BackgroundA huge outbreak in the men-having-sex-with-men (MSM) has hit Europe during the years 2016–2018. Outbreak control has been hampered by vaccine shortages in many countries, and to minimize their impact, reduction of antigen doses has been implemented. However, these measures may have consequences on the evolution of hepatitis A virus (HAV), leading to the emergence of antigenic variants. Cases in vaccinated MSM patients have been detected in Barcelona, opening the possibility to study HAV evolution under immune pressure.MethodsWe performed deep-sequencing analysis of ten overlapping fragments covering the complete capsid coding region of HAV. A total of 14578255 reads were obtained and used for the analysis of virus evolution in vaccinated versus non-vaccinated patients. We estimated maximum and minimum mutation frequencies, and Shannon entropy in the quasispecies of each patient. Non-synonymous (NSyn) mutations affecting residues exposed in the capsid surface were located, with respect to epitopes, using the recently described crystal structure of HAV, as an indication of its potential role in escaping to the effect of vaccines.FindingsHAV evolution at the quasispecies level, in non-vaccinated and vaccinated patients, revealed higher diversity in epitope-coding regions of the vaccinated group. Although amino acid replacements occurring in and around the epitopes were observed in both groups, their abundance was significantly higher in the quasispecies of vaccinated patients, indicating ongoing processes of fixation.InterpretationOur data suggest positive selection of antigenic variants in some vaccinated patients, raising concerns for new vaccination polices directed to the MSM group.
Hepatitis A (HA) has been a vaccine-preventable disease since 1995. In Catalonia, a universal combined hepatitis ACB vaccination program of preadolescents was initiated at the end of 1998. However, outbreaks are reported each year and post-exposure prophylaxis (PEP) with hepatitis A virus (HAV) vaccine or immunoglobulin (IG) is recommended to avoid cases.The aim of this study was to assess the effectiveness of HAV vaccine and IG in preventing hepatitis A cases in susceptible exposed people.A retrospective cohort study of contacts of HA cases involved in outbreaks reported in Catalonia between January 2006 and December 2012 was made. The rate ratios and 95% confidence intervals (CI) of HA in susceptible contacts receiving HAV or IG versus those without PEP were calculated.There were 3550 exposed persons in the outbreaks studied: 2381 received one dose of HAV vaccine (Hepatitis A or hepatitis ACB), 190 received IG, and 611 received no PEP. 368 exposed subjects received one dose of HAV vaccine and IG simultaneously and were excluded from the study. The effectiveness of PEP was 97.6% (95% CI 96.2-98.6) for HAV vaccine and 98.3% (95% CI 91.3-99.9) for IG; the differences were not statistically significant (p D 0.36).The elevated effectiveness of HAV vaccination for PEP in HA outbreaks, similar to that of IG, and the long-term protection of active immunization, supports the preferential use of vaccination to avoid secondary cases.
We retrospectively analysed the incidence rate of reported cases of pertussis in Barcelona during 2009-2012 according to age, sex, type of medical centre and vaccination status. We included 748 confirmed or suspected cases, 613 (82.0 %) of which were confirmed by laboratory testing and the remaining 135 (18.0 %) by epidemiological evidence. The highest reported incidence of pertussis was amongst ,1 year olds [96.1 per 100 000 person-years, 95 % confidence interval (CI): 84.3-109.1]. The majority of confirmed and suspected cases were reported in 2011 and 2012, and the total incidence (confirmed or suspected) was 6.3 (95 % CI: 5.6-6.9) and 4.2 (95 % CI: 3.6-4.7) per 100 000 person-years, respectively. Incidence increased significantly (P50.001) in 2011-2012 compared with 2009. Most confirmed cases occurred in children ,1 year old (87.9 %). Cases were confirmed by real-time (RT)-PCR (87.5 %; 95 % CI: 81.3-87.6) and bacterial culture (13.7 %; 95 % CI: 11.0-17.1). We recommend performing RT-PCR in suspected cases with no epidemiological link to a confirmed case.
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