The World Health Organization's Immunization and Vaccines-related Implementation Research Advisory Committee (IVIR-AC) serves to independently review and evaluate vaccine-related research to maximize the potential impact of vaccination programs. From 28 June - 1 July 2024, IVIR-AC was convened for an ad hoc meeting to discuss new evidence on criteria for rubella vaccine introduction and the risk of congenital rubella syndrome. This report summarizes background information on rubella virus transmission and the burden of congenital rubella syndrome, meeting structure and presentations, proceedings, and recommendations.

Measles is a highly contagious, vaccine-preventable disease that requires high population immunity for transmission to be interrupted. All six World Health Organization regions have committed to eliminating measles; however, no region has achieved and sustained measles elimination. This report describes measles elimination progress during 2000-2022. During 2000-2019, estimated coverage worldwide with the first dose of measles-containing vaccine (MCV) increased from 72% to 86%, then declined to 81% in 2021 during the COVID-19 pandemic, representing the lowest coverage since 2008. In 2022, first-dose MCV coverage increased to 83%. Only one half (72) of 144 countries reporting measles cases achieved the measles surveillance indicator target of two or more discarded cases per 100,000 population in 2022. During 2021-2022, estimated measles cases increased 18%, from 7,802,000 to 9,232,300, and the number of countries experiencing large or disruptive outbreaks increased from 22 to 37. Estimated measles deaths increased 43% during 2021-2022, from 95,000 to 136,200. Nonetheless, an estimated 57 million measles deaths were averted by vaccination during 2000-2022. In 2022, measles vaccination coverage and global surveillance showed some recovery from the COVID-19 pandemic setbacks; however, coverage declined in low-income countries, and globally, years of suboptimal immunization coverage left millions of children unprotected. Urgent reversal of coverage setbacks experienced during the COVID-19 pandemic can be accomplished by renewing efforts to vaccinate all children with 2 MCV doses and strengthening surveillance, thereby preventing outbreaks and accelerating progress toward measles elimination.

A better understanding of population-level factors related to measles case fatality is needed to estimate measles mortality burden and impact of interventions such as vaccination. This study aimed to develop a conceptual framework of mechanisms associated with measles case fatality ratios (CFRs) and assess the scope of evidence available for related indicators. Using expert consultation, we developed a conceptual framework of mechanisms associated with measles CFR and identified population-level indicators potentially associated with each mechanism. We conducted a literature review by searching PubMed on 31 October 2021 to determine the scope of evidence for the expert-identified indicators. Studies were included if they contained evidence of an association between an indicator and CFR and were excluded if they were from non-human studies or reported non-original data. Included studies were assessed for study quality. Expert consultation identified five mechanisms in a conceptual framework of factors related to measles CFR. We identified 3772 studies for review and found 49 studies showing at least one significant association with CFR for 15 indicators (average household size, educational attainment, first- and second-dose coverage of measles-containing vaccine, human immunodeficiency virus prevalence, level of health care available, stunting prevalence, surrounding conflict, travel time to major city or settlement, travel time to nearest health care facility, under-five mortality rate, underweight prevalence, vitamin A deficiency prevalence, vitamin A treatment, and general malnutrition) and only non-significant associations for five indicators (antibiotic use for measles-related pneumonia, malaria prevalence, percent living in urban settings, pneumococcal conjugate vaccination coverage, vitamin A supplementation). Our study used expert consultation and a literature review to provide additional insights and a summary of the available evidence of these underlying mechanisms and indicators that could inform future measles CFR estimations.

Introduction: A better understanding of population-level factors related to measles case fatality is needed to estimate measles mortality burden and impact of interventions such as vaccination. This study aimed to develop a conceptual framework of mechanisms associated with measles case fatality ratios (CFRs) and assess the scope of evidence available for related indicators in the published literature. Method(s): Using expert consultation, we developed a conceptual framework of mechanisms associated with measles CFR and identified population-level indicators potentially associated with each mechanism. We then conducted a literature review by searching PubMed on October 31, 2021 to determine and classify the scope of evidence for the indicators identified by expert consultation. Studies were included if they contained evidence of an association between an indicator and measles CFR and were excluded if they were from non-human studies or reported non-original data. Result(s): Expert consultation identified five mechanisms in a conceptual framework of factors related to measles CFR: health system access and care-seeking behaviors, health system quality, measles control and epidemiology, nutritional status, and risk of secondary infection. Thirty-seven measurable population-level indicators were identified by expert consultation as proxies for the mechanisms. We identified 3772 studies for review and found 49 studies showing at least one significant association with CFR for 15 indicators and only non-significant associations for 5 indicators. Inadequate data were available to evaluate the remaining 17 indicators. A randomized controlled trial provided evidence for a relationship between vitamin A treatment and measles CFR. Average household size, educational attainment, first-dose coverage of measles-containing vaccine, human immunodeficiency virus prevalence, second-dose coverage of measles-containing vaccine, stunting prevalence, surrounding conflict, travel time to major city or settlement, travel time to nearest health care facility, under-five mortality rate, underweight prevalence, vitamin A deficiency prevalence, and wasting prevalence had quantitative observational level evidence. Level of health care available had qualitative evidence of a relationship with measles CFR. Conclusion(s): To reduce uncertainty in measles CFR estimation, population-level factors representative of underlying mechanisms associated with CFR could be used. Our study used expert consultation and literature review to provide additional insights and a summary of the available evidence of these underlying mechanisms and indicators that could inform future estimations of measles CFR. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.

All six World Health Organization (WHO) regions have committed to eliminating measles.* The Immunization Agenda 2021-2030 (IA2030)(†) aims to achieve the regional targets as a core indicator of impact and positions measles as the tracer of a health system's ability to deliver essential childhood vaccines. IA2030 highlights the importance of ensuring rigorous measles surveillance systems to document immunity gaps and achieve 95% coverage with 2 timely doses of measles-containing vaccine (MCV) among children. This report describes progress toward measles elimination during 2000-2021 and updates a previous report (1). During 2000-2021, estimated global coverage with a first MCV dose (MCV1) increased from 72% to a peak of 86% in 2019, but decreased during the COVID-19 pandemic to 83% in 2020 and to 81% in 2021, the lowest MCV1 coverage recorded since 2008. All countries conducted measles surveillance, but only 47 (35%) of 135 countries reporting discarded cases(§) achieved the sensitivity indicator target of two or more discarded cases per 100,000 population in 2021, indicating surveillance system underperformance in certain countries. Annual reported measles incidence decreased 88% during 2000-2016, from 145 to 18 cases per 1 million population, then rebounded to 120 in 2019 during a global resurgence (2), before declining to 21 in 2020 and to 17 in 2021. Large and disruptive outbreaks were reported in 22 countries. During 2000-2021, the annual number of estimated measles deaths decreased 83%, from 761,000 to 128,000; an estimated 56 million measles deaths were averted by vaccination. To regain progress and achieve regional measles elimination targets during and after the COVID-19 pandemic, accelerating targeted efforts is necessary to reach all children with 2 MCV doses while implementing robust surveillance and identifying and closing immunity gaps to prevent cases and outbreaks.

Surgical N95 filtering facepiece respirators (surgical N95 FFRs) are National Institute for Occupational Safety and Health-approved N95 filtering facepiece respirators (N95 FFRs) cleared by the Food and Drug Administration for resistance to liquid penetration and flammability. A recent study showed that several N95 FFR models performed as well as surgical N95 FFRs in synthetic blood penetration tests that evaluate resistance to penetration by horizontal projection. This aspect, in addition to the influence of other factors on liquid penetration, are not well studied. To address this issue, the effect of liquid volume (1 mL and 2 mL), spray velocity (450 cm/sec and 635 cm/sec), and liquid composition (synthetic blood and diluted synthetic blood) were evaluated. Four types of common protective devices were studied: N95 FFRs, surgical N95 FFRs, surgical masks, and powered air-purifying respirator (PAPR) hoods. For each protective device type, five models were analyzed using a protocol based on the F1862 ASTM International (2017) test method. Reduced liquid volume had a significant effect in only 3 of 20 models. Increased velocity had significantly greater penetration in 9 of 20 models. Diluted synthetic blood had significantly more penetration in 8 of 20 models. This last result was not expected because, in hydrostatic tests, surface tension of the diluted blood would be expected to reduce penetrability; however, across all models tested, data showed that the diluted spray was more penetrable. The study results suggest that fluid composition may be as important as velocity when considering liquid spray penetration. Furthermore, the penetrability of a spray may be inversely related to the penetrability through direct hydrostatic contact.

Background: Methicillin-resistant Staphylococcus aureus contamination on surfaces including turnout gear had been found throughout a number of fire stations. As such, the outer shell barrier of turnout gear jackets may be an indirect transmission source and proper disinfection is essential to reduce the risk of exposure to fire fighters. Cleaning practices vary considerably among fire stations, and a method to assess disinfection of gear washed in commercial washer/extractors is needed. Methods: Swatches (1 in. × 1.5 in.) of the outer shell fabrics, Gemini™, Advance™, and Pioneer™, of turnout gear were inoculated with S. aureus, and washed with an Environmental Protection Agency-registered sanitizer commonly used to wash turnout gear. To initially assess the sanitizer, inoculated swatches were washed in small tubes according to the American Society for Testing Materials E2274 Protocol for evaluating laundry sanitizers. Inoculated swatches were also pinned to turnout gear jackets and washed in a Milnor commercial washer/extractor. Viable S. aureus that remained attached to fabric swatches after washing were recovered and quantified. Scanning Electron Microscopy was used to characterize the stages of S. aureus biofilm formation on the swatches that can result in resistance to disinfection. Results: Disinfection in small tubes for only 10 s reduced the viability of S. aureus on Gemini™, Advance™, and Pioneer™ by 73, 99, and 100%, respectively. In contrast, disinfection of S. aureus-contaminated Gemini™ swatches pinned to turnout gear and washed in the washer/extractor was 99.7% effective. Scanning Electron Microscopy showed that biofilm formation begins as early as 5 h after attachment of S. aureus. Conclusion: This sanitizer and, likely, others containing the anti-microbial agent didecyl dimethyl ammonium chloride, is an effective disinfectant of S. aureus. Inclusion of contaminated outer shell swatches in the wash cycle affords a simple and quantitative method to assess sanitization of gear by commercial gear cleaning facilities. This methodology can be extended to assess for other bacterial contaminants. Sanitizer-resistant strains will continue to pose problems, and biofilm formation may affect the cleanliness of the washed turnout gear. Our methodology for assessing effectiveness of disinfection may help reduce the occupational exposure to fire fighters from bacterial contaminants.

Mathematical modelling is commonly used to evaluate infectious disease control policy and is influential in shaping policy and budgets. Mathematical models necessarily make assumptions about disease natural history and, if these assumptions are not valid, the results of these studies can be biased. We did a systematic review of published tuberculosis transmission models to assess the validity of assumptions about progression to active disease after initial infection (PROSPERO ID CRD42016030009). We searched PubMed, Web of Science, Embase, Biosis, and Cochrane Library, and included studies from the earliest available date (Jan 1, 1962) to Aug 31, 2017. We identified 312 studies that met inclusion criteria. Predicted tuberculosis incidence varied widely across studies for each risk factor investigated. For population groups with no individual risk factors, annual incidence varied by several orders of magnitude, and 20-year cumulative incidence ranged from close to 0% to 100%. A substantial proportion of modelled results were inconsistent with empirical evidence: for 10-year cumulative incidence, 40% of modelled results were more than double or less than half the empirical estimates. These results demonstrate substantial disagreement between modelling studies on a central feature of tuberculosis natural history. Greater attention to reproducing known features of epidemiology would strengthen future tuberculosis modelling studies, and readers of modelling studies are recommended to assess how well those studies demonstrate their validity.

BACKGROUND: Surgical N95 filtering facepiece respirators (FFRs), certified by the National Institute for Occupational Safety and Health (NIOSH) as a respirator and cleared by the Food and Drug Administration (FDA) as a surgical mask, are often used to protect from the inhalation of infectious aerosols and from splashes/sprays of body fluids in health care facilities. A shortage of respirators can be expected during a pandemic. The availability of surgical N95 FFRs can potentially be increased by incorporating FDA clearance requirements in the NIOSH respirator approval process. METHODS: Fluid resistance of NIOSH-approved N95 FFRs, and FDA-cleared surgical N95 FFRs and surgical masks was tested using the ASTM F1862 method at 450 and 635 cm/sec velocities and compared with the results from a third-party independent laboratory. Blood penetration through different layers of filter media of masks were also analyzed visually. RESULTS: Four N95 FFR models showed no test failures at both velocities. The penetration results obtained in the NIOSH laboratory were comparable to those from the third-party independent laboratory. The number of respirator samples failing the test increased with increasing test velocity. CONCLUSIONS: The results indicate that several NIOSH-approved N95 FFR models would likely pass FDA clearance requirements for resistance to synthetic blood penetration.

The dissolution of metal-containing particles in the gastric compartment is poorly understood. The purpose of this study was to elucidate the influence of artificial gastric juice chemical composition on bioaccessibility of metals associated with ingestion-based health concerns. Dissolution rates were evaluated for well-characterized feedstock cobalt, tungsten metal, and tungsten carbide powders, chemically bonded pre-sintered (spray dryer material) and post-sintered (chamfer grinder) cemented tungsten carbide materials, and an admixture of pure cobalt and pure tungsten carbide, prepared by mechanically blending the two feedstock powders. Dissolution of each study material was evaluated in three different formulations of artificial gastric juice (from simplest to most chemically complex): American Society of Testing Materials (ASTM), U.S. Pharmacopoeia (USP), and National Institute for Occupational Safety and Health (NIOSH). Approximately 20% of cobalt dissolved in the first dissolution phase (t(1/2) = 0.02 days) and the remaining 80% was released in the second long-term dissolution phase (t(1/2) = 0.5 to 1 days). Artificial gastric juice chemical composition did not influence dissolution rate constant values (k, g/cm(2)day) of cobalt powder, either alone or as an admixture. Approximately 100% of the tungsten and tungsten carbide that dissolved was released in a single dissolution phase; k-values of each material differed significantly in the solvents: NIOSH > ASTM > USP (p<0.05). The k-values of cobalt and tungsten carbide in pre- and post-sintered cemented tungsten carbide powders were significantly different from values for the pure feedstock powders. Solvent composition had little influence on oral bioaccessibility of highly soluble cobalt and our data support consideration of the oral exposure route as a contributing pathway to total-body exposure. Solvent composition appeared to influence bioaccessibility of the low soluble tungsten compounds, though differences may be due to variability in the data associated with the small masses of materials that dissolved. Nonetheless, ingestion exposure may not contribute appreciably to total body burden given the short residence time of material in the stomach and relatively long dissolution half-times of these materials (t(1/2) = 60 to 380 days).