Estimating probabilities of malaria importation in southern Mozambique through P. falciparum genomics and mobility patterns

Background Imported malaria is a critical obstacle to achieving elimination in low transmission settings. Characterising malaria importation and transmission sources using human mobility and parasite genomics has the potential to inform elimination strategies, but tools combining both types of data are lacking. Methods We developed a novel Bayesian approach that provides individual importation probabilities and geographic origin of P. falciparum cases by combining epidemiological, human mobility and parasite genetic data. Spatial genetic structure and connectivity were assessed using microhaplotype-based genetic relatedness (identity-by-descent) from 1467 P. falciparum samples collected from 9 provinces in Mozambique during 2022, including 200 samples from two very-low transmission elimination-targeted districts (Magude and Matutuine) in the south. Travel reports were combined with genetic relatedness metrics to classify clinical cases as local or imported. Results Genetic relatedness between parasites from southern and northern/central Mozambique was lower (0.017) than average (0.024, p<0.001). 43.5% (87/200) of infections in elimination-targeted districts were classified as imported, had a higher genetic complexity (OR=1.4, CI=[1.0, 1.9], p=0.038) compared to local cases and originated mainly from Inhambane (62% [54/87]). Significant differences in the odds of a case being imported were found between the two study districts (OR=6.6, CI=[2.3,25.4], p<0.001), with Magude district (11.1%, 3/27) showing lower importation rates than Matutuine (48.6%, 84/173) district. Conclusions Differences in importation rates observed between both elimination districts suggest the need for fine-scale analysis to tailor cost-effective elimination strategies. Importation is strongly impacting malaria incidence in Matutuine district, and increasing efforts to reduce malaria burden in their sources of transmission (especially in Inhambane province), as well as targeting travelers to central and northern Mozambique, could significantly contribute to malaria elimination in the south.