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Background  Malaria has historically been entrenched in indigenous populations of the  República de Panamá . This scenario occurs despite the fact that successful methods for malaria elimination were developed during the creation of the Panamá Canal. Today, most malaria cases in the  República de Panamá  affect the  Gunas , an indigenous group, which mainly live in autonomous regions of eastern Panamá. Over recent decades several malaria outbreaks have affected the Gunas, and one hypothesis is that such outbreaks could have been exacerbated by climate change, especially by anomalous weather patterns driven by the EL Niño Southern Oscillation (ENSO).    Results  Monthly malaria cases in Guna Yala (1998–2016) were autocorrelated up to 2 months of lag, likely reflecting parasite transmission cycles between humans and mosquitoes, and cyclically for periods of 4 months that might reflect relapses of  Plasmodium vivax , the dominant malaria parasite transmitted in Panamá. Moreover, malaria case number was positively associated (P < 0.05) with rainfall (7 months of lag), and negatively with the El Niño 4 index (15 months of lag) and the Normalized Difference Vegetation Index, NDVI (8 months of lag), the sign and magnitude of these associations likely related to the impacts of weather patterns and vegetation on the ecology of  Anopheles albimanus , the main malaria vector in Guna Yala. Interannual cycles, of approximately 4-year periods, in monthly malaria case numbers were associated with the El Niño 4 index, a climatic index associated with weather and vegetation dynamics in Guna Yala at seasonal and interannual time scales.    Conclusion  The results showed that ENSO, rainfall and NDVI were associated with the number of malaria cases in Guna Yala during the study period. These results highlight the vulnerability of  Guna  populations to malaria, an infection sensitive to climate change, and call for further studies about weather impacts on malaria vector ecology, as well as the association of malaria vectors with  Gunas  paying attention to their socio-economic conditions of poverty and cultural differences as an ethnic minority.    Electronic supplementary material  The online version of this article (10.1186/s12936-018-2235-3) contains supplementary material, which is available to authorized users.

Climatic fluctuations and malaria transmission dynamics, prior to elimination, in Guna Yala, República de Panamá