Highly Sensitive Immunoassay Detects Malarial Histidine-Rich Protein 2

Malaria is a vector-borne disease of major public health relevance worldwide. The detection of submicroscopic infections in low prevalence settings has become an increasingly important challenge for malaria elimination strategies.

The current field rapid diagnostic tests (RDTs) for Plasmodium falciparum malaria are inadequate to detect low-density infections. Therefore, there is a need to develop more sensitive field diagnostic tools. In parallel, a highly sensitive laboratory reference assay will be essential to evaluate new diagnostic tools.

A team of international scientists mainly associated with PATH (Seattle, WA, USA) collected whole blood samples from participants of the study from Karen Village, Myanmar, and Nagongera, Uganda. The presence or absence of P. falciparum Histidine-Rich Protein 2 (HRP2) was determined by the Alere Malaria Ag P.f (HRP2) ELISA. The analytical and clinical performance of the HS ELISA was determined using recombinant P. falciparum HRP2, P. falciparum native culture parasites, and archived highly pedigreed clinical whole blood specimens.

The scientists reported that the HS ELISA has an analytical sensitivity of less than 25 pg/mL and shows strong specificity for P. falciparum HRP2 when tested against P. falciparum native culture strains with pfhrp2 and pfhrp3 gene deletions. Against clinical whole blood specimens with concordant microscopic and polymerase chain reaction (PCR) results, the HS ELISA showed 100% diagnostic sensitivity and 97.9% diagnostic specificity. For P. falciparum positive specimens with HRP2 concentrations below 400 pg/mL, the sensitivity and specificity were 100% and 88.9%, respectively. The overall sensitivity and specificity for all 352 samples were 100% and 97.3%.

The authors concluded that the HS ELISA demonstrated acceptable sensitivity and specificity for detecting P. falciparum HRP2, including recombinant protein, native culture P. falciparum parasites, and clinical whole blood specimens. This new assay will be useful in assessing new diagnostic tools and possibly other malaria intervention trials due to its lower limit of detection of P. falciparum HRP2. The study was published on November 1, 2018, in the Malaria Journal.

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