained, with the patient reporting no fever or other discomforts. Conclusion: The c.175C>T (p. Arg59Trp) mutation is a novel CARD9 gene mutation and is probably damaging. Clinicians should consider immune impairment as a contributing factor in the management of fungal infections among non-HIV/AIDS patients. For such patients, conducting multiple CSF and blood cultures and employing new technologies such as NGS are advisable. Treatment of NTM and C. albicans requires personalized treatment plans. Moreover, the long-term follow-up should not be overlooked.

Keywords: CARD9, Candida albicans, Mycobacterium intracellulare, immune deficiency, case report

Received: 17 Jun 2025; Accepted: 02 Sep 2025.

Copyright: © 2025 Tang, Chen, Lv, Yi, Li, Long and Ye. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Hui Ye, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China

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