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1.
J Infect Dis ; 229(2): 493-501, 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-37874918

RESUMEN

BACKGROUND: To investigate evidence of residual viral infection, intrathecal immune activation, central nervous system (CNS) injury, and humoral responses in cerebrospinal fluid (CSF) and plasma in patients recovering from coronavirus disease 2019 (COVID-19), with or without neurocognitive post-COVID condition (PCC). METHODS: Thirty-one participants (25 with neurocognitive PCC) underwent clinical examination, lumbar puncture, and venipuncture ≥3 months after COVID-19 symptom onset. Healthy volunteers were included. CSF and plasma severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid and spike antigen (N-Ag, S-Ag), and CSF biomarkers of immune activation and neuronal injury were analyzed. RESULTS: SARS-CoV-2 N-Ag or S-Ag were undetectable in all samples and no participant had pleocytosis. We detected no significant differences in CSF and plasma cytokine concentrations, albumin ratio, IgG index, neopterin, ß2M, or in CSF biomarkers of neuronal injury and astrocytic damage. Furthermore, principal component analysis (PCA1) analysis did not indicate any significant differences between the study groups in the marker sets cytokines, neuronal markers, or anti-cytokine autoantibodies. CONCLUSIONS: We found no evidence of ongoing viral replication, immune activation, or CNS injury in plasma or CSF in patients with neurocognitive PCC compared with COVID-19 controls or healthy volunteers, suggesting that neurocognitive PCC is a consequence of events suffered during acute COVID-19 rather than persistent viral CNS infection or residual CNS inflammation.


Asunto(s)
COVID-19 , Humanos , COVID-19/complicaciones , SARS-CoV-2 , Sistema Nervioso Central , Astrocitos , Citocinas , Biomarcadores
2.
Eur J Neurol ; 30(10): 3182-3189, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37431060

RESUMEN

BACKGROUND AND PURPOSE: Our aim was to examine the correlation between biomarkers of neuronal and glial cell damage and severity of disease in patients with tick-borne encephalitis. METHODS: One hundred and fifteen patients with tick-borne encephalitis diagnosed in Lithuania and Sweden were prospectively included, and cerebrospinal fluid (CSF) and serum samples were obtained shortly after hospitalization. Using pre-defined criteria, cases were classified as mild, moderate or severe tick-borne encephalitis. Additionally, the presence of spinal nerve paralysis (myelitis) and/or cranial nerve affection were noted. Concentrations of the brain cell biomarkers glial fibrillary acidic protein (GFAP), YKL-40, S100B, neurogranin, neurofilament light (NfL) and tau were analysed in CSF and, in addition, NfL, GFAP and S100B levels were measured in serum. The Jonckheere-Terpstra test was used for group comparisons of continuous variables and Spearman's partial correlation test was used to adjust for age. RESULTS: Cerebrospinal fluid and serum concentrations of GFAP and NfL correlated with disease severity, independent of age, and with the presence of nerve paralysis. The markers neurogranin, YKL-40, tau and S100B in CSF and S100B in serum were detected, but their concentrations did not correlate with disease severity. CONCLUSIONS: Neuronal cell damage and astroglial cell activation with increased NfL and GFAP in CSF and serum were associated with a more severe disease, independent of age. Increased GFAP and NfL concentrations in CSF and NfL in serum were also indicative of spinal and/or cranial nerve damage. NfL and GFAP are promising prognostic biomarkers in tick-borne encephalitis, and future studies should focus on determining the association between these biomarkers and long-term sequelae.


Asunto(s)
Lesiones Encefálicas , Encefalitis Transmitida por Garrapatas , Humanos , Proteína 1 Similar a Quitinasa-3 , Lituania , Suecia , Proteína Ácida Fibrilar de la Glía/líquido cefalorraquídeo , Filamentos Intermedios , Neurogranina , Biomarcadores , Encéfalo , Gravedad del Paciente , Proteínas de Neurofilamentos
3.
Eur J Clin Microbiol Infect Dis ; 42(5): 597-605, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36940049

RESUMEN

In 2015, an outbreak caused by OXA-48-producing Enterobacteriaceae affected a neonatal intensive care unit at a Swedish University Hospital. The aim was to explore the transmission of OXA-48-producing strains between infants and the transfer of resistance plasmids between strains during the outbreak. Twenty-four outbreak isolates from ten suspected cases were whole-genome sequenced. A complete assembly was created for the index isolate (Enterobacter cloacae) and used as a mapping reference to detect its plasmids in the remaining isolates (17 Klebsiella pneumoniae, 4 Klebsiella aerogenes, and 2 Escherichia coli). Strain typing was performed using core genome MLST and SNP analysis. As judged from sequencing and clinical epidemiological data, the outbreak involved nine cases (two developed sepsis) and four OXA-48-producing strains: E. cloacae ST1584 (index case), K. pneumoniae ST25 (eight cases), K. aerogenes ST93 (two cases), and E. coli ST453 (2 cases). Two plasmids from the index strain, pEclA2 and pEclA4, carrying blaOXA48 and blaCMY-4, respectively, were traced to all K. pneumoniae ST25 isolates. Klebsiella aerogenes ST93 and E. coli ST453 harboured either only pEclA2, or both pEclA2 and pEclA4. One suspected case harbouring OXA-162-producing K. pneumoniae ST37 could be excluded from the outbreak. Once initiated by an E. cloacae strain, the outbreak was caused by the dissemination of a K. pneumoniae ST25 strain and involved inter-species horizontal transfer of two resistance plasmids, one of which carried blaOXA-48. To our knowledge, this is the first description of an outbreak of OXA-48-producing Enterobacteriaceae in a neonatal setting in northern Europe.


Asunto(s)
Enterobacteriaceae , Infecciones por Klebsiella , Lactante , Recién Nacido , Humanos , Escherichia coli/genética , Suecia/epidemiología , Unidades de Cuidado Intensivo Neonatal , Tipificación de Secuencias Multilocus , beta-Lactamasas/genética , Klebsiella pneumoniae/genética , Enterobacter cloacae/genética , Plásmidos/genética , Brotes de Enfermedades , Infecciones por Klebsiella/epidemiología , Infecciones por Klebsiella/microbiología
4.
Emerg Infect Dis ; 28(2): 314-322, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-35075997

RESUMEN

In recent decades, the incidence of tick-borne encephalitis (TBE) in Sweden has increased. To calculate the burden of disease over a 17-year period, we analyzed data from the Swedish National Health Data Register for TBE cases diagnosed during 1998-2014. We compared healthcare use and sick leave associated with 2,429 persons with TBE with a referent cohort of 7,287 persons without TBE. Patients with TBE were hospitalized for significantly more days during the first year after disease onset (11.5 vs. 1.1 days), logged more specialist outpatient visits (3.6 vs. 1.2 visits), and logged more sick leave days (66 vs. 10.7 days). These differences generally increased over time. The case-fatality rate for TBE was 1.1%. Our calculated cost of TBE to society provides a baseline for decisions on immunization programs. Analyzing register data, our study adds to clinical studies of smaller cohorts and model-based studies that calculate disease burden.


Asunto(s)
Virus de la Encefalitis Transmitidos por Garrapatas , Encefalitis Transmitida por Garrapatas , Humanos , Suecia/epidemiología
5.
BMC Pediatr ; 20(1): 531, 2020 11 20.
Artículo en Inglés | MEDLINE | ID: mdl-33218324

RESUMEN

BACKGROUND: Early-onset sepsis (EOS) is a potentially life-threatening complication of birth. Clinical symptoms are often unspecific and biomarkers have low predictive values for EOS. Therefore, clinical suspicion often leads to antibiotic therapy in neonates with a negative blood culture. In the study we evaluated if a quality improvement initiative could reduce unwarranted antibiotic use in a safe way in term neonates with culture-negative sepsis. METHODS: The quality improvement initiative included new treatment guidelines and were introduced on 11 June 2018. The guidelines included C-reactive protein- and clinical symptoms-guided decision-making and shorter intravenous antibiotic therapy. All term neonates treated for EOS at Ryhov Hospital, Jönköping, Sweden were studied before (period 1: 2016-2017) and after the introduction of the new guidelines (period 2: 11 June 2018 to 30 Sept 2019). Laboratory and clinical data were analysed. RESULTS: There were 7618 term neonates in period 1 and 5005 term neonates in period 2. We identified 140 (1.8%) EOS in period 1 and 97 (1.9%) EOS in period 2. During period 1 and 2, there were 61 (61/140, 44%) and 59 (59/97, 61%) EOS neonates, respectively, who met the criteria for shorter antibiotic treatment. The number of positive blood cultures were seven (0.92/1000 live births) and five (1.0/1000 live births) in period 1 and 2. The median C-reactive protein were 52 mg/L (37-62) in period 1 and 42 mg/L (31-56) in period 2 in the group who met the criteria of the guidelines. The duration of antibiotic therapy (Median: seven vs. five days, p < 0.001) and hospital stay (Median: seven vs. five days, p < 0.001) as well as healthcare costs (decreased by €122,000/year) was reduced in the group who met the criteria after the introduction of the guidelines. CONCLUSION: C-reactive protein- and clinical symptoms-guided decision-making for EOS significantly decreased the duration of antibiotic therapy and hospital stay, and hence reduced healthcare costs, with no reinfection in a cohort of term infants. TRIAL REGISTRATION: Trial registration number: ISRCTN29535824 . Date of registration: 28 May 2020. Retrospectively registered.


Asunto(s)
Proteína C-Reactiva , Sepsis , Antibacterianos/uso terapéutico , Humanos , Recién Nacido , Tiempo de Internación , Mejoramiento de la Calidad , Sepsis/diagnóstico , Sepsis/tratamiento farmacológico , Suecia
6.
J Antimicrob Chemother ; 74(12): 3565-3572, 2019 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-31504577

RESUMEN

BACKGROUND: Aciclovir is effective in herpesvirus infections of the CNS. Aciclovir-induced neuropsychiatric symptoms (AINS) have been reported and are associated with high CSF concentrations of aciclovir metabolite 9-carboxymethoxymethylguanine (CMMG). Risk factors except for renal failure have not been explored, and disruption of the blood-brain barrier (BBB) in acute CNS infection may be of interest. OBJECTIVES: To investigate the impact of risk factors on aciclovir and CMMG concentrations, and to relate the results to AINS. METHODS: We investigated 21 consecutively included, consenting patients treated with aciclovir or valaciclovir for herpesvirus CNS infection. Regression models were constructed to study the impact of risk factors including BBB disruption, as measured with CSF:serum albumin ratio, on CSF aciclovir and CMMG concentrations. Medical records were assessed retrospectively to identify patients with AINS. RESULTS: Increased CSF:serum albumin ratio, as well as decreased renal function and high aciclovir doses, was associated with increased aciclovir and CMMG concentrations in the CSF. We identified five patients with new neuropsychiatric symptoms; four of those were considered to have AINS and had increased CSF CMMG concentrations. Only one patient without suspicion of AINS had an increased CSF CMMG concentration. CONCLUSIONS: In patients with herpesvirus CNS infections, BBB disruption is associated with increasing aciclovir and CMMG CSF concentrations. We also found an unexpectedly high number of patients with AINS. Evaluation of CSF:serum albumin ratios, renal function and CSF concentrations of aciclovir and CMMG may all contribute to the optimization of aciclovir dosing and avoidance of AINS.


Asunto(s)
Aciclovir/efectos adversos , Antivirales/efectos adversos , Enfermedades del Sistema Nervioso Central/inducido químicamente , Infecciones por Herpesviridae/tratamiento farmacológico , Aciclovir/líquido cefalorraquídeo , Adulto , Anciano , Antivirales/líquido cefalorraquídeo , Barrera Hematoencefálica/efectos de los fármacos , Femenino , Guanina/análogos & derivados , Guanina/sangre , Guanina/líquido cefalorraquídeo , Infecciones por Herpesviridae/líquido cefalorraquídeo , Humanos , Masculino , Trastornos Mentales/inducido químicamente , Persona de Mediana Edad , Estudios Prospectivos , Estudios Retrospectivos , Factores de Riesgo
7.
J Neurovirol ; 25(3): 397-404, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30850976

RESUMEN

Tick-borne encephalitis (TBE) is one of the most prevalent viral central nervous system (CNS) infections in Eurasia and neurological sequelae are common. The immune responses are considered crucial for the pathogenesis. The aim of this study was to explore the activation of the complement system in TBE. The complement system is a part of the innate immune response in the CNS, which previously has been reported to be activated in other flavivirus infections. We analyzed complement factors in 44 paired cerebrospinal fluid (CSF) and serum samples from 20 cases of TBE in the acute and later stages, as well as in serum and CSF from 32 healthy controls. The concentrations of complement factors C1q, C3a, C3b, and C5a were determined with commercially available ELISA kits. Clinical data to categorize the severity of disease and outcome was retrieved from the medical records of the TBE patients. We found significantly higher concentrations of all of the analyzed complement factors in the CSF from TBE patients compared to the healthy controls. In particular, the marked increment of C1q concentrations in the CSF (p < 0,001 as compared to controls) indicated an intrathecal activation by the classical pathway. There was no correlation between complement factor concentrations in the CSF and severity of the disease in the acute phase or with sequelae at 6 months follow-up. We have found an intrathecal complement activation in TBE, and the marked increase of complement factor C1q indicated an activation by the classical pathway.


Asunto(s)
Activación de Complemento/inmunología , Encefalitis Transmitida por Garrapatas/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Encefalitis Transmitida por Garrapatas/líquido cefalorraquídeo , Femenino , Humanos , Masculino , Persona de Mediana Edad
8.
Euro Surveill ; 24(17)2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31039835

RESUMEN

In an outbreak of measles in Gothenburg, Sweden, breakthrough infections (i.e. infections in individuals with a history of vaccination) were common. The objective of this study was to compare measles RNA levels between naïve (i.e. primary) and breakthrough infections. We also propose a fast provisional classification of breakthrough infections. Medical records were reviewed and real-time PCR-positive samples genotyped. Cases were classified as naïve, breakthrough or vaccine infections. We compared clinical symptoms and measles RNA cycle threshold (Ct) values between breakthrough and naïve infections. Sixteen of 28 confirmed cases of measles in this outbreak were breakthrough infections. A fast provisional classification, based on previous history of measles vaccination and detectable levels of measles IgG in acute serum, correctly identified 14 of the 16 breakthrough infections, confirmed by IgG avidity testing. Measles viral load was significantly lower in nasopharyngeal samples from individuals with breakthrough compared with naïve infections (median Ct-values: 32 and 19, respectively, p < 0.0001). No onward transmission from breakthrough infections was identified. Our results indicate that a high risk of onward transmission is limited to naïve infections. We propose a fast provisional classification of breakthrough measles that can guide contact tracing in outbreak settings.


Asunto(s)
Anticuerpos Antivirales/sangre , Brotes de Enfermedades , Inmunoglobulina G/sangre , Virus del Sarampión/genética , Virus del Sarampión/inmunología , Sarampión/diagnóstico , Sarampión/inmunología , Adolescente , Adulto , Niño , Preescolar , Femenino , Genotipo , Humanos , Inmunoglobulina M/sangre , Lactante , Recién Nacido , Masculino , Sarampión/sangre , Sarampión/epidemiología , Vacuna Antisarampión/inmunología , Virus del Sarampión/aislamiento & purificación , Persona de Mediana Edad , Nasofaringe/virología , Reacción en Cadena en Tiempo Real de la Polimerasa , Pruebas Serológicas , Suecia/epidemiología , Población Urbana , Vacunación , Carga Viral , Adulto Joven
9.
Emerg Infect Dis ; 24(6): 978-987, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29775178

RESUMEN

Nosocomial transmission of Lassa virus (LASV) is reported to be low when care for the index patient includes proper barrier nursing methods. We investigated whether asymptomatic LASV infection occurred in healthcare workers who used standard barrier nursing methods during the first 15 days of caring for a patient with Lassa fever in Sweden. Of 76 persons who were defined as having been potentially exposed to LASV, 53 provided blood samples for detection of LASV IgG. These persons also responded to a detailed questionnaire to evaluate exposure to different body fluids from the index patient. LASV-specific IgG was not detected in any of the 53 persons. Five of 53 persons had not been using proper barrier nursing methods. Our results strengthen the argument for a low risk of secondary transmission of LASV in humans when standard barrier nursing methods are used and the patient has only mild symptoms.


Asunto(s)
Enfermedades Transmisibles Importadas/epidemiología , Enfermedades Transmisibles Importadas/virología , Infección Hospitalaria/epidemiología , Infección Hospitalaria/virología , Fiebre de Lassa/epidemiología , Fiebre de Lassa/virología , Atención de Enfermería , Adulto , Anciano , Enfermedades Transmisibles Importadas/transmisión , Infección Hospitalaria/transmisión , Femenino , Personal de Salud , Humanos , Fiebre de Lassa/transmisión , Virus Lassa/clasificación , Virus Lassa/genética , Virus Lassa/inmunología , Masculino , Persona de Mediana Edad , Atención de Enfermería/métodos , Vigilancia de Guardia , Suecia/epidemiología
10.
J Neurovirol ; 24(6): 702-711, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30094629

RESUMEN

Herpes simplex encephalitis (HSE) is a common cause of viral encephalitis (HSV-1) characterised by pronounced inflammation and elevated intracranial pressure. We have shown in a rat model that HSV-1 infection causes an interaction between complement factors and proteasomes, leading to formation of proteasome/complement complexes (compleasomes). Exposure of the proteasome regulatory subunit antisecretory factor 1 (AF1) leads to a decrease in intracranial pressure. The aim of this study was to evaluate the acute and prolonged formation of compleasomes in cerebrospinal fluid (CSF) from patients with HSE. Cerebrospinal fluid samples (n = 55) from 24 HSE patients were analysed for compleasome complexes. Samples from healthy controls (n = 23) and patient controls (n = 27) served as baseline information. Sandwich enzyme-linked immunosorbent assay (ELISA) for proteasomes and their complex formation with complement factor 3 or 4, and Western blot for C3 activation were performed on CSF samples. Increased compleasome formation, both presenting as an initial formation and showing exposure of subunit AF1 in the compleasomes, was found in CSF samples drawn from patients with HSE compared with samples from the control groups (p < 0.0005). The total protein CSF concentration was equal in all groups. The levels were higher in the acute phase compared with late in the disease course (p < 0.0005). Complement 3 breakdown product iC3b was detected in CSF samples of the HSE patients. The early increased formation of compleasomes in CSF suggests that this complex may be involved in host defence against HSE.


Asunto(s)
Proteínas del Sistema Complemento/líquido cefalorraquídeo , Encefalitis por Herpes Simple/líquido cefalorraquídeo , Complejo de la Endopetidasa Proteasomal/líquido cefalorraquídeo , Adulto , Anciano , Anciano de 80 o más Años , Proteínas del Sistema Complemento/inmunología , Encefalitis por Herpes Simple/inmunología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Complejo de la Endopetidasa Proteasomal/inmunología
11.
Eur J Clin Microbiol Infect Dis ; 37(2): 339-344, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-29188467

RESUMEN

We set out to investigate the serological response of TBE virus (TBEV)-specific IgM and IgG antibodies in stored serum and cerebrospinal fluid (CSF) in notified TBE patients, in order to confirm or reject the diagnosis. We applied the ELISA methods used in clinical practice, Enzygnost and Immunozym, and assessed RT-PCR as a diagnostic tool. A total of 173 TBE cases were notified to the Public Health Agency. Samples from 129 patients were eligible for the study. Stored serum samples were found for 111 patients and CSF samples for 88 patients. All serum samples were analyzed with both Enzygnost and Immunozym, as well as an additional 140 control samples. CSF samples, including samples from ten controls, were analyzed with Immunozym. RT-PCR for TBEV was performed on 126 serum, two whole blood, 96 CSF, two feces and four nasopharynx samples. Only two of 111 notified patients lacked detectable TBEV IgM in serum, from whom one sample was RT-PCR positive. According to the ECDC definition, 117/129 (90.7%) of the reported TBE cases were confirmed. Positive RT-PCR results were obtained in eight patients, one from whole blood and eight from serum samples. Four out of eight of the RT-PCR positive patients were TBEV-IgM positive and none had detectable TBEV-specific IgG. All of the tested CSF, feces and nasopharynx samples were RT-PCR-negative. TBEV-specific IgG was detected in 88.4% and IgM in 31.6% of the CSF samples. RT-PCR on serum samples and CSF IgG antibodies can be used as complementary methods in TBE diagnostics, not least early in the disease course.


Asunto(s)
Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/líquido cefalorraquídeo , Virus de la Encefalitis Transmitidos por Garrapatas/inmunología , Encefalitis Transmitida por Garrapatas/diagnóstico , Adolescente , Adulto , Anciano , Anticuerpos Antivirales/inmunología , Virus de la Encefalitis Transmitidos por Garrapatas/aislamiento & purificación , Encefalitis Transmitida por Garrapatas/virología , Ensayo de Inmunoadsorción Enzimática/métodos , Femenino , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/líquido cefalorraquídeo , Inmunoglobulina G/inmunología , Inmunoglobulina M/sangre , Inmunoglobulina M/líquido cefalorraquídeo , Inmunoglobulina M/inmunología , Masculino , Persona de Mediana Edad , Suecia , Adulto Joven
12.
J Neuroinflammation ; 14(1): 134, 2017 07 10.
Artículo en Inglés | MEDLINE | ID: mdl-28693588

RESUMEN

BACKGROUND: The closely related herpes simplex viruses 1 and 2 can cause inflammations of the central nervous system (CNS), where type 1 most often manifest as encephalitis (HSE), and type 2 as meningitis (HSM). HSE is associated with severe neurological complications, while HSM is benign in adults. We proposed that studying the chemokine and cytokine production in cerebrospinal fluid (CSF) and serum could indicate why two closely related viruses exhibit different severity of their accompanied CNS inflammation. METHODS: Secretion patterns of 30 chemokines and 10 cytokines in CSF of adult patients with acute HSE (n = 14) and HSM (n = 20) in the initial stage of disease were analyzed and compared to control subjects without viral central nervous system infections and to levels in serum. RESULTS: Most measured chemokines and cytokines increased in CSF of HSE and HSM patients. Overall, the CSF chemokine levels were higher in CSF of HSM patients compared to HSE patients. However, only five chemokines reached levels in the CSF that exceeded those in serum facilitating a positive CSF-serum chemokine gradient. Of these, CXCL8, CXCL9, and CXCL10 were present at high levels both in HSE and HSM whereas CXCL11 and CCL8 were present in HSM alone. Several chemokines were also elevated in serum of HSE patients but only one in HSM patients. No chemokine in- or efflux between CSF and serum was indicated as the levels of chemokines in CSF and serum did not correlate. CONCLUSIONS: We show that HSM is associated with a stronger and more diverse inflammatory response in the CNS compared to HSE in the initial stage of disease. The chemokine patterns were distinguished by the exclusive local CNS production of CXCL11 and CCL8 in HSM. Inflammation in HSM appears to be restricted to the CNS whereas HSE also was associated with systemic inflammation.


Asunto(s)
Quimiocina CXCL11/líquido cefalorraquídeo , Encefalitis por Herpes Simple/líquido cefalorraquídeo , Herpesvirus Humano 1/aislamiento & purificación , Herpesvirus Humano 2/aislamiento & purificación , Meningitis Viral/líquido cefalorraquídeo , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/líquido cefalorraquídeo , Quimiocina CCL8/líquido cefalorraquídeo , Encefalitis por Herpes Simple/diagnóstico , Femenino , Humanos , Masculino , Meningitis Viral/diagnóstico , Persona de Mediana Edad , Adulto Joven
13.
Eur J Neurosci ; 44(11): 2944-2949, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27643680

RESUMEN

Reactivation of varicella zoster virus (VZV) can manifest with facial palsy diagnosed as Ramsay Hunt Syndrome (RHS) or Ramsay Hunt Syndrome zoster sine herpete (RHS-ZSH). These syndromes are associated with poor prognosis despite treatment with antivirals and corticosteroids. Concentrations of biomarkers such as neurofilament protein (NFL), S-100ß protein and glial fibrillary acidic protein (GFAp) have previously been measured in cerebrospinal fluid (CSF) to assess neuronal damage and glial pathology. We employed immunochemical methods to measure concentrations of NFL, S-100ß protein and GFAp in CSF from patients with RHS (n = 15) and RHS-ZSH (n = 13) diagnosed by detection of VZV DNA in the CSF by quantitative PCR, and compared with a control group (n = 52). The biomarker concentrations were correlated with CSF viral load and outcome measured by House-Brackmann score. NFL and GFAp concentrations were increased compared with controls (P = 0.008 and P = 0.04), while S-100ß levels were decreased. This pattern was more pronounced in patients with RHS compared to the patients with RHS-ZSH (NS and P = 0.028). The amount of viral DNA in CSF correlated with increased GFAp (P = 0.003) and NFL (P = 0.006). No correlations were found between biomarker concentrations and patient outcome. Patients with facial palsy caused by VZV had biochemical signs of neuronal damage and astrogliosis. High amounts of viral DNA may be associated with the degree of damage on neuronal and astroglial cells. Prospective studies are warranted to elucidate the association of elevated biomarkers in the CSF and outcome assessed by more sensitive tests.


Asunto(s)
ADN Viral/líquido cefalorraquídeo , Proteína Ácida Fibrilar de la Glía/líquido cefalorraquídeo , Herpes Zóster Ótico/líquido cefalorraquídeo , Proteínas de Neurofilamentos/líquido cefalorraquídeo , Subunidad beta de la Proteína de Unión al Calcio S100/líquido cefalorraquídeo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/líquido cefalorraquídeo , Estudios de Casos y Controles , Femenino , Herpes Zóster Ótico/patología , Humanos , Masculino , Persona de Mediana Edad , Neuroglía/metabolismo , Neuronas/metabolismo
14.
J Virol ; 89(14): 7133-46, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25926648

RESUMEN

UNLABELLED: Varicella-zoster virus (VZV) is a human herpesvirus, which during primary infection typically causes varicella (chicken pox) and establishes lifelong latency in sensory and autonomic ganglia. Later in life, the virus may reactivate to cause herpes zoster (HZ; also known as shingles). To prevent these diseases, a live-attenuated heterogeneous vaccine preparation, vOka, is used routinely in many countries worldwide. Recent studies of another alphaherpes virus, infectious laryngotracheitis virus, demonstrate that live-attenuated vaccine strains can recombine in vivo, creating virulent progeny. These findings raised concerns about using attenuated herpesvirus vaccines under conditions that favor recombination. To investigate whether VZV may undergo recombination, which is a prerequisite for VZV vaccination to create such conditions, we here analyzed 115 complete VZV genomes. Our results demonstrate that recombination occurs frequently for VZV. It thus seems that VZV is fully capable of recombination if given the opportunity, which may have important implications for continued VZV vaccination. Although no interclade vaccine wild-type recombinant strains were found, intraclade recombinants were frequently detected in clade 2, which harbors the vaccine strains, suggesting that the vaccine strains have already been involved in recombination events, either in vivo or in vitro during passages in cell culture. Finally, previous partial and complete genomic studies have described strains that do not cluster phylogenetically to any of the five established clades. The additional VZV strains sequenced here, in combination with those previously published, have enabled us to formally define a novel sixth VZV clade. IMPORTANCE: Although genetic recombination has been demonstrated to frequently occur for other human alphaherpesviruses, herpes simplex viruses 1 and 2, only a few ancient and isolated recent recombination events have hitherto been demonstrated for VZV. In the present study, we demonstrate that VZV also frequently undergoes genetic recombination, including strains belonging to the clade containing the vOKA strain.


Asunto(s)
Herpesvirus Humano 3/genética , Recombinación Genética , Adulto , Niño , Preescolar , Análisis por Conglomerados , ADN Viral/química , ADN Viral/genética , Variación Genética , Genoma Viral , Herpesvirus Humano 3/aislamiento & purificación , Humanos , Datos de Secuencia Molecular , Filogenia , Análisis de Secuencia de ADN , Homología de Secuencia
15.
Clin Infect Dis ; 61(5): 683-91, 2015 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-25956891

RESUMEN

BACKGROUND: Despite the proven efficacy of acyclovir (ACV) therapy, herpes simplex encephalitis (HSE) continues to cause substantial morbidity and mortality. Among patients with HSE treated with ACV, the mortality rate is approximately 14%-19%. Among survivors, 45%-60% have neuropsychological sequelae at 1 year. Thus, improving therapeutic approaches to HSE remains a high priority. METHODS: Following completion of a standard course of intravenous ACV, 87 adult patients with HSE (confirmed by positive polymerase chain reaction [PCR] for herpes simplex virus DNA in cerebrospinal fluid) were randomized to receive either valacyclovir (VACV) 2 g thrice daily (n = 40) or placebo tablets (n = 47) for 90 days (12 tablets of study medication daily). The primary endpoint was survival with no or mild neuropsychological impairment at 12 months, as measured by the Mattis Dementia Rating Scale (MDRS). Logistic regression was utilized to assess factors related to the primary endpoint. RESULTS: The demographic characteristics of the 2 randomization groups were statistically similar with no significant differences in age, sex, or race. At 12 months, there was no significant difference in the MDRS scoring for VACV-treated vs placebo recipients, with 85.7% and 90.2%, respectively, of patients demonstrating no or mild neuropsychological impairment (P = .72). No significant study-related adverse events were encountered in either treatment group. CONCLUSIONS: Following standard treatment with intravenous ACV for PCR-confirmed HSE, an additional 3-month course of oral VACV therapy did not provide added benefit as measured by neuropsychological testing 12 months later in a population of relatively high-functioning survivors. CLINICAL TRIALS REGISTRATION: NCT00031486.


Asunto(s)
Aciclovir/análogos & derivados , Antivirales/uso terapéutico , Encefalitis por Herpes Simple/tratamiento farmacológico , Encefalitis por Herpes Simple/epidemiología , Valina/análogos & derivados , Aciclovir/administración & dosificación , Aciclovir/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antivirales/administración & dosificación , Trastornos del Conocimiento , Encefalitis por Herpes Simple/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Valaciclovir , Valina/administración & dosificación , Valina/uso terapéutico , Adulto Joven
16.
Transpl Int ; 27(2): 197-203, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24289658

RESUMEN

We investigated the antibody persistence in solid organ transplant (SOT) recipients 1 year after immunization with two doses of monovalent AS03-adjuvanted influenza A(H1N1)pdm09 vaccine. We also assessed the boosting effect of the seasonal trivalent inactivated vaccine 2010 (TIV/10) that contained the influenza A(H1N1)pdm09 strain. A total of 49 SOT recipients and 11 healthy controls were included. After a blood sample was obtained to assess the persistent immunity, one dose of TIV/10 was administered and another blood sample was collected 1 month after vaccination. A(H1N1)pdm09 antibodies were measured using a haemagglutination inhibition assay. The percentage of SOT recipients with protective titres decreased between 1 month and 10-14 months after the monovalent influenza A(H1N1)pdm09 vaccination, from 79% (n = 38) to 47% (n = 23) (P = 0.02). The corresponding numbers for the control group were 100% and 63%, respectively (P = 0.008). After the TIV/10 boosting dose, the number of SOT recipients with protective titres increased from 47% (n = 23) to 71% (n = 35) (P = 0.2). All the controls reached a protective titre level. The median titre rise was significantly higher among controls when compared to SOT recipients (P = 0.0036). No rejection or adverse events were seen. The results show an obvious need for vaccine boosting doses in the SOT patients.


Asunto(s)
Anticuerpos Antivirales/sangre , Vacunas contra la Influenza/inmunología , Gripe Humana/prevención & control , Trasplante de Órganos , Adyuvantes Inmunológicos/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Formación de Anticuerpos , Estudios de Casos y Controles , Femenino , Pruebas de Inhibición de Hemaglutinación , Humanos , Huésped Inmunocomprometido , Subtipo H1N1 del Virus de la Influenza A , Vacunas contra la Influenza/uso terapéutico , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios , Resultado del Tratamiento , Vacunación/métodos
18.
Open Forum Infect Dis ; 11(5): ofae268, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38813262

RESUMEN

Background: Human parechovirus (HPeV) infections can cause sepsis and meningoencephalitis in infants. To improve our knowledge of the consequences of HPeV infections in young children, the incidence, clinical spectrum, and short-term outcome among infants infected with HPeV were investigated retrospectively. Methods: The presence of HPeV RNA was investigated by polymerase chain reaction in cerebrospinal fluid from 327 children aged 0 to 12 months sampled between 2014 and 2017. Eighty-one were infected with HPeV and included in the study. These infants were divided into 3 groups based on clinical assessment: HPeV was the presumed cause of disease (n = 35); HPeV could have contributed to or been considered the cause of disease (n = 24); and HPeV was not considered the cause of disease (n = 22). Results: Infection with HPeV type 3 was common in all groups (n = 54), and most children were younger than 3 months (n = 63). The children in the first group (HPeV as presumed cause) had meningoencephalitis (n = 20), viral sepsis (n = 9), or non-severe viral infection (n = 6). The youngest were more prone to develop meningoencephalitis, while the slightly older children had symptoms of viral sepsis or nonsevere viral infection (P < .05). Eleven had symptom onset within 2 days after birth. Two infants diagnosed with sudden infant death syndrome were HPeV infected when tested postmortem. Conclusions: HPeV infections were identified in 25% of children with suspected central nervous system infection. The clinical presentation of those infected with HPeV varied with age. HPeV infections may be associated with sudden infant death syndrome, although this is not well studied. The results suggest that HPeV infections may be underdiagnosed in young infants.

19.
JAMA Netw Open ; 7(3): e243362, 2024 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-38517437

RESUMEN

Importance: Antibiotic treatment saves lives in newborns with early-onset sepsis (EOS), but unwarranted antibiotic use is associated with resistant bacteria and adverse outcomes later in life. Surveillance is needed to optimize treatment strategies. Objective: To describe antibiotic use in association with the incidence and mortality from EOS among late-preterm and full-term newborns. Design, Setting, and Participants: The Sweden Neonatal Antibiotic Use study was a nationwide observational study that included all late-preterm and full-term neonates born from January 1, 2012, to December 31, 2020, in neonatal units of all levels. All hospital live births from 34 weeks' gestation during the study period were included in the study. Data were collected from the Swedish Neonatal Quality Register and the Swedish Medical Birth Register. Data were analyzed from August 2022 to May 2023. Exposure: Admission for neonatal intensive care during the first week of life. Main Outcomes and Measures: The main outcomes were the usage of intravenous antibiotics during the first week of life, the duration of antibiotic therapy, the rate of culture-proven EOS, and mortality associated with EOS. Results: A total of 1 025 515 newborns were included in the study; 19 286 neonates (1.88%; 7686 girls [39.9%]; median [IQR] gestational age, 40 [38-41] weeks; median [IQR] birth weight, 3610 [3140-4030] g) received antibiotics during the first week of life, of whom 647 (3.4%) had EOS. The median (IQR) duration of antibiotic treatment in newborns without EOS was 5 (3-7) days, and there were 113 antibiotic-days per 1000 live births. During the study period there was no significant change in the exposure to neonatal antibiotics or antibiotic-days per 1000 live births. The incidence of EOS was 0.63 per 1000 live births, with a significant decrease from 0.74 in 2012 to 0.34 in 2020. Mortality associated with EOS was 1.39% (9 of 647 newborns) and did not change significantly over time. For each newborn with EOS, antibiotic treatment was initiated in 29 newborns and 173 antibiotic-days were dispensed. Conclusions and Relevance: This large nationwide study found that a relatively low exposure to antibiotics is not associated with an increased risk of EOS or associated mortality. Still, future efforts to reduce unwarranted neonatal antibiotic use are needed.


Asunto(s)
Antibacterianos , Sepsis , Femenino , Humanos , Recién Nacido , Antibacterianos/uso terapéutico , Peso al Nacer , Edad Gestacional , Incidencia , Sepsis/etiología , Masculino
20.
Infect Dis (Lond) ; 56(9): 732-742, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38709658

RESUMEN

BACKGROUND: The aim of this study was to characterise long-term neurological and neurocognitive sequelae after tick-borne encephalitis (TBE) in adults. METHODS: 98 prospective consecutive TBE patients, classified by disease severity, were included. Immediate outcomes were evaluated with Glasgow Outcome Scale (GOS) and Rankin Scale (RS). After 6 and 18 months, long-term disability was evaluated using Modified Rankin Scale (MRS) and neurocognitive assessment was performed with Matrics Consensus Cognitive Battery (MCCB), measuring processing speed, attention/vigilance, working memory, verbal learning, visual learning, reasoning/problem solving and social cognition. The MCCB results were compared to healthy age, gender and education-matched controls. RESULTS: Mild, moderate, and severe TBE was diagnosed in 53.1%, 38.8%, and 8.2% of cases, respectively. At discharge, 25.5% of the patients had major or moderate impairments (GOS) and various levels of disability in 34.7% (RS). Up to 18 months from the onset of TBE, over 20% remained with slight to moderate disability (MRS). GOS, RS and MRS scores correlated with disease severity. At 6 months after the onset, TBE patients scored significantly lower than controls in processing speed, verbal, and visual learning. Two latter domains were significantly more impaired in patients with mild TBE. Patients aged 18-39 performed significantly worse in attention/vigilance and working memory, whereas aged 60+ in verbal learning. A year later, significant improvement was observed in six of seven cognitive domains. CONCLUSIONS: Long-term neurological sequelae persist in a substantial proportion of TBE patients with significant impairment in several cognitive domains, especially in younger patients and even after mild TBE.


Asunto(s)
Encefalitis Transmitida por Garrapatas , Humanos , Encefalitis Transmitida por Garrapatas/complicaciones , Masculino , Femenino , Estudios Prospectivos , Persona de Mediana Edad , Adulto , Lituania/epidemiología , Anciano , Disfunción Cognitiva/etiología , Disfunción Cognitiva/fisiopatología , Adulto Joven , Pruebas Neuropsicológicas , Adolescente , Índice de Severidad de la Enfermedad , Enfermedades del Sistema Nervioso/complicaciones , Enfermedades del Sistema Nervioso/etiología
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