Integrase strand-transfer inhibitor polymorphic and accessory resistance substitutions in patients with acute/recent HIV infection.

OBJECTIVES: The most recent guidelines suggest using integrase strand-transfer inhibitors (InSTIs) as the preferred antiretroviral regimens for naive HIV-infected individuals. However, resistance to InSTIs is not monitored in many centres at baseline. This study aimed to evaluate the prevalence of InSTI resistance substitutions in newly diagnosed patients with acute/recent HIV infection. METHODS: Genotypic drug resistance tests were performed in all consecutive patients prospectively enrolled with a documented infection of <6 months, from 12 May 2015 to 12 May 2016. Sequences were obtained by high-throughput sequencing. RESULTS: Five out of 36 consecutive patients (13.89%, 95% CI = 4.67-29.5) with acute/recent HIV infection were detected to have strains carrying InSTI polymorphisms or substitutions conferring low-level resistance to raltegravir and elvitegravir. Four patients had the 157Q polymorphism and one patient had the Q95K substitution. All cases were MSM patients infected with subtype B strains. Viral loads ranged from 2.92 to 6.95 log10 copies/mL. In all cases, the mutational viral load was high. Three patients initiated dolutegravir-based regimens and became undetectable at first viral load control. There were no major viral or epidemiological differences when compared with patients without InSTI substitutions. CONCLUSIONS: Although signature InSTI substitutions (such as Y143R/C, N155H or Q148K/R/H) were not detected, polymorphisms and substitutions conferring low-level resistance to raltegravir and elvitegravir were frequently found in a baseline genotypic test. All cases were infected with subtype B, the most frequent in Europe. In the context of primary HIV infection, virological response should be carefully monitored to evaluate the impact of these InSTI polymorphisms and substitutions.

Long-term transmission of measles virus in Central and continental Western Europe.

The World Health Organization (WHO) has adopted an elimination goal for measles and rubella, which is supposed to be met in the WHO European Region (EUR) by 2015. For verification of elimination, it is required that the genotyping data of detected measles viruses provide evidence for the interruption of endemic transmission. In order to record and assess the extent of endemic measles virus (MV) circulation in a part of the EUR, we analyzed transmission chains of the epidemiologically most relevant MV variants identified in Central and continental Western Europe (CCWE) from 2006 to 2013. Based on MV sequence data deposited in the WHO global database for molecular surveillance of measles (MeaNS), the circulation period was calculated for each MV variant at the country-level and for the entire region of CCWE. The MV variants "D5-Okinawa," "D4-Hamburg," "D4-Manchester," and "D8-Frankfurt-Main" spread widely in CCWE; they caused large and long-lasting outbreaks with secondary spread that resulted in additional outbreaks. Nation-wide outbreaks (epidemics) with thousands of measles cases occurred in four countries (Switzerland, France, Bulgaria, and Romania) and were characterized by continuous detection of the same MV variant for more than 12 months suggesting endemic transmission. In the entire region of CCWE, the circulation period of the four predominant MV variants ranged from 18 to 44 months. The long-lasting MV transmission which affected predominantly unvaccinated individuals in different hard-to-reach groups and in the general population is not consistent with the measles elimination goal. Additional efforts are necessary to meet the elimination target in the EUR.

Appearance of a novel measles G3 strain in multiple European countries within a two month period, 2010.

During late 2010, a previously unrecognised strain of measles genotype G3 virus was identified in five different European countries by the World Health Organization Measles and Rubella Laboratory Network.Apart from one, none had a travel history to south-east Asia, the usual source of G3 viruses, although epidemiological links could be established between some of the cases. This case series illustrates the value of genotyping and sequencing in tracking measles infections, and identifying otherwise unrecognised chains of transmission.

Phylogenetic analysis of rubella virus strains from an outbreak in Madrid, Spain, from 2004 to 2005.

An outbreak of rubella affected 460 individuals in 2004 and 2005 in the community of Madrid, Spain. Most of the patients were nonvaccinated Latin American immigrants or Spanish males. This study presents the first data on rubella virus genotypes in Spain. Forty selected clinical samples (2 urine, 5 serum, 3 blood, 2 saliva, and 28 pharyngeal exudate samples) from 40 cases were collected. The 739-nucleotide sequence recommended by the World Health Organization obtained from viral RNA in these samples was analyzed by using the MEGA v4.0 software. Seventeen isolates were obtained from 40 clinical samples from the outbreak, including two isolated from congenital rubella syndrome cases. Only viral RNA of genotype 1j was detected in both isolates and clinical specimens. Two variations in amino acids, G253C and T394S, which are involved in neutralization epitopes arose during the outbreak, but apparently there was no positive selection of either of them. The origin of the outbreak remains unknown because of poor virologic surveillance in Latin America and the African countries neighboring Spain. On the other hand, this is the first report of this genotype in Europe. The few published sequences of genotype 1j indicate that it comes from Japan and the Philippines, but there are no epidemiological data supporting this as the origin of the Madrid outbreak.

Seasonal influenza surveillance: Observational study on the 2017-2018 season with predominant B influenza virus circulation.

INTRODUCTION: Influenza is a common respiratory infectious disease affecting population worldwide yearly. The aim of this work is to describe the 2017-2018 influenza season and how it affected elderly population in Catalonia despite moderate vaccine coverage among this age group. METHODS: Influenza surveillance based on a primary care sentinel surveillance, virological indicators systematic sampling of ILI attended and severe influenza confirmed cases (SHLCI) admitted to hospital.Analysis of data by Chi-squared, ANOVA, multiple regression and negative control test or case to case for vaccine effectiveness assessment in primary care and SHLCI respectively. RESULTS: Moderate-high intensity and early onset season with predominance of influenza B virus (IVB) (63%) followed by an increase of circulation of influenza A virus (IVA). A total of 419 IV from primary care samples. Vaccine effectiveness (VE) in primary care setting was 14% (95%CI: 0-47%). 1306 severe cases (adjusted cumulative incidence 18.54/100,000 inhabitants (95%CI: 17.54-19.55)). The highest proportion of severe cases were in the >64 (65.1%) (aOR 15.70; 95%CI: 12.06-20.46; p < 0.001) followed by 45-64 yo (25.4%) (aOR 6.03; 95%CI: 4.57-7.97). VE in preventing intensive care unit (ICU) admission was 35% (95%CI: 10-54%). Final outcome death while hospitalized occurred in 175 SHLCI cases with a case fatality rate of 13.4%. CONCLUSIONS: 2017-2018 influenza season was an unusual epidemic season with an early onset, great predominance of influenza B (Yamagata strain) virus with a high hospitalization rate of severe cases among elderly stressing the need to upgrade vaccine uptake in this age group.

INTRODUCCIÓN: La gripe es una enfermedad infecciosa respiratoria común que afecta cada año a una proporción importante de la población mundial. El objetivo de este trabajo es describir la temporada de influenza 2017-2018 y cómo afectó a la población anciana en Cataluña a pesar de la cobertura moderada de vacunas en este grupo de edad. MÉTODOS: Vigilancia de la gripe basada en la vigilancia centinela de atención primaria (AP), indicadores virológicos por muestreo sistemático semanal de pacientes con síndrome gripal (SG) atendidos en AP y casos graves de gripe confirmada grave ingresados ??en el hospital.Las estadísticas utilizadas para el análisis fueron el test ANOVA, la prueba de Chi-cuadrado, el análisis de regresión múltiple y la prueba de control negativo y caso a caso para la evaluación de la efectividad de la vacuna (EV, por sus siglas en inglés) en AP y casos graves hospitalizados, respectivamente. RESULTADOS: La temporada 2017-2018 se caracterizó por presentar una intensidad moderadamente alta, con inicio temprano y de larga duración. El predominio del virus de la gripe B (VGB) (63%) seguido por un aumento de la circulación del virus de la gripe A (VGA). Un total de 419 IV de muestras de AP. La VE para prevención de la infección en casos con SG en AP fue del 14% (IC 95%: 0-47%). Se registraron 1.306 casos graves (incidencia acumulada ajustada 18,54/100.000 habitantes (IC 95%: 17,54-19,55)). La proporción más alta de casos graves fue en > 64 años (65,1%) (OR: 15,70: IC 95%: 12,06-20,46; p < 0,001) seguido del grupo de 45-64 años (25,4%) (OR: 6,03; IC 95%: 4,57-7,97). La VE en la prevención de ingreso en la UCI fue del 35% (IC 95%: 10-54%). Se registraron 175 defunciones con una tasa de letalidad del 13,4%. CONCLUSIONES: La temporada de gripe 2017-2018 fue una temporada epidémica inusual con un inicio temprano, gran predominio del VGB (cepa Yamagata) con una elevada tasa de hospitalización de casos graves en ancianos, lo que subraya la necesidad de mejorar la aceptación de la vacuna en este grupo de edad.

Epidemiological changes of acute/recent human immunodeficiency virus type 1 infection in Barcelona, Spain (1997-2015): a prospective cohort study.

OBJECTIVE: To describe the epidemiology of acute/recent human immunodeficiency virus (HIV) infection over two decades in Barcelona (Spain). METHODS: Prospective, single-centre cohort including all patients with an acute/recent HIV infection (<180 days) since 1997. Patients were stratified into four periods. Phylogenetic analysis was performed to determine clusters of transmission. RESULTS: A total of 346 consecutive acute/recently infected patients were included. The annual proportion of recent infections among total new HIV diagnoses increased over time from 1% (29 out of 1964) to 8% (112 out of 1474) (p <0.001). Proportion of men who have sex with men (MSM) in the cohort increased from 62% (18 out of 29) to 89% (100 out of 112) (p <0.001). The proportion of migrants showed a non-significant increasing trend (24% (7 of 29) to 40% (45 of 112)) likewise the non-B subtype (0% to 22% (22 of 112)). The mean time from infection to diagnosis was 53.6 days (interquartile range (IQR) 50-57), comparable among all periods. Mean time from infection to treatment decreased over the years from 575 (IQR 467-683) to 471 (IQR 394-549) days (p <0.001) without significant differences between migrants and non-migrants (133 (IQR 71-411) versus 208 (IQR 90-523) days p 0.089). Almost 50% (152 of 311) of recently infected individuals were included in a cluster of transmission, and 92% (137 of 149) of them were MSM. CONCLUSION: The MSM population has progressively grown within acutely/recently infected patients in Barcelona, and is frequently involved in transmission clusters. Although the time between diagnosis and treatment has been reduced, the time between infection and diagnosis still needs to be shortened.

A measles outbreak in children under 15 months of age in La Rioja, Spain, 2005-2006.

This paper describes a measles outbreak in La Rioja, Spain, which began in December 2005 and mainly affected children under 15 months of age who were not yet immunised with MMR vaccine. The measles cases were detected by the mandatory reporting system, under which laboratories must report every confirmed measles case. Cases were classified in accordance with the National Measles Elimination Plan: suspected and laboratory-confirmed. In the period 14 December 2005 to 19 February 2006, 29 suspected cases of measles were investigated, and 18 were confirmed. The mean incubation period was 13.8 days (range: 9 to 18). Of the 18 confirmed cases, only two were in adults. MMR vaccination was recommended for all household contacts, as well as for children aged 6 to 14 months who attended the daycare centres where the cases had appeared. At these centres, the second dose of MMR was administered ahead of schedule for children under three years of age. It was recommended that the first dose of MMR vaccine be administered ahead of schedule for all children aged 9 to 14 months. During an outbreak of measles, children aged 6 months or older, who have not previously been vaccinated against measles, mumps and rubella, should receive a first dose as soon as possible, and those who have had a first dose should receive a second dose as soon as possible, provided that a minimum of one month has elapsed between the two doses.

A measles outbreak in children under 15 months of age in La Rioja, Spain, 2005-2006.

This paper describes a measles outbreak in La Rioja, Spain, which began in December 2005 and mainly affected children under 15 months of age who were not yet immunised with MMR vaccine. The measles cases were detected by the mandatory reporting system, under which laboratories must report every confirmed measles case. Cases were classified in accordance with the National Measles Elimination Plan: suspected and laboratory-confirmed. In the period 14 December 2005 to 19 February 2006, 29 suspected cases of measles were investigated, and 18 were confirmed. The mean incubation period was 13.8 days (range: 9 to 18). Of the 18 confirmed cases, only two were in adults. MMR vaccination was recommended for all household contacts, as well as for children aged 6 to 14 months who attended the daycare centres where the cases had appeared. At these centres, the second dose of MMR was administered ahead of schedule for children under three years of age. It was recommended that the first dose of MMR vaccine be administered ahead of schedule for all children aged 9 to 14 months. During an outbreak of measles, children aged 6 months or older, who have not previously been vaccinated against measles, mumps and rubella, should receive a first dose as soon as possible, and those who have had a first dose should receive a second dose as soon as possible, provided that a minimum of one month has elapsed between the two doses.

[Outbreak of measles in the population of Spanish origin in North Madrid]. / Brote de 22 casos de sarampión autóctono en la zona norte de Madrid.

After being virtually eradicated in Europe, thousands of cases of measles in the population of Spanish origin have appeared in the last 3 years. We describe the cases diagnosed in the north of Madrid between January and June 2011. A total of 22 cases are reported, 18 of them grouped in 2 outbreaks (2 nurseries). The primary attack rate was 29% in the main outbreak. All cases were in unvaccinated patients (median = 14 months). Genotype D4 was predominant (95%). There was a 45% complication rate and 45% were admitted to hospitals. The Public Health Service recommended isolating cases and vaccinating susceptible contacts in advance. Health Centres established a specific protocol to respond to suspected cases. The Measles vaccination has been brought forward from 15 to 12 months in Madrid. Measles is a re-emerging disease in Europe. The coordinated management between public health and health facilities is essential to limiting outbreaks.

[The importance of polymerase chain reaction in the diagnosis of enterovirus infections of the central nervous system in children. Clinico-epidemiologic characteristics]. / Importancia de la reacción en cadena de la polimerasa en el diagnóstico de las infecciones del sistema nervioso central por Enterovirus en la población pediátrica. Características clinicoepidemiológicas.

BACKGROUND: To compare the diagnosis utility of a reverse transcription-polymerase chain reaction (RT-PCR) for detection of enteroviral RNA in cerebrospinal fluid (CSF) in comparison to viral culture for central nervous system infections in pediatric population and to know the clinic epidemiological characteristics of this infection. METHODS: From June to December of 1997, 116 CSF samples of children were included in the study. The samples were inoculated in MRC-5 and HEP-2 and the enterovirus RNA was detected with AMPLICOR-Enterovirus (Roche Diagnostic System). The virus were typed by neutralization. RESULTS: 36 samples were positive (30 were positive for RT-PCR and 6 for RT-PCR and viral culture). The media time in detect the CPE was 4.8 days. The viruses found were four echovirus 6, one echovirus 30 and one echovirus 7. Fifteen children were under 6 months (93.3% under two months) and 21 children over 6 months with a media age of 81 months (range, 38-160 months). In over 6 months old children, the most frequent clinical presentation was meningitis aseptic syndrome with pleocytosis and in under 6 months old ones was fever and only 60% of these children had pleocytosis. The evolution was good in all the cases. CONCLUSIONS: AMPLICOR-Enterovirus is a sensitive method for the diagnosis of enteroviral meningitis. The clinical manifestations are different with the age and due to the absence of neurological symptoms and pleocytosis in the patients under two months, we think that it is necessary to study the presence of enterovirus with genetic amplification methods in this population of patients.

[Prevalence of hepatitis C virus genotypes: epidemiology and histologic characteristics]. / Prevalencia de genotipos del virus de la hepatitis C: epidemiología y características histológicas.

OBJECTIVE: To analyse the prevalence of HCV genotypes among patients from Gran Canaria and the relation with the routes of viral transmission, date of primoinfection and severity of hepatic lesion. PATIENTS AND METHODS: 179 patients were studied. In 61 patients the date of exposure was determinate. Liver biopsies were obtained in 139 patients. Genotypes were determinate by reverse hybridisation using InnoLiPA genotyping kit (Innogenetics). RESULTS: The distribution of genotypes was: 1b, 114 (63.7%), 1a, 30 (16.7%); 1, 17 (9.5%); 3a, 7 (3.9%); 4c/4d, 6 (3.3%); 2, 1 (0.5%); 2a/2c, 2 (1.1%), 3, 1 (0.5%) and 4f, 1 (0.5%). We did not find any case of coinfection with a second genotype. In univariable analysis, we found statistically differences in sex (78.9% of women infected with genotype 1b compared with 55.1% of men, p < 0.01 and 31.6% of men infected with 1a, 3a and 4c/4d compared with 15.7% of women, p < 0.01) and age (median age in genotype 1b 45 +/- 12 years vs 36 +/- 9 years in the other genotypes, p < 0.01). HCV subtypes 1a and 3a were predominant in patients IVDA (47.6% and 23.85% respectively) and 1b in blood transfusion receptors (71.2%) (p < 0.01). In 40.2% of the patients, the sources of infection were unknown. In the multivariable logistical regression analysis we found the only factor influencing the genotypes distribution was the transmission mechanism (p < 0.001) and sex and age are relationated with the transmission mode. The media infection duration in patients infected with 1b was 22 +/- 11 years vs 9 +/- 6 years in the other genotypes. We found differences in the liver histologic findings and the age of the patient, but not in the different genotypes. CONCLUSIONS: Our study reflects the higher frequency of HCV subtype 1b in our area and a different prevalence of genotypes in relation to mode of transmission. Our results suggest that in our media the liver damage seems to be directly influenced by the age of the patient, but not influenced by HCV genotype.