Cryptococcal Antigen Screening in Asymptomatic HIV-Infected Antiretroviral Naïve Patients in Cameroon and Evaluation of the New Semi-Quantitative Biosynex CryptoPS Test

Frontiers in Microbiology

Sinata Koulla-Shiro¹  Síle F. Molloy²  Angela Loyse²  Thomas Harrison²  Charles Kouanfack³  Leonella Mossiang³  Elvis Temfack⁴  Eric Delaporte⁵  Olivier Lortholary⁶  Françoise Dromer⁷  Marie C. Fonkoua⁸ 

[1] Cameroon Site, French National Agency for Research on AIDS and Viral Hepatitis, Yaounde, Cameroun;Centre for Global Health, Institute for Infection and Immunity, St George’s, University of London, London, United Kingdom;Day Hospital, Yaoundé Central Hospital, Yaoundé, Cameroon;Department of Internal Medicine, Douala General Hospital, Douala, Cameroon;INSERM U1175-IRD UMI 233, University of Montpellier, Montpellier, France;Infectious Diseases and Tropical Medicine Department, Necker Pasteur Infectious Diseases Centre, Necker-Enfants Malades Hospital, APHP, Institut Hospitalo-Universitaire Imagine, Paris Descartes University, Paris, France;Institut Pasteur, Centre National de la Recherche Scientifique, Unité de Mycologie Moléculaire, UMR 2000, Paris, France;Microbiology Unit, Centre Pasteur du Cameroun, Yaoundé, Cameroon;

关键词: cryptococcosis;    cryptococcal antigen;    screening;    point of care;    lateral flow assay;   

DOI  :  10.3389/fmicb.2018.00409

来源: DOAJ

【 摘 要 】

Background: Cryptococcal meningitis (CM) is a major cause of AIDS-related mortality in Africa. Detection of serum cryptococcal antigen (CrAg) predicts development of CM in antiretroviral (ART) naïve HIV-infected patients with severe immune depression. Systematic pre-ART CrAg screening and pre-emptive oral fluconazole is thus recommended. We postulated that a semi-quantitative CrAg screening approach could offer clinically relevant advantages.Methods: ART-naïve asymptomatic adult outpatients with <100 CD4 cells/mm3 presenting to the Yaoundé Central Hospital, Cameroon were screened for CrAg using the IMMY lateral flow assay (LFA). CrAg positive patients were consented for lumbar puncture and those with proven CM were treated with combination antifungal therapy and those with no CM were offered long-term oral fluconazole. Simultaneous on-site evaluation of CrAg detection using the new LFA Biosynex® CryptoPS test was performed and both tests were subsequently compared to a reference commercialized CrAg enzyme immunoassay (EIA).Results: Prevalence of serum CrAg in 186 screened adults was 7.5% (95%CI: 4.5–12.4). In CrAg positive patients, CM prevalence was 45.5% (95%CI: 18.3–75.7). IMMY and Biosynex CryptoPS strongly agreed in serum, plasma, and cerebrospinal fluid (Kappa: 98.4, 99.5, 100%, respectively, p < 0.001), and disagreed in urine (29 isolated positive CrAg in urine with IMMY, none with Biosynex and none of whom had proven CM). Compared to EIA, serum specificities were 96.6 and 98.3%, respectively. With Biosynex CryptoPS, all CM patients were serum T2-band positive compared to nonewithout CM. Median EIA reciprocal titre was 160 (IQR: 13.5–718.8) and titres >160 strongly correlated with proven CM and Biosynex CryptoPS T2-band positivity. During the 1-year follow up period, there was no incident case of CM among screened patients and overall incidence of all-cause mortality was 31.5 per 100 person-years-at-risk (95%CI: 23.0–43.1).Conclusion: HIV-associated asymptomatic cryptococcosis is common in Cameroon, warranting integrated systematic screening and treatment. Biosynex CryptoPS holds promise, at point of care, for rapidly stratifying CrAg positive patients for optimal management including lumbar puncture and combination antifungal therapy when needed.Summary findings: Prevalence of CrAg and meningitis (CM) is high in Cameroon. Biosynex CryptoPS is comparable to IMMY LFA in CrAg screening. Its T2-band correlates with high antigen titres and CM, thus promising for identifying patients requiring effective induction therapy.Note: This study was presented in part at the 10th International Conference on Cryptococcus and Cryptococcosis (ICCC) in Iguazu in Brazil from 26 to 30th March 2017 and won a prize oral presentation.

【 授权许可】

Unknown