Translational Mycology Section
Seher H. Anjum, M.D.
Staff Clinician
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Specialty(s): Infectious Disease, Internal Medicine Provides direct clinical care to patients at NIH Clinical Center
Major Areas of Research
- Cryptococcal meningitis in previously healthy hosts
- Post-infectious neuro-inflammatory responses
- The use of steroid-sparing, immunomodulatory agents in neuro-inflammation
Program Description
Associate Investigator for Protocol 93-I-0106: Cryptococcosis in Previously Healthy Adults
Background:
Cryptococcus is a fungus that causes infections most commonly in immunocompromised patients, such as those with AIDS and solid organ transplant recipients and is currently responsible for an estimated 15% of all AIDS-related deaths globally. Within the U.S., approximately 15-20% have no identifiable immune defect and cryptococcal infection in these hosts has a mortality rate of 30-50% despite optimal antifungal therapy.
The objectives of this protocol can be broadly categorized as:
- Characterize the immunologic and genetic mechanisms predisposing to disease acquisition.
- Understand the post-infectious inflammatory response and distinguish its consequences from those directly due to fungal growth.
- Management of post-infectious neuro-inflammatory syndromes associated with cryptococcal meningitis
This protocol recruits patients who have microbiological evidence of cryptococcal neurologic or non-CNS disease (typically pulmonary or bone). Cerebrospinal fluid (CSF) and blood samples collected during clinical care, are used to measure serum and intrathecal cellular and soluble cytokines as well as to perform in-situ immunohistochemistry. Observational data detailing audiological, ophthalmological and neurocognitive deficits in these patients is also recorded.
We have recently described a post-infectious inflammatory syndrome (PIIRS) associated with cryptococcal meningoencephalitis (CM) which can be best described as a neuro-inflammatory state during which CM patients present with altered mental status (Montreal Cognitive Assessment Score <22/30), auditory deficits and/or vision loss despite having negative CSF fungal cultures after being treated with optimal antifungal therapy. Based on findings in CSF and brain tissue samples, the underlying mechanism behind this phenomenon is related to the intrathecal expansion of both the innate and adaptive immune system, including HLA-DR+ CD4+ and CD8+ lymphocytes and NK cells. In a cohort of 15 previously healthy CM patients, we have been able to demonstrate an improvement in clinical outcomes with pulse corticosteroid therapy for patients with PIIRS and are currently exploring alternative immunomodulatory agents as steroid-sparing therapy for this indication.
Biography
Education
M.D., 2010, Kasturba Medical College, India
Seher Anjum MD is a Staff Clinician within the Translational Mycology Section of the Laboratory of Clinical Immunology and Microbiology (LCIM) at NIAID, NIH. She obtained an M.D. from Kasturba Medical College, India in 2010 after which she completed an internal medicine residency at the University of Missouri, Kansas City followed by an Infectious Disease fellowship at the University of Texas Medical Branch in Galveston, TX.
She then joined the LCIM as Staff Clinician in 2018 and performed clinical research to understand the pathogenesis and management of post-infectious inflammatory response syndrome (PIIRS) in previously healthy patients with cryptococcal infections. Her role involves investigating disease susceptibility in this population, clinical care and the use of corticosteroids and alternative steroid-sparing immunomodulatory agents in controlling neuro-inflammation as a result of PIIRS. She has also described ocular, neurocognitive and auditory defects related to cryptococcal meningitis in collaboration with NIMH, NIDCD and NEI.
She attends on the LCIM ward service and Infectious Disease Consult Service at the NIH Clinical Center and received NIAID merit awards in 2020 and 2021 as a member of the COVID-19 Outbreak Response Team. Future projects include conducting large-scale clinical trials as part of the CINCH (Cryptococcus Infection Network in non-HIV Cohort) to assess outcomes with corticosteroid use in HIV negative CM-PIIRS and the use of newer, oral antifungal agents in the treatment of cryptococcal infections. She is also an active member of the Mycosis Study Group Education and Research Group Consortium (MSGERC) and the Infectious Disease Society of America (IDSA).
Clinical Studies
Selected Publications
Okeagu CU, Anjum SH, Vitale S, Wang J, Singh D, Rosen LB, Magone MT, Fitzgibbon EJ, Williamson PR. Ocular Findings of Cryptococcal Meningitis in Previously Health Adults. J Neuroophthalmol. 2022 Oct 18.
Anjum S, Dean O, Kosa P, Magone MT, King KA, Fitzgibbon E, Kim HJ, Zalewski C, Murphy E, Billioux BJ, Chisholm J, Brewer CC, Krieger C, Elsegeiny W, Scott TL, Wang J, Hunsberger S, Bennett JE, Nath A, Marr KA, Bielekova B, Wendler D, Hammoud DA, Williamson P. Outcomes in Previously Healthy Cryptococcal Meningoencephalitis Patients Treated With Pulse Taper Corticosteroids for Post-infectious Inflammatory Syndrome. Clin Infect Dis. 2021 Nov 2;73(9):e2789-e2798.
Yang DH, England MR, Salvator H, Anjum S, Park YD, Marr KA, Chu LA, Govender NP, Lockhart SR, Desnos-Ollivier M, Chen S, Halliday C, Kan A, Chen J, Wollenberg KR, Zelazny A, Perfect JR, Chang YC, Bennett JE, Holland SM, Meyer W, Williamson PR, Kwon-Chung KJ. Cryptococcus gattii Species Complex as an Opportunistic Pathogen: Underlying Medical Conditions Associated with the Infection. mBio. 2021 Oct 26;12(5):e0270821.
Anjum S, Williamson PR. Clinical Aspects of Immune Damage in Cryptococcosis. Curr Fungal Infect Rep. 2019 Sep;13(3):99-108.
Research Networks
CINCH (Cryptococcus Infection Network in non-HIV Cohort)
Training Programs
NIH-Duke Clinical Research Training Program