ABSTRACT
OBJECTIVES: Malaria is one of most common tropical diseases encountered in travellers and migrants. It requires an urgent and reliable diagnosis considering its potential severity. In this study, performance of five diagnostic assays were evaluated in a nonendemic region and compared prospectively to quantitative PCR (qPCR). METHODS: A prospective study was conducted at Toulouse Hospital from August 2017 to January 2018 and included all patients with initial Plasmodium screening. Thin and thick blood smears (TnS, TkS), quantitative buffy coat (QBC), rapid diagnostic tests (RDTs) and commercial loop-mediated isothermal amplification (LAMP) were independently performed on each blood sample and compared to our qPCR reference standard. RESULTS: The study encompassed 331 patients, mainly returning from Africa. qPCR detected 73 Plasmodium-positive samples (including 58 falciparum). Individually, LAMP had a 97.3% (71/73) sensitivity, far ahead of TnS (84.9%, 62/73), TkS (86.3%, 63/73), QBC (86.3%, 63/73) and RDT (86.3%, 63/73). RDT demonstrated a high sensitivity for falciparum (98.3%, 57/58) but missed all ovale, malariae and knowlesi infections. Specificity was excellent for all techniques (99.6-100%). The most sensitive diagnosis strategies were TnS + RDT (95.9%, 70/73), TnS + LAMP (97.3%, 71/73) and TnS + RDT + LAMP (100%, 73/73), about 10% higher than strategies using exclusively microscopy, TkS + TnS (87.7%, 64/73) or QBC + TnS (87.7%, 64/73). TnS remains necessary for Plasmodium species identification and quantification. Adding sequentially TnS only on LAMP-positive samples did not decrease TnS + LAMP strategy sensitivity. CONCLUSIONS: In nonendemic countries, the currently recommended microscopy-based strategies seem unsatisfactory for malaria diagnosis considering RDT and LAMP performance, two rapid and sensitive assays that require limited training.
Subject(s)
Communicable Diseases, Imported/diagnosis , Malaria/diagnosis , Microscopy/standards , Molecular Diagnostic Techniques/standards , Nucleic Acid Amplification Techniques/standards , Africa , Communicable Diseases, Imported/parasitology , France , Humans , Malaria/parasitology , Microscopy/methods , Molecular Diagnostic Techniques/methods , Nucleic Acid Amplification Techniques/methods , Plasmodium , Prospective Studies , Real-Time Polymerase Chain Reaction/standards , Sensitivity and Specificity , TemperatureABSTRACT
BACKGROUND AND OBJECTIVES: A human recombinant monoclonal anti-RhD IgG may be useful to prevent RhD allo-immunization. Roledumab is such an antibody with a glycosylation pattern optimized for biological activity. The objective of the study was to assess the safety and pharmacokinetics of roledumab in healthy RhD-negative volunteers. MATERIALS AND METHODS: A total of 46 subjects received doses of 30-3000 µg i.v. of roledumab or placebo using a double-blind escalating single-dose design; 12 of these subjects also received 300 µg i.m. of roledumab. Subjects were followed for 6 months after administration. Serum roledumab concentrations were determined using flow cytometry. RESULTS: Fourteen treatment-emergent adverse events related to treatment were reported in nine subjects, with no apparent difference in their frequency or nature after placebo or roledumab administration. No anti-roledumab antibodies were detected. AUC(last) increased from 4·4 ng/ml.day at 30 µg i.v. to 2257 ng/ml.day at 3000 g i.v. The t(½) ranged from 18 to 22 days, and the absolute bioavailability after i.m. administration was between 73% and 80%. CONCLUSION: Roledumab is safe and well tolerated in healthy RhD-negative volunteers and shows a pharmacokinetic profile similar to that of polyclonal anti-RhD immunoglobulin.
Subject(s)
Antibodies, Monoclonal/pharmacokinetics , Immunoglobulin Fc Fragments/immunology , Receptors, IgG/immunology , Rh-Hr Blood-Group System/immunology , Adult , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/adverse effects , Cross-Over Studies , Double-Blind Method , Female , Humans , Immunoglobulin Fc Fragments/genetics , Immunoglobulin Fc Fragments/metabolism , Male , Middle Aged , Receptors, IgG/genetics , Receptors, IgG/metabolism , Recombinant Proteins/genetics , Recombinant Proteins/immunology , Recombinant Proteins/metabolism , Recombinant Proteins/pharmacokinetics , Young AdultABSTRACT
Respimat (RMT) is a reusable, propellant-free, soft mist inhaler (SMI), a novel device for inhalation therapy. We conducted a three-period cross-over study to evaluate the safety and efficacy of cumulative doses of ipratropium bromide inhaled from RMT (Two dose levels) or from a pressurized metered dose inhaler (MDI), in 36 patients with chronic obstructive pulmonary disease (COPD). The bronchodilator effect of ipratropium bromide was greater when administered via RMT (10 or 20 microg per puff, given double-blind within device, to total doses of 160 or 320 microg) than via MDI (20 microg per puff, total dose 320 microg). The bronchodilator effects of the 160 and 320 microg doses delivered via RMT were similar. Cumulative ipratropium bromide doses of 320 microg given via MDI or RMT and 160 microg given via RMT produced similar safety profiles. Between 45 min after the first drug inhalation and 45 min after the final dose, greater bronchodilatory effect was obtained from half the cumulative dose of ipratropium (RMT 10 microg per puff) when compared with the MDI (20 microg per puff). Therefore, ipratropium bromide delivered by RMT is as safe as, and can be more effective than, the MDI on acute administration in patients with COPD.
