Immunity against Omicron from breakthrough infection could be a matter of timing

Nature ◽  
2022 ◽  
Author(s):  
Saima May Sidik
Keyword(s):  
Breakthrough Infection

scholarly journals Invasive infections with Purpureocillium lilacinum: clinical characteristics and outcome of 101 cases from FungiScope® and the literature

2021 ◽  
Author(s):  
Rosanne Sprute ◽  
Jon Salmanton-García ◽  
Ertan Sal ◽  
Xhorxha Malaj ◽  
Zdeněk Ráčil ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Organ Transplant ◽  
Solid Organ ◽  
Intrinsic Resistance ◽  
Breakthrough Infection ◽  
Purpureocillium Lilacinum ◽  
Invasive Infections ◽  
Oncological Diseases ◽  
Overall Mortality

Abstract Objectives To provide a basis for clinical management decisions in Purpureocillium lilacinum infection. Methods Unpublished cases of invasive P. lilacinum infection from the FungiScope® registry and all cases reported in the literature were analysed. Results We identified 101 cases with invasive P. lilacinum infection. Main predisposing factors were haematological and oncological diseases in 31 cases (30.7%), steroid treatment in 27 cases (26.7%), solid organ transplant in 26 cases (25.7%), and diabetes mellitus in 19 cases (18.8%). The most prevalent infection sites were skin (n = 37/101, 36.6%) and lungs (n = 26/101, 25.7%). Dissemination occurred in 22 cases (21.8%). Pain and fever were the most frequent symptoms (n = 40/101, 39.6% and n = 34/101, 33.7%, respectively). Diagnosis was established by culture in 98 cases (97.0%). P. lilacinum caused breakthrough infection in 10 patients (9.9%). Clinical isolates were frequently resistant to amphotericin B, whereas posaconazole and voriconazole showed good in vitro activity. Susceptibility to echinocandins varied considerably. Systemic antifungal treatment was administered in 90 patients (89.1%). Frequently employed antifungals were voriconazole in 51 (56.7%) and itraconazole in 26 patients (28.9%). Amphotericin B treatment was significantly associated with high mortality rates (n = 13/33, 39.4%, P = <0.001). Overall mortality was 21.8% (n = 22/101) and death was attributed to P. lilacinum infection in 45.5% (n = 10/22). Conclusions P. lilacinum mainly presents as soft-tissue, pulmonary or disseminated infection in immunocompromised patients. Owing to intrinsic resistance, accurate species identification and susceptibility testing are vital. Outcome is better in patients treated with triazoles compared with amphotericin B formulations.

scholarly journals Two cases of asymptomatic HBV “vaccine breakthrough” infection detected in blood donors screened for HBV DNA

2012 ◽  
Vol 196 (10) ◽  
pp. 651-652 ◽  
Author(s):  
Clive R Seed ◽  
Ngaire T Jones ◽  
Anne M Pickworth ◽  
Wendy R Graham
Keyword(s):  
Blood Donors ◽  
Hbv Dna ◽  
Breakthrough Infection ◽  
Hbv Vaccine

scholarly journals Clinical characteristics and outcomes of COVID-19 breakthrough infections among vaccinated patients with systemic autoimmune rheumatic diseases

2021 ◽  
Author(s):  
Claire Cook ◽  
Naomi Patel ◽  
Kristin D'Silva ◽  
Tiffany T-Y Hsu ◽  
Michael DiIorio ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Inflammatory Myopathy ◽  
Vaccination Status ◽  
Antibody Responses ◽  
Molecular Test ◽  
Breakthrough Infection ◽  
Autoimmune Rheumatic Diseases ◽  
Autoimmune Rheumatic Disease ◽  
Systemic Autoimmune Rheumatic Disease ◽  
The Us

Objective To describe the characteristics of COVID-19 vaccine breakthrough infections among systemic autoimmune rheumatic disease (SARD) patients. Methods We identified SARDs patients in a large healthcare system with COVID-19 vaccination at least 14 days prior to a positive SARS-CoV-2 molecular test. Details of the SARD diagnosis, vaccination status, and COVID-19 infection were extracted. Results Of 340 confirmed COVID-19 infections among SARDs patients between December 11th, 2020 (date of first COVID-19 vaccine approval in the US) and July 30th, 2021, we identified 16 breakthrough infections. Seven (44%) received the Pfizer-BioNtech vaccine, five (31%) received the Moderna vaccine, and four (25%) received the Janssen/Johnson & Johnson vaccine. The most common SARDs included rheumatoid arthritis (6, 38%), inflammatory myopathy (3, 19%), and systemic lupus erythematosus (3, 19%). Rituximab (5, 31%), glucocorticoids (4, 25%), and mycophenolate mofetil (4, 25%) were the most frequent treatments. Among the breakthrough infections, 15 (93%) were symptomatic, six (38%) were hospitalized, one (6%) required mechanical ventilation, and two (13%) died. Conclusions Symptomatic, including severe, breakthrough infections were observed in SARDs patients; many were on treatments associated with attenuated antibody responses to vaccination. Further studies are needed to determine the rate of breakthrough infection associated with SARD treatments and other features.

scholarly journals Chimeric spike mRNA vaccines protect against sarbecovirus challenge in mice

2021 ◽  
Author(s):  
David R. Martinez ◽  
Alexandra Schaefer ◽  
Sarah R. Leist ◽  
Gabriela De la Cruz ◽  
Ande West ◽  
...  
Keyword(s):  
South African ◽  
Neutralizing Antibodies ◽  
Lung Pathology ◽  
Breakthrough Infection ◽  
Neutralization Activity ◽  
Vaccination Strategies ◽  
Binding Domains ◽  
Limited Efficacy ◽  
Fold Reduction ◽  
Novel Strategy

AbstractThe emergence of SARS-CoV and SARS-CoV-2 in the 21st century highlights the need to develop universal vaccination strategies against the SARS-related Sarbecovirus subgenus. Using structure-guided chimeric spike designs and multiplexed immunizations, we demonstrate protection against SARS-CoV, SARS-CoV-2, and bat CoV (BtCoV) RsSHC014 challenge in highly vulnerable aged mice. Chimeric spike mRNAs containing N-terminal domain (NTD), and receptor binding domains (RBD) induced high levels of broadly protective neutralizing antibodies against three high-risk sarbecoviruses: SARS-CoV, RsSHC014, and WIV-1. In contrast, SARS-CoV-2 mRNA vaccination not only showed a 10 to >500-fold reduction in neutralizing titers against heterologous sarbecovirus strains, but SARS-CoV challenge in mice resulted in breakthrough infection including measurable lung pathology. Importantly, chimeric spike mRNA vaccines efficiently neutralized both the D614G and the South African B.1.351 variants of concern despite some reduction in neutralization activity. Thus, multiplexed-chimeric spikes may provide a novel strategy to prevent pandemic and SARS-like zoonotic coronavirus infections, while revealing the limited efficacy of SARS-CoV-2 spike vaccines against other sarbecoviruses.

scholarly journals Single Nucleotide Polymorphisms in IFN-γ Signaling Pathway Associated with Risk of Hepatitis B Virus Infection in Chinese Children

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Yang Zhuo ◽  
Yalan Yang ◽  
Mingjun Zhang ◽  
Ying Xu ◽  
Zhongping Chen ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Single Nucleotide Polymorphisms ◽  
Signaling Pathway ◽  
Public Health Problem ◽  
Hbv Infection ◽  
Nucleotide Polymorphisms ◽  
Breakthrough Infection ◽  
Single Nucleotide ◽  
B Virus

Hepatitis B virus (HBV) infection is a challenging public health problem in China and worldwide. Mother-to-child transmission is one of the main transmission routes of HBV in highly endemic regions. However, the mechanisms of HBV perinatal transmission in children have not been clearly defined. The aim of this study was to demonstrate the association between single-nucleotide polymorphisms (SNPs) in IFN-γ signaling pathway and HBV infection or breakthrough infection in children. Two hundred and seventy-four HBV-infected children defined as test positive for hepatitis B surface antigen (HBsAg) and 353 controls defined as negative for HBsAg in China were recruited from October 2013 to May 2015. SNPs in IFN-γ signaling pathway including IFNG, IFNGR1, IFNGR2, and IL12B were genotyped. Rs2234711 in IFNGR1 was significantly associated with HBV infection in children (OR = 0.641, 95% CI: 0.450–0.913). In addition, rs2234711 was also significantly associated with HBV breakthrough infection in children born to HBsAg-positive mothers (OR = 0.452, 95% CI: 0.205–0.998). Our study confirmed that genetic variants in IFN-γ signaling pathway have significant associations with HBV infection, especially with HBV breakthrough in children. This study provides insight into HBV infection in children and could be used to help design effective strategies for reducing immunoprophylaxis failure.

scholarly journals 2107. Azole Therapeutic Drug Monitoring (TDM) in a Multiracial Cohort with Varied Pharmacogenetics

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S713-S713
Author(s):  
Peijun Yvonne Zhou ◽  
Tze Peng Lim ◽  
Si Lin Sarah Tang ◽  
Yixin Liew ◽  
Nathalie Grace Sy. Chua ◽  
...  
Keyword(s):  
Hematological Malignancy ◽  
Organ Transplant ◽  
Drug Formulation ◽  
Therapeutic Drug ◽  
Solid Organ ◽  
Efficacy And Safety ◽  
Breakthrough Infection ◽  
Southeast Asians ◽  
Anti Fungal ◽  
Trough Levels

Abstract Background Voriconazole (VOR) and posaconazole (POS) exhibit wide pharmacokinetic variability. Various factors including race and genetic polymorphisms are at play and this may affect treatment response. We aim to evaluate the utility of VOR/POS TDM among Southeast Asians that are predominantly intermediate/poor VOR metabolizers. Methods All adults with VOR/POS TDM performed at our institution from 2015 to 2018 were included. We determined proportion of patients and doses required to achieve TDM targets [(2 – 5.5 mg/L (VOR) or ≥ 0.7 and ≥ 1.0 mg/L (POS prophylaxis and treatment respectively)], and correlate levels with treatment efficacy and safety. Results VOR/POS TDM was performed mostly among patients with hematological malignancy or solid-organ transplant (146/174, 83.9%). Less than half (32/70, 45.7%) of patients on VOR achieved target—18 (25.7%) were < 2 mg/L while 20 (28.5%) had levels > 5.5 mg/L. Doses required to achieve TDM target ranged from 1.9–11.4 mg/kg/day. Drug interactions, critically ill state and change in drug formulation were major causes of intra-patient variability. One-fifth (n = 14) experienced transaminitis; corresponding VOR trough levels were 0.5–> 7.5 mg/L. Neurotoxicity was also seen in 3 (4.3%) patients—all 3 had VOR trough ≥ 6.7 mg/L and saw symptom resolution upon dose reduction. There appears to be no association between the achievement of TDM targets and response rates. Majority (81/104, 77.9%) of patients on POS achieved TDM targets. Patients prescribed POS tablet were significantly more likely to attain targets compared with suspension 600 mg/day [19/26 (73.0%) vs. 27/62 (43.5%), P < 0.05] and 800 mg/day [17/26 (65.3%) vs. 4/16 (25.0%), P < 0.05)]. Of 23 with sub-therapeutic levels, 19 (82.6%) responded to dose increase and/or change in acid-reducing agents. Breakthrough infection occurred despite troughs ≥ 0.7 mg/L [5/42 (11.9%) vs. 2/40 (5.0%) when < 0.7 mg/L (P = 0.3)]. Treatment failure was observed in 2 patients (troughs > 1.0 mg/L). Conclusion VOR/POS TDM should be implemented in Southeast Asians due to significant unpredictability in dose exposure and potential to avoid need for switch to alternative anti-fungals due to intolerability. Higher POS trough cutoff may be required for effective anti-fungal prophylaxis. Disclosures All authors: No reported disclosures.

Evaluation of target attainment of oral posaconazole suspension in immunocompromised children

2019 ◽  
Vol 75 (3) ◽  
pp. 726-729
Author(s):  
Tony Lai ◽  
Jan-Willem Alffenaar ◽  
Alison Kesson ◽  
Sushil Bandodkar ◽  
Jason A Roberts
Keyword(s):  
Retrospective Study ◽  
Plasma Concentration ◽  
Plasma Concentrations ◽  
Invasive Fungal Disease ◽  
Target Attainment ◽  
Breakthrough Infection ◽  
H2 Antagonist ◽  
Starting Dose ◽  
Histamine H2 Antagonist ◽  
The Mean

Abstract Background Posaconazole is a broad-spectrum antifungal that is not licensed for use in children &lt;13 years of age. Despite this and by necessity, it is used extensively in paediatric hospitals for prophylaxis of invasive fungal disease. Objectives To determine whether initial prophylactic dosing recommendations attain a posaconazole plasma concentration of ≥700 ng/mL in immunocompromised children &lt;13 years of age. Patients and methods We performed a retrospective study of immunocompromised children &lt;13 years of age receiving posaconazole suspension prophylaxis at a starting dose of 5 mg/kg every 8 h for ≥7 days and who had a posaconazole concentration measured after ≥7 days. Posaconazole plasma concentrations and rate of breakthrough infection were recorded. Results A total of 70 patients were included with a median age of 5 years (range 3 months to 12 years). The mean posaconazole plasma concentration was 783.4 ng/mL (IQR 428.3–980 ng/mL) and the percentage of patients with a posaconazole plasma concentration ≥700ng/mL was 47.9%. Patients who were on a proton pump inhibitor, a histamine H2 antagonist or metoclopramide, had mucositis or were enterally fed had a lower posaconazole plasma concentration compared with patients without these co-administered drugs/mucositis/enteral feeding (542.3 versus 1069.8 ng/mL; P&lt;0.001). The breakthrough invasive fungal infection rate was 4.3% (3/70). Conclusions The studied 5 mg/kg posaconazole suspension every 8 h resulted in target concentrations in only 47.9% of patients and further studies looking at newer posaconazole formulations are needed.

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