View clinical trials related to Meningitis, Cryptococcal.
Filter by:Cryptococcal meningitis (CM) is a fungal infection that causes a severe syndrome of meningitis that is 100% fatal without antifungal therapy. Even with antifungal therapy, mortality rates remain high, especially in Africa where the ongoing HIV/AIDS pandemic leads to higher prevalence of cryptococcosis. Combination of amphotericin and flucytosine (5-FC) is the mainstay of therapy for the initial management of CM. Indeed, it has even been shown that effective delivery of these therapies in Africa can lower mortality rates by 90%. This is a prospective open-label trial to compare the efficacy and safety of lower doses of 5FC during induction therapy to historical controls with standard 5FC dosing. Participants in the trial will receive 60mg/kg/day of 5-FC in 3 divided doses for 10 days. Single-dose liposomal amphotericin (10mg/kg) is preferred, if available. Amphotericin B 0.7-1.0 mg/kg/day may be used if needed. Historical controls drawn from the AMBITION trial will be used as a comparison group, selected weighted by inclusion/exclusion criteria, baseline characteristics and therapies received. Induction therapy for control group participants followed the 2018 WHO cryptococcal guidelines with 7 days of 5-FC 100mg/kg/day and 7 days of IV Amphotericin deoxycholate followed by 1200mg fluconazole/day for 7 days. The intervention group received single- dose liposomal amphotericin plus 5-FC and fluconazole 1200 mg/day. All participants will receive fluconazole 1200mg/day during consolidation therapy from day 1 to 14 then 800mg/day from day 15 to 10 weeks, and 200mg/day after 10 weeks. All participants will receive lumbar punctures at diagnosis, day 3, day 5-7, day 10-14, and additionally as required for control of intracranial pressure and documentation of CSF sterilization. Controls from Ambition will be matched for the same LP windows. Therapeutic LPs conducted during the first week have a ~70% relative survival benefit.
This will be a randomized controlled trial of asymptomatic (Cryptococcal Antigen test)CrAg positive persons in Uganda. Patients will be randomized to receive preemptive treatment with 1 dose of liposomal amphotericin (10mg/kg) in addition to standard of care fluconazole therapy. How the enhanced antifungal therapy prevents progression to meningitis in the first 24-weeks and overall survival in those who receive the intervention compared with participants receiving fluconazole per World Health Organisation (WHO) and national standard of care therapy will be evaluated.
To evaluate the safety and efficacy of liposomal amphotericin B and amphotericin B deoxycholate with or without flucytosine followed by fluconazole for the treatment of cryptococcal meningitis.
Background: - Idiopathic CD4+ lymphocytopenia (ICL) is a condition in which there is a decreased level of CD4+ lymphocytes (a type of white blood cell), which can lead to opportunistic infections or autoimmune disorders and diseases. Objectives: - To characterize the natural history with regard to CD4+ T cell count and onset of infection, malignancy, and autoimmunity. - To describe the immunological status of patients affected by ICL while providing the best possible standard therapy to eradicate opportunistic infections. - To establish the timeline of CD4 lymphocytopenia, with particular focus on defining subgroups of patients according to the decline, stabilization, or rise of CD4+ T cell counts over time. - To characterize the opportunistic infections that occur in ICL patients at microbiologic and molecular levels. - To characterize the immunophenotype and possible genetic immunodeficiency causes of ICL. - To determine whether measurable immunologic parameters correlate with the development of opportunistic infections or other comorbidities such as lymphoma in patients with ICL. - To determine whether there is any association between ICL and autoimmunity. - To determine CD4+ T cell turnover, survival, functionality, and cytokine responsiveness in ICL patients. Eligibility: - Patients 2 years of age and older with an absolute CD4 count less than 300 in children 6 years or older and adults or less than 20% of T cells in children younger than 6 on two occasions at least 6 weeks apart. - Patients with negative results of HIV testing by ELISA, Western Blot, and viral load. - Patients must not have underlying immunodeficiency conditions, be receiving cytotoxic chemotherapy (anti-cancer drugs that kill cells), or have cancer. Design: - At the initial visit to the National Institutes of Health, the following evaluations will be conducted: - Personal and family medical histories. - Physical examination, including rheumatology evaluation and other consultations as medically indicated (e.g., dermatology, pulmonology, ophthalmology, imaging studies). - Blood samples for analysis of red and white blood cell counts, liver function, immune hormones, and antibody and autoantibody levels, white blood cell growth and function, and DNA. - Urinalysis and urine pregnancy testing for female patients of childbearing age. - Evaluation and treatment of active infections as medically indicated, including biopsies, buccal swabs, pulmonary function tests, and imaging studies. - Follow-up visits will take place approximately every 12 months or more frequently if indicated, and will continue for a minimum of 4 years and a maximum of 10 years. - Evaluations at follow-up will include blood samples (i.e., CBC with differential, biochemical profile, HIV testing, etc.) and urinalysis and rheumatology consults.
This study will follow the course of disease in previously healthy patients with cryptococcosis who developed the disease for no identifiable reason. Participants may be followed for up to 5 years. Individuals with a positive Cryptococcus (neoformans or gattii) culture that are 18 years of age and older without HIV infection or other condition predisposing to cryptococcosis (such as high-dose corticosteroid therapy, sarcoidosis, or a blood cancer) may be eligible for this study. Genetic relatives and healthy volunteers are also eligible for this study. Candidates who test positive for HIV infection may not participate. Study participants have the option to be completely remote through tele-health visits with cooperation from their PCP and local physicians, or participate through in-person visits at the NIH Clinical Center. Potential participants will have a physical examination, past medical and family history evaluations, routine laboratory tests, and assessment of disease activity performed during the initial screening and enrollment visit. Patients who have active cryptococcosis may also have a lumbar puncture (spinal tap), imaging, and/or additional laboratory tests performed, as clinically indicated. After the initial screening evaluation and study enrollment, patients receiving treatment for cryptococcosis can either continue to be seen remotely through tele-health visits, or they can come to the NIH Clinical Center as needed to manage their disease, typically no less than every 3 months. Other patients will be seen every 6 to 12 months. These follow-up visits may include a medical history, physical examination, routine laboratory tests, imaging, and updates to their treatment plan as indicated.