Should cryptococcal antigen screening be considered as a routine procedure in antiretroviral therapy naïve severely immunocompromised HIV-seropositives – a prevalence study from Eastern India to support recent 2018 WHO guidelines

Abstract

Introduction: Cryptococcal meningitis, a leading opportunistic infection, causes significant morbidity and mortality in people with advanced human immunodeficiency virus (HIV). It accounts for an estimated 15% of acquired immune deficiency syndrome-related deaths globally. As recommended by the World Health Organization (WHO) 2018 guidelines, this invasive disease is preventable by routine cryptococcal antigen (CrAg) screening of all advanced HIV patients followed by pre-emptive antifungal therapy. An estimate of disease prevalence in antiretroviral treatment (ART)-naïve HIV-positive adult Indian population is essential to include this in routine screening strategy. We estimated CrAg prevalence as a guiding resource in a public health approach. Material and methods:The study design was longitudinal. ART naïve HIV-seropositive patients with CD4 count ≤ 100 cells/μl, attending ART center at the School of Tropical Medicine, Kolkata, India were screened for CrAg using both latex agglutination and lateral flow assay kits. A total of 390 subjects were enrolled into the study, and evaluated for association of CrAg with age, sex, CD4, presence of opportunistic infections, WHO HIV staging, and clinical symptoms.Results: Of 390 subjects tested, the median CD4 count was 42 cells/μl in CrAg-positive and 46 in CrAg-negative patients. Median (IQR) age of all participants was 40 (range, 34-46) years. CrAg positivity was 12.56%, comparatively higher in those with CD4 ≤ 50 cells/μl. Asymptomatic patients had CrAg positivity of 4.6%. Statistically significant association was noted with male sex (p = 0.03), triad symptoms of fever, headache, vomiting (p = 0.013), and altered mental status (p = 0.033).Conclusions: This study aims to estimate CrAg prevalence in India to justify the need for routine screening and pre-emptive treatment in advanced HIV infection. Incorporating this screening would definitely reduce the risk of cryptococcus meningitis-induced mortality and morbidity, as recommended by the WHO guidelines.

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…”