Nagham Khanafer

Simulation of an SEIR infectious disease model on the dynamic contact network of conference attendees

BackgroundThe 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.MethodsWe 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.ResultsWe 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.ConclusionsThese 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

Meta-Analysis of Antibiotics and the Risk of Community-Associated Clostridium difficile Infection

ABSTRACT The rising incidence of Clostridium difficile infection (CDI) could be reduced by lowering exposure to high-risk antibiotics. The objective of this study was to determine the association between antibiotic class and the risk of CDI in the community setting. The EMBASE and PubMed databases were queried without restriction to time period or language. Comparative observational studies and randomized controlled trials (RCTs) considering the impact of exposure to antibiotics on CDI risk among nonhospitalized populations were considered. We estimated pooled odds ratios (OR) for antibiotic classes using random-effect meta-analysis. Our search criteria identified 465 articles, of which 7 met inclusion criteria; all were observational studies. Five studies considered antibiotic risk relative to no antibiotic exposure: clindamycin (OR = 16.80; 95% confidence interval [95% CI], 7.48 to 37.76), fluoroquinolones (OR = 5.50; 95% CI, 4.26 to 7.11), and cephalosporins, monobactams, and carbapenems (CMCs) (OR = 5.68; 95% CI, 2.12 to 15.23) had the largest effects, while macrolides (OR = 2.65; 95% CI, 1.92 to 3.64), sulfonamides and trimethoprim (OR = 1.81; 95% CI, 1.34 to 2.43), and penicillins (OR = 2.71; 95% CI, 1.75 to 4.21) had lower associations with CDI. We noted no effect of tetracyclines on CDI risk (OR = 0.92; 95% CI, 0.61 to 1.40). In the community setting, there is substantial variation in the risk of CDI associated with different antimicrobial classes. Avoidance of high-risk antibiotics (such as clindamycin, CMCs, and fluoroquinolones) in favor of lower-risk antibiotics (such as penicillins, macrolides, and tetracyclines) may help reduce the incidence of CDI.

Estimating Potential Infection Transmission Routes in Hospital Wards Using Wearable Proximity Sensors

Background 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. Conclusions 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.

Methicillin resistance is not a predictor of severity in community-acquired Staphylococcus aureus necrotizing pneumonia—results of a prospective observational study

Staphylococcal necrotizing pneumonia (NP) is a severe disease associated with Panton-Valentine leucocidin (PVL). NP was initially described for methicillin-susceptible Staphylococcus aureus (MSSA) infection, but cases associated with methicillin-resistant S. aureus (MRSA) infection have increased concomitantly with the incidence of community-acquired MRSA worldwide. The role of methicillin resistance in the severity of NP remains controversial. The characteristics and outcomes of 133 patients with PVL-positive S. aureus community-acquired pneumonia (CAP) were compared according to methicillin resistance. Data from patients hospitalized for PVL-positive S. aureus CAP in France from 1986 to 2010 were reported to the National Reference Centre for Staphylococci and were included in the study. The primary end point was mortality. Multivariate logistic modelling and the Cox regression were used for subsequent analyses. We analysed 29 cases of PVL-MRSA and 104 cases of PVL-MSSA pneumonia. Airway haemorrhages were more frequently associated with PVL-MSSA pneumonia. However, no differences in the initial severity or the management were found between these two types of pneumonia. The rate of lethality was 39% regardless of methicillin resistance. By Cox regression analysis, methicillin resistance was not found to be a significant independent predictor of mortality at 7 or 30 days (p 0.65 and p 0.71, respectively). Our study demonstrates that methicillin resistance is not associated with the severity of staphylococcal necrotizing pneumonia.

Combining High-Resolution Contact Data with Virological Data to Investigate Influenza Transmission in a Tertiary Care Hospital

OBJECTIVE Contact patterns and microbiological data contribute to a detailed understanding of infectious disease transmission. We explored the automated collection of high-resolution contact data by wearable sensors combined with virological data to investigate influenza transmission among patients and healthcare workers in a geriatric unit. DESIGN Proof-of-concept observational study. Detailed information on contact patterns were collected by wearable sensors over 12 days. Systematic nasopharyngeal swabs were taken, analyzed for influenza A and B viruses by real-time polymerase chain reaction, and cultured for phylogenetic analysis. SETTING An acute-care geriatric unit in a tertiary care hospital. PARTICIPANTS Patients, nurses, and medical doctors. RESULTS A total of 18,765 contacts were recorded among 37 patients, 32 nurses, and 15 medical doctors. Most contacts occurred between nurses or between a nurse and a patient. Fifteen individuals had influenza A (H3N2). Among these, 11 study participants were positive at the beginning of the study or at admission, and 3 patients and 1 nurse acquired laboratory-confirmed influenza during the study. Infectious medical doctors and nurses were identified as potential sources of hospital-acquired influenza (HA-Flu) for patients, and infectious patients were identified as likely sources for nurses. Only 1 potential transmission between nurses was observed. CONCLUSIONS Combining high-resolution contact data and virological data allowed us to identify a potential transmission route in each possible case of HA-Flu. This promising method should be applied for longer periods in larger populations, with more complete use of phylogenetic analyses, for a better understanding of influenza transmission dynamics in a hospital setting.

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, 3(rd) 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 ICUs patients.

Severe leukopenia in Staphylococcus aureus -necrotizing, community-acquired pneumonia: risk factors and impact on survival

BackgroundNecrotizing 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.MethodsIt 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).ResultsMedian 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).ConclusionS. 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.

Clostridium difficile infection in a French university hospital: Eight years of prospective surveillance study.

AbstractThe epidemiology of Clostridium difficile infection (CDI) has changed with an increase in incidence and severity. Prospective surveillance was therefore implemented in a French university hospital to monitor the characteristics of patients at risk and to recognize local trends. Between 2007 and 2014, all hospitalized patients (≥18 years) with CDI were included. During the survey, the mean incidence rate of CDI was 2.9 per 10,000 hospital-days. In all, 590 patients were included. Most of the episodes were healthcare-associated (76.1%). The remaining cases were community-acquired (18.1%) and unknown (5.9%). The comparison with healthcare-associated cases showed that the community-acquired group had a lower rate of antimicrobial exposure (P < 0.001), proton pump inhibitor (P < 0.001), and immunosuppressive drugs (P = 0.02). Over the study period, death occurred in 61 patients (10.3%), with 18 (29.5%) being related to CDI according to the physician in charge of the patient. Active surveillance of CDI is required to obtain an accurate picture of the real dimensions of CDI.

First presentation for care of HIV-infected patients with low CD4 cell count in Lyon, France: risk factors and consequences for survival.

Abstract To identify the risk factors associated with presentation for care with CD4 cell count ≤200 cells/mm3 and death in HIV-infected patients in Lyon, France. Data were analyzed on participants from mid-1992 to December 2006 in the Lyon section of the French Hospital Database on HIV Infection. Patients were stratified into two categories according to CD4 cell count at first presentation for care in University of Lyon hospitals: Group 1 (Gr1) patients with CD4 ≤200 cells/mm3 and Group 2 (Gr2) patients with CD4 >200 cells/mm3. Multivariate logistic regression assessed the risk factors associated with first presentation for care with CD4 ≤200 cells/mm3. Survival was analyzed according to the Cox regression model. Among 3569 eligible patients (838 females and 2731 males, mean age: 36.3±10.3 years), 1139 (31.9%) were categorized as Gr1. The factors associated with first presentation for care with CD4 ≤200 cells/mm3 were: older age, male gender, route of HIV transmission, migrant populations, geographical areas other than Rhône-Alpes, and access to care in 1992–1997. Overall mortality was higher in Gr1 than in Gr2 (24.4% [278/1139] vs. 4.1% [101/2430]; p<0.001). The risk of death was 5.81 [4.61–7.32] in Gr1 compared to Gr2. In addition to CD4 cell count, age and enrollment periods for care were factors independently related to death. Despite public health efforts in Lyon, one-third of HIV-infected patients reach the health care system with CD4 cell count ≤200 cells/mm3, which was linked with higher mortality.

Contacts between health care workers and patients in a short-stay geriatric unit during the peak of a seasonal influenza epidemic compared with a nonepidemic period

BACKGROUND Patterns of contacts between health care workers and patients during seasonal epidemics are unknown. Our study objective was to compare the number and duration of contacts between health care workers and patients during a nonepidemic period versus a community influenza epidemic, and to identify supercontactors. METHODS Our observational study was conducted in a short-stay geriatric unit of a university hospital. Contacts between individuals were recorded by active radio frequency identification devices. Contact patterns were compared between 2 periods according to contact number and duration. Each care period lasted 5 days in the nonepidemic and influenza epidemic periods. RESULTS The study included 21 medical doctors, 43 nurses, and 56 patients. In total, 3,200 contacts (61.4%; 152,700 seconds) were recorded during the nonepidemic period, with 2,013 contacts (38.6%; 92,740 seconds) in the epidemic period (P = .007). More cumulative contacts occurred during the nonepidemic period between nurses and patients (n = 2,638 [82%] vs n = 1,599 [79%]), but not between patients (n = 56 [18%] vs n = 414 [21%]). Contact duration between nurses and patients lasted longer during the nonepidemic period (P = .04). During the epidemic period, 6 nurses (15%) considered to be supercontactors accounted for 44.3% of the total number of contacts with patients. CONCLUSION The pattern of contacts between individuals differed according to the presence or not of the community influenza peak that might have influenced the risk of nosocomial influenza.