Efficacy of three COVID-19 vaccine doses in lung transplant recipients: a multicentre cohort study.

QUESTION ADDRESSED BY THE STUDY: Do three coronavirus disease 2019 (COVID-19) vaccine doses induce a serological response in lung transplant recipients? METHODS: We retrospectively included 1071 adults (551 (52%) males) at nine transplant centres in France. Each had received three COVID-19 vaccine doses in 2021, after lung transplantation. An anti-spike protein IgG response, defined as a titre >264 BAU·mL-1 after the third dose (median (interquartile range (IQR)) 3.0 (1.7-4.1) months), was the primary outcome and adverse events were the secondary outcomes. Median (IQR) age at the first vaccine dose was 54 (40-63) years and median (IQR) time from transplantation to the first dose was 64 (30-110) months. RESULTS: Median (IQR) follow-up after the first dose was 8.3 (6.7-9.3) months. A vaccine response developed in 173 (16%) patients. Factors independently associated with a response were younger age at vaccination, longer time from transplantation to vaccination and absence of corticosteroid or mycophenolate therapy. After vaccination, 51 (5%) patients (47 non-responders (47/898 (5%)) and four (4/173 (2%)) responders) experienced COVID-19, at a median (IQR) of 6.6 (5.1-7.3) months after the third dose. No responders had severe COVID-19 compared with 15 non-responders, including six who died of the disease. CONCLUSIONS: Few lung transplant recipients achieved a serological response to three COVID-19 vaccine doses, indicating a need for other protective measures. Older age and use of mycophenolate or corticosteroids were associated with absence of a response. The low incidence of COVID-19 might reflect vaccine protection via cellular immunity and/or good adherence to shielding measures.

Vaccine effectiveness against COVID-19 hospitalisation in adults (≥ 20 years) during Alpha- and Delta-dominant circulation: I-MOVE-COVID-19 and VEBIS SARI VE networks, Europe, 2021.

IntroductionTwo large multicentre European hospital networks have estimated vaccine effectiveness (VE) against COVID-19 since 2021.AimWe aimed to measure VE against PCR-confirmed SARS-CoV-2 in hospitalised severe acute respiratory illness (SARI) patients ≥ 20 years, combining data from these networks during Alpha (March-June)- and Delta (June-December)-dominant periods, 2021.MethodsForty-six participating hospitals across 14 countries follow a similar generic protocol using the test-negative case-control design. We defined complete primary series vaccination (PSV) as two doses of a two-dose or one of a single-dose vaccine ≥ 14 days before onset.ResultsWe included 1,087 cases (538 controls) and 1,669 cases (1,442 controls) in the Alpha- and Delta-dominant periods, respectively. During the Alpha period, VE against hospitalisation with SARS-CoV2 for complete Comirnaty PSV was 85% (95% CI: 69-92) overall and 75% (95% CI: 42-90) in those aged ≥ 80 years. During the Delta period, among SARI patients ≥ 20 years with symptom onset ≥ 150 days from last PSV dose, VE for complete Comirnaty PSV was 54% (95% CI: 18-74). Among those receiving Comirnaty PSV and mRNA booster (any product) ≥ 150 days after last PSV dose, VE was 91% (95% CI: 57-98). In time-since-vaccination analysis, complete all-product PSV VE was > 90% in those with their last dose < 90 days before onset; ≥ 70% in those 90-179 days before onset.ConclusionsOur results from this EU multi-country hospital setting showed that VE for complete PSV alone was higher in the Alpha- than the Delta-dominant period, and addition of a first booster dose during the latter period increased VE to over 90%.

Vaccine effectiveness against COVID-19 hospitalisation in adults (≥ 20 years) during Omicron-dominant circulation: I-MOVE-COVID-19 and VEBIS SARI VE networks, Europe, 2021 to 2022.

IntroductionThe I-MOVE-COVID-19 and VEBIS hospital networks have been measuring COVID-19 vaccine effectiveness (VE) in participating European countries since early 2021.AimWe aimed to measure VE against PCR-confirmed SARS-CoV-2 in patients ≥ 20 years hospitalised with severe acute respiratory infection (SARI) from December 2021 to July 2022 (Omicron-dominant period).MethodsIn both networks, 46 hospitals (13 countries) follow a similar test-negative case-control protocol. We defined complete primary series vaccination (PSV) and first booster dose vaccination as last dose of either vaccine received ≥ 14 days before symptom onset (stratifying first booster into received < 150 and ≥ 150 days after last PSV dose). We measured VE overall, by vaccine category/product, age group and time since first mRNA booster dose, adjusting by site as a fixed effect, and by swab date, age, sex, and presence/absence of at least one commonly collected chronic condition.ResultsWe included 2,779 cases and 2,362 controls. The VE of all vaccine products combined against hospitalisation for laboratory-confirmed SARS-CoV-2 was 43% (95% CI: 29-54) for complete PSV (with last dose received ≥ 150 days before onset), while it was 59% (95% CI: 51-66) after addition of one booster dose. The VE was 85% (95% CI: 78-89), 70% (95% CI: 61-77) and 36% (95% CI: 17-51) for those with onset 14-59 days, 60-119 days and 120-179 days after booster vaccination, respectively.ConclusionsOur results suggest that, during the Omicron period, observed VE against SARI hospitalisation improved with first mRNA booster dose, particularly for those having symptom onset < 120 days after first booster dose.

Cash interventions to improve clinical outcomes for pulmonary tuberculosis: systematic review and meta-analysis.

OBJECTIVE: To assess cash transfer interventions for improving treatment outcomes of active pulmonary tuberculosis in low- and middle-income countries. METHODS: We searched PubMed®, Embase®, Cochrane Library and ClinicalTrials.gov for studies published until 4 August 2017 that reported on cash transfer interventions during the treatment of active pulmonary tuberculosis in low- and middle-income countries. Our primary outcome was a positive clinical outcome, defined as treatment success, treatment completion or microbiologic cure. Using the purchasing power parity conversion factor, we converted the amount of cash received per patient within each study into international dollars (Int$). We calculated odds ratio (OR) for the primary outcome using a random effects meta-analysis. FINDINGS: Eight studies met eligibility criteria for review inclusion. Seven studies assessed a tuberculosis-specific intervention, with average amount of cash ranging from Int$ 193-858. One study assessed a tuberculosis-sensitive intervention, with average amount of Int$ 101. Four studies included non-cash co-interventions. All studies showed better primary outcome for the intervention group than the control group. After excluding three studies with high risk of bias, patients receiving tuberculosis-specific cash transfer were more likely to have a positive clinical outcome than patients in the control groups (OR: 1.77; 95% confidence interval: 1.57-2.01). CONCLUSION: The evidence available suggests that patients in low- and middle-income countries receiving cash during treatment for active pulmonary tuberculosis are more likely to have a positive clinical outcome. These findings support the incorporation of cash transfer interventions into social protection schemes within tuberculosis treatment programmes.

Health Literacy and Health Care System Confidence as Determinants of Attitudes to Vaccines in France: Representative Cross-Sectional Study.

BACKGROUND: Health literacy involves individuals' knowledge, personal skills, and confidence to take action to evaluate and appraise health-related information and improve their health or that of their community. OBJECTIVE: This study aimed to analyze the association between health literacy and attitude toward vaccines, adjusted with other factors. METHODS: We used the SLAVACO Wave 3, a survey conducted in December 2021 among a sample of 2022 individuals, representative of the French adult population. We investigated factors associated with the attitude toward vaccines using respondents' different sociodemographic data, health literacy levels, and the health care system confidence levels using a multinomial logistic regression analysis. RESULTS: Among the participants, 440.4 (21.8%) were classified as "distrustful of vaccines in general," 729.2 (36.1%) were "selectively hesitant," and 852.4 (42.2%) were "nonhesitant." In our model, the level of health literacy was not statistically different between the "distrustful of vaccines in general" and the "selectively hesitant" (P=.48), but it was associated with being a "nonhesitant" (adjusted odds ratio [aOR] 1.86, 95% CI 1.25-2.76). The confidence in the health care system was a strong predictor for a "nonhesitant" attitude toward vaccines (aOR 12.4, 95% CI 7.97-19.2). We found a positive correlation of 0.34 (P<.001) between health literacy and confidence in the health care system, but the interaction term between health literacy and health care system confidence was not significant in our model. CONCLUSIONS: Health literacy was associated with a "nonhesitant" attitude toward vaccines. The findings demonstrated that health literacy and confidence in the health care system are modestly correlated. Therefore, to tackle the subject of vaccine hesitancy, the main focus should be on increasing the population's confidence and on increasing their health literacy levels or providing vaccine information addressing the needs of less literate citizens.

A Comparison of Presentation, Treatment, and Survival After Hepatocellular Carcinoma of Viral and Non-Viral Etiology in Damietta, Egypt, 2007-2019.

Context: The difference in prognosis between patients diagnosed with viral versus non-viral hepatocellular carcinoma (HCC) in Egypt remains unclear. Methods: We used data from patients diagnosed with HCC between 2007 and 2019 from a large monocentric retrospective cohort at the Damietta Oncology referral center (northern Egypt). Presentation and treatment were compared between viral versus non-viral etiology HCC patients. Survival was compared relying on univariate and multivariate Cox regressions. Results: Data from 4714 HCC patients were analyzed. Among them, 204 (4.3%) presented with a non-viral etiology. Patients with non-viral versus viral etiology had a similar presentation overall, especially regarding the BCLC stage at HCC diagnosis. After controlling for various individual characteristics, patients with non-viral versus viral etiology had poorer survival (adjusted Hazard Ratio: 1.244; 95% Confidence Interval: 1.069-1.447). Conclusion: Despite similar features, patients with non-viral- related HCC had poorer survival compared to patients with viral-related HCC.

Changes in Presentation, Treatment, and Survival of Patients with Hepatocellular Carcinoma in Damietta, Egypt, 2007-2019: A Retrospective Monocentric Cohort Study.

Introduction: We aimed to assess temporal changes in the presentation and survival of patients with hepatocellular carcinoma (HCC) in the northern Egypt region, one of the regions reporting the highest incidence of the disease globally. Methods: We conducted a monocentric retrospective study. Patients presenting at the Damietta Oncology referral center between 2007 and 2019 with a diagnosed HCC were eligible. Individual, clinical and tumor characteristics at HCC diagnosis, including the Barcelona Clinic Liver Cancer (BCLC) staging, were retrieved from medical files and patients' final vital status was ascertained by combining various data sources. Patients were divided into 2 groups based on diagnosis period: pre- and post-2014. Survival was analysed based on Kaplan-Meier curves and differences in restricted mean survival time (RMST). Results: Data from 5097 patients (among 5210 eligible, 97.8%) were analyzed. We observed a significant trend toward HCC diagnosed at earlier stage in the post- vs pre-2014 period (BCLC stage 0/A or B: 37.2% vs 27.1%, p<10-3). Overall patient's survival after the HCC diagnosis was poor, with a median of 8.1 months. The BCLC staging system performed well in predicting survival. Despite a trend toward HCC diagnosed at earlier stages, we did not observe a significant improvement in survival over time. Overall, treatments offered in this medical center were in line with international guidelines, and 16.1% of the patients who received a curative treatment had an improved survival (30.7 months in median). However, HCC recurrence was frequent among patients cured for HCC, with a median time to recurrence of 22 months. Discussion: Overall survival after HCC diagnosis in Egypt remains poor but is significantly improved by curative therapy. Despite a trend toward earlier diagnosis of HCC, we did not observe a general improvement in survival over time, which remains to be clearly understood.

COVID-19 Vaccines against Omicron Variant: Real-World Data on Effectiveness.

The efficacy of vaccines against coronavirus disease 2019 (COVID-19) has now been well established in phase III clinical trials. However, clinical studies based on real-world data remain critical to assess vaccines effectiveness (VE), especially in specific populations and against variants of concern (VOC). This review presents the principles and methods of VE studies and the main available results on VE of COVID-19 vaccines at the time of Omicron circulation. References for this narrative review were identified through searches of PubMed database up to 13 September 2022. The results of phase III clinical trials have been globally confirmed by VE in real-life studies, including in the elderly. Emergence of VOC Omicron emphasized the importance of booster doses to maintain a high level of protection against severe forms. There are still numerous challenges regarding booster(s) and duration of immunity, particularly in specific subpopulations, and regarding the need for adapted vaccines.

Meta-analysis: risk of hepatitis C virus infection associated with hospital-based invasive procedures.

BACKGROUND: Healthcare settings, where invasive procedures are frequently performed, may play an important role in the transmission dynamics of blood-borne pathogens when compliance with infection control precautions is suboptimal. AIMS: To understand and quantify the role of hospital-based invasive procedures on hepatitis C virus (HCV) transmission. METHODS: We conducted a systematic review and meta-analysis to identify recent studies reporting association measures of HCV infection risk that are linked to iatrogenic procedures. Based on expert opinion, invasive procedures were categorised into 10 groups for which pooled measures were calculated. Finally, the relationship between pooled measures and the country-level HCV prevalence or the Healthcare Access and Quality (HAQ) index was assessed by meta-regression. RESULTS: We included 71 studies in the analysis. The most frequently evaluated procedures were blood transfusion (66 measures) and surgery (43 measures). The pooled odds ratio (OR) of HCV infection varied widely, ranging from 1.46 (95% confidence interval: 1.14-1.88) for dental procedures to 3.22 (1.7-6.11) for transplantation. The OR for blood transfusion was higher for transfusions performed before 1998 (3.77, 2.42-5.88) than for those without a specified/recent date (2.20, 1.77-2.75). In procedure-specific analyses, the HCV infection risk was significantly negatively associated with the HAQ for endoscopy and positively associated with HCV prevalence for endoscopy and surgery. CONCLUSIONS: Various invasive procedures were significantly associated with HCV infection. Our results provide a ranking of procedures in terms of HCV risk that may be used for prioritisation of infection control interventions, especially in high HCV prevalence settings.

A national platform for Covid-19 vaccine studies recruitment in France: Covireivac volunteer's characteristics.

During the Covid-19 pandemic, the urgent need for safe and effective vaccines has led to many vaccine trials, implying fast and extensive recruitment of volunteers. In France, until 2020, vaccine clinical research participants were usually recruited locally, through center-based pools of volunteers, and local communication plans. Covireivac is a French public online platform launched on 10/01/2020 that enables national, large-scale recruitment of volunteers for Covid-19 vaccine studies. On the Covireivac website, all adult participants registered online, gave their informed consent, and filled out two online forms with information on their identity, health status (comorbidities, treatments), and known exposure to SARS-CoV-2. Since July 2021, volunteers could mention if their children are interested in participating in a Covid-19 vaccine trial. The objective of this work is to describe Covireivac's volunteer characteristics registered from 10/01/2020 to 11/02/2022. To identify independent volunteer characteristics associated with a period of registration we performed a multivariate logistic regression. Among 54,424 registrations, 52,391 (96%) were analysed; 61% were male (n = 31,893), median age was 50 y; 13% (n = 6586) were healthcare workers. At registration, 15,879 volunteers (33%) reported at least one comorbidity, among whom 16% (n = 7349) were obese and 17% (n = 8346) had hypertension. Most volunteers registered during the first month (n = 35,876, 66%). The Covireivac platform allowed quick and large recruitment of potential volunteers for Covid-19 vaccine trials and could be used on a larger scale for vaccine trials in France. It could facilitate recruitment in vaccine trials and provide sponsors with better visibility of the recruitment capacities of clinical research centers.

Immunological and clinical efficacy of COVID-19 vaccines in immunocompromised populations: a systematic review.

BACKGROUND: Available data show that COVID-19 vaccines may be less effective in immunocompromised populations, who are at increased risk of severe COVID-19. OBJECTIVES: We conducted a systematic review of literature to assess immunogenicity, efficacy and effectiveness of COVID-19 vaccines in immunocompromised populations. DATA SOURCES: We searched Medline and Embase databases. STUDY ELIGIBILITY CRITERIA, PATIENTS, INTERVENTIONS: We included studies of COVID-19 vaccines after complete vaccination in immunocompromised patients until 31 August 2021. Studies with <10 patients, safety data only and case series of breakthrough infections were excluded. METHODS: Risk of bias was assessed via the tool developed by the National Institutes of Health on interventional and observational studies. Immunogenicity was assessed through non-response rate defined as no anti-SARS-CoV-2 spike protein antibodies, efficacy and effectiveness by the relative reduction in risk of SARS-CoV-2 infection or COVID-19. We collected factors associated with the risk of non-response. We presented collected data by immunosuppression type. RESULTS: We screened 5917 results, included 162 studies. There were 157 on immunogenicity in 25 209 participants, including 7835 cancer or haematological malignancy patients (31.1%), 6302 patients on dialysis (25.0%), 5974 solid organ transplant recipients (23.7%) and 4680 immune-mediated disease patients (18.6%). Proportion of non-responders seemed higher among solid organ transplant recipients (range 18-100%) and patients with haematological malignancy (range 14-61%), and lower in patients with cancer (range 2-36%) and patients on dialysis (range 2-30%). Risk factors for non-response included older age, use of corticosteroids, immunosuppressive or anti-CD20 agent. Ten studies evaluated immunogenicity of an additional dose. Five studies evaluated vaccine efficacy or effectiveness: three on SARS-CoV-2 infection (range 71-81%), one on COVID-19-related hospitalization (62.9%), one had a too small sample size. CONCLUSIONS: This systematic review highlights the risk of low immunogenicity of COVID-19 vaccines in immunocompromised populations, especially solid organ transplant recipients and patients with haematological malignancy. Despite lack of vaccine effectiveness data, enhanced vaccine regimens may be necessary.

Transmission of SARS-CoV-2 during indoor clubbing events: A clustered randomized, controlled, multicentre trial protocol.

Introduction: The SARS-CoV-2 pandemic led to the implementation of several non-pharmaceutical interventions (NPIs), from closings of bars and restaurants to curfews and lockdowns. Vaccination campaigns started hoping it could efficiently alleviate NPI. The primary objective of the "Indoor Transmission of COVID-19" (ITOC) study is to determine among a fully vaccinated population the relative risk of SARS-CoV-2 transmission during one indoor clubbing event. Secondary objectives are to assess the transmission of other respiratory viruses, risk exposure, and attitudes toward COVID-19 vaccination, health pass, and psychological impact of indoor club closing. Methods and analysis: Four thousand four hundred healthy volunteers aged 18-49 years and fully vaccinated will be included in Paris region. The intervention is an 8-hour indoor clubbing event with no masks, no social distance, maximum room capacity, and ventilation. A reservation group of up to 10 people will recruit participants, who will be randomized 1:1 to either the experimental group (2,200 volunteers in two venues with capacities of 1,000 people each) or the control group (2,200 volunteers asked not to go to the club). All participants will provide a salivary sample on the day of the experiment and 7 days later. They also will answer several questionnaires. Virological analyses include polymerase chain reaction (PCR) of salivary samples and air of the venue, investigating SARS-CoV-2 and 18 respiratory viruses. Ethics and dissemination: Ethical clearance was first obtained in France from the institutional review board (Comité de Protection des Personnes Ile de France VII - CPP), and the trial received clearance from the French National Agency for Medicines and Health Products (Agence National de Sécurité du Médicament - ANSM). The trial is supported and approved by The Agence Nationale Recherche sur le SIDA, les hépatites et maladies émergences (ANRS-MIE). Positive, negative, and inconclusive results will be published in peer-reviewed scientific journals. Trial registration number: IDR-CB 2021-A01473-38. Clinicaltrial.gov, identifier: NCT05311865.

Safety and immunogenicity of a measles-vectored SARS-CoV-2 vaccine candidate, V591 / TMV-083, in healthy adults: results of a randomized, placebo-controlled Phase I study.

BACKGROUND: V591 (TMV-083) is a live recombinant measles vector-based vaccine candidate expressing a pre-fusion stabilized SARS-CoV-2 spike protein. METHODS: We performed a randomized, placebo-controlled Phase I trial with an unblinded dose escalation and a double-blind treatment phase at 2 sites in France and Belgium to evaluate the safety and immunogenicity of V591. Ninety healthy SARS-CoV-2 sero-negative adults (18-55 years of age) were randomized into 3 cohorts, each comprising 24 vaccinees and 6 placebo recipients. Participants received two intramuscular injections of a low dose vaccine (1 × 105 median Tissue Culture Infectious Dose [TCID50]), one or two injections of a high dose vaccine (1 × 106 TCID50), or placebo with a 28 day interval. Safety was assessed by solicited and unsolicited adverse events. Immunogenicity was measured by SARS-CoV-2 spike protein-binding antibodies, neutralizing antibodies, spike-specific T cell responses, and anti-measles antibodies. ClinicalTrials.gov, NCT04497298. FINDINGS: Between Aug 10 and Oct 13, 2020, 148 volunteers were screened of whom 90 were randomized. V591 showed a good safety profile at both dose levels. No serious adverse events were reported. At least one treatment-related adverse event was reported by 15 (20.8%) participants receiving V591 vs. 6 (33.3%) of participants receiving placebo. Eighty-one percent of participants receiving two injections of V591 developed spike-binding antibodies after the second injection. However, neutralizing antibodies were detectable on day 56 only in 17% of participants receiving the low dose and 61% receiving the high dose (2 injections). Spike-specific T cell responses were not detected. Pre-existing anti-measles immunity had a statistically significant impact on the immune response to V591, which was in contrast to previous results with the measles vector-based chikungunya vaccine. INTERPRETATION: While V591 was generally well tolerated, the immunogenicity was not sufficient to support further development. FUNDING: Themis Bioscience GmbH, a subsidiary of Merck & Co. Inc., Kenilworth, NJ, USA; Coalition for Epidemic Preparedness Innovations (CEPI).

An Educational Game Evening for Medical Residents: A Proof of Concept to Evaluate the Impact on Learning of the Use of Games.

Insufficient knowledge of bacteria and antimicrobials leads to the emergence of multidrug-resistant-bacterium infections. Diversification of the teaching forms, such as the use of games, could be a solution. We organized an event around 3 games (Bacteria Game, KROBS, and Dawaa) to collect student feedback on the evening and assess their knowledge before and after the evening using multiple-choice questions. The preliminary results suggest a positive effect of this event, but due to the low number of participants, we see this report more as a proof of concept to assess the impact of games on the learning.

COVID-19 in Patients on Maintenance Dialysis in the Paris Region.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) represents a serious threat to patients on maintenance dialysis. The clinical setting, mortality rate, and prognostic factors in these patients have not been well established. METHODS: We included all dialyzed patients with COVID-19 referred to our dialysis center between March 11 and April 11, 2020. Data were obtained through the review of the medical records and were censored at the time of data cutoff, on May 11, 2020. RESULTS: Forty-four patients on maintenance dialysis with COVID-19 were referred to our dialysis unit during the COVID-19 epidemic. Median age was 61 years (interquartile range [IQR]: 51.5-72.5); 65.9% were men. Comorbidities included hypertension (97.7%), diabetes mellitus (50%), and chronic cardiac (38.6%) and respiratory (27.3%) diseases. Initial symptoms were fever (79.5%), shortness of breath (29.5%), cough (43.2%), and diarrhea (13.6%). Three profiles of severity were distinguished based on the World Health Organization (WHO) progression scale. Forty-one (93.2%) were hospitalized and only 3 were maintained on outpatient hemodialysis. Thirty-three (75%) patients required oxygen therapy, including 15 (45.5%) who were referred to the intensive care unit. Overall, 27.3% of patients died, and 58.5% were discharged from hospital, including only 2 (13.3%) of those admitted to the intensive care unit. By multivariate analysis, cough, thrombopenia <120 g/l, lactate dehydrogenase (LDH) level greater than 2 times the upper limit of normal, and blood C-reactive protein (CRP) >175 mg/l were significantly associated with death. CONCLUSION: A major outbreak of COVID-19 occurred in the Paris region, and spread among dialyzed patients. Our study underscores the severity of COVID-19 in these patients and identified prognostic markers.

Costs associated with implementation of a strict policy for controlling spread of highly resistant microorganisms in France.

OBJECTIVE: To assess costs associated with implementation of a strict 'search and isolate' strategy for controlling highly drug-resistant organisms (HDRO). DESIGN: Review of data from 2-year prospective surveillance (01/2012 to 12/2013) of HDRO. SETTING: Three university hospitals located in northern Paris. METHODS: Episodes were defined as single cases or outbreaks of glycopeptide-resistant enterococci (GRE) or carbapenemase-producing Enterobacteriacae (CPE) colonisation. Costs were related to staff reinforcement, costs of screening cultures, contact precautions and interruption of new admissions. Univariate analysis, along with simple and multiple linear regression analyses, was conducted to determine variables associated with cost of HDRO management. RESULTS: Overall, 41 consecutive episodes were included, 28 single cases and 13 outbreaks. The cost (mean ± SD) associated with management of a single case identified within and/or 48 h after admission was €4443 ± 11,552 and €11,445 ± 15,743, respectively (p<0.01). In an outbreak, the total cost varied from €14,864 ± 17,734 for an episode with one secondary case (€7432 ± 8867 per case) to €136,525 ± 151,231 (€12,845 ± 5129 per case) when more than one secondary case occurred. In episodes of single cases, contact precautions and microbiological analyses represented 51% and 30% of overall cost, respectively. In outbreaks, cost related to interruption of new admissions represented 77-94% of total costs, and had the greatest financial impact (R(2)=0.98, p<0.01). CONCLUSIONS: In HDRO episodes occurring at three university hospitals, interruption of new admissions constituted the most costly measure in an outbreak situation.