RESUMEN
BACKGROUND AND PURPOSE: This case illustrates for the first time the clinical and radiological evolution of SARS-CoV-2 meningo-encephalitis. METHODS: A case of a SARS-CoV-2 meningo-encephalitis is reported. RESULTS: A 65-year-old man with COVID-19 presenting with meningo-encephalitis without respiratory involvement is described. He had fever, diarrhea and vomiting, followed by diplopia, urinary retention and sleepiness. Examination disclosed a convergence strabismus and ataxia. Cerebrospinal fluid (CSF) showed lymphocytic pleocytosis, oligoclonal bands and increased interleukin 6 level. SARS-CoV-2 was detected in the CSF through reverse transcriptase polymerase chain reaction, but not in nasopharyngeal, tracheal secretion and rectal samples. Brain magnetic resonance imaging showed lesions on white matter hemispheres, the body and splenium of the corpus callosum and resembling the projection of corticospinal tract, remarkably on cerebellar peduncles. CONCLUSIONS: This demonstrates the challenges in diagnosing COVID-19 in patients with neurological presentations.
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COVID-19 , Encefalitis , Anciano , Cuerpo Calloso , Humanos , Imagen por Resonancia Magnética , Masculino , SARS-CoV-2RESUMEN
BACKGROUND: Haemophilus influenzae (Hi) serotype b (Hib) conjugate vaccine was incorporated into the infant immunisation schedule in Brazil in 1999, where Hib was one of the major etiologic sources of community-acquired bacterial meningitis. OBJECTIVES: The purpose of this study is to describe the molecular epidemiology of invasive Hi disease in Rio de Janeiro state, Brazil, before and after vaccine introduction. METHODS: Surveillance data from 1986 to 2014 were analysed. Hi isolates recovered from cerebrospinal fluid (CSF) or blood from 1993 to 2014 were serotyped by slide agglutination, genotyped by multilocus sequence typing (MLST), and the capsule type evaluation, differentiation of serologically non-typeable isolates, and characterisation of the capsule (cap) locus was done by polymerase chain reaction. Antimicrobial susceptibility testing was performed using E-test. FINDINGS: From 1986 to 1999 and from 2000 to 2014, 2580 and 197 (42% without serotype information) confirmed cases were reported, respectively. The case fatality rate was 17% and did not correlate with the strain. Hib and b- variant isolates belonged to ST-6, whereas serotype a isolates belonged to the ST-23 clonal complex. Serotype a appeared to emerge during the 2000s. Non-encapsulated isolates were non-clonal and distinct from the encapsulated isolates. Ampicillin-resistant isolates were either of serotype b or were non-encapsulated, and all of them were ß-lactamase-positive but amoxicillin-clavulanic acid susceptible. MAIN CONCLUSIONS: Although Hi meningitis became a relatively rare disease in Rio de Janeiro after the introduction of the Hib conjugate vaccine, the isolates recovered from patients have become more diverse. These results indicate the need to implement an enhanced surveillance system to continue monitoring the impact of the Hib conjugate vaccine.
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Cápsulas Bacterianas , Infecciones por Haemophilus/epidemiología , Vacunas contra Haemophilus , Haemophilus influenzae/genética , Antibacterianos/farmacología , Brasil/epidemiología , Genotipo , Infecciones por Haemophilus/microbiología , Haemophilus influenzae/efectos de los fármacos , Haemophilus influenzae/inmunología , Haemophilus influenzae/aislamiento & purificación , Humanos , Programas de Inmunización , Meningitis por Haemophilus/epidemiología , Meningitis por Haemophilus/microbiologíaRESUMEN
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: * There is large interindividual variability in the pharmacokinetics of protease inhibitors (PIs) among human immunodeficiency virus (HIV)-infected individuals under highly active antiretroviral therapy. * Protease inhibitor have been recently reported to be substrates of the SLCO1B1/OATP1 drug transporter. * A single nucleotide polymorphism (SNP) in the SLCO1B1 gene (521T-->C) was associated with plasma levels of lopinavir in HIV-infected individuals. WHAT THIS STUDY ADDS: * Data on the impact of three SLCO1B1 SNPs (521T-->C, 388A-->G, 463C-->A) on the trough plasma concentration of lopinavir and ritonavir in a cohort of 99 adult HIV-infected Brazilian men under stable highly active antiretroviral therapy. * Evidence that carriers of the 521C allele display significantly higher lopinavir, but not ritonavir plasma concentrations relative to the wild-type TT genotype. * No effect of either 388A-->G or 463C-->A SNPs on lopinavir or ritonavir plasma concentrations. * Further studies are required to confirm the clinical significance of the association between the SLCO1B1521T-->C polymorphism and lopinavir pharmacokinetics. AIMS: To investigate possible associations between three SLCO1B1 single nucleotide polymorphisms (388A-->G, 463C-->A, 521T-->C) and lopinavir/ritonavir plasma concentrations. METHODS: The study included 99 human immunodeficiency virus-infected men on stable highly active antiretroviral therapy containing lopinavir/ritonavir. Trough concentrations of lopinavir and ritonavir in plasma were quantified using liquid chromatography-tandem mass spectrometry. Genotyping of SLCO1B1388A-->G, 463C-->A and 521T-->C polymorphisms was performed by allelic discrimination using real-time polymerase chain reaction. RESULTS: The trough concentration of lopinavir in plasma is significantly associated with SLCO1B1521T-->C genotypes (P= 0.03). There is a significant trend for increasing concentrations of lopinavir from TT to TC to CC genotypes (P= 0.02). Carriers of the 521C allele display significantly higher lopinavir plasma concentrations relative to the wild-type TT genotype (P= 0.03). CONCLUSIONS: Reduced uptake of lopinavir by hepatocytes in carriers of the 521C allele may account for these results, but further studies to confirm the clinical importance of SLCO1B1 polymorphisms in lopinavir pharmacokinetics are warranted.
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Fármacos Anti-VIH/sangre , Infecciones por VIH/sangre , Transportadores de Anión Orgánico/genética , Polimorfismo de Nucleótido Simple , Pirimidinonas/sangre , Ritonavir/sangre , Adulto , Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa , Cromatografía Liquida , Frecuencia de los Genes , Genotipo , Infecciones por VIH/tratamiento farmacológico , Humanos , Transportador 1 de Anión Orgánico Específico del Hígado , Lopinavir , Masculino , Reacción en Cadena de la Polimerasa/métodos , Pirimidinonas/uso terapéutico , Ritonavir/uso terapéutico , Espectrometría de Masas en TándemRESUMEN
Clinical investigators are increasing their use of quantitative determinations of HIV viral load in their study populations. The distributions of these measures may be highly skewed, left-censored, and with an extra spike below the detection limit of the assay. We recommended use of a mixture model in this situation, with two sets of explanatory covariates. We extend this model to incorporate multiple measures across time, and to employ shared parameters as a way of increasing model efficiency and parsimony. Data from a cohort of HIV-infected men are used to illustrate these features, and simulations are performed to assess the utility of shared parameters.
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Infecciones por VIH/virología , VIH-1/aislamiento & purificación , Modelos Estadísticos , ARN Viral/sangre , Carga Viral/estadística & datos numéricos , Brasil , Estudios de Cohortes , VIH-1/genética , Humanos , Masculino , Semen/virologíaRESUMEN
BACKGROUND Haemophilus influenzae (Hi) serotype b (Hib) conjugate vaccine was incorporated into the infant immunisation schedule in Brazil in 1999, where Hib was one of the major etiologic sources of community-acquired bacterial meningitis. OBJECTIVES The purpose of this study is to describe the molecular epidemiology of invasive Hi disease in Rio de Janeiro state, Brazil, before and after vaccine introduction. METHODS Surveillance data from 1986 to 2014 were analysed. Hi isolates recovered from cerebrospinal fluid (CSF) or blood from 1993 to 2014 were serotyped by slide agglutination, genotyped by multilocus sequence typing (MLST), and the capsule type evaluation, differentiation of serologically non-typeable isolates, and characterisation of the capsule (cap) locus was done by polymerase chain reaction. Antimicrobial susceptibility testing was performed using E-test. FINDINGS From 1986 to 1999 and from 2000 to 2014, 2580 and 197 (42% without serotype information) confirmed cases were reported, respectively. The case fatality rate was 17% and did not correlate with the strain. Hib and b- variant isolates belonged to ST-6, whereas serotype a isolates belonged to the ST-23 clonal complex. Serotype a appeared to emerge during the 2000s. Non-encapsulated isolates were non-clonal and distinct from the encapsulated isolates. Ampicillin-resistant isolates were either of serotype b or were non-encapsulated, and all of them were β-lactamase-positive but amoxicillin-clavulanic acid susceptible. MAIN CONCLUSIONS Although Hi meningitis became a relatively rare disease in Rio de Janeiro after the introduction of the Hib conjugate vaccine, the isolates recovered from patients have become more diverse. These results indicate the need to implement an enhanced surveillance system to continue monitoring the impact of the Hib conjugate vaccine.
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Humanos , Haemophilus influenzae/efectos de los fármacos , Infecciones por Haemophilus/microbiología , Infecciones por Haemophilus/epidemiología , Antibacterianos/farmacología , Brasil/epidemiología , Cápsulas Bacterianas , Vacunas contra Haemophilus , GenotipoRESUMEN
We evaluated replication-defective poxvirus vectors (modified vaccinia Ankara [MVA] and fowlpox [FPV]) in a homologous and heterologous vector prime-boost vaccination regimen containing matching HIV inserts (MVA-HIV and FPV-HIV) given at months 0, 1, 3, 5 and 7 in 150 healthy HIV-negative vaccinia-naïve participants. FPV-HIV alone was poorly immunogenic, while the high dose (10(9)pfu/2 ml) of MVA-HIV alone elicited maximal responses after two injections: CD4+ and CD8+ T-cell responses in 26/55 (47.3%) and 5/60 (8.3%) of participants, respectively, and IFN-γ ELISpot responses in 28/62 (45.2%). The infrequent CD8+ T-cell responses following MVA-HIV priming were boosted only by the heterologous (FPV-HIV) construct in 14/27 (51.9%) of participants post 4th vaccination. Alternatively, HIV envelope-specific binding antibodies were demonstrated in approximately two-thirds of recipients of the homologous boosting regimen, but in less than 20% of subjects after the heterologous vector boost. Thus, a heterologous poxvirus vector prime-boost regimen can induce HIV-specific CD8+ T-cell and CD4+ T-cell responses, which may be an important feature of an optimal regimen for preventive HIV vaccination.
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Vacunas contra el SIDA/inmunología , Portadores de Fármacos , Virus de la Viruela de las Aves de Corral/genética , Vectores Genéticos , Infecciones por VIH/prevención & control , VIH-1/inmunología , Virus Vaccinia/genética , Vacunas contra el SIDA/genética , Adolescente , Adulto , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Femenino , Anticuerpos Anti-VIH/sangre , VIH-1/genética , Humanos , Inmunización Secundaria/métodos , Masculino , Factores de Tiempo , Vacunación/métodos , Adulto JovenRESUMEN
The authors present a fatal case of spotted fever group rickettsiosis (SFGR) caused by Rickettsia conorii conorii mimicking a hemorrhagic viral fever in a South African male on a business trip in Brazil. SFGR was confirmed by molecular and immunohistochemical analyses.
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Fiebre Botonosa/diagnóstico , Fiebres Hemorrágicas Virales/diagnóstico , Rickettsia conorii/aislamiento & purificación , Viaje , Brasil , ADN Viral/genética , Diagnóstico Diferencial , Resultado Fatal , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Rickettsia conorii/genética , Análisis de Secuencia de ADN , SudáfricaRESUMEN
INTRODUCTION: Lopinavir and ritonavir are frequently included in highly active antiretroviral therapy (HAART) regimens for HIV infection. These drugs are substrates, and may also inhibit and/or induce the P-glycoprotein (ABCB1) transporter, encoded by the polymorphic ABCB1 gene. We investigated the impact of three common exonic ABCB1 polymorphisms on the concentrations of lopinavir and ritonavir in blood, semen and saliva of HIV-infected men under stable HAART containing ritonavir-boosted lopinavir. MATERIALS & METHODS: Blood, semen and saliva samples were collected from 113 subjects, 30-35 minutes before the scheduled morning dose of lopinavir/ritonavir, and trough drug concentrations were measured using LC/MS/MS. The 1236C>T, 2677G>T/A and 3435C>T polymorphisms were genotyped using the single base extension-termination method and ABCB1 haplotypes were statistically inferred. RESULTS: Median (25th-75th percentile) trough concentrations (ng/ml) of lopinavir in plasma, semen and saliva were 6326 (4070-8617), 286.0 (128.4-475.5) and 72.7 (38.0-119.6), respectively. The corresponding concentrations (ng/ml) for ritonavir were 261.8 (172.2-398.6), 17.7 (9.2-27.6) and 5.3 (3.2-9.0), respectively. Univariate and multivariate regression analysis revealed no influence of ABCB1 genotypes or haplotypes on the concentrations of lopinavir and ritonavir in plasma, semen and saliva of HIV-infected men under stable HAART treatment. CONCLUSION: The ABCB1 1236C>T, 2667G>T/A and 3435C>T genotypes and haplotypes are not predictors of lopinavir and ritonavir concentrations in blood plasma, semen or saliva of HIV-infected men under stable HAART treatment. The concentrations of lopinavir and ritonavir in saliva are not reliable predictors of the concentration of these drugs in semen.
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Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa , Infecciones por VIH/tratamiento farmacológico , Polimorfismo Genético , Polimorfismo de Nucleótido Simple , Pirimidinonas/metabolismo , Ritonavir/metabolismo , Saliva/metabolismo , Semen/metabolismo , Subfamilia B de Transportador de Casetes de Unión a ATP , Adulto , Anciano , Fármacos Anti-VIH/sangre , Fármacos Anti-VIH/metabolismo , Genotipo , Infecciones por VIH/sangre , Humanos , Lopinavir , Masculino , Persona de Mediana Edad , Pirimidinonas/sangre , Pirimidinonas/uso terapéutico , Ritonavir/sangre , Ritonavir/uso terapéuticoRESUMEN
The concentrations of lopinavir and ritonavir in seminal and blood plasma and the seminal human immunodeficiency virus (HIV) viral load were quantified by HPLC and the Nuclisens assay, respectively, in a cross-sectional study of 16 HIV-1-infected Brazilian men under stable treatment with a lopinavir/ritonavir containing antiretroviral regimen. Semen and blood samples were collected on 2 occasions: at 6 to 60 minutes before ("trough"), and 5 to 6 hours after ("peak") ingestion of regular doses of lopinavir/ritonavir. Median seminal lopinavir levels were 120.6 ng/mL (range, <20-1481.8 ng/mL) and 233.1 ng/mL (range, 48.4-1133.4 ng/mL) at trough and peak points, respectively. The corresponding values for ritonavir were 9.2 ng/mL (range, <5-47 ng/mL) and 17.1 ng/mL (range, 6.6-66.7 ng/mL). The median concentrations of lopinavir and ritonavir in semen were, respectively, 1.9% to 3% and 3.7% to 4.4% of those measured in blood plasma samples collected within 30 minutes. HIV-1 viral load was detectable in the semen of 2 and in the blood of 6 of 16 patients. These results may have implications for drug-resistant HIV-1 evolution and transmission.
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Infecciones por VIH/tratamiento farmacológico , Pirimidinonas/farmacocinética , Ritonavir/farmacocinética , Sistema Urogenital/metabolismo , Disponibilidad Biológica , Brasil , Estudios Transversales , Infecciones por VIH/sangre , Infecciones por VIH/virología , Inhibidores de la Proteasa del VIH/sangre , Inhibidores de la Proteasa del VIH/farmacocinética , Inhibidores de la Proteasa del VIH/uso terapéutico , VIH-1/efectos de los fármacos , VIH-1/crecimiento & desarrollo , Humanos , Lopinavir , Masculino , Pirimidinonas/sangre , Pirimidinonas/uso terapéutico , Análisis de Regresión , Ritonavir/sangre , Ritonavir/uso terapéutico , Semen/química , Semen/efectos de los fármacos , Factores de Tiempo , Sistema Urogenital/efectos de los fármacos , Carga ViralRESUMEN
PURPOSE: Reliable predictors of HIV disease progression are scarce in developing countries, where most HIV infections occur. We describe early virologic and immunologic events among men who have sex with men in Rio de Janeiro, Brazil. METHODS: Seroconverters from 2 high-risk cohorts were followed for up to 36 months with periodic laboratory evaluations, plasma viral load, and CD4 count assessments. Viral load and CD4 count mean trajectories were computed. For the modeled viral loads, mean and median values were 24,480 (4.36 log10) and 19,720 (4.29 log10) copies/mL (range 14,880-58,090), respectively. Median CD4 count was 373 cells/microL (range 260-508). Overall variation on viral loads ranged from 4.3 to 5.2 log10 copies/mL with a visible increase in the viral load starting at approximately 600 days (n = 12) after estimated time of seroconversion. The initial period of HIV infection was characterized by an increase in CD4 count (n = 29) followed by a steep decline starting at approximately 200 days (508 cells, 95% CI: 425 to 569). A gradual decrease was observed in the median CD4 count thereafter, reaching 281 (95% CI: 100 to 466) at 1000 days after the estimated date of seroconversion. CONCLUSIONS: Although viral load dynamics resembled those observed in developed countries, CD4 counts seem to decline at a faster rate than in the Multicenter AIDS Cohort Study (MACS) cohort. Clinical and survival data are needed to assess the impact of interventions, such as antiretroviral therapy, on the clinical course of HIV infection in Brazil.
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Bisexualidad , Infecciones por VIH/inmunología , Seropositividad para VIH/inmunología , VIH-1/fisiología , Homosexualidad , Carga Viral , Adulto , Brasil , Recuento de Linfocito CD4 , Estudios de Cohortes , Infecciones por VIH/virología , Seropositividad para VIH/virología , VIH-1/genética , VIH-1/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , ARN Viral/sangreRESUMEN
CONTEXT: Long-term adherence to antiretrovirals is critical for sustained virologic response to HIV therapy in blood. Although antiretroviral therapy (ART) reduces HIV seminal shedding, little is known about the relationship between adherence to ART and HIV suppression in semen. OBJECTIVE: To determine predictors of seminal HIV RNA suppression after 6 months of ART. DESIGN: Prospective observational cohort of 93 HIV-infected subjects before and after introduction of ART. Seminal HIV RNA was measured at baseline and 1, 2, 3, and 6 months after the introduction of therapy. Adherence to therapy was measured by self-report. SETTING: A large academic HIV reference center in Rio de Janeiro, Brazil. MAIN OUTCOME MEASURE: Detectable HIV RNA in semen. RESULTS: In a multivariate logistic model with undetectable seminal HIV RNA after 6 months of therapy as the outcome variable, adjusting for baseline seminal viral load, both being adherent to therapy (OR = 11.8, < 0.01) and using triple-drug ART (OR = 6.48, = 0.04) were independently associated with seminal HIV RNA suppression. CONCLUSIONS: Inability to adhere to therapy was strongly associated with persistent shedding of HIV RNA in semen. Measures to improve adherence are urgently needed to reduce the sexual spread of potentially drug-resistant HIV among subjects using antiretrovirals.
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Antivirales/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , VIH/aislamiento & purificación , ARN Viral/aislamiento & purificación , Semen/virología , Adulto , Estudios de Cohortes , Infecciones por VIH/psicología , Infecciones por VIH/virología , Humanos , Masculino , Análisis Multivariante , Cooperación del Paciente , Factores de TiempoRESUMEN
We report the accidental needlestick inoculation of a laboratory worker with vaccinia virus. Although the patient had previously been vaccinated against smallpox, severe lesions appeared on the fingers. Western blot and polymerase chain reaction-restriction fragment length polymorphism were used to analyze the virus recovered from the lesions. The vaccinia virus-specific immunoglobulin G levels were measured by enzyme-linked immunosorbent assay. Our study supports the need for vaccination for laboratory workers that routinely handle orthopoxvirus.