**2.2 Epidemiology**

As of 2017, 20.9 million individuals were infected with *O. volvulus* [15]. Of these, 14.6 million are cases of severe forms of skin disease and 1.2 million were suffering from visual impairment and blindness, accounting for an estimated 205 million DALYs [15, 35]. 99% of all onchocerciasis cases are found in 31 countries of tropical sub-Saharan Africa. Rigorous Ivermectin distribution programs have eliminated onchocerciasis in most areas in South and Central America. Isolated transmission sites of this disease exist in the border region of Brazil and Venezuela as well in the western parts of Yemen [1, 35]. Taken together, 218 million people live in areas that are endemic for onchocerciasis [1]. The endemicity of onchocerciasis can be classified in hypoendemic, mesoendemic and hyperendemic areas according to the MF prevalence rates. In hypoendemic areas, less than 30% of the patients have microfilaridermia [44], in mesoendemic areas microfilaridermia is 30–60% and nodules are detectable in around 20% of the patients [44]. In hyperendemic areas with more than 60% microfilaridermia, 30–40% of patients have skin pathology. This classification is a very helpful tool to predict effects of treatment and vector control programmes as well as transmission dynamics [45]. As such, the activity of the Onchocerciasis Control Programme and the African Programme for Onchocerciasis Control (APOC) focused mainly on mesoendemic to hyperendemic areas, so areas where the disease risk is the highest [44]. Since its launch in 1995, the APOC has prevented an estimated 8.2 million onchocerciasis associated DALYs from 1995 to 2010 and another 9.2 million DALYs by 2015 [46]. However, in future hypoendemic areas must be included meet the formulated goal of onchocerciasis elimination. Based on the success of APOC and the following ESPEN (the Expanded Special Programme to Eliminate Neglected Tropical Diseases) program, the WHO targets the elimination of the transmission of onchocerciasis by 2030 as part of their roadmap 2021–2030 [1, 13].

#### **2.3 Pathology**

The vast majority of individuals infected with *O. volvulus* are associated with mild clinical symptoms. The adult worm-containing nodules contribute little to morbidity but can be uncomfortable and cosmetically bothersome. Individuals with onchocercomata formation, high parasite burden and mild dermatitis are referred to as generalized onchocerciasis (GEO). Clinically significant onchocerciasis results from inflammatory responses to MF and its *Wolbachia* in the skin and the eyes. Early symptoms of *O. volvulus*-induced dermatitis are itching or rash due to immune

#### *Biology of the Human Filariases DOI: http://dx.doi.org/10.5772/intechopen.102926*

responses against dead or dying MF. While the rash can disappear shortly after, in some cases the rash persists and results in intense pruritus with secondary infections with bacteria or fungi due to extensive scratching. As a consequence, repeated inflammation can lead to chronic onchodermatitis including large papules. Chronic skin inflammation can lead to severe dermatological changes including loss of elasticity, lichenification and thickening of skin ("lizard skin") as well as depigmentation and hyperpigmentation ("leopard skin") [47]. The most severe form of skin pathology is "Sowda", which presents hyperpigmented papules and plaques and local lymphadenopathy, accompanied by enlarged lymph nodes with prominent follicular hyperplasia [48–51]. This disease manifestation is called hyperreactive onchocerciasis (HO). interestingly, HO patients usually harbor low worm burden, but exhibit increased immune effector mechanisms [48]. These increased effector responses eliminate the MF, however simultaneously elicit dermatitis and the "Sowda" pathology [52]. Besides the skin pathology, onchocerciasis is commonly associated with blindness. In fact, onchocerciasis is the second most prominent infectious cause of blindness in the tropics. Loss of vision is due to immune responses against dead or dying MF and its exposed *Wolbachia* endosymbionts in the cornea and anterior chamber with keratitis and iridocyclitis, respectively. Opacity develops from the corners of the cornea to the center and permanent exposure to inflammation can lead to irreversible sclerosing keratitis which can develop into blindness [53, 54]. Laboratory studies have demonstrated a role for the *Wolbachia* endosymbionts in the ocular pathology of onchocerciasis [55]. Dying MF release *Wolbachia* which leads to infiltration and activation of fibroblasts, dendritic cells and macrophages which in turn induce neutrophil recruitment in a chemokine-dependent manner [54]. The neutrophilic responses, mostly degranulation but potentially also the release of DNA-mediated trap formation results in degradation of the corneal matrix. This leads to corneal haze, which can cause visual impairment and in worst cases blindness. The exact route of how the MF get into the eye is still unclear, but authors suggested that blood sheaths of the posterior ciliary arteries as well as cerebrospinal fluids as entry points [56, 57].
