Abstract
The evolution and persistence of ocular pathology was assessed in a cohort of Onchocerca volvulus infected patients treated annually with ivermectin for 23 years. Patients were resident in rural Central and Kara Region of Togo and ocular examinations included testing of visual acuity, slit lamp examination of the anterior eye segment and the eye fundus by ophthalmoscopy. Before ivermectin treatment, vivid O.volvulus microfilariae (MF) were observed in the right and left anterior eye chamber in 52% and 42% of patients (n = 82), and dead MF were seen in the right and left cornea in 24% and 15% of cases, respectively. At 23 years post initial treatment (PIT), none of the patients (n = 82) presented with MF in the anterior chamber and cornea. A complete resolution of punctate keratitis (PK) lesions without observable corneal scars was present at 23 years PIT (p<0.0001), and sclerosing keratitits (SK) lessened by half, but mainly in patients with lesions at early stage of evolution. Early-stage iridocyclitis diminished from 42%(rE) and 40%(lE) to 13% (rE+lE)(p<0.0001), but advanced iridocyclitis augmented (p<0.001) at 23 years PIT compared to before ivermectin. Advanced-stage papillitis and chorioretinitis did not regress, while early-stage papillitis present in 28%(rE) and 27%(lE) of patients at before ivermectin regressed to 17%(rE) and 18%(lE), and early-stage chorioretinitis present in 51%(rE+lE) of cases at before ivermectin was observed in 12%(rE) and 13%(lE) at 23 years PIT (p<0.0001). Thus, regular annual ivermectin treatment eliminated and prevented the migration of O. volvulus microfilariae into the anterior eye chamber and cornea; keratitis punctata lesions resolved completely and early-stage sclerosing keratitits and iridocyclitis regressed, whilst advanced lesions of the anterior and posterior eye segment remained progressive. In conclusion, annual ivermectin treatments may prevent the emergence of ocular pathology in those populations still exposed to O.volvulus infection. Trial Registration: www.pactr.org PACTR201303000464219)
Highlights
In West Africa, onchocerciasis is successfully controlled by the African Program for Onchocerciasis Control (APOC) and in large parts the disease is no longer considered a public health problem [1], and in certain onchocerciasis endemic foci in Mali and Senegal elimination is considered achievable [2,3]
Patients were initially enrolled in a phase III double-blind placebo-controlled dose finding study of ivermectin, and from month 18 post initial treatment (PIT) onwards all patients received annual ivermectin treatment with 150 ug/kg as a single dose
Patients were initially enrolled in a phase III double-blind placebo-controlled dose finding study of ivermectin and were treated either with 100, 150 or 200 ug/kg ivermectin or received placebo; from months 18 post initial treatment (PIT) onwards, all patients received annual ivermectin treatment with 150 mg/kg as a single dose
Summary
In West Africa, onchocerciasis is successfully controlled by the African Program for Onchocerciasis Control (APOC) and in large parts the disease is no longer considered a public health problem [1], and in certain onchocerciasis endemic foci in Mali and Senegal elimination is considered achievable [2,3]. Ivermectin therapy is associated with mild systemic adverse responses [6] and repeated treatments will alleviate hyper-reactive skin manifestations in patients and prevent the progression to chronic dermal pathology [12,13]. Despite repeated ivermectin treatments for years female adult O. volvulus remain reproductive [16], and unresponsiveness of O. volvulus to ivermectin treatment in some areas of West Africa might have emerged as a further problem for onchocerciasis control [17]
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