High-dose ivermectin in malaria and other parasitic diseases: a new step in the development of a neglected drug.

We highlight the absence of high-level evidence from dose-ranging studies regarding the use of oral ivermectin in susceptible parasitic diseases. We provide published data supporting the use of a higher dosage regimen of ivermectin in malaria and difficult-to-treat head lice, and announce an ongoing randomized clinical trial in severe scabies.

TITLE: Ivermectine à forte dose dans le paludisme et d'autres maladies parasitaires: une nouvelle étape dans le développement d'un médicament négligé. ABSTRACT: Nous soulignons l'absence de données probantes de haut niveau sur les études de dosage concernant l'utilisation de l'ivermectine par voie orale dans les maladies parasitaires sensibles. Nous fournissons des données publiées soutenant l'utilisation d'un régime plus élevé d'ivermectine dans le paludisme et les poux de tête difficiles à traiter, et nous annonçons un essai clinique randomisé en cours dans la gale sévère.

Epidermal necrolysis French national diagnosis and care protocol (PNDS; protocole national de diagnostic et de soins).

Epidermal necrolysis (EN) encompasses Stevens-Johnson syndrome (SJS, < 10% of the skin affected), Lyell syndrome (toxic epidermal necrolysis, TEN, with ≥30% of the skin affected) and an overlap syndrome (10 to 29% of the skin affected). These rare diseases are caused, in 85% of cases, by pharmacological treatments, with symptoms occurring 4 to 28 days after treatment initiation. Mortality is 20 to 25% during the acute phase, and almost all patients display disabling sequelae (mostly ocular impairment and psychological distress).The objective of this French national diagnosis and care protocol (protocole national de diagnostic et de soins; PNDS), based on a critical literature review and on a multidisciplinary expert consensus, is to provide health professionals with an explanation of the optimal management and care of patients with EN. This PNDS, written by the French National Reference Center for Toxic Bullous Dermatoses was updated in 2017 ( https://www.has-sante.fr/portail/jcms/c_1012735/fr/necrolyse-epidermique-syndromes-de-stevens-johnson-et-de-lyell ). The cornerstone of the management of these patients during the acute phase is an immediate withdrawal of the responsible drug, patient management in a dermatology department, intensive care or burn units used to dealing with this disease, supportive care and close monitoring, the prevention and treatment of infections, and a multidisciplinary approach to sequelae. Based on published data, it is not currently possible to recommend any specific immunomodulatory treatment. Only the culprit drug and chemically similar molecules must be lifelong contraindicated.

Designing randomized-controlled trials to improve head-louse treatment: systematic review using a vignette-based method.

Head-louse infestation remains a public health problem. Despite published randomized-controlled trials, no consensus-based clinical practice guidelines for its management emerged because of the heterogeneity of trial methodologies. Our study was undertaken to attempt to find an optimal trial framework: minimizing the risk of bias, while taking feasibility into account. To do so, we used the vignette-based method. A systematic review first identified trials on head-louse infestation; 49 were selected and their methodological constraints assessed. Methodological features were extracted and combined by arborescence to generate a broad spectrum of potential designs, called vignettes, yielding 357 vignettes. A panel of 48 experts then rated one-on-one comparisons of those vignettes to obtain a ranking of the designs. Methodological items retained for vignette generation were income level of the population, types of treatments compared, randomization unit, blinding, treatment-administration site, diagnosis method and criteria, and primary outcome measure. The expert panel selected vignettes with cluster randomization, centralized treatment administration, and blinding of the outcome assessor. The vignette method identified optimal designs to standardize future head-louse treatment trials, thereby obtaining valid conclusions and comparable data from future trials, and appears to be a reliable way to generate evidence-based guidelines.

Lice.

Pediculosis (capitis, corporis, and pubis) share well-known features: worldwide prevalence (involving millions of people annually); parasites inducing skin lesions directly, and indirectly as a result of itching and hypersensitivity to parasites; and treatment based on good entomological knowledge of the parasite and practical considerations (ie, most available treatments do not act on eggs and should be repeated, depending on the life cycle of the parasites). Infestations are spread most commonly by close contacts. Social stigma and persistent misconceptions complicate the implementation of appropriate management strategies. Head and pubic lice infestations are diagnosed by the visualization of insects or viable nits (eggs). Primary treatments are topical pediculicides (permethrin or malathion), used twice, but emergence of resistance against pediculicides has created the need of alternative treatments including topical or oral ivermectin. Pubic lice are treated the same as head lice, but this finding should prompt evaluation for other sexually transmitted diseases. Body lice infestation should be suspected when symptoms of generalized itching occur in persons who do not change or wash their clothing or bedding regularly; lice may be found in the seams of their clothing.Topically administered permethrin may help to eradicate body lice, but personal hygiene measures are essential for successful treatment. Environmental treatment is also necessary for the eradication of the infestation. Health care personnel who come into contact with this population need to be well informed of the facts in order to disseminate accurate information for diagnosis and management.