Use of high-dose, twice-yearly albendazole and ivermectin to suppress Wuchereria bancrofti microfilarial levels

Abstract

Background: Annual mass treatment with albendazole and ivermectin is the mainstay of current strategies to interrupt transmission of Wuchereria bancrofti in Africa. More-effective microfilarial suppression could potentially reduce the time necessary to interrupt transmission, easing the economic burden of mass treatment programs in countries with limited resources.

Methods: To determine the effect of increased dose and frequency of albendazole-ivermectin treatment on microfilarial clearance, 51 W. bancrofti microfilaremic residents of an area of W. bancrofti endemicity in Mali were randomized to receive 2 doses of annual, standard-dose albendazole-ivermectin therapy (400 mg and 150 μg/kg; n = 26) or 4 doses of twice-yearly, increased-dose albendazole-ivermectin therapy (800 mg and 400 μg/kg; n = 25).

Results: Although microfilarial levels decreased significantly after therapy in both groups, levels were significantly lower in the high-dose, twice-yearly group at 12, 18, and 24 months. Furthermore, there was complete clearance of detectable microfilariae at 12 months in the 19 patients in the twice-yearly therapy group with data available at 12 months, compared with 9 of 21 patients in the annual therapy group (P < .001, by Fisher's exact test). This difference between the 2 groups was sustained at 18 and 24 months, with no detectable microfilariae in the patients receiving twice-yearly treatment. Worm nests detectable by ultrasonography and W. bancrofti circulating antigen levels, as measured by enzyme-linked immunosorbent assay, were decreased to the same degree in both groups at 24 months, compared with baseline.

Conclusions: These findings suggest that increasing the dosage and frequency of albendazole-ivermectin treatment enhances suppression of microfilariae but that this effect may not be attributable to improved adulticidal activity.

Figure 1.

Flowchart of study participants.

Figure 2.

Reduction of microfilaremia after high-dose, twice-yearly albendazole and ivermectin (A), compared with standard-dose annual treatment (B). Each symbol represents the value for an individual patient. The horizontal line indicates the geometric mean for the group. *P<.05, annual versus twice-yearly treatment (Wilcoxon-Mann-Whitney U test).

Figure 3.

Clearance of microfilaremia after high-dose, twice-yearly albendazole and ivermectin, compared with standard-dose annual treatment. The bars represent the percentage of patients with detectable Wuchereria bancrofti microfilariae at baseline and 6, 12, 18, and 24 months after treatment. Annual, standard-dose treatment is indicated by the black bars and high-dose, twice-yearly treatment is indicated by the white bars. *P<.05, annual versus twice-yearly treatment (Fisher's exact test).

Figure 4.

Reduction of circulating antigen levels (CAg) after high-dose, twice-yearly albendazole and ivermectin (A), compared with standard-dose, annual treatment (B). Each solid line represents the percentage of pretreatment microfilarial level for an individual patient over time. The dashed line indicates the 100% pretreatment level. *P<.05, annual versus twice-yearly treatment (Wilcoxon-Mann-Whitney U test). BL, baseline.

Figure 5.

Reduction of Mansonella perstans microfilarial levels after high-dose, twice-yearly albendazole and ivermectin (A), compared with standard-dose, annual treatment (B). Each solid line represents the percentage of pretreatment microfilarial levels for an individual patient over time. The dashed line indicates the 100% pretreatment level. *P<.05, compared with baseline (Wilcoxon-Mann-Whitney U test).

Table 1.

Baseline Characteristics of the Study Population

Table 2.

Adverse Events in the 2 Study Groups