Histidine-rich protein 2 (HRP2): Difference between revisions

Latest revision as of 23:00, 17 March 2025

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The HRP2 antigen - practicalities P.falciparum parasites produce “histidine-rich” proteins (HRP). The HRP2 antigen is highly expressed and stable, and is therefore very useful in the detection of P.falciparum infection. Additionally, antibodies that detect HRP2 also cross react with the closely related HRP3 protein which can improve their sensitivity, particularly where there is HPR2 gene-deletion is not expressed. At a high parasitaemia the sensitivity of HRP2 (like LDH-based tests) is likely to exceed 90% detection for P.falciparum. However, at lower parasite levels (<1000 parasites/μL) the sensitivity will be significantly less (around 70%), although HRP2-based assays may still perform better than LDH-based assays in these circumstances. Characteristics of HRP2 to be aware of (1) Half-life: HRP2 has a long half-life in vivo and the antigen may persist in blood for some time following successful treatment. HRP2 should not therefore be used to monitor disease resolution (see sections on RDT ntepretation). (2) HRP2 may be affected by false negative results when HRP2 antigen levels are very high in very severe infection (the prozone-like or postzone phenomenon - see description in the RDT-interpretation sections (3) HRP2 is increasingly subject to gene deletion in some geographical areas* which may cause false negative results (see sections on RDT interpretation).

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 '''Navigation'''</br>
-[[Biology of the schizont|Go Back]]
+<span style="font-size:90%">>[[MalariaETC Index|Main Malaria Index]]''</span></br>
+<span style="font-size:90%">>>[[Rapid diagnostic tests (RDTs)|RDT main page]]''</span></br>
+<span style="font-size:90%">>>>[[RDT_test:_antigens|RDT test antigens]]</span></br>
+<span style="font-size:90%">>>>Current page: '''The HRP2 antigen'''</span>
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+{| class="wikitable" style="widthe:90%; border-style: solid; border-width: 4px; border-color:teal"
-{| class="wikitable" style="border-style: solid; border-width: 4px; color:black"
+|colspan="1" style = "font-size:140%; color:black; background: FFFAFA"|<span style="color:black>'''The HRP2 antigen - practicalities'''</span>
-|colspan="1" style = "font-size:100%; color:black; background: FFFAFA"|<span style="color:navy>'''How does schizont appearance change during their development?'''</span>
-Schizonts formation involves successive cycles of asexual division that eventually result in the formation of multiple separate "merozoite" forms. Those merozoites are released as the red cell breaks down then go on to infect another red cell. Schizonts therefre look very different depending on which stage of development they represent. Below are images of schizonts at different developmental stages.
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-'''THE INITIAL ASEXUAL DIVISION'''
+<span style="font-size:90%">''P.falciparum'' parasites produce “histidine-rich” proteins (HRP). The HRP2 antigen is highly expressed and stable, and is therefore very useful in the detection of ''P.falciparum'' infection. Additionally, antibodies that detect HRP2 also cross react with the closely related HRP3 protein which can improve their sensitivity, particularly where there is HPR2 gene-deletion is not expressed.</br></br>At a high parasitaemia the sensitivity of HRP2 (like LDH-based tests) is likely to exceed 90% detection for ''P.falciparum''. However, at lower parasite levels (<1000 parasites/μL) the sensitivity will be significantly less (around 70%), although HRP2-based assays may still perform better than LDH-based assays in these circumstances.
-The first recognisable stage occurs when the schizonts first divide their chromatin to form two distinct masses. This first stage is the least distinctive and can be difficult to distinguish from a late trophozoite or gametocyte with a double chromatin dot. But often the appearance is clear.
-<gallery mode="nolines" widths="200px" heights="220px" >
-File:Schizontcartoon1.jpg|A|link={{filepath:Schizontcartoon1.jpg}}
-File:Schizontreal1.jpg|B|link={{filepath:Schizontreal1.jpg}}
-</gallery>
-The cartoon image (A) shows the division of chromatin into two distinct purple chromatin masses within the blue parasite cytoplasm (at this point the cytoplams is not divided so indiviual merozoites are not really distinguishable). A clinical image of a parasite at this developmental stage (''P.ovale'' with well shown James'dots) is shown in panel (B).
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-'''IMMATURE SCHIZONT APPEARANCES'''
+<span style="font-size:90%"><span style="color:navy>'''Characteristics of HRP2 to be aware of'''</span></br></br>(1) Half-life: HRP2 has a long half-life ''in vivo'' and the antigen may persist in blood for some time following successful treatment. HRP2 should not therefore be used to monitor disease resolution (see sections on RDT ntepretation).</br>(2) HRP2 may be affected by false negative results when HRP2 antigen levels are very high in very severe infection (the prozone-like or postzone phenomenon - see description in the RDT-interpretation sections</br>(3) HRP2 is increasingly subject to gene deletion in some geographical areas* which may cause false negative results (see sections on RDT interpretation).</br></span>
-As schizont development proceeds further cycles of division cause the appearance of mutiple separate areas chromatin that will eventually form the merozoies, although at this stage they still lie within a single cytoplasmic mass. The number of divisions varies between species, so in mature schizonts this can contribute to species identification (see schizont gallery). Note that as the parasites develop the haemoglobin is metabolised so the red cell becomes more pale, and the products of red cell breakdown (malaria pigment) become more prominent.
-<gallery mode="nolines" widths="200px" heights="220px" >
-File:Schizontcartoon2.jpg|A|link={{filepath:Schizontcartoon2.jpg}}
-File:Schizontreal2.jpg|B|link={{filepath:Schizontreal2.jpg}}
-</gallery>
-The cartoon image (A) shows the further division of chromatin (Chr) into many discrete massed within the blue parasite cytoplasm (Cy). Indiviual merozoites are still not distinguishable but the malaria pigment is obvious (Pi). A clinical image of a parasite at this developmental stage (again from ''P.ovale'' with well shown James'dots and malaria pigment) is shown in panel (B).
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-'''MATURE SCHIZONT APPEARANCES'''
-By this stage the individual merozoites can be distinguished, each with a chromatin dot and cytoplasm; they are now ready for release from the red cell.
-<gallery mode="nolines" widths="200px" heights="220px" >
-File:Schizontcartoon3.jpg|A|link={{filepath:Schizontcartoon3.jpg}}
-File:Schizontreal3.jpg|B|link={{filepath:Schizontreal3.jpg}}
-</gallery>
-The asexual division cycles are now complete cartoon image (A) shows the merozoites (M) as discrete chromatin with blue cytoplasm. Malaria pigment is present (P). The clinical image of a parasite at this developmental stage (again from ''P.ovale'' with well shown James'dots and malaria pigment) is shown in panel (B).
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-'''MEROZOITE RELEASE'''
-In the final stage the red cell membrane is broken down, swelling then separating to release the merozoites and any malaria pigment into the blood where each merozoite enters a red cell to form a new early trophozoite and increasing the infection load.
-<gallery mode="nolines" widths="200px" heights="220px" >
-File:Schizontcartoon4.jpg|A|link={{filepath:Schizontcartoon4.jpg}}
-File:Schizontreal4.jpg|B|link={{filepath:Schizontreal4.jpg}}
-</gallery>
-Merozoites cause the red cell membrane to be expanded then to break down; the merozoites (M) are now clearly separate and move apart, the pigment (P) is also released during this process (A); this is shown in the clinical image (B) although this brief stage is rarely seen in practice (''P.malariae'').

Histidine-rich protein 2 (HRP2): Difference between revisions

From MalariaETC

Latest revision as of 23:00, 17 March 2025