Iñigo Ansa

The diagnosis and treatment of Helicobacter pylori infection in children represent a major public health problem worldwide, and although prevalence in developed countries has declined, concern about antibiotic resistance continues to grow. This retrospective study aimed to analyze H. pylori infections in children under 15 years of age in Gipuzkoa (Basque Country, Spain) over a 25-year period and to describe patterns of primary and secondary antimicrobial resistance. All diagnostic tests received at a tertiary referral hospital between 2000 and 2024 were reviewed: urea breath test, gastric biopsy culture, string test, and stool antigen detection. Antimicrobial susceptibility testing was performed using the E-test gradient diffusion method. Out of 2855 children investigated, 26.9 were infected with H. pylori. Eradication control was performed in 62.5% (n = 480) of cases. Antimicrobial susceptibility testing was achieved in 96.5% out of the 400 isolates studied. All isolates were sensitive to amoxicillin and tetracyclines. Primary resistance to clarithromycin, metronidazole, and levofloxacin was 28.9%, 19.4%, and 8.9%, respectively, and secondary resistance was 38.7%, 29.7%, and 5.9%, respectively. H.pylori infection remains a challenge in pediatric patients, and the high resistance observed to clarithromycin and metronidazole makes it necessary to monitor the susceptibility of H.pylori and confirms the need for targeted treatment.

Background: Streptococcus pneumoniae is currently the leading cause of acute bacterial meningitis. This study assessed the impact of pneumococcal conjugate vaccines (PCVs) on pneumococcal meningitis in Gipuzkoa, north of Spain, between 1993 and 2023. Methods: All cases were serotyped and tested for antimicrobial susceptibility, with medical records reviewed since 2013. Overall, 193 patients were diagnosed (178 patients), averaging 6.2 cases annually. Results: Pneumococcal meningitis annual incidence decreased significantly after PCVs introduction, from 1.99 cases per 100,000 inhabitants in 1993–2001 (before PCV7) to 1.64 in 2002–2010 (PCV7 period) and further to 1.13 in 2011–2023 (PCV13 period). This decline was observed in all age groups except for adults aged ≥65 years, in whom the reduction was observed only after PCV13 introduction. The greatest reduction was observed in children under five. The incidence of meningitis caused by vaccine serotypes decreased following the progressive introduction of PCVs, but non-PCV serotypes increased from 0.70 to 0.95 cases per 100,000 between 1993–2001 and 2011–2023. Otitis media was the most common source of infection, followed by CSF fistula. Most cases (85%) required ICU admission; 67.5% showed sequels at discharge, mainly sensorineural hearing loss, and the 30-day mortality rate was 11.1%. Recurrent pneumococcal meningitis represented 7.8% of cases, associated with head trauma, with favorable outcomes and no mortality. Between 1993–2001 and 2002–2010, penicillin and cefotaxime resistance decreased from 25.4% to 13.3% (47.6% reduction) and from 19.7% to 5% (74.6% reduction), respectively. In 2011–2023, cefotaxime resistance stabilized, but penicillin resistance rose to 32.3%, mainly due to non-PCV13 serotypes. Conclusions: The use of PCV reduced the incidence of pneumococcal meningitis in the region, but penicillin resistance has increased in recent years, due to the rise in non-PCV13 serotypes.

Since its re-emergence in Europe in 2015, enterovirus A71 (EV-A71) has been associated with sporadic cases of severe infections and outbreaks. Currently, there is no treatment but a few Asian countries have implemented vaccination programmes. The aim of our study was to characterize the EV-A71 cases in Europe and track the evolution of the virus between 2016 and 2022. For this retrospective study, we compiled the data of confirmed EV-A71 infections collected by 19 institutes participating in the European Non-Polio Enterovirus Network between 2016 and 2022. We also sequenced whole EV-A71 genomes to follow the viral evolutionary history of the virus and its molecular changes. Between 1 January 2016 and 31 December 2022, 627 EV-A71 cases were reported in 14 European countries. Most cases (59.3%) occurred in children under two years of age. Of the 537 subjects for whom clinical information was available, 52.7% were diagnosed with neurological signs, and 10.6% presented with acute flaccid paralysis or acute flaccid myelitis. EV-A71 infections were linked to two subclades, C1.2 and C1.3, within the C1 subgenogroup. Two marked epidemic waves, in 2016 and 2019, were characterized by the predominance of C1.3 viruses. Comparisons of 153 whole genomes revealed nine recombinant forms (RFs), each arising from multiple recombination events affecting different genomic regions. Only C1.3/RF5 and C1.3/RF6 lineages achieved widespread geographic dissemination initially in Europe and subsequently in Asia and the Americas, and long-term circulation. Phylodynamic analyses indicated that C1.3 viruses emerged around 2013–2014, displacing earlier C1.1 viruses, and the effective population size closely parallels the timing of clinical cases. Molecular analyses of the capsid revealed several amino acid changes, few of which occurred within known antigenic sites. These findings document the role of the C1.3/RF5 and C1.3/RF6 multi-recombinant lineages of EV-A71 as frequent causes of neurological disease in young children in Europe. The study highlights the need for sustained genome-informed surveillance to anticipate the emergence and spread of novel epidemic lineages, and to inform the evaluation of future EV-A71 vaccination strategies.

Chlamydia trachomatis infection is an important public health problem. Our objective was to assess the dynamics of the transmission of this infection, analysing the distribution of circulating ompA genotypes and multilocus sequence types of C. trachomatis in Spain as a function of clinical and epidemiological variables. During 2018 and 2019, we genetically characterized C. trachomatis in tertiary hospitals in six areas in Spain (Asturias, Barcelona, Gipuzkoa, Mallorca, Seville and Zaragoza), with a catchment population of 3.050 million people. Genotypes and sequence types were obtained using polymerase chain reaction techniques that amplify a fragment of the ompA gene, and five highly variable genes (hctB, CT058, CT144, CT172 and pbpB), respectively. Amplicons were sequenced and phylogenetic analysis was conducted. We obtained genotypes in 636/698 cases (91.1%). Overall and by area, genotype E was the most common (35%). Stratifying by sex, genotypes D and G were more common among men, and genotypes F and I among women (p < 0.05). Genotypes D, G and J were more common in men who have sex with men (MSM) than in men who have sex with women (MSW), in whom the most common genotypes were E and F. The diversity index was higher in sequence typing (0.981) than in genotyping (0.791), and the most common sequence types were ST52 and ST108 in MSM, and ST30, ST148, ST276 and ST327 in MSW. Differences in genotype distribution between geographical areas were attributable to differences in population characteristics. The transmission dynamics varied with sexual behaviour: the predominant genotypes and most frequent sequence types found in MSM were different to those detected in MSW and women.

The management of Mycoplasma genitalium sexually transmitted infection (STI) is hindered by increasing resistance to the recommended antibiotics, macrolides and quinolones, worldwide. In Gipuzkoa (Basque Country, Spain), macrolide and quinolone resistance rates in 2014–2018 were reported as n = 1019) and quinolones (n = 958) was studied, analysing mutations in 23S rRNA and parC/gyrA genes, respectively. The rate of macrolide resistance increased from 17.3% in 2014–2018 to 32.1% in 2019–2021, as much in the more prevalent A2058/2059G mutations (16.6–27.8%) as in the emergent A2058T mutations (0.5–4.1%) but with differences in the odds ratios and the relative risk increase between A2058T and A2058/2059G mutations. MG191 adhesin and MG309 lipoprotein of the 27 emergent strains detected with A2058T mutations were amplified, sequenced, and typed using phylogenetic and variable number tandem repeat analysis, respectively. Genetic clonal spread was ruled out, but most of the A2058T cases were men who had sex with men (24/27) with a history of STI and antibiotic treatments (19/27). No changes were observed in quinolone resistance trends, but the rate of resistance to both antibiotics rose from 2.9% to 8.3%, especially in cases with A2058T mutations. The genetic characterisation of strains and epidemiological surveillance of cases are needed to detect populations at increased risk of treatment failure in this infection.