Biomedical subjects

Antoine Flahault

Publications and source records attributed to Antoine Flahault.

At least 19 recordsLinked to original sources

PubMed2006

Key strategies for reducing spread of avian influenza among commercial poultry holdings: lessons for transmission to humans.

Recent avian flu epidemics (A/H5N1) in Southeast Asia and case reports from around the world have led to fears of a human pandemic. Control of these outbreaks in birds would probably lead to reduced transmission of the avian virus to humans. This study presents a mathematical model based on stochastic farm-to-farm transmission that incorporates flock size and spatial contacts to evaluate the impact of control strategies. Fit to data from the recent epidemic in the Netherlands, we evaluate the efficacy of control strategies and forecast avian influenza dynamics. Our results identify high-risk areas of spread by mapping of the farm level reproductive number. Results suggest that an immediate depopulation of infected flocks following an accurate and quick diagnosis would have a greater impact than simply depopulating surrounding flocks. Understanding the relative importance of different control measures is essential for response planning.

Animals↗

PubMed2006

Stage II colon cancer prognosis prediction by tumor gene expression profiling.

PURPOSE: This study mainly aimed to identify and assess the performance of a microarray-based prognosis predictor (PP) for stage II colon cancer. A previously suggested 23-gene prognosis signature (PS) was also evaluated. PATIENTS AND METHODS: Tumor mRNA samples from 50 patients were profiled using oligonucleotide microarrays. PPs were built and assessed by random divisions of patients into training and validation sets (TSs and VSs, respectively). For each TS/VS split, a 30-gene PP, identified on the TS by selecting the 30 most differentially expressed genes and applying diagonal linear discriminant analysis, was used to predict the prognoses of VS patients. Two schemes were considered: single-split validation, based on a single random split of patients into two groups of equal size (group 1 and group 2), and Monte Carlo cross validation (MCCV), whereby patients were repeatedly and randomly divided into TS and VS of various sizes. RESULTS: The 30-gene PP, identified from group 1 patients, yielded an 80% prognosis prediction accuracy on group 2 patients. MCCV yielded the following average prognosis prediction performance measures: 76.3% accuracy, 85.1% sensitivity, and 67.5% specificity. Improvements in prognosis prediction were observed with increasing TS size. The 30-gene PS were found to be highly-variable across TS/VS splits. Assessed on the same random splits of patients, the previously suggested 23-gene PS yielded a 67.7% mean prognosis prediction accuracy. CONCLUSION: Microarray gene expression profiling is able to predict the prognosis of stage II colon cancer patients. The present study also illustrates the usefulness of resampling techniques for honest performance assessment of microarray-based PPs.

Aged↗

PubMed2006

Natural rubber latex allergy among health care workers: a systematic review of the evidence.

BACKGROUND: Natural rubber latex is a recognized allergen, but a recent meta-analysis failed to find any association between latex exposure and allergy in health care workers (HCWs). OBJECTIVES: A meta-analysis was carried out under the auspices of the French National Regulatory Authority to assess the allergic risk induced by latex gloves in HCWs. METHODS: The risk of work-related exposure to latex for the development of latex allergy was assessed. Prevalence and incidence rates of latex sensitization or allergy were compared in HCWs and in the general population. Exposure-response relationships were assessed in HCWs. RESULTS: Latex allergy was found in 4.32% (range, 4.01% to 4.63%) of HCWs and in 1.37% (range, 0.43% to 2.31%) of the general population. Latex-positive skin prick test responses ranged from 2.1% to 3.7% in the general population and from 6.9% to 7.8% for the HCWs. HCWs exposed to latex showed an increased risk of hand dermatitis (odds ratio [OR], 2.46; 95% CI, 2.11-2.86), asthma or wheezing (OR, 1.55; 95% CI, 1.15-2.08), rhinoconjunctivitis (OR, 2.73; 95% CI, 1.97-3.81), and at least one generic symptom (OR, 1.27; 95% CI, 1.09-1.47). Sensitization to latex was significantly associated with asthma and rhinoconjunctivitis. By contrast, exposure to latex was not associated with a significantly increased risk of positive skin prick test responses to latex (OR, 1.47; 95% CI, 0.94-2.30). CONCLUSION: HCWs have an increased risk of sensitization and allergic symptoms to latex. CLINICAL IMPLICATIONS: Prevention of latex allergy in HCWs is needed.

Cross-Sectional Studies↗

PubMed2006

Strategies for containing a global influenza pandemic.

Mathematical modelling provides useful insight into the geographic and temporal spread of pandemic influenza. It has been recently used to assess the ability to stop a pandemic at a very early stage. Here, we model the global diffusion of pandemic influenza and the impact of available preventive and control measures. We refined a published SEIR deterministic model of disease dynamics within 52 cities interconnected via air transport to simulate the impact of five interventions in a variety of scenarios: vaccination, case isolation, therapeutic and prophylactic antiviral treatment, and air traffic reduction. The impact of these measures was assessed on the spread of a potential pandemic strain profile, with an average attack-rate of 26%, a case-fatality rate of 2.5% and a residual immunity of 25%. Our analysis highlighted the importance of: (1) a global perspective for dealing with pandemic risks; (2) the time factor and, hence, the importance of surveillance systems; (3) the complementary role of available control measures. Results provide general guidance for the issues of concern to public-health decision-makers: when to set up interventions, where, and at which administrative levels.

Antiviral Agents↗

PubMed2006

Real-time monitoring of the influenza vaccine field effectiveness.

Twice a year, the World Health Organization recommends the composition of the influenza vaccine depending on the strains which circulate several months before the beginning of the epidemic. Therefore, it is important to assess the field vaccine effectiveness (FVE) yearly. Thanks to data on vaccine coverage and data on influenza like illness cases collected by the French Sentinel Network, we are able to estimate the FVE few weeks after the beginning of the yearly influenza epidemic. In this paper, we have analysed the estimates obtained for the last 10 epidemic seasons for people over and under 65. Making the assumption that the vaccine coverage is stable from 1 year to another, we are able to assess the level of the FVE few weeks after the beginning of the epidemic and we should detect a lack of effectiveness of the vaccine.

Humans↗

PubMed2006

Decline in HCV testing and compliance with guidelines in patients of Sentinelles general practitioners, 1996-2002.

Between 1996 and 2002, the French Sentinelles Network observed a more than 2-fold decline in the annual rate of hepatitis C virus (HCV) screening tests prescribed by general practitioners. During this period it droped from 1080 to 450 per 100,000 inhabitants. The proportion of HCV-positives increased from 9.7% to 12.9% between 1996 and 1998 but declined steadily afterwards, reaching 7% in 2002. The majority of HCV-positive patients were men (57%), 38% were aged 30-39 years and 45% were injecting drug users. Two French guidelines for HCV screening were issued in 1997 and 2001. Of the 3462 patients with a known HCV test result, 27.4% were offered following the 1997 guidelines, among which 23.7% were HCV-positive. Of the same 3462 patients, 36.8% were offered following the extended definition of the risk group in the 2001 guidelines, among which 19.9% were positive. The percentage of subjects tested with no biological sign or clinical symptom and no HCV risk factor varies from 11% to 26% showing that SGPs carry out a targeted screening even if they deviate from the strict recommendations. Of the HCV-positive patients, 14% did not meet any criteria of the guidelines suggesting a lack of sensitivity in the current definition of patients recommended for testing.

Adolescent↗

PubMed2006

Global monitoring of influenza: potential contribution of national networks from a French perspective.

The aim of global monitoring of influenza is to help decision making in regular seasonal influenza and in the case of a new pandemic. FluNet is the main tool for information sharing among the WHO Global Influenza Surveillance Network, as well as the public. It allows 112 WHO National Influenza Centers in 83 countries access to remote data entry. Weekly information on recent isolates and epidemiological situations are available to the public through many functionalities, for example, maps (animated or static), charts and raw data are embedded in the system for data display. Thus far, FluNet has collected weekly influenza surveillance data from up to 1997. A major outcome of this global network is the influenza vaccine composition, which is proposed twice a year (i.e., for both hemispheres) on the basis of the collected data. However, FluNet is far from performing comprehensive monitoring of influenza at a global level; 109 WHO member states still do not participate in the network and participating national influenza centers have only limited resources, which do not allow them to implement a reliable, accurate and real-time epidemiology of influenza in the areas they deserve. By following the time and space dynamics of an influenza strain, an epidemiologically valid system would make assessment of decisions after adopting preventive measures (e.g., closing schools, travel restriction, use of antivirals or of protective masks and mass immunization) possible. This international cooperation in public health fields must be considerably reinforced in the future, and should encourage database linkage with environmental information, allowing for the evaluation of the role of climate change, animal behavior or pollution involvement in disease.

Disease Outbreaks↗

PubMed2006

Medication sales and syndromic surveillance, France.

Although syndromic surveillance systems using nonclinical data have been implemented in the United States, the approach has yet to be tested in France. We present the results of the first model based on drug sales that detects the onset of influenza season and forecasts its trend. Using weekly lagged sales of a selected set of medications, we forecast influenzalike illness (ILI) incidence at the national and regional level for 3 epidemic seasons (2000-01, 2001-02, and 2002-03) and validate the model with real-time updating on the fourth (2003-04). For national forecasts 1-3 weeks ahead, the correlation between observed ILI incidence and forecast was 0.85-0.96, an improvement over the current surveillance method in France. Our findings indicate that drug sales are a useful additional tool to syndromic surveillance, a complementary and independent source of information, and a potential improvement for early warning systems for both epidemic and pandemic planning.

Commerce↗

PubMed2006

Novel chikungunya virus variant in travelers returning from Indian Ocean islands.

Chikungunya virus (CHIKV) emerged in Indian Ocean islands in 2005 and is causing an ongoing outbreak that involves >260,000 patients, including travelers returning home from these islands. We investigated cases in 4 patients returning from Mayotte and Reunion Islands with CHIKV infection and a nurse infected in metropolitan France after direct contact with the blood of a traveler. Four patients had tenosynovitis and pain at wrist pressure, and 1 had life-threatening manifestations. Four CHIKV strains were isolated, including 1 from the patient with the autochthonous case. The complete genomic sequence identified a new CHIKV variant emerging from the East/ central African evolutionary lineage. Aedes albopictus, the implicated vector of CHIKV in Indian Ocean islands, has dispersed worldwide in recent decades. High viral loads in patients returning from Indian Ocean islands to countries where Ae. albopictus is prevalent may be a source of epidemics.

Adult↗

PubMed2006

Persistent increase in the incidence of acute male urethritis diagnosed in general practices in France.

BACKGROUND: At-risk sexual behaviour seems to have increased in Europe, possibly due to the reassuring efficacy of highly active antiretroviral treatments. AIM: To follow, from 1990 to 2003, in France, the trends in the incidence of acute male urethritis diagnosed in general practice, a marker of at-risk sexual behaviour. DESIGN OF STUDY: Electronic disease surveillance. SETTING: General practices located all over mainland France. METHOD: The GPs of the French Sentinelles network reported, via online computer systems, the acute urethritis cases they diagnosed, and for each case the characteristics of the patients. RESULTS: After a striking decrease between 1990 and 1995 from 460 per 100 000 men aged 15-64 years (95% confidence interval [CI] = 390 to 520) to 180 (95% CI = 150 to 200), when antiretroviral drugs became available on the French market, the incidence of acute male urethritis stopped decreasing. Between 1996 and 2003, it may have risen again from 190 per 100 000 men (95% CI = 160 to 210) to 325 per 100 000 men (95% CI = 280 to 370) aged 15-64 years. The percentage of homosexual/bisexual men among the cases reported was higher than in the general population (10% versus 4%, P<0.001). Homosexual/bisexual patients were younger than heterosexual patients (34 versus 37 years, P = 0.04), more of them had a discharge (88% versus 59%, P<0.001), a history of sexually transmitted disease (65% versus 32%, P<0.001), and at least two sexual partners (74% versus 38%, P<0.001). The most frequent pathogens were Chlamydia trachomatis (25%), Neisseria gonorrhoea (21%), Mycoplasma genitalium (8%), Ureaplasma urealyticum (5%), Trichomonas vaginalis (3%) and other bacteria (32%). Presence of co-infections was observed in 8.3% of patients. CONCLUSIONS: This increase in the incidence of urethritis, shows that the sexual health of men has worsened in France, and calls for urgent new preventive measures.

Acute Disease↗

PubMed2005

Colon cancer prognosis prediction by gene expression profiling.

This study assessed the possibility to build a prognosis predictor, based on microarray gene expression measures, in stage II and III colon cancer patients. Tumour (T) and non-neoplastic mucosa (NM) mRNA samples from 18 patients (nine with a recurrence, nine with no recurrence) were profiled using the Affymetrix HGU133A GeneChip. The k-nearest neighbour method was used for prognosis prediction using T and NM gene expression measures. Six-fold cross-validation was applied to select the number of neighbours and the number of informative genes to include in the predictors. Based on this information, one T-based and one NM-based predictor were proposed and their accuracies were estimated by double cross-validation. In six-fold cross-validation, the lowest numbers of informative genes giving the lowest numbers of false predictions (two out of 18) were 30 and 70 with the T and NM gene expression measures, respectively. A 30-gene T-based predictor and a 70-gene NM-based predictor were then built, with estimated accuracies of 78 and 83%, respectively. This study suggests that one can build an accurate prognosis predictor for stage II and III colon cancer patients, based on gene expression measures, and one can use either tumour or non-neoplastic mucosa for this purpose.

Adenocarcinoma↗

PubMed2005

The unexpected importance of mosquito oviposition behaviour for malaria: non-productive larval habitats can be sources for malaria transmission.

BACKGROUND: Mosquitoes commute between blood-meal hosts and water. Thus, heterogeneity in human biting reflects underlying spatial heterogeneity in the distribution and suitability of larval habitat as well as inherent differences in the attractiveness, suitability and distribution of blood-meal hosts. One of the possible strategies of malaria control is to identify local vector species and then attack water bodies that contain their larvae. METHODS: Biting and host seeking, not oviposition, have been the focus of most previous studies of mosquitoes and malaria transmission. This study presents a mathematical model that incorporates mosquito oviposition behaviour. RESULTS: The model demonstrates that oviposition is one potential factor explaining heterogeneous biting and vector distribution in a landscape with a heterogeneous distribution of larval habitat. Adult female mosquitoes tend to aggregate around places where they oviposit, thereby increasing the risk of malaria, regardless of the suitability of the habitat for larval development. Thus, a water body may be unsuitable for adult mosquito emergence, but simultaneously, be a source for human malaria. CONCLUSION: Larval density may be a misleading indicator of a habitat's importance for malaria control. Even if mosquitoes could be lured to oviposit in sprayed larval habitats, this would not necessarily mitigate -- and might aggravate -- the risk of malaria transmission. Forcing mosquitoes to fly away from humans in search of larval habitat may be a more efficient way to reduce the risk of malaria than killing larvae. Thus, draining, fouling, or filling standing water where mosquitoes oviposit can be more effective than applying larvicide.

Animals↗

PubMed2005

Mechanisms involved in the low-level regeneration of CD4+ cells in HIV-1-infected patients receiving highly active antiretroviral therapy who have prolonged undetectable plasma viral loads.

BACKGROUND: Persistent low CD4(+) cell counts are observed in 5%-27% of patients treated for human immunodeficiency virus (HIV)-1 infection despite their having prolonged undetectable plasma viral loads. METHODS: To understand the possible mechanisms of this discordant immunological situation, a prospective transsectional case-control study was designed. HIV-1-infected subjects who had a plasma viral load <200 copies/mL for >1 year were considered to be case patients if their CD4(+) cell count was <250/mm(3); control patients had CD4(+) cell counts >500/mm(3) and were matched by sex, age, and nadir CD4(+) cell count to case patients. T cell proliferation after stimulation with various antigens, T cell subset counts, T cell rearrangement excision circles (TRECs), T cells undergoing apoptosis, cytokines influencing apoptosis, and cellular proviral DNA and plasma viral RNA persistence were assessed. RESULTS: Compared with the 19 control patients, the 19 case patients had undistinguishable lymphoproliferative responses to candidin and cytomegalovirus, fewer naive CD4(+) cells (CD45RA(+)62L(+), 23%+/-13% vs. 47%+/-14%; P<.0001), lower thymic output (1.28 vs. 3.95 TRECs/microL of blood; P=.0015), increased cell death by apoptosis (spontaneous, 23.2%+/-8.3% vs. 11.9%+/-8.4% [P=.02]; Fas induced, 38.6%+/-13.7% vs. 16.4%+/-8.0% [P=.004]), higher levels of plasma soluble tumor necrosis factor receptor II (9.6 vs. 5.3 ng/mL; P=.0058), and undistinguishable plasma HIV-1 and cellular proviral DNA loads. CONCLUSIONS: The mechanisms responsible for the low-level regeneration of CD4(+) cells involve, at least, deficiency in the regeneration of central CD4(+) cells and excessive apoptosis.

Adult↗

PubMed2005

Gene expression profiling of nonneoplastic mucosa may predict clinical outcome of colon cancer patients.

PURPOSE: This study assessed the possibility to build a prognosis predictor, based on microarray gene expression measures, in Stage II and III colon cancer patients. METHODS: Tumor and nonneoplastic mucosa mRNA samples from 12 colon cancer patients were profiled using the Affymetrix HGU133A GeneChip. Six of 12 patients experienced a metachronous metastasis, whereas the 6 others remained disease-free for more than five years. Three datasets were constituted, including, respectively, the gene expression measures in tumor samples (T), in adjacent nonneoplastic mucosa samples (A), and the log-ratio of the gene expression measures (L). The step-down procedure of Westfall and Young and the k-nearest neighbor class prediction method were applied on T, A, and L. Leave-one-out cross-validation was used to estimate the generalization error of predictors based on different numbers of genes and neighbors. RESULTS: The most frequent results were one false prediction with the A-based predictors (95 percent) and two false predictions with the T- and L: -based predictors (65 and 60 percent, respectively). A-based predictors were more stable (i.e., less sensitive to changes of parameters, such as numbers of genes and neighbors) than T- and L: -based predictors. Informative genes in A-based predictors included genes involved in the oxidative and phosphorylative mitochondrial metabolism and genes involved in cell-signaling pathways and their receptors. CONCLUSIONS: This study suggests that one can build a prognosis predictor for Stage II and III colon cancer patients, based on microarray gene expression measures, and suggests the potential usefulness of nonneoplastic mucosa for this purpose.

Aged↗

PubMed2005

An axilla scoring system to predict non-sentinel lymph node status in breast cancer patients with sentinel lymph node involvement.

BACKGROUND: Axillary lymph node dissection (ALND) is the current standard of care for breast cancer patients with sentinel lymph node (SN) involvement. However, the SN is the only involved axillary node in a significant proportion of these patients. Here we examined factors predictive of non-SN involvement in patients with a metastatic SN, in order to develop a scoring system for predicting non-SN involvement. MATERIALS AND METHODS: This study was based on a prospective database of 337 patients who underwent SN biopsy for breast cancer, of whom 81 (24%) were SN-positive; we examined factors predictive of non SN involvement in the 71 of these 81 women who underwent complementary ALND. All clinical and histological criteria were recorded and analysed according to non-SN status, by using Chi-2 analysis, Student's t-test, and multivariate logistic regression. RESULTS: Univariate analysis showed a significant association between non-SN involvement and histological primary tumor size (p=0.0001), SN macrometastasis (p=0.01), the method used to detect SN metastasis (H&E versus immunohistochemistry) (p=0.03), the number of positive SNs (p=0.049), the proportion of involved SNs among all identified SNs (p=0.0001) and lymphovascular invasion (p=0.006). Histological primary tumor size (p=0.006), SN macrometastasis (p=0.02) and the proportion of involved SNs among all identified SNs (p=0.03) remained significantly associated with non-SN status in multivariate analysis. Based on the multivariate analysis, we developed an axilla scoring system (range 0-7) to predict the likelihood of non-SN metastasis in breast cancer patients with SN involvement. CONCLUSION: In patients with invasive breast cancer and a positive SN, histological primary tumor size, the size of SN metastases, and the proportion of involved SNs among all identified SNs were independently predictive of non-SN involvement.

Adult↗

PubMed2005

Trends in voluntary HIV testing in general practices in France between 1987 and 2002.

OBJECTIVES: To measure the level of voluntary HIV testing and to assess its changes in the French general population according to the evolution of HIV testing policies. METHODS: When general practitioners belonging to the Sentinelles network (SGP) offer HIV testing to their patients, they send the network an anonymous description of the patient and a report of the test results. RESULTS: The number of HIV tests peaked in 1993 at 1760 per 100,000 inhabitants. Since 1995 the rate has fallen slightly, from 1474 to 810 per 100,000 in 2002. Between 1987 and 2002 there was a significant fall in the proportion of persons with a history of STD (31.4-5.1%, p = 0.0001), clinical signs of HIV infection (9.1-4.5%, p = 0.0002) and a history of prior testing (19.3-13.6%, p = 0.0005). CONCLUSIONS: Our results show that demand for HIV testing among the French general practice patient population has fallen since 1995, along with the frequency with which GPs offer HIV testing.

AIDS Serodiagnosis↗

PubMed2005

Community epidemiology of Chlamydia and Mycoplasma pneumoniae in LRTI in France over 29 months.

BACKGROUND: The role of Chlamydia pneumoniae (CP) and Mycoplasma pneumoniae (MP) in lower respiratory tract infections (LRTI) is still little known in community settings. METHODS: In all, 3207 adult cases of LRTI (871 with pneumonia, and 2336 with acute bronchitis) were prospectively included in the ETIIC1 ETIIC : ETude de l'Incidence des Infections respiratoires basses d'origine Communautaire dues A Chlamydia pneumoniae et Mycoplasma pneumoniae (Incidence of CP and MP in LRTI in community settings) program by 303 general practitioners and 24 hospital physicians in France between September 1997 and February 2000. The polymerase chain reaction and immunoassays were used to detect CP or MP in 3198 pharyngeal specimens obtained by gargling. RESULTS: Of these 3198 patients, 232 (7.3%), were PCR-positive for CP and/or MP. Immunoassays were far less sensitive than PCRs (Se = 2 and 13% for MP and CP). Among the 2336 patients with acute bronchitis, PCR was positive for CP in 95 (4.1%), and for MP, in 54 (2.3%). Among the 671 patients with radiologically confirmed pneumonia, PCR was positive for CP in 23 (3.4%), and for MP in 49 (7.3%). CP and MP displayed significant geographic heterogeneity. Independent clinical determinants of positive PCR for CP and/or MP were age below 45 years, previous antimicrobial therapy (especially betalactams). Clinical signs were not of practical use in distinguishing accurately between etiologic diagnoses. CONCLUSIONS: CP or MP diagnosed by PCR were found in more than 7% of patients with LRTI in community settings with a significant geographical heterogeneity and significant temporal trends in the incidence.

Adult↗

PubMed2005

Sample size calculation should be performed for design accuracy in diagnostic test studies.

BACKGROUND AND OBJECTIVES: Guidelines for conducting studies and reading medical literature on diagnostic tests have been published: Requirements for the selection of cases and controls, and for ensuring a correct reference standard are now clarified. Our objective was to provide tables for sample size determination in this context. STUDY DESIGN AND SETTING: In the usual situation, where the prevalence Prev of the disease of interest is <0.50, one first determines the minimal number Ncases of cases required to ensure a given precision of the sensitivity estimate. Computations are based on the binomial distribution, for user-specified type I and type II error levels. The minimal number N(controls) of controls is then derived so as to allow for representativeness of the study population, according to Ncontrols=Ncases [(1-Prev)/Prev]. RESULTS: Tables give the values of Ncases corresponding to expected sensitivities from 0.60 to 0.99, acceptable lower 95% confidence limits from 0.50 to 0.98, and 5% probability of the estimated lower confidence limit being lower than the acceptable level. CONCLUSION: When designing diagnostic test studies, sample size calculations should be performed in order to guarantee the design accuracy.

Biomedical Research↗