Efficacy and safety of artesuante-amodiaquine and artemether lumefantrine, the first line malaria treatment in six sentinel's sites of Côte d'Ivoire, West Africa.

The purpose of this study was to update efficacy data of Artesunate-Amodiaquine (AS+AQ) and Artemether-Lumefantrine (AL) used as first-line malaria treatment in Côte d'Ivoire since 2005. This was an open-label, randomized trial conducted in patients older than 6 months with uncomplicated P. falciparum malaria at six sentinel sites. The WHO 2009 protocol on surveillance of anti-malaria drug efficacy was used with primary outcomes as ACPR corrected by PCR at day 42. Secondary endpoints were parasite and fever clearance times and safety. From January to July 2016, 712 patients were included in the trial. 353 and 359 patients were randomly assigned respectively to the AS+AQ and AL arm. Day 42 PCR-adjusted ACPR in the per-protocol analysis was 99.4% and 98.8% in AS+AQ and AL arm respectively. Delayed parasite clearance was observed in six patients at Abidjan and Yamousssoukro sites. Both ACTs were well tolerated. Both ACTs remain efficacious for uncomplicated P. falciparum malaria treatment in Côte d'Ivoire. But regarding delayed parasite clearance observed in this study, a close monitoring and supervision for ACT resistance are essential for future malaria treatment and control strategies in Côte d'Ivoire.

Using a sequential explanatory mixed method to evaluate the therapeutic window of opportunity for initiating osteoporosis treatment following fragility fractures.

Interventions targeting patients with recent fragility fracture and their physician were most successful at initiating osteoporosis treatment during the first 12 months. This window of opportunity had already closed after 1 year. The reasons for declining or accepting the intensive intervention were explored in patients still untreated at 12 months. INTRODUCTION: A fragility fracture (FF) event identifies patients most likely to benefit from osteoporosis treatment. Nonetheless, most FF patients go untreated. Our objective was to determine how long an incident FF remains a strong incentive to initiate osteoporosis treatment. METHODS: A total of 1086 men and women over age 50 with a recent FF event were assigned to either standard care (SC), to minimal (MIN), or intensive (INT) interventions targeting patients and their family physician to initiate osteoporosis treatment. Inpatients with FF (mainly hip) evaluated by rheumatologists were also included in a specialized group (SPE; n = 324). At 1 year, untreated patients in both the SC and the MIN groups were offered an INT intervention. The cohort was followed through 48 months. A qualitative analysis of patient-centered decision-making associated with initiation of treatment was conducted. RESULTS: In MIN and INT groups, osteoporosis treatment was initiated in 41.0 and 54.3% of untreated patients by 12 months, respectively, compared to 68.4% in SPE and 18.9% in SC groups; initiation rates drastically dropped thereafter. Over 4863 patient-years of follow-up, the rates of new FF were 3.4 per 100 patient-years, without significant differences between patients with initial major or minor FF, nor between control or intervention groups. Failure by patients and physicians to recognize FF as a sign of underlying bone disease contributed the most to lack of treatment. CONCLUSION: While incident FFs are an ideal opportunity for starting osteoporosis treatment, 1 year later, the therapeutic window of opportunity has already closed.

Plant-derived H7 VLP vaccine elicits protective immune response against H7N9 influenza virus in mice and ferrets.

In March 2013, the Chinese Centre for Disease Control and Prevention confirmed the first reported case of human infection with an avian influenza A H7N9 virus. Infection with this virus often caused severe pneumonia and acute respiratory distress syndrome resulting in a case fatality rate >35%. The risk of pandemic highlighted, once again, the need for a more rapid and scalable vaccine response capability. Here, we describe the rapid (19 days) development of a plant-derived VLP vaccine based on the hemagglutinin sequence of influenza H7N9 A/Hangzhou/1/2013. The immunogenicity of the H7 VLP vaccine was assessed in mice and ferrets after one or two intramuscular dose(s) with and without adjuvant (alum or GLA-SE™). In ferrets, we also measured H7-specific cell-mediated immunity. The mice and ferrets were then challenged with H7N9 A/Anhui/1/2013 influenza virus. A single immunization with the adjuvanted vaccine elicited a strong humoral response and protected mice against an otherwise lethal challenge. Two doses of unadjuvanted vaccine significantly increased humoral response and resulted in 100% protection with significant reduction of clinical signs leading to nearly asymptomatic infections. In ferrets, a single immunization with the alum-adjuvanted H7 VLP vaccine induced strong humoral and CMI responses with antigen-specific activation of CD3(+) T cells. Compared to animals injected with placebo, ferrets vaccinated with alum-adjuvanted vaccine displayed no weight loss during the challenge. Moreover, the vaccination significantly reduced the viral load in lungs and nasal washes 3 days after the infection. This candidate plant-made H7 vaccine therefore induced protective responses after either one adjuvanted or two unadjuvanted doses. Studies are currently ongoing to better characterize the immune response elicited by the plant-derived VLP vaccines. Regardless, these data are very promising for the rapid production of an immunogenic and protective vaccine against this potentially pandemic virus.

A radioimmunoassay for the measurement of paclitaxel and taxanes in biological specimens using commercially available reagents.

We have developed a rapid and sensitive radioimmunoassay for the measurement of paclitaxel and related taxanes in biological specimens using commercially available reagents. The presence of paclitaxel competitively inhibited the binding of radioactive paclitaxel to polyclonal anti-taxane antibody or anti-taxane monoclonal antibody. When using polyclonal antibody, this method detected paclitaxel in concentrations as low as 0.87 nM and was also effective in 20% methanol. This radioimmunoassay is useful for the measurement of paclitaxel and taxanes in biological specimens like culture medium of paclitaxel-producing microorganisms and may be useful for the measurement of paclitaxel and related compounds in other potential natural sources.