Plasmodium falciparum lactate dehydrogenase (PfLDH) - Revision history

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2024-08-01T09:29:26Z

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	~~{\| class="wikitable" style="border-style: solid; border-width: 4px; color:black"~~
	~~\|colspan="1" style = "font-size:110%; color:black; background: FFFAFA"\|<span style="color:navy>'''Use of PfLDH in diagnosis'''</span>~~


	The pLDH assays identify enzymes of the malaria glycolytic pathway, the proteins are distinct from human forms of LDH allowing them to be identified by RDT tests. There are also species specific features.

	~~This means that there are three forms of test antigen:~~
	*PpanLDH - this potentially detects all forms of malaria although sensitivity varies between species
	*PfLDH - specifically detects a form expressed by ''P.falciparum'' detecting the species with good sensitivity
	*PvLDH - detecting the parasite form of LDH that is specific for ''P.vivax''

	~~----~~

	~~<span style="color:navy>'''Characteristics of HRP2 to be aware of'''</span>~~


	1. '''P.falciparum-specific''' (PfLDH): has very good sensitivity at high parasitaemia that may meet or exceed 90%. However, at lower parasite levels (<1000 parasites/ μL) sensitivity of PfLDH may be less than that of HRP2 (around 45%). Two advantages over HRP2 sould be considered. First, this conserved antigen does not have reported gene-delection so may be an effective choice where malaria arises in ares with high rates of HRP2 deletion. Second, the antgen is relatively rapidly cleared from the blood, so PfLDH has value in testing rsponse to treatment or for malaria testing in recently infected patients.</br>

	~~2. '''P.vivax-specific''' (PvLDH):~~

	~~3. '''"Pan-malaria"''' (PpanLDH):~~

Admin at 09:27, 1 August 2024

2024-08-01T09:27:22Z

← Older revision		Revision as of 10:27, 1 August 2024
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	1. '''P.falciparum-specific ~~forms~~''' (PfLDH): has very good sensitivity at high parasitaemia that may meet or exceed 90%. However, at lower parasite levels (<1000 parasites/ μL) sensitivity of PfLDH may be ~~lower~~ than HRP2 (around 45%). Two advantages over HRP2 sould be considered. First, this conserved antigen does not have reported gene-delection so may be an effective choice where malaria arises in ares with high rates of HRP2 deletion. Second, the antgen is ~~realtively~~ rapidly cleared from the blood, so PfLDH has value in testing rsponse to treatment or for malaria testing in recently infected patients.</br>		1. '''P.falciparum-specific''' (PfLDH): has very good sensitivity at high parasitaemia that may meet or exceed 90%. However, at lower parasite levels (<1000 parasites/ μL) sensitivity of PfLDH may be less than that of HRP2 (around 45%). Two advantages over HRP2 sould be considered. First, this conserved antigen does not have reported gene-delection so may be an effective choice where malaria arises in ares with high rates of HRP2 deletion. Second, the antgen is relatively rapidly cleared from the blood, so PfLDH has value in testing rsponse to treatment or for malaria testing in recently infected patients.</br>

	'''P.vivax-specific ~~forms~~ (PvLDH)~~'''~~:		2. '''P.vivax-specific''' (PvLDH):

	'''"Pan-malaria" ~~forms~~ (PpanLDH)~~'''~~:		3. '''"Pan-malaria"''' (PpanLDH):

Admin at 09:25, 1 August 2024

2024-08-01T09:25:39Z

← Older revision		Revision as of 10:25, 1 August 2024
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	'''P.falciparum-specific forms (PfLDH)~~'''~~: has very good sensitivity at high parasitaemia that may meet or exceed 90%. However, at lower parasite levels (<1000 parasites/ μL) sensitivity of PfLDH may be lower than HRP2 (around 45%). Two advantages over HRP2 sould be considered. First, this conserved antigen does not have reported gene-delection so may be an effective choice where malaria arises in ares with high rates of HRP2 deletion. Second, the antgen is realtively rapidly cleared from the blood, so PfLDH has value in testing rsponse to treatment or for malaria testing in recently infected patients.		1. '''P.falciparum-specific forms''' (PfLDH): has very good sensitivity at high parasitaemia that may meet or exceed 90%. However, at lower parasite levels (<1000 parasites/ μL) sensitivity of PfLDH may be lower than HRP2 (around 45%). Two advantages over HRP2 sould be considered. First, this conserved antigen does not have reported gene-delection so may be an effective choice where malaria arises in ares with high rates of HRP2 deletion. Second, the antgen is realtively rapidly cleared from the blood, so PfLDH has value in testing rsponse to treatment or for malaria testing in recently infected patients.</br>

	'''P.vivax-specific forms (PvLDH)''':		'''P.vivax-specific forms (PvLDH)''':

	'''"Pan-malaria" forms (PpanLDH)''':		'''"Pan-malaria" forms (PpanLDH)''':

Admin at 09:24, 1 August 2024

2024-08-01T09:24:06Z

← Older revision		Revision as of 10:24, 1 August 2024
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	'''P.falciparum-specific forms (PfLDH)''': has very good sensitivity at high parasitaemia that may meet or exceed 90%. However, at lower parasite levels (<1000 parasites/ μL) sensitivity of PfLDH may be lower than HRP2 (around 45%). Two advantages over HRP2 sould be considered. First, this conserved antigen does not have reported gene-delection so may be an effective choice where malaria arises in ares with high rates of HRP2 deletion. Second, the antgen is realtively rapidly cleared from the blood, so PfLDH has value in testing rsponse to treatment or for malaria testing in recently infected patients.		'''P.falciparum-specific forms (PfLDH)''': has very good sensitivity at high parasitaemia that may meet or exceed 90%. However, at lower parasite levels (<1000 parasites/ μL) sensitivity of PfLDH may be lower than HRP2 (around 45%). Two advantages over HRP2 sould be considered. First, this conserved antigen does not have reported gene-delection so may be an effective choice where malaria arises in ares with high rates of HRP2 deletion. Second, the antgen is realtively rapidly cleared from the blood, so PfLDH has value in testing rsponse to treatment or for malaria testing in recently infected patients.

			'''P.vivax-specific forms (PvLDH)''':

			'''"Pan-malaria" forms (PpanLDH)''':

Admin at 09:21, 1 August 2024

2024-08-01T09:21:20Z

← Older revision		Revision as of 10:21, 1 August 2024
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	*PfLDH - specifically detects a form expressed by ''P.falciparum'' detecting the species with good sensitivity		*PfLDH - specifically detects a form expressed by ''P.falciparum'' detecting the species with good sensitivity
	*PvLDH - detecting the parasite form of LDH that is specific for ''P.vivax''		*PvLDH - detecting the parasite form of LDH that is specific for ''P.vivax''

	~~Practical use~~

	PfLDH: excellent sensitivity at high parasitaemia that may meet or exceed 90%. However, at lower parasite levels (<1000 parasites/ μL) sensitivity of PfLDH may be lower than HRP2 (around 45%). Two advantages over HRP2 sould be considered. First, this conserved antigen does not have reported gene-delection so may be an effective choice where malaria arises in ares with high rates of HRP2 deletion. Second, the antgen is realtively rapidly cleared from the blood, so PfLDH has value in testing rsponse to treatment or for malaria testing in recently infected patients.


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	~~A much more~~ effective ~~test~~ of ~~cure as~~ the ~~antigen~~ is cleared ~~more rapidly after effective~~ treatment		'''P.falciparum-specific forms (PfLDH)''': has very good sensitivity at high parasitaemia that may meet or exceed 90%. However, at lower parasite levels (<1000 parasites/ μL) sensitivity of PfLDH may be lower than HRP2 (around 45%). Two advantages over HRP2 sould be considered. First, this conserved antigen does not have reported gene-delection so may be an effective choice where malaria arises in ares with high rates of HRP2 deletion. Second, the antgen is realtively rapidly cleared from the blood, so PfLDH has value in testing rsponse to treatment or for malaria testing in recently infected patients.

	~~Less affected by prozne and no mutation~~

Admin at 09:19, 1 August 2024

2024-08-01T09:19:36Z

← Older revision		Revision as of 10:19, 1 August 2024
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	The pLDH assays identify enzymes ~~specific to~~ the malaria glycolytic pathway, ~~three~~ forms of ~~test antigen exist: a PpanLDH which has capability~~ to ~~detect all forms of malaria (see separate description) and "~~species specific~~" forms that detect forms found only in particular malaria forms: a ''P.falciparum''-specific form (PfLDH) and a ''P.vavax''-specific form (PvLDH)~~.		The pLDH assays identify enzymes of the malaria glycolytic pathway, the proteins are distinct from human forms of LDH allowing them to be identified by RDT tests. There are also species specific features.

			This means that there are three forms of test antigen:
			*PpanLDH - this potentially detects all forms of malaria although sensitivity varies between species
			*PfLDH - specifically detects a form expressed by ''P.falciparum'' detecting the species with good sensitivity
			*PvLDH - detecting the parasite form of LDH that is specific for ''P.vivax''

	~~The~~ PfLDH ~~has~~ excellent sensitivity at high parasitaemia~~, with sensitivity~~ that may meet or exceed 90%. However, at lower parasite levels (<1000 parasites/ μL) sensitivity of PfLDH may be lower than HRP2 (around 45%).		Practical use

			PfLDH: excellent sensitivity at high parasitaemia that may meet or exceed 90%. However, at lower parasite levels (<1000 parasites/ μL) sensitivity of PfLDH may be lower than HRP2 (around 45%). Two advantages over HRP2 sould be considered. First, this conserved antigen does not have reported gene-delection so may be an effective choice where malaria arises in ares with high rates of HRP2 deletion. Second, the antgen is realtively rapidly cleared from the blood, so PfLDH has value in testing rsponse to treatment or for malaria testing in recently infected patients.

Admin at 09:27, 19 July 2024

2024-07-19T09:27:39Z

← Older revision		Revision as of 10:27, 19 July 2024
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	{\| class="wikitable" style="border-style: solid; border-width: 4px; color:black"		{\| class="wikitable" style="border-style: solid; border-width: 4px; color:black"
	\|colspan="1" style = "font-size:110%; color:black; background: FFFAFA"\|<span style="color:navy>'''Use of ~~HRP2~~ in diagnosis'''</span>		\|colspan="1" style = "font-size:110%; color:black; background: FFFAFA"\|<span style="color:navy>'''Use of PfLDH in diagnosis'''</span>


	~~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~~.		The pLDH assays identify enzymes specific to the malaria glycolytic pathway, three forms of test antigen exist: a PpanLDH which has capability to detect all forms of malaria (see separate description) and "species specific" forms that detect forms found only in particular malaria forms: a ''P.falciparum''-specific form (PfLDH) and a ''P.vavax''-specific form (PvLDH).

	~~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~~).
			The PfLDH has excellent sensitivity at high parasitaemia, with sensitivity that may meet or exceed 90%. However, at lower parasite levels (<1000 parasites/ μL) sensitivity of PfLDH may be lower than HRP2 (around 45%).


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	~~(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.</br>~~		A much more effective test of cure as the antigen is cleared more rapidly after effective treatment
	~~(2) HRP2 may be affected by the prozone effect (see below)</br>~~
	~~(3) HRP2 is increasingly subject to gene deletion in some geographical areas* which may cause false negative results (see below).</br>~~

	~~----~~


	~~'''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.</br>~~

	~~'''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.		Less affected by prozne and no mutation

Admin at 09:19, 19 July 2024

2024-07-19T09:19:22Z

← Older revision		Revision as of 10:19, 19 July 2024
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	{\| class="wikitable" style="border-style: solid; border-width: 4px; color:black"		{\| class="wikitable" style="border-style: solid; border-width: 4px; color:black"
	\|colspan="1" style = "font-size:~~100~~%; color:black; background: FFFAFA"\|<span style="color:navy>'''~~Title~~'''</span>		\|colspan="1" style = "font-size:110%; color:black; background: FFFAFA"\|<span style="color:navy>'''Use of HRP2 in diagnosis'''</span>


	~~TEXT 1~~		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).


			----

			<span style="color:navy>'''Characteristics of HRP2 to be aware of'''</span>


			(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.</br>
			(2) HRP2 may be affected by the prozone effect (see below)</br>
			(3) HRP2 is increasingly subject to gene deletion in some geographical areas* which may cause false negative results (see below).</br>

	----		----

	~~TEXT 2~~
			'''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.</br>

			'''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.

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2024-07-18T08:05:37Z

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