Detection of Antibodies against Feline Morbillivirus by Recombinant Matrix Enzyme-Linked Immunosorbent Assay.

Feline morbillivirus (FeMV) has been associated with feline health, although its exact role in pathogenesis is still debated. In this study, an indirect enzyme-linked immunosorbent assay (i-ELISA) targeting a recombinant matrix protein of FeMV (rFeMV-M) was developed and assessed in comparison to a Western blotting (WB) assay. The i-ELISA was evaluated using blood samples from 136 cats that were additionally tested with real-time reverse-transcription PCR (RT-qPCR). The i-ELISA exhibited a sensitivity of 90.1%, specificity of 75.6%, positive predictive value of 88.2%, and negative predictive value of 79.1%. The agreement between i-ELISA and WB analyses was substantial (a κ coefficient of 0.664 with a 95% confidence interval of 0.529 to 0.799). Within the study group, 68.4% (93/136) of the cats were serologically positive in the i-ELISA and 66.9% (91/136) in the WB assay, with 11.8% (11/93) of false positivity with the i-ELISA. However, only 8.1% (11/136) of the cats tested positive for FeMV using RT-qPCR (p < 0.001). The developed i-ELISA proved effective in identifying FeMV-infected cats and indicated the prevalence of FeMV exposure. Combining FeMV antibody detection through i-ELISA with FeMV RT-qPCR could offer a comprehensive method to determine and monitor FeMV infection status. Nevertheless, this assay still requires refinement due to a significant number of false positive results, which can lead to the misdiagnosis of cats without antibodies as having antibodies. This study also provided the first evidence of seroprevalence against FeMV among cat populations in Thailand, contributing valuable insights into the geographic distribution and prevalence of this virus.

Seroprevalence of Infection with Feline Morbilliviruses Is Associated with FLUTD and Increased Blood Creatinine Concentrations in Domestic Cats.

Feline morbilliviruses (FeMV) are fairly newly discovered paramyxoviruses found in cats. The first description indicated an association with widely distributed chronic kidney disease (CKD) in the host species. In various studies, a global prevalence and a further genotype, designated FeMV-2, and the involvement of other organ systems in infected individuals were shown. Using an immunofluorescence assay, we detected an overall seroprevalence of FeMV in almost half of the cats investigated (n = 380), with a significantly increased proportion in younger animals. In comparison to European Shorthair cats, the rate of seropositivity is higher in pedigree cats. Regardless of the breed, FeMV infection was associated with increased blood creatinine concentrations, suggesting an association with CKD. Further analysis indicated that this association was the strongest in animals having high IFA titers against FeMV-2. In addition, a significant association between FeMV-positive status and the prevalence of feline lower urinary tract disease (FLUTD, or idiopathic cystitis) was detected. This association was dominated by cats having antibodies against FeMV-1 only. To further evaluate the positive correlation between FeMV seroprevalence and CKD as well as FLUTD, consideration of additional clinical characteristics and laboratory parameters is warranted, and controlled infection studies with both FeMV genotypes are necessary. Clinicians should, however, be aware of a possible link between renal and lower urinary tract disease and FeMV infections.

What Is the Prevalence of Measles Immunity among Pregnant Women?

OBJECTIVE: This study aimed to estimate the prevalence of measles immunity in a cohort of pregnant women in New York City and determine if there is a positive correlation of measles immunity with patient demographics, rubella immunity, number of measles, mumps, and rubella vaccine (MMR) doses received, and age at last vaccination. STUDY DESIGN: This is a cross-sectional study of pregnant patients seen at a single institution from January 2019 to May 2019. Patients were classified as measles and rubella immune or nonimmune using commercial immunoglobulin G (IgG) tests. Patient characteristics were compared using t-tests, Chi-square tests, or Fisher's exact tests as appropriate. The association of age at last vaccination with immunity status was assessed using multivariable logistic regression adjusted for age at presentation. The utility of rubella IgG for distinguishing measles immunity was assessed using receiver operating characteristic curve analysis. RESULTS: Serologic immunity for measles and rubella was obtained for 1,366 patients. Of these, 1,047 (77%) were measles immune and 1,291 (95%) were rubella immune. Patients born after 1989 were less likely to be immune to measles, while multiparity and private insurance were associated with increased measles immunity. Documentation of MMR vaccination was available for 140 (10%) patients. Of these, 44 (31%) were serologically nonimmune to measles and 9 (6.4%) were nonimmune to rubella. In patients known to have received one dose of MMR, 62% (24/39) were immune to measles with an improvement to 72% (69/96) among those who received two or more doses. Age at last vaccination was not associated with measles immunity. Rubella IgG level was a poor predictor of positive measles titer (area under the curve = 0.59). CONCLUSION: Approximately one of every four pregnant patients is serologically measles nonimmune, even among women with documented MMR vaccination or documented rubella immunity. These findings raise concerns that relying on vaccination history or rubella immune status may not be sufficient to assure protection from infection with measles. If further suggests that measles serology should be added to routine prenatal laboratory testing to identify nonimmune patients that may benefit from postpartum vaccination. KEY POINTS: · Approximately one of every four pregnant patients were serologically measles nonimmune.. · Rubella immunoglobulin G was a poor predictor of measles immunity status.. · Measles serology should be added to routine prenatal laboratory testing..

High seroprevalence of feline morbilliviruses in free-roaming domestic cats in Chile.

Feline morbillivirus infections have gained increased attention due to repeated reports of their association with urinary tract disease in cats. In the present study, 112 serum samples from free-roaming domestic cats in Chile were tested for antibodies against feline morbillivirus genotypes 1 and 2 (FeMV-1 and FeMV-2) using an indirect immunofluorescence assay. In total, 63% of the animals showed antibodies against one or both FeMV genotypes. Antibodies directed exclusively against FeMV-2 were significantly more prevalent in male cats. The correlation of sex and FeMV-2 infection might give insight into potential routes of transmission. We provide, for the first time, serological data on FeMV in Chile.

Measles Outbreak in a Rural Population in Bahar District, Hamadan Province, West of Iran in 2018.

BACKGROUND: Measles is in elimination phase in Iran. Following occurrence of two cases of measles in two children under six years old with the history of measles immunization in one of the villages affiliated to Bahar District, west of Hamadan Province, northwest of Iran, this study was conducted to determine the immunity status of people living in the village affected by the measles outbreak in spring of 2018. STUDY DESIGN: A cross-sectional (descriptive-analytical) study. METHODS: Overall, 272 populations of 0-40 yr old in the village affected by outbreak were enrolled. Multistage sampling was used for choosing participants. The data collection tool was a researcher-made checklist used to collect epidemiological data including demographic characteristics and vaccination status. Blood samples were taken from them and sent to the measles reference laboratory for IgG testing. The amount of optical density (OD) greater than 0.2 was considered as positive and less than 0.1 negative, respectively. RESULTS: The mean age of the study population was 17.4 ±11.8 yr and the sex ratio was almost the same. Levels of antibodies against measles were positive in 63.24%, intermediate in 12.5% ​​and negative in 24.26%. There was no significant difference between the immunity status of the subjects with gender (P=0.236) and age group (P=0.113). Pearson correlation results showed that in males there was a significant positive correlation between the age of the participants and the serum IgG level (r = 0.26, P=0.003). CONCLUSION: Measles immunity in communities is not sufficient to prevent outbreaks and small epidemics, and it is recommended that periodically, serological assessments carried out at community level and especially at high-risk groups.

Inequalities in measles immunization coverage in Ethiopia: a cross-sectional analysis of demographic and health surveys 2000-2016.

BACKGROUND: Ethiopia has low measles immunization coverage and little is known about the disparities surrounding what coverage is provided. This study assessed disparities in measles immunization and its change over time using the four Ethiopia Demographic and Health Surveys conducted between 2000 and 2016. METHODS: This is a cross-sectional analysis of data using Ethiopia Demographic and Health Surveys (EDHS) conducted between 2000 and 2016. We used the World Health Organization's (WHO) Health Equity Assessment Toolkit (HEAT) to present the inequalities. Four measures of inequality were calculated: Difference (D), Ratio (R), Population Attributable Fraction (PAF) and Population Attributable Risk (PAR). The results were disaggregated by wealth, education, residence, sex and sub-national regions and 95% Uncertainty Intervals (UIs) were computed for each point estimate to boost confidence of the findings. RESULTS: Measles immunization coverage was higher among the richest and secondary and above schools' subgroup by nearly 30 to 31 percentage points based on point estimates (D = 31%; 95% CI; 19.48, 42.66) and 29.8 percentage points (D = 29.8%; 95% CI; 16.57, 43.06) as compared to the poorest and no education subgroup respectively in the 2016 survey. Still, in the 2016 survey, substantial economic status (PAF = 36.73; 95%CI: 29.78, 43.68), (R = 1.71; 95%CI: 1.35, 2.08), education status (PAF = 45.07; 95% CI: 41.95, 48.18), (R = 1.60; 95% CI: 1.30, 1.90), place of residence (PAF = 39.84, 95% CI: 38.40, 41.27), (R = 1.47, 95% CI: 1.20, 1. 74) and regional (PAF = 71.35, 95% CI: 31.76, 110.95), (R = 3.09, 95%CI: 2.01, 4.17) inequality were observed with both simple and complex measures. There was no statistically significant difference in the prevalence of measles immunization between male and female children in all the studied years, as indicated, for instance, by measures of PAF in 2000 (PAF = 0; 95%CI: - 6.79, 6.79), 2005 (PAF = 0; 95%CI: - 6.04, 6.04), 2011(PAF = 0; 95%CI: - 3.79, 3.79) and 2016 (PAF = 2.66; - 1.67; 6.99). Overall, the inequality of measles immunization narrowed significantly by at least some of the measures between the first and the last survey periods across all the studied subgroups. CONCLUSIONS: National, regional and district levels of government should make a pledge to reduce inequalities in coverage of measles immunization. Equity-sensitive strategies, sufficient human and financial resources as well as continued research and monitoring of immunization coverage inequalities are necessary to achieve related sustainable development goals.

Measles outbreak amplified in a pediatric ward: Lyantonde District, Uganda, August 2017.

BACKGROUND: Measles is a highly infectious viral disease. In August 2017, Lyantonde District, Uganda reported a measles outbreak to Uganda Ministry of Health. We investigated the outbreak to assess the scope, factors facilitating transmission, and recommend control measures. METHODS: We defined a probable case as sudden onset of fever and generalized rash in a resident of Lyantonde, Lwengo, or Rakai Districts from 1 June-30 September 2017, plus ≥1 of the following: coryza, conjunctivitis, or cough. A confirmed case was a probable case with serum positivity of measles-specific IgM. We conducted a neighborhood- and age-matched case-control study to identified exposure factors, and used conditional logistic regression to analyze the data. We estimated vaccine effectiveness and vaccination coverage. RESULTS: We identified 81 cases (75 probable, 6 confirmed); 4 patients (4.9%) died. In the case-control study, 47% of case-patients and 2.3% of controls were hospitalized at Lyantonde Hospital pediatric department for non-measles conditions 7-21 days before case-patient's onset (ORadj = 34, 95%CI: 5.1-225). Estimated vaccine effectiveness was 95% (95%CI: 75-99%) and vaccination coverage was 76% (95%CI: 68-82%). During the outbreak, an "isolation" ward was established inside the general pediatric ward where there was mixing of both measles and non-measles patients. CONCLUSIONS: This outbreak was amplified by nosocomial transmission and facilitated by low vaccination coverage. We recommended moving the isolation ward outside of the building, supplemental vaccination, and vaccinating pediatric patients during measles outbreaks.

Special Issue "Recent Advances in Morbillivirus Vaccine Development and Oncolytic Virotherapy".

Members of the Morbillivirus genus are enveloped, negative-strand RNA viruses that include a number of highly contagious pathogens important to humans and animals. They are known to be transmitted via the respiratory route and cause febrile diseases that can be fatal. Despite the availability of attenuated vaccines against several members, these viruses remain responsible for significant morbidity and mortality in their natural hosts worldwide. The development of molecular biology techniques over the past decades has helped increase the understanding of morbillivirus pathogenesis and explore the possibility to engineer their genomes as viral vectors. This Special Issue of Viruses explores recent advances in recombinant morbilliviruses platforms, especially measles virus (MV) and canine distemper virus (CDV), for novel vaccine development and oncolytic virotherapy against cancers. Topics in this special issue include parameters involved during the viral vector production, strategies of viral vector engineering, and the underlying mechanisms of the therapeutic effects exhibited by these vectors.

Measles and mumps outbreaks in Lebanon: trends and links.

BACKGROUND: Lebanon has experienced several measles and mumps outbreaks in the past 20 years. In this article, a case-based surveillance of both measles and mumps outbreaks in Lebanon was carried out in an attempt to outline factors contributing to the failure of elimination plans and to provide potential solutions. The relationship between the outbreaks of both diseases was described and explored. METHODS: A retrospective descriptive study of confirmed cases of measles and mumps in Lebanon between 2003 and 2018 collected from the Lebanese Ministry of Public Health Epidemiological Surveillance Unit public database was carried out. The information collected was graphically represented taking into consideration dates of reported cases, age groups affected, and vaccination status. RESULTS: The mean number of measles cases was 150.25 cases/year in the 1-4 years age group, 87 cases/year in individuals aging between 5 and 14, and 63.68 cases/year in those > 14 years old. In the latter group, only 18.05% were unvaccinated. The mean number of mumps cases was 30.4 cases/year in the < 4 year age group and 53.8 cases/year in the 10-19 years age group. During the study period, every spike in measles cases was followed by a similar spike in mumps. 9.66% of measles cases occurred in individuals who received at least 2 doses of the vaccine, 52.26% in the unvaccinated, and 38% in those whose vaccination status was undetermined. CONCLUSIONS: Measles in Lebanon is a disease of the pediatric population, but adults remain at risk. Outbreaks of mumps followed those of measles and were mainly among adolescents. Presence of a large number of Syrian refugees in the country may further complicate the situation. Vaccination activities need to be intensified.

Long-term Immunogenicity of Measles Vaccine: An Italian Retrospective Cohort Study.

BACKGROUND: Levels of antibodies induced by the measles virus-containing vaccine have been shown to decline over time, but there is no formal recommendation about testing immunized subjects (in particular, healthcare workers [HCWs]) to investigate the persistence of measles immunoglobulin G (IgG). METHODS: This study aims to evaluate the long-term immunogenicity of measles vaccine in a sample of medical students and residents of the University of Bari who attended the Hygiene Department for a biological risk assessment (April 2014-June 2018). RESULTS: Two thousand immunized (2 doses of measles-mumps-rubella [MMR] vaccine) students and residents were tested; 305 of these (15%) did not show protective anti-measles IgG. This proportion was higher among subjects who received vaccination at ≤15 months (20%) than in those who received vaccination at 16-23 months (17%) and at ≥24 months (10%) (P < .0001). After an MMR vaccine booster dose, we noted a seroconversion of 74% of seronegative HCWs. The overall seroconversion rate after a second dose (booster) was 93%. No serious adverse events were noted after the booster doses. CONCLUSIONS: An important proportion of subjects immunized for measles do not show a protective IgG titer in the 10 years after vaccination. Our management strategy seems consistent with the purpose of evidencing immunological memory.

Antibodies against measles and rubella virus among different age groups in Thailand: A population-based serological survey.

Measles and rubella are highly contagious viral diseases transmitted via respiratory secretions and aerosolized droplets. Thailand has implemented universal vaccination against measles using the monovalent measles (M) or the trivalent measles-mumps-rubella (MMR) vaccine for the past 30 years. Nevertheless, incidence of measles and rubella remains in some parts of the country. We conducted a seroprevalence study to evaluate the antibodies to measles and rubella virus among Thais of all ages and to determine pre-existing immunity resulting from either vaccination and/or natural exposure. A total of 1,781 serum samples collected in 2014 was tested for IgG to measles and rubella virus by commercial enzyme-linked immunosorbent assays (ELISA). Percentages of individuals with protective antibody levels and the geometric mean concentrations (GMC) of IgG in each age group were analysed. The GMC of anti-measles IgG and anti-rubella IgG were 653.7 IU/L (95% confidence interval (CI); 555.9-751.4) and 39.5 IU/mL (95% CI;35.0-43.9), respectively. Thais between the ages of six months and 25 years did not demonstrate sufficient protective herd immunity for measles. This observation is consistent with the recent measles outbreaks in this age group. Lower prevalence of immunity against rubella was found among children ages 5-6 years who may not have completed vaccination as infants. Our findings identify gaps in rubella and measles immunity in specific age groups and support recommendations for catch-up MMR vaccination in individuals 30 years of age or younger.

A cross-sectional study on serum measles antibody levels of a healthy population in southwest China.

This study aimed to investigate measles antibody level and its associated factors in a healthy Chinese population, so as to provide evidence to measles prevention and control measures in the future.We conducted a cross-sectional survey by using probability proportionate to size sampling (PPS) among a healthy population aged 8 months to 45 years. Information on measles vaccination status was obtained from the vaccination certificates. Serum measles IgG antibody was detected by enzyme-linked immunosorbent assay. Multivariate logistic and linear regression models were used to analysis the associated factors of measles antibody.Of the 663 study subjects, the positive rate, protective rate, and geometric mean concentration (GMC) of measles antibodies were 92.76%, 77.53%, 1612.55 mIU/ml, respectively. The antibody concentration was higher in Han ethnical majority than in Hui minority. The positive rate, protective rate and concentration of antibodies in different age groups and regions were clearly disparate. Age, area, and measles-containing vaccine (MCV) immunization history were the prominent influencing factors of antibody positive rate and protective rate. Ethnicity, age, area, and MVC immunization history were the influencing factors of antibody concentration.Our major findings suggest that, children in rural China, especially in impoverished mountainous regions, were more likely to suffer from delays in measles vaccination. Various measures in optimizing vaccination practices should be implemented in order to prevent possible measles epidemic, even outbreak in these regions.

Mumps outbreak and MMR IgG surveillance as a predictor for immunity in military trainees.

In 2017, a mumps outbreak occurred in a barrack holding 249 service members. Suspected cases were evaluated with a combination of mumps IgG, IgM, viral culture, PCR and sequencing. Seven cases were diagnosed in febrile patients presenting with parotitis or orchitis. Mumps infection was confirmed by IgM or positive PCR with 5/7 cases having notable IgG levels before infection. Sequencing confirmed mumps genotype G strain. Serum from all 249 service members collected prior to the outbreak was withdrawn from the Department of Defense (DoD) Serum Repository and the IgG values of measles, mumps and rubella determined with 20.2%, 12.3% and 9.7% service members being seronegative, respectively. No specific IgG seronegativity combination predicted IgG marker levels to another virus within the same vaccine. This paper provides additional evidence that mumps serology is not a reliable surrogate for mumps immunity and that we need better laboratory correlates to confirm immunity.

Blood Lead Concentrations and Antibody Levels to Measles, Mumps, and Rubella among U.S. Children.

Child blood lead concentrations have been associated with measures of immune dysregulation in nationally representative study samples. However, response to vaccination-often considered the gold standard in immunotoxicity testing-has not been examined in relation to typical background lead concentrations common among U.S. children. The present study estimated the association between blood lead concentrations and antigen-specific antibody levels to measles, mumps, and rubella in a nationally representative sample of 7005 U.S. children aged 6-17 years. Data from the 1999-2004 cycles of the National Health and Nutrition Examination Survey (NHANES) were used. In the adjusted models, children with blood lead concentrations between 1 and 5 µg/dL had an 11% lower anti-measles (95% CI: -16, -5) and a 6% lower anti-mumps antibody level (95% CI: -11, -2) compared to children with blood lead concentrations <1 µg/dL. The odds of a seronegative anti-measles antibody level was approximately two-fold greater for children with blood lead concentrations between 1 and 5 µg/dL compared to children with blood lead concentrations <1 µg/dL (OR = 2.0, 95% CI: 1.4, 3.1). The adverse associations observed in the present study provide further evidence of potential immunosuppression at blood lead concentrations <5 µg/dL, the present Centers for Disease Control and Prevention action level.

MMRdb: Measles, mumps, and rubella viruses database and analysis resource.

Measles, mumps, and rubella viruses are well known human pathogens that cause mild to severe illnesses. Despite the existence of MMR vaccines since 1971, outbreaks have been largely documented even in highly vaccinated populations. There is a pressing need to develop a resource to monitor genetic and antigenic variations among these viruses. Here, we introduced MMRdb, a web central database and analysis resource for measles, mumps, and rubella viruses. Users can search viruses at gene level and obtain sequence information based on gene product, geographic location, year, or host. The MMRdb also catalogs experimentally verified B cells and T cells antigenic epitopes data. A set of computation tools such as multiple sequence alignment, Geo Chart, and sequence similarity BLAST search has been implemented in a user-friendly database. The main features of this database will assist researchers in monitoring genetics and antigenic variations, tracking geographic spread with regards of sequence information, and facilitate the development of diagnostics, vaccines, and immunotherapeutics. Database URL: http://mmrdb.org.

Comparative Immunopathology of Cetacean morbillivirus Infection in Free-Ranging Dolphins From Western Mediterranean, Northeast-Central, and Southwestern Atlantic.

Cetacean morbillivirus (CeMV; Paramyxoviridae) causes epizootic and interepizootic fatalities in odontocetes and mysticetes worldwide. Studies suggest there is different species-specific susceptibility to CeMV infection, with striped dolphins (Stenella coeruleoalba), bottlenose dolphins (Tursiops truncatus), and Guiana dolphins (Sotalia guianensis) ranking among the most susceptible cetacean hosts. The pathogenesis of CeMV infection is not fully resolved. Since no previous studies have evaluated the organ-specific immunopathogenetic features of CeMV infection in tissues from infected dolphins, this study was aimed at characterizing and comparing immunophenotypic profiles of local immune responses in lymphoid organs (lymph nodes, spleen), lung and CNS in CeMV-molecularly (RT-PCR)-positive cetaceans from Western Mediterranean, Northeast-Central, and Southwestern Atlantic. Immunohistochemical (IHC) analyses targeted molecules of immunologic interest: caspase 3, CD3, CD20, CD57, CD68, FoxP3, MHCII, Iba1, IFNγ, IgG, IL4, IL10, lysozyme, TGFß, and PAX5. We detected consistent CeMV-associated inflammatory response patterns. Within CNS, inflammation was dominated by CD3+ (T cells), and CD20+ and PAX5+ (B cells) lymphocytes, accompanied by fewer Iba1+, CD68+, and lysozyme+ histiocytes, mainly in striped dolphins and bottlenose dolphins. Multicentric lymphoid depletion was characterized by reduced numbers of T cells and B cells, more pronounced in Guiana dolphins. Striped dolphins and bottlenose dolphins often had hyperplastic (regenerative) phenomena involving the aforementioned cell populations, particularly chronically infected animals. In the lung, there was mild to moderate increase in T cells, B cells, and histiocytes. Additionally, there was a generalized increased expression of caspase 3 in lymphoid, lung, and CNS tissues. Apoptosis, therefore, is believed to play a major role in generalized lymphoid depletion and likely overt immunosuppression during CeMV infection. No differences were detected regarding cytokine immunoreactivity in lymph nodes, spleen, and lung from infected and non-infected dolphins by semiquantitative analysis; however, there was striking immunoreactivity for IFNγ in the CNS of infected dolphins. These novel results set the basis for tissue-specific immunophenotypic responses during CeMV infection in three highly susceptible delphinid species. They also suggest a complex interplay between viral and host's immune factors, thereby contributing to gain valuable insights into similarities, and differences of CeMV infection's immunopathogenesis in relation to body tissues, CeMV strains, and cetacean hosts.

Immunogenicity and safety of measles-rubella vaccine co-administered with attenuated Japanese encephalitis SA 14-14-2 vaccine in infants aged 8 months in China: a non-inferiority randomised controlled trial.

BACKGROUND: In China, measles-rubella vaccine and live attenuated SA 14-14-2 Japanese encephalitis vaccine (LJEV) are recommended for simultaneous administration at 8 months of age, which is the youngest recommended age for these vaccines worldwide. We aimed to assess the effect of the co-administration of these vaccines at 8 months of age on the immunogenicity of measles-rubella vaccine. METHODS: We did a multicentre, open-label, non-inferiority, two-group randomised controlled trial in eight counties or districts in China. We recruited healthy infants aged 8 months who had received all scheduled vaccinations according to the national immunisation recommendations and who lived in the county of the study site. Enrolled infants were randomly assigned (1:1) to receive either measles-rubella vaccine and LJEV simultaneously (measles-rubella plus LJEV group) or measles-rubella vaccine alone (measles-rubella group). The primary outcome was the proportion of infants with IgG antibody seroconversion for measles 6 weeks after vaccination, and a secondary outcome was the proportion of infants with IgG antibody seroconversion for rubella 6 weeks after vaccination. Analyses included all infants who completed the study. We used a 5% margin to establish non-inferiority. This trial was registered at ClinicalTrials.gov (NCT02643433). FINDINGS: 1173 infants were assessed for eligibility between Aug 13, 2015, and June 10, 2016. Of 1093 (93%) enrolled infants, 545 were randomly assigned to the measles-rubella plus LJEV group and 548 to the measles-rubella group. Of the infants assigned to each group, 507 in the measles-rubella plus LJEV group and 506 in the measles-rubella group completed the study. Before vaccination, six (1%) of 507 infants in the measles-rubella plus LJEV group and one (<1%) of 506 in the measles-rubella group were seropositive for measles; eight (2%) infants in the measles-rubella plus LJEV group and two (<1%) in the measles-rubella group were seropositive for rubella. 6 weeks after vaccination, measles seroconversion in the measles-rubella plus LJEV group (496 [98%] of 507) was non-inferior to that in the measles-rubella group (499 [99%] of 506; difference -0·8% [90% CI -2·6 to 1·1]) and rubella seroconversion in the measles-rubella plus LJEV group (478 [94%] of 507) was non-inferior to that in the measles-rubella group (473 [94%] of 506 infants; difference 0·8% [90% CI -1·8 to 3·4]). There were no serious adverse events in either group and no evidence of a difference between the two groups in the prevalence of any local adverse event (redness, rashes, and pain) or systemic adverse event (fever, allergy, respiratory infections, diarrhoea, and vomiting). Fever was the most common adverse event (97 [19%] of 507 infants in the measles-rubella plus LJEV group; 108 [21%] of 506 infants in the measles-rubella group). INTERPRETATION: The evidence of similar seroconversion and safety with co-administered LJEV and measles-rubella vaccines supports the co-administration of these vaccines to infants aged 8 months. These results will be important for measles and rubella elimination and the expansion of Japanese encephalitis vaccination in countries where it is endemic. FUNDING: US Centers for Disease Control and Prevention, US Department of Health and Human Services; China-US Collaborative Program on Emerging and Re-emerging Infectious Diseases.

Herd immunity and primary immune deficiencies.

This letter addresses the issues adjoining the article by Bernadou et al. Measles outbreak linked to insufficient vaccination coverage in Nouvelle-Aquitaine Region, France, October 2017 to July 2018. Euro Surveill. 2018;23(30):pii = 1800373. https://doi.org/10.2807/1560-7917.ES.2018.23.30.1800373. The decreased vaccination rates against measles are decreasing herd immunity to this agent, posing a risk for patients with Patient Immune Deficiency as the measles antibody titre decreases in products used to provide prophylactic cover against this illness.