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To the Editor—We thank Yamaoka and colleagues for their interest and comments on our paper [1]. Yamaoka et al point out that there are cross-reactivities of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) full-length nucleoprotein (FL-NP) with antibodies to other common human coronaviruses (HCoVs), which may cause false positive results in serological assays. They propose to use a truncated version of NP lacking the N-terminal (ΔNP) to detect SARS-CoV-2 antibodies.

AbstractBackgroundAntimicrobial-resistant infections are commonly encountered in US hospitals and result in significant morbidity and mortality. This guidance document provides recommendations for the treatment of infections caused by extended-spectrum β-lactamase–producing Enterobacterales (ESBL-E), carbapenem-resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with difficult-to-treat resistance (DTR-P. aeruginosa).MethodsA panel of 6 infectious diseases specialists with expertise in managing antimicrobial-resistant infections formulated common questions regarding the treatment of ESBL-E, CRE, and DTR-P. aeruginosa infections. Based on review of the published literature and clinical experience, the panel provide recommendations and associated rationale for each recommendation. Because of significant differences in the molecular epidemiology of resistance and the availability of specific anti-infective agents globally, this document focuses on treatment of antimicrobial-resistant infections in the United States.ResultsApproaches to empiric treatment selection, duration of therapy, and other management considerations are briefly discussed. The majority of guidance focuses on preferred and alternative treatment recommendations for antimicrobial-resistant infections, assuming that the causative organism has been identified and antibiotic susceptibility testing results are known. Treatment recommendations apply to both adults and children.ConclusionsThe field of antimicrobial resistance is dynamic and rapidly evolving, and the treatment of antimicrobial-resistant infections will continue to challenge clinicians. This guidance document is current as of 17 September 2020. Updates to this guidance document will occur periodically as new data emerge. Furthermore, the panel will expand recommendations to include other problematic gram-negative pathogens in future versions. The most current version of the guidance including the date of publication can be found at www.idsociety.org/practice-guideline/amr-guidance/.

A 48-year-old female with no past medical history presented to the emergency department in June 2020 with a 6-month history of productive cough associated with nausea, vomiting, and 20-kg weight loss. She had no other symptoms. She lived in mainland France for 20 years, and had been living in Martinique for the past 9 years. She works as a caregiver, and her husband is a goat breeder. She has a dog and a cat. At clinical examination, the patient had no fever and no evidence of respiratory distress. She had a normal oxygen saturation. Heart and lung auscultation were unremarkable. The rest of the examination was normal. The peripheral white blood cell count was 5.84 G/L, of which 0.42 G/L were eosinophils. A mild normochromic normocytic anemia (hemoglobin, 11.6 g/dL) was found. There was no thrombocytopenia, and the C-reactive protein level was <3 mg/L. Liver and kidney function markers were also within normal ranges. Computed tomography of the chest revealed a ground-glass opacity at the base of the middle lobe (Figure 1). A bronchoscopy was performed. Bronchial mucosa appeared to be slightly inflamed with yellowish mucous secretions. During exploration of the right basal pyramid, the endoscopist found and removed a Y-shaped whitish–red motile body. The entire structure was sent to the parasitology laboratory for further identification (Figure 2).

AbstractIn 208 children seeking medical care, the seropositivity rate of anti–SARS-CoV-2 IgG antibodies was 8.7%, suggesting an infection rate similar to that observed in adults but >100-fold the incidence of RT-PCR–confirmed pediatric cases. Compared with the gold-standard combined ELISA + immunofluorescence, the MEDsan IgG rapid diagnostic test performed accurately.

AbstractBackgroundMany countries have implemented nonpharmaceutical interventions (NPIs) to slow the spread of coronavirus disease 2019 (COVID-19). We aimed to determine whether NPIs led to the decline in the incidences of respiratory infections.MethodsWe conducted a retrospective, ecological study using a nationwide notifiable diseases database and a respiratory virus sample surveillance collected from January 2016 through July 2020 in the Republic of Korea. Intervention period was defined as February–July 2020, when the government implemented NPIs nationwide. Observed incidences in the intervention period were compared with the predicted incidences by an autoregressive integrated moving average model and the 4-year mean cumulative incidences (CuIs) in the same months of the preintervention period.ResultsFive infectious diseases met the inclusion criteria: chickenpox, mumps, invasive pneumococcal disease, scarlet fever, and pertussis. The incidences of chickenpox and mumps during the intervention period were significantly lower than the prediction model. The CuIs (95% confidence interval) of chickenpox and mumps were 36.4% (23.9–76.3%) and 63.4% (48.0–93.3%) of the predicted values. Subgroup analysis showed that the decrease in the incidence was universal for chickenpox, while mumps showed a marginal reduction among those aged <18 years, but not in adults. The incidence of respiratory viruses was significantly lower than both the predicted incidence (19.5%; 95% confidence interval, 11.8–55.4%) and the 4-year mean CuIs in the preintervention period (24.5%; P < .001).ConclusionsThe implementation of NPIs was associated with a significant reduction in the incidences of several respiratory infections in Korea.

AbstractBackgroundAntimicrobial-resistant infections are commonly encountered in US hospitals and result in significant morbidity and mortality. This guidance document provides recommendations for the treatment of infections caused by extended-spectrum β-lactamase–producing Enterobacterales (ESBL-E), carbapenem-resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with difficult-to-treat resistance (DTR-P. aeruginosa).MethodsA panel of 6 infectious diseases specialists with expertise in managing antimicrobial-resistant infections formulated common questions regarding the treatment of ESBL-E, CRE, and DTR-P. aeruginosa infections. Based on review of the published literature and clinical experience, the panel provide recommendations and associated rationale for each recommendation. Because of significant differences in the molecular epidemiology of resistance and the availability of specific anti-infective agents globally, this document focuses on treatment of antimicrobial-resistant infections in the United States.ResultsApproaches to empiric treatment selection, duration of therapy, and other management considerations are briefly discussed. The majority of guidance focuses on preferred and alternative treatment recommendations for antimicrobial-resistant infections, assuming that the causative organism has been identified and antibiotic susceptibility testing results are known. Treatment recommendations apply to both adults and children.ConclusionsThe field of antimicrobial resistance is dynamic and rapidly evolving, and the treatment of antimicrobial-resistant infections will continue to challenge clinicians. This guidance document is current as of 17 September 2020. Updates to this guidance document will occur periodically as new data emerge. Furthermore, the panel will expand recommendations to include other problematic gram-negative pathogens in future versions. The most current version of the guidance including the date of publication can be found at www.idsociety.org/practice-guideline/amr-guidance/.

AbstractCryptococcal antigen (CrAg) detection could direct the timely initiation of antifungal therapy. We searched MEDLINE and Embase for studies where CrAg detection in serum/cerebrospinal fluid (CSF) and CSF fungal culture were done on adults living with human immunodeficiency virus (HIV) who had suspected cryptococcal meningitis (CM). With Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2), we evaluated the risk of bias in 11 included studies with 3600 participants, and used a random-effects meta-analysis to obtain summary sensitivity and specificity of serum and CSF CrAg, as well as agreement between CSF CrAg and CSF culture. Summary sensitivity and specificity of serum CrAg were 99.7% (97.4–100) and 94.1% (88.3–98.1), respectively, and summary sensitivity and specificity of CSF CrAg were 98.8% (96.2–99.6) and 99.3% (96.7–99.9), respectively. Agreement between CSF CrAg and CSF culture was 98% (97–99). In adults living with HIV who have CM symptoms, serum CrAg negativity may rule out CM, while positivity should prompt induction antifungal therapy if lumbar puncture is not feasible. In a first episode of CM, CSF CrAg positivity is diagnostic.

AbstractGrowing evidence suggests that 2-deoxy-2-[18F]fluoro-D-glucose (18FDG)–positron emission tomography/computed tomography (PET/CT) is a useful imaging technique for the evaluation of fever of unknown origin (FUO). This imaging technique allows for accurate localization of foci of hypermetabolism based on 18FDG uptake in glycolytically active cells that may represent inflammation, infection, or neoplasia. The presence of abnormal uptake can help direct further investigation that may yield a final diagnosis. A lack of abnormal uptake can be reasonably reassuring that these conditions are not present, thereby avoiding unnecessary additional testing. Insurers have not routinely covered outpatient 18FDG-PET/CT for the indication of FUO in the United States. However, data published since 2007 suggest early use in FUO diagnostic evaluations improves diagnostic efficiency and reduces costs. Clinicians and insurers should consider 18FDG-PET/CT as a useful tool when preliminary studies are unrevealing.

AbstractRecently, results from at least six major randomized clinical trials studying management of COVID-19 have been announced via press release. Given the unique nature of the pandemic, results of such trials often have immediate and worldwide relevance. Yet, while press releases serve the important purpose of disseminating top-level results quickly, they are inherently limited in scope, and rarely include sufficient data to inform practice. Herein, we propose a minimum set of trial characteristics and results to be released simultaneously with clinical trial announcements. This practice will ensure data related to the management of COVID-19 can be used to appropriately impact care, while responding to the needs of diverse stakeholders in the scientific and publishing communities, as well as the public at large.

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AbstractRandomized controlled trials (RCTs) conducted by the industry are expensive, especially trials conducted for registration of new drugs for multidrug-resistant (MDR) bacteria. Lower-cost investigator-initiated trials have recently been successful in recruiting patients with severe infections caused by MDR bacteria. In this viewpoint, we contrast the aims, methods, and resulting costs of industry-led and investigator-initiated trials and ask whether contemporary registration trial costs are justified. Contract research organizations, delivering and monitoring industry-sponsored trials at a significant cost, have little incentive to make trials more efficient or less expensive. The value of universal monitoring of all trial data is questionable. We propose that clinical trial networks play a more influential role in RCT design and planning, lead adaptive risk-based trial monitoring, and work with the industry to maximize efficient recruitment and lower costs in registration trials for the approval of new antimicrobials.

AbstractHyperinflammation is associated with increased mortality in coronavirus disease 2019 (COVID-19). In this retrospective, uncontrolled patient cohort with moderate -severe COVID-19, treatment with baricitinib plus hydroxychloroquine was associated with recovery in 11 of 15 patients. Baricitinib for the treatment of COVID-19 should be further investigated in randomized, controlled clinical trials.

AbstractTesting of paired midturbinate (MT) nasal and nasopharyngeal (NP) swabs, collected by trained personnel from 40 patients with coronavirus disease 2019 (COVID-19), showed that more NP (76/95 [80%]) than MT swabs tested positive (61/95 [64%]) (P = .02). Among samples collected a week after study enrollment, fewer MT than NP samples were positive (45% vs 76%; P = .001).

AbstractAmong 283 symptomatic healthcare personnel (HCP) tested for SARS-CoV-2, 51 (18%) were positive. Among those 51 HCP, self reported loss of smell and taste were present in 51% and 52.9%, respectively, with either present in 60.8%. These symptoms had high specificity (93% each, 96% for either) for a positive SARS-CoV-2 test.

Abstract Background Malaria and helminths diseases are co-endemic in most parts of sub-Saharan Africa. Immune responses from each of these pathogens interact, and these interactions may have implications on vaccines. The GMZ2 malaria vaccine candidate is a fusion protein of Plasmodium falciparum merozoite surface protein 3 (MSP3) and glutamate rich protein (GLURP R0). GMZ2 has recently showed modest efficacy in a phase IIb multicenter trial. Here, we assessed the effect of hookworm (Necator americanus) infection and anthelmintic treatment on naturally acquired antibody responses against GMZ2 and constituent antigens. Methods This longitudinal cross-sectional study was conducted in the Kintampo North Municipality of Ghana. Blood and stool samples were taken from 158 individuals (4–88 years old) infected with either P. falciparum alone (n = 59) or both hookworm and P. falciparum (n = 63) and uninfected endemic controls (n = 36). Stool hookworm infection was detected by the Kato-Katz method and PCR. Malaria parasitaemia was detected by RDT, light microscopy and P. falciparum-specific 18S rRNA gene PCR. Serum samples were obtained prior to hookworm treatment with a single dose of albendazole (400 mg) and 3 weeks (21 days) after treatment. Levels of IgG1, IgG3 and IgM against GMZ2, MSP3 and GLURP R0 were measured by ELISA and compared among the groups, before and after treatment. Results Participants with P. falciparum and hookworm co-infection had significantly higher IgG3 levels to GMZ2 than those with only P. falciparum infection and negative control (p < 0.05) at baseline. Treatment with albendazole led to a significant reduction in IgG3 levels against both GMZ2 and GLURP R0. Similarly, IgM and IgG1 levels against MSP3 also decreased following deworming treatment. Conclusion Individuals with co-infection had higher antibody responses to GMZ2 antigen. Treatment of hookworm/malaria co-infection resulted in a reduction in antibody responses against GMZ2 and constituent antigens after albendazole treatment. Thus, hookworm infection and treatment could have a potential implication on malaria vaccine efficacy.

Abstract Background The clinical and imaging features of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections that progressed to coronavirus disease 2019 (COVID-19) have been explored in numerous studies. However, little is known about these features in patients who received negative respiratory nucleic acid test results after the infections resolved. In this study, we aim to describe these features in a group of Chinese patients. Methods This retrospective study includes 51 patients with mild-to-moderate COVID-19 (median age: 34.0 years and 47.1% male) between January 31 and February 28, 2020. Demographic, clinical, laboratory, and computed tomography (CT) imaging data were collected before and after two consecutive negative respiratory SARS-CoV-2 tests. Results Following a negative test result, the patients’ clinical symptoms continued to recover, but abnormal imaging findings were observed in all moderate cases. Specifically, 77.4% of patients with moderate COVID-19 exhibited multi-lobar lung involvement and lesions were more frequently observed in the lower lobes. The most common CT imaging manifestations were ground-glass opacities (51.6%) and fibrous stripes (54.8%%). Twelve of the 31 patients with moderate COVID-19 underwent repeated chest CT scans after a negative SARS-CoV-2 test. Among them, the ground-glass opacities decreased by > 60% within 1 week in seven patients (58.3%), but by < 5% in four patients (13.8%). Conclusions Following a positive and subsequent negative SARS-CoV-2 tests, patients with COVID-19 continued to recover despite exhibiting persistent clinical symptoms and abnormal imaging findings.

Abstract Background Previous studies have reported that presence and severity of Buruli ulcer (BU) may reflect the underlying immunosuppression in HIV infected individuals by causing increased incidence of multiple, larger and ulcerated lesions. We report cases of BU-HIV coinfection and the accompanying programmatic challenges encountered in central Ghana. Methods Patients with PCR confirmed BU in central Ghana who were HIV positive were identified and their BU01 forms were retrieved and reviewed in further detail. A combined 16S rRNA reverse transcriptase / IS2404 qPCR assay was used to assess the Mycobacterium ulcerans load. The characteristics of coinfected patients (BU+HIV+) were compared with a group of matched controls. Results The prevalence of HIV in this BU cohort was 2.4% (compared to national HIV prevalence of 1.7%). Eight of 9 BU+HIV+ patients had a single lesion and ulcers were the most common lesion type. The lesions presented were predominantly category II (5/9) followed by category I lesions. The median (IQR) time to healing was 14 (8–28) weeks in the BU+HIV+ compared to 28 (12–33) weeks in the control BU+HIV− group (p = 0.360). Only one BU+HIV+ developed a paradoxical reaction at week 16 but the lesion healed completely at week 20. The median bacterial load (16SrRNA) of BU+HIV+ patients was 750 copies /ml (95% CI 0–398,000) versus 500 copies/ml (95% CI 0–126,855,500) in BU+HIV− group. Similarly, the median count using the IS2404 assay was 500 copies/ml (95% CI 0–500) for BU+HIV+ patients versus 500 copies/ml (95% CI 500–31,000) for BU+HIV− patients. BU+HIV− patients mounted a significantly higher interferon-γ response compared to the BU+HIV+ co-infected patients with respective median (range) responses of [1687(81.11–4399) pg/ml] versus [137.5(4.436–1406) pg/ml, p = 0.03]. There were challenges with the integration of HIV and BU care in this cohort. Conclusion The prevalence of HIV in the BU+ infected population was not significantly increased when compared to the prevalence of HIV in the general population. There was no clear relationship between BU lesion severity and HIV viral load or CD4 counts. Efforts should be made to encourage the integration of care of patients with BU-HIV coinfection.

Abstract Objectives To explore the drug susceptibility of levofloxacin (LFX), moxifloxacin (MFX), bedaquiline (BDQ), linezolid (LZD), clofazimine (CFZ) and delamanid (DLM) against multidrug resistant tuberculosis (MDR-TB) isolates from drug resistance survey of southwest China, and to illustrate the genetic characteristics of MDR-TB isolates with acquired drug resistance. Methods A total of 339 strains were collected from smear-positive TB patients in the drug resistance survey of southwest China between January 2014 and December 2016. The MICs for the above mentioned drugs were determined for MDR-TB by conventional drug susceptibility testing. Genes related to drug resistance were amplified with their corresponding pairs of primers. Results MDR was observed in 88 (26.0%; 88/339) isolates. LFX had the highest resistance rate (50.0%; 44/88), followed by MFX (38.6%; 34/88). The resistance rate to LZD, CFZ, and DLM was 4.5% (4/88), 3.4% (3/88), and 4.5% (4/88), respectively, and the lowest resistance rate was observed in BDQ (2.3%; 2/88). Of the 45 isolates resistant to LFX and MFX, the most prevalent resistance mutation was found in gyrA with the substitution of codon 94 (34/45, 75.6%). Two strains with CFZ - BDQ cross resistance had a mutation in the Rv0678 gene. Of the four LZD resistant isolates, two carried mutations in rplC gene. For the four isolates resistant to DLM, one isolate had mutations in codon 318 of fbiC gene, and two isolates were with mutations in codon 81 of ddn gene. Conclusion This study provided evidence of the usefulness of new anti-TB drugs in the treatment of MDR-TB in China.

New England Journal of Medicine, Volume 384, Issue 14, April 2021.

New England Journal of Medicine, Ahead of Print.

New England Journal of Medicine, Ahead of Print.

New England Journal of Medicine, Ahead of Print.

New England Journal of Medicine, Ahead of Print.

by Béke Pannewick, Claas Baier, Frank Schwab, Ralf-Peter Vonberg There is a lack of data on factors that contribute to the implementation of hygiene measures during nosocomial outbreaks (NO) caused by Methicillin-resistant Staphylococcus aureus (MRSA). Therefore, we first conducted a systematic literature analysis to identify MRSA outbreak reports. The expenditure for infection control in each outbreak was then evaluated by a weighted cumulative hygiene score (WCHS). Effects of factors on this score were determined by multivariable linear regression analysis. 104 NO got included, mostly from neonatology (n = 32), surgery (n = 27), internal medicine and burn units (n = 10 each), including 4,361 patients (thereof 657 infections and 73 deaths) and 279 employees. The outbreak sources remained unknown in 10 NO and were not reported from further 61 NO. The national MRSA prevalence did not correlate with the WCHS (p = .714). There were significant WCHS differences for internal medicine (p = 0.014), burn units (p<0.01), for Japanese NO (p<0.01), and NO with an unknown source (p<0.01). In sum, management of a NO due to MRSA does not depend on the local MRSA burden. However, differences of MRSA management among medical departments do exist. Strict adherence to the Outbreak Reports and Intervention Studies Of Nosocomial infection (ORION) statement is highly recommended for. The WCHS may also serve as a useful tool to quantify infection control effort and could therefore be used for further investigations.

by Nicola Sweeney, Blair Merrick, Rui Pedro Galão, Suzanne Pickering, Alina Botgros, Harry D. Wilson, Adrian W. Signell, Gilberto Betancor, Mark Kia Ik Tan, John Ramble, Neophytos Kouphou, Sam Acors, Carl Graham, Jeffrey Seow, Eithne MacMahon, Stuart J. D. Neil, Michael H. Malim, Katie Doores, Sam Douthwaite, Rahul Batra, Gaia Nebbia, Jonathan D. Edgeworth During the first wave of the global COVID-19 pandemic the clinical utility and indications for SARS-CoV-2 serological testing were not clearly defined. The urgency to deploy serological assays required rapid evaluation of their performance characteristics. We undertook an internal validation of a CE marked lateral flow immunoassay (LFIA) (SureScreen Diagnostics) using serum from SARS-CoV-2 RNA positive individuals and pre-pandemic samples. This was followed by the delivery of a same-day named patient SARS-CoV-2 serology service using LFIA on vetted referrals at central London teaching hospital with clinical interpretation of result provided to the direct care team. Assay performance, source and nature of referrals, feasibility and clinical utility of the service, particularly benefit in clinical decision-making, were recorded. Sensitivity and specificity of LFIA were 96.1% and 99.3% respectively. 113 tests were performed on 108 participants during three-week pilot. 44% participants (n = 48) had detectable antibodies. Three main indications were identified for serological testing; new acute presentations potentially triggered by recent COVID-19 e.g. pulmonary embolism (n = 5), potential missed diagnoses in context of a recent COVID-19 compatible illness (n = 40), and making infection control or immunosuppression management decisions in persistently SARS-CoV-2 RNA PCR positive individuals (n = 6). We demonstrate acceptable performance characteristics, feasibility and clinical utility of using a LFIA that detects anti-spike antibodies to deliver SARS-CoV-2 serology service in adults and children. Greatest benefit was seen where there is reasonable pre-test probability and results can be linked with clinical advice or intervention. Experience from this pilot can help inform practicalities and benefits of rapidly implementing new tests such as LFIAs into clinical service as the pandemic evolves.

by Teresa López-Castro, Laura Brandt, Nishanthi J. Anthonipillai, Adriana Espinosa, Robert Melara In March 2020, New York City (NYC) experienced an outbreak of coronavirus disease 2019 (COVID-19) which resulted in a 78-day mass confinement of all residents other than essential workers. The aims of the current study were to (1) document the breadth of COVID-19 experiences and their impacts on college students of a minority-serving academic institution in NYC; (2) explore associations between patterns of COVID-19 experiences and psychosocial functioning during the prolonged lockdown, and (3) explore sex and racial/ethnic differences in COVID-19-related experiences and mental health correlates. A total of 909 ethnically and racially diverse students completed an online survey in May 2020. Findings highlight significant impediments to multiple areas of students’ daily life during this period (i.e., home life, work life, social environment, and emotional and physical health) and a vast majority reported heightened symptoms of depression and generalized anxiety. These life disruptions were significantly related to poorer mental health. Moreover, those who reported the loss of a close friend or loved one from COVID-19 (17%) experienced significantly more psychological distress than counterparts with other types of infection-related histories. Nonetheless, the majority (96%) reported at least one positive experience since the pandemic began. Our findings add to a growing understanding of COVID-19 impacts on psychological health and contribute the important perspective of the North American epicenter of the pandemic during the time frame of this investigation. We discuss how the results may inform best practices to support students’ well-being and serve as a benchmark for future studies of US student populations facing COVID-19 and its aftermath.

by Jacob M. Bezemer, Jacob van der Ende, Jacqueline Limpens, Henry J. C. de Vries, Henk D. F. H. Schallig Cutaneous and mucocutaneous leishmaniasis affect a million people yearly, leading to skin lesions and potentially disfiguring mucosal disease. Current treatments can have severe side effects. Allylamine drugs, like terbinafine, are safe, including during pregnancy. This review assesses efficacy and safety of allylamines for the treatment of cutaneous and mucocutaneous leishmaniasis. It followed the PRISMA statement for reporting and was preregistered in PROSPERO(CRD4201809068). MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Global Health Library, Web of Science, Google Scholar, and clinical trial registers were searched from their creation to May 24th, 2020. All original human, animal, and in vitro studies concerning allylamines and cutaneous or mucocutaneous leishmaniasis were eligible for inclusion. Comparators—if any—included both placebo or alternative cutaneous or mucocutaneous leishmaniasis treatments. Complete cure, growth inhibition, or adverse events served as outcomes. The search identified 312 publications, of which 22 were included in this systematic review. There were one uncontrolled and two randomised controlled trials. The only well-designed randomised controlled trial that compared the treatment efficacy of oral terbinafine versus intramuscular meglumine antimoniate in 80 Leismania tropica infected patients showed a non-significant lower cure rate for terbinafine vs meglumine antimoniate (38% vs 53%). A meta-analysis could not be performed due to the small number of studies, their heterogeneity, and low quality. This systematic review shows that there is no evidence of efficacy of allylamine monotherapy against cutaneous and mucocutaneous leishmaniasis. Further trials of allylamines should be carefully considered as the outcomes of an adequately designed trial were disappointing and in vitro studies indicate minimal effective concentrations that are not achieved in the skin during standard doses. However, the in vitro synergistic effects of allylamines combined with triazole drugs warrant further exploration.

by Shana Kushner Gadarian, Sara Wallace Goodman, Thomas B. Pepinsky Objective To study the U.S. public’s health behaviors, attitudes, and policy opinions about COVID-19 in the earliest weeks of the national health crisis (March 20–23, 2020). Method We designed and fielded an original representative survey of 3,000 American adults between March 20–23, 2020 to collect data on a battery of 38 health-related behaviors, government policy preferences on COVID-19 response and worries about the pandemic. We test for partisan differences COVID-19 related policy attitudes and behaviors, measured in three different ways: party affiliation, intended 2020 Presidential vote, and self-placed ideological positioning. Our multivariate approach adjusts for a wide range of individual demographic and geographic characteristics that might confound the relationship between partisanship and health behaviors, attitudes, and preferences. Results We find that partisanship—measured as party identification, support for President Trump, or left-right ideological positioning—explains differences in Americans across a wide range of health behaviors and policy preferences. We find no consistent evidence that controlling for individual news consumption, the local policy environment, and local pandemic-related deaths erases the observed partisan differences in health behaviors, beliefs, and attitudes. In further analyses, we use a LASSO regression approach to select predictors, and find that a partisanship indicator is the most commonly selected predictor across the 38 dependent variables that we study. Conclusion Our analysis of individual self-reported behavior, attitudes, and policy preferences in response to COVID-19 reveals that partisanship played a central role in shaping individual responses in the earliest months of the COVID-19 pandemic. These results indicate that partisan differences in responding to a national public health emergency were entrenched from the earliest days of the pandemic.

by Maider Muñoz-Culla, Andres Roncancio-Clavijo, Bruno Martínez, Miriam Gorostidi-Aicua, Luis Piñeiro, Arkaitz Azkune, Ainhoa Alberro, Jorge Monge-Ruiz, Tamara Castillo-Trivino, Alvaro Prada, David Otaegui ABO blood groups have recently been related to COVID19 infection. In the present work, we performed this analysis using data from 412 COVID19 patients and 17796 blood donors, all of them from Gipuzkoa, a region in Northern Spain. The results obtained confirmed this relation, in addition to showing a clear importance of group O as a protective factor in COVID19 disease, with an OR = 0.59 (CI95% 0.481–0.7177, p<0.0001) while A, B and AB are risk factors. ABO blood groups are slightly differently distributed in the populations and therefore these results should be replicated in the specific areas with a proper control population.

by Reaz Mahmud, Mohammad Aftab Rassel, Farhana Binte Monayem, S. K. Jakaria Been Sayeed, Md Shahidul Islam, Mohammed Monirul Islam, Mohammad Abdullah Yusuf, Sabrina Rahman, K. M. Nazmul Islam, Imran Mahmud, Mohammad Zaid Hossain, Ahmed Hossain Chowdhury, A. K. M. Humayon Kabir, Kazi Gias Uddin Ahmed, Md. Mujibur Rahman Background Globally, studies have shown conflicting results regarding the association of blood groups with SARS CoV-2 infection. Objective To observe the association between ABO blood groups and the presentation and outcomes of confirmed COVID-19 cases. Design, setting, and participants This was a prospective cohort study of patients with mild-to-moderately severe COVID-19 infections who presented in the COVID-19 unit of Dhaka Medical College Hospital and were enrolled between 01 June and 25 August, 2020. Patients were followed up for at least 30 days after disease onset. We grouped participants with A-positive and A-negative blood groups into group I and participants with other blood groups into group II. Results The cohort included 438 patients; 52 patients were lost to follow-up, five died, and 381 completed the study. The prevalence of blood group A [144 (32.9%)] was significantly higher among COVID-19 patients than in the general population (p < 0.001). The presenting age [mean (SD)] of group I [42.1 (14.5)] was higher than that of group II [38.8 (12.4), p = 0.014]. Sex (p = 0.23) and co-morbidity (hypertension, p = 0.34; diabetes, p = 0.13) did not differ between the patients in groups I and II. No differences were observed regarding important presenting symptoms, including fever (p = 0.72), cough (p = 0.69), and respiratory distress (p = 0.09). There was no significant difference in the median duration of symptoms in the two group (12 days), and conversion to the next level of severity was observed in 26 (20.6%) and 36 patients (13.8%) in group I and II, respectively. However, persistent positivity of RT-PCR at 14 days of initial positivity was more frequent among the patients in group I [24 (19%)] than among those in group II [29 (11.1%)]. Conclusions The prevalence of blood group A was higher among COVID-19 patients. Although ABO blood groups were not associated with the presentation or recovery period of COVID-19, patients with blood group A had delayed seroconversion.

by Shailja Jakhar, Ramamurthy Sakamuri, Dung Vu, Priya Dighe, Loreen R. Stromberg, Laura Lilley, Nicolas Hengartner, Basil I. Swanson, Emmanuel Moreau, Susan E. Dorman, Harshini Mukundan Lipoarabinomannan (LAM), an amphiphilic lipoglycan of the Mycobacterium tuberculosis cell wall, is a diagnostic target for tuberculosis. Previous work from our laboratory and others suggests that LAM is associated with host serum lipoproteins, which may in turn have implications for diagnostic assays. Our team has developed two serum assays for amphiphile detection: lipoprotein capture and membrane insertion. The lipoprotein capture assay relies on capture of the host lipoproteins, exploiting the biological association of host lipoprotein with microbial amphiphilic biomarkers to “concentrate” LAM. In contrast, the membrane insertion assay is independent of the association between pathogen amphiphiles and host lipoprotein association, and directly captures LAM based on its thermodynamic propensity for association with a supported lipid membrane, which forms the functional surface of an optical biosensor. In this manuscript, we explored the use of these assays for the detection of LAM in sera from adults whose tuberculosis status had been well-characterized using conventional microbiological tests, and endemic controls. Using the lipoprotein capture assay, LAM signal/noise ratios were >1.0 in 29/35 (83%) individuals with culture-confirmed active tuberculosis, 8/13 (62%) individuals with tuberculosis symptoms, but no positive culture for M. tuberculosis, and 0/6 (0%) symptom-free endemic controls. To evaluate serum LAM levels without bias associated with potential differences in circulating host lipoprotein concentrations between individuals, we subsequently processed available samples to liberate LAM from associated host lipoprotein assemblies followed by direct detection of the pathogen biomarker using the membrane insertion approach. Using the membrane insertion assay, signal/noise for detection of serum LAM was greater than that observed using the lipoprotein capture method for culture-confirmed TB patients (6/6), yet remained negative for controls (2/2). Taken together, these results suggest that detection of serum LAM is a promising TB diagnostic approach, but that further work is required to optimize assay performance and to decipher the implications of LAM/host lipoprotein associations for diagnostic assay performance and TB pathogenesis.