The Impact of Geographical Variation in Plasmodium knowlesi Apical Membrane Protein 1 (PkAMA-1) on Invasion Dynamics of P. knowlesi

Ng, Yee Ling; Lee, Wenn-Chyau; Lau, Yee-Ling; Fong, Mun Yik

doi:10.3390/tropicalmed8010056

Cited by 4 publications

(2 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hence, this serves as a determinant of a vaccine candidate for human knowlesi malaria. Recently, Ng et al (2023) found that rabbit-raised antibodies against the region II of pkama-1 displayed significant differences when compared to the negative control group, with close to 50% invasion inhibition [ 56 ]. The findings by Muh and colleagues (2018) are similar but with a lower antibody concentration used [ 57 ].…”

Section: Discussionmentioning

confidence: 99%

Inter-Population Genetic Diversity and Clustering of Merozoite Surface Protein-1 (pkmsp-1) of Plasmodium knowlesi Isolates from Malaysia and Thailand

et al. 2023

Self Cite

View full text Add to dashboard Cite

The genetic diversity of pkmsp-1 of Malaysian Plasmodium knowlesi isolates was studied recently. However, the study only included three relatively older strains from Peninsular Malaysia and focused mainly on the conserved blocks of this gene. In this study, the full-length pkmsp-1 sequence of recent P. knowlesi isolates from Peninsular Malaysia was characterized, along with Malaysian Borneo and Thailand pkmsp-1 sequences that were retrieved from GenBank. Genomic DNA of P. knowlesi was extracted from human blood specimens and the pkmsp-1 gene was PCR-amplified, cloned, and sequenced. The sequences were analysed for genetic diversity, departure from neutrality, and geographical clustering. The pkmsp-1 gene was found to be under purifying/negative selection and grouped into three clusters via a neighbour-joining tree and neighbour net inferences. Of the four polymorphic blocks in pkmsp-1, block IV, was most polymorphic, with the highest insertion–deletion (indel) sites. Two allelic families were identified in block IV, thereby highlighting the importance of this block as a promising genotyping marker for the multiplicity of infection study of P. knowlesi malaria. A single locus marker may provide an alternate, simpler method to type P. knowlesi in a population.

show abstract

Section: Discussionmentioning

confidence: 99%

Inter-Population Genetic Diversity and Clustering of Merozoite Surface Protein-1 (pkmsp-1) of Plasmodium knowlesi Isolates from Malaysia and Thailand

et al. 2023

Self Cite

View full text Add to dashboard Cite

show abstract

“…Both Pk and Pf merozoites use Apical Membrane Antigen 1 (AMA1 or AMA-1) to reorient the parasite's apical end toward the host cell [45,46]. Anti-PkAMA1 IgG antibodies can block Pk invasion into human RBCs in vitro [47].…”

Section: Rbc Invasionmentioning

confidence: 99%

Plasmodium knowlesi (Pk) Malaria: A Review & Proposal of Therapeutically Rational Exchange (T-REX) of Pk-Resistant Red Blood Cells

Jajosky,

Wu,

Jajosky

et al. 2023

TropicalMed

View full text Add to dashboard Cite

Plasmodium knowlesi (Pk) causes zoonotic malaria and is known as the “fifth human malaria parasite”. Pk malaria is an emerging threat because infections are increasing and can be fatal. While most infections are in Southeast Asia (SEA), especially Malaysia, travelers frequently visit this region and can present with Pk malaria around the world. So, clinicians need to know (1) patients who present with fever after recent travel to SEA might be infected with Pk and (2) Pk is often misdiagnosed as P. malariae (which typically causes less severe malaria). Here we review the history, pathophysiology, clinical features, diagnosis, and treatment of Pk malaria. Severe disease is most common in adults. Signs and symptoms can include fever, abdominal pain, jaundice, acute kidney injury, acute respiratory distress syndrome, hyponatremia, hyperparasitemia, and thrombocytopenia. Dengue is one of the diseases to be considered in the differential. Regarding pathophysiologic mechanisms, when Pk parasites invade mature red blood cells (RBCs, i.e., normocytes) and reticulocytes, changes in the red blood cell (RBC) surface can result in life-threatening cytoadherence, sequestration, and reduced RBC deformability. Since molecular mechanisms involving the erythrocytic stage are responsible for onset of severe disease and lethal outcomes, it is biologically plausible that manual exchange transfusion (ET) or automated RBC exchange (RBCX) could be highly beneficial by replacing “sticky” parasitized RBCs with uninfected, deformable, healthy donor RBCs. Here we suggest use of special Pk-resistant donor RBCs to optimize adjunctive manual ET/RBCX for malaria. “Therapeutically-rational exchange transfusion” (T-REX) is proposed in which Pk-resistant RBCs are transfused (instead of disease-promoting RBCs). Because expression of the Duffy antigen on the surface of human RBCs is essential for parasite invasion, T-REX of Duffy-negative RBCs—also known as Fy(a-b-) RBCs—could replace the majority of the patient’s circulating normocytes with Pk invasion-resistant RBCs (in a single procedure lasting about 2 h). When sequestered or non-sequestered iRBCs rupture—in a 24 h Pk asexual life cycle—the released merozoites cannot invade Fy(a-b-) RBCs. When Fy(a-b-) RBC units are scarce (e.g., in Malaysia), clinicians can consider the risks and benefits of transfusing plausibly Pk-resistant RBCs, such as glucose-6-phosphate dehydrogenase deficient (G6PDd) RBCs and Southeast Asian ovalocytes (SAO). Patients typically require a very short recovery time (<1 h) after the procedure. Fy(a-b-) RBCs should have a normal lifespan, while SAO and G6PDd RBCs may have mildly reduced half-lives. Because SAO and G6PDd RBCs come from screened blood donors who are healthy and not anemic, these RBCs have a low-risk for hemolysis and do not need to be removed after the patient recovers from malaria. T-REX could be especially useful if (1) antimalarial medications are not readily available, (2) patients are likely to progress to severe disease, or (3) drug-resistant strains emerge. In conclusion, T-REX is a proposed optimization of manual ET/RBCX that has not yet been utilized but can be considered by physicians to treat Pk malaria patients.

show abstract

Recent advances on patents of Plasmodium falciparum dihydroorotate dehydrogenase ( Pf DHODH) inhibitors as antimalarial agents

Gehlot,

Vyas

2023

Expert Opinion on Therapeutic Patents

View full text Add to dashboard Cite

The Impact of Geographical Variation in Plasmodium knowlesi Apical Membrane Protein 1 (PkAMA-1) on Invasion Dynamics of P. knowlesi

Cited by 4 publications

References 37 publications

Inter-Population Genetic Diversity and Clustering of Merozoite Surface Protein-1 (pkmsp-1) of Plasmodium knowlesi Isolates from Malaysia and Thailand

Inter-Population Genetic Diversity and Clustering of Merozoite Surface Protein-1 (pkmsp-1) of Plasmodium knowlesi Isolates from Malaysia and Thailand

Plasmodium knowlesi (Pk) Malaria: A Review & Proposal of Therapeutically Rational Exchange (T-REX) of Pk-Resistant Red Blood Cells

Recent advances on patents of Plasmodium falciparum dihydroorotate dehydrogenase ( Pf DHODH) inhibitors as antimalarial agents

Contact Info

Product

Resources

About