Hepatitis E virus genotype 3 microbiological surveillance by the Spanish Reference Laboratory: geographic distribution and phylogenetic analysis of subtypes from 2009 to 2019.

BackgroundHepatitis E virus genotype 3 (HEV-3) is widely distributed throughout Europe, with incidence of infections increasing in many countries. Belgium, Bulgaria, France, Germany, Italy, the Netherlands and the United Kingdom have reported the distribution of HEV-3 subtypes in cohorts of patients with hepatic disease.AimTo describe the distribution of the HEV-3 subtypes in Spain at national and autonomous community (AC) levels between 2009 and 2019. The study was also extended to Andorra.MethodsOf 5,197 samples received by the National Reference Laboratory during the study, 409 were HEV-RNA-positive. Among these, 294 (71.9%) were further typed based on an ORF2 sequence fragment, or, for a subset of 74, based on the full-coding genome sequence.ResultsHEV-3 was detected in 291 samples. The dominant subtype in Spain was HEV-3f (88.3%; 257/291), which occurred in all ACs, with no change in detection level over time. Within this subtype, three subclusters were characterised: HEV-3f-B, HEV-3f-A1 and HEV-3f-A2. The second most common HEV subtype was the recently described HEV-3m (7%; 21/291), with two subclusters identified: HEV-3m-A, which has been known since 2010, and HEV-3m-B, since 2014. The third most encountered subtype was HEV-3c (4.1%; 12/291), with a frequency not increasing over time, unlike observations in some European countries.ConclusionThe importance of the surveillance of HEV-3 subtype and subcluster circulation is yet to be assessed. This surveillance together with the comprehensive epidemiological characterisation of clinical cases, could support the identification of sources of transmission and the establishment of control measures nationally and internationally.

Simple models to include influenza vaccination history when evaluating the effect of influenza vaccination.

BackgroundMost reports of influenza vaccine effectiveness consider current-season vaccination only.AimWe evaluated a method to estimate the effect of influenza vaccinations (EIV) considering vaccination history.MethodsWe used a test-negative design with well-documented vaccination history to evaluate the average EIV over eight influenza seasons (2011/12-2018/19; n = 10,356). Modifying effect was considered as difference in effects of vaccination in current and previous seasons and current-season vaccination only. We also explored differences between current-season estimates excluding from the reference category people vaccinated in any of the five previous seasons and estimates without this exclusion or only for one or three previous seasons.ResultsThe EIV was 50%, 45% and 38% in people vaccinated in the current season who had previously received none, one to two and three to five doses, respectively, and it was 30% and 43% for one to two and three to five prior doses only. Vaccination in at least three previous seasons reduced the effect of current-season vaccination by 12 percentage points overall, 31 among outpatients, 22 in 9-65 year-olds, and 23 against influenza B. Including people vaccinated in previous seasons only in the unvaccinated category underestimated EIV by 9 percentage points on average (31% vs 40%). Estimates considering vaccination of three or five previous seasons were similar.ConclusionsVaccine effectiveness studies should consider influenza vaccination in previous seasons, as it can retain effect and is often an effect modifier. Vaccination status in three categories (current season, previous seasons only, unvaccinated) reflects the whole EIV.

Prevalencia y detección de las infecciones activas por el virus de la hepatitis C no diagnosticadas en Navarra, 2017-2019 / No disponible

ANTECEDENTES: las infecciones activas por el virus de la hepatitis C (VHC) no diagnosticadas son un obstáculo para avanzar en su eliminación. El objetivo fue estimar su prevalencia y describir los avances en su diagnóstico. MÉTODOS: se analizó la actividad diagnóstica de infecciones por VHC en Atención Primaria y especializada en Navarra entre 2017 y 2019. La prevalencia de infección no diagnosticada se estimó en pacientes con cirugía programada no relacionada con la infección por VHC, a los que se les realizó determinación rutinaria de anticuerpos del VHC (anti-VHC). En aquellos con anti-VHC positivo se determinó ARN-VHC. La prevalencia se estandarizó según sexo y edad de la población general. RESULTADOS: entre 63.405 pacientes estudiados para anti-VHC se diagnosticaron 84 infecciones activas (cinco por 100.000 personas-año). Atención Primaria analizó 20.363 pacientes y diagnosticó 47 infecciones activas, una por cada 433 personas analizadas, que supusieron el 56 % de todas las infecciones activas detectadas. Por otra parte, se analizaron 9.399 pacientes quirúrgicos y se detectaron 120 con anti-VHC (prevalencia ajustada: 1,47 %; intervalo de confianza [IC] del 95 %: 1,24-1,52); 66 (0,61 %) habían tenido carga viral positiva alguna vez y cinco eran infecciones activas no diagnosticadas (prevalencia ajustada: 0,04 %; IC 95 %: 0,01-0,11). El cribado prequirúrgico detectó una infección no diagnosticada por cada 795 personas analizadas de 45 a 64 años. CONCLUSIÓN: Atención Primaria está contribuyendo eficientemente a la detección de infecciones activas por VHC no diagnosticadas. Este objetivo podría acelerarse mediante un cribado poblacional dirigido a edades entre 45 y 64 años

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Prevalence and detection of undiagnosed active hepatitis C virus infections in Navarre, Spain, 2017-2019.

BACKGROUND: undiagnosed active hepatitis C virus (HCV) infection remains an obstacle towards its eradication. This study aimed to estimate the prevalence of HCV infection and to describe the diagnostic advances in Navarre, Spain. METHODS: HCV-infection diagnostic performance was analyzed in Navarre's primary and specialized health care between 2017 and 2019. The prevalence of undiagnosed infections was estimated for patients with programmed surgeries unrelated to HCV infection, who underwent a routine HCV antibody (anti-HCV) determination. HCV-RNA (viral load) was quantified in anti-HCV positive cases. The prevalence was standardized according to the sex and age distribution in the general population. RESULTS: from the 63,405 subjects examined for anti-HCV, 84 (five per 100,000 person-years) were diagnosed with an active infection. In Primary Health Care, 20,363 patients were analyzed and 47 active infections were detected, i.e. one case for every 433 people tested, implying 56 % of all identified active infections. On the other hand, 9,399 surgical patients were analyzed and 120 anti-HCV positive cases were detected (adjusted prevalence: 1.47 %; 95 % CI: 1.24-1.52). A positive viral load had been determined at any time in 66 cases (0.61 %), of which five were undiagnosed active infections (adjusted prevalence: 0.04 %; 95 % CI: 0.01-0.11). Preoperative screening allowed the detection of one undiagnosed infection per 795 people analyzed aged between 45 and 64 years. CONCLUSIONS: Primary Health Care efficiently contributes to the detection of undiagnosed HCV active infections. This may be speeded up by performing population screening, targeting subjects between 45 and 64 years of age.

Trends and causes of mortality in a population-based cohort of HIV-infected adults in Spain: comparison with the general population.

Combination antiretroviral therapy reduces mortality of HIV-infected persons. In Spain, where this therapy is widely available, we aim to evaluate mortality trends and causes of death in HIV-infected adults, and to estimate the excess mortality compared to the general population. From 1999 to 2018 mortality by causes was analyzed in a population-based cohort of adults aged 25 to 74 years diagnosed with HIV infection in Spain. Observed deaths and expected deaths according mortality in the general population of the same sex and age were compared using standardized mortality ratios (SMRs). HIV-infected people increased from 839 in 1999-2003 to 1059 in 2014-2018, median age increased from 37 to 47 years, the annual mortality rate decreased from 33.5 to 20.7 per 1000 person-years and the proportion of HIV-related deaths declined from 64% to 35%. HIV-related mortality declined from 21.4 to 7.3 (p < 0.001), while non-HIV-related mortality remained stable: 12.1 and 13.4 per 1000, respectively. Mortality decreased principally in persons diagnosed with AIDS-defining events. In the last decade, 2009-2018, mortality was still 8.1 times higher among HIV-infected people than in the general population, and even after excluding HIV-related deaths, remained 4.8 times higher. Excess mortality was observed in non-AIDS cancer (SMR = 3.7), cardiovascular disease (SMR = 4.2), respiratory diseases (SMR = 7.9), liver diseases (SMR = 8.8), drug abuse (SMR = 47), suicide (SMR = 5.3) and other external causes (SMR = 6). In conclusion, HIV-related mortality continued to decline, while non-HIV-related mortality remained stable. HIV-infected people maintained important excess mortality. Prevention of HIV infections in the population and promotion of healthy life styles in HIV-infected people must be a priority.

Hepatitis C core antigen: Diagnosis and monitoring of patients infected with hepatitis C virus.

INTRODUCTION: New efficient strategies are needed for the assessment of active hepatitis C virus (HCV) infection. The aim of this study was to evaluate the ability of HCV core antigen (HCV-cAg) as a marker of active HCV infection in newly diagnosed patients, for treatment monitoring, and for the detection of therapeutic failure. MATERIALS AND METHODS: A prospective study was conducted at a regional reference hospital in Spain. HCV-cAg and viral load (RNA-HCV) were tested in plasma or serum samples from three patient groups: new diagnosis, treatment monitoring, and treatment failure. The treatment monitoring group was tested at the beginning of treatment, at 4 weeks post-initiation, at the end of treatment, and at 12 weeks post-treatment completion. The Architect HCV core antigen assay was performed for HCV-cAg testing, and viral load was quantified with the Cobas 6800 system. RESULTS: A total of 303 samples from 124 patients were analyzed. Excellent correlation was seen between HCV-cAg and HCV-RNA (R2=0.932). The optimal cut-off value was 3fmol/l in the receiver operating characteristics curve analysis, and the area under the curve was 0.987 (95% confidence interval 0.972-1.000). HCV-cAg sensitivity and specificity were 97% and 95%, respectively. Most diverging results were observed in the treatment follow-up group. CONCLUSIONS: HCV-cAg demonstrated good sensitivity and specificity as a marker for active HCV infection, new diagnosis, detection of antiviral therapeutic failure, and treatment monitoring.

Traveller's diarrhoea by Vibrio cholerae in patients returning from the Dominican Republic / Diarrea del viajero por Vibrio cholerae en pacientes que regresan de República Dominicana

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Remaining Effect of Influenza Vaccines Received in Prior Seasons.

This study evaluates the remaining effect of influenza vaccines received in the 5 prior seasons. During 7 influenza seasons, 8933 patients were enrolled and 47% were confirmed for influenza. Compared with unvaccinated individuals in the current and 5 prior seasons, vaccination was protective when the last dose had been received in the current season (40% [95% confidence interval {CI}, 32%-47%]), and 1 (42% [95% CI, 27%-54%]), 2-3 (35% [95% CI, 16%-49%]), or 4-5 seasons (31% [95% CI, 4%-51%]) prior. This effect lasted for fewer seasons in the elderly and in patients with chronic conditions. On average, several recent prior doses were as protective as current-season vaccination.

Enfermedad de Weil autóctona: a propósito de un caso / Autochthonous Weil's disease: A case report

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Progress in the elimination of hepatitis C virus infection: A population-based cohort study in Spain.

BACKGROUND: The World Health Organization set targets to eliminate hepatitis C virus (HCV) infection through detection and treatment of all cases by 2030. This study aimed to describe the progress and difficulties in the elimination of HCV infection in Navarra, Spain. METHODS: Using electronic healthcare databases, we performed a population-based prospective cohort study to describe changes in the prevalence of diagnosed active HCV infection at the beginning of 2015 and the end of 2017, the rate of new diagnoses and the rate of post-treatment viral clearance (PTVC) during this period. RESULTS: At the beginning of 2015 there were 1503 patients diagnosed with positive HCV-RNA, 2.4 per 1000 inhabitants, and at the end of 2017 the prevalence had decreased by 47%. In the study period, 333 (18 per 100,000 person-years) new positive HCV-RNA cases were detected, but only 76 (23%; 4.2 per 100,000 person-years) did not have anti-HCV antibodies previously detected. Prevalent cases and new diagnoses of active infection were more frequent in men, people born in 1950-1979, HIV-infected patients and in those with lower income levels. Among patients with HCV-RNA, 984 achieved PTVC (22.7 per 100 person-years). PTVC was less frequent in patients born before 1940, in immigrants and in patients with lower income levels. CONCLUSIONS: The prevalence of diagnosed active HCV infection has dropped by almost half over three years, because the number of patients with PTVC was much higher than the number of new diagnoses. Interventions specifically targeted at population groups with less favourable trends may be necessary.

Estimación de la prevalencia de infección diagnosticada y no diagnosticada por el virus de la hepatitis C en Navarra, 2014-2016 / The prevalence of diagnosed and undiagnosed hepatitis C virus infection in Navarra, Spain, 2014-2016

OBJETIVO: Estimar la prevalencia de infección por el virus de la hepatitis C (VHC) en Navarra, distinguiendo entre infecciones diagnosticadas y no diagnosticadas. MÉTODOS: Se estudiaron pacientes con cirugía programada no relacionada con la infección por VHC, a los que se les realizó de forma sistemática la determinación de anticuerpos del VHC entre enero de 2014 y septiembre de 2016. En los pacientes con enzimoinmunoanálisis positivo se confirmó el diagnóstico mediante inmunoblot y/o determinación de ARN-VHC. También se comprobó la existencia de resultados positivos previos. La prevalencia se estandarizó por sexo y edad a la población de Navarra. RESULTADOS: Se analizaron 7.378 pacientes, 50% mujeres, con una mediana de edad de 46 años. En 69 se detectaron anticuerpos del VHC, lo que supone una prevalencia poblacional estimada de 0,83% (intervalo de confianza del 95%: 0,64-1,05), mayor en hombres (1,11%) que en mujeres (0,56%; p = 0,0102). Entre los que resultaron anti-VHC positivos, 67 (97%) habían tenido alguna prueba positiva previa. La prevalencia poblacional de diagnóstico previo de anti-VHC fue del 0,80%, y la de nuevos diagnósticos, del 0,03%. El 78% de los pacientes con anti-VHC positivo habían presentado alguna determinación de ARN-VHC detectable. Se estima que el 0,65% de la población había tenido ARN-VHC detectable y el 0,51% lo seguía teniendo en el momento del estudio. CONCLUSIÓN: Estos resultados revisan a la baja las estimaciones previas de prevalencia de infección por VHC. Una proporción mínima de las personas con anti-VHC permanecen sin diagnosticar, y solo una parte mantienen infección activa

OBJECTIVE: To estimate the prevalence of hepatitis C virus (HCV) infection in Navarra, Spain, as well as to distinguish between diagnosed and undiagnosed infections. METHODS: A study was conducted on patients scheduled for surgery unrelated to HCV infection. They were all tested for HCV antibodies, under a routine scheme, from January 2014 to September 2016. Patients with a positive result by enzyme immunoassay were confirmed using immunoblot and/or HCV-RNA. Previous laboratory results were also taken into account. The prevalence was adjusted to the sex and age structure of the Navarra population. RESULTS: The study included a total of 7,378 patients with a median age 46 years, of whom 50% women. HCV antibodies were detected in 69 patients, which is a prevalence in the population of 0.83% (95% confidence interval: 0.64-1.05), and was higher in men (1.11%) than in women (0.56%; P = .0102). Among the HCV positive patients, 67 (97%) had had another previous positive result. Population prevalence of previous positive HCV was 0.80%, and was 0.03% for a new diagnosis. Of the HCV positive patients, 78% had detectable HCV-RNA. It was estimated that 0.65% of the population had had detectable HCV-RNA, and 0.51% continued to have it when recruited into the study. CONCLUSION: Previous estimates of prevalence of HCV infection should be revised downwards. Only a small proportion of HCV positive patients remain undiagnosed, and only a small part have active infection

Detection of Respiratory Viruses in Deceased Persons, Spain, 2017.

During the 2016-17 influenza season in Spain, we tested specimens from 57 elderly deceased persons for respiratory viruses. Influenza viruses were detected in 18% of the specimens and any respiratory virus in 47%. Only 7% of participants had received a diagnosis of infection with the detected virus before death.

Interim effectiveness of trivalent influenza vaccine in a season dominated by lineage mismatched influenza B, northern Spain, 2017/18.

The 2017/18 interim estimate of trivalent influenza vaccine effectiveness (VE) was 39% (95% confidence interval: 20-54) in Navarre. Compared with individuals unvaccinated in the current and five previous seasons, VE against influenza B was 41% for current and any prior doses, 67% for current vaccination only, and 22% for any prior doses, and 43%, 51% and 54%, respectively against influenza A(H3N2). This suggests moderate VE despite predominance of lineage mismatched influenza B.

Comparison of influenza vaccine effectiveness in preventing outpatient and inpatient influenza cases in older adults, northern Spain, 2010/11 to 2015/16.

IntroductionWe compared trivalent inactivated influenza vaccine effectiveness (VE) in preventing outpatient and inpatient influenza cases in Navarre, Spain. Methods: During seasons 2010/11 to 2015/16, community-dwelling patients with influenza-like illness aged 50 years or older were tested for influenza when attended by sentinel general practitioners or admitted to hospitals. The test-negative design was used to estimate and compare the VE by healthcare setting. Results: We compared 1,242 laboratory-confirmed influenza cases (557 outpatient and 685 inpatient cases) and 1,641 test-negative controls. Influenza VE was 34% (95% confidence interval (CI): 6 to 54) in outpatients and 32% (95% CI: 15 to 45) in inpatients. VE in outpatients and inpatients was, respectively, 41% (95% CI: -1 to 65) and 36% (95% CI: 12 to 53) against A(H1N1)pdm09, 5% (95% CI: -58 to 43) and 22% (95% CI: -9 to 44) against A(H3N2), and 49% (95% CI, 6 to 73) and 37% (95% CI: 2 to 59) against influenza B. Trivalent inactivated influenza vaccine was not associated with a different probability of hospitalisation among influenza cases, apart from a 54% (95% CI: 10 to 76) reduction in hospitalisation of influenza A(H3N2) cases. Conclusions: On average, influenza VE was moderate and similar in preventing outpatient and inpatient influenza cases over six influenza seasons in patients above 50 years of age. In some instances of low VE, vaccination may still reduce the risk of hospitalisation in older adults with vaccine failure.

The prevalence of diagnosed and undiagnosed hepatitis C virus infection in Navarra, Spain, 2014-2016. / Estimación de la prevalencia de infección diagnosticada y no diagnosticada por el virus de la hepatitis C en Navarra, 2014-2016.

OBJECTIVE: To estimate the prevalence of hepatitis C virus (HCV) infection in Navarra, Spain, as well as to distinguish between diagnosed and undiagnosed infections. METHODS: A study was conducted on patients scheduled for surgery unrelated to HCV infection. They were all tested for HCV antibodies, under a routine scheme, from January 2014 to September 2016. Patients with a positive result by enzyme immunoassay were confirmed using immunoblot and/or HCV-RNA. Previous laboratory results were also taken into account. The prevalence was adjusted to the sex and age structure of the Navarra population. RESULTS: The study included a total of 7,378 patients with a median age 46 years, of whom 50% women. HCV antibodies were detected in 69 patients, which is a prevalence in the population of 0.83% (95% confidence interval: 0.64-1.05), and was higher in men (1.11%) than in women (0.56%; P=.0102). Among the HCV positive patients, 67 (97%) had had another previous positive result. Population prevalence of previous positive HCV was 0.80%, and was 0.03% for a new diagnosis. Of the HCV positive patients, 78% had detectable HCV-RNA. It was estimated that 0.65% of the population had had detectable HCV-RNA, and 0.51% continued to have it when recruited into the study. CONCLUSION: Previous estimates of prevalence of HCV infection should be revised downwards. Only a small proportion of HCV positive patients remain undiagnosed, and only a small part have active infection.

Human T-lymphotropic virus type 1 infection and disease in Spain.

: Human T-lymphotropic virus type 1 (HTLV-1) infection is a neglected disease despite roughly 15 million people are chronically infected worldwide. Lifelong less than 10% of carriers develop life-threatening diseases, mostly a subacute myelopathy known as tropical spastic paraparesis (TSP) and a lymphoproliferative disorder named adult T-cell leukemia (ATL). HTLV-1 is efficiently transmitted perinatally (breastfeeding), sexually (more from men to women) and parenterally (transfusions, injection drug user (IDU), and transplants). To date there is neither prophylactic vaccine nor effective antiviral therapy. A total of 327 cases of HTLV-1 infection had been reported at the HTLV-1 Spanish registry until December 2016, of whom 34 had been diagnosed with TSP and 25 with ATL. Overall 62% were Latin American immigrants and 13% were persons of African origin. The incidence of HTLV-1 in Spain has remained stable for nearly a decade with 20-25 new cases yearly. Of the 21 newly diagnosed HTLV-1 cases during year 2016, one was a native Spaniard pregnant woman, and four presented with symptomatic disease, including three with ATL and one with TSP. Underdiagnosis of HTLV-1 in Spain must be high (iceberg model), which may account for the disproportionate high rate of symptomatic cases (almost 20%) and the late recognition of preventable HTLV-1 transmissions in special populations, such as newborns and transplant recipients. Our current estimate is of 10 000 persons living with HTLV-1 infection in Spain. Given the large flux of immigrants and visitors from HTLV-1 endemic regions to Spain, the expansion of HTLV-1 screening policies is warranted. At this time, it seems worth recommending HTLV testing to all donor/recipient organ transplants and pregnant women regardless place of birth. Although current leukoreduction procedures largely prevent HTLV-1 transmission by blood transfusions, HTLV testing of all first-time donors should be cost-effective contributing to unveil asymptomatic unaware HTLV-1 carriers.

Effect of Repeated Vaccination With the Same Vaccine Component Against 2009 Pandemic Influenza A(H1N1) Virus.

Background: The 2009 pandemic influenza A(H1N1) (A[H1N1]pdm09) vaccine component has remained unchanged from 2009. We estimate the effectiveness of current and prior inactivated influenza A(H1N1)pdm09 vaccination from influenza seasons 2010-2011 to 2015-2016. Methods: Patients attended with influenza-like illness were tested for influenza. Four periods with continued A(H1N1)pdm09 circulation were included in a test-negative design. Results: We enrolled 1278 cases and 2343 controls. As compared to individuals never vaccinated against influenza A(H1N1)pdm09, the highest effectiveness (66%; 95% confidence interval, 49%-78%) was observed in those vaccinated in the current season who had received 1-2 prior doses. The effectiveness was not statistically lower in individuals vaccinated in the current season only (52%) or in those without current vaccination and >2 prior doses (47%). However, the protection was lower in individuals vaccinated in the current season after >2 prior doses (38%; P = .009) or those currently unvaccinated with 1-2 prior doses (10%; P < .001). Current-season vaccination improved the effect in individuals with 1-2 prior doses and did not modify significantly the risk of influenza in individuals with >2 prior doses. Conclusion: Current vaccination or several prior doses were needed for high protection. Despite the decreasing effect of repeated vaccination, current-season vaccination was not inferior to no current-season vaccination.