Plasmodium vivax malaria serological exposure markers: Assessing the degree and implications of cross-reactivity with P. knowlesi

Longley, Rhea J.; Grigg, Matthew J.; Schoffer, Kael L.; Obadia, Thomas; Hyslop, Stephanie; Piera, Kim A.; Nekkab, Narimane; Mazhari, Ramin; Takashima, Eizo; Tsuboi, Takafumi; Harbers, Matthias; Tetteh, Kevin K. A.; Drakeley, Chris; Chitnis, Chetan E.; Healer, Julie; Tham, Wai‐Hong; Sattabongkot, Jetsumon; White, Michael; Cooper, Daniel J.; Rajahram, Giri Shan; Barber, Bridget E.; William, Timothy; Anstey, Nicholas M.; Müeller, Ivo

doi:10.1016/j.xcrm.2022.100662

Cited by 10 publications

(8 citation statements)

References 61 publications

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“…Nevertheless, this work provides an example of a validated, built-for-purpose tool specific to the local epidemiological context. Since performing the initial literature search for this scoping review, further work exploring the cross-reactivity between Plasmodium species has been published [ 106 ]. The authors explored IgG cross-reactivity between P. vivax and P. knowlesi and found that although P. knowlesi induces cross-reactive antibodies to P. vivax , these are short-lived, and cross-reactivity can be reduced through appropriate antigen selection.…”

Section: Discussionmentioning

confidence: 99%

Using Serological Markers for the Surveillance of Plasmodium vivax Malaria: A Scoping Review

Kartal,

Mueller,

Longley

2023

Pathogens

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The utilisation of serological surveillance methods for malaria has the potential to identify individuals exposed to Plasmodium vivax, including asymptomatic carriers. However, the application of serosurveillance varies globally, including variations in methodology and transmission context. No systematic review exists describing the advantages and disadvantages of utilising serosurveillance in various settings. Collation and comparison of these results is a necessary first step to standardise and validate the use of serology for the surveillance of P. vivax in specific transmission contexts. A scoping review was performed of P. vivax serosurveillance applications globally. Ninety-four studies were found that met predefined inclusion and exclusion criteria. These studies were examined to determine the advantages and disadvantages of serosurveillance experienced in each study. If studies reported seroprevalence results, this information was also captured. Measurement of antibodies serves as a proxy by which individuals exposed to P. vivax may be indirectly identified, including those with asymptomatic infections, which may be missed by other technologies. Other thematic advantages identified included the ease and simplicity of serological assays compared to both microscopy and molecular diagnostics. Seroprevalence rates varied widely from 0–93%. Methodologies must be validated across various transmission contexts to ensure the applicability and comparability of results. Other thematic disadvantages identified included challenges with species cross-reactivity and determining changes in transmission patterns in both the short- and long-term. Serosurveillance requires further refinement to be fully realised as an actionable tool. Some work has begun in this area, but more is required.

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Section: Discussionmentioning

confidence: 99%

Using Serological Markers for the Surveillance of Plasmodium vivax Malaria: A Scoping Review

Kartal,

Mueller,

Longley

2023

Pathogens

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“…Moreover, antibodies against P. vivax are acquired quickly but are less durable than antibodies against P. falciparum , which accumulate and degrade slowly over time ( Yap et al., 2021 ). Given recent evidence of high levels of antibody cross-reactivity, particularly for MSP-1 19 between P. vivax and P. knowlesi (>81% sequence identity between the Sal1 and H strains, respectively) in patients from Malaysia ( Longley et al., 2022 ), further analyses could be conducted to run the serological assay against more antigenic targets to optimise P. vivax antibody detection. Hence, it will be important to reduce the potential misclassification of Plasmodium species by serology in co-endemic areas.…”

Section: Discussionmentioning

confidence: 99%

Naturally acquired antibody response to Plasmodium falciparum and Plasmodium vivax among indigenous Orang Asli communities in Peninsular Malaysia

Rahim

Munajat

Dian

et al. 2023

Front. Cell. Infect. Microbiol.

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Malaria remains a public health problem in many parts of the world. In Malaysia, the significant progress towards the national elimination programme and effective disease notification on malaria has resulted in zero indigenous human malaria cases since 2018. However, the country still needs to determine the extent of malaria exposure and transmission patterns, particularly in high-risk populations. In this study, a serological method was used to measure transmission levels of Plasmodium falciparum and Plasmodium vivax among indigenous Orang Asli communities in Kelantan, Peninsular Malaysia. A community-based cross-sectional survey was conducted in three Orang Asli communities (i.e., Pos Bihai, Pos Gob, and Pos Kuala Betis) in Kelantan from June to July 2019. Antibody responses to malaria were assessed by enzyme-linked immunosorbent assay (ELISA) using two P. falciparum (PfAMA-1 and PfMSP-119) and two P. vivax (PvAMA-1 and PvMSP-119) antigens. Age-adjusted antibody responses were analysed using a reversible catalytic model to calculate seroconversion rates (SCRs). Multiple logistic regression was used to investigate factors associated with malaria exposure. The overall malaria seroprevalence was 38.8% for PfAMA-1, 36.4% for PfMSP-119, 2.2% for PvAMA-1, and 9.3% for PvMSP-119. Between study areas, the proportion of seropositivity for any P. falciparum and P. vivax antigens was significantly highest in Pos Kuala Betis with 34.7% (p < 0.001) and 13.6% (p < 0.001), respectively. For all parasite antigens except for PvAMA-1, the proportion of seropositive individuals significantly increased with age (all p < 0.001). Based on the SCR, there was a higher level of P. falciparum transmission than P. vivax in the study area. Multivariate regression analyses showed that living in Pos Kuala Betis was associated with both P. falciparum (adjusted odds ratio [aOR] 5.6, p < 0.001) and P. vivax (aOR 2.1, p < 0.001) seropositivities. Significant associations were also found between age and seropositivity to P. falciparum and P. vivax antigens. Analysis of community-based serological data helps describe the level of transmission, heterogeneity, and factors associated with malaria exposure among indigenous communities in Peninsular Malaysia. This approach could be an important adjunct tool for malaria monitoring and surveillance in low malaria transmission settings in the country.

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“…It assumes that the folded protein structure puts minimum strain on side-chain conformations, favoring low-energy positions during folding [ 48 ]. Since P. knowlesi and P. vivax are phylogenetically close and several studies have shown the importance of conserved cross-species vaccine candidates [ 11 , 49 , 50 ]. Therefore, in addition to identifying epitopes in P. knowlesi, this study examined the likelihood of epitope conservation with P. vivax .…”

Section: Methodsmentioning

confidence: 99%

In Silico Analysis Reveals High Levels of Genetic Diversity of Plasmodium knowlesi Cell Traversal Protein for Ookinetes and Sporozoites (PkCelTOS) in Clinical Samples

et al. 2023

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The cell-traversal protein for ookinetes and sporozoites (CelTOS), expressed on the surface of ookinetes and sporozoitesin Plasmodium species, is a promising malaria vaccine candidate. CelTOS is essential for parasite invasion into mosquito midgut and human hepatocytes, thereby contributing to malaria transmission and disease pathogenesis. This study explores the genetic diversity, polymorphisms, haplotypes, natural selection, phylogenetic analysis, and epitope prediction in the full-length Plasmodium knowlesi CelTOS gene in clinical samples from Sarawak, Malaysian Borneo, and long-term laboratory strains from Peninsular Malaysia and the Philippines. Our analysis revealed a high level of genetic variation in the PkCelTOS gene, with a nucleotide diversity of π ~ 0.021, which was skewed towards the 3’ end of the gene. This level of diversity is double that observed in PfCelTOS and 20 times that observed in PvCelTOS from worldwide clinical samples. Tests of natural selection revealed evidence for positive selection within clinical samples. Phylogenetic analysis of the amino acid sequence of PkCelTOS revealed the presence of two distinct groups, although no geographical clustering was observed. Epitope prediction analysis identified two potential epitopes (96AQLKATA102 and 124TIKPPRIKED133) using the IEDB server and one epitope (125IKPPRIKED133) by Bcepred server on the C’ terminal region of PkCelTOS protein. Both the servers predicted a common epitope region of nine amino acid length (IKPPRIKED) peptide, which can be studied in the future as a potential candidate for vaccine development. These findings shed light on the genetic diversity, polymorphism, haplotypes, and natural selection within PkCelTOS in clinical samples and provide insights about its future prospects as a potential candidate for P. knowlesi malaria vaccine development.

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Plasmodium vivax malaria serological exposure markers: Assessing the degree and implications of cross-reactivity with P. knowlesi

Cited by 10 publications

References 61 publications

Using Serological Markers for the Surveillance of Plasmodium vivax Malaria: A Scoping Review

Using Serological Markers for the Surveillance of Plasmodium vivax Malaria: A Scoping Review

Naturally acquired antibody response to Plasmodium falciparum and Plasmodium vivax among indigenous Orang Asli communities in Peninsular Malaysia

In Silico Analysis Reveals High Levels of Genetic Diversity of Plasmodium knowlesi Cell Traversal Protein for Ookinetes and Sporozoites (PkCelTOS) in Clinical Samples

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