While ivermectin plus albendazole was not superior in the treatment of onchocerciasis compared with ivermectin alone, semiannual treatment with or without albendazole was superior to annual treatment for suppressing microfilaria in the skin, according to research results published in Clinical Infectious Diseases.

Although ivermectin has good activity against microfilaria, it does not kill Onchocerca volvulus adult worms in the doses commonly used in onchocerciasis control programs in many African countries. Because albendazole has been demonstrated to have embryotoxic effects in adult female O volvulus worms, researchers compared the effects of repeated doses of ivermectin plus albendazole with those of ivermectin alone for killing and/or sterilization of adult female O volvulus worms and for clearing/suppressing skin microfilaria.

In this randomized, open-label clinical trial, 272 microfilaria-positive participants from 36 onchocerciasis-endemic communities in Ghana that had practiced mass drug administration of ivermectin since 2009 were randomly assigned into 4 treatment groups:

  • Ivermectin annual: Ivermectin 200 μg/kg single dose given at 0, 12, and 24 months
  • Ivermectin semiannual: Ivermectin 200 μg/kg single dose given at 0, 6, 12, 18, and 24 months
  • Ivermectin+albendazole annual: Ivermectin 200 μg/kg plus albendazole 800 mg single dose, given at 0, 12, and 24 months
  • Ivermectin+albendazole semiannual: Ivermectin 200 μg/kg plus albendazole 800 mg single dose, given at 0, 6, 12, 18, and 24 months

The primary outcome was the proportion of fertile and viable female worms in onchocercomata excised at 36 months. Two data sets were used to analyze the data: intention-to-treat (ITT) and per protocol. The ITT included all participants randomly assigned to 1 of the 4 treatment arms and who took the drugs at least once. The per protocol set included all participants who completed the treatment without any violations of the protocol and were present for nodulectomies at 36 months. The ITT set was used for the primary analysis of all parameters and the per-protocol set was used to confirm the ITT results.

The percentage of dead female worms did not differ between the treatment groups (ITT analysis, P =.9198; PP analysis, P =.7206) and remained the same when only patients with previous ivermectin treatment were considered. Post-treatment nodule histology showed that 15/135 (11.1%), 22/155 (14.2%), 35/154 (22.7%), and 20/125 (16.0%) living female worms had normal embryogenesis in the ivermectin annual, ivermectin semiannual, ivermectin+albendazole annual, and ivermectin+albendazole semiannual arms, respectively (P =.1229). Per-protocol analysis confirmed the ITT analysis (P =.1722).

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The percentage of individuals who completely cleared microfilaria at 36 months was 35/56 (63%) after annual ivermectin, 42/59 (71%) after semiannual ivermectin, 39/64 (61%) after annual ivermectin+albendazole, and 43/53 (81%) after semiannual ivermectin+albendazole. Microfilaria clearance was not improved or sustained with the addition of albendazole. However, the semiannual drug administration resulted in superior sustained microfilaria clearance (annual, 62%; semiannual, 76%; P =.024). Multivariable analysis confirmed these findings.

Adverse events included cutaneous itching, different types of pain, swollen limbs, headache, cutaneous rash, fever, swollen face, and other conditions such as nausea, dizziness, vomiting, abdominal discomfort, and ocular reactions. There were 6 deaths among the study cohort, but none were related to the study drugs.

Findings from this study suggested that switching from annual to semiannual treatment with ivermectin, with or without albendazole, may result in significantly lower microfilaria burdens. Although ivermectin plus albendazole did not show increased activity against O volvulus worms, researchers postulated that one could “argue that the combination should be used for onchocerciasis elimination even in areas without [lymphatic filariasis] because of the [soil transmitted helminths] benefit that albendazole provides.”

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Reference

Batsa Debrah L, Klarmann-Schulz U, Osei-Mensah J, et al. Comparison of repeated doses of ivermectin versus ivermectin plus albendazole for treatment of onchocerciasis – a randomized open-label clinical trial [published online September 19, 2019]. Clin Infect Dis. doi:10.1093/cid/ciz889

This article originally appeared on Infectious Disease Advisor