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Fulltext Case Report: Case Series of Human Plasmodium knowlesi Infection on the Southern Border of Thailand

Ngernna S, Rachaphaew N, Thammapalo S, Prikchoo P, Kaewnah O, Manopwisedjaroen K, et al.

Am J Trop Med Hyg, 2019 12;101(6):1397-1401.
PMID: 31595871 DOI: 10.4269/ajtmh.19-0063

Although human infections of Plasmodium knowlesi have been found throughout Southeast Asia, most cases originated from Malaysian Borneo. In Thailand, P. knowlesi malaria was considered extremely rare. However, during October 2017-September 2018, there was a surge in the number of reported P. knowlesi cases. Here, a series of six cases of P. knowlesi malaria found during this period in Songkhla and Narathiwat provinces of southern Thailand are presented. All cases were confirmed by polymerase chain reaction. The unprecedented case number in the affected area is a warning sign of an increasing P. knowlesi burden in the south of Thailand.
Fulltext Declining Genetic Polymorphisms of the C-terminus Merozoite Surface Protein-1 Amidst Increased Plasmodium knowlesi Transmission in Thailand

Tapaopong P, Chainarin S, Mala A, Rannarong A, Kangkasikorn N, Kusolsuk T, et al.

bioRxiv, 2024 Jun 27.
PMID: 38979329 DOI: 10.1101/2024.06.27.600943

Recent reports from Thailand reveal a substantial surge in Plasmodium knowlesi cases over the past decade, with a more than eightfold increase in incidence by 2023 compared to 2018. This study investigates temporal changes in genetic polymorphism associated with the escalating transmission of P. knowlesi malaria in Thailand over the past two decades. Twenty-five P. knowlesi samples collected in 2018-2023 were sequenced for the 42-kDa region of pkmsp1 and compared with 24 samples collected in 2000-2009, focusing on nucleotide diversity, natural selection, recombination rate, and population differentiation. Seven unique haplotypes were identified in recent samples, compared to 15 in earlier samples. Nucleotide and haplotype diversities were lower in recent samples (π = 0.016, Hd = 0.817) than in earlier samples (π = 0.018, Hd = 0.942). Significantly higher synonymous substitution rates were observed in both sample sets (dS - dN = 2.77 and 2.43, p < 0.05), indicating purifying selection and reduced genetic diversity over time. Additionally, 8 out of 17 mutation points were located on B-cell epitopes, suggesting an adaptive response by the parasites to evade immune recognition. Population differentiation analysis using the fixation index (Fst) revealed high genetic differentiation between parasite populations in central and southern Thailand or Malaysia. Conversely, the relatively lower Fst value between southern Thailand and Malaysia suggests a closer genetic relationship, possibly reflecting historical gene flow. In conclusion, our findings highlight a decline in genetic diversity and evidence of purifying selection associated with the recently increased incidence of P. knowlesi malaria in Thailand. The minor genetic differentiation between P. knowlesi populations from southern Thailand and Malaysia suggests a shared recent ancestry of these parasites and underscores the need for coordinated efforts between the two countries for the elimination of P. knowlesi.
Declining genetic polymorphism of the C-terminus Merozoite Surface Protein-1 amidst increased Plasmodium knowlesi transmission in Thailand

Tapaopong P, Chainarin S, Mala A, Rannarong A, Kangkasikorn N, Kusolsuk T, et al.

Malar J, 2024 Nov 13;23(1):342.
PMID: 39538241 DOI: 10.1186/s12936-024-05162-z

BACKGROUND: Recent reports from Thailand reveal a substantial surge in Plasmodium knowlesi cases over the past decades, with a more than eightfold increase in incidence by 2023 compared to 2018. This study investigates temporal changes in genetic polymorphism associated with the escalating transmission of P. knowlesi malaria in Thailand over time using the prominent vaccine candidate, pkmsp1 as a marker.
METHODS: Twenty-five P. knowlesi samples collected in 2018-2023 were sequenced for the 42-kDa region of pkmsp1 and compared with 24 retrieved sequences in 2000-2009, focusing on nucleotide diversity, natural selection, recombination rate, and population differentiation.
RESULTS: Seven unique haplotypes were identified in recent samples, compared to 15 in earlier samples. Nucleotide and haplotype diversity were lower in recent samples (π = 0.016, Hd = 0.817) than in earlier samples (π = 0.018, Hd = 0.942). Significantly higher synonymous substitution rates were observed in both sample sets (dS-dN = 2.77 and 2.43, p
Fulltext Plasmodium knowlesi can adapt to infect Duffy-negative erythrocytes

Zinga M, Ibrahim A, Mohring F, Chainarin S, Jonsdottir TK, Ngernna S, et al.

Blood, 2026 Apr 30;147(18):2132-2142.
PMID: 41701978 DOI: 10.1182/blood.2025029557

Plasmodium knowlesi, a zoonotic malaria species, has become a significant public health concern in Southeast Asia. In regions such as Malaysia and southern Thailand, P knowlesi incidence has risen, even as other human malaria parasites are nearing elimination. Similar to its close relative Plasmodium vivax, P knowlesi relies on the Duffy antigen receptor for chemokine (DARC) as a key receptor for erythrocyte invasion. Only Duffy-positive individuals are thought to be susceptible to clinical infection. Here, we demonstrate that P knowlesi possesses greater invasion plasticity than previously recognized. This parasite can bypass the need for DARC, as shown by its in vitro adaptation to invade and replicate within Duffy-negative (Fy-) erythrocytes. This adaptation is stable and independent of DARC binding, enabling the adapted parasite line to be maintained in Fy- erythrocytes and to resist inhibition by α-DARC antibodies. Genomic analysis identified a genomic recombination event between the parasite's dbpα and dbpγ genes, resulting in a new chimeric gene dbpαγ. Using CRISPR-Cas9 targeted reversion, we could demonstrate that dbpαγ is essential for invasion of Fy- erythrocytes. These findings shed new light on the invasion plasticity of P knowlesi, with implications for the parasite's potential spread beyond Southeast Asia and for understanding the complex host-cell specificity and atypical invasion pathways seen in P vivax.
Fulltext Spectrum of glucose-6-phosphate dehydrogenase (G6PD) mutations and trends in hemoglobin levels among adult dengue patients in Thailand

Chamnanchanunt S, Jacob BAC, Thanachartwet V, Desakorn V, Singha-Art N, Sahassananda D, et al.

PLoS One, 2025;20(9):e0332039.
PMID: 40966243 DOI: 10.1371/journal.pone.0332039

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathy in humans that may exacerbate clinical outcomes during viral infections such as dengue, particularly in regions where both conditions are endemic. This study aimed to characterize the spectrum of G6PD mutations and explore trends in hemoglobin levels among adult dengue patients in Thailand. Samples from 231 adult patients diagnosed with dengue were analyzed. G6PD deficiency was identified in 24 individuals (10.4%), while G6PD mutations were detected in 111 patients (48.1%). The most frequently observed mutations include a combination of synonymous and intronic mutations (c.1311C > T and c.1365-13T > C), compound mutation of G6PD Viangchan (c. 871G > A, c.1311C > T and c.1365-13T > C), and a deletion variant (c.486-34delT). Additionally, a novel variant, c.1439T > C, was identified and named "G6PD Phaya Thai". Patients carrying G6PD mutations exhibited different hemoglobin level trends compared to those without mutations. Specifically, while hemoglobin levels increased from the febrile to critical phase in patients without mutations, a significant decline was observed in mutation carriers. Median hemoglobin levels differed significantly between the two groups during both the febrile and critical phases (p = 0.02 and p
Fulltext Challenges for achieving safe and effective radical cure of Plasmodium vivax: a round table discussion of the APMEN Vivax Working Group

Thriemer K, Ley B, Bobogare A, Dysoley L, Alam MS, Pasaribu AP, et al.

Malar J, 2017 04 05;16(1):141.
PMID: 28381261 DOI: 10.1186/s12936-017-1784-1

The delivery of safe and effective radical cure for Plasmodium vivax is one of the greatest challenges for achieving malaria elimination from the Asia-Pacific by 2030. During the annual meeting of the Asia Pacific Malaria Elimination Network Vivax Working Group in October 2016, a round table discussion was held to discuss the programmatic issues hindering the widespread use of primaquine (PQ) radical cure. Participants included 73 representatives from 16 partner countries and 33 institutional partners and other research institutes. In this meeting report, the key discussion points are presented and grouped into five themes: (i) current barriers for glucose-6-phosphate deficiency (G6PD) testing prior to PQ radical cure, (ii) necessary properties of G6PD tests for wide scale deployment, (iii) the promotion of G6PD testing, (iv) improving adherence to PQ regimens and (v) the challenges for future tafenoquine (TQ) roll out. Robust point of care (PoC) G6PD tests are needed, which are suitable and cost-effective for clinical settings with limited infrastructure. An affordable and competitive test price is needed, accompanied by sustainable funding for the product with appropriate training of healthcare staff, and robust quality control and assurance processes. In the absence of quantitative PoC G6PD tests, G6PD status can be gauged with qualitative diagnostics, however none of the available tests is currently sensitive enough to guide TQ treatment. TQ introduction will require overcoming additional challenges including the management of severely and intermediately G6PD deficient individuals. Robust strategies are needed to ensure that effective treatment practices can be deployed widely, and these should ensure that the caveats are outweighed by the benefits of radical cure for both the patients and the community. Widespread access to quality controlled G6PD testing will be critical.