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Background As more regions approach malaria elimination, understanding howdifferent interventions interact to reduce transmission becomes critical. TheLake Kariba area of Southern Province, Zambia, is part of a multi-countryelimination effort and presents a particular challenge as it is aninterconnected region of variable transmission intensities.  Methods In 2012-13, six rounds of mass-screen-and-treat drug campaigns werecarried out in the Lake Kariba region. A spatial dynamical model of malariatransmission in the Lake Kariba area, with transmission and climate modeled atthe village scale, was calibrated to the 2012-13 prevalence survey data, withcase management rates, insecticide-treated net usage, and drug campaigncoverage informed by surveillance. The model was used to simulate the effect ofvarious interventions implemented in 2014-22 on reducing regional transmission,achieving elimination by 2022, and maintaining elimination through 2028.  Findings The model captured the spatio-temporal trends of decline and reboundin malaria prevalence in 2012-13 at the village scale. Simulations predictedthat elimination required repeated mass drug administrations coupled withsimultaneous increase in net usage. Drug campaigns targeted only at high-burdenareas were as successful as campaigns covering the entire region.  Interpretation Elimination in the Lake Kariba region is possible throughcoordinating mass drug campaigns with high-coverage vector control. Targetingregional hotspots is a viable alternative to global campaigns when humanmigration within an interconnected area is responsible for maintainingtransmission in low-burden areas.

Malaria elimination campaigns in the Lake Kariba region of Zambia: a spatial dynamical model