Loa loa encephalopathy temporally related to ivermectin administration reported from onchocerciasis mass treatment programs from 1989 to 2001: implications for the future.

Of the 207 Serious Adverse Events (SAEs) following treatment with Mectizan(R) (ivermectin, Merck, Sharpe & Dohme) that were reported from 1989 to 2001 through the passive SAE surveillance system required of all onchocerciasis mass treatment programs, 65 were cases of 'Probable' or 'Possible' Loa loa Encephalopathy temporally Related to treatment with Mectizan(R) (PLERM).A retrospective analysis of these 65 PLERM cases revealed that 97% were from southern Cameroon, 85% were male and 93% were being treated with ivermectin for the first time. The mean time to onset of symptoms was 1.7 days (95% CI: 1.3, 2.2) but the mean time to receiving medical attention after the onset of symptoms was 2.0 days (95% CI: 1.5, 2.6). Hospitalization was reported in 53 cases with a mean duration of 27.5 days (95% CI: 13.3, 41.6, n = 35). Clinical outcome was reported in 34 cases: 64.7% recovered fully, 11.8% had partial neurologic deficit and 23.5% died. For the 32 cases where quantitative L. loa data were reported, the arithmetic means with 95% confidence intervals were for 1) peripheral blood: pre-treatment - 164,250 mf/ml (79,537, 248,963; n = 4); post-treatment within 1 month - 3926 mf/ml (2,128, 5,725; n = 21) and within 5 to 6 months - 7800 mf/ml (3417, 12,183; n = 7); and for 2) cerebrospinal fluid: 32 mf/ml (7, 37; n = 10) within 1 month post-treatment.Pending further research on practical methods to exclude individuals with high intensity L. loa infection from onchocerciasis mass treatment programs, more emphasis should be placed on surveillance and monitoring to ensure early recognition, referral and management of SAEs, during the first 2 years when majority of the population is presumably naïve to ivermectin.