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

Abstract

Objective: Cryptococcal meningitis is an important cause of morbidity and mortality in HIV infected individuals. In the era of universal antiretroviral therapy 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 pre-emptive 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 material: 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 analysed. Asymptomatic cryptococcal antigenemia was detected in 5.17% patients and it correlated with increased risk of cryptococcal meningitis and mortality on follow-up in PLHIV. Conclusion: Serum cryptococcal positivity is correlated with 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.

Screening for cryptococcal antigen in asymptomatic people with HIV: urgent need in Eastern India

“…The serum CrAg positivity in patients with advanced HIV disease was 15.49% in our cohort which was very high compared to other studies from India but lower than some studies from Africa [20,21]. There is a marked regional variation in the prevalence of serum cryptococcemia in India with 0% in the southern state of Kerala [8], 2.67–8% in western India [9,10,12,15], 3.1–6.8% in Delhi [11,13,14], 9.6–12.56% in Northeast and Eastern India [16,17]. This variation may be attributed to geographical and soil habitats.…”

“…There is a marked regional variation in the prevalence of serum cryptococcemia in India with 0% in the southern state of Kerala [8], 2.67-8% in western India [9,10,12,15], 3.1-6.8% in Delhi [11,13,14], 9.6-12.56% in Northeast and Eastern India [16,17]. This variation may be attributed to geographical and soil habitats.…”

“…Cryptococcal meningitis (CM) is a life-threatening fungal infection in people with HIV (PWH) with low CD4 þ T cell count. CM has been reported to cause 15% [95% confidence interval (CI) [10][11][12][13][14][15][16][17][18][19] of AIDS-related deaths after tuberculosis [1]. Worldwide, 223 100 new cases (95% CI: 150 600-282 400) of cryptococcal meningitis with 181 100 (95% CI 119 400-234 300) deaths were reported in 2014.…”

“…However, data on the frequency of this potentially preventable disease in India is limited. In recent studies from India, the prevalence of cryptococcal antigenemia varies from 0 to 12.5%; highest in the North East and Eastern region and least in the southern part of the country [8][9][10][11][12][13][14][15][16][17]. None of these studies have systematically screened for serum CrAg followed by CSF testing in those positive.…”

Implementation of point-of-care testing and prevalence of cryptococcal antigenaemia among patients with advanced HIV disease in Mumbai, India

“…Pooled estimated proportions of OIs among PLHIV in India ranks tuberculosis (TB) as the major OI (56.7%) with CM at 4.3% 12. The prevalence of cryptococcal antigenaemia among adults with CD4 cells <100 cells/mm 3 varied between 0% and 12.6% in the studies from India 13–18…”