Pediatric Coccidioidal Meningitis: A Systematic Review and Proportional Synthesis of Cases Reported in the Fluconazole Era (2000–2025)
Abstract
1. Introduction
2. Materials and Methods
3. Results
3.1. Demographics and Immunodeficiency
3.2. Diagnostics
3.3. CNS Complications
3.4. Medical Treatment
3.5. Neurosurgical Management
3.6. Follow-Up and Outcomes
3.7. Long-Term Therapy and Prognostic Factors
4. Discussion
4.1. Diagnosis
4.2. Neurological Complications
4.3. Medical Treatment
4.4. Neurosurgical Procedures
4.5. Follow-Up and Outcomes
4.6. Limitations
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
ACA | Anterior cerebral artery |
ALL | Acute lymphoblastic leukemia |
AmB | Amphotericin B |
AmB-D | Amphotericin B deoxycholate |
CA | California |
CASPO | Caspofungin |
CDPH | California Department of Public Health, Richmond, CA, USA |
CF | Complement fixation |
CH-HIS | Children’s Hospital, Iowa Health Systems, Des Moines, IA, USA |
CHCC/VCH | Children’s Hospital Central California/Valley Children’s Healthcare, Madera, CA, USA |
CHLA | Children’s Hospital Los Angeles, Los Angeles, CA, USA |
CHOC | Children’s Hospital of Orange County, Orange, CA, USA |
CMC | Cohen Medical Center, Long Island, NY, USA |
CM | Coccidioidal meningitis |
CNS | Central nervous system |
CRS | Children’s Research Center |
CSF | Cerebrospinal fluid |
CT | Computed tomography |
CXR | Chest radiography |
d | Days |
DAVID syndrome | Deficient anterior pituitary function and variable immune deficiency |
D-AmB | Deoxycholate amphotericin B |
DPGN | Diffuse proliferative glomerulonephritis |
EIA | Enzyme immunoassay |
ELISA | Enzyme-linked immunosorbent assay |
EVD | External ventricular derivation |
F | Female |
FLU | Fluconazole |
FOM-CU | Faculty of Medicine, Cairo University, Cairo, Egypt |
FU | Follow-up |
GMS | Gomori’s methenamine silver |
HE | Hematoxylin and eosin |
HIES | Hyperimmunoglobulin E syndrome (Job’s syndrome) |
HIV | Human immunodeficiency virus |
ICA | Internal carotid artery |
ID | Immunodiffusion |
IFN-γ | Interferon gamma |
IFV | Isolated fourth ventricle |
Ig | Immunoglobulin |
IgG | Immunoglobulin G |
INNN | National Institute of Neurology and Neurosurgery, Mexico City, Mexico |
INT-γ | Interferon gamma |
IQR | Interquartile range |
ISA | Isavuconazole |
IT | Intrathecal |
ITRA | Itraconazole |
IV | Intravenous |
JHUSOM | Johns Hopkins University School of Medicine, Baltimore, MD, USA |
JIA | Juvenile idiopathic arthritis |
Keck SOM USC | Keck School of Medicine, University of Southern California, Los Angeles, CA, USA |
KET | Ketoconazole |
LAC + USC | Los Angeles County + University of Southern California Medical Center |
L-AmB | Liposomal amphotericin B |
LN | Lupus nephritis |
LoS | Length of hospital stay |
M | Male |
MCA | Middle cerebral artery |
MRI | Magnetic resonance imaging |
NA | Not available |
ND | Not described |
NE | Not evaluated |
NIAID | National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA |
NIH | National Institutes of Health, Bethesda, MD, USA |
PCR | Polymerase chain reaction |
PCA | Posterior cerebral artery |
POSA | Posaconazole |
PPD | Purified protein derivative |
RT-PCR | Reverse transcription polymerase chain reaction |
SAVAHCS | Southern Arizona VA Healthcare System, Tucson, AZ, USA |
SCVMC | Santa Clara Valley Medical Center, San Jose, CA, USA |
SD | Standard deviation |
Stanford SOM | Stanford University School of Medicine, Stanford, CA, USA |
STAT1 | Signal transducer and activator of transcription 1 |
STAT3 | Signal transducer and activator of transcription 3 |
Steele CRS | Steele Children’s Research Center, University of Arizona, Tucson, AZ, USA |
TVE | Third ventriculostomy endoscopic |
UACOM | University of Arizona College of Medicine, Tucson, AZ, USA |
UCSF | University of California, San Francisco Benioff Children’s Hospital, San Francisco, CA, USA |
UH-UANL | University Hospital “Dr. José Eleuterio González”, Universidad Autónoma de Nuevo León, Monterrey, Mexico |
UUSOM | University of Utah School of Medicine, Salt Lake City, UT, USA |
V/C | Voriconazole plus caspofungin |
VP shunt | Ventriculoperitoneal shunt |
VORI | Voriconazole |
y | Years |
mo | Months |
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Variable | n (%) |
---|---|
Age (months) | mean 105.1 SD = 75.6 |
Sex | |
Male | 24 (50) |
Female | 23 (48) |
Unknown | 1 (2) |
Ethnicity | |
Hispanic/Latinx | 23 (48) |
White (no Hispanic) | 9 (19) |
Black or African American | 4 (8) |
Asian | 3 (6) |
Other/unknown | 9 (19) |
Immunodeficiency (yes) | 18 (37.5) |
No/unknown | 30 (62.5) |
CXR normal/negative | 6 (12.5) |
CRX abnormal/prior pneumonia | 15 (31.3) |
Unknown | 27 (56.3) |
CNS complications (Neuroimaging or autopsy) | |
Hydrocephalus | 34 (70.8) |
Cerebral vasculitis/stroke | 10 (20.8) |
Brain/cerebellar abscess | 6 (12.5) |
Spinal alterations | 9 (18.8) |
IFV | 3 (6.3) |
Hydrocephalus + stroke | 38 (79.2) |
Status | |
Alive/stable | 34 (71) |
Relapse/progressive diseases | 5 (10) |
Died | 9 (19) |
Method | n (%) |
---|---|
Serologies (CF, ID, EIA) | |
Positive | 38 (79) |
Negative/unknown | 10 (21) |
CF serum | |
Positive | 21 (44) |
Negative/unknown | 27 (56) |
CF serum (initial diagnostic level) | Median 1:16 (range 1:2 to 1:2048) |
CF serum (highest level) | Median 1:32 (range 1:2 to 1:2048) |
CSF CF | |
Positive | 21 (44) |
Negative/unknown | 27 (56) |
CSF CF (level initial diagnostic) | 1:2 (range 1:2 to 1:32) |
Culture | |
Positive | 20 (42) |
Negative/unknown | 28 (58) |
Positive cultures | (n = 20) |
Cultures (CNS or CSF) | 13 (65) |
Other sites | 7 (35) |
Histopathological findings/cytology | |
Positive | 11 (23) |
Negative/unknowns | 37 (77) |
RT-PCR/DNA | |
Positive | 3 (6) |
Negative/unknown | 45 (94) |
Therapy | n (%) |
---|---|
Initial antifungal therapy | |
FLU | 31 (65) |
Monotherapy | 20 (65) |
Combination therapy | 11 (35) |
Other therapy | 17 (35) |
AmB IT or IV | 10 (37) |
Itraconazole | 1 (6) |
Voriconazole | 1 (6) |
L-AmB + voriconazole | 4 (24) |
Patient died before treatment | 1 (6) |
Maintenance therapy | |
L-AmB monotherapy | 10 (21) |
Azole monotherapy | 21 (44) |
AmB + azole | 8 (17) |
V/C | 3 (7) |
Triple therapy/other combinations | 5 (10) |
Patient died before treatment | 1(2) |
Treatment schemas | |
Monotherapy | 31 (66) |
Doble therapy | 11 (23) |
Triple therapy | 5 (11) |
Other therapies | |
INF- γ | 2 (4) |
Long-term/lifelong azole therapy | 26 (54) |
Variable | OR | 95% CI Lower | 95% CI Upper | p-Value |
---|---|---|---|---|
Serum CF titers ≥ 1:16 | 4.500 | 1.097 | 18.465 | 0.037 |
Lifelong azole | 0.250 | 0.060 | 1.040 | 0.057 |
Constant | 0.444 | - | - | 0.139 |
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De la Cerda-Vargas, M.F.; Navarro-Dominguez, P.; Meza-Mata, E.; Muñoz-Hernandez, M.A.; Segura-Lopez, F.K.; Gonzalez-Martinez, M.D.R.; Delgado-Aguirre, H.A.; Flores-Miranda, S.V.; Mercado-Rubio, D.d.J.; Adame-Martínez, Y.O.; et al. Pediatric Coccidioidal Meningitis: A Systematic Review and Proportional Synthesis of Cases Reported in the Fluconazole Era (2000–2025). J. Fungi 2025, 11, 713. https://doi.org/10.3390/jof11100713
De la Cerda-Vargas MF, Navarro-Dominguez P, Meza-Mata E, Muñoz-Hernandez MA, Segura-Lopez FK, Gonzalez-Martinez MDR, Delgado-Aguirre HA, Flores-Miranda SV, Mercado-Rubio DdJ, Adame-Martínez YO, et al. Pediatric Coccidioidal Meningitis: A Systematic Review and Proportional Synthesis of Cases Reported in the Fluconazole Era (2000–2025). Journal of Fungi. 2025; 11(10):713. https://doi.org/10.3390/jof11100713
Chicago/Turabian StyleDe la Cerda-Vargas, Maria F., Pedro Navarro-Dominguez, Elizabeth Meza-Mata, Melisa A. Muñoz-Hernandez, Fany Karina Segura-Lopez, Marisela Del Rocio Gonzalez-Martinez, Hector A. Delgado-Aguirre, Sergio Valente Flores-Miranda, David de Jesús Mercado-Rubio, Yair O. Adame-Martínez, and et al. 2025. "Pediatric Coccidioidal Meningitis: A Systematic Review and Proportional Synthesis of Cases Reported in the Fluconazole Era (2000–2025)" Journal of Fungi 11, no. 10: 713. https://doi.org/10.3390/jof11100713
APA StyleDe la Cerda-Vargas, M. F., Navarro-Dominguez, P., Meza-Mata, E., Muñoz-Hernandez, M. A., Segura-Lopez, F. K., Gonzalez-Martinez, M. D. R., Delgado-Aguirre, H. A., Flores-Miranda, S. V., Mercado-Rubio, D. d. J., Adame-Martínez, Y. O., Valadez-Altamira, G. A., & Candelas-Rangel, J. A. (2025). Pediatric Coccidioidal Meningitis: A Systematic Review and Proportional Synthesis of Cases Reported in the Fluconazole Era (2000–2025). Journal of Fungi, 11(10), 713. https://doi.org/10.3390/jof11100713