Accuracy of two malaria rapid diagnostic tests (RDTS) for initial diagnosis and treatment monitoring in a high transmission setting in Uganda

Abstract

Malaria rapid diagnostic tests (RDTs) may improve fever management in areas without microscopy. We compared the accuracy of histidine-rich protein 2 (HRP2) and Plasmodium lactate dehydrogenase (pLDH)-based RDTs, using expert microscopy as a gold standard, for initial diagnosis, treatment monitoring, and diagnosis of recurrent malaria in a cohort of children followed longitudinally in a high-transmission area in Uganda. For 305 initial fever episodes, sensitivity was 98% for HRP2 and 87% for pLDH, whereas specificity was 55% and 96%, respectively. The HRP2 gave 51% false-positive results on Day 28, whereas pLDH gave no false positives after Day 7. For 59 recurrent fever episodes during follow-up, sensitivity was 100% for HRP2 and 91% for pLDH, whereas specificity was 33% and 100%, respectively. The HRP2-based RDTs are useful for initial diagnosis of malaria caused by superior sensitivity; however, as a result of superior specificity, pLDH-based RDTs are more appropriate to monitor treatment and diagnose recurrent malaria.

Figure 1.

Study profile. Trial profile showing screened and enrolled patients, blood smear results, and those enrolled for follow-up. Of the 140 cases that were enrolled for follow-up, 131 were included in the final analysis.

Figure 2.

Relationship between parasite density and sensitivity of histidine-rich protein 2 (HRP2) and Plasmodium lactate dehydrogenase (pLDH) rapid diagnostic tests (RDTs). At parasite densities < 1,000/μL, the sensitivity of pLDH is very low compared with HRP2.

Figure 3.

Relationship between specificity of histidine-rich protein 2 (HRP2) and Plasmodium lactate dehydrogenase (pLDH),and time since last malaria episode. The pLDH had acceptable specificity when used in patients with a recent malaria episode, unlike HRP2, which showed poorer specificity.

Figure 4.

Duration of antigenemia detected by histidine-rich protein 2 (HRP2) and Plasmodium lactate dehydrogenase (pLDH)-based rapid diagnostic tests (RDTs) during follow-up. The figure shows duration of antigenemia of HRP2 and pLDH during follow-up represented by percentage of false-positive HRP2 and pLDH RDTs, as compared with expert microscopy, obtained on each day of follow-up in 79 children without recurrent parasitemia. There was no false-positive pLDH result after Day 7, although 51% of HRP2 results were false positive on Day 28.

Figure 5.

Proportion of children with continued false-positive histidine-rich protein 2 (HRP2) results during follow-up, stratified by Day 0 parasite density. The figure shows the proportion of children with false-positive HRP2 results on each day of follow-up, stratified into four groups of pretreatment parasite density, in 79 children without recurrent parasitemia during follow-up. Children with initial parasite density ≤ 10,000 had a smaller proportion of false-positive results on each day of follow-up when compared with those with parasite density > 100,000.