Last data update: May 13, 2024. (Total: 46773 publications since 2009)
Records 1-9 (of 9 Records) |
Query Trace: Harcourt Brian H[original query] |
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Exploring inactivation of SARS-CoV-2, MERS-CoV, Ebola, Lassa, and Nipah viruses on N95 and KN95 respirator material using photoactivated methylene blue to enable reuse.
Scholte Florine EM , Kabra Kareem B , Tritsch Sarah R , Montgomery Joel M , Spiropoulou Christina F , Mores Christopher N , Harcourt Brian H . Am J Infect Control 2022 50 (8) 863-870 The photoactivated dye methylene blue inactivates many human pathogens. The technique inactivates SARS-CoV-2, Ebola, Lassa and Nipah viruses on respirators. Decontamination of N95 and KN95 respirators allows safe limited reuse. Methylene blue can be used for pretreatment and decontamination of respirators. Pretreatment of PPE could allow for real-time virus inactivation. The COVID-19 pandemic resulted in a worldwide shortage of N95 respirators, prompting the development of decontamination methods to enable limited reuse. Countries lacking reliable supply chains would also benefit from the ability to safely reuse PPE. Methylene blue (MB) is a light-activated dye with demonstrated antimicrobial activity used to sterilize blood plasma. Decontamination of respirators using photoactivated MB requires no specialized equipment, making it attractive for use in the field during outbreaks. We examined decontamination of N95 and KN95 respirators using photoactivated MB and 3 variants of SARS-CoV-2, the virus that causes COVID-19; and 4 World Health Organization priority pathogens: Ebola virus, Middle East respiratory syndrome coronavirus, Nipah virus, and Lassa virus. Virus inactivation by pretreating respirator material was also tested. Photoactivated MB inactivated all tested viruses on respirator material, albeit with varying efficiency. Virus applied to respirator material pre-treated with MB was also inactivated, thus MB pretreatment may potentially protect respirator wearers from virus exposure in real-time. These results demonstrate that photoactivated MB represents a cost-effective, rapid, and widely deployable method to decontaminate N95 respirators for reuse during supply shortages. |
Of masks and methylene blue-The use of methylene blue photochemical treatment to decontaminate surgical masks contaminated with a tenacious small nonenveloped norovirus.
Wielick Constance , Fries Allyson , Dams Lorène , Razafimahefa Ravo M , Heyne Belinda , Harcourt Brian H , Lendvay Thomas S , Willaert Jean-François , de Jaeger Simon , Haubruge Eric , Thiry Etienne , Ludwig-Begall Louisa F . Am J Infect Control 2022 50 (8) 871-877 PPE reuse necessitates reliable respiratory and oral human pathogen decontamination. Equitable decontamination technologies must be available in low-resource settings. Methylene blue photochemical treatment decontaminates noroviruses on surgical masks. Norovirus inactivation predicts inactivation of any less resistant viral contaminant. Role of low-cost – low-tech photochemical decontamination in pandemic preparedness. In the context of the SARS-CoV-2 pandemic, reuse of personal protective equipment, specifically that of medical face coverings, has been recommended. The reuse of these typically single-use only items necessitates procedures to inactivate contaminating human respiratory and gastrointestinal pathogens. We previously demonstrated decontamination of surgical masks and respirators contaminated with infectious SARS-CoV-2 and various animal coronaviruses via low concentration- and short exposure methylene blue photochemical treatment (10 µM methylene blue, 30 minutes of 12,500-lux red light or 50,000 lux white light exposure). Here, we describe the adaptation of this protocol to the decontamination of a more resistant, non-enveloped gastrointestinal virus and demonstrate efficient photodynamic inactivation of murine norovirus, a human norovirus surrogate. Methylene blue photochemical treatment (100 µM methylene blue, 30 minutes of 12,500-lux red light exposure) of murine norovirus-contaminated masks reduced infectious viral titers by over four orders of magnitude on surgical mask surfaces. Inactivation of a norovirus, the most difficult to inactivate of the respiratory and gastrointestinal human viruses, can predict the inactivation of any less resistant viral mask contaminant. The protocol developed here thus solidifies the position of methylene blue photochemical decontamination as an important tool in the package of practical pandemic preparedness. |
Addressing personal protective equipment (PPE) decontamination: Methylene blue and light inactivates severe acute respiratory coronavirus virus 2 (SARS-CoV-2) on N95 respirators and medical masks with maintenance of integrity and fit.
Lendvay TS , Chen J , Harcourt BH , Scholte FE , Lin YL , Kilinc-Balci FS , Lamb MM , Homdayjanakul K , Cui Y , Price A , Heyne B , Sahni J , Kabra KB , Lin YC , Evans D , Mores CN , Page K , Chu LF , Haubruge E , Thiry E , Ludwig-Begall LF , Wielick C , Clark T , Wagner T , Timm E , Gallagher T , Faris P , Macia N , Mackie CJ , Simmons SM , Reader S , Malott R , Hope K , Davies JM , Tritsch SR , Dams L , Nauwynck H , Willaert JF , De Jaeger S , Liao L , Zhao M , Laperre J , Jolois O , Smit SJ , Patel AN , Mayo M , Parker R , Molloy-Simard V , Lemyre JL , Chu S , Conly JM , Chu MC . Infect Control Hosp Epidemiol 2021 43 (7) 1-83 OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has resulted in shortages of personal protective equipment (PPE) underscoring the urgent need for simple, efficient, and inexpensive methods to decontaminate SARS-CoV-2-exposed masks and respirators. We hypothesized that methylene blue (MB) photochemical treatment, which has various clinical applications, could decontaminate PPE contaminated with coronavirus. DESIGN: The two arms of the study included: 1) PPE inoculation with coronaviruses followed by MB with light (MBL) decontamination treatment, and 2) PPE treatment with MBL for 5 cycles of decontamination (5CD) to determine maintenance of PPE performance. METHODS: MBL treatment was used to inactivate coronaviruses on three N95 filtering facepiece respirator (FFR) and two medical mask (MM) models. We inoculated FFR and MM materials with three coronaviruses, including SARS-CoV-2, and treated with 10 µM MB and exposed to 50,000 lux of white light or 12,500 lux of red light for 30 minutes. In parallel, integrity was assessed after 5CD using multiple US and international test methods and compared to the FDA-authorized vaporized hydrogen peroxide plus ozone (VHP+O3) decontamination method. RESULTS: Overall, MBL robustly and consistently inactivated all three coronaviruses with 99.8 - to >99.9% virus inactivation across all FFRs and MMs tested. FFR and MM integrity was maintained after 5 cycles of MBL treatment, whereas one FFR model failed after 5 cycles of VHP+O3. CONCLUSIONS: MBL treatment decontaminated respirators and masks by inactivating three tested coronaviruses without compromising integrity through 5CD. MBL decontamination is effective, low-cost and does not require specialized equipment, making it applicable in all-resource settings. |
Lessons Learned from a COVID-19 Biohazard Spill During Swabbing at a Quarantine Facility.
Mayer O , Pfundt T , Fortenberry GZ , Harcourt BH , Bower WA . Disaster Med Public Health Prep 2020 16 (3) 1-9 The need for increased testing for SARS-CoV-2, the virus that causes COVID-19, has resulted in an increase of testing facilities outside of traditional clinical settings and sample handling by individuals without appropriate biohazard and biocontainment training. During the repatriation and quarantine of passengers from the Grand Princess cruise ship at a U.S. military base, biocontainment of a potentially infectious sample from a passenger was compromised. This paper describes the steps taken to contain the spill, decontaminate the area, and discusses the needs for adequate training in a biohazard response. |
Population-Based Surveillance of Neisseria meningitidis Antimicrobial Resistance in the United States.
Harcourt BH , Anderson RD , Wu HM , Cohn AC , MacNeil JR , Taylor TH , Wang X , Clark TA , Messonnier NE , Mayer LW . Open Forum Infect Dis 2015 2 (3) ofv117 BACKGROUND: Antimicrobial treatment and chemoprophylaxis of patients and their close contacts is critical to reduce the morbidity and mortality and prevent secondary cases of meningococcal disease. Through the 1990's, the prevalence of antimicrobial resistance to commonly used antimicrobials among Neisseria meningitidis was low in the United States. Susceptibility testing was performed to ascertain whether the proportions of isolates with reduced susceptibility to antimicrobials commonly used for N meningitidis have increased since 2004 in the United States. METHODS: Antimicrobial susceptibility testing was performed by broth microdilution on 466 isolates of N meningitidis collected in 2004, 2008, 2010, and 2011 from an active, population-based surveillance system for susceptibility to ceftriaxone, ciprofloxacin, penicillin G, rifampin, and azithromycin. The molecular mechanism of reduced susceptibility was investigated for isolates with intermediate or resistant phenotypes. RESULTS: All isolates were susceptible to ceftriaxone and azithromycin, 10.3% were penicillin G intermediate (range, 8% in 2008-16.7% in 2010), and <1% were ciprofloxacin, rifampin, or penicillin G resistant. Of the penicillin G intermediate or resistant isolates, 63% contained mutations in the penA gene associated with reduced susceptibility to penicillin G. All ciprofloxacin-resistant isolates contained mutations in the gyrA gene associated with reduced susceptibility. CONCLUSIONS:. Resistance of N meningitidis to antimicrobials used for empirical treatment of meningitis in the United States has not been detected, and resistance to penicillin G and chemoprophylaxis agents remains uncommon. Therapeutic agent recommendations remain valid. Although periodic surveillance is warranted to monitor trends in susceptibility, routine clinical testing may be of little use. |
Accuracy of real-time PCR, Gram stain and culture for Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae meningitis diagnosis.
Wu HM , Cordeiro SM , Harcourt BH , Carvalho M , Azevedo J , Oliveira TQ , Leite MC , Salgado K , Reis MG , Plikaytis BD , Clark TA , Mayer LW , Ko AI , Martin SW , Reis JN . BMC Infect Dis 2013 13 26 BACKGROUND: Although cerebrospinal fluid (CSF) culture is the diagnostic reference standard for bacterial meningitis, its sensitivity is limited, particularly when antibiotics were previously administered. CSF Gram staining and real-time PCR are theoretically less affected by antibiotics; however, it is difficult to evaluate these tests with an imperfect reference standard. METHODS AND FINDINGS: CSF from patients with suspected meningitis from Salvador, Brazil were tested with culture, Gram stain, and real-time PCR using S. pneumoniae, N. meningitidis, and H. influenzae specific primers and probes. An antibiotic detection disk bioassay was used to test for the presence of antibiotic activity in CSF. The diagnostic accuracy of tests were evaluated using multiple methods, including direct evaluation of Gram stain and real-time PCR against CSF culture, evaluation of real-time PCR against a composite reference standard, and latent class analysis modeling to evaluate all three tests simultaneously. RESULTS: Among 451 CSF specimens, 80 (17.7%) had culture isolation of one of the three pathogens (40 S. pneumoniae, 36 N. meningitidis, and 4 H. influenzae), and 113 (25.1%) were real-time PCR positive (51 S. pneumoniae, 57 N. meningitidis, and 5 H. influenzae). Compared to culture, real-time PCR sensitivity and specificity were 95.0% and 90.0%, respectively. In a latent class analysis model, the sensitivity and specificity estimates were: culture, 81.3% and 99.7%; Gram stain, 98.2% and 98.7%; and real-time PCR, 95.7% and 94.3%, respectively. Gram stain and real-time PCR sensitivity did not change significantly when there was antibiotic activity in the CSF. CONCLUSION: Real-time PCR and Gram stain were highly accurate in diagnosing meningitis caused by S. pneumoniae, N. meningitidis, and H. influenzae, though there were few cases of H. influenzae. Furthermore, real-time PCR and Gram staining were less affected by antibiotic presence and might be useful when antibiotics were previously administered. Gram staining, which is inexpensive and commonly available, should be encouraged in all clinical settings. |
Genomic basis of a polyagglutinating isolate of Neisseria meningitidis.
Rishishwar L , Katz LS , Sharma NV , Rowe L , Frace M , Thomas JD , Harcourt BH , Mayer LW , Jordan IK . J Bacteriol 2012 194 (20) 5649-56 Containment strategies for outbreaks of invasive Neisseria meningitidis disease are informed by serogroup assays that characterize the polysaccharide capsule. We sought to uncover the genomic basis of conflicting serogroup assay results for an isolate (M16917) from a patient with acute meningococcal disease. To this end, we characterized the complete genome sequence of the M16917 isolate and performed a variety of comparative sequence analyses against N. meningitidis reference genome sequences of known serogroups. Multilocus sequence typing and whole-genome sequence comparison revealed that M16917 is a member of the ST-11 sequence group, which is most often associated with serogroup C. However, sequence similarity comparisons and phylogenetic analysis showed that the serogroup diagnostic capsule polymerase gene (synD) of M16917 belongs to serogroup B. These results suggest that a capsule-switching event occurred based on homologous recombination at or around the capsule locus of M16917. Detailed analysis of this locus uncovered the locations of recombination breakpoints in the M16917 genome sequence, which led to the introduction of an approximately 2-kb serogroup B sequence cassette into the serogroup C genomic background. Since there is no currently available vaccine for serogroup B strains of N. meningitidis, this kind capsule-switching event could have public health relevance as a vaccine escape mutant. |
Using single-nucleotide polymorphisms to discriminate disease-associated from carried genomes of Neisseria meningitidis.
Katz LS , Sharma NV , Harcourt BH , Thomas JD , Wang X , Mayer LW , Jordan IK . J Bacteriol 2011 193 (14) 3633-41 Neisseria meningitidis is one of the main agents of bacterial meningitis, causing substantial morbidity and mortality worldwide. However, most of the time N. meningitidis is carried as a commensal not associated with invasive disease. The genomic basis of the difference between disease-associated and carried isolates of N. meningitidis may provide critical insight into mechanisms of virulence, yet it has remained elusive. Here, we have taken a comparative genomics approach to interrogate the difference between disease-associated and carried isolates of N. meningitidis at the level of individual nucleotide variations (i.e., single nucleotide polymorphisms [SNPs]). We aligned complete genome sequences of 8 disease-associated and 4 carried isolates of N. meningitidis to search for SNPs that show mutually exclusive patterns of variation between the two groups. We found 63 SNPs that distinguish the 8 disease-associated genomes from the 4 carried genomes of N. meningitidis, which is far more than can be expected by chance alone given the level of nucleotide variation among the genomes. The putative list of SNPs that discriminate between disease-associated and carriage genomes may be expected to change with increased sampling or changes in the identities of the isolates being compared. Nevertheless, we show that these discriminating SNPs are more likely to reflect phenotypic differences than shared evolutionary history. Discriminating SNPs were mapped to genes, and the functions of the genes were evaluated for possible connections to virulence mechanisms. A number of overrepresented functional categories related to virulence were uncovered among SNP-associated genes, including genes related to the category "symbiosis, encompassing mutualism through parasitism." |
Detection of bacterial pathogens in Mongolia meningitis surveillance with a new real-time PCR assay to detect Haemophilus influenzae.
Wang X , Mair R , Hatcher C , Theodore MJ , Edmond K , Wu HM , Harcourt BH , Carvalho MD , Pimenta F , Nymadawa P , Altantsetseg D , Kirsch M , Satola SW , Cohn A , Messonnier NE , Mayer LW . Int J Med Microbiol 2011 301 (4) 303-9 Since the implementation of Haemophilus influenzae (Hi) serotype b vaccine, other serotypes and non-typeable strains have taken on greater importance as a cause of Hi diseases. A rapid and accurate method is needed to detect all Hi regardless of the encapsulation status. We developed 2 real-time PCR (rt-PCR) assays to detect specific regions of the protein D gene (hpd). Both hpd assays are very specific and sensitive for detection of Hi. Of the 63 non-Hi isolates representing 21 bacterial species, none was detected by the hpd #1 assay, and only one of 2 H. aphrophilus isolates was detected by the hpd #3 assay. The hpd #1 and #3 assays detected 97% (229/237) and 99% (234/237) of Hi isolates, respectively, and were superior for detection of both typeable and non-typeable Hi isolates, as compared to previously developed rt-PCR targeting ompP2 or bexA. The diagnostic sensitivity and specificity of these rt-PCR assays were assessed on cerebrospinal fluid specimens collected as part of meningitis surveillance in Ulaanbaatar, Mongolia. The etiology (Neisseria meningitidis, Hi, and Streptococcus pneumoniae) of 111 suspected meningitis cases was determined by conventional methods (culture and latex agglutination), previously developed rt-PCR assays, and the new hpd assays. The rt-PCR assays were more sensitive for detection of meningitis pathogens than other classical methods and improved detection from 50% (56/111) to 75% (83/111). The hpd #3 assay identified a non-b Hi that was missed by the bexA assay and other methods. A sensitive rt-PCR assay to detect both typeable and non-typeable Hi is a useful tool for improving Hi disease surveillance especially after Hib vaccine introduction. |
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