Spatial clustering of filarial transmission before and after a Mass Drug Administration in a setting of low infection prevalence

Abstract

BACKGROUND: In the global program for the elimination of lymphatic filariasis (LF) longitudinal assessment of the prevalence of microfilaremia and antigenemia is recommended to monitor the effect of mass treatment on transmission. Additional monitoring tools such as entomologic and antibody methods may be useful in identifying residual foci of infection. In this study, we characterized serologic markers of infection and exposure spatially both before and after mass treatment, in an area of initial low Wuchereria bancrofti infection prevalence. METHODS: Consenting persons in the sentinel community were tested for circulating microfilaria and antigen (by immunochromatographic test) before and after the 1st annual mass drug administration of diethylcarbamazine and albendazole. A cohort of 161 persons provided serum specimens both years that were tested for antifilarial IgG (1 and 4) antibody. Every house was mapped using a differential Global Positioning System; this information was linked to the serologic data. W. bancrofti infection in the mosquito vector was assessed with year-round collection. Multiple linear regression was used to investigate the influence of antigen-positive persons on the antifilarial antibody responses of antigen-negative neighbors. RESULTS: After mass treatment, decreases were observed in the sentinel site in the overall prevalence of antigen (10.4% to 6.3%) and microfilaremia (0.9 to 0.4%). Of the persons in the cohort that provided serum specimens both years, 79% received treatment. Antigen prevalence decreased from 15.0% to 8.7%. Among 126 persons who received treatment, antigen and antifilarial IgG1 prevalence decreased significantly (p = 0.002 and 0.001, respectively). Among 34 persons who did not receive treatment, antifilarial IgG1 prevalence increased significantly (p = 0.003). Average antifilarial IgG1 levels decreased in households with high treatment coverage and increased in households that refused treatment. Each 10-meter increase in distance from the residence of a person who was antigen-positive in 2000 was associated a 4.68 unit decrease in antifilarial IgG1 level in 2001, controlling for other factors (p = 0.04). DISCUSSION: Antifilarial antibody assays can be used as a measure of filarial exposure. Our results suggest that micro-scale spatial heterogeneity exists in LF exposure and infection. Treatment appeared to be associated with reduced exposure at the sub-community level, suggesting the need to achieve high and homogeneous coverage. Public health messages should note the benefits of having one's neighbors receive treatment with antifilarial drugs.

Figure 1

Map of Haiti, indicating the commune of Léogâne and the community of Mapou.

Figure 2

GPS generated map of Mapou, showing houses, schools, mosquito trap locations, and other landmarks as indicated.

Figure 3

Antigen and antifilarial antibody prevalence for A, persons who received treatment (n = 126) and B, persons who did not receive treatment (n = 34) in 2000 (solid bars) and 2001 (cross-hatched bars). The error bar represents the upper 95% confidence interval. Among persons who received treatment antigen and antifilarial IgG1 prevalences decreased significantly. Among person who did not receive treatment, antifilarial IgG1 prevalence increased significantly.

Figure 4

Change in antifilarial antibody response among antibody positive persons who received treatment by year. The error bars represent the non-outlier maximum and minimum values. Outliers were more than 3 standard errors away from the mean. There was a significant decrease in antifilarial IgG1 responses (p < 0.001).

Figure 5

Average antifilarial IgG1 response by household for 2000 (top) and 2001 (bottom), and percent of household members who received treatment (middle). The black line represents the road. Three numbered sections of the community are boxed. Average antifilarial IgG1 response by household were defined by: the small red circles represent a low level positive response for the household; the large red circles represent a high level positive response for the household; and the green circles represent a negative response. Household treatment coverage was defined by: the small orange circles represent households with no treatment coverage. The small light blue circles represent households with low treatment coverage. The large light blue circles represent households with high treatment coverage.

Figure 6

Smoothed household antifilarial IgG1 response for 2000 (top) and 2001 (bottom) for the third boxed section of the community as identified in Figure 5. The purple lines represent change in total antifilarial IgG1 response by 100 units. The colored zones represent the total household antifilarial IgG1 level in the area of the community. The darker the red area the higher the total household antifilarial IgG1 level.