Irreversible Effects of Ivermectin on Adult Parasites in Onchocerciasis Patients in the Onchocerciasis Control Programme in West Africa

Abstract

Ivermectin is an effective drug for the treatment of human onchocerciasis, a disease caused by the parasitic filarial nematode Onchocerca volvulus. When humans are treated, the microfilariae normally found in the skin are rapidly and very nearly completely eliminated. Nonetheless, after a delay, microfilariae gradually reappear in the skin. This study is concerned with the causes of this delay. Hypotheses are tested by comparing the results of model calculations with skin microfilaria counts collected from 114 patients during a trial of five annual treatments in the focus area of Asubende, Ghana. The results obtained strongly suggest that annual treatment with ivermectin causes an irreversible decline in microfilariae production of~30%/treatment. This result has important implications for public health strategies designed to eliminate onchocerciasis as a significant health hazard.The registration ofthe anthelminthic drug ivermectin (Mectizan; Merck, Rahway, NJ) in 1987 was a landmark in the control of human onchocerciasis or river blindness, a parasitic disease caused by the filarial nematode Onchocerca volvulus. Oral administration in a standard dose of 150-200 j.Lg/kg of body weight is followed by rapid elimination of microfilariae (Mf) from the skin and gradual reduction of ocular Mf levels [1]. Side effects are generally mild. This makes ivermectin a better therapeutic option than diethylcarbamazine, which is often accompanied by severe Mazotti reactions and ocular damage. Ivermectin also produces a longer suppression ofMfrepopulation of the skin [2,3]. To explain this difference, which was obvious in all studies done so far, the effects of ivermectin on adult parasites were studied.Adult female parasites in treated persons show an interruption of the normal embryogenesis, but after a single treatment, this appears to be reversible for most of the worms [4,5]. Excess worm mortality was not observed after a single treatment [1, 2, 6], although significant numbers of dead and mori-

Rates of microfilarial production by Onchocerca volvulus are not cumulatively reduced by multiple ivermectin treatments

“…Although their modelling approach is different from ours, and the frequency of treatment in Asubende, Ghana (Alley et al 1994) was annual rather than 6-monthly as in Guatemala, the results of both studies are compatible and also comparable to those obtained by Basáñ ez et al (2008), who modelled the effect of a single ivermectin dose. However, Plaisier et al (1995) found that a progressive reduction of microfilarial production with each dose would be the scenario most consistent with the data. It would be very interesting to reanalyse such data with the modelling approach presented here, as projections of onchocerciasis elimination assume operation of such cumulative effects (Winnen et al 2002).…”

“…45) were releasing live microfilariae. This finding is less easy to compare to our result although the two may be consistent if ivermectin eliminates microfilarial production in a proportion of worms and has little or no effect in the remaining worms, as proposed by Plaisier et al (1995).…”

“…Basáñ ez et al (2008) have conducted a systematic review and mathematical modelling of meta-analysed data both for the microfilaricidal and embryostatic effects of single-dose ivermectin, and their results agreed with those of Plaisier et al (1995) who found that about 10-12 months after treatment microfilarial production would have recovered only to y65-70 % of its initial value. However, the question still remains as to whether or not this effect is cumulative, i.e.…”

Identifying sub-optimal responses to ivermectin in the treatment of River Blindness

“…1B, Table 1). Transmission intensity was concomitantly measured only in the Guatemalan study (18), so it is difficult to ascertain whether this is due to a reduction in the force of infection or a cumulative impact of ivermectin on female worm fertility (13,14). No significant difference in the rate of skin repopulation was seen between rounds 1, 2, and 4 if hosts with no detectable microfilariae at the time of treatment were excluded from the analysis (Table 1).…”

Nodding syndrome in Mundri county, South Sudan: Environmental, nutritional and infectious factors

“…Ivermectin has a limited effect on the viability of O. volvulus microfilaria, [91][92][93][94][95] which have an estimated reproductive life span of 12-15 years. [96][97] Consequently single treatments with ivermectin do not change the infection status of treated subjects, and the effect of ivermectin mass treatment on infection prevalence is primarily due to reduction in transmission. [98][99][100][101][102][103] Between 1987 and 2011, the Mectizan Donation programme approved 139,265,010 ivermectin treatments for Africa.…”