Randomized Clinical Trial on Ivermectin versus Thiabendazole for the Treatment of Strongyloidiasis

Abstract

BackgroundStrongyloidiasis may cause a life-threatening disease in immunosuppressed patients. This can only be prevented by effective cure of chronic infections. Direct parasitologic exams are not sensitive enough to prove cure if negative. We used an indirect immune fluorescent antibody test (IFAT) along with direct methods for patient inclusion and efficacy assessment.Methodology/Principal FindingsProspective, randomized, open label, phase III trial conducted at the Centre for Tropical Diseases (Verona, Italy) to compare efficacy and safety of ivermectin (single dose, 200 µg/kg) and thiabendazole (two daily doses of 25 mg/Kg for two days) to cure strongyloidiasis. The first patient was recruited on 6th December, 2004. Follow-up visit of the last patient was on 11th January, 2007. Consenting patients responding to inclusion criteria were randomly assigned to one of the treatment arms. Primary outcome was: negative direct and indirect (IFAT) tests at follow-up (4 to 6 months after treatment) or subjects with negative direct test and drop of two or more IFAT titers. Considering 198 patients who concluded follow-up, efficacy was 56.6% for ivermectin and 52.2% for thiabendazole (p = 0.53). If the analysis is restricted to 92 patients with IFAT titer 80 or more before treatment (virtually 100% specific), efficacy would be 68.1% for ivermectin and 68.9% for thiabendazole (p = 0.93). Considering direct parasitological diagnosis only, efficacy would be 85.7% for ivermectin and 94.6% for thiabendazole (p = 0.21). In ivermectin arm, mild to moderate side effects were observed in 24/115 patients (20.9%), versus 79/108 (73.1%) in thiabendazole arm (p = 0.00).ConclusionNo significant difference in efficacy was observed, while side effects were far more frequent in thiabendazole arm. Ivermectin is the drug of choice, but efficacy of single dose is suboptimal. Different dose schedules should be assessed by future, larger studies.Trial Registration Portal of Clinical Research with Medicines in Italy 2004–004693–87

Usefulness of Strongyloides stercoralis Serology in the Management of Patients with Eosinophilia

“…Serological cure ranged from 27% to 91.7% depending on cure criteria, treatment protocol, and time of evaluation after treatment. 8,9,[19][20][21][22][23] Time of evaluation seems to be critical, and cure rate in our study could be higher if evaluation was at 12 months or over; Loufty and others 22 reported a serological cure from 38.4% at 3 months to 91.7% at 18 months. Nevertheless, it is important to note that reduction in OD index does not necessarily indicate eradication of S. stercoralis, but a reduction in the total parasite burden.…”

Five Cases of Recurrent Meningitis Associated with Chronic Strongyloidiasis

“…There is a recent report of a randomized clinical trial on ivermectin versus thiabendazole for the treatment of strongyloidiasis. 19 A single dose of 200 mcg/kg ivermectin and two daily doses of 25 mg/kg thiabendazole for 2 days were compared. The study concluded that there were no significant differences.…”

Advances in the Diagnosis of Human Strongyloidiasis

“…It is possible that levels take longer to fall below the cut-off for positivity in patients who have been infected for many years [83]. A post-treatment OD value of over 0.6 has been proposed for defining response to treatment.…”

“…Fecal-based methods (DS, formol-ether concentration, and stool culture) tend to overestimate treatment efficacy compared with serologic methods. One clinical trial comparing the efficacy of ivermectin and thiabendazole for treating strongyloidiasis [83], for instance, reported cure rates of 56.6 % for ivermectin and 52.2 % for thiabendazole based on serologic testing (in-house IFAT) but rates of 85.7 % and 94.6 %, respectively, for direct stool testing.…”