Alinity m, a Random-Access System, for Hepatitis B Virus DNA Quantification in Plasma and Whole Blood Collected on Dried Blood Spots.

The International Liver Association recommends the use of accurate and sensitive molecular methods for determination of hepatitis B virus (HBV) DNA levels in plasma or serum of chronic HBsAg carriers. The level of HBV replication represents the strongest predictive biomarker associated with disease progression and long-term outcome of chronic HBV infection. The purpose of this study was to evaluate the ability to the new Alinity m System to detect and quantify HBV DNA in plasma and whole blood collected on dried blood spots (DBS). Paired plasma and DBS samples from patients chronically infected with various HBV genotypes were tested in parallel for HBV DNA detection and quantification. There is a linear relationship between HBV DNA levels measured in plasma samples using the Alinity m HBV assay and the Xpert HBV viral load assay, used for comparison. A slight deviation (0.03 ± 0.31 log IU/mL) was observed within the quantitative range. In DBS, HBV DNA levels closely correlated with levels measured in plasma. All patients had detectable and quantifiable HBV DNA by DBS testing, except for one patient with a plasma HBV DNA level above 2,000 IU/mL. In conclusion, the newly developed real-time PCR-based assay Alinity m HBV assay can correctly detect HBV DNA in DBS, especially for patients with blood HBV DNA levels above 2,000 IU/mL, and also accurately quantify HBV DNA in plasma samples. IMPORTANCE Hepatitis B virus is one of the most prevalent blood-borne viruses affecting the liver and causing acute and chronic hepatitis. Only a small proportion of people with HBV infection are diagnosed. HBV DNA measurement is critical in clinical practice for the diagnosis and treatment decisions of patients requiring antiviral therapy. Dried blood spot (DBS) collection provides a simple, practical, and acceptable alternative to venous blood collection, especially in community settings. We have demonstrated high sensitivity and specificity for HBV DNA detection in DBS compared to plasma samples, especially when using clinically relevant cutoffs of 2,000 and 20,000 IU/mL. Results support the use of DBS in community-based settings.

Performance of a high-throughput, automated enzyme immunoassay for the detection of SARS-CoV-2 antigen, including in viral "variants of concern": Implications for clinical use.

Direct detection of SARS-CoV-2 viral antigens could replace RT-PCR, provided that its clinical performance is validated in different epidemiological settings. Here, we evaluated the performance of the VITROS Antigen test, an enzyme immunoassay detecting a SARS-CoV-2 antigen, in NPSs from 3 cohorts of patients. METHODS: Three cohorts including SARS-CoV-2 RNA-positive samples collected during the first and second wave of the French epidemic between March 2020 and February 2021 (including variant B.1.1.7/α and variant B.1.351/ß). RESULTS: Among the 1763 prospectively tested subjects, 8.2% (145/1763) were SARS-CoV-2 RNA-positive by RT-PCR. Using Ct ≤ 30 and Ct ≤ 35 as thresholds, the sensitivities of the antigen assay were 98.8% (93.6-100%) and 93.5% (87.0-97.3%), respectively. The overall specificity of the assay was 100% (1614/1614; 99.8-100%). In a retrospective cohort of subjects infected with variants of concern, 90.4% (47/52) of NPSs containing B. B.1.1.7/α (Ct ≤ 35) and 100% (7/7) of those containing B.1.351/ß were positive with the VITROS EIA SARS-CoV-2 Antigen test. CONCLUSION: The excellent performance of the EIA Antigen test reported here, including in patients infected with viral "variants of concern", support the use of high-throughput, EIA-based SARS-CoV-2 antigen assays as an alternative or complement to nucleic acid testing in order to scale-up laboratory screening and diagnostic capacities.

Performance of six rapid diagnostic tests for SARS-CoV-2 antigen detection and implications for practical use.

BACKGROUND: Direct detection of SARS-CoV-2 viral proteins in nasopharyngeal swabs using lateral flow immunoassays is a simple, fast and cheap approach to diagnose the infection. AIMS AND METHODS: The performance of 6 SARS-CoV-2 antigen rapid diagnostic tests has been assessed in 634 hospitalized patients or outpatients including 297 patients found to be positive for SARS-CoV-2 RNA by means of RT-PCR and 337 patients presumed to be SARS-CoV-2 RNA-negative. RESULTS: The specificity of SARS-CoV-2 RDTs was generally high (398.5%). One assay had a lower specificity of 93.2%. The overall sensitivity of the 6 RDTs was variable, from 32.3% to 61.7%. Sensitivity correlated with the delay of sampling after the onset of symptoms and the viral load estimated by the Ct value in RT-PCR. Four out of 6 RDTs tested achieved sensitivities 380% when clinical specimens were collected during the first 3 days following symptom onset or with a Ct value ≤25. CONCLUSIONS: The present study shows that SARS-CoV-2 antigen can be easily and reliably detected by RDTs. These tests are easy and rapid to perform. However, the specificity and sensitivity of COVID-19 antigen RDTs may widely vary across different tests and must therefore be carefully evaluated before releasing these assays for realworld applications.

Performance of 30 commercial SARS-CoV-2 serology assays in testing symptomatic COVID-19 patients.

We report evaluation of 30 assays' (17 rapid tests (RDTs) and 13 automated/manual ELISA/CLIA assay (IAs)) clinical performances with 2594 sera collected from symptomatic patients with positive SARS-CoV-2 rRT-PCR on a respiratory sample, and 1996 pre-epidemic serum samples expected to be negative. Only 4 RDT and 3 IAs fitted both specificity (> 98%) and sensitivity (> 90%) criteria according to French recommendations. Serology may offer valuable information during COVID-19 pandemic, but inconsistent performances observed among the 30 commercial assays evaluated, which underlines the importance of independent evaluation before clinical implementation.

[Improvement of the pre-examination phase of medical biology exams at the Henri Mondor University Hospitals: a pilot study]. / Une étude pilote pour l'amélioration de l'étape pré-analytique des examens de biologie médicale pris en charge au sein des hôpitaux universitaires Henri Mondor.

The medical and university department of biology pathology at Henri Mondor hospital in Créteil has been engaged in an NF EN ISO 15189 accreditation process since 2014. One of the elements of this process concerns the quality of handling of samples and their transportation to laboratories, including the implementation place requires fighting against pre-examination non-conformities, which are the source of many dysfunctions. The pre-examination group has implemented several actions in a targeted care service. Thanks to these, the rate of non-conformities has halved in 18 months. In parallel, a work project targeting student nurses on internship was born to follow up on the results of a statistical study carried out by the pre-examination group on non-conformities. The objective of the project was to include nursing students on internship in a full support course on good sampling practices and pre-analytical non-conformities. This was based on the realization of two knowledge quizzes (before and after training), theoretical training, and visits to several laboratories. This study lasted 10 months with the participation of 37 students. The results showed a marked improvement in knowledge of pre-analytics as well as total satisfaction of all students. Our approach has helped to better understand the needs of laboratories and demonstrates the usefulness of training students in good sampling practices in order to ensure better patient care as well as an improvement in their comfort and well-being.

Indeterminate genotypes of hepatitis C virus by the Abbott RealTime HCV Genotype II assay in Morocco. About eight cases resolved by a sequencing method.

The early detection and genotyping of the hepatitis C virus (HCV) are important in the management of this infection. The genotype is the major factor influencing treatment decisions. That's why it is necessary to use fast and accurate methods in its determination. This study reports, over a period of 3 years (from May 2012 to July 2015), the percentage of indeterminate genotypes by the Abbott RealTime HCV Genotype II test and their results using a sequencing technique. Of 309 samples of 309 patients tested, 11 were indeterminate (4.4%). There were three cases of cross-reactivity (1b/4 in one case, 2/5 in two cases) and a possible co-infection 1 + 4. Among those indeterminate genotypes, cross-reactivities and co-infections, ten samples were tested by sequencing. The results were for four of them a 1d subtype, five were a 2i subtype and one was a 2l subtype. These results support the thesis of complementarity between the two methods: genotyping for the detection of mixed reactions and sequencing for resolving indeterminate cases by genotyping.

Performance of rapid diagnostic tests for the detection of anti-HBs in various patient populations.

BACKGROUND: Rapid diagnostic tests (RDTs) represent an attractive alternative method to conventional diagnosis of hepatitis B virus (HBV) infection. OBJECTIVE: The aim of the present study was to evaluate the diagnostic performance of commercially available RDTs for the detection of anti-HBs in various patient populations. STUDY DESIGN: A total of 347 individuals, 198 positive and 149 negative for anti-HBs, were studied. RESULTS: The specificity of RDT detection of anti-HBs in serum was 98.0%, 96.0% and 97.3% with TOYO® HBsAb Test, QuickProfile™ HBsAb test and QuickProfile™ HBV-3 Panel test, respectively. The diagnostic sensitivity varied between 60.4% and 69.5%. The sensitivity of the three RDTs was markedly better when testing serum samples with an anti-HBs titer higher than 100IU/L, and reached 90% or more for an anti-HBs titer above 150IU/L. CONCLUSIONS: This performance was disappointing because the assays were not sensitive enough to detect low antibody titers. Thus, these tests require further improvement before they can be widely used in clinical practice.

Evaluation of a new random-access HBV DNA molecular assay: The VERIS HBV assay.

BACKGROUND: Detection and quantification of HBV DNA are essential to diagnose chronic HBV infection, monitor the virological response to treatment and the possible selection of resistant viruses in order to tailor therapy. The VERIS/MDx System HBV Assay is a random-access system that quantifies HBV DNA in clinical samples using unique single sample and reagent access during the workflow process without the need to reload other tests and delivers results within 1.2h following sampling. OBJECTIVE AND STUDY DESIGN: The goal of this study was to evaluate the analytical performance of the VERIS HBV assay for HBV DNA detection and quantification in clinical samples from a series of patients chronically infected with different HBV genotypes. RESULTS: The specificity of the VERIS HBV assay was estimated to be over 99.5%. The limit of detection (LOD) was estimated to be 4.1IU/mL (95%CI: 3.20-5.90IU/mL). Using an HBV linearity panel and controls (Seracare LifeScience), intra-assay and inter-assay coefficients of variation ranged from 0.12% to 3.64% and from 1.05% to 7.35%, respectively. The influence of the HBV genotype was evaluated from 120 clinical specimens containing HBV genotypes A to G tested in parallel with the VERIS HBV assay and the COBAS AmpliPrep/COBAS TaqMan HBV v2.0 assay. A linear relationship between the HBV DNA levels measured with both assays was found. A modest bias of HBV DNA levels was observed in the VERIS assay as compared to CAP/CTM HBV v2.0 in most of the samples tested (mean VERIS minus CAP/CTM difference: -0.395 log IU/mL). Overall, the VERIS HBV assay is well suited to monitoring clinical HBV DNA levels in infected patients according to current clinical practice guidelines.

Spectrum of adult Parvovirus B19 infection according to the underlying predisposing condition and proposals for clinical practice.

The virological diagnosis of Parvovirus B19 (PvB19) infection is currently based on sero-diagnosis, molecular methods or both, yet without clear recommendations. We retrospectively identified patients with polymerase chain reaction-positive PvB19 and/or positive serological assay between 2007 and 2013. Eighty-two adults with at least one diagnostic criterion of recent PvB19 infection (IgM antibodies, viral DNA in blood and/or in marrow) were included and classified into three homogeneous groups: 30 patients had no underlying predisposing condition, 25 a hereditary haemolytic anaemia, 27 an underlying immunodeficiency. The classical PvB19-related manifestations were less frequent in immunocompromised than in immunocompetent patients (arthromyalgia: 5 vs. 14; erythema: 4 vs. 17, respectively). Only 41·4% of patients with no underlying disease were anaemic. Bicytopenia and pancytopenia were observed mainly in immunocompromised patients. Classical pure red cell aplasia was observed in only 9 of the 27 marrow smears performed. Specific IgM were found in 93% of immunocompetent patients, whereas only 58% had detectable viral DNA in blood. IgM and DNA were present alone or together in all patients with hereditary haemolytic anaemia. In immunocompromised patients, the diagnosis was confirmed by marrow analysis in 91% of cases. We make some proposals based on this large series of PvB19-infected patients.

Performance of a new rapid test for the detection of hepatitis B surface antigen in various patient populations.

BACKGROUND: Rapid diagnostic tests (RDT) have been developed for the detection of hepatitis B surface antigen (HBsAg). They represent a promising alternative to enzyme immunoassays and a powerful tool for large-scale screening and diagnosis of HBV infection, especially in regions without easy access to serological and molecular testing. OBJECTIVES: The aims of the present study were to evaluate the characteristics and clinical performance of a new CE-marked HBsAg RDT, DRW-HBsAg v2.0 assay (Diagnostics for the Real World™, Ltd., USA), in various patient populations, including those chronically infected with HBV, patients with severe acute hepatitis of unknown origin and pregnant women with unknown HBV serological status at delivery. RESULTS: The lower limit of detection of the assay, evaluated in 21 clinical samples, ranged from 0.30 ± 0.07 to 0.97 ± 0.26 international units/mL (using Abbott Architect as a reference), depending on the HBV genotype. The assay tested positive in 100% of patients with chronic hepatitis B, 96.3% of HBsAg-positive acute hepatitis patients, and 95.2% of HBsAg-positive pregnant women. Its specificity was 98.8% in HBsAg-negative patients, 98.7% in HBsAg-negative patients with acute hepatitis of unknown origin and 97.8% in HBsAg-negative pregnant women. Amino acid substitutions in the HBsAg major hydrophilic region did not affect HBsAg detection by DRW-HBsAg v2.0. CONCLUSIONS: The new DRW-HBsAg v2.0 assay is a simple, rapid, easy-to-run and highly sensitive assay that can be used in both high- and low-risk populations for the diagnosis of HBsAg carriage. It appears to be a promising new tool for large-scale screening and diagnosis of HBV infection.

Targeting intratumoral B cells with rituximab in addition to CHOP in angioimmunoblastic T-cell lymphoma. A clinicobiological study of the GELA.

BACKGROUND: In angioimmunoblastic T-cell lymphoma, symptoms linked to B-lymphocyte activation are common, and variable numbers of CD20(+) large B-blasts, often infected by Epstein-Barr virus, are found in tumor tissues. We postulated that the disruption of putative B-T interactions and/or depletion of the Epstein-Barr virus reservoir by an anti-CD20 monoclonal antibody (rituximab) could improve the clinical outcome produced by conventional chemotherapy. DESIGN AND METHODS: Twenty-five newly diagnosed patients were treated, in a phase II study, with eight cycles of rituximab + chemotherapy (R-CHOP21). Tumor infiltration, B-blasts and Epstein-Barr virus status in tumor tissue and peripheral blood were fully characterized at diagnosis and were correlated with clinical outcome. RESULTS: A complete response rate of 44% (95% CI, 24% to 65%) was observed. With a median follow-up of 24 months, the 2-year progression-free survival rate was 42% (95% CI, 22% to 61%) and overall survival rate was 62% (95% CI, 40% to 78%). The presence of Epstein-Barr virus DNA in peripheral blood mononuclear cells (14/21 patients) correlated with Epstein-Barr virus score in lymph nodes (P<0.004) and the detection of circulating tumor cells (P=0.0019). Despite peripheral Epstein-Barr virus clearance after treatment, the viral load at diagnosis (>100 copy/µg DNA) was associated with shorter progression-free survival (P=0.06). CONCLUSIONS: We report here the results of the first clinical trial targeting both the neoplastic T cells and the microenvironment-associated CD20(+) B lymphocytes in angioimmunoblastic T-cell lymphoma, showing no clear benefit of adding rituximab to conventional chemotherapy. A strong relationship, not previously described, between circulating Epstein-Barr virus and circulating tumor cells is highlighted.

Successful treatment of aciclovir and foscarnet resistant Herpes simplex virus lesions with topical imiquimod in patients infected with human immunodeficiency virus type 1.

Aciclovir (ACV)-resistant Herpes simplex virus type-2 (HSV-2) infections are observed commonly in patients also infected with HIV-1. The use of foscarnet (FOS) in these patients may also lead to resistance. This situation can become a difficult therapeutic challenge. Four cases of patients infected with HIV and with mucocutaneous HSV-2 resistant to ACV and FOS are reported. These patients were treated successfully with topical 5% imiquimod. Imiquimod treatment also appeared to delay the time to recurrence of HSV lesions.

Efficacy of serologic marker screening in identifying hepatitis B virus infection in organ, tissue, and cell donors.

BACKGROUND & AIMS: Screens for serologic markers of hepatitis B virus (HBV) are used to prevent its transmission through transplantation. However, exclusion of noninfectious seropositive donors exacerbates graft shortages, and a residual risk of transmission by seronegative donors also exists. This study assessed the risk of HBV associated with different HBV serologic profiles in organ, tissue, and cell transplants, as well as the risk of HBV transmission from seronegative donors. METHODS: A total of 11,155 consecutive organ, tissue, and cell donors were screened for HBV serologic markers. HBV DNA was screened for in 626 donors with at least one HBV serologic marker and 1433 multiple organ donors who were HBV seronegative or had anti-hepatitis B surface antigens (HBs) antibodies alone. RESULTS: HBV DNA was detected in most HBs-antigen-positive donors, but HBV-DNA levels were considerably lower than in patients with chronic hepatitis B. HBV DNA also was found in organ and cornea donors without HBs antigen. The prevalence of HBV DNA in organ donors with no HBV serologic markers or isolated anti-HBs antibodies was 0.07% (95% confidence interval, 0.01%-0.40%). One HBV-DNA-positive organ donor with isolated anti-HBs antibodies had amino acid substitutions in the hepatitis B surface antigen sequence. CONCLUSIONS: The analytic sensitivity of commercial hepatitis B surface antigen assays and their ability to detect HBsAg mutants should be improved. The utility and cost-efficacy ratio of systematic HBV-DNA testing should be assessed with the goal of excluding HBV-DNA-positive donations not identified through serologic testing while retaining donations that carry no risk of HBV transmission.

Determinant roles of environmental contamination and noncompliance with standard precautions in the risk of hepatitis C virus transmission in a hemodialysis unit.

BACKGROUND: Nosocomial transmission is the second most frequent cause of hepatitis C virus (HCV) infection. A prospective observational study was conducted to assess the roles of environmental contamination and noncompliance with standard precautions in HCV cross-transmission in a hemodialysis unit. METHODS: Patients undergoing chronic hemodialysis in a French university hospital unit were systematically screened, revealing 2 sporadic cases of HCV transmission. An investigation was launched to determine whether the patients were infected in the hemodialysis unit and the possible roles of environmental contamination and noncompliance with standard precautions. We examined possible relationships among new cases of HCV infection, environmental contamination by blood and HCV RNA, and compliance with guidelines on hand hygiene and glove use. RESULTS: Two patients experienced seroconversion to HCV during the study period. Phylogenetic analyses showed that 1 of these patients was infected with the same strain as that affecting a chronically infected patient also treated in the unit. Of 740 environmental surface samples, 82 (11%) contained hemoglobin; 6 (7%) of those contained HCV RNA. The rate of compliance with hand hygiene was 37% (95% confidence interval, 35%-39%), and gloves were immediately removed after patient care in 33% (95% confidence interval, 29%-37%) of cases. A low ratio of nurses to patients and poor hand hygiene were independent predictors of the presence of hemoglobin on environmental surfaces. CONCLUSION: Blood-contaminated surfaces may be a source of HCV cross-transmission in a hemodialysis unit. Strict compliance with hand hygiene and glove use and strict organization of care procedures are needed to reduce the risk of HCV cross-transmission among patients undergoing hemodialysis.

Serological viral testing of cadaveric cornea donors.

BACKGROUND: Cornea graft recipients are exposed to viral transmission from the donor. Cadaveric donor serum is often of poor quality and frequently yields falsely positive results in serological assays that may result in the graft being needlessly discarded. OBJECTIVE: We examined the influence of the time of blood collection after death, and the macroscopic aspect of serum, on serological test results in cadaveric cornea donors. METHODS: Five hundred sixty-five consecutive cadaveric cornea donors were systematically tested for serological markers of human immunodeficiency virus type 1 and 2, human T-cell leukemia virus type 1, hepatitis B and hepatitis C viruses (HCV). We studied the influence of the macroscopic aspect of the donor's serum and the time of blood collection after death on the results of serological testing and on the subsequent decision to use or discard the graft. RESULTS: Twenty-one and a half percent of corneas were rejected on the basis of virological test results. We found significant relationships between the macroscopic aspect of serum at the time of testing and: (i) a positive, equivocal or discrepant result of immunoassays, for all markers except anti-HCV antibodies, (ii) non acceptance of cornea grafts, and (iii) the time of blood sampling after death. CONCLUSIONS: The macroscopic aspect of postmortem blood samples is the best predictor of the specificity of serological testing in cornea donors. Serological results should be interpreted with care when serum is macroscopically abnormal, and cadaveric donors should not be sampled more than 12 hr after death.

HIV and hepatitis C virus RNA in seronegative organ and tissue donors.

The objective of our study was to determine whether nucleic acid testing could detect HIV RNA or hepatitis C virus (HCV) RNA in a large series of seronegative organ and tissue donors, and whether this technique should be routinely used to improve viral safety of grafts. We studied 2236 organ donors, 636 tissue donors, and 177 cornea donors. We identified five HCV RNA-positive donors in 2119 HCV-seronegative organ donors, and one HCV RNA-positive donor in 631 HCV-seronegative tissue donors. No HIV-seronegative, HIV RNA-positive donor was identified. Our data suggest that routine nucleic acid testing of organ and tissue donors might increase viral safety in transplantation.

Infliximab therapy for rheumatic diseases in patients with chronic hepatitis B or C.

OBJECTIVE: To describe the safety of tumor necrosis factor-a blockade in 2 patients with inflammatory rheumatic disease with chronic hepatitis B and C. METHODS: We used infliximab therapy in 2 patients with chronic inflammatory joint disease and chronic hepatitis B or C. We describe the clinical and laboratory test data obtained in these patients during the first year of treatment. Disease activity, liver function tests, and HCV and HBV status were evaluated before infliximab therapy was started and were reevaluated before each infusion. Liver biopsy was performed in both patients before infliximab therapy. RESULT: After more than one year of treatment, no worsening in liver function or virological status was observed, while a dramatic clinical improvement of joint disease was observed in both patients. CONCLUSION: These cases suggest that infliximab therapy may be safe in some quiescent or controlled chronic HBV or HCV infection.

Hepatitis C virus-Epstein-Barr virus interaction in patients with AIDS.

Immortalization of B cells by Epstein-Barr virus (EBV) and their subsequent proliferation leads to B-cell non-Hodgkin's lymphoma in immunocompromised patients. The role of hepatitis C virus (HCV) in B-cell non-Hodgkin's lymphoma has recently been raised, and an interaction between HCV and EBV is supported by recent in vitro experiments. The aim of this study was to investigate in vivo interactions between HCV and EBV in patients with AIDS, i.e., patients exposed to the risk of EBV-related B-cell non-Hodgkin's lymphoma. A total of 135 patients were prospectively studied. Serological and molecular markers of HCV, EBV, and human immunodeficiency virus (HIV) infection were sought. All the patients harbored latent EBV infection, and 20% had detectable HCV RNA in serum. No significant relationship was found between HIV, HCV, and EBV viral load in peripheral blood mononuclear cells or plasma. There was no difference between anti-HCV-positive and -negative patients or between HCV RNA-positive and -negative patients with regard to the prevalence of EBV markers, especially EBV replication markers. The presence of EBV replication markers was not related to HCV RNA seropositivity or to HCV viral load. Five patients subsequently developed B-cell non-Hodgkin's lymphoma, none of whom had markers of EBV or HCV replication. These results argue against an in vivo interaction between HCV and EBV in patients with AIDS, and against a role of HCV infection in the occurrence of B-cell non-Hodgkin's lymphoma in these patients.

Prospective evaluation of risk factors of cutaneous drug reactions to sulfonamides in patients with AIDS.

BACKGROUND: Persons with HIV infection have increased rates of drug eruptions. OBJECTIVE: Our aim was to evaluate the risk factors of drug eruptions in response to sulfonamides in patients with AIDS, using a case-control analysis. METHODS: One hundred thirty-six patients who were hospitalized for pneumocystosis or toxoplasmosis were evaluated at the onset of treatment for various risk factors, which were then compared among patients with (48, 36%) and without (88, 64%) a drug eruption. RESULTS: In multivariate analysis, high CD8(+) cell count and age less than 36 years indicated a risk of drug eruption (respective odds ratios: 3.5 [95% CI 1.6-7.8], P =.002, and 2.1 [95% CI 1-4.6], P =.06). Markers of viral replication for HIV, Epstein-Barr virus, cytomegalovirus, human herpesvirus 6, and parvovirus B19, slow acetylation phenotype or genotype, and glutathione level were not associated with a risk. Administration of corticosteroids had no preventive effect. CONCLUSIONS: Our results challenge several current concepts regarding drug eruptions by discarding a strong association with glutathione deficiency, slow acetylation, or active viral infections and by showing no preventive effect of corticosteroids.