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| Name | Class |
|---|---|
| Centers for Disease Control and Prevention | FED |
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The study will determine if the initiation of a 'screen and treat' program for cryptococcal disease among HIV positive individuals decreases morbidity and mortality among individuals with CD4 count < 100 cells/mm3. The study will screen individuals who are asymptomatic for CM and are either ART naïve or ART experienced with CD4 count < 100 cells/mm3.
The introduction of an cheap, easy to use point of care diagnostic test the lateral flow assay will facilitate rapid diagnosis of cryptococcal disease in resource limited settings. The investigators will determine the efficacy of the lateral flow assay in identifying latent and asymptomatic cryptococcal disease. The investigators will determine the efficacy of the test in detecting disease in readily available body fluids such as urine and whole blood obtained via finger-stick method. The investigators will also determine the cost effectiveness of a screen and treat approach for cryptococcal disease in Zimbabwe.
The investigators also wish to understand why some individuals with low CD4 counts reactivate cryptococcal disease and screen positive for cryptococcal antigen (CrAg) while others with similar levels of immunocompromised do not.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Screening | There are no arms to the study. All participants will undergo screening. Preemptive treatment will only be provided to those who are CrAg positive. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pre-emptive screening and treatment for cryptococcal disease | Other | Preemptive screening for cryptococcal disease among individuals with CD4 counts below 100 cells/mm3 with anti fungal therapy for those what are Cryptococcus antigen positive. These participants will be followed longitudinally for 12 months to determine clinical outcome, with their outcome compared with similar patients who are cryptococcal antigen negative, who will also be followed longitudinally for 12 months. |
| Measure | Description | Time Frame |
|---|---|---|
| 12- month survival in CrAg-positive persons vs. CrAg-negative persons screened | 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Seroprevalence of asymptomatic cryptococcal antigenemia among individuals with CD4≤100 cells/mm3 in an urban population in Zimbabwe | 24 months | |
| Sensitivity, specificity, positive and negative predictive values of point-of-care urine CrAg LFAs | 24 months |
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Inclusion Criteria:
Exclusion Criteria:
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The study will recruit Asymptomatic participants with severe immunosuppression at risk of cryptococcal disease. The individuals will have a CD4 count <100cells/mm3 and can be ART naive or ART experienced with no symptoms of active Cryptococcal disease.
They will be recruited from outpatient HIV/ART clinics.
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| Name | Affiliation | Role |
|---|---|---|
| Chiratidzo E Ndhlovu, MBBS, MSc | University of Zimbabwe College of Health Sciences | Principal Investigator |
| Azure T Makadzange, MD DPhil | Massachusetts General Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Parirenyatwa Hospital | Harare | Zimbabwe |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36924288 | Derived | Kouamou V, Gundidza P, Ndhlovu CE, Makadzange AT; CryptoART Study Team. Effects of Gender and Baseline CD4 Count on Post-Treatment CD4 Count Recovery and Outcomes in Patients with Advanced HIV Disease: A Retrospective Cohort Study. AIDS Res Hum Retroviruses. 2023 Jul;39(7):340-349. doi: 10.1089/AID.2022.0117. Epub 2023 Apr 26. | |
| 35924841 | Derived | Boyd K, Kouamou V, Hlupeni A, Tangwena Z, Ndhlovu CE, Makadzange AT; CryptoART Study Team. Diagnostic Accuracy of Point of Care Cryptococcal Antigen Lateral Flow Assay in Fingerprick Whole Blood and Urine Samples for the Detection of Asymptomatic Cryptococcal Disease in Patients with Advanced HIV Disease. Microbiol Spectr. 2022 Aug 31;10(4):e0107522. doi: 10.1128/spectrum.01075-22. Epub 2022 Aug 4. |
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| ID | Term |
|---|---|
| D016919 | Meningitis, Cryptococcal |
| ID | Term |
|---|---|
| D016921 | Meningitis, Fungal |
| D020314 | Central Nervous System Fungal Infections |
| D009181 | Mycoses |
| D001423 | Bacterial Infections and Mycoses |
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| ID | Term |
|---|---|
| D013812 | Therapeutics |
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Plasma, and peripheral blood mononuclear cells
|
| Sensitivity, specificity, positive and negative predictive values of point-of-care whole blood CrAg LFAs | 24 months |
| Proportion of individuals with CD4≤100 cells/mm3 and a positive CrAg assay who have disseminated cryptococcal infection with either blood infection or CSF involvement | 24 months |
| 12-month survival among individuals with CD4≤100 cells/mm3 prior to implementation of CrAg screening program using historical controls | Retrospective analysis | 24 months |
| Cost of implementation of CrAg screening among individuals with CD4≤100 cells/mm3 | 24 months |
| Cryptococcus-associated mortality among individuals with CD4≤100 cells/mm3, | 24 months |
| Incidence of cryptococcal and non-cryptococcal IRIS | 24 months |
| Barriers to uptake of diagnostic LP by individuals with asymptomatic cryptococcal antigenemia. | Questionnaire will be administered to participants who are serum cryptococcal antigen positive who decline to undergo LP. | 24 months |
| Inflammatory cytokines and functional impairments in antigen specific T cells that are associated with the development of cryptococcal antigenemia and meningitis. | Analysis will be done by ELISA and Luminex assays, cell culture and flow cytometry techniques, data collected will be entered into a database and analyzed by patient characteristics. | 24 months |
| Impact of ART mediated immune reconstitution on the inflammatory cytokine profile and the cryptococcal antigen specific CD4+ T cell response in those with serum and CSF cryptococcal antigenemia compared with those without. | Analysis will be done by ELISA and Luminex assays, cell culture and flow cytometry techniques, data collected will be entered into a database and analyzed by patient characteristics. Data will be longitudinal including baseline characteristics and subsequent follow-up data at 6 months and 12 months. | 24 months |
| D007239 | Infections |
| D003453 | Cryptococcosis |
| D002494 | Central Nervous System Infections |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D008581 | Meningitis |
| D000090862 | Neuroinflammatory Diseases |