Parity status and the relationship between antenatal rubella serology with obstetric outcome.

Routine antenatal rubella serological testing is adopted in many countries. In a population covered by universal childhood rubella immunization for four decades, we have observed an association between pre-eclampsia with maternal rubella seronegativity among multiparous gravidae. This retrospective cohort study was further performed to elucidate the interaction between parity status and rubella seronegativity on obstetric outcome in singleton pregnancies carried to ≥ 24 weeks gestation managed from 1997 to 2019, with the data retrieved from a computerized database used for annual statistics and auditing. Of the 133,926 singleton pregnancies eligible for the study, the 13,320 (9.9%) rubella seronegative gravidae had higher mean booking weight and body mass index (BMI), but shorter height, and higher incidence of advanced age (≥ 35 years), high BMI, short stature, and lower incidence of nulliparas. Univariate analysis showed that adverse obstetric outcomes were more frequently found among the multiparas. On multivariate analysis, there was increased postdated (> 41 weeks) pregnancy irrespective of parity status, while nulliparas had reduced gestational hypertension (aRR 0.714, 95% CI 0.567-0.899) and gestational diabetes (aRR 0.850, 95% CI 0.762-0.950), and multiparas had increased pre-eclampsia (aRR 1.261, 95% CI 1.005-1.582), neonatal death (aRR 2.796, 95% CI 1.243-6.291), and perinatal death (aRR 2.123, 95% CI 1.257-3.587). In conclusion, in a population covered by universal childhood rubella immunization, antenatal rubella seronegativity is associated with increased pre-eclampsia and perinatal loss only in multiparas, suggesting that the rubella seronegativity in these women served as proxy for some form of altered immune response which increases adverse pregnancy outcome.

Rubella vaccine-induced granulomas are a novel phenotype with incomplete penetrance of genetic defects in cytotoxicity.

BACKGROUND: Rubella virus-induced granulomas have been described in patients with various inborn errors of immunity. Most defects impair T-cell immunity, suggesting a critical role of T cells in rubella elimination. However, the molecular mechanism of virus control remains elusive. OBJECTIVE: This study sought to understand the defective effector mechanism allowing rubella vaccine virus persistence in granulomas. METHODS: Starting from an index case with Griscelli syndrome type 2 and rubella skin granulomas, this study combined an international survey with a literature search to identify patients with cytotoxicity defects and granuloma. The investigators performed rubella virus immunohistochemistry and PCR and T-cell migration assays. RESULTS: This study identified 21 patients with various genetically confirmed cytotoxicity defects, who presented with skin and visceral granulomas. Rubella virus was demonstrated in all 12 accessible biopsies. Granuloma onset was typically before 2 years of age and lesions persisted from months to years. Granulomas were particularly frequent in MUNC13-4 and RAB27A deficiency, where 50% of patients at risk were affected. Although these proteins have also been implicated in lymphocyte migration, 3-dimensional migration assays revealed no evidence of impaired migration of patient T cells. Notably, patients showed no evidence of reduced control of concomitantly given measles, mumps, or varicella live-attenuated vaccine or severe infections with other viruses. CONCLUSIONS: This study identified lymphocyte cytotoxicity as a key effector mechanism for control of rubella vaccine virus, without evidence for its need in control of live measles, mumps, or varicella vaccines. Rubella vaccine-induced granulomas are a novel phenotype with incomplete penetrance of genetic disorders of cytotoxicity.

Seroprevalence of Rubella among Women of Reproductive Age in Iran: A Prisma-Based Systematic Review and Meta-Analysis.

OBJECTIVE: Rubella is a highly contagious viral disease with a significant teratogenic effect. Various results have been published about the seroprevalence of rubella in Iran. A PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses)-systematic review and meta-analysis were conducted to assess the immunity against rubella in Iranian women. METHODS: Eleven English and Persian electronic databases including PubMed, ScienceDirect, Scopus, Web of Science, Google Scholar, Embase, Scientific Information Database, Iran doc, Iran Medex, Magiran, and Medlib were searched using the keywords: Epidemiology, Prevalence, Rubella, Women, Childbearing age, Reproductive age, and Iran. A mathematician (NS) reviewed all steps for accuracy. RESULTS: Out of 1,520 articles, 25 well-conducted studies with a total amount of 10,145 women were reviewed. The pooled prevalence rate of anti-rubella IgG was 84% (95% CI: 83%-86%). The highest prevalence rate of IgG was in Zahedan, Rasht, and Arak (each 100%), while the lowest prevalence was in Jahrom (54%). Subgroup analysis showed that from 1989 through 2012, the IgG prevalence rate increased from 78% (95% CI: 73-83%) to 99% (95% CI: 98 100%). CONCLUSIONS: Although the vaccination program seems working in Iran, some peripheral regions may be a target to improve health care policies.

Seroprevalence of Toxoplasma gondii, Rubella, Group A Streptococcus, CMV and HSV-1 in COVID-19 Patients with Vitamin D Deficiency.

<b>Background and Objective:</b> In recent years, respiratory tract viral infections have caused many pandemics that impact the whole world. To investigate the seropositivity of <i>Toxoplasma gondii</i>, rubella, CMV, HSV-1 and group A <i>Streptococcus</i> in recovered COVID-19 patients and correlate these findings with vitamin D levels. <b>Materials and Methods:</b> A total of 417 COVID-19 patients with diarrhoea were enrolled in this study. Vitamin D and seroprevalence for <i>Toxoplasma gondii</i>, rubella, CMV, HSV-1 and group A <i>Streptococcus</i> were evaluated and correlated. <b>Results:</b> It was found that recent infection in COVID-19 patients with HSV-1, rubella, <i>Toxoplasma</i> and CMV, respectively. IgG was detected indicating the development of adaptive immunity with all microbes. <b>Conclusion:</b> Current study detected a correlation between vitamin D levels and HSV-1 and no correlation between this infection and vitamin D deficiency with the other microbes.

Implementing Serosurveys in India: Experiences, Lessons Learned, and Recommendations.

Serological surveillance for vaccine-preventable diseases, such as measles and rubella, can provide direct measures of population immunity across age groups, identify gaps in immunity, and document changes in immunity over time. Rigorously conducted, representative household serosurveys provide high-quality estimates with minimal bias. However, they can be logistically challenging, expensive, and have higher refusal rates than vaccine coverage surveys. This article shares lessons learned through implementing nine measles and rubella household serosurveys in five districts in India-the challenges faced, the potential impact on results, and recommendations to facilitate the conduct of serosurveys. Specific lessons learned arose from challenges related to community mobilization owing to lack of cooperation in certain settings and populations, limitations of outdated census information, nonresponse due to refusal or unavailability during survey enumeration and enrollment, data collection issues, and specimen collection and handling issues. Although some experiences are specific to serosurveys in India, these lessons are generalizable to other household surveys, particularly vaccination coverage and serosurveys conducted in low- and middle-income settings.

Diagnostic Accuracy of Dried Blood Spots Collected on HemaSpot HF Devices Compared to Venous Blood Specimens To Estimate Measles and Rubella Seroprevalence.

Fingerprick blood spotted onto filter paper offers an alternative to venous blood for use in population-based surveillance because it is comparatively inexpensive, acceptable, and easy to manage in the field. Prior studies have shown excellent agreement for immunoglobulin G (IgG) antibody detection from dried blood spots (DBS) and venous blood samples. However, much of this evidence is from high-income settings or laboratories where the samples were unlikely to be exposed to extreme temperatures and humidity, factors known to degrade DBS. We report the diagnostic accuracy of DBS collected using HemaSpot HF devices against venous sera in measuring measles- and rubella-specific IgG antibodies in a household serosurvey conducted in two districts in India. Paired serum and DBS samples collected by fingerprick were collected from women aged 15 to 50 years enrolled in a serosurvey in Palghar District of Maharashtra and Kanpur Nagar District of Uttar Pradesh in India. Specimen quality and volume were assessed in the laboratory. Samples were tested for antimeasles and antirubella IgG antibodies by an enzyme-linked immunosorbent assay (ELISA) (Euroimmun). Sensitivity of antibody detection by DBS was greater than 98%, and specificity was 90% and 98%, for measles and rubella IgG, respectively. Antibody concentrations were strongly correlated between paired specimens with adequate volume (measles R2 = 0.94; rubella R2 = 0.89). Although correlation was poor if DBS specimens had lower volumes, impact on qualitative results was minimal. This study showed DBS collected with HemaSpot HF devices can generate highly accurate results of measles- and rubella-specific IgG compared to sera in community-based surveys when protocols are optimized for DBS specimens. IMPORTANCE Dried blood spot (DBS) collection provides an easy, practical, and acceptable alternative to venous blood collection, especially for community-based studies, provided that results from DBS are accurate. We demonstrated high sensitivity and specificity for measles- and rubella-specific immunoglobulin G (IgG) with DBS collected via HemaSpot HF devices compared to serum samples. This is one of the largest community-based diagnostic accuracy studies of measles and rubella antibody testing with DBS and the first application we are aware of using HemaSpot HF device for measles and rubella serology. Results support the use of DBS in community-based serosurveillance.

Optimization and Stability Testing of Four Commercially Available Dried Blood Spot Devices for Estimating Measles and Rubella IgG Antibodies.

Blood collection using dried blood spots (DBS) provides an easier alternative to venipuncture for sample collection, transport, and storage but requires additional processing that can cause variability in results. Whole-blood samples spotted on four DBS devices and respective paired serum samples were tested for antimeasles and antirubella IgG antibody concentrations by enzyme immunoassay. Elution protocols for DBS devices were optimized for comparability relative to serum samples using 12 adult volunteers. Stability of DBS collected on HemaSpot HF was assessed under various temperature conditions (+4, 22 to 25, and 45°C) at six time points (0, 7, 15, 30, 60, and 90 days) in a controlled laboratory setting using six adult volunteers. Devices were shipped and stored for 30 days at four settings with variable temperature and humidity conditions to assess the impact on antibody concentrations. Three DBS devices demonstrated comparable antibody concentrations with paired sera following optimization. Antibodies recovered from DBS were stable for at least 90 days at 4°C and for 30 days at ambient temperature (22 to 25°C) using the HemaSpot HF device. A drastic decline in antibody concentrations was observed at 45°C, resulting in quantitative and qualitative discrepancies by day 7. HemaSpot HF devices shipped to field sites and stored at ambient temperature and humidity resulted in quantitative, but not qualitative, variability. Measurement of antimeasles and antirubella IgG antibodies with DBS devices is an accurate alternative to testing serum, provided elution protocols are optimized. Stability of HemaSpot HF devices at ambient temperature enables broader use in surveys when serum processing and cold storage are not feasible. IMPORTANCE Dried blood spot (DBS) collection offers various advantages over conventional methods of blood collection, especially when collecting and transporting samples for a serosurvey. Yet use of DBS requires additional processing steps in the laboratory that can add to variability in results. We optimized a protocol to elute IgG antibodies against measles and rubella viruses in four DBS devices, demonstrating high concordance with paired venous sera for most devices. Extensive stability studies with various temperature and storage conditions in the laboratory and in the field were conducted using HemaSpot HF DBS devices prior to its use in one of the largest community-based measles and rubella serological surveys in the world.

Impact of a Measles and Rubella Vaccination Campaign on Seroprevalence in Southern Province, Zambia.

Zambia conducted a measles and rubella (MR) vaccination campaign targeting children 9 months to younger than 15 years of age in 2016. This campaign was the first introduction of a rubella-containing vaccine in Zambia. To evaluate the impact of the campaign, we compared the MR seroprevalence estimates from serosurveys conducted before and after the campaign in Southern Province, Zambia. The measles seroprevalence increased from 77.8% (95% confidence interval [CI], 73.2-81.9) to 96.4% (95% CI, 91.7-98.5) among children younger than 15 years. The rubella seroprevalence increased from 51.3% (95% CI, 45.6-57.0) to 98.3% (95% CI, 95.5-99.4). After the campaign, slightly lower seroprevalence remained for young adults 15 to 19 years old, who were not included in the campaign because of their age. These serosurveys highlighted the significant impact of the vaccination campaign and identified immunity gaps for those beyond the targeted vaccination age. Continued monitoring of population immunity can signal the need for future targeted vaccination strategies.

Low immunity against vaccine preventable diseases in Turkish HIV cohort

Background/aim: HIV infection increase the risk of serious disease resulting from common vaccine-preventable infections. Vaccinations are particularly important for HIV infected adults. We aimed to investigate the immunity rates against measles, mumps, rubella, hepatitis A, B, and tetanus in newly diagnosed HIV patients. Materials and methods: Patients who admitted to outpatient clinics of three centers with newly diagnosed HIV infection, between 1 January 2015 and 31 June 2017 were included. Measles, mumps, rubella, varicella zoster virus, hepatitis A, hepatitis B, and tetanus antibody levels were measured by commercial diagnostic kits. Demographical and laboratory data of the patients were recorded. Results: Five hundred and twenty-three patients were enrolled in the study. Of the patients 87% were male (n = 455) and the mean age was 38 ± 13 years. Serology was available for measles 74.2% (388/523), mumps 73.8% (386/523), rubella 77.8% (407/523), hepatitis A 88.5% (463/523), hepatitis B 97.7% (511/523), tetanus 8.6% (45/523), and VZV 79.9% (418/523). Seropositivity was 82% for measles, 75.6% for mumps, 92.1% for rubella. Of the patients whom all three of the components of the MMR vaccine was tested, 37.7% (127/337) were susceptible at least one and needed the vaccine. Mean age was lower in patients who are nonimmune to measles and mumps (p = 0.008). Younger patients were also nonimmune for hepatitis A, while older patients were nonimmune for hepatitis B. Conclusion: In our study we found that rates of nonimmunity can increase up to one third of the patients even though there is a national vaccination program. Nonimmune individuals should be detected and vaccinated in line with recent guidelines and response should be monitored because of the possibility of impaired immunity and possible suboptimal response. National campaigns can be launched for adult immunization and physicians should be aware of the importance of adult immunization.

Serum Concentration of Antibodies to Mumps, but Not Measles, Rubella, or Varicella, Is Associated with Intake of Dietary Fiber in the NHANES, 1999-2004.

Treatment with prebiotics, a type of dietary fiber, was recently shown to increase antibody concentrations following influenza vaccination in a meta-analysis of clinical trials. In observational epidemiologic studies it is not possible to estimate intake of prebiotics, but quantifying intake of dietary fiber is routine. Our objective was to investigate the potential effect of dietary fiber on immunogenicity. We examined serum antibody concentrations (Measles, Mumps, Rubella, and Varicella) in relation to dietary fiber in more than 12,000 subjects in the U.S. National Health and Nutrition Examination Survey (NHANES) for the period 1999-2004. Data from one (1999-2002) or two (2003-2004) dietary recalls were used to calculate fiber intake. For Mumps the adjusted percentage difference in antibody concentration per interquartile range intake in energy-adjusted dietary fiber was 6.34% (95% confidence interval, 3.10, 9.68). Fiber from grain-based foods was more positively associated than fiber from other fiber-containing food groups. The association was slightly larger among subgroups with higher fiber intake, greater interquartile range in fiber intake, and less measurement error. Furthermore, based on the reliability of the diet recalls in 2003-2004, we calculated that the percentage difference per interquartile increment was substantially attenuated by measurement error. Dietary fiber may have a favorable influence on the immunogenicity of some vaccines or natural infections.

Transcriptional signatures associated with rubella virus-specific humoral immunity after a third dose of MMR vaccine in women of childbearing age.

Multiple factors linked to host genetics/inherent biology play a role in interindividual variability in immune response outcomes after rubella vaccination. In order to identify these factors, we conducted a study of rubella-specific humoral immunity before (Baseline) and after (Day 28) a third dose of MMR-II vaccine in a cohort of 109 women of childbearing age. We performed mRNA-Seq profiling of PBMCs after rubella virus in vitro stimulation to delineate genes associated with post-vaccination rubella humoral immunity and to define genes mediating the association between prior immune response status (high or low antibody) and subsequent immune response outcome. Our study identified novel genes that mediated the association between prior immune response and neutralizing antibody titer after a third MMR vaccine dose. These genes included the following: CDC34; CSNK1D; APOBEC3F; RAD18; AAAS; SLC37A1; FAS; and JAK2. The encoded proteins are involved in innate antiviral response, IFN/cytokine signaling, B cell repertoire generation, the clonal selection of B lymphocytes in germinal centers, and somatic hypermutation/antibody affinity maturation to promote optimal antigen-specific B cell immune function. These data advance our understanding of how subjects' prior immune status and/or genetic propensity to respond to rubella/MMR vaccination ultimately affects innate immunity and humoral immune outcomes after vaccination.

Inadequate Measles, Mumps, Rubella, and Varicella Immunity Among Employees.

OBJECTIVES: The purpose of this cohort study was to evaluate measles, mumps, rubella (MMR), and varicella immunity among a population of adult employees receiving primary care in an employer-sponsored health center. METHODS: Participants were eligible for MMR and varicella immunity screening if they were an employee receiving primary care in an employer-sponsored health center between January 1, 2019 and November 1, 2020 who could not provide proof of immunization and 1) had it recommended by their provider, 2) specifically requested immunity testing (often because they had heard of measles outbreaks in their country of origin), or 3) were seen for an immigration physical for their Green Card application. RESULTS: Overall, 3494 patients were screened for their MMR immunity. Of these, 3057 were also screened for varicella immunity. Among these patients, 13.9% lacked measles immunity, 0.83% lacked immunity to all 3 components of MMR, and 13.2% lacked varicella immunity. Among the 262 patients who presented specifically for immunity screening, the rates of lacking immunity were higher for all conditions: 22.7% lacked measles immunity and 9.2% lacked varicella immunity. CONCLUSION: Given declines in immunizations during the COVID-19 pandemic, there is reason to be concerned that measles and varicella-associated morbidity and mortality may rise. Employers, especially those with large foreign-born populations or who require international travel may want to educate their populations about common contagious illnesses and offer immunity validation or vaccinations at no or low cost.

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

BACKGROUND: Iranian 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. METHODS: This 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. RESULTS: A 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. CONCLUSION: Despite 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.

The Immunogenicity and Safety Profile for KM-248, a Combined Measles, Mumps, and Rubella Vaccine, and Its Noninferiority to the Measles Vaccine in Healthy Japanese Children: a Phase 3 Randomized Multicenter Single-Blind Clinical Trial.

The domestic combined measles-mumps-rubella (MMR) vaccine was withdrawn in Japan in 1993 following an outbreak of aseptic meningitis attributed to the mumps component of the cocktail. KM-248 is an MMR vaccine (M-M-R®II), manufactured by Merck & Co., Inc. (Kenilworth, NJ, USA) and registered and approved in 74 countries, but which has not been approved in Japan. This multicenter, randomized, single-blind study, was designed to evaluate the noninferiority of the KM-248 measles component in terms of immunogenicity when compared to the control measles vaccine already approved in Japan and the seroconversion rates for these three viruses following KM-248 administration. Vaccination with KM-248 in children aged 12-90 months (n = 178) induced robust immune responses to measles, mumps, and rubella viruses. The seroconversion rate for the measles virus by the measles component of KM-248 (n = 172) was shown to be non-inferior to that of the control measles vaccine (n = 85). No serious adverse reactions, such as aseptic meningitis or anaphylaxis, were observed. Fever is one of the most common adverse reactions associated with vaccination and was observed in approximately half of the participants. KM-248 administered to healthy Japanese children aged between 12 and 90 months demonstrated a comparable safety and efficacy profile to the control vaccine.

Study of the teratogenicity of the vaccine strain of the Rubella virus «Orlov-V¼ (Matonaviridae: Rubivirus: Rubella virus) in experience on rhesus macaques.

INTRODUCTION: Rubella virus has pronounced teratogenic properties that can cause generalized and persistent intrauterine infection of the fetus. As a result, the control of the loss of teratogenicity inherent in «wild-type¼ virus strains is a necessary stage of a preclinical study of the vaccine strain for a live attenuated rubella vaccine.The purpose of the study is to comprehensively study the teratogenic properties of the vaccine strain of rubella virus «Orlov-V¼ in the experiment on rhesus macaques. MATERIAL AND METHODS: Seronegative to rubella virus female rhesus macaques in early pregnancy at the age of 4-7 years (n = 13) were used in the experiment. Animals of the experimental group (n = 9) received single immunization intramuscularly with a preparation from the «Orlov-V¼ strain. The control group of the monkeys (n = 3) were immunized with a commercial vaccine containing Wistar RA27/3 strain. The female of the control group (n = 1) was injected with a solvent used in the rubella vaccine. Study of possible teratogenic properties of vaccine strains of rubella virus was carried out using a complex of clinical, immunological, pathomorphological and virological methods. Clinical observations were made within 3 months after the monkeys' birth. Determination of antibody titers in the blood serum of immunized monkeys was performed in HI test on the 28th-30th day after infection. The ELISA method was applied to determine IgM antibodies in the blood serum of newborns within the first month of life. Detection of rubella virus RNA was performed by PCR with electrophoretic detection of amplicons. RESULTS: No markers of congenital rubella infection were found in infants born from monkeys vaccinated during the pregnancy. It is shown that PCR can be an informative method to confirm the absence of teratogenic properties of vaccine strains of rubella virus. DISCUSSION: The obtained data demonstrated that vaccine strains of the «Orlov-V¼ rubella virus and Wistar RA27/3 have lost their teratogenic properties. The possibility of using an alternative strategy for preclinical assessment of specific safety of antiviral vaccines including a complex of clinical, immunological, pathologic and virological methods instead of the classical pathologic method is discussed. CONCLUSION: The results obtained in this study showed the absence of teratogenic properties and high immunogenic activity of the vaccine strain of rubella virus «Orlov-V¼.

The Impact of Rubella Virus Infection on a Secondary Inflammatory Response in Polarized Human Macrophages.

Macrophages (MΦ) are known to exhibit distinct responses to viral and bacterial infection, but how they react when exposed to the pathogens in succession is less well understood. Accordingly, we determined the effect of a rubella virus (RV)-induced infection followed by an LPS-induced challenge on cytokine production, signal transduction and metabolic pathways in human GM (M1-like)- and M (M2-like)-MΦ. We found that infection of both subsets with RV resulted in a low TNF-α and a high interferon (IFN, type I and type III) release whereby M-MΦ produced far more IFNs than GM-MΦ. Thus, TNF-α production in contrast to IFN production is not a dominant feature of RV infection in these cells. Upon addition of LPS to RV-infected MΦ compared to the addition of LPS to the uninfected cells the TNF-α response only slightly increased, whereas the IFN-response of both subtypes was greatly enhanced. The subset specific cytokine expression pattern remained unchanged under these assay conditions. The priming effect of RV was also observed when replacing RV by IFN-ß one putative priming stimulus induced by RV. Small amounts of IFN-ß were sufficient for phosphorylation of Stat1 and to induce IFN-production in response to LPS. Analysis of signal transduction pathways activated by successive exposure of MΦ to RV and LPS revealed an increased phosphorylation of NFκB (M-MΦ), but different to uninfected MΦ a reduced phosphorylation of ERK1/2 (both subtypes). Furthermore, metabolic pathways were affected; the LPS-induced increase in glycolysis was dampened in both subtypes after RV infection. In conclusion, we show that RV infection and exogenously added IFN-ß can prime MΦ to produce high amounts of IFNs in response to LPS and that changes in glycolysis and signal transduction are associated with the priming effect. These findings will help to understand to what extent MΦ defense to viral infection is modulated by a following exposure to a bacterial infection.

Rubella Virus Infected Macrophages and Neutrophils Define Patterns of Granulomatous Inflammation in Inborn and Acquired Errors of Immunity.

Rubella virus (RuV) has recently been found in association with granulomatous inflammation of the skin and several internal organs in patients with inborn errors of immunity (IEI). The cellular tropism and molecular mechanisms of RuV persistence and pathogenesis in select immunocompromised hosts are not clear. We provide clinical, immunological, virological, and histological data on a cohort of 28 patients with a broad spectrum of IEI and RuV-associated granulomas in skin and nine extracutaneous tissues to further delineate this relationship. Combined immunodeficiency was the most frequent diagnosis (67.8%) among patients. Patients with previously undocumented conditions, i.e., humoral immunodeficiencies, a secondary immunodeficiency, and a defect of innate immunity were identified as being susceptible to RuV-associated granulomas. Hematopoietic cell transplantation was the most successful treatment in this case series resulting in granuloma resolution; steroids, and TNF-α and IL-1R inhibitors were moderately effective. In addition to M2 macrophages, neutrophils were identified by immunohistochemical analysis as a novel cell type infected with RuV. Four patterns of RuV-associated granulomatous inflammation were classified based on the structural organization of granulomas and identity and location of cell types harboring RuV antigen. Identification of conditions that increase susceptibility to RuV-associated granulomas combined with structural characterization of the granulomas may lead to a better understanding of the pathogenesis of RuV-associated granulomas and discover new targets for therapeutic interventions.

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..

Performance evaluation of immunoassay for infectious diseases on the Alinity i system.

BACKGROUND: Although a diagnosis of infectious diseases is essential for timely treatment, the performance of diagnostic tests has been hardly evaluated due to variable results that are influenced by multiple factors in different conditions. In the present study, the performance of the Alinity i system, which is a newly developed immunoassay to diagnose infectious diseases, was evaluated. METHODS: We evaluated the precision, linearity, correlation, and carryover of 16 analytes (HAV Ab IgG, HBsAg, HBeAg, anti-HBc, anti-HBe, anti-HBs, anti-HCV, HIV Ag/Ab, EBV VCA IgM, EBV VCA IgG, EBV EBNA IgG, CMV IgM, CMV IgG, Toxoplasma IgG, Rubella IgG, and Syphilis TP) of Alinity i by comparison with ARCHITECT i2000SR system following the rationale of the Clinical and Laboratory Standards Institute (CLSI). RESULTS: For quantitative tests, the coefficients of variation (CV) % of repeatability and intermediate precision were between 0% and 4.18%. The coefficients of the linearity (r2 ) over a widely tested analytical range were ≥ 0.990 and the correlation between Alinity i and the ARCHITECT i2000SR system was strong (r ≥ 0.994). For qualitative tests, the agreement between Alinity i and the ARCHITECT i2000SR system was excellent (kappa coefficient 1) with 100% sensitivity and specificity. Carryover rates for all analytes were less than 1.0% (-0.11% ~ 0.21%). CONCLUSION: The Alinity i system showed good analytical performance and favorable comparability with the ARCHITECT i2000SR. It could be suitable as a routine immunoassay analyzer for screening and diagnosis of infectious disease.

Associations between markers of cellular and humoral immunity to rubella virus following a third dose of measles-mumps-rubella vaccine.

INTRODUCTION: Rubella virus (RV) was eliminated in the United States in 2004, although a small portion of the population fails to develop long-term immunity against RV even after two doses of the measles-mumps-rubella (MMR) vaccine. We hypothesized that inherent biological differences in cytokine and chemokine signaling likely govern an individual's response to a third dose of the vaccine. METHODS: Healthy young women (n = 97) were selected as study participants if they had either low or high extremes of RV-specific antibody titer after two previous doses of MMR vaccine. We measured cytokine and chemokine secretion from RV-stimulated PBMCs before and 28 days after they received a third dose of MMR vaccine and assessed correlations with humoral immune response outcomes. RESULTS: High and low antibody vaccine responders exhibited a strong pro-inflammatory cellular response, with an underlying Th1-associated signature (IL-2, IFN-γ, MIP-1ß, IP-10) and suppressed production of most Th2-associated cytokines (IL-4, IL-10, IL-13). IL-10 and IL-4 exhibited significant negative associations with neutralizing antibody titers and memory B cell ELISpot responses among low vaccine responders. CONCLUSION: IL-4 and IL-10 signaling pathways may be potential targets for understanding and improving the immune response to rubella vaccination or for designing new vaccines that induce more durable immunity.