RESUMEN
BACKGROUND: Human parainfluenza viruses (hPIV) are respiratory pathogens responsible for upper and lower respiratory tract infections. In most labs, the clinical diagnosis of hPIV is routinely done using techniques based on the detection of viral antigens such as immunofluorescence assay or/and viral isolation. STUDY DESIGN: Five hPIV-2 isolated from respiratory samples exhibited unusual phenotypic and antigenic characteristics. These isolates showed important syncytial cytopathic effect and failed to react with one specific monoclonal antibody. These variant strains were subsequently compared with hPIV-2 prototype strain by cellular and molecular techniques. RESULTS: Both variant and prototype strains showed similar growth kinetics. Observation of plaque formation and syncytia assay indicated a more important fusogenic activity for the variant strains. Sequencing of fusion (F) and hemagglutinin-neuraminidase (HN) genes showed differences between the "atypical" hPIV-2 isolates and the Greer hPIV-2 prototype strain. These differences were analyzed with molecular modelling and structure prediction soft wares. A potential new glycosylation site in HN, in addition to minor changes observed in the predicted structure for the variant strains could explain their antigenic variation. Genetic changes in the fusion peptide and the cleavage site of F could also explain the difference observed in the fusion activity. CONCLUSIONS: Continuous global viral surveillance is essential to monitor antigenic changes that may occur in nature particularly with regards to the implementation of diagnostic assays. The differences observed in F and HN between the prototype strain and clinical hPIV-2 variants could also provide new data for the analysis of Paramyxovirus fusion mechanisms and their pathogenesis.
Asunto(s)
Proteína HN/genética , Virus de la Parainfluenza 2 Humana/fisiología , ARN Viral , Infecciones por Rubulavirus/virología , Proteínas Virales de Fusión/genética , Adulto , Secuencia de Aminoácidos , Animales , Variación Antigénica , Línea Celular , Niño , Glicosilación , Proteína HN/química , Proteína HN/inmunología , Haplorrinos , Humanos , Modelos Moleculares , Datos de Secuencia Molecular , Virus de la Parainfluenza 2 Humana/clasificación , Virus de la Parainfluenza 2 Humana/genética , Virus de la Parainfluenza 2 Humana/aislamiento & purificación , Filogenia , Conformación Proteica , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Proteínas Virales de Fusión/química , Proteínas Virales de Fusión/inmunología , Ensayo de Placa ViralRESUMEN
Herpes simplex virus resistant to acyclovir (ACV) is a major concern among immunocompromised patients. ACV resistance might be due to mutations located in one of the two genes involved in ACV mechanism of action, the thymidine kinase gene (TK, involved in 95% of the cases) and the DNA polymerase gene. TK gene mutations consist, in half of the cases, in nucleotide insertion or deletion, occurring most of the time in G or C homopolymers considered as hot spots. Half of the other cases involves nucleotide substitutions leading to amino acids substitutions. Studies of sensitive strains revealed a high degree of TK polymorphism, many mutations being not implied in ACV resistance. At the present time, resistance detection can be performed by phenotypic tests that require virus culture and results cannot be given to the physician before 7 to 10 days. Genotyping diagnosis performed directly from clinical samples would allow to detect resistance more rapidly, in order to switch quickly to an appropriate treatment by foscarnet or cidofovir.
Asunto(s)
Aciclovir/farmacología , Infecciones por Herpesviridae/tratamiento farmacológico , Simplexvirus/efectos de los fármacos , Simplexvirus/genética , Sustitución de Aminoácidos , ADN Polimerasa Dirigida por ADN/genética , Farmacorresistencia Viral , Genotipo , Humanos , Inmunidad Innata/genética , Mutación , Reacción en Cadena de la Polimerasa , Simplexvirus/enzimología , Timidina Quinasa/genéticaRESUMEN
Herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) are members of the Herpesviridae family. HSV infections have been known since ancient times and are one of the most common communicable diseases in humans. Although infections are often subclinical, HSV can cause mild to severe diseases, especially in immunocompromised patients. Herpes simplex viruses establish latency in the nuclei of neuronal cells and may reactivate, with or without symptoms, throughout the host's lifetime. Over one third of the world's population suffer from recurrent HSV infections several times a year and are thus capable of transmitting HSV by close personal contact. There are few drugs licensed for the treatment of HSV infections. Most target the viral DNA polymerase, and indeed acyclovir remains the reference treatment some thirty years after its discovery! Extensive clinical use of this drug has led to the emergence of resistant viral strains, mainly in immunocompromised patients. This highlights the crucial need for the development of new anti-herpes drugs that can inhibit infection by both wild-type viruses and drug-resistant strains. Over the last few years, significant efforts have been made to set up a range of strategies for the identification of potential new anti-viral drugs. One alternative is to develop drugs with different mechanisms of action. The present article reviews potential viral and cellular targets that are now known to be involved in HSV infection and for which specific inhibitors with anti-HSV activity, at least in cell culture, have been identified.
Asunto(s)
Antivirales/farmacología , Sistemas de Liberación de Medicamentos , Diseño de Fármacos , Herpes Simple/tratamiento farmacológico , Aciclovir/uso terapéutico , Antivirales/uso terapéutico , ADN Polimerasa Dirigida por ADN/efectos de los fármacos , Farmacorresistencia Viral , Herpesvirus Humano 1/efectos de los fármacos , Herpesvirus Humano 2/efectos de los fármacos , Humanos , Huésped Inmunocomprometido , Neuronas , Latencia del VirusRESUMEN
Although infections are often subclinical, herpes simplex virus (HSV) can cause mild to severe diseases, especially in immunocompromised patients. There are few drugs licensed for the treatment of HSV infections. Most target the viral DNA polymerase, such as acyclovir that remains the reference treatment some thirty years after its discovery! Extensive clinical use of this drug has led to the emergence of resistant strains, mainly in immunocompromised patients, these infections can be managed with only two drugs, foscarnet and cidofovir, both much more toxic than acyclovir. This highlights the crucial need for the development of new anti-herpes drugs that can inhibit infection by both wild-type viruses and drug-resistant strains. Over the last few years, significant efforts have been made to set up a range of strategies for the identification of potential new antiviral drugs. One alternative is to develop drugs with different mechanisms of action. The present article reviews potential viral and cellular targets that are now known to be involved in HSV multiplication and for which specific inhibitors with anti-HSV activity, at least in cell culture, have been identified. These drugs inhibit viral proteins involved in viral replication (DNA polymerase, ribonucleotide reductase or helicase-primase complex). Other drugs acting on cellular proteins needed for viral replication have also been described; these drugs are targetting cyclin-dependent kinases or the polyamine biosynthetic pathway.
RESUMEN
Mutations in the thymidine kinase (TK) gene of herpes simplex virus (HSV) may confer resistance to acyclovir (ACV). Because of the high genetic polymorphism of this gene, discriminating between mutations related to resistance and mutations related to gene polymorphism can be difficult, especially when no sensitive strain has been previously isolated from the same patient. To assess the role of the mutations located at codons 51, 77, 83, and 175, previously detected in HSV-1 clinical isolates (F. Morfin, G. Souillet, K. Bilger, T. Ooka, M. Aymard, and D. Thouvenot, J. Infect. Dis. 182:290-293, 2000), in the acquisition of resistance to ACV, four mutants with site-directed mutations at these respective codons were constructed. The enzymatic activity of the proteins, produced using both a reticulocyte lysate system and a bacterial system, was evaluated using [(3)H]thymidine as substrate. This site-directed mutagenesis revealed that mutations at codons 51, 83, and 175 induce a loss of HSV-1 TK activity and are thus clearly involved in the acquisition of resistance to ACV. On the other hand, the mutation at codon 77 does not affect enzyme activity.
Asunto(s)
Aciclovir/farmacología , Antivirales/farmacología , Mutación , Simplexvirus/efectos de los fármacos , Simplexvirus/enzimología , Timidina Quinasa/genética , Farmacorresistencia Viral , Mutagénesis Sitio-Dirigida , Timidina Quinasa/biosíntesisAsunto(s)
Infecciones por Adenovirus Humanos/inmunología , Infecciones por Adenovirus Humanos/patología , Neumonía Viral/inmunología , Neumonía Viral/patología , Infecciones por Adenovirus Humanos/tratamiento farmacológico , Adulto , Resultado Fatal , Humanos , Inmunocompetencia , Masculino , Neumonía Viral/tratamiento farmacológicoRESUMEN
OBJECTIVE: We carried out a retrospective analysis of an outbreak of adenovirus (AdV) infections in a paediatric unit. The aim of the study was to analyse cases, determine the route of transmission and to evaluate the efficacy of the prevention measures. PATIENTS AND METHODS: The study was performed by recollection of AdV infection cases during a period of 1 year and the results were compared with the list of clinical cases recorded during the epidemic. The clinical files of children with a positive specimen were retrospectively analysed. During that period, five members of the medical staff showed clinical signs and symptoms of AdV infection. A throat swab was collected from a subset of the staff. RESULTS: Among nine patients with positive AdV detection, six were infected with an Adv type 2. Six were nosocomially-acquired, the other two were only probable nosocomial infections. The index case was a child presenting a febrile diarrhoea 48 h prior to being admitted to the hospital. Nosocomial transmission was associated with the prolonged shedding of the virus with faeces of the infected cases. The specimens collected from the staff remained negative. The outcome was favourable for all children. CONCLUSIONS: Prevention measures, implemented when the epidemic was characterised, allowed the control of the nosocomial outbreak.
Asunto(s)
Infecciones por Adenovirus Humanos/epidemiología , Infecciones por Adenovirus Humanos/prevención & control , Infección Hospitalaria/virología , Adolescente , Niño , Preescolar , Infección Hospitalaria/epidemiología , Infección Hospitalaria/prevención & control , Diarrea/etiología , Diarrea/virología , Brotes de Enfermedades , Femenino , Fiebre , Francia/epidemiología , Humanos , Recién Nacido , Masculino , Reproducibilidad de los Resultados , Estudios RetrospectivosRESUMEN
Herpes simplex virus (HSV) infections are very common in the general population and among immunocompromised patients. Acyclovir (ACV) is an effective treatment which is widely used. We deemed it essential to conduct a wide and coordinated survey of the emergence of ACV-resistant HSV strains. We have formed a network of 15 virology laboratories which have isolated and identified, between May 1999 and April 2002, HSV type 1 (HSV-1) and HSV-2 strains among hospitalized subjects. The sensitivity of each isolate to ACV was evaluated by a colorimetric test (C. Danve, F. Morfin, D. Thouvenot, and M. Aymard, J. Virol. Methods 105:207-217, 2002). During this study, 3900 isolated strains among 3357 patients were collected; 55% of the patients were immunocompetent. Only six immunocompetent patients excreted ACV-resistant HSV strains (0.32%), including one female patient not treated with ACV who was infected primary by an ACV-resistant strain. Among the 54 immunocompromised patients from whom ACV-resistant HSV strains were isolated (3.5%), the bone marrow transplantation patients showed the highest prevalence of resistance (10.9%), whereas among patients infected by human immunodeficiency virus, the prevalence was 4.2%. In 38% of the cases, the patients who excreted the ACV-resistant strains were treated with foscarnet (PFA), and 61% of them developed resistance to PFA. The collection of a large number of isolates enabled an evaluation of the prevalence of resistance of HSV strains to antiviral drugs to be made. This prevalence has remained stable over the last 10 years, as much among immunocompetent patients as among immunocompromised patients.
Asunto(s)
Aciclovir/farmacología , Antivirales/farmacología , Simplexvirus/efectos de los fármacos , Adulto , Anciano , Anciano de 80 o más Años , Animales , Trasplante de Médula Ósea , Chlorocebus aethiops , Farmacorresistencia Viral , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trasplante de Órganos , Células VeroRESUMEN
During the year 2000 in the Rhône-Alpes region of France, 559 cases of aseptic meningitis due to enterovirus infection were recorded (approximate incidence, 10 cases per 100,000 population compared with a mean of 0.3 cases during endemic years in this region; P<0.001). Cerebrospinal fluid samples were collected from all 559 patients and processed for enterovirus RNA detection using a reverse transcriptase polymerase chain reaction assay only. In addition to the cerebrospinal fluid samples, 40 stool and 76 throat samples were collected from 116 patients (20.7% of cases); the following three enterovirus serotypes were isolated from the stool and throat samples only: ECHOvirus 13 (48/116; 41.3%), ECHOvirus 30 (44/116;37.9%) and ECHOvirus 6 (24/116, 20.7%). This is the first report that demonstrates the involvement of three different ECHOvirus serotypes, particularly ECHOvirus 13, in an outbreak of aseptic meningitis, in the French Rhône-Alpes region.
Asunto(s)
Brotes de Enfermedades , Enterovirus Humano B/clasificación , Infecciones por Enterovirus/epidemiología , Meningitis Aséptica/epidemiología , Adolescente , Adulto , Preescolar , Enterovirus Humano B/genética , Enterovirus Humano B/aislamiento & purificación , Infecciones por Enterovirus/virología , Heces/virología , Femenino , Francia/epidemiología , Humanos , Lactante , Masculino , Meningitis Aséptica/virología , Persona de Mediana Edad , Faringe/virología , ARN Viral/líquido cefalorraquídeo , SerotipificaciónRESUMEN
Herpes simplex virus (HSV) and varicella zoster virus (VZV) are susceptible to acyclovir which inhibits viral replication through two viral enzymes, thymidine kinase (TK) and DNA polymerase. Resistance may occur, it is a rare phenomenon among immunocompetent patients but resistance is more frequent and may be associated with serious complications among immunocompromised patients. Virological survey of these at risk patients is needed to detect resistant virus as soon as possible through phenotypic tests performed on virus isolated on cell cultures. Resistant virus may also be genetically characterised by detection of mutations within TK and DNA polymerase genes. Pharmacological parameters also have to be taken into consideration and a determination of acyclovir blood concentration should be performed in case of unexplained therapeutic failure. Improvement of immune system, when possible, may resolve these infections. Alternative treatments using drugs such as foscarnet or cidofovir which have a different mechanism of action compared to acyclovir, are recommended but these molecules are often more toxic than acyclovir.
Asunto(s)
Aciclovir/farmacología , Antivirales/farmacología , Farmacorresistencia Viral , Herpesvirus Humano 3/efectos de los fármacos , Simplexvirus/efectos de los fármacos , Varicela/tratamiento farmacológico , Herpes Simple/tratamiento farmacológico , Herpes Zóster/tratamiento farmacológico , Herpesvirus Humano 3/genética , Humanos , Mutación , Fenotipo , Simplexvirus/genéticaRESUMEN
Herpes simplex virus (HSV) infections are very common and may present various manifestations. Mostly asymptomatic, often mild, these infections may become life-threatening, specially in neonates. The acute and rapid diagnosis of HSV infections can prevent infections in these patients and is also helpful to confirm clinical diagnosis. The sensitivity of "classical" diagnosis methods, such as culture and antigen detection by immunofluorescence and ELISA, is highly dependent on the quality of the sample. Antigen detection techniques give results in short delays, compatible with the initiation of antiviral treatment; however their sensitivity decreases when lesions get older and they are not convenient for the diagnosis of asymptomatic infections. Isolation of HSV on cell culture remains the gold standard, because it is easy to perform and exhibits good sensitivity whatever the stage of the lesions; the isolation of the virus is required for HSV typing and to determine susceptibility to antiviral agents in case of clinical resistance to the treatment. Serodiagnosis is helpful to determine the immune status of a patient and to distinguish between primary infection and recurrence. It is now possible to differentiate HSV1 and HSV2 antibodies; the benefit of type-specific serology is clear for epidemiological surveys but may be discussed for individual follow-up, specially for genital herpes, both for the diagnosis and the prevention of HSV infections.
Asunto(s)
Herpes Genital/diagnóstico , Herpes Simple/diagnóstico , Ensayo de Inmunoadsorción Enzimática , Técnica del Anticuerpo Fluorescente/métodos , Herpesvirus Humano 1 , Herpesvirus Humano 2 , Humanos , Inmunocompetencia , Sensibilidad y EspecificidadRESUMEN
Two competitive immunoassays, a laboratory assay based on microwell plates and a field test based on the use of polystyrene tubes, have been developed for the quantification of thiram in lettuces. Concerning the laboratory assay, the calibration curve for thiram had a linear range of 11 to 90 ng/mL and a detection limit of 5 ng/mL. Precision of the assay presented coefficient of variation values <9% and the recovery of thiram from lettuce averaged 89% across the range of the immunoassay method using 30 min extraction with water/acetone (50:50, v/v). The tube-based method was developed in order that an extract of lettuce, containing thiram at the MRL (8 ppm), would be found on the linear part of the standard curve. The calibration curve for thiram has a linear range of 100 to 800 ng/mL (1.39 to 11.1 ppm in lettuce) and a detection limit of 40 ng/mL.
Asunto(s)
Fungicidas Industriales/análisis , Lactuca/química , Residuos de Plaguicidas/análisis , Tiram/análisis , Ensayo de Inmunoadsorción Enzimática/métodos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Tiram/inmunología , Factores de TiempoRESUMEN
Human cytomegalovirus (HCMV) infections are frequent in immuno-compromised patients. The recent development of real-time PCR procedures that allow the rapid quantification of genome load will be helpful for accurate monitoring of these infections. Two extraction procedures were evaluated using 30 blood samples that were processed pure and diluted (1/10). Repeatability and reproducibility of the quantitative PCR procedure using an internal control for amplification were analysed, and its sensitivity compared to a qualitative PCR procedure using 50 HCMV culture positive blood samples. The real-time PCR and qualitative PCR procedures were positive in 46 and 48 of the samples tested, respectively. Discrepancies were observed for samples with a low viral load. The sensitivity of the real-time PCR procedure was evaluated at 500 HCMV DNA copies per ml of sera. The use of an internal control concomitantly processed during the HCMV quantification did not alter the sensitivity of the procedure, and was relevant for the detection of putative PCR inhibitors that may interfere with the amplification process. This procedure was used to measure genome load in two bone marrow transplant patients with HCMV disease, confirming that this new PCR procedure should be used widely for diagnosing and monitoring HCMV infections in transplant patients.
Asunto(s)
Infecciones por Citomegalovirus/virología , Citomegalovirus/aislamiento & purificación , Reacción en Cadena de la Polimerasa/métodos , Trasplante de Médula Ósea , Citomegalovirus/genética , ADN Viral/análisis , Humanos , Trasplante de Hígado , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Carga ViralRESUMEN
"Sapporo-like viruses" (SLVs) and "Norwalk-like viruses" (NLVs) are an important cause of acute gastroenteritis in humans. While NLVs have been genetically classified into three major genetic groups consisting of 17 genetic subgroups, a classification of SLVs into comparable genetic groups remains to be determined. In an attempt to classify both SLVs and NLVs uniformly, the sequences of 2 SLV strains newly detected from French infants were analysed together with the published sequences of 9 SLV and 19 NLV strains. Distance and phylogenetic analyses were conducted on the sequences of the capsid gene, RNA polymerase gene, 3' open reading frame (3'ORF), ORF overlapping the capsid gene, and 3' untranslated region (3'UTR). The histogram showing frequency distribution of pairwise distances and the topology of the phylogenetic tree demonstrated that SLVs and NLVs could be classified uniformly on the basis of the entire capsid sequences and that the 11 SLV strains could be genetically classified into 3 major genetic groups, genogroups I, II and III, comprised of 5 genetic subgroups. The differentiation of the 11 SLV strains into these genetic groups was also maintained in the 4 remaining genome regions, while the sequences at the junction between the RNA polymerase and capsid genes were shown to be genogroup-specific.
Asunto(s)
Sapovirus/clasificación , Regiones no Traducidas 3'/química , Secuencia de Bases , Cápside/genética , Niño , ARN Polimerasas Dirigidas por ADN/química , ARN Polimerasas Dirigidas por ADN/genética , Humanos , Datos de Secuencia Molecular , Norovirus/clasificación , Norovirus/genética , Sistemas de Lectura Abierta , Filogenia , Sapovirus/genética , Alineación de SecuenciaRESUMEN
Fourteen cases of severe acyclovir-resistant herpes simplex virus type 1 (HSV-1) infection, 7 of which showed resistance to foscarnet, were diagnosed among 196 allogeneic stem cell transplant recipients within a 29-month period. Recipients of unrelated stem cell transplants were at higher risk. All patients received foscarnet; 8 subsequently received cidofovir. Strains were initially foscarnet-resistant in 3 patients and secondarily so in 4 patients. In vitro resistance to acyclovir or foscarnet was associated with clinical failure of these drugs; however, in vitro susceptibility to foscarnet was associated with complete response in only 5 of 7 patients. No strain from any of the 7 patients was resistant in vitro to cidofovir; however, only 3 of 7 patients achieved complete response. Therefore, acyclovir- and/or foscarnet-resistant HSV-1 infections after allogeneic stem cell transplantation have become a concern; current strategies need to be reassessed and new strategies must be evaluated in this setting.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/efectos adversos , Herpes Simple/tratamiento farmacológico , Herpes Simple/etiología , Organofosfonatos , Aciclovir/uso terapéutico , Adolescente , Adulto , Antivirales/uso terapéutico , Niño , Cidofovir , Citosina/análogos & derivados , Citosina/uso terapéutico , Farmacorresistencia Microbiana , Femenino , Foscarnet/uso terapéutico , Herpes Simple/virología , Herpesvirus Humano 1/efectos de los fármacos , Herpesvirus Humano 1/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Compuestos Organofosforados/uso terapéutico , Trasplante HomólogoRESUMEN
An enzyme-linked immunosorbent assay (ELISA) was developed for the fungicide thiram. Two types of haptens were synthesized. The first type exhibits the two symmetrical N-alkyl dithiocarbamate patterns of thiram with a spacer arm linked to one of the N-methyl terminal group. The second type exhibits one of the two symmetrical N-alkyl dithiocarbamate patterns of thiram with a variable-length spacer arm linked to one sulfur atom. Polyclonal antibodies suitable for thiram detection were obtained from immunization with an hapten of the first type, while haptens of the second type were used as coating antigens to develop a competitive ELISA against thiram. The IC(50) value for thiram was estimated to be 0.24 microg/mL, with a detection limit of 0.03 microg/mL. The assay seems to be thiram-specific since no or little cross-reaction with other dithiocarbamates were observed.
Asunto(s)
Fungicidas Industriales/análisis , Haptenos/química , Tiram/análisis , Unión Competitiva , Ensayo de Inmunoadsorción EnzimáticaRESUMEN
HSV infections are treated efficiently and prevented by acyclovir, although resistant strains have been reported. Resistance to acyclovir involves mainly mutations in the viral gene encoding thymidine kinase; mutations may lead to an altered or, more frequently, deficient TK. These acyclovir-resistant TK deficient strains are not able to reactivate from a latent infection in an experimental model, compared to TK positive strains. A case is reported of a bone marrow transplant child who developed HSV infection at 11 days post-transplantation. Acyclovir-resistant HSV 1 was isolated on day 19 post-transplantation. The patient was cured of his infection. A resistant virus was detected 20 months later that harboured the same TK gene mutation as the first resistant virus. This mutation is an insertion of one guanine in a homopolymer repeat of seven guanines located at codon 146 of TK. It has previously been reported and associated with the expression of a deficient TK activity and the ability to reactivate in mice. These results corroborate the clinical relevance of this mutation, which is associated with acyclovir-resistant recurrent infections in humans.
Asunto(s)
Aciclovir/farmacología , Antivirales/farmacología , Trasplante de Médula Ósea/efectos adversos , Herpes Simple/virología , Herpesvirus Humano 1/fisiología , Timidina Quinasa/genética , Niño , Farmacorresistencia Microbiana , Herpes Simple/diagnóstico , Herpesvirus Humano 1/efectos de los fármacos , Herpesvirus Humano 1/enzimología , Herpesvirus Humano 1/genética , Humanos , Masculino , Mutación , Timidina Quinasa/metabolismo , Activación ViralRESUMEN
Herpes simplex viruses (HSV) are responsible for neurological disorders that require rapid diagnostic methods and specific antiviral therapy. During 1997, 1431 cerebrospinal fluid samples (CSF) collected from 1339 patients with neurological disorder presentations were processed for HSV detection. Eleven patients were positive for HSV, seven presenting with encephalitis (6/7 due to HSV1) and 4 with aseptic meningitis (4/4 due to HSV2). The incidence of HSV encephalitis was 2.33 cases / 10(6) inhabitants/year. Among encephalitis (HSV encephalitis) cases, 1 patient died due to the late implementation of antiviral therapy, and sequelae were observed in 4 cases. No sequelae were observed in aseptic meningitis cases. Four HSV encephalitis cases were monitored by PCR detection in CSF. Despite acyclovir therapy, PCR remained positive in CSF up to 20 days in 2 cases. This result suggest that the antiviral treatment for HSV encephalitis should be monitored by PCR detection of HSV in CSF.
Asunto(s)
Infecciones del Sistema Nervioso Central/virología , Herpes Simple/virología , Herpesvirus Humano 1/aislamiento & purificación , Herpesvirus Humano 2/aislamiento & purificación , Aciclovir/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antivirales/uso terapéutico , Infecciones del Sistema Nervioso Central/tratamiento farmacológico , Líquido Cefalorraquídeo/virología , Niño , Preescolar , ADN Viral/líquido cefalorraquídeo , Encefalitis/epidemiología , Encefalitis/virología , Femenino , Estudios de Seguimiento , Francia/epidemiología , Herpes Simple/tratamiento farmacológico , Herpesvirus Humano 1/genética , Herpesvirus Humano 2/genética , Humanos , Incidencia , Lactante , Masculino , Meningitis Aséptica/epidemiología , Meningitis Aséptica/virología , Persona de Mediana Edad , Reacción en Cadena de la PolimerasaRESUMEN
Emergence of acyclovir (Acy)-resistant herpes simplex virus (HSV) is a major concern in bone marrow transplant recipients. Phenotypic and genetic characterization of thymidine kinase (TK) was done for 7 Acy-susceptible and 11 Acy-resistant HSV-1 isolated from 11 patients. In total, 19 amino acid substitutions were detected that were not related to Acy resistance but to TK gene polymorphism, including 5 mutations that have not been previously reported. The Acy-resistant strain from 1 patient presented no TK gene mutation related to resistance. Five patients (45%) had isolates that harbored point mutations leading to amino acid substitutions that could be associated with Acy resistance. Of the 5 substitutions detected, 3 have not been previously reported (codons 51, 83, and 175). A nucleotide insertion or deletion was detected in resistant isolates from 5 patients (45%); these mutations are located in homopolymer repeats at codon 92 (1 subject) and at codon 146 (4 subjects).