House-to-house human movement drives dengue virus transmission

Abstract

Dengue is a mosquito-borne disease of growing global health importance. Prevention efforts focus on mosquito control, with limited success. New insights into the spatiotemporal drivers of dengue dynamics are needed to design improved disease-prevention strategies. Given the restricted range of movement of the primary mosquito vector, Aedes aegypti, local human movements may be an important driver of dengue virus (DENV) amplification and spread. Using contact-site cluster investigations in a case-control design, we demonstrate that, at an individual level, risk for human infection is defined by visits to places where contact with infected mosquitoes is likely, independent of distance from the home. Our data indicate that house-to-house human movements underlie spatial patterns of DENV incidence, causing marked heterogeneity in transmission rates. At a collective level, transmission appears to be shaped by social connections because routine movements among the same places, such as the homes of family and friends, are often similar for the infected individual and their contacts. Thus, routine, house-to-house human movements do play a key role in spread of this vector-borne pathogen at fine spatial scales. This finding has important implications for dengue prevention, challenging the appropriateness of current approaches to vector control. We argue that reexamination of existing paradigms regarding the spatiotemporal dynamics of DENV and other vector-borne pathogens, especially the importance of human movement, will lead to improvements in disease prevention.

Fig. 1.

Summary of cluster investigations. Geographic distribution of households participating in DENV⁻ (A) and DENV⁺ (B) cluster investigations (n = 48). Lines connect contact sites with the homes of index cases. Symbols denote the neighborhood of the index case’s home: circle, MY neighborhood; triangle, TA neighborhood. Filled symbols indicate any house with ≥one acute DENV infection (in all cluster investigations). (C) DENV isolates by week from febrile cases enrolled in the two study neighborhoods (green, DENV-3; black, DENV-4). The dashed vertical line indicates the beginning of the study period. Red vertical lines indicate when city-wide insecticide fumigation campaigns were instigated by local health authorities.

Fig. 2.

Individual movement and infection risk. (A) Distribution of the number of houses included in each cluster. Our analysis was restricted to individuals who reported visiting ≥one house beyond the home (SI Appendix). (B) Relationship between σ_i, cluster-infestation rates, and the total number of acute infections in a cluster [binomial generalized additive model, adjusted R² = 76.7%; SI Appendix]. (C) Predicted risk for infection as a function of σ_i (black line, no prior exposure to DENV-4 in a cluster; green line, ≥one person with prior DENV-4 exposure). Open circles indicate DENV diagnosis for index cases (1 = DENV⁺). (D) Cumulative and frequency distribution of distance to visited houses (black, all houses; red, houses with ≥one acute DENV-4 infection). Although nearby houses were most common, most individuals (72.2%) visited places relatively far away from their home, with nearly half of all visited houses located >100 m away.

Fig. 3.

DENV transmission in contact clusters. (A) Average prevalence of DENV-4–neutralizing antibodies within clusters at their initiation, across both transmission seasons (solid circle, MY neighborhood; triangle, TA neighborhood). (B) Cluster attack rates. (C) Cluster infestation rates. (D) Household attack rates (Methods, Data Analysis, Endpoints). In B through D, black represents DENV⁻ clusters, and red represents DENV⁺ clusters. In all cases, the point indicates the predicted rate based on the best model selected by AIC_c (SI Appendix, Tables S7–S11). Error bars are ±1 SEM.

Fig. 4.

DENV-infection risk among contacts. Diagrams A and B show two clusters plotted in relative space (index house is at the center). Each segment represents one participant, color indicates serological status (recent, elevated acute IgM; acute, virus isolation or IgM seroconversion; pre, previous exposure). Distances on the x and y axes are the cube-root of actual distances; concentric circles around the index house demarcate different radii. (A) DENV⁺ cluster (σ = 1.1). (B) DENV⁻ cluster (σ = −0.71). Both clusters were initiated in the same neighborhood, in the same week of the second season of transmission. (C) Estimates of infection risk over the period of the study based on a model assuming seasonally forced transmission (SI Appendix). Red indicates infection probability within DENV⁺ activity spaces, and black indicates infection probability within DENV⁻ activity spaces. (D) Actual (solid symbols) and predicted (open symbols) number of cases based on the model. In C and D: circle, MY neighborhood; triangle, TA neighborhood.