Neisseria genes required for persistence identified via in vivo screening of a transposon mutant library.

The mechanisms used by human adapted commensal Neisseria to shape and maintain a niche in their host are poorly defined. These organisms are common members of the mucosal microbiota and share many putative host interaction factors with Neisseria meningitidis and Neisseria gonorrhoeae. Evaluating the role of these shared factors during host carriage may provide insight into bacterial mechanisms driving both commensalism and asymptomatic infection across the genus. We identified host interaction factors required for niche development and maintenance through in vivo screening of a transposon mutant library of Neisseria musculi, a commensal of wild-caught mice which persistently and asymptomatically colonizes the oral cavity and gut of CAST/EiJ and A/J mice. Approximately 500 candidate genes involved in long-term host interaction were identified. These included homologs of putative N. meningitidis and N. gonorrhoeae virulence factors which have been shown to modulate host interactions in vitro. Importantly, many candidate genes have no assigned function, illustrating how much remains to be learned about Neisseria persistence. Many genes of unknown function are conserved in human adapted Neisseria species; they are likely to provide a gateway for understanding the mechanisms allowing pathogenic and commensal Neisseria to establish and maintain a niche in their natural hosts. Validation of a subset of candidate genes confirmed a role for a polysaccharide capsule in N. musculi persistence but not colonization. Our findings highlight the potential utility of the Neisseria musculi-mouse model as a tool for studying the pathogenic Neisseria; our work represents a first step towards the identification of novel host interaction factors conserved across the genus.

Real-time alerting system for COVID-19 and other stress events using wearable data.

Early detection of infectious diseases is crucial for reducing transmission and facilitating early intervention. In this study, we built a real-time smartwatch-based alerting system that detects aberrant physiological and activity signals (heart rates and steps) associated with the onset of early infection and implemented this system in a prospective study. In a cohort of 3,318 participants, of whom 84 were infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), this system generated alerts for pre-symptomatic and asymptomatic SARS-CoV-2 infection in 67 (80%) of the infected individuals. Pre-symptomatic signals were observed at a median of 3 days before symptom onset. Examination of detailed survey responses provided by the participants revealed that other respiratory infections as well as events not associated with infection, such as stress, alcohol consumption and travel, could also trigger alerts, albeit at a much lower mean frequency (1.15 alert days per person compared to 3.42 alert days per person for coronavirus disease 2019 cases). Thus, analysis of smartwatch signals by an online detection algorithm provides advance warning of SARS-CoV-2 infection in a high percentage of cases. This study shows that a real-time alerting system can be used for early detection of infection and other stressors and employed on an open-source platform that is scalable to millions of users.

Detection-based prioritisation: Framework of multi-laboratory characteristics for asymptomatic COVID-19 carriers based on integrated Entropy-TOPSIS methods.

CONTEXT AND BACKGROUND: Corona virus (COVID) has rapidly gained a foothold and caused a global pandemic. Particularists try their best to tackle this global crisis. New challenges outlined from various medical perspectives may require a novel design solution. Asymptomatic COVID-19 carriers show different health conditions and no symptoms; hence, a differentiation process is required to avert the risk of chronic virus carriers. OBJECTIVES: Laboratory criteria and patient dataset are compulsory in constructing a new framework. Prioritisation is a popular topic and a complex issue for patients with COVID-19, especially for asymptomatic carriers due to multi-laboratory criteria, criterion importance and trade-off amongst these criteria. This study presents new integrated decision-making framework that handles the prioritisation of patients with COVID-19 and can detect the health conditions of asymptomatic carriers. METHODS: The methodology includes four phases. Firstly, eight important laboratory criteria are chosen using two feature selection approaches. Real and simulation datasets from various medical perspectives are integrated to produce a new dataset involving 56 patients with different health conditions and can be used to check asymptomatic cases that can be detected within the prioritisation configuration. The first phase aims to develop a new decision matrix depending on the intersection between 'multi-laboratory criteria' and 'COVID-19 patient list'. In the second phase, entropy is utilised to set the objective weight, and TOPSIS is adapted to prioritise patients in the third phase. Finally, objective validation is performed. RESULTS: The patients are prioritised based on the selected criteria in descending order of health situation starting from the worst to the best. The proposed framework can discriminate among mild, serious and critical conditions and put patients in a queue while considering asymptomatic carriers. Validation findings revealed that the patients are classified into four equal groups and showed significant differences in their scores, indicating the validity of ranking. CONCLUSIONS: This study implies and discusses the numerous benefits of the suggested framework in detecting/recognising the health condition of patients prior to discharge, supporting the hospitalisation characteristics, managing patient care and optimising clinical prediction rule.

Alteration of Smell and Taste in Asymptomatic and Symptomatic COVID-19 Patients in Sicily, Italy.

OBJECTIVES: Alteration of smell and taste has been reported in patients with coronavirus disease 2019 (COVID-19). The incidence and clinical-symptomatic manifestation of COVID-19 is different between northern and southern Italy. This study aims to evaluate the onset of alteration of smell and taste in asymptomatic and symptomatic patients in Sicily (extreme south of Italy). METHODS: This prospective cross-sectional study was performed on asymptomatic and symptomatic COVID-19 patients tested for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) from May 1 to May 15, 2020. A questionnaire was used for evaluating the prevalence of smell and taste disorders in COVID-19 patients before performing nasopharyngeal swab. RESULTS: Of the total 292 patients, 242 (83.2%) were negative for SARS-CoV-2 and 50 were positive (16.8%). Twenty-six of the 50 (52%) SARS-CoV-2 positive patients reported smell/taste disorders. Twenty-eight of the 50 (57.1%) SARS-CoV-2 positive patients were hospitalized (group A), and 22 (42.9%) were nonhospitalized (group B). The mean age in group A and group B was 45.4 ± 13.7 years and 57.0 ± 15.0, respectively (P = .007). The symptoms reported by hospitalized patients were fever (71.4%), cough (64.2%), fatigue (82.1%), and dyspnea (100%), while in nonhospitalized patients, the most reported symptoms were sore throat (72.7%), rhinorrhea (77.2%), and altered smell (81.8%). Anosmia/hyposmia reported in group A and group B was 28.5% and 81.8%, respectively (P = .001). CONCLUSION: These preliminary results indicate that the majority of SARS-Cov-2 positive patients in southern Italy did not require hospitalization and presented with milder symptoms or no symptoms and the alterations in smell and taste occurred.

Is systematic fecal carriage screening of extended-spectrum beta-lactamase-producing Enterobacteriaceae still useful in intensive care unit: a systematic review.

BACKGROUND: Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) are disseminating worldwide leading to increased hospital length of stay and mortality in intensive care units (ICU). ESBL-E dissemination was first due to outbreaks in hospital settings which led to the implementation of systematic fecal carriage screening to improve hygiene procedures by contact precautions. ESBLs have since spread in the community, and the relevance of contact precautions is questioned. ESBL-E dissemination led to an overuse of carbapenems triggering the emergence of carbapenem-resistant Enterobacteriaceae. Empirical antimicrobial therapy based on ESBL-E fecal carriage has been proposed but is debated as it could increase the consumption of carbapenems among ESBL-E carriers without any clinical benefit. Finally, selective decontamination among ESBL-E fecal carriers is evoked to decrease the risk for subsequent ESBL-E infection, but its efficacy remains debated. We propose to systematically review the evidence to recommend or not such systematic ESBL-E fecal carriage screening in adult ICU. METHODS: Every article focusing on ESBL-E and ICU available on the MEDLINE database was assessed. Articles were included if focusing on cross-transmission, efficacy of hygiene procedures, link between ESBL-E colonization and infection or guidance of empirical therapy or selective decontamination efficacy. RESULTS: Among 330 articles referenced on PubMed, 39 abstracts were selected for full-text assessment and 25 studies were included. Systematic screening of ESBL-E fecal carriage to guide contact precautions do not seem to decrease the rate of ESBL-E cross-transmission. It has a very good negative predictive value for subsequent ESBL-E infections but a positive predictive value between 40 and 50% and so does not help to spare carbapenems. Cessation of ESBL-E carriage systematic screening could decrease the use of carbapenems in ICU without any clinical harm. Nevertheless, further studies are needed to validate these results from monocentric before-after study. Selective decontamination strategy applied to ESBL-E fecal carriers could be helpful, but available data are conflicting. CONCLUSION: Current knowledge lacks of high-quality evidence to strongly recommend in favor of or against a systematic ESBL-E fecal carriage screening policy for ICU patients in a non-outbreak situation. Further evaluation of selective decontamination or fecal microbiota transplantation among ESBL-E fecal carriers is needed.

HIV co-infection in HTLV-1 carriers in Spain.

BACKGROUND: Human retroviruses HIV and HTLV share transmission routes. HIV widely spread in Spain during the 80 s through injection drug use and sex, and nowadays HIV rates in Spain account for one of the largest in Europe. In contrast, HTLV-1 is not endemic in Spain, despite hosting huge numbers of migrants from highly endemic regions. Herein, we report the rate and main features of the HIV-HTLV co-infected population in Spain. METHODS: A national registry exists in Spain for HTLV since year 1989. Data from standardized case report forms and one centralized lab repository were reviewed, especially for the subset with HTLV-HIV co-infection. RESULTS: Up to December 2018, a total of 369 individuals with HTLV-1 had been diagnosed in Spain. 64% of the population were females, and Latin American individuals accounted for 64.5%. Classical HTLV-associated illnesses were found in 12.7% (myelopathy) and 7.6% (leukemia). HIV coinfection was found in 12 (3.2%). Of those, 3 patients (25%) were female and 39 (75%) were of non-Spanish origin. All but two harbored HIV-1 subtype B, being non-B variants found in the two West Africans. Exposure had been sexual in most cases, being 4 homosexual men. Seven HTLV-HIV co-infected patients had developed AIDS and two had developed myelopathy. There was no evidence for increased HTLV-1 clinical pathogenicity due to HIV coinfection. CONCLUSION: HIV coinfection is infrequent (<5%) among HTLV-1 carriers in Spain. More than half of co-infected patients come from Latin America. Sexual contact is the most frequent risk behavior, being MSM one third of cases. Late diagnosis explains the high rate (9/12) of clinical manifestations in our HIV-HTLV co-infected population.

Different roles of CXCR1 and CXCR2 in HTLV-1 carriers and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients.

One of the prominent features of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is the excessive recruitment of leukocytes to the central nervous system (CNS), which leads to an inflammatory response-with chemokines and their receptors playing the main role in this recruitment. The aim of the study was to examine the relation of CXCR1 and CXCR2, both of which are involved in the trafficking of lymphocytes into the CNS, with the outcome of HTLV-1 infection. The mRNA levels of CXCR1 and CXCR2 were examined in peripheral blood mononuclear cells (PBMCs) of HAM/TSP patients, HTLV-1 asymptomatic carriers (ACs), and healthy controls (HCs). Furthermore, the frequency of CD4+ and CD8+ T cells expressing CXCR1 and CXCR2 was evaluated in the studied groups. The results of the present study showed a substantial increase in the mean mRNA expression of CXCR2 in the HAM/TSP patients compared to the HCs and ACs (p < 0.001). A positive correlation was also found between PVL and CXCR2 mRNA expression in the total population of HTLV-1-infected subjects (R = 0.526, p < 0.001). Moreover, the percentage of CD8+ CXCR2-expressing cells was higher in HAM/TSP patients compared to ACs and HCs (p < 0.05, p < 0.01, respectively). Although the percentage of CD4+ CXCR2-expressing cells was higher in HAM/TSP patients than in ACs and HCs, a significant difference was only found between HAM/TSP patients and HCs (p < 0.05). No significant difference in the CXCR1 mRNA expression was observed in the studied groups. The frequency of the CD8+ CXCR1- and CD4+ CXCR1-expressing cells was significantly lower in HAM/TSP patients than in ACs and HCs (p < 0.001 and p < 0.01, respectively). In conclusion, the high frequency of CXCR2 CD8+ T cells and the high levels of CXCR2 mRNA expression in HAM/TSP patients are associated with disease pathogenesis, while the high frequencies of CXCR1 T cells in ACs might suggest that these cells act as effector CD8 T cells and are involved in controlling the viral spread and modulation of the immune response.

Excess body weight and age associated with the carriage of fluoroquinolone and third-generation cephalosporin resistance genes in commensal Escherichia coli from a cohort of urban Vietnamese children.

PURPOSE: Antimicrobial-resistant bacterial infections in low- and middle-income countries (LMICs) are a well-established global health issue. We aimed to assess the prevalence of and epidemiological factors associated with the carriage of ciprofloxacin- and ceftriaxone-resistant Escherichia coli and associated resistance genes in a cohort of 498 healthy children residing in urban Vietnam. METHODOLOGY: We cultured rectal swabs onto MacConkey agar supplemented with resistant concentrations of ciprofloxacin and ceftriaxone. Additionally, we screened meta-E. coli populations by conventional PCR to detect plasmid-mediated quinolone resistance (PMQR)- and extended-spectrum ß-lactamase (ESBL)-encoding genes. We measured the associations between phenotypic/genotypic resistance and demographic characteristics using logistic regression.Results/Key findings. Ciprofloxacin- and ceftriaxone-resistant E. coli were cultured from the faecal samples of 67.7 % (337/498) and 80.3 % (400/498) of children, respectively. The prevalence of any associated resistance marker in the individual samples was 86.7 % (432/498) for PMQR genes and 90.6 % (451/498) for ß-lactamase genes. Overweight children were significantly more likely to carry qnr genes than children with lower weight-for-height z-scores [odds ratios (OR): 1.24; 95 % confidence interval (CI): 10.5-1.48 for each unit increase in weight for height; P=0.01]. Additionally, younger children were significantly more likely to carry ESBL CTX-M genes than older children (OR: 0.97, 95 % CI: 0.94-0.99 for each additional year, P=0.01). CONCLUSION: The carriage of genotypic and phenotypic antimicrobial resistance is highly prevalent among E. coli in healthy children in the community in Vietnam. Future investigations on the carriage of antimicrobial resistant organisms in LMICs should focus on the progression of carriage from birth and structure of the microbiome in obesity.

Clinical impact of Pseudomonas aeruginosa colonization in patients with Primary Ciliary Dyskinesia.

BACKGROUND: Airway infections in Primary Ciliary Dyskinesia (PCD) are caused by different microorganisms, including pseudomonas aeruginosa (PA). The aim of this study was to investigate the association of PA colonization and the progression of lung disease in PCD. METHODS: Data from 11PCD centers were retrospectively collected from 2008 to 2013. Patients were considered colonized if PA grew on at least two separate sputum cultures; otherwise, they were classified as non-colonized. These two groups were compared on the lung function computed tomography (CT) Brody score and other clinical parameters. RESULTS: Data were available from 217 patients; 60 (27.6%) of whom were assigned to the colonized group. Patients colonized with PA were older and were diagnosed at a later age. Baseline forced expiratory volume at 1 s (FEV1) was lower in the colonized group (72.4 ± 22.0 vs. 80.1 ± 18.9, % predicted, p = 0.015), but FEV1 declined throughout the study period was similar in both groups. The colonized group had significantly worse CT-Brody scores (36.07 ± 24.38 vs. 25.56 ± 24.2, p = 0.034). A subgroup analysis with more stringent definitions of colonization revealed similar results. CONCLUSIONS: Lung PA colonization in PCD is associated with more severe disease as shown by the FEV1 and CT score. However, the magnitude of decline in pulmonary function was similar in colonized and non-colonized PCD patients.

The Objective Assessment of Cough Frequency in Bronchiectasis.

INTRODUCTION: Cough in bronchiectasis is associated with significant impairment in health status. This study aimed to quantify cough frequency objectively with a cough monitor and investigate its relationship with health status. A secondary aim was to identify clinical predictors of cough frequency. METHODS: Fifty-four patients with bronchiectasis were compared with thirty-five healthy controls. Objective 24-h cough, health status (cough-specific: Leicester Cough Questionnaire LCQ and bronchiectasis specific: Bronchiectasis Health Questionnaire BHQ), cough severity and lung function were measured. The clinical predictors of cough frequency in bronchiectasis were determined in a multivariate analysis. RESULTS: Objective cough frequency was significantly raised in patients with bronchiectasis compared to healthy controls [geometric mean (standard deviation)] 184.5 (4.0) vs. 20.6 (3.2) coughs/24-h; mean fold-difference (95% confidence interval) 8.9 (5.2, 15.2); p < 0.001 and they had impaired health status. There was a significant correlation between objective cough frequency and subjective measures; LCQ r = -0.52 and BHQ r = -0.62, both p < 0.001. Sputum production, exacerbations (between past 2 weeks to 12 months) and age were significantly associated with objective cough frequency in multivariate analysis, explaining 52% of the variance (p < 0.001). There was no statistically significant association between cough frequency and lung function. CONCLUSIONS: Cough is a common and significant symptom in patients with bronchiectasis. Sputum production, exacerbations and age, but not lung function, were independent predictors of cough frequency. Ambulatory objective cough monitoring provides novel insights and should be further investigated as an outcome measure in bronchiectasis.

Rapid Deterioration of Latent HBV Hepatitis during Cushing Disease and Posttraumatic Stress Disorder after Earthquake.

Reactivation of the hepatitis B virus (HBV) is a risk in the 350 million HBV carriers worldwide. HBV reactivation may cause hepatocellular carcinoma, cirrhosis, and fulminant hepatitis, and HBV reactivation accompanied with malignant tumor and/or chemotherapy is a critical problem for patients with chronic HBV infection. Multiple risk factors causing an immunosuppressive state can also induce HBV reactivation.We present a case of HBV reactivation during an immunosuppressive state caused by Cushing disease and physical and psychological stress after a disaster. A 47-year-old Japanese woman was an inactive HBV carrier until the Great East Japan Earthquake occurred and follow-up was discontinued. One year after the earthquake she had intractable hypertension, and her visual acuity gradually worsened. Head magnetic resonance imaging showed a sellar tumor compressing the optic chiasm, and hepatic dysfunction with HBV reactivation was identified. Endocrinologic examination established the diagnosis as Cushing disease. After normalization of hepatic dysfunction with antiviral therapy, transsphenoidal tumor removal was performed that resulted in subtotal removal except the right cavernous portion. Steroid hormone supplementation was discontinued after 3 days of administration, and gamma knife therapy was performed for the residual tumor. Eighteen months after the operation, adrenocorticotropic hormone and cortisol values returned to normal. The patient has been free from tumor regrowth and HBV reactivation throughout the postoperative course.Accomplishment of normalization with intrinsic steroid value with minimization of steroid supplementation should be established. Precise operative procedures and careful treatment planning are essential to avoid HBV reactivation in patients with this threatening condition.

The impact of chronic carrier of hepatitis B virus on liver function in a 7-day ultramarathon race.

BACKGROUND: Several changes in physiological characteristics occur during long-distance and 24-hour ultramarathons, including hyponatremia, skeletal muscle breakdown, plasma volume changes, iron depletion, anemia, and possible hepatic damage. The purpose of this study was to investigate the impact of hepatitis B virus (HBV) carrier status on liver function during multi-day races. METHODS: This prospective study recruited 10 Taiwanese runners who were scheduled to participate in the 7-day 2008 Athens Ultramarathon Festival Race, and three of them were chronic carriers of HBV. Blood samples were collected before, during, and 3 days after the race, including alkaline phosphatase (ALP), albumin (ALB), total protein (TP) levels, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (T-BIL) RESULTS: Ten Taiwanese runners (40% female; average age 52.3 ± 7.9 years) who all planned to run in the race were recruited. Three runners were chronic carriers of HBV (HBV carrier), and all participants were anti-HCV antibody-negative and anti-hepatitis A virus (HAV) IgG-positive. There were no significant time-by-group effects on ALP, ALB, and TP levels, but the change over time effects were significant (p < 0.001, p = 0.001 and p = 0.010, respectively). ALT, AST, and T-BIL increased significantly to markedly higher levels in the HBV carrier group compared to the non-carrier group (group effect p = 0.009, p = 0.004, and p = 0.05, respectively), and the time-by-group interaction was also significant for these liver function markers (p < 0.001, p < 0.001, and p = 0.001, respectively). CONCLUSION: Compared to their counterparts, runners who are HBV carriers had significantly greater increases in levels of ALT, AST, and T-BIL during a 7-day ultramarathon, indicating that the liver function of carriers is more highly impacted in these races.

Burkholderia cepacia complex: clinical course in cystic fibrosis patients.

BACKGROUND: Pulmonary deterioration after B.cepacia complex (BCC) colonization has a heterogeneous pattern. The aim was to investigate the clinical outcome of BCC colonization in CF patients chronically colonized with P. aeruginosa. METHODS: CF patients chronically colonized with P. aeruginosa were divided into three groups: intermittent (I), chronic (II) and no colonization (III) with BCC. Body mass index (BMI) percentile and spirometric parameters were analyzed at three different times in each group. RESULTS: Fifty-six patients chronically colonized with P. aeruginosa were included. Of these, 27 also had evidence of BCC colonization (13 intermittent and 14 chronic). BMI percentile was significantly lower among patients chronically colonized by both P. aeruginosa and BCC. Mean values of FEV1 and FVC % were also significantly lower in these patients, both at the time of chronic BCC colonization and 24 months forward. CONCLUSIONS: Chronic BCC colonization is associated with significant loss of lung function. Lower BMI might be a risk factor for chronic BCC colonization, preceding these events.

A Chinese medicine, Kuan-Sin-Yin decoction, improves liver function in hepatitis B virus carriers: a randomized, controlled study.

OBJECTIVE: To examine the effects of a Chinese medical herb complex formula, Kuan-Sin-Yin (KSY) decoction, on hepatitis B virus (HBV) carriers. METHODS: Of 86 HBV carriers, 57 who met the inclusion criteria completed this study from February 2011 to December 2011 in Taipei City Hospital, Taiwan. The participants were randomly assigned to one of two groups: the KSY group (n=29) and a control group (n=28) that received KSY diluted 16 times. The participants took one packet of decoction per day after dinner for 6 weeks. The major outcome measurements were the percentage reduction in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and the log of the HBV DNA level. The other measurements included seroconversion of hepatitis B e antigen and responses to the World Health Organization Quality of Life-Brief Version (WHOQOL-BREF) and Short-Form-12. The measurements were collected before the first treatment and 6 weeks later. RESULTS: In the KSY group, AST and ALT levels decreased significantly and the score on the physical component of WHOQOL-BREF increased significantly. However, in the control group, there was no significant change after 6 weeks of treatment. Only the KSY group had a significant percentage reduction in ALT (change, -25.2% versus -0.74% in the control group) after 6 weeks of treatment. No major adverse effects occurred after 6 weeks of treatment. CONCLUSIONS: KSY significantly improved ALT levels. The study suggests that a longer-term study testing the efficacy of KSY in a larger sample is warranted.

Hepatitis B inactive carriers: clinical course and outcomes.

OBJECTIVE: Hepatitis B virus (HBV) inactive carriers are HBV e antigen (HBeAg)-negative patients with normal alanine aminotransferase (ALT) levels and HBV DNA of ≤ 10000 copies/mL. We aimed to determine the clinical impact of ALT and HBV DNA elevations during the course of HBV infection. METHODS: From January 1989 to January 2012, 146 inactive carriers were prospectively followed every 6-12 months with ALT and HBV DNA measurements and with hepatocellular carcinoma (HCC) surveillance. RESULTS: During the follow-up of 8 ± 6.3 years, 56 of the 146 patients maintained ALT ≤ 40 U/L and HBV DNA ≤ 10000 copies/mL. However, 39 had rises of ALT > 40-80 U/L and 4 had ALT > 80 U/L; all except one reverted to baseline values. Also, during follow up, 69 (47.3%) inactive carriers had increases in HBV DNA of > 10000-999999 copies/mL; 38 of these patients' HBV DNA returned to baseline levels, while the remaining 31 patients maintained elevated HBV DNA values but had corresponding ALT of ≤ 40 U/L. There were four liver-related outcomes: 129 (88.4%) remained "inactive carriers", 13 (8.9%) had loss of hepatitis B surface antigen (HBsAg), one (0.7%) had a spontaneous reactivation to HBeAg-negative chronic hepatitis, and two (1.4%) developed HCC. CONCLUSIONS: Although the prognosis of inactive carrier is favorable, transient ALT and HBV DNA elevations may be observed but have minimal clinical significance. Moreover, continuous HCC surveillance remains necessary since the risk of development still exists.

Pathophysiology of Escherichia coli ventilator-associated pneumonia: implication of highly virulent extraintestinal pathogenic strains.

PURPOSE: To characterize Escherichia coli ventilator-associated pneumonia (VAP) in intensive care unit (ICU) patients by determining antibioresistance and genotypic characteristics of E. coli isolates responsible for VAP or lung colonization, by comparing them with their oropharyngeal and rectal counterparts and by assessing representative isolates' virulence in a pneumonia mouse model. METHODS: Patients under mechanical ventilation for more than 72 h were screened for simultaneous presence of E. coli in rectal, oropharyngeal, and respiratory samples (colonization or VAP). If present, E. coli isolates were characterized by antimicrobial susceptibility, phylogenetic grouping, and virulence factor (VF) gene content determination. BALB/c mice were challenged intranasally with 3.6 × 10(8) colony-forming units (CFU) of patients' E. coli isolates. RESULTS: Multisite E. coli colonization was observed in 19 % of patients (25 patients, 12 with E. coli VAP). One hundred fifteen distinct E. coli isolates were analyzed. B2 phylogenetic group was predominant, with high VF gene content and low antimicrobial resistance. Antimicrobial resistance diversity was observed in four patients with VAP. E. coli isolates from VAP patients were more frequently B2 isolates, with significantly greater VF gene content than lung colonization isolates. Among screened VF genes, iroN and sfa appeared important for lung infection. A very strong correlation (R (2) = 0.99) was found between VF gene content and mortality in the mouse model. CONCLUSIONS: This is the first study establishing antibioresistance and genotypic characteristics of E. coli isolates responsible for VAP in adult ICU patients. These isolates are highly virulent specific extraintestinal pathogenic E. coli strains expressing virulence factors, representing potential targets for new therapies.

Correlation between LTR point mutations and proviral load levels among human T cell lymphotropic virus type 1 (HTLV-1) asymptomatic carriers.

BACKGROUND: In vitro studies have demonstrated that deletions and point mutations introduced into each 21 bp imperfect repeat of Tax-responsive element (TRE) of the genuine human T-cell leukemia virus type I (HTLV-1) viral promoter abolishes Tax induction. Given these data, we hypothesized that similar mutations may affect the proliferation of HTLV-1-infected cells and alter the proviral load (PvL). To test this hypothesis, we conducted a cross-sectional genetic analysis to compare the near-complete LTR nucleotide sequences that cover the TRE1 region in a sample of HTLV-1 asymptomatic carriers with different PvL burden. METHODS: A total of 94 asymptomatic HTLV-1 carriers with both sequence from the 5' long terminal repeat (LTR) and a PvL for Tax DNA measured using a sensitive SYBR Green real-time PCR were studied. The 94 subjects were divided into three groups based on PvL measurement: 31 low, 29 intermediate, and 34 high. In addition, each group was compared based on sex, age, and viral genotypes. In another analysis, the median PvLs between individuals infected with mutant and wild-type viruses were compared. RESULTS: Using a categorical analysis, a G232A substitution, located in domain A of the TRE-1 motif, was detected in 38.7% (12/31), 27.5% (8/29), and 61.8% (21/34) of subjects with low, intermediate, or high PvLs, respectively. A significant difference in the detection of this mutation was found between subjects with a high or low PvL and between those with a high or intermediate PvL (both p < 0.05), but not between subjects with a low or intermediate PvL (p > 0.05). This result was confirmed by a non-parametric analysis that showed strong evidence for higher PvLs among HTLV-1 positive individuals with the G232A mutation than those without this mutation (p < 0.03). No significant difference was found between the groups in relation to age, sex or viral subtypes (p > 0. 05). CONCLUSIONS: The data described here show that changes in domain A of the HTLV-1 TRE-1 motif resulting in the G232A mutation may increase HTLV-1 replication in a majority of infected subjects.

Amendments to hypotheses on the proximate causes of variation in human sex ratios at birth with parental infection with hepatitis B virus or Toxoplasma gondii.

In a recent paper in this Journal, I offered hypotheses on the offspring sex ratios of women infected with the parasite Toxoplasma gondii, and on the offspring sex ratios of people who are carriers of hepatitis B virus (HBV) (James, 2008). Subsequent research suggests that these hypotheses need amending. A detailed account of the amendments is given elsewhere in a specialized journal (James, 2010a). Here they are summarized.