Evaluation of Alinity m CMV assay performance for detecting CMV in plasma, cerebrospinal fluid, and bronchoalveolar lavage specimens.

Accurate detection and quantification of cytomegalovirus (CMV) is crucial to preventing adverse outcomes in immunocompromised individuals. Current assays were developed for use with plasma specimens, but CMV may be present in bronchoalveolar lavage (BAL) fluid and cerebrospinal fluid (CSF). We evaluated the performance of the Abbott Alinity m CMV assay compared to the Abbott RealTime CMV assay for quantification of CMV in plasma, BAL, and CSF specimens. To evaluate clinical performance, 190 plasma, 78 BAL, and 20 CSF specimens were tested with the Alinity m assay and compared to the RealTime assay. The Alinity m CMV assay showed high precision (SD <0.01 to 0.13) for all 3 specimen types. Clincal plasma and BAL specimens with quantifiable CMV DNA demonstrated strong correlation to RealTime CMV assay results (r2 = 0.9779 for plasma, r2 = 0.9373 for BAL). The Alinity m CMV assay may be useful for quantification of CMV in plasma, BAL, and CSF specimens.

The Limitations of Cytomegalovirus DNA Detection in Cerebrospinal Fluid of Newborn Infants With Congenital CMV Infection: A Tertiary Care Neonatal Center Experience.

BACKGROUND: Congenital cytomegalovirus (cCMV) infection of the central nervous system (CNS) can cause ventriculomegaly, gliosis, calcifications and cortical defects. Detection of CMV DNA in cerebrospinal fluid by PCR (CSF-CMV-PCR) is a marker of CNS involvement. OBJECTIVE: To evaluate a diagnostic value of the positive CSF-CMV-PCR in cCMV. METHODS: Analysis of clinical, laboratory, neuroimaging and single-nucleotide polymorphisms (SNPs) data according to the results of CSF-CMV-PCR were performed in infants with cCMV. RESULTS: A total of 168 infants were included; 145 (86.3%) had negative and 23 (13.7%) had positive CSF-CMV-PCR results. Associations between the positive CSF-CMV-PCR results and prematurity (odds ratio [OR] = 3.24; 95% confidence interval [CI]: 1.30-8.07), microcephaly (OR = 5.67; 95% CI: 2.08-15.41), seizures (OR = 4.15; 95% CI: 1.10-15.67), sensorineural hearing loss (OR = 6.6; 95% CI: 2.49-17.46), splenomegaly (OR = 8.13; 95% CI: 3.12-21.16), hepatitis (OR = 10.51; 95% CI: 3.31-33.35), petechiae (OR = 10.21; 95% CI: 3.78-27.57) and heterozygous T/C genotype at TLR4rs4986791 (OR = 7.88; 95% CI: 1.55-40.12) were observed. When using a multivariate logistic regression analysis, only the presence of severe sensorineural hearing loss (OR = 7.18; 95% CI: 1.75-29.34, P = 0.006), cystic lesions on MRI (OR 5.29; 95% CI: 1.31-21.36, P = 0.02), and calcifications on MRI (OR = 7.19; 95% CI: 1.67-30.97, P = 0.008) remained as the significant independent predictors of the positive CSF-CMV-PCR results. CONCLUSIONS: The detection of CMV DNA in CSF is associated with a higher rate of CNS damage including abnormal MRI neuroimaging and severe hearing loss. Therefore, detection of CMV DNA in CSF may be considered as a marker of severe CNS injury in cCMV infection. However, the very low prevalence of the positive CSF-CMV-PCR results, even in infants with proven CNS involvement, may imply its limited role in clinical practice.

Clinical significance of Epstein-Barr virus in the cerebrospinal fluid of immunocompetent patients.

INTRODUCTION: Polymerase chain reaction (PCR)-based testing of cerebrospinal fluid (CSF) samples has greatly facilitated the diagnosis of central nervous system (CNS) infections. However, the clinical significance of Epstein-Barr virus (EBV) DNA in CSF of individuals with suspected CNS infection remains unclear. We wanted to gain a better understanding of EBV as an infectious agent in immunocompetent patients with CNS disorders. METHODS: We identified cases of EBV-associated CNS infections and reviewed their clinical and laboratory characteristics. The study population was drawn from patients with EBV PCR positivity in CSF who visited Pusan National University Hospital between 2010 and 2019. RESULTS: Of the 780 CSF samples examined during the 10-year study period, 42 (5.4 %) were positive for EBV DNA; 9 of the patients (21.4 %) were diagnosed with non-CNS infectious diseases, such as optic neuritis, Guillain-Barré syndrome, and idiopathic intracranial hypotension, and the other 33 cases were classified as CNS infections (22 as encephalitis and 11 as meningitis). Intensive care unit admission (13/33 patients, 39.3 %) and presence of severe neurological sequelae at discharge (8/33 patients, 24.2 %) were relatively frequent. In 10 patients (30.3 %), the following pathogens were detected in CSF in addition to EBV: varicella-zoster virus (n = 3), cytomegalovirus (n = 2), herpes simplex virus 1 (n = 1), herpes simplex virus 2 (n = 1), Streptococcus pneumomiae (n = 2), and Enterococcus faecalis (n = 1). The EBV-only group (n = 23) and the co-infection group (n = 10) did not differ in age, gender, laboratory data, results of brain imaging studies, clinical manifestations, or prognosis; however, the co-infected patients had higher CSF protein levels. CONCLUSION: EBV DNA in CSF is occasionally found in the immunocompetent population; the virus was commonly associated with encephalitis and poor prognosis, and frequently found together with other microbes in CSF.

Etiology of Pediatric Meningitis in West Africa Using Molecular Methods in the Era of Conjugate Vaccines against Pneumococcus, Meningococcus, and Haemophilus influenzae Type b.

Despite the implementation of effective conjugate vaccines against the three main bacterial pathogens that cause meningitis, Streptococcus pneumoniae, Haemophilus influenzae type b (Hib), and Neisseria meningitidis serogroup A, the burden of meningitis in West Africa remains high. The relative importance of other bacterial, viral, and parasitic pathogens in central nervous system infections is poorly characterized. Cerebrospinal fluid (CSF) specimens were collected from children younger than 5 years with suspected meningitis, presenting at pediatric teaching hospitals across West Africa in five countries including Senegal, Ghana, Togo, Nigeria, and Niger. Cerebrospinal fluid specimens were initially tested using bacteriologic culture and a triplex real-time polymerase chain reaction (PCR) assay for N. meningitidis, S. pneumoniae, and H. influenzae used in routine meningitis surveillance. A custom TaqMan Array Card (TAC) assay was later used to detect 35 pathogens including 15 bacteria, 17 viruses, one fungus, and two protozoans. Among 711 CSF specimens tested, the pathogen positivity rates were 2% and 20% by the triplex real-time PCR (three pathogens) and TAC (35 pathogens), respectively. TAC detected 10 bacterial pathogens, eight viral pathogens, and Plasmodium. Overall, Escherichia coli was the most prevalent (4.8%), followed by S. pneumoniae (3.5%) and Plasmodium (3.5%). Multiple pathogens were detected in 4.4% of the specimens. Children with human immunodeficiency virus (HIV) and Plasmodium detected in CSF had high mortality. Among 220 neonates, 17% had at least one pathogen detected, dominated by gram-negative bacteria. The meningitis TAC enhanced the detection of pathogens in children with meningitis and may be useful for case-based meningitis surveillance.

Compartmentalization of a Multidrug-Resistant Cytomegalovirus UL54 Mutant in a Stem Cell Transplant Recipient with Encephalitis.

We report a case of cytomegalovirus encephalitis in a hematopoietic stem cell transplant recipient. A previously uncharacterized V787E mutation in UL54 was identified in cerebrospinal fluid but not plasma specimens. For the V787E recombinant virus, the half maximal effective concentrations for ganciclovir, foscarnet, and cidofovir were 8.6-, 3.4- and 2.9-fold higher than for wild-type virus, and the replicative capacity was lower. The introduction of a bulkier and negatively charged glutamate residue at position 787 could destabilize the finger domain of UL54 DNA polymerase. Viral genotyping of cerebrospinal fluid is warranted in subjects with cytomegalovirus encephalitis, owing to the low penetration of antivirals in this compartment.

Presentación del síndrome de Wernicke-Korsakoff secundario a encefalitis por citomegalovirus, a propósito de un caso / Wernicke-Korsakoff syndrome secondary to cytomegalovirus encephalitis: A case report

Resumen El citomegalovirus (CMV) es uno de los microorganismos oportunistas con mayor prevalencia en pacientes inmunocomprometidos, aunque su reactivación ha descendido después de la introducción de la terapia antirretroviral altamente activa (Highly Active Antiretroviral Therapy, HAART). En las coinfecciones, la encefalitis se ha reportado como una de las condiciones más frecuentes. Se presenta el caso de un paciente adulto joven con infección por virus de la inmunodeficiencia humana (HIV) que tuvo un rápido deterioro neurológico evidenciado en síntomas y signos clínicos clásicos del síndrome de Wernicke-Korsakoff y que no presentaba factores de riesgo para deficiencia de tiamina. En las imágenes de la resonancia magnética cerebral, se detectaron hallazgos típicos del síndrome, y se identificó citomegalovirus (CMV) en el líquido cefalorraquídeo. Con el tratamiento específico para el CMV, se logró el control de los síntomas, aunque hubo secuelas neurológicas que mejoraron. Este es uno de los pocos casos reportados a nivel mundial de síndrome de Wernicke secundario a encefalitis por citomegalovirus.

Abstract Cytomegalovirus (CMV) is one of the opportunistic microorganisms with the highest prevalence in immunocompromised patients. Reactivation has decreased after the introduction of highly active antiretroviral therapy (HAART). Encephalitis has been reported in the coinfection as one of the most frequent presentations. We present the case of a young adult patient with HIV infection and rapid neurological deterioration due to classic clinical symptoms and signs of the Wernicke-Korsakoff syndrome, with no risk factors for thiamine deficiency, with images by nuclear magnetic resonance typical of the syndrome, and identification of cytomegalovirus in cerebrospinal fluid. The specific treatment for CMV managed to control the symptoms with neurological sequelae in progression towards improvement. This is one of the few cases reported in the literature of Wernicke syndrome secondary to cytomegalovirus encephalitis.

[Wernicke-Korsakoff syndrome secondary to cytomegalovirus encephalitis: A case report].

Cytomegalovirus (CMV) is one of the opportunistic microorganisms with the highest prevalence in immunocompromised patients. Reactivation has decreased after the introduction of highly active antiretroviral therapy (HAART). Encephalitis has been reported in the coinfection as one of the most frequent presentations.We present the case of a young adult patient with HIV infection and rapid neurological deterioration due to classic clinical symptoms and signs of the Wernicke-Korsakoff syndrome, with no risk factors for thiamine deficiency, with images by nuclear magnetic resonance typical of the syndrome, and identification of cytomegalovirus in cerebrospinal fluid. The specific treatment for CMV managed to control the symptoms with neurological sequelae in progression towards improvement.This is one of the few cases reported in the literature of Wernicke syndrome secondary to cytomegalovirus encephalitis.

Cytomegalovirus-associated encephalomyelitis in an immunocompetent adult: a two-stage attack of direct viral and delayed immune-mediated invasions. case report.

BACKGROUND: It is clinically rare to find cytomegalovirus (CMV)-associated encephalomyelitis in immunocompetent adults. Here, we present the case of an adult patient who developed acute transverse myelitis that was followed by immune-mediated disseminated encephalomyelitis. CASE PRESENTATION: A 38-year-old man developed acute paraplegia with paresthesia below the level of the T7-8 dermatome. Both brain and spinal cord MRIs performed at admission appeared normal. Corticosteroid therapy was initiated, with the later addition of high-dose intravenous immunoglobulins. After polymerase chain reaction analysis indicated the presence of CMV DNA in his cerebrospinal fluid (CSF), anti-viral therapy was added. Forty days after symptom onset, despite an initial positive response to this therapy, he developed dysarthria and truncal ataxia. Repeated magnetic resonance imaging scans demonstrated progressively expanding lesions involving not only the spinal cord but also the cerebral white matter, suggestive of extensive immune-mediated demyelination involving the central nervous system (CNS), as is observed in acute disseminated encephalomyelitis (ADEM). CONCLUSION: This case report underscores the importance of careful patient observation following the initial diagnosis of a CMV-associated CNS infection, such as transverse myelitis, on the possibility that post-infectious ADEM may appear.

[Cerebrospinal fluid shunt malfunction not associated with ventricular enlargement. A case report and literature review]. / Disfunktsiya shunta tserebrospinal'noi zhidkosti bez rasshireniya zheludochkov mozga. Sluchai iz praktiki i obzor literatury.

Substantiation of the shunt failure diagnosis and subsequent consideration of indications for surgical elimination of the malfunction is a laborious and challenging process. Identification of a malfunction in doubtful cases requires, in addition to standard examinations, extra diagnostic procedures, which may delay making a decision for several weeks to several months. The article describes a case of mechanical CSF shunt malfunction (breakage and failure of a peritoneal catheter in a 7-year-old girl) with intracranial hypertension symptoms, but without typical enlargement of the brain ventricles. According to the medical history, congenital hydrocephalus in the child was accompanied by an inflammatory process of bacterial and viral etiology. The absence of brain ventricle enlargement was shown not to exclude a probability of shunt malfunction. In this case, a specific phenomenon, an intraparenchymatous cerebrospinal fluid "lake" surrounding a ventricular catheter, was observed. Shunting recovery did not lead to a significant reduction in the phenomenon size. Causes underlying this phenomenon require further investigation.

Virological testing of cerebrospinal fluid in children aged less than 14 years with a suspected central nervous system infection: A retrospective study on 304 consecutive children from January 2012 to May 2015.

OBJECTIVE: The study aimed to describe the prevalence of HSV DNA, VZV DNA, Enterovirus RNA, Parechovirus RNA, CMV DNA, EBV DNA, adenovirus DNA, HHV-6 DNA, HHV-7 DNA, HHV-8 DNA and Parvovirus B19DNA in children aged less 14 years with a suspected viral infection of the central nervous system in a clinical practice setting. METHODS: Between January 2012 and May 2015, cerebrospinal fluids from 304 children were tested with an in-house real-time PCR method. RESULTS: A positive PCR was detected in 64 subjects (21%): the mean number of tests performed in patients who showed a viral infection was 7.5, significantly higher (p = 0.001) with respect to that reported in negative samples (6.4). Enterovirus is the leading virus detected: 12 out of the 37 positive children reported were newborns (85.7% of all the newborns with a positive result). The second most frequently identified virus was HHV-7 (5 positive PCR out of 105 samples tested, 4.8%, if we excluded a child with a concomitant S. pneumoniae isolated), a prevalence significantly higher with respect to VZV (p = 0.02) and to CMV (p = 0.04). HHV-6 was the third most commonly identified aetiology (4.2%). All children were immunocompetent. SIGNIFICANCE: Only a minority of children had a specific viral aetiology identified: the rate of HHV-7 positivity suggests a routine testing of these viruses within the diagnostic algorithm in immunocompetent paediatric patients. This approach could help to define the clinical role of this herpesvirus.

Epidemiological surveillance of herpes viral encephalitis in Cordoba, Colombia.

Objective To establish an epidemiological surveillance of viral herpes encephalitis in major hospitals of Monteria, Cordoba. Methods From September 2009 to December 2011, a descriptive study of cases of viral encephalitis was made in three hospitals in the city of Monteria. Cerebrospinal fluid (CSF) samples from 118 patients were included in the study. Clinical aspects, as well as cytochemical and microbiological analysis (Gram stain and culture) of CSF, were used for selecting the patients. Virus detection was performed by using multiplex nested PCR for Herpes simplex virus 1 and 2, Epstein Barr virus, Cytomegalovirus and Varicella zoster virus. Results Viral DNA of herpesvirus was detected in the CSFs of 30 (25.4 %) participants, as follows: 22 (18.6 %) Herpes simplex 1 and 2 viruses, 4 (3.3 %) Cytomegalovirus and 1 (0.8 %) Varicella zoster virus. Co-infections were observed in 3 patients (2.5 %), 1 case by HSV-VZV and 2 cases by CMV/HSV. The clinical manifestations of the patients included: headache (18.6 %), fever (14.4 %), asthenia (10.1 %), seizures (9.3 %), vomiting (8.4 %), and stiff neck (5.9 %). Thirty percent of the patients also had HIV-AIDS. A case fatality rate of 20 % was observed for the patients. Conclusions This paper shows that herpesvirus is a cause of infection of the CNS in patients from Cordoba. This study contributes to the epidemiology of encephalitis, as well as to patient management.

Ganciclovir penetrates into the cerebrospinal fluid of an infant with congenital cytomegalovirus infection.

Currently, there is no evidence whether ganciclovir, or its oral prodrug valganciclovir, penetrates into the cerebrospinal fluid of human infants treated for congenital cytomegalovirus infection. Here, we report a case study providing evidence that ganciclovir, administered as valganciclovir, reaches the infant's cerebrospinal fluid when used at the currently recommended dose for congenital cytomegalovirus infection.

Cytomegalovirus meningoencephalitis after rituximab treatment for primary central nervous system lymphoma.

The efficacy and safety of rituximab against B-cell lymphomas is well established. However, there has been an increased incidence of infectious complications after rituximab treatment, mostly hepatitis B reactivation and progressive multifocal leukoencephalopathy. This is the case of a 67-year-old patient with primary central nervous system lymphoma, who developed cytomegalovirus meningoencephalitis after receiving high-dose chemotherapy and rituximab. As there was no evidence of lymphoma relapse or additional immunosuppression, besides his previous treatment, an association between rituximab and cytomegalovirus meningoencephalitis cannot be ruled out.

Development of recombinant antigen array for simultaneous detection of viral antibodies.

Protein microarrays have been developed to study antibody reactivity against a large number of antigens, demonstrating extensive perspective for clinical application. We developed a viral antigen array by spotting four recombinant antigens and synthetic peptide, including glycoprotein G of herpes simplex virus (HSV) type 1 and 2, phosphoprotein 150 of cytomegalovirus (CMV), Rubella virus (RV) core plus glycoprotein E1 and E2 as well as a E1 peptide with the optimal concentrations on activated glass slides to simultaneously detect IgG and IgM against HSV1, HSV2, CMV and RV in clinical specimens of sera and cerebrospinal fluids (CSFs). The positive reference sera were initially used to measure the sensitivity and specificity of the array with the optimal conditions. Then clinical specimens of 144 sera and 93 CSFs were tested for IgG and IgM antibodies directed against HSV1, HSV2, CMV and RV by the antigen array. Specificity of the antigen array for viral antibodies detection was satisfying compared to commercial ELISA kits but sensitivity of the array varied relying on quality and antigenic epitopes of the spotting antigens. In short, the recombinant antigen array has potential to simultaneous detect multiple viral antibodies using minute amount (3 µl) of samples, which holds the particularly advantage to detect viral antibodies in clinical CSFs being suspicious of neonatal meningitis and encephalitis.

Cytomegalovirus associated transverse myelitis in an immunocompetent host with DNA detection in cerebrospinal fluid; a case report.

BACKGROUND: Cytomegalovirus associated transverse myelitis among immunocompetent adults has been rarely reported. We report a patient presenting with clinical myelitis followed by previously unreported finding of cytomegalovirus deoxyribonucleic acid in cerebrospinal fluid. CASE REPORT: A forty year old immunocompetent male presented with acute onset progressive bilateral lower limb weakness. His spinal magnetic resonance imaging findings, cerebrospinal fluid analysis and clinical picture were compatible with transverse myelitis. Polymerase chain reaction of the cerebrospinal fluid for cytomegalovirus was positive while other infectious agents were not detected by serology or polymerase chain reaction. He was treated with intravenous ganciclovir with partial clinical response. CONCLUSION: Viral genome detection in the cerebrospinal fluid was performed but negative in five out of ten reported cases of cytomegalovirus associated transverse myelitis in the immunocompetent host. In previous cases the inability to isolate the virus in cerebrospinal fluid was considered favouring an immunological mechanism leading to pathogenesis rather than direct viral toxicity but this case is against that theory. This case highlights the fact that Cytomegalovirus should be considered as an aetiological agent in patients with transverse myelitis and that the virus may cause serious infections in immunocompetent host. Therefore this report is of importance to neurologists and physicians in general.

Epstein-barr virus coinfection in cerebrospinal fluid is associated with increased mortality in Malawian adults with bacterial meningitis.

Mortality from adult bacterial meningitis exceeds 50% in sub-Saharan Africa. We postulated that-particularly in individuals infected with human immunodeficiency virus (HIV)-herpes simplex virus, varicella zoster virus, Epstein-Barr virus (EBV), and cytomegalovirus (CMV) in the cerebrospinal fluid (CSF) contribute to poor outcome. CSF from 149 Malawian adults with bacterial meningitis and 39 controls were analyzed using polymerase chain reaction. EBV was detected in 79 of 149 bacterial meningitis patients. Mortality (54%) was associated with higher CSF EBV load when adjusted for HIV (P = .01). CMV was detected in 11 of 115 HIV-infected patients, 8 of whom died. The mechanisms by which EBV and CMV contribute to poor outcome require further investigation.