Ophthalmologic Manifestations of Onchocerciasis Treatment & Management

On the basis of the principle that microfilariae cannot mature in the human host, it was once believed that eradication of the adult worm could potentially cure the infection. Nodulectomy was practiced through a systematic denodulization in most endemic areas of Guatemala. No evidence exists that the prevalence of onchocerciasis was reduced by this mode of treatment.

Drugs used in the treatment of onchocerciasis are described below.

• DEC is an anthelmintic that was used in the past for the treatment of the microfilarial phase of onchocerciasis. It is administered orally as tablets. It is absorbed rapidly from the gastrointestinal tract, skin, and conjunctiva.

  • The microfilaricidal activity of DEC is associated with a series of dermal, ocular, and systemic reactions known as the Mazzotti reaction. These reactions may be mild to severe and include itching, rash, headache, joint pain, swollen lymph nodes, fever, tachycardia, vertigo, and hypotension.
  • Mobilization of the microfilariae leads to other serious signs of ocular toxicity, such as punctate keratitis, optic neuritis, and visual field loss. (DEC is no longer recommended for the treatment of onchocerciasis.)
• Suramin (Antrypol) is the only drug in clinical use that is effective against adult worms of onchocerciasis. It is administered by slow intravenous injection, usually as a 10% solution. A total dose of 66.7 mg/kg in 6 incremental weekly doses is recommended.

  • Severe adverse effects, such as thrombocytopenia, neutropenia, and hemolytic anemia, limit the use of suramin. Ocular toxicity includes photophobia, foreign body sensation, lacrimation, edema, cornea deposits (verticillata), and a high incidence of optic atrophy.
  • Because of the toxic effects, suramin is only considered for treatment of severe hyperreactive onchodermatitis that does not respond to ivermectin for individuals in areas without transmission of onchocerciasis and individuals living in endemic areas.
• Amocarzine (CGP-6140), an antifilarial anthelmintic drug, is derived from amoscanate. It has the advantage of killing adult worms.
• Ivermectin

  • A semisynthetic macrocyclic lactone, ivermectin (Stromectol, Mectizan) was introduced in 1982 by its producers Merck, Sharp, and Dohme, who offered the drug free of cost for use in developing countries. Isolated from the fermentation products of Streptomyces avermitilis, ivermectin has balanced activity against the spectrum of nematodes and arthropods.
  • Given as a single dose of 150 µg/kg, it reduces the number of microfilariae in the skin to 83.2% after 3 days and 99.5% after 3 months. A reduction greater than 90% is maintained up to 1 year after a single dose. In some patients, an increase of microfilariae in the anterior chamber is noticed at day 3 after treatment, but it reduces greatly after 3 months. Ivermectin is considered to be an excellent tool for the treatment of onchocerciasis and reduction of blindness rates.
  • Because a single dose of 12 mg reduces the microfilariae count to a low level for as long as 2 years, retreatment of the patients at 6- to 18-month intervals is required in endemic areas.
  • Since its availability, ivermectin has been given to 55 million Africans. It is projected that 80 million people will be treated by the year 2015.
  • Stromectol has no activity against adult O volvulus parasites in the onchocercomata. Therefore, follow-up care and retreatment is required.
  • The macrofilaria (adult worms) can live in a human host for about 12 years. For this reason, annual treatment is required. To interrupt transmission, treatment must continue indefinitely. The search for a new drug that can permanently treat this disease without the need for repeated annual treatments is desired. Moxidectin is believed to be one such drug. Moxidectin is a parasiticide used for the prevention of heartworms and intestinal worms in cats, horses, cattle, and sheep. It is a fermentation product from Streptomyces cyaneogriseus spp noncyanogenus. Moxidectin is being evaluated in a phase II clinical trial, in which 192 persons infected with onchocerciasis are enrolled. Following the trial period, moxidectin will hopefully be available to endemic countries by the year 2012.
  • About 1-5% of patients on ivermectin may experience allergic and inflammatory reactions to dead microfilariae. These reactions may include facial and peripheral edema, headache, myalgia, arthralgia/synovitis, axillary, cervical and inguinal lymph node enlargement, orthostatic hypotension, and tachycardia.
  • Ocular toxicity includes eyelid edema, anterior uveitis, conjunctivitis, limbitis, punctate keratitis, chorioretinitis, or choroiditis.
  • Increased hemoglobin and eosinophilia is seen in 1% of patients.
  • Pretreatment with aspirin and antihistamines usually prevents discomfort. Concomitant community-based treatment has reduced the incidence of new infections.
  • In countries covered under the Onchocerciasis Control Programme (OCP), vector control is combined with large-scale ivermectin distribution. In 1996, more than 2.6 million people were treated with ivermectin within the program area.
  • In Uganda, vector control combined with ivermectin significantly reduced onchocercal dermatitis from 34% (precontrol) to 2.9% (P < 0.001), microfilariae carrier rates from 88% to 7.5% (P < 0.001), and nodule prevalence from 49% to 19.2% (P < 0.001). Because ivermectin in parallel with vector elimination had a greater impact on onchocercal dermatitis and microfilariae carrier rates than ivermectin alone, considering ivermectin supplementation with vector elimination in all isolated foci with Simulium neavei transmission is worthwhile to hasten the elimination of onchocerciasis.
  • The African Programme for Onchocerciasis Control (APOC), which supports onchocerciasis control in endemic African countries outside the OCP, distributes ivermectin to communities in high-risk areas as determined by rapid epidemiological mapping of onchocerciasis (REMO) and geographic information systems (GIS).
  • Yearly or biannually ivermectin prophylaxis is not advisable for everyone. This drug is not safe for pregnant women; lactating mothers; breastfeeding babies; children younger than 5 years; and people with heart, liver, and kidney diseases.
  • Ivermectin treatment improves ocular manifestations. All anterior segment morbidity, including advanced sclerosing keratitis, advanced uveitis, and optic neuropathy, improve, while chorioretinal lesions continue to expand despite treatment.
  • Efforts thus far have focused on another chemotherapeutic approach, doxycycline. This agent acts on endosymbiotic bacteria, Wolbachia, in O volvulus. Many filarial nematodes harbor Wolbachia endobacteria, which, as symbionts, are essential for the fertility of their hosts. Doxycycline (100 mg/d PO for 6 wk) targets endosymbiotic bacteria and results in long-term sterility of adult female worms and in a corresponding absence of microfilariae. In Ghana, when ivermectin was given after doxycycline, it resulted in a strong and sustained (18 mo) reduction of microfilariae loads to levels of less than 0.3 mf/mg. This may be a useful adjunctive therapy to ivermectin.
  • Levamisole had little effect on the efficacy of ivermectin when given in combination with this agent. Similarly, the combination of levamisole and albendazole was not efficacious. In fact, the combination of levamisole with ivermectin or albendazole induced unexpected adverse events.

Nodulectomy was practiced through a systematic denodulization in most endemic areas of Guatemala.