Local and regional spread of chikungunya fever in the Americas.

Chikungunya fever (CHIKV), a viral disease transmitted by mosquitoes, is currently affecting several areas in the Caribbean. The vector is found in the Americas from southern Florida to Brazil, and the Caribbean is a highly connected region in terms of population movements. There is therefore a significant risk for the epidemic to quickly expand to a wide area in the Americas. Here, we describe the spread of CHIKV in the first three areas to report cases and between areas in the region. Local transmission of CHIKV in the Caribbean is very effective, the mean number of cases generated by a human case ranging from two to four. There is a strong spatial signature in the regional epidemic, with the risk of transmission between areas estimated to be inversely proportional to the distance rather than driven by air transportation. So far, this simple distance-based model has successfully predicted observed patterns of spread. The spatial structure allows ranking areas according to their risk of invasion. This characterisation may help national and international agencies to optimise resource allocation for monitoring and control and encourage areas with elevated risks to act.

Assessment of the Middle East respiratory syndrome coronavirus (MERS-CoV) epidemic in the Middle East and risk of international spread using a novel maximum likelihood analysis approach.

The emergence of the novel Middle East (ME) respiratory syndrome coronavirus (MERS-CoV) has raised global public health concerns regarding the current situation and its future evolution. Here we propose an integrative maximum likelihood analysis of both cluster data in the ME and importations in a set of European countries to assess the transmission scenario and incidence of sporadic infections. Our approach is based on a spatial-transmission model integrating mobility data worldwide and allows for variations in the zoonotic/environmental transmission and under-ascertainment. Maximum likelihood estimates for the ME, considering outbreak data up to 31 August 2013, indicate the occurrence of a subcritical epidemic with a reproductive number R of 0.50 (95% confidence interval (CI): 0.30-0.77) associated with a daily rate of sporadic introductions psp of 0.28 (95% CI: 0.12-0.85). Infections in the ME appear to be mainly dominated by zoonotic/environmental transmissions, with possible under-ascertainment (ratio of estimated to observed (0.116) sporadic cases equal to 2.41, 95% CI: 1.03-7.32). No time evolution of the situation emerges. Analyses of flight passenger data from ME countries indicate areas at high risk of importation. While dismissing an immediate threat for global health security, this analysis provides a baseline scenario for future reference and updates, suggests reinforced surveillance to limit under-ascertainment, and calls for alertness in high importation risk areas worldwide.

Cost and cost-effectiveness of childhood vaccination against rotavirus in France.

OBJECTIVES: To assess the effectiveness and cost-effectiveness of routine childhood vaccination by new vaccines against rotavirus in France. METHODS: We constructed a Markov decision tree to compare two alternatives: "no vaccination" and "vaccination". A hypothetical birth cohort of 750,000 children was followed until 3 years of age. First, the disease burden without vaccine was estimated using data from French databases and medical literature. Incidence rates in unvaccinated children were modelled as a function of age and seasons. Next, using data from the medical literature, the vaccine's protective effect on rotavirus diarrhoea was considered. RESULTS: A routine universal rotavirus immunization programme was estimated capable of annually avoiding 89,000 cases of diarrhoea, 10,500 hospitalizations, and 8 deaths. At a vaccination cost of euro 150/course, assuming 75% vaccine coverage, the programme would cost euro 95 million and involve a net loss of euro 68 million to the health care system. The vaccination programme would cost euro 298,000/year of life saved, and euro 138,000/QALY saved. Key variables affecting the results were disease incidence, mortality rates and vaccine price. CONCLUSION: In France, childhood rotavirus vaccination with new anti-rotavirus vaccines would reduce the morbidity burden of rotavirus infection, but would not be cost-effective unless the price of vaccine decreased considerably.

[Morbidity and cost of rotavirus infections in France]. / Morbidité et coût des infections à rotavirus en France.

BACKGROUND: Rotavirus is the most common cause of severe diarrhea in children. Morbidity and mortality related to rotavirus infection is not well known in temperate countries in general, and in France in particular. OBJECTIVES: The aim of this study was estimate the morbidity, mortality, and cost related to the rotavirus infection in France, in order to assess the potential impact of a vaccination program. METHODS: A birth cohort was followed until 5 years of age using a decision tree model. Rotavirus infection incidence rates were modeled according to age, seasons, and breast-feeding status. RESULTS: Based on estimates from a decision model, we found that in France, rotavirus infection was responsible for 300,000 annual episodes of acute diarrhea, 138,000 visits to general practitioners, 18,000 hospitalizations, and 9 deaths. The annual direct cost related to rotavirus infection care was estimated at 28 million euros. CONCLUSION: This study demonstrates the high morbidity and cost of care associated with rotavirus infection in France. The decision tree model developed in this study could be used in the future to estimate the potential effectiveness, cost and cost-effectiveness of childhood vaccination strategies using new rotavirus vaccines.

Area-level determinants of specialty care utilization in France: a multilevel analysis.

OBJECTIVES: We investigated the effects of the density of specialists and of the area-level percentage of highly educated individuals on the odds of consulting a specialist, and examined whether these variables could explain the observed urban/rural contrast in utilization of specialty care. STUDY DESIGN: The study sample, representative of the French population aged 18-75 years in 1999, comprised 12,435 individuals. METHODS: Multilevel logistic models allowed us to investigate predictors of the odds of consulting a specialist occasionally, regularly and frequently over the previous 12 months. RESULTS: We observed a modest but significant clustering within areas of the utilization of specialty care, with higher levels of clustering for behaviours representing heavy consumption of care. After adjustment for individual factors, the odds of consulting a specialist were higher in larger cities compared with rural areas, but most of this effect was attributable to other area-level variables. These area-level effects were different in magnitude and nature among males and females. Among males, the odds of consulting a specialist increased with the area-level density of specialists. Among females, such an effect was not significant, but the odds of consulting a specialist increased with the area-level percentage of highly educated individuals. CONCLUSIONS: Further investigation is required to better understand the processes operating at the area level that were shown to affect healthcare utilization in a different way for males and females. Policies may be needed to address problems of geographical access to specialty care, as well as situations of overuse of specialty care without regular recourse to primary care.

A Bayesian MCMC approach to study transmission of influenza: application to household longitudinal data.

We propose a transmission model to estimate the main characteristics of influenza transmission in households. The model details the risks of infection in the household and in the community at the individual scale. Heterogeneity among subjects is investigated considering both individual susceptibility and infectiousness. The model was applied to a data set consisting of the follow-up of influenza symptoms in 334 households during 15 days after an index case visited a general practitioner with virologically confirmed influenza. Estimating the parameters of the transmission model was challenging because a large part of the infectious process was not observed: only the dates when new cases were detected were observed. For each case, the data were augmented with the unobserved dates of the start and the end of the infectious period. The transmission model was included in a 3-levels hierarchical structure: (i) the observation level ensured that the augmented data were consistent with the observed data, (ii) the transmission level described the underlying epidemic process, (iii) the prior level specified the distribution of the parameters. From a Bayesian perspective, the joint posterior distribution of model parameters and augmented data was explored by Markov chain Monte Carlo (MCMC) sampling. The mean duration of influenza infectious period was estimated at 3.8 days (95 per cent credible interval, 95 per cent CI [3.1,4.6]) with a standard deviation of 2.0 days (95 per cent CI [1.1,2.8]). The instantaneous risk of influenza transmission between an infective and a susceptible within a household was found to decrease with the size of the household, and established at 0.32 person day(-1) (95 per cent CI [0.26,0.39]); the instantaneous risk of infection from the community was 0.0056 day(-1) (95 per cent CI [0.0029,0.0087]). Focusing on the differences in transmission between children (less than 15 years old) and adults, we estimated that the former were more likely to transmit than adults (posterior probability larger than 99 per cent), but that the mean duration of the infectious period was similar in children (3.6 days, 95 per cent CI [2.3,5.2]) and adults (3.9 days, 95 per cent CI [3.2,4.9]). The posterior probability that children had a larger community risk was 76 per cent and the posterior probability that they were more susceptible than adults was 79 per cent.

[An epidemiological model of genital herpes for assessment of potential impact of therapy and prophylaxis: application to France]. / Un modèle épidémiologique de l'herpès génital pour l'évaluation des interventions thérapeutiques et prophylactiques.

OBJECTIVES: This study was performed to quantify the development of the number of cases of genital herpes and to assess the impact of different treatment strategies in France. METHOD: A model for the natural history of herpes simplex virus genital infection is presented and applied to the French population. The model encompasses infection by herpes simplex virus type 1 (HSV-1) or type 2 (HSV-2), first episodes, recurrences, viral shedding and the effect of treatment on infected individuals. RESULTS: In the Year 2000, 270,000 individuals would have suffered from genital herpes in France. A total annual cumulated number of 1.5 million episodes of recurrence and 23 million days of viral shedding were estimated. Seventy percent of viral shedding occurred in sub-clinical seropositive individuals. The expected number of attributable neonatal deaths remained very low. Systematic treatment of clinical episodes might reduce the number of days with lesions (- 27 p. 100), and is also effective on viral shedding (symptomatic: - 50 p. 100). Continuous treatment of the most severe patients (>or=6 recurrences per Year) might reduce viral shedding slightly more (- 85 p. 100). Antiviral treatment might have a major impact on the quality of life of these patients but would only slightly curb the number of new infections. DISCUSSION: This model tries to integrate the various data currently available at international level on the epidemiology of genital herpes. However, many aspects are still not well documented and remain uncertain. It is therefore necessary to define various assumptions in order to simulate the natural history of the disease in a population. The lack of French data especially on the HSV-1 and HSV-2 seroprevalence profiles reinforces these uncertainties. Our results should hence be considered as exploratory. However, this modeling approach is the only possible way to integrate the multiple parameters describing the pathology and predicting of the public health impact of different interventions. This model is an open tool which may be modified when new data become available.

Blue light dose distribution and retinitis pigmentosa visual field defects: an hypothesis.

The hypothesis that retinitis pigmentosa (RP) is worsened by blue light has been raised a century ago. In order to check this hypothesis we calculated the theoretical dose distribution of light on the retinal surface. The relative dose to the different parts of the retina was calculated using a Monte-Carlo method. The changes in the peripheral isopters were calculated both degrading at a constant rate and degrading proportionally to light exposure. There is a considerably greater exposure to the superior compared to the inferior visual field. The maximum dose of UV and blue light is located on the superior field about 4mm above the macula. The dose received by the peripheral retina is markedly lower than the dose received by the central retina. The visual field defects most commonly described in RP are concentric, centered by the macula. These defects cannot, therefore, be explained by the impact of light on the retina. But some regional form of RP with a superior field defect can result from an abnormal genetically encoded sensitivity to ultraviolet and blue light.

Comparison of the statistical efficiency of case-crossover and case-control designs: application to severe cutaneous adverse reactions.

Although case-crossover analyses have lately emerged as an alternative to case-control analyses in epidemiological studies, it is not yet known in which situations they give reliable conclusions. In this work, the case-crossover and the case-control designs were first compared on the basis of a dataset from a published study of severe cutaneous adverse reactions resulting from drug exposures of various durations and prevalences of use (245 cases, 1147 controls, and exposures to 23 drug classes). Next, the statistical efficiency of each design was compared via Monte Carlo simulations. Eight of the 13 risk factors identified by case-control analysis of the published data were also identified by the case-crossover analysis, with fairly good agreement on ranks of risk estimates (Spearman's correlation coefficient = 0.71, P < 0.001 ). Simulation studies showed that for relative risks below 8, the case-crossover design (250 cases, 4 control periods/case) had a higher power than the case-control design (250 cases, 4 controls/case), and that the case-crossover design was more conservative than the case-control design for prevalences of drug use below 10%. We conclude that the case-crossover design is not suitable for long-term exposures, but is an appropriate alternative for assessing rare risks associated with transient to short-term exposures.

The control chart: an epidemiological tool for public health monitoring.

The objective of the authors is to apply the control chart, a statistical method for quality control used in industry, to public health surveillance. A pilot study was conducted during the 1998 World Football Cup (WFC) by 553 sentinel general practitioners (GPs) throughout France. The average number of cases of communicable, environmental and societal diseases relating to mass gatherings, and the total number of referrals to hospital reported daily by a GP, were plotted on a u-chart for each condition monitored. This average was beyond the statistical control limits if it fell outside the 99.7% confidence interval of the baseline incidences estimated before the WFC. Seven hundred and forty data points representing 262 279 medical encounters were plotted. Nineteen points exceeded the statistical control limits. None of these alerts was confirmed for two consecutive days. Control charts ensured that the level of the items chosen for general community health surveillance remained under control.

Sentinel monitoring of general community health during the 1998 World Football Cup.

BACKGROUND: Present knowledge of the consequences of mass gatherings for the health of the community is scant. Our objective was to determine the impact of the 1998 World Football Cup on general community health. METHODS: We set up an electronic sentinel disease surveillance, before, during and after the World Football Cup tournament held in France from June 10 to July 12, 1998. Medical activity, and the daily number of cases of communicable, environmental, and societal diseases relating to mass gatherings were surveyed. The incidence of the pathologies surveyed in real time during and after the World Cup versus the pre-Cup reference period was the main outcome measure. Five sentinel networks participated, comprising 553 general practitioners, 60 hospital adult emergency departments, 19 private emergency community services, 4 community health centres, and the medical centre of the Paris airports. RESULTS: Throughout the 66-day study period, physicians reported 558,829 medical encounters via 21,532 connections to the computer. Compared to the reference period, the level of medical activity reflected by the pathological items surveyed remained stable during the study period. CONCLUSION: The 1998 World Football Cup had no epidemiological impact on general community health, as observed by sentinel networks located downstream of the specific health services provided by the French authorities to ensure high standards of safety.

Voluntary reporting system in anaesthesia: is there a link between undesirable and critical events?

BACKGROUND: Reporting systems in anaesthesia have generally focused on critical events (including death) to trigger investigations of latent and active errors. The decrease in the rate of these critical events calls for a broader definition of significant anaesthetic events, such as hypotension and bradycardia, to monitor anaesthetic care. The association between merely undesirable events and critical events has not been established and needs to be investigated by voluntary reporting systems. OBJECTIVES: To establish whether undesirable anaesthetic events are correlated with critical events in anaesthetic voluntary reporting systems. METHODS: As part of a quality improvement project, a systematic reporting system was implemented for monitoring 32 events during elective surgery in our hospital in 1996. The events were classified according to severity (critical/undesirable) and nature (process/outcome) and control charts and logistic regression were used to analyse the data. RESULTS: During a period of 30 months 22% of the 6439 procedures were associated with anaesthetic events, 15% of which were critical and 31% process related. A strong association was found between critical outcome events and critical process events (OR 11.5 (95% confidence interval (CI) 4.4 to 27.8)), undesirable outcome events (OR 4.8 (95% CI 2.0 to 11.8)), and undesirable process events (OR 4.8 (95% CI 1.3 to 13.4)). For other classes of events, risk factors were related to the course of anaesthesia (duration, occurrence of other events) and included factors determined during the pre-anaesthetic visit (risk of haemorrhage, difficult intubation or allergic reaction). CONCLUSION: Undesirable events are associated with more severe events and with pre-anaesthetic risk factors. The way in which information on significant events can be used is discussed, including better use of preoperative information, reduction in the collection of redundant information, and more structured reporting.

SHARE: a tool to analyze and assess strategies in health care organization management.

In health care organizations, management of both human and material resources implies decision making. When seemingly equivalent strategies are possible, simulation can help to make a decision on better grounds. The SHARE workframe was designed to address the specificities of health care and to provide a comprehensive environment for modelling and simulating health care processes. The typology of objects is defined as Actors, subdivided in Clients and Resources and Elementary Operations. Graphical tools allow us to build processes from these objects and to create their relationships. Various strategies based on either clinical or managerial changes may be investigated. After a simulation, graphical tools allow us to display summary information on the utilization of all actors, waiting times, and goodness of execution. The use of SHARE is exemplified with the analysis and simulation of changes in the Pulmonary Function Testing Laboratory of the Saint-Antoine Hospital, Paris.

A sequential procedure to test the progressive decrease of rare adverse events.

A program to construct the Rapid Sequential Test (R-ST), a sequential procedure to test the decrease of the rate of rare adverse events, is described. This sequential procedure is constructed with the Sequential Probability Ratio method. It relies on a model for the progressive decrease in the rate of adverse events from a given initial rate to a target rate, during a transition period. The program allows one to calculate the bounds of rejection of the R-ST, and to study its power under various types of decrease. It is shown that the R-ST gives a conclusion faster than standard sequential procedures for the same type I and II error, saving at least one quarter of the trials completed during the transition period. The use of the software to construct R-STs is discussed with respect to the specification of the model.