Measles Infection Research Articles

Measles and immunological amnesia

Measles virus remains the most important cause of childhood mortality, causing a transient immunosuppression that accompanies and follows measles making the patients susceptible to secondary infections accounting for most of the measles-related complications and deaths. The majority of measles virus in the body uses Signaling Lymphocyte Activation Molecule (SLAM) as a receptor and only a minority of the virus may also use CD46. Infection and subsequent demise of SLAM cells may explain the severe immunosuppressive characteristic of this viral disease. Measles also reduce the nonspecific naïve B cells in the bone marrow, which fight unfamiliar infections and SLAM signaling intensifies CD95-mediated apoptosis of B cells. Furthermore, in experimentally infected non-human primates (NHPs) measles virus infects and depletes pre-existing memory lymphocytes, causing immune amnesia. Results from different studies explain the long-term immunologic sequelae of measles resulting in overall childhood infectious disease mortality. As measles infection is tightly coupled to measles-associated immune memory loss, advancement in research regarding post measles immunological amnesia is needed to investigate immune pathogenesis and host immune responses.
 J Bangladesh Coll Phys Surg 2020; 38(4): 191-196

Area deprivation is inversely associated with measles incidence: A spatiotemporal analysis in Germany

Abstract Background Although measles is endemic in all WHO European regions, very few studies have directly analysed socioeconomic inequalities in disease incidence of measles. We examined the spatiotemporal association between socioeconomic deprivation and measles incidence considering relevant demographic and geographical factors at district level. Methods We conducted a longitudinal small-area analysis using nationally representative data of 401 districts from 2001 to 2017. We used Bayesian spatiotemporal regression models to assess the potential effects of area deprivation on measles incidence, adjusted for relevant demographic (district population size, sex, age, and proportion of non-nationals) and geographical factors (north-south-west-east effect) as well as spatial and temporal effects. We computed risk ratios (RR) for deprivation quintiles (Q1 - Q5), and district-specific adjusted relative risks (ARR) to assess the area-level risk profile of measles in Germany. Results The risk of measles infection in areas with lowest deprivation quintile (Q1) was 1.58 times higher (95%-credible interval [CrI] 1.32-2.00) than in those with highest deprivation (Q5). Areas with medium-low (Q2), medium (Q3), and medium-high deprivation (Q4) had higher adjusted risks of measles relative to areas with highest deprivation (Q5) (RR: 1.23 (0.99-1.51), 1.05 (0.87-1.26), and 1.23 (1.05-1.43), respectively). We identified 22 areas at high risk and 56 at medium-high risk for measles infections, with highest area-level risks in south-western Germany. Conclusions Socioeconomic deprivation in Germany is inversely associated with measles incidence, with elevated risk for measles infections in areas with higher socioeconomic status. Our findings contribute to current global and national debates on measles elimination strategies, and demonstrate the importance of spatial modelling techniques in identifying socioeconomic inequalities and spatial risk patterns of measles for public health actions. Key messages Socioeconomic deprivation is inversely associated with measles incidence in Germany, with higher risk of infection in areas with highest socioeconomic status. The social, spatial, and temporal patterns of elevated risk of measles infection require targeted public health action and policy to address the complexity underlying measles epidemiology.

Elevated expansion of follicular helper T cells in peripheral blood from children with acute measles infection

BackgroundMeasles outbreaks have threatened the global elimination and eradication of measles in recent years. Measles virus (MeV)-specific antibodies are successful in clearing MeV infection. Follicular helper T (Tfh) cells play a crucial role in promoting antibody production. This study investigated the potential role of Tfh cells in peripheral blood mononuclear cells (PBMCs) from children with acute MeV infection.ResultsThe frequencies of CXCR5+CD4+ Tfh, ICOShigh Tfh, and PD-1high Tfh cells in PBMCs and levels of IL-6 and IL-21 in plasma were significantly elevated in patients with acute MeV infection. Moreover, a positive correlation was discovered among the frequency of ICOShigh Tfh cells, plasma levels of IL-21 and optical density (OD) values of MeV-specific IgM antibodies in the patients with acute MeV infection. However, elevated plasma MeV-specific NAb titres were not associated with the frequency of Tfh, ICOShigh Tfh, or PD-1high Tfh cells in the patients with acute MeV infection.ConclusionThese results suggest that an elevated Tfh cell frequency and associated molecules possibly play a key role in children with acute MeV infection, which contributes to the prevention and treatment of MeV infection in children.

Molecular mimicry between varicella, measles virus and Hsp60 in type 1 diabetes associated HLA-DR3/DR4 molecules

Background and aimsType 1 diabetes (T1D) is a multifactorial autoimmune disease that combines genetics and environmental factors. The aim of this study is to determine the environmental risk factors and to investigate how virals infections are risks factors for type 1 diabetics whom have HLA DR3/DR4 predisposition in our population. MethodsThis study includes 233 subjects, 145 diabetics and 88 controls from regions of the extreme western of Algeria. All the informations related to the disease were collected using predesigned questionnaire.Using in silico approach, we attempt to improve the understanding of this analytical result by molecular mimicry, which is associated with the breakdown of several autoimmune pathologies. ResultsThe statistical study showed that history of varicella and measles infection and T1D related inheritance and type 2 diabetes are risk factors for T1D in the population of Tlemcen.We have determined the homologous antigenic regions between the glycoprotein “gE” of the varicella virus, the “hemagglutinin” of measles and the human protein “HSP60” at the level of their sequence and 3D structure. These cross-reactive epitopes bind to MHC class II molecules (HLA DR3/DR4) that predispose to T1D but not to MHC class II molecules (HLA DR2) that protect against T1D.This epitopes induce Th2 cells but only “hemagglutinin” and “Hsp60” can activate Th1 differentiation. This indicates their potential to destroy pancreatic cells β. ConclusionOur study can allow us to adapt biological markers to genetically predisposed T1D and to establish a preventive strategy for healthy genetic predisposed individuals in Tlemcen population.

Clinical characteristics and outcomes of measles outbreak in adults: A multicenter retrospective observational study of 93 hospitalized adults in Greece.

Measles outbreaks are increasingly reported among countries that were close-to-eliminate measles infection. There are few reports of clinical characteristics of measles in adults in the contemporary literature. In this study we aim to describe the clinical characteristics and complications of measles infection in hospitalized adults during the recent epidemic in Greece. A multicentre observational retrospective study was conducted in three tertiary hospitals in Greece. All adult hospitalized patients (≥18 years old) with serologically confirmed and/or clinical features compatible with measles were included. Pediatric patients and patients with missing data were excluded. In total, 93 patients, 40 males (43 %) and 53 females (57 %), mostly young patients were included. Most of them (87 %) had no past medical history. Among women, 4 were pregnant. 56 (60.2 %) and 25 (26.9 %) patients reported either unknown or incomplete vaccination for measles. Ribavirin was administered in 8 (8.6 %) patients. Pneumonitis and hepatic involvement were the most common complications, occurring in 43 (46.2 %) and 75 (80.6 %) patients respectively. Pneumonitis was significantly associated with male sex, older age, lower lymphocyte counts and higher C-reactive protein (CRP) on admission. One pregnant woman suffered spontaneous fetal miscarriage and one patient died due to acute respiratory distress syndrome (ARDS) and high-risk pulmonary embolism. Considerable proportions of incompletely vaccinated or unvaccinated adults have led to the re-emergence of measles in countries with reported close-to-elimination rates. Pneumonitis is a major complication among adults with measles. More studies are imperative in order to explore the role of immune paresis in measles.

Comparative evaluation of assays for IgM detection of rubella and measles infections

BackgroundSerological diagnosis of infections due to measles and rubella viruses is done by IgM detection. The aim of this study was to comparatively evaluate commercial systems for detecting IgM against both viruses, including those of ELISA, in indirect and capture formats, chemiluminescence and electrochemiluminescence. MethodsSeven (for rubella) and six (for measles) assays were studied. One hundred and sixty two samples were included in the study (from 90 rubella and 72 measles cases), and all were analyzed in all the assays. ResultsThe ranges of sensitivity, specificity and agreement for rubella were 94.8–100%, 52.4–100% and 75.5–98.1%, respectively. The corresponding ranges for measles assays were 87.0–100%, 53.3–100%, and 73.0–99.4%. ConclusionThe best-performing assays were chemiluminescence (for measles and rubella IgM), and electrochemiluminescence (for rubella IgM).

Socio-demographic correlates of first dose of measles (MCV1) vaccination coverage in India

BackgroundBetween 2010 and 2018, measles-related mortality had halved in India mainly with effective measles vaccination campaigns and widespread coverage across the states and population subgroups. Despite the commendable vaccination coverage, 2.9 million children in India missed the first dose of measles vaccine (MCV1) in 2017, and many of those vaccinated were not vaccinated at the recommended age (i.e. between 9 and 12 months). This study analyzed pattern and correlates of MCV1 coverage and MCV1 administration at recommended age among children aged 12–23 months in India.MethodsWe used the official data from the recent round of National Family Health Survey (NFHS-4), a nationally representative cross-sectional household survey in India conducted in 2015–16. Descriptive statistics and logistic regression analysis were applied to ascertain the influence of specified socio-demographic variables affecting measles vaccination coverage in India.ResultsThe study revealed the distinct variations in coverage of MCV1 between the districts of India. There were also major challenges with age recommended vaccination, with about 15% of eligible children not vaccinated within the recommended age range, attributable to several socio-demographic factors. Significantly, antenatal care utilization of mothers strongly influenced MCV1 coverage and age recommended MCV1 coverage in India. The study also identified that children who missed MCV1 had one or more adverse health risks such as malnutrition, anemia and diarrhea disease.ConclusionsA socio-economic gradient exists in India’s MCV1 coverage, mediated by antenatal visits, education of mothers, and highlighted socio-demographic factors. Infection with measles was significantly correlated with greater anthropometric deficits among the study cohort, indicating a wider range of benefits from preventing measles infection. Eliminating morbidity and mortality from measles in India is feasible, although it will require efficient expanded program on immunization management, enhanced health literacy among mothers, continuing commitment from central state and district political authorities.

Measles outbreaks – potential threat for health care professionals

SummaryThe ongoing spread of measles is a major concern for public health. Optimal vaccination coverage amongst health care professionals (HCP) is essential for individual protection. This is illustrated by our two cases of measles infection in HCP during the 2018 outbreak in Europe.We developed a questionnaire to assess protection against measles amongst HCP working in acute care of a tertiary hospital in The Netherlands. In total, 29% of these professionals were not protected against measles. During current worldwide measles outbreaks, it is paramount for employee health protection, patient protection and disease control to register and optimize employees' immunity.

Investigation and control of a measles outbreak at the Hong Kong Special Administrative Region International Airport, 2019.

IntroductionHong Kong Special Administrative Region SAR (China) achieved measles elimination status in 2016, and the incidence of measles infection had been low over the past few years. However, the Centre for Health Protection (CHP) at the Department of Health was notified on 22 March 2019 of an outbreak of three cases of measles infection among workers at the Hong Kong Special Administrative Region International Airport (HKIA).MethodsWe reviewed notifications of measles received by CHP from 1 January to 17 May 2019. We defined a confirmed case of measles as having laboratory evidence of measles infection. All confirmed cases among airport workers or those with epidemiological information suggesting they had been infected by contact with airport workers were included in the review. We described the epidemiological features and reviewed the control measures against the outbreak.ResultsWe identified 33 cases, 29 of which were among airport workers. They comprised 22 men and 11 women, aged 20–49 years (median 25 years). The majority of people with confirmed measles presented with fever and rash. All required hospitalization. None developed complications. Control measures, including enhanced environmental hygiene and improved ventilation at HKIA and vaccinations for the airport community, were implemented. Vaccinations were provided to 8501 eligible airport workers, and the outbreak was declared over on 17 May 2019.DiscussionEarly recognition of the outbreak and prompt control measures, especially targeted vaccination of the exposed population, effectively controlled the outbreak in just two weeks.

Association of CD46 Cellular Receptor Gene SNP in Measles Vaccine Response

Background: Measles is a highly contagious viral disease. It remains an important cause of death among young children globally, despite the availability of a safe and effective vaccine. Measles transmitted via droplets from the nose, mouth or throat of infected persons. Objective: To evaluate the immune response to measles infection among immunized school aged children, and to detect the cluster of differentiation 46 single nucleotide polymorphism (CD46 SNP) in association with the immune response. Methods: The current study is a cross sectional study including 158 hospitalized patients were previously vaccinated with two doses of measles-mumps-rubella vaccine. The ages of patients were 5-10 years school aged children. All samples were collected from blood collection unit in Al-Imamein Al-Kadhimein Medical city during the period from December 2018 to April 2019. The detection was based on the presence of IgG Antibody to measles. The positive results were considered according to enzyme linked immunosorbant assay and conventional polymerase chain reaction to detect CD46 SNP. Results: Among those 158 subjects' male children count for 62% and female children were 38%. Forty-one (41) immunized children (with mean age 7.98±1.92 years) were low immune response to measles vaccine (MV). On the other hand, only two cases (with mean age 5.50±0.71 years) were negative to measles virus vaccine. Conclusion: Ensuring two doses of MV give protective immune response to MV may declines with aging. CD46 cellular receptor gene SNP (rs7144) may play role in reduction in immune response to MV. Keywords: Measles, MMR, CD46, SNP, Iraq Citation: Al-Gburi SAJ, Kadhim HS, Ghazi HF. Association of CD46 Cellular Receptor Gene SNP in measles vaccine response. Iraqi JMS. 2020; 18(1): 39-46. doi: 10.22578/IJMS.18.1.6

Measles, Mumps, Rubella, and Varicella Zoster Virus Serology and Infections in Solid Organ Transplant Recipients During the First Year Posttransplantation.

Mumps, measles, rubella, and varicella zoster (MMRV) viruses may cause severe infections in seronegative adult solid organ transplant (SOT) recipients, but can be prevented by vaccination. We aimed to determine MMRV serostatus in adult SOT recipients before and 1 year after transplantation as well as evidence of MMRV infections in a large, prospective cohort of SOT recipients. This was a prospective study of 1182 adult SOT recipients included in the Management of Posttransplant Infections in Collaborating Hospitals (MATCH) cohort from 2011 to 2017 with a 1-year follow-up. Systematic monitoring of MMRV serology was performed prior to transplantation and 1 year posttransplantation. Polymerase chain reaction (PCR) was used to confirm viral replication in SOT recipients presenting with clinical evidence of infection. Among 1182 adult SOT recipients, 28 (2.4%), 77 (6.5%), 65 (5.5%), and 22 (1.9%) were seronegative for measles, mumps, rubella, and varicella zoster virus (VZV), respectively, and 165 (14%) were seronegative for at least 1 of the MMRV viruses. One year posttransplantation, 29 of 823 (3.5%) of seropositive SOT recipients had seroreverted, and 63 of 111 (57%) of seronegative SOT recipients seroconverted for at least 1 MMRV virus. No evidence of measles, mumps, or rubella infection was found, but 8 (0.7%) SOT recipients developed symptoms and had a positive VZV PCR. A large proportion of SOT recipients were seronegative for at least 1 of the MMRV viruses. MMRV infections in SOT recipients may disseminate and become fatal, and although only a few cases of VZV infection were detected, results from this study suggest increase attention toward vaccination of patients waiting for SOT.

Trends in measles cases in Bayelsa state, Nigeria: a five-year review of case-based surveillance data (2014\u20132018)

BackgroundMeasles is a vaccine preventable, highly transmissible viral infection that affects mostly children under five years. It has been ear marked for elimination and Nigeria adopted the measles elimination strategies of the World Health Organization (WHO) African region to reduce cases and deaths. This study was done to determine trends in measles cases in Bayelsa state, to describe cases in terms of person and place, identify gaps in the case-based surveillance data collection system and identify risk factors for measles infection.MethodsWe carried out a secondary data analysis of measles case-based surveillance data for the period of January 2014 to December 2018 obtained in Microsoft Excel from the State Ministry of Health. Cases were defined according to WHO standard case definitions. We calculated frequencies, proportions, estimated odds ratios (OR), 95% confidence intervals (CI) and multivariate analysis.ResultsA total of 449 cases of measles were reported. There were 245(54.6%) males and the most affected age group was 1–4 years with 288(64.1%) cases. Of all cases, 289(9.35%) were confirmed and 70 (48.27%) had received at least one dose of measles vaccine. There was an all-year transmission with increased cases in the 4th quarter of the year. Yenegoa local government area had the highest number of cases. Timeliness of specimen reaching the laboratory and the proportion of specimens received at the laboratory with results sent to the national level timely were below WHO recommended 80% respectively. Predictors of measles infection were, age less than 5 years (AOR: 0.57, 95% CI: 0.36–0.91) and residing in an urban area (AOR: 1.55, 95% CI:1.02–2.34).ConclusionsMeasles infection occurred all-year round, with children less than 5 years being more affected. Measles case-based surveillance system showed high levels of case investigation with poor data quality and poor but improving indicators. Being less than 5 years was protective of measles while living in urban areas increased risk for infection. We recommended to the state government to prioritize immunization activities in the urban centers, start campaigns by the 4th quarter and continue to support measles surveillance activities and the federal government to strengthen regional laboratory capacities.

COVID-19 and Autism Research: Perspectives from Around the Globe.

COVID-19 and Autism Research: Perspectives from Around the Globe.

Measles vaccination of young infants in China: A cost-effectiveness analysis

BackgroundAlthough global progress in measles control has been realized, achieving elimination has proven difficult in many regions of the world. China has adopted a goal of measles elimination but recent outbreaks predominantly affecting children <8 months who are ineligible for vaccination and incompletely protected by maternal antibodies has impeded progress. We assess the cost-effectiveness of adding an initial measles vaccine dose in China to earlier than the currently recommended 8 months of age. MethodsWe conducted a cost-utility analysis comparing the costs and health benefits associated with adding a measles vaccine dose to the routine schedule at 4, 5, 6 or 7 months compared to the current recommendation for the first dose at age 8 months. A decision analytic model was developed in Microsoft Excel, including five non-severe and two fatal health outcomes associated with measles infection. Model parameters were informed by the literature and surveillance data. Future costs and health benefits were discounted at 3%. Primary outcomes included costs, Quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) over a lifetime time horizon. ResultsLowering the recommended age for initiating the measles vaccination series to address susceptibility in children <8 months provided incremental health gains compared to minimal costs at the individual-level. The ICER was most favorable ($232.70 per QALY gain) for administering an initial dose at 4 months of age due to fewer incremental program costs when shifting measles administration to an immunization visit already established under the Chinese vaccination program. ConclusionWe found potential beneficial health gains at a minimum cost associated with adding an earlier measles dose <8 months of age in China. Further investigation about disease transmission dynamics is required to more fully assess the tradeoffs of administering measles at a younger age to infants in China.

Laboratory monitoring of postvaccination measles immunity

Measles vaccination In Russian Federation was introduced in 1967. It was assumed that the twodose vaccination regime would lead to a decrease in the incidence and elimination of measles. A number of studies have shown that up to 10% of individuals who received two doses of measles vaccine do not develop a specific humoral immunity, or do not maintain it at a protective level. This fact may contribute to gradual accumulation of persons susceptible for measles infection in the population, thus leading to emergence of new viral outbreaks in the future. The aim of this study was to perform dynamic monitoring of the post-vaccination measles immunity. The study involved 149 people. All the examined persons were divided into 2 groups. The group of comparison included persons, aged 19 to 51 years, in whom absence of measles immunity was serologically confirmed (n = 76). This group was twice vaccinated with live measles culture vaccine (NPO “Microgen”, Russia). Determination of IgG to measles virus was carried out 1 month after vaccination and revaccination. The control group consisted of persons with documented evidence of double immunization against measles virus, with laboratory-confirmed measles immunity (n = 73), aged 19 to 53 years. The comparative dynamics of development and contents of antibodies in the comparison-control groups were considered, with respect to the WHO age classification. Basic and postvaccinal dynamic determination of IgG to measles virus in serum was performed by ELISA using the “VectoKor-IgG” test system (Vector-Best, Novosibirsk). When analyzing the results of the study, it was noted that the level of measles immunity group in older persons from control group (over 45 years old) was initially higher, than in younger subjects. Among young people, the titers of specific measles antibodies reached the values of the control group of the corresponding age after the first vaccination, whereas the level of specific measles antibodies in older age group was significantly lower compared to the control group even after revaccination. A month after the first immunization, 4 people did not reach the protective level of anti-measles IgG. However, revaccination allowed them to form anti-measles immunity. In the course of our work, a case of non-response to vaccination was identified. Thus, our study showed a sufficient interindividual variability in humoral immune responses to measles vaccination.

The psychology of social media communication in influencing prevention intentions during the 2019 U.S. measles outbreak

This study investigates beneficial effects of social media communication on encouraging positive health prevention behaviors among U. S. parents. The ongoing 2019 U. S. measles outbreak was the topical focus due to its urgency, highly contagious nature, societal impact, and high relevance to public health. Applying the Extended Parallel Process Model as a theoretical framework, social media expression and reception effects on different prevention intentions were examined along with self-efficacy, perceived susceptibility, and perceived severity as potential mediators. The study found that both social media expression and reception were effective in encouraging preventive hygiene intention, but only through improved self-efficacy and perceived severity. For information seeking intention, both social media expression and reception were effective directly and indirectly through increased susceptibility and severity perceptions of measles infection on their child. Practical implications and study contributions are further discussed.

The Resurgence of Measles Infection and its Associated Complications in Early Childhood at a Tertiary Care Hospital in Peshawar, Pakistan.

Measles infection is of substantial interest to immunologists due to its paradoxical interaction with the immune system. After the acquisition of the measles infection, secondary infection plays a pivotal role in measles-related deaths. A cross-sectional study conducted between December 2018 and July 2019 is presented here. A total of one hundred children of both genders presented with measles complications were included following WHO criteria. Measles confirmation was done by quantitative determination of anti-measles antibodies (IgM) in patients’ sera while patient-related demographic data, vaccination status, and other clinical information were obtained on a separate form. The number of female patients (52%) slightly exceeded the number of males (48%). 43% of patients’ parents were illiterate, and half of the patients (50%) were from a poor background. The majority of children (76%) who presented with the complications did not receive a measles vaccine. 56% of children were breastfed while 58% received vitamin A supplements but developed complications. The elevated levels of anti-measles IgM were observed in 77% of cases. In both genders, the major complications were pneumonia, lower respiratory tract infection (LRTI), acute diarrhea, diarrhea and LRTI, pneumonia and diarrhea, otitis media and pneumonia, myocarditis and LRTI, and pneumothorax. The majority of the infected children (n = 48) under 12 months of age had associated complications. It has been observed that the measles virus strikes early age children in the northwestern region of Pakistan, which is an alarming situation and is associated with the aforementioned complications, especially in unvaccinated children. Anti-measles IgM is an important serological parameter for early diagnosis of measles infection.

Measles outbreak investigation in Ginnir district of Bale zone, Oromia region, Southeast Ethiopia, May 2019.

IntroductionMeasles is a vaccine-preventable viral infection of humans, primarily affecting children <5 years. During early 2019, outbreak of measles occurred in Ginnir district of Bale zone, Southeast Ethiopia. We investigated to describe the outbreak and identify risk factors.MethodsWe conducted a descriptive and 1:2 unmatched case-control study in Ginnir district from March 18 to April 29, 2019. Fifty-six cases and 112 controls were recruited. For descriptive study, we identified 1043 cases recorded on the line-list and for case-control study, cases were identified using national standard case-definition. Mothers of case-patients and controls were interviewed using structured questionnaire. We estimated vaccine efficacy (VE) from case-control study. We conducted bivariate and multivariable logistic regression.ResultsIn four-months period, a total of 1,043 suspected measles cases epidemiologically linked to five laboratory confirmed cases reported. Of which, 555 (53.2%) were males and 714 (68.5%) were <5 years. The median age of cases was 36 months (IQR=12-60 months). The overall attack rate (AR) was 63/10,000 population with case fatality ratio of 0.5% (5 deaths/1043). Infant <9 months were the most affected age groups (AR=31/1000). Majority (79%) of measles cases were not vaccinated against measles. Last-year (2017/18) administrative measle vaccine coverage of the district was 76.7%. Being unvaccinated against measles (AOR=5.4, 95%CI=2.2-13.4), travel history (AOR=4.02, 95%CI=1.2-13.6), contact with measles case-patient (AOR=5.6, 95%CI=2.12-14.4) and mothers knowledge of measles transmission (AOR=0.36, 95%CI=0.15-0.87) were associated with measles infection. VE in children aged 9-59 months was 90% (95%CI=69-97%).ConclusionThis confirmed measles outbreak was caused by failure to vaccinate, as indicated by the high VE, low administrative coverage, and 79% unvaccinated cases. Strengthening routine and supplementary immunization are required.

Review of pediatric encephalitis and encephalopathy cases following immunization reported to the Canadian Immunization Monitoring Program Active (IMPACT) from 1992 to 2012

BackgroundNeurological adverse events following immunization (AEFI) remain poorly characterized. Our objective was to describe pediatric acute and chronic encephalopathy and encephalitis cases following immunization reported via active sentinel surveillance from 1992 to 2012. MethodsThis case series provides a descriptive analysis of encephalopathy/encephalitis admissions reported to the Canadian Immunization Monitoring Program ACTive (IMPACT). Acute cases were reported if symptom onset (seizures, decreased level of consciousness, change in mental status) occurred 0–7 days after tetanus or pertussis-containing vaccines, 0–15 days after other inactivated vaccines, or 5–30 days after live vaccines. Chronic cases of subacute sclerosing panencephalitis or subacute progressive rubella encephalitis were reported at any interval after vaccination. Clinical data were examined to identify possible causes for encephalopathy/encephalitis other than vaccination. ResultsSixty-one cases of encephalopathy/encephalitis following immunization were reported to IMPACT over 21 years; 57 (93.4%) were classified as acute and 4 (6.6%) were chronic cases of subacute sclerosing panencephalitis. Most patients (73.8%) were previously healthy and immunocompetent. The vaccines most frequently administered prior to presentation were diphtheria-tetanus-pertussis, measles-mumps-rubella, and influenza. At discharge, 38 patients (62.3%) had normal neurological status or were expected to recover. Forty patients (70.2%) with acute encephalopathy/encephalitis had a more likely alternate etiology besides vaccination based on neuroimaging, symptoms suggestive of infection, laboratory-confirmed non-vaccine-related infection, or clinical diagnosis. No cases of encephalitis were causally associated with pertussis or influenza vaccines. Two patients (50%) with subacute sclerosing panencephalitis had known wild-type measles infection prior to immunization. Three deaths were reported during hospitalization (4.9%); all were acute encephalitis/encephalopathy cases and none were confirmed to be vaccine-related. ConclusionsEncephalopathy/encephalitis following immunization remains a rare but serious adverse event. Most cases had another more likely etiology than vaccination. Continued monitoring and analysis of AEFI is paramount to ensure the safety of immunization programs.

Characterizing Infection of B Lymphocytes with Measles Virus

Abstract Wild-type (w.t.) measles virus (MeV) infection generates a state of immunosuppression, which does not occur after vaccination with live attenuated vaccine. MeV has been shown to alter the function of immune cells such as dendritic cells and lymphocytes. Though altered B cell functions contribute to immune suppression, the pathogenesis of measles infection of B cells is not understood. Here, we characterized the differences in viral replication and cytokine expression in human B cells infected with vaccine (Edmonston-Zagreb [EZ]) or w.t. MeV. To measure viral replication, human B cells were infected with an EZ virus expressing GFP and the number of GFP expressing cells and mean fluorescence intensity (MFI) were measured after 24 hours. To measure differences in cytokine responses following infection of B cells with EZ or w.t., transcription of IL-1β, IL-6, IL-10, TNFα, IFNβ, and IFNγ was measured at 24, 48, and 72 hours after infection by quantitative RT-PCR. The number of B cells expressing GFP and the MFI increased 3-fold from 0 to 24 hours after infection. Preliminary data suggested that IL-1β transcription is higher in w.t. infected B cells, while IL-6 and IL-10 transcription were higher in EZ-infected B cells. Measles virus replication was detected 24 hours after infection of isolated, human B cells. The differential expression of cytokines in B cells suggest differences in the B cell response to infection with w.t and vaccine strains of MeV. Differential cytokine expression in w.t. infected B cells could play a role in the development of immune cell dysregulation, and the mechanism could be elucidated through further functional studies of infected B cells.