Diagnosis Of Cryptococcal Meningitis Research Articles

Baseline Cytomegalovirus Viremia at Cryptococcal Meningitis Diagnosis Is Associated With Long-term Increased Incident TB Disease and Mortality in a Prospective Cohort of Ugandan Adults With HIV.

Adults with HIV-associated cryptococcal meningitis have overlapping burdens of cytomegalovirus (CMV) and tuberculosis (TB) coinfections. CMV infection/reactivation is strongly associated with CMV-specific memory T-cell activation and upregulation of type 1 interferons, which may lead to increased risk of TB disease and poor outcomes. We conducted a cohort study of 2-week survivors of cryptococcal meningitis during 2010-2021 to determine TB incidence and all-cause mortality over time stratified by baseline CMV status. We followed 497 Ugandans with HIV-associated cryptococcal meningitis for a median (interquartile range) of 4.6 (2.6-53.9) months. Overall, 42% (210/497) developed incident TB disease or died. One-fifth (98/497, 19.7%) developed incident TB disease, and 29% (142/497) of participants died during follow-up. Of 259 participants with CMV viral load measured at baseline, 37% (96/259) had concurrent CMV viremia (defined as anyone with detectable CMV DNA in plasma/serum by qualitative polymerase chain reaction [PCR] detection). Of 59 with measured CMV immunoglobulin G (IgG), 100% had positive CMV IgG antibody serology (≥10 enzyme-linked immunosorbent assay units/mL). CMV viremia was positively associated with higher HIV viral load (196 667 vs 73 295 copies/mL; P = .002) and higher cerebrospinal fluid fungal burden (68 500 vs 14 000 cfu/mL; P = .002) compared with those without. Participants with high-level CMV viremia (defined as CMV viral load ≥1000 IU/mL) had twice the risk of incident TB (subdistribution adjusted hazard ratio [aHR], 2.18; 95% CI, 1.11-4.27) and death (aHR, 1.99; 95% CI, 1.14-3.49) compared with participants with no or low-level CMV viremia. There was no association between the CMV IgG index and the incidence of TB/death (P = .75). CMV viremia >1000 IU/mL at meningitis diagnosis was associated with increased incident TB disease and mortality during long-term follow-up. Future studies to determine the causal relationship and potential for therapeutic intervention are warranted.

Cryptococcal Meningitis Developing in a Patient with Neurosarcoidosis.

Cryptococcal meningitis is a critical disease that occasionally involves immunosuppressed patients. We herein report a 79-year-old Japanese man who received low-dose prednisolone therapy for neurosarcoidosis and panhypopituitarism. He presented a 10-day history of a fever and altered mental status. The FilmArray® Meningitis/Encephalitis Panel and serum cryptococcal antigen tests were both negative, but the cerebrospinal fluid sample became positive for Cryptococcus neoformans after seven-day incubation. After the diagnosis of cryptococcal meningitis, we successfully treated the patient with a recommended treatment regimen. When an immunocompromised patient presents with a subacute fever accompanying any central nervous symptoms, cryptococcal meningitis should be screened for.

Cryptococcal Meningitis in a Human Immunodeficiency Virus Sero-positive Patient: A Case Study

A 42-year-old female patient was admitted to the hospital with moderate-grade fever, severe headache, loss of appetite, and sore throat. She was suspected of Meningitis and her CSF sample was sent to the Laboratory for Microbiological Examination. The CSF sample obtained showed the presence of Capsulated budding yeast cells on India Ink Examination and Cryptococcus neoformans was isolated on SDA culture. The patient was recently diagnosed as HIV-Sero Positive and was immunocompromised leading to acquiring Cryptococcal meningitis. The lack of awareness of HIV-AIDS and delayed diagnosis of Cryptococcal meningitis led to a poor prognosis. Early diagnosis of HIV and timely treatment can improve the prognosis of the disease.

1H NMR Using Metabolic Study in Body Fluids for Diagnosis of Cryptococcal Meningitis in Adults.

Cryptococcal meningitis is considered to affect HIV patients and those with impaired immune systems. Early identification and treatment are the keys to decreasing morbidity and mortality related to CM. Using 1H NMR spectroscopy, a prospective case-control study will assess the metabolic profile of adults' serum, urine, and CSF. The present multicentric study was conducted at Lucknow. The study included 150 participants, out of which there were 31 cryptococcal meningitis cases, 34 positive meningitis controls, and the rest, 85, were disease controls. The discriminant function analysis (DFA) of the three biofluids was used to find significant metabolites between the cases and the control group collectively. A group categorization between control group and the cases in serum, urine, and CSF samples was also made possible by the NMR spectral bin-based orthogonal signal correction and principal component analysis score plots of important metabolites produced from DFA. The cases group had a higher proportion of patients with higher CSF protein levels than the positive control group (BM and TM). Acetone was found among urine samples in both control samples, i.e., positive and negative. This is the first study to explore biomarkers in serum, urine, and CSF in addition to radiological features and clinical symptoms. Hence, a quick, non-invasive prognosis and diagnosis of cryptococcal meningitis in adults can be made using clinical and microbiological investigation, as well as metabolomic analysis of urine samples. This study shows that urine can be used as a biofluid to differentiate between Cryptococcus meningitis in adults. However, when compared to the negative control, our sample size was significantly smaller, necessitating further confirmation on a larger sample size.

Assessment of an Antigen Lateral Flow Assay (LFA) For Point of Care Diagnosis of Cryptococcosis in Senegal

Background: Cryptococcal meningitis is a medical emergency. Therefore, simple, rapid and efficient diagnostic techniques are needed. New rapid diagnostic tests based on the detection of cryptococcal antigen have been developed. The aim of our study was to evaluate the performance of the Dynamiker Cryptococcal Antigen Lateral Flow Assay (LFA) in our routine diagnosis activities. Materials and Methods: We performed a prospective study from November 2017 to August 2018 at the ParasitologyMycology laboratory of the CHNU of Fann in Dakar. Biological samples collected from HIV-infected patients hospitalized at the infectious diseases department of CHUN de Fann were used. Serum, CSF and urine samples received in the laboratory were examined using mycological techniques and the cryptococcal latex agglutination test (CLAT). The performance of the Dynamiker test was evaluated considering CLAT as the reference method. Results: A total of 39 samples were examined: 14 CSF, 24 sera and 1 urine sample. The average age was 44.5 years with a predominance of female patients (64.1%). The mean CD4 count was 73 cells/mm3 . Among the 39 samples tested, 23.1% were CLAT positive while 30.8% were LFA positive. The sensitivity and specificity rates were 100% and 75% respectively. The percentage of correlation between the two methods was 92.3%. The intensity of the bands on the LFA was high en 66.7% of cases. Conclusion: The excellent sensitivity of the rapid Cryptococcal Antigen Lateral Flow Assay and the rapidity of obtaining results (less than 15 minutes) make it suitable for routine diagnosis of cryptococcal meningitis.

Sterile Cerebrospinal Fluid Culture at Cryptococcal Meningitis Diagnosis Is Associated with High Mortality.

Cryptococcus is the leading cause of AIDS-related meningitis in sub-Saharan Africa. The clinical implications of a sterile cerebrospinal fluid (CSF) culture among individuals diagnosed with cryptococcal meningitis using CSF cryptococcal antigen (CrAg) are unclear. We prospectively enrolled 765 HIV-positive Ugandans with first-episode cryptococcal meningitis from November 2010 to May 2017. All persons were treated with amphotericin-based induction therapy. We grouped participants by tertile of baseline CSF quantitative Cryptococcus culture burden and compared clinical characteristics, CSF immune profiles, and 18-week mortality. We found 55 (7%) CSF CrAg-positive participants with sterile CSF cultures. Compared to the non-sterile groups, participants with sterile CSF cultures had higher CD4 counts, lower CSF opening pressures, and were more frequently receiving ART. By 18 weeks, 47% [26/55] died in the sterile culture group versus 35% [83/235] in the low culture tertile, 46% [107/234] in the middle tertile, and 56% [135/241] in the high tertile (p < 0.001). The sterile group had higher levels of CSF interferon-gamma (IFN-γ), IFN-α, interleukin (IL)-6, IL-17, G-CSF, GM-CSF, and chemokine CXCL2 compared with non-sterile groups. Despite persons with sterile CSF cultures having higher CD4 counts, lower CSF opening pressures, and CSF cytokine profiles associated with better Cryptococcus control (e.g., IFN-γ predominant), mortality was similar to those with higher fungal burdens. This unexpected finding challenges the traditional paradigm that increasing CSF fungal burdens are associated with increased mortality but is consistent with a damage-response framework model.

2361. Timing of antiretroviral therapy prior to diagnosis of cryptococcal meningitis

Abstract Background Cryptococcal meningitis (CM) is the most common cause of meningitis in adults in Sub-Saharan Africa (SSA), causing significant morbidity and mortality in people living with HIV. Early initiation of antiretroviral therapy (ART) after cryptococcal diagnosis is associated with increased mortality. With increasing access to ART in SSA, an increasing proportion of CM patients are now presenting on ART, and outcomes remain unclear. Methods We performed a retrospective study of 724 participants with positive CSF cryptococcal antigen in four clinical trials performed in Uganda from June 2017 to February 2022. We compared survival outcomes based on ART experience at the time of CM diagnosis. We had implemented structured ART interruption when ART had recently been initiated (&amp;lt; 2weeks). Results Sixty-one percent (445/724) of participants were ART-naïve at the time of CM diagnosis. Compared to those receiving ART, those ART-naïve had lower CD4 counts and higher Cryptococcus colony forming units (CFUs)/mL on quantitative CSF culture (p&amp;lt; 0.001). However, the two-week mortality between ART-naïve and ART-experienced groups did not statistically differ (16.6% vs. 16.8%, Hazard Ratio = 0.97 (95%CI, 0.67–1.40) as well as for ten-week mortality (25.4% vs. 26.2%, Hazard Ratio = 0.98 (95%CI, 0.73–1.31)). Further stratification of ART-experienced participants by length of ART experience (&amp;lt; =2 weeks vs. &amp;gt;2 weeks prior to diagnosis) and ART continuation status (ART continued vs. discontinued if ART started &amp;lt; =2 weeks prior to diagnosis) demonstrated no statistically significant difference between the groups for two- or ten-week mortality. Conclusion Cryptococcal diagnosis after ART initiation is now increasingly common. In this study, we found no significant mortality differences between ART-naïve and ART-experienced participants at 2 weeks and 10 weeks. Accounting for length of ART experience did not change these short-term mortality outcomes. One potential limitation of our study is different CM treatment regimens were used across clinical trials. Disclosures All Authors: No reported disclosures.

Cryptococcal meningitis in people living with human immunodeficiency virus in Nepal: Perspectives from resource limited setting.

Early diagnosis of cryptococcal meningitis among people living with HIV (PLHIV) is crucial for its therapeutic success. The objective of this study was to diagnose cryptococcal meningitis in PLHIV cases using the available laboratory techniques for its confirmation in resource limited setting. This cross-sectional prospective study was conducted among 72 PLHIV with clinical suspicion of meningitis. Each cerebrospinal fluid (CSF) sample received at the National Public Health Laboratory, Kathmandu was processed for India ink staining, cryptococcal antigen lateral flow assay, and fungal culture following standard protocols. The laboratory-confirmed cryptococcal meningitis cases were between 24 and 69 years of age (median age 39 years) with 87.5% (12/14) of cases being male. Cryptococcus was detected in 22.22% (16/72) by any of the three tests, 19.44% (14/72) by cryptococcal antigen lateral flow assay, 16.66% (12/72) by India ink staining, and 8.33% (6/72) by culture. High percentage of cryptococcal meningitis among PLHIV warrants early microbiological diagnosis for better case management. Cryptococcal antigen detection immunoassay should be the priority test for laboratory diagnosis of cryptococcal meningitis in PLHIV. Alternatively, very simple and economic India ink staining of CSF specimens could be used in resource limited settings.

Prevalence of Cryptococcus gattii in Ugandan HIV-infected patients presenting with cryptococcal meningitis.

IntroductionCryptococcal meningitis (CM) is a life threatening disease and leading cause of opportunistic fungal-related mortality in HIV/AIDS. Most CM infections are caused by C. neoformans species complexes but the prevalence of Cryptococcus gattii species complexes in Uganda is unknown however, it is known in a few other parts of Africa. We estimated the prevalence of C. gattii in patients living with HIV and a diagnosis of cryptococcal meningitis in Uganda.MethodsCryptococcus isolates (n = 200) obtained from cerebrospinal fluid of patients with CM recruited at the Infectious Diseases Institute, Kampala, Uganda, were tested by phenotypic methods. The Cryptococcus isolates were sub-cultured on Sabouraud Dextrose Agar plates for 48 hours. The yeast colonies were examined by India ink stain, urea hydrolysis, and C. gattii was identified by blue pigmentation on CGB agar. The results were analyzed for frequency of C. gattii. Patient demographic characteristics were collected from the case record forms.ResultsFrom the 200 patients’ case record forms, 87 (43.5%) were female and 113 (56.5%) were male. The median age was 35 (19–64) years. Most patients, 93% (187/200) were from Central Uganda in the districts of Kampala and Wakiso. 97.51% (157/161) of the patients had absolute CD4 lymphocyte counts of less than 200 cells per cubic millimeter; 1.86% (3/161) 200–350 cells per cubic millimeter and 0.62% (1/161) above 500 cells per cubic millimeter. 45.4% (74/163) were not yet on HAART and 54.6% (89/163) were on HAART. 66.7% (58/87) had poor adherence to HAART treatment and 33.3% (29/87) had reported good adherence to HAART treatment. A total of 200 clinical isolates of Cryptococcus isolates were tested. No (0% (0/200) C. gattii was identified among the Cryptococcus isolates.ConclusionIn this study among patients living with HIV and a diagnosis of cryptococcal meningitis in Uganda, we found no C. gattii infections.

Case Report: Cryptococcal Infection in Renal Transplant Patient

A significant portion of all invasive fungal infections in solid organ transplants are due to cryptococcus. It can be a debilitating infection and affects the quality of life in transplant patients. We report a case of a 57-year-old male patient with recent kidney transplant, who presented with cryptococcal meningitis, after exposure to birds during a trip to Mexico 1 week ago. In addition to a two-day history of generalized weakness, dizziness, intermittent fever, and lightheadedness, the patient presented with on and off headaches, increased sinus pressure, neck stiffness, clogged ear sensation, confusion, and night sweats. The patient was initially treated empirically with fluconazole. Lumber punctuation showed elevated opening pressure, increased WBC, with neutrophil predominance. Cryptococcal antigen tests were positive in both serum and cerebrospinal fluid sources. After confirmation from CSF analysis, he was administered liposomal amphotericin B and flucytosine. Patient’s symptoms rapidly improved. Due to his immunocompromised state, the patient will require lifelong fluconazole maintenance therapy. Even though kidney transplant recipients have a positive outcome in terms of longevity, they are at increased risk of post-transplant infection, such as zoonotic infections. Therefore, in any recent kidney transplant patient with meningitis symptoms, cryptococcal meningitis should always be considered. We report the appropriate criteria, procedures, and tests that allow for a cryptococcal meningitis diagnosis in immunocompromised patients.

Impact of a Cryptococcal meningitis diagnosis and treatment program at Lira Regional Referral Hospital in rural, Northern Uganda.

In rural areas of sub-Saharan Africa, infrastructure and resources for treatment of cryptococcal meningitis (CM) are often lacking. We introduced a CM diagnosis and treatment program (CM-DTP) at Lira Regional Referral Hospital (LRRH) in rural Uganda to determine if implementing high-quality standard of care protocols would improve outcomes. Information extracted from hospital charts and clinical record forms at LRRH were used to compare diagnoses, treatments, and outcomes for all patients diagnosed with meningitis (n = 281) over a two-year period after initiation of the CM-DTP in February of 2017 to all patients diagnosed with meningitis (n = 215) in the two preceding years. After implementation of the CM-DTP, we observed increased confirmed diagnoses of CM from 22.2% (48 of 215) to 35.2% (99 of 281), (p = 0.002) among all patients diagnosed with meningitis. Among all patients treated for CM, the proportion who received standard of care treatment with amphotericin B plus fluconazole increased from 63 of 127 (49.6%) to 109 of 146 (74.7%), (p <0.001) and mortality improved from 66 of 127 (52.0%) to 57 of 146 (39.0%), (p = 0.04) after implementation of the CM-DTP. Implementation of the CM-DTP was associated with increased number of lumbar punctures and decreased use of antibiotics in patients with CM, as well as decreased mortality among patients with meningitis from all causes. Improved diagnosis, treatment, and mortality were observed following implementation of the CM-DTP. Our results demonstrate that quality treatment of CM in rural Uganda is feasible.

Performance of Metagenomic Next-Generation Sequencing for the Diagnosis of Cryptococcal Meningitis in HIV-Negative Patients.

ObjectivesMetagenomic next-generation sequencing (mNGS) has been applied more and more widely for the diagnosis of infectious diseases, but its performance in the diagnosis of cryptococcal meningitis (CM) remains unclear.MethodsCerebrospinal fluid (CSF) samples from 197 HIV-negative patients with suspected central nervous system infections were tested simultaneously by mNGS and routine methods [India ink staining, fungal culture, or cryptococcal antigen (CrAg) tests]. The performance of mNGS was evaluated.ResultsOf the 197 enrolled cases, 46 (23.4%) cases were finally diagnosed with CM, including 43 (93.5%) Cryptococcus neoformans infections and 3 (6.5%) Cryptococcus gattii infections. The sensitivity, specificity, positive predictive value, negative predictive value, and concordance rate of mNGS were 93.5% [95% confidence interval (CI) at 86.4%~100.0%], 96.0% (95% CI at 92.9%~99.1%), 87.8%, 98.0%, and 95.4%, respectively. Comparing to the conventional diagnostic methods, the sensitivity and concordance rate of mNGS were slightly lower than those of CrAg tests (97.4%) but higher than those of India ink (63.0%) and culture (76.7%). Besides, mNGS had a sensitivity of 100.0% against culture. It should be noted that mNGS could identify Cryptococcus at species level; C. gattii of the 3 cases was only distinguished by mNGS.ConclusionsCSF mNGS can be considered as a supplementary test to diagnose CM and directly distinguish C. gattii from C. neoformans in clinical specimens.

Delays in Cryptococcal Meningitis Diagnosis and Care: A Mixed Methods Study in Rural Uganda.

Background:Cryptococcal meningitis (CM) remains a major cause of mortality for HIV-infected persons in sub-Saharan Africa, despite widespread access to antiretroviral therapy. Delays in CM diagnosis and treatment contribute to high mortality, with patients often arriving “too late” for treatment to be effective. Little is known about patient-related delays and their experiences with CM.Objectives:This study seeks to identify the factors related to delays in diagnosis and care among patients with cryptococcal meningitis.Methods:A convergent mixed-methods approach was used to understand delays related to diagnosis and treatment of CM among patients admitted to Lira Regional Referral Hospital in rural northern Uganda. We collected data from February to March 2020 using surveys followed by semi-structured interviews from 20 CM patients who survived hospitalization and 20 family members of deceased patients during February 2017–November 2019. Interviews were audio-recorded, transcribed, and thematically coded for analysis.Findings:Delays to CM care were related to 1) self-medication, 2) lack of CM education, 3) seeking treatment multiple times at health centers with 4) missed/misdiagnosis, and 5) cultural factors. Among patients who died, 70% sought care ≥3 times, while those who survived, 35% of sought care ≥3 times before CM diagnosis. Only 10% of patients and 40% of family members knew what caused CM, indicating a lack of knowledge.Conclusions:Patients sought medical care for CM symptoms, but several factors contributed to CM diagnosis and care delays. Many of these factors relate to a lack of CM education and knowledge among patients and providers. A CM awareness campaign for the general public, targeted education for HIV patients, and continuing medical education for healthcare providers can decrease delays and improve outcomes.

Evaluation of Lateral Flow Assay for the Diagnosis of Cryptococcal Meningitis and its Comparison with the Gold Standard and Other Laboratory Tests

Introduction: Cryptococcosis is a potentially fatal fungal disease affecting both immunocompromised and immunocompetent individuals. Hence, a Point Of Care Test (POCT) is required with higher sensitivity and specificity (100%), for the rapid detection of cryptococcosis which will be life saving for the patient. Aim: To evaluate the usefulness of Lateral Flow Assay (LFA) for rapid detection of Cryptococcal Antigen (CrAg) from Cerebrospinal Fluid (CSF) sample. Materials and Methods: This diagnostic study was conducted in Mycology Laboratory, Sri Ramachandra Medical College and Research Institute, Chennai, Tamil Nadu, India, over a period of six months (June 2019-November 2019). The CSF samples (n=37) from patients with suspected meningitis were considered for the study. Direct microscopy with gram stain, negative stain and histopathological stains was performed for all the CSF samples. Culture was done on basal medium, enriched media and special media. Cryptococcus genus specific Polymerase Chain Reaction (PCR) was also performed to confirm the isolates grown on the culture. Serological tests like Latex Agglutination Test (LAT) and LFA were also performed on all the samples. The LFA results were compared with microscopy, culture and LAT. Results: Among the 37 suspected meningitis patients, three grew Cryptococcus in culture which was considered as the gold standard in the diagnosis of Cryptococcal Meningitis (CM). Direct microscopic techniques had 100% specificity however their sensitivity was less i.e., 67%. LAT had a sensitivity of 100% and specificity of 94%. However, LFA in present study had a very good sensitivity, specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV) (100%). Conclusion: LFA for the detection of CM is considered to be an effective method when compared to the other conventional and serological methods with higher sensitivity and specificity. Hence, in present study authors evaluated the use of LFA in diagnosis of CM and found that this assay when used as a POCT, can give the results in short duration. Considering this as a pilot study, further studies including higher number of samples are essential to confirm the effectiveness of the findings.

Cost-Effectiveness Analysis of the Implementation of Cryptococcal Antigen Lateral Flow Assay for the Diagnosis of Cryptococcal Meningitis in Symptomatic People Living With Human Immunodeficiency Virus in Brazil

ObjectivesCryptococcal meningitis constitutes a significant source of mortality in the developing world. Annually, approximately 625 000 deaths occur worldwide among patients with human immunodeficiency virus (HIV) infection. This study aims to assess the cost-effectiveness of implementing cryptococcal antigen lateral flow assay (CRAG-LFA) screening in Brazil compared with the current practice. MethodsAn economic evaluation using a Monte Carlo microsimulation was conducted, considering the perspective of the Brazilian Public Health System, to calculate the cost-effectiveness of 4 diagnosis tests: (1) CRAG-LFA, (2) the cryptococcal antigen latex agglutination (CRAG-LA) test, (3) India ink, and (4) nontracking as a baseline. The time horizon comprised 1 year for the intervention and 5 years for the budgetary impact analysis. Two primary effectiveness outcomes were considered: years of life and quality-adjusted life-years. ResultsCRAG-LFA has extended dominance vis à vis CRAG-LA and India ink. CRAG-LFA would cost $418.46 more than CRAG-LA for the treatment of each symptomatic patient living with HIV, with an incremental cost effectiveness ratio of $2478.75/quality-adjusted life year. The budgetary impact analysis estimated that the incorporation of CRAG-LFA would have an additional cost of $1 959 236.50 in 5 years. ConclusionsThese findings suggest that, for patients living with HIV in the Brazilian Public Health System, the adoption of CRAG-LFA screening is cost-effective compared with the use of CRAG-LA and India ink. It represents an opportunity to prevent cryptococcal meningitis and its mortality in Brazil.

Invasive Fungal Infections in Persons Living with HIV in an Amazonian Context: French Guiana, 2009-2019.

Although the burden of histoplasmosis in patients with advanced HIV has been the focus of detailed estimations, knowledge about invasive fungal infections in patients living with HIV in an Amazonian context is somewhat scattered. Our goal was thus to adopt a broader view integrating all invasive fungal infections diagnosed over a decade in French Guiana. All patients hospitalized at Cayenne hospital from 1 January 2009 to 31 December 2018 with a proven diagnosis of invasive fungal infection were included (n = 227). Histoplasmosis was the most common (48.2%), followed by Cryptococcus infection (26.3%), and pneumocystosis (12.5%). For cryptococcal infection, there was a discordance between the actual diagnosis of cryptococcal meningitis n = (26) and the isolated presence of antigen in the serum (n = 46). Among the latter when the information was available (n = 34), 21(65.6%) were treated with antifungals but not coded as cryptococcocosis. Most fungal infections were simultaneous to the discovery of HIV (38%) and were the AIDS-defining event (66%). The proportion of major invasive fungal infections appeared to remain stable over the course of the study, with a clear predominance of documented H. capsulatum infections. Until now, the focus of attention has been histoplasmosis, but such attention should not overshadow other less-studied invasive fungal infections.

Comparison of two commercial tests (Immy vs. Dynamiker) for cryptococcal capsular antigen.

INTRODUCTION Lateral flow assay is an advanced method useful in the early diagnosis of cryptococcal meningitis. We aimed to compare two commercial tests for cryptococcal capsular antigen in the sera of asymptomatic patients with human immunodeficiency virus in Barranquilla, Colombia. METHODS Thawed (n=162) previously collected serums (2016-2019) were processed using IMMY and Dynamiker cryptococcal antigen lateral flow assay. RESULTS Compared to IMMY’s results, Dynamiker’s sensitivity, specificity, positive predictive value, negative predictive value, and kappa index were 100%, 89.9%, 48.3%, 100.0%, and 0.61, respectively.CONCLUSIONS The Dynamiker test had excellent sensitivity, acceptable specificity, and a low detection threshold for cryptococcal antigen in the tested samples.

Cerebrospinal Fluid Lactate as a Prognostic Marker of Disease Severity and Mortality in Cryptococcal Meningitis.

Cerebrospinal fluid (CSF) lactate levels can be used to differentiate between bacterial and viral meningitis. We measured CSF lactate in individuals with cryptococcal meningitis to determine its clinical significance. We measured point-of-care CSF lactate at the bedside of 319 Ugandan adults living with human immunodeficiency virus at diagnosis of cryptococcal meningitis. We summarized demographic variables and clinical characteristics by CSF lactate tertiles. We evaluated the association of CSF lactate with clinical characteristics and survival. Individuals with high CSF lactate >5 mmol/L at cryptococcal diagnosis more likely presented with altered mental status (P < .0001), seizures (P = .0005), elevated intracranial opening pressure (P = .03), higher CSF white cells (P = .007), and lower CSF glucose (P = .0003) compared with those with mid-range (3.1 to 5 mmol/L) or low (≤3 mmol/L) CSF lactate levels. Two-week mortality was higher among individuals with high baseline CSF lactate >5 mmol/L (35%; 38 of 109) compared with individuals with mid-range (22%; 25 of 112) or low CSF lactate (9%; 9 of 97; P =<.0001). After multivariate adjustment, CSF lactate >5 mmol/L remained independently associated with excess mortality (adjusted hazard ratio = 3.41; 95% confidence interval, 1.55-7.51; P = .002). We found no correlation between baseline CSF lactate levels and blood capillary lactate levels. Baseline point-of-care CSF lactate levels are a prognostic marker of disease severity and mortality in cryptococcal meningitis. Individuals with an elevated baseline CSF lactate level are more likely to present with altered mental status, seizures, and elevated CSF opening pressure and are at a greater risk of death. Future studies are needed to determine targeted therapeutic management strategies in persons with high CSF lactate.

Audiovestibular neuropathy in an immunocompetent man with cryptococcal meningitis

IntroductionCryptococcus spp. is a fungus responsible for 600,000 deaths per year worldwide, mainly in immunosuppressed subjects. However, 20% of cases occur in immunocompetent subjects. Neuropathic disorders involving the auditory nerve have been reported, but vestibular disorders have never been described in detail. We report the case of an immunocompetent man, who presented audiovestibular disorders leading to a diagnosis of cryptococcal meningitis. Case reportA 39-year-old man was referred for balance disorders and right sensorineural hearing loss. He presented right vestibulo-saccular impairment and bilateral absence of auditory brainstem responses. Brain MRI was suggestive of cryptococcal meningitis. A cystic lesion in the right flocculus compressed the vestibulocochlear nerve. During monthly follow-up, pure tone audiometry gradually improved and speech audiometry in silence returned to normal. Partial resynchronization of the auditory afferent pathways was observed only on the contralateral side to vestibulocochlear nerve compression, while complete recovery of saccular function was observed. DiscussionCryptococcal meningitis in immunocompetent subjects may be accompanied by lesions of the auditory and vestibular afferent pathways. Recovery of hearing and balance was observed in response to medical treatment and early vestibular rehabilitation.

Cryptococcus meningitis mimicking cerebral septic emboli, a case report series demonstrating injection drug use as a risk factor for development of disseminated disease

BackgroundClinicians may be less inclined to consider a diagnosis of cryptococcal meningitis in people without HIV infection or transplant-related immunosuppression. This may lead to a delay in diagnosis particularly if disseminated cryptococcal disease mimics cerebral septic emboli in injection drug use (IDU) leading to a search for endocarditis or other infectious sources. Though, IDU has been described as a potential risk for disseminated cryptococcal disease.Case presentationsWe present two cases of cryptococcal meningitis in IDU without HIV or other obvious immune deficits. Both patients presented with at least 2 weeks of headache and blurred vision. They developed central nervous system (CNS) vasculitis, one of which mimicked septic cerebral emboli, but both resulted with poor neurologic outcomes.ConclusionsIDU likely induces an underappreciated immune deficit and is a risk factor for developing cryptococcal meningitis. This diagnosis, which can mimic cerebral septic emboli through involvement of a CNS vasculitis, should be considered in the setting of IDU.