Quantifying Leishmania Metacyclic Promastigotes from Individual Sandfly Bites Reveals the Efficiency of Vector...

Predicting how Leishmania will respond to control efforts requires an understanding of their transmission strategy. Using real-time quantitative PCR to quantify infectious metacyclic and non-metacyclic forms in mouse skin from single sandfly bites we show that most transmissions were highly enriched for infectious parasites. However, a quarter of sandflies were capable of transmitting high doses containing more non-infectious promastigotes from the vector's midgut. Mouse infections replicating "high" to "low" quality, low-dose transmissions confirmed clear differences in the pathology of the infection and their onward transmissibility back to sandflies. Borrowing methods originally developed to account for exposure heterogeneity among hosts, we show how these high-dose, low-quality transmitters act as super-spreading vectors, capable of inflating Leishmania transmission potential by as much as six-fold. These results highlight the hidden potential of transmission of mixed Leishmania promastigote stages on disease prevalence and the role of dose heterogeneity as an underlying strategy for efficient transmission.