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Background  The performance of different malaria rapid diagnostic tests (RDT) may be influenced by transmission intensity and by the length of time each test requires to become negative after treatment and patient’s recovery.    Methods  Results of three RDTs (two HRP2 and one pLDH antigen-based tests) were compared to blood smear microscopy (the gold standard method) in children under 5 years of age living in a high versus low malaria intensity setting in southwestern Uganda. In each setting, 212 children, who tested positive by at least one RDT and by microscopy, were treated with artemether-lumefantrine. RDTs and microscopy were then repeated at fixed intervals to estimate each test’s time to negativity after treatment and patient recovery.    Results  In the two settings, sensitivities ranged from 98.4 to 99.2 % for the HRP2 tests and 94.7 to 96.1 % for the pLDH test. Specificities were 98.9 and 98.8 % for the HRP2 tests and 99.7 % for the pLDH test in the low-transmission setting and 79.7, 80.7 and 93.9 %, respectively, in the high-transmission setting. Median time to become negative was 35–42 or more days for the HRP2 tests and 2 days for the pLDH test.    Conclusions  High transmission contexts and a long time to become negative resulted in considerably reduced specificities for the HRP2 tests. Choice of RDT for low- versus high-transmission settings should balance risks and benefits of over-treatment  versus  missing malaria cases.    Trial registration : Registry number at ClinicalTrial.gov: NCT01325974    Electronic supplementary material  The online version of this article (doi:10.1186/s12936-016-1529-6) contains supplementary material, which is available to authorized users.

Performance and time to become negative after treatment of three malaria rapid diagnostic tests in low and high malaria transmission settings