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Schultz, Jacob; Andersen, Asger; Lyhne, Mads D.; Arcanjo, Daniel D. R.; Kjaergaard, Benedict; Simonsen, Ulf; Nielsen-Kudsk, Jens Erik

Objectives: We investigated whether the vasopressin-analog, terlipressin induces systemic vasoconstriction and pulmonary vasodilation in a porcine model of acute pulmonary embolism. Design: Controlled, animal study. Setting: Tertiary medical center research laboratory. Subjects: Female pigs (n = 12, Cross of Land Race, Duroc, and Yorkshire ~ 60 kg). Interventions: Acute pulmonary embolism was induced by administration of three large autologous emboli. Animals then received four increasing doses of either terlipressin (n = 6) or vehicle (n = 6). Measurements and Main Results: Effects were evaluated in vivo at baseline, after pulmonary embolism and after each dose by invasive hemodynamic measures, transesophageal echocardiography, and blood analysis. Isolated pulmonary arteries were evaluated ex vivo in a myograph. Pulmonary embolism caused a four-fold increase in pulmonary vascular resistance (p < 0.0001) and a two-fold increase in mean pulmonary arterial pressure (p < 0.0001) compared with baseline. Terlipressin increased mean systemic blood pressure (28 ± 5 mm Hg; p < 0.0001) and systemic vascular resistance (1,320 ± 143 dynes; p < 0.0001) compared with vehicle. In the pulmonary circulation, terlipressin decreased mean pulmonary arterial pressure (–6.5 ± 1.8 mm Hg; p = 0.005) and tended to decrease pulmonary vascular resistance (–83 ± 33 dynes; p = 0.07). Terlipressin decreased cardiac output (–2.5 ± 0.5 L/min; p < 0.0001) and increased plasma lactate (2.7 ± 0.2 mmol/L; p < 0.0001), possibly indicating systemic hypoperfusion. A biomarker of cerebral ischemia, S100b, remained unchanged, suggesting preserved cerebral perfusion (0.17 ± 0.11 µg/L; p = 0.51). Ex vivo, terlipressin relaxed pulmonary and constricted mesenteric arteries. Conclusions: Terlipressin caused systemic vasoconstriction and pulmonary vasodilation in a porcine in vivo model of acute pulmonary embolism and vasorelaxation in isolated pulmonary arteries. Despite positive vascular effects, cardiac output declined and plasma lactate increased probably due to a predominantly systemic vasoconstrictor effect of terlipressin. These findings should warrant careful translation to the clinical setting and does not suggest routine use in acute pulmonary embolism. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). This work was performed at Aarhus University, Aarhus, Denmark. Dr. Schultz disclosed that the study was funded by Aarhus UniversityGraduate School, The Novo Nordisk foundation (NNF16OC0023244,NNF17OC0024868), The Danish Heart Foundation (18-R125-A8410-22115), Holger og Ruth Hesses mindefond, Søster og Verner Lipperts Fond. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: jacobgschultz@clin.au.dk Copyright © by 2020 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Abstract Background Pyogenic liver abscess (PLA) is an inflammatory disease with increasing incidence. When it occurs with diabetes mellitus (DM), the risk of recurrence and mortality may increase. However, the effect of DM on the short-term prognosis of PLA patients after hospitalization remained unknown. Methods Two hundred twenty-seven PLA patients who received treatment at the First Affiliated Hospital of Xi’an Jiaotong University from January 2011 to January 2018 were retrospectively enrolled. They were divided into two groups as the DM group (n = 61) and the Non-DM group (n = 166). In the DM group, HbA1C level 

Santos A, Oliveira R, Lemos E, et al.

AbstractBackgroundTuberculosis is a major cause of morbidity and mortality among incarcerated populations globally. We performed mass tuberculosis screening in three prisons and assessed yield, efficiency, and costs associated with various screening algorithms.MethodsBetween 2017 and 2018, inmates from the three prisons in Brazil were screened for tuberculosis by symptom assessment, chest radiography, sputum testing by Xpert MTB/RIF 4th generation and culture. Chest radiographs were scored by an automated interpretation algorithm (CAD4TB) that was locally calibrated to establish a positivity threshold. Four diagnostic algorithms were evaluated. We assessed the yield (percent of total cases found) and efficiency (prevalence among those screened) for each algorithm. We performed unit costing to estimate the costs of each screening or diagnostic test and calculated the cost per case detected for each algorithm.ResultsWe screened 5,387 prisoners, of whom 214 (3.9%) were diagnosed with tuberculosis. Compared to other screening strategies initiated with radiography or chest symptoms, the trial of all participants with a single Xpert MTB / RIF sputum test detected 74% of all tuberculosis cases at a cost of $ 249. Performing Xpert MTB/RIF screening tests only on those with symptoms had a similar cost per case diagnosed (US$ 255) but missed as many cases (73 vs 54) as screening all inmates.ConclusionIn this prospective study in three with prisons in high tuberculosis burden countries Brazilian prisons, we found that testing all participants with sputum Xpert MTB/RIF was sensitive approach, while remaining cost-efficient. These results support use of Xpert MTB/RIF for mass screening in tuberculosis-endemic prisons.

Woodman M, Grandjean L.

Parker R, Ferré E, Myint-Hpu K, et al.

Zelenev A, Li J, Shea P, et al.

AbstractBackgroundHCV treatment as prevention (TasP) strategies can contribute to HCV micro-elimination, yet complimentary interventions like opioid agonist therapies (OAT) and syringe services programs (SSP) may improve the prevention impact. This modeling study estimates the impact of scaling up the combination of OAT and SSP with HCV TasP in a network of people who inject drugs (PWID) in the U.S.MethodsUsing empirical data from Hartford, Connecticut, we deployed a stochastic block model to simulate an injection network of 1,574 PWID. We used a susceptible-infected model for HCV and HIV to evaluate the effectiveness of several HCV TasP strategies, including in combination with OAT and SSP scale-up, over 20 years.ResultsAt the highest HCV prevalence (75%), when OAT coverage is increased from 10% to 40%, combined with HCV treatment of 10 % per year, the time to achieve micro-elimination reduces from 18.4 to 11.6 years. At the current HCV prevalence (60%), HCV TasP strategies as low as 10% coverage per year may achieve HCV micro-elimination within 10-years, with minimal impact from additional OAT scale-up.  Strategies based on mass initial HCV treatment (50 per 100 PWID the first year followed by 5 per 100 PWID thereafter) were most effective in settings with HCV prevalence of 60% or lower.ConclusionsScale up of HCV TasP is the most effective strategy for micro-elimination of HCV. However, OAT scale-up may be synergistic toward achieving micro-elimination goals when HCV prevalence exceeds 60% and when HCV treatment coverage is 10 per 100 PWID per year or lower.

McGee L, Chochua S, Li Z, et al.

AbstractBackgroundGroup B Streptococcus (GBS) is a leading cause of neonatal sepsis and meningitis and an important cause of invasive infections in pregnant and nonpregnant adults. Vaccines targeting capsule polysaccharides and common proteins are under development.MethodsUsing whole genome sequencing (WGS), a validated bioinformatics pipeline, and targeted antimicrobial susceptibility testing, we characterized 6,340 invasive GBS recovered during 2015-2017 through population-based Active Bacterial Core surveillance (ABCs) in eight states.ResultsSix serotypes accounted for 98.4% of isolates (21.8% Ia, 17.6% V, 17.1% II, 15.6% III, 14.5% Ib, 11.8% IV). Most (94.2%) isolates were in eleven clonal complexes (CCs) comprised of multilocus sequence types (MLSTs) identical or closely related to STs 1, 8, 12, 17, 19, 22, 23, 28, 88, 452 and 459. Fifty-four isolates (0.87%) had point mutations within pbp2x associated with non-susceptibility to one or more β-lactam antibiotics. Genes conferring resistance to macrolides and/or lincosamides were found in 56% of isolates; 85.2% of isolates had tetracycline resistance genes. Two isolates carrying vanG were vancomycin-nonsusceptible (MIC 2µg/ml). Nearly all isolates possessed capsule genes, 1-2 of the three main pilus gene clusters, and one of four homologous Alpha/Rib family determinants. Presence of hvgA virulence gene was primarily restricted to serotype III/CC17 isolates (465 isolates), but 8 exceptions (7 IV/CC452 and 1 IV/CC17) were observed.ConclusionsThis first comprehensive, population-based quantitation of strain features in the United States suggests current vaccine candidates should have good coverage. Beta-lactams remain appropriate for first line treatment and prophylaxis, but emergence of nonsusceptibility warrants ongoing monitoring.

Staat M, Payne D, Halasa N, et al.

AbstractBACKGROUNDSince 2006, the New Vaccine Surveillance Network has conducted active, population-based surveillance for acute gastroenteritis (AGE) hospitalizations and emergency department (ED) visits in three US counties. Trends in the epidemiology and disease burden of rotavirus hospitalizations and ED visits were examined from 2006-2016.METHODSChildren

Shlaes D.

Årdal C, , Lacotte Y, et al.

AbstractAntibiotic innovation is in serious jeopardy as companies continue to abandon the market due to a lack of profitability. Novel antibiotics must be used sparingly to hinder the spread of resistance, but small companies cannot survive on revenues that do not cover operational costs. When these companies go either bankrupt or move onto other therapeutic areas, these antibiotics may be no longer accessible to patients. While significant research efforts have detailed incentives to stimulate antibiotic innovation, little attention has been paid to the financing of these incentives. In this article, we take a closer look at four potential financing models (diagnosis-related group carve-out, stewardship taxes, transferable exclusivity voucher, and a European-based “pay or play” model) and evaluate them from a European perspective. The attractiveness of these models and the willingness for countries to test them are currently being vetted through the European Joint Action on AMR and Healthcare-Associated Infections (EU-JAMRAI).

Dunn A, Radakovich N, Ancker J, et al.

AbstractObjectiveSeveral studies have investigated the utility of electronic decision support alerts in diagnostic stewardship for Clostridioides difficile infection (CDI). However, it is unclear if alerts are effective in reducing inappropriate CDI testing and/or CDI rates. The aim of this systematic review was to determine if alerts related to CDI diagnostic stewardship are effective at reducing inappropriate CDI testing volume and CDI rates among hospitalized adult patients.DesignWe searched Ovid MEDLINE and 5 other databases for original studies evaluating the association between alerts for CDI diagnosis and CDI testing volume and/or CDI rate. Two investigators independently extracted data on study characteristics, study design, alert triggers, co-interventions, and study outcomes.ResultsEleven studies met criteria for inclusion. Studies varied significantly in alert triggers and in study outcomes. Six of eleven studies demonstrated a statistically significant decrease in CDI testing volume, six of six studies evaluating appropriateness of CDI testing found a significant reduction in the proportion of inappropriate testing, and four of seven studies measuring CDI rate demonstrated a significant decrease in the CDI rate in the post- vs pre-intervention periods. The magnitude of the increase in appropriate CDI testing varied, with some studies reporting an increase with minimal clinical significance.ConclusionsThe use of electronic alerts for diagnostic stewardship for C. difficile was associated with reductions in CDI testing, the proportion of inappropriate CDI testing, and rates of CDI in most studies. However, broader concerns related to alerts remain understudied, including unintended adverse consequences and alert fatigue.

Humphries R.

Didier K. Ekouevi, Alexandra Bitty-Anderson, Fifonsi A. Gbeasor-Komlanvi, Ahuatchi P. Coffie, Serge Paul Eholie

Basile N Landis, Abel-Jan Tasman

We congratulate Machteld van Egmond and colleagues for improving our understanding of the role of surgery in the treatment of nasal obstruction.1 Septoplasty is the most frequently performed ear, nose, and throat procedure in many countries. The value of septoplasty is undisputed for treating symptomatic nasal obstruction caused by significant anterior septal deformity with ipsilateral mechanical obstruction. In most patients, however, a combination of mucosal dysregulation, septal pathology, inspiratory collapse of the ala, psychological factors, and potentially altered trigeminal airflow perception have an influence on nasal obstruction.

Alberto Novaes Ramos, Jorg Heukelbach, Maria Leide Wand-Del-Rey Oliveira

Despite advances in the past three decades in implementing multidrug therapy against leprosy, by the end of 2018 approximately 210 000 new leprosy cases globally have been reported to WHO.1 Brazil, in particular, has a high burden of neglected tropical diseases,2 including leprosy. The country has an important role in generating scientific evidence to achieve leprosy control, as it accounts for the second highest number of new leprosy cases worldwide notified by a single country. There have been about 30 000 new cases notified in Brazil in 2018, representing 93% of all cases in the WHO region of the Americas.

Julia M Pescarini, Elizabeth Williamson, Joilda S Nery, Anna Ramond, Maria Yury Ichihara, Rosemeire L Fiaccone, Maria Lucia F Penna, Liam Smeeth, Laura C Rodrigues, Gerson O Penna, Elizabeth B Brickley, Mauricio L Barreto

Our results suggest that being a beneficiary of the PBF, which facilitates cash transfers and improved access to health care, is associated with greater leprosy multidrug therapy adherence and cure in multibacillary cases. These results are especially relevant for patients with multibacillary disease, who are treated for a longer period and have lower cure rates than those with paucibacillary disease.

Lu L, Das J, Grace P, et al.

AbstractBackgroundMycobacterium tuberculosis remains a global health problem and clinical management is complicated by difficulty in discriminating between latent infection and active disease. While M. tuberculosis-reactive antibody levels are heterogeneous, studies suggest that levels of IgG glycosylation differ between disease states. Here we extend this observation across antibody domains and M. tuberculosis specificities to define changes with the greatest resolving power.MethodsCapillary electrophoretic glycan analysis was performed on bulk non-antigen–specific IgG, bulk Fc domain, bulk Fab domain, and purified protein derivative (PPD)- and Ag85A-specific IgG from subjects with latent (n = 10) and active (n = 20) tuberculosis. PPD-specific isotype/subclass, PPD-specific antibody-dependent phagocytosis, cellular cytotoxicity, and natural killer cell activation were assessed. Discriminatory potentials of antibody features were evaluated individually and by multivariate analysis.ResultsParallel profiling of whole, Fc, and Fab domain-specific IgG glycosylation pointed to enhanced differential glycosylation on the Fc domain. Differential glycosylation was observed across antigen-specific antibody populations. Multivariate modeling highlighted Fc domain glycan species as the top discriminatory features, with combined PPD IgG titers and Fc domain glycans providing the highest classification accuracy.ConclusionsDifferential glycosylation occurs preferentially on the Fc domain, providing significant discriminatory power between different states of M. tuberculosis infection and disease.

Xing M, Yang N, Jiang N, et al.

AbstractMany members of obligate intracellular apicomplexan parasites have adapted a distinct invasion mechanism involving a close interaction between the parasite ligands and the sialic acid (SA) receptor. We found that the sialic acid-binding protein-1 (SABP1), localized on the outer membrane of the zoonotic parasite Toxoplasma gondii, readily binds to sialic acid on the host cell surface. The binding was sensitive to neuraminidase treatment. Cells preincubated with the recombinant SABP1 protein resisted parasite invasion in vitro. The parasite lost its invasion capacity and animal infectivity after the SABP1 gene being deleted, whereas complementation of the SABP1 gene restored the virulence of the knockout parasite. These data established the critical role of SABP1 in the invasion process of T. gondii. The previously uncharacterized protein, SABP1, facilitated T. gondii attachment and invasion via sialic acid receptors.

Godwin W, Prada J, Emerson P, et al.

AbstractBackgroundAs the World Health Organization seeks to eliminate trachoma by 2020, countries are beginning to control the transmission of trachomatous inflammation–follicular (TF) and discontinue mass drug administration (MDA) with oral azithromycin. We evaluated the effect of MDA discontinuation on TF1–9 prevalence at the district level.MethodsWe extracted from the available data districts with an impact survey at the end of their program cycle that initiated discontinuation of MDA (TF1–9 prevalence 5% from impact to surveillance survey in 9% of districts. Regression analysis indicated that impact survey TF1–9 prevalence was a significant predictor of surveillance survey TF1–9 prevalence. The proportion of simulations with >5% TF1–9 prevalence in the surveillance survey was 2%, assuming the survey was conducted 4 years after MDA.ConclusionAn increase in TF1–9 prevalence may represent disease resurgence but could also be due to measurement error. Improved diagnostic tests are crucial to elimination of TF1–9 as a public health problem.

Behrens G, Brehm M, Groß R, et al.

AbstractBackgroundBuccal swab sampling constitutes an attractive non-invasive alternative to blood drawings for antibody serostatus assays. Here we describe a method to determine the CMV IgG serostatus from dried buccal swab samples.MethodsUpon solubilisation, CMV IgG is determined by an ELISA assay specifically adapted to cope with low IgG concentrations. The derived CMV titer is normalised against the total protein concentration to adjust for incorrectly or less efficiently sampled buccal swabs. Assay parameters were optimised on a set of 713 samples.ResultsValidation with 1,784 samples revealed distinct results for >80% of samples with 98.6% specificity and 99.1% sensitivity. Based on the analysis of 1.2 million samples we derived age and sex stratified CMV prevalence statistics for Germany, Poland, UK, and Chile. To confirm accuracy of the assay in routine operation, the CMV status of 6,518 donors was reassessed by independent laboratories based on conventional blood samples revealing 96.9% specificity and 97.4% sensitivity.ConclusionsThe assay accurately delivers the CMV IgG serostatus from dried buccal swab samples for >80% of the participants. Thereby it provides a non-invasive alternative to plasma-based CMV monitoring for non-diagnostic purposes such as haematopoietic stem cell transplantation donor screening or population studies.

Huits R, De Smet B, Grard G, et al.

AbstractPersistence of Zika virus (ZIKV) RNA in semen is common after infection. We designed a RT-PCR assay that targets antisense ZIKV RNA (asRNA) to assess ZIKV replication competence in ZIKV RNA positive semen samples.We detected ZIKV asRNA in semen of nine of nineteen men (47.4%) diagnosed with ZIKV infection. All asRNA positive samples had high ZIKV loads (Ct-values

Rowley A, Baker S, Arrollo D, et al.

AbstractBackgroundKawasaki disease (KD) is the leading cause of childhood acquired heart disease in developed nations and can result in coronary artery aneurysms and death. Clinical and epidemiologic features implicate an infectious cause, but specific antigenic targets of the disease are unknown. Peripheral blood plasmablasts are normally highly clonally diverse but the antibodies they encode are ~70% antigen-specific 1-2 weeks after infection.MethodsWe isolated single peripheral blood plasmablasts from children with KD at 1-3 weeks after onset and prepared 60 monoclonal antibodies (mAbs). We used the mAbs to identify their target antigens and assessed serologic response among KD patients and controls to specific antigen.ResultsThirty-two mAbs from 9 of 11 patients recognize antigen within intracytoplasmic inclusion bodies in ciliated bronchial epithelial cells of fatal cases. Five of these mAbs, from 3 patients with coronary aneurysms, recognize a specific peptide, which blocks binding to the inclusion bodies. Sera from 5/8 KD patients at day >8 after illness onset, compared with 0/17 infant controls (p

Welty, Susie; Motoku, John; Muriithi, Chris; Rice, Brian; de Wit, Mariken; Ashanda, Brenda; Waruiru, Wanjiru; Mirjahangir, J.; Kingwara, L.; Bauer, Richard; Njoroge, David; Karimi, Jesse; Njoroge, Alice; Rutherford, George W.

Background: Serological tests can distinguish recent (in the prior 12 months) from long-term HIV infection. Integrating recency testing into routine HIV testing services (HTS) can provide important information on transmission clusters and prioritize clients for partner testing. This study assessed the feasibility and utility of integrating HIV recency into routine testing. Methods: We conducted a multi-method study at fourteen facilities in Kenya, and key informant interviews with healthcare providers. We abstracted clinical record data, collected specimens, tested specimens for recent infection, returned results to participants, and conducted a follow-up survey for those recently infected. Results: From March to October 2018, we enrolled 532 clients who were diagnosed HIV positive for the first time. Of these, 46 (8.6%) were recently infected. Women aged 15- 24 years had 2.9 (95% CI, 1.46-5.78) times higher adjusted odds of recent infection compared to 15-24-year-old men and those tested within the past 12 months having 2.55 (95% CI .38-4.70) times higher adjusted odds compared to those tested ≥12 months previously. Fourteen of seventeen providers interviewed found the integration of receny testing into routine HTS services acceptable and feasible. Among clients who completed the follow up interview, majority (92%) felt that the recency results were useful. Conclusions: Integrating recent infection testing into routine HTS services in Kenya is feasible and largely acceptable to clients and providers. More studies should be done on possible physical and social harms related to returning results, and the best uses of the recent infection data at an individual and population level. Corresponding author: Susie Welty, Institute for Global Health Science, University of California, San Francisco, 550 16th Street Box 1224, San Francisco, California, 94143-1224 USA, 415-476-5797, Susie.welty@ucsf.edu The authors report no conflicts of interest. E-mail addresses of authors: SW: Susie.welty@ucsf.edu MPH, JM: motoku@edarp.org MbCHB, CM: Chris@edarp.org BSc Msc, BR: Brian.Rice@lshtm.ac.uk BSc MSc PhD, MdW: Mariken.De-Wit@lshtm.ac.uk MPH, BA: brenda.ashanda@ucglobalprograms.org MPH, WW: Wanjiru.Waruiru@ucsf.edu MPH, JM: Joy.Mirjahangir@ucsf.edu MPH, LK: leonard.kingwara@gmail.com BSC MPH PhD, RB: RBauer@edarp.org BA, DN: David@edarp.org BSc, JK: jessikarimi@gmail.com BSc, AN: Alice@edarp.org RN BA, GR: George.Rutherford@ucsf.edu MD PhD This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Bingjie Wang, Fen Pan, Chun Wang, Wantong Zhao, Yan Sun, Tiandong Zhang, Yingying Shi, Hong Zhang

Arachchillage, Deepa R. J.; Laffan, Mike; Khanna, Sanjay; Vandenbriele, Christophe; Kamani, Farah; Passariello, Maurizio; Rosenberg, Alex; Aw, TC; Banya, Winston; Ledot, Stephane; Patel, Brijesh V.

Objectives: To ascertain: 1) the frequency of thrombocytopenia and heparin-induced thrombocytopenia; 2) positive predictive value of the Pretest Probability Score in identifying heparin-induced thrombocytopenia; and 3) clinical outcome of heparin-induced thrombocytopenia in adult patients receiving venovenous- or venoarterial-extracorporeal membrane oxygenation, compared with cardiopulmonary bypass. Design: A single-center, retrospective, observational cohort study from January 2016 to April 2018. Setting: Tertiary referral center for cardiac and respiratory failure. Patients: Patients who received extracorporeal membrane oxygenation for more than 48 hours or had cardiopulmonary bypass during specified period. Interventions: None. Measurements and Main Results: Clinical and laboratory data were collected retrospectively. Pretest Probability Score and heparin-induced thrombocytopenia testing results were collected prospectively. Mean age (± SD) of the extracorporeal membrane oxygenation and cardiopulmonary bypass cohorts was 45.4 (± 15.6) and 64.9 (± 13), respectively (p < 0.00001). Median duration of cardiopulmonary bypass was 4.6 hours (2–16.5 hr) compared with 170.4 hours (70–1,008 hr) on extracorporeal membrane oxygenation. Moderate and severe thrombocytopenia were more common in extracorporeal membrane oxygenation compared with cardiopulmonary bypass throughout (p < 0.0001). Thrombocytopenia increased in cardiopulmonary bypass patients on day 2 but was normal in 83% compared with 42.3% of extracorporeal membrane oxygenation patients at day 10. Patients on extracorporeal membrane oxygenation also followed a similar pattern of platelet recovery following cessation of extracorporeal membrane oxygenation. The frequency of heparin-induced thrombocytopenia in extracorporeal membrane oxygenation and cardiopulmonary bypass were 6.4% (19/298) and 0.6% (18/2,998), respectively (p < 0.0001). There was no difference in prevalence of heparin-induced thrombocytopenia in patients on venovenous-extracorporeal membrane oxygenation (8/156, 5.1%) versus venoarterial-extracorporeal membrane oxygenation (11/142, 7.7%) (p = 0.47). The positive predictive value of the Pretest Probability Score in identifying heparin-induced thrombocytopenia in patients post cardiopulmonary bypass and on extracorporeal membrane oxygenation was 56.25% (18/32) and 25% (15/60), respectively. Mortality was not different with (6/19, 31.6%) or without (89/279, 32.2%) heparin-induced thrombocytopenia in patients on extracorporeal membrane oxygenation (p = 0.79). Conclusions: Thrombocytopenia is already common at extracorporeal membrane oxygenation initiation. Heparin-induced thrombocytopenia is more frequent in both venovenous- and venoarterial-extracorporeal membrane oxygenation compared with cardiopulmonary bypass. Positive predictive value of Pretest Probability Score in identifying heparin-induced thrombocytopenia was lower in extracorporeal membrane oxygenation patients. Heparin-induced thrombocytopenia had no effect on mortality. This work was performed at the Royal Brompton & Harefield NHS Foundation Trust, London, United Kingdom. Dr. Arachchillage was responsible for design of the study, acquiring data, some of the statistical analysis, interpretation of the data, and writing the first draft of the article. Prof. Laffan, Dr. Ledot, and Dr. Patel reviewed the article. Drs. Khanna and Vandenbriele, Ms. Kamani, and Drs. Passariello, Rosenberg, Aw, Rosenberg, and Ledot collected the data. Mr. Banya performed statistically analysis. All authors reviewed and approved the final article. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Prof. Laffan received funding from Pfizer, Sobi, and Leopharma. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: d.arachchillage@imperial.ac.uk Copyright © by 2020 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Herrick J, Makiya M, Holland-Thomas N, et al.

AbstractBackgroundWe have previously demonstrated that eosinophil-associated processes underly some of the differences in clinical presentation among patients with Loa loa infection prior to therapy and that some post-treatment adverse events appear to be dependent on eosinophil activation.MethodsWe first conducted a retrospective review of 204 patients (70 microfilaria- positive/134 -negative) with Loa loa both before and following definitive therapy. We then measured filarial-specific antibodies, eosinophil- and Th2-associated cytokines, and eosinophil granule proteins in their banked serum prior to and at 1 year following definitive treatment. We also evaluated the influence of pre-treatment corticosteroids and/or apheresis in altering the efficacy of treatment.ResultsPatients without circulating microfilariae (MF-negative) not only had a higher likelihood of peripheral eosinophilia and increased antifilarial antibody levels, but also had significantly increased concentrations of GM-CSF, IL-5, and IL-4 compared to MF-positive patients. However, these differences had all resolved by 1-year post-treatment, when all parameters approached the levels seen in uninfected individuals. Neither pre-treatment with corticosteroids nor apheresis reduced the efficacy of the diethylcarbamazine used to treat these subjects.ConclusionsOur results highlight that by a year following treatment, infection-associated immunologic abnormalities had resolved in nearly all patients treated for loiasis, and pre-treatment corticosteroids had no influence on the resolution of the immunologic perturbations nor on the efficacy of DEC as a curative agent in loiasis.

Morgan D, Roghmann M, Pineles L.

Popping S, , Verwijs R, et al.

AbstractTransmission of direct-acting antiviral(DAA) resistance associated substitutions(RAS) could hamper hepatitis C virus (HCV) cure rates and ultimately jeopardize elimination efforts. A phylogenetic analysis of 87 men-who-have-sex-with-men recently infected with HCV genotype 1a demonstrated that one-third(28/87) belonged to a single large cluster in which 96% harbored the NS5A M28V RAS.

Lester R, Haigh K, Wood A, et al.

AbstractBackgroundThird-generation cephalosporins (3GC) remain the first-choice empiric antibiotic for severe infection in many sub-Saharan African hospitals. In Malawi, limited availability of alternatives, mean that strategies to prevent spread of 3GC-resistance (3GC-R) are imperative, however suitable approaches to antimicrobial stewardship (AMS) in low-income settings are not well studied.MethodsWe introduced an AMS intervention to Queen Elizabeth Central Hospital (QECH) in Blantyre. The intervention consisted of a smartphone prescribing application and regular point-prevalence surveys (PPS) with prescriber feedback. We evaluate the effects of the intervention on 3GC usage and on cost of providing antibiotics. Using thematic analysis of semi-structured interviews and participant observations, we additionally evaluate the acceptability of the stewardship program.ResultsThe proportion of antibiotic prescriptions for a 3GC reduced from 193/241 (80.1%) to 177/330 (53.6%) (percentage decrease 26.5% [95%CI; 18.7 to 34.1]) with no change in case-fatality rate. Cost analysis estimated annual savings of US$15,000. Qualitative research revealed trust in the guideline and found its accessibility through smartphones helpful to guide clinical decisions. Operational health-system barriers and hierarchal clinical relationships lead to continued reliance on 3GC.ConclusionsWe report the successful introduction of an antimicrobial stewardship approach in Malawi. By focusing on pragmatic interventions and simple aims, we demonstrate the feasibility, acceptability and cost-saving of a stewardship program where resources are limited. In doing so, we provide a suitable starting point for expansion of AMS interventions in this and other low-income settings.

Abstract Background The aim of this field trial was to evaluate the efficacy of attractive toxic sugar baits (ATSB) in Mali, where sustained malaria transmission occurs despite the use of long-lasting insecticidal nets (LLINs). ATSB bait stations were deployed in seven of 14 similar study villages, where LLINs were already in widespread use. The combined use of ATSB and LLINs was tested to see if it would substantially reduce parasite transmission by Anopheles gambiae sensu lato beyond use of LLINs alone. Methods A 2-day field experiment was conducted to determine the number of mosquitoes feeding on natural sugar versus those feeding on bait stations containing attractive sugar bait without toxin (ASB)—but with food dye. This was done each month in seven random villages from April to December 2016. In the following year, in seven treatment villages from May to December 2017, two ATSB bait stations containing the insecticide dinotefuran were placed on the outer walls of each building. Vector population density was evaluated monthly by CDC UV light traps, malaise traps, pyrethrum spray (PSCs) and human landing catches (HLCs). Female samples of the catch were tested for age by examination of the ovarioles in dissected ovaries and identification of Plasmodium falciparum sporozoite infection by ELISA. Entomological inoculation rates (EIR) were calculated, and reductions between treated and untreated villages were determined. Results In the 2-day experiment with ASB each month, there was a lower number of male and female mosquitoes feeding on the natural sugar sources than on the ASB. ATSB deployment reduced CDC-UV trap female catches in September, when catches were highest, were by 57.4% compared to catches in control sites. Similarly, malaise trap catches showed a 44.3% reduction of females in August and PSC catches of females were reduced by 48.7% in September. Reductions of females in HLCs were lower by 19.8% indoors and 26.3% outdoors in September. The high reduction seen in the rainy season was similar for males and reductions in population density for both males and females were > 70% during the dry season. Reductions of females with ≥ 3 gonotrophic cycles were recorded every month amounting to 97.1% in October and 100.0% in December. Reductions in monthly EIRs ranged from 77.76 to 100.00% indoors and 84.95% to 100.00% outdoors. The number of sporozoite infected females from traps was reduced by 97.83% at treated villages compared to controls. Conclusions Attractive toxic sugar baits used against Anopheles mosquitoes in Mali drastically reduced the density of mosquitoes, the number of older females, the number of sporozoite infected females and the EIR demonstrating how ATSB significantly reduces malaria parasite transmission.…

Abstract Long-lasting insecticidal nets, or LLINs, have significantly reduced malaria morbidity and mortality over the past two decades. The net provides a physical barrier that decreases human-mosquito contact and the impregnated insecticide kills susceptible mosquito vectors upon contact and may repel them. However, the future of LLINs is threatened as resistance to pyrethroids is now widespread, the chemical arsenal for LLINs is very limited, time from discovery of next-generation insecticides to market is long, and persistent transmission is frequently caused by vector populations avoiding contact with LLINs. Here we ask the question whether, given these challenges, insecticides should be incorporated in nets at all. We argue that developing long-lasting nets without insecticide(s) can still reduce vector populations and provide both personal and community protection, if combined with other approaches or technologies. Taking the insecticide out of the equation (i) allows for a faster response to the current pyrethroid resistance crisis, (ii) avoids an LLIN-treadmill aimed at replacing failing bed nets due to insecticide resistance, and (iii) permits the utilization of our current and future insecticidal arsenal for other vector control tools to target persistent malaria transmission.…

Abstract Background Obligate anaerobes usually account for less than 10% of bacteria recovered from blood cultures (BC). The relevance of routine use of the anaerobic bottle is under debate. The aim of this study was to evaluate the utility of anaerobic bottles for the diagnosis of bloodstream infections (BSI). Methods We conducted a 6-month, retrospective, monocentric study in a tertiary hospital. All positive BC were grouped into a single episode of bacteremia when drawn within 7 consecutive days. Bacteremia were classified into contaminants and BSI. Charts of patients with BSI due to obligate anaerobes were studied. Results A total of 19,739 blood cultures were collected, 2341 of which (11.9%) were positive. Anaerobic bottles were positive in 1528 (65.3%) of all positive BC but were positive alone (aerobic bottles negative) in 369 (15.8%). Overall 1081 episodes of bacteremia were identified, of which 209 (19.3%) had positive anaerobic bottles alone. The majority 126/209 (60.3%) were contaminants and 83 (39.7%) were BSI. BSI due to facultative anaerobes, obligate aerobes and obligate anaerobes were identified in 67 (80.7%), 3 (3.6%) and 13 (15.7%) of these 83 episodes, respectively. BSI due to obligate anaerobic bacteria were reported in 9 patients with gastro-intestinal disease, in 3 with febrile neutropenia and in 1 burned patient. Conclusions Anaerobic bottles contributed to the diagnosis of a significant number of episodes of bacteremia. Isolated bacteria were mostly contaminants and non-obligate anaerobic pathogens. Rare BSI due to obligate anaerobes were reported mainly in patients with gastro-intestinal disorders and during febrile neutropenia.…

Abstract Background The global annual estimate for cryptococcal disease-related deaths exceeds 180,000, with three fourth occurring in sub-Saharan Africa. The World Health Organization (WHO) recommends cryptococcal antigen (CrAg) screening in all HIV patients with CD4 count

Abstract Background The southeastern US is an epicenter for incident HIV in the US with high prevalence of human papillomavirus (HPV) co-infections. However, epidemiologies of HPV-associated clinical conditions (CC) among people living with HIV-1 infection (PLWH) are not fully known. Methods Electronic medical records (EMR) of PLWH attending one of the leading HIV clinics in the southeastern US between 2006 and 2018 were reviewed and analyzed. The retrospective study was nested within the University of Alabama at Birmingham HIV clinical cohort, which has electronically collected over 7000 PLWH’s clinical and sociobehavioral data since 1999. Incidence rates of HPV-related CC including anogenital warts, penile, anal, cervical, and vaginal/vulvar low- and high-grade squamous intraepithelial lesions (LSIL and HSIL) were estimated per 10,000 person years. Joinpoint regressions were performed to examine temporal changes in the trends of incident CC. All rates and trends were stratified by gender and race. Results Of the 4484 PLWH included in the study (3429 men, 1031 women, and 24 transgender), we observed 1038 patients with HPV-related CC. The median nadir CD4 count (cells/uL) was higher in the HPV-condition free group than the case groups (P 

Abstract Background Chagas disease is caused by the haemoflagellate protozoan Trypanosoma cruzi. Currently, T. cruzi recognizes seven discrete typing units (DTUs): TcI to TcVI and Tcbat. The genetic diversity of T. cruzi is suspected to influence the clinical outcome. Acute clinical manifestations, which include myocarditis and meningoencephalitis, are sometimes fatal; occur most frequently in children and in immunocompromised individuals. Acute disease is often overlooked, leading to a poor prognosis. Case presentation A 38-year-old man from a subtropical area of the Andes mountains of Ecuador was hospitalized after 3 weeks of evolution with high fever, chills, an enlarged liver, spleen, and lymph nodes, as well as facial edema. ECG changes were also observed. T. cruzi was identified in blood smears, culture and amplification of DNA by PCR. Tests for anti-T. cruzi IgG and IgM and HIV were negative. Molecular typing by restriction fragment length polymorphism (PCR-RFLP) determined the parasite to DTU TcI. In the absence of a timely anti-T. cruzi medication, the patient died. Conclusions This is a case of severe pathogenicity and the virulence of a DTU TcI strain in an adult patient. The severe acute Chagas disease was probably overlooked due to limited awareness and its low incidence. Our findings suggest that T. cruzi DTU TcI strains circulating in Ecuador are capable of causing fatal acute disease. Early diagnosis and prompt treatment is of paramount importance to avoid fatalities in acute infections.…

Abstract Background Anthrax is an endemic disease that persists in the rural regions of China. The global genetic population structure of B.anthracis has also been defined by the canonical single-nucleotide polymorphisms (canSNP) and multiple-locus variable-number tandem repeat analysis (MLVA). Five canSNP lineages were found in China, and the A.Br.Ames lineage has been the second predominant group in recent years in China. The objective of this study was to reveal genetic diversity of the Ames lineage strains by MLVA. Methods Two molecular typing methods, canSNP and MLVA with 15markers were used to study the genetic relationship among the Ames lineage strains. The outbreak information associated with these strains was also collected and investigated. Results From 2007 to 2018, a total of 21 human anthrax infection outbreaks (68 patients) associated with B. anthracis Ames lineage strains were reported in China. Ames lineage strain-associated human anthrax is mainly distributed in the northern part of China, including the provinces of Inner Mongolia, Liaoning, Gansu, and Xinjiang. In the study, a total of 30 Ames lineage strains were included and 10 MLVA15 genotypes were identified. These strains were mainly found in northeast China, Inner Mongolia and Liaoning. In recent years, the Ames lineage strains were isolated in the two provinces every year. The 18 Ames lineage strains isolated from Inner Mongolia were divided into eight MLVA15 genotypes. From 2010 to 2015, there were continuous reports of outbreaks in Keyouzhongqi County, Inner Mongolia, and the strains that were isolated annually in succession belonged to the MLVA15–30 genotype. Conclusions The Ames lineage strains are widely distributed in northern China. Their genetic diversity can be illustrated by the results of the MLVA. The genetic characteristics of the Ames lineage strains from outbreaks in different provinces varied. In some areas, human anthrax outbreaks occurred annually in succession, and these related strains grouped together. These observations indicate that the local environment was persistently contaminated with B. anthracis spores, vaccination of livestock should become the fundamental control measure in the areas.…

Abstract Background Diabetes mellitus (DM) is thought to affect tuberculosis (TB) clinical presentation and treatment response. Whether DM impacts radiological manifestations of pulmonary TB is still not clear. This study investigated the impact of glycemic status on radiological manifestations of pulmonary TB cases and its relationship with concentration of biochemical parameters in peripheral blood. Methods A retrospective cross-sectional study used data from 132 microbiologically confirmed pulmonary TB patients from Lima, Peru, evaluated in a previous investigation performed between February and December 2017. Chest radiographs were analyzed by a radiologist and a pulmonologist. Radiographic lesions were identified as cavities, alveolar infiltrates and fibrous tracts. Hyperglycemia in TB patients was identified by use of fasting plasma glucose, HbA1c and oral glucose tolerance test. Clinical, biochemical and hematological parameters were also analyzed. Results TB patients with hyperglycemia presented more frequently with cavities, alveolar infiltrates and fibrous tracts than those with normoglycemia. Hierarchical clustering analysis indicated that patients with more diverse and higher number of lung lesions exhibited a distinct laboratorial profile characterized by heightened white blood cell counts and circulating levels of total cholesterol, triglycerides and transaminases and simultaneously low levels of albumin and hemoglobin. Multivariable regression analyses adjusted for age, sex, prior TB, hemoglobin levels and acid-fast bacilli ≥2+ in sputum smears, demonstrated that presence of prediabetes or diabetes in TB patients was associated with increased odds of having 3 pulmonary lesion types (p = 0.003 and p 

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Libing Yang, Daniel G. Dunlap, Shulin Qin, Adam Fitch, Kelvin Li, Carl D. Koch, Mehdi Nouraie, Rebecca DeSensi, Ken S. Ho, Jeremy J. Martinson, Barbara Methé, Alison Morris

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