Temporal variability and social heterogeneity in disease transmission: The case of SARS in Hong Kong

The extent to which self-adopted or intervention-related changes in behaviors affect the course of epidemics remains a key issue for outbreak control. This study attempted to quantify the effect of such changes on the risk of infection in different settings, i.e., the community and hospitals. The 2002-2003 severe acute respiratory syndrome (SARS) outbreak in Hong Kong, where 27% of cases were healthcare workers, was used as an example. A stochastic compartmental SEIR (susceptible-exposed-infectious-removed) model was used: the population was split into healthcare workers, hospitalized people and general population. Super spreading events (SSEs) were taken into account in the model. The temporal evolutions of the daily effective contact rates in the community and hospitals were modeled with smooth functions. Data augmentation techniques and Markov chain Monte Carlo (MCMC) methods were applied to estimate SARS epidemiological parameters. In particular, estimates of daily reproduction numbers were provided for each subpopulation. The average duration of the SARS infectious period was estimated to be 9.3 days (±0.3 days). The model was able to disentangle the impact of the two SSEs from background transmission rates. The effective contact rates, which were estimated on a daily basis, decreased with time, reaching zero inside hospitals. This observation suggests that public health measures and possible changes in individual behaviors effectively reduced transmission, especially in hospitals. The temporal patterns of reproduction numbers were similar for healthcare workers and the general population, indicating that on average, an infectious healthcare worker did not infect more people than any other infectious person. We provide a general method to estimate time dependence of parameters in structured epidemic models, which enables investigation of the impact of control measures and behavioral changes in different settings. © 2009 Cori et al.published_or_final_versio

Toward unsupervised outbreak detection through visual perception of new patterns

<p>Abstract</p> <p>Background</p> <p>Statistical algorithms are routinely used to detect outbreaks of well-defined syndromes, such as influenza-like illness. These methods cannot be applied to the detection of emerging diseases for which no preexisting information is available.</p> <p>This paper presents a method aimed at facilitating the detection of outbreaks, when there is no a priori knowledge of the clinical presentation of cases.</p> <p>Methods</p> <p>The method uses a visual representation of the symptoms and diseases coded during a patient consultation according to the International Classification of Primary Care 2^ndversion (ICPC-2). The surveillance data are transformed into color-coded cells, ranging from white to red, reflecting the increasing frequency of observed signs. They are placed in a graphic reference frame mimicking body anatomy. Simple visual observation of color-change patterns over time, concerning a single code or a combination of codes, enables detection in the setting of interest.</p> <p>Results</p> <p>The method is demonstrated through retrospective analyses of two data sets: description of the patients referred to the hospital by their general practitioners (GPs) participating in the French Sentinel Network and description of patients directly consulting at a hospital emergency department (HED).</p> <p>Informative image color-change alert patterns emerged in both cases: the health consequences of the August 2003 heat wave were visualized with GPs' data (but passed unnoticed with conventional surveillance systems), and the flu epidemics, which are routinely detected by standard statistical techniques, were recognized visually with HED data.</p> <p>Conclusion</p> <p>Using human visual pattern-recognition capacities to detect the onset of unexpected health events implies a convenient image representation of epidemiological surveillance and well-trained "epidemiology watchers". Once these two conditions are met, one could imagine that the epidemiology watchers could signal epidemiological alerts, based on "image walls" presenting the local, regional and/or national surveillance patterns, with specialized field epidemiologists assigned to validate the signals detected.</p

Survival Analysis to Estimate Association between Short-Term Mortality and Air Pollution

BACKGROUND: Ecologic studies are commonly used to report associations between short-term air pollution and mortality. In such studies, the unit of observation is the day rather than the individual. Moreover, individual data on the subjects are rarely available, which limits the assessment of individual risk factors. These associations can also be investigated using case–crossover studies. However, by definition, individual risk factors are not studied, and such studies analyze only dead subjects, which limits the statistical power. OBJECTIVE: We suggest that the survival analysis is more suitable when cohorts are examined with a time-dependent ecologic exposure. To our knowledge, to date this type of analysis has never been proposed. DESIGN, PARTICIPANTS, MEASUREMENTS: In the present study we used a Cox proportional hazards model to investigate the distribution over time of the short-term effect of black smoke and sulfur dioxide in 439 nonaccidental and 158 cardiorespiratory deaths among the 1,469 subjects of the Personnes Agées QUID (PAQUID) cohort in Bordeaux, France. The model has a delayed entry and a polynomial distributed lag from 0 to 5 days. Results are adjusted for individual risk factors, temperature, relative humidity, weekday, season, influenza epidemics, and a time function to control temporal trends. RESULTS: We identified a positive and significant association between cardiorespiratory mortality and black smoke, with a 24% increase in deaths 3 days after a 10-μg/m(3) increase in black smoke (95% confidence interval, 4–47%). CONCLUSIONS: We conclude that the Cox proportional hazards model with time-dependent covariates is very suitable to investigate simultaneously the short-term effect of air pollution on health and the effect of individual risk factors on a cohort study

Epidemiological evidence of higher susceptibility to vCJD in the young

BACKGROUND: The strikingly young age of new variant Creutzfeldt-Jacob disease (vCJD) cases remains unexplained. Age dependent susceptibility to infection has been put forward, but differential dietary exposure to contaminated food products in the UK population according to age and sex during the bovine spongiform encephalopathy (BSE) epidemic may provide a simpler explanation. METHODS: Using recently published estimates of dietary exposure in mathematical models of the epidemiology of the new variant Creutzfeldt Jacob disease (vCJD), we examine whether the age characteristics of vCJD cases may be reproduced. RESULTS: The susceptibility/exposure risk function has likely peaked in adolescents and was followed by a sharp decrease with age, evocative of the profile of exposure to bovine material consumption according to age. However, assuming that the risk of contamination was proportional to exposure, with no age dependent susceptibility, the model failed to reproduce the observed age characteristics of the vCJD cases: The predicted cumulated proportion of cases over 40 years was 48%, in strong disagreement with the observed 10%. Incorporating age dependent susceptibility led to a cumulated proportion of cases over 40 years old of 12%. CONCLUSIONS: This analysis provides evidence that differential dietary exposure alone fails to explain the pattern of age in vCJD cases. Decreasing age related susceptibility is required to reproduce the characteristics of the age distribution of vCJD cases

The Relation Between Temperature, Ozone, and Mortality in Nine French Cities During the Heat Wave of 2003

BACKGROUND: During August 2003, record high temperatures were observed across Europe, and France was the country most affected. During this period, elevated ozone concentrations were measured all over the country. Questions were raised concerning the contribution of O(3) to the health impact of the summer 2003 heat wave. METHODS: We used a time-series design to analyze short-term effects of temperature and O(3) pollution on mortality. Counts of deaths were regressed on temperatures and O(3) levels, controlling for possible confounders: long-term trends, season, influenza outbreaks, day of the week, and bank holiday effects. For comparison with previous results of the nine cities, we calculated pooled excess risk using a random effect approach and an empirical Bayes approach. FINDINGS: For the nine cities, the excess risk of death is significant (1.01%; 95% confidence interval, 0.58–1.44) for an increase of 10 μg/m(3) in O(3) level. For the 3–17 August 2003 period, the excess risk of deaths linked to O(3) and temperatures together ranged from 10.6% in Le Havre to 174.7% in Paris. When we compared the relative contributions of O(3) and temperature to this joint excess risk, the contribution of O(3) varied according to the city, ranging from 2.5% in Bordeaux to 85.3% in Toulouse. INTERPRETATION: We observed heterogeneity among the nine cities not only for the joint effect of O(3) and temperatures, but also for the relative contribution of each factor. These results confirmed that in urban areas O(3) levels have a non-negligible impact in terms of public health

Modelers' Perception of Mathematical Modeling in Epidemiology: A Web-Based Survey

International audienceBackground: Mathematical modeling in epidemiology (MME) is being used increasingly. However, there are many uncertainties in terms of definitions, uses and quality features of MME. Methodology/Principal Findings: To delineate the current status of these models, a 10-item questionnaire on MME was devised. Proposed via an anonymous internet-based survey, the questionnaire was completed by 189 scientists who had published in the domain of MME. A small minority (18%) of respondents claimed to have in mind a concise definition of MME. Some techniques were identified by the researchers as characterizing MME (e.g. Markov models), while others–at the same level of sophistication in terms of mathematics–were not (e.g. Cox regression). The researchers' opinions were also contrasted about the potential applications of MME, perceived as higly relevant for providing insight into complex mechanisms and less relevant for identifying causal factors. The quality criteria were those of good science and were not related to the size and the nature of the public health problems addressed. Conclusions/Significance: This study shows that perceptions on the nature, uses and quality criteria of MME are contrasted, even among the very community of published authors in this domain. Nevertheless, MME is an emerging discipline in epidemiology and this study underlines that it is associated with specific areas of application and methods. The development of this discipline is likely to deserve a framework providing recommendations and guidance at various steps of the studies, from design to report

Uncertainty in the Tail of the Variant Creutzfeldt-Jakob Disease Epidemic in the UK

Despite low case numbers the variant Creutzfeldt-Jakob disease epidemic poses many challenges for public health planning due to remaining uncertainties in disease biology and transmission routes. We develop a stochastic model for variant CJD transmission, taking into account the known transmission routes (food and red-cell transfusion) to assess the remaining uncertainty in the epidemic. We use Bayesian methods to obtain scenarios consistent with current data. Our results show a potentially long but uncertain tail in the epidemic, with a peak annual incidence of around 11 cases, but the 95% credibility interval between 1 and 65 cases. These cases are predicted to be due to past food-borne transmissions occurring in previously mostly unaffected genotypes and to transmissions via blood transfusion in all genotypes. However, we also show that the latter are unlikely to be identifiable as transfusion-associated cases by case-linking. Regardless of the numbers of future cases, even in the absence of any further control measures, we do not find any self-sustaining epidemics

Modelling the Effects of Population Structure on Childhood Disease: The Case of Varicella

Realistic, individual-based models based on detailed census data are increasingly used to study disease transmission. Whether the rich structure of such models improves predictions is debated. This is studied here for the spread of varicella, a childhood disease, in a realistic population of children where infection occurs in the household, at school, or in the community at large. A methodology is first presented for simulating households with births and aging. Transmission probabilities were fitted for schools and community, which reproduced the overall cumulative incidence of varicella over the age range of 0–11 years old

Prominent and Persistent Extraneural Infection in Human PrP Transgenic Mice Infected with Variant CJD

Background. The evolution of the variant Creutzfeldt-Jakob disease (vCJD) epidemic is hazardous to predict due to uncertainty in ascertaining the prevalence of infection and because the disease might remain asymptomatic or produce an alternate, sporadic-like phenotype. Methodology/Principal Findings. Transgenic mice were produced that overexpress human prion protein with methionine at codon 129, the only allele found so far in vCJD-affected patients. These mice were infected with prions derived from variant and sporadic CJD (sCJD) cases by intracerebral or intraperitoneal route, and transmission efficiency and strain phenotype were analyzed in brain and spleen. We showed that i) the main features of vCJD infection in humans, including a prominent involvement of the lymphoid tissues compared to that in sCJD infection were faithfully reproduced in such mice; ii) transmission of vCJD agent by intracerebral route could lead to the propagation of either vCJD or sCJD-like prion in the brain, whereas vCJD prion was invariably propagated in the spleen, iii) after peripheral exposure, inefficient neuroinvasion was observed, resulting in an asymptomatic infection with life-long persistence of vCJD prion in the spleen at stable and elevated levels. Conclusion/Significance. Our findings emphasize the possibility that human-to-human transmission of vCJD might produce alternative neuropathogical phenotypes and that lymphoid tissue examination of CJD cases classified as sporadic might reveal an infection by vCJD-type prions. They also provide evidence for the strong propensity of this agent to establish long-lasting, subclinical vCJD infection of lymphoreticular tissues, thus amplifying the risk for iatrogenic transmission

Human Prion Diseases in the United States

BACKGROUND: Prion diseases are a family of rare, progressive, neurodegenerative disorders that affect humans and animals. The most common form of human prion disease, Creutzfeldt-Jakob disease (CJD), occurs worldwide. Variant CJD (vCJD), a recently emerged human prion disease, is a zoonotic foodborne disorder that occurs almost exclusively in countries with outbreaks of bovine spongiform encephalopathy. This study describes the occurrence and epidemiology of CJD and vCJD in the United States. METHODOLOGY/PRINCIPAL FINDINGS: Analysis of CJD and vCJD deaths using death certificates of US residents for 1979-2006, and those identified through other surveillance mechanisms during 1996-2008. Since CJD is invariably fatal and illness duration is usually less than one year, the CJD incidence is estimated as the death rate. During 1979 through 2006, an estimated 6,917 deaths with CJD as a cause of death were reported in the United States, an annual average of approximately 247 deaths (range 172-304 deaths). The average annual age-adjusted incidence for CJD was 0.97 per 1,000,000 persons. Most (61.8%) of the CJD deaths occurred among persons >or=65 years of age for an average annual incidence of 4.8 per 1,000,000 persons in this population. Most deaths were among whites (94.6%); the age-adjusted incidence for whites was 2.7 times higher than that for blacks (1.04 and 0.40, respectively). Three patients who died since 2004 were reported with vCJD; epidemiologic evidence indicated that their infection was acquired outside of the United States. CONCLUSION/SIGNIFICANCE: Surveillance continues to show an annual CJD incidence rate of about 1 case per 1,000,000 persons and marked differences in CJD rates by age and race in the United States. Ongoing surveillance remains important for monitoring the stability of the CJD incidence rates, and detecting occurrences of vCJD and possibly other novel prion diseases in the United States