The MMR vaccination program was introduced in Spain in 1981. Consistently high vaccination coverage has led to Spain being declared free of endemic measles transmission since 2014. A few imported and import-related cases were reported during the post-elimination phase (2014 to 2020), with very low incidence: three cases per million of inhabitants a year, 70% in adults. In the post-elimination phase an increasing proportion of measles appeared in two-dose vaccinated individuals (up to 14%), posing a challenge to surveillance and laboratory investigations. Severity and clinical presentation were milder among the vaccinated. The IgM response varied and the viral load decreased, making the virus more difficult to detect. A valid set of samples (serum, urine and throat swab) is strongly recommended for accurate case classification. One third of measles in fully vaccinated people was contracted in healthcare settings, mainly in doctors and nurses, consistent with the important role of high intensity exposure in measles breakthrough cases. Surveillance protocols and laboratory algorithms should be adapted in advanced elimination settings. Reinforcing the immunity of people working in high exposure environments, such as healthcare settings, and implementing additional infection control measures, such as masking and social distancing, are becoming crucial for the global aim of measles eradication.

The mumps vaccine (Jeryl-Lynn-strain) was introduced in Spain in 1981, and a vaccination policy which included a second dose was added in 1995. From 1992-1999, a Rubini-strain based vaccine was administered in many regions but later withdrawn due to lack of effectiveness. Despite high levels of vaccination coverage, epidemics have continued to appear. We characterized the three epidemic waves of mumps between 1998 and 2014, identifying major changes in susceptible populations using Poisson regression. For the period 1998-2003 (P1), the most affected group was from 1 to 4years old (y) [Incidence Rate (IR)=71.7 cases/100,000 population]; in the periods 2004-2009 (P2) and 2010-2014 (P3) IR ratio (IRR) increased among 15-24y (P2=1.46; P3=2.68) and 25-34y (P2=2.17; P3=4.05). Hospitalization rate (HR), complication rate (CR) and neurological complication rate (NR) among hospitalized subjects decreased across the epidemics, except for 25-34y which increased: HR ratio (HRR) (P2=2.18; P3=2.16), CRR (P3=2.48), NRR (P3=2.41). In Spain mumps incidence increased, while an overall decrease of hospitalizations and severe complications occurred across the epidemics. Cohorts born during periods of low vaccination coverage and those vaccinated with Rubini-strain were the most affected populations, leading to a shift in mumps cases from children to adolescents and young adults; this also reveals the waning immunity provided by the mumps vaccine. Despite not preventing all mumps cases, the vaccine appears to prevent serious forms of the disease.

In recent decades, vaccination has substantially reduced the number of measles cases to levels close to the elimination stage. However, major measles outbreaks occurred in Europe during 2010–2012, after the introduction of the D4-Enfield lineage. We have performed a molecular characterization of 75 measles virus genotype D4 strains from patients infected in Spain between 2004 and 2012 by sequencing the N-450 region and the M-F non-coding region (M-F NCR) in order to identify genetic features of these viruses. The analysis of the N-450 region confirmed that all samples obtained since 2008 belonged to variants or sets of identical sequences of the D4-Enfield lineage, including a new one named MVs/Madrid.ESP/46.10/. Analysis of the M-F NCR showed insertions and deletions associated with previously described, uncommon non-standard genome length measles viruses. This genetic feature was identified in the D4-Enfield lineage viruses, but not in the other D4 viruses that were circulating in Spain before 2008, suggesting that these non-standard length M-F NCR sequences are characteristic of the D4-Enfield lineage. The results of the phylogenetic analysis of Spanish M-F NCRs suggest higher resolution in discriminating strains than did the N-450 analysis. In addition, the results of the analysis of the M-F NCR on the MVs/Madrid.ESP/46.10/ sub-lineage seem to support the potential utility of this region as a tool for epidemiological surveillance complementary to the N-450 region, as previously suggested. Further investigation on this question, as well as the surveillance of new potentially emerging strains with non-standard length M-F NCR are strongly recommended as part of future strategies for measles elimination.

Objective: To estimate the range of the age- and sex-specific infection fatality risk (IFR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on confirmed coronavirus disease 2019 (COVID-19) deaths and excess all-cause deaths. Design: Nationwide population-based seroepidemiological study combined with two national surveillance systems. Setting and participants: Non-institutionalized Spanish population of all ages. Main outcome measures: The range of IFR was calculated as the observed number of COVID-19 deaths and excess deaths divided by the estimated number of SARS-CoV-2 infections in the non-institutionalized Spanish population. Laboratory-confirmed COVID-19 deaths were obtained from the National Epidemiological Surveillance Network (RENAVE) and excess all-cause deaths from the Monitoring Mortality System (MoMo) up to July 15, 2020. SARS-CoV-2 infections were derived from the estimated seroprevalence by a chemiluminiscent microparticle immunoassay for IgG antibodies in 61,092 participants in the ENE-COVID nationwide serosurvey between April 27 and June 22, 2020. Results: The overall IFR (95% confidence interval) was 0.8% (0.8% to 0.9%) for confirmed COVID-19 deaths and 1.1% (1.0% to 1.2%) for excess deaths. The IFR ranged between 1.1% (1.0% to 1.2%) and 1.4% (1.3% to 1.5%) in men and between 0.6% (0.5% to 0.6%) and 0.8% (0.7% to 0.8%) in women. The IFR increased sharply after age 50, ranging between 11.6% (8.1% to 16.5%) and 16.4% (11.4% to 23.2%) in men ≥80 years and between 4.6% (3.4% to 6.3%) and 6.5% (4.7% to 8.8%) in women ≥80 years. Conclusion: The sharp increase in SARS-CoV-2 IFR after age 50 was more marked in men than in women. Fatality from COVID-19 is substantially greater than that reported for other common respiratory diseases such as seasonal influenza. WHAT IS ALREADY KNOWN ON THIS TOPIC: Infection fatality risk (IFR) for SARS-CoV-2 is a key indicator for policy decision making, but its magnitude remains under debate. Case fatality risk, which accounts for deaths among confirmed COVID-19 cases, overestimates SARS-CoV-2 fatality as it excludes a large proportion of asymptomatic and mild-symptomatic infections. Population-based seroepidemiological studies are a valuable tool to properly estimate the number of infected individuals, regardless of symptoms. Also, because ascertainment of deaths due to COVID-19 is often incomplete, the calculation of the IFR should be complemented with data on excess all-cause mortality. In addition, data on age- and sex-specific IFR are scarce, even though age and sex are well known modifiers of the clinical evolution of COVID-19. WHAT THIS STUDY ADDS: Using the ENE-COVID nationwide serosurvey and two national surveillance systems in Spain, this study provides a range of age- and sex-specific IFR estimates for SARS-CoV-2 based on laboratory-confirmed COVID-19 deaths and excess all-cause deaths. The risk of death was very low among infected individuals younger than 50 years, but it increased sharply with age, particularly among men. In the oldest age group (≥80 years), it was estimated that 12% to 16% of infected men and 5% to 6% of infected women died during the first epidemic wave.