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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.
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.
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.
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.
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.firstname.lastname@example.org
The authors report no conflicts of interest.
E-mail addresses of authors: SW: Susie.email@example.com MPH, JM: firstname.lastname@example.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: email@example.com MPH, WW: Wanjiru.Waruiru@ucsf.edu MPH, JM: Joy.Mirjahangir@ucsf.edu MPH, LK: firstname.lastname@example.org BSC MPH PhD, RB: RBauer@edarp.org BA, DN: David@edarp.org BSc, JK: email@example.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.
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.
A single-center, retrospective, observational cohort study from January 2016 to April 2018.
Tertiary referral center for cardiac and respiratory failure.
Patients who received extracorporeal membrane oxygenation for more than 48 hours or had cardiopulmonary bypass during specified period.
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).
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: firstname.lastname@example.org
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.
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.
International Liver Congress (ILC) 2020
15.04.2020 - 19.04.2020
European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 2020
18.04.2020 - 21.04.2020
DSI årsmøde 2020 (aflyst)
Hindsgavl Slot, Middelfart
1.05.2020 - 2.05.2020
Kursus i rejsemedicin 2020
Statens Serum Institut
4.05.2020 - 6.05.2020
5.05.2020 - 7.05.2020
COVID-19 retningslinje (2020)
National handlingsplan for antibiotika til mennesker (2017)
Retningslinjer til sundhedsprofessionelle vedr. håndtering af infektion med zikavirus (2019)
Antiviral behandling af hiv smittede personer (2019)
A real-world evaluation of a Case-Based Reasoning algorithm to support antimicrobial prescribing decisions in acute care
4.04.2020Clinical Infectious Diseases Advance Access
Open versus endovascular repair of aortic aneurysms
COVID-19 will not leave behind refugees and migrants
Redefining vulnerability in the era of COVID-19
The COVID-19 pandemic in the USA: what might we expect?
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