What Is the #Evidence to Support a Correlate of #Protection for #Measles? A Systematic Review (J Infect Dis., abstract)

[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

What Is the Evidence to Support a Correlate of Protection for Measles? A Systematic Review

Shelly Bolotin, Stephanie L Hughes, Nazish Gul, Sumaiya Khan, Paul A Rota, Alberto Severini, Susan Hahné, Andrea Tricco, William J Moss, Walter Orenstein, Nikki Turner, David Durrheim, Jane M Heffernan, Natasha Crowcroft

The Journal of Infectious Diseases, jiz380, https://doi.org/10.1093/infdis/jiz380

Published: 01 November 2019

 

Abstract

Background

Many studies assume that the serologic correlate of protection from measles disease is 120 mIU/mL. We systematically reviewed the literature to examine the evidence supporting this correlate of protection.

Methods

We searched peer-reviewed and gray literature for articles reporting a measles correlate of protection. We excluded studies focusing on special populations, infants aged <9 months, and those using animal models or nonstandard vaccines or administration routes. We extracted and synthesized data from full-text articles that met inclusion criteria.

Results

We screened 14 778 articles and included 5 studies in our review. The studies reported either preexposure antibody concentrations of individuals along with a description of symptoms postexposure, or the proportion of measles cases that had preexposure antibody concentrations above a threshold of immunity specified by the authors. Some studies also described secondary antibody responses upon exposure. The variation in laboratory methods between studies made comparisons difficult. Some of the studies that assumed 120 mIU/mL as a correlate of protection identified symptomatic individuals with preexposure titers exceeding this threshold.

Conclusions

Our findings underscore the scant data upon which the commonly used 120 mIU/mL measles threshold of protection is based, suggesting that further work is required to characterize the measles immunity threshold.

correlate of protection, threshold of protection, measles immunity, systematic review

Issue Section: Review

Keywords: Measles; Serology.

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#Measles virus #infection diminishes preexisting #antibodies that offer #protection from other #pathogens (Science, abstract)

[Source: Science, full page: (LINK). Abstract, edited.]

Measles virus infection diminishes preexisting antibodies that offer protection from other pathogens

Michael J. Mina1,2,3,*,†, Tomasz Kula1,2, Yumei Leng1, Mamie Li2, Rory D. de Vries4, Mikael Knip5,6, Heli Siljander5,6, Marian Rewers7, David F. Choy8, Mark S. Wilson8, H. Benjamin Larman9, Ashley N. Nelson10,‡, Diane E. Griffin10, Rik L. de Swart4, Stephen J. Elledge1,2,11,†

1 Division of Genetics, Brigham and Women’s Hospital, Howard Hughes Medical Institute, Boston, MA 02115, USA. 2 Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. 3 Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA. 4 Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus MC, University Medical Centre Rotterdam, 3015 CN, Rotterdam, Netherlands. 5 Children’s Hospital, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, Finland. 6 Research Program for Clinical and Molecular Metabolism, University of Helsinki, 00014 Helsinki, Finland. 7 Barbara Davis Center for Diabetes, University of Colorado School of Medicine, Denver, CO 80045, USA. 8 Genentech Inc., South San Francisco, CA 94080, USA. 9 Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. 10 W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA. 11 Program in Virology, Harvard Medical School, Boston, MA 02115, USA.

†Corresponding author. Email: selledge@genetics.med.harvard.edu (S.J.E.); mmina@hsph.harvard.edu (M.J.M.)

* Present address: Center for Communicable Disease Dynamics, Department of Epidemiology and Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.

‡ Present address: Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA.

Science  01 Nov 2019: Vol. 366, Issue 6465, pp. 599-606 / DOI: 10.1126/science.aay6485

 

The toll of measles on the immune system

Many of the deaths attributable to measles virus are caused by secondary infections because the virus infects and functionally impairs immune cells. Whether measles infection causes long-term damage to immune memory has been unclear. This question has become increasingly important given the resurgence in measles epidemics worldwide. Using a blood test called VirScan, Mina et al. comprehensively analyzed the antibody repertoire in children before and after natural infection with measles virus as well as in children before and after measles vaccination. They found that measles infection can greatly diminish previously acquired immune memory, potentially leaving individuals at risk for infection by other pathogens. These adverse effects on the immune system were not seen in vaccinated children.

Science, this issue p. 599

 

Abstract

Measles virus is directly responsible for more than 100,000 deaths yearly. Epidemiological studies have associated measles with increased morbidity and mortality for years after infection, but the reasons why are poorly understood. Measles virus infects immune cells, causing acute immune suppression. To identify and quantify long-term effects of measles on the immune system, we used VirScan, an assay that tracks antibodies to thousands of pathogen epitopes in blood. We studied 77 unvaccinated children before and 2 months after natural measles virus infection. Measles caused elimination of 11 to 73% of the antibody repertoire across individuals. Recovery of antibodies was detected after natural reexposure to pathogens. Notably, these immune system effects were not observed in infants vaccinated against MMR (measles, mumps, and rubella), but were confirmed in measles-infected macaques. The reduction in humoral immune memory after measles infection generates potential vulnerability to future infections, underscoring the need for widespread vaccination.

Keywords: Measles; Immunopathology.

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Hypoxemic #measles #pneumonitis in an immunocompetent adult (Rev Med Liege., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Rev Med Liege. 2019 Oct;74(10):499-502.

[Hypoxemic measles pneumonitis in an immunocompetent adult].

[Article in French; Abstract available in French from the publisher]

Ali D1, Gorur Y2, Bosquée L3, Cardos B4, Lorenzo VN5.

Author information: 1 Service des Urgences, CHC Saint-Joseph, Liège, Belgique. 2 Service d’Imagerie médicale, CHU Liège, Belgique. 3 Service de Pneumologie. 4 Service des Urgences, Clinique André Renard, Herstal, Belgique. 5 Service de Médecine interne, Diabète et Maladies métaboliques, Hôpitaux Universitaires de Strasbourg, France.

Abstract in English, French

Measles is a highly contagious viral disease and one of the biggest causes of morbidity and mortality in the world. Transmission occurs from person to person through direct contact or by aerosolization of pharyngeal secretions. It can be responsible for severe respiratory and neurological complications. The diagnosis is clinical, confirmed by serology, PCR or culture of the measles virus. Treatment is symptomatic and prevention is based on a well conducted vaccination. In severe cases, the use of vitamin A is recommended by the World Health Organization, at least in chidren. Antivirals (ribavirin) have not been shown to be effective in clinical practice. We present a severe respiratory form of measles, affecting a young immunocompetent adult.

KEYWORDS: Antivirals ; Respiratory complication; Vitamin A ; Measles

PMID: 31609551

Keywords: Measles; Pneumonitis.

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Long-term #immunogenicity of #Measles #vaccine: an #Italian retrospective cohort study (J Infect Dis., abstract)

[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

Long-term immunogenicity of Measles vaccine: an Italian retrospective cohort study

Francesco Paolo Bianchi, Pasquale Stefanizzi, Sara De Nitto, Angela Maria Vittoria Larocca, Cinzia Germinario, Silvio Tafuri

The Journal of Infectious Diseases, jiz508, https://doi.org/10.1093/infdis/jiz508

Published:  03 October 2019

 

Abstract

Background

Levels of antibodies induced by the Measles virus containing vaccine have been shown to decline over time, but actually there is not a formal recommendation about the opportunity of testing immunized subjects (in particular, HCWs) to investigate the persistence of Measles IgG.

Methods

This study aims to evaluate the long-time immunogenicity of Measles vaccine in a sample of medical students and residents of the University of Bari who attended the Hygiene Department for the biological risk assessment (April 2014-June 2018).

Results

2,000 immunized (2 doses of MMR vaccine) students and residents have been tested. 305/2,000 (15%) subjects didn’t show protective anti-Measles IgG. This proportion was higher among vaccinated at ≤15 months (20%) than in vaccinated at 16-23 months (17%) and at ≥24 months (10%; p<0.0001). After an MMR vaccine booster dose, we noted a seroconversion of 74% of seronegative HCWs. The overall seroconversion rate after a second dose booster was of 93%. No serious adverse events were noted after the booster doses.

Conclusions

An important proportion of subjects immunized for Measles don’t show a protective IgG titer in the 10 years after the vaccination. Our management strategy seems consistent with the purpose of evidencing immunological memory.

healthcare workers, booster dose, duration of immunization

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© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.

This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

Keywords: Measles; Vaccines.

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#Effect of #measles #vaccination in #infants younger than 9 months on the immune response to subsequent measles vaccine doses: a systematic review and meta-analysis (Lancet Infect Dis., abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

Effect of measles vaccination in infants younger than 9 months on the immune response to subsequent measles vaccine doses: a systematic review and meta-analysis

Laura M Nic Lochlainn, PhD, Brechje de Gier, PhD, Nicoline van der Maas, PhD, Rob van Binnendijk, PhD, Peter M Strebel, MBChB, Tracey Goodman, MA, Hester E de Melker, PhD, Prof William J Moss, MD, Susan J M Hahné, PhD

Open Access / Published: September 20, 2019 / DOI: https://doi.org/10.1016/S1473-3099(19)30396-2

 

Summary

Background

Vaccinating infants with a first dose of measles-containing vaccine (MCV1) before 9 months of age in high-risk settings has the potential to reduce measles-related morbidity and mortality. However, there is concern that early vaccination might blunt the immune response to subsequent measles vaccine doses. We systematically reviewed the available evidence on the effect of MCV1 administration to infants younger than 9 months on their immune responses to subsequent MCV doses.

Methods

For this systematic review and meta-analysis, we searched for randomised and quasi-randomised controlled trials, outbreak investigations, and cohort and case-control studies without restriction on publication dates, in which MCV1 was administered to infants younger than 9 months. We did the literature search on June 2, 2015, and updated it on Jan 14, 2019. We included studies reporting data on strength or duration of humoral and cellular immune responses, and on vaccine efficacy or vaccine effectiveness after two-dose or three-dose MCV schedules. Our outcome measures were proportion of seropositive infants, geometric mean titre, vaccine efficacy, vaccine effectiveness, antibody avidity index, and T-cell stimulation index. We used random-effects meta-analysis to derive pooled estimates of the outcomes, where appropriate. We assessed the methodological quality of included studies using Grading of Recommendation Assessment, Development and Evaluation (GRADE) guidelines.

Findings

Our search retrieved 1156 records and 85 were excluded due to duplication. 1071 records were screened for eligibility, of which 351 were eligible for full-text screening and 21 were eligible for inclusion in the review. From 13 studies, the pooled proportion of infants seropositive after two MCV doses, with MCV1 administered before 9 months of age, was 98% (95% CI 96–99; I2=79·8%, p<0·0001), which was not significantly different from seropositivity after a two-dose MCV schedule starting later (p=0·087). Only one of four studies found geometric mean titres after MCV2 administration to be significantly lower when MCV1 was administered before 9 months of age than at 9 months of age or later. There was insufficient evidence to determine an effect of age at MCV1 administration on antibody avidity. The pooled vaccine effectiveness estimate derived from two studies of a two-dose MCV schedule with MCV1 vaccination before 9 months of age was 95% (95% CI 89–100; I2=12·6%, p=0·29). Seven studies reporting on measles virus-specific cellular immune responses found that T-cell responses and T-cell memory were sustained, irrespective of the age of MCV1 administration. Overall, the quality of evidence was moderate to very low.

Interpretation

Our findings suggest that administering MCV1 to infants younger than 9 months followed by additional MCV doses results in high seropositivity, vaccine effectiveness, and T-cell responses, which are independent of the age at MCV1, supporting the vaccination of very young infants in high-risk settings. However, we also found some evidence that MCV1 administered to infants younger than 9 months resulted in lower antibody titres after one or two subsequent doses of MCV than when measles vaccination is started at age 9 months or older. The clinical and public-health relevance of this immunity blunting effect are uncertain.

Funding

WHO.

Keywords: Measles; Vaccines; Pediatrics.

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Immunogenicity, #effectiveness, and #safety of #measles #vaccination in #infants younger than 9 months: a systematic review and meta-analysis (Lancet Infect Dis., abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

Immunogenicity, effectiveness, and safety of measles vaccination in infants younger than 9 months: a systematic review and meta-analysis

Laura M Nic Lochlainn, PhD, Brechje de Gier, PhD, Nicoline van der Maas, PhD, Peter M Strebel, MBChB, Tracey Goodman, MA, Rob S van Binnendijk, PhD, Hester E de Melker, PhD, Susan J M Hahné, PhD

Open Access / Published: September 20, 2019 / DOI: https://doi.org/10.1016/S1473-3099(19)30395-0

 

Summary

Background

Measles is an important cause of death in children, despite the availability of safe and cost-saving measles-containing vaccines (MCVs). The first MCV dose (MCV1) is recommended at 9 months of age in countries with ongoing measles transmission, and at 12 months in countries with low risk of measles. To assess whether bringing forward the age of MCV1 is beneficial, we did a systematic review and meta-analysis of the benefits and risks of MCV1 in infants younger than 9 months.

Methods

For this systematic review and meta-analysis, we searched MEDLINE, EMBASE, Scopus, Proquest, Global Health, the WHO library database, and the WHO Institutional Repository for Information Sharing database, and consulted experts. We included randomised and quasi-randomised controlled trials, outbreak investigations, and cohort and case-control studies without restriction on publication dates, in which MCV1 was administered to infants younger than 9 months. We did the literature search on June 2, 2015, and updated it on Jan 14, 2019. We assessed: proportion of infants seroconverted, geometric mean antibody titre, avidity, cellular immunity, duration of immunity, vaccine efficacy, vaccine effectiveness, and safety. We used random-effects models to derive pooled estimates of the endpoints, where appropriate. We assessed methodological quality using the Grading of Recommendations, Assessment, Development, and Evaluation guidelines.

Findings

Our search identified 1156 studies, of which 1071 were screened for eligibility. 351 were eligible for full-text screening, and data from 56 studies that met all inclusion criteria were used for analysis. The proportion of infants who seroconverted increased from 50% (95% CI 29–71) for those vaccinated with MCV1 at 4 months of age to 85% (69–97) for those were vaccinated at 8 months. The pooled geometric mean titre ratio for infants aged 4–8 months vaccinated with MCV1 compared with infants vaccinated with MCV1 at age 9 months or older was 0·46 (95% CI 0·33–0·66; I2=99·9%, p<0·0001). Only one study reported on avidity and suggested that there was lower avidity and a shorter duration of immunity following MCV1 administration at 6 months of age than at 9 months of age (p=0·0016) or 12 months of age (p<0·001). No effect of age at MCV1 administration on cellular immunity was found. One study reported that vaccine efficacy against laboratory-confirmed measles virus infection was 94% (95% CI 74–98) in infants vaccinated with MCV1 at 4·5 months of age. The pooled vaccine effectiveness of MCV1 in infants younger than 9 months against measles was 58% (95% CI 9–80; I2=84·9%, p<0·0001). The pooled vaccine effectiveness estimate from within-study comparisons of infants younger than 9 months vaccinated with MCV1 were 51% (95% CI −44 to 83; I2=92·3%, p<0·0001), and for those aged 9 months and older at vaccination it was 83% (76–88; I2=93·8%, p<0·0001). No differences in the risk of adverse events after MCV1 administration were found between infants younger than 9 months and those aged 9 months of older. Overall, the quality of evidence ranged from moderate to very low.

Interpretation

MCV1 administered to infants younger than 9 months induces a good immune response, whereby the proportion of infants seroconverted increases with increased age at vaccination. A large proportion of infants receiving MCV1 before 9 months of age are protected and the vaccine is safe, although higher antibody titres and vaccine effectiveness are found when MCV1 is administered at older ages. Recommending MCV1 administration to infants younger than 9 months for those at high risk of measles is an important step towards reducing measles-related mortality and morbidity.

Funding

WHO.

Keywords: Measles; Vaccines; Pediatrics.

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Long-term #dynamics of #measles in #London: Titrating the impact of #wars, the 1918 #pandemic, and #vaccination (PLoS Comput Biol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

PLoS Comput Biol. 2019 Sep 12;15(9):e1007305. doi: 10.1371/journal.pcbi.1007305. eCollection 2019 Sep.

Long-term dynamics of measles in London: Titrating the impact of wars, the 1918 pandemic, and vaccination.

Becker AD1, Wesolowski A2, Bjørnstad ON3,4, Grenfell BT1,4,5.

Author information: 1 Department of Ecology and Evolutionary Biology, Princeton, New Jersey, United States of America. 2 Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America. 3 Center for Infectious Disease Dynamics, Pennsylvania State University, University Park, Pennsylvania, United States of America. 4 Fogarty International Center, National Institutes of Health, Bethesda, Maryland, United States of America. 5 Woodrow Wilson School of Public and International Affairs, Princeton University, Princeton, New Jersey, United States of America.

 

Abstract

A key question in ecology is the relative impact of internal nonlinear dynamics and external perturbations on the long-term trajectories of natural systems. Measles has been analyzed extensively as a paradigm for consumer-resource dynamics due to the oscillatory nature of the host-pathogen life cycle, the abundance of rich data to test theory, and public health relevance. The dynamics of measles in London, in particular, has acted as a prototypical test bed for such analysis using incidence data from the pre-vaccination era (1944-1967). However, during this timeframe there were few external large-scale perturbations, limiting an assessment of the relative impact of internal and extra demographic perturbations to the host population. Here, we extended the previous London analyses to include nearly a century of data that also contains four major demographic changes: the First and Second World Wars, the 1918 influenza pandemic, and the start of a measles mass vaccination program. By combining mortality and incidence data using particle filtering methods, we show that a simple stochastic epidemic model, with minimal historical specifications, can capture the nearly 100 years of dynamics including changes caused by each of the major perturbations. We show that the majority of dynamic changes are explainable by the internal nonlinear dynamics of the system, tuned by demographic changes. In addition, the 1918 influenza pandemic and World War II acted as extra perturbations to this basic epidemic oscillator. Our analysis underlines that long-term ecological and epidemiological dynamics can follow very simple rules, even in a non-stationary population subject to significant perturbations and major secular changes.

PMID: 31513578 DOI: 10.1371/journal.pcbi.1007305

Keywords: Pandemic Influenza; Spanish Flu; Wars; Society; Measles.

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