Estimates of Potential Demand for Measles and Rubella Microarray Patches.

Global measles vaccine coverage has stagnated at approximately 85% for over a decade. By simplifying vaccine logistics and administration, the measles and rubella microarray patch (MR-MAP) may improve coverage. Clinical trials have demonstrated similar safety and immunogenicity in 9-month-old infants for MR-MAPs compared with syringe-and-needle vaccination. To aid commercialization, we present estimates of MR-MAP demand. We created a spreadsheet-based tool to estimate demand for MR-MAPs using data from 180 WHO countries during 2000-2016. Five immunization scenarios were analyzed: (1a) Supplementary Immunization Activities (SIAs) in Gavi, the Vaccine Alliance (Gavi)-eligible countries and (1b) WHO countries where preventive SIAs are routinely conducted; (2) SIAs and outbreak response immunization in all WHO countries; (3) routine immunization (RI) and SIAs in six high-burden measles countries (the Democratic Republic of the Congo, Ethiopia, India, Indonesia, Nigeria, and Pakistan); (4) RI and SIAs in six high-burden countries and Gavi-eligible countries; and (5) hard-to-reach populations. MR-MAP demand varied greatly across scenarios. Forecasts for 2025-2034 estimate from 137 million doses in hard-to-reach populations (scenario 5) to 2.587 billion doses for RI and SIAs in six high-burden countries and Gavi-eligible countries (scenario 4). When policymakers and manufacturers assess MR-MAP demand, they may consider multiple scenarios to allow for a complete consideration of potential markets and public health needs.

Feasibility of measles and rubella vaccination programmes for disease elimination: a modelling study.

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.

Both Nramp1 and DMT1 are necessary for efficient macrophage iron recycling.

OBJECTIVE: Divalent metal transporter 1 (DMT1) and natural resistance-associated macrophage protein 1 (Nramp1) are iron transporters that localize, respectively, to the early and late endosomal compartments. DMT1 is ubiquitously expressed, while Nramp1 is found only within macrophages and neutrophils. Our previous studies have identified a role for Nramp1 during macrophage erythrophagocytosis; however, little is known about the function of DMT1 during this process. MATERIALS AND METHODS: Wild-type RAW264.7 macrophages (RAW), and those stably transfected with Nramp1 (RAW/Nramp1) were treated with either DMT1-small interfering RNA, or with ebselen, a selective inhibitor of DMT1. RESULTS: Although macrophages lacking either functional DMT1 or Nramp1 experienced a moderate reduction in iron recycling efficiency, the ability of macrophages lacking both functional DMT1 and Nramp1 to recycle hemoglobin-derived iron was severely compromised. Compared to macrophages singly deficient in either DMT1 or Nramp1 transport ability, macrophages where DMT1 and Nramp1 were both compromised exhibited an abrogated increase in labile iron pool content, released less iron, and experienced diminished upregulation of ferroportin and heme-oxygenase 1 levels following erythrophagocytosis. CONCLUSIONS: These results suggest that although the loss of either Nramp1 or DMT1 transport ability results in minor impairment after erythrophagocytosis, the simultaneous loss of both Nramp1 and DMT1 iron transport activity is detrimental to the iron recycling capacity of the macrophage.