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.

Background: Malaria control in sub-Saharan Africa faces significant challenges from biological threats, such as insecticide resistance and adaptive vector behaviours, as well as increasing financial constraints, which necessitate strategic intervention planning to maximize impact. This study assesses the effectiveness of combining vector control methods, case management, and immunoprevention to reduce malaria in Tanzania, considering varying intensities of insecticide resistance in the main vector species. Methods: A compartmental model was developed to simulate malaria transmission, incorporating the dominant vectors: Anopheles funestus (anthropophilic and endophilic) and Anopheles arabiensis (zoophilic and exophilic). The model was used to analyse the impacts of insecticide-treated nets (ITNs), indoor residual spraying (IRS), and biolarvicides, used singly or in combinations, under varying intensities of pyrethroid resistance. The analysis was further expanded to explore the impacts of adding case management (treatment using artemisinin-based combinations) and immunization (RTS,S/AS01 and R21/Matrix-M vaccines). Results: At moderate levels of pyrethroid resistance (50%), achieving at least 71% ITN coverage combined with either 50% IRS or 32% biolarvicide coverage reduces the effective reproduction number ( ) to below 1. However, at high resistance levels (exceeding 75%), the effective reproduction number ( ) consistently remains above 1, irrespective of the type or combination of vector control interventions. Adding immunization ( 40% coverage) to ITNs (80% coverage), along with effective treatment (80% coverage), can further reduce the proportion of infectious individuals to <20% and below 1, even under high resistance intensities. Conclusions: Compared to ITNs alone, combining ITNs with IRS and/or biolarvicides greatly improves malaria control at low to moderate intensities of pyrethroid resistance but yields no additional benefits at high resistance intensities. However, integrating these vector control strategies with immunization and effective case management using artemisinin-based combination therapy (ACT) further enhances impact by reducing both parasite transmission and the infectious reservoir.

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.

Background: Intermittent preventive treatment (IPT) of school-aged children with antimalarial drugs decreases rates of infection, anaemia, and clinical malaria. Since school-aged children are a major transmission reservoir, we estimated the effect of IPT for this group on Plasmodium falciparum transmission to younger children and adults across three epidemiological settings. Methods: Using an established malaria transmission model, three epidemiological archetypes (Sahelian, Central, and Southern African) were developed and the effect of IPT of school-age children was estimated across transmission levels (P. falciparum parasite rate in children aged 2–10 years [PfPR2–10]: 5–40%). Baseline interventions included long-lasting insecticide-treated nets and clinical case management. Scenarios compared three drug options (dihydroartemisinin–piperaquine, artesunate–amodiaquine, sulfadoxine–pyrimethamine–amodiaquine) with different delivery options. Findings: With frequent administration of long-acting drugs (monthly dihydroartemisinin–piperaquine), modelled IPT averted 70–90% of cases in school-aged children and 20–60% in younger children and adults, with greater benefit at lower transmission levels. Shorter-acting drugs administered with various schedules averted 40–60% of cases in school-aged children and 15–50% in other ages. Interpretation: Our model suggests that adding IPT of school-age children to current control tools could decrease malaria burden in this group and reduce P. falciparum transmission.

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.

Background Primary care networks (PCNs) are increasingly being adopted in low- and middle-income countries (LMICs) to improve the delivery of primary health care (PHC). Kenya has identified PCNs as a key reform to strengthen PHC delivery and has passed a law to guide its implementation. PCNs were piloted in two counties in Kenya in 2020 and implemented nationally in October 2023. This protocol outlines methods for a study that examines the impact, implementation experience and political economy of the PCN reform in Kenya. Methods We will adopt the parallel databases variant of convergent mixed methods study design to concurrently but separately collect quantitative and qualitative data. The two strands will be mixed during data collection to refine questions, with findings triangulated during analysis and interpretation to provide a comprehensive understanding of PCN implementation. The quantitative study will use a controlled before and after study design and collect data using health facility and client exit surveys. The primary outcome measure will be the service delivery readiness of PHC facilities. We will use a random sample of 228 health facilities and 2560 clients in four currently implementing PCNs, four planning to implement and four control counties at baseline and post-implementation. We shall undertake a preliminary cross-sectional analysis of the data at baseline from October to December 2023, followed by a difference-in-difference analysis at the endline from October to December 2024 to compare the outcome differences between the intervention and control counties over a 12-month period. The qualitative study will include a cross-sectional process evaluation and political economy analysis (PEA) using document reviews and approximately 80 in-depth interviews with national and sub-national stakeholders. The process evaluation will assess the emergence of PCN reforms, the implementation experience, the mechanism of impact and how the context affects implementation and outcomes. The PEA will examine the interaction of structural factors, institutions and actors/stakeholders’ interests and power relations in implementing PCNs. We will also examine the gendered effects of the PCNs, including power relations and norms, and their implications on PHC from the supply and demand sides. We shall undertake a thematic analysis of the qualitative data. Discussion This evaluation will contribute robust evidence on the impact, implementation experience, political economy and gendered implications of PCNs in a LMIC setting, as well as guide the refining of PCN implementation in Kenya and other LMICs implementing or planning to implement PCNs to enhance their effectiveness.

Uncertainty Quantification (UQ) is vital to safety-critical model-based analyses, but the widespread adoption of sophisticated UQ methods is limited by technical complexity. In this paper, we introduce UM-Bridge (the UQ and Modeling Bridge), a high-level abstraction and software protocol that facilitates universal interoperability of UQ software with simulation codes. It breaks down the technical complexity of advanced UQ applications and enables separation of concerns between experts. UM-Bridge democratizes UQ by allowing effective interdisciplinary collaboration, accelerating the development of advanced UQ methods, and making it easy to perform UQ analyses from prototype to High Performance Computing (HPC) scale. In addition, we present a library of ready-to-run UQ benchmark problems, all easily accessible through UM-Bridge. These benchmarks support UQ methodology research, enabling reproducible performance comparisons. We demonstrate UM-Bridge with several scientific applications, harnessing HPC resources even using UQ codes not designed with HPC support.

Cassava is a key source of calories for smallholder farmers in sub-Saharan Africa but its role as a food security crop is threatened by the cross-continental spread of cassava brown streak disease (CBSD) that causes high yield losses. In order to mitigate the impact of CBSD, it is important to minimise the delay in first detection of CBSD after introduction to a new country or state so that interventions can be deployed more effectively. Using a computational model that combines simulations of CBSD spread at both the landscape and field scales, we model the effectiveness of different country level survey strategies in Nigeria when CBSD is directly introduced. We find that the main limitation to the rapid CBSD detection in Nigeria, using the current survey strategy, is that an insufficient number of fields are surveyed in newly infected Nigerian states, not the total number of fields surveyed across the country, nor the limitation of only surveying fields near a road. We explored different strategies for geographically selecting fields to survey and found that early and consistent CBSD detection will involve confining candidate survey fields to states where CBSD has not yet been detected and where survey locations are allocated in proportion to the density of cassava crops, detects CBSD sooner, more consistently, and when the epidemic is smaller compared with distributing surveys uniformly across Nigeria.