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. It is important to be aware of some features of HRP2 detection: (1) Half-life: HRP2 has a long half-life in vivo and persists following successful treatment. It should not therefore be used to monitor disease resolution (2) HRP2 may be affected by the prozone effect* (3) HRP2 is increasingly subject to gene deletion in some geographical areas* which may cause false negative results. Prozone effect (mainly affects HRP2) – 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 (mainly HRP2): Described in South America, sub-Saharan Africa and Asia, these deletions cause reduced sensitivity or false negative results. In high parasitaemia the tests are often still positive 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) can overcome these problems.