Search

Background: Malaria still kills young children in rural endemic areas because early treatment is not available. Thus, the World Health Organization recommends the administration of artesunate suppositories as pre-referral treatment before transportation to the hospital in case of severe symptoms with an unavailable parenteral and oral treatment. However, negative cultural perception of the rectal route, and limited access to artesunate suppositories, could limit the use of artesunate suppositories. There is therefore a need for an alternative route for malaria pre-referral treatment. The aim of this study was to assess the potential of intranasal route for malaria pre-referral treatment.Methods: The permeability of artesunate through human nasal mucosa was tested in vitro. The Transepithelial Electrical Resistance (TEER) of the nasal mucosa was followed during the permeation tests. Beside, regional deposition of artesunate powder was assessed with a unidose drug delivery device in each nostril of a nasal cast. Artesunate quantification was performed using Liquid Chromatography coupled to tandem Mass Spectrometry. Results: The experimental model of human nasal mucosa was successfully implemented. Using this model, artesunate powder showed a much better passage rate through human nasal mucosa than solution (26.8 ± 6.6% versus 2.1 ± 0.3%). More than half (62.3%) of the artesunate dose sprayed in the nostrils of the nasal cast was recovered in the olfactory areas (44.7 ± 8.6%) and turbinates (17.6 ± 3.3%) allowing nose-to-brain and systemic drug diffusion, respectively.Conclusion: Artesunate powder showed a good permeation efficiency on human nasal mucosa. Moreover it can be efficiently sprayed in the nostrils using unidose device to reach the olfactory area leading to a fast nose-to-brain delivery as well as a systemic effect. Taken together, those results are part of the proof-of-concept for the use of intranasal artesunate as a malaria pre-referral treatment.

Laryngeal mobility disorder after a pediatric heart surgery is common (between 5 and 10% of cases), and has important consequences on swallowing, breathing and speaking. After reviewing the literature, the recovery rate is variable and the postoperative follow-up is often done on a short time frame. The primary objective of the study is to describe the recovery from laryngeal mobility disorder with a follow-up time of at least 5 years. The secondary objective is to describe of the quality of life of the child in terms of phonation and swallowing, and to identify potential risk factors for a lasting laryngeal mobility disorder.We collected data (morphological characteristics and details of the procedures and medical care) on children who had undergone a heart surgery with risks of complications, between 2010 and 2015, and with a laryngeal mobility disorder detected after the surgery through nasal flexible laryngoscopy. During a follow-up consultation, carried at least 5 years after the surgery, we performed a nasal flexible laryngoscopy to assess whether or not the patient had recovered a full mobility of the larynx. Two questionnaires were also given to the patients, the pVHI and the PEDI EAT-10, to assess respectively the quality of their speech and of their swallowing function.The recovery rate for a laryngeal mobility disorder more than 5 years after surgery was found to be 65% (9 children out of the 14 included in the study). We identified a risk factor for the persistence of a laryngeal mobility disorder after surgery: the presence of an associated genetic syndrome, p = 0.025. Children with persistent laryngeal mobility disorder have an impaired quality of life score, using the pVHI scale, which correlates well with the flexible laryngoscopy findings, p = 0.033.Children with a lasting laryngeal mobility disorder have disabling respiratory and vocal symptoms in their daily lives. Nasal flexible laryngoscopy should therefore be systematically performed postoperatively after a surgery carrying risks. For improved patient management, early detection of these disorders by pharyngolaryngeal nasal flexible laryngoscopy in the aftermath of high-risk cardiac surgery is strongly advised, with prolonged follow-up.