Wang JF, Soter NA, Morrison SA.

This Arts and Medicine feature reviews the American Ballet Theatre’s 2017 production of Richard Strauss’ Whipped Cream (Schlagobers), a collaboration between choreographer Alexei Ratmansky and pop surrealist Mark Ryden, which tells the story of a boy’s admission to and rescue from a nightmarish hospitalization.

Joseph W S Timothy, Yper Hall, Joseph Akoi-Boré, Boubacar Diallo, Thomas R W Tipton, Hilary Bower, Thomas Strecker, Judith R Glynn, Miles W Carroll

Ebola virus infection was more widespread in this spillover population than previously recognised (21 vs 11 cases). We show the first serological evidence of survivors in this population (eight anti-Ebola virus IgG seropositive) and report a case fatality lower than previously reported (55·6% vs 100% in adults). These data show the high community coverage achievable by using a non-invasive test and, by accurately documenting the beginnings of the west African Ebola virus outbreak, reveal important insight into transmission dynamics and risk factors that underpin Ebola virus spillover events.

GBD 2017 Typhoid and Paratyphoid Collaborators

Despite notable progress, typhoid and paratyphoid fevers remain major causes of disability and death, with billions of people likely to be exposed to the pathogens. Although improvements in water and sanitation remain essential, increased vaccine use (including with typhoid conjugate vaccines that are effective in infants and young children and protective for longer periods) and improved data and surveillance to inform vaccine rollout are likely to drive the greatest improvements in the global burden of the disease.

The Lancet

On Feb 14, the last Closing the Gap report on Aboriginal people in Australia was released. In a feeling of déjà vu, the 11th annual report again showed little progress. In 2018, just two of seven targets designed to narrow inequalities for Aboriginal and Torres Strait Islander peoples on health, education, and employment were on track. Ten years after the initiative was launched, life expectancy at birth is 71·6 years for Indigenous men and 75·6 years for Indigenous women, a massive gap of 8·6 years and 7·8 years, respectively, compared with non-Indigenous Australians.

Lan-Lan Smith

The setting is a single bench on an empty railway platform. We meet Em here, as she sobs into the darkness. A train passes. The only other presence is that of a baby in a car seat. “Whose baby is this?”, Em asks. Rattled, a powerful one-woman play, has writer and actor Rachel Harper explore what brought Em to this point.

Paul Adepoju

The attack on the hospital comes as tensions run high between the Cameroonian Government and the anglophone Cameroon separatists. Paul Adepoju reports.

Xun Yuan

Officials now say that there is no detectable HIV antibody in the suspect plasma batch, but no explanation has been offered to explain original test results. Xun Yuan reports.

Yuan-Yuei Chen, Wen-Hui Fang, Chung-Ching Wang, Tung-Wei Kao, Yaw-Wen Chang, Chen-Jung Wu, Yi-Chao Zhou, Yu-Shan Sun, Wei-Liang Chen

by Yuan-Yuei Chen, Wen-Hui Fang, Chung-Ching Wang, Tung-Wei Kao, Yaw-Wen Chang, Chen-Jung Wu, Yi-Chao Zhou, Yu-Shan Sun, Wei-Liang Chen Emerging studies have shed light on the association between Helicobacter pylori (HP) infection and cardiometabolic risk. However, there is no evidence to support a causal link for the relationship in the general population. Our aim was to determine whether HP infection is associated with the risks of incident type II diabetes mellitus (DM) in a population-based cohort consisting of adults from the general population. A total of 69235 adults enrolled in the study obtained health examinations at the Tri-Service General Hospital in Taiwan from 2010 to 2016. HP infection detection was performed by rapid urease tests (RUTs), and endoscopic examinations were used to diagnose gastroesophageal reflux disease (GERD), gastric ulcers (GUs) and duodenal ulcers (DUs). Cross-sectional and longitudinal analyses were performed to examine the association between HP infection and cardiometabolic diseases using logistic regression and Cox regression in a large population-based study. HP infection was significantly associated with the presence of metabolic syndrome (MetS) (OR = 1.26, 95%CI: 1.00–1.57) and DM (OR = 1.59, 95%CI: 1.17–2.17) only in male subjects, and abnormal endoscopic findings were also correlated with cardiometabolic diseases. Our findings demonstrated that participants with HP infection had an elevated risk of developing incident DM (HR = 1.54, 95%CI: 1.11–2.13). In addition, endoscopic findings of a DU (HR = 1.63, 95%CI: 1.02–2.63), rather than GERD or a GU, were also predictive of incident DM. In this cohort, HP infection was a statistically significant predictor of incident DM among male population.

Abstract Background Despite malaria control programmes having successfully increased the number of households owning insecticide-treated nets (ITNs) in Malawi, the population of people with ITN access but still not using them fluctuated from 13% in 2010, 5% in 2012 and then 12% in 2015. This study aimed to compare the rate and factors associated with ITN usage among children under 5 years of age, living in household with at least one ITN, in Malawi between 2010 and 2015. Methods The 2010 and 2015–2016 Malawi Demographic and Health Surveys (MDHSs) were utilized. Only children from households that owned at least one ITN were selected. Multivariate logistic regression analyses were performed to examine associations of child, maternal and household factors with ITN usage. Results In total, 12,378 and 10,196 children under 5 years of age were examined from 2010 and 2015–2016, respectively. ITN usage increased from 57.8% (95% Confidence interval (CI): 56.1%–59.4%) in 2010 to 69.0% (95% CI 67.4%–70.5%) in 2015. The multivariate analysis revealed that, among others, being aged ≥ 24 months, having mothers with no formal education or with primary education, residing in a female-headed household, and residing in households that had poor household ITN supply were significantly associated with reduced odds of ITN usage. Conclusions ITNs are a key vector control intervention in malaria prevention. This study revealed increased ITN usage among children under 5 years old in the 5-year period, suggesting that considerable improvements have been made. However, continued efforts to increase awareness of the importance of using ITNs in malaria prevention in Malawi are necessary. Findings from this research provide some policy implications, especially for improving household ITN supply, to improve ITN utilization in Malawi.…

Abstract Background Detecting the onset of influenza epidemic is important for epidemiological surveillance and for investigating the factors driving spatiotemporal transmission patterns. Most approaches define the epidemic onset based on thresholds, which use subjective criteria and are specific to individual surveillance systems. Methods We applied the empirical threshold method (ETM), together with two non-thresholding methods, including the maximum curvature method (MCM) that we proposed and the segmented regression method (SRM), to determine onsets of influenza epidemics in each prefecture of Japan, using sentinel surveillance data of influenza-like illness (ILI) from 2012/2013 through 2017/2018. Performance of the MCM and SRM was evaluated, in terms of epidemic onset, end, and duration, with those derived from the ETM using the nationwide epidemic onset indicator of 1.0 ILI case per sentinel per week. Results The MCM and SRM yielded complete estimates for each of Japan’s 47 prefectures. In contrast, ETM estimates for Kagoshima during 2012/2013 and for Okinawa during all six influenza seasons, except 2013/2014, were invalid. The MCM showed better agreement in all estimates with the ETM than the SRM (R2 = 0.82, p 

Kross EK, Pollak KI, Curtis J.

Admission to the intensive care unit (ICU) represents a time when patients and families are at high risk for a variety of poor outcomes, including physical and psychological morbidity. However, studies of interventions to improve these outcomes have resulted in high-profile, high-quality clinical trials that show no statistically significant benefit of the intervention (ie, trials with “negative” or “null” results). Several reasons may explain the preponderance of these negative trials. First, critical care often involves the care of patients with complex disease, making successful interventions difficult to achieve. Second, relatively few interventions in the ICU have been preceded by high-quality preliminary phase 1 and 2 trials. Third, some trials conducted in critically ill patients are limited by sample sizes that may be too small to detect potentially important outcomes with small effect sizes. Trials to mitigate the effects of the psychological “postintensive care syndromes” are no exception. However, it is important to highlight that negative trials can be valuable for 2 reasons. These trials can help deimplement (or not implement) ineffective interventions. Perhaps more important, lessons from these trials can help identify and develop new interventions that will improve patient outcomes.

Kim, J.-H., Chaurasia, A. K., Batool, N., Ko, K. S., Kim, K. K.

Precise enumeration of living intracellular bacteria is the key step to estimate invasion potential of pathogens and host immune responses, and understand the mechanism and kinetics of bacterial pathogenesis. Therefore, quantitative assessment of host-pathogen interaction is essential for developing novel antibacterial therapeutics for infectious disease. Gentamicin protection assay (GPA) is the most widely used method for these estimations by counting the colony forming units (CFU) of intracellular living pathogens. Here, we assessed the longstanding drawbacks of GPA by employing an anti-staphylococcal endopeptidase, as a bactericidal agent to kill the extracellular Staphylococcus aureus. We found that the difference between two methods in the recovery of intracellular CFU of S. aureus was about five times. We proved that the accurate intracellular CFU could not be precisely determined by GPA due to the internalization of gentamicin into host cells during the extracellular bacterial killing. We further demonstrated that the lysostaphin-mediated extracellular bacterial clearing has advantages for measuring the kinetics of bacterial internalization within a minute timescale due to the fast and tunable activity, and impermeability of protein to host cell membrane. From these results, we propose that accurate quantification of intracellular bacteria and measurement of internalization kinetics can be achieved by employing an enzyme-mediated killing of extracellular bacteria (enzyme protection assay, EPA) than the host-permeable gentamicin which is known to alter the host physiology.…

Keshri, V., Diene, S. M., Estienne, A., Dardaillon, J., Chabrol, O., Tichit, L., Rolain, J.-M., Raoult, D., Pontarotti, P.

Beta-lactamase enzymes have attracted substential medical attention from researchers and clinicians because of their clinical, ecological, and evolutionary interest. Here, we present an online comprehensive database of β-lactamase enzymes. The current database is manually curated and incorporates the primary amino acid sequences, closest structural information in the external structure database (Protein Data Bank) and the functional profiles and phylogenetic trees of the four molecular classes (A, B, C, and D) of β-lactamases. The functional profiles are presented according to the minimum inhibitory concentrations and kinetic parameters that make them more useful for the investigators. Here, a total of 1,147 β-lactam resistance genes are analysed and described in the database. The latter is implemented in MySQL and the related website is developed with Zend Framework 2 on an Apache server, supporting all major web browsers. Users can easily retrieve and visualize biologically important information using a set of efficient queries from a graphical interface. This database is freely accessible at http://ifr48.timone.univ-mrs.fr/beta-lactamase/public/.…

Getachew Alemkere, Admasu Tenna, Ephrem Engidawork

by Getachew Alemkere, Admasu Tenna, Ephrem Engidawork Background Malpractice and excess use of antimicrobials have been associated with multiple costs, including the development of resistant bacteria, which has become a threat to the human health. The aim of this study, therefore, was to assess the antibiotic use practice and to identify predictors of hospital outcome to uncover targets for stewardship. Methods An Institution-based prospective observational study was performed from 9 April to 7 July 2014 in the internal medicine wards of Tikur Anbessa Specialized Hospital. Patients with suspected systemic bacterial infections during this period were strictly followed and data were abstracted using data abstraction format. Descriptive statistics and binary logistic regression were used for statistical analysis. Results About half of the attended patients had suspected systemic bacterial infections, in which pneumonia is the most common. Cephalosporins were the most widely prescribed class of drugs in all the wards. Initial antibiotics were empiric in almost all of the cases. About 28% of the ward and 59% of the ICU patients died during the in-hospital stay. The mean length of stay (LoS) was 18.5+12.2 in the wards and 8.9+4.9 days in the ICU. Whilst digestive disease (AOR = 6.94, 95% CI: 2.24, 21.49), different signs and symptoms of disease (AOR = 2.43, 95% CI: 1.30, 4.56), sepsis (AOR = 2.59, 95% CI: 1.12, 5.99) and vancomycin use (AOR = 2.60, 95% CI: 1.30, 5.21) were independent positive predictors, antibiotic days (> 10) (AOR = 0.37, 95% CI: 0.20, 0.70) was a negative predictor for mortality. On the other hand, hospital-acquired infection (AOR = 3.01, 95% CI: 1.05, 8.62), beyond the median antibiotic days (> 10) (AOR = 4.05, 95% CI: 1.96, 8.37) and agent days beyond 21 days (AOR = 2.18, 95% CI: 1.01–4.68) were independently associated with prolonged LoS. Conclusion Generally, this observation entails an appropriate infection management and antimicrobial use policy. Any future policy should better start by addressing cases like pneumonia, and sepsis and drugs like cephalosporins.…

Yingshan Han, Hanh T. Pham, Hongtao Xu, Yudong Quan, Thibault Mesplède

ABSTRACT Studies aimed at repurposing existing drugs revealed that some antimalarial compounds possess anti‐Zika virus (ZIKV) activity. Here, we further tested fourteen additional antimalarial drugs and their metabolites or analogs for anti‐ZIKV activity using a phenotypic screening approach. We identified four compounds with varying anti‐ZIKV activity, including a metabolite of amodiaquine termed desethylamodiaquine (DAQ) and desethylchloroquine (DECQ), a metabolite of chloroquine, which both exhibited low micromolar effective concentrations against three different ZIKV strains. Two other compounds termed dihydroartemisinin (DHA) and quinidine (QD) exhibited only partial inhibition of ZIKV replication. Characterization of the inhibitory mechanisms of DAQ and DECQ showed that both drugs target the entry step as well as post‐entry events of the viral replication cycle. These hits represent attractive starting points for future optimization of new anti‐ZIKV drug candidates derived from antimalarial drugs and their analogs. This article is protected by copyright. All rights reserved.

Mike T. Wei, An K. Le, Matthew S. Chang, Holden Hsu, Pauline Nguyen, Jian Q. Zhang, Chris Wong, Clifford Wong, Ramsey Cheung, Mindie H. Nguyen

ABSTRACT Background Recent studies have suggested a potential increase in the incidence of osteoporosis for patients receiving tenofovir disoproxil fumarate (TDF), but this issue remains controversial. Methods Retrospective cohort study of 1,224 Asian chronic hepatitis B (CHB) patients >18 years without baseline osteopenia/osteoporosis seen at four U.S. centers from 2008‐2016. Patients were categorized into three groups‐treatment naive patients who initiated therapy with TDF (1) or entecavir (ETV) (2), or untreated patients (3). Patients were followed until development of osteopenia/osteoporosis or end of study. Results Of the 1,224 study patients, 276 were treated with TDF, 335 with ETV, and 613 were untreated. The prevalence of cirrhosis was lower for untreated patients (2.6% vs. 16.3% for TDF and 17.6% for ETV, p

Lucio Boglione, Tommaso Lupia, Giuseppe Cariti, Valeria Ghisetti, Maria Grazia Milia, Elisa Burdino, Giovanni Di Perri

Abstract Chronic hepatitis delta (CHD) is the most severe chronic hepatitis, with not satisfactory treatment options and severe clinical outcomes. This infection is frequent in the migrant subjects from endemic areas, especially from Africa and East‐Europe. The pegylated (PEG)‐interferon alfa (IFN) is limited by side‐effects and poor response. In this retrospective analysis, we reported our experience of treatment with PEG‐IFN in a cohort of immigrant patients affected by CHD. We evaluated the virological response as following: complete response (CR, clearance of HBsAg and HDV‐RNA), partial response (PR, HBsAg clearance with HDV‐RNA+) and null response (NR, HBsAg and HDV‐RNA+). Clinical outcomes were: clinical stabilization, disease progression, hepatic decompesation, hepatocellular carcinoma (HCC), death, liver transplantation. Forty‐six patients were included. At the end of treatment (ET), 11 patients gained a CR (23.9%), 10 a PR (21.7%) and 16 were non responders (34.8%). After 1 year, 10 remained with CR (21.7%), after 2 year 9 (19.5%) and at 3 years 8 (17.4%). Relapse rate was 2.2%, 4.4% and 6.5% at year 1, 2 and 3, respectively. Favorable factors were: CR at the ET (OR=4.559, 95%CI: 2.219‐7.116; p=0.003), PEG‐IFN course >1 (OR=1.240, 95%CI: 0.998‐4.839; p=0.012), prolonged treatment (OR=1.276, 95%CI: 0.816‐3.108; p=0.018), qHBsAg decline at 12 weeks >0.5 LogIU/ml (OR=4.816, 95%CI: 2.190‐8.194; p

Ambrose, P. G., VanScoy, B. D., Luna, B. M., Yan, J., Ulhaq, A., Nielsen, T., Rudin, S., Hujer, K., Bonomo, R., Actis, L., Skaar, E., Spellberg, B.

There has been a renewed interest in combining traditional small-molecule antimicrobial agents with non-traditional therapies to potentiate antimicrobial effects. Apotransferrin, which decreases iron availability to microbes, is one such approach. We conducted a 48-h one-compartment in vitro infection model to explore the impact of apotransferrin on the bactericidal activity of ciprofloxacin. The challenge panel included four Klebsiella pneumoniae isolates, with ciprofloxacin minimum inhibitory concentrations (MIC) values ranging from 0.08 to 32 mg/L. Each challenge isolate was subjected to an ineffective ciprofloxacin monotherapy exposure (free-drug area under the concentration-time curve over 24 h divided by the MIC [AUC:MIC ratio] ranging from 0.19 to 96.6) with and without apotransferrin. As expected, the no-treatment and apotransferrin control arms showed unaltered, prototypical logarithmic bacterial growth. We identified relationships between exposure and change in bacterial density for ciprofloxacin alone (R2 = 0.64) and ciprofloxacin in combination with apotransferrin (R2 = 0.84). Addition of apotransferrin to ciprofloxacin enabled a remarkable reduction in bacterial density, across a wide range of ciprofloxacin exposures. For instance, at a ciprofloxacin AUC:MIC ratio of 20, ciprofloxacin monotherapy resulted in nearly 2 log10 CFU increase in bacterial density, while the combination of apotransferrin and ciprofloxacin resulted in 2 log10 CFU reduction in bacterial density. Furthermore, addition of apotransferrin significantly reduced the emergence of ciprofloxacin-resistant subpopulations compared to monotherapy. These data demonstrate that decreasing the rate of bacterial replication with apotransferrin in combination with antimicrobial therapy represents an opportunity to increase the magnitude of bactericidal effect and suppress the growth rate of drug-resistant subpopulations.…

Francis Badia‐Boungou, Famara Sane, Kazali Enagnon Alidjinou, Thierry hennebelle, Vincent Roumy, Adolphe Christian Ngakegni‐Limbili, Etienne Nguimbi, Donatien Moukassa, Ange Antoine Abena, Didier Hober

Abstract Traditional practitioners commonly use plant crude extracts to treat various diseases in patients with symptoms that can be seen during enterovirus infections. In this study, the anti‐enteroviral activity of medicinal plants from Republic of Congo has been evaluated in vitro. Through an ethnopharmacological approach, seven plants grouped into 6 families were identified. Aqueous and organics extracts of various organs from these plants were prepared. The organic extracts at subcytotoxic concentrations did not inhibit the cytopathic effect (CPE) induced by coxsackievirus (CV)B1‐5, CVA6, poliovirus type 1 and enterovirus 71. The aqueous extract of Syzygium brazzavillense, but not those of other plants, inhibited the CPE induced by CVB3 and CVB4 at 30 µg/mL (CC50 2800 µg/mL, IC50 0.8 µg/ml) and by CVB2 and poliovirus type 1 at higher concentrations. When aqueous extract of this plant was mixed with CVB4, the replication of the virus was inhibited. In conclusion, aqueous extracts of Syzygium brazzavillense can inhibit the the infection with CVB4 and other enteroviruses in vitro. The present ethnopharmacological investigation helped to identify a plant with potential properties useful to combat enterovirus infections. This article is protected by copyright. All rights reserved.

Abbasi J.

This Medical News article discusses recent studies that question the one-size-fits-all approach to probiotic supplementation for gastrointestinal health, arguing for a more personalized approach.

André B. B. Wilke, Augusto Carvajal, Johana Medina, Melissa Anderson, Veronica J. Nieves, Monica Ramirez, Chalmers Vasquez, William Petrie, Gabriel Cardenas, John C. Beier

by André B. B. Wilke, Augusto Carvajal, Johana Medina, Melissa Anderson, Veronica J. Nieves, Monica Ramirez, Chalmers Vasquez, William Petrie, Gabriel Cardenas, John C. Beier Vector-borne diseases are an increasing issue to public health, endangering billions of people worldwide. Controlling vector mosquitoes is widely accepted as the most effective way to prevent vector-borne disease outbreaks. Mosquito surveillance is critical for the development of control strategies under the integrated vector management framework. We hypothesize that the effectiveness and reliability of using BG-Sentinel traps for the surveillance strongly depend on the bait used to attract mosquitoes. The objective of this study was to compare the effectiveness of BG-Sentinel traps baited with CO2 and BG-Lure. A total of 72 traps were deployed for 48 hours once a week for four weeks. For the initial 24-hour period, the traps were baited with CO2, and then for an additional 24 hours using the BG-Lure. Collected mosquitoes were analyzed using the Generalized Estimating Equation for repeated measures analysis. Biodiversity was assessed by the Shannon and Simpson indices and by individual rarefaction curves and SHE profiles. A total of 5,154 mosquitoes were collected, from which 3,514 by traps baited with CO2 and 1,640 mosquitoes by traps baited with BG-Lure. Aedes aegypti and Culex quinquefasciatus were the most abundant and dominant species. Results from the Generalized Estimating Equation models indicated that more than twice as many mosquitoes were attracted CO2 than to the BG-Lure. The comparison of attractiveness of CO2 and BG-Lure to Ae. aegypti and Cx. quinquefasciatus was non-significant, suggesting that both species were equally attracted by the baits. The individual rarefaction curves for Ae. aegypti and Cx. quinquefasciatus imply that traps baited with BG-Lure underestimated mosquito species richness compared to those baited with CO2. BG-Lure were less effective in attracting mosquitoes with low abundances and failed to collect Cx. coronator and Cx. nigripalpus, which were consistently collected by traps baited with CO2. According to our results, CO2 significantly (P…

Rollman J, Heyward J, Olson L, et al.

This study uses FDA documents to describe transmucosal immediate-release fentanyl (TIRF) prescribing patterns after the agency’s 2011 REMS intended to reduce the rate of TIRF-related adverse outcomes, misuse, abuse, addiction, and overdose.

Abstract Background Entomological monitoring is important for public health because it provides data on the distribution, abundance and host-seeking behaviour of disease vectors. Various methods for sampling mosquitoes exist, most of which are biased towards, or specifically target, certain portions of a mosquito population. This study assessed the Suna trap, an odour-baited trap for sampling host-seeking mosquitoes both indoors and outdoors. Methods Two separate field experiments were conducted in villages in southern Malawi. The efficiency of the Suna trap in sampling mosquitoes was compared to that of the human landing catch (HLC) indoors and outdoors and the Centers for Disease, Control and Prevention Light Trap (CDC-LT) indoors. Potential competition between two Suna traps during simultaneous use of the traps indoors and outdoors was assessed by comparing mosquito catch sizes across three treatments: one trap indoors only; one trap outdoors only; and one trap indoors and one trap outdoors used simultaneously at the same house. Results The efficiency of the Suna trap in sampling female anophelines was similar to that of HLC indoors (P = 0.271) and HLC outdoors (P = 0.125), but lower than that of CDC-LT indoors (P = 0.001). Anopheline catch sizes in the Suna trap used alone indoors were similar to indoor Suna trap catch sizes when another Suna trap was simultaneously present outdoors (P = 0.891). Similarly, catch sizes of female anophelines with the Suna trap outdoors were similar to those that were caught outdoors when another Suna trap was simultaneously present indoors (P = 0.731). Conclusions The efficiency of the Suna trap in sampling mosquitoes was equivalent to that of the HLC. Whereas the CDC-LT was more efficient in collecting female anophelines indoors, the use of this trap outdoors is limited given the requirement of setting it next to an occupied bed net. As demonstrated in this research, outdoor collections are also essential because they provide data on the relative contribution of outdoor biting to malaria transmission. Therefore, the Suna trap could serve as an alternative to the HLC and the CDC-LT, because it does not require the use of humans as natural baits, allows standardised sampling conditions across sampling points, and can be used outdoors. Furthermore, using two Suna traps simultaneously indoors and outdoors does not interfere with the sampling efficiency of either trap, which would save a considerable amount of time, energy, and resources compared to setting the traps indoors and then outdoors in two consecutive nights.…

Hadara L. Norowitz, Timothy Morello, Hadassah M. Kupfer, Stephan A. Kohlhoff, Tamar A. Smith-Norowitz

by Hadara L. Norowitz, Timothy Morello, Hadassah M. Kupfer, Stephan A. Kohlhoff, Tamar A. Smith-Norowitz This study aims to assess prospectively whether there is an association between frequencies of upper respiratory tract infections (URTI) or asthma in early childhood and failed otoacoustic emission (OAE) screenings later in life. There are no clear recommendations for hearing testing following acute otitis media (AOM) infection. This is a retrospective, practice based chart review. Participants from a primary care setting were 517 pre-adolescent and adolescent children (49.9% female) (ages 10–21; mean, 15 y/o), who had presented with at least one specific bacterial URTI (AOM, Group A Streptococcus (GAS) tonsillitis, or Influenza) during childhood. Hearing testing was recorded incidentally at all subsequent routine health care maintenance visits (OAE hearing screen). Simple linear regression analyses were performed using R (v3.4.4). We found that number of episodes of AOM infections strongly correlated with number of failed OAE screenings later in life (F = 76.37; P =…

Abstract Background Malaria is a leading cause of mortality and morbidity in tropical countries, especially in sub-Saharan Africa. In Senegal, a control plan implemented in the beginning of the 2000s has enabled a substantial reduction of mortality and morbidity due to malaria. However, eradication of malaria requires a vaccine that protects against Plasmodium falciparum the deadliest species of the parasite that causes this disease. Plasmodium falciparum is characterized by an extensive genetic diversity that makes vaccine development challenging. In this study, the diversity of P. falciparum isolates was analysed from asymptomatic children residing in the district of Toubacouta, Senegal. Methods A nested PCR approach was used to perform genotyping of the msp-1 and msp-2 loci in samples from 87 asymptomatic children infected with P. falciparum, collected during a cross sectional survey in November and December 2010. Parasite densities in blood samples were determined by microscopic examination and statistical analyses were used to identify association of parasite genotype and parasitaemia. Results Genotyping was successful in 84/87 and 82/87 samples for msp-1 and msp-2, respectively. A strong genetic diversity was found with a total of 15 and 21 different alleles identified for msp-1 and msp-2, respectively. RO33 was the most frequent allelic family of msp-1 followed by MAD20, then by K1. Regarding msp-2 allelic families, 3D7 was more common than FC27. Multiple infections were predominant, since 69% and 89% of the samples genotyped for msp-1 and msp-2 showed more than one clone of P. falciparum with complexity of infection (COI) of 2.5 and 4.7, respectively. Expected heterozygosity (HE) was 0.57 and 0.55 for msp-1 and msp-2, respectively. Interestingly, polyclonal infections were significantly associated with higher parasitaemia. Conclusions The strong genetic diversity of P. falciparum clones and the association of polyclonal infection with high parasitaemia call for a multi-allelic approach in the design of vaccine candidates for efficient malaria eradication.…

Man Yang, Ling-Li Lu, Miao Zhao, Jun Liu, Qiu-Lan Li, Qin Li, Peng Xu, Lin Fu, Ling-Min Luo, Jun-Hui He, Wen-Bo Meng, Ping-Guang Lei, Jin-Qiu Yuan

by Man Yang, Ling-Li Lu, Miao Zhao, Jun Liu, Qiu-Lan Li, Qin Li, Peng Xu, Lin Fu, Ling-Min Luo, Jun-Hui He, Wen-Bo Meng, Ping-Guang Lei, Jin-Qiu Yuan Objectives To evaluate the associations of pre-endoscopy anxiety with discomfort and tolerance in patients undergoing unsedated esophagogastroduodenoscopy (EGD). Methods This is a hospital-based cohort study of 348 patients undergoing routine, non-advanced EGD without sedation. The primary outcomes were discomfort and tolerance. The anxiety before endoscopy was evaluated with a 10-point visual analogue scale (VAS). The associations of pre-endoscopy anxiety with the outcomes were evaluated with logistic regression adjusting for potential confounders like age, sex, and body mass index. Results Seventy patients reported severe discomfort and 56 patients reported poor tolerance after endoscopy. The risk of severe discomfort increased with pre-endoscopy anxiety and reached a platform around 7–10 points. Compared with the participants with low pre-endoscopy anxiety, those with moderate (adjusted odds ratio [OR] 2.70, 95% confidence interval [CI] 1.17 to 6.22) and high level of anxiety (adjusted OR 6.87, 95% CI 2.16 to 21.79) were associated with a gradual increase in the risk of severe discomfort (P-trend < 0.001). The association between pre-endoscopy anxiety and tolerance was linear, with an adjusted OR of 1.67(95% CI 1.33 to 2.08) for a 1-score increase in pre-endoscopy anxiety VAS. The associations were not modified by age, sex, pharyngitis, duration of endoscopy, and diameter of the endoscope. Conclusions Pre-endoscopy anxiety was an independent predictor of severe discomfort and poor tolerance in Chinese patients undergoing unsedated EGD. Our findings suggested the importance of the management of anxiety to reduce adverse endoscopic experience and taking high level of anxiety as an indication for sedation.…

Nobuyuki Kobayashi, Toshiko Nishiyama, Takashi Yamauchi, Kazuya Shimada, Machi Suka, Kazuhiro Kondo, Hiroyuki Yanagisawa

ABSTRACT Objective: There has been little research on human herpesvirus 6B (HHV‐6B) in healthy adults and prevalences in different age groups have been unclear. Therefore, the major objective of this study was to evaluate seroprevalence to HHV‐6 antibodies in ordinary working people and examine the effect of aging on seroprevalence. Also, as HHV‐6B is reactivated in saliva, another objective was to investigate an association between age and HHV‐6B reactivation based on measured salivary HHV‐6 DNA levels. Methods: Our subjects were 77 ordinary office workers who underwent a health check‐up. In this population, we measured anti‐HHV‐6 antibody titers using ELISA and salivary HHV‐6 DNA levels. In addition to examining an association with age, we examined associations with body mass index, smoking habit and alcohol consumption as confounding factors. Results: There was a significant decrease in the seropositivity to HHV‐6 antibodies in subjects of 50 years and older and age was significantly negatively correlated with anti‐HHV‐6 antibody titers. Age and salivary HHV‐6 DNA levels were also significantly negatively correlated but there were no significant correlations with other factors. Conclusions: Our results suggest that HHV‐6B reactivation is attenuated by aging. Thus, HHV‐6 antibodies steadily decrease in the body with aging. This article is protected by copyright. All rights reserved.

Robert, M. G., Tsombeng, F. F., Gendrot, M., Diawara, S., Madamet, M., Kounta, M. B., Wade, K. A., Fall, M., Gueye, M. W., Benoit, N., Nakoulima, A., Bercion, R., Amalvict, R., Fall, B., Wade, B., Diatta, B., Pradines, B.

Dihydroartemisinin-piperaquine, which was registered in 2017 in Senegal, is not currently used as the first-line treatment against uncomplicated malaria. A total of 6.6 to 17.1% of P. falciparum isolates collected in Dakar in 2013-2015 showed ex vivo reduced susceptibility to piperaquine. Neither the exonuclease-E415G mutation nor the copy number variation of the Plasmepsin II gene (Pfpm2), associated with piperaquine resistance in Cambodia, was detected in Senegalese parasites.…

Das L.

Piggott KD, Rao P.

A 26-year-old white man had recurrent episodes of ocular redness and blurry vision coincident with nodular skin elevation in a left-arm tattoo. Slit lamp examination revealed inflammatory cells in the anterior chamber of the left eye; punch biopsy of the tattooed skin revealed pigment-containing macrophages. What is the diagnosis and what would you do next?…

Aranjuez, G. F., Kuhn, H. W., Adams, P. P., Jewett, M. W.

Lyme disease is caused by the spirochete Borrelia burgdorferi and is transmitted via the bite of an infected tick. B. burgdorferi enters the skin, disseminates via the bloodstream, and infects various distal tissues leading to inflammatory sequelae such as Lyme arthritis and Lyme carditis. B. burgdorferi linear plasmid 36 (lp36) is critical for mammalian infectivity, however, the full complement of lp36-encoded genes that contribute to this process remains unknown. Through a targeted mutagenesis screen of genes on lp36, we identified a novel infectivity gene of unknown function, bbk13, which encodes an immunogenic, non-surface exposed membrane protein that is important for efficient mammalian infection. Loss of bbk13 resulted in reduced spirochete loads in distal tissues in a mouse model of infection. Through a detailed analysis of B. burgdorferi infection kinetics, we discovered that bbk13 is important for promoting spirochete proliferation in the skin inoculation site. The attenuated ability of bbk13 spirochetes to proliferate in the inoculation site was followed by reduced numbers of B. burgdorferi in the bloodstream and, ultimately, consistently reduced spirochete loads in distal tissues. Together, our data indicate that bbk13 contributes to disseminated infection by promoting spirochete proliferation in the early phase of infection in the skin. This work not only increases understanding of the contribution of lp36-encoded genes to B. burgdorferi infection, but also begins to define the genetic basis for B. burgdorferi expansion in the skin during localized infection and highlights the influence of early expansion of spirochetes in the skin on the outcome of infection.…

Weinberger SE.

This Viewpoint assesses the prospects for reform of maintenance of certification (MOC) programs administered by physician specialty boards, distinguishing between reforms in summative knowledge testing using formal examination and formative programs that support ongoing incremental and personalizable education.

Abstract Background The emergence of norovirus genotype GII.4 variants has been associated with gastroenteritis pandemics worldwide, prompting molecular surveillance for early detection of novel strains. In this study, we aimed to analyze the outbreak activity of norovirus and characterize the norovirus strains circulating in Alberta between July 2012 and February 2018. Methods Stool samples from gastroenteritis outbreaks in Alberta were tested for norovirus at the Provincial Laboratory for Public Health using a multiplex real time-RT PCR assay. The ORF1 and ORF2-genotypes of norovirus positive samples were assigned based on phylogenetic analyses of partial polymerase and capsid sequences, respectively. Results A total of 530 norovirus outbreaks were identified. During July 2012 and June 2017 there was a gradual decrease in the annual number of GII.4 outbreaks, however, outbreak numbers increased from June 2017–February 2018. Four novel strains emerged: GII.17 Kawasaki in July 2014–June 2015, GII.P16/GII.4 Sydney in July 2015–June 2016, GII.P16/GII.2 and GII.P4 New Orleans/GII.4 Sydney in July 2016–June 2017. GII.Pe/GII.4 Sydney was the single predominant strain responsible for the majority (over 50%) of all norovirus outbreaks up to June 2015. Between June 2017 and February 2018, GII.P16/GII.4 Sydney was the leading strain causing 63% of all norovirus outbreaks. Conclusions GII.4 stands as the predominant capsid genotype causing a large majority of the norovirus outbreaks in early 2018. An increase in genotype diversity was observed in the last years, characterized by a high circulation of non-GII.4 strains and GII.4 recombinants.…

Yu-jen Tseng, Wei-qun Ding, Liang Zhong, Jian Chen, Zhong-guang Luo

Sarah Tschudin-Sutter

In this issue of CMI, a study by Barbut et al. reports about the detection of toxigenic Clostridioides difficile in patients presenting to general practitioners due to diarrhoea or other gastrointestinal disorders. Among 2541 patients included in this study, toxigenic C. difficile was detected in 3.3%. The findings of this study add to our knowledge on the epidemiology of toxigenic C. difficile in community settings in central Europe and bring up the question regarding useful recommendations and diagnostic algorithms for identifying patients most likely suffering from C.

Utzat, H., Sun, W., Kaplan, A. E. K., Krieg, F., Ginterseder, M., Spokoyny, B., Klein, N. D., Shulenberger, K. E., Perkinson, C. F., Kovalenko, M. V., Bawendi, M. G.

Chemically made colloidal semiconductor quantum dots have long been proposed as scalable and color-tunable single emitters in quantum optics, but they have typically suffered from prohibitively incoherent emission. We now demonstrate that individual colloidal lead halide perovskite quantum dots (PQDs) display highly efficient single photon emission with optical coherence times as long as 80 ps, an appreciable fraction of their 210 ps radiative lifetimes. These measurements suggest that PQDs should be explored as building blocks in sources of indistinguishable single photons and entangled photon pairs. Our results present a starting point for the rational design of lead halide perovskite-based quantum emitters with fast emission, wide spectral-tunability, scalable production, and which benefit from the hybrid-integration with nano-photonic components that has been demonstrated for colloidal materials.…

Abstract Background Innovative and cost-effective strategies that clear asymptomatic malaria infections are required to reach malaria elimination goals, but remain a challenge. This mixed methods study explored people’s attitudes towards the reactive treatment of compound contacts of malaria cases with a 3-day course of dihydroartemisinin-piperaquine (DHAP), the socio-cultural representations of asymptomatic infections, and more specifically their treatment. Methods Prior to the start of the intervention, a sequential mixed method study was carried out. Qualitative data collection involved in-depth interviews and participant observations (including informal conversations) with key informants from the trial communities and the trial staff. Quantitative data were derived from a pre-trial cross-sectional survey on health literacy and health-seeking behaviour among randomly selected members of the study communities. Results In the pre-trial cross-sectional survey, 73% of respondents reported that malaria could be hidden in the body without symptoms. Whilst this may be interpreted as people’s comprehension of asymptomatic malaria, qualitative data indicated that informants had different interpretations of asymptomatic disease than the biomedical model. It was described as: (i) a minor illness that does not prevent people carrying out daily activities; (ii) an illness that oscillates between symptomatic and asymptomatic phases; and, (iii) a condition where disease agents are present in the body but remain hidden, without signs and symptoms, until something triggers their manifestation. Furthermore, this form of hidden malaria was reported to be most present in those living in the same compound with a malaria case (71%). Conclusion Treating asymptomatic malaria with pharmaceuticals was considered acceptable. However, people felt uncertain to take treatment without screening for malaria first, largely due to the lack of symptoms. Knowledge of asymptomatic malaria was not a strong re-inforcement for treatment adherence. In this study, the pre-intervention active engagement of communities existed of having people co-design accurate information messages about their personal risk of malaria, which increased their trust in expert knowledge and thus proved essential for the successful implementation of the community-based intervention.…

Ghirlanda, G., Salafia, O. S., Paragi, Z., Giroletti, M., Yang, J., Marcote, B., Blanchard, J., Agudo, I., An, T., Bernardini, M. G., Beswick, R., Branchesi, M., Campana, S., Casadio, C., Chassande-Mottin, E., Colpi, M., Covino, S., DAvanzo, P., DElia, V., Frey, S., Gawronski, M., Ghisellini, G., Gurvits, L. I., Jonker, P. G., van Langevelde, H. J., Melandri, A., Moldon, J., Nava, L., Perego, A., Perez-Torres, M. A., Reynolds, C., Salvaterra, R., Tagliaferri, G., Venturi, T., Vergani, S. D., Zhang, M.

The binary neutron star merger event GW170817 was detected through both electromagnetic radiation and gravitational waves. Its afterglow emission may have been produced by either a narrow relativistic jet or an isotropic outflow. High-spatial-resolution measurements of the source size and displacement can discriminate between these scenarios. We present very-long-baseline interferometry observations, performed 207.4 days after the merger by using a global network of 32 radio telescopes. The apparent source size is constrained to be smaller than 2.5 milli–arc seconds at the 90% confidence level. This excludes the isotropic outflow scenario, which would have produced a larger apparent size, indicating that GW170817 produced a structured relativistic jet. Our rate calculations show that at least 10% of neutron star mergers produce such a jet.…

Edith Reuschel, Wolfgang Jilg, Birgit Seelbach-Goebel, Ludwig Deml

by Edith Reuschel, Wolfgang Jilg, Birgit Seelbach-Goebel, Ludwig Deml This study describes the comparative expression and purification of hepatitis B surface antigen (HBsAg) particles produced upon infection of human primary hepatocytes and human hepatoma cell lines (HuH-7 and HepG2) with recombinant vaccinia viruses. The highest levels of HBsAg expression were found in HuH-7 hepatoma cells following infection with recombinant vaccinia viruses, which contain the S gene under control of a 7.5 k-promoter. Four different methods for purification of the HBsAg particles were examined: isopycnic ultracentrifugation, sucrose cushion sedimentation, isocratic column gel filtration, and binding to anti-HBs-coated microparticles. The highest degree of purity of HBsAg particles was reached by the method based on anti-HBs-coated microparticles. The resulting product was >98% pure. Biochemical analysis and characterization of purified HBsAg particles were performed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), western blotting, and electron microscopy. The HBsAg, purified from human hepatoma cell lines and from human primary hepatocytes, consisted of both the non-glycosylated (p25) and the glycosylated (gp27) form and assembled into typical 22-nm particles, and thus may be of great interest and importance for research, diagnostics, and medical treatments.

Musa Hindiyeh, Orna Mor, Rakefet Pando, Batya Mannasse, Areej Kabat, Hadar Assraf-Zarfati, Ella Mendelson, Danit Sofer, Michal Mandelboim

by Musa Hindiyeh, Orna Mor, Rakefet Pando, Batya Mannasse, Areej Kabat, Hadar Assraf-Zarfati, Ella Mendelson, Danit Sofer, Michal Mandelboim Respiratory viral infections constitute the majority of samples tested in the clinical virology laboratory during the winter season, and are mainly diagnosed using molecular assays, namely real-time PCR (qPCR). Therefore, a high-quality extraction process is critical for successful, reliable and sensitive qPCR results. Here we aimed to evaluate the performance of the newly launched eMAG compared to the fully automated MagNA PURE 96 (Roche, Germany) and to the semi-automated easyMAG (bioMerieux, France) extraction platforms. For this analysis, we assessed and compared the analytic and clinical performance of the three platforms, using 262 archived respiratory samples positive or negative to common viruses regularly examined in our laboratory (influenza A, B, H1N1pdm, Respiratory Syncytial Virus (RSV), human Metapneumovirus (hMPV), parainfluenza-3, adenovirus and negative samples). In addition, quantitated virus controls were used to determine the limit of detection of each extraction method. In all categories tested, eMAG results were comparable to those of the easyMAG and MagNa PURE 96, highly sensitive for all viruses and over 98% clinical specificity and sensitivity for all viruses tested. Together with its high level of automation, the bioMerieux eMAG is a high-quality extraction platform enabling effective molecular analysis and is mostly suitable for medium-sized laboratories.

Following publication of the original article [1], the authors reported that they have provided the wrong caption.…

Junru Cui, Caitlin M. O’Connell, Antonio Costa, Yan Pan, Joan A. Smyth, Paulo H. Verardi, Diane J. Burgess, Herbert J. Van Kruiningen, Antonio E. Garmendia

by Junru Cui, Caitlin M. O’Connell, Antonio Costa, Yan Pan, Joan A. Smyth, Paulo H. Verardi, Diane J. Burgess, Herbert J. Van Kruiningen, Antonio E. Garmendia…

Mini Singh, Jenny-Ann Toribio, Angela Bullanday Scott, Peter Groves, Belinda Barnes, Kathryn Glass, Barbara Moloney, Amanda Black, Marta Hernandez-Jover

by Mini Singh, Jenny-Ann Toribio, Angela Bullanday Scott, Peter Groves, Belinda Barnes, Kathryn Glass, Barbara Moloney, Amanda Black, Marta Hernandez-Jover…

Mahdi Moshki, Fereshteh Zamani-Alavijeh, Mehdi Mojadam

by Mahdi Moshki, Fereshteh Zamani-Alavijeh, Mehdi Mojadam…

Lukas Richter, Daniela Schmid, Elisabeth Eva Kanitz, Ines Zwazl, Eva Pöllabauer, Joanna Jasinska, Heinz Burgmann, Michael Kundi, Ursula Wiedermann

by Lukas Richter, Daniela Schmid, Elisabeth Eva Kanitz, Ines Zwazl, Eva Pöllabauer, Joanna Jasinska, Heinz Burgmann, Michael Kundi, Ursula Wiedermann…

Immaculate Kambutse, Grace Igiraneza, Sheela Shenoi, Onyema Ogbuagu

by Immaculate Kambutse, Grace Igiraneza, Sheela Shenoi, Onyema Ogbuagu…

The PLOS ONE Staff

by The PLOS ONE Staff …

The PLOS ONE Staff

by The PLOS ONE Staff …

Nava, S., White, A. C., Castellanos-Gonzalez, A.

Despite the severity and global burden of Cryptosporidium infection, treatments are less than optimal and there is no effective vaccine. Egress from host cells is a key process to the completion of the parasitic life cycle of apicomplexan parasites. For Plasmodium, subtilisin-like serine proteases (SUB1) is a key mediator of egress. For Toxoplasma, calcium-dependent protein kinases (CDPK) are critical. In this study, we characterized Cryptosporidium SUB1 expression and evaluated its effect using an infection model. We found increased expression between 12-20 hours after in vitro infection, prior to egress. We induced silencing of SUB1 (SUB1) mRNA using SUB1 single-stranded antisense RNA coupled with human Argonaute 2. Silencing of SUB1 mRNA expression did not affect parasite viability, excystation, or invasion of target cells. However, knockdown led to a 95% decrease of released merozoites in vitro (P

Holloway, A. J., Yu, J., Arulanandam, B. P., Milligan, G. N., Eaves-Pyles, T. D.

We have identified recombinant human cystatin 9 (rCST9) and C (rCSTC) as a combination, immunotherapeutic treatment against multi-drug resistant (MDR) New Delhi metallo-beta-lactamase-1 (NDM-1) producing Klebsiella pneumoniae (Kp). We evaluated the lasting protection of rCST9/rCSTC treatment against MDR NDM-1 Kp pneumonia. Results showed that rCST9/rCSTC treatment modulated endogenous serum biomarkers, cystatin 9 and C and amyloid A, associated with poor patient outcomes and provided prophylactic and long-term protection in a murine model of pneumonia.…