| 1. |
- Ulfhammer, Gustaf, et al.
(författare)
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Cerebrospinal Fluid Viral Load Across the Spectrum of Untreated Human Immunodeficiency Virus Type 1 (HIV-1) Infection: A Cross-Sectional Multicenter Study
- 2022
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 75:3, s. 493-502
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Tidskriftsartikel (refereegranskat)abstract
- Background The aim of this large multicenter study was to determine variations in cerebrospinal fluid (CSF) HIV-RNA in different phases of untreated human immunodeficiency virus type 1 (HIV-1) infection and its associations with plasma HIV-RNA and other biomarkers. Methods Treatment naive adults with available CSF HIV-RNA quantification were included and divided into groups representing significant disease phases. Plasma HIV-RNA, CSF white blood cell count (WBC), neopterin, and albumin ratio were included when available. Results In total, 1018 patients were included. CSF HIV-RNA was in median (interquartile range [IQR]) 1.03 log(10) (0.37-1.86) copies/mL lower than in plasma, and correlated with plasma HIV-RNA (r = 0.44, P < .01), neopterin concentration in CSF (r = 0.49, P < .01) and in serum (r = 0.29, P < .01), CSF WBC (r = 0.34, P < .01) and albumin ratio (r = 0.25, P < .01). CSF HIV-RNA paralleled plasma HIV-RNA in all groups except neuroasymptomatic patients with advanced immunodeficiency (CD4 < 200) and patients with HIV-associated dementia (HAD) or opportunistic central nervous system (CNS) infections. Patients with HAD had the highest CSF HIV-RNA (in median [IQR] 4.73 (3.84-5.35) log(10) copies/mL). CSF > plasma discordance was found in 126 of 972 individuals (13%) and varied between groups, from 1% in primary HIV, 11% in neuroasymptomatic groups, up to 30% of patients with HAD. Conclusions Our study confirms previous smaller observations of variations in CSF HIV-RNA in different stages of HIV disease. Overall, CSF HIV-RNA was approximately 1 log(10) copies/mL lower in CSF than in plasma, but CSF discordance was found in a substantial minority of subjects, most commonly in patients with HAD, indicating increasing CNS compartmentalization paralleling disease progression. HIV-RNA is detectable in cerebrospinal fluid (CSF) across all stages of untreated HIV and usually parallel plasma HIV-RNA at a lower level. A substantial proportion (13%) of patients have CSF>plasma HIV-RNA, most commonly in patients with HIV-associated dementia.
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| 2. |
- Boutry, Céline, et al.
(författare)
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The Adjuvanted Recombinant Zoster Vaccine Confers Long-Term Protection Against Herpes Zoster : Interim Results of an Extension Study of the Pivotal Phase 3 Clinical Trials ZOE-50 and ZOE-70
- 2022
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press. - 1058-4838 .- 1537-6591. ; 74:8, s. 1459-1467
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Tidskriftsartikel (refereegranskat)abstract
- Efficacy against herpes zoster and immune responses to the adjuvanted recombinant zoster vaccine plateaued at high levels between 5.1 and 7.1 years (mean) post-vaccination, suggesting that its clinical benefit in older adults is sustained for at least 7 years post-vaccination. Background This ongoing follow-up study evaluated the persistence of efficacy and immune responses for 6 additional years in adults vaccinated with the glycoprotein E (gE)-based adjuvanted recombinant zoster vaccine (RZV) at age >= 50 years in 2 pivotal efficacy trials (ZOE-50 and ZOE-70). The present interim analysis was performed after >= 2 additional years of follow-up (between 5.1 and 7.1 years [mean] post-vaccination) and includes partial data for year (Y) 8 post-vaccination. Methods Annual assessments were performed for efficacy against herpes zoster (HZ) from Y6 post-vaccination and for anti-gE antibody concentrations and gE-specific CD4[2+] T-cell (expressing >= 2 of 4 assessed activation markers) frequencies from Y5 post-vaccination. Results Of 7413 participants enrolled for the long-term efficacy assessment, 7277 (mean age at vaccination, 67.2 years), 813, and 108 were included in the cohorts evaluating efficacy, humoral immune responses, and cell-mediated immune responses, respectively. Efficacy of RZV against HZ through this interim analysis was 84.0% (95% confidence interval [CI], 75.9-89.8) from the start of this follow-up study and 90.9% (95% CI, 88.2-93.2) from vaccination in ZOE-50/70. Annual vaccine efficacy estimates were >84% for each year since vaccination and remained stable through this interim analysis. Anti-gE antibody geometric mean concentrations and median frequencies of gE-specific CD4[2+] T cells reached a plateau at approximately 6-fold above pre-vaccination levels. Conclusions Efficacy against HZ and immune responses to RZV remained high, suggesting that the clinical benefit of RZV in older adults is sustained for at least 7 years post-vaccination.
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| 3. |
- Vahasarja, N., et al.
(författare)
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Infective Endocarditis Among High-risk Individuals Before and After the Cessation of Antibiotic Prophylaxis in Dentistry: A National Cohort Study
- 2022
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 75:7, s. 1171-1178
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Tidskriftsartikel (refereegranskat)abstract
- The findings of this cohort study suggest no increased incidence of oral streptococcal infective endocarditis among high-risk individuals in Sweden since the recommended cessation of antibiotic prophylaxis in dentistry for the prevention of endocarditis in October 2012. Background A few years after the publication of the British guidelines, national recommendations were published by the Swedish Medical Products Agency in October 2012, promoting the cessation of antibiotic prophylaxis in dentistry for the prevention of infective endocarditis (IE). The aim of this study was to evaluate whether the incidence of oral streptococcal IE increased among high-risk individuals after October 2012. Methods This nationwide cohort study included all adult individuals (>17 years) living in Sweden from January 2008 to January 2018, with a diagnose code or surgical procedure code indicating high risk of IE. Cox proportional hazard models were performed to calculate adjusted ratios of oral streptococcal IE before and after October 2012 between high-risk individuals and references. Results This study found no increased incidence of oral streptococcal IE among high-risk individuals during the 5 years after the cessation, compared with before. Hazard rate ratios were 15.4 (95% confidence interval [CI]: 8.3-28.5) before and 20.7 (95% CI: 10.0-42.7) after October 2012 for prevalent high-risk individuals. Corresponding ratios for incident high-risk individuals were 66.8 (95% CI: 28.7-155.6) and 44.6 (95% CI: 22.9-86.9). Point estimates for interaction with time period were 1.4 (95% CI: .6-3.5) and 0.8 (95% CI: .5-1.3) for prevalent and incident high-risk individuals, respectively. Conclusion The results suggest that the current Swedish recommendation not to administer antibiotic prophylaxis for the prevention of IE in dentistry has not led to an increased incidence of oral streptococcal IE among high-risk individuals.
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| 4. |
- Alsved, Malin, et al.
(författare)
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SARS-CoV-2 in exhaled aerosol particles from covid-19 cases and its association to household transmission
- 2022
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Ingår i: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. - : Oxford University Press (OUP). - 1537-6591. ; 75:1, s. 50-56
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Covid-19 transmission via exhaled aerosol particles has been considered an important route for the spread of infection, especially during super-spreading events involving loud talking or singing. However, no study has previously linked measurements of viral aerosol emissions to transmission rates.METHODS: During Feb-Mar 2021, covid-19 cases that were close to symptom onset were visited with a mobile laboratory for collection of exhaled aerosol particles during breathing, talking and singing, respectively, and of nasopharyngeal and saliva samples. Aerosol samples were collected using a BioSpot-VIVAS and a NIOSH bc-251 two-stage cyclone, and all samples were analyzed by RT-qPCR for SARS-CoV-2 RNA detection. We compared transmission rates between households with aerosol-positive and aerosol-negative index cases.RESULTS: SARS-CoV-2 RNA was detected in at least one aerosol sample from 19 of 38 (50%) included cases. The odds ratio of finding positive aerosol samples decreased with each day from symptom onset (OR 0.55, 95CI 0.30-1.0, p=0.049). The highest number of positive aerosol samples were from singing, 16 (42%), followed by talking, 11 (30%), and the least from breathing, 3 (8%). Index cases were identified for 13 households with 31 exposed contacts. Higher transmission rates were observed in households with aerosol-positive index cases, 10/16 infected (63%), compared to households with aerosol-negative index cases, 4/15 infected (27%) (Chi-square test, p=0.045).CONCLUSIONS: Covid-19 cases were more likely to exhale SARS-CoV-2-containing aerosol particles close to symptom onset and during singing or talking as compared to breathing. This study supports that individuals with SARS-CoV-2 in exhaled aerosols are more likely to transmit covid-19.
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| 5. |
- Denti, Paolo, et al.
(författare)
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Optimizing Dosing and Fixed-Dose Combinations of Rifampicin, Isoniazid, and Pyrazinamide in Pediatric Patients With Tuberculosis : A Prospective Population Pharmacokinetic Study
- 2022
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Ingår i: Clinical Infectious Diseases. - : OXFORD UNIV PRESS INC. - 1058-4838 .- 1537-6591. ; 75:1, s. 141-151
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Tidskriftsartikel (refereegranskat)abstract
- Background In 2010, the World Health Organization (WHO) revised dosing guidelines for treatment of childhood tuberculosis. Our aim was to investigate first-line antituberculosis drug exposures under these guidelines, explore dose optimization using the current dispersible fixed-dose combination (FDC) tablet of rifampicin/isoniazid/pyrazinamide; 75/50/150 mg, and suggest a new FDC with revised weight bands. Methods Children with drug-susceptible tuberculosis in Malawi and South Africa underwent pharmacokinetic sampling while receiving first-line tuberculosis drugs as single formulations according the 2010 WHO recommended doses. Nonlinear mixed-effects modeling and simulation was used to design the optimal FDC and weight-band dosing strategy for achieving the pharmacokinetic targets based on literature-derived adult AUC(0-24h) for rifampicin (38.7-72.9), isoniazid (11.6-26.3), and pyrazinamide (233-429 mg center dot h/L). Results In total, 180 children (42% female; 13.9% living with human immunodeficiency virus [HIV]; median [range] age 1.9 [0.22-12] years; weight 10.7 [3.20-28.8] kg) were administered 1, 2, 3, or 4 FDC tablets (rifampicin/isoniazid/pyrazinamide 75/50/150 mg) daily for 4-8, 8-12, 12-16, and 16-25 kg weight bands, respectively. Rifampicin exposure (for weight and age) was up to 50% lower than in adults. Increasing the tablet number resulted in adequate rifampicin but relatively high isoniazid and pyrazinamide exposures. Administering 1, 2, 3, or 4 optimized FDC tablets (rifampicin/isoniazid/pyrazinamide 120/35/130 mg) to children < 6, 6-13, 13-20. and 20-25 kg, and 0.5 tablet in < 3-month-olds with immature metabolism, improved exposures to all 3 drugs. Conclusions Current pediatric FDC doses resulted in low rifampicin exposures. Optimal dosing of all drugs cannot be achieved with the current FDCs. We propose a new FDC formulation and revised weight bands. Current pediatric dosing guidelines lead to infant rifampicin exposures much lower than in adults, whereas isoniazid and pyrazinamide exposures are similar. A new fixed-dose combination (FDC) with rifampicin/isoniazid/pyrazinamide 120/35/130 mg and weight bands of < 6, 6-13, 13-20, and 20-25 kg could improve treatment.
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| 6. |
- Imlay, Hannah, et al.
(författare)
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Consensus Definitions of BK Polyomavirus Nephropathy in Renal Transplant Recipients for Clinical Trials
- 2022
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 75:7, s. 1210-1216
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Tidskriftsartikel (refereegranskat)abstract
- Background BK polyomavirus (BKPyV) infection and BK polyomavirus nephropathy (BKPyVAN) are important causes of allograft dysfunction and premature allograft loss in renal transplant recipients. Results and Discussion Controlled clinical trials to evaluate new agents for prevention and treatment are needed but are hampered by the lack of outcome measures that accurately assess the effect of the intervention, are clinically relevant, and are acceptable from a regulatory perspective. Methods To facilitate consistent end points in clinical trials and to support clinical research and drug development, definitions of BKPyV infection and disease have been developed by the BK Disease Definitions Working Group of the Transplantation Associated Virus Infection Forum with the Forum for Collaborative Research, which consists of scientists, clinicians, regulators, and industry representatives. Conclusions These definitions refine established principles of "proven" BKPyV disease and introduce a "probable" disease category that could be used in clinical trials to prevent or treat BKPyVAN in renal transplant recipients. Standardized BK polyomavirus nephropathy (BKPyVAN) definitions are needed to evaluate therapeutics. We refine established criteria for "proven" BKPyVAN and introduce a "probable disease" category based on allograft dysfunction and plasma DNAemia. Plasma DNAemia thresholds for BKPyVAN are needed.
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| 7. |
- Musa, Ahmed M, et al.
(författare)
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Paromomycin and Miltefosine Combination as an Alternative to Treat Patients With Visceral Leishmaniasis in Eastern Africa : A Randomized, Controlled, Multicountry Trial.
- 2022
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 76:3, s. e1177-e1185
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: This study aimed to determine whether paromomycin plus miltefosine (PM/MF) is noninferior to sodium stibogluconate plus paromomycin (SSG/PM) for treatment of primary visceral leishmaniasis in eastern Africa.METHODS: An open-label, phase 3, randomized, controlled trial was conducted in adult and pediatric patients at 7 sites in eastern Africa. Patients were randomly assigned to either 20 mg/kg paromomycin plus allometric dose of miltefosine (14 days), or 20 mg/kg sodium stibogluconate plus 15 mg/kg paromomycin (17 days). The primary endpoint was definitive cure after 6 months.RESULTS: Of 439 randomized patients, 424 completed the trial. Definitive cure at 6 months was 91.2% (155 of 170) and 91.8% (156 of 170) in the PM/MF and SSG/PM arms in primary efficacy modified intention-to-treat analysis (difference, 0.6%; 97.5% confidence interval [CI], -6.2 to 7.4), narrowly missing the noninferiority margin of 7%. In the per-protocol analysis, efficacy was 92% (149 of 162) and 91.7% (155 of 169) in the PM/MF and SSG/PM arms (difference, -0.3%; 97.5% CI, -7.0 to 6.5), demonstrating noninferiority. Treatments were well tolerated. Four of 18 serious adverse events were study drug-related, and 1 death was SSG-related. Allometric dosing ensured similar MF exposure in children (<12 years) and adults.CONCLUSIONS: PM/MF and SSG/PM efficacies were similar, and adverse drug reactions were as expected given the drugs safety profiles. With 1 less injection each day, reduced treatment duration, and no risk of SSG-associated life-threatening cardiotoxicity, PM/MF is a more patient-friendly alternative for children and adults with primary visceral leishmaniasis in eastern Africa. Clinical Trials Registration. NCT03129646.
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| 8. |
- Nibell, Olof, et al.
(författare)
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Reply to Rezahosseini
- 2022
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Ingår i: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. - : Oxford University Press (OUP). - 1537-6591. ; 74:12, s. 2262-2262
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 9. |
- Rasmussen, Magnus, et al.
(författare)
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One Scoring System Does Not Fit All Healthcare Settings
- 2022
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Ingår i: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. - : Oxford University Press (OUP). - 1537-6591. ; 74:1, s. 166-167
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Tidskriftsartikel (refereegranskat)
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| 10. |
- Thuresson, Sara, et al.
(författare)
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Airborne Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Hospitals : Effects of Aerosol-Generating Procedures, HEPA-Filtration Units, Patient Viral Load, and Physical Distance
- 2022
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Ingår i: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. - : Oxford University Press (OUP). - 1537-6591. ; 75:1, s. 89-96
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Transmission of coronavirus disease 2019 (COVID-19) can occur through inhalation of fine droplets or aerosols containing infectious virus. The objective of this study was to identify situations, patient characteristics, environmental parameters, and aerosol-generating procedures (AGPs) associated with airborne severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus.METHODS: Air samples were collected near hospitalized COVID-19 patients and analyzed by RT-qPCR. Results were related to distance to the patient, most recent patient diagnostic PCR cycle threshold (Ct) value, room ventilation, and ongoing potential AGPs.RESULTS: In total, 310 air samples were collected; of these, 26 (8%) were positive for SARS-CoV-2. Of the 231 samples from patient rooms, 22 (10%) were positive for SARS-CoV-2. Positive air samples were associated with a low patient Ct value (OR, 5.0 for Ct <25 vs >25; P = .01; 95% CI: 1.18-29.5) and a shorter physical distance to the patient (OR, 2.0 for every meter closer to the patient; P = .05; 95% CI: 1.0-3.8). A mobile HEPA-filtration unit in the room decreased the proportion of positive samples (OR, .3; P = .02; 95% CI: .12-.98). No association was observed between SARS-CoV-2-positive air samples and mechanical ventilation, high-flow nasal cannula, nebulizer treatment, or noninvasive ventilation. An association was found with positive expiratory pressure training (P < .01) and a trend towards an association for airway manipulation, including bronchoscopies and in- and extubations.CONCLUSIONS: Our results show that major risk factors for airborne SARS-CoV-2 include short physical distance, high patient viral load, and poor room ventilation. AGPs, as traditionally defined, seem to be of secondary importance.
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