Cristina Rius

Clonal hematopoiesis associated with Tet2 deficiency accelerates atherosclerosis development in mice

Faulty blood cells and heart disease Recent studies have shown that elderly peoples blood cells often harbor mutations in genes encoding certain epigenetic regulators. These mutations can lead to clonal expansion of the mutant blood cells, which increases the risk of blood cancers and cardiovascular disease. Fuster et al. generated a mouse model to investigate how one of these genes, Tet2, affects atherosclerosis development (see the Perspective by Zhu et al.). They found that the disease progressed more rapidly in mice transplanted with Tet2-deficient bone marrow cells. This was due to increased secretion of interleukin-1β by Tet2-deficient macrophages in a process that depended on the action of inflammasomes. Science, this issue p. 842; see also p. 798 Bone marrow deficient in a gene frequently mutated in blood cells of elderly humans promotes atherosclerosis in mice. Human aging is associated with an increased frequency of somatic mutations in hematopoietic cells. Several of these recurrent mutations, including those in the gene encoding the epigenetic modifier enzyme TET2, promote expansion of the mutant blood cells. This clonal hematopoiesis correlates with an increased risk of atherosclerotic cardiovascular disease. We studied the effects of the expansion of Tet2-mutant cells in atherosclerosis-prone, low-density lipoprotein receptor–deficient (Ldlr–/–) mice. We found that partial bone marrow reconstitution with TET2-deficient cells was sufficient for their clonal expansion and led to a marked increase in atherosclerotic plaque size. TET2-deficient macrophages exhibited an increase in NLRP3 inflammasome–mediated interleukin-1β secretion. An NLRP3 inhibitor showed greater atheroprotective activity in chimeric mice reconstituted with TET2-deficient cells than in nonchimeric mice. These results support the hypothesis that somatic TET2 mutations in blood cells play a causal role in atherosclerosis.

Large Outbreak of Measles in a Community with High Vaccination Coverage: Implications for the Vaccination Schedule

BACKGROUND Attempts to eliminate measles from a country or region may be disrupted by an imported case that affects indigenous persons. The objective of this study was to analyze epidemiological and clinical characteristics of a measles outbreak in Catalonia, Spain, in 2006. METHODS Data on cases of measles reported to the Department of Health, Generalitat of Catalonia, during the period 28 August 2006 through 8 July 2007 were collected. Suspected cases were confirmed by determination of measles-specific immunoglobulin M antibodies and/or detection of virus genome. Incidences were calculated using the estimated population of Catalonia for 2006, and 95% confidence intervals were determined assuming a Poisson distribution. The association between proportions was determined using the chi(2) test and Fishers exact test. The level of statistical significance was set at alpha = .05. RESULTS A total of 381 cases were confirmed, for an incidence of 6.6 cases per 100,000 persons. A total of 89.5% of cases occurred in nonvaccinated persons, mainly those aged < or =15 months (incidence, 278.2 cases per 100,000 persons; mean age of patients, 12 months). Indigenous subjects accounted for 89.8% of cases, and laboratory confirmation of results was obtained for 87.1%. Measles genotype D4 was identified in all sequenced samples. CONCLUSIONS The age distribution of cases of measles among children aged <15 months suggests that the first dose of vaccine should be routinely administered at the age of 12 months.

Tuberculosis recurrence and its associated risk factors among successfully treated patients

Background: Little is known about recurrent tuberculosis (TB) in developed countries. The objective of this study was to determine the probability of TB recurrence and the associated risk factors among cured patients in a city with moderate TB incidence. Methods: A population-based retrospective longitudinal study was carried out in Barcelona, Spain. All patients with culture-confirmed TB and drug susceptibility testing were included between 1995 and 1997 and followed until December 2005. The authors defined recurrence as a new TB event after a patient was considered cured and had remained free of the disease for a minimum of 1 year. Kaplan–Meier and Cox regression were used in the statistical analysis. HRs with 95% CIs were calculated. Results: Among the 681 patients studied, the authors observed 29 recurrences (recurrence rate 0.53/100 person-years of follow-up). The mean incidence of TB in Barcelona from 1995 to 2005 was 36.25 cases per 100 000 inhabitants. The incidence of recurrence was 14.6 times higher in the cohort than the incidence of a first TB episode in the general population. The factors associated with recurrence at bivariate level were being male, being an immigrant, being an intravenous drug user (IDU), having human immunodeficiency virus, smoking, being an alcoholic, being in prison, and having both pulmonary and extrapulmonary TB. At multivariate level, only being an immigrant (HR 3.2, 95% CI 1.2 to 9), an IDU (HR 2.9, 95% CI 1.3 to 6.4) and male (HR 4.3, 95% CI 1.3 to 14.6) were associated. Conclusion: Having TB in the past is a risk factor for developing TB. Social policies must be implemented in populations at risk of recurrence, especially in immigrants and IDUs.

Predictors of death among patients who completed tuberculosis treatment: a population-based cohort study.

Background Mortality among patients who complete tuberculosis (TB) treatment is still high among vulnerable populations. The objective of the study was to identify the probability of death and its predictive factors in a cohort of successfully treated TB patients. Methods A population-based retrospective longitudinal study was performed in Barcelona, Spain. All patients who successfully completed TB treatment with culture-confirmation and available drug susceptibility testing between 1995–1997 were retrospectively followed-up until December 31, 2005 by the Barcelona TB Control Program. Socio-demographic, clinical, microbiological and treatment variables were examined. Mortality, TB Program and AIDS registries were reviewed. Kaplan-Meier and a Cox regression methods with time-dependent covariates were used for the survival analysis, calculating the hazard ratio (HR) with 95% confidence intervals (CI). Results Among the 762 included patients, the median age was 36 years, 520 (68.2%) were male, 178 (23.4%) HIV-infected, and 208 (27.3%) were alcohol abusers. Of the 134 (17.6%) injecting drug users (IDU), 123 (91.8%) were HIV-infected. A total of 30 (3.9%) recurrences and 173 deaths (22.7%) occurred (mortality rate: 3.4/100 person-years of follow-up). The predictors of death were: age between 41–60 years old (HR: 3.5; CI:2.1–5.7), age greater than 60 years (HR: 14.6; CI:8.9–24), alcohol abuse (HR: 1.7; CI:1.2–2.4) and HIV-infected IDU (HR: 7.9; CI:4.7–13.3). Conclusions The mortality rate among TB patients who completed treatment is associated with vulnerable populations such as the elderly, alcohol abusers, and HIV-infected IDU. We therefore need to fight against poverty, and promote and develop interventions and social policies directed towards these populations to improve their survival.

Mumps vaccine effectiveness in highly immunized populations.

The aim of the study was to investigate effectiveness of mumps MMR component in communities with high MMR coverage. Outbreak-related cases of mumps born between 1995 and 2005 notified to Navarre and Catalonia public health services during the period 2005-2007 were studied. Vaccine effectiveness (VE) and their 95%CI were calculated using the screening method. Of 47 confirmed, 85.1% immunized with at least one dose (1MMR) and 44.9% with two (2MMR). Estimated VE was 85.4% (95%CI: 67.3-93.4) for 1MMR and 88.5% (95%CI: 78.1-93.9) for 2MMR. High 2MMR coverage, improved confirmation techniques and further VE studies with all confirmed cases are needed to prevent further outbreaks.

Effectiveness of measles vaccination for control of exposed children

The effectiveness of measles vaccine for postexposure prophylaxis at educational centers was investigated. A total of 166 children who shared the classroom with 10 confirmed cases during the infectious period of cases were studied. Of total susceptible exposed children, 72% (54/75) were vaccinated and 25 contracted measles. Vaccine effectiveness in children vaccinated within 72 hours of exposure was 90.5% (95% confidence interval, 34%–99%).

Nosocomial transmission of hepatitis C virus during contrast-enhanced computed tomography scanning.

We have investigated two cases of acute hepatitis C that occurred in patients who underwent digestive endoscopy and contrast-enhanced computed tomography (CT) scanning at two different centers. Investigations to identify the sources of infection included an on-site review of diagnostic procedures, interview of the involved healthcare staff, serological testing of the patients who underwent the procedures before and after the index cases and a molecular analysis of viral isolates from the patients and from potential viremic sources. In both cases, the epidemiological investigation identified a chronic hepatitis C virus (HCV) carrier who had been subjected to CT-scanning immediately before the index patient. Genetic distance and molecular phylogenetic analyzes of HCV sequences showed a close relationship between the isolates from these carriers and those from the acute-hepatitis patients, strongly suggesting that patient-to-patient transmission had occurred during CT. This is the first report describing two well documented cases of HCV nosocomial patient-to-patient transmission during contrast-enhanced CT scanning.

Transmission of Hepatitis C Virus during Computed Tomography Scanning with Contrast

Six cases of acute hepatitis C related to computed tomography scanning with contrast were identified in 3 hospitals. A patient with chronic hepatitis C had been subjected to the same procedure immediately before each patient who developed acute infection. Viral molecular analysis showed identity between isolates from cases with acute and chronic hepatitis C.

Comorbidity index was successfully validated among men but not in women

OBJECTIVE To validate the prognostic accuracy of a previously proposed comorbidity index using information of a different and separate population-based cohort. STUDY DESIGN AND SETTING We assessed the predictive accuracy of a comorbidity index to predict mortality by looking at calibration and discrimination in the development cohort as well as in a new cohort for validation. Calibration of the model was assessed by comparing predicted and current mortality in the new cohort by means of Hosmer-Lemeshow test (HL). Discrimination of the models was analyzed using the area under the receiver operating characteristic curves (ROC). RESULTS In the development cohort, we have not detected differences between the predicted and the observed mortality in both, men (HL=7.7, P=0.46) and women (HL=11.7, P=0.16). The discrimination of the model accounted 81% in men and 79% in women. In the validation cohort, we obtained a good calibration among men (HL=10.1, P=0.43) but not in women (HL=21.4, P=0.01). The discrimination was quite similar to the development cohort in both sexes (ROC area=80% in men, ROC area=78% in women). CONCLUSION The comorbidity index has good calibration and discrimination and was successfully validated in a different population-based cohort among men but not among women.

Visualizing knowledge and attitude factors related to influenza vaccination of physicians

PURPOSE To characterize groups of primary healthcare physicians according to sociodemographic data, years of professional experience and knowledge of and attitudes to influenza, and to evaluate differences between groups with respect to influenza vaccination in the 2011-2012 season. METHODS We carried out an anonymous web survey of Spanish primary healthcare physicians in 2012. Information on vaccination, and knowledge of and attitudes to influenza was collected. Multiple correspondence analysis and cluster analysis were used to define groups of physicians. RESULTS We included 835 physicians and identified three types. Type B were physicians with low professional experience of influenza. Types A and C were physicians with high professional experience with influenza, type A also had a high awareness of influenza and seasonal vaccination. Types A and C were older and more often male than type B (p<0.0001). Knowledge of influenza was greatest in type A and lowest in type B. Awareness of influenza was greatest in type A and lowest in type C. In type A, 71.0% of physicians were vaccinated in the 2011-2012 season, compared with 48.1% and 33.6% from types B and C, respectively (p<0.001). CONCLUSIONS Additional efforts should be made to increase interest and concerns about preventing the transmission of influenza in physicians who do not believe influenza is a severe disease and are not concerned about its transmission.