| Background:Cryptococcal meningitis(CM)is a serious infection with the characteristics of high morbidity and mortality.Current diagnostic methods lack sensitivity(direct microscopy)or are time-consuming(culture).An initial report indicated that metagenomic next-generation sequencing(m NGS),a new detection method,might be useful for diagnosis but excluding other differential diagnoses such as tuberculous meningitis,listeria encephalitis and brucellosis encephalomyelitis.Objective:To analyze the clinical characteristics and therapies of patients with cryptococcal meningoencephalitis/meningitis,and evaluate the diagnostic value to detect potential pathogenic microorganisms(PPMs)of m NGS for Cryptococcus infection in central nervous system(CNS).We aimed to determine the specificity,sensitivity,and area under the curve(AUC)for the use of m NGS as a novel method for diagnosing CM.Methods:We retrospectively collected and analyzed the clinical data of patients with clinically diagnosed CM in Henan Provincial People’s Hospital between February 20,2017 and September 20,2019,including detailed medical history and general conditions,peripheral blood tests such as white blood cell counts and cultures,as well as relevant laboratory test such as CSF routine,biochemical,cytology,Cryptococcus capsular antigen,ink staining,culture and auxiliary examinations including brain magnetic resonance imaging(MRI).During their hospitalization,CSF was collected and analyzed for sequencing was performed via m NGS using BGISEQ-100 sequencing platform.Results:The study enrolled 14 patients(10 male)with an average age of the patients was48.86±14.894 years vary from 25 to 77(N=14),including 10 were male and 4 were female.Among our patient cohort,4 patients were not treated with steroids and immunosuppressive drugs,1 patient had an organ transplant,1 patient had the right-kidney removed,2 patients with diabetes for several years,9 patients received prolonged immunosuppressive therapy;specifically,5 had cranial nerve damage,and 7 had different degrees of consciousness disorder.The first symptoms reported were headache in 11 cases and fever in 9 cases,nausea and vomiting in 8 cases.Meningeal signs were positive in 8cases.Moreover,the brain parenchyma or meninges were the sole site of cryptococcal infection with abnormal magnetic resonance imaging(MRI)findings in 11 cases.10 patients had related complications with CM rapidly progressive or medical management,2patients were performed Ventricular drainage of cerebrospinal fluid in whom unchecked increased intracranial pressure with hydrocephalus and poor prognosis.Among the 14 patients,1 was positive for blood culture,2 were abnormal in G-M test.We also determined that 7 patients had a dynamic greater than 300 mm H2O in 9 cases were lumbar puncture with increased intracranial pressure,and 3 of them underwent lumbar cistern drainage.India ink staining and Cryptococcal antigen tests were positive in 8 and 12 cases,respectively,while the mycological CSF culture was positive in 8 cases.In 9 cases,Cryptococcus species were identified by m NGS,with the number of nucleic acids associated with CM ranging from 1 to 97979 and genomic coverage varying from 0.0004%to 11%.Calculate the sensitivity,specificity,and area under curve using m NGS for the early diagnosis of unknown meningoencephalitis/meningitis were 75%,50%,and 0.625,respectively,compared to traditional detection methods.Conclusions:Presently,we believe that the CSF detection rates are the highest for Cryptococcus capsular antigen,followed by m NGS,ink staining,and culture.Our results showed that for cryptococcal meningoencephalitis/meningitis,m NGS can be used as a supplementary tool for the early diagnosis to improve the timeliness of CM diagnosis,and the positive rate of repeated submissions may be higher.Furthermore,m NGS can also identify subtypes of strains,find new pathogens,and merge or exclude infections of other pathogens,which is helpful for the selection of CM diagnostic protocols and management of complications. |
PDF Full Text Request