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Background  To successfully eliminate malaria, an integrated system that includes a number of approaches and interventions—aimed at overcoming the threat of antimalarial drug resistance—is required. Significant progress has been made in reducing malaria incidence through large-scale use of artemisinin-based combination therapies and insecticide-treated nets. To consolidate these gains, attention should be paid to the missing links in the elimination of malaria. One of these gaps is the residual reservoir of submicroscopic resistant parasites, which remains after case management or other control measures have been carried out. Therefore, the present opinion piece highlights the importance of exploring the role that submicroscopic resistant parasites could play in hindering malaria elimination by allowing the persistence of transmission, particularly in areas of low transmission or in the pre-elimination and/or elimination phase.    Discussion  If malaria elimination interventions are to be effective, the relative role of the hidden reservoir of resistant parasites needs to be assessed, particularly in regions that are low-transmission settings and/or in pre-elimination and/or elimination phases. Various ongoing studies are focusing on the role of submicroscopic malaria infections in malaria transmission but overlook the possible build-up of resistance to antimalarial drugs among submicroscopic parasite populations. This is an important factor as it may eventually limit the effectiveness of malaria elimination strategies.    Conclusions  An evidence-based estimation of the “true” reservoir of resistant parasites can help target the existing and emerging foci of resistant parasites before they spread. Emergence and spread of artemisinin-resistant  Plasmodium falciparum  malaria in Southeast Asia underline the need to contain drug resistance.    Electronic supplementary material  The online version of this article (doi:10.1186/s40249-016-0227-5) contains supplementary material, which is available to authorized users.

Hidden reservoir of resistant parasites: the missing link in the elimination of falciparum malaria