Open Forum Infectious Diseases

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ISSN / EISSN : 23288957 / 23288957
Current Publisher: Oxford University Press (OUP) (10.1093)
Total articles ≅ 13,678
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Kirsten Hanke, Stefan Fiedler, Christina Grumann, Oliver Ratmann, Andrea Hauser, Patrycja Klink, Karolin Meixenberger, Britta Altmann, Ruth Zimmermann, Ulrich Marcus, et al.
Open Forum Infectious Diseases; doi:10.1093/ofid/ofaa192

Abstract:
Background Needle and syringe sharing among people who inject drugs (PWID) can result in a rapid regional spread of a Human Immunodeficiency Virus (HIV) variant. Such outbreaks have been identified recently in several countries and have raised public health attention because of an association with New Psychoactive Substances (NPS). Methods Dried Serum Spots (DSS) from about 60% of newly diagnosed German HIV cases in 2013-2018 were received together with statutory notification data. Samples were sequenced in the pol-region, genotyped and viral phylogenies analyzed. For selected samples the Hepatitis C Virus (HCV) status and the presence of NPS were determined. Results An outbreak of closely related 27 subtype C infections with a core of 11 cases with almost identical sequences was identified using phylogenetic analyses. The first case of the outbreak was diagnosed in 2015, and the last one in 2018. With exception of three infections all were reported from Munich, the capital of the federal state of Bavaria. Of 26 analyzed outbreak members 24 (92.3%) had a resolved or viremic HCV co-infection. In 8/18 (44%) cases α-pyrrolidinopentiothiophenone (α–PVT) and/or the related substance α-pyrrolidinoheptiophenone (PV8) was identified. Conclusion Despite harm reduction services in place HIV outbreaks of considerable size can occur in PWID. The establishment of a real time molecular surveillance is advised in order to rapidly identify outbreaks and target prevention measures.
Kellee English, Sarah B May, Jessica A Davila, Jeffrey A Cully, Lilian Dindo, K Rivet Amico, Michael A Kallen, Thomas P Giordano
Open Forum Infectious Diseases; doi:10.1093/ofid/ofaa193

Abstract:
Background Understanding factors influencing retention in care (RIC) and VL improvement (VLI) in people with HIV (PWH) who are out of care and hospitalized will assist in intervention development for this vulnerable population. Methods The study was a post-hoc analysis of prospectively collected data. Hospitalized participants were enrolled if they were newly diagnosed with HIV during the hospitalization or out of HIV care. Participants completed surveys at baseline and 6 months post-enrollment and laboratory studies of viral load (VL). Outcomes were RIC (2 completed visits, one within 30 days of discharge) and VLI (VL<400 or at least a 1 log10 decrease) 6 months after discharge. Univariate and multivariate regression analyses were conducted examining contributions of predisposing, enabling, and need factors to outcomes. Results The study cohort included 417 participants enrolled between 2010 and 2013. The population was 73% male; 67% non-Hispanic Black and 19% Hispanic; 70% uninsured; 65% with a baseline CD4<200 cells/mm3; 79% with a VL>400 copies/mL or missing; and generally poor with low education attainment. After discharge from the hospital, 60% did not meet the definition for RIC, and 49% did not have VLI. Modifiable factors associated with the outcomes include drug use (including marijuana alone and other drugs), life instability (e.g., housing, employment, and life chaos), and using avoidance coping strategies in coping with HIV. Conclusions Hospitalized out-of-care PWH in the US are at high risk of poor re-engagement in care after discharge. Interventions for this population should focus on improving socioeconomic stability and coping with HIV and reducing drug use.
L Gayani Tillekeratne, Sunil Suchindran, Emily R Ko, Elizabeth A Petzold, Champica K Bodinayake, Ajith Nagahawatte, Vasantha Devasiri, Ruvini Kurukulasooriya, Bradly P Nicholson, Micah T McClain, et al.
Open Forum Infectious Diseases; doi:10.1093/ofid/ofaa194

Abstract:
Background Pathogen-based diagnostics for acute respiratory infection (ARI) have limited ability to detect etiology of illness. We previously showed that peripheral blood-based host gene expression classifiers accurately identify bacterial and viral ARI in cohorts of European and African descent. We determined classifier performance in a South Asian cohort. Methods Patients ≥15 years with fever and respiratory symptoms were enrolled in Sri Lanka. Comprehensive pathogen-based testing was performed. Peripheral blood RNA was sequenced and previously developed signatures were applied: a pan-viral classifier (viral vs non-viral) and an ARI classifier (bacterial vs viral vs non-infectious). Results RNA sequencing was performed in 79 subjects: 58 viral infections (36 influenza, 22 dengue) and 21 bacterial infections (10 leptospirosis, 11 scrub typhus). The pan-viral classifier had an overall classification accuracy of 95%. The ARI classifier had an overall classification accuracy of 94%, with sensitivity and specificity of 91% and 95%, respectively, for bacterial infection. The sensitivity and specificity of C-reactive protein (>10mg/L) and procalcitonin (>0.25ng/mL) for bacterial infection were 100% and 34%, and 100% and 41%, respectively. Conclusions Previously derived gene expression classifiers had high predictive accuracy at distinguishing viral and bacterial infection in South Asian patients with ARI caused by typical and atypical pathogens.
Lucia Taramasso, Paolo Bonfanti, Elena Ricci, Giancarlo Orofino, Nicola Squillace, Barbara Menzaghi, Giuseppe Vittorio De Socio, Giordano Madeddu, Giovanni Francesco Pellicanò, Layla Pagnucco, et al.
Open Forum Infectious Diseases; doi:10.1093/ofid/ofaa195

Abstract:
BACKGROUND An unexpected excess in weight gain has recently been reported in course of dolutegravir (DTG) treatment. Aim of the present study is to investigate whether weight gain differs among different DTG-containing regimens. METHODS Adult naïve and experienced people with HIV (PWH) initiating DTG–based ART between July 2014 and December 2019 in SCOLTA prospective cohort (Surveillance Cohort Long-Term Toxicity Antiretrovirals) were included. We used an adjusted general linear model to compare weight change among backbone groups, and a Cox proportional hazard regression model to calculate hazard ratios (HR) and 95%CI for weight increase >10% from baseline. RESULTS A total of 713 participants, 25.3% women, 91% Caucasian were included. Of them, 195 (27.4%) started DTG as first ART regimen, while 518 (72.6%) were ART-experienced. DTG was associated with abacavir/lamivudine in 326 participants, tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in 148, boosted protease inhibitors in 60, rilpivirine in 45, lamivudine in 75 and tenofovir alafenamide (TAF)/FTC in 59. At six and twelve months, weight gain was highest among PWH on TDF/FTC+DTG and TAF/FTC+DTG. Baseline CD4 <200 cells/mm3 (HR 1.84, 95%CI 1.15-2.96), being ART-naïve (HR 2.24, 95%CI 1.24-4.18), and treatment with TDF/FTC+DTG (HR 1.92, 95%CI 1.23-2.98) or TAF/FTC+DTG (HR3.80, 95%CI 1.75-8.23) was associated with weight gain >10% from baseline. Higher weight (HR 0.97 by one kg, 95%CI 0.96-0.99) and female gender (HR 0.54, 95%CI 0.33-0.88) resulted protective. CONCLUSIONS Naïve PWH with lower CD4 counts and those on TAF/FTC or TDF/FTC backbones resulted at higher risk of weight increase in course of DTG-based ART.
Stéphane Chevaliez, Mélanie Wlassow, Johann Volant, Françoise Roudot-Thoraval, Antoine Bachelard, Lila Poiteau, Jean-Baptiste Trabut, Christophe Hézode, Anne Bourdel, Stéphanie Dominguez
Open Forum Infectious Diseases; doi:10.1093/ofid/ofaa196

Abstract:
Background Injecting drug use is a major driver of hepatitis C virus (HCV) spread worldwide and the World Health Organization (WHO) has identified people who inject drugs (PWID) as a key population to target for HCV screening and care. Point-of-care hepatitis C tests and dried blood spot (DBS) sampling offer benefits for the management of patients with HCV infection by increasing HCV testing and linkage to care in different non-clinical settings. The aims of this prospective study were to evaluate the feasibility and the acceptability of use HCV RNA POC and fingerstick DBS testing in social-medical risk-reduction centres and to describe the cascade of care among PWID in France. Methods Between June 2018 to February 2019, 89 consecutive HCV seropositive PWID attending two drug treatment services and one supervised consumption room in inner-Paris were invited to participate in further evaluation, undergoing a clinical review with a liver assessment and blood tests including fingerstick capillary whole blood POC HCV RNA testing and fingerstick dried blood spot (DBS) sampling. Results Of the 89 participants enrolled, HCV RNA was detected in 34 (38.6%) participants. Fingerstick whole blood POC RNA testing and HCV RNA detection from DBS sample were feasible and acceptable among PWID with no major difference in terms of HCV RNA detection rate. Overall, 16 participants received pangenotypic antiviral treatment. The proportion of PWID with SVR12 was 81.2%, with data for three patients still pending. Conclusions One-step screening strategy based on the detection of HCV RNA would engage people in care for treatment scale-up and HCV elimination.
Joshua G Petrie, Adam S Lauring, Emily T Martin, Keith S Kaye
Open Forum Infectious Diseases; doi:10.1093/ofid/ofaa200

Abstract:
Hospital-associated respiratory virus infections (HARVI) are an underappreciated source of morbidity and mortality. We examined HARVI incidence and clinical respiratory virus testing practices in a cohort of hospitalized patients with acute respiratory illness. HARVIs were identified in patients of all ages, both during and outside of the influenza season.
Joanna Von Hofsten, Johan Ringlander, Peter Norberg, Madeleine Zetterberg, Maria Andersson, Magnus Lindh, Tomas Bergström
Open Forum Infectious Diseases; doi:10.1093/ofid/ofaa198

Abstract:
We report a case of Acute Retinal Necrosis presenting with acute glaucoma preceding inflammatory signs by several days. High-throughput sequencing on aqueous humor revealed a low-level diversity in the viral genome comparable to diversity seen in cutaneous vesicles in contrast to high diversity in encephalitis.
Claire E Hannah, Bradley A Ford, Jina Chung, Dilek Ince, Karolyn A Wanat
Open Forum Infectious Diseases; doi:10.1093/ofid/ofaa173

Abstract:
Background The prevalence of infections due to nontuberculous mycobacteria (NTM) is increasing worldwide, yet little is known about the epidemiology and pathophysiology of these ubiquitous environmental organisms. Pulmonary disease due to Mycobacterium avium complex (MAC) is most prevalent, but many other NTM species can cause disease in virtually any organ system. As NTM becomes an increasingly common cause of morbidity and mortality, more information is needed about the epidemiology of NTM disease. Methods We conducted a retrospective chart review of all patients with cultures that grew NTM at a Midwestern tertiary hospital from 1996 to 2017. Information on demographics, medical history, clinical findings, treatment, and outcome was obtained from medical records of all NTM isolates. American Thoracic Society/Infectious Diseases Society of America criteria were used to define pulmonary NTM infections. Results We identified 1064 NTM isolates, 365 of which met criteria for NTM infection. Pulmonary cases predominated (185/365; 50.7%), followed by skin/soft tissue (56/365; 15.3%), disseminated (40/365; 11%), and lymphatic (28/365; 7.7%) disease. MAC was the most common species (184/365; 50.4%). Individuals aged >50 years were most affected (207/365; 56.7%). Common comorbidities included structural lung disease (116/365; 31.8%), use of immunosuppressive medications (78/365; 21.4%), malignancy (59/365; 16.2%), and HIV (42/365; 11.5%). Conclusions This large cohort provides information on the demographics, risk factors, and disease course of patients with pulmonary and extrapulmonary NTM infections. Most patients had medical comorbidities that resulted in anatomic, genetic, or immunologic risk factors for NTM infection. Further population-based studies and increased disease surveillance are warranted to further characterize NTM infection prevalence and trends.
Ethan Valinetz, Helen Stankiewicz Karita, Paul S Pottinger, Rupali Jain
Open Forum Infectious Diseases; doi:10.1093/ofid/ofaa183

Abstract:
Clofazimine has demonstrated in vitro activity against many non-tuberculous mycobacteria. We present the case of a woman with cystic fibrosis who developed disseminated macrolide-resistant Mycobacterium avium infection following lung transplantation treated in part with clofazimine. We describe the novel administration of clofazimine via gastrostomy tube.
Zulema Udaondo, Piroon Jenjaroenpun, Thidathip Wongsurawat, Erik Meyers, Courtney Anderson, James Lopez, Meera Mohan, Ruslana Tytarenko, Brian Walker, David Ussery, et al.
Open Forum Infectious Diseases; doi:10.1093/ofid/ofaa180

Abstract:
In this work, we report two cases of vancomycin resistant Enterococcus faecium bacteremia with development of daptomycin resistance from two patients with acute myeloid leukemia (AML), and myelodysplastic syndrome. Mutations related to daptomycin non-susceptible phenotype in liaSR genes were found in all strains of the study, including those with MIC < 1 µg/ml collected before daptomycin therapy. Epidemiological investigation using cgSNP and cgMLST revealed clonality of all the isolates. In this study, we conclude that real-time genome sequencing of clinical isolates can provide rapid access to timely information of daptomycin resistant genotypes that would help clinicians speed up and optimize the selection of the antibiotic for treatment.
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