| DB ID | MyCo_3137 |
| Title | Cerebrospinal Fluid Early Fungicidal Activity as a Surrogate Endpoint for Cryptococcal Meningitis Survival in Clinical Trials |
| Year | 2020 |
| PMID | 31912875 |
| Fungal Diseases involved | Cryptococcal meningitis |
| Associated Medical Condition | None |
| Genus | Cryptococcus |
| Species | spp. |
| Organism | Cryptococcus spp. |
| Ethical Statement | None |
| Site of Infection | None |
| Opportunistic invasive | Opportunistic |
| Sample type | Body fluid |
| Sample source | Cerebrospinal fluid (CSF) |
| Host Group | Human |
| Host Common name | Human |
| Host Scientific name | Homo sapiens |
| Biomarker Name | EFA Threshold [threshold of > = 0.20 log10 CFU/ mL/day] |
| Biomarker Full Name | Early fungicidal activity (EFA) Threshold [threshold of > = 0.20 log10 CFU/ mL/day] |
| Biomarker Type | Predictive |
| Biomolecule | mRNA |
| Geographical Location | USA |
| Cohort | Three sequential clinical trials were pooled in this analysis: the “Cryptococcal Optimal ART Timing” (COAT; n = 162) trial, the “Adjunctive Sertraline for the Treatment of HIV-associated Cryptococcal Meningitis” (ASTRO-CM; n = 179) phase 2 pilot trial, and ASTRO-CM randomized trial (n = 397). Participants were Ugandan adults living with human immunodeficiency virus (HIV) who presented to Mulago National Referral Hospital, Kampala or Mbarara Regional Referral Hospital, between November 2010 and June 2017 and who were diagnosed with cryptococcal meningitis by CSF cryptococcal antigen. The COAT trial additionally included participants from GF Jooste Hospital in Cape Town, South Africa. We analyzed data from 738 participants with a calculable EFA within the first 10 days of meningitis diagnosis. Overall, 1249 individuals were screened during the studies used for this analysis. Of these, 56 were not enrolled, 133 had an initial sterile culture, 135 died prior to day 10 with <2 LPs performed, and 189 had had <2 LPs despite surviving to day 10, leaving 738 participants. Of the 738 participants, 62% (461/738) were ART-naive with a median [P25, P75] CD4 count of 16 [6, 49] cells/μL. Mortality at 10 weeks was 36% (262/738) and 40% (297/738) by 18 weeks. |
| Cohort No. | 738 Participants |
| Age Group | None |
| P Value | None |
| Sensitivity | None |
| Specificity | None |
| Positive Predictive Value | None |
| MIC | None |
| Fold Change | None |
| Pathway | None |
| Disease Introduction Mechanism | Cryptococcal meningitis causes 15% of AIDS-related deaths globally. Despite this significant disease burden, Cryptococcus remains a neglected disease. Antifungal therapies exist, but less toxic, more effective therapies are needed. The most recent US Food and Drug Administration (FDA) approval for antifungals effective for Cryptococcus date back to 1997 for Ambisome® and 1990 for fluconazole. |
| Technique | Analytic |
| Analysis Method | FDA Approved Therapy |
| ELISA kits | None |
| Assay Data | None |
| Validation Techniques used | FDA approved Therapy |
| Up Regulation Down Regulation | None |
| Sequence Data | None |
| External Link | None |
