Answer to Case 820

 Answer to the Parasite Case of the Week 820: Onchocercoma due to Onchocerca volvulus, the causative agent of onchocerciasis (a.k.a. river blindness).

Great job to everyone who recognized this classic filarial worm! The history of a subcutaneous nodule in a man from Liberia is certainly suggestive, and the histopathology gives us some beautiful diagnostic features.

At low power, we can see the skin overlying a portion of a somewhat circumscribed subcutaneous nodule containing multiple sections of adult nematodes. Note the overlying skin:

This is an onchocercoma, the fibrous nodule that forms around adult O. volvulus worms. Adult worms may live within these nodules for many years - female worms can reach an impressive 30-50 cm in length - so it isn't surprising that a single histologic section may contain multiple profiles of the same long, coiled worm. The surrounding fibrous and inflammatory response can vary depending on the viability and condition of the worms. 

Below we can see a higher power view of a cross-section through an adult female worm. Note the thick cuticle, relatively weak somatic musculature, small intestine, and the paired uterine tubes - the characteristic "double-barrel uterus." In this section, the uteri contain developing eggs/embryos. Nearby, we have also caught part of the worm in longitudinal section, where numerous developing microfilariae can be seen lined up within the uterus. 

The presence of developing microfilariae is particularly helpful for identification. Dirofilaria species can also produce subcutaneous nodules in humans and may have a somewhat similar appearance in histologic sections. However, humans are accidental hosts for Dirofilaria, and the worms generally don't mature sufficiently to produce microfilariae. The same holds true for zoonotic filariae. In contrast, humans are the definitive host for O. volvulus, and gravid females packed with developing microfilariae are just what we would expect to find in an onchocercoma. 

Here's an even closer look of the intrauterine microfilariae:

When mature, microfilariae of O. volvulus are unsheathed, slender, and measure approximately 220–360 µm in length. Their nuclei extend along the body but do not reach the tip of the tapered tail. These features are particularly useful when examining microfilariae in skin snips, which is the traditional method for diagnosing active onchocerciasis.

And, right on cue, here is one that has made its escape:

Adult females release microfilariae into the surrounding tissues, where they migrate through the dermis and superficial lymphatics. Unlike many of the other human filarial worms, O. volvulus microfilariae are primarily skin dwellers rather than blood dwellers. This is an important adaptation for transmission: the vector is a blackfly of the genus Simulium, which acquires microfilariae while taking a blood meal. The microfilariae develop within the fly to infective third-stage larvae, which are then transmitted to another person during a subsequent bite.

Much of the pathology of onchocerciasis results from the inflammatory response to dying microfilariae and their Wolbachia endosymbionts. In the skin, this can result in intense pruritus, dermatitis, pigmentary changes, and eventually skin atrophy. When microfilariae migrate through ocular tissues, repeated inflammation may cause keratitis, uveitis, chorioretinitis, and ultimately blindness - hence the well-known name "river blindness." The "river" part of the name comes from the ecology of the Simulium vectors, whose immature stages develop in rapidly flowing, well-oxygenated rivers and streams. Communities near suitable blackfly breeding sites can experience intense transmission. O. volvulus remains primarily an infection of sub-Saharan Africa and parts of Latin America, making our patient's Liberian origin an important clue.

One last interesting fact: adult worms can survive in their human host for approximately 15 years, and female worms may produce microfilariae for around 9 years. That's quite a long-term relationship—although decidedly one-sided!