Although no patients had test results negative for W. bancrofti circulating antigen by 24 months, circulating antigen levels decreased in both groups over time. Median percentages of pretreatment levels at 12, 18, and 24 months were 21%, 97%, and 28% in the twice‐yearly treatment group, compared with 23%, 60%, and 31% in the annual treatment group (P values were nonsignificant for differences between the groups all time points). The number of patients with worm nests detectable by ultrasonography also decreased significantly from baseline to 24 months in both groups ( for the annual therapy group and for the twice‐yearly therapy group, by exact McNemar’s test) over time, with only 1 patient with positive results in each group by 24 months.
Effect of treatment on clinical parameters. Progression of clinical disease was comparable in the 2 groups, with 2 previously asymptomatic patients (1 in each group) reporting an episode of lymphangitis and lymphedema at the 6‐month study time point and no new cases of hydrocele, chyluria, or elephantiasis. Eosinophilia (absolute eosinophil count >500 cells/mm3) was present at baseline in 25 (60%) of 42 patients with a median baseline eosinophil count of 584 cells/mm3 (range, 92–3484 cells/mm3). Both the number of patients with eosinophilia and the degree of eosinophilia decreased after treatment, with the most significant change occurring at 6 months after baseline, at which time 11 (29%) of 38 patients had peripheral eosinophilia ( for both groups combined, by exact McNemar’s test) with a median eosinophil count of 286 cells/mm3 (range, 0–1133 cells/mm3) ( , by Wilcoxon signed rank test). Hemoglobin levels did not change in either group over time (data not shown).
Although mass treatment with albendazole and ivermectin has proven to be a successful strategy for the suppression of W. bancrofti microfilarial counts in a variety of settings, elimination of transmission has been reported exclusively in countries where diethylcarbamazine has been administered for many years. Early estimates of the length of time required to eliminate transmission of W. bancrofti infection were based on the assumption that single‐dose antifilarial therapy administered annually for the 4‐ to 6‐year mean reproductive life span of the parasite would be sufficient to permanently interrupt transmission. More recently, computer simulations have demonstrated that the number of years needed to eliminate transmission depends not only on the life span of the parasite but also on the vector species, treatment coverage, drug efficacy, and baseline endemicity. The influence of at least 1 of these parameters, baseline endemicity, on the reduction of transmission has been validated in the field. Drug efficacy is likely to play at least as important a role.
Although a number of studies have suggested that diethylcarbamazine‐containing regimens are more effective than ivermectin and albendazole, the use of diethylcarbamazine to enhance efficacy of mass treatment is contraindicated in most of Africa, including Mali, because of the presence of onchocerciasis. Thus, other methods of enhancing drug efficacy are required in these regions. In the present study, we examined the effects of increased dose and duration of albendazole and ivermectin treatment on the suppression of microfilaremia in an area of lymphatic filariasis endemicity in Mali. Not only did the higher, more frequent dosing lead to reduced levels of microfilaremia at 12, 18, and 24 months, but also microfilariae were undetectable in the peripheral blood specimens of all patients in the high‐dose, twice‐yearly group at these time points. At the community level, enhanced clearance of blood microfilariae could accelerate the interruption of transmission and potentially shorten the duration of mass treatment. Interestingly, no differences in circulating antigen levels or the number of worm nests were seen between the 2 groups, suggesting that the increased efficacy was not due to killing of adult worms.