Histidine-rich protein 2 (HRP2)

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Use of HRP2 in diagnosis P.falciparum parasites produces “histidine-rich” proteins. The antigen is highly expressed and stable, and is therefore very useful in the detection of P.falciparum infection. Antibodies that detect HRP2 also cross react with the closely related HRP3 protein which can improve their sensitivity, particularly where HPR2 is not expressed. At a high parasitaemia the sensitivity of HRP2 (like LDH-based tests) will meet or exceed 90% detection for P.falciparum. However, at lower parasite levels (<1000 parasites/μL) the sensitivity is significantly less (around 70% for HRP2, which may perform better than LDH at low parasite levels). Characteristics of HRP2 to be aware of (1) Half-life: HRP2 has a long half-life in vivo and expression persists following successful treatment. It should not therefore be used to monitor disease resolution. (2) HRP2 may be affected by the prozone effect (see below) (3) HRP2 is increasingly subject to gene deletion in some geographical areas* which may cause false negative results (see below). NOTES The Prozone effect - a very rare but recognised effect that particularly affects HRP2 and means that in very high parasitaemia the presence of excess antigen may prevent the formation of appropriate antibody-antigen complexes causing the test to appear negative. Gene deletion mutation These gene-deletion are specific for HRP2 and HRP3 genes: Described in South America, sub-Saharan Africa and Asia, deletions of HRP2 prevent its synthesis, causing reduced sensitivity or false negative test results. In high parasitaemia the tests may still work in the presence of single gene deletions of HRP2 since the test also detects HRP3. However, deletions affecting both HRP2 and HRP3 genes are now recognised and cause negative tests. The use of HRP to detect malaria may not be appropriate where the HRP2 deletion rate is 5% or greater. Tests that combine HRP2 is combined with antibody (either aldolase or pLDH) may overcome these problems.