Residual blood specimens provide a sample repository that could be analyzed to estimate and track changes in seroprevalence with fewer resources than household-based surveys. We conducted parallel facility and community-based cross-sectional serological surveys in two districts in India, Kanpur Nagar District, Uttar Pradesh, and Palghar District, Maharashtra, before and after a measles-rubella supplemental immunization activity (MR-SIA) from 2018 to 2019. Anonymized residual specimens from children 9 months to younger than 15 years of age were collected from public and private diagnostic laboratories and public hospitals and tested for IgG antibodies to measles and rubella viruses. Significant increases in seroprevalence were observed following the MR SIA using the facility-based specimens. Younger children whose specimens were tested at a public facility in Kanpur Nagar District had significantly lower rubella seroprevalence prior to the SIA compared to those attending a private hospital, but this difference was not observed following the SIA. Similar increases in rubella seroprevalence were observed in facility-based and community-based serosurveys following the MR SIA, but trends in measles seroprevalence were inconsistent between the two specimen sources. Despite challenges with representativeness and limited metadata, residual specimens can be useful in estimating seroprevalence and assessing trends through facility-based sentinel surveillance.

Women infected during pregnancy with TORCH (Toxoplasmosis, Other, Rubella, Cytomegalovirus, and Herpes simplex viruses) pathogens have a higher risk of adverse birth outcomes including stillbirth / miscarriage because of mother-to-child transmission. To investigate these risks in pregnant women in Kenya, we analyzed serum specimens from a pregnancy cohort study at three healthcare facilities. A sample of 481 participants was selected for TORCH pathogen antibody testing to determine seroprevalence. A random selection of 285 from the 481 participants was selected to measure seroconversion. These sera were tested using an IgG enzyme-linked immunosorbent assay against 10 TORCH pathogens. We found that the seroprevalence of all but three of the 10 TORCH pathogens at enrollment was >30%, except for Bordetella pertussis (3.8%), Treponema pallidum (11.4%), and varicella zoster virus (0.5%). Conversely, very few participants seroconverted during their pregnancy and were herpes simplex virus type 2 (n = 24, 11.2%), parvovirus B19 (n = 14, 6.2%), and rubella (n = 12, 5.1%). For birth outcomes, 88% of the participant had live births and 12% had stillbirths or miscarriage. Cytomegalovirus positivity at enrolment had a statistically significant positive association with a live birth outcome (p = 0.0394). Of the 10 TORCH pathogens tested, none had an association with adverse pregnancy outcome.

The rubella disease burden in Zambia may be under-estimated. Using models, we describe the transmission dynamics, determine the incidence estimates and assess the level of underestimation of the real burden of rubella infection in Zambia during the pre-vaccination period 2005–2016. This study used both the deterministic compartmental model and likelihood-based method using a Bayesian framework to describe the epidemiology of rubella. A total of 1313 cases of rubella were confirmed with the highest annual number of 255 new cases recorded in 2008. However, 2014 recorded the highest monthly median positivity rate of 9.0%. The observed median rubella cases were 5.5. There was a seasonal pattern in the occurrence of laboratory-confirmed rubella, with higher test positivity rates of rubella infection usually recorded in the months of September, October and November. The modelled monthly median incidence of rubella infection among the general population was 76 and 20 among pregnant women. The incidence of rubella among the non-pregnant women was 44. The average effective reproductive number (Rt) between 2005 and 2016 was estimated as 1.2 with the peak of infection occurring in 2016. The measles surveillance system underestimates the observed burden of rubella. A mass vaccination campaign conducted between January and July is recommended.

Rubella is a highly contagious mild viral illness. It is a leading cause of congenital rubella syndrome (CRS). Routine data of rubella do not exist in Ethiopia. However, laboratory-based conformation of rubella cases from measles negative samples were collected from a measles surveillance system. The current study was to analyse the epidemiological distribution of rubella cases from measles-suspected cases in Ethiopia from 2011 to 2015. National-based secondary data analysis of rubella through measles-based surveillances was carried out. Measles-suspected cases were investigated using the case investigation form, and a serum sample collected and sent to the Ethiopian laboratory for conformation. Samples tested for measles immunoglobulin M (IgM) were tested for rubella. The investigation results were entered into an electronic database using SPSS version 25 for analysis. Out of 11749 samples tested for rubella IgM from 2011 to 2015, 2295 (19.5%) were positive for rubella IgM and 51% of rubella-positive cases were female. Five per cent of all cases were female aged between 15 and 49. Cases were confirmed from all regions, two administrative towns and seasonal variations were observed with peaks in the first and fourth seasonal periods of the years. As fear of congenital abnormality (CRS), the Ethiopian government should focus on rubella syndrome surveillance with the aim of starting a rubella vaccine.

In Hungary, between February 2017 and July 2019, 70 confirmed measles cases were reported, raising questions about the adequacy of population-level immunity. Although the assumed vaccination coverage is ≥99%, in a recent study, we detected potential gaps in the anti-measles humoral immunity. In Hungary, according to a decree by the Ministry of Public Welfare, beginning from 2021, the healthcare provider should conduct a serosurvey of anti-measles protection levels of healthcare professionals. To facilitate the compliance with this requirement, we developed a quick ‘three-in-one’ or ‘triple’ MMR (measles, mumps and rubella) indirect ELISA (IgG); an assay format that is currently not available commercially. High throughput applicability of the ‘three-in-one’ ELISA was verified using 1736 sera from routine laboratory residual samples, using an automated platform (Siemens BEP 2000 Advance). Assay verification was performed by comparing the full antigen repertoire-based ‘target’ assay with in-house ‘control’ assays using recombinant viral antigen coatings, and by validated commercially available kits. Indirect immunofluorescence was used as an independent reference method. Data were analysed using OriginLab, IBM SPSS, RStudio and MedCalc. In case of measles, we combined our current results with previously published data (Ntotal measles = 3523). Evaluation of anti-mumps and anti-rubella humoral antibody levels was based on the measurement of 1736 samples. The lowest anti-measles seropositivity (79.3%) was detected in sera of individuals vaccinated between 1978 and 1987. Considering the antigen-specific seropositivity ratios of all samples measured, anti-measles, -mumps and -rubella IgG antibody titres were adequate in 89.84%, 91.82% and 92.28%, respectively. Based on the virus-specific herd immunity threshold (HIT) values (HITMeasles = 92–95%, HITMumps = 75–86%, HITRubella = 83–86), it can be stated that regarding anti-measles immunity, certain age clusters of the population may have inadequate levels of humoral immunity. Despite the potential gaps in herd immunity, the use of MMR vaccine remains an effective and low-cost approach for the prevention of measles, mumps and rubella infections.

As part of the evaluation of the French plan for the elimination of measles and rubella, we conducted a seroprevalence survey in 2013, aimed at updating seroprevalence data for people 18–32 years old. A secondary objective was to estimate measles incidence in this population during the 2009–2011 outbreak, and thus estimate the exhaustiveness of measles mandatory reporting. We used a cross-sectional survey design, targeting blood donors 18–32 years old, living in France since 2009, who came to give blood in a blood collecting site. We included 4647 people in metropolitan France, 806 people in Réunion Island and 496 in the French Caribbean. A further 3942 individuals were interviewed in the south-east region of metropolitan France to estimate the exhaustiveness of measles mandatory reporting. One of the main findings of this survey is that the proportion of people 18–32 years old susceptible to both measles and rubella infections remained high in France in 2013, 9.2% and 5.4%, respectively, in metropolitan France, even after the promotion campaigns about vaccination catch-up during and following the major measles epidemic in 2009–2011. Applying our results to French census data would suggest that around 1 million people aged 18–32 years old are currently susceptible to measles in France, despite this age group being one of the vaccination targets of the national measles elimination plan. Another important finding is that only an estimated 45% of the true number of cases in this age group was actually notified, despite notification being mandatory.

Measles is a target for elimination in all six WHO regions by 2020, and over the last decade, there has been considerable progress towards this goal. Surveillance is recognised as a cornerstone of elimination programmes, allowing early identification of outbreaks, thus enabling control and preventing re-emergence. Fever–rash surveillance is increasingly available across WHO regions, and this symptom-based reporting is broadly used for measles surveillance. However, as measles control increases, symptom-based cases are increasingly likely to reflect infection with other diseases with similar symptoms such as rubella, which affects the same populations, and can have a similar seasonality. The WHO recommends that cases from suspected measles outbreaks be laboratory-confirmed, to identify ‘true’ cases, corresponding to measles IgM titres exceeding a threshold indicative of infection. Although serological testing for IgM has been integrated into the fever–rash surveillance systems in many countries, the logistics of sending in every suspected case are often beyond the health system's capacity. We show how age data from serologically confirmed cases can be leveraged to infer the status of non-tested samples, thus strengthening the information we can extract from symptom-based surveillance. Applying an age-specific confirmation model to data from three countries with divergent epidemiology across Africa, we identify the proportion of cases that need to be serologically tested to achieve target levels of accuracy in estimated infected numbers and discuss how this varies depending on the epidemiological context. Our analysis provides an approach to refining estimates of incidence leveraging all available data, which has the potential to improve allocation of resources, and thus contribute to rapid and efficient control of outbreaks.

Common childhood infectious diseases have been associated with a reduced risk of following haematopoietic malignancies, but investigations on multiple myeloma (MM) are scarce. Information about 213 MM cases and 1128 healthy controls were obtained from a multicentre population-based Italian case-control study. The association between chickenpox, measles, mumps, pertussis and rubella and the MM risk was estimated by unconditional logistic regression, adjusting for age, gender and residence area. No association was found between MM risk and any considered infectious disease. The number of infections was slightly inversely associated with the risk of MM, but statistical significance was not reached (OR 0.87, 95% CI 0.55–1.4 for 1-2 diseases vs. none and OR 0.68, 95% CI 0.41–1.1 for 3-5 diseases, respectively, P = 0.131). We did not find a clear evidence that common infections during childhood are associated with the subsequent risk of developing MM.

This study aimed at evaluating the integrated measles and rubella surveillance system (IMRSS) in Apulia region, Italy, from its introduction in 2013 to 30 June 2016. Measles and rubella case reports were extracted from IMRSS. We estimated system sensitivity at the level of case reporting, using the capture–recapture method for three data sources. Data quality was described as the completeness of variables and timeliness of notification as the median-time interval from symptoms onset to initial alert. The proportion of suspected cases with laboratory investigation, the rate of discarded cases and the origin of infection were also computed. A total of 127 measles and four rubella suspected cases were reported to IMRSS and 82 were laboratory confirmed. Focusing our analysis on measles, IMRSS sensitivity was 82% (95% CI: 75–87). Completeness was >98% for mandatory variables and 57% for ‘genotyping’. The median-time interval from symptoms onset to initial alert was 4.5 days, with a timeliness of notification of 33% (41 cases reported ⩽48 h). The proportion of laboratory investigation was 87%. The rate of discarded cases was 0.1 per 100 000 inhabitants per year. The origin of infection was identified for 85% of cases. It is concluded that IMRSS provides good quality data and has good sensitivity; still efforts should be made to improve the completeness of laboratory-related variables, timeliness and to increase the rate of discarded cases.

This study evaluated the impact of maternal vaccination against rubella on the levels of specific rubella IgG (rIgG) in 198 newborn cord sera samples. Detailed maternal vaccination data were available. Specific rIgG was measured using a commercial enzyme immunoassay. Most mothers (78.8%) had been vaccinated against rubella at least once in their lives. In 15 (7.6%) cord sera samples, the concentration of specific rIgG was below 11 IU/ml, which was classified as seronegative. Statistical analysis using multiple logistic regression (n = 198) showed that newborns of mothers born between 1986 and 1995, and those born to unvaccinated mothers, were more likely to be seronegative (odds ratio (ORs) 5.2 and 4.9, respectively, adjusted for sex and gestational age). For vaccinated mothers (n = 156), those born between 1986 and 1995 were more likely to have seronegative newborns (OR 11.5 adjusting for sex, gestational age and time since last vaccination). Mothers of the 15 (7.6%) seronegative newborns might have been susceptible to rubella during pregnancy. Checking the vaccination status therefore recommended.

Rubella virus infection typically presents as a mild illness in children; however, infection during pregnancy may cause the birth of an infant with congenital rubella syndrome (CRS). As of February 2017, India began introducing rubella-containing vaccine (RCV) into the public-sector childhood vaccination programme. Low-level RCV coverage among children over several years can result in an increase in CRS incidence by increasing the average age of infection without sufficiently reducing rubella incidence. We evaluated the impact of RCV introduction on CRS incidence across India's heterogeneous demographic and epidemiological contexts. We used a deterministic age-structured model that reflects Indian states’ rural and urban area-specific demography and vaccination coverage levels to simulate rubella dynamics and estimate CRS incidence with and without RCV introduction to the public sector. Our analysis suggests that current low-level private-sector vaccination has already slightly increased the burden of CRS in India. We additionally found that the effect of public-sector RCV introduction depends on the basic reproductive number, R0, of rubella. If R0 is five, a value empirically estimated from an array of settings, CRS incidence post-RCV introduction will likely decrease. However, if R0 is seven or nine, some states may experience short-term or annual increases in CRS, even if a long-term total reduction in cases (30 years) is expected. Investment in population-based serological surveys and India's fever/rash surveillance system will be key to monitoring the success of the vaccination programme.

In Portugal, the recommended age for the second dose of MMR (MMR2) was changed from 10–13 years to 5–6 years for those born in 1994 and afterwards. This study aimed to assess if MMR schedule and time elapsed from the last dose are associated with the concentration of rubella and mumps IgG antibodies. Three Portuguese birth cohorts (convenience samples) were selected for this study (66, 59 and 41 participants born respectively in 1990–1993, 1994–1995 and 2001–2003). Geometric mean concentrations (GMC) for mumps IgG were respectively 36, 30 and 38 RU/ml (P = 0·236) and for rubella IgG were 18, 20 and 17 IU/ml (P = 0·641). For both specific antibodies, no differences were observed with time since MMR2. Receiving MMR2 at 5–6 or 10–13 years was not associated with concentration of both antibodies. The GMC of rubella IgG was lower in males (P = 0·029). Taking into account previous evidence and the logistics needed to change vaccination schedules, it seems reasonable that sustaining very high coverage with two doses of MMR is currently the most pragmatic way to control mumps and rubella rather than any changes to the schedule.

Significant gaps in immunity to polio, measles, and rubella may exist in adults in Cambodia and threaten vaccine-preventable disease (VPD) elimination and control goals, despite high childhood vaccination coverage. We conducted a nationwide serological survey during November–December 2012 of 2154 women aged 15–39 years to assess immunity to polio, measles, and rubella and to estimate congenital rubella syndrome (CRS) incidence. Measles and rubella antibodies were detected by IgG ELISA and polio antibodies by microneutralization testing. Age-structured catalytic models were fitted to rubella serological data to predict CRS cases. Overall, 29·8% of women lacked immunity to at least one poliovirus (PV); seroprevalence to PV1, PV2 and PV3 was 85·9%, 93·4% and 83·3%, respectively. Rubella and measles antibody seroprevalence was 73·3% and 95·9%, respectively. In the 15–19 years age group, 48·2% [95% confidence interval (CI) 42·4–54·1] were susceptible to either PV1 or PV3, and 40·3% (95% CI 33·0–47·5) to rubella virus. Based on rubella antibody seroprevalence, we estimate that >600 infants are born with CRS in Cambodia annually. Significant numbers of Cambodian women are still susceptible to polio and rubella, especially those aged 15–19 years, emphasizing the need to include adults in VPD surveillance and a potential role for vaccination strategies targeted at adults.

Measles vaccination is estimated to have averted 13·8 million deaths between 2000 and 2012. Persisting heterogeneity in coverage is a major contributor to continued measles mortality, and a barrier to measles elimination and introduction of rubella-containing vaccine. Our objective is to identify determinants of inequities in coverage, and how vaccine delivery must change to achieve elimination goals, which is a focus of the WHO Decade of Vaccines. We combined estimates of travel time to the nearest urban centre (⩾50 000 people) with vaccination data from Demographic Health Surveys to assess how remoteness affects coverage in 26 African countries. Building on a statistical mapping of coverage against age and geographical isolation, we quantified how modifying the rate and age range of vaccine delivery affects national coverage. Our scenario analysis considers increasing the rate of delivery of routine vaccination, increasing the target age range of routine vaccination, and enhanced delivery to remote areas. Geographical isolation plays a key role in defining vaccine inequity, with greater inequity in countries with lower measles vaccine coverage. Eliminating geographical inequities alone will not achieve thresholds for herd immunity, indicating that changes in delivery rate or age range of routine vaccination will be required. Measles vaccine coverage remains far below targets for herd immunity in many countries on the African continent and is likely to be inadequate for achieving rubella elimination. The impact of strategies such as increasing the upper age range eligible for routine vaccination should be considered.

In recent years the number of pregnant women susceptible to rubella has increased markedly. In the West Midlands the proportion has risen from 1·4% in 2004 to 6·9% in 2011. Locally, the proportion of non-immune women ranges from 1·6% in those born prior to 1976 to 17·8% in those born since 1986. The latter group comprises those given MMR in their second year with no further booster doses. The number of non-immune women will continue to rise as a consequence of low MMR uptake in the late 1990s. Repeat testing of samples with values <10 IU/ml and the need to vaccinate women postnatally have increased the workload of laboratory and maternity units. Screening for rubella in pregnancy has no advantages for the current pregnancy and it may be time to review the universal MMR vaccination programme which in turn would remove the need for continuing this practice.

A seroprevalence survey on measles, mumps, rubella and varicella was conducted on healthcare workers (HCWs) at Shimane University Hospital, Japan utilizing an enzyme immunoassay. Of 1811 HCWs tested, 91·8% were seropositive to measles, 92·1% to mumps, 89·5% to rubella and 96·3% to varicella. Sex-related differences in seroprevalence were found in rubella (males vs. females: 84·7 vs. 92·2%, P < 0·001). Moreover, males aged 30–39 years were most susceptible to rubella (22·4%), which may be attributed to the design of childhood immunization programmes in Japan. Individuals aged ⩽29 years were more susceptible to measles (14·3%) and mumps (10·9%), compared to other age groups. There were no significant sex- and age-related differences in varicella seroprevalence. The physician occupational group was more susceptible to rubella, but no significant occupational-related difference was observed in the other diseases. Susceptible subjects, with negative or equivocal serological results were given a vaccine which induced seroconversion in most vaccinees. Seroconversion occurred more frequently in the equivocal group than in the negative group. These findings provide a new insight for the seroprevalence survey of vaccine-preventable diseases in Japanese HCWs with special reference to vaccine efficacy.

Childhood rubella infection in early pregnancy can lead to fetal death or congenital rubella syndrome (CRS) with multiple disabilities. Reduction of transmission via universal vaccination can prevent CRS, but inadequate coverage may increase CRS numbers by increasing the average age at infection. Consequently, many countries do not vaccinate against rubella. The World Health Organization recommends that for safe rubella vaccination, at least 80% coverage of each birth cohort should be sustained. The nonlinear relationship between CRS burden and infection dynamics has been much studied; however, how the complex interaction between epidemic and demographic dynamics affects minimum safe levels of coverage has not been quantitatively evaluated across scales necessary for a global assessment. We modelled 30-year CRS burdens across epidemiological and demographic settings, including the effect of local interruption of transmission via stochastic fadeout. Necessary minimum vaccination coverage increases markedly with birth and transmission rates, independent of amplitude of seasonal fluctuations in transmission. Susceptible build-up in older age groups following local stochastic extinction of rubella increased CRS burden, indicating that spatial context is important. In low birth-rate settings, 80% routine coverage is a conservative guideline, particularly if supplemented with campaigns and vaccination of women of childbearing age. Where birth and transmission rates are high, immunization coverage must be well above 80% and campaigns may be needed. Policy-makers should be aware of the potential negative effect of local extinction of rubella, since heterogeneity in vaccination coverage will shape extinction patterns, potentially increasing CRS burdens.