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Use of malaria rapid diagnostic test to identify Plasmodium knowlesi infection.

McCutchan TF, Piper RC, Makler MT - Emerging Infect. Dis. (2008)

Bottom Line: Reports of human infection with Plasmodium knowlesi, a monkey malaria, suggest that it and other nonhuman malaria species may be an emerging health problem.We report the use of a rapid test to supplement microscopic analysis in distinguishing the 5 malaria species that infect humans.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 12735 Twinbrook Pkwy, Rockville, MD 20892, USA. tmccutchan@niaid.nih.gov

ABSTRACT
Reports of human infection with Plasmodium knowlesi, a monkey malaria, suggest that it and other nonhuman malaria species may be an emerging health problem. We report the use of a rapid test to supplement microscopic analysis in distinguishing the 5 malaria species that infect humans.

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Related in: MedlinePlus

Modeling of the analysis of Plasmodium knowlesi lactate dehydrogenase (LDH). A) Sequence of LDH from P. knowlesi deduced from genomic DNA fragments sequenced by the Sanger malaria genome project (www.sanger.ac.uk/Projects/P_knowlesi). LDH isoforms from P. vivax, P. malariae, P. ovale, P. berghei, P. yoelli, and P. falciparum were compared with that of P. knowlesi. Residues unique to P. knowlesi and P. vivax are shown in blue; residues unique to P. knowlesi and P. falciparum are shown in red. B) Model of P. knowlesi LDH and specific epitopes. A model for P. knowlesi LDH was calculated by using WURST protein threading server (www.zbh.uni-hamburg.de/wurst/index.php) and the P. falciparum and P. vivax crystal structures (PDB: 2A94 and 3 2AA3). Shown is the monomer, as well as the assembled tetramer, aligned to the backbone of the P. vivax tetramer using pymol. The nicotinamide adenine dinucleotide cofactor analog 3-acetyl pyridine adenine dinucleotide is shown in black. Residues important for substrate binding and catalysis are shown in yellow. P. knowlesi residues shared only with P. vivax are shown in blue and indicate where the 11D9/13H11 epitopes could be. P. knowlesi residues shared only with P. falciparum are shown in red and indicate a critical determinant of the 17E4/7G9 epitopes.
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Figure 2: Modeling of the analysis of Plasmodium knowlesi lactate dehydrogenase (LDH). A) Sequence of LDH from P. knowlesi deduced from genomic DNA fragments sequenced by the Sanger malaria genome project (www.sanger.ac.uk/Projects/P_knowlesi). LDH isoforms from P. vivax, P. malariae, P. ovale, P. berghei, P. yoelli, and P. falciparum were compared with that of P. knowlesi. Residues unique to P. knowlesi and P. vivax are shown in blue; residues unique to P. knowlesi and P. falciparum are shown in red. B) Model of P. knowlesi LDH and specific epitopes. A model for P. knowlesi LDH was calculated by using WURST protein threading server (www.zbh.uni-hamburg.de/wurst/index.php) and the P. falciparum and P. vivax crystal structures (PDB: 2A94 and 3 2AA3). Shown is the monomer, as well as the assembled tetramer, aligned to the backbone of the P. vivax tetramer using pymol. The nicotinamide adenine dinucleotide cofactor analog 3-acetyl pyridine adenine dinucleotide is shown in black. Residues important for substrate binding and catalysis are shown in yellow. P. knowlesi residues shared only with P. vivax are shown in blue and indicate where the 11D9/13H11 epitopes could be. P. knowlesi residues shared only with P. falciparum are shown in red and indicate a critical determinant of the 17E4/7G9 epitopes.

Mentions: The unexpected pattern of antibody recognition on which we based our tests led us to examine the molecular basis of recognition (Figure 2). As expected, P. knowlesi LDH is highly similar to the known pLDH isoforms. We found that only a few residue differences could account for the epitope differences detected by the 17E4/7G9 and 11D9/13H11 antibodies. We first generated a 3-dimensional model of P. knowlesi LDH and then mapped surface-exposed residues that were uniquely shared by P. falciparum or P. vivax isoforms. The protein structure was calculated by using the structures of P. falciparum and P. vivax LDH (PDB: 2A94 and 2AA3) and the WURST threading server (13). Here, only a few patches of residues were found to describe the P. vivax–specific epitope, and only 1 residue (K115) was found to describe the P. falciparum–specific epitope (Figure 2, panel B). Thus, the existing MAbs perform well at distinguishing pLDH isoforms despite only a small number of different surface-exposed residues.


Use of malaria rapid diagnostic test to identify Plasmodium knowlesi infection.

McCutchan TF, Piper RC, Makler MT - Emerging Infect. Dis. (2008)

Modeling of the analysis of Plasmodium knowlesi lactate dehydrogenase (LDH). A) Sequence of LDH from P. knowlesi deduced from genomic DNA fragments sequenced by the Sanger malaria genome project (www.sanger.ac.uk/Projects/P_knowlesi). LDH isoforms from P. vivax, P. malariae, P. ovale, P. berghei, P. yoelli, and P. falciparum were compared with that of P. knowlesi. Residues unique to P. knowlesi and P. vivax are shown in blue; residues unique to P. knowlesi and P. falciparum are shown in red. B) Model of P. knowlesi LDH and specific epitopes. A model for P. knowlesi LDH was calculated by using WURST protein threading server (www.zbh.uni-hamburg.de/wurst/index.php) and the P. falciparum and P. vivax crystal structures (PDB: 2A94 and 3 2AA3). Shown is the monomer, as well as the assembled tetramer, aligned to the backbone of the P. vivax tetramer using pymol. The nicotinamide adenine dinucleotide cofactor analog 3-acetyl pyridine adenine dinucleotide is shown in black. Residues important for substrate binding and catalysis are shown in yellow. P. knowlesi residues shared only with P. vivax are shown in blue and indicate where the 11D9/13H11 epitopes could be. P. knowlesi residues shared only with P. falciparum are shown in red and indicate a critical determinant of the 17E4/7G9 epitopes.
© Copyright Policy
Related In: Results  -  Collection

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Figure 2: Modeling of the analysis of Plasmodium knowlesi lactate dehydrogenase (LDH). A) Sequence of LDH from P. knowlesi deduced from genomic DNA fragments sequenced by the Sanger malaria genome project (www.sanger.ac.uk/Projects/P_knowlesi). LDH isoforms from P. vivax, P. malariae, P. ovale, P. berghei, P. yoelli, and P. falciparum were compared with that of P. knowlesi. Residues unique to P. knowlesi and P. vivax are shown in blue; residues unique to P. knowlesi and P. falciparum are shown in red. B) Model of P. knowlesi LDH and specific epitopes. A model for P. knowlesi LDH was calculated by using WURST protein threading server (www.zbh.uni-hamburg.de/wurst/index.php) and the P. falciparum and P. vivax crystal structures (PDB: 2A94 and 3 2AA3). Shown is the monomer, as well as the assembled tetramer, aligned to the backbone of the P. vivax tetramer using pymol. The nicotinamide adenine dinucleotide cofactor analog 3-acetyl pyridine adenine dinucleotide is shown in black. Residues important for substrate binding and catalysis are shown in yellow. P. knowlesi residues shared only with P. vivax are shown in blue and indicate where the 11D9/13H11 epitopes could be. P. knowlesi residues shared only with P. falciparum are shown in red and indicate a critical determinant of the 17E4/7G9 epitopes.
Mentions: The unexpected pattern of antibody recognition on which we based our tests led us to examine the molecular basis of recognition (Figure 2). As expected, P. knowlesi LDH is highly similar to the known pLDH isoforms. We found that only a few residue differences could account for the epitope differences detected by the 17E4/7G9 and 11D9/13H11 antibodies. We first generated a 3-dimensional model of P. knowlesi LDH and then mapped surface-exposed residues that were uniquely shared by P. falciparum or P. vivax isoforms. The protein structure was calculated by using the structures of P. falciparum and P. vivax LDH (PDB: 2A94 and 2AA3) and the WURST threading server (13). Here, only a few patches of residues were found to describe the P. vivax–specific epitope, and only 1 residue (K115) was found to describe the P. falciparum–specific epitope (Figure 2, panel B). Thus, the existing MAbs perform well at distinguishing pLDH isoforms despite only a small number of different surface-exposed residues.

Bottom Line: Reports of human infection with Plasmodium knowlesi, a monkey malaria, suggest that it and other nonhuman malaria species may be an emerging health problem.We report the use of a rapid test to supplement microscopic analysis in distinguishing the 5 malaria species that infect humans.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 12735 Twinbrook Pkwy, Rockville, MD 20892, USA. tmccutchan@niaid.nih.gov

ABSTRACT
Reports of human infection with Plasmodium knowlesi, a monkey malaria, suggest that it and other nonhuman malaria species may be an emerging health problem. We report the use of a rapid test to supplement microscopic analysis in distinguishing the 5 malaria species that infect humans.

Show MeSH
Related in: MedlinePlus