Profiling the imported human malaria in Sarawak, Malaysia in 2011–2019

Ooi, Choo Huck; Phang, Wei Kit; Liew, Jonathan Wee Kent; Atroosh, Wahib M.; Lau, Yee Ling

doi:10.1111/tmi.13875

Cited by 2 publications

(2 citation statements)

References 56 publications

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“…They suggest that a diagnosis of Pk malaria can be made based on the following: morphology resembling Pm, severe disease, parasite density > 5000/uL, and recent time in forest fringes in SEA [71]. Since 2018, Malaysia has not reported indigenous cases of Pf, Pv, Pm, nor P. ovale malaria, but they still have imported cases, which must be distinguished from Pk [118].…”

Section: Microscopymentioning

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

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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.

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Section: Microscopymentioning

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

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“…Nevertheless, Malaysia has achieved zero indigenous human malaria cases since 2018. However, imported human malaria has increased (Ooi et al, 2023). By analysing the genetic diversity of P. knowlesi isolates, a recent study has revealed the distribution of P. knowlesi subpopulations in East and West Malaysia (Scott, 2020).…”

Section: Introductionmentioning

confidence: 99%

Investigation of genetic diversity of Plasmodium knowlesi kelch13-propeller region in Sabah, Malaysia

Chee, J. K. L.,

Chong, E. T. J.,

Lee, P. C.

2023

MJM

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Aims:The kelch13 gene mutations of Plasmodium falciparum is associated with delayed parasite clearance after artemisinin-based combination therapy (ACT). It is unclear for P. knowlesi that is predominantly reported in Sabah. Therefore, this study aims to analyse the diversity of the P. knowlesi kelch13 gene in five divisions of Sabah. Methodology and results: Ninety-five blood samples infected with P. knowlesi were obtained. The DNA of P. knowlesi samples was extracted and the kelch13 gene was amplified. The amplicons were cloned and sequenced. The sequencing data were aligned and analysed using MEGA 11 and DnaSP v6 software. A phylogenetic tree was constructed using the Neighbour-joining approach, which showed a diverse clade of P. knowlesi in Sabah, with a nucleotide diversity (π) of 0.451 and a haplotype diversity of 0.947. The deduced amino acid sequences were classified into 14 haplotypes, providing evidence of distinct P. knowlesi lineages in Sabah. When compared to P. falciparum, the kelch13 sequences of P. knowlesi exhibited a higher π of 0.490 and haplotype diversity of 1.000, and similar mutations that conferred drug resistance to ACT in P. falciparum were detected in P. knowlesi in this study. Conclusion, significance and impact of study:The kelch13 gene of P. knowlesi isolates in Sabah has high nucleotide and haplotype diversities. Additionally, mutations conferring drug resistance to ACT in P. falciparum were identified in P. knowlesi in Sabah. The findings in this study can be used to better understand the emergence of drug resistance of P. knowlesi in Sabah.

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Profiling the imported human malaria in Sarawak, Malaysia in 2011–2019

Cited by 2 publications

References 56 publications

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

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

Investigation of genetic diversity of Plasmodium knowlesi kelch13-propeller region in Sabah, Malaysia

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