Prevalence of Asymptomatic Cryptococcal Antigenemia and Association with Follow-up Risk of Cryptococcal Meningitis and Mortality among HIV Infected Patients in North West India: A Prospective Cohort Study

Author(s): Rajendra Bhati, Sirohi Pramendra, Bharat Sejoo, Deepak Kumar*, Gopal K. Bohra, Durga S. Meena, Diwakar Verma, Naresh K. Midha

Journal Name: Current HIV Research
HIV and Viral Immune Diseases

Volume 19 , Issue 1 , 2021

Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Objective: Cryptococcal meningitis is an important cause of morbidity and mortality in HIV infected individuals. In the era of universal antiretroviral therapy, the incidence of immune reconstitution inflammatory syndrome (IRIS) related cryptococcal meningitis has increased. Detection of serum cryptococcal antigen in asymptomatic PLHIV (People Living With HIV) and preemptive treatment with fluconazole can decrease the burden of cryptococcal disease. We conducted this study to find the prevalence of asymptomatic cryptococcal antigenemia in India and its correlation with mortality in PLHIV.

Method and Materials: This was a prospective observational study. HIV infected ART naïve patients with age of ≥ 18 years who had CD4 counts ≤ 100 /μL were included and serum cryptococcal antigen test was done. These patients were followed for six months to look for the development of Cryptococcal meningitis and mortality.

Results: A total of 116 patients were analyzed. Asymptomatic cryptococcal antigenemia was detected in 5.17% of patients and is correlated with increased risk of cryptococcal meningitis and mortality on follow-up in PLHIV.

Conclusion: Serum cryptococcal antigen positivity is correlated with an increased risk of Cryptococcal meningitis and mortality in PLHIV. We recommend the screening of asymptomatic PLHIV with CD4 ≤ 100/μL for serum cryptococcal antigen, so that pre-emptive treatment can be initiated to reduce morbidity and mortality.

Keywords: Cryptococcal meningitis, serum cryptococcal antigen, asymptomatic cryptococcal antigenemia, CD4 counts, HIV infection, antiretroviral therapy.

Park BJ, Wannemuehler KA, Marston BJ, Govender N, Pappas PG, Chiller TM. Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS. AIDS 2009; 23(4): 525-30.
[] [PMID: 19182676]
Kumarasamy N, Solomon S, Flanigan TP, Hemalatha R, Thyagarajan SP, Mayer KH. Natural history of human immunodeficiency virus disease in southern India. Clin Infect Dis 2003; 36(1): 79-85.
[] [PMID: 12491206]
Rajasingham R, Wake RM, Beyene T, Katende A, Letang E, Boulware DR. Cryptococcal meningitis diagnostics and screening in the era of point-of-care laboratory testing. J Clin Microbiol 2019; 57(1): e01238-18.
[PMID: 30257903]
WHO. Rapid Advice: Diagnosis, Prevention and Management of Cryptococcal Disease in HIV-Infected Adults, Adolescents and Children World Health Organization 2011. hiv/pub/cryptococcal_disease2011/en/
Kimaro GD, Mfinanga S, Simms V, et al. REMSTART trial team. The costs of providing antiretroviral therapy services to HIV-infected individuals presenting with advanced HIV disease at public health centres in Dar es Salaam, Tanzania: Findings from a randomised trial evaluating different health care strategies. PLoS One 2017; 12(2): e0171917.
[] [PMID: 28234969]
French N, Gray K, Watera C, et al. Cryptococcal infection in a cohort of HIV-1-infected Ugandan adults. AIDS 2002; 16(7): 1031-8.
[] [PMID: 11953469]
Ford N, Shubber Z, Jarvis JN, Chiller T, Greene G, Migone C, et al. CD4 Cell Count Threshold for Cryptococcal Antigen Screening of HIV-Infected Individuals: A Systematic Review and Meta-analysis 2018; 66(2): s152-9.
Vidal JE, Toniolo C, Paulino A, et al. Asymptomatic cryptococcal antigen prevalence detected by lateral flow assay in hospitalised HIV-infected patients in São Paulo, Brazil. Trop Med Int Health 2016; 21(12): 1539-44.
[] [PMID: 27699970]
Ezeanolue EE, Nwizu C, Greene GS, et al. Brief Report: Geographical Variation in Prevalence of Cryptococcal Antigenemia Among HIV-Infected, Treatment-Naive Patients in Nigeria: A Multicenter Cross-Sectional Study. J Acquir Immune Defic Syndr 2016; 73(1): 117-21.
[] [PMID: 27144527]
Letang E, Müller MC, Ntamatungiro AJ, et al. Cryptococcal antigenemia in immunocompromised human immunodeficiency virus patients in rural tanzania: A preventable cause of early mortality. Open Forum Infect Dis 2015; 2(2): ofv046.
[] [PMID: 26213690]
Ogouyèmi-Hounto A, Zannou DM, Ayihounton G, et al. Prévalence de l’antigénémie cryptococcique et les facteurs associés chez les patients infectés par le VIH à Cotonou au Bénin. J Mycol Med 2016; 26(4): 391-7.
[] [PMID: 27641486]
Kadam D, Chandanwale A, Bharadwaj R, et al. High prevalence of cryptococcal antigenaemia amongst asymptomatic advanced HIV patients in Pune, India. Indian J Med Microbiol 2017; 35(1): 105-8.
[] [PMID: 28303828]
Anuradha S, Abhaya NH, Dewan R, Kaur R, Rajeshwari K. Asymptomatic cryptococcal antigenemia in people living with HIV (PLHIV) with severe immununosuppression: Is routine Cryptococcal antigen screening indicated in India? J Assoc Physicians India 2017; 85: 14-7.
[PMID: 28527158]
Liechty CA, Solberg P, Were W, et al. Asymptomatic serum cryptococcal antigenemia and early mortality during antiretroviral therapy in rural Uganda. Trop Med Int Health 2007; 12(8): 929-35.
[] [PMID: 17697087]
Meya DB, Manabe YC, Castelnuovo B, et al. Cost-effectiveness of serum cryptococcal antigen screening to prevent deaths among HIV-infected persons with a CD4+ cell count < or = 100 cells/microL who start HIV therapy in resource-limited settings. Clin Infect Dis 2010; 51(4): 448-55.
[] [PMID: 20597693]
Sawadogo S, Makumbi B, Purfield A, et al. Estimated prevalence of cryptococcus antigenemia (CrAg) among HIV-infected adults with advanced immunosuppression in namibia justifies routine screening and preemptive treatment. PLoS One 2016; 11(10): e0161830.
[] [PMID: 27760140]
Ganiem AR, Indrati AR, Wisaksana R, et al. Asymptomatic cryptococcal antigenemia is associated with mortality among HIV-positive patients in Indonesia. J Int AIDS Soc 2014; 17: 18821.
[] [PMID: 24476751]
Mfinanga S, Chanda D, Kivuyo SL, et al. REMSTART trial team. Cryptococcal meningitis screening and community-based early adherence support in people with advanced HIV infection starting antiretroviral therapy in Tanzania and Zambia: an open-label, randomised controlled trial. Lancet 2015; 385(9983): 2173-82.
[] [PMID: 25765698]
Jarvis JN, Harrison TS, Lawn SD, Meintjes G, Wood R, Cleary S. Cost effectiveness of cryptococcal antigen screening as a strategy to prevent HIV-associated cryptococcal meningitis in South Africa. PLoS One 2013; 8(7): e69288.
[] [PMID: 23894442]
Parkes-Ratanshi R, Wakeham K, Levin J, et al. Cryptococcal Trial Team. Primary prophylaxis of cryptococcal disease with fluconazole in HIV-positive Ugandan adults: a double-blind, randomised, placebo-controlled trial. Lancet Infect Dis 2011; 11(12): 933-41.
[] [PMID: 21982529]

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2021
Published on: 27 August, 2020
Page: [35 - 39]
Pages: 5
DOI: 10.2174/1570162X18666200827113816
Price: $65

Article Metrics

PDF: 27