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1.  Multicenter case–control study protocol of pneumonia etiology in children: Global Approach to Biological Research, Infectious diseases and Epidemics in Low-income countries (GABRIEL network) 
BMC Infectious Diseases  2014;14(1):635.
Data on the etiologies of pneumonia among children are inadequate, especially in developing countries. The principal objective is to undertake a multicenter incident case–control study of <5-year-old children hospitalized with pneumonia in developing and emerging countries, aiming to identify the causative agents involved in pneumonia while assessing individual and microbial factors associated with the risk of severe pneumonia.
A multicenter case–control study, based on the GABRIEL network, is ongoing. Ten study sites are located in 9 countries over 3 continents: Brazil, Cambodia, China, Haiti, India, Madagascar, Mali, Mongolia, and Paraguay. At least 1,000 incident cases and 1,000 controls will be enrolled and matched for age and date. Cases are hospitalized children <5 years with radiologically confirmed pneumonia, and the controls are children without any features suggestive of pneumonia. Respiratory specimens are collected from all enrolled subjects to identify 19 viruses and 5 bacteria. Whole blood from pneumonia cases is being tested for 3 major bacteria. S. pneumoniae-positive specimens are serotyped. Urine samples from cases only are tested for detection of antimicrobial activity. The association between procalcitonin, C-reactive protein and pathogens is being evaluated. A discovery platform will enable pathogen identification in undiagnosed samples.
This multicenter study will provide descriptive results for better understanding of pathogens responsible for pneumonia among children in developing countries. The identification of determinants related to microorganisms associated with pneumonia and its severity should facilitate treatment and prevention.
PMCID: PMC4272811
Pneumonia; Children; Case–control; Etiology; Developing and emerging countries
2.  The effect of adherence to guidelines for initial antiretroviral therapy on 1-year outcomes: a French cohort study 
BMC Infectious Diseases  2014;14(1):596.
Guidelines for antiretroviral treatment (cART) are published regularly, but there is little information regarding the effect of adherence to guidelines on patient outcomes. We assessed the effect of following the “when-to-start” and “what-to-start” guidelines, on treatment modifications, and on immunological and virological outcome at 12 months in a cohort of HIV-1 infected patients initiating cART from 2000 to 2010.
Consecutive HIV-1 infected patients, antiretroviral naive, initiating cART from 2000 to 2010 at a University Hospital were enrolled. HIV-2 infection, cART for prevention of mother-to-child transmission or during primary HIV-infection and unlicensed drugs were excluded. The respect or not of the “when-to-start” and “what-to-start” guidelines was based on French guidelines published from 2000 to 2010. Factors associated with cART modifications at 12 months and factors associated with an HIV viral load of <50 copies/mL at 12 months were assessed by univariate and multivariate logistic regression modeling. Variations in CD4 counts from baseline were assessed by univariate and multivariate linear regression.
Of 1365 patients starting cART, 151 were treated outside “when-to-start” guidelines and 150 were treated outside “what-to-start” guidelines. Not using “when-to-start” guidelines was mainly related to early initiation in young men having sex with men, and was not associated with a significantly different outcome at 12 months. Treatments that did not follow “what-to-start” guidelines were not observed in any specific population and were associated with more treatment modifications and a poorer virological outcome at 12 months.
Adherence to “what-to-start” guidelines is associated with a better outcome at 12 months in HIV-infected patients initiating antiretroviral therapy. Efforts should be made to promote adherence to these guidelines.
PMCID: PMC4233095  PMID: 25395106
HIV infection; Antiretroviral treatment; Adherence to guidelines; Prognosis
3.  Disparities of Perceptions and Practices Related to Cervical Cancer Prevention and the Acceptability of HPV Vaccination According to Educational Level in a French Cross-Sectional Survey of 18–65 Years Old Women 
PLoS ONE  2014;9(10):e109320.
We aimed to study the relationships between educational level, women's knowledge about cervical cancer (CC), and acceptance of HPV vaccination for their daughters.
We analysed data from a quantitative (self-administrated questionnaire) and qualitative (semi-structured interviews) cross-sectional study performed in 2008 among 1,229 French 18–65-year-old women recruited by general practitioners. Women were categorized into three educational level groups: low (LEL: 43.9%), medium (MEL: 33.4%) and high (HEL: 22.6%).
Knowledge about CC and its prevention was lower among LEL women. In the 180 mothers of 14–18-year-old daughters (99 LEL, 54 MEL, 45 HEL), acceptance of HPV vaccine was higher in LEL (60.4%) and MEL (68.6%) than in HEL mothers (46.8%). Among LEL mothers, those who were favourable to HPV vaccination were more likely to be young (OR = 8.44 [2.10–34.00]), to be vaccinated against hepatitis B (OR = 4.59 [1.14–18.52]), to have vaccinated their children against pneumococcus (OR = 3.52 [0.99–12.48]) and to present a history of abnormal Pap smear (OR = 6.71 [0.70–64.01]).
Although LEL women had poorer knowledge about CC and its prevention, they were more likely to accept HPV vaccination than HEL mothers.
PMCID: PMC4193774  PMID: 25303180
4.  Infections, antibiotic treatment and mortality in patients admitted to ICUs in countries considered to have high levels of antibiotic resistance compared to those with low levels 
BMC Infectious Diseases  2014;14(1):513.
Antimicrobial resistance is an increasing concern in ICUs worldwide. Infection with an antibiotic resistant (ABR) strain of an organism is associated with greater mortality than infection with the non-resistant strain, but there are few data assessing whether being admitted to an intensive care unit (ICU) with high levels of antimicrobial resistance is associated with a worse outcome than being admitted to an ICU with low rates of resistance. The aim of this study was, therefore, to compare the characteristics of infections and antibiotic treatments and patient outcomes in patients admitted to ICUs in countries considered as having high levels of antibiotic resistance and those admitted to ICUs in countries considered as having low levels of antibiotic resistance.
Data from the large, international EPIC II one-day point prevalence study on infections in patients hospitalized in ICUs were used. For the current study, we compared the data obtained from patients from two groups of countries: countries with reported MRSA rates of ≥ 25% (highABR: Greece, Israel, Italy, Malta, Portugal, Spain, and Turkey) and countries with MRSA rates of < 5% (lowABR: Denmark, Finland, Netherlands, Norway, and Sweden).
On the study day, 1187/2204 (53.9%) patients in the HighABR ICUs were infected and 255/558 (45.7%) in the LowABR ICUs (P < 0.01). Patients in the HighABR ICUs were more severely ill than those in the LowABR ICUs, as reflected by a higher SAPS II score (35.6 vs 32.7, P < 0.05) and had longer median ICU (12 days vs 5 days) and hospital (24 days vs 16 days) lengths of stay. They also had higher crude ICU (20.0% vs 15.4%) and hospital (27.0% vs 21.5%) mortality rates (both P < 0.05). However, after multivariable adjustment and matched pair analysis there were no differences in ICU or hospital mortality rates between High or LowABR ICU patients overall or among those with infections.
Being hospitalized in an ICU in a region with high levels of antimicrobial resistance is not associated per se with a worse outcome.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2334-14-513) contains supplementary material, which is available to authorized users.
PMCID: PMC4181425  PMID: 25245620
Infection; Critically ill; Antibiotic; Resistance
5.  Abdominal infections in the intensive care unit: characteristics, treatment and determinants of outcome 
BMC Infectious Diseases  2014;14(1):420.
Abdominal infections are frequent causes of sepsis and septic shock in the intensive care unit (ICU) and are associated with adverse outcomes. We analyzed the characteristics, treatments and outcome of ICU patients with abdominal infections using data extracted from a one-day point prevalence study, the Extended Prevalence of Infection in the ICU (EPIC) II.
EPIC II included 13,796 adult patients from 1,265 ICUs in 75 countries. Infection was defined using the International Sepsis Forum criteria. Microbiological analyses were performed locally. Participating ICUs provided patient follow-up until hospital discharge or for 60 days.
Of the 7,087 infected patients, 1,392 (19.6%) had an abdominal infection on the study day (60% male, mean age 62 ± 16 years, SAPS II score 39 ± 16, SOFA score 7.6 ± 4.6). Microbiological cultures were positive in 931 (67%) patients, most commonly Gram-negative bacteria (48.0%). Antibiotics were administered to 1366 (98.1%) patients. Patients who had been in the ICU for ≤2 days prior to the study day had more Escherichia coli, methicillin-sensitive Staphylococcus aureus and anaerobic isolates, and fewer enterococci than patients who had been in the ICU longer. ICU and hospital mortality rates were 29.4% and 36.3%, respectively. ICU mortality was higher in patients with abdominal infections than in those with other infections (29.4% vs. 24.4%, p < 0.001). In multivariable analysis, hematological malignancy, mechanical ventilation, cirrhosis, need for renal replacement therapy and SAPS II score were independently associated with increased mortality.
The characteristics, microbiology and antibiotic treatment of abdominal infections in critically ill patients are diverse. Mortality in patients with isolated abdominal infections was higher than in those who had other infections.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2334-14-420) contains supplementary material, which is available to authorized users.
PMCID: PMC4122779  PMID: 25074742
Abdominal infection; Abscess; Peritonitis; Severe sepsis; Critical care; Antibiotic therapy; Microbiology
6.  Five years of hospital based surveillance of influenza-like illness and influenza in a short-stay geriatric unit 
BMC Research Notes  2014;7:99.
Data on influenza in the healthcare setting are often based on retrospective investigations of outbreaks and a few studies described influenza during several consecutive seasons.
The aim of the present work is to report data on influenza like illness (ILI) and influenza from 5-year prospective surveillance in a short-stay geriatrics unit.
A short stay geriatrics unit underwent 5 years of ILI surveillance from November 2004 to March 2009, with the aim of describing ILI in a non-outbreak context. The study was proposed to patients who presented ILI, defined as fever >37.8°C or cough or sore throat. Among 1,353 admitted patients, 115 presented an ILI, and 34 had hospital-acquired ILI (HA-ILI). Influenza was confirmed in 23 patients, 13 of whom had been vaccinated. Overall attack rates were 2.78% and 0.02% for HA-ILI and HA-confirmed influenza respectively, during the 5 seasons.
This 5-year surveillance study supports the notion that influenza infections are common in hospitals, mostly impacting the elderly hospitalized in short-stay units. It highlights the need for appropriate control measures to prevent HA-ILI in geriatric units and protect elderly patients.
PMCID: PMC3943500  PMID: 24555834
Influenza; Hospital-acquired; Geriatrics, Surveillance
7.  Predictors of Clostridium difficile infection severity in patients hospitalised in medical intensive care 
AIM: To describe and analyse factors associated with Clostridium difficile infection (CDI) severity in hospitalised medical intensive care unit patients.
METHODS: We performed a retrospective cohort study of 40 patients with CDI in a medical intensive care unit (MICU) at a French university hospital. We include patients hospitalised between January 1, 2007 and December 31, 2011. Data on demographics characteristics, past medical history, CDI description was collected. Exposure to risk factors associated with CDI within 8 wk before CDI was recorded, including previous hospitalisation, nursing home residency, antibiotics, antisecretory drugs, and surgical procedures.
RESULTS: All included cases had their first episode of CDI. The mean incidence rate was 12.94 cases/1000 admitted patients, and 14.93, 8.52, 13.24, 19.70, and 8.31 respectively per 1000 admitted patients annually from 2007 to 2011. Median age was 62.9 [interquartile range (IQR) 55.4-72.40] years, and 13 (32.5%) were women. Median length of MICU stay was 14.0 d (IQR 5.0-22.8). In addition to diarrhoea, the clinical symptoms of CDI were fever (> 38 °C) in 23 patients, abdominal pain in 15 patients, and ileus in 1 patient. The duration of diarrhoea was 13.0 (8.0-19.5) d. In addition to diarrhoea, the clinical symptoms of CDI were fever (> 38 °C) in 23 patients, abdominal pain in 15 patients, and ileus in 1 patient. Prior to CDI, 38 patients (95.0%) were exposed to antibiotics, and 12 (30%) received at least 4 antibiotics. Fluoroquinolones, 3rd generation cephalosporins, coamoxiclav and tazocillin were prescribed most frequently (65%, 55%, 40% and 37.5%, respectively). The majority of cases were hospital-acquired (n = 36, 90%), with 5 cases (13.9%) being MICU-acquired. Fifteen patients had severe CDI. The crude mortality rate within 30 d after diagnosis was 40% (n = 16), with 9 deaths (9 over 16; 56.3%) related to CDI. Of our 40 patients, 15 (37.5%) had severe CDI. Multivariate logistic regression showed that male gender [odds ratio (OR): 8.45; 95%CI: 1.06-67.16, P = 0.044], rising serum C-reactive protein levels (OR = 1.11; 95%CI: 1.02-1.21, P = 0.021), and previous exposure to fluoroquinolones (OR = 9.29; 95%CI: 1.16-74.284, P = 0.036) were independently associated with severe CDI.
CONCLUSION: We report predictors of severe CDI not dependent on time of assessment. Such factors could help in the development of a quantitative score in ICU’s patients.
PMCID: PMC3848151  PMID: 24307797
Clostridium difficile; Health-care associated infection; Hospital-acquired infection; Intensive care unit; Nosocomial infection; Severe Clostridium difficile infection
8.  Symptomatic Illness and Low CD4 Cell Count at HIV Seroconversion as Markers of Severe Primary HIV Infection 
PLoS ONE  2013;8(11):e78642.
The risk/benefit of initiating ART in primary HIV infection (PHI) is unclear. The benefits are more likely to outweigh the risks in patients with severe PHI. An accepted definition of severe PHI is, however, lacking.
CASCADE patients with HIV test interval <6 months were classified as severe and non-severe PHI based on whether the following traits were recorded in the first 6 months following seroconversion: severe specific pre-defined symptoms, central nervous system-implicated illness, and ≥1, ≥2 CD4<350 (and <500) cells/mm3. For each definition, we used Kaplan-Meier curves and Cox survival models to compare time to AIDS/death, censoring at the earlier of last clinic visit or 1/1/1997, when combination antiretroviral therapy (cART) became available.
Among 1108 included patients mostly males (85%) infected through sex between men (71%), 366 were diagnosed with AIDS/died. The risk of AIDS/death was significantly higher for individuals with severe symptoms, those with ≥1 CD4<350 cells/mm3 or ≥2 CD4 <500 cells/mm3 in the first 6 months [aHR (95% confidence interval) 2.1 (1.4,3.2), 2.0 (1.5,2.7), and 2.3, (1.5–3.5) respectively]. Median [interquantile range] survival for patients with ≥2, ≥1 and no CD4<350 cells/mm3 within 6 months of seroconversion was 3.9 [2.7,6.5], 5.4 [4.5,8.4] and 8.1 [4.3,10.3] years, respectively. The diagnosis of CNS-implicated symptoms was rare and did not appear to be prognostic.
One CD4 count <350 or two <500 cells/mm3 within 6 months of seroconversion and/or severe illness in PHI may be useful early indicators of individuals at high risk of disease progression.
PMCID: PMC3828389  PMID: 24244330
9.  Correction: Estimating Potential Infection Transmission Routes in Hospital Wards Using Wearable Proximity Sensors 
PLoS ONE  2013;8(9):10.1371/annotation/b20d3cec-62b7-44ec-9150-8a06a9b30a9b.
PMCID: PMC3779279
10.  Anti-Trypanosoma cruzi Cross-Reactive Antibodies Detected at High Rate in Non-Exposed Individuals Living in Non-Endemic Regions: Seroprevalence and Association to Other Viral Serologies 
PLoS ONE  2013;8(9):e74493.
Cross-reactive antibodies are characterized by their recognition of antigens that are different from the trigger immunogen. This happens when the similarity between two different antigenic determinants becomes adequate enough to enable a specific binding with such cross-reactive antibodies. In the present manuscript, we report the presence, at an “abnormal” high frequency, of antibodies in blood samples from French human subjects cross-reacting with a synthetic-peptide antigen derived from a Trypanosoma cruzi (T. cruzi) protein sequence. As the vector of T. cruzi is virtually confined to South America, the parasite is unlikely to be the trigger immunogen of the cross-reactive antibodies detected in France. At present, the cross-reactive antibodies are measured by using an in-house ELISA method that employs the T. cruzi -peptide antigen. However, to underline their cross-reactive characteristics, we called these antibodies “Trypanosoma cruzi Cross Reactive Antibodies” or TcCRA. To validate their cross-reactive nature, these antibodies were affinity-purified from plasma of healthy blood donor and were then shown to specifically react with the T. cruzi parasite by immunofluorescence. Seroprevalence of TcCRA was estimated at 45% in serum samples of French blood donors while the same peptide-antigen reacts with about 96% of T. cruzi -infected Brazilian individuals. In addition, we compared the serology of TcCRA to other serologies such as HSV 1/2, EBV, HHV-6, CMV, VZV, adenovirus, parvovirus B19, mumps virus, rubella virus, respiratory syncytial virus, measles and enterovirus. No association was identified to any of the tested viruses. Furthermore, we tested sera from different age groups for TcCRA and found a progressive acquisition starting from early childhood. Our findings show a large seroprevalence of cross-reactive antibodies to a well-defined T. cruzi antigen and suggest they are induced by a widely spread immunogen, acquired from childhood. The etiology of TcCRA and their clinical relevance still need to be investigated.
PMCID: PMC3775794  PMID: 24069315
11.  Estimating Potential Infection Transmission Routes in Hospital Wards Using Wearable Proximity Sensors 
PLoS ONE  2013;8(9):e73970.
Contacts between patients, patients and health care workers (HCWs) and among HCWs represent one of the important routes of transmission of hospital-acquired infections (HAI). A detailed description and quantification of contacts in hospitals provides key information for HAIs epidemiology and for the design and validation of control measures.
Methods and Findings
We used wearable sensors to detect close-range interactions (“contacts”) between individuals in the geriatric unit of a university hospital. Contact events were measured with a spatial resolution of about 1.5 meters and a temporal resolution of 20 seconds. The study included 46 HCWs and 29 patients and lasted for 4 days and 4 nights. 14,037 contacts were recorded overall, 94.1% of which during daytime. The number and duration of contacts varied between mornings, afternoons and nights, and contact matrices describing the mixing patterns between HCW and patients were built for each time period. Contact patterns were qualitatively similar from one day to the next. 38% of the contacts occurred between pairs of HCWs and 6 HCWs accounted for 42% of all the contacts including at least one patient, suggesting a population of individuals who could potentially act as super-spreaders.
Wearable sensors represent a novel tool for the measurement of contact patterns in hospitals. The collected data can provide information on important aspects that impact the spreading patterns of infectious diseases, such as the strong heterogeneity of contact numbers and durations across individuals, the variability in the number of contacts during a day, and the fraction of repeated contacts across days. This variability is however associated with a marked statistical stability of contact and mixing patterns across days. Our results highlight the need for such measurement efforts in order to correctly inform mathematical models of HAIs and use them to inform the design and evaluation of prevention strategies.
PMCID: PMC3770639  PMID: 24040129
12.  Severe leukopenia in Staphylococcus aureus-necrotizing, community-acquired pneumonia: risk factors and impact on survival 
BMC Infectious Diseases  2013;13:359.
Necrotizing pneumonia attributed to Panton-Valentine leukocidin-positive Staphylococcus aureus has mainly been reported in otherwise healthy children and young adults, with a high mortality rate. Erythroderma, airway bleeding, and leukopenia have been shown to be predictive of mortality. The objectives of this study were to define the characteristics of patients with severe leukopenia at 48-h hospitalization and to update our data regarding mortality predicting factors in a larger population than we had previously described.
It was designed as a case-case study nested in a cohort study. A total of 148 cases of community-acquired, necrotizing pneumonia were included. The following data were collected: basic demographic information, medical history, signs and symptoms, radiological findings and laboratory results during the first 48 h of hospitalization. The study population was divided into 2 groups: (1) with severe leukopenia (leukocyte count ≤3,000 leukocytes/mL, n=62) and (2) without severe leukopenia (>3,000 leukocytes/mL, n=86).
Median age was 22 years, and the male-to-female gender ratio was 1.5. The overall in-hospital mortality rate was 41.2%. Death occurred in 75.8% of severe leukopenia cases with median survival time of 4 days, and in 16.3% of cases with leukocyte count >3,000/mL (P<0.001). Multivariate analysis indicated that the factors associated with severe leukopenia were influenza-like illness (adjusted odds ratio (aOR) 4.45, 95% CI (95% confidence interval) 1.67-11.88, P=0.003), airway bleeding (aOR 4.53, 95% CI 1.85-11.13, P=0.001) and age over 30 years (aOR 2.69, 95% CI 1.08-6.68, P=0.033). A personal history of furuncles appeared to be protective (OR 0.11, 95% CI 0.01-0.96, P=0.046).
S. aureus-necrotizing pneumonia is still an extremely severe disease in patients with severe leukopenia. Some factors could distinguish these patients, allowing better initial identification to initiate adapted, rapid administration of appropriate therapy.
PMCID: PMC3750359  PMID: 23915338
Community-acquired pneumonia; Staphylococcus aureus; Panton valentine leukocidin; Leukopenia
13.  Incidence of Hospital-Acquired Pneumonia, Bacteraemia and Urinary Tract Infections in Patients with Haematological Malignancies, 2004–2010: A Surveillance-Based Study 
PLoS ONE  2013;8(3):e58121.
This study charted incidence trends of hospital-acquired (HA) pneumonia, bacteraemia and urinary tract infections (UTI) in a haematology department.
Prospective surveillance of hospital-acquired infections (HAI) was undertaken in a 42-bed haematology department of a university hospital. All patients hospitalized ≥48 hours between 1st January 2004 and 31st December 2010 were included. Definitions of HAI were based on a standardized protocol. The incidence was the number of events per 1000 patient-days at risk; only the first HAI was counted. Multivariate Poisson regression was fitted to assess temporal trends.
Among 3 355 patients (58 063 patient-days at risk) included, 1 055 (31%) had HAI. The incidence of HA pneumonia, HA bacteraemia and HA UTI was respectively 3.3, 12.0 and 2.9 per 1000 patient-days at risk. HA bacteraemia incidence increased by 11% (95% confidence interval: +6%, +15%, P<0.001) per year, independently of neutropenia, central venous catheterization (CVC) and haematological disease. The incidences of HA pneumonia and HA UTI were stable. The most frequently isolated pathogens were Aspergillus spp. (59.2%) for pneumonia, coagulase-negative Staphylococcus (44.2%) for bacteraemia and enterobacteria (60%) for UTI.
The incidence of bacteraemia increased, indicating that factors other than CVC exposure, including chemotherapy with its impact on the immune system, could explain this trend. Further analytic studies are needed to explore the factors that could explain this trend.
PMCID: PMC3589363  PMID: 23472145
14.  A statistical model to assess the risk of communicable diseases associated with multiple exposures in healthcare settings 
The occurrence of communicable diseases (CD) depends on exposure to contagious persons. The effects of exposure to CD are delayed in time and contagious persons remain contagious for several days during which their contagiousness varies. Moreover when multiple exposures occur, it is difficult to know which exposure is associated with the CD.
A statistical model at the individual level is presented to estimate the risk of CD to patients, in healthcare settings, with multiple observed exposures to other patients and healthcare workers and unobserved exposures to unobserved or unobservable sources. The model explores the delayed effect of observed exposure, of source contagiousness and of unobserved exposure. It was applied to data on influenza-like illness (ILI) among patients in a university hospital during 3 influenza seasons: from 2004 to 2007. Over a total of 138,411 patients-days of follow-up, 64 incident ILI cases were observed among 21,519 patients at risk of ILI.
The ILI risk per 10,000 patients-days associated with observed exposure was about 129.1 (95% Credible Interval (CrI): 84.5, 182.9) and was associated at 72% with exposures to patients or healthcare workers 1 day earlier and at 41% with the 1st day of source contagiousness. The ILI risk associated with unobserved exposure was 0.8 (95% CrI: 0.3, 1.6) per 10,000 patients-days in non-epidemic situation in the community and 4.3 (95% CrI: 0.4, 11.0) in epidemic situation.
The model could be an interesting epidemiological tool to further assess the relative contributions of observed and unobserved exposures to CD risk in healthcare settings.
PMCID: PMC3599894  PMID: 23425160
Disease transmission; Infectious; Health facilities; Influenza; Human; Models; Statistical; Risk
15.  Diversity of Trends of Viremia and T-Cell Markers in Experimental Acute Feline Immunodeficiency Virus Infection 
PLoS ONE  2013;8(2):e56135.
The early events of human immunodeficiency virus infection seem critical for progression toward disease and antiretroviral therapy initiation. We wanted to clarify some still unknown prognostic relationships between inoculum size and changes in various immunological and virological markers. Feline immunodeficiency virus infection could be a helpful model.
Viremia and T-cell markers (number of CD4, CD8, CD8βlowCD62Lneg T-cells, CD4/CD8 ratio, and percentage of CD8βlowCD62Lneg cells among CD8 T-cells) were measured over 12 weeks in 102 cats infected with different feline immunodeficiency virus strains and doses. Viremia and T-cell markers trajectory groups were determined and the dose-response relationships between inoculum titres and trajectory groups investigated.
Cats given the same inoculum showed different patterns of changes in viremia and T-cell markers. A statistically significant positive dose-response relationship was observed between inoculum titre and i) viremia trajectory-groups (r = 0.80, p<0.01), ii) CD8βlowCD62Lneg cell-fraction trajectory-groups (r = 0.56, p<0.01). Significant correlations were also found between viremia and the CD4/CD8 ratio and between seven out of ten T-cell markers.
In cats, the infectious dose determines early kinetics of viremia and initial CD8+ T-cell activation. An expansion of the CD8βlowCD62Lneg T-cells might be an early predictor of progression toward disease. The same might be expected in humans but needs confirmation.
PMCID: PMC3567045  PMID: 23409138
16.  Pneumocystis jirovecii Genotype Associated with Increased Death Rate of HIV-infected Patients with Pneumonia 
Emerging Infectious Diseases  2013;19(1):21-28.
Comorbidities might predict presence of specific fungal genotypes.
PMCID: PMC3557975  PMID: 23260763
Pneumocystis jirovecii pneumonia; Pneumocystis jirovecii dihydropteroate synthase; DHPS; HIV; homosexuality; intravenous drug use; dihydropteroate synthase mutations; opportunistic infection; immunocompromised; virus; fungus; fungi; fungal; sulfa resistance; sulfamethoxazole/trimethoprim; SMX/TMP; dapsone; pentamidine; atovaquone; antimicrobial drugs; antibiotic; antifungal drugs
17.  French women’s knowledge of and attitudes towards cervical cancer prevention and the acceptability of HPV vaccination among those with 14 – 18 year old daughters: a quantitative-qualitative study 
BMC Public Health  2012;12:1034.
In France, it is recommended that girls and women aged 14–23 are vaccinated against the human papillomavirus (HPV). However, French women’s knowledge of and attitude towards the vaccine has been little studied.
Thirty-nine general practitioners, representative of those working in the large Rhône-Alpes region, offered a self-administered questionnaire on cervical cancer (CC) prevention to all 18–65 year-old women who came for consultation during June and July 2008. In addition, semi-structured interviews were undertaken with a sample of those who had daughters aged 14–18.
Of the 1,478 women who completed the questionnaire, only 16.9% mentioned HPV as the cause of CC, even though 76.2% knew of the vaccine. 210 women had daughters aged 14–18, and 32 were interviewed. Compared with the wider group, more of these women were aware of the HPV vaccine (91.4%). 44.8% knew the target population and 17.1% the recommended ages for vaccination. 54.3% favoured HPV vaccination; 37.2% were undecided and only 0.9% were opposed. The main barrier to acceptance was the recency of the vaccine’s introduction and concern about possible side effects (54.9%); 14.1% preferred to rely on their GP’s decision. Factors associated with acceptance of the HPV vaccine were having previously vaccinated a child against pneumococcus (OR=3.28 [1.32-8.11]) and knowing the target population for HPV vaccination (OR=2.12 [1.15-3.90]). Knowing the recommended frequency of Papanicolaou smear testing (Pap test) screening was associated with lower acceptance (OR=0.32 [0.13-0.82]).
Few mothers are opposed to HPV vaccination. Factors associated with acceptability were knowledge about the vaccine, acceptance of other vaccines and, unexpectedly, lack of knowledge about the recommended frequency of Pap testing. On multivariate analysis, compliance with recommendations for Pap test screening and socioeconomic factors had no effect on views about HPV vaccination. Given that concern about possible side effects is the major barrier to wider acceptance of the HPV vaccine in France, GPs have a key role in providing information.
PMCID: PMC3533507  PMID: 23186288
Papillomavirus; HPV vaccine; Cervical cancer prevention; Acceptability; Women; Mothers
18.  Evaluation of adult dTPaP vaccination coverage in France: experience in Lyon city, 2010–2011 
BMC Public Health  2012;12:940.
Compliance with official recommendations can be assessed by evaluating vaccination coverage (VC) in populations. The main objective of our study was to assess VC of adults against diphtheria, tetanus, poliomyelitis and pertussis (dTPaP) according to age. The second objective was to explore if vaccination status could be confirmed by documentation.
A cross-sectional study was conducted in 680 adults consulting for biological examination in private laboratories in Lyon (France) to evaluate VC for diphtheria, tetanus, poliomyelitis and pertussis (dTPaP) and enabled reported vaccinations to be compared with documented, confirmed vaccinations.
Verification of documented, confirmed vaccinations disclosed VC of 78.7% for tetanus, 63.6% for poliomyelitis, 57.8% for diphtheria and 10.7% for pertussis. Comparison of confirmed and self-reported vaccinations revealed that a large percentage of people who thought that they were vaccinated were not. VC significantly decreased with age for diphtheria and poliomyelitis and did not vary by gender. The VC rate for pertussis has increased since the 2008 recommendations were made.
The main thrust of this study was to compare reported and confirmed data. A significant percentage of people wrongly believed that they were up to date with their vaccination.
PMCID: PMC3526515  PMID: 23114050
Vaccination coverage; Adults; Diphtheria; Tetanus; Poliomyelitis; Pertussis
19.  Impact of surveillance of hospital-acquired infections on the incidence of ventilator-associated pneumonia in intensive care units: a quasi-experimental study 
Critical Care  2012;16(4):R161.
The preventive impact of hospital-acquired infection (HAI) surveillance is difficult to assess. Our objective was to investigate the effect of HAI surveillance disruption on ventilator-associated pneumonia (VAP) incidence.
A quasi-experimental study with an intervention group and a control group was conducted between 1 January 2004 and 31 December 2010 in two intensive care units (ICUs) of a university hospital that participated in a national HAI surveillance network. Surveillance was interrupted during the year 2007 in unit A (intervention group) and was continuous in unit B (control group). Period 1 (pre-test period) comprised patients hospitalized during 2004 to 2006, and period 2 (post-test period) involved patients hospitalized during 2008 to 2010. Patients hospitalized ≥48 hours and intubated during their stay were included. Multivariate Poisson regression was fitted to ascertain the influence of surveillance disruption.
A total of 2,771 patients, accounting for 19,848 intubation-days at risk, were studied; 307 had VAP. The VAP attack rate increased in unit A from 7.8% during period 1 to 17.1% during period 2 (P <0.001); in unit B, it was 7.2% and 11.2% for the two periods respectively (P = 0.17). Adjusted VAP incidence rose in unit A after surveillance disruption (incidence rate ratio = 2.17, 95% confidence interval 1.05 to 4.47, P = 0.036), independently of VAP trend; no change was observed in unit B. All-cause mortality and length of stay increased (P = 0.028 and P = 0.038, respectively) in unit A between periods 1 and 2. In unit B, no change in mortality was observed (P = 0.22), while length of stay decreased between periods 1 and 2 (P = 0.002).
VAP incidence, length of stay and all-cause mortality rose after HAI surveillance disruption in ICU, which suggests a specific effect of HAI surveillance on VAP prevention and reinforces the role of data feedback and counselling as a mechanism to facilitate performance improvement.
PMCID: PMC3580751  PMID: 22909033
20.  Professional Exposure to Goats Increases the Risk of Pneumonic-Type Lung Adenocarcinoma: Results of the IFCT-0504-Epidemio Study 
PLoS ONE  2012;7(5):e37889.
Pneumonic-type lung adenocarcinoma (P-ADC) represents a distinct subset of lung cancer with specific clinical, radiological, and pathological features. Given the weak association with tobacco-smoking and the striking similarities with jaagsiekte sheep retrovirus (JSRV)-induced ovine pulmonary adenocarcinoma, it has been suggested that a zoonotic viral agent infecting pulmonary cells may predispose to P-ADC in humans. Our objective was to explore whether exposure to domestic small ruminants may represent a risk factor for P-ADC. We performed a multicenter case-control study recruiting patients with P-ADC as cases and patients with non-P-ADC non-small cell lung cancer as controls. A dedicated 356-item questionnaire was built to evaluate exposure to livestock. A total of 44 cases and 132 controls were included. At multivariate analysis, P-ADC was significantly more associated with female gender (Odds-ratio (OR) = 3.23, 95% confidence interval (CI): 1.32–7.87, p = 0.010), never- smoker status (OR = 3.57, 95% CI: 1.27–10.00, p = 0.015), personal history of extra-thoracic cancer before P-ADC diagnosis (OR = 3.43, 95% CI: 1.10–10.72, p = 0.034), and professional exposure to goats (OR = 5.09, 95% CI: 1.05–24.69, p = 0.043), as compared to other subtypes of lung cancer. This case-control suggests a link between professional exposure to goats and P-ADC, and prompts for further epidemiological evaluation of potential environmental risk factors for P-ADC.
PMCID: PMC3360000  PMID: 22655078
21.  Influenza vaccination of healthcare workers in acute-care hospitals: a case-control study of its effect on hospital-acquired influenza among patients 
In acute-care hospitals, no evidence of a protective effect of healthcare worker (HCW) vaccination on hospital-acquired influenza (HAI) in patients has been documented. Our study objective was to ascertain the effectiveness of influenza vaccination of HCW on HAI among patients.
A nested case-control investigation was implemented in a prospective surveillance study of influenza-like illness (ILI) in a tertiary acute-care university hospital. Cases were patients with virologically-confirmed influenza occurring ≥ 72 h after admission, and controls were patients with ILI presenting during hospitalisation with negative influenza results after nasal swab testing. Four controls per case, matched per influenza season (2004-05, 2005-06 and 2006-07), were randomly selected. Univariate and multivariate conditional logistic regression models were fitted to assess factors associated with HAI among patients.
In total, among 55 patients analysed, 11 (20%) had laboratory-confirmed HAI. The median HCW vaccination rate in the units was 36%. The median proportion of vaccinated HCW in these units was 11.5% for cases vs. 36.1% for the controls (P = 0.11); 2 (20%) cases and 21 (48%) controls were vaccinated against influenza in the current season (P = 0.16). The proportion of ≥ 35% vaccinated HCW in short-stay units appeared to protect against HAI among patients (odds ratio = 0.07; 95% confidence interval 0.005-0.98), independently of patient age, influenza season and potential influenza source in the units.
Our observational study indicates a shielding effect of more than 35% of vaccinated HCW on HAI among patients in acute-care units. Investigations, such as controlled clinical trials, are needed to validate the benefits of HCW vaccination on HAI incidence in patients.
PMCID: PMC3293022  PMID: 22292886
22.  Early-onset ventilator-associated pneumonia incidence in intensive care units: a surveillance-based study 
BMC Infectious Diseases  2011;11:236.
The incidence of ventilator-associated pneumonia (VAP) within the first 48 hours of intensive care unit (ICU) stay has been poorly investigated. The objective was to estimate early-onset VAP occurrence in ICUs within 48 hours after admission.
We analyzed data from prospective surveillance between 01/01/2001 and 31/12/2009 in 11 ICUs of Lyon hospitals (France). The inclusion criteria were: first ICU admission, not hospitalized before admission, invasive mechanical ventilation during first ICU day, free of antibiotics at admission, and ICU stay ≥ 48 hours. VAP was defined according to a national protocol. Its incidence was the number of events per 1,000 invasive mechanical ventilation-days. The Poisson regression model was fitted from day 2 (D2) to D8 to incident VAP to estimate the expected VAP incidence from D0 to D1 of ICU stay.
Totally, 367 (10.8%) of 3,387 patients in 45,760 patient-days developed VAP within the first 9 days. The predicted cumulative VAP incidence at D0 and D1 was 5.3 (2.6-9.8) and 8.3 (6.1-11.1), respectively. The predicted cumulative VAP incidence was 23.0 (20.8-25.3) at D8. The proportion of missed VAP within 48 hours from admission was 11% (9%-17%).
Our study indicates underestimation of early-onset VAP incidence in ICUs, if only VAP occurring ≥ 48 hours are considered to be hospital-acquired. Clinicians should be encouraged to develop a strategy for early detection after ICU admission.
PMCID: PMC3190374  PMID: 21896188
23.  High-Resolution Measurements of Face-to-Face Contact Patterns in a Primary School 
PLoS ONE  2011;6(8):e23176.
Little quantitative information is available on the mixing patterns of children in school environments. Describing and understanding contacts between children at school would help quantify the transmission opportunities of respiratory infections and identify situations within schools where the risk of transmission is higher. We report on measurements carried out in a French school (6–12 years children), where we collected data on the time-resolved face-to-face proximity of children and teachers using a proximity-sensing infrastructure based on radio frequency identification devices.
Methods and Findings
Data on face-to-face interactions were collected on Thursday, October 1st and Friday, October 2nd 2009. We recorded 77,602 contact events between 242 individuals (232 children and 10 teachers). In this setting, each child has on average 323 contacts per day with 47 other children, leading to an average daily interaction time of 176 minutes. Most contacts are brief, but long contacts are also observed. Contacts occur mostly within each class, and each child spends on average three times more time in contact with classmates than with children of other classes. We describe the temporal evolution of the contact network and the trajectories followed by the children in the school, which constrain the contact patterns. We determine an exposure matrix aimed at informing mathematical models. This matrix exhibits a class and age structure which is very different from the homogeneous mixing hypothesis.
We report on important properties of the contact patterns between school children that are relevant for modeling the propagation of diseases and for evaluating control measures. We discuss public health implications related to the management of schools in case of epidemics and pandemics. Our results can help define a prioritization of control measures based on preventive measures, case isolation, classes and school closures, that could reduce the disruption to education during epidemics.
PMCID: PMC3156713  PMID: 21858018
24.  Simulation of an SEIR infectious disease model on the dynamic contact network of conference attendees 
BMC Medicine  2011;9:87.
The spread of infectious diseases crucially depends on the pattern of contacts between individuals. Knowledge of these patterns is thus essential to inform models and computational efforts. However, there are few empirical studies available that provide estimates of the number and duration of contacts between social groups. Moreover, their space and time resolutions are limited, so that data are not explicit at the person-to-person level, and the dynamic nature of the contacts is disregarded. In this study, we aimed to assess the role of data-driven dynamic contact patterns between individuals, and in particular of their temporal aspects, in shaping the spread of a simulated epidemic in the population.
We considered high-resolution data about face-to-face interactions between the attendees at a conference, obtained from the deployment of an infrastructure based on radiofrequency identification (RFID) devices that assessed mutual face-to-face proximity. The spread of epidemics along these interactions was simulated using an SEIR (Susceptible, Exposed, Infectious, Recovered) model, using both the dynamic network of contacts defined by the collected data, and two aggregated versions of such networks, to assess the role of the data temporal aspects.
We show that, on the timescales considered, an aggregated network taking into account the daily duration of contacts is a good approximation to the full resolution network, whereas a homogeneous representation that retains only the topology of the contact network fails to reproduce the size of the epidemic.
These results have important implications for understanding the level of detail needed to correctly inform computational models for the study and management of real epidemics.
Please see related article BMC Medicine, 2011, 9:88
PMCID: PMC3162551  PMID: 21771290
25.  A multiplicative hazard regression model to assess the risk of disease transmission at hospital during community epidemics 
During community epidemics, infections may be imported within hospital and transmitted to hospitalized patients. Hospital outbreaks of communicable diseases have been increasingly reported during the last decades and have had significant consequences in terms of patient morbidity, mortality, and associated costs. Quantitative studies are thus needed to estimate the risks of communicable diseases among hospital patients, taking into account the epidemiological process outside, hospital and host-related risk factors of infection and the role of other patients and healthcare workers as sources of infection.
We propose a multiplicative hazard regression model to analyze the risk of acquiring a communicable disease by patients at hospital. This model derives from epidemiological data on communicable disease epidemics in the community, hospital ward, patient susceptibility to infection, and exposure of patients to infection at hospital. The model estimates the relative effect of each of these factors on a patient's risk of communicable disease.
Using individual data on patients and health care workers in a teaching hospital during the 2004-2005 influenza season in Lyon (France), we show the ability of the model to assess the risk of influenza-like illness among hospitalized patients. The significant effects on the risk of influenza-like illness were those of old age, exposure to infectious patients or health care workers, and a stay in a medical care unit.
The proposed multiplicative hazard regression model could be an interesting epidemiological tool to quantify the risk of communicable disease at hospital during community epidemics and the uncertainty inherent in such quantification. Furthermore, key epidemiological, environmental, host, or exposure factors that influence this risk can be identified.
PMCID: PMC3110120  PMID: 21507247

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