Amy L. Greer

Estimated epidemiologic parameters and morbidity associated with pandemic H1N1 influenza

Background: In the face of an influenza pandemic, accurate estimates of epidemiologic parameters are required to help guide decision-making. We sought to estimate epidemiologic parameters for pandemic H1N1 influenza using data from initial reports of laboratory-confirmed cases. Methods: We obtained data on laboratory-confirmed cases of pandemic H1N1 influenza reported in the province of Ontario, Canada, with dates of symptom onset between Apr. 13 and June 20, 2009. Incubation periods and duration of symptoms were estimated and fit to parametric distributions. We used competing-risk models to estimate risk of hospital admission and case-fatality rates. We used a Markov Chain Monte Carlo model to simulate disease transmission. Results: The median incubation period was 4 days and the duration of symptoms was 7 days. Recovery was faster among patients less than 18 years old than among older patients (hazard ratio 1.23, 95% confidence interval 1.06–1.44). The risk of hospital admission was 4.5% (95% CI 3.8%–5.2%) and the case-fatality rate was 0.3% (95% CI 0.1%–0.5%). The risk of hospital admission was highest among patients less than 1 year old and those 65 years or older. Adults more than 50 years old comprised 7% of cases but accounted for 7 of 10 initial deaths (odds ratio 28.6, 95% confidence interval 7.3–111.2). From the simulation models, we estimated the following values (and 95% credible intervals): a mean basic reproductive number (R0, the number of new cases created by a single primary case in a susceptible population) of 1.31 (1.25–1.38), a mean latent period of 2.62 (2.28–3.12) days and a mean duration of infectiousness of 3.38 (2.06–4.69) days. From these values we estimated a serial interval (the average time from onset of infectiousness in a case to the onset of infectiousness in a person infected by that case) of 4–5 days. Interpretation: The low estimates for R0 indicate that effective mitigation strategies may reduce the final epidemic impact of pandemic H1N1 influenza.

Climate change and infectious diseases in North America: the road ahead

Global climate change is inevitable — the combustion of fossil fuels has resulted in a buildup of greenhouse gases within the atmosphere, causing unprecedented changes to the earths climate. The Fourth Assessment Report of the Intergovernmental Panel on Climate Change suggests that North America will experience marked changes in weather patterns in coming decades, including warmer temperatures and increased rainfall, summertime droughts and extreme weather events (e.g., tornadoes and hurricanes). Although these events may have direct consequences for health (e.g., injuries and displacement of populations due to thermal stress), they are also likely to cause important changes in the incidence and distribution of infectious diseases, including vector-borne and zoonotic diseases, water-and food-borne diseases and diseases with environmental reservoirs (e.g., endemic fungal diseases). Changes in weather patterns and ecosystems, and health consequences of climate change will probably be most severe in far northern regions (e.g., the Arctic). We provide an overview of the expected nature and direction of such changes, which pose current and future challenges to health care providers and public health agencies.

Keeping vulnerable children safe from pertussis: preventing nosocomial pertussis transmission in the neonatal intensive care unit.

OBJECTIVE To examine the impact of different acellular pertussis booster vaccination strategies on the probability of a nosocomial pertussis outbreak occurring and the distribution of outbreak sizes observed for each intervention strategy. SETTING Neonatal intensive care unit. METHODS We developed a stochastic, agent-based simulation model to examine the impact of booster vaccination strategies for pertussis on health care-related transmission. RESULTS Our results demonstrate that healthcare worker booster vaccination decreases the probability of secondary transmission from 49% (base case, no boosting) to 2% (if 95% of healthcare workers are boosted) and decreases final outbreak size. Boosting family caregivers did not have a clinically significant impact on nosocomial disease transmission. CONCLUSION The provision of booster vaccine to healthcare workers in the neonatal intensive care unit substantially reduces the risk of hospital-centered pertussis outbreaks in a manner that enhances the health of hospitalized children. A formal health economic analysis of this finding is currently under way. Policies to protect patient safety in pediatric facilities should include compliance with the United States Advisory Committee on Immunization Practices, which recommends provision of pertussis booster vaccination to healthcare workers.

An IDEA for Short Term Outbreak Projection: Nearcasting Using the Basic Reproduction Number

Background Communicable disease outbreaks of novel or existing pathogens threaten human health around the globe. It would be desirable to rapidly characterize such outbreaks and develop accurate projections of their duration and cumulative size even when limited preliminary data are available. Here we develop a mathematical model to aid public health authorities in tracking the expansion and contraction of outbreaks with explicit representation of factors (other than population immunity) that may slow epidemic growth. Methodology The Incidence Decay and Exponential Adjustment (IDEA) model is a parsimonious function that uses the basic reproduction number R0, along with a discounting factor to project the growth of outbreaks using only basic epidemiological information (e.g., daily incidence counts). Principal Findings Compared to simulated data, IDEA provides highly accurate estimates of total size and duration for a given outbreak when R0 is low or moderate, and also identifies turning points or new waves. When tested with an outbreak of pandemic influenza A (H1N1), the model generates estimated incidence at the i+1th serial interval using data from the ith serial interval within an average of 20% of actual incidence. Conclusions and Significance This model for communicable disease outbreaks provides rapid assessments of outbreak growth and public health interventions. Further evaluation in the context of real-world outbreaks will establish the utility of IDEA as a tool for front-line epidemiologists.

Sensitivity of a Diagnostic Test for Amphibian Ranavirus Varies with Sampling Protocol

Field samples are commonly used to estimate disease prevalence in wild populations. Our confidence in these estimates requires understanding the sensitivity and specificity of the diagnostic tests. We assessed the sensitivity of the most commonly used diagnostic tests for amphibian Ranavirus by infecting salamanders (Ambystoma tigrinum; Amphibia, Caudata) with Ambystoma tigrinum virus (ATV) and then sampling euthanized animals (whole animal) and noneuthanized animals (tail clip) at five time intervals after exposure. We used a standard polymerase chain reaction (PCR) protocol to screen for ATV. Agreement between test results from whole-animal and tail-clip samples increased with time postexposure. This indicates that the ability to identify infected animals increases following exposure, leading to a more accurate estimate of prevalence in a population. Our results indicate that tail-clip sampling can underestimate the true prevalence of ATV in wild amphibian populations.

Vaccination against 2009 pandemic H1N1 in a population dynamical model of Vancouver, Canada: timing is everything

BackgroundMuch remains unknown about the effect of timing and prioritization of vaccination against pandemic (pH1N1) 2009 virus on health outcomes. We adapted a city-level contact network model to study different campaigns on influenza morbidity and mortality.MethodsWe modeled different distribution strategies initiated between July and November 2009 using a compartmental epidemic model that includes age structure and transmission network dynamics. The model represents the Greater Vancouver Regional District, a major North American city and surrounding suburbs with a population of 2 million, and is parameterized using data from the British Columbia Ministry of Health, published studies, and expert opinion. Outcomes are expressed as the number of infections and deaths averted due to vaccination.ResultsThe model output was consistent with provincial surveillance data. Assuming a basic reproduction number = 1.4, an 8-week vaccination campaign initiated 2 weeks before the epidemic onset reduced morbidity and mortality by 79-91% and 80-87%, respectively, compared to no vaccination. Prioritizing children and parents for vaccination may have reduced transmission compared to actual practice, but the mortality benefit of this strategy appears highly sensitive to campaign timing. Modeling the actual late October start date resulted in modest reductions in morbidity and mortality (13-25% and 16-20%, respectively) with little variation by prioritization scheme.ConclusionDelays in vaccine production due to technological or logistical barriers may reduce potential benefits of vaccination for pandemic influenza, and these temporal effects can outweigh any additional theoretical benefits from population targeting. Careful modeling may provide decision makers with estimates of these effects before the epidemic peak to guide production goals and inform policy. Integration of real-time surveillance data with mathematical models holds the promise of enabling public health planners to optimize the community benefits from proposed interventions before the pandemic peak.

Spatial and temporal patterns of Ambystoma tigrinum virus (ATV) prevalence in tiger salamanders Ambystoma tigrinum nebulosum

Amphibian ranaviruses have been documented as causes of mass mortality in amphibian populations throughout the world. The temporal and spatial dynamics of ranavirus infections when epidemics are not apparent remains unclear. To address this question, we collected tissue samples from 2003 to 2006 in 4 geographically separated tiger salamander Ambystoma tigrinum nebulosum host populations on the Kaibab Plateau in northern Arizona. We tested for Ambystoma tigrinum virus (ATV), a lethal ranavirus of tiger salamanders, calculated ATV prevalence for each sampling date, and examined temporal and spatial patterns by quantifying the annual level of ATV synchrony among populations using the intraclass correlation coefficient. Salamander populations were commonly infected with ATV. We observed no morbidity or mortality in these populations even as ATV prevalence values varied from 0 to 57%. Infection prevalence across the landscape was more similar within a given year than between years. There was no statistically significant spatial pattern in prevalence across the landscape. Our findings highlight the need to explore new hypotheses regarding the population level impact of these pathogens on amphibian communities.

Use of Models to Identify Cost-effective Interventions: Pertussis Vaccination for Pediatric Health Care Workers

OBJECTIVE: Acellular pertussis vaccine is safe and effective in adults. An explicit recommendation for pertussis booster vaccination in pediatric health care workers is based on the importance of health care workers as a potential source of infection for patients. However, limited information is available on the economic attractiveness of this intervention. We sought to evaluate the health-economic attractiveness of a diphtheria-tetanus-acellular pertussis booster vaccination program for health care workers in a pediatric intensive care setting. METHODS: We developed a Markov model to calculate the cost-effectiveness of vaccinating NICU health care workers in different proportions ranging from the current strategy of no pertussis booster vaccination program to a vaccination program that achieves between 25% and 95% vaccine coverage. RESULTS: Implementation of a vaccination program that achieves 25% coverage was projected to be cost-saving compared with no vaccine program. At all coverage levels the intervention reduced costs, increased life expectancy, and was cost-effective. Projections were most sensitive to the risk of a pertussis introduction via an infected health care worker. Once the monthly risk of an introduction exceeded ∼0.3%, implementation of an immunization program with at least 25% coverage provided both greater health and greater economic benefits than having no vaccine program. CONCLUSIONS: The implementation of a hospital-based and funded diphtheria-tetanus-acellular pertussis vaccine program administered through an occupational health program is cost-effective or cost-saving in the context of pediatric health care facilities in which many of the patients are at risk of serious morbidity and mortality should they acquire pertussis while hospitalized.

Of gastro and the gold standard: evaluation and policy implications of norovirus test performance for outbreak detection

BackgroundThe norovirus group (NVG) of caliciviruses are the etiological agents of most institutional outbreaks of gastroenteritis in North America and Europe. Identification of NVG is complicated by the non-culturable nature of this virus, and the absence of a diagnostic gold standard makes traditional evaluation of test characteristics problematic.MethodsWe evaluated 189 specimens derived from 440 acute gastroenteritis outbreaks investigated in Ontario in 2006–07. Parallel testing for NVG was performed with real-time reverse-transcriptase polymerase chain reaction (RT2-PCR), enzyme immunoassay (EIA) and electron microscopy (EM). Test characteristics (sensitivity and specificity) were estimated using latent class models and composite reference standard methods. The practical implications of test characteristics were evaluated using binomial probability models.ResultsLatent class modelling estimated sensitivities of RT2-PCR, EIA, and EM as 100%, 86%, and 17% respectively; specificities were 84%, 92%, and 100%; estimates obtained using a composite reference standard were similar. If all specimens contained norovirus, RT2-PCR or EIA would be associated with > 99.9% likelihood of at least one test being positive after three specimens tested. Testing of more than 5 true negative specimens with RT2-PCR would be associated with a greater than 50% likelihood of a false positive test.ConclusionOur findings support the characterization of EM as lacking sensitivity for NVG outbreaks. The high sensitivity of RT2-PCR and EIA permit identification of NVG outbreaks with testing of limited numbers of clinical specimens. Given risks of false positive test results, it is reasonable to limit the number of specimens tested when RT2-PCR or EIA are available.

Transmissibility of the 2009 H1N1 pandemic in remote and isolated Canadian communities: a modelling study

Objectives During the first wave of the 2009 influenza pH1N1, disease burden was distributed in a geographically heterogeneous fashion. It was particularly high in some remote and isolated Canadian communities when compared with urban centres. We sought to estimate the transmissibility (the basic reproduction number) of pH1N1 strain in some remote and isolated Canadian communities. Design A discrete time susceptible-exposed-infected transmission model was fit to infection curves simulated from laboratory-confirmed case counts for pH1N1 on each day. The sampling from Poisson distribution was used to estimate the basic reproduction number, R0, of pH1N1 during the spring wave for five different communities in Manitoba and Nunavut, Canada, where remote and isolated communities experienced a high incidence of infection, and high rates of hospitalisation and intensive care unit admission. Setting Remote and isolated communities in Northern Manitoba, Nunavut, and the largest urban centre (Winnipeg) in the province of Manitoba, Canada. Results Using published values of the exposed and infectious periods specific to H1N1 infection, corresponding to the average generation time of 2.78 days, we estimated a mean value of 2.26 for R0 (95% CI 1.57 to 3.75) in a community located in northern Manitoba. Estimates of R0 for other communities in Nunavut varied considerably with higher mean values of 3.91 (95% CI 3.08 to 4.87); 2.03 (95% CI 1.50 to 3.19); and 2.45 (95% CI 1.68 to 3.44). We estimated a lower mean value of 1.57 (95% CI 1.35 to 1.87) for R0 in the Winnipeg health region, as the largest urban centre in Manitoba. Conclusions Influenza pH1N1 appears to have been far more transmissible in rural and isolated Canadian communities than other large urban areas. The differential severity of the pandemic in these regions may be explained partly by differential transmissibility, and suggests the need for more nuanced, targeted or population-specific control strategies in Canada.