Evaluation of a rapid diagnostic test (CareStart™ Malaria HRP-2/pLDH (Pf/pan) Combo Test) for the diagnosis of malaria in a reference setting

Abstract

BackgroundMalaria Rapid Diagnostic Tests (RDTs) are widely used for diagnosing malaria. The present retrospective study evaluated the CareStart™ Malaria HRP-2/pLDH (Pf/pan) Combo Test targeting the Plasmodium falciparum specific antigen histidine-rich protein (HRP-2) and the pan-Plasmodium antigen lactate dehydrogenase (pLDH) in a reference setting.MethodsThe CareStart™ Malaria HRP-2/pLDH (Pf/pan) Combo Test was evaluated on a collection of samples obtained in returned international travellers using microscopy corrected by PCR as the reference method. Included were P. falciparum (n = 320), Plasmodium vivax (n = 76), Plasmodium ovale (n = 76), Plasmodium malariae (n = 23) and Plasmodium negative samples (n = 95).ResultsOverall sensitivity for the detection of P. falciparum was 88.8%, increasing to 94.3% and 99.3% at parasite densities above 100 and 1,000/μl respectively. For P. vivax, P. ovale and P. malariae, overall sensitivities were 77.6%, 18.4% and 30.4% respectively. For P. vivax sensitivity reached 90.2% for parasite densities above 500/μl. Incorrect species identification occurred in 11/495 samples (2.2%), including 8/320 (2.5%) P. falciparum samples which generated only the pan-pLDH line. For P. falciparum samples, 205/284 (72.2%) HRP-2 test lines had strong or medium line intensities, while for all species the pan-pLDH lines were less intense, especially in the case of P. ovale. Agreement between observers was excellent (kappa values > 0.81 for positive and negative readings) and test results were reproducible. The test was easy to perform with good clearing of the background.ConclusionThe CareStart™ Malaria HRP-2/pLDH (Pf/pan) Combo Test performed well for the detection of P. falciparum and P. vivax, but sensitivities for P. ovale and P. malariae were poor.

Assessing the Performance of CareStart Malaria Pf/Pv Combo Test Against Thick Blood Film in the Diagnosis of Malaria in Northwest Ethiopia

“…The sensitivity (99.7%) that we report here for the CareStart Malaria Pf/Pv Combo Test to detect P. falciparum species was comparable with the sensitivity findings reported as 99.4% in Wondogenet, 14 98% in Uganda, 21 and 96.91% in Karachi, 16 but our finding was higher than the reports of 88.8% in Belgium, 13 89.1% in Myanmar, 22 and 88.52% in ChinaMyanmar. 19 Because the parasite density in the present study was greater than 100 parasites/μL blood, which was shown in the microscopic examination of thick film, the sensitivity was higher.…”

“…19 Because the parasite density in the present study was greater than 100 parasites/μL blood, which was shown in the microscopic examination of thick film, the sensitivity was higher. This type of relationship between parasite density and RDT performance has also been indicated earlier, 13 showing that, when the parasite load is 100 parasites/μL, the performance of CareStart will be high. However, the sensitivity of the RDT is low when the parasite density is below 100 parasites/μL blood (mostly in asymptomatic cases).…”

“…Invalid tests were retested by taking fresh blood from each patient who had an invalid test result, and the number of invalid tests was recorded. 13 In all cases, the results of the CareStart Test were determined earlier than microscopic results, with strict blinding to microscopic examination of the thick blood smears. The independent readings of the thick blood smears determined by the experienced malaria technologists were checked by the principal investigator, who was also experienced.…”

Comparison of PfHRP-2/pLDH RDTs with Light Microscopy in a Low Prevalence Setting in Southeastern Iran, Sistan and Baluchestan: Due to Implementation of Malaria Elimination Program

“…The sensitivity of the RDT in the current study for P. falciparum corresponded with the reports by Bruno B Andrade et al (20). The sensitivity of the RDT in the current study for P. falciparum was also higher than Maltha et al, (21) and lower than China Myanmar endemic borders (17), Indonesia (22) and Jimma, as well as southwest Ethiopia (14). The specificity of the RDT in the present study for P. falciparum was similar to the reports from Jimma, southwestern Ethiopia (14), and higher than the reports from southern (23) and Ethiopia and Madagascar (15,24).…”

False-Negative Rapid Diagnostic Tests for Malaria and Deletion of the Histidine-Rich Repeat Region of the hrp2 Gene

“…In addition, the association between false-negative RDTs and a low MOI suggests that this discrepancy may become increasingly important as malaria control becomes more effective. Based on these results, we suggest that the RDTs used to diagnose P. falciparum infection in humans should target parasite proteins thought to be essential (e.g., parasite lactic dehydrogenase) 1,[27][28][29] and should also consider proteins with identifiable (distinguishable) variants in other plasmodial species. hrp2 PCR results for smear-positive specimens with negative vs. positive HRP2-based RDT results.…”