**2.1 Biology of the parasite**

The life cycle of *O. volvulus* is similar to the LF-causing nematodes. Humans harbor the adult worms while blood-feeding arthropod vectors transmit the larval stages. Onchocerciasis is closely associated with fast-flowing rivers that serve as breeding grounds for *Simulium* blackflies. The predominant *Simulium* vector in Africa is *S. damnosum*, with *S. naevei* driving transmission in parts of East and Central Africa [32–34]. In South and Central America, the disease is transmitted mainly by *S. ochraceum* [35] with other species have been active in transmission before elimination of the disease in most countries [36]. Female blackflies transmit the infectious L3 stage of *O. volvulus* during the blood meal into the human body. Within 10 days, the L3 larvae molt once to become L4, which then persists in the host for 6–12 months before molting into an adult worm. The adult worms reside in so called onchocercomata, subcutaneous nodules commonly located around the hip regions of an infected person, but also on head and torso [36]. Onchocercomata are granulomatous reactions around the adult worms, they are painless for the infected person and have a diameter of 0.5–3 cm. They often consist of separate chambers with thick fibrous walls and cellular infiltration around the adult worms residing in the chambers. The ratio of females and males residing in a nodule is approximately 3:1. The worms mate here and gravid females produce and subsequently release thousands of unsheated MF into the subcutaneous tissue [37]. Female worms are long-lived, with their reproductive life span being an estimated 9–11 years, in extreme cases up to 15 years [38, 39]. The MF of *O. volvulus* are 220–360 μm long and 5–9 μm wide, female adult worms are 33–70 cm long and 270–440 μm wide, adult males are significantly smaller with 19–42 mm length and a width of 130–210 μm (**Table 2**). MF migrate and reside within the host's skin for 6–30 months and can be taken up by the aforementioned insect

vector during a blood meal. MF do not exhibit any form of periodicity. Therefore skin snips for diagnostics can be collected at any time. The MF can also be found in the lymphatics, sputum, urine and blood and it is their migration into the ocular regions which causes ocular pathology. Within the blackflies, the MF penetrate the membranes of the mid gut and migrate through the haemolymph where they then settle in the syncytial cells of the thoracic longitudinal flight muscles. The MF molt twice to become the infectious L3 larvae [40]. Similar to other human-pathogenic filariae, *O. volvulus* contain the endosymbiontic bacteria *Wolbachia*. These bacteria are found in the hypodermis and are essential for filarial development, embryogenesis and survival [41, 42]. Depleting these endosymbionts using doxycycline leads to inhibition of filarial embryogenesis and death of adult worms, currently representing the macrofilaricidal drug for onchocerciasis [43].
