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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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BackgroundNeglected Tropical Diseases (NTDs) afflict around one billion individuals in the poorest parts of the world with many more at risk. Lymphatic filariasis is one of the most prevalent of the infections and causes significant morbidity in those who suffer the clinical conditions, particularly lymphedema and hydrocele. Depressive illness has been recognised as a prevalent disability in those with the disease because of the stigmatising nature of the condition. No estimates of the burden of depressive illness of any neglected tropical disease have been undertaken to date despite the recognition that such diseases have major consequences for mental health not only for patients but also their caregivers.MethodsWe developed a mathematical model to calculate the burden of Disability- Adjusted Life Years (DALY) attributable to depressive illness in lymphatic filariasis and that of their caregivers using standard methods for calculating DALYs. Estimates of numbers with clinical disease was based on published estimates in 2012 and the numbers with depressive illness from the available literature.ResultsWe calculated that the burden of depressive illness in filariasis patients was 5.09 million disability-adjusted life years (DALYs) and 229,537 DALYs attributable to their caregivers. These figures are around twice that of 2.78 million DALYs attributed to filariasis by the Global Burden of Disease study of 2010.ConclusionsLymphatic filariasis and other neglected tropical diseases, notably Buruli Ulcer, cutaneous leishmaniasis, leprosy, yaws, onchocerciasis and trachoma cause significant co morbidity associated with mental illness in patients. Studies to assess the prevalence of the burden of this co-morbidity should be incorporated into any future assessment of the Global Burden of neglected tropical diseases. The prevalence of depressive illness in caregivers who support those who suffer from these conditions is required. Such assessments are critical for neglected tropical diseases which have such a huge global prevalence and thus will contribute a significant burden of co-morbidity attributable to mental illness.Electronic supplementary materialThe online version of this article (doi:10.1186/s40249-015-0068-7) contains supplementary material, which is available to authorized users.

Filarial nematodes cause chronic and profoundly debilitating diseases in both humans and animals. Applications of novel technology are providing unprecedented opportunities to improve diagnosis and our understanding of the molecular basis for host-parasite interactions. As a first step, we investigated the presence of circulating miRNAs released by filarial nematodes into the host bloodstream. miRNA deep-sequencing combined with bioinformatics revealed over 200 mature miRNA sequences of potential nematode origin in Dirofilaria immitis-infected dog plasma in two independent analyses, and 21 in Onchocerca volvulus-infected human serum. Total RNA obtained from D. immitis-infected dog plasma was subjected to stem-loop RT-qPCR assays targeting two detected miRNA candidates, miR-71 and miR-34. Additionally, Brugia pahangi-infected dog samples were included in the analysis, as these miRNAs were previously detected in extracts prepared from this species. The presence of miR-71 and miR-34 discriminated infected samples (both species) from uninfected samples, in which no specific miRNA amplification occurred. However, absolute miRNA copy numbers were not significantly correlated with microfilaraemia for either parasite. This may be due to the imprecision of mf counts to estimate infection intensity or to miRNA contributions from the unknown number of adult worms present. Nonetheless, parasite-derived circulating miRNAs are found in plasma or serum even for those species that do not live in the bloodstream.

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