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Biomedical subjects

A J Valleron

Publications and source records attributed to A J Valleron.

At least 19 recordsLinked to original sources

Modelling outbreak control for pneumonic plague.

Although pneumonic plague is listed by the Centers of Disease Control in the leading 'critical biological agents', very few studies exist on this subject. In this study, a mathematical compartment model was used to describe the geographical and temporal spread of an epidemic of pneumonic plague following its use as a biological weapon. Univariate and multivariate analyses were performed in order to assess the key parameters for the control of an outbreak in France. If interventions were taken 10 days after an attack, a reference scenario of 1000 index cases in Paris would lead to 2500 deaths. The results of the study indicate that the rapidity of onset of interventions has the largest effect on the final size of the epidemic, followed by wearing masks, treating contacts preventively and quarantine. Limiting inter-regional mixing does little to reduce casualties, although it does confine them to a single region.

Disease Outbreaks↗

Understanding the dynamics of Ebola epidemics.

Ebola is a highly lethal virus, which has caused at least 14 confirmed outbreaks in Africa between 1976 and 2006. Using data from two epidemics [in Democratic Republic of Congo (DRC) in 1995 and in Uganda in 2000], we built a mathematical model for the spread of Ebola haemorrhagic fever epidemics taking into account transmission in different epidemiological settings. We estimated the basic reproduction number (R0) to be 2.7 (95% CI 1.9-2.8) for the 1995 epidemic in DRC, and 2.7 (95% CI 2.5-4.1) for the 2000 epidemic in Uganda. For each epidemic, we quantified transmission in different settings (illness in the community, hospitalization, and traditional burial) and simulated various epidemic scenarios to explore the impact of control interventions on a potential epidemic. A key parameter was the rapid institution of control measures. For both epidemic profiles identified, increasing hospitalization rate reduced the predicted epidemic size.

Africa, Central↗

Can a second wave of new variant of the CJD be discarded in absence of observation of clinical non Met-Met cases?

BACKGROUND: Presently, all patients with clinical variant Creutzfeldt-Jakob disease in the United Kingdom have been Met-Met at codon 129 of the PrP gene. There is much worry about the possibility of a second wave of the epidemic in the 60% of the United Kingdom population which are not Met-Met. METHODS: A mathematical model of a putative United Kingdom variant Creutzfeldt-Jakob disease epidemic that could occur in non Met-Met is derived. The risk of infection is assumed to parallel the Met-Met risk which has been previously modelled. The reason for the present absence of clinical non Met-Met cases is assumed to be a longer incubation period in these subjects than in others. The incubation period is assumed to be lognormally distributed. The means and coefficients of variation compatible with the present absence of clinical cases are systematically searched. RESULTS: We show that the present absence of clinical cases of variant Creutzfeldt-Jakob disease in the Met-Val or Val-Val population can be compatible with a second wave only if the mean incubation period is more than 25 years. The best estimates of the size of the second wave are always below 250. A fraction of these cases however will never be observed, as they will die from other causes before the onset of the new variant. CONCLUSION: The mean incubation period values compatible with the absence of non Met-Met clinical cases that we found are not implausible, and the possibility of a second wave cannot yet be ruled out. However, should this second wave occur, it would be below 250 in the worst hypothesis.

Creutzfeldt-Jakob Syndrome↗

Virtual surveillance of communicable diseases: a 20-year experience in France.

Inserm has developed, since 1984, an information system based on a computer network of physicians in France. It allows for constitution of large databases on diseases, with individual description of cases, and to explore some aspects of the mathematical theory of communicable diseases. We developed user-friendly interfaces for remote data entry and GIS tools providing real-time atlas of the epidemiologic situation in any location. The continuous and ongoing surveillance network is constituted of about 1200 sentinel voluntary and unpaid investigators. We studied their motivation, reasons for either withdrawal or compliance using survival analyses. We implemented early warning systems for outbreak detection and for time-space forecasting. We conducted epidemiological surveys for investigating outbreaks. Large available time and space series allowed us to calibrate and explore synchronism of influenza epidemics, to test the assumption of panmixing in susceptibles-infectious-removed type models and to study the role of closing school in influenza morbidity and mortality in elderly. More than 250 000 cases of influenza, 150 000 cases of acute diarrheas, 35,000 patients for whom HIV tests have been prescribed by general practitioners and 25,000 cases of chickenpox have been collected. Detection of regional influenza or acute diarrhea outbreaks and forecasting of epidemic trends three weeks ahead are currently broadcasted to the French media and published on Sentiweb on a weekly basis. Age-cohort-period models assessed field effectiveness of mass immunization strategies against measles and influenza in the country. Case-control studies with more than 1200 sets of cases of acute diarrheas and their matched controls showed the role of calicivirus and rotavirus as probable major causes of gastroenteritis during recurrent widespread outbreaks in winter in France. An age-specific model for chickenpox showed the probable role of children in disease transmission to their susceptible parents or grandparents. High level of synchronism between influenza epidemics has been demonstrated, either at a regional level (in France) or between France and the USA. The designation of our lab as a WHO collaborating center for electronic disease surveillance stimulates the development of global monitoring of diseases. We developed operational systems that are now available for the global monitoring of influenza (FluNet), and human and animal rabies (RABNET). Extension of electronic syndromic surveillance is needed in the world for improving surveillance capacities and real-time response against emerging diseases.

Case-Control Studies↗

[The evaluation of health care outcomes and hospital performance indicators].

INTRODUCTION: The assessment of the performance of health care establishments has undergone a considerable development over the past 15 years in the United States and to a lesser extent in other developed countries. BACKGROUND: The aim of measurement of performance indicators is to improve the quality of care (outcomes), patient information and the contractual arrangements with purchasers. However, this approach poses numerous methodological problems in the choice of performance indicators as well as the collection and interpretation of data. Specific structural patterns such as social and geographic environment, research and educational assignments, are often inadequately considered. In terms of public health the impact of the publication of these measurements has not been well studied. Based on the data in the literature this revue defines the measures of hospital performance and describes the main studies, their impacts and limitations. VIEWPOINT: It seems likely that the French public authorities will, in the short term, ask health care establishments to undertake this approach. CONCLUSIONS: Complimentary studies are needed to clarify the links between performance indicators and health care outcomes.

Europe↗

Penicillin-resistant pneumococcal meningitis: high antibiotic exposure impedes new vaccine protection.

The frequency of meningitis due to penicillin-resistant Streptococcus pneumoniae (PRP) has increased in recent years, making treatment failure more likely. It is currently expected that pneumococcal conjugate vaccines might curb this trend. We investigated this issue using a mathematical model applied to the current prevalence of resistance and antibiotic exposure in the United States and in France. Our main finding was that the level of antibiotic exposure may limit the effect of the vaccine. In relatively low antibiotic exposure environments such as the United States, large-scale vaccination prevents a large part of PRP meningitis cases, whereas in high antibiotic-exposure environments such as France, vaccination alone does not lead to a substantial reduction in PRP meningitis incidence. Our results suggest that antibiotic exposure reduction will remain of primary importance for the control of PRP meningitis despite wide scale use of pneumococcal conjugate vaccines.

Adolescent↗

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.

Adolescent↗

Modelling responses to a smallpox epidemic taking into account uncertainty.

Epidemiology and modelling are currently under pressure to build consistent scenarios of control in case of deliberate release of biological weapons. In order to assess the key parameters for the control of a smallpox outbreak in a large city (2 million inhabitants), we built a stochastic model to simulate the course of an epidemic controlled by ring vaccination and case isolation. Assuming a reference scenario with 100 index cases and implementation of intervention 25 days after the attack, the model forecasts an epidemic of 730 cases with an epidemic duration of 240 days. Setting intervention 20 days later would result in an almost fourfold increase in the epidemic size. A multivariate sensitivity analysis has selected three key parameters: the basic reproduction number (i.e. the number of secondary cases infected by one case in an entirely susceptible population, equal to 3 in the reference scenario), time to intervention, and proportion of traced and vaccinated contacts.

Algorithms↗

[Complications due to peripheral venous catheterization. Prospective study].

OBJECTIVE: Peripheral venous catheter (PVC)-associated complications were prospectively evaluated in a 2 month-study performed in 3 different wards. METHODS: For each inserted PVC, the following complications were observed daily by an external investigator: tenderness, erythema, swelling or induration, palpable cord and purulence. PVC that were removed were systematically sent to the Microbiology department and analysed according to the semi-quantitative method described by Brun-Buisson et al. RESULTS: A total of 525 PVC (corresponding to 1,036 catheterisation-days) were included. Main clinical complications were erythema (22.1%), tenderness (21.9%), swelling or induration (20.9%), palpable cord (2.7%) and purulence (0.2%). Phlebitis, defined by 2 or more of the following signs: tenderness, erythema, swelling or induration and palpable cord, was observed in 22%. Catheter colonization (> or = 103 CFU/ml) occurred in 13%. Bacteria isolated from colonized catheters were coagulase-negative staphylococci (88.1%), Staphylococcus aureus (7.1%) and Candida sp. (4.8%). Multivariate risk factor analysis showed that age > or = 55 y. (OR = 3.16, p = 0.003), insertion on articulation site (OR = 2.94, p = 0.01) or in jugular vein (OR = 8.18, p = 0.01) and > 72 hour-catheterisation (OR = 4.74, p = 0.0003) were significantly associated with PVC colonization. Risk factors for phlebitis were skin lesions (OR = 1.88, p < 0.016), active infection unrelated to PVC (OR = 2.8, p = 0.001), "poor quality" peripheral vein (OR = 2.46, p < 0.02) and > 72 hour-catherisation (OR = 2.38, p = 0.009). CONCLUSION: Complications associated with peripheral venous catheters are frequent but remain benign. They could probably be reduced by a systematic change every 72-96 hours as recommended by different guidelines.

Adolescent↗

A mathematical model for evaluating the impact of vaccination schedules: application to Neisseria meningitidis.

A mathematical model is described which determines the impact of a schedule of vaccination on the time course of a certain class of diseases. The data are the demographic variables and parameters and age-dependent non-fatal and fatal case rates. Given the age- and time-dependent rates of vaccination including coverage and corresponding efficacies, various schedules may be distinguished by either the absolute numbers of cases and deaths avoided or the numbers of cases and deaths avoided per dose of vaccine. The model was applied to meningo-coccal serogroup C disease in France. The outcomes of six different vaccination schedules were examined. In absolute terms, a schedule in which all individuals aged between 2 and 20 years were vaccinated performed best, but this schedule and that in which only 1-year olds were vaccinated performed equally and best in terms of cases prevented, but not lives saved, per dose.

Adolescent↗

Estimation of epidemic size and incubation time based on age characteristics of vCJD in the United Kingdom.

The size of the variant Creutzfeldt-Jakob Disease (vCJD) epidemic in the United Kingdom is a major public health concern and a subject of speculation. The cases are young (mean age = 28). Assuming that the risk of developing the disease in susceptible exposed subjects decreases exponentially with age after age 15, that all infections occurred between 1980 and 1989, and that the distribution of the incubation period is lognormal, we estimate that the mean duration of the incubation period is 16.7 years [95% confidence interval (CI): 12.4 to 23.2] and that the total number of cases will be 205 (upper limit of the 95% CI: 403).

Adolescent↗

An integrated system for significant anaesthetic events monitoring.

Patient safety assessment in anaesthesia increasingly relies on the monitoring of frequent but merely undesirable events, like hypotension. We report on the design and implementation of such a monitoring system, where 8032 patients were included over a three years period. Thirty two 'Significant Anaesthetic Events' were defined and their occurrence was routinely collected for each patient. A total of 2106 significant anaesthetic events were reported. The data were analysed using control charts, which showed that an undesirable event was recorded in 1 out of 4 interventions. The control chart showed that the incidence of significant anaesthetic events was out of the expected boundaries during one month. The system sensitivity to change in the frequency of significant anaesthetic events was investigated by a controlled intervention, designed to increase the incidence of bradycardia by changing anxyolitic medication. During the intervention, the incidence of bradycardia doubled, while the incidence of other undesirable events was not affected. The system described for the collection of significant anaesthetic events was easy to set up, sensitive to changes and provided valuable tools in performance monitoring.

Anesthesia↗

[The roles for modeling in epidemiology].

Mathematical modelling in epidemiology was pioneered by D. Bernoulli in 1760 in his work demonstrating the effectiveness of the technique of variolation against smallpox. Mathematical epidemiology concerns presently infectious diseases (such as HIV infection, hepatitis C, Prion diseases, influenza, etc.) as well as non-infectious diseases (e.g. cancer). The roles of modelling in epidemiology are: 1) description of complex data in order to facilitate the dissemination of results; 2) demonstration of general laws governing the dynamics of epidemics; 3) estimation of the values of parameters that cannot be directly measured; 4) prediction of future disease burdens; 5) selection of optimal experimental designs.

Adult↗

[Demonstration of the facts and research of the causes in environmental epidemiology: methodological aspects].

There are usually three major steps in the study of the possible impact of environmental factors on health: 1) to demonstrate that there is an association between exposure to the factor and the disease under study; 2) to demonstrate that this association is causal; 3) to evaluate the health benefit that could be obtained by removing the source of exposure. Statistical methods are commonly assumed to provide an objective way of achieving these three steps. This paper reviews some of the conditions that have to be met to allow proper interpretations and to avoid some of the controversies that are often found in health-environment studies. First, it should be remembered that the so-called P value which is used to qualify 'statistically significant' associations between risk factors and diseases does not give any indication of the probability that this association is actual, while far too often it is believed that it does. The probability that an association between an environmental factor and a disease is real could, however, be estimated by using Bayesian methods. These methods require that the a priori probabilities be stated, which is difficult to do in practice. Some directions to overcome this difficulty are presented. Second, the analysis of causality cannot be carried out on statistical grounds alone and the so-called 'causality criteria' are of limited practical interest. Definition of what is a cause, and upon which conditions a candidate factor of a disease can be considered as a cause, deserves much research effort, and careful consideration of the huge literature (mostly outside of the epidemiological field, for example in logic) which is devoted to this subject. Finally, the measurement of the role of a factor in a disease is very often assessed through the use of 'attributable fraction' or 'attributable mortality'. This should be done only when it is demonstrated that the considered factor is causal. Moreover, the interpretation of attributable fractions to a specific factor may be difficult in the (general) case where there are multiple causal factors implied in the development of the disease. Demographic measures of 'potential years (or days, etc.) of life lost' should in general be used, rather than 'numbers of deaths' to quantify the possible impact of environmental factors. Also, as the personal factors are generally extremely important in the determinism of the causes of death associated to environmental factors, and as they cannot be controlled through ecological studies, epidemiological designs where these cofactors can be evaluated individually on cases and controls should be preferred.

Disease↗

Modeling the hepatitis C virus epidemic in France.

A backcalculation approach allows a reconstruction of the history of hepatitis C virus (HCV) infection in France and predictions of mortality from hepatocellular carcinoma (HCC) related to the virus. The model uses information from the literature about the natural history of the disease, epidemiological data about infected subjects in three French cohorts, and mortality data from national statistics. It seeks to determine the annual transition probabilities from chronic hepatitis to cirrhosis and the HCV incidence per year in the past. These unknowns are found by fitting the observed deaths from HCC that are attributable to HCV. Optimal values for these unknowns then allow to project the number of HCC deaths attributable to HCV for each year through 2025 (for patients infected before 1996). The model traces the HCV epidemic in France back to around the 1940s. It predicts that HCC mortality related to HCV will continue to increase through 2020 in the absence of treatment, with a 150% increase in the yearly incidence among men and 200% among women. The model also confirms that progression to cirrhosis depends strongly on sex and age. At any age, the annual probability of progression is 10 times greater for men than for women. Moreover, for men aged between 61 and 70 years, this probability is 300 times greater than that for men aged between 21 and 40 years.

Adult↗

Risk of hepatitis C virus transmission to surgeons and nurses from infected patients: model-based estimates in France.

BACKGROUND/AIM: The aim of this study was to estimate the annual number of cases of hepatitis C virus transmission from infected patients to uninfected surgeons or nurses due to percutaneous injury during invasive procedures. METHODS: The risk of transmission was estimated using a model involving three probabilities: A, that a health care worker sustains at least one percutaneous injury during a procedure; B, that 1 to 10% of patients are seropositive for hepatitis C virus; and C, that infection by this virus is transmitted to the Health Care Worker after such exposure. Probability A was estimated from the results of 2 French multicentric prospective trials. Probability C was estimated from the results of 9 international prospective studies. A ten-fold decreased risk was assumed for surgeons who wear gloves and use solid-bore suture needles. RESULTS: During a single procedure, the estimated probability of hepatitis C virus transmission from an infected patient to an uninfected surgeon ranged from 4.2x10(-5)% to 4.2x10(-4)%, and from 2.98x10(-6)% to 2.98x10(-5)% to an uninfected nurse. For surgeons, the estimated annual cumulative risk of occupational infection ranged from 0.01% to 0.1% (1 in 10000 to 1 in 1000), and for nurses from 0.0054% to 0.054% (1 in 18700 to 1 in 1900). CONCLUSIONS: Between 2 and 21 surgeons out of a total 20000 are estimated to acquire occupationally-related hepatitis C virus infection, and between 16 and 167 nurses out of a total 300000. These estimates strongly justify introducing preventive measures to protect health care workers from bloodborne infection.

France↗