Plasmodium vivax malaria serological exposure markers: Assessing the degree and implications of cross-reactivity with P. knowlesi
Rhea J Longley, Matthew J Grigg, Kael Schoffer, Thomas Obadia, Stephanie Hyslop, Kim A Piera, Narimane Nekkab, Ramin Mazhari, Eizo Takashima, Takafumi Tsuboi, Matthias Harbers, Kevin Tetteh, Chris Drakeley, Chetan E Chitnis, Julie Healer, Wai-Hong Tham, Jetsumon Sattabongkot, Michael T White, Daniel J Cooper, Giri S Rajahram, Bridget E Barber, Timothy William, Nicholas M Anstey, Ivo Mueller, Rhea J Longley, Matthew J Grigg, Kael Schoffer, Thomas Obadia, Stephanie Hyslop, Kim A Piera, Narimane Nekkab, Ramin Mazhari, Eizo Takashima, Takafumi Tsuboi, Matthias Harbers, Kevin Tetteh, Chris Drakeley, Chetan E Chitnis, Julie Healer, Wai-Hong Tham, Jetsumon Sattabongkot, Michael T White, Daniel J Cooper, Giri S Rajahram, Bridget E Barber, Timothy William, Nicholas M Anstey, Ivo Mueller
Abstract
Serological markers are a promising tool for surveillance and targeted interventions for Plasmodium vivax malaria. P. vivax is closely related to the zoonotic parasite P. knowlesi, which also infects humans. P. vivax and P. knowlesi are co-endemic across much of South East Asia, making it important to design serological markers that minimize cross-reactivity in this region. To determine the degree of IgG cross-reactivity against a panel of P. vivax serological markers, we assayed samples from human patients with P. knowlesi malaria. IgG antibody reactivity is high against P. vivax proteins with high sequence identity with their P. knowlesi ortholog. IgG reactivity peaks at 7 days post-P. knowlesi infection and is short-lived, with minimal responses 1 year post-infection. We designed a panel of eight P. vivax proteins with low levels of cross-reactivity with P. knowlesi. This panel can accurately classify recent P. vivax infections while reducing misclassification of recent P. knowlesi infections.
Trial registration: ClinicalTrials.gov NCT01708876 NCT03056391.
Keywords: Plasmodium knowlesi; Plasmodium vivax; antibodies; antibody cross-reactivity; malaria; malaria elimination; serological exposure markers; serosurveillance; species cross-reactivity.
Conflict of interest statement
Declaration of interests R.L., M.W., T.T., and and I.M. are inventors on filed patent PCT/US17/67926 on a system, method, apparatus, and diagnostic test for P. vivax. M.H. was an employee of the company CellFree Sciences Co., Ltd.
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
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References
- Auburn S., Cheng Q., Marfurt J., Price R.N. The changing epidemiology of Plasmodium vivax: insights from conventional and novel surveillance tools. PLoS Med. 2021;18:e1003560. doi: 10.1371/journal.pmed.1003560.
- Kho S., Qotrunnada L., Leonardo L., Andries B., Wardani P.A.I., Fricot A., Henry B., Hardy D., Margyaningsih N.I., Apriyanti D., et al. Hidden biomass of intact malaria parasites in the human spleen. N. Engl. J. Med. 2021;384:2067–2069. doi: 10.1056/NEJMc2023884.
- Kho S., Qotrunnada L., Leonardo L., Andries B., Wardani P.A.I., Fricot A., Henry B., Hardy D., Margyaningsih N.I., Apriyanti D., et al. Evaluation of splenic accumulation and colocalization of immature reticulocytes and Plasmodium vivax in asymptomatic malaria: a prospective human splenectomy study. PLoS Med. 2021;18:e1003632. doi: 10.1371/journal.pmed.1003632.
- Moreira C.M., Abo-Shehada M., Price R.N., Drakeley C.J. A systematic review of sub-microscopic Plasmodium vivax infection. Malar. J. 2015;14:360. doi: 10.1186/s12936-015-0884-z.
- Kiattibutr K., Roobsoong W., Sriwichai P., Saeseu T., Rachaphaew N., Suansomjit C., Buates S., Obadia T., Mueller I., Cui L., et al. Infectivity of symptomatic and asymptomatic Plasmodium vivax infections to a Southeast Asian vector, Anopheles dirus. Int. J. Parasitol. 2017;47:163–170. doi: 10.1016/j.ijpara.2016.10.006.
- Robinson L.J., Wampfler R., Betuela I., Karl S., White M.T., Li Wai Suen C.S.N., Hofmann N.E., Kinboro B., Waltmann A., Brewster J., et al. Strategies for understanding and reducing the Plasmodium vivax and Plasmodium ovale hypnozoite reservoir in Papua New Guinean children: a randomised placebo-controlled trial and mathematical model. PLoS Med. 2015;12:e1001891. doi: 10.1371/journal.pmed.1001891.
- Commons R.J., Simpson J.A., Watson J., White N.J., Price R.N. Estimating the proportion of Plasmodium vivax recurrences caused by relapse: a systematic review and meta-analysis. Am. J. Trop. Med. Hyg. 2020;103:1094–1099. doi: 10.4269/ajtmh.20-0186.
- Adekunle A.I., Pinkevych M., McGready R., Luxemburger C., White L.J., Nosten F., Cromer D., Davenport M.P. Modeling the dynamics of Plasmodium vivax infection and hypnozoite reactivation in vivo. PLoS Negl. Trop. Dis. 2015;9:e0003595. doi: 10.1371/journal.pntd.0003595.
- Longley R.J., White M.T., Takashima E., Brewster J., Morita M., Harbers M., Obadia T., Robinson L.J., Matsuura F., Liu Z.S.J., et al. Development and validation of serological markers for detecting recent Plasmodium vivax infection. Nat. Med. 2020;26:741–749. doi: 10.1038/s41591-020-0841-4.
- White N.J. Determinants of relapse periodicity in Plasmodium vivax malaria. Malar. J. 2011;10:297. doi: 10.1186/1475-2875-10-297.
- Chotirat S., Nekkab N., Kumpitak C., Hietanen J., White M.T., Kiattibutr K., Sa-angchai P., Brewster J., Schoffer K., Takashima E., et al. Application of 23 novel serological markers for identifying recent exposure to Plasmodium vivax parasites in an endemic population of western Thailand. Front. Microbiol. 2021;12:643501. doi: 10.3389/fmicb.2021.643501.
- Greenhouse B., Daily J., Guinovart C., Goncalves B., Beeson J., Bell D., Chang M.A., Cohen J.M., Ding X., Domingo G., et al. Priority use cases for antibody-detecting assays of recent malaria exposure as tools to achieve and sustain malaria elimination. Gates Open Res. 2019;3:131. doi: 10.12688/gatesopenres.12897.1.
- WHO . World Health Organisation; 2021. World Malaria Report.
- Loy D.E., Liu W., Li Y., Learn G.H., Plenderleith L.J., Sundararaman S.A., Sharp P.M., Hahn B.H. Out of Africa: origins and evolution of the human malaria parasites Plasmodium falciparum and plasmodium vivax. Int. J. Parasitol. 2017;47:87–97. doi: 10.1016/j.ijpara.2016.05.008.
- Mitran C.J., Yanow S.K. The case for exploiting cross-species epitopes in malaria vaccine design. Front. Immunol. 2020;11:335. doi: 10.3389/fimmu.2020.00335.
- Priest J.W., Plucinski M.M., Huber C.S., Rogier E., Mao B., Gregory C.J., Candrinho B., Colborn J., Barnwell J.W. Specificity of the IgG antibody response to Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, and Plasmodium ovale MSP1(19) subunit proteins in multiplexed serologic assays. Malar. J. 2018;17:417. doi: 10.1186/s12936-018-2566-0.
- Woodberry T., Minigo G., Piera K.A., Hanley J.C., de Silva H.D., Salwati E., Kenangalem E., Tjitra E., Coppel R.L., Price R.N., et al. Antibodies to Plasmodium falciparum and Plasmodium vivax merozoite surface protein 5 in Indonesia: species-specific and cross-reactive responses. J. Infect. Dis. 2008;198:134–142. doi: 10.1086/588711.
- Diggs C.L., Sadun E.H. Serological cross reactivity between plasmodium vivax and plasmodium falciparum as determined BY a modified fluorescent antibody test. Exp. Parasitol. 1965;16:217–223. doi: 10.1016/0014-4894(65)90046-9.
- Lacerda M.V.G., Bassat Q. Primaquine for all: is it time to simplify malaria treatment in co-endemic areas? Lancet Infect. Dis. 2019;19:10–12. doi: 10.1016/s1473-3099(18)30612-1.
- Looareesuwan S., White N.J., Chittamas S., Bunnag D., Harinasuta T. High rate of Plasmodium vivax relapse following treatment of falciparum malaria in Thailand. Lancet. 1987;330:1052–1055. doi: 10.1016/s0140-6736(87)91479-6.
- Douglas N.M., Nosten F., Ashley E.A., Phaiphun L., van Vugt M., Singhasivanon P., White N.J., Price R.N. Plasmodium vivax recurrence following falciparum and mixed species malaria: risk factors and effect of antimalarial kinetics. Clin. Infect. Dis. 2011;52:612–620. doi: 10.1093/cid/ciq249.
- Hossain M.S., Commons R.J., Douglas N.M., Thriemer K., Alemayehu B.H., Amaratunga C., Anvikar A.R., Ashley E.A., Asih P.B.S., Carrara V.I., et al. The risk of Plasmodium vivax parasitaemia after P. falciparum malaria: an individual patient data meta-analysis from the WorldWide Antimalarial Resistance Network. PLoS Med. 2020;17:e1003393. doi: 10.1371/journal.pmed.1003393.
- Eziefula A.C., Bousema T., Yeung S., Kamya M., Owaraganise A., Gabagaya G., Bradley J., Grignard L., Lanke K.H., Wanzira H., et al. Single dose primaquine for clearance of Plasmodium falciparum gametocytes in children with uncomplicated malaria in Uganda: a randomised, controlled, double-blind, dose-ranging trial. Lancet Infect. Dis. 2014;14:130–139. doi: 10.1016/s1473-3099(13)70268-8.
- Ashley E.A., Recht J., White N.J. Primaquine: the risks and the benefits. Malar. J. 2014;13:418. doi: 10.1186/1475-2875-13-418.
- Ley B., Winasti Satyagraha A., Rahmat H., von Fricken M.E., Douglas N.M., Pfeffer D.A., Espino F., von Seidlein L., Henriques G., Oo N.N., et al. Performance of the Access Bio/CareStart rapid diagnostic test for the detection of glucose-6-phosphate dehydrogenase deficiency: a systematic review and meta-analysis. PLoS Med. 2019;16:e1002992. doi: 10.1371/journal.pmed.1002992.
- Ley B., Alam M.S., Kibria M.G., Marfurt J., Phru C.S., Ami J.Q., Thriemer K., Auburn S., Jahan N., Johora F.T., et al. Glucose-6-phosphate dehydrogenase activity in individuals with and without malaria: analysis of clinical trial, cross-sectional and case-control data from Bangladesh. PLoS Med. 2021;18:e1003576. doi: 10.1371/journal.pmed.1003576.
- Muh F., Kim N., Nyunt M.H., Firdaus E.R., Han J.H., Hoque M.R., Lee S.K., Park J.H., Moon R.W., Lau Y.L., et al. Cross-species reactivity of antibodies against Plasmodium vivax blood-stage antigens to Plasmodium knowlesi. PLoS Negl. Trop. Dis. 2020;14 doi: 10.1371/journal.pntd.0008323.
- Herman L.S., Fornace K., Phelan J., Grigg M.J., Anstey N.M., William T., Moon R.W., Blackman M.J., Drakeley C.J., Tetteh K.K.A. Identification and validation of a novel panel of Plasmodium knowlesi biomarkers of serological exposure. PLoS Negl. Trop. Dis. 2018;12:e0006457. doi: 10.1371/journal.pntd.0006457.
- Fornace K.M., Herman L.S., Abidin T.R., Chua T.H., Daim S., Lorenzo P.J., Grignard L., Nuin N.A., Ying L.T., Grigg M.J., et al. Exposure and infection to Plasmodium knowlesi in case study communities in Northern Sabah, Malaysia and Palawan, the Philippines. PLoS Negl. Trop. Dis. 2018;12:e0006432. doi: 10.1371/journal.pntd.0006432.
- Cuenca P.R., Key S., Jumail A., Surendra H., Ferguson H.M., Drakeley C.J., Fornace K. Epidemiology of the zoonotic malaria Plasmodium knowlesi in changing landscapes. Adv. Parasitol. 2021;113:225–286. doi: 10.1016/bs.apar.2021.08.006.
- Grigg M.J., Cox J., William T., Jelip J., Fornace K.M., Brock P.M., von Seidlein L., Barber B.E., Anstey N.M., Yeo T.W., Drakeley C.J. Individual-level factors associated with the risk of acquiring human Plasmodium knowlesi malaria in Malaysia: a case-control study. Lancet Planet. Health. 2017;1:e97–e104. doi: 10.1016/s2542-5196(17)30031-1.
- Barber B.E., Grigg M.J., William T., Yeo T.W., Anstey N.M. The treatment of Plasmodium knowlesi malaria. Trends Parasitol. 2017;33:242–253. doi: 10.1016/j.pt.2016.09.002.
- Pain A., Böhme U., Berry A.E., Mungall K., Finn R.D., Jackson A.P., Mourier T., Mistry J., Pasini E.M., Aslett M.A., et al. The genome of the simian and human malaria parasite Plasmodium knowlesi. Nature. 2008;455:799–803. doi: 10.1038/nature07306.
- Benavente E.D., de Sessions P.F., Moon R.W., Grainger M., Holder A.A., Blackman M.J., Roper C., Drakeley C.J., Pain A., Sutherland C.J., et al. A reference genome and methylome for the Plasmodium knowlesi A1-H.1 line. Int. J. Parasitol. 2018;48:191–196. doi: 10.1016/j.ijpara.2017.09.008.
- Needleman S.B., Wunsch C.D. A general method applicable to the search for similarities in the amino acid sequence of two proteins. J. Mol. Biol. 1970;48:443–453. doi: 10.1016/0022-2836(70)90057-4.
- Grigg M.J., William T., Menon J., Dhanaraj P., Barber B.E., Wilkes C.S., von Seidlein L., Rajahram G.S., Pasay C., McCarthy J.S., et al. Artesunate-mefloquine versus chloroquine for treatment of uncomplicated Plasmodium knowlesi malaria in Malaysia (ACT KNOW): an open-label, randomised controlled trial. Lancet Infect. Dis. 2016;16:180–188. doi: 10.1016/s1473-3099(15)00415-6.
- Cooper D.J., Plewes K., Grigg M.J., Rajahram G.S., Piera K.A., William T., Chatfield M.D., Yeo T.W., Dondorp A.M., Anstey N.M., Barber B.E. The effect of regularly dosed paracetamol versus no paracetamol on renal function in Plasmodium knowlesi malaria (PACKNOW): study protocol for a randomised controlled trial. Trials. 2018;19:250. doi: 10.1186/s13063-018-2600-0.
- Cooper D.J., Grigg M.J., Plewes K., Rajahram G.S., Piera K.A., William T., Menon J., Koleth G., Edstein M.D., Birrell G.W., et al. The effect of regularly dosed acetaminophen versus no acetaminophen on renal function in Plasmodium knowlesi malaria (PACKNOW): a randomised controlled trial. Clin. Infect. Dis. 2022:ciac152.
- Cooper D.J., Rajahram G.S., William T., Jelip J., Mohammad R., Benedict J., Alaza D.A., Malacova E., Yeo T.W., Grigg M.J., et al. Plasmodium knowlesi malaria in Sabah, Malaysia, 2015-2017: ongoing increase in incidence despite near-elimination of the human-only Plasmodium species. Clin. Infect. Dis. 2020;70:361–367. doi: 10.1093/cid/ciz237.
- Singh B., Daneshvar C. Human infections and detection of Plasmodium knowlesi. Clin. Microbiol. Rev. 2013;26:165–184. doi: 10.1128/cmr.00079-12.
- Grigg M.J., William T., Barber B.E., Rajahram G.S., Menon J., Schimann E., Piera K., Wilkes C.S., Patel K., Chandna A., et al. Age-related clinical spectrum of Plasmodium knowlesi malaria and predictors of severity. Clin. Infect. Dis. 2018;67:350–359. doi: 10.1093/cid/ciy065.
- Barber B.E., Grigg M.J., William T., Piera K.A., Boyle M.J., Yeo T.W., Anstey N.M. Effects of aging on parasite biomass, inflammation, endothelial activation, microvascular dysfunction and disease severity in Plasmodium knowlesi and Plasmodium falciparum malaria. J. Infect. Dis. 2017;215:1908–1917. doi: 10.1093/infdis/jix193.
- Rogier E., Nace D., Dimbu P.R., Wakeman B., Pohl J., Beeson J.G., Drakeley C., Tetteh K., Plucinski M. Framework for characterizing longitudinal antibody response in children after Plasmodium falciparum infection. Front. Immunol. 2021;12:617951. doi: 10.3389/fimmu.2021.617951.
- Yman V., White M.T., Asghar M., Sundling C., Sondén K., Draper S.J., Osier F.H.A., Färnert A. Antibody responses to merozoite antigens after natural Plasmodium falciparum infection: kinetics and longevity in absence of re-exposure. BMC Med. 2019;17:22. doi: 10.1186/s12916-019-1255-3.
- Liu Z.S.J., Sattabongkot J., White M., Chotirat S., Kumpitak C., Takashima E., Harbers M., Tham W.H., Healer J., Chitnis C.E., et al. Naturally acquired antibody kinetics against Plasmodium vivax antigens in people from a low malaria transmission region in western Thailand. BMC Med. 2022;20:89. doi: 10.1186/s12916-022-02281-9.
- Muh F., Ahmed M.A., Han J.H., Nyunt M.H., Lee S.K., Lau Y.L., Kaneko O., Han E.T. Cross-species analysis of apical asparagine-rich protein of Plasmodium vivax and Plasmodium knowlesi. Sci. Rep. 2018;8:5781. doi: 10.1038/s41598-018-23728-1.
- Rosa D.S., Iwai L.K., Tzelepis F., Bargieri D.Y., Medeiros M.A., Soares I.S., Sidney J., Sette A., Kalil J., Mello L.E., et al. Immunogenicity of a recombinant protein containing the Plasmodium vivax vaccine candidate MSP1(19) and two human CD4+ T-cell epitopes administered to non-human primates (Callithrix jacchus jacchus) Microb. Infect. 2006;8:2130–2137. doi: 10.1016/j.micinf.2006.03.012.
- De S.L., Ntumngia F.B., Nicholas J., Adams J.H. Progress towards the development of a P. vivax vaccine. Expert Rev. Vaccines. 2021;20:97–112. doi: 10.1080/14760584.2021.1880898.
- Kale S., Yadav C.P., Rao P.N., Shalini S., Eapen A., Srivasatava H.C., Sharma S.K., Pande V., Carlton J.M., Singh O.P., Mallick P.K. Antibody responses within two leading Plasmodium vivax vaccine candidate antigens in three geographically diverse malaria-endemic regions of India. Malar. J. 2019;18:425. doi: 10.1186/s12936-019-3066-6.
- McCaffery J.N., Fonseca J.A., Singh B., Cabrera-Mora M., Bohannon C., Jacob J., Arévalo-Herrera M., Moreno A. A multi-stage Plasmodium vivax malaria vaccine candidate able to induce long-lived antibody responses against blood stage parasites and robust transmission-blocking activity. Front. Cell. Infect. Microbiol. 2019;9:135. doi: 10.3389/fcimb.2019.00135.
- Ndegwa D.N., Kundu P., Hostetler J.B., Marin-Menendez A., Sanderson T., Mwikali K., Verzier L.H., Coyle R., Adjalley S., Rayner J.C. Using Plasmodium knowlesi as a model for screening Plasmodium vivax blood-stage malaria vaccine targets reveals new candidates. PLoS Pathog. 2021;17:e1008864. doi: 10.1371/journal.ppat.1008864.
- Anstey N.M., Grigg M.J. Zoonotic malaria: the better you look, the more you find. J. Infect. Dis. 2019;219:679–681. doi: 10.1093/infdis/jiy520.
- França C.T., White M.T., He W.Q., Hostetler J.B., Brewster J., Frato G., Malhotra I., Gruszczyk J., Huon C., Lin E., et al. Identification of highly-protective combinations of Plasmodium vivax recombinant proteins for vaccine development. Elife. 2017;6:e28673. doi: 10.7554/eLife.28673.
- Ssewanyana I., Rek J., Rodriguez I., Wu L., Arinaitwe E., Nankabirwa J.I., Beeson J.G., Mayanja-Kizza H., Rosenthal P.J., Dorsey G., et al. Impact of a rapid decline in malaria transmission on antimalarial IgG subclasses and avidity. Front. Immunol. 2020;11:576663. doi: 10.3389/fimmu.2020.576663.
- Yap N.J., Hossain H., Nada-Raja T., Ngui R., Muslim A., Hoh B.P., Khaw L.T., Kadir K.A., Simon Divis P.C., Vythilingam I., et al. Natural human infections with Plasmodium cynomolgi, P. Inui, and 4 other simian malaria parasites, Malaysia. Emerg. Infect. Dis. 2021;27:2187–2191. doi: 10.3201/eid2708.204502.
- Obadia T., Nekkab N., Robinson L., Drakeley C., Mueller I., White M.T. Developing sero-diagnostic tests to facilitate Plasmodium vivax Serological Test-and-Treat approaches: modelling the balance between public health impact and overtreatment. BMC Med. 2022;20:98.
- Mazhari R., Brewster J., Fong R., Bourke C., Liu Z.S.J., Takashima E., Tsuboi T., Tham W.H., Harbers M., Chitnis C., et al. A comparison of non-magnetic and magnetic beads for measuring IgG antibodies against Plasmodium vivax antigens in a multiplexed bead-based assay using Luminex technology (Bio-Plex 200 or MAGPIX) PLoS One. 2020;15:e0238010. doi: 10.1371/journal.pone.0238010.
- Nuin N.A., Tan A.F., Lew Y.L., Piera K.A., William T., Rajahram G.S., Jelip J., Dony J.F., Mohammad R., Cooper D.J., et al. Comparative evaluation of two commercial real-time PCR kits (QuantiFast™ and abTES™) for the detection of Plasmodium knowlesi and other Plasmodium species in Sabah, Malaysia. Malar. J. 2020;19:306. doi: 10.1186/s12936-020-03379-2.
- Amos B., Aurrecoechea C., Barba M., Barreto A., Basenko E.Y., Bażant W., Bażant W., Belnap R., Blevins A.S., Böhme U., et al. VEuPathDB: the eukaryotic pathogen, vector and host bioinformatics resource center. Nucleic Acids Res. 2022;50 doi: 10.1093/nar/gkab929. D898–D911.
- Garzón-Ospina D., Forero-Rodríguez J., Patarroyo M.A. Evidence of functional divergence in MSP7 paralogous proteins: a molecular-evolutionary and phylogenetic analysis. BMC Evol. Biol. 2016;16:256. doi: 10.1186/s12862-016-0830-x.
- Kuamsab N., Putaporntip C., Pattanawong U., Jongwutiwes S. Insights into the molecular diversity of Plasmodium vivax merozoite surface protein-3γ (pvmsp3γ), a polymorphic member in the msp3 multi-gene family. Sci. Rep. 2020;10:10977. doi: 10.1038/s41598-020-67222-z.
- Camacho C., Coulouris G., Avagyan V., Ma N., Papadopoulos J., Bealer K., Madden T.L. BLAST+: architecture and applications. BMC Bioinf. 2009;10:421. doi: 10.1186/1471-2105-10-421.
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