by Michael E. Gyasi; Ogugua N. Okonkwo; Koushik Tripathy
Introduction
Onchocerciasis, also known as the African river blindness, is the second most important cause of infectious blindness worldwide after trachoma. It is caused by the filarial nematode, Onchocerca volvulus, and transmitted by repeated bites of the vector, female black fly of the genus Simulium damnosum. The vector breeds in fast-flowing and oxygen-rich rivers in affected areas with transmission and disease prevalence usually stretching along these river basins and thereby the name river blindness. Aside from blindness, onchocerciasis results in a troubling chronic dermatitis.
Etiology
The definitive hosts of Onchocerca volvulus are humans, while the larval stages grow exclusively in the Simulium black fly, of which there are several cyto-species based on their flying characteristics and chromosomal banding patterns. Further classifications into savanna, rainforest, and transitional zone clades are done based on their habitats and mitochondrial gene sequencing. These show different biting characteristics and propensity towards causing blinding disease.
Infective microfilariae larvae (L3 stage) are injected into a host during the blood meal of the female black fly. For 6 to 12 months, these larvae would develop into adult worms (microfilariae) that reside in fibrous sub-cutaneous nodules, located commonly around the iliac crest, the head, and torso. Each nodule may contain one or two female worms and a single male that is usually smaller in size. Fertilized adult worms produce about 1000 to 1,500 microfilariae (L1 stages) daily and have a life span of 10 to 15 years. These baby worms measure 250 to 300 microns and 8 microns in cross-section and live for 1 to 2 years.
At any given time, millions of microfilariae are moving through subcutaneous tissues and, to a lesser extent, the lymphatic system of an affected patient. During a subsequent blood meal, these L1 forms are ingested by a biting fly. They then transform over 1 to 3 weeks first by migrating from the gut into the thoracic flight muscles as an L2 larval stage. From here, they develop into an infective L3 larval stage and migrate into the salivary gland for subsequent transmission during the next blood meal. Once in the human body, the injected larvae transform into the L4 stage from where they mature in about one year.
Epidemiology
The disease is endemic in 31 sub-Saharan African countries, the Arabian peninsula, and a small locality in Latin America that stretches across the Bolivarian Republic of Venezuela and Brazil. About 90% of the disease occurs in sub-Saharan Africa. The World Health Organization (WHO) estimates that at least 25 million people are infected worldwide, and another 90 million are at risk, with more than 99% of them in Africa. Vision loss is estimated to affect 1.15 million population.
Worldwide ongoing mass drug administration (MDA) with ivermectin has significantly reduced the burden of infection and associated ocular disease. A recent study (in 2018) from Togo with the identification of ocular disease in children and young adults despite ongoing MDA programs with a reduction of microfilariae rates is creating concerns. Onchocerciasis is more likely to be found in persons involved in the agricultural industry and especially so in those living closer to rivers that serve as breeding grounds for the Simulium black fly. In a risk factors assessment study in Ethiopia, the male gender, a distance less than 2 km from the riverbank, noncompliance to ivermectin therapy, and age of above 35 years were all associated with a higher prevalence of onchocerciasis.
Symptoms
The most common presentation is one of recurrent severe pruritus, papular dermatitis, lichenified dermatitis, and areas of skin depigmentation, especially around the shins, giving rise to the name “leopard skin.” Skin depigmentation happens as a result of chronic rubbing of the skin (which may involve the use of stones and other coarse materials) in response to severe itchiness induced by an immunological response to dying or dead microfilariae.
These normally present years before ocular manifestations ensue. Ocular features include recurrent conjunctivitis, punctate keratitis, photophobia, and progressive visual loss from either anterior(cornea scarring) or posterior segment pathologies (optic nerve and chorioretinal atrophies) or both. Typically dead microfilariae induce focal corneal reaction (snowflake keratitis) that mimics stage 3 adenoviral keratitis. Continuous corneal insult and healing result in progressive corneal scarring that starts from the limbal areas in the interpalpebral fissure, and eventually leading to corneal blindness. Posterior segment diseases are related to the optic nerve and chorioretinal atrophy.
Treatment and Management
In the past, treatment had involved the use of diethylcarbamazine, which was effective but also caused very serious systemic and ocular complications, especially in patients with high microfilaridermia. The current standard of care is oral ivermectin 150 mcg/kg given once or twice a year for 10 to 15 years, corresponding to the life span of the adult worm, or as long as the infected patient has evidence of active infection. It paralyzes or kills the microfilariae but has no effects on the life of an adult worm, though it reduces the fertility of female adult worm at least temporarily.
Ivermectin reduces the occurrence of blindness and skin disease due to onchocerciasis. Prolonged daily treatments are not needed as there is no evidence that it offers benefits compared to annual or 6 monthly treatments. A higher dose than the recommendation may be harmful. Evidence of active infection includes microfilaria on skin examination or skin biopsy and skin symptoms like pruritus. The presence of the adult worm in skin nodules may not necessarily need continued treatment, as adult worms are not killed by ivermectin, and these do not cause symptoms. More frequent dosage of ivermectin (every 6 months or every 3 months) can reduce the duration of symptoms and cause more rapid sterilization of the adult worm, especially in persons who are not returning to live in an endemic region.
The clearance of microfilariae from the skin and the anterior chamber has been studied extensively. A previous meta-analysis has shown that skin microfilariae are reduced by half in 24 hours, 94% in one week, and 98% to 99% by 1 to 2 months, following a single dose of ivermectin. Similar clearance happens in the anterior chamber, but this lags behind the skin clearance by several months. Microfilariae repopulation of skin and eye resumes in a few months, and this is due to continuous production by the adult worm.
A major limitation of currently available treatment is the absence of good and safe drugs to kill the adult worm, which causes the persistence of infection. Tablet doxycycline is promising in this regard, and may kill the adult worm by killing Wolbachia; however, doxycycline does not kill the microfilaria for which another drug has to be used concurrently. Wolbachia is endosymbiotic, rickettsia-like bacteria, which is important for the survival of adult worm and embryogenesis. The used dose is oral 100mg or 200mg once daily for 6 weeks. Ivermectin should be started at least 1 week before doxycycline for optimal benefits. Doxycycline can sterilize up to 90% of adult female worms and kill at least 60% adult female worms 20 months after treatment.
Older treatments, including suramin and diethylcarbamazine, are avoided as less toxic and effective alternative treatments are available. Diethylcarbamazine may accelerate the development of blindness. Patients coinfected with Loa loa can have a life-threatening encephalitic reaction to ivermectin, and the opinion of infectious disease specialists or experts on loiasis is a must before starting therapy. Doxycycline has only been tested in coinfected persons with a Loa microfilariae load of less than 8000/ml.
Prognosis and Complication
Often ocular and dermatologic complications of onchocerciasis improve with ivermectin treatment, especially if the disease is not advanced. When the disease is advanced, blindness due to optic atrophy or cornea scarring and vascularization is often irreversible. Also, the dermatological manifestations of advanced diseases such as skin depigmentation and atrophy are irreversible.
Ocular complications of onchocerciasis include blindness as a result of keratitis, the formation of pannus, and corneal scarring. Other causes of blindness include optic atrophy, open-angle glaucoma, and chorioretinitis, as previously stated. Posterior segment complications have been noted to be responsible for over half of the blindness from onchocerciasis in a report. Specific posterior segment complications reported in this study include; chorioretinal changes including intraretinal pigment (IRP) clumping and retinal pigment epithelium atrophy, retinitis, subretinal fibrosis, and optic neuritis.
Other ocular complications include live and dead microfilariae presence in anterior chamber and cornea, punctate cornea opacity, sclerosis keratitis, pannus formation, and uveitis (iridocyclitis).
More Educative Information
Onchocerciasis infection can be avoided by avoiding exposure or bites from the vector. This can be achieved by the use of protective clothing or applying repellants on the skin. Travelers to endemic regions should receive advice on this. There are efforts targeted at deterring infection by abolishing vector habitats through the promotion of vector habitat control programs. Also, population-based strategies in some endemic regions are targeted at vector elimination and yearly mass ivermectin treatment.
Patients with a high load of microfilaria should be informed of the risk of severe reaction following treatment. This can often be associated with coinfection from Loa loa and can result in severe morbidity and a threat to life. Also, when there is a heavy burden of microfilariae and ocular involvement, patients should be informed of the potential complications that can occur from ivermectin use.
Source
Gyasi ME, Okonkwo ON, Tripathy K. Onchocerciasis. [Updated 2023 Aug 25]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK559027/