Serious adverse events following treatment with ivermectin for onchocerciasis control: a review of reported cases

Abstract

This paper presents a summary of reported cases of Serious Adverse Events (SAEs) following treatment with Mectizan(R) (ivermectin, Merck, Sharpe & Dohme) in onchocerciasis mass treatment programs from January 1, 1989 to December 31, 2001 through a passive surveillance system. A total of 207 SAE cases were reported out of approximately 165 million reported treatments delivered during the period under review, giving rise to a cumulative incidence of 1 reported SAE per 800,000 reported treatments. The mean age was 40 years and 70% of the cases were males. The mean time between ivermectin intake and onset of illness was 1 day. For 57% of the cases (n = 118), that was their first exposure to ivermectin. The majority of cases were reported from Cameroon (n = 176; 85%) with peaks in the incidence of SAE reporting in 1989-1991 and 1994-1995 when the program expanded to ivermectin-naïve populations. Fifty-five percent of the cases from Cameroon (i.e. 97 out of 176 cases) were encephalopathic and were reported from the central-southern region of the country; two-thirds of these cases were 'probable' or 'possible' cases of Loa loa encephalopathy temporally related to ivermectin treatment. Reporting bias may explain some but not all of the differences in SAE reporting between the 34 onchocerciasis-endemic countries that have, or have had, mass treatment programs. Further research is needed to understand the apparent clustering of encephalopathy cases in central-southern Cameroon since L. loa infection alone probably does not explain the increased incidence of this type of SAE from this region.

Figure 1

Annual frequency of SAEs reported to have occurred following ivermectin mass treatment from 1989 to 2001* *cases reported as of August 31, 2002

Figure 2

Geographical distribution of all SAEs reported to have occurred following mass treatment with ivermectin from 1989 to 2001 (as of August 31, 2002)

Figure 3

Proportion of SAEs reported to have occurred following ivermectin mass treatment from 1989 to 2001*, by reporting country; *cases reported as of August 31, 2002; † all reported cases from Sudan are from the southern region; ‡other reporting countries are Ethiopia (n = 1), Liberia (n = 1) and Central African Republic (n = 1).

Figure 4

Annual frequency of SAEs reported to have occurred following ivermectin mass treatment from 1989 to 2001*, by reporting country; *cases reported as of August 31, 2002; †all reported cases from Sudan are from the southern region; ‡other reporting countries are Ethiopia (n = 1), Liberia (n = 1) and Central African Republic (n = 1).

Figure 5

Incidence of reported SAEs following ivermectin mass treatment from selected countries in Central Africa, 1989 to 2001*; *cases reported as of August 31, 2002; † CAR=Central African Republic; DRC=Democratic Republic of Congo; ‡ all reported cases from Sudan are from the southern region.