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Objectives: To explore the association between drug exposure and SARS-CoV-2 prognosis among elderly people living in long-term care facilities (LTC) DESIGN: We carried out a cross-sectional study among old people living in LTC that had a proven SARS-CoV-2 infection, including socio-demographic data, comorbidities and drug intake at the moment of the diagnosis. The study was focused on ACE2 inhibitors, ARA-II blockers, inhaled bronchodilators, oral corticoids, platelet antiaggregants, oral anti-coagulants, statins and Vitamin D., Results: 1 306 individuals were included, with a mean age of 86.7 years, and 72.3% were females. The case fatality rate was 24.4%. Among the studied exposures platelet antiaggregants were the most prevalent (24.7%). After adjusting for propensity score, the intake of inhaled corticoids (OR 0.73; p=0.03) and statins (OR 0.65; p=0.03) were found to be protective factors of death, whereas ACE2 inhibitor showed an almost significant association (OR 0.73, p=0.07)., Conclusions: Considering the high prevalence of drug intake among elderly people, drug exposure may be an important Covid-19 disease modifier in LTC residents and should be considered when exploring prognostic risk factors associated to Covid-19., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The use of high-dose of intravenous immunoglobulins (IVIGs) as immunomodulators for the treatment of COVID-19-affected individuals has shown promising results. IVIG reduced inflammation in these patients, who progressively restored respiratory function. However, little is known about how they may modulate immune responses in COVID-19 individuals. Here, we have analyzed the levels of 41 inflammatory biomarkers in plasma samples obtained at day 0 (pretreatment initiation), 3, 7, and 14 from five hospitalized COVID-19 patients treated with a 5-d course of 400 mg/kg/d of IVIG. The plasmatic levels of several cytokines (Tumor Necrosis Factor, IL-10, IL-5, and IL-7), chemokines (macrophage inflammatory protein-1α), growth/tissue repairing factors (hepatic growth factor), complement activation (C5a), and intestinal damage such as Fatty acid-binding protein 2 and LPS-binding protein showed a progressive decreasing trend during the next 2 wk after treatment initiation. This trend was not observed in IVIG-untreated COVID-19 patients. Thus, the administration of high-dose IVIG to hospitalized COVID-19 patients may improve their clinical evolution by modulating their hyperinflammatory and immunosuppressive status., (© 2021 Rodríguez de la Concepción et al.)

Background: Chagas disease (CD) is regarded as a possible risk for travellers to endemic areas of continental Latin America (LA). The aim of the study is to determine the risk of Trypanosoma cruzi (TC) infection among travellers to CD endemic areas and to identify risk factors for acquiring TC infection., Methods/principal Finding: We designed a multicenter cross-sectional study among travellers in Spain (Badalona, Barcelona and Madrid). All available adults with laboratory confirmed proof of absence of TC infection from January 2012 to December 2015 were contacted. Participants referring a trip to LA after the negative TC screening were offered to participate. We performed a standardized questionnaire of travel related factors and measurement of TC antibodies in serum. A total of 971 participants with baseline negative TC serology were selected from the microbiology records. After excluding participants not meeting inclusion criteria, eighty participants were selected. Sixty three (78.8%) were female, and the median age was 38 (IQR 34-47) years. The reason to travel was visiting friends and relatives in 98.8% of the participants. The median duration of travel was 40 (IQR 30-60) days, with 4911 participants-day of exposure. Seventy seven cases (96.25%) participants had two negative TC serology tests after the travel, two cases (2.5%) had discordant serology results (considered false positive results) and one case was infected before travelling to LA. According to our data, the upper limit of the 95% confidence interval of the incidence rate of TC acquisition in travellers is 0.8 per 1000 participant-days., Conclusions/significance: Among 79 non-CD travellers to TC endemic areas, we found no cases of newly acquired TC infection. The incidence rate of TC acquisition in travellers to endemic countries is less than or equal to 0.8 per 1000 traveller-days., Competing Interests: The authors have declared that no competing interests exist.

Strongyloidiasis affects an estimated 600 million people worldwide, especially in tropical and subtropical areas. Single-dose ivermectin treatment has shown to be effective among immunocompetent patients with uncomplicated strongyloidiasis. Here, we present the protocol of the ImmunoStrong study, a prospective observational study aiming to evaluate the effectiveness and safety of a single-dose ivermectin for treatment of uncomplicated strongyloidiasis in immunosuppressed patients. The secondary objectives are to assess accuracy of molecular techniques for the follow-up of these patients and to determine the population pharmacokinetics of ivermectin. The information retrieved by this study will cover relevant information gaps in the strongyloidiasis management among immunosuppressed patients.

The aim was to assess the appropriateness of recommended regimens for empirical MIC coverage in critically ill patients with open-abdomen and negative-pressure therapy (OA/NPT). Over a 5-year period, every critically ill patient who received amikacin and who underwent therapeutic drug monitoring (TDM) while being treated by OA/NPT was retrospectively included. A population pharmacokinetic (PK) modeling was performed considering the effect of 10 covariates (age, sex, total body weight [TBW], adapted body weight [ABW], body surface area [BSA], modified sepsis-related organ failure assessment [SOFA] score, vasopressor use, creatinine clearance [CL CR ], fluid balance, and amount of fluids collected by the NPT over the sampling day) in patients who underwent continuous renal replacement therapy (CRRT) or did not receive CRRT. Monte Carlo simulations were employed to determine the fractional target attainment (FTA) for the PK/pharmacodynamic [PD] targets (maximum concentration of drug [ C max ]/MIC ratio of ≥8 and a ratio of the area under the concentration-time curve from 0 to 24 h [AUC 0-24 ]/MIC of ≥75). Seventy critically ill patients treated by OA/NPT (contributing 179 concentration values) were included. Amikacin PK concentrations were best described by a two-compartment model with linear elimination and proportional residual error, with CL CR and ABW as significant covariates for volume of distribution ( V ) and CL CR for CL. The reported V ) in non-CRRT and CRRT patients was 35.8 and 40.2 liters, respectively. In Monte Carlo simulations, ABW-adjusted doses between 25 and 35 mg/kg were needed to reach an FTA of >85% for various renal functions. Despite an increased V and a wide interindividual variability, desirable PK/PD targets may be achieved using an ABW-based loading dose of 25 to 30 mg/kg. When less susceptible pathogens are targeted, higher dosing regimens are probably needed in patients with augmented renal clearance (ARC). Further studies are needed to assess the effect of OA/NPT on the PK parameters of antimicrobial agents., (Copyright © 2020 American Society for Microbiology.)

The biogenesis of bacterial cell-envelope polysaccharides requires the translocation, across the plasma membrane, of sugar sub-units that are produced inside the cytoplasm. To this end, the hydrophilic sugars are anchored to a lipid phosphate carrier (undecaprenyl phosphate (C55-P)), yielding membrane intermediates which are translocated to the outer face of the membrane. Finally, the glycan moiety is transferred to a nascent acceptor polymer, releasing the carrier in the "inactive" undecaprenyl pyrophosphate (C55-PP) form. Thus, C55-P is generated through the dephosphorylation of C55-PP, itself arising from either de novo synthesis or recycling. Two types of integral membrane C55-PP phosphatases were described: BacA enzymes and a sub-group of PAP2 enzymes (type 2 phosphatidic acid phosphatases). The human pathogen Helicobacter pylori does not contain BacA homologue but has four membrane PAP2 proteins: LpxE, LpxF, HP0350 and HP0851. Here, we report the physiological role of HP0851, renamed HupA, via multiple and complementary approaches ranging from a detailed biochemical characterization to the assessment of its effect on cell envelope metabolism and microbe-host interactions. HupA displays a dual function as being the main C55-PP pyrophosphatase (UppP) and phosphatidylglycerol phosphate phosphatase (PGPase). Although not essential in vitro, HupA was essential in vivo for stomach colonization. In vitro, the remaining UppP activity was carried out by LpxE in addition to its lipid A 1-phosphate phosphatase activity. Both HupA and LpxE have crucial roles in the biosynthesis of several cell wall polysaccharides and thus constitute potential targets for new therapeutic strategies., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Chikungunya virus infection causes arthralgia and arthritis in the acute phase of the disease but, in more than half of the cases, musculoskeletal manifestations can be prolonged over time and, in some cases, become chronic. Although polyarthralgia is the most frequent chronic manifestation, forms with polyarthritis, tenosynovitis and enthesopathy are also common., Objective: To analyze the clinical characteristics of patients with persistent articular manifestations after infection with the Chikungunya virus., Patients: Report of 3 cases of chronic arthritis after infection with chikungunya virus diagnosed at outpatient care in a university hospital of Catalonia, all of them imported after exposure in areas of epidemic infection between 2013-2015., Results: All three patients had inflammatory joint pain for more than one year after acute disease (3, 2 and 1 years, respectively). In all cases, it appeared as polyarthritis with involvement of small joints of hands and feet (pseudorheumatoid arthritis-like). Laboratory tests showed a slight elevation of acute phase reactants, and analyses for immune markers were negative. Two of the patients required treatment with glucocorticoids and hydroxychloroquine. The course led to slow clinical improvement, but only one of them came to be completely asymptomatic., Conclusion: In the differential diagnosis of chronic polyarthritis, Chikungunya virus disease should also be considered in areas in which it is not endemic., (Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.)

Background: Amoebic colitis is the most frequent clinical manifestation of invasive intestinal infection due to Entamoeba histolytica and a common cause of diarrhoea worldwide. Since higher transmission rates are usually related to poor health and exposure to unhygienic conditions, cases reported in Europe usually involve immigrants and international travellers. The goal of this study was to characterise both the clinical and the epidemiological features of a European population diagnosed with amoebic colitis and then to evaluate the diagnostic tools and therapeutic options applied., Methods and Results: This was a retrospective observational study in which data from all patients diagnosed with amoebic colitis attending at the International Health Units of two tertiary referral hospitals, Germans Trias i Pujol University Hospital (Badalona, North Barcelona Metropolitan Area) and Vall d'Hebron University Hospital (Barcelona city) between 2007 and 2017 were analysed. During the study period 50 patients were diagnosed with amoebic colitis. Thirty-six (72%) were men, and immigrants accounted for 46% of all cases. Antecedents of any international travel were reported for 28 (56%), the most frequent destinations having been the Indian subcontinent, South and Central America and sub-Saharan Africa. Preexisting pathological conditions or any kind of immunosuppression were identified in 29 (58%) patients; of these, 13 (26%) had HIV infection-all of them men who have sex with men-and 5 (10%) had inflammatory bowel disease. Diarrhoea, abdominal pain and dysentery were the most frequently recorded symptoms of invasive amoebae. Diagnosis was made through microbiological study in 45 (90%) and/or histological identification of amoebae in colon biopsies in 10 (20%). After treatment with metronidazole (82%) or tinidazole (8%), all patients had good outcomes. Post-acute intraluminal treatment was indicated in 28 (56%)., Conclusions: Amoebic colitis should be suspected in patients with diarrhoea and compatible epidemiological risk factors (immigration, travelling abroad or men who have sex with men), especially if some degree of immunosuppression concurs. These risk factors must be taken into account in any diagnostic approach to inflammatory bowel disease (IBD), and active searches for stool parasites should be performed in such cases to rule out misdiagnosis or simultaneous amoebic infection. Treatment should include intraluminal anti-amoebic treatment in order to avoid relapse and prevent further spread of the disease., Competing Interests: The authors have declared that no competing interests exist.

Background: Schistosomiasis, one of the neglected tropical diseases (NTD) listed by the WHO, is an acute and chronic parasitic disease caused by blood flukes (trematode worms) of the genus Schistosoma. Complications of long-term infestation include liver cirrhosis, bladder tumors and kidney failure. The objective of this study was to carry out a clinical and epidemiological characterization of a schistosomiasis-diagnosed immigrant population with long-term residencein the EU as well as to evaluate the diagnostic methods available to date., Methods and Results: A total of 61 individuals with Schistosoma infection who received medical attention between June 2002 and June 2016 at the North Metropolitan International Health Unit in Barcelona (Catalonia, Spain), were included in the study. All patients were sub-Saharan African immigrants. The majority were male (91.8%) with a median age of 34 years. Symptoms attributable to infection such as haematuria, abdominal pain and dysuria were recorded in up to 90% of patients. The percentage of eosinophils decreased amongst older patients (p = 0.002) and those with symptoms associated with urinary tract infections (p = 0.017). Serology was used for diagnosis in 80.3% of the cases, with microscopic examination showing the remaining 9.8% positive for parasite eggs. Direct microbiological diagnosis was more useful in patients with less than 5 years of residence in the EU (p = 0.05). Chronic complications were present in 22 (36%) of the patients, with renal failure affecting 20 (33%). Of these 20, 6(10%) developed terminal renal failure and required hemodialysis, while 3 (5%) received a renal transplantation., Conclusion: Morbidity associated with chronic long-term schistosomiasis is frequent among African immigrants in non-endemic countries. Better diagnostic tools and appropriate early treatment would prevent the development of visceral damage. Thorough screening in selected patients would also be useful to avoid chronic complications.

Background: Malaria remains a major source of morbi-mortality among travellers. In 2007, a consensual multicenter Primary Care-Hospital shared guideline on travel-prior chemoprophylaxis, diagnosis and clinical management of imported malaria was set up in the Barcelona North Metropolitan area. The aim of the study is to assess the evolution of malaria cases in the area as well as its clinical management over the 10 years of its implementation., Results: A total of 190 malaria cases, all them imported, have been recorded. The overall estimated malaria crude incidence was of 0.47 cases per 10,000 population/year (95% CI 0.34-0.59) with a slight significant positive slope especially at the expense of an increase in Indian sub-continent Plasmodium vivax cases. The number of patients who attended the pre-travel consultation was low (13.7%) as well as those with prescribed chemoprophylaxis (10%). Severe malaria was diagnosed in 34 (17.9%) patients and ICU admittance was required in 2.6% of them. Organ sequelae (two renal failures and one post-acute distress respiratory syndrome) were recorded in 3 patients at hospital discharge, although all three were recovered at 30 days. None of the patients died. Patients complying with severity criteria were significantly males (p = 0.04), came from Africa (p = 0.02), were mainly non-immigrant travellers (p = 0.01) and were attended in a hospital setting (p < 0.001). The most frequently identified species was Plasmodium falciparum (64.2%), P. vivax (23.2%), Plasmodium malariae (1.6%) and Plasmodium ovale (1.1%). Those patients diagnosed with P. falciparum malaria came more often from sub-Saharan Africa (p < 0.001) and those with P. vivax came largely from the Indian sub-continent (p = 0.003). Among the 126 patients in whom an immunochromatographic antigenic test was performed, the result was interpreted as falsely negative in 12.1% of them. False negative results can be related to cases with <1% parasitaemia., Conclusions: After 10 years of surveillance, a moderate increase in malaria incidence was observed, mostly P. vivax cases imported from the Indian sub-continent. Although severe malaria cases have been frequently reported, none of the patients died and organ sequelae were rare. Conceivably, the participation of the Primary Care and the District and Third Level Hospital professionals defining surveillance, diagnostic tests, referral criteria and clinical management can be considered a useful tool to minimize malaria morbi-mortality.

Type 2 phosphatidic acid phosphatases (PAP2s) can be either soluble or integral membrane enzymes. In bacteria, integral membrane PAP2s play major roles in the metabolisms of glycerophospholipids, undecaprenyl-phosphate (C 55 -P) lipid carrier and lipopolysaccharides. By in vivo functional experiments and biochemical characterization we show that the membrane PAP2 coded by the Bacillus subtilis yodM gene is the principal phosphatidylglycerol phosphate (PGP) phosphatase of B. subtilis. We also confirm that this enzyme, renamed bsPgpB, has a weaker activity on C 55 -PP. Moreover, we solved the crystal structure of bsPgpB at 2.25 Å resolution, with tungstate (a phosphate analog) in the active site. The structure reveals two lipid chains in the active site vicinity, allowing for PGP substrate modeling and molecular dynamic simulation. Site-directed mutagenesis confirmed the residues important for substrate specificity, providing a basis for predicting the lipids preferentially dephosphorylated by membrane PAP2s.

Objectives: The aim of this study was to determine the incidence of active tuberculosis (TB) among household contacts of TB-index cases diagnosed during a 7-year period in a public Primary Care Center located in a high-incidence area., Design and Sample: A retrospective cohort study was performed. Data collection was based on the capture-recapture method; the two main sources crossed information from TB-index and contact cases from the El Fondo Primary Care Center (Santa Coloma de Gramenet, Spain) and their reports to the National Epidemiologic Surveillance Service., Measures: Variables were divided into demographic and health data (result of the Mantoux test, chest X-ray, presence of risk factors, and indication for chemoprophylaxis)., Results: Community nurses identified 103 household contacts that underwent the conventional contact study. Overall, 60.19% were male; the mean age was 29.08 years. Only one case of secondary active TB was found, representing an incidence of 0.56% per TB-index case and year., Conclusion: The incidence of new secondary TB among household contacts with TB-index cases was of a case. Nevertheless, a long-term follow-up of these householders beyond the conventional contacts study should be considered in areas with higher incidences of TB or among specific high-risk populations., (© 2016 Wiley Periodicals, Inc.)

Background: Immigration-related new diseases pose a growing challenge for healthcare services in receptor countries. Following Latin American migration, Chagas disease has inevitably appeared in Europe., Aim: To determine the prevalence and characteristics of oesophageal motility disorders in immigrants infected with Trypanosoma cruzi, using high resolution oesophageal manometry (HREM)., Methods: In all newly-diagnosed cases with chronic Chagas infection referring upper digestive symptoms, a protocolized clinical evaluation and complementary tests including barium oesophagogram and HREM were carried out. As control group, 14 healthy subjects from the same endemic areas were studied with HREM., Results: We included 61 patients (46 female, 15 male; age range 26-63 years). Only seven patients (11%) had a minor alteration on barium oesophagogram. By contrast, 23 (37%) patients showed an alteration in oesophageal manometry, mainly minor motility disorders (34%). Only one healthy control (7%) had a minor motility disorder at HREM (p = 0.029 vs. patients)., Conclusions: Oesophageal motor disorders in infected immigrants with Chagas disease are common, and mainly characterized by a minor motility disorder that is not detected by barium oesophagogram. Hence, as well as barium oesophagogram examination, HREM should be considered, to assess oesophageal damage in this specific group of patients.

Background: Chagas disease (CD) is a major cause of cardiomyopathy in Latin America, and migration movements have now spread the disease worldwide. However, data regarding Chagas cardiomyopathy (CC) and the usefulness of echocardiography in non endemic countries are still scarce., Methods and Results: We selected 485 patients in the chronic phase of CD from two Spanish settings. Data from physical examination, electrocardiogram (EKG), x-ray, and two dimensional transthoracic echocardiogram were recorded. Trypanosoma cruzi DNA was assessed by PCR in peripheral blood. Patients were stratified according to the Kuschnir classification and a combination of echocardiogram and electrocardiogram findings. Patients mainly came from Bolivia (459; 94.6%). One hundred and forty three patients (31.5%) had at least one electrocardiogram abnormality. Twenty seven patients (5.3%) had an abnormal echocardiography. Patients with abnormal echocardiography were older (47 (IQR 38-57) years vs 41 (IQR 38-57) years); p = 0.019) and there was a greater proportion of males (66.7% vs 29.7%); p<0.001). Among echocardiographic variables, diastolic dysfunction was associated with poor cardiac status. In the multivariate analysis, abnormal EKG and gender were associated with abnormal echocardiography. Echocardiography may be spared for males under 30 and females under 45 years old with normal EKG as the likelihood of having an abnormal echocardiography is minimal. Association between T. cruzi DNA in the peripheral blood and cardiac involvement was not observed., Conclusion: CC rates in the studied population are low. Age and sex are important determinants for the development of CC, and with the EKG should guide echocardiogram performance.

Background: The Chikungunya virus (CKIKV) is currently present in America. Travel between America and Europe is particularly intense and one of the main vectors of CHIKV, Aedes albopictus, is well established in the Mediterranean basin. We describe a series of imported cases that could originate a European outbreak., Methods: We retrospectively studied cases of CHIKV originating in America and diagnosed in the last year in three Tropical Medicine Units of Barcelona of the International Health Program of the Catalan Health Institute (PROSICS). Clinical, microbiological and epidemiological data were analyzed., Results: Forty-two CHIKV cases who had returned from 11 American countries were included. Fever was the most common symptom at onset (96.1%). Three months after symptom onset 50% continued with arthralgias, 35.3% fatigue and 11.8% arthritis. Three patients were viremic at the time of diagnosis by RT-PCR, and the remaining were diagnosed by serology (CHIKV IgM or IgG). Five (11.9%) patients had positive IgM for both dengue virus and CHIKV., Conclusions: The origin of the cases was diverse, the most frequent being initially the Dominican Republic, followed later by Venezuela and Colombia. Symptoms were not severe but persisted, accompanied by unremitting positive IgM. Diagnosis was mainly based on serology and RT-PCR, with the performance of the rapid immunochromatographic test being low. Phylogenetic studies showed that two viremic cases were caused by a strain of Asian lineage with a lower adaptability to Aedes albopictus. Co-infection with the dengue virus was common, but the clinical course was not affected by coinfection. Non-steroidal anti-inflammatory drugs were administered to 71.4% and steroids to 21.4%. The number of imported cases of CHIKV in Spain is rising due to introduction of this virus in America, and this could lead to an autochthonous outbreak if Public Health measures are not taken., (© International Society of Travel Medicine, 2016. All rights reserved. Published by Oxford University Press. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The invasive mosquito Aedes albopictus, with proven vectorial ability to transmit European autochthonous cycles of dengue and chikungunya virus, has currently colonized every coastal department of Eastern Spain. The main objective of the study was to define the epidemiological and clinical characteristics as well as the trends of these two arboviral diseases in a European area heavily colonized by Ae. albopictus., Method: A voluntarily-based, prospective and multicenter surveillance study was performed in all medical units of the North Metropolitan area of Barcelona (406,000 inhabitants, Catalonia; Spain) with diagnostic capability from 2009 to 2013. Since any possible increase in arboviral cases could be justified by changes in traveling behaviors along the study period (especially longer trips) the trend showed by these two arboviral diseases was compared with that displayed by malaria cases during the same period., Results: 38 out of 52 (73.1%) suspected cases could be serologically confirmed (IgM+): dengue 34/38 (89.5%) and chikungunya 4/38 (11.5%). No autochthonous cases were identified. The overall incidence of both arboviruses was 0.19 cases/10,000 inhabitants-year (95% CI: 0.07-0.3); dengue = 0.17 cases/10,000 inhabitants-year (95% CI: 0.05-0.3), and chikungunya = 0.02 cases/10,000 inhabitants-year (95% CI: 0.001-0.03). The Incidence Relative Risk of arboviral disease between 2009 and 2013 shown a significant trend (IRR = 1.27. IC 95%: 1.01-1.59; p = 0.043) when compared with that displayed by malaria (IRR = 1.04. IC 95%: 0.924-1.192). If no unexpected circumstances concur, the arboviral disease incidence tax would equal that of malaria about 2021-2022., Conclusions: The incidence of dengue and chikungunya is steadily increasing in the North Metropolitan area of Barcelona, a region densely colonized by Ae. albopictus, at the entire expense of imported cases (especially Visiting Friends and Relatives travelers). To date, no secondary autochthonous cases have been identified and, thus, they have not taken part in this rise., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

During the biogenesis of bacterial cell-wall polysaccharides, such as peptidoglycan, cytoplasmic synthesized precursors should be trafficked across the plasma membrane. This essential process requires a dedicated lipid, undecaprenyl-phosphate that is used as a glycan lipid carrier. The sugar is linked to the lipid carrier at the inner face of the membrane and is translocated toward the periplasm, where the glycan moiety is transferred to the growing polymer. Undecaprenyl-phosphate originates from the dephosphorylation of its precursor undecaprenyl-diphosphate, with itself generated by de novo synthesis or by recycling after the final glycan transfer. Undecaprenyl-diphosphate is de novo synthesized by the cytosolic cis-prenyltransferase undecaprenyl-diphosphate synthase, which has been structurally and mechanistically characterized in great detail highlighting the condensation process. In contrast, the next step toward the formation of the lipid carrier, the dephosphorylation step, which has been overlooked for many years, has only started revealing surprising features. In contrast to the previous step, two unrelated families of integral membrane proteins exhibit undecaprenyl-diphosphate phosphatase activity: BacA and members of the phosphatidic acid phosphatase type 2 super-family, raising the question of the significance of this multiplicity. Moreover, these enzymes establish an unexpected link between the synthesis of bacterial cell-wall polymers and other biological processes. In the present review, the current knowledge in the field of the bacterial lipid carrier, its mechanism of action, biogenesis, recycling, regulation, and future perspective works are presented.

Background: Current therapeutic options for Chagas' disease are limited to benznidazole and nifurtimox, which have been associated with low cure rates in the chronic stage of the disease and which have considerable toxicity. Posaconazole has shown trypanocidal activity in murine models., Methods: We performed a prospective, randomized clinical trial to assess the efficacy and safety of posaconazole as compared with the efficacy and safety of benznidazole in adults with chronic Trypanosoma cruzi infection. We randomly assigned patients to receive posaconazole at a dose of 400 mg twice daily (high-dose posaconazole), posaconazole at a dose of 100 mg twice daily (low-dose posaconazole), or benznidazole at a dose of 150 mg twice daily; all the study drugs were administered for 60 days. We assessed antiparasitic activity by testing for the presence of T. cruzi DNA, using real-time polymerase-chain-reaction (rt-PCR) assays, during the treatment period and 10 months after the end of treatment. Posaconazole absorption was assessed on day 14., Results: The intention-to-treat population included 78 patients. During the treatment period, all the patients tested negative for T. cruzi DNA on rt-PCR assay beyond day 14, except for 2 patients in the low-dose posaconazole group who tested positive on day 60. During the follow-up period, in the intention-to-treat analysis, 92% of the patients receiving low-dose posaconazole and 81% receiving high-dose posaconazole, as compared with 38% receiving benznidazole, tested positive for T. cruzi DNA on rt-PCR assay (P<0.01 for the comparison of the benznidazole group with either posaconazole group); in the per-protocol analysis, 90% of the patients receiving low-dose posaconazole and 80% of those receiving high-dose posaconazole, as compared with 6% receiving benznidazole, tested positive on rt-PCR assay (P<0.001 for the comparison of the benznidazole group with either posaconazole group). In the benznidazole group, treatment was discontinued in 5 patients because of severe cutaneous reactions; in the posaconazole groups, 4 patients had aminotransferase levels that were more than 3 times the upper limit of the normal range, but there were no discontinuations of treatment., Conclusions: Posaconazole showed antitrypanosomal activity in patients with chronic Chagas' disease. However, significantly more patients in the posaconazole groups than in the benznidazole group had treatment failure during follow-up. (Funded by the Ministry of Health, Spain; CHAGASAZOL ClinicalTrials.gov number, NCT01162967.).

Background: Hospital-acquired pneumonia (HAP) is one of the leading nosocomial infections and is associated with high morbidity and mortality. Numerous studies on HAP have been performed in intensive care units (ICUs), whereas very few have focused on patients in general wards. This study examined the incidence of, risk factors for, and outcomes of HAP outside the ICU., Methods: An incident case-control study was conducted in a 600-bed hospital between January 2006 and April 2008. Each case of HAP was randomly matched with 2 paired controls. Data on risk factors, patient characteristics, and outcomes were collected., Results: The study group comprised 119 patients with HAP and 238 controls. The incidence of HAP outside the ICU was 2.45 cases per 1,000 discharges. Multivariate analysis identified malnutrition, chronic renal failure, anemia, depression of consciousness, Charlson comorbidity index ≥3, previous hospitalization, and thoracic surgery as significant risk factors for HAP. Complications occurred in 57.1% patients. The mortality attributed to HAP was 27.7%., Conclusions: HAP outside the ICU prevailed in patients with malnutrition, chronic renal failure, anemia, depression of consciousness, comorbidity, recent hospitalization, and thoracic surgery. HAP in general wards carries an elevated morbidity and mortality and is associated with increased length of hospital stay and increased rate of discharge to a skilled nursing facility., (Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.)

Background: The nematode Strongyloides stercoralis has a very particular autoinfection life-cycle which leads to chronic infections remaining undetected for decades. However, hyperinfection can occur in patients receiving immunotherapy resulting in high mortality rates. The main objective of this study was to assess the results of a 10-year multicenter surveillance program performed in an area with dense immigration in Barcelona, Spain., Methods: From January 2003 to December 2012, all individuals with Strongyloides stercoralis infection attending the four centers with diagnostic capability in the North Metropolitan area of Barcelona were recorded., Results: The annual detection rate was 0.2 new diagnosed cases x10 000 inhabitants/year and 1 case x10 000 immigrants/year. Many patients were immigrants (63; 90.0%), asymptomatic (45; 64.3%) and with a high eosinophil count (63; 90.0%). Immunosuppression was present in 11 (15.7%) patients, among whom two (2.8%) cases of disseminated hyperinfection were recorded. Ivermectin was prescribed in 45 (76.3%) and albendazole in 14 (23.7%). Following treatment seven patients (11.9%) receiving albendazole presented relapse, that is, albendazole failed to clear the parasite in 50% of these drug-treated patients (p < 0.001)., Conclusions: During the study period, 90% of the cases of Strongyloides stercoralis diagnosed could be considered as imported by immigrants, most being asymptomatic and with eosinophilia. The infection is probably largely underestimated and population-based studies are needed to determine its true prevalence. Meanwhile, diagnosis must be based on active investigation of the helminth (serology and feces culture), especially in immunocompromised patients. The implementation of pre-immunosuppression protocols with the aim of identifying Strongyloides stercoralis is encouraged with empirical treatment with ivermectin being recommended in sites without diagnostic facilities.

The flagellar machinery is a highly complex organelle composed of a free rotating flagellum and a fixed stator that converts energy into movement. The assembly of the flagella and the stator requires interactions with the peptidoglycan layer through which the organelle has to pass for externalization. Lytic transglycosylases are peptidoglycan degrading enzymes that cleave the sugar backbone of peptidoglycan layer. We show that an endogenous lytic transglycosylase is required for full motility of Helicobacter pylori and colonization of the gastric mucosa. Deficiency of motility resulted from a paralysed phenotype implying an altered ability to generate flagellar rotation. Similarly, another Gram-negative pathogen Salmonella typhimurium and the Gram-positive pathogen Listeria monocytogenes required the activity of lytic transglycosylases, Slt or MltC, and a glucosaminidase (Auto), respectively, for full motility. Furthermore, we show that in absence of the appropriate lytic transglycosylase, the flagellar motor protein MotB from H. pylori does not localize properly to the bacterial pole. We present a new model involving the maturation of the surrounding peptidoglycan for the proper anchoring and functionality of the flagellar motor., (© 2012 Blackwell Publishing Ltd.)

Background: As an inevitable consequence of Latin American immigration to Europe, Spain and other European countries, it is necessary to confront the approach to cases of Chagas infection/disease for which, epidemiologically, there are more questions than answers. This study has aimed to describe all the Chagas-infected population in the north metropolitan area of Barcelona (406,000 inhabitants)., Patients and Methods: A prospective and multicentric study was performed in 3 hospitals and 1 International Health Unit. It included all patients with Trypanosoma cruzi positive serology, regardless of the requesting reason.Results The 139 diagnosed cases represent an annual incidence of: a) 0.68/10,000 inhabitants and, b) 73.2/10,000 immigrants coming from endemic zones. Of the patients, 80 (57.6%) had alterations in some complementary tests: cardiologic 62 (44.6%), digestive 38 (27.3%) and 20 (14.4%) both. According to the Brazilian Consensus of Chagas cardiomyopathy, they were classified as: 0=84 (60.4%); a=40 (28.7%); b1=4 (2.9%), b2=10 (7.2%) and c/d=1 (0.7%). Treatment with benznidazole (5mg/kg/24h for 60 days) was prescribed in 116 (83.4%) patients, 89 (76.7%) of whom completed it. Secondary effects were recorded in 56 (50.9%), which made it necessary to withdraw it in 21 (19.1%)., Conclusions: Fewer cases of Chagas infection/disease than expected have been diagnosed in the North Metropolitan area of Barcelona. The series contains a high number of patients and there may be an elevated number of immigrants from endemic zones who have the asymptomatic chronic stages of the infection and who were unaware of their condition., (Copyright © 2012 Elsevier España, S.L. All rights reserved.)

Introduction: Religious pilgrimage to Saudi Arabia, or Hajj, is a basic tenet of the Islamic doctrine and, after Ramadan, annually represents the largest human concentration (with up to 5% of from the EU) around the world. Such a gathering entails health risks., Methods: A prospective observational study was conducted of a cohort of pilgrims attended for pre-travel preventive activities in the North Metropolitan International Health Unit (Santa Coloma de Gramenet, Barcelona, Spain) from 2009-2010., Results: A total of 193 pilgrims were assessed and 135 (69.9%) were men. Their mean age (SD) was 37.1 (16.9) years. Among the pilgrims, 176 (91.2%) were immigrants, mainly from Pakistan (54.9%), Morocco (29%), Bangladesh (4.1%) or other countries (7.2%). The pilgrims stayed in Saudi Arabia a mean (SD) of 16.3 (9.2) days. Eighty (41.5%) opted for the 1 month-long pilgrimage (Hajj) and 113 (58.5%) for the shorter Umra. One or more pathological antecedent was recorded in 29 (15%). Vaccination coverage was >75% for tetanus-diphtheria, pneumococcal and quadrivalent meningitis but was only 70.4% for influenza. After returning, 41 (13.5%) pilgrims reported some health problem; of these, 61% were respiratory tract symptoms. The risk factors independently correlated with the presence of diseases was the number of days in Saudi Arabia (OR=1.06; 95% CI: 1.01-1.11) and taking part in the Hajj compared with the Umra (OR=1.08; 95% CI: 1.07-1.12)., Conclusions: Religious pilgrims from Spain to Saudi Arabia are mainly young and healthy. Those with longer stays abroad contracted a higher number of diseases., (Copyright © 2011 SESPAS. Published by Elsevier España. All rights reserved.)

Background: Imported diseases recorded in the European Union (EU) increasingly involve traveling immigrants returning from visits to their relatives and friends (VFR). Children of these immigrant families can represent a population of extreme vulnerability., Methods: A randomized cross-sectional study of 698 traveling children under the age of 15 was performed. VFR traveling children and non-VFR (or tourist) children groups were compared., Results: A total of 698 individuals were analyzed: 354 males (50.7%) and 344 females (49.3%), with a median age (interquartile range) of 4 (2-9) years. Of these, 578 (82.8%) had been born in the EU with 542 (77.7%) being considered as VFR, whereas 156 (22.3%) were considered tourists. VFR children were younger (4.7 vs 8.2 yr; p < 0.001), they had more frequently been born in the EU (62.8% vs 20.1%; p < 0.01) and were more frequently lodged in private homes (76.6% vs 3.2%: p < 0.001) and rural areas (23.2% vs 1.6%; p < 0.001). Furthermore, VFR remained abroad longer (51.6 vs 16.6 d; p < 0.001), the visit/travel time interval was shorter (21.8 vs 32.2 d; p < 0.001) than tourists, and consultation was within 10 days prior to the departure (26.4% vs 2.7%; p < 0.001). The risk factor most differentiating VFR children from tourists was accommodation in a rural setting [odds ratio(OR) = 5.26;95%CI = 2.704-10.262;p < 0.001]., Conclusions: VFR traveling children showed a greater risk of exposure to infectious diseases compared with tourists. Immigrant families may represent a target group to prioritize international preventive activities., (© 2011 International Society of Travel Medicine.)

Objective: To describe the infectious diseases imported by immigrants visiting friends and relatives in their countries of origin., Methods: We performed a cross-sectional descriptive study of all imported infectious diseases among adult patients between 01/2001-12/2008. The study population was classified in 3 groups: a) immigrants visiting friends and relatives; b) tourists, and c) non-travelling immigrants. Diseases were classified as (a) cosmopolitan or (b) tropical endemic, and, according to their severity as (a) mild, (b) serious, and (c) potentially lethal., Results: A total of 761 patients were analyzed. The mean age was 31.7 (SD: 12.4) years. Of these, there were 90 immigrants visiting friends and relatives, 269 tourists and 402 non-travelling immigrants. Immigrants visiting friends and relatives attended International Health Centres prior to travel significantly less than tourists (32.2% vs. 57.2%; p <0.001) and more frequently travelled to sub-Saharan Africa (33.3% vs. 20.4%; p=0.01). Imported diseases considered as potentially lethal were more likely among immigrants visiting friends and relatives than tourists [OR=5.16 (95%CI: 2.08-12.8)] and non-travelling immigrants [OR=7.17 (95%CI: 2.82-18.2)]., Conclusions: Immigrants visiting friends and relatives travelled more to sub-Saharan Africa and more frequently imported potentially lethal acute diseases.