What have we learnt about rotavirus in Spain in the last 10 years?

En España, las vacunas frente a rotavirus (RV) están disponibles desde 2006 pero no están ni recomendadas ni financiadas por el Sistema Nacional de Salud. Sin embargo, a través de las recomendaciones de la Asociación Española de Pediatría se han alcanzado coberturas de vacunación intermedias. Se ha realizado una revisión sistemática de la literatura sobre los estudios realizados en España en los últimos 12 a˜nos (2006-2018) en relación con la infección y las vacunas frente a RV. Se identifican 43 estudios que cumplían los criterios de selección. La carga de enfermedad en población <5 a˜nos en atención primaria oscila entre 15 y 19 casos por 1.000 ni˜nos y en hospitalaria entre 120 y 480 casos por 100.000, lo que supone una importante repercusión económica y social. Las vacunas frente a RV han mostrado en España una efectividad de entre el 83 y el 96% y un impacto de hasta un 70% de reducción de hospitalizaciones, que es dependiente de la cobertura de vacunación alcanzada. Se identifican además nuevas líneas de investigación relacionadas con el papel de la vacuna del RV y la protección frente a convulsiones, o el papel del microbiota, entre otros. La información actualmente disponible refrenda la importante carga de enfermedad por RV en España y la elevada efectividad de las vacunas disponibles. Estas evidencias permiten una reevaluación de las recomendaciones nacionales sobre vacunación frente a RV.Vaccines against rotavirus (RV) have been available in Spain since 2006, but they are neither recommended nor financed by the National Health System. Nevertheless, through recommendations of the Spanish Association of Paediatrics vaccination has achieved interme- diate coverage. A systematic literature review was performed on studies carried out in Spain in the last 12 years (2006-2018) on RV infection and vaccination. Results: A total of 43 studies were identified that met the inclusion criteria. The disease burden in children less than 5 years in the Primary Care setting ranged from 15 to 19 cases per 1,000 children, and between 120 and 480 cases per 100,000 in the hospital setting, which has a significant economic and social impact. Vaccines against RV have shown an effectiveness of between 83% and 96%, and an impact of up to 70% in reducing hospital admissions, which is dependent on the achieved vaccine coverage. New research lines are identified, such as the role of the rotavirus vaccine and protection against seizures or the impact on the gut microbiota. The current available information supports the significant burden of rotavirus disease in Spain and the high effectiveness of the available vaccines. This evidence should allow for an updated re-evaluation of the national recommendations on rotavirus vaccination.La redacción de este artículo ha sido apoyada en parte a través de una beca de MSD España.Medicin

Prevalence of X4 tropic viruses in patients recently infected with HIV-1 and lack of association with transmission of drug resistance

Producción CientíficaBackground: HIV-1 co-receptor usage may play a critical role in AIDS pathogenesis. Information on viral tropism in HIV-1 seroconverters is scarce, as is the relationship with transmission of drug-resistant viruse

Antiretroviral recommendations may influence the rate of transmission of drug-resistant HIV type 1

Producción CientíficaHuman immunodeficiency virus (HIV) treatment guidelines have evolved, shifting from more-aggressive to more-conservative approaches. The potential impact of these shifts on the transmission of drug-resistant virus is unknown. Drug-resistance genotypes were examined in all consecutive patients with recent HIV type 1 (HIV-1) seroconversion (hereafter, "HIV-1 seroconverters") seen at 10 Spanish hospitals since 1997. During the same period, the proportion of patients with chronic HIV-1 infection having undetectable viremia was examined, to estimate the extent and effectiveness of antiretroviral therapy. A total of 141 recent HIV-1 seroconverters were identified, 67.4% of whom were men who have sex with men. The rate of primary drug-resistance mutations, by year of infection, was 33.3% for 1997, 29.4% for 1998, 20% for 1999, 14.3% for 2000, 3.4% for 2001, 15.4% for 2002, and 10.9% for 2003. On the other hand, the proportion of 8388 persons with chronic HIV-1 carriage who had an undetectable virus load was 33.4% for 1997, 34.6% for 1998, 39.7% for 1999, 47.5% for 2000, 52.9% for 2001, 39.7% for 2002, and 58.1% for 2003. A significant inverse correlation between transmission of drug-resistant HIV-1 and undetectable virus load was found (r=-0.955, by Spearman's test; P=.001). The lowest rate of transmission of drug-resistant HIV-1 was seen in 2001, when relatively "aggressive" treatment guidelines were used. Transmission of drug-resistant HIV-1 increased in 2002, in parallel with a reduction in the number of patients with chronic HIV-1 carriage and undetectable virus load, reflecting the popularity of drug holidays or treatment interruptions. The rate of drug resistance in recent HIV-1 seroconverters inversely correlates with the proportion of chronically HIV-1-infected individuals who have undetectable virus loads in the same region, which indirectly reflects antiretroviral treatment rules at any given time

The CARBA-MAP study: national mapping of carbapenemases in Spain (2014–2018)

Introduction:Infections caused by carbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant Pseudomonas aeruginosa, including isolates producing acquired carbapenemases, constitute a prevalent health problem worldwide. The primary objective of this study was to determine the distribution of the different carbapenemases among carbapenemase-producing Enterobacterales (CPE, specifically Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae complex, and Klebsiella aerogenes) and carbapenemase-producing P. aeruginosa (CPPA) in Spain from January 2014 to December 2018.Methods: A national, retrospective, cross-sectional multicenter study was performed. The study included the first isolate per patient and year obtained from clinical samples and obtained for diagnosis of infection in hospitalized patients. A structured questionnaire was completed by the participating centers using the REDCap platform, and results were analyzed using IBM SPSS Statistics 29.0.0.Results: A total of 2,704 carbapenemase-producing microorganisms were included, for which the type of carbapenemase was determined in 2692 cases: 2280 CPE (84.7%) and 412 CPPA (15.3%), most often using molecular methods and immunochromatographic assays. Globally, the most frequent types of carbapenemase in Enterobacterales and P. aeruginosa were OXA-48-like, alone or in combination with other enzymes (1,523 cases, 66.8%) and VIM (365 cases, 88.6%), respectively. Among Enterobacterales, carbapenemase-producing K. pneumoniae was reported in 1821 cases (79.9%), followed by E. cloacae complex in 334 cases (14.6%). In Enterobacterales, KPC is mainly present in the South and South-East regions of Spain and OXA-48-like in the rest of the country. Regarding P. aeruginosa, VIM is widely distributed all over the country. Globally, an increasing percentage of OXA-48-like enzymes was observed from 2014 to 2017. KPC enzymes were more frequent in 2017–2018 compared to 2014–2016.Discussion: Data from this study help to understand the situation and evolution of the main species of CPE and CPPA in Spain, with practical implications for control and optimal treatment of infections caused by these multi-drug resistant organisms

Role of the first WHO mutation catalogue in the diagnosis of antibiotic resistance in Mycobacterium tuberculosis in the Valencia Region, Spain: a retrospective genomic analysis

9 páginas, 2 figuras, 1 tablaBackground: In June, 2021, WHO published the most complete catalogue to date of resistance-conferring mutations in Mycobacterium tuberculosis. Here, we aimed to assess the performance of genome-based antimicrobial resistance prediction using the catalogue and its potential for improving diagnostics in a real low-burden setting. Methods: In this retrospective population-based genomic study M tuberculosis isolates were collected from 25 clinical laboratories in the low-burden setting of the Valencia Region, Spain. Culture-positive tuberculosis cases reported by regional public health authorities between Jan 1, 2014, and Dec 31, 2016, were included. The drug resistance profiles of these isolates were predicted by the genomic identification, via whole-genome sequencing (WGS), of the high-confidence resistance-causing variants included in the catalogue and compared with the phenotype. We determined the minimum inhibitory concentration (MIC) of the isolates with discordant resistance profiles using the resazurin microtitre assay. Findings: WGS was performed on 785 M tuberculosis complex culture-positive isolates, and the WGS resistance prediction sensitivities were: 85·4% (95% CI 70·8–94·4) for isoniazid, 73·3% (44·9–92·2) for rifampicin, 50·0% (21·1–78·9) for ethambutol, and 57·1% (34·0–78·2) for pyrazinamide; all specificities were more than 99·6%. Sensitivity values were lower than previously reported, but the overall pan-susceptibility accuracy was 96·4%. Genotypic analysis revealed that four phenotypically susceptible isolates carried mutations (rpoB Leu430Pro and rpoB Ile491Phe for rifampicin and fabG1 Leu203Leu for isoniazid) known to give borderline resistance in standard phenotypic tests. Additionally, we identified three putative resistance-associated mutations (inhA Ser94Ala, katG Leu48Pro, and katG Gly273Arg for isoniazid) in samples with substantially higher MICs than those of susceptible isolates. Combining both genomic and phenotypic data, in accordance with the WHO diagnostic guidelines, we could detect two new multidrug-resistant cases. Additionally, we detected 11 (1·6%) of 706 isolates to be monoresistant to fluoroquinolone, which had been previously undetected. Interpretation: We showed that the WHO catalogue enables the detection of resistant cases missed in phenotypic testing in a low-burden region, thus allowing for better patient-tailored treatment. We also identified mutations not included in the catalogue, relevant at the local level. Evidence from this study, together with future updates of the catalogue, will probably lead in the future to the partial replacement of culture testing with WGS-based drug susceptibility testing in our setting. Funding: European Research Council and the Spanish Ministerio de Ciencia.This project received funding from the European Research Council under the European Union’s Horizon 2020 Research and Innovation Program Grant 101001038 (TB-RECONNECT; awarded to IC), from Ministerio de Ciencia (Spanish Government) Project PID2019-104477RB-I00 (awarded to IC), and from Generalitat Valenciana Project AICO/2018/113 (awarded to IC). AMG-M is funded by a Formación deProfesorado Universitario grant programme (FPU19/04562) from Ministerio de Universidades (Spanish Government). IC is also supported by the European Commission–NextGenerationEU, through Centro Superior de Investigaciones Científicas Global Health Platform (PTI Salud Global). We thank all the members of the Valencia RegionTuberculosis Working Group

Population-based sequencing of Mycobacterium tuberculosis reveals how current population dynamics are shaped by past epidemics

23 páginas, 4 figuras, 1 tabla.Transmission is a driver of tuberculosis (TB) epidemics in high-burden regions, with assumed negligible impact in low-burden areas. However, we still lack a full characterization of transmission dynamics in settings with similar and different burdens. Genomic epidemiology can greatly help to quantify transmission, but the lack of whole genome sequencing population-based studies has hampered its application. Here, we generate a population-based dataset from Valencia region and compare it with available datasets from different TB-burden settings to reveal transmission dynamics heterogeneity and its public health implications. We sequenced the whole genome of 785 Mycobacterium tuberculosis strains and linked genomes to patient epidemiological data. We use a pairwise distance clustering approach and phylodynamic methods to characterize transmission events over the last 150 years, in different TB-burden regions. Our results underscore significant differences in transmission between low-burden TB settings, i.e., clustering in Valencia region is higher (47.4%) than in Oxfordshire (27%), and similar to a high-burden area as Malawi (49.8%). By modeling times of the transmission links, we observed that settings with high transmission rate are associated with decades of uninterrupted transmission, irrespective of burden. Together, our results reveal that burden and transmission are not necessarily linked due to the role of past epidemics in the ongoing TB incidence, and highlight the need for in-depth characterization of transmission dynamics and specifically tailored TB control strategies.European Research Council 638553-TB-ACCELERATE; European Research Council 101001038-TBRECONNECT; Ministerio de Ciencia e Innovación SAF2016-77346-RPeer reviewe