This work is a contribution to the development and implementation of non-thermal plasma technology for decontamination in the perspective of nosocomial and chronic wound innovative therapies. Multi jets devices based on Plasma Gun® technology in static and scanning operation modes and bacterial lawns inoculated with resistant and non-resistant bacterial strains were designed and used. A pilot toxicity study exploring plasma treatment of wound bearing patients, performed with a low voltage plasma applicator, is documented as a first step for the translation of in vitro experiments to clinical care. Bacterial inactivation was demonstrated for Staphylococcus aureus, Pseudomonas aeruginosa and drug resistant S. aureus, P. aeruginosa and Escherichia Coli strains collected from patient wounds at Orleans (France) hospital. A few square centimeter large contaminated samples were inactivated following a single plasma exposure as short as one minute. Samples inoculated with a single but also a mix of three resistant pathogens were successfully inactivated not only right after their contamination but for mature lawns as well. Similar bactericidal action was demonstrated for antibiotic-resistant and non-resistant P. aeruginosa. The time exposure dependent increase of the inhibition spots, following multi jets exposure, is discussed as either the accumulation of reactive species or the likely combinatory action of both the reactive species and transient electric field delivery on inoculated samples.
The emergence of Omicron sublineages impacts the therapeutic efficacy of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibodies (mAbs). Here, we evaluate neutralization and antibody-dependent cellular cytotoxicity (ADCC) activities of 6 therapeutic mAbs against Delta, BA.2, BA.4, and BA.5. The Omicron subvariants escape most antibodies but remain sensitive to bebtelovimab and cilgavimab. Consistent with their shared spike sequence, BA.4 and BA.5 display identical neutralization profiles. Sotrovimab is the most efficient at eliciting ADCC. We also analyze 121 sera from 40 immunocompromised individuals up to 6 months after infusion of Ronapreve (imdevimab + casirivimab) or Evusheld (cilgavimab + tixagevimab). Sera from Ronapreve-treated individuals do not neutralize Omicron subvariants. Evusheld-treated individuals neutralize BA.2 and BA.5, but titers are reduced. A longitudinal evaluation of sera from Evusheld-treated patients reveals a slow decay of mAb levels and neutralization, which is faster against BA.5. Our data shed light on antiviral activities of therapeutic mAbs and the duration of effectiveness of Evusheld pre-exposure prophylaxis.
Dolutegravir is a powerful, well-tolerated integrase inhibitor with a high genetic barrier to resistance and may thus constitute the backbone of lightened regimens. This was a monocentric, retrospective study. HIV-1-infected patients receiving dolutegravir as monotherapy (mDGV) or dual therapy (dDGV) were systematically identified. The primary outcome was the proportion of patients who maintained undetectable (<50 copies/mL) plasma HIV RNA [plasma viral load (PVL)]. We identified 21 patients on mDGV (50 mg/day) and 31 on dDGV (50 or 100 mg/day, with atazanavir ± ritonavir, n = 12; rilpivirine, n = 11; maraviroc, n = 3; lamivudine, n = 3; darunavir/ritonavir, n = 1; or abacavir, n = 1). All of the patients were treatment experienced and 48% had experienced at least one virological failure. The baseline characteristics were as follows (for the mDGV/dDGV patients, respectively): 5%/29% had a history of AIDS; the median (IQR) highest PVL was 4.5 (4.3–5.5)/5.3 (4.7–5.6) log copies/mL; the median (IQR) nadir CD4+ count was 310 (280–468)/199 (134–281) cells/mm3; 100% had undetectable PVL before the mDGV for a median (IQR) duration of 5.9 (3.5–9.9) years/81% had undetectable PVL before the dDGV for a median (IQR) duration of 3.7 (1.4–8.3) years; and the median (IQR) HIV DNA level was 2.7 (2.1–3.1)/2.9 (2.7–3) log copies/106 PBMCs. At the last follow-up visit, 100% and 97% of patients showed undetectable PVL following mDGV and dDGV, respectively [median (IQR) follow-up of 32 (29–45) and 50 (30–74) weeks, respectively]. In our experience, dolutegravir-based lightened regimens provided a high proportion of viral suppression, even in highly treatment-experienced patients.
Schools are a source of epidemic seasonal dissemination-in particular gastroenteritis among children and the general population. We assessed the impact of an alcohol-based sanitizer on gastroenteritis and its subsequent consequences.A study was conducted in 2 primary schools over a 17-week period, before and throughout the seasonal gastroenteritis period. The intervention, under strict teacher supervision and in a realistic and long lasting manner, consisted of 1 school rubbing an alcohol-based sanitizer into the hands of the school children. The primary outcome was the proportion of children without any occurrence of gastroenteritis during the study period both in the treated group and the control group, which were 2 separate schools. A Cox proportional hazards model was used to assess the hazard ratio. Secondary outcomes were the number of gastroenteritis episodes, doctor appointments, absenteeism, and working days lost by a parent.Four thousand six hundred fifty-four weekly questionnaires were collected. One hundred fifty-five children presented with at least 1 occurrence of gastroenteritis during the study period: 64 of 259 in the treatment group and 91 of 217 in the control group (χ2 = 16.4, P < 0.0001). The instantaneous risk of primary infection, at any time of the study, for children receiving the treatment was multiplied by 0.52 (95% CI: [0.37,0.71]) compared with children not receiving the treatment. The average number of gastroenteritis episodes was 0.31 in the treatment group and 0.53 in the control group (P < 0.001).Systematic and controlled use of alcohol-based sanitizers during the epidemic season could significantly reduce the incidence of gastroenteritis in primary school children.
Abstract Background Raltegravir (RAL) has favorable tolerability and safety profile, with few and manageable drug interactions. The use of RAL 1200 mg once daily (qd) for first-line therapy is well established. We assessed efficacy and safety of RAL 1200 mg qd, as part of triple combined antiretroviral therapy (cART), for maintenance strategy. Methods The QDISS trial (NCT03195452) was a 48-week multicenter, single-arm, open-label study designed to evaluate the ability of 2 NRTIs + RAL 1200 mg qd to maintain virological suppression in HIV-1 infected subjects on a stable cART with 2 NRTIs and a third agent for at least 6 months. The primary endpoint was the proportion of participants with HIV-1 RNA < 50 copies/mL at week 24, by the FDA snapshot algorithm. Results Of 100 participants 91% maintained viral suppression (95% CI: 83.6–95.8) at week 24 and 89% (81.2–94.4) at week 48. At week 24, there was one virological failure, without emergence of resistance-associated mutation and 10 participants had discontinued, 4 because of adverse events (AEs). Over 48 weeks, 7 AEs of grade 3–4 were reported, one possibly study-drug related (spontaneous abortion). BMI remained stable regardless of previous therapy or baseline BMI category. Over 48 weeks, total cholesterol ( p = 0.023) and LDL-cholesterol ( p = 0.009) decreased, lifestyle and ease subscale significantly improved ( p = 0.04). The quality of life and Patients Reported Outcomes (PROs) also improved at W12 ( p = 0.007). Conclusion RAL 1200 mg qd as part of a maintenance triple therapy showed a high efficacy in virologically suppressed HIV-1 infected subjects, with good safety profile and improved lipid profile and patient reported outcomes. Trial registration: Clinical trials.gov NCT03195452 and EudraCT 2016-003702-13.
Abstract Background. Little is known on headaches long-term persistence after bacterial meningitis and on their impact on patients’ quality of life. Methods. In an ancillary study of the French national prospective cohort of community-acquired bacterial meningitis in adults (COMBAT) conducted between February 2013 and July 2015, we collected self-reported headaches before, at onset, and 12 months (M12) after meningitis. Determinants of persistent headache (PH) at M12, their association with M12 quality of life (SF 12), depression (Center for Epidemiologic Studies Depression Scale) and neuro-functional disability were analysed. Results. Among the 277 alive patients at M12 87/274 (31.8%), 213/271 (78.6%) and 86/277 (31.0%) reported headaches before, at the onset, and at M12, respectively. In multivariate analysis, female sex (OR: 2.75 [1.54–4.90]; p < 0.001), pre-existing headaches before meningitis (OR: 2.38 [1.32–4.30]; p < 0.01), higher neutrophilic polynuclei percentage in the CSF of the initial lumbar puncture (OR: 1.02 [1.00-1.04]; p < 0.05), and brain abscess during the initial hospitalisation (OR: 8.32 [1.97–35.16]; p < 0.01) were associated with M12 persistent headaches. Neither the responsible microorganism, nor the corticoids use were associated with M12 persistent headaches. M12 neuro-functional disability (altered Glasgow Outcome Scale; p < 0.01), M12 physical handicap (altered modified Rankin score; p < 0.001), M12 depressive symptoms (p < 0.0001), and M12 altered physical (p < 0.05) and mental (p < 0.0001) qualities of life were associated with M12 headaches. Conclusion. Persistent headaches are frequent one year after meningitis and are associated with quality of life alteration.
To evaluate the stability of essential drugs stored in realistic tropical conditions, we have carried out a two-year prospective study in western Burkina Faso. Twenty-seven essential drugs were stored in a rural site and a urban one where temperature and hygrometry were recorded daily. Samples of each drug were taken for further analysis to the World Health Organization Collaborative Center for the Study of Stability of Drugs in Nantes, France every three months. Quantitative analysis showed that the majority of samples suffered no significant loss of their active ingredient. In contrast, ampicillin, erythromycin, sulfaguanidine, injectable furosemide, penicillin G, trimethoprim, and chloroquine showed more than a 10% quantitative loss of their active ingredient. Thus, it is not recommended that these essential drugs be stored for more than one year in a tropical climate.
