To assess the efficacy and safety of single dose ivermectin, and to compare its performance with that of diethylcarbamazine (DEC).

MEDLINE was searched using the terms 'filariasis', 'Wuchereria bancrofti' and 'clinical trial'. The reference lists of the retrieved publications were also reviewed for additional articles. Proceedings of conference abstracts and published abstracts were excluded.

Study designs of evaluations included in the review

Randomised controlled trials (RCTs) and controlled trials were included.

Specific interventions included in the review

One course (single dose) of ivermectin (some studies compared different dosages). DEC was the comparator, and was administered as either a standard course of 6 mg/kg for 12 days or as a single dose.

Participants included in the review

People with Wuchereria bancrofti infection were included. The participants' ages ranged from 15 to 84 years.

Outcomes assessed in the review

Microfilaraemia (mf) prevalence and adverse reactions were assessed.

How were decisions on the relevance of primary studies made?

The authors do not state how the papers were selected for the review, or how many of the authors performed the selection.

The quality of the trials was assessed on the basis of criteria adopted from Chalmers et al. (see Other Publications of Related Interest). The maximum achievable score was 100 points. Two reviewers assessed the studies independently using the criteria described, and any discrepancies were adjudicated by a consensus meeting.

The data were abstracted independently by two investigators onto data extraction forms. The two investigators met afterwards to cross-check their reports and reconcile any differences.

How were the studies combined?

The effect size was defined as the percentage reduction of the pre-treatment mf-density (per mL) and the prevalence (%) of mf-positive patients. The chi-squared test for trend analysis was performed to compare mf prevalence and the incidence of adverse reactions for groups given different doses of ivermectin. groups. Chi-squared or Fisher's exact test was used to examine the difference in mf prevalence between ivermectin and DEC regimens. Analyses were performed with weighting based on both sample size and study quality.

How were differences between studies investigated?

The authors do not state how differences between the studies were investigated.

Fifteen studies (748 participants) were included: 8 RCTs (435 participants) comparing ivermectin with DEC, and 7trials (313 participants) comparing different doses of ivermectin.

1. Dose-finding trials.

Efficacy: when combining all dose groups, approximately 90% of the patients became mf-negative within one week after treatment. After one month, microfilariae were subsequently detected in the blood in one third of the patients. By 3 months, the prevalence rose to around three-quarters, which was sustained until the one-year follow-up. Prevalence reduction did not appear to depend on the dose; only after one month was prevalence lower for those given higher doses (chi-squared test for trend 12.16, p<0.001).

Safety: 80% (316 out of 395) of patients experienced at least one adverse event. The most commonly reported adverse reactions were: fever, 66% (208 out of 313); headache, 72% (203 out of 280); weakness, 49% (122 out of 250); myalgia, 48% (151 out of 313); chill, 51% (121 out of 239); and lethargy, 74% (73 out of 99). A chi-squared test for trend showed no significant difference in the frequency of adverse reactions among the different dose groups (chi-squared 2.06, p=0.152).

2. Ivermectin compared with DEC.

Efficacy: during the first month of treatment, mf-density was 1.5 to 1.9% in participants treated with ivermectin, compared with 3.6% in those given the standard course of DEC and 18.9% in those given single-dose DEC. Compared with low-dose ivermectin (20 to 150 microg/kg), both DEC regimens suppressed the mf-counts for longer. The standard DEC treatment seemed to be the most effective for suppression of microfilaraemia at the 2-year follow-up, but the numbers were small. From the one-month follow-up onwards, mf-prevalences after a standard course of DEC were significantly lower (p<=0.003) than for both the other regimes. Except for the first week, no significant differences were found between single-dose DEC and ivermectin.

Adverse effects: systemic adverse effects were similar for both drugs. However, some studies demonstrated that localised reactions were more prominent with DEC.

The meta-analysis found that ivermectin given at a single annual dose of 200 microg/kg body weight or higher, whether or not in combination with DEC, has great potential for therapeutic strategies to control bancroftian filariasis.

The review was clearly written with well-defined inclusion criteria and an assessment of study validity. Although MEDLINE was searched, other studies may have been retrieved by searching other databases such as EMBASE. Furthermore, the exclusion of conference abstracts could have resulted in publication bias. The authors' conclusions do not appear to be supported by the results of the review. Firstly, the authors state that 200 microg/kg of ivermectin should be used. The results suggest, however, that DEC was more effective than ivermectin at suppressing mf-counts and lowering mf-prevalence. Furthermore, within the dose-finding trials, the authors reported that prevalence reduction does not depend on the dose. Secondly, the authors allude to the efficacy of ivermectin in combination with DEC, but there were no trials included in the review that compared ivermectin with or without DEC.

The authors did not state any implications for further research.

Chalmers TC, Smith H, Blackburn B, Silverman B, Schroeder B, Reitman D, et al. A method for assessing the quality of a randomized control trial. Control Clin Trials 1981;2:31-49.

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.