Filariasis, Onchocerca volvulus (Pathogen – Tissue Nematode)

Organism:
Onchocerciasis, which is also known as river blindness, is a major public health problem because the infection is a leading cause of blindness in the world and may also cause significant disfigurement of the skin. Currently, 17.7 million people are infected with Onchocerca volvulus; of these, 270,000 are blind and 500,000 have severe visual impairment.

Oncocherca nodules	Nodule removal	Adult worm	“Leopard” skin"

Adult worm within nodule	Histologic section of nodule

Life Cycle:
Adult female and male worms lie within fibrous tissue capsules in the dermis and subcutaneous tissues. After being ingested, the microfilariae migrate to the flight muscles, become infective in about 6 to 12 days, and migrate to the proboscis, where they are transmitted when the next blood meal is taken.  Humans are infected when bitten by the infected fly, and larvae are deposited into the bite site. Microfilariae are normally found in the dermis and rarely in the blood, sputum, or urine.

Acquired:
Infection in humans is acquired through the bite of infected Simulium (blackfly or buffalo gnat) flies. Apparently, the blackflies are pool feeders, and the saliva probably contains anticoagulants, as well as attractants for the skin‑dwelling microfilariae.

Epidemiology:
Onchocerciasis is widely distributed throughout Central Africa, occurs in Saudi Arabia and Yemen, and is found in areas of Brazil, Colombia, Venezuela, Ecuador, Guatemala, and Mexico.  An estimated 85.6 million people are considered at risk for onchocerciasis worldwide.  There appear to be no known important animal reservoirs, although natural infections in gorillas have been found in Africa.

Clinical Features:
The Chrysops bite results in erythema, swelling, and itching, symptoms which can worsen with the presence of infective larvae.  The adult worms normally migrate through the subcutaneous tissue at a rate of about 1 cm/min. This migration is not painful and is seldom noticed unless the worm is passing over the bridge of the nose or through the conjunctiva of the eye. Many patients with active L. loa infections do not have a microfilaremia.
The most common pathologic sequelae associated with L. loa infections are Calabar or fugitive swellings (angioedema).  Calabar swellings are localized subcutaneous edemas, a type of inflammatory reaction brought about by a host response to the worm or its metabolic products. Calabar swellings may be found anywhere on the body but predominate on the extremities. The swellings develop rapidly over a few hours and may be preceded by localized pain, pruritus, and urticaria; the swellings usually last 1 to 3 days. Serious complications due to loiasis have included cardiomyopathy, encephalopathy, nephropathy, and pleural effusions.
Light infections may produce no symptoms, and worms may be free in the tissue; however, in heavy infections, major disease manifestations include dermatitis, onchocercomas (subcutaneous nodules containing adult worms), lymphadenitis, and blindness. Eye damage is caused by living and dead microfilariae in the cornea, anterior and posterior chambers, iris, retrolental space, vitreous, choroid, retina, sclera, and optic nerve.  Progressive pathology generally develops over time, with resulting blindness seen in adults.  Even though there is an inflammatory reaction that causes the formation of a fibrotic capsule (onchocercoma) around the adult, the main pathology appears to be directed against the microfilariae.
Chronically infected skin loses its elasticity and becomes hypertrophic or thickened. As a result of atrophy and loss of skin elasticity, patients may develop premature exaggerated wrinkling of the skin.  Skin may become hypo‑ or hyperpigmented. In Africa, patients may exhibit localized areas of spotty depigmentation surrounded by slightly hyperpigmented zones occurring mainly on the shins; this condition is known as leopard skin.

Clinical Specimen:
Skin snips:  In areas of endemic infection around the world, the presumptive diagnosis of filarial infections is frequently based on clinical evidence; however, definitive diagnosis is based on the detection of microfilariae, primarily in the skin. 

Laboratory Diagnosis:
Skin snips:  Microfilariae are commonly detected in the skin and must be differentiated from M. streptocerca microfilariae, which are also found in the skin. Multiple skin snips are recommended, with a sensitivity of six snips per person estimated at 91.6%. Infrequently, microfilariae are found in the urine, blood, or sputum, particularly after initiation of DEC treatment. Skin snips should be examined 3 to 6 months after therapy to determine whether treatment was successful. PCR has been used successfully to detect infections using skin snips. The PCR method is significantly more sensitive than routine microscopic methods in detecting microfilariae in skin snips and would be more reliable in detecting active infections than are serologic assays. Microscopic diagnosis cannot detect prepatent infections or low‑level infections from examination of skin snips.

Organism Description:
Adult: The female adult is very long and thin, measuring up to 50 cm by 0.3 mm, while the adult male is 2.5 to 5 cm by 125 to 200 μm. 
Microfilariae:  They are unsheathed, with body nuclei that do not extend to the tail tip, and are 221 to 360 μm long.

Laboratory Report:
Microfilariae identified and reported.

Treatment:
Surgical removal of the adult worms as they are migrating across the bridge of the nose or through the conjunctiva is relatively simple. Diethylcarbamazine (DEC) is an effective treatment; however, in patients with a heavy microfilaremia, anti‑inflammatory drugs may also have to be administered to reduce severe side effects. The most serious sequelae are neurologic complications resembling the encephalitis that is commonly associated with a high microfilaremia. If neurological disorders develop, it is mandatory that therapy with DEC be stopped.  Some individuals may require multiple courses of therapy to be clinically cured. Although DEC is curative in most individuals, relapses can occur within the first 12 months and up to 8 years after treatment.
Both mebendazole and ivermectin have been used to treat loiasis. The use of mebendazole is not promising, whereas ivermectin is effective in reducing microfilaremia. Albendazole, a benzimidazole derivative related to mebendazole, is effective in reducing microfilaremia, and there is a lower risk of encephalopathy; however, repeated courses of therapy may be required. Individuals treated with albendazole have a significant reduction in the levels of eosinophils, antifilarial IgG, and IgG4. Although there were no cures, there is the suggestion that albendazole directly affects the adult stages.    
Garcia, L.S. 2007.  Diagnostic Medical Parasitology, 5th ed., ASM Press, Washington, D.C.

Control:
Treatment of streams and rivers with insecticides has successfully reduced or eliminated transmission. A significant problem in vector control has been the development of resistance to larvicides. A solution to this problem is the rotational use of different larvicides during the treatment campaign. Because of the long life span of the adult worms (15 years or more), campaigns must be continued for extended periods.
In areas where application of insecticides would be difficult, surgical removal of nodules has been used as a means of controlling as well as preventing blindness. Chemotherapy as a means of control has not been previously used because of severe side effects from microfilarial death. Because ivermectin can be given orally, the number of doses is limited in comparison with DEC, and compliance is better than with DEC because ivermectin has fewer side effects. Ivermectin therapy could be used as a control measure to reduce transmission in areas of endemicity. The disadvantages of this approach are cost, the fact that ivermectin is not effective against adult worms unless used in multiple doses, and the finding that in areas where L. loa also exists, treatment may induce encephalitis in L. loa‑infected individuals.