Onchocerciasis medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Kalsang Dolma, M.B.B.S.[2]

Overview

The treatment of choice for onchocerciasis is ivermectin, which has been shown to reduce the occurrence of blindness and to reduce the occurrence and severity of skin symptoms. An evolving treatment is doxycycline, which has been shown in studies to kill Wolbachia, an endosymbiotic rickettsia-like bacteria that appears to be required for the survival of the O.volvulus macrofilariae and for embryogenesis. Doxycycline does not kill the microfilariae, so treatment with ivermectin would be needed to result in a more rapid decrease of symptoms.

Medical Therapy

The treatment of choice for onchocerciasis is ivermectin, which has been shown to reduce the occurrence of blindness and to reduce the occurrence and severity of skin symptoms. Ivermectin kills the microfilariae (larvae), but not the macrofilariae (adult worms). There is no evidence that prolonged daily treatment provides any benefit over annual treatment, as one dose results in a significant decrease in microfilarial load that lasts a year or more. Treatment with higher than recommended doses has an increased incidence of side effects and may even be harmful. Although ivermectin does not kill the macrofilariae, it does sterilize the females. There is evidence that treating people with ivermectin more frequently than once a year facilitates more rapid sterilization of the female and that treating a person who no longer lives in an endemic area more frequently, such as every 3 to 6 months could result in a shorter duration of symptoms. Treatment for a patient who will not be returning to live in an endemic area should be given every six months (and dosing as frequent as every 3 months could be considered) for as long as there is evidence of continued infection. Evidence of continued infection would include skin symptoms such as pruritus, microfilariae in skin biopsies, and microfilariae on eye exam. Finding adult worms in nodules would not necessarily constitute evidence of the need for continued treatment, as the macrofilariae do not cause symptoms and ivermectin does not kill the macrofilariae. Treatment with ivermectin can cause mild symptoms associated with death of the microfilariae, such as increase itching, but there is no worsening of eye symptoms. Severe adverse reactions to ivermectin in the absence of Loa loa co-infection are rare. An evolving treatment is doxycycline, which has been shown in studies to kill Wolbachia, an endosymbiotic rickettsia-like bacteria that appears to be required for the survival of the O. volvulus macrofilariae and for embryogenesis. Treatment with a 6-week course of doxycycline has been shown to kill more than 60% of the adult female worms and to sterilize 80 to 90% of the females 20 months after treatment. Doxycycline does not kill the microfilariae, so treatment with ivermectin would be needed to result in a more rapid decrease of symptoms. Most protocols that have examined the effectiveness of doxycycline had given treatment with ivermectin 4 to 6 months after treatment with doxycycline, so the safety of simultaneous treatment is not known. As doxycycline does not result in the rapid death of the parasites and as most of the mild side effects of ivermectin treatment are thought to be related to rapid release of Wolbachia antigens, the side effect profile of the medication when used for the treatment of onchocerciasis does not appear to be different than that of its use for other indications. There is limited data to suggest that treatment of onchocerciasis in patients co-infected with Loa loa is safe, but this is limited to one randomized controlled trial where only people with Loa microfilarial loads < 8,000 per mL were treated and one community-based study of doxycycline treatment in co-endemic areas in which Loa microfilarial loads were not determined. Older treatments for onchocerchiasis, such as suramin and diethylcarbamazine should not be used. Suramin has multiple systemic toxicities that limit its use in the presence of other less toxic and effective therapies. Diethylcarbamazine accelerates the development of onchocercal blindness.

Shown below is a table summarizing the preferred and alternative empiric treatment for Onchocerciasis

Characteristics of the Patient	Possible Pathogens	Preferred Treatment	Duration of Treatment	Alternative Treatment
Adult	Onchocerca volvulus (microfilariae)	Ivermectin 150 mcg/kg orally in one dose	Every 6 months	Doxycycline 200 mg orally daily for 6 weeks
Pediatric	Onchocerca volvulus (microfilariae)	Ivermectin 150 mcg/kg orally in one dose	Every 6 months	Doxycycline 200 mg orally daily for 6 weeks

Doxycycline is not standard therapy, but several studies support its use and safety. Treatment with ivermectin should be given several days prior to treatment with doxycycline in order to provide symptom relief to the patient. If the patient cannot tolerate 200 mg PO daily of doxycycline, 100mg PO daily is sufficient to sterilize female Onchocerca.

Note on Treatment in Pregnancy

Data on the use of ivermectin in pregnant women is limited, though the available evidence suggests no difference in congenital abnormalities in the children of women who were accidentally treated with ivermectin compared with those who were not. The risk of blindness probably outweighs the risk of treatment with ivermectin after the first trimester. Doxycycline is contraindicated in pregnant and lactating women.

Note on Treatment in Pediatric Patients

The safety of ivermectin in children who weigh less than 15kg has not been demonstrated. Doxycycline in contraindicated in children less than 9 years old and has not been studied in the treatment of onchocerciasis in children less than 12 years old.

Note on Treatment in Patients Co-infected with Loa loa

Patients with Loa loa co-infection should not be treated for onchocerciasis without consulting an expert on loaiasis due to the risk of a fatal encephalitic reaction to ivermectin. Treatment of co-infected people with doxycycline has only been studied in persons with Loa counts of <8000 microfilariae per mL.