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Scabies is a parasitic disease of the skin that disproportionately affects disadvantaged populations. Scabies causes considerable morbidity and leads to severe bacterial infection and immune-mediated disease. Recent scientific advances suggest that scabies is amenable to population-level control, particularly through mass drug administration. In recognition of these issues, WHO added scabies to the list of neglected tropical diseases (NTDs) in 2017. In order to develop a global control program, key operational research questions must now be addressed. Standardised approaches to diagnosis and methods for mapping are required to further understand the burden of disease. The safety of treatments for young children, including with ivermectin and moxidectin, should be investigated. Studies are needed to inform optimum implementation of mass treatment, including the threshold for intervention, target, dosing, and frequency. Frameworks for surveillance, monitoring and evaluation of control strategies are also necessary.

Ivermectin (IVM) is a broad-spectrum anthelmintic used in filariasis control programs. By binding to nematode glutamate-gated chloride channels (GluCls), IVM disrupts neurotransmission processes regulated by GluCl activity. IVM treatment of filarial infections is characterized by an initial dramatic drop in the levels of circulating microfilariae, followed by long-term suppression of their production, but the drug has little direct effect on microfilariae in culture at pharmacologically relevant concentrations. We localized Brugia malayi GluCl expression solely in a muscle structure that surrounds the microfilarial excretory-secretory (ES) vesicle, which suggests that protein release from the ES vesicle is regulated by GluCl activity. Consistent with this hypothesis, exposure to IVM in vitro decreased the amount of protein released from microfilariae. To better understand the scope of IVM effects on protein release by the parasite, three different expression patterns were identified from immunolocalization assays on a representative group of five microfilarial ES products. Patterns of expression suggest that the ES apparatus is the main source of regulated ES product release from microfilariae, as it is the only compartment that appears to be under neuromuscular control. Our results show that IVM treatment of microfilariae results in a marked reduction of protein release from the ES apparatus. Under in vivo conditions, the rapid microfilarial clearance induced by IVM treatment is proposed to result from suppression of the ability of the parasite to secrete proteins that enable evasion of the host immune system. filarial nematode | macrocyclic lactone | glutamate-gated chloride channels

Background:The most important risk encountered in distributing Mectizan® for the control of onchocerciasis in areas where Loa loa is co-endemic is the development of an encephalopathic syndrome in people with very high levels of L. loa [> 30,000 microfilariae/milliliter blood (mf/ml)] following treatment with Mectizan®. This syndrome, which occurs rarely, is characterized by symptoms such as confusion, lethargy, coma, and urinary incontinence.The reason this syndrome develops is that Mectizan®, in addition to being an effective drug against the microfilariae of Onchocerca volvulus (the causative agent of onchocerciasis), is also effective against L. loa microfilariae, the rapid killing of which has been associated with this encephalopathy. Like all serious illnesses, this encephalopathy requires prompt medical and nursing care to provide supportive treatment and to prevent nosocomial infections. With competent and timely medical care, patients usually recover fully. The pathogenesis of this encephalopathy remains unknown.L. loa is known, or suspected, to be endemic in humid forest areas of Central and East Africa. The precise distribution of L. loa is still being defined and mapped. Methodologies for mapping include parasitologic surveys, rapid assessment of L. loa based on the restricted definition of eye worm passage (RAPLOA), and predicted prevalence based on environmental factors conducive to the breeding of the vector of L. loa, Chrysops spp.Recent epidemiologic studies have shown that in areas where the prevalence of L. loa microfilaremia in adults exceeds 20%, the percentage of adults with L. loa microfilaremia greater than 30,000 mf/ml is about 1%.1 The threshold for increased community risk of L. loa encephalopathy following Mectizan® treatment has been defined as 20% microfilaremia prevalence which corresponds to a 40% prevalence of history of eye worm passage as measured by RAPLOA.

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