pGluDH
An accurate diagnosis is becoming more and more important, in view of the increasing resistance of ''Plasmodium falciparum'' and the high price of alternatives to chloroquine. The enzyme pGluDH does not occur in the host red blood cell and was recommended as marker enzyme for ''Plasmodium'' species by Picard-Maureau et al. in 1975. The malaria marker enzyme test is suitable for routine work and is now a standard test in most departments dealing with malaria. Presence of pGluDH is known to represent parasite viability and a rapid diagnostic test using pGluDH as antigen would have the ability to differentiate live from dead organisms. A complete RDT with pGluDH as antigen has been developed in China and is now undergoing clinical trials.GluDHs are ubiquitous enzymes that occupy an important branch-point between carbon and nitrogen metabolism. Both NAD [ EC 1.4.1.2] and NADP dependend GluDH [EC 1.4.1.4] enzymes are present in ''Plasmodia''; the NAD dependend GluDH is relatively unstable and not useful for diagnostic purposes. Glutamate dehydrogenase provides an oxidizable carbon source used for the production of energy as well as a reduced electron carrier, NADH. Glutamate is a principal amino donor to other amino acids in subsequent transamination reactions. The multiple roles of glutamate in nitrogen balance make it a gateway between free ammonia and the amino groups of most amino acids. Its crystal structure is published. The GluDH activity in ''P.vivax'', ''P.ovale'' and ''P. malariae'' has never been tested, but given the importance of GluDH as a branch point enzyme, every cell must have a high concentration of GluDH. It is well known that enzymes with a high molecular weight (like GluDH) have many isozymes, which allows strain differentiations (given the right monoclonal antibody). The host produces antibodies against the parasitic enzyme indicating a low sequence identity.
Histidine Rich Protein II
The histidine-rich protein II (HRP II) is a histidine - and alanine -rich, water-soluble protein, which is localized in several cell compartments including the parasite cytoplasm. The antigen is expressed only by ''P. falciparum'' trophozoites. HRP II from ''P. falciparum'' has been implicated in the biocrystallization of hemozoin, an inert, crystalline form of ferriprotoporphyrin IX (Fe(3+)-PPIX) produced by the parasite. A substantial amount of the HRP II is secreted by the parasite into the host bloodstream and the antigen can be detected in erythrocytes, serum, plasma, cerebrospinal fluid and even urine as a secreted water-soluble protein. These antigens persist in the circulating blood after the parasitaemia has cleared or has been greatly reduced. It generally takes around two weeks after successful treatment for HRP2-based tests to turn negative, but may take as long as one month, which compromises their value in the detection of active infection. False positive dipstick results were reported in patients with rheumatoid-factor-positive rheumatoid arthritis. Since HPR-2 is expressed only by ''P. falciparum'', these tests will give negative results with samples containing only ''P. vivax'', ''P. ovale'', or ''P. malariae''; many cases of non-falciparum malaria may therefore be misdiagnosed as malaria negative (some ''P.falciparum'' strains also don’t have HRP II). The variability in the results of pHRP2-based RDTs is related to the variability in the target antigen.pLDH
''P.falciparum'' lactate dehydrogenase (pLDH) is a 33 kDa oxidoreductase [EC 1.1.1.27]. It is the last enzyme of the glycolytic pathway, essential for ATP generation and one o the most abundant enzymes expressed by ''P.falciparum''. PLDH does not persist in the blood but clears about the same time as the parasites following successful treatment. The lack of antigen persistence after treatment makes the pLDH test useful in predicting treatment failure. In this respect, pLDH is similar to pGluDH. LDH from ''P. vivax'', ''P.malariae'', and ''P.ovale'' exhibit 90-92% identity to pLDH from ''P.falciparum''.pAldo
Fructose-bisphosphate aldolase [EC 4.1.2.13] catalyzes a key reaction in glycolysis and energy production and is produced by all four species. The ''P.falciparum'' aldolase is a 41 kDa protein and is 61-68% homologous to known eukaryotic aldolases. Its crystal structure has been published. The presence of antibodies against p41 in the sera of human adults partially immune to malaria suggest that p41 is implicated in protective immune response against the parasite.==External links * [http://www.nzdl.org/cgi-bin/library.cgi?e=d-00000-00---off-0who--00-0----0-10-0---0---0direct-10---4-------0-1l--11-en-50---20-about---00-0-1-00-0-0-11-1-0utfZz-8-00&cl=CL3.8&d=HASH01a1fed9cc1f60857681ff68.1&x=1 Malaria Diagnosis: New Perspectives ]
* [http://www.ichrc.org/pdf/MalariaRDT.pdf Precision of rapid diagnostic tests for malaria]
* [http://www.rapid-diagnostics.org/rti-malaria-diag.htm RDT Info website ]
* [http://www.rollbackmalaria.org/psm/rdts.html Roll back malaria]
* [http://apps.who.int/tdr/publications/tdr-research-publications/rdt-performance/pdf/full-report-malaria-RDTs.pdf WHO product testing 2008 ]
* [http://www.wpro.who.int/sites/rdt WHO Rapid Diagnostic Tests (RDTs)]
Category:Malaria
Adapted from the Wikipedia article Malaria antigen detection tests, under the G. N. U. Free Documentation License. Please also see http://en.wikipedia.org/wiki
