Publications

Outbreaks of vaccine-derived poliovirus type 2 (cVDPV2) have become a major threat to polio eradication. However, variations in spatiotemporal spread have not been quantified. Here we analysed cVDPV2 cases and wild poliovirus type 1 sequences to uncover spatiotemporal patterns and drivers of poliovirus spread. Between 1 May 2016 and 29 September 2023, 3,120 cVDPV2 poliomyelitis cases were reported across 75 outbreaks in 39 countries. Outbreaks had a median observed circulation of 202 (range 0–1,905) days and a median maximum distance of 231 (range 0–4,442) km. Wavefront velocity analysis of large outbreaks revealed a median velocity of spread of 2.3 (5th–95th percentile 0.7–9.2) km per day. International borders were associated with a slower velocity of spread (P < 0.001), in periods with high estimated population immunity. Phylogeographic analysis of 1,572 global wild poliovirus 1 sequences revealed that historic spread resembles recent cVDPV2 patterns and that international spread is largely sustained by unidirectional movement between neighbouring countries. Our findings offer insights for enhancing the geographical scope of vaccination response in the final phases of poliovirus eradication.

Despite concerted global vaccination efforts, wild poliovirus remains endemic in two countries in 2024, Pakistan and Afghanistan. This study uses phylogeographic analysis of poliovirus genetic and epidemiological data from clinical and wastewater surveillance to identify the causes of poliovirus persistence and routes of spread over the last decade (2012 to 2023). Poliovirus genetic diversity declined after 2020, with one of two major genetic clusters dying out, and recent detections are now closely related genetically. High-risk and hard-to-access regions have sustained polio transmission over the past decade, even when interrupted elsewhere. Karachi, one of the most densely populated cities globally, has acted as a hub for the amplification and spread of poliovirus to other regions, many of which we show to be dead-end for onwards transmission despite frequent virus detection. Phylogenetic analysis has long been central to the polio surveillance network, and advancing the approaches used can provide critical epidemiological insights to accelerate eradication efforts.

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.

Measles is one of the most contagious vaccine preventable diseases, causing severe complications and deaths globally. While vaccination with a measles-containing vaccine (MCV) has prevented millions of measles deaths, recent trends, especially from low- and middle-income countries, are discouraging. Measles cases have increased since 2021 as MCV coverage has decreased; and an estimated 107,500 measles deaths, mostly in children under-five years, occurred in 2023. Thus, a renewed focus on proven and innovative strategies to control measles is needed. The World Health Organization (WHO) recommends a first MCV dose administered at 9–15 months of age (routine MCV1), however MCV1 below 9 months of age (early MCV1) may increase vaccination coverage because uptake of all vaccines tends to be higher the younger the child, and this might protect vulnerable infants earlier in life. However, due to concerns about possible reduced vaccine performance, early MCV1 is not routinely recommended by WHO. WHO hosted an informal technical consultation on December 6–7, 2023, in Geneva, Switzerland to evaluate recent evidence on early MCV1 and identify evidence gaps for policy making. The recent evidence suggests a robust humoral immune response shortly after early MCV1 at 5–8 months of age. Immune blunting of a routine second MCV dose (e.g., MCV2) after early MCV1 was not demonstrated in the presented data. However, 3–7 years after MCV1, children receiving early MCV1 had lower measles antibodies than children receiving routine MCV1, suggesting faster waning of immunity. The totality of evidence on immune blunting remains inconsistent. Meeting participants thought more data are needed before revisiting WHO’s current recommendation for a potential revision. Evidence gaps include: understanding measles disease burden and severity in infants; early MCV1 effectiveness and duration; vaccine-induced cellular immunogenicity; whether measles in infants is acquired from other infants or older children or adults; and blunting of routine MCV2. Addressing evidence gaps through targeted studies and measles outbreak investigations, as well as evaluations of country-level introductions of early MCV1 are warranted. Ensuring high MCV1 and MCV2 coverage remains the priority in measles control.

Development of microneedle array patches (MAPs) for potential use in immunization is ongoing, but the cost of manufacturing is expected to be higher than that of existing needle-and-syringe vial systems. The potential benefits of MAPs in reaching previously unvaccinated populations have been touted, but affordability, especially in low- and middle-income countries, remains an open question. In this study, we quantify the expected impact on operational costs of switching to MAPs for immunization for measles-rubella, human papilloma virus, and typhoid in both routine and campaign-based delivery modes. We endeavor to make a comprehensive estimate, including the costs of labor, syringes, waste management (i.e., sharps and trash), wastage (unused vaccine), freight and in-country cold chain transportation. We examined five potential use cases and our results show that in total, operational cost savings from a switch to MAPs are expected to range from a low of $0.24 per dose delivered (HPV, 1-dose vial, campaign) up to $0.61 per dose delivered (MR, 10-dose vial, routine). Excluding the allocated cost of labor, the estimated range of cost savings are $0.18 and $0.43, respectively. Confidence intervals are wide, due to the uncertainty in the assumptions, but in all five use cases tested, there was at least an 87 % probability of savings. These results show that operational savings from a switch to MAPs may offset at least part of the expected incremental manufacturing costs, which will make the transition more viable in settings with limited budget space. With this in mind, development agencies should continue to invest in MAPs technology and, if the product does come to market, use this evidence as part of total value of vaccines assessments and to inform investment strategies for implementation of vaccine MAPs, including alignment with policy makers.

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.

Rubella infection is typically mild or asymptomatic except when infection occurs during pregnancy. Infection in early pregnancy can cause miscarriage, stillbirth, or congenital rubella syndrome. Only individuals that are still susceptible to rubella infection during child-bearing age are vulnerable to this burden. Rubella-containing vaccine (RCV) is safe and effective, providing life-long immunity. However, average age-at-infection increases with increasing vaccination coverage, which could potentially lead to increased disease burden if the absolute risk of infection during child-bearing age increases. The dynamics of rubella transmission were explored using EMOD, a software tool for building stochastic, agent-based infection models. Simulations of pre-vaccine, endemic transmission of rubella virus introduced RCV at varying levels of coverage to determine the expected future trajectories of disease burden. Introducing RCV reduces both rubella virus transmission and disease burden for a period of around 15 years. Increased disease burden is only possible more than a decade post-introduction, and only for contexts with persistently high transmission intensity. Low or declining rubella virus transmission intensity is associated with both greater burden without vaccination and greater burden reduction with vaccination. The risk of resurgent burden due to incomplete vaccination only exists for locations with persistently high infectivity, high connectivity, and high fertility. A trade-off between the risk of a small, future burden increase versus a large, immediate burden decrease strongly favors RCV introduction.

Somalia is a complex and fragile setting with a demonstrated potential for disruptive, high-burden measles outbreaks. In response, since 2018, Somalian authorities have partnered with UNICEF and the WHO to implement measles vaccination campaigns across the country. In this paper, we create a Somalia-specific model of measles transmission based on a comprehensive epidemiological dataset including case-based surveillance, vaccine registries, and serological surveys. We use this model to assess the impact of these campaign interventions on Somalian’s measles susceptibility, showing, for example, that across the roughly 10 million doses delivered, 1 of every 5 immunized a susceptible child. Finally, we use the model to explore a counter-factual epidemiology without the 2019–2020 campaigns, and we estimate that those interventions prevented over 10,000 deaths.

Background Novel oral poliovirus vaccine (OPV) type 2 (nOPV2) has been made available for outbreak response under an emergency use listing authorization based on supportive clinical trial data. Since 2021 more than 350 million doses of nOPV2 were used for control of a large outbreak of circulating vaccine-derived poliovirus type 2 (cVDPV2) in Nigeria. Methods Using a bayesian time-series susceptible-infectious-recovered model, we evaluate the field effectiveness of nOPV2 immunization campaigns in Nigeria compared with campaigns using monovalent OPV type 2 (mOPV2). Results We found that both nOPV2 and mOPV2 campaigns were highly effective in reducing transmission of cVDPV2, on average reducing the susceptible population by 42% (95% confidence interval, 28–54%) and 38% (20–51%) per campaign, respectively, which were indistinguishable from each other in this analysis (relative effect, 1.1 [.7–1.9]). Impact was found to vary across areas and between immunization campaigns. Conclusions These results are consistent with the comparable individual immunogenicity of nOPV2 and mOPV2 found in clinical trials but also suggest that outbreak response campaigns may have small impacts in some areas requiring more campaigns than are suggested in current outbreak response procedures.

Much of the world’s population had already been infected with COVID-19 by the time the Omicron variant emerged at the end of 2021, but the scale of the Omicron wave was larger than any that had come before or has happened since, and it left a global imprinting of immunity that changed the COVID-19 landscape. In this study, we simulate a South African population and demonstrate how population-level vaccine effectiveness and efficiency changed over the course of the first 2 years of the pandemic. We then introduce three hypothetical variants and evaluate the impact of vaccines with different properties. We find that variant-chasing vaccines have a narrow window of dominating pre-existing vaccines but that a variant-chasing vaccine strategy may have global utility, depending on the rate of spread from setting to setting. Next-generation vaccines might be able to overcome uncertainty in pace and degree of viral evolution.