Cryptococcosis screening
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Serge Korjian M.D.; Yazan Daaboul, M.D.
Overview
Asymptomatic cryptococcal antigenemia is very common in areas with endemic HIV/AIDS, and is associated with increased mortality and incidence of cryptococcal meningitis. Screening is not recommended for HIV/AIDS patients in the United States or Europe. However, screening may be beneficial in countries with limited HAART availability, high levels of antiretroviral drug resistance, and a high burden of disease. In the absence of symptoms, positive cryptococcal antigenemia should be treated with fluconazole 400 mg PO qd.[1]
Screening
- Early studies demonstrated that asymptomatic cryptococcal antigenemia can be detected in up to 12% of patients with HIV/AIDS in endemic regions.
- Cryptococcus neoformans was also demonstrated by direct microscopy and culture in the cerebrospinal fluid of approximately 2/3 of patients.[2]
- Further studies conducted in endemic regions in Africa (South Africa, Uganda) demonstrated that asymptomatic cryptococcal antigenemia ranged from 7 to 38%.[3][4]
- Asymptomatic antigenemia was also demonstrated to be an independent predictor of mortality among these patients, and, during the first year of ART, an antigen titer greater than 1:8 was 100% sensitive and 96% specific for predicting the incidence of cryptococcal meningitis.[4]
- These alarming findings raised a question about the possibility of developing screening programs among high risk HIV/AIDS patients, and providing patients with fluconazole prophylaxis the decrease the risk of active infections.
- Concerns about the cost-effectiveness and efficacy of screening and subsequent prophylaxis have not been addressed in adequately designed and powered studies.
- The limited body of evidence suggests that screening and treatment reduces the incidence of cryptococcal meningitis and death in persons with AIDS.[5]
Methods of Screening
- The majority of studies on cryptococcal screening have used cryptococcal antigen also know as CrAg.[5]
- New point-of-care methods for detecting CrAg have been developed.
- A dipstick test that requires a small blood sample can detect silent antigenemia with high sensitivity in less than 10 minutes and for a small cost (less than $2) has been introduced in 2014.[6][7]
Recommendations
- Given that the efficacy of such an approach has not been thoroughly studied, the IDSA does not recommend routine screening for asymptomatic antigenemia in HIV-infected patients in the United States and Europe.
- However, the IDSA recommends that areas with limited HAART availability, high levels of antiretroviral drug resistance, and a high burden of disease should consider it.
- Cryptococcal meningitis commonly affects patients with CD4 count are ≤ 100 cells/μl. It is responsible for major cause of mortality and morbidity in HIV individuals. It is recommended that patients with CD4 counts ≤ 100 cells/μl, should have routine cryptococcal antigen screening. Patients with positive result are offered preemptive anti-fungal therapy.[8][9]
- In the case of asymptomatic antigenemia, a lumbar puncture and a blood culture are recommended.
- Positive results should warrant treatment as symptomatic meningoencephalitis and/or disseminated disease if any signs/symptoms are present.
- However, without evidence of meningoencephalitis, patients should be treated with fluconazole 400 mg PO qd.[1]
References
- ↑ 1.0 1.1 Perfect JR, Dismukes WE, Dromer F, Goldman DL, Graybill JR, Hamill RJ; et al. (2010). "Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america". Clin Infect Dis. 50 (3): 291–322. doi:10.1086/649858. PMID 20047480.
- ↑ Desmet P, Kayembe KD, De Vroey C (1989). "The value of cryptococcal serum antigen screening among HIV-positive/AIDS patients in Kinshasa, Zaire". AIDS. 3 (2): 77–8. PMID 2496722.
- ↑ Tassie JM, Pepper L, Fogg C, Biraro S, Mayanja B, Andia I; et al. (2003). "Systematic screening of cryptococcal antigenemia in HIV-positive adults in Uganda". J Acquir Immune Defic Syndr. 33 (3): 411–2. PMID 12843756.
- ↑ 4.0 4.1 Jarvis JN, Lawn SD, Vogt M, Bangani N, Wood R, Harrison TS (2009). "Screening for cryptococcal antigenemia in patients accessing an antiretroviral treatment program in South Africa". Clin Infect Dis. 48 (7): 856–62. doi:10.1086/597262. PMC 2875173. PMID 19222372.
- ↑ 5.0 5.1 Kaplan JE, Vallabhaneni S, Smith RM, Chideya-Chihota S, Chehab J, Park B (2015). "Cryptococcal antigen screening and early antifungal treatment to prevent cryptococcal meningitis: a review of the literature". J Acquir Immune Defic Syndr. 68 Suppl 3: S331–9. doi:10.1097/QAI.0000000000000484. PMID 25768872.
- ↑ Preventing Deaths Due to Cryptococcus with Targeted Screening. Centers for Disease Control and Prevention (2015). http://www.cdc.gov/fungal/diseases/cryptococcosis-neoformans/screening.html. Accessed on December 20, 2015
- ↑ Kabanda T, Siedner MJ, Klausner JD, Muzoora C, Boulware DR (2014). "Point-of-care diagnosis and prognostication of cryptococcal meningitis with the cryptococcal antigen lateral flow assay on cerebrospinal fluid". Clin Infect Dis. 58 (1): 113–6. doi:10.1093/cid/cit641. PMC 3864499. PMID 24065327.
- ↑ Cassim N, Schnippel K, Coetzee LM, Glencross DK (2017). "Establishing a cost-per-result of laboratory-based, reflex Cryptococcal antigenaemia screening (CrAg) in HIV+ patients with CD4 counts less than 100 cells/μl using a Lateral Flow Assay (LFA) at a typical busy CD4 laboratory in South Africa". PLoS One. 12 (2): e0171675. doi:10.1371/journal.pone.0171675. PMID 28166254.
- ↑ Greene G, Sriruttan C, Le T, Chiller T, Govender NP (2017). "Looking for fungi in all the right places: screening for cryptococcal disease and other AIDS-related mycoses among patients with advanced HIV disease". Curr Opin HIV AIDS. 12 (2): 139–147. doi:10.1097/COH.0000000000000347. PMID 28134711.