Key Mectizan Expert Committee Recommendations

Mectizan Expert Committee Statement on Nonresponders in Ghana

Onchocerciasis, or river blindness, is found in 34 countries in which there are estimated to be some 100 million persons at risk of infection. Since 1988, active Mectizan distribution programs have been conducted in 32 countries. To date over 540 million treatments have been approved by the Mectizan Donation Program. The distribution of Mectizan through the Program’s many partners has controlled the public health consequences of infections in many of the world’s worst affected regions.

From the beginning of mass distribution the Program has been alert to the potential for changes in responsiveness by the parasite to Mectizan. A report in the Lancet by Osei-Atweneboana and colleagues has raised concerns about responsiveness to Mectizan in some villages in Ghana.¹  A newly released study from McGill University reported genetic changes in the β-tublin gene following treatment.² 

The methods by which Mectizan acts on Onchocera volvulus parasites are not well understood. However there appear to be three separate actions on parasites: destruction of microfilariae, the reduction in embryo formation in the female macrofilariae (adult worms) and a poorly understand effect on the adult worms themselves. These recent reports have concerned changes in embryo formation within the female macrofilarae and perhaps within the embryo themselves. 

Clearly, as the authors note, these are areas requiring further investigation.Any change in responsiveness of onchocerciasis to Mectizan is of great concern to MDP, and to the countless number of persons from professionals to the communities which direct annual treatment. In consultation with its partners MDP is reviewing these recent reports, assessing their implication for distribution, treatment and monitoring strategies in the control strategies for onchocerciasis.                   

1 Osei-Atweneboana MY, Eng JK, Boakye DA, Gyapong JO, Prichard RK. Prevalence and intensity of Onchocerca volvului infection and the efficacy of ivermectin in endemic communities in Ghana: A two-phase epidemiological study. Lancet, 2007;369:2021-2029.

2 Bourguinat C, Pion SDS, Kamgno J, Gardon J, Duke BOL,Boussinesq M, Prichard RK. Genetic selection of low fertile Onchocerca volvulus by ivermectin treatment. PLoS Neglected Tropical Diseases, 2007; 1: 1-11.

January 2006  Recommendation of the Mectizan Expert Committee for mass drug Administration of ivermectin and albendazole for LF elimination in Loa loa-endemic areas where onchocerciasis is also hyper- or meso-Endemic

After a re-review and discussion of the available data by a sub-group of the MEC/AC, the MEC/AC concluded that, there is neither a biological rationale nor available data to suggest that the addition of albendazole to Mectizan would increase the number or severity of adverse reactions if the two drugs were to be used together to treat populations co-endemic for onchocerciasis, LF and loiasis. However, for optimal safety when the combination of albendazole and Mectizan is first utilized in such co-endemic or potentially co-endemic areas, enhanced pharmacovigilance would be appropriate. Based on these assessments and in view of the well recognized inverse relationship between the number of cycles of Mectizan treatment and the incidence of SAEs seen in populations with any of these filarial infections, the specifics of the enhanced pharmacovigilance required need not be the same for all loa/LF/hyper-meso oncho co-endemic or potentially co-endemic areas. In those areas that have already received two or more cycles of Mectizan treatment with good coverage, the level of Loa loa microfilaraemia is likely to be reduced far below levels associated with encephalopathy and other SAEs.

Consequently, it can be recommended that the addition of albendazole could proceed with enhanced passive surveillance as currently recommended for Mectizan administration for onchocerciasis in Loa-endemic areas.

In areas that have received no previous Mectizan treatment, 1 round of prior treatment or have had poor prior coverage, active surveillance similar to that employed at the initiation of the global LF elimination programme should be undertaken until a minimum of 15,000 individuals have been assessed.

Based on the prior data from Cameroon, statistical considerations indicate that this number of individuals would permit the detection of any significant increase in SAEs that might be associated with the addition of albendazole to Mectizan in such Loa-endemic areas. If no increase is seen during this active surveillance, enhanced passive surveillance could then be instituted. To address the risk of Loa loa associated Serious Adverse Experiences (SAEs) after treatment with Mectizan for onchocerciasis, recommendations for the use of Mectizan in areas where the two diseases are co-endemic have been issued by the Mectizan Expert Committee in consultation with the Technical Consultative Committee of the African Programme for Onchocerciasis Control (APOC).

The following pdf files contain the recommendations, which take into account the endemicity of L. loa when assessing the risk of SAEs occurring after Mectizan® treatment for onchocerciasis. Included in the recommendations are annexes that provide guidance for the clinical management of cases of L. loa encephalopathy and a list of suggested medical supplies and equipment for the management of such cases.

We hope that these recommendations will be useful to you.

Should you need further information or clarification of their content, please contact the Mectizan Donation Program.