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The time-series Susceptible-Infectious-Recovered (TSIR) model has been a standard tool for studying the non-linear dynamics of acute, immunizing infectious diseases. The standard assumption of the TSIR model, that vaccination is equivalent to a reduction in the recruitment of susceptible individuals, or the birth rate, can lead to a bias in the estimate of the reporting fraction and of the total incidence. We show that this bias increases with the level of vaccination due to a double counting of individuals who are infected prior to the age of vaccination. We present a simple correction for this bias by discounting the observed number of cases by the product of the number that occur prior to the average age of vaccination and the vaccination coverage during the initial susceptible reconstruction step of the TSIR model fitting. We generate a time series of measles cases using an age-structured SIR transmission model with vaccination after birth (at 9 months of age) and illustrate the bias with the standard TSIR fitting method. We then illustrate that our proposed correction eliminates the bias in the estimated reporting fraction and total incidence. We note further that this bias does not impact the estimates of the seasonality of transmission.

WHO, as requested by its member states, launched the Expanded Programme on Immunization (EPI) in 1974 to make life-saving vaccines available to all globally. To mark the 50-year anniversary of EPI, we sought to quantify the public health impact of vaccination globally since the programme's inception. In this modelling study, we used a suite of mathematical and statistical models to estimate the global and regional public health impact of 50 years of vaccination against 14 pathogens in EPI. For the modelled pathogens, we considered coverage of all routine and supplementary vaccines delivered since 1974 and estimated the mortality and morbidity averted for each age cohort relative to a hypothetical scenario of no historical vaccination. We then used these modelled outcomes to estimate the contribution of vaccination to globally declining infant and child mortality rates over this period. Since 1974, vaccination has averted 154 million deaths, including 146 million among children younger than 5 years of whom 101 million were infants younger than 1 year. For every death averted, 66 years of full health were gained on average, translating to 10·2 billion years of full health gained. We estimate that vaccination has accounted for 40% of the observed decline in global infant mortality, 52% in the African region. In 2024, a child younger than 10 years is 40% more likely to survive to their next birthday relative to a hypothetical scenario of no historical vaccination. Increased survival probability is observed even well into late adulthood. Since 1974 substantial gains in childhood survival have occurred in every global region. We estimate that EPI has provided the single greatest contribution to improved infant survival over the past 50 years. In the context of strengthening primary health care, our results show that equitable universal access to immunisation remains crucial to sustain health gains and continue to save future lives from preventable infectious mortality. WHO.

The structure of contact networks affects the likelihood of disease spread at the population scale and the risk of infection at any given node. Though this has been well characterized for both theoretical and empirical networks for the spread of epidemics on completely susceptible networks, the long-term impact of network structure on risk of infection with an endemic pathogen, where nodes can be infected more than once, has been less well characterized. Here, we analyze detailed records of the transportation of cattle among farms in Turkey to characterize the global and local attributes of the directed—weighted shipments network between 2007-2012. We then study the correlations between network properties and the likelihood of infection with, or exposure to, foot-and-mouth disease (FMD) over the same time period using recorded outbreaks. The shipments network shows a complex combination of features (local and global) that have not been previously reported in other networks of shipments; i.e. small-worldness, scale-freeness, modular structure, among others. We find that nodes that were either infected or at high risk of infection with FMD (within one link from an infected farm) had disproportionately higher degree, were more central (eigenvector centrality and coreness), and were more likely to be net recipients of shipments compared to those that were always more than 2 links away from an infected farm. High in-degree (i.e. many shipments received) was the best univariate predictor of infection. Low in-coreness (i.e. peripheral nodes) was the best univariate predictor of nodes always more than 2 links away from an infected farm. These results are robust across the three different serotypes of FMD observed in Turkey and during periods of low-endemic prevalence and high-prevalence outbreaks.

The success of vaccination programs depends largely on the mechanisms used in vaccine delivery. National immunization programs offer childhood vaccines through fixed and outreach services within the health system and often, additional supplementary immunization activities (SIAs) are undertaken to fill gaps and boost coverage. Here, we map predicted coverage at 1 × 1 km spatial resolution in five low- and middle-income countries to identify areas that are under-vaccinated via each delivery method using Demographic and Health Surveys data. We compare estimates of the coverage of the third dose of diphtheria-tetanus-pertussis-containing vaccine (DTP3), which is typically delivered through routine immunization (RI), with those of measles-containing vaccine (MCV) for which SIAs are also undertaken. We find that SIAs have boosted MCV coverage in some places, but not in others, particularly where RI had been deficient, as depicted by DTP coverage. The modelling approaches outlined here can help to guide geographical prioritization and strategy design. The success of vaccination programs depends largely on the mechanisms used in vaccine delivery. Here, the authors evaluate the relative effectiveness of two major vaccine delivery strategies, namely routine immunization and supplementary immunization activities in five study countries.

Optimal intervention for disease outbreaks is often impeded by severe scientific uncertainty. Adaptive management (AM), long-used in natural resource management, is a structured decision-making approach to solving dynamic problems that accounts for the value of resolving uncertainty via real-time evaluation of alternative models. We propose an AM approach to design and evaluate intervention strategies in epidemiology, using real-time surveillance to resolve model uncertainty as management proceeds, with foot-and-mouth disease (FMD) culling and measles vaccination as case studies. We use simulations of alternative intervention strategies under competing models to quantify the effect of model uncertainty on decision making, in terms of the value of information, and quantify the benefit of adaptive versus static intervention strategies. Culling decisions during the 2001 UK FMD outbreak were contentious due to uncertainty about the spatial scale of transmission. The expected benefit of resolving this uncertainty prior to a new outbreak on a UK-like landscape would be £45-£60 million relative to the strategy that minimizes livestock losses averaged over alternate transmission models. AM during the outbreak would be expected to recover up to £20.1 million of this expected benefit. AM would also recommend a more conservative initial approach (culling of infected premises and dangerous contact farms) than would a fixed strategy (which would additionally require culling of contiguous premises). For optimal targeting of measles vaccination, based on an outbreak in Malawi in 2010, AM allows better distribution of resources across the affected region; its utility depends on uncertainty about both the at-risk population and logistical capacity. When daily vaccination rates are highly constrained, the optimal initial strategy is to conduct a small, quick campaign; a reduction in expected burden of approximately 10,000 cases could result if campaign targets can be updated on the basis of the true susceptible population. Formal incorporation of a policy to update future management actions in response to information gained in the course of an outbreak can change the optimal initial response and result in significant cost savings. AM provides a framework for using multiple models to facilitate public-health decision making and an objective basis for updating management actions in response to improved scientific understanding.

Many countries schedule a second dose of measles-containing vaccine (MCV2) for children in their second year of life. The correlation between recipients of the first dose of measles-containing vaccine (MCV1) and MCV2 is poorly understood but is important for estimating population levels of measles immunity and for meeting elimination targets. Using data from 19 surveys from Demographic and Health Surveys (DHS) we computed the percentage of MCV1 recipients with subsequent MCV2 and of MCV2 recipients with previous MCV1. All countries included in our study recommended MCV1 in the first year of life and MCV2 in the second year of life. For 2 surveys we computed the variation of those percentages over the country’s geographical regions. We computed adjusted odds ratios for the association of this percentage with age, sex, residency, mother’s education, wealth and birth order. For most of the surveys, over 50% of MCV1 recipients received MCV2, but there was more than 30% MCV1 to MCV2 dropout in more than half of the surveys. The percentage of MCV1 recipients with MCV2 was statistically significantly higher if they received MCV1 below age 12 months and the percentage increased with increasing education status of the mother and higher income levels. A small number of MCV2 recipients were not found to have received MCV1, despite marked on record as having received MCV2 implies having previously received MCV1 (by definition of the survey data collection methodology). Our analyses have highlighted important shortfalls by age, country, mother’s education and income status in the proportion of MCV1 recipients who subsequently receive MCV2. Targeting those differentials is essential for achieving the goals of measles elimination.

In 2008 all WHO member states endorsed a target of 90% reduction in measles mortality by 2010 over 2000 levels. We developed a model to estimate progress made towards this goal. We constructed a state-space model with population and immunisation coverage estimates and reported surveillance data to estimate annual national measles cases, distributed across age classes. We estimated deaths by applying age-specific and country-specific case-fatality ratios to estimated cases in each age-country class. Estimated global measles mortality decreased 74% from 535 300 deaths (95% CI 347 200–976 400) in 2000 to 139 300 (71 200–447 800) in 2010. Measles mortality was reduced by more than three-quarters in all WHO regions except the WHO southeast Asia region. India accounted for 47% of estimated measles mortality in 2010, and the WHO African region accounted for 36%. Despite rapid progress in measles control from 2000 to 2007, delayed implementation of accelerated disease control in India and continued outbreaks in Africa stalled momentum towards the 2010 global measles mortality reduction goal. Intensified control measures and renewed political and financial commitment are needed to achieve mortality reduction targets and lay the foundation for future global eradication of measles. US Centers for Disease Control and Prevention (PMS 5U66/IP000161).

Expanded access to measles vaccination was among the most successful public health interventions of recent decades. All WHO regions currently target measles elimination by 2020, yet continued measles circulation makes that goal seem elusive. Using Demographic and Health Surveys with generalized additive models, we quantify spatial patterns of measles vaccination in ten contiguous countries in the African Great Lakes region between 2009–2014. Seven countries have ‘coldspots’ where vaccine coverage is below the WHO target of 80%. Over 14 million children under 5 years of age live in coldspots across the region, and a total of 8–12 million children are unvaccinated. Spatial patterns of vaccination do not map directly onto sub-national administrative units and transnational coldspots exist. Clustering of low vaccination areas may allow for pockets of susceptibility that sustain circulation despite high overall coverage. Targeting at-risk areas and transnational coordination are likely required to eliminate measles in the region. The WHO targets measles elimination by 2020, a goal that relies on high vaccination coverage. Here, Takahashi et al . identify ‘coldspots’ in the African Great Lakes region where measles vaccine coverage is below 80%, suggesting that these regions should be targeted in future vaccination campaigns.

The Ebola epidemic in West Africa has caused substantial morbidity and mortality. The outbreak has also disrupted health care services, including childhood vaccinations, creating a second public health crisis. We project that after 6 to 18 months of disruptions, a large connected cluster of children unvaccinated for measles will accumulate across Guinea, Liberia, and Sierra Leone. This pool of susceptibility increases the expected size of a regional measles outbreak from 127,000 to 227,000 cases after 18 months, resulting in 2000 to 16,000 additional deaths (comparable to the numbers of Ebola deaths reported thus far). There is a clear path to avoiding outbreaks of childhood vaccine-preventable diseases once the threat of Ebola begins to recede: an aggressive regional vaccination campaign aimed at age groups left unprotected because of health care disruptions.

The past two decades have seen expansion of childhood vaccination programmes in low-income and middle-income countries (LMICs). We quantify the health impact of these programmes by estimating the deaths and disability-adjusted life-years (DALYs) averted by vaccination against ten pathogens in 98 LMICs between 2000 and 2030. 16 independent research groups provided model-based disease burden estimates under a range of vaccination coverage scenarios for ten pathogens: hepatitis B virus, Haemophilus influenzae type B, human papillomavirus, Japanese encephalitis, measles, Neisseria meningitidis serogroup A, Streptococcus pneumoniae, rotavirus, rubella, and yellow fever. Using standardised demographic data and vaccine coverage, the impact of vaccination programmes was determined by comparing model estimates from a no-vaccination counterfactual scenario with those from a reported and projected vaccination scenario. We present deaths and DALYs averted between 2000 and 2030 by calendar year and by annual birth cohort. We estimate that vaccination of the ten selected pathogens will have averted 69 million (95% credible interval 52–88) deaths between 2000 and 2030, of which 37 million (30–48) were averted between 2000 and 2019. From 2000 to 2019, this represents a 45% (36–58) reduction in deaths compared with the counterfactual scenario of no vaccination. Most of this impact is concentrated in a reduction in mortality among children younger than 5 years (57% reduction [52–66]), most notably from measles. Over the lifetime of birth cohorts born between 2000 and 2030, we predict that 120 million (93–150) deaths will be averted by vaccination, of which 58 million (39–76) are due to measles vaccination and 38 million (25–52) are due to hepatitis B vaccination. We estimate that increases in vaccine coverage and introductions of additional vaccines will result in a 72% (59–81) reduction in lifetime mortality in the 2019 birth cohort. Increases in vaccine coverage and the introduction of new vaccines into LMICs have had a major impact in reducing mortality. These public health gains are predicted to increase in coming decades if progress in increasing coverage is sustained. Gavi, the Vaccine Alliance and the Bill & Melinda Gates Foundation.