Inferring transmission trees to guide targeting of interventions against visceral leishmaniasis and post-kala-azar dermal leishmaniasis

Lloyd A. C. Chapman; Simon E. F. Spencer; Timothy M. Pollington; Chris P. Jewell; Dinesh Mondal; Jorge Alvar; T. Deirdre Hollingsworth; Mary M. Cameron; Caryn Bern; Graham F. Medley

mission. We assess the contribution of di erent infectious 172 groups to transmission in terms of their relative contribu-173 tion to the transmission experienced by susceptible individuals 174 ( Fig. 2A and Fig. S17 ). The contribution of VL cases was 175 fairly stable at around 75% from 2002 to the end of 2004 176 before decreasing steadily to 0 at the end of the epidemic, 177 while the contribution of PKDL cases increased from 0 in 178 2002 to ≥73% in 2010 (95% CI: 63, 80%) (Fig. S17) . Only a 179 small proportion of the total infection pressure on susceptible 180 individuals, varying between 9% and 14% over the course of 181 the epidemic, was estimated to have come from asymptomatic 182 and pre-symptomatic individuals. Reconstructing the Transmission Tree. By sampling 1,000 193 transmission trees from the joint posterior distribution of 194 the transmission parameters and the unobserved data (as de-195 scribed in Materials and Methods), we can build a picture of 196 the most likely source of infection for each case and how infec-197 tion spread in space and time. Fig. 3 shows the transmission 198 tree at di erent points in time in part of the south-east cluster 199 of villages. Early in the epidemic and at its peak (Figures 3A 200 and 3B), most new infections were due to VL cases. Towards 201 the end of the epidemic, some infections were most likely due 202 to PKDL cases and there was some saturation of infection 203 around VL cases (Fig. 3C) . The inferred patterns of trans-204 mission suggest that disease did not spread radially outward 205 from index cases over time, but instead made a combination 206 of short and long jumps around cases with long durations of 207 symptoms and households with multiple cases. . Arrows show the most likely source of infection for each case infected up to that point in time over 1,000 sampled transmission trees, and are coloured by the type of infection source and shaded according to the proportion of trees in which that individual was the most likely infector (darker shading indicating a higher proportion). Asymptomatic infections are not shown for clarity. S/A = susceptible or asymptomatic, E = pre-symptomatic, I = VL, R = recovered, D = dormantly infected, P = PKDL (see SI Text). GPS locations of individuals are jittered slightly so that individuals from the same household are more visible. An animated version showing all months is provided in SI movie 1. There is considerable heterogeneity in the estimated contri- by each VL/PKDL case is typically less than 1 (Fig. S19A ).