Rotavirus vaccine efficacy ranges from >90% in high socio-economic settings (SES) to 50% in low SES. With the imminent introduction of rotavirus vaccine in low SES countries, understanding reasons ...for reduced efficacy in these settings could identify strategies to improve vaccine performance.
We developed a mathematical model to predict rotavirus vaccine efficacy in high, middle and low SES based on data specific for each setting on incidence, protection conferred by natural infection and immune response to vaccination. We then examined factors affecting efficacy.
Vaccination was predicted to prevent 93%, 86% and 51% of severe rotavirus gastroenteritis in high, middle and low SES, respectively. Also predicted was that vaccines are most effective against severe disease and efficacy declines with age in low but not high SES. Reduced immunogenicity of vaccination and reduced protection conferred by natural infection are the main factors that compromise efficacy in low SES.
The continued risk of severe disease in non-primary natural infections in low SES is a key factor underpinning reduced efficacy of rotavirus vaccines. Predicted efficacy was remarkably consistent with observed clinical trial results from different SES, validating the model. The phenomenon of reduced vaccine efficacy can be predicted by intrinsic immunological and epidemiological factors of low SES populations. Modifying aspects of the vaccine (e.g. improving immunogenicity in low SES) and vaccination program (e.g. additional doses) may bring improvements.
Dengue is the fastest spreading vector-borne viral disease, resulting in an estimated 390 million infections annually. Precise prediction of many attributes related to dengue is still a challenge due ...to the complex dynamics of the disease. Important attributes to predict include: the risk of and risk factors for an infection; infection severity; and the timing and magnitude of outbreaks. In this work, we build a model for predicting the risk of dengue transmission using high-resolution weather data. The level of dengue transmission risk depends on the vector density, hence we predict risk via vector prediction.
We make use of surveillance data on Aedes aegypti larvae collected by the Taiwan Centers for Disease Control as part of the national routine entomological surveillance of dengue, and weather data simulated using the IBM's Containerized Forecasting Workflow, a high spatial- and temporal-resolution forecasting system. We propose a two stage risk prediction system for assessing dengue transmission via Aedes aegypti mosquitoes. In stage one, we perform a logistic regression to determine whether larvae are present or absent at the locations of interest using weather attributes as the explanatory variables. The results are then aggregated to an administrative division, with presence in the division determined by a threshold percentage of larvae positive locations resulting from a bootstrap approach. In stage two, larvae counts are estimated for the predicted larvae positive divisions from stage one, using a zero-inflated negative binomial model. This model identifies the larvae positive locations with 71% accuracy and predicts the larvae numbers producing a coverage probability of 98% over 95% nominal prediction intervals. This two-stage model improves the overall accuracy of identifying larvae positive locations by 29%, and the mean squared error of predicted larvae numbers by 9.6%, against a single-stage approach which uses a zero-inflated binomial regression approach.
We demonstrate a risk prediction system using high resolution weather data can provide valuable insight to the distribution of risk over a geographical region. The work also shows that a two-stage approach is beneficial in predicting risk in non-homogeneous regions, where the risk is localised.
While the majority of cochlear implant recipients benefit from the device, it remains difficult to estimate the degree of benefit for a specific patient prior to implantation. Using data from 2,735 ...cochlear-implant recipients from across three clinics, the largest retrospective study of cochlear-implant outcomes to date, we investigate the association between 21 preoperative factors and speech recognition approximately one year after implantation and explore the consistency of their effects across the three constituent datasets. We provide evidence of 17 statistically significant associations, in either univariate or multivariate analysis, including confirmation of associations for several predictive factors, which have only been examined in prior smaller studies. Despite the large sample size, a multivariate analysis shows that the variance explained by our models remains modest across the datasets (
R
2
=
0.12
–0.21). Finally, we report a novel statistical interaction indicating that the duration of deafness in the implanted ear has a stronger impact on hearing outcome when considered relative to a candidate’s age. Our multicenter study highlights several real-world complexities that impact the clinical translation of predictive factors for cochlear implantation outcome. We suggest several directions to overcome these challenges and further improve our ability to model patient outcomes with increased accuracy.
In current epidemiology of tuberculosis (TB), heterogeneity in infectiousness among TB patients is a challenge, which is not well studied. We aimed to quantify this heterogeneity and the presence of ..."super-spreading" events that can assist in designing optimal public health interventions.
TB epidemiologic investigation data notified between 1 January 2005 and 31 December 2015 from Victoria, Australia were used to quantify TB patients' heterogeneity in infectiousness and super-spreading events. We fitted a negative binomial offspring distribution (NBD) for the number of secondary infections and secondary active TB disease each TB patient produced. The dispersion parameter, k, of the NBD measures the level of heterogeneity, where low values of k (e.g. k < 1) indicate over-dispersion. Super-spreading was defined as patients causing as many or more secondary infections as the 99th centile of an equivalent homogeneous distribution. Contact infection was determined based on a tuberculin skin test (TST) result of ≥10 mm. A NBD model was fitted to identify index characteristics that were associated with the number of contacts infected and risk ratios (RRs) were used to quantify the strength of this association.
There were 4190 (2312 pulmonary and 1878 extrapulmonary) index TB patients and 18,030 contacts. A total of 15,522 contacts were tested with TST, of whom 3213 had a result of ≥10 mm. The dispersion parameter, k for secondary infections was estimated at 0.16 (95%CI 0.14-0.17) and there were 414 (9.9%) super-spreading events. From the 3213 secondary infections, 2415 (75.2%) were due to super-spreading events. There were 226 contacts who developed active TB disease and a higher level of heterogeneity was found for this outcome than for secondary infection, with k estimated at 0.036 (95%CI 0.025-0.046). In regression analyses, we found that infectiousness was greater among index patients found by clinical presentation and those with bacteriological confirmation.
TB transmission is highly over dispersed and super-spreading events are responsible for a substantial majority of secondary infections. Heterogeneity of transmission and super-spreading are critical issues to consider in the design of interventions and models of TB transmission dynamics.
The role of mass drug administration (MDA) and the implementation of transmission reduction measures are essential to successfully control and eliminate a wide range of NTDs, including the ocular ...disease trachoma. Immunity to trachoma infection acts by reducing the duration of an individual's infectious period and by reducing their infectivity with each successive infection.
In this study, we use a model of trachoma infection, which includes population immunity, to explore the impact of treatment and transmission reduction measures on trachoma prevalence. Specifically, we investigate the possibility of increasing transmissibility of trachoma arising as MDA and transmission reduction measures are scaled up in endemic settings.
We demonstrate this increase in transmissibility by calculating the effective reproduction number during several simulated control programmes and show that it is related to a decrease in the level of immunity in the population.
This effect should be studied in the field by measuring the rate of return of infection and disease in at least two separate age groups. If the decline of population immunity is operating, it should be accounted for when planning for the GET2020 goal of eliminating blinding trachoma by 2020.
Causal diagrams in systems epidemiology Joffe, Michael; Gambhir, Manoj; Chadeau-Hyam, Marc ...
Emerging themes in epidemiology,
03/2012, Letnik:
9, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Methods of diagrammatic modelling have been greatly developed in the past two decades. Outside the context of infectious diseases, systematic use of diagrams in epidemiology has been mainly confined ...to the analysis of a single link: that between a disease outcome and its proximal determinant(s). Transmitted causes ("causes of causes") tend not to be systematically analysed.The infectious disease epidemiology modelling tradition models the human population in its environment, typically with the exposure-health relationship and the determinants of exposure being considered at individual and group/ecological levels, respectively. Some properties of the resulting systems are quite general, and are seen in unrelated contexts such as biochemical pathways. Confining analysis to a single link misses the opportunity to discover such properties.The structure of a causal diagram is derived from knowledge about how the world works, as well as from statistical evidence. A single diagram can be used to characterise a whole research area, not just a single analysis - although this depends on the degree of consistency of the causal relationships between different populations - and can therefore be used to integrate multiple datasets.Additional advantages of system-wide models include: the use of instrumental variables - now emerging as an important technique in epidemiology in the context of mendelian randomisation, but under-used in the exploitation of "natural experiments"; the explicit use of change models, which have advantages with respect to inferring causation; and in the detection and elucidation of feedback.
•School dismissals are particularly effective in delaying the epidemic peak.•Dismissals at the city or county level yield the greatest reduction in disease incidence for all but the most severe ...pandemic scenarios.•Broader (multi-county) dismissals should be considered for the most severe and fast-spreading (1918-like) pandemics.
We used individual-based computer simulation models at community, regional and national levels to evaluate the likely impact of coordinated pre-emptive school dismissal policies during an influenza pandemic. Such policies involve three key decisions: when, over what geographical scale, and how long to keep schools closed. Our evaluation includes uncertainty and sensitivity analyses, as well as model output uncertainties arising from variability in serial intervals and presumed modifications of social contacts during school dismissal periods. During the period before vaccines become widely available, school dismissals are particularly effective in delaying the epidemic peak, typically by 4–6 days for each additional week of dismissal. Assuming the surveillance is able to correctly and promptly diagnose at least 5–10% of symptomatic individuals within the jurisdiction, dismissals at the city or county level yield the greatest reduction in disease incidence for a given dismissal duration for all but the most severe pandemic scenarios considered here. Broader (multi-county) dismissals should be considered for the most severe and fast-spreading (1918-like) pandemics, in which multi-month closures may be necessary to delay the epidemic peak sufficiently to allow for vaccines to be implemented.
Summary Background Safe and effective vaccines could help to end the ongoing Ebola virus disease epidemic in parts of west Africa, and mitigate future outbreaks of the virus. We assess the ...statistical validity and power of randomised controlled trial (RCT) and stepped-wedge cluster trial (SWCT) designs in Sierra Leone, where the incidence of Ebola virus disease is spatiotemporally heterogeneous, and is decreasing rapidly. Methods We projected district-level Ebola virus disease incidence for the next 6 months, using a stochastic model fitted to data from Sierra Leone. We then simulated RCT and SWCT designs in trial populations comprising geographically distinct clusters at high risk, taking into account realistic logistical constraints, and both individual-level and cluster-level variations in risk. We assessed false-positive rates and power for parametric and non-parametric analyses of simulated trial data, across a range of vaccine efficacies and trial start dates. Findings For an SWCT, regional variation in Ebola virus disease incidence trends produced increased false-positive rates (up to 0·15 at α=0·05) under standard statistical models, but not when analysed by a permutation test, whereas analyses of RCTs remained statistically valid under all models. With the assumption of a 6-month trial starting on Feb 18, 2015, we estimate the power to detect a 90% effective vaccine to be between 49% and 89% for an RCT, and between 6% and 26% for an SWCT, depending on the Ebola virus disease incidence within the trial population. We estimate that a 1-month delay in trial initiation will reduce the power of the RCT by 20% and that of the SWCT by 49%. Interpretation Spatiotemporal variation in infection risk undermines the statistical power of the SWCT. This variation also undercuts the SWCT's expected ethical advantages over the RCT, because an RCT, but not an SWCT, can prioritise vaccination of high-risk clusters. Funding US National Institutes of Health, US National Science Foundation, and Canadian Institutes of Health Research.
Dog rabies annually causes 24,000-70,000 deaths globally. We built a spreadsheet tool, RabiesEcon, to aid public health officials to estimate the cost-effectiveness of dog rabies vaccination programs ...in East Africa.
RabiesEcon uses a mathematical model of dog-dog and dog-human rabies transmission to estimate dog rabies cases averted, the cost per human rabies death averted and cost per year of life gained (YLG) due to dog vaccination programs (US 2015 dollars). We used an East African human population of 1 million (approximately 2/3 living in urban setting, 1/3 rural). We considered, using data from the literature, three vaccination options; no vaccination, annual vaccination of 50% of dogs and 20% of dogs vaccinated semi-annually. We assessed 2 transmission scenarios: low (1.2 dogs infected per infectious dog) and high (1.7 dogs infected). We also examined the impact of annually vaccinating 70% of all dogs (World Health Organization recommendation for dog rabies elimination).
Without dog vaccination, over 10 years there would a total of be approximately 44,000-65,000 rabid dogs and 2,100-2,900 human deaths. Annually vaccinating 50% of dogs results in 10-year reductions of 97% and 75% in rabid dogs (low and high transmissions scenarios, respectively), approximately 2,000-1,600 human deaths averted, and an undiscounted cost-effectiveness of $451-$385 per life saved. Semi-annual vaccination of 20% of dogs results in in 10-year reductions of 94% and 78% in rabid dogs, and approximately 2,000-1,900 human deaths averted, and cost $404-$305 per life saved. In the low transmission scenario, vaccinating either 50% or 70% of dogs eliminated dog rabies. Results were most sensitive to dog birth rate and the initial rate of dog-to-dog transmission (Ro).
Dog rabies vaccination programs can control, and potentially eliminate, dog rabies. The frequency and coverage of vaccination programs, along with the level of dog rabies transmission, can affect the cost-effectiveness of such programs. RabiesEcon can aid both the planning and assessment of dog rabies vaccination programs.
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