Last data update: Dec 09, 2024. (Total: 48320 publications since 2009)
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On the path to measles and rubella elimination following rubella-containing vaccine introduction, 2000-2023, Namibia
Masresha BG , Shibeshi ME , de Wee R , Shapumba N , Sayi T , Reef SE , Goodson JL . Vaccines (Basel) 2024 12 (9) INTRODUCTION: The WHO Measles and Rubella Strategic Framework 2021-2030 within the Immunization Agenda 2030 includes both measles and rubella elimination goals and provides guidance to countries for planning and implementing the measles and rubella elimination strategies. Namibia has been implementing measles elimination strategies since 1997. METHODS: We reviewed and described the implementation of measles and rubella elimination strategies and the programmatic and epidemiological situation in Namibia during 2000-2023. Namibia introduced a rubella-containing vaccine (RCV) in 2016 as a combined measles-rubella (MR) vaccine using a MR catch-up campaign, targeting a wide age range based on detailed analysis and triangulation of multiple key data sources including MR vaccination coverage, MR case-based surveillance, detailed measles outbreak investigations, and serosurveys. RESULTS: In 2020, estimated MCV1 coverage in Namibia reached 90% and has been sustained at 91% in 2021 and 2022. MCV2 was introduced in 2016, and the estimated MCV2 coverage has steadily increased to 79% in 2022. Following the MCV2 introduction and the implementation of the wide age range MR catch-up campaign in 2016, annual measles and rubella incidence decreased substantially. During 2017-2023, the period following the implementation of the catch-up MR vaccination SIA in 2016, average annual measles incidence per million population in Namibia decreased by 97% from the average during 2010-2016. Similarly, the average annual rubella incidence decreased by 95% from 2010-2016 to 2017-2023. DISCUSSION: Successful implementation of the 2016 wide age range campaign and maintaining high routine immunization coverage likely led to the significant reduction in measles and rubella incidence in Namibia. To sustain the reduction in measles and rubella incidence and attain the elimination targets, Namibia needs to attain and maintain high routine immunization coverage with both doses of the MR vaccine and implement timely and high-quality periodic MR follow-up SIAs. High-quality elimination-standard measles and rubella surveillance will help guide strategies and serve as the basis for the eventual verification of measles and rubella elimination in Namibia according to the WHO-recommended framework. |
The path to eradication of rubella
Reef SE , Icenogle JP , Plotkin SA . Vaccine 2023 41 (50) 7525-7531 Since 1969, rubella and its harmful effect on fetuses infected in utero can be prevented by rubella vaccine, usually given in combination with measles vaccine. The rubella vaccine is highly protective both in children and in adults including women intending to become pregnant. Owing to the use of combined measles and rubella vaccines, congenital rubella infection has been eliminated from the Western Hemisphere and nearly all of Europe. Such combined vaccination is now being applied throughout the world, posing the possibility of eventual rubella eradication. The existence of viruses of animals related to rubella does not appear to be a barrier to eradication of the human virus. However, persistent rubella virus in infants infected in utero and of immunosuppressed patients with granulomas may pose a problem for eradication. Nevertheless, this review posits that eradication of rubella is now feasible if routine vaccination of infants and surveillance for chronic infection are correctly applied. |
Estimates of the global burden of Congenital Rubella Syndrome, 1996-2019
Vynnycky EPhD , Knapp JKPhD , Papadopoulos TPhD , Cutts Ft Md , Hachiya MPhD , Miyano SPhD , Reef Se Md . Int J Infect Dis 2023 137 149-156 OBJECTIVES: Many countries introduced rubella-containing vaccination (RCV) after 2011, following changes in recommended World Health Organization (WHO) vaccination strategies and external support. We evaluated the impact of these introductions. METHODS: We estimated the country-specific, region-specific and global Congenital Rubella Syndrome (CRS) incidence during 1996-2019 using mathematical modelling, including routine and campaign vaccination coverage and seroprevalence data. RESULTS: In 2019, WHO African and Eastern Mediterranean regions had the highest estimated CRS incidence (64 (95% CI: 24-123) and 27 (95% CI: 4-67) per 100,000 live births respectively), where nearly half of births occur in countries that have introduced RCV. Other regions, where >95% of births occurred in countries which had introduced RCV, had a low estimated CRS incidence (<1 (95% CI: <1-8) and <1 (95% CI: <1-12) per 100,000 live births in South East Asia (SEAR) and the Western Pacific (WPR) respectively, and similarly in Europe and the Americas). The estimated number of CRS births globally declined by approximately two thirds during 2010-2019, from 100,000 (95% CI: 54,000-166,000) to 32,000 (95% CI: 13,000-60,000), representing a 73% reduction since 1996, largely following RCV introductions in WPR and SEAR, where the greatest reductions occurred. CONCLUSIONS: Further reductions can occur by introducing RCV in remaining countries and maintaining high RCV coverage. |
Combining serological and contact data to derive target immunity levels for achieving and maintaining measles elimination (preprint)
Funk S , Knapp JK , Lebo E , Reef SE , Dabbagh AJ , Kretsinger K , Jit M , Edmunds WJ , Strebel PM . bioRxiv 2019 201574 Background Vaccination has reduced the global incidence of measles to the lowest rates in history. However, local interruption of measles virus transmission requires sustained high levels of population immunity that can be challenging to achieve and maintain. The herd immunity threshold for measles is typically stipulated at 90–95%. This figure does not easily translate into age-specific immunity levels required to interrupt transmission. Previous estimates of such levels were based on speculative contact patterns based on historical data from high-income countries. The aim of this study was to determine age-specific immunity levels that would ensure elimination of measles when taking into account empirically observed contact patterns.Methods We combined estimated immunity levels from serological data in 17 countries with studies of age-specific mixing patterns to derive contact-adjusted immunity levels. We then compared these to case data from the 10 years following the seroprevalence studies to establish a contact-adjusted immunity threshold for elimination. We lastly combined a range of hypothetical immunity profiles with contact data from a wide range of socioeconomic and demographic settings to determine whether they would be sufficient for elimination.Results We found that contact-adjusted immunity levels were able to predict whether countries would experience outbreaks in the decade following the serological studies in about 70% of countries. The corresponding threshold level of contact-adjusted immunity was found to be 93%, corresponding to an average basic reproduction number of approximately 14. Testing different scenarios of immunity with this threshold level using contact studies from around the world, we found that 95% immunity would have to be achieved by the age of five and maintained across older age groups to guarantee elimination. This reflects a greater level of immunity required in 5–9 year olds than established previously.Conclusions The immunity levels we found necessary for measles elimination are higher than previous guidance. The importance of achieving high immunity levels in 5–9 year olds presents both a challenge and an opportunity. While such high levels can be difficult to achieve, school entry provides an opportunity to ensure sufficient vaccination coverage. Combined with observations of contact patterns, further national and sub-national serological studies could serve to highlight key gaps in immunity that need to be filled in order to achieve national and regional measles elimination.ESEN2European Sero-Epidemiology Network 2EUROEuropean RegionMCEMisclassification errorWHOWorld Health Organization |
Immune response to co-administration of measles, mumps, and rubella (MMR), and yellow fever vaccines: a randomized non-inferiority trial among one-year-old children in Argentina
Vizzotti C , Harris JB , Aquino A , Rancaño C , Biscayart C , Bonaventura R , Pontoriero A , Baumeister E , Freire MC , Magariños M , Duarte B , Grant G , Reef S , Laven J , Wannemuehler KA , Alvarez AMR , Staples JE . BMC Infect Dis 2023 23 (1) 165 BACKGROUND: In yellow fever (YF) endemic areas, measles, mumps, and rubella (MMR), and YF vaccines are often co-administered in childhood vaccination schedules. Because these are live vaccines, we assessed potential immune interference that could result from co-administration. METHODS: We conducted an open-label, randomized non-inferiority trial among healthy 1-year-olds in Misiones Province, Argentina. Children were randomized to one of three groups (1:1:1): Co-administration of MMR and YF vaccines (MMR(1)YF(1)), MMR followed by YF vaccine four weeks later (MMR(1)YF(2)), or YF followed by MMR vaccine four weeks later (YF(1)MMR(2)). Blood samples obtained pre-vaccination and 28 days post-vaccination were tested for immunoglobulin G antibodies against measles, mumps, and rubella, and for YF virus-specific neutralizing antibodies. Non-inferiority in seroconversion was assessed using a -5% non-inferiority margin. Antibody concentrations were compared with Kruskal-Wallis tests. RESULTS: Of 851 randomized children, 738 were correctly vaccinated, had ≥ 1 follow-up sample, and were included in the intention-to-treat population. Non-inferior seroconversion was observed for all antigens (measles seroconversion: 97.9% in the MMR(1)YF(1) group versus 96.3% in the MMR(1)YF(2) group, a difference of 1.6% [90% CI -1.5, 4.7]; rubella: 97.9% MMR(1)YF(1) versus 94.7% MMR(1)YF(2), a difference of 3.3% [-0.1, 6.7]; mumps: 96.7% MMR(1)YF(1) versus 97.9% MMR(1)YF(2), a difference of -1.3% [-4.1, 1.5]; and YF: 96.3% MMR(1)YF(1) versus 97.5% YF(1)MMR(2), a difference of -1.2% [-4.2, 1.7]). Rubella antibody concentrations and YF titers were significantly lower following co-administration; measles and mumps concentrations were not impacted. CONCLUSION: Effective seroconversion was achieved and was not impacted by the co-administration, although antibody levels for two antigens were lower. The impact of lower antibody levels needs to be weighed against missed opportunities for vaccination to determine optimal timing for MMR and YF vaccine administration. TRIAL REGISTRATION: The study was retrospectively registered in ClinicalTrials.gov (NCT03368495) on 11/12/2017. |
Past as prologue-use of rubella vaccination program lessons to inform COVID-19 vaccination
Dixon MG , Reef SE , Zimmerman LA , Grant GB . Emerg Infect Dis 2022 28 (13) S225-s231 The rapid rollout of vaccines against COVID-19 as a key mitigation strategy to end the global pandemic might be informed by lessons learned from rubella vaccine implementation in response to the global rubella epidemic of 1963-1965. That rubella epidemic led to the development of a rubella vaccine that has been introduced in all but 21 countries worldwide and has led to elimination of rubella in 93 countries. Although widespread introduction and use of rubella vaccines was slower than that for COVID-19 vaccines, the process can provide valuable insights for the continued battle against COVID-19. Experiences from the rubella disease control program highlight the critical and evolving elements of a vaccination program, including clearly delineated goals and strategies, regular data-driven revisions to the program based on disease and vaccine safety surveillance, and evaluations to identify the vaccine most capable of achieving disease control targets. |
Natural history of pulmonary coccidioidomycosis: Further examination of the VA-Armed Forces database
Shemuel J , Bays DJ , Thompson GR , Reef S , Snyder L , Freifeld AJ , Huppert M , Salkin D , Wilson MD , Galgiani JN . Med Mycol 2022 60 (10) There are still many limitations related to the understanding of the natural history of differing forms of coccidioidomycosis, including characterizing the spectrum of pulmonary disease. The historical Veterans Administration-Armed Forces database, recorded primarily before the advent of antifungal therapy, presents an opportunity to characterize the natural history of pulmonary CM. We performed a retrospective cohort study of 342 armed forces service members who were diagnosed with pulmonary CM at VA facilities between 1955-1958, followed to 1966, who did not receive antifungal therapy. Patients were grouped by predominant pulmonary finding on chest radiograph. The all-cause mortality was low for all patients (4.6%). Cavities had a median size of 3-3.9 cm (IQR: 2-2.9 cm - 4-4.9 cm), with heterogeneous wall thickness and no fluid level, while nodules had a median size of 1-1.19 cm (IQR 1-1.9 cm - 2-2.9 cm) and sharp borders. The majority of cavities were chronic (85.6%), and just under half were found incidentally. Median complement fixation titers in both the nodular and cavitary groups were negative, with higher titers in the cavitary group overall. This retrospective cohort study of non-disseminated coccidioidomycosis, the largest to date, sheds light on the natural history, serologic markers, and radiologic characteristics of this understudied disease. These findings have implications for the evaluation and management of CM. | Coccidioidomycosis (CM), also known as San Joaquin Valley Fever, causes a variety of symptoms including pneumonia. This historical study investigates CM of the lungs in American soldiers with CM in the 1950s, prior to modern antifungals, to better understand the natural history. | eng |
Feasibility of measles and rubella vaccination programmes for disease elimination: a modelling study
Winter AK , Lambert B , Klein D , Klepac P , Papadopoulos T , Truelove S , Burgess C , Santos H , Knapp JK , Reef SE , Kayembe LK , Shendale S , Kretsinger K , Lessler J , Vynnycky E , McCarthy K , Ferrari M , Jit M . Lancet Glob Health 2022 10 (10) e1412-e1422 BACKGROUND: Marked reductions in the incidence of measles and rubella have been observed since the widespread use of the measles and rubella vaccines. Although no global goal for measles eradication has been established, all six WHO regions have set measles elimination targets. However, a gap remains between current control levels and elimination targets, as shown by large measles outbreaks between 2017 and 2019. We aimed to model the potential for measles and rubella elimination globally to inform a WHO report to the 73rd World Health Assembly on the feasibility of measles and rubella eradication. METHODS: In this study, we modelled the probability of measles and rubella elimination between 2020 and 2100 under different vaccination scenarios in 93 countries of interest. We evaluated measles and rubella burden and elimination across two national transmission models each (Dynamic Measles Immunisation Calculation Engine [DynaMICE], Pennsylvania State University [PSU], Johns Hopkins University, and Public Health England models), and one subnational measles transmission model (Institute for Disease Modeling model). The vaccination scenarios included a so-called business as usual approach, which continues present vaccination coverage, and an intensified investment approach, which increases coverage into the future. The annual numbers of infections projected by each model, country, and vaccination scenario were used to explore if, when, and for how long the infections would be below a threshold for elimination. FINDINGS: The intensified investment scenario led to large reductions in measles and rubella incidence and burden. Rubella elimination is likely to be achievable in all countries and measles elimination is likely in some countries, but not all. The PSU and DynaMICE national measles models estimated that by 2050, the probability of elimination would exceed 75% in 14 (16%) and 36 (39%) of 93 modelled countries, respectively. The subnational model of measles transmission highlighted inequity in routine coverage as a likely driver of the continuance of endemic measles transmission in a subset of countries. INTERPRETATION: To reach regional elimination goals, it will be necessary to innovate vaccination strategies and technologies that increase spatial equity of routine vaccination, in addition to investing in existing surveillance and outbreak response programmes. FUNDING: WHO, Gavi, the Vaccine Alliance, US Centers for Disease Control and Prevention, and the Bill & Melinda Gates Foundation. |
Progress toward rubella and congenital rubella syndrome control and elimination - worldwide, 2012-2020
Zimmerman LA , Knapp JK , Antoni S , Grant GB , Reef SE . MMWR Morb Mortal Wkly Rep 2022 71 (6) 196-201 Rubella virus is a leading cause of vaccine-preventable birth defects and can cause epidemics. Although rubella virus infection usually produces a mild febrile rash illness in children and adults, infection during pregnancy, especially during the first trimester, can result in miscarriage, fetal death, stillbirth, or an infant born with a constellation of birth defects known as congenital rubella syndrome (CRS). A single dose of rubella-containing vaccine (RCV) can provide lifelong protection against rubella (1). The Global Vaccine Action Plan 2011-2020 (GVAP) included a target to achieve elimination of rubella in at least five of the six World Health Organization (WHO) regions* by 2020 (2), and WHO recommends capitalizing on the accelerated measles elimination activities as an opportunity to introduce RCV (1). This report updates a previous report (3) and summarizes global progress toward control and elimination of rubella and CRS from 2012, when accelerated rubella control activities were initiated, through 2020. Among 194 WHO Member States, the number with RCV in their immunization schedules has increased from 132 (68%) in 2012 to 173 (89%) in 2020; 70% of the world's infants were vaccinated against rubella in 2020. Reported rubella cases declined by 48%, from 94,277 in 2012 to 49,136 in 2019, and decreased further to 10,194 in 2020. Rubella elimination has been verified in 93 (48%) of 194 countries including the entire Region of the Americas (AMR). To increase the equity of protection and make further progress to eliminate rubella, it is important that the 21 countries that have not yet done so should introduce RCV. Likewise, countries that have introduced RCV can achieve and maintain rubella elimination with high vaccination coverage and surveillance for rubella and CRS. Four of six WHO regions have established rubella elimination goals; the two WHO regions that have not yet established an elimination goal (the African [AFR] and Eastern Mediterranean [EMR] regions) have expressed a commitment to rubella elimination and should consider establishing a goal. |
Progress towards rubella elimination - WHO European Region, 2005-2019
O'Connor P , Jankovic D , Zimmerman L , Mamou MB , Reef S . Wkly Epidemiol Rec 2021 96 (24) 229-240 This study reports the elimination of rubella across Europe, focusing on (1) immunisation activities, (2) surveillance activities, (3) Rubella incidence and genotypes, and (4) regional verification commission and progress towards elimination. Substantial progress towards rubella elimination has been made in the WHO European Region. Verification of elimination is nearly complete, which would make the European Region the second WHO region to achieve rubella elimination, after the Region of the Americas. Sustaining regional rubella elimination will require maintaining high coverage with RCVs through routine immunisation programmes at national and subnational levels, offering supplementary rubella vaccination to susceptible adults, maintaining high-quality laboratory-supported rubella and CRS surveillance for outbreak detection and response and a fully functioning Regional Verification Commission. Because of the COVID-19 pandemic, additional efforts might be needed to strengthen surveillance systems and fill in the immunity gaps. |
Progress Toward Rubella Elimination - World Health Organization European Region, 2005-2019
O'Connor P , Yankovic D , Zimmerman L , Ben Mamou M , Reef S . MMWR Morb Mortal Wkly Rep 2021 70 (23) 833-839 In 2005, the Regional Committee of the World Health Organization (WHO) European Region (EUR) passed a resolution calling for the regional elimination of measles, rubella, and congenital rubella syndrome (CRS) (1). In 2010, all 53 countries in EUR* reaffirmed their commitment to eliminating measles, rubella, and CRS (2); this goal was included in the European Vaccine Action Plan 2015-2020 (3,4). Rubella, which typically manifests as a mild febrile rash illness, is the leading vaccine-preventable cause of birth defects. Rubella infection during pregnancy can result in miscarriage, fetal death, or a constellation of malformations known as CRS, which usually includes one or more visual, auditory, or cardiac defects (5). The WHO-recommended measles and rubella elimination strategies in EUR include 1) achieving and maintaining ≥95% coverage with 2 doses of measles- and rubella-containing vaccine (MRCV) 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 to clearly communicate the benefits and risks of preventing these diseases through vaccination to health professionals and the public (6). This report updates a previous report and describes progress toward rubella and CRS elimination in EUR during 2005-2019 (7). In 2000, estimated coverage with the first dose of a rubella-containing vaccine (RCV1) in EUR was 60%, and 621,039 rubella cases were reported (incidence = 716.9 per 1 million population). During 2005-2019, estimated regional coverage with RCV1 was 93%-95%, and in 2019, 31 (58%) countries achieved ≥95% coverage with the RCV1. During 2005-2019, approximately 38 million persons received an RCV during SIAs in 20 (37%) countries. Rubella incidence declined by >99%, from 234.9 cases per 1 million population (206,359 cases) in 2005 to 0.67 cases per 1 million population (620 cases) by 2019. CRS cases declined by 50%, from 16 cases in 2005 to eight cases in 2019. For rubella and CRS elimination in EUR to be achieved and maintained, measures are needed to strengthen immunization programs by ensuring high coverage with an RCV in every district of each country, offering supplementary rubella vaccination to susceptible adults, maintaining high-quality surveillance for rapid case detection and confirmation, and ensuring effective outbreak preparedness and response. |
Natural history of disseminated coccidioidomycosis: Examination of the VA-Armed Forces Database
Bays DJ , Thompson GR , Reef S , Snyder L , Freifeld AJ , Huppert M , Salkin D , Wilson MD , Galgiani JN . Clin Infect Dis 2020 73 (11) e3814-e3819 BACKGROUND: The natural history of non-central nervous system (CNS) disseminated coccidioidomycosis (DCM) has not been previously characterized. The historical VA-Armed Forces coccidioidomycosis patient group provides a unique cohort of patients not treated with standard antifungal therapy allowing for characterization of the natural history of coccidioidomycosis. METHODS: We conducted a retrospective study of 531 VA-Armed Forces coccidioidomycosis patients diagnosed between 1955-1958 and followed to 1966. Groups were identified as non-disseminated coccidioidomycosis (non-DCM, 462 patients), DCM (44 patients), and CNS (25 patients). The duration of initial infection, fate of primary infection, all-cause mortality and mortality secondary to coccidioidomycosis were assessed and compared between groups. RESULTS: Mortality due to coccidioidomycosis at last known follow up was significantly different across the groups: 0.65% in non-DCM, 25% in DCM, and 88% in CNS (P<0.001). The primary fate of pulmonary infection demonstrated key differences with pulmonary nodules observed in 39.61% in non-DCM, 13.64% in DCM, and 20% in CNS (P<0.001). There were differences in cavity formation with 34.20% in non-DCM, 9.09% DCM, and 8 % in CNS (P <0.001). Forty-one percent and 56% of patients in the non-CNS DCM and CNS groups, respectively, developed dissemination as the presenting manifestation or concurrent with initial infection. CONCLUSIONS: This large retrospective cohort study helps characterize the natural history of DCM, provides insight into the host immunologic response, and has direct clinical implications for the management and follow-up of patients. |
Progress toward rubella elimination - Western Pacific Region, 2000-2019
Knapp JK , Mariano KM , Pastore R , Grabovac V , Takashima Y , Alexander JP Jr , Reef SE , Hagan JE . MMWR Morb Mortal Wkly Rep 2020 69 (24) 744-750 Rubella is the leading vaccine-preventable cause of birth defects. Rubella typically manifests as a mild febrile rash illness; however, infection during pregnancy, particularly during the first trimester, can result in miscarriage, fetal death, or a constellation of malformations known as congenital rubella syndrome (CRS), commonly including one or more visual, auditory, or cardiac defects (1). In 2012, the Regional Committee of the World Health Organization (WHO) Western Pacific Region (WPR)* committed to accelerate rubella control, and in 2017, resolved that all countries or areas (countries) in WPR should aim for rubella elimination(dagger) as soon as possible (2,3). WPR countries are capitalizing on measles elimination activities, using a combined measles and rubella vaccine, case-based surveillance for febrile rash illness, and integrated diagnostic testing for measles and rubella. This report summarizes progress toward rubella elimination and CRS prevention in WPR during 2000-2019. Coverage with a first dose of rubella-containing vaccine (RCV1) increased from 11% in 2000 to 96% in 2019. During 1970-2019, approximately 84 million persons were vaccinated through 62 supplementary immunization activities (SIAs) conducted in 27 countries. Reported rubella incidence increased from 35.5 to 71.3 cases per million population among reporting countries during 2000-2008, decreased to 2.1 in 2017, and then increased to 18.4 in 2019 as a result of outbreaks in China and Japan. Strong sustainable immunization programs, closing of existing immunity gaps, and maintenance of high-quality surveillance to respond rapidly to and contain outbreaks are needed in every WPR country to achieve rubella elimination in the region. |
Progress toward rubella and congenital rubella syndrome control and elimination - worldwide, 2000-2018
Grant GB , Desai S , Dumolard L , Kretsinger K , Reef SE . MMWR Morb Mortal Wkly Rep 2019 68 (39) 855-859 Rubella is a leading cause of vaccine-preventable birth defects. Although rubella virus infection usually causes a mild febrile rash illness in children and adults, infection during pregnancy, especially during the first trimester, can result in miscarriage, fetal death, stillbirth, or a constellation of birth defects known as congenital rubella syndrome (CRS). A single dose of rubella-containing vaccine (RCV) can provide lifelong protection (1). In 2011, the World Health Organization (WHO) updated guidance on the use of RCV and recommended capitalizing on the accelerated measles elimination activities as an opportunity to introduce RCV (1). The Global Vaccine Action Plan 2011-2020 (GVAP) includes a target to achieve elimination of rubella in at least five of the six WHO regions by 2020 (2). This report on the progress toward rubella and CRS control and elimination updates the 2017 report (3), summarizing global progress toward the control and elimination of rubella and CRS from 2000 (the initiation of accelerated measles control activities) and 2012 (the initiation of accelerated rubella control activities) to 2018 (the most recent data) using WHO immunization and surveillance data. Among WHO Member States,* the number with RCV in their immunization schedules has increased from 99 (52% of 191) in 2000 to 168 (87% of 194) in 2018(dagger); 69% of the world's infants were vaccinated against rubella in 2018. Rubella elimination has been verified in 81 (42%) countries. To make further progress to control and eliminate rubella, and to reduce the equity gap, introduction of RCV in all countries is important. Likewise, countries that have introduced RCV can achieve and maintain elimination with high vaccination coverage and surveillance for rubella and CRS. The two WHO regions that have not established an elimination goal (African [AFR] and Eastern Mediterranean [EMR]) should consider establishing a goal.( section sign). |
Combining serological and contact data to derive target immunity levels for achieving and maintaining measles elimination
Funk S , Knapp JK , Lebo E , Reef SE , Dabbagh AJ , Kretsinger K , Jit M , Edmunds WJ , Strebel PM . BMC Med 2019 17 (1) 180 BACKGROUND: Vaccination has reduced the global incidence of measles to the lowest rates in history. However, local interruption of measles virus transmission requires sustained high levels of population immunity that can be challenging to achieve and maintain. The herd immunity threshold for measles is typically stipulated at 90-95%. This figure does not easily translate into age-specific immunity levels required to interrupt transmission. Previous estimates of such levels were based on speculative contact patterns based on historical data from high-income countries. The aim of this study was to determine age-specific immunity levels that would ensure elimination of measles when taking into account empirically observed contact patterns. METHODS: We combined estimated immunity levels from serological data in 17 countries with studies of age-specific mixing patterns to derive contact-adjusted immunity levels. We then compared these to case data from the 10 years following the seroprevalence studies to establish a contact-adjusted immunity threshold for elimination. We lastly combined a range of hypothetical immunity profiles with contact data from a wide range of socioeconomic and demographic settings to determine whether they would be sufficient for elimination. RESULTS: We found that contact-adjusted immunity levels were able to predict whether countries would experience outbreaks in the decade following the serological studies in about 70% of countries. The corresponding threshold level of contact-adjusted immunity was found to be 93%, corresponding to an average basic reproduction number of approximately 14. Testing different scenarios of immunity with this threshold level using contact studies from around the world, we found that 95% immunity would have to be achieved by the age of five and maintained across older age groups to guarantee elimination. This reflects a greater level of immunity required in 5-9-year-olds than established previously. CONCLUSIONS: The immunity levels we found necessary for measles elimination are higher than previous guidance. The importance of achieving high immunity levels in 5-9-year-olds presents both a challenge and an opportunity. While such high levels can be difficult to achieve, school entry provides an opportunity to ensure sufficient vaccination coverage. Combined with observations of contact patterns, further national and sub-national serological studies could serve to highlight key gaps in immunity that need to be filled in order to achieve national and regional measles elimination. |
Assessment of economic burden of concurrent measles and rubella outbreaks, Romania, 2011-2012
Njau J , Janta D , Stanescu A , Pallas SS , Pistol A , Khetsuriani N , Reef S , Ciurea D , Butu C , Wallace AS , Zimmerman L . Emerg Infect Dis 2019 25 (6) 1101-1109 We estimated the economic impact of concurrent measles and rubella outbreaks in Romania during 2011-2012. We collected costs from surveys of 428 case-patients and caretakers, government records, and health staff interviews. We then estimated financial and opportunity costs. During the study period, 12,427 measles cases and 24,627 rubella cases were recorded; 27 infants had congenital rubella syndrome (CRS). The cost of the outbreaks was US $9.9 million. Cost per case was US $439 for measles, US $132 for rubella, and US $44,051 for CRS. Up to 36% of households needed to borrow money to pay for illness treatment. Approximately 17% of patients continued to work while ill to pay their treatment expenses. Our key study findings were that households incurred a high economic burden compared with their incomes, the health sector bore most costs, and CRS costs were substantial and relevant to include in rubella outbreak cost studies. |
Spread of measles in Europe and implications for US travelers
Angelo KM , Gastanaduy PA , Walker AT , Patel M , Reef S , Lee CV , Nemhauser J . Pediatrics 2019 144 (1) From January 2018 to June 2018, World Health Organization (WHO) European Region countries reported >41 000 measles cases, including 37 deaths, a record high since the 1990s. Low vaccination coverage in previous years is the biggest contributing factor to the increase in cases. The Ukraine reported the majority of cases, but France, Georgia, Greece, Italy, the Russian Federation, and Serbia also reported high case counts. Europe is the most common travel destination worldwide and is widely perceived as being without substantial infectious disease risks. For this reason, travelers may not consider the relevance of a pretravel health consultation, including vaccination, in their predeparture plans. Measles is highly contagious, and the record number of measles cases in the WHO European Region not only puts unvaccinated and inadequately vaccinated travelers at risk but also increases the risk for nontraveling US residents who come into close contact with returned travelers who are ill. The US Centers for Disease Control and Prevention encourage US travelers to be aware of measles virus transmission in Europe and receive all recommended vaccinations, including for measles, before traveling abroad. Health care providers must maintain a high degree of suspicion for measles among travelers returning from Europe or people with close contact with international travelers who present with a febrile rash illness. The current WHO European Region outbreak should serve to remind health care providers to stay current with the epidemiology of highly transmissible diseases, such as measles, through media, WHO, and Centers for Disease Control and Prevention reports and encourage measles vaccination for international travelers. |
Progress toward rubella and congenital rubella syndrome control - South-East Asia Region, 2000-2016
Khanal S , Bahl S , Sharifuzzaman M , Dhongde D , Pattamadilok S , Reef S , Morales M , Dabbagh A , Kretsinger K , Patel M . MMWR Morb Mortal Wkly Rep 2018 67 (21) 602-606 In 2013, the 66th session of the Regional Committee of the World Health Organization (WHO) South-East Asia Region (SEAR)* adopted the goal of elimination of measles and control(dagger) of rubella and congenital rubella syndrome (CRS) by 2020 (1). Rubella is the leading vaccine-preventable cause of birth defects. Although rubella typically causes a mild fever and rash in children and adults, rubella virus infection during pregnancy, especially during the first trimester, can result in miscarriage, fetal death, or a constellation of congenital malformations known as CRS, commonly including visual, auditory, and/or cardiac defects, and developmental delay (2). Rubella and CRS control capitalizes on the momentum created by pursuing measles elimination because the efforts are programmatically linked. Rubella-containing vaccine (RCV) is administered as a combined measles and rubella vaccine, and rubella cases are detected through case-based surveillance for measles or fever and rash illness (3). This report summarizes progress toward rubella and CRS control in SEAR during 2000-2016. Estimated coverage with a first RCV dose (RCV1) increased from 3% of the birth cohort in 2000 to 15% in 2016 because of RCV introduction in six countries. RCV1 coverage is expected to increase rapidly with the phased introduction of RCV in India and Indonesia beginning in 2017; these countries are home to 83% of the SEAR birth cohort. During 2000-2016, approximately 83 million persons were vaccinated through 13 supplemental immunization activities (SIAs) conducted in eight countries. During 2010-2016, reported rubella incidence decreased by 37%, from 8.6 to 5.4 cases per 1 million population, and four countries (Bangladesh, Maldives, Sri Lanka, and Thailand) reported a decrease in incidence of >/=95% since 2010. To achieve rubella and CRS control in SEAR, sustained investment to increase routine RCV coverage, periodic high-quality SIAs to close immunity gaps, and strengthened rubella and CRS surveillance are needed. |
Rubella vaccine - a tale of appropriate caution and remarkable success
Zimmerman LA , Reef SE , Orenstein WA . JAMA Pediatr 2018 172 (1) 95-96 Lyerly et al refer to historical aspects of the rubella vaccination program as “a cautionary tale about caution” concerning Zika vaccine research.1 The US rubella vaccination program has been a tale of appropriate caution and a remarkable success in rubella and congenital rubella syndrome (CRS) elimination2. We concur with the authors' assertion that safety studies in pregnant women are important and could have overcome the initial reluctance to give rubella vaccine to women of childbearing age (WCBA). However, points within the article warrant comment. |
Progress in rubella and congenital rubella syndrome control and elimination - worldwide, 2000-2016
Grant GB , Reef SE , Patel M , Knapp JK , Dabbagh A . MMWR Morb Mortal Wkly Rep 2017 66 (45) 1256-1260 Although rubella virus infection usually causes a mild fever and rash illness in children and adults, infection during pregnancy, especially during the first trimester, can result in miscarriage, fetal death, stillbirth, or infants with a constellation of congenital malformations known as congenital rubella syndrome (CRS) (1). Rubella is a leading vaccine-preventable cause of birth defects. Preventing these adverse pregnancy outcomes is the focus of rubella vaccination programs. In 2011, the World Health Organization (WHO) updated guidance on the preferred strategy for introduction of rubella-containing vaccine (RCV) into national immunization schedules and recommended an initial vaccination campaign, usually targeting children aged 9 months-14 years (1). The Global Vaccine Action Plan 2011-2020 (GVAP), endorsed by the World Health Assembly in 2012, includes goals to eliminate rubella in at least five of the six WHO regions by 2020 (2). This report updates a previous report (3) and summarizes global progress toward rubella and CRS control and elimination from 2000 to 2016. As of December 2016, 152 (78%) of 194 countries had introduced RCV into the national immunization schedule, representing an increase of 53 countries since 2000, including 20 countries that introduced RCV after 2012. |
National, regional and global certification bodies for polio eradication: A framework for verifying measles elimination
Deblina Datta S , Tangermann RH , Reef S , William Schluter W , Adams A . J Infect Dis 2017 216 S351-S354 The Global Certification Commission (GCC), Regional Certification Commissions (RCCs), and National Certification Committees (NCCs) provide a framework of independent bodies to assist the Global Polio Eradication Initiative (GPEI) in certifying and maintaining polio eradication in a standardized, ongoing, and credible manner. Their members meet regularly to comprehensively review population immunity, surveillance, laboratory, and other data to assess polio status in the country (NCC), World Health Organization (WHO) region (RCC), or globally (GCC). These highly visible bodies provide a framework to be replicated to independently verify measles and rubella elimination in the regions and globally. |
Progress and challenges in measles and rubella elimination in the WHO European Region
Datta SS , O'Connor PM , Jankovic D , Muscat M , Ben Mamou MC , Singh S , Kaloumenos T , Reef S , Papania M , Butler R . Vaccine 2017 36 (36) 5408-5415 INTRODUCTION: Despite availability of safe and cost-effective vaccines to prevent it, measles remains one of the significant causes of death among children under five years of age globally. The World Health Organization (WHO) European Region has seen a drastic decline in measles and rubella cases in recent years, and a few of the once common measles genotypes are no longer detected. Buoyed by this success, all Member States of the Region reconfirmed their commitment in 2010 to eliminating measles and rubella, and made this a central objective of the European Vaccine Action Plan 2015-2020 (EVAP). Nevertheless, sporadic outbreaks continue, recently affecting primarily adolescents and young adults with no vaccination or an incomplete vaccination history. The European Regional Verification Commission for Measles and Rubella Elimination was established in 2011 to evaluate the status of measles and rubella elimination based on documentation submitted annually by each country's national verification committee. DISCUSSION: Each country's commitment to eliminate measles and rubella is influenced by competing health priorities, and in some cases lack of capacity and resources. All countries need to improve case-base surveillance for both measles and rubella, ensure documentation of each outbreak and strengthen the link between epidemiology and laboratory data. Achieving high coverage with measles- and rubella-containing vaccines will require a multisectoral approach to address the root causes of lower uptake in identified communities including service delivery challenges or vaccine safety concerns caused by circulating myths about vaccination. CONCLUSIONS: The WHO European Region has made steady progress towards eliminating measles and rubella and over half of the countries interrupted endemic transmission of both diseases by 2015. The programmatic challenges in disease surveillance, vaccination service delivery and communication in the remaining endemic countries should be addressed through periodic evaluation of the strategies by all stakeholders and exploring additional opportunities to accelerate the ongoing elimination activities. |
Impact of a participatory analysis of a campus sustainability social network: A case study of Emory University
Chuvileva IM , Reef L , Wilt GE , Shriber J , Aleman M , Smith B . Sustainability 2017 10 (3) 193-203 Social network analysis makes visible the invisible connections and flows that underlie complex social relationships. Applied organizational researchers have used social network analysis to assess and improve organizational and leadership effectiveness by helping organizations design interventions to overcome siloing, enhance collaboration and productivity, and implement strategic innovations. Some analysts of sustainability in higher education have explicitly called for a similar use of social network analysis to enhance sustainability progress on campuses. Addressing this call and literature gap, this article details the purpose, process, and results of the Mapping Emory's Sustainability Social Network project at Emory University (Atlanta, Georgia). The project had three major components: 1.) researching and creating visual maps of the university's sustainability collaboration networks, 2.) engaging key stakeholders and the wider campus sustainability community in participatory analysis of the results, and 3.) evaluating the effectiveness of this information for community members in deepening their own sustainability thinking and practice. The project demonstrates the power of social network analysis as a critical tool to engage and mobilize staff, faculty, and students in sustainability on campus by supporting evidence-based, strategic decision making among community leaders. |
Measles and rubella elimination in the WHO Region for Europe: progress and challenges
O'Connor P , Jankovic D , Muscat M , Ben-Mamou M , Reef S , Papania M , Singh S , Kaloumenos T , Butler R , Datta S . Clin Microbiol Infect 2017 23 (8) 504-510 Globally measles remains one of the leading causes of death among young children even though a safe and cost-effective vaccine is available. The World Health Organization (WHO) European Region has seen a decline in measles and rubella cases in recent years. The recent outbreaks have primarily affected adolescents and young adults with no vaccination or an incomplete vaccination history. Eliminating measles and rubella is one of the top immunization priorities of the European Region as outlined in the European Vaccine Action Plan 2015-2020. Following the 2010 decision by the Member States in the Region to initiate the process of verifying elimination, the European Regional Verification Commission for Measles and Rubella Elimination (RVC) was established in 2011. The RVC meets every year to evaluate the status of measles and rubella elimination in the Region based on documentation submitted by each country's National Verification Committees. The verification process was however modified in late 2014 to assess the elimination status at the individual country level instead of at regional level. The WHO European Region has made substantial progress towards measles and rubella elimination over the past 5 years. The RVC's conclusion in 2016 that 70% and 66% of the 53 Member States in the Region had interrupted the endemic transmission of measles and rubella, respectively, by 2015 is a testament to this progress. Nevertheless, where measles and rubella remain endemic, challenges in vaccination service delivery and disease surveillance will need to be addressed through focused technical assistance from WHO and development partners. |
Hospital-based surveillance of congenital rubella syndrome in Indonesia
Herini ES , Gunadi , Triono A , Mulyadi AW , Mardin N , Rusipah , Soenarto Y , Reef SE . Eur J Pediatr 2017 176 (3) 387-393 Congenital rubella syndrome (CRS) has serious consequences, such as miscarriage, stillbirth, and severe birth defects in infants, resulting from rubella virus infection during pregnancy. However, rubella vaccine has not yet been implemented in Indonesia. This study aimed (1) to estimate the incidence of CRS in Indonesia, (2) describe the clinical features of CRS at our referral hospital, and (3) pilot a CRS surveillance system to be extended to other hospitals. We conducted a 4-month prospective surveillance study of infants aged <1 year with suspected CRS in 2013 at an Indonesian hospital. Infants with suspected CRS were examined for rubella-specific IgM antibody or rubella IgG antibody levels. Of 47 suspected cases of CRS, 11/47 (23.4%), 9/47 (19.1%), and 27/47 (57.5%) were diagnosed as laboratory-confirmed, clinically compatible, and discarded CRS, respectively. The most common defects among laboratory-confirmed CRS cases were hearing impairment (100%), congenital cataracts (72.7%), microcephaly (72.7%), and congenital heart defects (45.5%). CONCLUSION: The number of laboratory-confirmed CRS cases among Indonesian infants is high. Furthermore, hearing impairment is the most common clinical feature of CRS in infants. Our findings indicate the importance of implementation of rubella vaccine in Indonesia. Conducting hospital-based surveillance of CRS in other hospitals in Indonesia may be appropriate. What is Known: *Congenital rubella syndrome (CRS) has serious consequences in infants resulting from rubella virus infection during pregnancy. *The incidence of CRS in most developed countries has greatly decreased since implementation of rubella vaccination. *Rubella vaccine has not yet been implemented in many developing countries. What is New: *The number of laboratory-confirmed CRS cases among Indonesian infants was high. *Implementation of rubella vaccine into immunization programs in Indonesia is important because of the high number of CRS cases. *Our study highlights the need for ongoing prospective surveillance of CRS in Indonesia. |
Estimating the burden of rubella virus infection and congenital rubella syndrome through a rubella immunity assessment among pregnant women in the Democratic Republic of the Congo: Potential impact on vaccination policy
Alleman MM , Wannemuehler KA , Hao L , Perelygina L , Icenogle JP , Vynnycky E , Fwamba F , Edidi S , Mulumba A , Sidibe K , Reef SE . Vaccine 2016 34 (51) 6502-6511 BACKGROUND: Rubella-containing vaccines (RCV) are not yet part of the Democratic Republic of the Congo's (DRC) vaccination program; however RCV introduction is planned before 2020. Because documentation of DRC's historical burden of rubella virus infection and congenital rubella syndrome (CRS) has been minimal, estimates of the burden of rubella virus infection and of CRS would help inform the country's strategy for RCV introduction. METHODS: A rubella antibody seroprevalence assessment was conducted using serum collected during 2008-2009 from 1605 pregnant women aged 15-46years attending 7 antenatal care sites in 3 of DRC's provinces. Estimates of age- and site-specific rubella antibody seroprevalence, population, and fertility rates were used in catalytic models to estimate the incidence of CRS per 100,000 live births and the number of CRS cases born in 2013 in DRC. RESULTS: Overall 84% (95% CI 82, 86) of the women tested were estimated to be rubella antibody seropositive. The association between age and estimated antibody seroprevalence, adjusting for study site, was not significant (p=0.10). Differences in overall estimated seroprevalence by study site were observed indicating variation by geographical area (p0.03 for all). Estimated seroprevalence was similar for women declaring residence in urban (84%) versus rural (83%) settings (p=0.67). In 2013 for DRC nationally, the estimated incidence of CRS was 69/100,000 live births (95% CI 0, 186), corresponding to 2886 infants (95% CI 342, 6395) born with CRS. CONCLUSIONS: In the 3 provinces, rubella virus transmission is endemic, and most viral exposure and seroconversion occurs before age 15years. However, approximately 10-20% of the women were susceptible to rubella virus infection and thus at risk for having an infant with CRS. This analysis can guide plans for introduction of RCV in DRC. Per World Health Organization recommendations, introduction of RCV should be accompanied by a campaign targeting all children 9months to 14years of age as well as vaccination of women of child bearing age through routine services. |
Characterization of the risks of adverse outcomes following rubella infection in pregnancy
Thompson KM , Simons EA , Badizadegan K , Reef SE , Cooper LZ . Risk Anal 2016 36 (7) 1315-31 Although most infections with the rubella virus result in relatively minor sequelae, rubella infection in early pregnancy may lead to severe adverse outcomes for the fetus. First recognized in 1941, congenital rubella syndrome (CRS) can manifest with a diverse range of symptoms, including congenital cataracts, glaucoma, and cardiac defects, as well as hearing and intellectual disability. The gestational age of the fetus at the time of the maternal rubella infection impacts the probability and severity of outcomes, with infection in early pregnancy increasing the risks of spontaneous termination (miscarriage), fetal death (stillbirth), birth defects, and reduced survival for live-born infants. Rubella vaccination continues to change the epidemiology of rubella and CRS globally, but no models currently exist to evaluate the economic benefits of rubella management. This systematic review provides an overall assessment of the weight of the evidence for the outcomes associated with rubella infections in the first 20 weeks of pregnancy. We identified, evaluated, and graded 31 studies (all from developed countries) that reported on the pregnancy outcomes of at least 30 maternal rubella infections. We used the available evidence to estimate the increased risks of spontaneous termination, fetal death, infant death, and CRS as a function of the timing of rubella infection in pregnancy and decisions about induced termination. These data support the characterization of the disability-adjusted life years for outcomes associated with rubella infection in pregnancy. We find significant impacts associated with maternal rubella infections in early pregnancy, which economic analyses will miss if they only focus on live births of CRS cases. Our estimates of fetal loss from increased induced terminations due to maternal rubella infections provide context that may help to explain the relatively low numbers of observed CRS cases per year despite potentially large burdens of disease. Our comprehensive review of the weight of the evidence of all pregnancy outcomes demonstrates the importance of including all outcomes in models that characterize rubella-related disease burdens and costs. |
Systematic review of the manifestations of congenital rubella syndrome in infants and characterization of disability-adjusted life years (DALYs)
Simons EA , Reef SE , Cooper LZ , Zimmerman L , Thompson KM . Risk Anal 2016 36 (7) 1332-56 Congenital rubella syndrome (CRS) continues to cause disability among unvaccinated populations in countries with no or insufficient rubella vaccine coverage to prevent transmission. We systematically reviewed the literature on birth outcomes associated with CRS to estimate the duration, severity, and frequency of combinations of morbidities. We searched PubMed, the Science Citation Index, and references from relevant articles for studies in English with primary data on the frequency of CRS manifestations for ≥20 cases and identified 65 studies representing 66 study populations that met our inclusion criteria. We abstracted available data on CRS cases with one or more hearing, heart, and/or eye defect following maternal rubella infection during the period of 0-20 weeks since the last menstrual period. We assessed the quality and weight of the available evidence using a modified Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Most of the evidence originates from studies in developed countries of cohorts of infants identified with CRS in the 1960s and 1970s, prior to the development of standardized definitions for CRS and widespread use of vaccine. We developed estimates of undiscounted disability-adjusted life years (DALYs) lost per CRS case for countries of different income levels. The estimates ranged from approximately 19 to 39 for high-income countries assuming optimal treatment and from approximately 29 to 39 DALYs lost per CRS case in low- and lower- middle-income countries assuming minimal treatment, with the lower bound based on 2010 general global burden of disease disability weights and the upper bound based on 1990 age-specific and treatment-specific global burden of disease disability weights. Policymakers and analysts should appreciate the significant burden of disability caused by CRS as they evaluate opportunities to manage rubella. |
Using seroprevalence and immunisation coverage data to estimate the global burden of Congenital Rubella Syndrome, 1996-2010: A systematic review
Vynnycky E , Adams EJ , Cutts FT , Reef SE , Navar AM , Simons E , Yoshida LM , Brown DW , Jackson C , Strebel PM , Dabbagh AJ . PLoS One 2016 11 (3) e0149160 BACKGROUND: The burden of Congenital Rubella Syndrome (CRS) is typically underestimated in routine surveillance. Updated estimates are needed following the recent WHO position paper on rubella and recent GAVI initiatives, funding rubella vaccination in eligible countries. Previous estimates considered the year 1996 and only 78 (developing) countries. METHODS: We reviewed the literature to identify rubella seroprevalence studies conducted before countries introduced rubella-containing vaccination (RCV). These data and the estimated vaccination coverage in the routine schedule and mass campaigns were incorporated in mathematical models to estimate the CRS incidence in 1996 and 2000-2010 for each country, region and globally. RESULTS: The estimated CRS decreased in the three regions (Americas, Europe and Eastern Mediterranean) which had introduced widespread RCV by 2010, reaching <2 per 100,000 live births (the Americas and Europe) and 25 (95% CI 4-61) per 100,000 live births (the Eastern Mediterranean). The estimated incidence in 2010 ranged from 90 (95% CI: 46-195) in the Western Pacific, excluding China, to 116 (95% CI: 56-235) and 121 (95% CI: 31-238) per 100,000 live births in Africa and SE Asia respectively. Highest numbers of cases were predicted in Africa (39,000, 95% CI: 18,000-80,000) and SE Asia (49,000, 95% CI: 11,000-97,000). In 2010, 105,000 (95% CI: 54,000-158,000) CRS cases were estimated globally, compared to 119,000 (95% CI: 72,000-169,000) in 1996. CONCLUSIONS: Whilst falling dramatically in the Americas, Europe and the Eastern Mediterranean after vaccination, the estimated CRS incidence remains high elsewhere. Well-conducted seroprevalence studies can help to improve the reliability of these estimates and monitor the impact of rubella vaccination. |
Identification of Serologic Markers for School-Aged Children With Congenital Rubella Syndrome
Hyde TB , Sato HK , Hao L , Flannery B , Zheng Q , Wannemuehler K , Ciccone FH , de Sousa Marques H , Weckx LY , Sáfadi MA , de Oliveira Moraes E , Pinhata MM , Olbrich Neto J , Bevilacqua MC , Tabith Junior A , Monteiro TA , Figueiredo CA , Andrus JK , Reef SE , Toscano CM , Castillo-Solorzano C , Icenogle JP . J Infect Dis 2015 212 (1) 57-66 BACKGROUND: Congenital rubella syndrome (CRS) case identification is challenging in older children since laboratory markers of congenital rubella virus (RUBV) infection do not persist beyond age 12 months. METHODS: We enrolled children with CRS born between 1998 and 2003 and compared their immune responses to RUBV with those of their mothers and a group of similarly aged children without CRS. Demographic data and sera were collected. Sera were tested for anti-RUBV immunoglobulin G (IgG), IgG avidity, and IgG response to the 3 viral structural proteins (E1, E2, and C), reflected by immunoblot fluorescent signals. RESULTS: We enrolled 32 children with CRS, 31 mothers, and 62 children without CRS. The immunoblot signal strength to C and the ratio of the C signal to the RUBV-specific IgG concentration were higher (P < .029 for both) and the ratio of the E1 signal to the RUBV-specific IgG concentration lower (P = .001) in children with CRS, compared with their mothers. Compared with children without CRS, children with CRS had more RUBV-specific IgG (P < .001), a stronger C signal (P < .001), and a stronger E2 signal (P ≤ .001). Two classification rules for children with versus children without CRS gave 100% specificity with >65% sensitivity. CONCLUSIONS: This study was the first to establish classification rules for identifying CRS in school-aged children, using laboratory biomarkers. These biomarkers should allow improved burden of disease estimates and monitoring of CRS control programs. |
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