Last data update: Apr 22, 2024. (Total: 46599 publications since 2009)
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Lessons learnt from the applying the Centers for Disease Control and Prevention (CDC) evaluation framework to the Measles Incident Management System response, USA, 2020-2021
Jacenko S , Blough S , Grant G , Tohme R , McFarland J , Hatcher C , Goodson JL , Papania M , Pella DG , Li X , Yee SL . BMJ Glob Health 2023 8 (3) The functionality and performance of public health programmes at all levels of government play a critical role in preventing, detecting, mitigating and responding to public health threats, including infectious disease outbreaks. Multiple and concurrent outbreaks in recent years, such as COVID-19, Ebola and Zika, have highlighted the importance of documenting lessons learnt from public health responses of national and global agencies. In February 2020, the US Centers for Disease Control and Prevention (CDC) Center for Global Health (CGH) activated the Measles Incident Management System (MIMS) to accelerate the ability to detect, mitigate and respond to measles outbreaks globally and advance progress towards regional measles elimination goals. The activation was triggered by a global resurgence in reported measles cases during 2018-2019 and supported emergency response activities conducted by partner organisations and countries. MIMS leadership decided early in the response to form an evaluation team to design and implement an evaluation approach for producing real-time data to document progress of response activities and inform timely decision-making. In this manuscript, we describe how establishing an evaluation unit within MIMS, and engaging MIMS leadership and subject matter experts in the evaluation activities, was critical to monitor progress and document lessons learnt to inform decision making. We also explain the CDC's Framework for Evaluation in Public Health Practice applied to evaluate the dynamic events throughout the MIMS response. Evaluators supporting emergency response should use a flexible framework that can be adaptable in dynamic contexts and document response activities in real-time. |
Study protocol for a phase 1/2, single-centre, double-blind, double-dummy, randomized, active-controlled, age de-escalation trial to assess the safety, tolerability and immunogenicity of a measles and rubella vaccine delivered by a microneedle patch in healthy adults (18 to 40 years), measles and rubella vaccine-primed toddlers (15 to 18 months) and measles and rubella vaccine-nave infants (9 to 10 months) in The Gambia [Measles and Rubella Vaccine Microneedle Patch Phase 1/2 Age De-escalation Trial]
Adigweme I , Akpalu E , Yisa M , Donkor S , Jarju LB , Danso B , Mendy A , Jeffries D , Njie A , Bruce A , Royals M , Goodson JL , Prausnitz MR , McAllister D , Rota PA , Henry S , Clarke E . Trials 2022 23 (1) 775 BACKGROUND: New strategies to increase measles and rubella vaccine coverage, particularly in low- and middle-income countries, are needed if elimination goals are to be achieved. With this regard, measles and rubella vaccine microneedle patches (MRV-MNP), in which the vaccine is embedded in dissolving microneedles, offer several potential advantages over subcutaneous delivery. These include ease of administration, increased thermostability, an absence of sharps waste, reduced overall costs and pain-free administration. This trial will provide the first clinical trial data on MRV-MNP use and the first clinical vaccine trial of MNP technology in children and infants. METHODS: This is a phase 1/2, randomized, active-controlled, double-blind, double-dummy, age de-escalation trial. Based on the defined eligibility criteria for the trial, including screening laboratory investigations, 45 adults [18-40 years] followed by 120 toddlers [15-18 months] and 120 infants [9-10 months] will be enrolled in series. To allow double-blinding, participants will receive either the MRV-MNP and a placebo (0.9% sodium chloride) subcutaneous (SC) injection or a placebo MNP and the MRV by SC injection (MRV-SC). Local and systemic adverse event data will be collected for 14 days following study product administration. Safety laboratories will be repeated on day 7 and, in the adult cohort alone, on day 14. Unsolicited adverse events including serious adverse events will be collected until the final study visit for each participant on day 180. Measles and rubella serum neutralizing antibodies will be measured at baseline, on day 42 and on day 180. Cohort progression will be dependent on review of the unblinded safety data by an independent data monitoring committee. DISCUSSION: This trial will provide the first clinical data on the use of a MNP to deliver the MRV and the first data on the use of MNPs in a paediatric population. It will guide future product development decisions for what may be a key technology for future measles and rubella elimination. TRIAL REGISTRATION: Pan-African Clinical Trials Registry 202008836432905 . CLINICALTRIALS: gov NCT04394689. |
Innovations in vaccine delivery: increasing access, coverage, and equity and lessons learnt from measles and rubella elimination
Goodson JL , Rota PA . Drug Deliv Transl Res 2022 12 (5) 1-9 Disease eradication and elimination programs drive innovations based on progress toward measurable objectives, evaluations of new strategies and methods, programmatic experiences, and lessons learned from the field. Following progress toward global measles elimination, reducing measles mortality, and increasing introductions of measles and rubella vaccines to national programs, the measles and rubella immunization program has faced setbacks in recent years. Currently available vaccine delivery methods have complicated logistics and drawbacks that create barriers to vaccination; innovations for easier, more efficient, and safer vaccine delivery are needed. Progress can be accelerated by new technologies like microarray patches (MAPs) that are now widely recognized as a potential new tool for enhancing global immunizations efforts. Clinical trials of measles-rubella vaccine MAPs have begun, and several other vaccine MAPs are in the pre-clinical development pathway. MAPs could significantly contribute to Immunization Agenda 2030 priorities, including reaching zero-dose children; increasing vaccine access, demand, coverage, and equity; and achieving measles and rubella elimination. With strong partnerships between public health agencies and biotechnology companies, translational novel vaccine delivery systems can be developed to help solve public health problems and achieve global health priorities. |
Measles in the 21st century: Progress toward achieving and sustaining elimination
Gastañaduy PA , Goodson JL , Panagiotakopoulos L , Rota PA , Orenstein WA , Patel M . J Infect Dis 2021 224 S420-s428 The global measles vaccination program has been extraordinarily successful in reducing measles-related disease and deaths worldwide. Eradication of measles is feasible because of several key attributes, including humans as the only reservoir for the virus, broad access to diagnostic tools that can rapidly detect measles-infectious persons, and availability of highly safe and effective measles-containing vaccines (MCVs). All 6 World Health Organization (WHO) regions have established measles elimination goals. Globally, during 2000-2018, measles incidence decreased by 66% (from 145 to 49 cases per million population) and deaths decreased by 73% (from 535 600 to 142 300), drastically reducing global disease burden. Routine immunization with MCV has been the cornerstone for the control and prevention of measles. Two doses of MCV are 97% effective in preventing measles, qualifying MCV as one of the most effective vaccines ever developed. Mild adverse events occur in <20% of recipients and serious adverse events are extremely rare. The economic benefits of measles vaccination are highlighted by an overall return on investment of 58 times the cost of the vaccine, supply chains, and vaccination. Because measles is one of the most contagious human diseases, maintenance of high (≥95%) 2-dose MCV coverage is crucial for controlling the spread of measles and successfully reaching measles elimination; however, the plateauing of global MCV coverage for nearly a decade and the global measles resurgence during 2018-2019 demonstrate that much work remains. Global commitments to increase community access to and demand for immunizations, strengthen national and regional partnerships for building public health infrastructure, and implement innovations that can overcome access barriers and enhance vaccine confidence, are essential to achieve a world free of measles. |
Development of a Measles and Rubella Multiplex Bead Serological Assay for Assessing Population Immunity
Coughlin MM , Matson Z , Sowers SB , Priest JW , Smits GP , van der Klis FRM , Mitchell A , Hickman CJ , Scobie HM , Goodson JL , Alexander JPJr , Rota PA , Bankamp B . J Clin Microbiol 2021 59 (6) Serosurveys are important tools for estimating population immunity and providing immunization activity guidance. The measles and rubella multiplex bead assay (MBA) offers multiple advantages over standard serological assays and was validated by comparison with the enzyme-linked immunosorbent assay (ELISA) and the measles plaque reduction neutralization (PRN) assay. Results from a laboratory-produced purified measles whole virus antigen MBA (MeV WVA(L)) correlated better with ELISA and PRN than results from the baculovirus-expressed measles nucleoprotein (N) MBA. Therefore, a commercially produced whole virus antigen (MeV WVA(C)) was evaluated. Serum IgG antibody concentrations correlated significantly with a strong linear relationship between the MeV WVA(C) and MeV WVA(L) MBAs (R=0.962, R(2)=0.926). IgG concentrations from the MeV WVA(C) MBA showed strong correlation with PRN titers (R=0.846) with a linear relationship comparable to values obtained with the MeV WVA(L) MBA and PRN assay (R(2)=0.716 and R(2)=0.768, respectively). Receiver-operating characteristic (ROC) curve analysis of the MeV WVA(C) using PRN titer as the comparator resulted in a seroprotection cutoff of 153 mIU/ml, similar to the established correlate of protection of 120 mIU/ml, with a sensitivity of 98% and a specificity of 84%. IgG concentrations correlated strongly between the rubella WVA MBA and ELISA (R=0.959 and R(2)=0.919). ROC analysis of the rubella MBA using ELISA as the comparator yielded a cutoff of 9.36 IU/ml, similar to the accepted cutoff of 10 IU/ml for seroprotection, with a sensitivity of 99% and a specificity of 100%. These results support use of the MBA for multi-antigen serosurveys assessing measles and rubella population immunity. |
Progress toward regional measles elimination - worldwide, 2000-2019
Patel MK , Goodson JL , Alexander JP Jr , Kretsinger K , Sodha SV , Steulet C , Gacic-Dobo M , Rota PA , McFarland J , Menning L , Mulders MN , Crowcroft NS . MMWR Morb Mortal Wkly Rep 2020 69 (45) 1700-1705 In 2010, the World Health Assembly (WHA) set the following three milestones for measles control to be achieved by 2015: 1) increase routine coverage with the first dose of measles-containing vaccine (MCV1) among children aged 1 year to ≥90% at the national level and to ≥80% in every district, 2) reduce global annual measles incidence to <5 cases per 1 million population, and 3) reduce global measles mortality by 95% from the 2000 estimate* (1). In 2012, WHA endorsed the Global Vaccine Action Plan,(†) with the objective of eliminating measles(§) in five of the six World Health Organization (WHO) regions by 2020. This report describes progress toward WHA milestones and regional measles elimination during 2000-2019 and updates a previous report (2). During 2000-2010, estimated MCV1 coverage increased globally from 72% to 84% but has since plateaued at 84%-85%. All countries conducted measles surveillance; however, approximately half did not achieve the sensitivity indicator target of two or more discarded measles and rubella cases per 100,000 population. Annual reported measles incidence decreased 88%, from 145 to 18 cases per 1 million population during 2000-2016; the lowest incidence occurred in 2016, but by 2019 incidence had risen to 120 cases per 1 million population. During 2000-2019, the annual number of estimated measles deaths decreased 62%, from 539,000 to 207,500; an estimated 25.5 million measles deaths were averted. To drive progress toward the regional measles elimination targets, additional strategies are needed to help countries reach all children with 2 doses of measles-containing vaccine, identify and close immunity gaps, and improve surveillance. |
A microneedle patch for measles and rubella vaccination: a game changer for achieving elimination
Prausnitz MR , Goodson JL , Rota PA , Orenstein WA . Curr Opin Virol 2020 41 68-76 While morbidity and mortality associated with measles and rubella (MR) have dramatically decreased, there are still >100000 estimated deaths due to measles and an estimated 100000 infants born with congenital rubella syndrome annually. Given highly effective MR vaccines, the primary barrier to global elimination of these diseases is low vaccination coverage, especially among the most underserved populations in resource-limited settings. In contrast to conventional MR vaccination by hypodermic injection, microneedle patches are being developed to enable MR vaccination by minimally trained personnel. Simplified supply chain, reduced need for cold chain storage, elimination of vaccine reconstitution, no sharps waste, reduced vaccine wastage, and reduced total system cost of vaccination are advantages of this approach. Preclinical work to develop a MR vaccine patch has proceeded through successful immunization studies in rodents and non-human primates. On-going programs seek to make MR vaccine patches available to support MR elimination efforts around the world. |
Recent setbacks in measles elimination: the importance of investing in innovations for immunizations
Goodson JL . Pan Afr Med J 2020 35 15 The recent setbacks in efforts to achieve measles elimination goals are alarming. To reverse the current trends, it is imperative that the global health community urgently intensify efforts and make resource commitments to implement evidence-based elimination strategies fully, including supporting research and innovations. The Immunization Agenda 2030: A Global Strategy to Leave No One Behind (IA2030) is the new global guidance document that builds on lessons learned and progress made toward the GVAP goals, includes research and innovation as a core strategic priority, and identifies measles as a "tracer" for improving immunisation services and strengthening primary health care systems. To achieve vaccination coverage and equity targets that leave no one behind, and accelerate progress toward disease eradication and elimination goals, sustained and predictable investments are needed for the identified research and innovations priorities for the new decade. |
Progress toward measles elimination - Eastern Mediterranean Region, 2013-2019
Goodson JL , Teleb N , Ashmony H , Musa N , Ghoniem A , Hassan Q , Waciqi AS , Mere MO , Farid M , Mukhtar HEA , Iqbal J , Alexander JP Jr . MMWR Morb Mortal Wkly Rep 2020 69 (15) 439-445 In 1997, during the 41st session of the Regional Committee for the Eastern Mediterranean, the 21 countries in the World Health Organization (WHO) Eastern Mediterranean Region* (EMR) passed a resolution to eliminate(dagger) measles (1). In 2015, this goal was included as a priority in the Eastern Mediterranean Vaccine Action Plan 2016-2020 (EMVAP) (2), endorsed at the 62nd session of the Regional Committee (3). To achieve this goal, the WHO Regional Office for the Eastern Mediterranean developed a four-pronged strategy: 1) achieve >/=95% vaccination coverage with the first dose of measles-containing vaccine (MCV1) among children in every district of each country through routine immunization services; 2) achieve >/=95% vaccination coverage with a second MCV dose (MCV2) in every district of each country either through implementation of a routine 2-dose vaccination schedule or through supplementary immunization activities( section sign) (SIAs); 3) conduct high-quality, case-based surveillance in all countries; and 4) provide optimal measles clinical case management, including dietary supplementation with vitamin A (4). This report describes progress toward measles elimination in EMR during 2013-2019 and updates a previous report (5). Estimated MCV1 coverage increased from 79% in 2013 to 82% in 2018. MCV2 coverage increased from 59% in 2013 to 74% in 2018. In addition, during 2013-2019, approximately 326.4 million children received MCV during SIAs. Reported confirmed measles incidence increased from 33.5 per 1 million persons in 2013 to 91.2 in 2018, with large outbreaks occurring in Pakistan, Somalia, and Yemen; incidence decreased to 23.3 in 2019. In 2019, the rate of discarded nonmeasles cases( paragraph sign) was 5.4 per 100,000 population. To achieve measles elimination in the EMR, increased visibility of efforts to achieve the measles elimination goal is critically needed, as are sustained and predictable investments to increase MCV1 and MCV2 coverage, conduct high-quality SIAs, and reach populations at risk for not accessing immunization services or living in areas with civil strife. |
The potential role of using vaccine patches to induce immunity: platform and pathways to innovation and commercialization
Badizadegan K , Goodson JL , Rota PA , Thompson KM . Expert Rev Vaccines 2020 19 (2) 175-194 Introduction: In the last two decades, the evidence related to using vaccine patches with multiple short projections (</=1 mm) to deliver vaccines through the skin increased significantly and demonstrated their potential as an innovative delivery platform.Areas covered: We review the vaccine patch literature published in English as of 1 March 2019, as well as available information from key stakeholders related to vaccine patches as a platform. We identify key research topics related to basic and translational science on skin physical properties and immunobiology, patch development, and vaccine manufacturing.Expert opinion: Currently, vaccine patch developers continue to address some basic science and other platform issues in the context of developing a potential vaccine patch presentation for an existing or new vaccine. Additional clinical data and manufacturing experience could shift the balance toward incentivizing existing vaccine manufactures to further explore the use of vaccine patches to deliver their products. Incentives for innovation of vaccine patches differ for developed and developing countries, which will necessitate different strategies (e.g. public-private partnerships, push, or pull mechanisms) to support the basic and applied research needed to ensure a strong evidence base and to overcome translational barriers for vaccine patches as a delivery platform. |
Progress toward measles elimination - China, January 2013-June 2019
Ma C , Rodewald L , Hao L , Su Q , Zhang Y , Wen N , Fan C , Yang H , Luo H , Wang H , Goodson JL , Yin Z , Feng Z . MMWR Morb Mortal Wkly Rep 2019 68 (48) 1112-1116 In 2005, the World Health Organization (WHO) Western Pacific Region countries, including China, resolved to eliminate measles by 2012 or as soon as feasible thereafter (1). As of 2018, nine* of the 37 Western Pacific Region countries or areas(dagger) had eliminated( section sign) measles. China's Measles Elimination Action Plan 2006-2012 included strengthening routine immunization; conducting measles risk assessments, followed by supplementary immunization activities (SIAs) with measles-containing vaccine (MCV) at national and subnational levels; strengthening surveillance and laboratory capacity; and investigating and responding to measles outbreaks. Most recently, progress toward measles elimination in China was described in a 2014 report documenting measles elimination efforts in China during 2008-2012 and a resurgence in 2013 (2). This report describes progress toward measles elimination in China during January 2013-June 2019.( paragraph sign) Measles incidence per million persons decreased from 20.4 in 2013 to 2.8 in 2018; reported measles-related deaths decreased from 32 in 2015 to one in 2018 and no deaths in 2019 through June. Measles elimination in China can be achieved through strengthening the immunization program's existing strategy by ensuring sufficient vaccine supply; continuing to improve laboratory-supported surveillance, outbreak investigation and response; strengthening school entry vaccination record checks; vaccinating students who do not have documentation of receipt of 2 doses of measles-rubella vaccine; and vaccinating health care professionals and other adults at risk for measles. |
Progress toward regional measles elimination - worldwide, 2000-2018
Patel MK , Dumolard L , Nedelec Y , Sodha SV , Steulet C , Gacic-Dobo M , Kretsinger K , McFarland J , Rota PA , Goodson JL . MMWR Morb Mortal Wkly Rep 2019 68 (48) 1105-1111 In 2010, the World Health Assembly (WHA) set the following three milestones for measles control to be achieved by 2015: 1) increase routine coverage with the first dose of measles-containing vaccine (MCV1) among children aged 1 year to >/=90% at the national level and to >/=80% in every district, 2) reduce global annual measles incidence to less than five cases per 1 million population, and 3) reduce global measles mortality by 95% from the 2000 estimate* (1). In 2012, WHA endorsed the Global Vaccine Action Plan,(dagger) with the objective of eliminating measles( section sign) in five of the six World Health Organization (WHO) regions by 2020. This report updates a previous report (2) and describes progress toward WHA milestones and regional measles elimination during 2000-2018. During 2000-2018, estimated MCV1 coverage increased globally from 72% to 86%; annual reported measles incidence decreased 66%, from 145 to 49 cases per 1 million population; and annual estimated measles deaths decreased 73%, from 535,600 to 142,300. During 2000-2018, measles vaccination averted an estimated 23.2 million deaths. However, the number of measles cases in 2018 increased 167% globally compared with 2016, and estimated global measles mortality has increased since 2017. To continue progress toward the regional measles elimination targets, resource commitments are needed to strengthen routine immunization systems, close historical immunity gaps, and improve surveillance. To achieve measles elimination, all communities and countries need coordinated efforts aiming to reach >/=95% coverage with 2 doses of measles vaccine (3). |
Genetic Characterization of Measles and Rubella Viruses Detected Through Global Measles and Rubella Elimination Surveillance, 2016-2018.
Brown KE , Rota PA , Goodson JL , Williams D , Abernathy E , Takeda M , Mulders MN . MMWR Morb Mortal Wkly Rep 2019 68 (26) 587-591 All six World Health Organization (WHO) regions have established measles elimination goals, and three regions have a rubella elimination goal. Each region has established a regional verification commission to monitor progress toward measles elimination, rubella elimination, or both, and to provide verification of elimination* (1,2). To verify elimination, high-quality case-based surveillance is essential, including laboratory confirmation of suspected cases and genotyping of viruses from confirmed cases to track transmission pathways. In 2000, WHO established the Global Measles and Rubella Laboratory Network (GMRLN) to provide high-quality laboratory support for surveillance for measles, rubella, and congenital rubella syndrome (3). GMRLN is the largest globally coordinated laboratory network, with 704 laboratories supporting surveillance in 191 countries (4). This report updates a previous report and describes the genetic characterization of measles and rubella viruses during 2016-2018 (5). The genetic diversity of measles viruses (MeVs) and rubella viruses (RuVs) has decreased globally following implementation of measles and rubella elimination strategies. Among 10,857 MeV sequences reported to the global Measles Nucleotide Surveillance (MeaNS) database during 2016-2018, the number of MeV genotypes detected in ongoing transmission decreased from six in 2016 to four in 2018. Among the 1,296 RuV sequences submitted to the global Rubella Nucleotide Surveillance (RubeNS) database during the same period, the number of RuV genotypes detected decreased from five in 2016 to two in 2018. To strengthen laboratory surveillance for measles and rubella elimination, specimens should be collected from all confirmed cases for genotyping, and sequences from all wild-type measles and rubella viruses should be submitted to MeaNS and RubeNS in a timely manner. |
Progress toward measles elimination - Pakistan, 2000-2018
Mere MO , Goodson JL , Chandio AK , Rana MS , Hasan Q , Teleb N , Alexander JP Jr . MMWR Morb Mortal Wkly Rep 2019 68 (22) 505-510 In 1997, the 21 countries in the World Health Organization (WHO) Eastern Mediterranean Region* (EMR) passed a resolution during the 41st session of the Regional Committee for the Eastern Mediterranean to eliminate measles(dagger) (1). In 2015, this goal was included as a priority in the Eastern Mediterranean Vaccine Action Plan 2016-2020 (2), approved at the 62nd session of the Regional Committee (3). To achieve measles elimination, the WHO Regional Office for the Eastern Mediterranean developed the following four-pronged strategy: 1) achieve >/=95% vaccination coverage with the first dose of measles-containing vaccine (MCV) among children in every district of each country through routine immunization services; 2) achieve >/=95% vaccination coverage with a second MCV dose in every district of each country either through implementation of a routine 2-dose vaccination schedule or through supplementary immunization activities (SIAs)( section sign); 3) conduct high-quality, case-based measles surveillance in all countries; and 4) provide optimal measles clinical case management, including dietary supplementation with vitamin A (4). Pakistan, an EMR country with a population of approximately 200 million, accounts for nearly one third of the overall EMR population. This report describes progress and challenges toward measles elimination in Pakistan during 2000-2018. During the study period, estimated coverage with the first MCV dose (MCV1) increased from 57% in 2000 to 76% in 2017. The second MCV dose (MCV2) was introduced nationwide in 2009, and MCV2 coverage increased from 30% in 2009 to 45% in 2017. During 2000-2018, approximately 232.5 million children received doses of MCV during SIAs. Reported confirmed measles incidence increased from an average of 24.6 per 1 million persons during 2000-2009 to an average of 80.4 during 2010-2018, with peaks in 2013 (230.3) and 2018 (153.6). In 2017 and 2018, the rates of suspected cases discarded as nonmeasles after investigation were 2.1 and 1.5 per 100,000 population, reflecting underreporting of cases. To achieve measles elimination, additional efforts are needed to increase MCV1 and MCV2 coverage, develop strategies to identify and reach communities not accessing immunization services, and increase sensitivity of case-based measles surveillance in all districts. |
Progress toward measles elimination - European Region, 2009-2018
Zimmerman LA , Muscat M , Singh S , Ben Mamou M , Jankovic D , Datta S , Alexander JP , Goodson JL , O'Connor P . MMWR Morb Mortal Wkly Rep 2019 68 (17) 396-401 In 2010, all 53 countries* in the World Health Organization (WHO) European Region (EUR) reconfirmed their commitment to eliminating measles and rubella and congenital rubella syndrome (1); this goal was included as a priority in the European Vaccine Action Plan 2015-2020 (2). The WHO-recommended elimination strategies in EUR include 1) achieving and maintaining >/=95% coverage with 2 doses of measles-containing vaccine (MCV) through routine immunization services; 2) providing measles and rubella vaccination opportunities, including supplementary immunization activities (SIAs), to populations susceptible to measles or rubella; 3) strengthening surveillance by conducting case investigations and confirming suspected cases and outbreaks with laboratory results; and 4) improving the availability and use of evidence for the benefits and risks associated with vaccination (3). This report updates a previous report (4) and describes progress toward measles elimination in EUR during 2009-2018. During 2009-2017, estimated regional coverage with the first MCV dose (MCV1) was 93%-95%, and coverage with the second dose (MCV2) increased from 73% to 90%. In 2017, 30 (57%) countries achieved >/=95% MCV1 coverage, and 15 (28%) achieved >/=95% coverage with both doses. During 2009-2018, >16 million persons were vaccinated during SIAs in 13 (24%) countries. Measles incidence declined to 5.8 per 1 million population in 2016, but increased to 89.5 in 2018, because of large outbreaks in several EUR countries. To achieve measles elimination in EUR, measures are needed to strengthen immunization programs by ensuring >/=95% 2-dose MCV coverage in every district of each country, offering supplemental measles vaccination to susceptible adults, maintaining high-quality surveillance for rapid case detection and confirmation, and ensuring effective outbreak preparedness and response. |
Increase in infant measles deaths during a nationwide measles outbreak - Mongolia, 2015-2016
Lee CT , Hagan JE , Jantsansengee B , Tumurbaatar OE , Altanchimeg S , Yadamsuren B , Demberelsuren S , Tserendorj C , Munkhtogoo O , Badarch D , Gunregjav N , Baatarkhuu B , Ochir C , Berman L , Anderson R , Patel MK , Gregory CJ , Goodson JL . J Infect Dis 2019 220 (11) 1771-1779 BACKGROUND: Surveillance data from a large measles outbreak in Mongolia suggested an increased case fatality ratio (CFR) in the second of two waves. To confirm the increase in CFR and identify risk factors for measles death, we enhanced mortality ascertainment and conducted a case-control study among infants hospitalized for measles. METHODS: We linked national vital records with surveillance data of clinically- or laboratory-confirmed infant (aged <12 months) measles cases with rash onset during March-September 2015 (wave 1) and October 2015-June 2016 (wave 2). We abstracted medical charts of 95 fatal cases and 273 nonfatal cases hospitalized for measles, matched by age and sex. We calculated adjusted matched odds ratios (amORs) and 95% confidence intervals (CIs) for risk factors. RESULTS: Infant measles deaths increased from 3 among 2,224 cases (CFR: 0.13%) in wave 1 to 113 among 4,884 cases (CFR: 2.31%) in wave 2 (p<0.001). Inpatient admission, 7-21 days before measles rash onset, for pneumonia or influenza (amOR: 4.5; CI 2.6-8.0), but not other diagnoses, was significantly associated with death. DISCUSSION: Measles infection among children hospitalized with respiratory infections likely increased deaths due to measles during wave 2. Preventing measles virus nosocomial transmission likely decreases measles mortality. |
Accelerating measles and rubella elimination through research and innovation - Findings from the Measles & Rubella Initiative research prioritization process, 2016
Grant GB , Masresha BG , Moss WJ , Mulders MN , Rota PA , Omer SB , Shefer A , Kriss JL , Hanson M , Durrheim DN , Linkins R , Goodson JL . Vaccine 2019 37 (38) 5754-5761 The Measles & Rubella Initiative (M&RI) identified five key strategies to achieve measles and rubella elimination, including research and innovation to support cost-effective operations and improve vaccination and diagnostic tools. In 2016, the M&RI Research and Innovation Working Group (R&IWG) completed a research prioritization process to identify key research questions and update the global research agenda. The R&IWG reviewed meeting reports and strategic planning documents and solicited programmatic inputs from vaccination experts at the program operational level through a web survey, to identify previous research priorities and new research questions. The R&IWG then convened a meeting of experts to prioritize the identified research questions in four strategic areas: (1) epidemiology and economics, (2) surveillance and laboratory, (3) immunization strategies, and (4) demand creation and communications. The experts identified 19 priority research questions in the four strategic areas to address key areas of work necessary to further progress toward elimination. Future commitments from partners will be needed to develop a platform for improved coordination with adequate and predictable resources for research implementation and innovation to address these identified priorities. |
Research priorities for accelerating progress toward measles and rubella elimination identified by a cross-sectional web-based survey
Kriss JL , Grant GB , Moss WJ , Durrheim DN , Shefer A , Rota PA , Omer SB , Masresha BG , Mulders MN , Hanson M , Linkins RW , Goodson JL . Vaccine 2019 37 (38) 5745-5753 BACKGROUND: In 2012, the World Health Assembly endorsed the Global Vaccine Action Plan (GVAP) that set a target to eliminate measles and rubella in five of the six World Health Organization (WHO) regions by 2020. Significant progress has been made toward achieving this goal through intensive efforts by countries and Measles & Rubella Initiative (M&RI) partners. Accelerating progress will require evidence-based approaches to improve implementation of the core strategies in the Global Measles and Rubella Strategic Plan. The M&RI Research and Innovation Working Group (R&IWG) conducted a web-based survey as part of a process to identify measles and rubella research priorities. Survey findings were used to inform discussions during a meeting of experts convened by the M&RI at the Pan American Health Organization in November 2016. METHODS: The cross-sectional web-based survey of scientific and programmatic experts included questions in four main topic areas: (1) epidemiology and economics (epidemiology); (2) new tools for surveillance, vaccine delivery, and laboratory testing (new tools); (3) immunization strategies and outbreak response (strategies); and (4) vaccine demand and communications (demand). Analyses were stratified by the six WHO regions and by global, regional, or national/sub-national level of respondents. RESULTS: The six highest priority research questions selected by survey respondents from the four topic areas were the following: (1) What are the causes of outbreaks in settings with high reported vaccination coverage? (epidemiology); (2) Can affordable diagnostic tests be developed to confirm measles and rubella cases rapidly and accurately at the point of care? (new tools); (3) What are effective strategies for increasing coverage of the routine first dose of measles vaccine administered at 9 or 12months? (strategies); (4) What are effective strategies for increasing coverage of the second dose given after the first year of life? (strategies); (5) How can communities best be engaged in planning, implementing and monitoring health services including vaccinations? (demand); (6) What capacity building is needed for health workers to be able to identify and work more effectively with community leaders? (demand). Research priorities varied by region and by global/regional/national levels for all topic areas. CONCLUSIONS: Research and innovation will be critical to make further progress toward achieving the GVAP measles and rubella elimination goals. The results of this survey can be used to inform decision-making for investments in research activities at the global, regional, and national levels. |
Use of FTA® cards to transport throat swabs and oral fluid samples for molecular detection and genotyping of measles and rubella viruses.
Bankamp B , Sein C , Pukuta Simbu E , Anderson R , Abernathy E , Chen MH , Muyembe Tamfum JJ , Wannemuehler KA , Waku-Kouomou D , Lopareva EN , Icenogle JP , Rota PA , Goodson JL . J Clin Microbiol 2019 57 (5) The genetic characterization of measles viruses is an important tool for measles surveillance. Reverse cold chain requirements for the transportation of samples to reference laboratories are challenging in resource-limited settings. FTA(R) cards facilitate transport of virologic samples at ambient temperature as non-infectious material; however, the utility of FTA(R) cards for detection and genotyping of measles virus from clinical samples had not been evaluated. Throat swabs (TS) and oral fluid (OF) samples were collected from suspected measles cases in the Democratic Republic of the Congo. Virus detection (RT-qPCR) and genotyping (end-point RT-PCR) were compared for samples from 238 suspected cases; these samples were either transported using the reverse cold chain or at ambient temperature on FTA(R) cards. Virus detection showed excellent positive agreement for OF compared to TS (95.3%, CI [91.6, 97.4]), in contrast to 79.4% (CI 73.5, 84.3) for TS on FTA, and 85.5% (CI 80.2, 89.6) for OF on FTA compared to OF. Genotyping results obtained for a subset of samples indicated that 77.3% of all TS and 71.0% of OF would produce genotype information compared to 41.6% of TS and 41.3% of OF on FTA(R) cards. Similar results were found for 16 measles-negative samples that were confirmed as rubella cases. Measles genotype B3 and rubella genotype 2B were detected. FTA(R) cards have limited utility for virologic surveillance of sporadic cases of measles; however, they can be a useful tool for the expansion of virologic surveillance in countries where the reverse cold chain is not available. |
Evaluating vaccination policies to accelerate measles elimination in China: a meta-population modelling study
Hao L , Glasser JW , Su Q , Ma C , Feng Z , Yin Z , Goodson JL , Wen N , Fan C , Yang H , Rodewald LE , Feng Z , Wang H . Int J Epidemiol 2019 48 (4) 1240-1251 BACKGROUND: Measles is among the most highly infectious human diseases. By virtue of increasingly effective childhood vaccination, together with targeted supplemental immunization activities (SIAs), health authorities in the People's Republic of China have reduced measles' reproduction number from about 18 to 2.3. Despite substantial residual susceptibility among young adults, more in some locales than others, sustained routine childhood immunization likely would eliminate measles eventually. To support global eradication efforts, as well as expedite morbidity and mortality reductions in China, we evaluated alternative SIAs via mechanistic mathematical modelling. METHODS: Our model Chinese population is stratified by immune status (susceptible to measles infection; infected, but not yet infectious; infectious; and recovered or immunized), age (0, 1-4, 5-9, ..., 65+ years) and location (31 provinces). Contacts between sub-populations are either empirical or a mixture of preferential and proportionate with respect to age and decline exponentially with distance between locations at age-dependent rates. We estimated initial conditions and most parameters from recent cross-sectional serological surveys, disease surveillance and demographic observations. Then we calculated the reproduction numbers and gradient of the effective number with respect to age- and location-specific immunization rates. We corroborated these analytical results by simulating adolescent and young adult SIAs using a version of our model in which the age-specific contact rates vary seasonally. RESULTS: Whereas the gradient indicates that vaccinating young adults generally is the optimal strategy, simulations indicate that a catch-up campaign among susceptible adolescent schoolchildren would accelerate elimination, with timing dependent on uptake. CONCLUSIONS: These results are largely due to indirect effects (i.e. fewer infections than immunized people might otherwise cause), which meta-population models with realistic mixing are uniquely capable of reproducing accurately. |
Progress toward regional measles elimination - worldwide, 2000-2017
Dabbagh A , Laws RL , Steulet C , Dumolard L , Mulders MN , Kretsinger K , Alexander JP , Rota PA , Goodson JL . MMWR Morb Mortal Wkly Rep 2018 67 (47) 1323-1329 In 2010, the World Health Assembly set three milestones for measles prevention to be achieved by 2015: 1) increase routine coverage with the first dose of measles-containing vaccine (MCV1) among children aged 1 year to >/=90% at the national level and to >/=80% in every district; 2) reduce global annual measles incidence to less than five cases per million population; and 3) reduce global measles mortality by 95% from the 2000 estimate (1). In 2012, the World Health Assembly endorsed the Global Vaccine Action Plan (GVAP),(dagger) with the objective of eliminating measles( section sign) in four of the six World Health Organization (WHO) regions by 2015 and in five regions by 2020. Countries in all six WHO regions have adopted goals for measles elimination by 2020. This report describes progress toward global measles control milestones and regional measles elimination goals during 2000-2017 and updates a previous report (2). During 2000-2017, estimated MCV1 coverage increased globally from 72% to 85%; annual reported measles incidence decreased 83%, from 145 to 25 cases per million population; and annual estimated measles deaths decreased 80%, from 545,174 to 109,638. During this period, measles vaccination prevented an estimated 21.1 million deaths. However, measles elimination milestones have not been met, and three regions are experiencing a large measles resurgence. To make further progress, case-based surveillance needs to be strengthened, and coverage with MCV1 and the second dose of measles-containing vaccine (MCV2) needs to increase; in addition, it will be important to maintain political commitment and ensure substantial, sustained investments to achieve global and regional measles elimination goals. |
Measles-rubella supplementary immunization activity readiness assessment - India, 2017-2018
Gurnani V , Haldar P , Khanal S , Bhatnagar P , Singh B , Ahmed D , Samiuddin M , Kumar A , Negi Y , Gupta S , Harvey P , Bahl S , Dabbagh A , Alexander JP , Goodson JL . MMWR Morb Mortal Wkly Rep 2018 67 (26) 742-746 In 2013, during the 66th session of the Regional Committee of the World Health Organization (WHO) South-East Asia Region (SEAR), the 11 SEAR countries* adopted goals to eliminate measles and control rubella and congenital rubella syndrome by 2020(dagger) (1). To accelerate progress in India (2,3), a phased( section sign) nationwide supplementary immunization activity (SIA)( paragraph sign) using measles-rubella vaccine and targeting approximately 410 million children aged 9 months-14 years commenced in 2017 and will be completed by first quarter of 2019. To ensure a high-quality SIA, planning and preparation were monitored using a readiness assessment tool adapted from the WHO global field guide** (4) by the India Ministry of Health and Family Welfare. This report describes the results and experience gained from conducting SIA readiness assessments in 24 districts of three Indian states (Andhra Pradesh, Kerala, and Telangana) during the second phase of the SIA. In each selected area, assessments were conducted 4-6 weeks and 1-2 weeks before the scheduled SIA. At the first assessment, none of the states and districts were on track with preparations for the SIA. However, at the second assessment, two (67%) states and 21 (88%) districts were on track. The SIA readiness assessment identified several preparedness gaps; early assessment results were immediately communicated to authorities and led to necessary corrective actions to ensure high-quality SIA implementation. |
A microneedle patch for measles and rubella vaccination is immunogenic and protective in infant rhesus macaques
Joyce JC , Carroll TD , Collins ML , Chen MH , Fritts L , Dutra JC , Rourke TL , Goodson JL , McChesney MB , Prausnitz MR , Rota PA . J Infect Dis 2018 218 (1) 124-132 Background: New methods to increase measles and rubella (MR) vaccination coverage are needed to achieve global and regional MR elimination goals. Methods: Here, we developed microneedle (MN) patches designed to administer MR vaccine by minimally trained personnel, leave no biohazardous sharps waste, remove the need for vaccine reconstitution, and provide thermostability outside the cold chain. This study evaluated the immunogenicity of MN patches delivering MR vaccine to infant rhesus macaques. Results: Protective titers of measles neutralizing antibodies (>120 mIU/mL) were detected in 100% of macaques in the MN group and 75% of macaques in the subcutaneous (SC) injection group. Rubella neutralizing antibody titers were >10 IU/mL for all groups. All macaques in the MN group were protected from challenge with wild-type measles virus, whereas 75% were protected in the SC group. However, vaccination by the MN or SC route was unable to generate protective immune responses to measles in infant macaques pretreated with measles immunoglobulin to simulate maternal antibody. Conclusions: These results show, for the first time, that MR vaccine delivered by MN patch generated protective titers of neutralizing antibodies to both measles and rubella in infant rhesus macaques and afforded complete protection from measles virus challenge. |
Progress toward measles elimination - Western Pacific Region, 2013-2017
Hagan JE , Kriss JL , Takashima Y , Mariano KML , Pastore R , Grabovac V , Dabbagh AJ , Goodson JL . MMWR Morb Mortal Wkly Rep 2018 67 (17) 491-495 In 2005, the Regional Committee for the World Health Organization (WHO) Western Pacific Region (WPR)* established a goal for measles elimination(dagger) by 2012 (1). To achieve this goal, the 37 WPR countries and areas implemented the recommended strategies in the WPR Plan of Action for Measles Elimination (2) and the Field Guidelines for Measles Elimination (3). The strategies include 1) achieving and maintaining >/=95% coverage with 2 doses of measles-containing vaccine (MCV) through routine immunization services and supplementary immunization activities (SIAs), when required; 2) conducting high-quality case-based measles surveillance, including timely and accurate testing of specimens to confirm or discard suspected cases and detect measles virus for genotyping and molecular analysis; and 3) establishing and maintaining measles outbreak preparedness to ensure rapid response and appropriate case management. This report updates the previous report (4) and describes progress toward measles elimination in WPR during 2013-2017. During 2013-2016, estimated regional coverage with the first MCV dose (MCV1) decreased from 97% to 96%, and coverage with the routine second MCV dose (MCV2) increased from 91% to 93%. Eighteen (50%) countries achieved >/=95% MCV1 coverage in 2016. Seven (39%) of 18 nationwide SIAs during 2013-2017 reported achieving >/=95% administrative coverage. After a record low of 5.9 cases per million population in 2012, measles incidence increased during 2013-2016 to a high of 68.9 in 2014, because of outbreaks in the Philippines and Vietnam, as well as increased incidence in China, and then declined to 5.2 in 2017. To achieve measles elimination in WPR, additional measures are needed to strengthen immunization programs to achieve high population immunity, maintain high-quality surveillance for rapid case detection and confirmation, and ensure outbreak preparedness and prompt response to contain outbreaks. |
Measles outbreak response decision-making under uncertainty: a retrospective analysis
Fonnesbeck CJ , Shea K , Carran S , Cassio de Moraes J , Gregory C , Goodson JL , Ferrari MJ . J R Soc Interface 2018 15 (140) Resurgent outbreaks of vaccine-preventable diseases that have previously been controlled or eliminated have been observed in many settings. Reactive vaccination campaigns may successfully control outbreaks but must necessarily be implemented in the face of considerable uncertainty. Real-time surveillance may provide critical information about at-risk population and optimal vaccination targets, but may itself be limited by the specificity of disease confirmation. We propose an integrated modelling approach that synthesizes historical demographic and vaccination data with real-time outbreak surveillance via a dynamic transmission model and an age-specific disease confirmation model. We apply this framework to data from the 1996-1997 measles outbreak in Sao Paulo, Brazil. To simulate the information available to decision-makers, we truncated the surveillance data to what would have been available at 1 or 2 months prior to the realized interventions. We use the model, fitted to real-time observations, to evaluate the likelihood that candidate age-targeted interventions could control the outbreak. Using only data available prior to the interventions, we estimate that a significant excess of susceptible adults would prevent child-targeted campaigns from controlling the outbreak and that failing to account for age-specific confirmation rates would underestimate the importance of adult-targeted vaccination. |
Use of a diagonal approach to health system strengthening and measles elimination after a large nationwide outbreak in Mongolia
Hagan JE , Greiner A , Luvsansharav UO , Lake J , Lee C , Pastore R , Takashima Y , Sarankhuu A , Demberelsuren S , Smith R , Park B , Goodson JL . Emerg Infect Dis 2017 23 (13) S77-84 Measles is a highly transmissible infectious disease that causes serious illness and death worldwide. Efforts to eliminate measles through achieving high immunization coverage, well-performing surveillance systems, and rapid and effective outbreak response mechanisms while strategically engaging and strengthening health systems have been termed a diagonal approach. In March 2015, a large nationwide measles epidemic occurred in Mongolia, 1 year after verification of measles elimination in this country. A multidisciplinary team conducted an outbreak investigation that included a broad health system assessment, organized around the Global Health Security Agenda framework of Prevent-Detect-Respond, to provide recommendations for evidence-based interventions to interrupt the epidemic and strengthen the overall health system to prevent future outbreaks of measles and other epidemic-prone infectious threats. This investigation demonstrated the value of evaluating elements of the broader health system in investigating measles outbreaks and the need for using a diagonal approach to achieving sustainable measles elimination. |
Healthcare-associated measles following a nationwide outbreak in Mongolia
Lake JG , Luvsansharav UO , Hagan JE , Goodson JL , Jigjidsuren N , Gombojamts N , Park BJ , Smith R . Clin Infect Dis 2018 67 (2) 288-290 Measles virus is highly infectious and can spread rapidly through healthcare settings where vaccine coverage is low and isolation precautions are suboptimal. We describe healthcare-associated measles transmission during the large 2015-2016 measles outbreak in Mongolia, describe observed infection prevention gaps, and outline practical strategies to prevent healthcare-associated measles transmission. |
Progress toward regional measles elimination - worldwide, 2000-2016
Dabbagh A , Patel MK , Dumolard L , Gacic-Dobo M , Mulders MN , Okwo-Bele JM , Kretsinger K , Papania MJ , Rota PA , Goodson JL . MMWR Morb Mortal Wkly Rep 2017 66 (42) 1148-1153 The fourth United Nations Millennium Development Goal, adopted in 2000, set a target to reduce child mortality by two thirds by 2015. One indicator of progress toward this target was measles vaccination coverage (1). In 2010, the World Health Assembly (WHA) set three milestones for measles control by 2015: 1) increase routine coverage with the first dose of a measles-containing vaccine (MCV1) among children aged 1 year to ≥90% at the national level and to ≥80% in every district; 2) reduce global annual measles incidence to <5 cases per million population; and 3) reduce global measles mortality by 95% from the 2000 estimate (2).* In 2012, WHA endorsed the Global Vaccine Action Plan,dagger with the objective of eliminating measles in four World Health Organization (WHO) regions by 2015 and in five regions by 2020. Countries in all six WHO regions have adopted goals for measles elimination by or before 2020. Measles elimination is defined as the absence of endemic measles virus transmission in a region or other defined geographic area for ≥12 months, in the presence of a high quality surveillance system that meets targets of key performance indicators. This report updates a previous report (3) and describes progress toward global measles control milestones and regional measles elimination goals during 2000-2016. During this period, annual reported measles incidence decreased 87%, from 145 to 19 cases per million persons, and annual estimated measles deaths decreased 84%, from 550,100 to 89,780; measles vaccination prevented an estimated 20.4 million deaths. However, the 2015 milestones have not yet been met; only one WHO region has been verified as having eliminated measles. Improved implementation of elimination strategies by countries and their partners is needed, with focus on increasing vaccination coverage through substantial and sustained additional investments in health systems, strengthening surveillance systems, using surveillance data to drive programmatic actions, securing political commitment, and raising the visibility of measles elimination goals. |
Risk factors for measles virus infection among adults during a large outbreak in postelimination era in Mongolia, 2015
Hagan JE , Takashima Y , Sarankhuu A , Dashpagma O , Jantsansengee B , Pastore R , Nyamaa G , Yadamsuren B , Mulders MN , Wannemuehler KA , Anderson R , Bankamp B , Rota P , Goodson JL . J Infect Dis 2017 216 (10) 1187-1195 Background: In 2015, a large nationwide measles outbreak occurred in Mongolia, with very high incidence in the capital city of Ulaanbaatar and among young adults. Methods: We conducted an outbreak investigation including a matched case-control study of risk factors for laboratory-confirmed measles among young adults living in Ulaanbaatar. Young adults with laboratory-confirmed measles, living in the capital city of Ulaanbaatar, were matched with 2-3 neighborhood controls. Conditional logistic regression was used to estimate adjusted matched odds ratios (aMORs) for risk factors, with 95% confidence intervals. Results: During March 1-September 30, 2015, 20 077 suspected measles cases were reported; 14 010 cases were confirmed. Independent risk factors for measles included being unvaccinated (adjusted matched odds ratio [aMOR] 2.0, P < .01), being a high school graduate without college education (aMOR 2.6, P < .01), remaining in Ulaanbaatar during the outbreak (aMOR 2.5, P < .01), exposure to an inpatient healthcare facility (aMOR 4.5 P < .01), and being born outside of Ulaanbaatar (aMOR 1.8, P = .02). Conclusions: This large, nationwide outbreak shortly after verification of elimination had high incidence among young adults, particularly those born outside the national capital. In addition, findings indicated that nosocomial transmission within health facilities helped amplify the outbreak. |
Measles and rubella elimination: Learning from polio eradication and moving forward with a diagonal approach
Goodson JL , Alexander JP , Linkins RW , Orenstein WA . Expert Rev Vaccines 2017 16 (12) 1203-1216 INTRODUCTION: In 1988, an estimated 350,000 children were paralyzed by polio and 125 countries reported polio cases, the World Health Assembly passed a resolution to achieve polio eradication by 2000, and the Global Polio Eradication Initiative (GPEI) was established as a partnership focused on eradication. Today, following eradication efforts, polio cases have decreased >99% and eradication of all three types of wild polioviruses is approaching. However, since polio resources substantially support disease surveillance and other health programs, losing polio assets could reverse progress toward achieving Global Vaccine Action Plan goals. Areas covered: As the end of polio approaches and GPEI funds and capacity decrease, we document knowledge, experience, and lessons learned from 30 years of polio eradication. Expert commentary: Transitioning polio assets to measles and rubella (MR) elimination efforts would accelerate progress toward global vaccination coverage and equity. MR elimination feasibility and benefits have long been established. Focusing efforts on MR elimination after achieving polio eradication would make a permanent impact on reducing child mortality but should be done through a 'diagonal approach' of using measles disease transmission to identify areas possibly susceptible to other vaccine-preventable diseases and to strengthen the overall immunization and health systems to achieve disease-specific goals. |
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