Epidemiology of Multiple Herpes Viremia in Previously Immunocompetent Patients With Septic Shock.

Background: Systemic reactivations of herpesviruses may occur in intensive care unit (ICU) patients, even in those without prior immune deficiency. However, the clinical relevance of these events is uncertain. Methods: In this study we selected patients admitted with septic shock and treated for more than 4 days from a prospectively enrolled cohort of consecutive adults in the mixed ICUs of 2 tertiary care hospitals in the Netherlands. We excluded patients who had received antiviral treatment in the week before ICU admission and those with known immunodeficiency. We studied viremia episodes with cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), herpes simplex virus types 1 (HSV-1) and 2 (HSV-2), and varicella zoster virus (VZV) by weekly polymerase chain reaction in plasma. Results: Among 329 patients, we observed 399 viremia episodes in 223 (68%) patients. Viremia with CMV, EBV, HHV-6, HSV-1, HSV-2, and VZV was detected in 60 (18%), 157 (48%), 80 (24%), 87 (26%), 13 (4%), and 2 (0.6%) patients, respectively; 112 (34%) patients had multiple concurrent viremia events. Crude mortality in the ICU was 36% in this latter group compared to 19% in remaining patients (P < .01). After adjustment for potential confounders, time-dependent bias, and competing risks, only concurrent CMV and EBV reactivations remained independently associated with increased mortality (adjusted subdistribution hazard ratio, 3.17; 95% confidence interval, 1.41-7.13). Conclusions: Herpesvirus reactivations were documented in 68% of septic shock patients without prior immunodeficiency and frequently occurred simultaneously. Concurrent reactivations could be independently associated with mortality. Clinical Trials Registration: NCT01905033.

Cytomegalovirus Status and the Outcome of T Cell-Replete Reduced-Intensity Allogeneic Hematopoietic Stem Cell Transplantation.

Cytomegalovirus (CMV) serostatus of donor and recipient are frequently used in algorithms of donor selection, whereas the impact of CMV reactivation on transplantation-related mortality, leukemia control, and overall survival (OS) remains controversial. Therefore, we retrospectively studied the impact of latent or active CMV infections on the outcome and occurrence of graft-versus-host disease (GVHD) after reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (SCT) in 294 patients during the period from 2004 to 2010. CMV viral load was routinely monitored in plasma using a quantitative PCR. Preemptive antiviral therapy was initiated when the viral load in plasma exceeded a predefined threshold. In a proportional hazards model, a seropositive recipient was significantly associated with increased occurrence of acute GVHD. However the CMV serostatus of both recipient and donor and the presence of active CMV infection was not associated with the occurrence of relapses, chronic GVHD, or OS. We conclude that in the presence of viral load monitoring and preemptive treatment, latent or active CMV infection does not substantially affect the OS after T cell-replete RIC allogeneic SCT.

Cytomegalovirus seroprevalence as a risk factor for poor outcome in acute respiratory distress syndrome*.

OBJECTIVE: Cytomegalovirus reactivation may complicate critical illness in latent carriers of the virus, even in patients who were previously immunocompetent. Patients with acute respiratory distress syndrome are considered to be prone for reactivation. Prophylactic antiviral therapy in immunocompetent cytomegalovirus seropositive patients admitted to the ICU with acute respiratory distress syndrome has therefore been proposed. We assessed cytomegalovirus seroprevalence as a risk factor for morbidity and mortality in patients with acute respiratory distress syndrome. DESIGN: Prospective observational cohort study. We used the number of days alive and free of mechanical ventilation on day 28 as a composite outcome measure and used multivariable ordinal logistic regression analyses to adjust for potential confounders. SETTING: ICUs of two tertiary care hospitals in The Netherlands. PATIENTS: We included all newly admitted patients with acute respiratory distress syndrome who received mechanical ventilation for at least 4 days. Patients with known immunocompromise and those receiving antiviral treatment prior to ICU admission were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Over a 2-year period, 306 patients were included, 209 (68%) of whom were cytomegalovirus seropositive. Cytomegalovirus reactivation occurred in 53 of these cases (26%). One hundred patients (33%) died or continued to be mechanically ventilated by day 28. After adjustment for confounding, cytomegalovirus seroprevalence was not associated with the primary outcome (crude odds ratio, 1.09; 95% CI, 0.70-1.70; adjusted odds ratio, 1.01; 95% CI, 0.64-1.59). Seroprevalence was also not associated with poor outcome in any of the prespecified subgroup analyses. However, a significant association was found in a post hoc subgroup of patients who had developed acute respiratory distress syndrome in a setting of septic shock (adjusted odds ratio, 2.86; 95% CI, 1.32-6.23). The time course of pulmonary markers in survivors was comparable between the two serogroups. CONCLUSIONS: Cytomegalovirus seroprevalence is not associated with prolonged mechanical ventilation or increased mortality in critically ill patients with acute respiratory distress syndrome, with possible exception of patients presenting with septic shock. Therefore, a prevention strategy targeting an unselected cohort of seropositive patients with acute respiratory distress syndrome is unlikely to show any meaningful benefit.

Reactivation of Multidrug-Resistant HSV-1 in a Post-Allogenic Hematopoietic Stem Cell Transplant Patient: Dynamic Detection of the Rare A605V Mutation by Next-Generation Sequencing.

We present an immunocompromised patient with a multiresistant herpes simplex virus-1 reactivation with a rare mutation (A605V) in the viral DNA polymerase gene. Next-generation sequencing suggests the presence of multiple drug-resistant strains before treatment and altered ratios during treatment, affecting the clinical response to aciclovir and foscarnet.

Infectious Diseases and Basal Ganglia Calcifications: A Cross-Sectional Study in Patients with Fahr's Disease and Systematic Review.

Background: It is unclear whether patients with basal ganglia calcifications (BGC) should undergo infectious disease testing as part of their diagnostic work-up. We investigated the occurrence of possibly associated infections in patients with BGC diagnosed with Fahr's disease or syndrome and consecutively performed a systematic review of published infectious diseases associated with BGC. Methods: In a cross-sectional study, we evaluated infections in non-immunocompromised patients aged ≥ 18 years with BGC in the Netherlands, who were diagnosed with Fahr's disease or syndrome after an extensive multidisciplinary diagnostic work-up. Pathogens that were assessed included the following: Brucella sp., cytomegalovirus, human herpesvirus type 6/8, human immunodeficiency virus (HIV), Mycobacterium tuberculosis, rubella virus, and Toxoplasma gondii. Next, a systematic review was performed using MEDLINE and Embase (2002-2023). Results: The cross-sectional study included 54 patients (median age 65 years). We did not observe any possible related infections to the BGC in this population. Prior infection with Toxoplasma gondii occurred in 28%, and in 94%, IgG rubella antibodies were present. The positive tests were considered to be incidental findings by the multidisciplinary team since these infections are only associated with BGC when congenitally contracted and all patients presented with adult-onset symptoms. The systematic search yielded 47 articles, including 24 narrative reviews/textbooks and 23 original studies (11 case series, 6 cross-sectional and 4 cohort studies, and 2 systematic reviews). Most studies reported congenital infections associated with BGC (cytomegalovirus, HIV, rubella virus, Zika virus). Only two studies reported acquired pathogens (chronic active Epstein-Barr virus and Mycobacterium tuberculosis). The quality of evidence was low. Conclusions: In our cross-sectional study and systematic review, we found no convincing evidence that acquired infections are causing BGC in adults. Therefore, we argue against routine testing for infections in non-immunocompromised adults with BGC in Western countries.

Humoral and cellular immunogenicity, effectiveness and safety of COVID-19 mRNA vaccination in patients with pediatric rheumatic diseases: A prospective cohort study.

OBJECTIVES: To evaluate immunogenicity, effectiveness and safety of COVID-19 vaccination in patients with pediatric autoimmune inflammatory rheumatic disease (pedAIIRD). METHODS: A prospective cohort study was performed at the pediatric rheumatology department of the Wilhelmina Children's Hospital in Utrecht, the Netherlands. Vaccination dates, COVID-19 cases and vaccine-related adverse events (AEs) were registered for all pedAIIRD patients during regular clinic visits from March 2021 - August 2022. SARS-CoV-2 IgG antibody levels and T-cell responses were measured from serum samples after vaccination, and clinical and drug therapy data were collected from electronic medical records. Rate of COVID-19 disease was compared between vaccinated and unvaccinated patients in a time-varying Cox regression analysis. RESULTS: A total of 157 patients were included in this study and 88 % had juvenile idiopathic arthritis (JIA). One hundred thirty-seven patients were fully vaccinated, of which 47 % used biological agents at the time of vaccination, and 20 patients were unvaccinated. Geometric mean concentrations (GMCs) of post-vaccine antibody levels against SARS-CoV-2 were above the threshold for positivity in patients who did and did not use biological agents at the time of vaccination, although biological users demonstrated significantly lower antibody levels (adjusted GMC ratio: 0.38, 95 % CI: 0.21 - 0.70). T-cell responses were adequate in all but two patients (9 %). The adjusted rate of reported COVID-19 was significantly lower for fully vaccinated patients compared to non-vaccinated patients (HR: 0.53, 95 % CI: 0.29 - 0.97). JIA disease activity scores were not significantly different after vaccination, and no serious AEs were reported. CONCLUSIONS: COVID-19 mRNA vaccines were immunogenic (both cellular and humoral), effective and safe in a large cohort of pedAIIRD patients despite their use of immunosuppressive medication.

Assessing and improving the quality of guideline-adherent hepatitis B virus care in people with HIV: A cross-sectional study.

The increasing use of non-tenofovir containing antiretroviral regimens calls for renewed attention to the prevention and management of hepatitis B virus (HBV) in people with HIV (PWH). We retrospectively assessed adherence to HBV guidelines, including complete HBV screening in PWH. In people with HIV/HBV co-infection, this included HBV therapy, screening for hepatitis delta virus (HDV) and on-therapy virologic response monitoring. HIV/HBV co-infection in PWH was defined as the presence of hepatitis B surface antigen (HBsAg) at the last measurement before study entry or detectable HBV-DNA for ≥6 months. After assessment, missing laboratory tests were performed to optimize HBV monitoring and screening for co-infections. Of all PWH under follow-up, 1484/1633 (90.9%) were adequately screened for HBV. After performing missing screening tests, 466 of 1618 PWH with complete screening results (28.8%) were non-immune for HBV infection. Fifty-one (3.2%) with HIV/HBV co-infection were identified. HBV treatment was adequate in 51/51 (100%). Screening for hepatitis A, C and delta virus antibodies and fibrosis was performed in 51/51 (100%), 49/51 (96.1%), 17/51 (35.3%) and 38/51 (74.5%). Annual HBV-DNA or HBsAg monitoring was done in 18/51 (35.3%) and hepatocellular carcinoma (HCC) surveillance in 2/9 (22.2%) of those indicated. Additional testing in those with missing data identified 4/34 (11.8%) persons with HDV antibodies and 3/30 (10%) with HBsAg seroclearance. Our study demonstrates the feasibility and added value of evaluating HBV care components and performing missing laboratory tests, identifying a large number of HBV vaccination candidates and HDV antibody screening, HBsAg monitoring and HCC surveillance as key areas for improvement.

Long-term immunoprotection after live attenuated measles-mumps-rubella booster vaccination in children with juvenile idiopathic arthritis.

INTRODUCTION: Vaccines, especially live attenuated vaccines, in children with JIA pose a great challenge due to both potential lower immunogenicity and safety as a result of immunosuppressive treatment. For many years, in the Netherlands, JIA patients receive a measles-mumps-rubella (MMR) booster vaccine at the age of nine years as part of the national immunization program. OBJECTIVES: To study long-term humoral immunoprotection in a large cohort of JIA patients who received the MMR booster vaccine while being treated with immunomodulatory therapies at the Wilhelmina Children's Hospital in Utrecht, the Netherlands. METHODS: MMR-specific IgG antibody concentrations in stored serum samples of vaccinated JIA patients were determined with chemiluminescent microparticle immunoassays (CMIA). Samples were analyzed five years after MMR booster vaccination and at last available follow-up visit using both crude and adjusted analyses. Additional clinical data were collected from electronic medical records. RESULTS: In total, 236 samples from 182 patients were analyzed, including 67 samples that were available five years post-vaccination, and an additional 169 samples available from last visits with a median duration after vaccination of 6.9 years (IQR: 2.8-8.8). Twenty-eight patients were using biologic disease-modifying antirheumatic drugs (bDMARDS) of whom 96% anti-TNF agents and 4% tocilizumab. Percentages of protective antibody levels against measles after five years were significantly lower for patients who used bDMARD therapy at vaccination compared to patients who did not: 60% versus 86% (P = 0.03). For mumps (80% versus 94%) and rubella (60% versus 83%) this difference did not reach statistical significance (P = 0.11 and P = 0.07, respectively). Antibody levels post-vaccination decreased over time, albeit not significantly different between bDMARD users and non-bDMARD users. CONCLUSION: The MMR booster vaccine demonstrated long-term immunogenicity in the majority of children with JIA from a large cohort, although lower percentages of protective measles antibody levels were observed in bDMARD users. Hence, it might be indicated to measure antibody levels at least five years after MMR booster vaccination in the latter group and advice an extra booster accordingly.

Changes in Local and Systemic Adverse Effects following Primary and Booster Immunisation against COVID-19 in an Observational Cohort of Dutch Healthcare Workers Vaccinated with BNT162b2 (Comirnaty®).

In healthcare workers (HCWs) and in the general population, fear of adverse effects is among the main reasons behind COVID-19 vaccine hesitancy. We present data on self-reported adverse effects from a large cohort of HCWs who underwent primary (N = 470) and booster (N = 990) mRNA vaccination against SARS-CoV-2. We described general patterns in, and predictors of self-reported adverse effect profiles. Adverse effects following immunisation (AEFI) were reported more often after the second dose of primary immunisation than after the first dose, but there was no further increase in adverse effects following the booster round. Self-reported severity of systemic adverse effects was less following booster immunisation. Prior infection with SARS-CoV-2 was found to be a significant predictor of AEFI following primary immunisation, but was no longer a predictor after booster vaccination. Compared to other studies reporting specifically on adverse effects of SARS-CoV-2 vaccination in healthcare workers, we have a relatively large cohort size, and are the first to compare adverse effects between different rounds of vaccination. Compared to studies in the general population, we have a considerably homogenous population. Insights in AEFI following primary and booster vaccinations may help in addressing vaccine hesitancy, both in HCWs and in the general population.

Meningococcal ACWY conjugate vaccine immunogenicity in adolescents with primary or secondary immune deficiencies, a prospective observational cohort study.

BACKGROUND: Immunization with meningococcal ACWY conjugate vaccine induces protective antibodies against invasive meningococcal disease (IMD) caused by serogroups A, C, W and Y. We studied MenACWY-TT vaccine immunogenicity in adolescents with a heterogenous group of primary and secondary immune deficiency including patients with systemic lupus erythematosus, mixed connective tissue disease, vasculitis, uveitis, 22Q11 syndrome, sickle cell disease, and patients who underwent stem cell transplantation for bone marrow failure. FINDINGS: We enrolled 69 individuals aged 14-18 years diagnosed with a primary or secondary immune deficiency in a prospective observational cohort study. All patients received a single dose of MenACWY-TT vaccine during the catch-up campaign 2018-19 because of the IMD-W outbreak in the Netherlands. Capsular polysaccharide-specific (PS) IgG concentrations against MenACWY were measured before and 3-6, 12, and 24 months after vaccination. Overall, geometric mean concentrations (GMCs) of MenACWY-PS-specific IgG were lower in patients compared to data from healthy, aged-matched controls (n = 75) reaching significance at 12 months postvaccination for serogroup A and W (adjusted GMC ratios 0.26 [95% CI: 0.15-0.47] and 0.22 [95% CI: 0.10-0.49], respectively). No serious adverse events were reported by study participants. CONCLUSIONS: The MenACWY conjugate vaccine was less immunogenic in adolescent patients with primary or secondary immunodeficiency compared to healthy controls, urging the need for further surveillance of these patients and supporting considerations for booster MenACWY conjugate vaccinations in these patient groups.

Meningococcal ACWY conjugate vaccine immunogenicity and safety in adolescents with juvenile idiopathic arthritis and inflammatory bowel disease: A prospective observational cohort study.

BACKGROUND: Immunogenicity to meningococcal serogroup ACWY (MenACWY) conjugate vaccine has not been studied in immunocompromised minors with juvenile idiopathic arthritis (JIA) or inflammatory bowel disease (IBD). We determined immunogenicity of a MenACWY-TT vaccine in JIA and IBD patients at adolescent age and compared results to data from aged-matched healthy controls (HCs). METHODS: We performed a prospective observational cohort study in JIA and IBD patients (14-18 years old), who received a MenACWY vaccination during a nationwide catch-up campaign (2018-2019) in the Netherlands. Primary aim was to compare MenACWY polysaccharide-specific serum IgG geometric mean concentrations (GMCs) in patients with HCs and secondary between patients with or without anti-TNF therapy. GMCs were determined before and 3-6, 12, and 24 months postvaccination and compared with data from HCs at baseline and 12 months postvaccination. Serum bactericidal antibody (SBA) titers were determined in a subset of patients at 12 months postvaccination. RESULTS: We included 226 JIA and IBD patients (66 % and 34 % respectively). GMCs were lower for MenA and MenW (GMC ratio 0·24 [0·17-0·34] and 0·16 [0·10-0·26] respectively, p < 0·01) in patients compared to HCs at 12 months postvaccination. Anti-TNF users had lower MenACWY GMCs postvaccination compared with those without anti-TNF (p < 0·01). The proportion protected (SBA ≥ 8) for MenW was reduced in anti-TNF users (76 % versus 92 % in non-anti-TNF and 100 % in HCs, p < 0.01). CONCLUSION: The MenACWY conjugate vaccine was immunogenic in the vast majority of JIA and IBD patients at adolescent age, but seroprotection was lower in patients using anti-TNF agents. Therefore, an extra booster MenACWY vaccination should be considered.

High Predictive Value of the Soluble ZEBRA Antigen (Epstein-Barr Virus Trans-Activator Zta) in Transplant Patients with PTLD.

The ZEBRA (Z EBV replication activator) protein is the major transcription factor of EBV, expressed upon EBV lytic cycle activation. An increasing body of studies have highlighted the critical role of EBV lytic infection as a risk factor for lymphoproliferative disorders, such as post-transplant lymphoproliferative disease (PTLD). We studied 108 transplanted patients (17 PTLD and 91 controls), retrospectively selected from different hospitals in France and in the Netherlands. The majority of PTLD were EBV-positive diffuse large B-cell lymphomas, five patients experienced atypical PTLD forms (EBV-negative lymphomas, Hodgkin's lymphomas, and T-cell lymphomas). Fourteen patients among the seventeen who developed a pathologically confirmed PTLD were sZEBRA positive (soluble ZEBRA, plasma level above 20 ng/mL, measured by an ELISA test). The specificity and positive predictive value (PPV) of the sZEBRA detection in plasma were 98% and 85%, respectively. Considering a positivity threshold of 20 ng/mL, the sensitivity of the sZEBRA was 82.35% and the specificity was 94.51%. The mean of the sZEBRA values in the PTLD cases were significantly higher than in the controls (p < 0.0001). The relevance of the lytic cycle and, particularly, the role of ZEBRA in lymphomagenesis is a new paradigm pertaining to the prevention and treatment strategies for PTLD. Given the high-specificity and the predictive values of this test, it now appears relevant to investigate the lytic EBV infection in transplanted patients as a prognostic biomarker.

Saffold virus, a human Theiler's-like cardiovirus, is ubiquitous and causes infection early in life.

The family Picornaviridae contains well-known human pathogens (e.g., poliovirus, coxsackievirus, rhinovirus, and parechovirus). In addition, this family contains a number of viruses that infect animals, including members of the genus Cardiovirus such as Encephalomyocarditis virus (EMCV) and Theiler's murine encephalomyelits virus (TMEV). The latter are important murine pathogens that cause myocarditis, type 1 diabetes and chronic inflammation in the brains, mimicking multiple sclerosis. Recently, a new picornavirus was isolated from humans, named Saffold virus (SAFV). The virus is genetically related to Theiler's virus and classified as a new species in the genus Cardiovirus, which until the discovery of SAFV did not contain human viruses. By analogy with the rodent cardioviruses, SAFV may be a relevant new human pathogen. Thus far, SAFVs have sporadically been detected by molecular techniques in respiratory and fecal specimens, but the epidemiology and clinical significance remained unclear. Here we describe the first cultivated SAFV type 3 (SAFV-3) isolate, its growth characteristics, full-length sequence, and epidemiology. Unlike the previously isolated SAFV-1 and -2 viruses, SAFV-3 showed efficient growth in several cell lines with a clear cytopathic effect. The latter allowed us to conduct a large-scale serological survey by a virus-neutralization assay. This survey showed that infection by SAFV-3 occurs early in life (>75% positive at 24 months) and that the seroprevalence reaches >90% in older children and adults. Neutralizing antibodies were found in serum samples collected in several countries in Europe, Africa, and Asia. In conclusion, this study describes the first cultivated SAFV-3 isolate, its full-length sequence, and epidemiology. SAFV-3 is a highly common and widespread human virus causing infection in early childhood. This finding has important implications for understanding the impact of these ubiquitous viruses and their possible role in acute and/or chronic disease.

Predictive factors for vaccine failure to guide vaccination in allogeneic hematopoietic stem cell transplant recipients.

Vaccination after hematopoietic stem cell transplantation (HSCT) is essential to protect high-risk patients against potentially lethal infections. Though multiple studies have evaluated vaccine specific responses, no comprehensive analysis of a complete vaccination schedule post-HSCT has been performed and little is known about predictors for vaccine failure. In this context, allogeneic HSCT (alloHSCT) patients were included and vaccinated starting one year post-transplantation. Antibody responses were measured by Multiplex Immuno Assay for pneumococcal (PCV13), meningococcal C, diphtheria, pertussis, tetanus and Haemophilus influenza type b one month after the last vaccination and correlated to clinical and immunological parameters. Vaccine failure was defined as antibody response above vaccine-specific cut-off values for less than four out of six vaccines. Ninety-six patients were included of which 27.1% was found to have vaccine failure. Only 40.6% of all patients responded adequately to all six vaccines. In multivariate analysis, viral reactivation post-HSCT (OR 6.53; P = 0.03), B-cells <135 per mm3 (OR 7.24; P = 0.00) and NK-cells <170 per mm3 (OR 11.06; P = 0.00) were identified as predictors for vaccine failure for vaccination at one year post-alloHSCT. Measurement of antibody responses and an individualized approach for revaccination guided by clinical status and immune reconstitution of B-cells and NK-cells may improve vaccine responses.

Cytomegalovirus reactivation and mortality in patients with acute respiratory distress syndrome.

PURPOSE: Cytomegalovirus (CMV) reactivation occurs frequently in patients with the acute respiratory distress syndrome (ARDS) and has been associated with increased mortality. However, it remains unknown whether this association represents an independent risk for poor outcome. We aimed to estimate the attributable effect of CMV reactivation on mortality in immunocompetent ARDS patients. METHODS: We prospectively studied immunocompetent ARDS patients who tested seropositive for CMV and remained mechanically ventilated beyond day 4 in two tertiary intensive care units in the Netherlands from 2011 to 2013. CMV loads were determined in plasma weekly. Competing risks Cox regression was used with CMV reactivation status as a time-dependent exposure variable. Subsequently, in sensitivity analyses we adjusted for the evolution of disease severity until onset of reactivation using marginal structural modeling. RESULTS: Of 399 ARDS patients, 271 (68%) were CMV seropositive and reactivation occurred in 74 (27%) of them. After adjustment for confounding and competing risks, CMV reactivation was associated with overall increased ICU mortality (adjusted subdistribution hazard ratio (SHR) 2.74, 95% CI 1.51-4.97), which resulted from the joint action of trends toward an increased mortality rate (direct effect; cause specific hazard ratio (HR) 1.58, 95% CI 0.86-2.90) and a reduced successful weaning rate (indirect effect; cause specific HR 0.83, 95% CI 0.58-1.18). These associations remained in sensitivity analyses. The population-attributable fraction of ICU mortality was 23% (95% CI 6-41) by day 30 (risk difference 4.4, 95% CI 1.1-7.9). CONCLUSION: CMV reactivation is independently associated with increased case fatality in immunocompetent ARDS patients who are CMV seropositive.

Detection of the Candida antigen mannan in cerebrospinal fluid specimens from patients suspected of having Candida meningitis.

Cerebrospinal fluid samples from five patients from which Candida cells were cultured were tested for the presence of mannan. Samples from four patients categorized as having proven candidosis reacted positively. Samples from the remaining patient and from patients with other central nervous system infections were negative. Detection of mannan may be valuable in the diagnosis of Candida meningitis.