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Clin Microbiol Infect,
2011]
Lymphatic filariasis (LF) and onchocerciasis are parasitic nematode infections that are responsible for a major disease burden in the African continent. Disease symptoms are induced by the immune reactions of the host, with lymphoedema and hydrocoele in LF, and dermatitis and ocular inflammation in onchocerciasis. Wuchereria bancrofti and Onchocerca volvulus, the species causing LF and onchocerciasis in Africa, live in mutual symbiosis with Wolbachia endobacteria, which cause a major part of the inflammation leading to symptoms and are antibiotic targets for treatment. The standard microfilaricidal drugs ivermectin and albendazole are used in mass drug administration programmes, with the aim of interrupting transmission, with a consequent reduction in the burden of infection and, in some situations, leading to regional elimination of LF and onchocerciasis. Co-endemicity of Loa loa with W. bancrofti or O. volvulus is an impediment to mass drug administration with ivermectin and albendazole, owing to the risk of encephalopathy being encountered upon administration of ivermectin. Research into new treatment options is exploring several improved delivery strategies for the classic drugs or new antibiotic treatment regimens for anti-wolbachial chemotherapy.
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Parasitology,
2000]
This detailed review of the published studies underlying ivermectin's recent registration for use in lymphatic filariasis (LF) demonstrates the drug's single-dose efficacy (over the range of 20-400 microg/kg) in clearing microfilaraemia associated with both Wuchereria bancrofti and Brugia malayi infections of humans. While doses as low as 20 microg/kg could effect transient microfilarial (mf) clearance, higher dosages induced greater and more sustained mf reduction. The single dose of 400 microg/kg yielded maximal responses, but a number of practical considerations suggest that either 400 microg/kg or 200 microg/kg doses would be acceptable for use in LF control programmes. Associated safety assessments indicate that adverse events, which occur commonly following treatment of microfilaraemic individuals, develop not because of drug toxicity but because of host inflammatory responses to dying microfilariae killed by the ivermectin treatment. Ivermectin is, therefore, a highly effective and generally well tolerated microfilaricide that may soon become an essential component of many public health initiatives to interrupt transmission of lymphatic filarial infection in an effort to eliminate LF globally.
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Adv Parasitol,
2010]
Approximately 15 million people with lymphatic filariasis (LF) live in Southeast Asia. Wuchereria bancrofti (transmitted by the Mansonia and Anopheles vectors), Brugia malayi and Brugia timori (both transmitted by Culex quinquefasciatus) are the filarial species in this region. The endemic countries are: Cambodia, Lao People's Democratic Republic, the Philippines, Indonesia, Thailand and Timor-Leste, which have all agreed to eliminate transmission of the disease by 2020. The public health interventions with respect to LF are based on the 1997 World Health Assembly resolution (WHA 50.29) which recommends elimination of the disease through mass drug administration (MDA) using diethylcarbamazine (DEC) and albendazole. The drugs are generally donated and as governments contribute 60-90% of the operational costs, MDA is deemed to be comparatively inexpensive for local administrations in relation to other public health programmes. So far, elimination has been accomplished only in the People's Republic of China (P.R. China) and this achievement is therefore described here in some detail. Resurgences have occurred but they have been successfully dealt with. Historically, the endemic areas in P.R. China covered 16,514 townships (or urban sub-districts), situated in 864 counties (or cities) in 14 provinces (or autonomous regions or municipalities). The total population at risk of infection in all endemic areas of P.R. China was originally 342 million.
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Parasite Immunol,
2009]
Among the causes of lymphoedema (LE), secondary LE due to filariasis is the most prevalent. It affects only a minority of the 120 million people infected with the causative organisms of lymphatic filariasis (LF), Wuchereria bancrofti and Brugia malayi/timori, but is clustered in families, indicating a genetic basis for development of this pathology. The majority of infected individuals develop filarial-specific immunosuppression that starts even before birth in cases where mothers are infected and is characterized by regulatory T-cell responses and high levels of IgG4, thus tolerating high parasite loads and microfilaraemia. In contrast, individuals with this pathology show stronger immune reactions biased towards Th1, Th2 and probably also Th17. Importantly, as for the aberrant lymph vessel development, innate immune responses that are triggered by the filarial antigen ultimately result in the activation of vascular endothelial growth factors (VEGF), thus promoting lymph vessel hyperplasia as a first step to lymphoedema development. Wolbachia endosymbionts are major inducers of these responses in vitro, and their depletion by doxycycline in LF patients reduces plasma VEGF and soluble VEGF-receptor-3 levels to those seen in endemic normals preceding pathology improvement. The search for the immunogenetic basis for LE could lead to the identification of risk factors and thus, to prevention; and has so far led to the identification of single-nucleotide polymorphisms (SNP) with potential functional relevance to VEGF, cytokine and toll-like receptor (TLR) genes. Hydrocele, a pathology with some similarity to LE in which both lymph vessel dilation and lymph extravasation are shared sequelae, has been found to be strongly associated with a VEGF-A SNP known for upregulation of this (lymph-)angiogenesis factor.
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2017]
Since their discovery in late 1970, transient receptor potential (TRP) channels have been implicated in a variety of cellular and physiological functions (Minke, 2010). The superfamily of TRP channels consists of nearly 30 members that are organized into seven major subgroups based on their specific function and sequence similarities (Owsianik et al., 2006; Ramsey et al., 2006). With the exception of TRPN channels that are only found in invertebrates and fish, mammalian genomes contain representatives of all six subfamilies: (1) TRPV (vanilloid); (2) TRPC (canonical); (3) TRPM (melastatin); (4) TRPA (ankyrin); (5) TRPML (mucolipin); and (6) TRPP (polycystin). TRP channels play crucial regulatory roles in many physiological processes, including those associated with reproductive tissues. As calcium-permeable cation channels that respond to a variety of signals (Clapham et al., 2003; Wu et al., 2010), TRP channels exert their role as sensory detectors in both male and female gametes, and play regulatory functions in germ cell development and maturation. Recent evidence obtained from Caenorhabditis elegans studies point to the importance of these proteins during fertilization where certain sperm TRP channels could migrate from a spermatozoon into an egg to ensure successful fertilization and embryo development. In this chapter we discuss how TRP channels can regulate both female and male fertility in different species and their specific roles.