Rubella is a leading cause of vaccine-preventable birth defects. Rubella virus infection during early pregnancy can result in miscarriage, fetal death, stillbirth, or a constellation of birth defects known as congenital rubella syndrome (CRS). This report describes current and future estimated CRS incidence in countries that have not yet introduced rubella-containing vaccine (RCV) into their national childhood immunization schedules and the estimated effect of implementing a recent recommendation to introduce RCV into these programs even if population coverage with measles-containing vaccine is <80%. During 2000-2022, the number of countries that introduced RCV increased from 99 (52%) of 191 in 2000 to 175 (90%) of 194 in 2022. By the end of 2023, 19 lower- and middle-income countries had not yet introduced RCV. In 2019, an estimated 24,000 CRS cases occurred in these countries, representing 75% of the estimated 32,000 cases worldwide. In a modeling study estimating the effect of RCV introduction in these countries during 2025-2055, an estimated 1.03 million CRS cases are projected to occur without RCV. In contrast, fewer than 60,000 cases are estimated if RCV is introduced with catch-up and follow-up supplementary immunization activities, averting more than an estimated 986,000 CRS cases over 30 years. Based in part on these estimates, in September 2024, the World Health Organization Strategic Advisory Group of Experts on Immunization recommended removing the ≥80% coverage threshold and instituting universal RCV introduction in these countries. RCV introduction in these 19 countries during 2025-2030 could rapidly accelerate progress toward rubella and CRS elimination worldwide.

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.

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.

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.

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 modeling, 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% confidence intervals (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 that had introduced RCV, had a low estimated CRS incidence (<1 [95% CI: <1 to 8] and <1 [95% CI: <1 to 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.

Lay Summary 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. There are still many limitations related to the understanding of the natural history of differing forms of coccidioidomycosis (CM), 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 to 1958, followed through 1966, who did not receive antifungal therapy. Patients were grouped by predominant pulmonary finding on chest radiographs. The all-cause mortality was low for all patients (4.6%). Cavities had a median size of 3-3.9 cm (IQR: 2-2.9-4-4.9 cm), with heterogeneous wall thickness and no fluid level, while nodules had a median size of 1-1.19 cm (Interquartile range [IQR] 1-1.9-2-2.9 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.

Summary 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.

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.

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.

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.

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.

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† 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.

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.

Abstract Background Prior studies to characterize pulmonary coccidioidomycosis (CM) have been limited by small samples. The historical VA-Armed forces CM patient group provides a unique cohort of patients not treated with conventional antifungals to better characterize and describe chronic pulmonary CM with an emphasis on chronic nodules and cavities. Methods A retrospective study of 374 VA-Armed forces non-disseminated CM patients diagnosed between 1955 and 1958 and followed to 1966. Patients had a pulmonary nodule or a pulmonary cavity secondary to CM. Basic demographic information, complement fixation serology, and details regarding the nodules and cavities were investigated. Results The studied population had a median age of 34 with 97% men and 84% white. Eighty percent had no underlying pulmonary disease and concurrent tuberculosis was the most common comorbid pulmonary condition (11%). Patients with cavities had a median complement fixation (CF) serology of 1:2 (interquartile range (IQR) negative 1:8). Patients with nodules had a median CF serology of negative (IQR negative 1:2). The median number of pulmonary nodules was 1 with a median size of 1–1.9 cm. Sixty-nine percent of the nodules had a sharp, well-defined border, while 10% had a calcified border. The median number of cavities was 1 with a median size of 3–3.9 cm. Forty-five percent of the cavity walls were thin, 31% were thick, and 19% were variable in size. Twenty-six percent of the cavities developed during acute infection with 46% developing without a prior history of primary infection. Twenty-nine percent of the cavities were stable in size, 20% increased in size, 5% disappeared, 4% ruptured, and 2% decreased in size. Conclusion This study helps further characterize chronic pulmonary nodules and cavities caused by CM. To the best of our knowledge, this is the largest study of the natural history of chronic CM pulmonary cavities and nodules providing valuable descriptive features. Disclosures All authors: No reported disclosures.

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.

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.