We tested 240 patients with Plasmodium falciparum monoinfection for persistent parasite antigenemia after successful standardized antimalarial therapy by using the ICT Malaria Pf/Pv and OptiMAL-IT assays that detect the malaria antigens Plasmodium falciparum histidine-rich protein 2 (HRP2) and parasite lactate dehydrogenase (pLDH), respectively, as well as a panmalarial antigen (PMA). The patients were screened for antigenemia on days 0, 3, 7, and 14 of follow-up. On day 0, all 240 patients showed positive reactivity with both assays. Of the 229 cases with negative parasitemia on day 3, persistent antigenemia was observed in 207 (90.4%) of the cases: 188 (82.1%) for HRP2 antigen and 75 (32.8%) for PMA. There was a gradual decrease in antigenemia on follow-up to day 14; however, the drop in reactivity to PMA was less than that for HRP2 antigen. In contrast to HRP2 antigenemia, there was a significant decrease in pLDH antigenemia to 38.4% and to 14.8% (PMA) on day 3 (P < 0.03). The pLDH antigenemia level dropped further to 14.8% on day 7. There was no significant association of persistent antigenemia with gametocytemia. One case with gametocytemia was negative for both the antigens. In conclusion, the OptiMAL-IT assay is more sensitive than the ICT Malaria Pf/Pv test for monitoring therapeutic responses after antimalarial therapy since the LDH activity ceases when the malarial parasite dies.Clinical diagnosis of malaria still relies upon identification of malaria parasites in Giemsa-stained blood smears of the peripheral blood. Recently, rapid diagnostic tests for the detection of Plasmodium falciparum infection has been introduced to overcome the problem of time constraints and low sensitivity in diagnosing malaria infections with a low level of parasitemia by microscopy. These rapid diagnostic tests are the immunochromatographic tests (ICT) based on the detection of antigen(s) released from the parasitized red blood cells. In the case of P. falciparum infection, these new rapid methods are based on detection of the histidine-rich protein 2 (HRP2; e.g., the ICT Malaria Pf, ParaSight-F, and ICT Malaria Pf/Pv tests) (1-6, 11, 20) or parasite lactate dehydrogenase (pLDH; e.g., OptiMAL-IT) (7-9, 11, 18-20). The sensitivities and specificities of each of these tests have been assessed in a range of clinical situations (1,2,5,7,11,19), although the overall sensitivity and specificity of all of these assays to detect P. falciparum infection is high (Ͼ90%). However, the sensitivity of these assays decreases to Ͻ70% in parasitemia Ͻ50/l. Further, these assays may remain positive due to persistence of P. falciparum HRP2 antigenemia after antimalarial therapy. This may result in a false-positive (FP) diagnosis of infection and thus may reduce the usefulness of the test in predicting treatment failure (4,11,12,19). FP reactions have been reported in individuals with a history of recent fever and antimalarial treatment due to persistent circulation of HRP2 for up to 2 weeks after clearance of parasites or in patients who had...