Secondary Vaccine Failure Research Articles

The Effects of Vaccination Status and Age on Clinical Characteristics and Severity of Measles Cases in the United States in the Post-Elimination Era, 2001-2022.

Despite high vaccine-effectiveness, wild-type measles can occur in previously vaccinated persons. We compared the clinical presentation and disease severity of measles by vaccination status and age in the post-elimination era in the United States. We included U.S. measles cases reported from 2001-2022. Breakthrough measles was defined as cases with ≥1 documented dose of measles-containing vaccine, classic measles as the presence of rash, fever, and ≥1 symptoms (cough, coryza, or conjunctivitis), and severe disease as the presence of pneumonia, encephalitis, hospitalization, or death. Vaccinated cases with low and high avidity IgG were classified as primary (PVF) and secondary (SVF) vaccine failures, respectively. Among 4,056 confirmed measles cases, 2,799 (69%) were unvaccinated, 475 (12%) were breakthrough infections, and 782 (19%) had unknown vaccination; 1,526 (38%), 1,174 (29%), and 1,355 (33%) were aged <5, 5-19, and ≥20 years, respectively. We observed a general decline in classic presentation and severe disease with an increase in the number of doses, and less complications among children aged 5-19 years compared to other age-groups. Among 93 breakthrough cases with avidity results, 11 (12%) and 76 (82%) were classified as PVF and SVF, respectively, with a higher proportion of PVFs having a classic measles presentation and severe disease than SVFs. Breakthrough measles cases tended to have milder disease with less complications. A small proportion of breakthrough infections were due to PVF than SVF. It is critical to maintain high MMR vaccination coverage in the United States to prevent serious measles illnesses.

Comparison of measles plaque reduction neutralization test (PRNT) and measles virus-specific IgG ELISA for assessment of immunogenicity of measles-mumps-rubella vaccination at 5–7 months of age and maternal measles antibodies

BackgroundAssessing the risk of measles outbreaks and identifying the susceptible parts of the population is essential to timely intervention. Infants between 6–12 months are increasingly susceptible to measles but evaluating the performance of high throughput enzyme immunoassays (ELISAs) in infants < 9 months of age is lacking. MethodsA commercially available ELISA kit (Creative Diagnostics, DEIA359) for estimating measles seroprotection was evaluated in infants 5–7 months of age. In an immunogenicity substudy in the Danish MMR trial conducted between 2019–2021, infants (and mothers at baseline) were sampled before and one month after measles-mumps-rubella vaccination (MMR) or placebo as well as one month after routine MMR at 15 months. Measles IgG ELISA was compared to the gold standard but labor-intensive measles plaque reduction neutralization test (PRNT) by Pearson and Spearman correlations and by estimating sensitivity, specificity, and positive and negative predictive values (PPV and NPV). FindingsMeasles IgG levels compared to PRNT antibodies had a Pearson’s correlation coefficient between 0.10–0.24. Seroprotection rates measured by ELISA in young infants were 10–14% lower than measured by PRNT. The sensitivity of the ELISA to detect serological protection compared to PRNT in the infant population differed markedly across sampling time points and was 14%, 40%, and 92% at baseline, post-intervention, and post-routine MMR, whereas the specificity was 99%, 93%, and 43%, respectively. The PPV and NPV were 68% and 87% in infants at baseline. InterpretationThe correlation between measles IgG and PRNT antibodies was low. Seroprotection was underestimated using ELISA. High-accuracy tests are needed to avoid misclassifications and practices that lead to primary or secondary vaccine failure or retention of vaccination in outbreak settings. Baseline PPV and NPV suggested some applicability of ELISA in predicting serological protection in this age group. However, PRNT may be the only accurate estimator of serological protection in young infants.

Breakthrough Measles among Vaccinated Adults Born during the Post-Soviet Transition Period in Mongolia.

Mongolia experienced a nationwide measles outbreak during 1 March 2015-31 December 2016, with 49,077 cases reported to the WHO; many were among vaccinated young adults, suggesting a possible role of vaccine failure. Advanced laboratory methods, coupled with detailed epidemiological investigations, can help classify cases as vaccine failure, failure to vaccinate, or both. In this report, we conducted a study of cases to identify risk factors for breakthrough infection for a subset of laboratory-confirmed measles cases. Of the 193 cases analyzed, only 19 (9.8%) reported measles vaccination history, and 170 (88%) were uncertain. Measles-specific IgG avidity testing classified 120 (62%) cases as low IgG avidity, indicating no prior exposure to measles. Ten of these cases with low IgG avidity had a history of measles vaccination, indicating primary vaccine failure. Overall, sixty cases (31%) had high IgG avidity, indicating breakthrough infection after prior exposure to measles antigen through vaccination or natural infection, but the IgG avidity results were highly age-dependent. This study found that among young children aged 9 months-5 years, breakthrough infection was rare (4/82, 5%); however, among young adults aged 15-25 years, breakthrough infection due to secondary vaccine failure (SVF) occurred on a large scale during this outbreak, accounting for the majority of cases (42/69 cases, 61%). The study found that large-scale secondary vaccine failure occurred in Mongolia, which highlights the potential for sustained outbreaks in post-elimination settings due to "hidden" cohorts of young adults who may have experienced waning immunity. This phenomenon may have implications for the sustainability of measles elimination in countries that remain vulnerable to the importation of the virus from areas where it is still endemic. Until global measles elimination is achieved, enhanced surveillance and preparedness for future outbreaks in post- or peri-elimination countries may be required.

Seroepidemiology of measles in immune generation in Taiwan: Prevalence of neutralizing antibody and immune response to reimmunization.

Secondary vaccine failure was the principal mechanic of measles reemergence in countries with high measles vaccine coverage. The information on neutralizing antibody (nAb) prevalence, epidemiological factors of waned immunity and immune response after reimmunization was essential to measles control but largely lacking in Taiwan. The nAb and factors of wanned immunity to measles were evaluated in a cohort of 333 subjects aged 11-30 years in 2010. The longitudinal immune response to reimmunization (n=30) and potential virus exposure (n=24) were assessed in young healthcare workers (HCWs) during a hospital outbreak. The nAb titer was used to define susceptibility to measles disease (<120 mIU/mL) and infection (120-900 mIU/mL). In the 2010 cohort, the susceptibility to measles diseases and infections was respectively identified in 35 (10.5%) and 226 (67.9%) subjects. A generalized linear model identified earlier ages of first immunization in childhood (P=0.0214) and subjects aged ≥18 years (versus <18 years, P=0.0425) as significant factors associated with lower nAb titers. Reimmunization of 30 seronegative HCWs resulted in seroconversion for all, with nAb titers significantly rising on day 5, peaking on day 15 and declining in month 4 post-immunization. Similar measles-specific IgG levels were observed in 24 seropositive HCWs before and 4 months after measles contact (P=0.2352). A lack of protective immunity to measles diseases might be identified in 10% of the Taiwanese population aged 11-30 years and associated with a trend toward earlier ages of the first measles vaccination. The wanned immunity can be boosted promptly by reimmunization but with uncertain durability.

Causes of a Low Measles Seroprevalence among Young Healthcare Workers in Korea.

Sporadic measles outbreaks have continued to occur in Korea, mainly in adults in their 20s and 30s, most notably in 2014 and 2019. We here evaluated the possible causes of a low seroprevalance of measles by testing young healthcare workers (HCWs). This study was conducted in a 2,743-bed tertiary-care hospital in Seoul between 2020 and 2021. We performed a measles antibody test (chemiluminescence immunoassay), measured the IgM/IgG index ratio, and conducted an avidity test at 1-month after Measles-Mumps-Rubella (MMR) vaccination in HCWs who had been seronegative for measles. Measles vaccination histories were obtained from the national vaccine registry. Of the 3,173 HCWs newly employed in our hospital during the study period, 54 with a negative measles IgG at commencement were enrolled. Thirty six (67%) of these subjects were female, and the median age was 25 years (interquartile range [IQR]: 24 - 27). Fourty nine (91%) showed seroconversion at 1 month after the first vaccination. Of these individuals, 38 received both measles IgM and IgG test, and all had an IgM/IgG index <1. Of the 49 seroconverters, all HCWs showed a high avidity index. According to the national immunization registry, 45 (83%) received at least 2 doses of an MMR vaccination. Secondary vaccine failure may underlie vaccine failure in young Korean adults. HCWs born after 1985 with a negative measles antibody may need only a single dose booster vaccination rather than a 2-dose vaccination regimen.

435. Investigation of the cause of low measles seroprevalence among young healthcare workers in South Korea

Abstract Background After a large measles outbreak in 2000∼2001, national measles vaccination program was implemented in Korea, and more than 95% of people born after 1985 have been vaccinated with 2-dose MMR. But sporadic outbreaks have continued to occur mainly in adults in their 20’s and 30’s in 2014 and 2019. Although low prevalence in young adults have been reported, there are limited data regarding the cause of low seropositivity (positive vaccine failure vs. secondary vaccine failure). We aimed to evaluate the cause of low seroprevalence of measles. Methods This study was performed in a 2743-bed tertiary-care hospital in South Korea. At 1-month after MMR vaccination in healthcare workers (HCWs) who were seronegative for measles, we performed measles antibody test(enzyme immunoassay), IgM/IgG index ratio, and avidity test. Results Of the 1,698 new HCWs in 2020 and, 1,686 in 2021, 54 HCWs with negative measles IgG at their entering at our hospital were enrolled in this study. Of these, 36(67%) were female, and the median age was 25 (IQR, 24-27) years. Of 43 HCWs who measured IgM/IgG index 1 month after MMR vaccination, 38 HCWs had IgM/IgG index of less than 1 and remaining 5 had negative IgG results (seroconversion rate of 88%). All 54 healthcare workers who performed avidity test showed high avidity index Measles vaccination record in KCDA showed that 45 had documented vaccination record during their childhood (of these, 11 received MMR vaccine again during their adult age) and remaining 9 had no documented vaccination record during their childhood. Of these 9 healthcare workers without record in their childhood, 3 had a history of vaccination at adult. Analyzing 48 healthcare workers with vaccination record, they received MMR vaccination median 18 years (IQR, 7-20) before. Therefore, at least 48 received at least 2 dose MMR vaccination, and 11 received at least 3 dose MMR vaccination. Conclusion Secondary vaccine failure may be the reason for vaccine failure in young adults in Korea. Therefore, HCWs with negative measles antibody who were born after 1985 may receive 1 dose booster vaccination rather than 2 dose vaccination. Disclosures All Authors: No reported disclosures.

Immunogenicity after outbreak response immunization activities among young healthcare workers with secondary vaccine failure during the measles epidemic in Korea, 2019.

BackgroundDespite high vaccination coverage, measles outbreaks have been reported in measles elimination countries, especially among healthcare workers in their 20 and 30 s. This study was designed to identify measles-susceptible individuals and to evaluate whether primary or secondary vaccine failure occurred during measles outbreak response immunization (ORI) activities.MethodsThe study population was divided into three groups as follows: natural immunity group (Group 1), vaccine-induced immunity group (Group 2), and vaccine failure group (Group 3). We evaluated the immunogenicity of measles among healthcare workers using three methods—enzyme-linked immunoassays, plaque reduction neutralization tests, and avidity assays. The results were assessed at baseline, 4 weeks after, and 6 months after the completion of measles-mumps-rubella (MMR) vaccination.ResultsIn total, 120 subjects were enrolled, with 40 subjects in each group. The median age of Group 3 was 29 years, which was significantly lower than that of the other groups. The baseline negative measles virus (MeV) IgG in Group 3 increased to a median value of 165 AU/mL at 4 weeks after ORI and was lower than that in Groups 1 and 2. The median neutralizing antibody titer was highest in Group 1, and this was significantly different from that in Group 2 or Group 3 at 4 weeks (944 vs. 405 vs. 482 mIU/mL, P = 0.001) and 6 months (826 vs. 401 vs. 470, P = 0.011) after ORI. The rates of high MeV avidity IgG were highest in Group 2, and these were significantly different from those in Groups 1 or 3 at 4 weeks (77.5 vs. 90% vs. 88.6%, P = 0.03) and 6 months (81 vs. 94.8 vs. 82.1%, P = 0.01) after ORI.ConclusionsConsidering the MeV-neutralizing antibodies and IgG avidity after MMR vaccination in measles-susceptible group, vaccine failure is inferred as secondary vaccine failure, and further data regarding the maintenance of immunogenicity are needed based on long-term data. The MeV-neutralizing antibody levels were highest in the natural immunity group, and the primary vaccine-induced immunity group showed the highest rates of high MeV IgG avidity.

Classification of measles breakthrough cases in an elimination setting using a comprehensive algorithm of laboratory results: why sensitive and specific IgM assays are important

ObjectiveIn 2006, a measles outbreak occurred in Catalonia (Spain), six years after endemic measles was declared eliminated. This study aimed to classify 19 confirmed measles breakthrough cases (BC) using a high-performance avidity assay developed in 2010. MethodsSerum specimens were tested by indirect IgG, indirect IgM, capture IgM enzyme immunoassay, an endpoint-titer IgG avidity assay, and a plaque reduction neutralization assay. Serology and RNA detection results were combined in an algorithm for measles confirmation and classification of breakthrough cases and analyzed with clinical and epidemiological data. ResultsOf 19 samples, thirteen (68%) were conclusive with the classification of BCs, and six (32%) had false-positive IgM results on an indirect-format assay; they were classified as rash and fever illness of undetermined etiology. BCs were primary vaccine failures (seven or 54%), secondary vaccine failures (four or 31%), and two (15%) could not be classified. ConclusionsIn measles elimination settings, high-performing assays and a comprehensive algorithm of laboratory results (IgG, IgM, and RNA detection), including IgG avidity and PRN results when necessary, can assist in accurate laboratory confirmation and classification of suspected measles cases for surveillance. Highly specific IgM assays are required to minimize the number of false-positive results.

Measles infection in persons with secondary vaccine failure, New York City, 2018–19

A large measles outbreak in New York City, which included cases among vaccinated persons and adults presumed to be immune, provided the opportunity to better understand vaccine failure and the potential impact on measles transmission. Immunoglobulin G (IgG) avidity can distinguish primary (low avidity IgG, indicating no evidence of prior immunity) versus secondary vaccine failure (high avidity IgG, indicating prior immune response and waning antibody). Measles IgG avidity was measured on samples from 62 persons: avidity was high in 53 (16 vaccinated and 37 with unknown vaccination history) and low in 9 (1 recently vaccinated and 8 with unknown vaccination history). Secondary transmission from 2 persons with high-avidity IgG results occurred. These findings illustrate that in settings of sustained measles elimination, measles infection and transmission can occur in persons with secondary vaccine failure, underscoring the need to maintain a high index of suspicion for measles during an outbreak despite prior or presumed prior vaccination.

Relationship between biochemical markers and measles viral load in patients with immunologically naive cases and secondary vaccine failure: LDH is one of the potential auxiliary indicators for secondary vaccine failure.

This study investigated the correlation between biochemical markers and viral load among 38 measles cases, including 15 immunologically naive patients and 23 patients with secondary vaccine failure (SVF). We examined four biochemical markers, namely, aspartate aminotransferase, alanine aminotransferase, C-reactive protein, and lactate dehydrogenase (LDH) and their relationship between virus genome copy numbers in peripheral blood mononuclear cells (PBMCs) and throat swabs as well as the concentration of measles-specific IgG. Although viral genome copies in both clinical specimens showed a significant correlation with specific IgG concentration, they had a higher correlation in PBMCs (Pearson's product-moment correlation coefficient, -0.662; p < .0001) than in throat swabs (Spearman's rank correlation coefficient, -0.443; p = .0078). The viral load in PBMCs also significantly correlated with LDH values (correlation coefficient, 0.360; p = .036). Thus, the serum LDH level might be a potential auxiliary indicator to distinguish immunologically naive patients with measles from those with SVF.

Measles and rubella serosusceptibity among population vaccinated with different schedules: the potential impact on measles-rubella elimination in Iran

BackgroundIranian children were vaccinated with the scheduled two doses of monovalent measles vaccine (mMV) from 1984. In December 2003, a nationwide campaign of measles-rubella (MR) immunization was established to vaccinate 5–25 year- old individuals. In 2004, the mMV was replaced with measles- mumps- rubella (MMR) vaccine. Despite the high vaccination coverage, the outbreaks of measles still occur in the country. In this Study, the MR immunity status of various age groups, vaccinated with different schedules was investigated, and the immunologic response of seronegative subjects to revaccination was examined.MethodsThis cross-sectional study was conducted among 7–33-year-old healthy individuals with a documented history of measles vaccination from November 2017 to June 2018. The subjects were categorized as follows: group A, including 20–33 year-old individuals; vaccinated with 1–2 doses of mMV at ages 9 and 15 months, and revaccinated with MR, group B, including 15–19-year-old individuals, vaccinated with two doses of mMV at 9 and 15 months of age, and received additional dose of MMR upon school entrance, group C, including 11–14 year-old individuals, vaccinated with two-doses of MMR at the ages of 15 months and 6 years, and group D, including 7–10 year-old individuals vaccinated with two-doses of MMR vaccine at the ages 12 and 18 months, respectively. Levels of antimeasles- antirubella IgG antibodies in the collected sera were measured. Also antimeasles- antirubella IgM and IgG of seronegative individuals were reexamined at 4–6 weeks after MMR revaccination. The collected data were analyzed using descriptive statistical methods.ResultsA total of 635 individuals were investigated in this study. Group A, 98; group B, 295; group C, 139; and group D, 103 persons. Overall, 12.3 and 18.4% of the population were seronegative for measles and rubella antibodies. This rate varied greatly between the 4 groups: group A, 0/0–2%; group B,15.2–25.0%; group C,11.5–17.2%; and groupD,14.6–18.4%. After revaccination, 92 and 94.9% of seronegative individuals showed IgG response to measles and rubella vaccines, respectively.ConclusionDespite the high coverage rate of M-R containing vaccines, a significant number of vaccinated subjects were seronegative for measles and rubella, possibly because of secondary vaccine failure; this may negatively affect measles-rubella elimination targets in the country. If these findings are confirmed in similar future studies, a more robust regional/national supplementary immunization activity will be considered.

A measles outbreak in Kansai International Airport, Japan, 2016: Analysis of the quantitative difference and infectivity of measles virus between patients who are immunologically naive versus those with secondary vaccine failure.

Since the elimination of the measles virus, patients with vaccination records for the measles-containing vaccine have increased in Japan. According to several studies, the transmission risk from previously immunized patients, especially those with secondary vaccine failure (SVF), is lower than that from those with primary measles infections. Immunological features of SVF were identified per specific immunoglobulin G (IgG) induction with high avidity and high plaque reduction neutralization antibody concentration. However, the virological features of SVF have not been well investigated. To examine not only immunological but also virological differences between SVF and immunologically naive patients, throat swabs and blood and urine specimens of 25 patients with confirmed measles infection after an outbreak at the Kansai International Airport in 2016 were analyzed. Patients were categorized as naive (n = 3) or with SVF (n = 22) based on measles-specific IgG antibody concentrations and their avidity. Virus isolation and quantitative real-time polymerase chain reaction were performed to quantify the viral load in clinical specimens and estimate the infectivity in each specimen. The number of viral genome copies in the blood specimens of those with SVF was significantly different and approximately 1 out of 100 of that in immunologically naive patients. However, genome copy numbers in throat swabs and urine specimens were not significantly different between the groups. The virus was isolated only from those in the naive group. Our study indicated low transmission risk of the virus in patients with SVF.

Mumps Outbreaks in Vaccinated Populations-Is It Time to Re-assess the Clinical Efficacy of Vaccines?

History illustrates the remarkable public health impact of mass vaccination, by dramatically improving life expectancy and reducing the burden of infectious diseases and co-morbidities worldwide. It has been perceived that if an individual adhered to the MMR vaccine schedule that immunity to mumps virus (MuV) would be lifelong. Recent mumps outbreaks in individuals who had received two doses of the Measles Mumps Rubella (MMR) vaccine has challenged the efficacy of the MMR vaccine. However, clinical symptoms, complications, viral shedding and transmission associated with mumps infection has been shown to be reduced in vaccinated individuals, demonstrating a benefit of this vaccine. Therefore, the question of what constitutes a good mumps vaccine and how its impact is assessed in this modern era remains to be addressed. Epidemiology of the individuals most affected by the outbreaks (predominantly young adults) and variance in the circulating MuV genotype have been well-described alluding to a collection of influences such as vaccine hesitancy, heterogeneous vaccine uptake, primary, and/or secondary vaccine failures. This review aims to discuss in detail the interplay of factors thought to be contributing to the current mumps outbreaks seen in highly vaccinated populations. In addition, how mumps diagnoses has progressed and impacted the understanding of mumps infection since a mumps vaccine was first developed, the limitations of current laboratory tests in confirming protection in vaccinated individuals and how vaccine effectiveness is quantified are also considered. By highlighting knowledge gaps within this area, this state-of-the-art review proposes a change of perspective regarding the impact of a vaccine in a highly vaccinated population from a clinical, diagnostic and public perspective, highlighting a need for a paradigm shift on what is considered vaccine immunity.

Immunogenicity and persistence of trivalent measles, mumps, and rubella vaccines: a systematic review and meta-analysis

Despite the universal use of the two-dose trivalent measles-mumps-rubella (MMR) vaccine in the past two decades, outbreaks of these diseases still occur in countries with high vaccine uptake, giving rise to concerns about primary and secondary failure of MMR vaccine components. We aimed to provide seroconversion and waning rate estimates for the measles, mumps, and rubella components of MMR vaccines. In this systematic review and meta-analysis we searched PubMed (including MEDLINE), Web of Science, and Embase for randomised controlled trials, cohort studies, or longitudinal studies reporting the immunogenicity and persistence of MMR vaccines, published in English from database inception to Dec 31, 2019. Studies were included if they investigated vaccine-induced immunity in healthy individuals who received a trivalent MMR vaccine, including different dosages and timepoints of vaccine administration. Studies featuring coadministration of MMR with other vaccines, maternal immunity to the MMR vaccine, or non-trivalent formulations of the vaccine were excluded. Pooled seroconversion and waning rates were estimated by random-effects meta-analyses. This study is registered with PROSPERO, CRD42019116705. We identified 3615 unique studies, 62 (1·7%) of which were eligible for analysis. Estimated overall seroconversion rates were 96·0% (95% CI 94·5-97·4; I2=91·1%) for measles, 93·3% (91·1-95·2; I2=94·9%) for mumps when excluding the Rubini strain, 91·1% (87·4-94·1; I2=96·6%) for mumps when including the Rubini strain, and 98·3% (97·3-99·2; I2=93·0%) for rubella. Estimated overall annual waning rates were 0·009 (95% CI 0·005-0·016; I2=85·2%) for measles, 0·024 (0·016-0·039; I2=94·7%) for mumps, and 0·012 (0·010-0·014; I2=93·3%) for rubella. Our meta-analysis provides estimates of primary and secondary vaccine failure, which are essential to improve the accuracy of mathematical and statistical modelling to understand and predict the occurrence of future measles, mumps, and rubella outbreaks in countries with high vaccine uptake. European Research Council.

Using the Surveillance Tool EpiWATCH to Rapidly Detect Global Mumps Outbreaks.

Background: Non-validated, rapid intelligence surveillance data is becoming more important in detecting and responding to public health emergencies in the absence of readily available, validated surveillance data published by reputable sources such as WHO or the CDC. There is a lack of timely mumps surveillance data, which is particularly concerning as a resurgence of mumps outbreaks seem to be occurring worldwide in fully vaccinated young adults. Methods: Using open-source mumps data obtained between 2016-2019 from the rapid intelligence surveillance tool EpiWATCH, a descriptive analysis was conducted to identify information about the number of confirmed/probable/suspected mumps cases and also the date, country, and location of outbreaks. Results: Data entries logged into EpiWATCH detected 65 mumps outbreaks worldwide with a majority of outbreaks occurring in university settings, where a majority of students had been fully vaccinated against the disease. School and university settings were identified as high-risk environments susceptible to mumps outbreaks explained by the prolonged, close-contact nature in which students interact. EpiWATCH was able to detect reported cases of mumps within days of news outlets publishing this information; far quicker than the months it takes for case data to be published by validated sources. EpiWATCH was also able to capture mumps outbreak data not previously detected by WHO or the CDC. Conclusions: The resurgence of mumps in fully vaccinated young adults is likely due to secondary vaccine failure and possibly genetic drift of WT mumps strains. Global and readily available mumps surveillance data is lacking; however, EpiWATCH has been successful in somewhat filling these gaps of information and, more importantly, providing surveillance data in a timely fashion. Thus, data from EpiWATCH could be used in the field to improve the speed of detection and response to mumps outbreaks.

Measles Virus IgG Avidity Assay for Use in Identification of Measles Vaccine Failures in Tianjin, China

ObjectiveTo identify measles vaccine failures in Tianjin, China using a measles virus IgG avidity assay. MethodsThe China Information System for Disease Control and Prevention (CISDCP) was used to collect information about measles cases and blood specimens in Tianjin from 2013 to 2015. Measles-specific IgM and IgG antibodies were detected using Enzyme-Linked Immunosorbent Assay (ELISA). Avidity testing for measles IgG was performed using a commercial enzyme immunoassay (EIA). ResultsA total of 284 confirmed measles cases were identified. Of this total, 262 (92.25%) were in patients aged ≥ 20 years. High avidity was exhibited in 172 (60.56%) cases, while 80 (28.17%) cases demonstrated low avidity. High avidity was detected in only 21.43% of cases in patients aged < 1 year. The proportion of high avidity increased with age, and was significantly higher in patients aged 30–39 years at 70.07% (χ2 = 17.27, P = 0.002). Of the 52 measles cases in patients with a history of vaccinations, 41 (78.85%) cases showed high avidity, indicating secondary vaccine failures (SVF). In these vaccinations, there was no significant difference (P > 0.05) in clinical severity between high avidity and low avidity cases. However, regardless of vaccination status, clinical severity was significantly lower in high avidity cases (P < 0.001) than in low avidity cases. The percentages of positive measles IgM results in high avidity and low avidity cases were 66.28% and 91.25%, respectively. Geometric Mean Concentration (GMC) was significantly lower in high avidity cases at 33.73 U/mL, compared to 166.07 U/mL in low avidity cases. ConclusionsLow clinical severity and inconclusive IgM antibody results are more likely in high avidity measles cases. Measles cases were more common in adults. Therefore, a further dose of vaccines should be recommended for 30–39 years in Tianjin.

A measles outbreak from an index case with immunologically confirmed secondary vaccine failure

During the elimination stage of measles, the development of such disease in individuals who received measles-containing vaccine (MCV) is a concern from an epidemiological standpoint. A few cases in which measles was transmitted from a patient who received two doses of MCV have been reported. However, whether such transmissions were caused by primary vaccine failure (PVF) or secondary vaccine failure (SVF) remains unclear. All patients suspected of measles in Osaka Prefecture between November and December 2018 were enrolled. Data about age, gender, immunization record, and clinical signs were obtained. Laboratory examinations were performed, which included virus isolation in tissue culture, a nucleic acid test based on virus-specific real-time polymerase chain reaction and humoral responses to the measles virus measuring immunoglobulin (Ig) M, IgG, avidity of IgG, and neutralizing antibody concentration. The measles outbreak comprised 10 laboratory confirmed cases, including three secondary and six tertiary patients. Among them, three secondary patients were unvaccinated. The index case had received two MCV doses, and the six tertiary patients were vaccinated. Both the index and tertiary patients had high specific IgG concentration with high avidity. In particular, the index patient had a markedly high neutralization antibody concentration of 425,590 mIU/mL, which indicated immunological SVF. This study first reported about measles transmission from an individual with SVF who received two vaccination doses. To prevent measles transmission and outbreak particularly in countries where measles was almost eliminated, patients with SVF for measles should be cautiously monitored.

Measles outbreak from Hong Kong International Airport to the hospital due to secondary vaccine failure in healthcare workers.

To report an outbreak of measles with epidemiological link between Hong Kong International Airport (HKIA) and a hospital. Epidemiological investigations, patients' measles serology, and phylogenetic analysis of the hemagglutinin (H) and nucleoprotein (N) genes of measles virus isolates were conducted. In total, 29 HKIA staff of diverse ranks and working locations were infected with measles within 1 month. Significantly fewer affected staff had history of travel than non-HKIA-related measles patients [10 of 29 (34.5%) vs 28 of 35 (80%); P < .01]. Of 9 airport staff who could recall detailed exposure history, 6 (66.7%) had visited self-service food premises at HKIA during the incubation period, where food trays, as observed during the epidemiological field investigation, were not washed after use. Furthermore, 1 airport baggage handler who was admitted to hospital A before rash onset infected 2 healthcare workers (HCWs) known to have 2 doses of MMR vaccination with positive measles IgG and lower viral loads in respiratory specimens. Infections in these 2 HCWs warranted contact tracing of another 168 persons (97 patients and 71 HCWs). Phylogenetic comparison of H and N gene sequences confirmed the clonality of outbreak strains. Despite good herd immunity with overall seroprevalence of >95% against measles, major outbreaks of measles occurred among HKIA staff having daily contact with many international pssengers. Lessons from severe acute respiratory syndrome (SARS) and measles outbreaks suggested that an airport can be a strategic epidemic center. Pre-exanthem transmission of measles from airport staff to HCWs with secondary vaccine failure poses a grave challenge to hospital infection control.

Continuing rotavirus circulation in children and adults despite high coverage rotavirus vaccination in Finland

ObjectivesTo determine occurrence of residual rotavirus (RV) disease in different age groups in Finland after five to nine years of high coverage (≥90%) mass-vaccination with RotaTeqⓇ vaccine, and to examine the vaccine effect on circulating genotypes. MethodsSince 2013 all clinical laboratories in the country were obliged to send RV positive stool samples for typing. RVs were genotyped by RT-PCR for VP7 and VP4 proteins, sequenced and compared to reference strains. ResultsRV continued to circulate throughout the study period at low level with a small increase in 2017–2018. There were three age-related clusters: young children representing primary or secondary vaccine failures, school-age children who may not have been vaccinated, and the elderly. Genotype distribution differed from the pre-vaccination period with a steady decline of G1P[8], emergence of G9P[8] and especially more recently G12P[8]. In the elderly, G2P[4] was predominant but was also replaced by G12P[8] in 2017–18. ConclusionsRV vaccination with a high coverage keeps RV disease at low level but does not prevent RV circulation. New RV genotypes have emerged replacing largely the previously predominant G1P[8]. Increase of overall RV activity with emergence of G12P[8] in the latest follow-up season 2017–18 might be a potential alarm sign.

Outbreak of measles among persons with secondary vaccine failure, China, 2018

ABSTRACTAlthough the incidence of measles has been dramatically reduced by the highly effective measles vaccine, cases of measles and outbreaks continue to occur in vaccinated population because of immunization failure. We report on an outbreak in which two cases had previous evidence of measles immunity and then one of them transmitted measles infection to an unvaccinated contact. The cases and contacts exposed during the outbreak were investigated. Clinical information and epidemiological information were obtained. Serum samples were collected for measles-specific immunoglobulin M (IgM), immunoglobulin G (IgG) and IgG avidity. Throat swabs were obtained to test for measles virus RNA. Two measles cases (case 1 and case 2) who have received one dose of MCV in past 5 years, and both working at a hospital in Beijing, occurred in 18th and 20nd of January, respectively. Out of the 102 contacts, one additional case (case 3) who had a close, long-term co-exposure with case 1 was reported subsequently. No additional cases of measles occurred among 15 contacts of case 3. The index case was not ascertained through the outbreak review. All three cases had laboratory confirmation of measles infection. Both case 1 and case 2 had high-avidity IgG antibody characteristic of a secondary immune response and developed a modified clinical presentation. This report confirms that a vaccinated individual with documented secondary vaccine failure (SVF) could transmit measles and is the second report since a New York City outbreak (the first report in China). The outbreak represented a series of rare events, so we can conclude that the SVF individuals in the transmission chain of measles are unlikely to threaten measles elimination. The importance of the herd immunity in preventing transmission and sensitive surveillance activities in case of misdiagnosis is emphasized.