Severe relapse of SARS-CoV-2 infection in a kidney transplant recipient with negative nasopharyngeal SARS-CoV-2 RT-PCR after rituximab.

Immunocompromised patients may experience prolonged viral shedding after their initial SARS-CoV-2 infection, however, symptomatic relapses after remission currently remain rare. We herein describe a severe COVID-19 relapse case of a kidney transplant recipient (KTR) following rituximab therapy, 3 months after a moderate COVID-19 infection, despite viral clearance after recovery of the first episode. During the clinical relapse, the diagnosis was established on a broncho-alveolar lavage specimen (BAL) by RT-PCR. The infectivity of the BAL sample was confirmed on a cell culture assay. Whole genome sequencing confirmed the presence of an identical stain (Clade 20A). However, it had an acquired G142D mutation and a larger deletion of 3-amino-acids at position 143-145. These mutations located within the N-terminal domain are suggested to play a role in viral entry. The diagnosis of a COVID-19 relapse should be considered in the setting of unexplained persistent fever and/or respiratory symptoms in KTRs (especially for those after rituximab therapy), even in patients with previous negative naso-pharyngeal SARS-CoV-2 PCR.

Analytical performances of simultaneous detection of HIV-1, HIV-2 and hepatitis C- specific antibodies and hepatitis B surface antigen (HBsAg) by multiplex immunochromatographic rapid test with serum samples: A cross-sectional study.

BACKGROUND: The HIV/HCV/HBsAg Triplex consists in manually performed, visually interpreted, lateral flow, immunochromatographic rapid diagnostic test simultaneously detecting in 15min human immunodeficiency virus (HIV)-1 and HIV-2 and hepatitis C virus (HCV)- specific antibodies (Ab) (IgG and IgM) and hepatitis B virus (HBV) surface antigen (HBsAg) in serum, plasma and whole blood. METHODS: A hospital-based cross-sectional study was conducted on a prospective panel of serum samples from adult inpatients included from routine analysis irrespectively of age and sex, including 250 sera positive for HIV-1-specific Ab, 250 for HCV-specific Ab, 250 for HBsAg and 250 sera negative for HIV- and HCV- Ab and HBsAg, and from 110 HIV-2-infected patients living in Ivory Coast, according to the results obtained by the reference chemiluminiscent microparticle immunoassay (CMIA) Abbott Architect i2000SR analyzer (Abbott Diagnostic, Chicago, IL, USA). Among HCV-seropositive sera, 187 were positive for HCV RNA (chronic infection), whereas 63 were negative (resolved infection), respectively. Serum samples were further tested blindly by HIV/HCV/HBsAg Triplex according to manufacturers' recommendations. RESULTS: HIV/HCV/HBsAg Triplex showed very high sensitivity and specificity, as well as excellent concordance with CMIA Abbott results, as shown in the Table. Lower sensitivity was observed only in individuals who had cleared their HCV infection (presence of HCV-specific Ab in absence of HCV RNA). The mean lower limit of HBsAg detection was 2.38±0.63 IU/ml. Erythrocytes-spiked serum samples gave similar results than serum samples. CONCLUSIONS: Advantages of HIV/HCV/HBsAg Triplex for HIV-1, HIV-2, HCV and HBV include the requirement for less overall specimen volume, fewer finger-sticks if capillary whole blood is used, cost savings through lower cost per virus tested, improved patient flow with results for multiple viruses available at the same time, overall service delivery efficiencies with less time required per infected patient; and patient benefits from fewer visits and lower cost associated with each clinic attendance. The screening of chronic HIV, HCV and HBV by multiplex HIV-1/HIV-2/HCV/HBsAg Triplex may improve the "cascade of screening" and quite possibly linkage-to-care with reduced cost.

Accuracy of MIC determination for Streptococcus pneumoniae using the Sirscan2000automatic MIC determination system.

The Sirscan2000automatic MIC determination (SIR-MD) system is a new system for MIC determination based on the automatic detection of growth of bacteria spotted onto agar medium using a camera scan. To evaluate its accuracy, 3608 Streptococcus pneumoniae clinical isolates yielding 18,165 MICs were tested in parallel with the SIR-MD and a standard interpretive antibiogram procedure. The overall percent agreement between the 2 methods within 1 log(2) dilution was 86.9%. After exclusion of the 11.8% noninterpretable results, errors in the deduction of susceptibilities were very major in 0.03%, major in 0.2%, and minor in 1.3%.

The effect of assay formats on the estimation of melanocortin agonist affinity and efficacy using the operation model of agonism.

Melanocortin MC(3) and MC(4) receptor agonists have pharmaceutical benefit in the regulation of energy homeostasis. These agonists are defined by two parameters, their potency and their efficacy. However, these parameters are dependent upon the system in which they are measured. Herein, we have used the operational model of agonism to define agonist properties. We have used two different assay formats, cAMP accumulation and a cAMP response element (CRE)-beta-lactamase gene reporter to measure melanocortin MC(3) and MC(4) receptor agonist profiles, in the presence and absence of the irreversible receptor inactivator N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) and fitted these data to the operational model of agonism to define agonist affinity and efficacy. Data generated using the cAMP accumulation assay fitted well to assumptions made in the operational model and provided estimations of affinity and efficacy in line with those expected. However, data generated in the gene reporter assays showed over a 100-fold increase in agonist affinity compared with cAMP data and unexpectedly low values for efficacy. These data show that the operational model can be used to determine the efficacies of melanocortin agonists which appear as full agonists in cAMP assays, but that this is not the case for gene reporter assays in which agonist efficacies cannot be distinguished.

Reduction of antibiotic use in the community reduces the rate of colonization with penicillin G-nonsusceptible Streptococcus pneumoniae.

BACKGROUND: There is a lack of evidence documenting the impact of optimized antibiotic use on the rates of colonization with penicillin G-nonsusceptible Streptococcus pneumoniae (PNSP) in children. This study evaluates the effect of community-based intervention strategies on the prevalence of pnsp colonization. METHODS: A controlled, population-based pharmacoepidemiological trial was conducted from January through May 2000. Three French geographic areas were selected on the basis of demographic similarities. Two intervention strategies were implemented: (1) reduced antibiotic use, which was achieved by not prescribing antibiotics for presumed viral respiratory tract infections (the prescription-reduction group); and (2) better adaptation of dose and duration (the dose/duration group). A control group received no intervention. The target population was children aged 3-6 years who were attending kindergarten. Oropharyngeal pneumococcus colonization and antibiotic use were monitored throughout the 5-month study. RESULTS: The prescription-reduction, dose/duration, and control groups included 601, 483, and 405 children, respectively. The interventions induced significantly larger decreases in antibiotic use in the prescription-reduction group (-18.8%) and dose/duration group (-17.1%) than in the control group (-3.8%), and the rates of PNSP colonization were initially similar for the 3 groups (52.5%, 55.1%, and 50.0%, respectively). At the end of the 5-month study, the rates of PNSP colonization were 34.5% for the prescription-reduction group (P=.05) and 44.3% for the dose/duration group (P=.8), compared with 46.2% for the control group. CONCLUSIONS: Intensive educational strategies aimed at optimizing antibiotic use can significantly reduce the rate of PNSP colonization in areas with high resistance rates.

Amoxicillin-clavulanate therapy increases childhood nasal colonization by methicillin-susceptible Staphylococcus aureus strains producing high levels of penicillinase.

We examined factors associated with penicillinase production by nasal carriage Staphylococcus aureus strains in 648 children aged 3 to 6 years attending 20 randomly sampled playschools. The children were prospectively monitored for drug use and medical events for 6 months and were then screened for S. aureus carriage. Isolates were tested for their susceptibility to penicillin G and methicillin, and penicillinase production by methicillin-susceptible, penicillin-resistant strains was quantified. S. aureus was isolated from 166 children (25.6%). Exposure to amoxicillin-clavulanate during the previous 3 months was associated with higher penicillinase production by penicillin-resistant, methicillin-susceptible strains (odds ratio, 3.6; P = 0.03). These results suggest that use of the amoxicillin-clavulanate combination could induce a herd selection process of S. aureus strains producing higher levels of penicillinase.

The complete genome sequence of Mycobacterium bovis.

Mycobacterium bovis is the causative agent of tuberculosis in a range of animal species and man, with worldwide annual losses to agriculture of $3 billion. The human burden of tuberculosis caused by the bovine tubercle bacillus is still largely unknown. M. bovis was also the progenitor for the M. bovis bacillus Calmette-Guérin vaccine strain, the most widely used human vaccine. Here we describe the 4,345,492-bp genome sequence of M. bovis AF2122/97 and its comparison with the genomes of Mycobacterium tuberculosis and Mycobacterium leprae. Strikingly, the genome sequence of M. bovis is >99.95% identical to that of M. tuberculosis, but deletion of genetic information has led to a reduced genome size. Comparison with M. leprae reveals a number of common gene losses, suggesting the removal of functional redundancy. Cell wall components and secreted proteins show the greatest variation, indicating their potential role in host-bacillus interactions or immune evasion. Furthermore, there are no genes unique to M. bovis, implying that differential gene expression may be the key to the host tropisms of human and bovine bacilli. The genome sequence therefore offers major insight on the evolution, host preference, and pathobiology of M. bovis.