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Randomized Controlled Trial
. 2010 Dec 1;51(11):1229-35.
doi: 10.1086/657063. Epub 2010 Nov 1.

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

Benoit Dembele  1 , Yaya I Coulibaly, Housseini Dolo, Siaka Konate, Siaka Y Coulibaly, Dramane Sanogo, Lamine Soumaoro, Michel E Coulibaly, Salif Seriba Doumbia, Abdallah A Diallo, Sekou F Traore, Adama Diaman Keita, Michael P Fay, Thomas B Nutman, Amy D Klion
Affiliations
Randomized Controlled Trial

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

Benoit Dembele et al. Clin Infect Dis. .

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.

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Figures

Figure 1.
Figure 1.
Flowchart of study participants.
Figure 2.
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.
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.
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.
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.
Table 1.
Baseline Characteristics of the Study Population
Table 2.
Table 2.
Adverse Events in the 2 Study Groups
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Comment in

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