464 research outputs found
Estimation of the Health Impact and Cost-Effectiveness of Influenza Vaccination with Enhanced Effectiveness in Canada
INTRODUCTION: The propensity for influenza viruses to mutate and recombine makes them both a familiar threat and a prototype emerging infectious disease. Emerging evidence suggests that the use of MF59-adjuvanted vaccines in older adults and young children enhances protection against influenza infection and reduces adverse influenza-attributable outcomes compared to unadjuvanted vaccines. The health and economic impact of such vaccines in the Canadian population are uncertain. METHODS: We constructed an age-structured compartmental model simulating the transmission of influenza in the Canadian population over a ten-year period. We compared projected health outcomes (quality-adjusted life years (QALY) lost), costs, and incremental cost-effectiveness ratios (ICERs) for three strategies: (i) current use of unadjuvanted trivalent influenza vaccine; (ii) use of MF59-adjuvanted influenza vaccine adults ≥65 in the Canadian population, and (iii) adjuvanted vaccine used in both older adults and children aged < 6. RESULTS: In the base case analysis, use of adjuvanted vaccine in older adults was highly cost-effective (ICER = 1612/QALY). Results were similar whether or not a universal influenza immunization program was used in other age groups; projections were robust in the face of wide-ranging sensitivity analyses. INTERPRETATION: Based on the best available data, it is projected that replacement of traditional trivalent influenza vaccines with MF59-adjuvanted vaccines would confer substantial benefits to vaccinated and unvaccinated individuals, and would be economically attractive relative to other widely-used preventive interventions
The Cost-Effectiveness of Directly Observed Highly-Active Antiretroviral Therapy in the Third Trimester in HIV-Infected Pregnant Women
Background: In HIV-infected pregnant women, viral suppression prevents mother-to-child HIV transmission. Directly observed highly-active antiretroviral therapy (HAART) enhances virological suppression, and could prevent transmission. Our objective was to project the effectiveness and cost-effectiveness of directly observed administration of antiretroviral drugs in pregnancy.
Methods and Findings: A mathematical model was created to simulate cohorts of one million asymptomatic HIV-infected pregnant women on HAART, with women randomly assigned self-administered or directly observed antiretroviral therapy (DOT), or no HAART, in a series of Monte Carlo simulations. Our primary outcome was the quality-adjusted life expectancy in years (QALY) of infants born to HIV-infected women, with the rates of Caesarean section and HIV-transmission after DOT use as intermediate outcomes. Both self-administered HAART and DOT were associated with decreased costs and increased life-expectancy relative to no HAART. The use of DOT was associated with a relative risk of HIV transmission of 0.39 relative to conventional HAART; was highly cost-effective in the cohort as a whole (cost-utility ratio $14,233 per QALY); and was cost-saving in women whose viral loads on self-administered HAART would have exceeded 1000 copies/ml. Results were stable in wide-ranging sensitivity analyses, with directly observed therapy cost-saving or highly cost-effective in almost all cases.
Conclusions: Based on the best available data, programs that optimize adherence to HAART through direct observation in pregnancy have the potential to diminish mother-to-child HIV transmission in a highly cost-effective manner. Targeted use of DOT in pregnant women with high viral loads, who could otherwise receive self-administered HAART would be a cost-saving intervention. These projections should be tested with randomized clinical trials
Optimal Pandemic Influenza Vaccine Allocation Strategies for the Canadian Population
BACKGROUND: The world is currently confronting the first influenza pandemic of the 21(st) century. Influenza vaccination is an effective preventive measure, but the unique epidemiological features of swine-origin influenza A (H1N1) (pH1N1) introduce uncertainty as to the best strategy for prioritization of vaccine allocation. We sought to determine optimal prioritization of vaccine distribution among different age and risk groups within the Canadian population, to minimize influenza-attributable morbidity and mortality. METHODOLOGY/PRINCIPAL FINDINGS: We developed a deterministic, age-structured compartmental model of influenza transmission, with key parameter values estimated from data collected during the initial phase of the epidemic in Ontario, Canada. We examined the effect of different vaccination strategies on attack rates, hospitalizations, intensive care unit admissions, and mortality. In all scenarios, prioritization of high-risk individuals (those with underlying chronic conditions and pregnant women), regardless of age, markedly decreased the frequency of severe outcomes. When individuals with underlying medical conditions were not prioritized and an age group-based approach was used, preferential vaccination of age groups at increased risk of severe outcomes following infection generally resulted in decreased mortality compared to targeting vaccine to age groups with higher transmission, at a cost of higher population-level attack rates. All simulations were sensitive to the timing of the epidemic peak in relation to vaccine availability, with vaccination having the greatest impact when it was implemented well in advance of the epidemic peak. CONCLUSIONS/SIGNIFICANCE: Our model simulations suggest that vaccine should be allocated to high-risk groups, regardless of age, followed by age groups at increased risk of severe outcomes. Vaccination may significantly reduce influenza-attributable morbidity and mortality, but the benefits are dependent on epidemic dynamics, time for program roll-out, and vaccine uptake
Dynamic Transmission Modeling:A Report of the ISPOR-SMDM Modeling Good Research Practices Task Force-5
AbstractThe transmissible nature of communicable diseases is what sets them apart from other diseases modeled by health economists. The probability of a susceptible individual becoming infected at any one point in time (the force of infection) is related to the number of infectious individuals in the population, will change over time, and will feed back into the future force of infection. These nonlinear interactions produce transmission dynamics that require specific consideration when modeling an intervention that has an impact on the transmission of a pathogen. Best practices for designing and building these models are set out in this article
Reactive strategies for containing developing outbreaks of pandemic influenza
Abstract
Background
In 2009 and the early part of 2010, the northern hemisphere had to cope with the first waves of the new influenza A (H1N1) pandemic. Despite high-profile vaccination campaigns in many countries, delays in administration of vaccination programs were common, and high vaccination coverage levels were not achieved. This experience suggests the need to explore the epidemiological and economic effectiveness of additional, reactive strategies for combating pandemic influenza.
Methods
We use a stochastic model of pandemic influenza to investigate realistic strategies that can be used in reaction to developing outbreaks. The model is calibrated to documented illness attack rates and basic reproductive number (R0) estimates, and constructed to represent a typical mid-sized North American city.
Results
Our model predicts an average illness attack rate of 34.1% in the absence of intervention, with total costs associated with morbidity and mortality of US37 million, respectively, when low-coverage reactive vaccination and limited antiviral use are combined with practical, minimally disruptive social distancing strategies, including short-term, as-needed closure of individual schools, even when vaccine supply-chain-related delays occur. Results improve with increasing vaccination coverage and higher vaccine efficacy.
Conclusions
Such combination strategies can be substantially more effective than vaccination alone from epidemiological and economic standpoints, and warrant strong consideration by public health authorities when reacting to future outbreaks of pandemic influenza
Heterogeneity in transmissibility and shedding SARS-CoV-2 via droplets and aerosols
Background: Which virological factors mediate overdispersion in the transmissibility of emerging viruses remains a longstanding question in infectious disease epidemiology. Methods: Here, we use systematic review to develop a comprehensive dataset of respiratory viral loads (rVLs) of SARS-CoV-2, SARS-CoV-1 and influenza A(H1N1)pdm09. We then comparatively meta-analyze the data and model individual infectiousness by shedding viable virus via respiratory droplets and aerosols. Results: The analyses indicate heterogeneity in rVL as an intrinsic virological factor facilitating greater overdispersion for SARS-CoV-2 in the COVID-19 pandemic than A(H1N1)pdm09 in the 2009 influenza pandemic. For COVID-19, case heterogeneity remains broad throughout the infectious period, including for pediatric and asymptomatic infections. Hence, many COVID-19 cases inherently present minimal transmission risk, whereas highly infectious individuals shed tens to thousands of SARS-CoV-2 virions/min via droplets and aerosols while breathing, talking and singing. Coughing increases the contagiousness, especially in close contact, of symptomatic cases relative to asymptomatic ones. Infectiousness tends to be elevated between 1-5 days post-symptom onset. Conclusions: Intrinsic case variation in rVL facilitates overdispersion in the transmissibility of emerging respiratory viruses. Our findings present considerations for disease control in the COVID-19 pandemic as well as future outbreaks of novel viruses.</p
Let the sun shine in: effects of ultraviolet radiation on invasive pneumococcal disease risk in Philadelphia, Pennsylvania
BACKGROUND: Streptococcus pneumoniae is a common cause of community acquired pneumonia and
bacteremia. Excess wintertime mortality related to pneumonia has been noted for over a century,
but the seasonality of invasive pneumococcal disease (IPD) has been described relatively recently
and is poorly understood. Improved understanding of environmental influence on disease
seasonality has taken on new urgency due to global climate change.
METHODS: We evaluated 602 cases of IPD reported in Philadelphia County, Pennsylvania, from
2002 to 2007. Poisson regression models incorporating seasonal smoothers were used to identify
associations between weekly weather patterns and case counts. Associations between acute (dayto-
day) environmental fluctuations and IPD occurrence were evaluated using a case-crossover
approach. Effect modification across age and sex strata was explored, and meta-regression models
were created using stratum-specific estimates for effect.
RESULTS: IPD incidence was greatest in the wintertime, and spectral decomposition revealed a peak
at 51.0 weeks, consistent with annual periodicity. After adjustment for seasonality, yearly increases
in reporting, and temperature, weekly incidence was found to be associated with clear-sky UV
index (IRR per unit increase in index: 0.70 [95% CI 0.54-0.91]). The effect of UV index was highest
among young strata and decreased with age. At shorter time scales, only an association with
increases in ambient sulphur oxides was linked to disease risk (OR for highest tertile of exposure
0.75, 95% CI 0.60 to 0.93).
CONCLUSION: We confirmed the wintertime predominance of IPD in a major urban center. The
major predictor of IPD in Philadelphia is extended periods of low UV radiation, which may explain
observed wintertime seasonality. The mechanism of action of diminished light exposure on disease
occurrence may be due to direct effects on pathogen survival or host immune function via altered
1,25-(OH)2-vitamin-D metabolism. These findings may suggest less diminution in future IPD risk
with climate change than would be expected if wintertime seasonality was driven by temperature
Infectious Disease in a Warming World: How Weather Influenced West Nile Virus in the United States (2001–2005)
Background: The effects of weather on West Nile virus (WNV) mosquito populations in the United States have been widely reported, but few studies assess their overall impact on transmission to humans. Objectives: We investigated meteorologic conditions associated with reported human WNV cases in the United States. Methods: We conducted a case–crossover study to assess 16,298 human WNV cases reported to the Centers for Disease Control and Prevention from 2001 to 2005. The primary outcome measures were the incidence rate ratio of disease occurrence associated with mean weekly maximum temperature, cumulative weekly temperature, mean weekly dew point temperature, cumulative weekly precipitation, and the presence of ≥ 1 day of heavy rainfall (≥ 50 mm) during the month prior to symptom onset. Results: Increasing weekly maximum temperature and weekly cumulative temperature were similarly and significantly associated with a 35–83% higher incidence of reported WNV infection over the next month. An increase in mean weekly dew point temperature was significantly associated with a 9–38% higher incidence over the subsequent 3 weeks. The presence of at least 1 day of heavy rainfall within a week was associated with a 29–66% higher incidence during the same week and over the subsequent 2 weeks. A 20-mm increase in cumulative weekly precipitation was significantly associated with a 4–8% increase in incidence of reported WNV infection over the subsequent 2 weeks. Conclusions: Warmer temperatures, elevated humidity, and heavy precipitation increased the rate of human WNV infection in the United States independent of season and each others’ effects
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