Wild-type Measles Research Articles

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

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

Vaccine-associated measles in an immunocompromised host: Hospital infection prevention and control and public health response

Introduction: Vaccine-associated measles is generally not considered to be transmissible, as opposed to wild-type measles, which is one of the most highly contagious diseases. Data on contact and exposure management of vaccine-associated measles is limited, with varied approaches to such cases described in the literature. Methods: We report the case of a 2-year-old immunosuppressed child who developed a febrile exanthem with mild conjunctivitis 18 days after receiving the measles-mumps-rubella-varicella vaccine. Results: Given the patient's recent measles-containing vaccination while on immunosuppressive medications, consistent clinical findings and the lack of epidemiological risk factors for wild-type infection, the decision was made to treat this as a presumptive case of vaccine-associated measles virus prior to return of confirmatory genotyping results. After consultation with public health experts, contact tracing was not considered necessary. No secondary measles cases were identified, despite a large exposure potential due to lack of consistent airborne precautions during hospital admission. Discussion: This case highlights the lack of transmissibility of vaccine-associated measles in immunocompromised hosts, adding to the scant body of literature on this topic, with the potential to inform hospital infection prevention and control as well as public health management in similar situations.

Measles Infection Dose Responses: Insights from Mathematical Modeling

How viral infections develop can change based on the number of viruses initially entering the body. The understanding of the impacts of infection doses remains incomplete, in part due to challenging constraints, and a lack of research. Gaining more insights is crucial regarding the measles virus (MV). The higher the MV infection dose, the earlier the peak of acute viremia, but the magnitude of the peak viremia remains almost constant. Measles is highly contagious, causes immunosuppression such as lymphopenia, and contributes substantially to childhood morbidity and mortality. This work investigated mechanisms underlying the observed wild-type measles infection dose responses in cynomolgus monkeys. We fitted longitudinal data on viremia using maximum likelihood estimation, and used the Akaike Information Criterion (AIC) to evaluate relevant biological hypotheses and their respective model parameterizations. The lowest AIC indicates a linear relationship between the infection dose, the initial viral load, and the initial number of activated MV-specific T cells. Early peak viremia is associated with high initial number of activated MV-specific T cells. Thus, when MV infection dose increases, the initial viremia and associated immune cell stimulation increase, and reduce the time it takes for T cell killing to be sufficient, thereby allowing dose-independent peaks for viremia, MV-specific T cells, and lymphocyte depletion. Together, these results suggest that the development of measles depends on virus-host interactions at the start and the efficiency of viral control by cellular immunity. These relationships are additional motivations for prevention, vaccination, and early treatment for measles.Graphical abstractMeasles infection dose responses: insights from mathematical modeling. Top: Model-data fits for acute viremia in response to changes in measles infection doses. 104\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$10^4$$\\end{document}, 103\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$10^3$$\\end{document}, 102\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$10^2$$\\end{document}, 10 and 1 TCID50\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$_{50}$$\\end{document} correspond to red diamonds, blue stars, orange triangles, magenta dots, and green squares respectively. The solid lines represent the trajectories generated by the proposed model parameterization. The shapes represent data. The dark grey dotted dashed line represents the limit of detection < 0.3. Bottom: Cartoon illustrating that when the measles infection dose increases, the stimulation of the measles-specific cellular immune responses increases early on post-infection. This enhanced immune response reduces the time required to clear the infectious viral load and helps maintain similar levels of viral loads and lymphocyte depletion irrespective of the initial dose.

Genetic Characterization of Wild-Type Measles Viruses Isolated in Peshawar Pakistan

Background: Measles is a highly contagious disease, caused by the Measles Virus (MV). Knowledge of genotypes prevalent in any region is important in effective measles surveillance; by mapping distribution of prevalent MV genotypes at different points of time, in a region, gives an idea about the success of measles control through vaccination programs, by documenting the interruption of transmission of the endemic viral genotype. Objectives: To detect genotypes of wild type measles virus isolated from the samples collected of measles patients in Peshawar valley of Khyber Pakhtunkhwa (KPK) province, Pakistan.Material and Methods: This was a cross-sectional descriptive study. Nasopharyngeal and/or throat swab samples were collected during a measles outbreak, from February to March 2014, from clinically diagnosed measles patients (cases who met the clinical case definition of WHO). Collection and processing were done according to the standard protocols. RNA (Ribo-Nucleic Acid) was extracted directly from samples; cDNA (Complimentary Deoxy-Ribonucleic Acid) was synthesized, amplification and sequencing of 528bp of carboxy-terminal of N gene was carried out. Sequences were analyzed and data were compared with the standard reference strains of measles virus.Results: A total of nine sequences obtained were of good quality and enough in length to meet WHO criteria for genotype assignment. It was found that all the nine strains of measles virus belonged to clade B, genotype B3 and cluster B3.1. The rest of the 13 sequences which were shorter in length for genotype assignment also showed close resemblance to Genotype B3.Conclusion: Wild type measles virus strains, isolated from the samples of measles patients, in Peshawar valley of Khyber Pakhtunkhwa province of Pakistan were found to be genotype B3. It shows that genotype B3 may be the predominate genotype prevalent in Peshawar region at the time of this study.Keywords: B3 genotype, Genotyping of measles, Measles Virus, Molecular epidemiology.

Neutralizing Antibody Response to Genotypically Diverse Measles Viruses in Clinically Suspected Measles Cases.

The neutralizing antibody (Nt-Ab) response to vaccine and wild-type measles viruses (MeV) was studied in suspected measles cases reported during the years 2012-2016. The neutralization activity against MeV A, D4 and D8 genotypes was studied on sera (Panel A; n = 68 (measles-immunized) and Panel B; n = 50 (unvaccinated)) that were either laboratory confirmed or not confirmed by the presence of IgM antibodies. Additionally, the Nt-Ab response in Panel A was measured against the MeV vaccine and four wild-type viruses. Neutralization results were compared using homology modeling and molecular dynamics simulation (MDS) of MeV-hemagglutinin (H) and fusion (F) proteins. Overall, the Nt-Ab titres for MeV-A were found to be significantly lower than MeV-D4 and MeV-D8 viruses for Panel A. No major difference was noted in Nt-Ab titres between MeV-D8 viruses (Jamnagar and New Delhi), whereas MeV-D4 (Sindhudurg and Bagalkot (BGK) viruses) showed significant differences between Nt-Ab titres for Panel B. Interestingly, the substitutions observed in epitopes of H-protein, L249P and G316A are observed to be unique to MeV-BGK. MDS of H-protein revealed significant fluctuations in neutralizing epitopes due to L249P substitution. The majority of the clinically suspected cases showed Nt-Abs to MeV wild-types. Higher IgG antibody avidity and Nt-Ab titres were noted in IgM-negatives than in IgM-positives cases, indicating reinfection or breakthrough. MDS revealed reduced neutralization due to decreased conformational flexibility in the H-epitope.

Measles virus transmission patterns and public health responses during Operation Allies Welcome: a descriptive epidemiological study

On Aug 29, 2021, Operation Allies Welcome (OAW) was established to support the resettlement of more than 80 000 Afghan evacuees in the USA. After identification of measles among evacuees, incoming evacuee flights were temporarily paused, and mass measles vaccination of evacuees aged 6 months or older was introduced domestically and overseas, with a 21-day quarantine period after vaccination. We aimed to evaluate patterns of measles virus transmission during this outbreak and the impact of control measures. We conducted a measles outbreak investigation among Afghan evacuees who were resettled in the USA as part of OAW. Patients with measles were defined as individuals with an acute febrile rash illness between Aug 29, 2021, and Nov 26, 2021, and either laboratory confirmation of infection or epidemiological link to a patient with measles with laboratory confirmation. We analysed the demographics and clinical characteristics of patients with measles and used epidemiological information and whole-genome sequencing to track transmission pathways. A transmission model was used to evaluate the effects of vaccination and other interventions. 47 people with measles (attack rate: 0·65 per 1000 evacuees) were reported in six US locations housing evacuees in four states. The median age of patients was 1 year (range 0-26); 33 (70%) were younger than 5 years. The age distribution shifted during the outbreak towards infants younger than 12 months. 20 (43%) patients with wild-type measles virus had rash onset after vaccination. No fatalities or community spread were identified, nor further importations after flight resumption. In a non-intervention scenario, transmission models estimated that a median of 5506 cases (IQR 10-5626) could have occurred. Infection clusters based on epidemiological criteria could be delineated into smaller clusters using phylogenetic analyses; however, sequences with few substitution count differences did not always indicate single lines of transmission. Implementation of control measures limited measles transmission during OAW. Our findings highlight the importance of integration between epidemiological and genetic information in discerning between individual lines of transmission in an elimination setting. US Centers for Disease Control and Prevention.

Mechanistic insight into immune amnesia and immunity induced by wild-type measles virus compared to live-attenuated measles vaccine

Abstract Despite the availability of a safe and effective vaccine, measles still causes significant mortality and morbidity among children in developing countries. As a disease that induces immune amnesia with increased susceptibility to other infections but also life-long immunity to measles, little is known about the immunogenetics of B cells that elicit measles-specific antibodies (Abs) in natural infection vs vaccination. We therefore conducted single-cell RNA sequencing (scRNA-seq) of longitudinal peripheral blood mononuclear cells (PBMC) and lymph node (LN) samples from wild-type (WT) measles virus (MeV) and live-attenuated measles vaccine (LAMV)-infected rhesus macaques (RMs) and characterized their gene expression, B cell repertoires and clonotype changes via bioinformatic pipelines. Preliminary analysis of two RMs across four timepoints (one WT MeV- and one LAMV-infected RM) revealed similarities and differences in immune cell populations and B cell repertoires, providing important mechanistic insights into B cell clonal development in natural infection as compared to vaccination. Supported by grants from NIH R01 AI153140 and the Jeffrey Richardson Fellowship

Mechanism(s) of long-term humoral immunity and immune suppression induced by wildtype Measles virus in rhesus macaques

Abstract Measles virus (MeV) causes a highly contagious systemic viral infection that remains an important cause of morbidity and mortality in children worldwide. While recovery from measles infection induces life-long protective immunity, it also causes immune amnesia which can lead to higher susceptibility to other infections. To better understand the long-term immune responses induced by the MeV vaccine versus wildtype (WT) MeV, first, we studied rhesus macaques for six months after WT MeV or Measles-Mumps-Rubella (MMR) inoculation. We quantified total antibody secreting cells (ASC) and MeV-specific ASCs in peripheral blood mononuclear cells (PBMCs) using well-characterized in house methods for ELISpot; and assessed MeV-specific IgG, avidity, and plaque reduction neutralization titers. Second, we assessed whether the loss in immune memory post WT MeV infection is linked to eviction of B cells from the bone marrow (BM) into circulation. BM and PBMCs from live attenuated MeV (LAMV) vaccinated monkeys were cultured and supernatant were assessed for isotype and antigen specificity by ELISA. PBMC cultures produced detectable amount of MeV-specific antibody and antibody recognition profiles will be compared via Virscan, a phage-display technology for epitope mapping. A novel panel of non-human primate (NHP) pathogen peptides representing Herpesviruses, Retroviruses, Adenoviruses, Pneumoviruses, and Enteroviruses were developed and expressed using the system with plans to use them to characterize changes in antibody production. We hypothesis that the robust immune response to WT MeV is accompanied by eviction of long-lived plasma cells from BM niches resulting in a loss of Ab diversity that does not occur after infection with LAMV. Supported by grants from NIH (5R01AI153140-03)

Development of real-time RT-PCR assays to detect measles virus on the Hologic Panther Fusion® System.

In 2019, Aotearoa New Zealand (NZ) experienced its worst measles outbreak since 1997. Due to declining childhood vaccination rates since the beginning of the SARS-CoV-2 pandemic, NZ is at serious risk of another major measles outbreak. Our laboratory provides diagnostic services to NZ's Southern region. In 2019 the Southern region experienced the greatest number of cases outside of Auckland and Northland, however we did not have a validated measles PCR assay in our laboratory. We sought to develop reverse transcription real-time polymerase chain reaction (RT-PCR) assays for measles on the Hologic Panther Fusion® System by utilising its open access function. Previously published real-time RT-PCR assays were modified and optimised to detect wild-type measles virus (LDT-Mea), and the vaccine strain of measles virus (LDT-MeaVacA), on the Hologic Panther Fusion® System. The assays were clinically validated. The LDT-Mea assay has a limit of detection (LoD) of 0.1 CCID50, while the LDT-MeaVacA assay is less sensitive with a LoD of 1 CCID50. Using 27 samples, the clinical sensitivity and specificity was 100% for both assays. Other common respiratory viruses were found not to cross-react with either the LDT-Mea or LDT-MeaVacA assays. We have successfully adapted and validated for diagnostic use on the Hologic Panther Fusion® System previously published assays to detect wild-type and vaccine strains of the measles virus. The implementation of measles testing on this system will greatly improve the turn-around time for measles testing, and better support the measles public health response, for our region.

A defined anthocyanin mixture sourced from bilberry and black currant inhibits Measles virus and various herpesviruses

BackgroundAnthocyanin-containing plant extracts and carotenoids, such as astaxanthin, have been well-known for their antiviral and anti-inflammatory activity, respectively. We hypothesised that a mixture of Ribes nigrum L. (Grossulariaceae) (common name black currant (BC)) and Vaccinium myrtillus L. (Ericaceae) (common name bilberry (BL)) extracts (BC/BL) with standardised anthocyanin content as well as single plant extracts interfered with the replication of Measles virus and Herpesviruses in vitro.MethodsWe treated cell cultures with BC/BL or defined single plant extracts, purified anthocyanins and astaxanthin in different concentrations and subsequently infected the cultures with the Measles virus (wild-type or vaccine strain Edmonston), Herpesvirus 1 or 8, or murine Cytomegalovirus. Then, we analysed the number of infected cells and viral infectivity and compared the data to non-treated controls.ResultsThe BC/BL extract inhibited wild-type Measles virus replication, syncytia formation and cell-to-cell spread. This suppression was dependent on the wild-type virus-receptor-interaction since the Measles vaccine strain was unaffected by BC/BL treatment. Furthermore, the evidence was provided that the delphinidin-3-rutinoside chloride, a component of BC/BL, and purified astaxanthin, were effective anti-Measles virus compounds. Human Herpesvirus 1 and murine Cytomegalovirus replication was inhibited by BC/BL, single bilberry or black currant extracts, and the BC/BL component delphinidin-3-glucoside chloride. Additionally, we observed that BC/BL seemed to act synergistically with aciclovir. Moreover, BC/BL, the single bilberry and black currant extracts, and the BC/BL components delphinidin-3-glucoside chloride, cyanidin-3-glucoside, delphinidin-3-rutinoside chloride, and petunidin-3-galactoside inhibited human Herpesvirus 8 replication.ConclusionsOur data indicate that Measles viruses and Herpesviruses are differentially susceptible to a specific BC/BL mixture, single plant extracts, purified anthocyanins and astaxanthin. These compounds might be used in the prevention of viral diseases and in addition to direct-acting antivirals, such as aciclovir.

Australian vaccine preventable disease epidemiological review series: measles, 2012-2019.

Data sources, relevant to measles epidemiology from 2012 to 2019, were reviewed in the context of Australia's certification, by the World Health Organization in 2014, of the elimination of measles. Data on measles notifications, hospitalisations, and deaths were obtained from the National Notifiable Diseases Surveillance System, the National Hospital Morbidity Database, and the Australian Coordinating Registry. Data were analysed by age group, state/territory, Aboriginal and Torres Strait Islander status, genotype, place of acquisition, source of infection (importation status), and vaccination status. Between 2012 and 2019, there were 1,337 measles notifications (average annual notifications 0.7 per 100,000 population per year) and 425 hospitalisations with measles as principal diagnosis (0.3 per 100,000 population per year) were recorded. The highest annual notification rate was in 2014, when the rate in the Northern Territory was 21.4 per 100,000 population per year. Although notification and hospitalisation rates were highest in infants < 12 months (respectively 5.8 and 2.1 per 100,000 population per year), people aged 10 to 39 years (10-19y: 272 notifications; 20-29y: 347; 30-39y: 266) accounted for 66% of notified cases. Of cases with a known vaccination status, only 20/169 (11.8%) of those aged 1-9 years had received at least one dose of measles-containing vaccine, compared with 215/571 (37.7%) of those aged 10-39 years. Persons born before 1966 (at least 47 years of age during the study period) are likely to have immunity from wild-type measles infection and had the lowest notification rates in each year. Of notified cases, 98.1% were imported or import related, and of the 900 measles viruses genotyped, D8 and B3 accounted for 89.1%. This review's findings of low measles incidence, in the presence of robust surveillance and high two-dose measles vaccination coverage, provide evidence of continued elimination of endemic measles in Australia, with almost all cases imported or epidemiologically linked to an imported case. Most cases eligible for vaccination are unvaccinated, which should remain the primary focus for prevention. Potential waning immunity in older age groups requires monitoring. Continued high population immunity and high-quality public health response to cases will be needed to maintain Australia's elimination status, particularly once international borders reopen.

COVID-19 Australia: Epidemiology Report 60: Reporting period ending 10 April 2022.

Background Data sources, relevant to measles epidemiology from 2012 to 2019, were reviewed in the context of Australia’s certification, by the World Health Organization in 2014, of the elimination of measles. Methods Data on measles notifications, hospitalisations, and deaths were obtained from the National Notifiable Diseases Surveillance System, the National Hospital Morbidity Database, and the Australian Coordinating Registry. Data were analysed by age group, state/territory, Aboriginal and Torres Strait Islander status, genotype, place of acquisition, source of infection (importation status), and vaccination status. Results Between 2012 and 2019, there were 1,337 measles notifications (average annual notifications 0.7 per 100,000 population per year) and 425 hospitalisations with measles as principal diagnosis (0.3 per 100,000 population per year) were recorded. The highest annual notification rate was in 2014, when the rate in the Northern Territory was 21.4 per 100,000 population per year. Although notification and hospitalisation rates were highest in infants &lt; 12 months (respectively 5.8 and 2.1 per 100,000 population per year), people aged 10 to 39 years (10–19y: 272 notifications; 20–29y: 347; 30–39y: 266) accounted for 66% of notified cases. Of cases with a known vaccination status, only 20/169 (11.8%) of those aged 1–9 years had received at least one dose of measles-containing vaccine, compared with 215/571 (37.7%) of those aged 10–39 years. Persons born before 1966 (at least 47 years of age during the study period) are likely to have immunity from wild-type measles infection and had the lowest notification rates in each year. Of notified cases, 98.1% were imported or import related, and of the 900 measles viruses genotyped, D8 and B3 accounted for 89.1%. Conclusion This review’s findings of low measles incidence, in the presence of robust surveillance and high two-dose measles vaccination coverage, provide evidence of continued elimination of endemic measles in Australia, with almost all cases imported or epidemiologically linked to an imported case. Most cases eligible for vaccination are unvaccinated, which should remain the primary focus for prevention. Potential waning immunity in older age groups requires monitoring. Continued high population immunity and high-quality public health response to cases will be needed to maintain Australia’s elimination status, particularly once international borders reopen.

In Elimination Settings, Measles Antibodies Wane After Vaccination but Not After Infection: A Systematic Review and Meta-Analysis.

We conducted a systematic review to assess whether measles humoral immunity wanes in previously infected or vaccinated populations in measles elimination settings. After screening 16 822 citations, we identified 9 articles from populations exposed to wild-type measles and 16 articles from vaccinated populations that met our inclusion criteria. Using linear regression, we found that geometric mean titers (GMTs) decreased significantly in individuals who received 2 doses of measles-containing vaccine (MCV) by 121.8 mIU/mL (95% confidence interval [CI], -212.4 to -31.1) per year since vaccination over 1 to 5 years, 53.7 mIU/mL (95% CI, -95.3 to -12.2) 5 to 10 years, 33.2 mIU/mL (95% CI, -62.6 to -3.9), 10 to 15 years, and 24.1 mIU/mL (95% CI, -51.5 to 3.3) 15 to 20 years since vaccination. Decreases in GMT over time were not significant after 1 dose of MCV or after infection. Decreases in the proportion of seropositive individuals over time were not significant after 1 or 2 doses of MCV or after infection. Measles antibody waning in vaccinated populations should be considered in planning for measles elimination.

Co-detection of the measles vaccine and wild-type virus by real-time PCR: public health laboratory protocol.

In rare cases vaccination with the measles virus vaccine genotype A (MeVA) may cause a vaccine reaction with clinical signs similar to infection with wild-type measles virus (MeVwt). Rapid differentiation between MeVA and MeVwt infection is important for taking adequate public health measures. Recently, a few MeVA real-time reverse-transcription quantitative PCR methods (RT-qPCRs) were described that can distinguish between MeVA and MeVwt. However, detection of MeVA does in theory not exclude infection with MeVwt. In the present study, we established a protocol for determination of co-infections with MeVA and MeVwt. To this end, MeVA RT-qPCRs were used in combination with the routine measles virus (MeV) RT-qPCR, and the results suggested that the differences between the RT-qPCR Ct values (delta Ct, ∆Ct) could be used as criteria. Subsequently, we tested samples from vaccine-associated measles cases that were confirmed by genotyping. In addition, experimental mixtures of MeVA and MeVwt were tested in different concentrations. All tested MeVA clinical samples had ∆Ct ≤3.6. The results of experimental mixtures showed a mean ∆Ct ≤2.8 for genotype A alone and >3.2 when combined with either genotype B3 or D8. The results of a receiver operator characteristic analysis indicated that the optimum ∆Ct for use as a cut-off value was 3.5, while with ∆Ct values of 2.9 and 3.7 sensitivity and specificity were respectively 1.00. Thus, ∆Ct could be used to exclude the presence of MeVwt if MeVA is detected and ∆Ct is <2.9, while ∆Ct >3.7 were highly suggestive of co-infection and ≥2.9 ∆Ct <3.7 warranted additional confirmation, such as next-generation sequencing. This RT-qPCR-based protocol could be used for the exclusion of infection with MeVwt in cases with vaccine-associated measles reaction, crucial for the timely implementation of public health prevention and control measures.

Measles like syndrome after measles and rubella vaccination

National vaccination program (NIS, IAP) provides vaccination for measles and rubella (MR vaccine) for all children below 15 years of age. After vaccination with live attenuated viruses, the virus replicates on a limited scale. Replication may lead to mild symptoms occurring 5-14 days after MR-vaccination including fever, conjunctivitis and rash but sometimes it leads to florid type of severe rashes which are indistinguishable from a wildtype measles infection. A measles like syndrome may occur following MR vaccination, although it seems to be a rare event and therefore as a pediatrician we must take out time to educate and reassurance the parents about this benign nature and so as to avoid unnecessary problems in future. A 14 year old female child was admitted in our hospital with an impressive (florid) rashes, 7 days after MR vaccination in our vaccination clinic. Diagnostic tests were negative for measles and other infections and was discharged after 7 days of nursing and supportive care. Within 14 days after MR vaccination, a child can present with symptoms very similar to a wildtype measles virus infection. The low incidence of wildtype measles infection after MR vaccination, strongly suggests that these symptoms will likely be a reaction to MR vaccination. To elaborate lots of diagnostic procedures may cause the parents a lot of stress and therefore offering nursing care, supportive care and reassurance to parents may be more appropriate and effective in such cases.

Is it or is it not? Lessons learned from a case of suspected vaccine-associated measles

Background: Measles is a highly infectious viral disease that can cause serious illness and complications. Despite Australia's measles elimination status declared in 2014, the risk of acquiring measles through importation by overseas travellers who are non-immune remains. Identifying wild-type measles in a female who was recently vaccinated with measles mumps rubella (MMR) is a challenge one metropolitan Public Health Unit (PHU) experienced. Case Description: In 2018, a metropolitan Sydney PHU was notified of a positive polymerase chain reaction (PCR) result for measles on a nasopharyngeal swab for a 32 y old female who had recently received an MMR-II vaccination seven days prior to developing symptoms of measles. The case had no known epidemiological link, no recent overseas travel and no contact with recent measles cases during her incubation period. The reference laboratory ran sequencing on the clinical specimen to distinguish between wild-strain and vaccine-type measles. The results of this were inconclusive, however given the recent vaccination and inconsistent clinical symptoms and no identified epidemiological link, a decision was made to re-run the genotyping, collect additional specimens for testing, and quarantine the case until a definitive result was obtained. Subsequently, sequencing and genotyping test results revealed that this indeed was a wild-type measles strain, genotype D8. Discussion: A change in the epidemiology of measles, especially in low incidence countries like Australia, means distinguishing between wild type and vaccine–associated measles has become a new challenge, but critical in implementing a timely public health response. The initial decision to classify this case as vaccine-associated measles was based on the clinical context, epidemiological risk and inconclusive sequencing results. The lack of an epidemiological link created confusion for public health staff when investigating this case. Conclusion: This case investigation and response has demonstrated the challenge for public health with non-typical presentations of wild-type measles, particularly in people who have received one MMR. The reflection of the public health management of this case has provided an opportunity to learn from this experience and can become a valuable teaching tool for public health professionals globally, particularly in low incidence measles countries.

Measles Vaccine-Associated Rash Illness in China: an Emerging Issue in the Process of Measles Elimination.

Along with the implementation of measles case-based surveillance, measles vaccine-associated rash illness (VARI) cases were detected in China. To better understand the characteristics of VARI, 101 VARI cases confirmed by measles virus genotyping in 2011 to 2018 were analyzed in this study. With the decrease in measles incidence, the detection rate of VARI cases increased among the cases confirmed by genotyping. Compared with genotype H1 wild-type measles, VARI occurred throughout the year, without obvious seasonal distribution. Infants and children of ages 8 to 23 months were the main population of VARI. VARI mainly occurred within 14 days after measles vaccination. The number of VARI cases peaked on the 8th day after measles vaccination, which was later than that of genotype H1 wild-type measles cases with a measles vaccination history. VARI presents clinical symptoms similar to those of measles. The frequencies of the "3Cs" (cough, coryza, and conjunctivitis), Koplik spots, and complications in VARI cases were significantly lower than those in wild-type measles cases. In total, 94.06% of sequences from VARI cases were identical to measles vaccine strain S191 in the C-terminal 450-nucleotide sequence of the nucleoprotein (N-450) gene. A few substitutions were found in N-450 sequences of the VARI cases. The confirmation of VARI has become an emerging issue in the process of measles elimination. Rapid confirmation of VARI is critical for measles surveillance and will help to determine the response measures for measles, especially in measles preelimination and elimination settings. The suspected measles cases with measles-containing vaccine (MCV) vaccination were recommended to be tested by the laboratory to identify wild-type measles or VARI.

Is it or is it not? Lessons learned from a case of suspected vaccine strain measles

Abstract Background Measles continues to be a threat to Australia. While post eradication risks are low, imported measles cases from overseas travellers who are non-immune can cause small outbreaks. This case report discusses the challenge of identifying wild-type measles in an individual who was recently vaccinated with measles - containing vaccine (MCV). Methods A positive polymerase chain reaction (PCR) result for measles for an adult who had recently received a measles -containing vaccine was notified. Investigation revealed no known epidemiological link, recent overseas travel or contact with recent measles cases during the incubation period. Results The results of the initial sequencing to distinguish between wild-type and vaccine-strain measles were inconclusive. A decision was made to re-run the genotyping, collect additional specimens, and quarantine the case until a definitive result was obtained. Sequencing and genotyping revealed that this indeed was a wild-type measles strain. Conclusions Changing epidemiology of measles means distinguishing between wild-type and vaccine-strain measles has become a new challenge. The reflection of the public health management of this case has provided is a valuable teaching tool for public health professionals globally, particularly in low incidence measles countries. Key messages The lack of an epidemiological link can create confusion for public health staff when investigating possible measles cases. Changes in the epidemiology of measles means distinguishing between wild type and vaccine strain measles is a challenge.

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.

A durable protective immune response to wild-type measles virus infection of macaques is due to viral replication and spread in lymphoid tissues.

Infection with wild-type (WT) measles virus (MeV) is an important cause of childhood mortality that leads to lifelong protective immunity in survivors. WT MeV and the live-attenuated MeV used in the measles vaccine (LAMV) are antigenically similar, but the determinants of attenuation are unknown, and protective immunity induced by LAMV is less robust than that induced by WT MeV. To identify factors that contribute to these differences, we compared virologic and immunologic responses after respiratory infection of rhesus macaques with WT MeV or LAMV. In infected macaques, WT MeV replicated efficiently in B and T lymphocytes with spreading throughout lymphoid tissues resulting in prolonged persistence of viral RNA. In contrast, LAMV replicated efficiently in the respiratory tract but displayed limited spread to lymphoid tissue or peripheral blood mononuclear cells. In vitro, WT MeV and LAMV replicated similarly in macaque primary respiratory epithelial cells and human lymphocytes, but LAMV-infected lymphocytes produced little virus. Plasma concentrations of interleukin-1β (IL-1β), IL-12, interferon-γ (IFN-γ), CCL2, CCL11, CXCL9, and CXCL11 increased in macaques after WT MeV but not LAMV infection. WT MeV infection induced more protective neutralizing, hemagglutinin-specific antibodies and bone marrow plasma cells than did LAMV infection, although numbers of MeV-specific IFN-γ- and IL-4-producing T cells were comparable. Therefore, MeV attenuation may involve altered viral replication in lymphoid tissue that limited spread and decreased the host antibody response, suggesting a link between lifelong protective immunity and the ability of WT MeV, but not LAMV, to spread in lymphocytes.