Hostname: page-component-8448b6f56d-m8qmq Total loading time: 0 Render date: 2024-04-24T12:58:09.750Z Has data issue: false hasContentIssue false

Biological concepts in recurrent Plasmodium vivax malaria

Published online by Cambridge University Press:  22 March 2018

Miles B. Markus*
Affiliation:
School of Animal, Plant, and Environmental Sciences, Faculty of Science, University of the Witwatersrand, Private Bag 3, Wits, Johannesburg, 2050South Africa Wits Research Institute for Malaria, Faculty of Health Sciences, University of the Witwatersrand, York Road, Parktown, Johannesburg, 2193South Africa
*
Author for correspondence: Miles B. Markus, E-mail: medsynth@yahoo.co.uk

Abstract

A curious aspect of the evolution of the hypnozoite theory of malarial relapse is its transmogrification from theory into ‘fact’, this being of historical, linguistic, scientific and sociological interest. As far as it goes, the hypnozoite explanation for relapse is almost certainly correct. I contend, however, that many of the genotypically homologous, non-reinfection, relapse-like Plasmodium vivax recurrences that researchers ascribe to hypnozoite activation are probably hypnozoite-independent. Indeed, some malariologists are starting to recognize that homologous P. vivax recurrences have most likely been overattributed to activation of hypnozoites. Hitherto identified, non-hypnozoite, possible plasmodial sources of recurrence that must be considered, besides circulating erythrocytic stages, include parasites in splenic dendritic cells, other cells in the spleen (in addition to infected erythrocytes there), bone marrow (importantly) and the skin. I argue that we need to take into account the possibility of a dual or multiple extra-vascular origin of P. vivax non-reinfection recurrences, not arbitrarily discount it. The existence of a P. vivax reservoir(s) is a topical subject and one of practical importance for malaria eradication. Pertinent drug-associated matters are also discussed, as is the dormancy-related significance of clues provided by blood-stage-induced malarial infection.

Type
Special Issue Review
Copyright
Copyright © Cambridge University Press 2018 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Baird, JK (2013) Evidence and implications of mortality associated with acute Plasmodium vivax malaria. Clinical Microbiology Reviews 26, 3657.Google Scholar
Baird, JK, Battle, KE and Howes, RE (2018) Primaquine ineligibility in anti-relapse therapy of Plasmodium vivax malaria: the problem of G6PD deficiency and cytochrome P-450 2D6 polymorphisms. Malaria Journal 17, 42.Google Scholar
Barber, BE, William, T, Grigg, MJ, Parameswaran, U, Piera, KA, Price, RN, Yeo, TW and Anstey, NM (2015) Parasite biomass-related inflammation, endothelial activation, microvascular dysfunction and disease severity in vivax malaria. PLoS Pathogens 11, e1004558.Google Scholar
Baro, B, Deroost, K, Raiol, T, Brito, M, Almeida, ACG, de Menezes-Neto, A, Figueiredo, EFG, Alencar, A, Leitão, R, Val, F, Monteiro, W, Oliveira, A, del Pilar Armengol, M, Fernández-Becerra, C, Lacerda, MV and del Portillo, HA (2017) Plasmodium vivax gametocytes in the bone marrow of an acute malaria patient and changes in the erythroid miRNA profile. PLoS Neglected Tropical Diseases 11, e0005365.Google Scholar
Betson, M, Clifford, S, Stanton, M, Kabatereine, NB and Stothard, JR (2018) Emergence of nonfalciparum Plasmodium infection despite regular artemisinin combination therapy in an 18-month longitudinal study of Ugandan children and their mothers. Journal of Infectious Diseases 217, 10991109.Google Scholar
Boyd, MF and Kitchen, SF (1944) Renewed clinical activity in naturally induced vivax malaria. American Journal of Tropical Medicine and Hygiene s1–24, 221234.Google Scholar
Bray, RS (1984) The response of Plasmodium vivax to antifols. Transactions of the Royal Society of Tropical Medicine and Hygiene 78, 420421.Google Scholar
Bray, RS and Garnham, PCC (1982) The life-cycle of primate malaria parasites. British Medical Bulletin 38, 117122.Google Scholar
Campo, B, Vandal, O, Wesche, DL and Burrows, JN (2015) Killing the hypnozoite – drug discovery approaches to prevent relapse in Plasmodium vivax. Pathogens and Global Health 109, 107122.Google Scholar
Carmona-Fonseca, J (2015) Primaquine and relapses of Plasmodium vivax: meta-analysis of controlled clinical trials. Revista Brasileira de Epidemiologia 18, 174193.Google Scholar
Chaorattanakawee, S, Lon, C, Chann, S, Thay, KH, Kong, N, You, Y, Sundrakes, S, Thamnurak, C, Chattrakarn, S, Praditpol, C, Yingyuen, K, Wojnarski, M, Huy, R, Spring, MD, Walsh, DS, Patel, JC, Lin, J, Juliano, JJ, Lanteri, CA and Saunders, DL (2017) Measuring ex vivo drug susceptibility in Plasmodium vivax isolates from Cambodia. Malaria Journal 16, 392.Google Scholar
Claser, C, Chang, ZW, Russell, B and Rénia, L (2017) Adaptive immunity is essential in preventing recrudescence of Plasmodium yoelii malaria parasites after artesunate treatment. Cellular Microbiology 19, e12763.Google Scholar
Commons, RJ, Thriemer, K, Humphreys, G, Suay, I, Sibley, CH, Guerin, PJ and Price, RN (2017) The vivax surveyor: online mapping database for Plasmodium vivax clinical trials. International Journal for Parasitology: Drugs and Drug Resistance 7, 181190.Google Scholar
Corradetti, A (1966) The Origin of Relapses in Human and Simian Malaria Infections. WHO document WHO/Mal/66.565. Geneva, Switzerland: World Health Organization. http://apps.who.int/iris/handle/10665/65341Google Scholar
Corradetti, A (1982) Relapses and delayed primary attacks in malaria. Transactions of the Royal Society of Tropical Medicine and Hygiene 76, 279280.Google Scholar
Cowell, AN, Loy, DE, Sundararaman, SA, Valdivia, H, Fisch, K, Lescano, AG, Baldeviano, GC, Durand, S, Gerbasi, V, Sutherland, CJ, Nolder, D, Vinetz, JM, Hahn, BH and Winzeler, EA (2017) Selective whole-genome amplification is a robust method that enables scalable whole-genome sequencing of Plasmodium vivax from unprocessed clinical samples. mBio 8, e0225716.Google Scholar
Cubi, R, Vembar, SS, Biton, A, Franetich, J-F, Bordessoulles, M, Sossau, D, Zanghi, G, Bosson-Vanga, H, Benard, M, Moreno, A, Dereuddre-Bosquet, N, Le Grand, R, Scherf, A and Mazier, D (2017) Laser capture microdissection enables transcriptomic analysis of dividing and quiescent liver stages of Plasmodium relapsing species. Cellular Microbiology 19, e12735.Google Scholar
Dembélé, L, Ang, X, Chavchich, M, Bonamy, GMC, Selva, JJ, Yi-Xiu Lim, M, Bodenreider, C, Yeung, BKS, Nosten, F, Russell, BM, Edstein, MD, Straimer, J, Fidock, DA, Diagana, TT and Bifani, P (2017) The Plasmodium PI(4)K inhibitor KDU691 selectively inhibits dihydroartemisinin-pretreated Plasmodium falciparum ring-stage parasites. Scientific Reports 7, 2325.Google Scholar
Desowitz, RS (2000) The fate of sporozoites. Bulletin of the World Health Organization 78, 14451446.Google Scholar
Fonseca, LL, Joyner, CJ, MaHPIC Consortium, , Galinski, MR and Voit, EO (2017) A model of Plasmodium vivax concealment based on Plasmodium cynomolgi infections in Macaca mulatta. Malaria Journal 16, 375.Google Scholar
Franken, G, Bruijns-Pötschke, M, Richter, J, Mehlhorn, H and Labisch, A (2017) Malaria relapses were already known before 1900 – a discussion. Parasitology Research 116, 185189.Google Scholar
Garnham, PCC (1985) Rechutes dans la malaria: revue des travaux récents. Annales de la Société Belge de Médecine Tropicale 65, 233242.Google Scholar
Garnham, PCC (1988) Swellengrebel lecture: hypnozoites and ‘relapses’ in Plasmodium vivax and in vivax-like malaria. Tropical and Geographical Medicine 40, 187195.Google Scholar
Gray, K-A, Gresty, KJ, Chen, N, Zhang, V, Gutteridge, CE, Peatey, CL, Chavchich, M, Waters, NC and Cheng, Q (2016) Correlation between cyclin dependent kinases and artemisinin-induced dormancy in Plasmodium falciparum in vitro. PLoS ONE 11, e0157906.Google Scholar
Gruenberg, M, Moniz, CA, Hofmann, NE, Wampfler, R, Koepfli, C, Mueller, I, Monteiro, WM, Lacerda, M, de Melo, GC, Kuehn, A, Siqueira, AM and Felger, I (2018) Plasmodium vivax molecular diagnostics in community surveys: pitfalls and solutions. Malaria Journal 17, 55.Google Scholar
Gueirard, P, Tavares, J, Thiberge, S, Bernex, F, Ishino, T, Milon, G, Franke-Fayard, B, Janse, CJ, Ménard, R and Amino, R (2010) Development of the malaria parasite in the skin of the mammalian host. Proceedings of the National Academy of Sciences of the United States of America 107, 1864018645.Google Scholar
Holmes, MJ, da Silva Augusto, L, Zhang, M, Wek, RC and Sullivan, WJ (2017) Translational control in the latency of apicomplexan parasites. Trends in Parasitology 33, 947960.Google Scholar
Imwong, M, Boel, ME, Pagornrat, W, Pimanpanarak, M, McGready, R, Day, NPJ, Nosten, F. and White, NJ (2012) The first Plasmodium vivax relapses of life are usually genetically homologous. Journal of Infectious Diseases 205, 680683.Google Scholar
Joyner, CJ, MaHPIC Consortium, , Wood, JS, Moreno, A, Garcia, A and Galinski, MR (2017) Case report: severe and complicated cynomolgi malaria in a rhesus macaque resulted in similar histopathological changes as those seen in human malaria. American Journal of Tropical Medicine and Hygiene 97, 548555.Google Scholar
Koepfli, C and Mueller, I (2017) Malaria epidemiology at the clone level. Trends in Parasitology 33, 974985.Google Scholar
Krotoski, WA, Krotoski, DM, Garnham, PCC, Bray, RS, Killick-Kendrick, R, Draper, CC, Targett, GAT and Guy, MW (1980) Relapses in primate malaria: discovery of two populations of exoerythrocytic stages. Preliminary note. British Medical Journal 1, 153154.Google Scholar
Krotoski, WA (1989) The hypnozoite and malarial relapse. Progress in Clinical Parasitology 1, 119.Google Scholar
Landau, I, Chabaud, AG, Mora-Silvera, E, Coquelin, F, Boulard, Y, Rénia, L and Snounou, G (1999) Survival of rodent malaria merozoites in the lymphatic network: potential role in chronicity of the infection. Parasite 6, 311322.Google Scholar
Lim, C, Pereira, L, Shaw-Saliba, K, Mascarenhas, A, Maki, JN, Chery, L, Gomes, E, Rathod, PK and Duraisingh, MT (2016) Reticulocyte preference and stage development of Plasmodium vivax isolates. Journal of Infectious Diseases 214, 10811084.Google Scholar
Malleret, B, Li, A, Zhang, R, Tan, KSW, Suwanarusk, R, Claser, C, Cho, JS, Koh, EGL, Chu, CS, Pukrittayakamee, S, Ng, ML, Ginhoux, F, Ng, LG, Lim, CT, Nosten, F, Snounou, G, Rénia, L and Russell, B (2015) Plasmodium vivax: restricted tropism and rapid remodeling of CD71-positive reticulocytes. Blood 125, 13141324.Google Scholar
Malleret, B, Rénia, L and Russell, B (2017) The unhealthy attraction of Plasmodium vivax to reticulocytes expressing transferrin receptor 1 (CD41). International Journal for Parasitology 47, 379383.Google Scholar
Markus, MB (1975) Studies on Isosporan Coccidia of Mammals, Including Man. PhD thesis, Imperial College, University of London, United Kingdom.Google Scholar
Markus, MB (1976) Possible support for the sporozoite hypothesis of relapse and latency in malaria. Transactions of the Royal Society of Tropical Medicine and Hygiene 70, 535.Google Scholar
Markus, MB (1978) Terminology for invasive stages of protozoa of the subphylum Apicomplexa (Sporozoa). South African Journal of Science 74, 105106.Google Scholar
Markus, MB (2011 a) Malaria: origin of the term ‘hypnozoite’. Journal of the History of Biology 44, 781786.Google Scholar
Markus, MB (2011 b) The hypnozoite concept, with particular reference to malaria. Parasitology Research 108, 247252.Google Scholar
Markus, MB (2011c) Origin of recurrent Plasmodium vivax malaria – a new theory. South African Medical Journal 101, 682684.Google Scholar
Markus, MB (2012 a) Source of homologous parasites in recurrent Plasmodium vivax malaria. Journal of Infectious Diseases 206, 622623.Google Scholar
Markus, MB (2012 b) Dormancy in mammalian malaria. Trends in Parasitology 28, 3945.Google Scholar
Markus, MB (2015) Do hypnozoites cause relapse in malaria? Trends in Parasitology 31, 239245.Google Scholar
Markus, MB (2016 a) Malaria relapse. In Mehlhorn, H (ed). Encyclopedia of Parasitology, 4th edn. Berlin & Heidelberg, Germany: Springer-Verlag, pp. 15291531.Google Scholar
Markus, MB (2016 b) Mouse-based research on quiescent primate malaria parasites. Trends in Parasitology 32, 271273.Google Scholar
Markus, MB (2017) Malaria eradication and the hidden parasite reservoir. Trends in Parasitology 33, 492495.Google Scholar
Markus, MB, Killick-Kendrick, R and Garnham, PCC (1974) The coccidial nature and life-cycle of Sarcocystis. Journal of Tropical Medicine and Hygiene 77, 248259.Google Scholar
Mehlhorn, H and Markus, MB (1976) Electron microscopy of stages of Isospora felis of the cat in the mesenteric lymph node of the mouse. Zeitschrift für Parasitenkunde 51, 1524.Google Scholar
Ménard, R, Tavares, J, Cockburn, I, Markus, M, Zavala, F and Amino, R (2013) Looking under the skin: the first steps in malarial infection and immunity. Nature Reviews Microbiology 11, 701712.Google Scholar
Mikolajczak, SA, Vaughan, AM, Kangwanrangsan, N, Roobsoong, W, Fishbaugher, M, Yimamnuaychok, N, Rezakhani, N, Lakshmanan, V, Singh, N, Kaushansky, A, Camargo, N, Baldwin, M, Lindner, SE, Adams, JH, Sattabongkot, J and Kappe, SHI (2015) Plasmodium vivax liver stage development and hypnozoite persistence in human liver-chimeric mice. Cell Host & Microbe 17, 526535.Google Scholar
Milner, EE, Berman, J, Caridha, D, Dickson, SP, Hickman, M, Lee, PJ, Marcsisin, SR, Read, LT, Roncal, N, Vesely, BA, Xie, LH, Zhang, J, Zhang, P and Li, Q (2016) Cytochrome P450 2D-mediated metabolism is not necessary for tafenoquine and primaquine to eradicate the erythrocytic stages of Plasmodium berghei. Malaria Journal 15, 588.Google Scholar
Mons, B and Sinden, RE (1990) Laboratory models for research in vivo and in vitro on malaria parasites of mammals: current status. Parasitology Today 6, 37.Google Scholar
Pays, JF (2012) The painstaking discovery of the hidden face of the human plasmodia. Parasitology Research 111, 13011307.Google Scholar
Pewkliang, Y, Rungin, S, Lerdpanyangam, K, Duangmanee, A, Kanjanasirirat, P, Suthivanich, P, Sa-ngiamsuntorn, K, Borwornpinyo, S, Sattabongkot, J, Patrapuvich, R and Hongeng, S (2018) A novel immortalized hepatocyte-like cell line (imHC) supports in vitro liver stage development of the human malarial parasite Plasmodium vivax. Malaria Journal 17, 50.Google Scholar
Popovici, J, Friedrich, LR, Kim, S, Bin, S, Run, V, Lek, D, Cannon, MV, Ménard, D and Serre, D (2018) Genomic analyses reveal the common occurrence and complexity of Plasmodium vivax relapses in Cambodia. mBio 9, e0188817.Google Scholar
Pukrittayakamee, S, Chantra, A, Simpson, JA, Vanijanonta, S, Clemens, R, Looareesuwan, S and White, NJ (2000) Therapeutic responses to different antimalarial drugs in vivax malaria. Antimicrobial Agents and Chemotherapy 44, 16801685.Google Scholar
Rabinovich, RN, Drakeley, C, Djimde, AA, Hall, BF, Hay, SI, Hemmingway, J, Kaslow, DC, Noor, A, Okumu, F, Steketee, R, Tanner, M, Wells, TNC, Whittaker, MA, Winzeler, EA, Wirth, DF, Whitfield, K and Alonso, PL (2017) malERA: an updated research agenda for malaria elimination and eradication. PLoS Medicine 14, e1002456.Google Scholar
Richter, J, Franken, G, Holtfreter, MC, Walter, S, Labisch, A and Mehlhorn, H (2016) Clinical implications of a gradual dormancy concept in malaria. Parasitology Research 115, 21392148.Google Scholar
Ru, Y-X, Mao, B-Y, Zhang, F-K, Pang, T-X, Zhao, S-X, Liu, J-H and Wickramasinghe, SN (2009) Invasion of erythroblasts by Plasmodium vivax: a new mechanism contributing to malarial anemia. Ultrastructural Pathology 33, 236242.Google Scholar
Rutledge, GG, Marr, I, Huang, GKL, Auburn, S, Marfurt, J, Sanders, M, White, NJ, Berriman, M, Newbold, CI, Anstey, NM, Otto, TD and Price, RN (2017) Genomic characterization of recrudescent Plasmodium malariae after treatment with artemether/lumefantrine. Emerging Infectious Diseases 23, 13001307.Google Scholar
Safeukui, I, Correas, J-M, Brousse, V, Hirt, D, Deplaine, G, Mulé, S, Lesurtel, M, Goasguen, N, Sauvanet, A, Couvelard, A, Kerneis, S, Khun, H, Vigan-Womas, I, Ottone, C, Molina, TJ, Tréluyer, J-M, Mercereau-Puijalon, O, Milon, G, David, PH and Buffet, PA (2008) Retention of Plasmodium falciparum ring-infected erythrocytes in the slow, open microcirculation of the human spleen. Blood 112, 25202528.Google Scholar
Schmidt, LH (1986) Compatibility of relapse patterns of Plasmodium cynomolgi infections in rhesus monkeys with continuous cyclical development and hypnozoite concepts of relapse. American Journal of Tropical Medicine and Hygiene 35, 10771099.Google Scholar
Shanks, GD (2015) Historical review: does stress provoke Plasmodium falciparum recrudescence? Transactions of the Royal Society of Tropical Medicine and Hygiene 109, 360365.Google Scholar
Shortt, HE and Garnham, PCC (1948) Demonstration of a persisting exo-erythrocytic cycle in Plasmodium cynomolgi and its bearing on the production of relapses. British Medical Journal 1, 12251228.Google Scholar
Silvino, ACR, Costa, GL, de Araújo, FCF, Ascher, DB, Pires, DEV, Fontes, CJF, Carvalho, LH, de Brito, CFA and Sousa, TN (2016) Variation in human cytochrome P-450 drug-metabolism genes: a gateway to the understanding of Plasmodium vivax relapses. PLoS ONE 11, e0160172.Google Scholar
Siqueira, AM, Magalhães, BML, Melo, GC, Ferrer, M, Castillo, P, Martin-Jaular, L, Fernández-Becerra, C, Ordi, J, Martinez, A, Lacerda, MVG and del Portillo, HA (2012) Spleen rupture in a case of untreated Plasmodium vivax infection. PLoS Neglected Tropical Diseases 6, e1934.Google Scholar
Soulard, V, Bosson-Vanga, H, Lorthiois, A, Roucher, C, Franetich, J-F, Zanghi, G, Bordessoulles, M, Tefit, M, Thellier, M, Morosan, S, Le Naour, G, Capron, F, Suemizu, H, Snounou, G, Moreno-Sabater, A and Mazier, D (2015) Plasmodium falciparum full life cycle and Plasmodium ovale liver stages in humanized mice. Nature Communications 6, 7690.Google Scholar
Sutherland, CJ (2016) Persistent parasitism: the adaptive biology of malariae and ovale malaria. Trends in Parasitology 32, 808819.Google Scholar
Thomson-Luque, R, Shaw-Saliba, K, Kocken, CHM and Pasini, EM (2017) A continuous, long-term Plasmodium vivax in vitro blood-stage culture: what are we missing? Trends in Parasitology 33, 921924.Google Scholar
van Schalkwyk, DA, Moon, RW, Blasco, B and Sutherland, CJ (2017) Comparison of the susceptibility of Plasmodium knowlesi and Plasmodium falciparum to antimalarial agents. Journal of Antimicrobial Chemotherapy 72, 30513058.Google Scholar
Voorberg-van der Wel, A, Roma, G, Gupta, DK, Schuierer, S, Nigsch, F, Carbone, W, Zeeman, A-M, Lee, BH, Hofman, SO, Faber, BW, Knehr, J, Pasini, EM, Kinzel, B, Bifani, P, Bonamy, GMC, Bouwmeester, T, Kocken, CHM and Diagana, TT (2017) A comparative transcriptomic analysis of replicating and dormant liver stages of the relapsing malaria parasite Plasmodium cynomolgi. eLife 6, e29605.Google Scholar
Voza, T, Miller, JL, Kappe, SHI and Sinnis, P (2012) Extrahepatic exoerythrocytic forms of rodent malaria parasites at the site of inoculation: clearance after immunization, susceptibility to primaquine, and contribution to blood-stage infection. Infection and Immunity 80, 21582164.Google Scholar
Waters, AP, Higgins, DG and McCutchan, TF (1993) Evolutionary relatedness of some primate models of Plasmodium. Molecular Biology and Evolution 10, 914923.Google Scholar
Wykes, MN and Horne-Debets, J (2012) Dendritic cells: the Trojan horse of malaria? International Journal for Parasitology 42, 583587.Google Scholar
Wykes, MN, Kay, JG, Manderson, A, Liu, XQ, Brown, DL, Richard, DJ, Wipasa, J, Jiang, SH, Jones, MK, Janse, CJ, Waters, AP, Pierce, SK, Miller, LH, Stow, JL and Good, MF (2011) Rodent blood-stage Plasmodium survive in dendritic cells that infect naive mice. Proceedings of the National Academy of Sciences of the United States of America 108, 1120511210.Google Scholar
Zhang, M, Gallego-Delgado, J, Fernández-Arias, C, Waters, NC, Rodriguez, A, Tsuji, M, Wek, RC, Nussenzweig, V and Sullivan, WJ (2017) Inhibiting the Plasmodium eIF2α kinase PK4 prevents artemisinin-induced latency. Cell Host & Microbe 22, 766776.Google Scholar
Zuluaga-Idarraga, LM, Perez, M-ET and Aguirre-Acevedo, DC (2015) Therapeutic efficacy of alternative primaquine regimens to standard treatment in preventing relapses by Plasmodium vivax: a systematic review and meta-analysis. Colombia Médica 46, 183191.Google Scholar