Cytoadhesion of Plasmodium falciparum-infected erythrocytes and the infected placenta: a two-way pathway

Malaria is undoubtedly the world's most devastating parasitic disease, affecting 300 to 500 million people every year. Some cases of Plasmodium falciparum infection progress to the deadly forms of the disease responsible for 1 to 3 million deaths annually. P. falciparum-infected erythrocytes adhere to host receptors in the deep microvasculature of several organs. The cytoadhesion of infected erythrocytes to placental syncytiotrophoblast receptors leads to pregnancy-associated malaria (PAM). This specific maternal-fetal syndrome causes maternal anemia, low birth weight and the death of 62,000 to 363,000 infants per year in sub-Saharan Africa, and thus has a poor outcome for both mother and fetus. However, PAM and non-PAM parasites have been shown to differ antigenically and genetically. After multiple pregnancies, women from different geographical areas develop adhesion-blocking antibodies that protect against placental parasitemia and clinical symptoms of PAM. The recent description of a new parasite ligand encoded by the var2CSA gene as the only gene up-regulated in PAM parasites renders the development of an anti-PAM vaccine more feasible. The search for a vaccine to prevent P. falciparum sequestration in the placenta by eliciting adhesion-blocking antibodies and a cellular immune response, and the development of new methods for evaluating such antibodies should be key priorities in mother-child health programs in areas of endemic malaria. This review summarizes the main molecular, immunological and physiopathological aspects of PAM, including findings related to new targets in the P. falciparum var gene family. Finally, we focus on a new methodology for mimicking cytoadhesion under blood flow conditions in human placental tissue.1525153

Cytoadhesion of Plasmodium falciparum-infected erythrocytes and the infected placenta: a two-way pathway

This find is registered at Portable Antiquities of the Netherlands with number PAN-0005548

A new heparan sulfate from the mollusk nodipecten nodosus inhibits merozoite invasion and disrupts rosetting and cytoadherence of plasmodium falciparum

Despite treatment with effective antimalarial drugs, the mortality rate is still high in severe cases of the disease, highlighting the need to find adjunct therapies that can inhibit the adhesion of Pf-iEs. In this context, we evaluated a new heparan sulfate (HS) from Nodipecten nodosus for antimalarial activity and inhibition of P. falciparum cytoadhesion and rosetting. Parasite inhibition was measured by SYBR green using a cytometer. HS was assessed in rosetting and cytoadhesion assays under static and flow conditions using CHO and HLEC cells expressing ICAM1 and CSA, respectively. This HS inhibited merozoite invasion similar to heparin. Moreover, mollusk HS decreased cytoadherence of P. falciparum to CSA (chondroitin sulfate A) and ICAM-1 (intercellular adhesion molecule-1) on the surface of endothelial cells under static and flow conditions. In addition, this glycan efficiently disrupted rosettes. These findings support a potential use for mollusk HS as adjunct therapy for severe malaria114CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO CARLOS CHAGAS FILHO DE AMPARO À PESQUISA DO ESTADO DO RIO DE JANEIRO - FAPERJFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPnão temnão tem2012/16525-2; 2017/18611-7; 2010/18571-6; 2015/20774-

Significant Biochemical, Biophysical and Metabolic Diversity in Circulating Human Cord Blood Reticulocytes

10.1371/journal.pone.0076062PLoS ONE810-POLN

Cytoadhesion of Plasmodium falciparum-infected erythrocytes and the infected placenta: a two-way pathway

Malaria is undoubtedly the world's most devastating parasitic disease, affecting 300 to 500 million people every year. Some cases of Plasmodium falciparum infection progress to the deadly forms of the disease responsible for 1 to 3 million deaths annually. P. falciparum-infected erythrocytes adhere to host receptors in the deep microvasculature of several organs. The cytoadhesion of infected erythrocytes to placental syncytiotrophoblast receptors leads to pregnancy-associated malaria (PAM). This specific maternal-fetal syndrome causes maternal anemia, low birth weight and the death of 62,000 to 363,000 infants per year in sub-Saharan Africa, and thus has a poor outcome for both mother and fetus. However, PAM and non-PAM parasites have been shown to differ antigenically and genetically. After multiple pregnancies, women from different geographical areas develop adhesion-blocking antibodies that protect against placental parasitemia and clinical symptoms of PAM. The recent description of a new parasite ligand encoded by the var2CSA gene as the only gene up-regulated in PAM parasites renders the development of an anti-PAM vaccine more feasible. The search for a vaccine to prevent P. falciparum sequestration in the placenta by eliciting adhesion-blocking antibodies and a cellular immune response, and the development of new methods for evaluating such antibodies should be key priorities in mother-child health programs in areas of endemic malaria. This review summarizes the main molecular, immunological and physiopathological aspects of PAM, including findings related to new targets in the P. falciparum var gene family. Finally, we focus on a new methodology for mimicking cytoadhesion under blood flow conditions in human placental tissue

Chloroquine: Modes Of Action Of An Undervalued Drug

For more than two decades, chloroquine (CQ) was largely and deliberately used as first choice drug for malaria treatment. However, worldwide increasing cases of resistant strains of Plasmodium have hampered its use. Nevertheless, CQ has recently been tested as adjunct therapy in several inflammatory situations, such as rheumatoid arthritis and transplantation procedures, presenting intriguing and promising results. In this review, we discuss recent findings and CQ mechanisms of action vis-à-vis its use as a broad adjunct therapy. © 2013 Elsevier B.V.1531/Fev5057(2011) World Malaria Report 2011, , World Health Organization, Geneva World Health OrganizationA research agenda for malaria eradication: drugs (2011) PLoS Medicine, 8, pp. e1000402. , malERA Consultative Group on DrugsPlowe, C.V., The evolution of drug-resistant malaria (2009) Transactions of the Royal Society of Tropical Medicine and Hygiene, 103 (SUPPL. 1), pp. S11-S14Summers, R.L., Nash, M.N., Martin, R.E., Know your enemy: understanding the role of PfCRT in drug resistance could lead to new antimalarial tactics (2012) Cellular and Molecular Life Sciences, 69, pp. 1967-1995A randomized trial of hydroxychloroquine in early rheumatoid arthritis: the HERA Study (1995) American Journal of Medicine, 98, pp. 156-168Bezerra, E.L., Vilar, M.J., da Trindade Neto, P.B., Sato, E.L., Double-blind, randomized, controlled clinical trial of clofazimine compared with chloroquine in patients with systemic lupus erythematosus (2005) Arthritis and Rheumatism, 52, pp. 3073-3078Ben-Zvi, I., Kivity, S., Langevitz, P., Shoenfeld, Y., Hydroxychloroquine: from malaria to autoimmunity (2012) Clinical Reviews in Allergy & Immunology, 42, pp. 145-153Homewood, C.A., Warhurst, D.C., Peters, W., Baggaley, V.C., Lysosomes, pH and the anti-malarial action of chloroquine (1972) Nature, 235, pp. 50-52Chiang, G., Sassaroli, M., Louie, M., Chen, H., Stecher, V.J., Sperber, K., Inhibition of HIV-1 replication by hydroxychloroquine: mechanism of action and comparison with zidovudine (1996) Clinical Therapeutics, 18, pp. 1080-1092Sperber, K., Chiang, G., Chen, H., Ross, W., Chusid, E., Gonchar, M., Comparison of hydroxychloroquine with zidovudine in asymptomatic patients infected with human immunodeficiency virus type 1 (1997) Clinical Therapeutics, 19, pp. 913-923Bernstein, H.N., Ophthalmologic considerations and testing in patients receiving long-term antimalarial therapy (1983) American Journal of Medicine, 75, pp. 25-34Karres, I., Chloroquine inhibits proinflammatory cytokine release into human whole blood (1998) American Journal of Physiology, 274, pp. R1058-R1064Ertel, W., Morrison, M.H., Ayala, A., Chaudry, I.H., Chloroquine attenuates hemorrhagic shock-induced immunosuppression and decreases susceptibility to sepsis (1992) Archives of Surgery, 127, pp. 70-75. , [discussion 75-76]Loehberg, C.R., Strissel, P.L., Dittrich, R., Strick, R., Dittmer, J., Dittmer, A., Akt and p53 are potential mediators of reduced mammary tumor growth by Chloroquine and the mTOR inhibitor RAD001 (2012) Biochemical Pharmacology, 83, pp. 480-488Sperber, K., Kalb, T.H., Stecher, V.J., Banerjee, R., Mayer, L., Inhibition of human immunodeficiency virus type 1 replication by hydroxychloroquine in T cells and monocytes (1993) AIDS Research and Human Retroviruses, 9, pp. 91-98Yoshimura, A., Kuroda, K., Kawasaki, K., Yamashina, S., Maeda, T., Ohnishi, S., Infectious cell entry mechanism of influenza virus (1982) Journal of Virology, 43, pp. 284-293Shibata, M., Aoki, H., Tsurumi, T., Sugiura, Y., Nishiyama, Y., Suzuki, S., Mechanism of uncoating of influenza B virus in MDCK cells: action of chloroquine (1983) Journal of General Virology, 64, pp. 1149-1156Ooi, E.E., Chew, J.S., Loh, J.P., Chua, R.C., In vitro inhibition of human influenza A virus replication by chloroquine (2006) Virology Journal, 3, p. 39Di Trani, L., Savarino, A., Campitelli, L., Norelli, S., Puzelli, S., D'Ostilio, D., Different pH requirements are associated with divergent inhibitory effects of chloroquine on human and avian influenza A viruses (2007) Virology Journal, 4, p. 39Misinzo, G., Delputte, P.L., Nauwynck, H.J., Inhibition of endosome-lysosome system acidification enhances porcine circovirus 2 infection of porcine epithelial cells (2008) Journal of Virology, 82, pp. 1128-1135Savarino, A., A historical sketch of the discovery and development of HIV-1 integrase inhibitors (2006) Expert Opinion on Investigational Drugs, 15, pp. 1507-1522Bernstein, H.N., Chloroquine ocular toxicity (1967) Survey of Ophthalmology, 12, pp. 415-447Sperber, K., Louie, M., Kraus, T., Proner, J., Sapira, E., Lin, S., Hydroxychloroquine treatment of patients with human immunodeficiency virus type 1 (1995) Clinical Therapeutics, 17, pp. 622-636Murray, S.M., Down, C.M., Boulware, D.R., Stauffer, W.M., Cavert, W.P., Schacker, T.W., Reduction of immune activation with chloroquine therapy during chronic HIV infection (2010) Journal of Virology, 84, pp. 12082-12086Piconi, S., Parisotto, S., Rizzardini, G., Passerini, S., Terzi, R., Argenteri, B., Hydroxychloroquine drastically reduces immune activation in HIV-infected, antiretroviral therapy-treated immunologic nonresponders (2011) Blood, 118, pp. 3263-3272Soumelis, V., Scott, I., Gheyas, F., Bouhour, D., Cozon, G., Cotte, L., Depletion of circulating natural type 1 interferon-producing cells in HIV-infected AIDS patients (2001) Blood, 98, pp. 906-912Martinson, J.A., Montoya, C.J., Usuga, X., Ronquillo, R., Landay, A.L., Desai, S.N., Chloroquine modulates HIV-1-induced plasmacytoid dendritic cell alpha interferon: implication for T-cell activation (2010) Antimicrobial Agents and Chemotherapy, 54, pp. 871-881Jiang, M.C., Lin, J.K., Chen, S.S., Inhibition of HIV-1 Tat-mediated transactivation by quinacrine and chloroquine (1996) Biochemical and Biophysical Research Communications, 226, pp. 1-7Fredericksen, B.L., Wei, B.L., Yao, J., Luo, T., Garcia, J.V., Inhibition of endosomal/lysosomal degradation increases the infectivity of human immunodeficiency virus (2002) Journal of Virology, 76, pp. 11440-11446Canadian Consensus Conference on hydroxychloroquine (2000) Journal of Rheumatology, 27, pp. 2919-2921. , Canadian Rheumatology AssociationGladman, D.D., Urowitz, M.B., Senecal, J.L., Fortin, P.J., Petty, R.E., Esdaile, J.M., Aspects of use of antimalarials in systemic lupus erythematosus (1998) Journal of Rheumatology, 25, pp. 983-985Rahman, A., Isenberg, D.A., Systemic lupus erythematosus (2008) New England Journal of Medicine, 358, pp. 929-939Slater, A.F., Chloroquine: mechanism of drug action and resistance in Plasmodium falciparum (1993) Pharmacology & Therapeutics, 57, pp. 203-235Tan, E.M., Antinuclear antibodies: diagnostic markers for autoimmune diseases and probes for cell biology (1989) Advances in Immunology, 44, pp. 93-151Casciola-Rosen, L.A., Anhalt, G., Rosen, A., Autoantigens targeted in systemic lupus erythematosus are clustered in two populations of surface structures on apoptotic keratinocytes (1994) Journal of Experimental Medicine, 179, pp. 1317-1330A randomized study of the effect of withdrawing hydroxychloroquine sulfate in systemic lupus erythematosus. The Canadian Hydroxychloroquine Study Group (1991) N Engl J Med, 324, pp. 150-154Fessler, B.J., Systemic lupus erythematosus in three ethnic groups: XVI. Association of hydroxychloroquine use with reduced risk of damage accrual (2005) Arthritis and Rheumatism, 52, pp. 1473-1480Alarcon, G.S., Effect of hydroxychloroquine on the survival of patients with systemic lupus erythematosus: data from LUMINA, a multiethnic US cohort (LUMINAL) (2007) Annals of the Rheumatic Diseases, 66, pp. 1168-1172Ruiz-Irastorza, G., Effect of antimalarials on thrombosis and survival in patients with systemic lupus erythematosus (2006) Lupus, 15, pp. 577-583Tam, L.S., Gladman, D.D., Hallett, D.C., Rahman, P., Urowitz, M.B., Effect of antimalarial agents on the fasting lipid profile in systemic lupus erythematosus (2000) Journal of Rheumatology, 27, pp. 2142-2145Levy, R.A., Hydroxychloroquine (HCQ) in lupus pregnancy: double-blind and placebo-controlled study (2001) Lupus, 10, pp. 401-404Lesiak, A., Narbutt, J., Kobos, J., Kordek, R., Sysa-Jedrzejowska, A., Norval, M., Systematic administration of chloroquine in discoid lupus erythematosus reduces skin lesions via inhibition of angiogenesis (2009) Clinical and Experimental Dermatology, 34, pp. 570-575Kreuter, A., Gaifullina, R., Tigges, C., Kirschke, J., Altmeyer, P., Gambichler, T., Lupus erythematosus tumidus: response to antimalarial treatment in 36 patients with emphasis on smoking (2009) Archives of Dermatology, 145, pp. 244-248Coatney, G.R., Pitfalls in a discovery: the chronicle of chloroquine (1963) American Journal of Tropical Medicine and Hygiene, 12, pp. 121-128Ikeda, T., Kanazawa, N., Furukawa, F., Hydroxychloroquine administration for Japanese lupus erythematosus in Wakayama: a pilot study (2012) Journal of Dermatology, 39, pp. 531-535Kuhn, A., Ruland, V., Bonsmann, G., Cutaneous lupus erythematosus: update of therapeutic options. Part I (2011) Journal of the American Academy of Dermatology, 65, pp. e179-e193Momose, Y., Arai, S., Eto, H., Kishimoto, M., Okada, M., Experience with the use of hydroxychloroquine for the treatment of lupus erythematosus (2013) Journal of Dermatology, 40, pp. 94-97Arnett, F.C., Edworthy, S.M., Bloch, D.A., McShane, D.J., Fries, J.F., Cooper, N.S., The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis (1988) Arthritis and Rheumatism, 31, pp. 315-324Louzada-Junior, P., Freitas, M.V., Oliveira, R.D., Deghaide, N.H., Conde, R.A., Bertolo, M.B., A majority of Brazilian patients with rheumatoid arthritis HLA-DRB1 alleles carry both the HLA-DRB1 shared epitope and anti-citrunillated peptide antibodies (2008) Brazilian Journal of Medical and Biological Research, 41, pp. 493-499Perricone, C., Ceccarelli, F., Valesini, G., An overview on the genetic of rheumatoid arthritis: a never-ending story (2011) Autoimmunity Reviews, 10, pp. 599-608Takayanagi, H., Inflammatory bone destruction and osteoimmunology (2005) Journal of Periodontal Research, 40, pp. 287-293Takayanagi, H., Oda, H., Yamamoto, S., Kawaguchi, H., Tanaka, S., Nishikawa, T., A new mechanism of bone destruction in rheumatoid arthritis: synovial fibroblasts induce osteoclastogenesis (1997) Biochemical and Biophysical Research Communications, 240, pp. 279-286Yamada, H., Nakashima, Y., Okazaki, K., Mawatari, T., Fukushi, J.I., Kaibara, N., Th1 but not Th17 cells predominate in the joints of patients with rheumatoid arthritis (2008) Annals of the Rheumatic Diseases, 67, pp. 1299-1304Hashimoto, M., Hirota, K., Yoshitomi, H., Maeda, S., Teradaira, S., Akizuki, S., Complement drives Th17 cell differentiation and triggers autoimmune arthritis (2009) Journal of Experimental Medicine, 207, pp. 1135-1143Loeb, R.F., Clark, W.M., Coatney, G.R., Coggeshall, T., Dieuaide, F.R., Dochez, A.R., Activity of a new antimalarial agent, chloroquine (SN 7618) (1946) Journal of the American Medical Association, 130, p. 1069Korn, T., Bettelli, E., Oukka, M., Kuchroo, V.K., IL-17 and Th17 Cells (2009) Annual Review of Immunology, 27, pp. 485-517Felson, D.T., Anderson, J.J., Meenan, R.F., The comparative efficacy and toxicity of second-line drugs in rheumatoid arthritis. Results of two metaanalyses (1990) Arthritis and Rheumatism, 33, pp. 1449-1461Scott, D.L., Dawes, P.T., Tunn, E., Fowler, P.D., Shadforth, M.F., Fisher, J., Combination therapy with gold and hydroxychloroquine in rheumatoid arthritis: a prospective, randomized, placebo-controlled study (1989) British Journal of Rheumatology, 28, pp. 128-133McCarty, D.J., Carrera, G.F., Intractable rheumatoid arthritis. Treatment with combined cyclophosphamide, azathioprine, and hydroxychloroquine (1982) JAMA: Journal of the American Medical Association, 248, pp. 1718-1723Bunch, T.W., O'Duffy, J.D., Tompkins, R.B., O'Fallon, W.M., Controlled trial of hydroxychloroquine and D-penicillamine singly and in combination in the treatment of rheumatoid arthritis (1984) Arthritis and Rheumatism, 27, pp. 267-276Gibson, T., Emery, P., Armstrong, R.D., Crisp, A.J., Combined, P.G.S., D-penicillamine and chloroquine treatment of rheumatoid arthritis - a comparative study (1987) British Journal of Rheumatology, 26, pp. 279-284Thome, R., Moraes, A.S., Bombeiro, A.L., Farias, A.D., Francelin, C., da Costa, T.A., Chloroquine treatment enhances regulatory T cells and reduces the severity of experimental autoimmune encephalomyelitis (2013) PLoS ONE, 8, pp. e65913Schultz, K.R., Gilman, A.L., The lysosomotropic amines, chloroquine and hydroxychloroquine: a potentially novel therapy for graft-versus-host disease (1997) Leukemia & Lymphoma, 24, pp. 201-210Schultz, K.R., Su, W.N., Hsiao, C.C., Doho, G., Jevon, G., Bader, S., Chloroquine prevention of murine MHC-disparate acute graft-versus-host disease correlates with inhibition of splenic response to CpG oligodeoxynucleotides and alterations in T-cell cytokine production (2002) Biology of Blood and Marrow Transplantation, 8, pp. 648-655Gilman, A.L., Beams, F., Tefft, M., Mazumder, A., The effect of hydroxychloroquine on alloreactivity and its potential use for graft-versus-host disease (1996) Bone Marrow Transplantation, 17, pp. 1069-1075Harinasuta, T., Suntharasamai, P., Viravan, C., Chloroquine-resistant falciparum malaria in Thailand (1965) Lancet, 2, pp. 657-660Gilman, A.L., Chan, K.W., Mogul, A., Morris, C., Goldman, F.D., Boyer, M., Hydroxychloroquine for the treatment of chronic graft-versus-host disease (2000) Biology of Blood and Marrow Transplantation, 6, pp. 327-334Schultz, K.R., Bader, S., Paquet, J., Li, W., Chloroquine treatment affects T-cell priming to minor histocompatibility antigens and graft-versus-host disease (1995) Blood, 86, pp. 4344-4352Hobbs, H.E., Sorsby, A., Freedman, A., Retinopathy following chloroquine therapy (1959) Lancet, 2, pp. 478-480Madalena, B.V., Oshima, A., Serracarbassa, P.D., Amsler grid and visual field on screening for chloroquine retinopathy (2012) Arquivos brasileiros de oftalmologia, 75, pp. 170-173Levy, G.D., Incidence of hydroxychloroquine retinopathy in 1,207 patients in a large multicenter outpatient practice (1997) Arthritis and Rheumatism, 40, pp. 1482-1486Marmor, M.F., Kellner, U., Lai, T.Y., Lyons, J.S., Meiler, W.F., Revised recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2011) Ophthalmology, 118, pp. 415-422Marmor, M.F., Carr, R.E., Easterbrook, M., Farjo, A.A., Mieler, W.F., Recommendations on screening for chloroquine and hydroxychloroquine retinopathy: a report by the American Academy of Ophthalmology (2002) Ophthalmology, 109, pp. 1377-1382Rossi, P., Fossaluzza, V., Gonano, L., Localized scleroderma evolving into systemic sclerosis (1985) Journal of Rheumatology, 12, pp. 629-630Raines, M.F., Bhargava, S.K., Rosen, E.S., The blood-retinal barrier in chSidhu, A.B., Verdier-Pinard, D., Fidock, D.A., Chloroquine resistance in Plasmodium falciparum malaria parasites conferred by pfcrt mutations (2002) Science, 298, pp. 210-213Kublin, J.G., Cortese, J.F., Njunju, E.M., Mukadam, R.A., Wirima, J.J., Kazembe, P.N., Reemergence of chloroquine-sensitive Plasmodium falciparum malaria after cessation of chloroquine use in Malawi (2003) Journal of Infectious Diseases, 187, pp. 1870-1875Mita, T., Kaneko, A., Lum, J.K., Bwijo, B., Takechi, M., Zungu, I.L., Recovery of chloroquine sensitivity and low prevalence of the Plasmodium falciparum chloroquine resistance transporter gene mutation K76T following the discontinuance of chloroquine use in Malawi (2003) American Journal of Tropical Medicine and Hygiene, 68, pp. 413-415Mwai, L., Ochong, E., Abdirahman, A., Kiara, S.M., Ward, S., Kokwaro, G., Chloroquine resistance before and after its withdrawal in Kenya (2009) Malaria Journal, 8, p. 106Laufer, M.K., Thesing, P.C., Eddington, N.D., Masonga, R., Dzinjalamala, F.K., Takala, S.L., Return of chloroquine antimalarial efficacy in Malawi (2006) The New England Journal of Medicine, 355, pp. 1959-1966Ndiaye, M., Faye, B., Tine, R., Ndiaye, J.L., Lo, A., Abiola, A., Assessment of the molecular marker of Plasmodium falciparum chloroquine resistance (Pfcrt) in Senegal after several years of chloroquine withdrawal (2012) American Journal of Tropical Medicine and Hygiene, 87, pp. 640-645Wurtz, N., Fall, B., Pascual, A., Diawara, S., Sow, K., Baret, E., Prevalence of molecular markers of Plasmodium falciparum drug resistance in Dakar, Senegal (2012) Malaria Journal, 11, p. 197Gharbi, M., Flegg, J.A., Hubert, V., Kendjo, E., Metcalf, J.E., Bertaux, L., Longitudinal study assessing the return of chloroquine susceptibility of Plasmodium falciparum in isolates from travellers returning from West and Central Africa, 2000-2011 (2013) Malaria Journal, 12, p. 35Baird, J.K., Resistance to therapies for infection by Plasmodium vivax (2009) Clinical Microbiology Reviews, 22, pp. 508-534Rieckmann, K.H., Davis, D.R., Hutton, D.C., Plasmodium vivax resistance to chloroquine (1989) Lancet, 2, pp. 1183-1184Castillo, C.M., Osorio, L.E., Palma, G.I., Assessment of therapeutic response of Plasmodium vivax and Plasmodium falciparum to chloroquine in a Malaria transmission free area in Colombia (2002) Memorias do Instituto Oswaldo Cruz, 97, pp. 559-562Ruebush, T.K., Zegarra, J., Cairo, J., Andersen, E.M., Green, M., Pillai, D.R., Chloroquine-resistant Plasmodium vivax malaria in Peru (2003) American Journal of Tropical Medicine and Hygiene, 69, pp. 548-552Soto, J., Toledo, J., Gutierrez, P., Luzz, M., Llinas, N., Cedeno, N., Plasmodium vivax clinically resistant to chloroquine in Colombia (2001) American Journal of Tropical Medicine and Hygiene, 65, pp. 90-93Sumawinata, I.W., Bernadeta Leksana, B., Sutamihardja, A., Purnomo Subianto, B., Very high risk of therapeutic failure with chloroquine for uncomplicated Plasmodium falciparum and P. vivax malaria in Indonesian Papua (2003) American Journal of Tropical Medicine and Hygiene, 68, pp. 416-420Ratcliff, A., Siswantoro, H., Kenangalem, E., Wuwung, M., Brockman, A., Edstein, M.D., Therapeutic response of multidrug-resistant Plasmodium falciparum and P. vivax to chloroquine and sulfadoxine-pyrimethamine in southern Papua, Indonesia (2007) Transactions of the Royal Society of Tropical Medicine and Hygiene, 101, pp. 351-359Tjitra, E., Anstey, N.M., Sugiarto, P., Warikar, N., Kenangalem, E., Karyana, M., Multidrug-resistant Plasmodium vivax associated with severe and fatal malaria: a prospective study in Papua, Indonesia (2008) PLoS Medicine, 5, pp. e128Bray, P.G., Hawley, S.R., Mungthin, M., Ward, S.A., Physicochemical properties correlated with drug resistance and the reversal of drug resistance in Plasmodium falciparum (1996) Molecular Pharmacology, 50, pp. 1559-1566Slater, A.F., Swiggard, W.J., Orton, B.R., Flitter, W.D., Goldberg, D.E., Cerami, A., An iron-carboxylate bond links the heme units of malaria pigment (1991) Proceedings of the National Academy of Sciences of the United States of America, 88, pp. 325-329Bray, P.G., Janneh, O., Raynes, K.J., Mungthin, M., Ginsburg, H., Ward, S.A., Cellular uptake of chloroquine is dependent on binding to ferriprotoporphyrin IX and is independent of NHE activity in Plasmodium falciparum (1999) Journal of Cell Biology, 145, pp. 363-376Bray, P.G., Mungthin, M., Ridley, R.G., Ward, S.A., Access to hematin: the basis of chloroquine resistance (1998) Molecular Pharmacology, 54, pp. 170-179Pagola, S., Stephens, P.W., Bohle, D.S., Kosar, A.D., Madsen, S.K., The structure of malaria pigment beta-haematin (2000) Nature, 404, pp. 307-310Sullivan, D.J., Gluzman, I.Y., Russell, D.G., Goldberg, D.E., On the molecular mechanism of chloroquine's antimalarial action (1996) Proceedings of the National Academy of Sciences of the United States of America, 93, pp. 11865-11870Sullivan, D.J., Matile, H., Ridley, R.G., Goldberg, D.E., A common mechanism for blockade of heme polymerization by antimalarial quinolines (1998) Journal of Biological Chemistry, 273, pp. 31103-31107Fitch, C.D., Chevli, R., Banyal, H.S., Phillips, G., Pfaller, M.A., Krogstad, D.J., Lysis of Plasmodium falciparum by ferriprotoporphyrin IX and a chloroquine-ferriprotoporphyrin IX complex (1982) Antimicrobial Agents and Chemotherapy, 21, pp. 819-822Krogstad, D.J., Schlesinger, P.H., A perspective on antimalarial action: effects of weak bases on Plasmodium falciparum (1986) Biochemical Pharmacology, 35, pp. 547-552Krogstad, D.J., Schlesinger, P.H., Gluzman, I.Y., Antimalarials increase vesicle pH in Plasmodium falciparum (1985) Journal of Cell Biology, 101, pp. 2302-2309Wunsch, S., Sanchez, C.P., Gekle, M., Grosse-Wortmann, L., Wiesner, J., Lanzer, M., Differential stimulation of the Na+/H+ exchanger determines chloroquine uptake in Plasmodium falciparum (1998) Journal of Cell Biology, 140, pp. 335-345Sanchez, C.P., Wunsch, S., Lanzer, M., Identification of a chloroquine importer in Plasmodium falciparum. Differences in import kinetics are genetically linked with the chloroquine-resistant phenotype (1997) Journal of Biological Chemistry, 272, pp. 2652-2658Fitch, C.D., Chloroquine resistance in malaria: a deficiency of chloroquine binding (1969) Proceedings of the National Academy of Sciences of the United States of America, 64, pp. 1181-1187Krogstad, D.J., Gluzman, I.Y., Kyle, D.E., Oduola, A.M., Martin, S.K., Milhous, W.K., Efflux of chloroquine from Plasmodium falciparum: mechanism of chloroquine resistance (1987) Science, 238, pp. 1283-1285Fidock, D.A., Nomura, T., Talley, A.K., Cooper, R.A., Dzekunov, S.M., Ferdig, M.T., Mutations in the P. falciparum digestive vacuole transmembrane protein PfCRT and evidence for their role in chloroquine resistance (2000) Molecula

Human Ex Vivo Studies On Asexual Plasmodium Vivax: The Best Way Forward

The lack of a continuous culture method for Plasmodium vivax has given the impression that investigations on this important species are severely curtailed. However, the use of new or improved ex vivo methods and tools to study fresh and thawed isolates from vivax malaria patients is currently providing useful data on P. vivax, such as sensitivity to antimalarial drugs, invasion mechanisms and pathobiology. This review discusses a practical framework for conducting ex vivo studies on the asexual erythrocytic stages of P. vivax and considers the synergies between ex vivo defined phenotypes, ex vivo derived 'omic' studies and in vivo clinical studies. © 2012 Australian Society for Parasitology Inc.421210631070Aikawa, M., Miller, L.H., Rabbege, J., Caveola-vesicle complexes in the plasmalemma of erythrocytes infected by Plasmodium vivax and P. cynomolgi. Unique structures related to Schuffner's dots (1975) Am. J. Pathol., 79, pp. 285-300Auliff, A., Wilson, D.W., Russell, B., Gao, Q., Chen, N., Anh, L.N., Maguire, J., Cheng, Q., Amino acid mutations in Plasmodium vivax DHFR and DHPS from several geographical regions and susceptibility to antifolate drugs (2006) Am. J. Trop. Med. Hyg., 75, pp. 617-621Baird, J.K., Neglect of Plasmodium vivax malaria (2007) Trends Parasitol., 23, pp. 533-539Baird, J.K., Tropical health and sustainability (2012) Encyclopedia of Sustainability Science and Technology, pp. 11134-11163. , Springer Verlag, R.A. Meyers (Ed.)Barnwell, J.W., Nichols, M.E., Rubinstein, P., In vitro evaluation of the role of the Duffy blood group in erythrocyte invasion by Plasmodium vivax (1989) J. Exp. Med., 169, pp. 1795-1802Barnwell, J.W., Ingravallo, P., Galinski, M.R., Matsumoto, Y., Aikawa, M., Plasmodium vivax: malarial proteins associated with the membrane-bound caveola-vesicle complexes and cytoplasmic cleft structures of infected erythrocytes (1990) Exp. Parasitol., 70, pp. 85-99Basco, L.K., Le Bras, J., Short-term in vitro culture of Plasmodium vivax and P. ovale for drug-susceptibility testing (1994) Parasitol. Res., 80, pp. 262-264Basco, L.K., Marquet, F., Makler, M.M., Le Bras, J., Plasmodium falciparum and P. vivax: lactate dehydrogenase activity and its application for in vitro drug susceptibility assay (1995) Exp. Parasitol., 80, pp. 260-271Borlon, C., Russell, B., Sriprawat, K., Suwanarusk, R., Erhart, A., Renia, L., Nosten, F., D'Alessandro, U., Cryopreserved Plasmodium vivax and cord blood reticulocytes can be used for invasion and short term culture (2012) Int. J. Parasitol., 42, pp. 155-160Bouillet, L.E., Dias, M.O., Dorigo, N.A., Moura, A.D., Russell, B., Nosten, F., Renia, L., Bruna-Romero, O., Long-term humoral and cellular immune responses elicited by a heterologous Plasmodium vivax apical membrane antigen 1 protein-prime/adenovirus-boost immunization protocol (2011) Infect. Immun., 79, pp. 3642-3652Bozdech, Z., Mok, S., Hu, G., Imwong, M., Jaidee, A., Russell, B., Ginsburg, H., Preiser, P.R., The transcriptome of Plasmodium vivax reveals divergence and diversity of transcriptional regulation in malaria parasites (2008) Proc. Natl. Acad. Sci. USA, 105, pp. 16290-16295Carlton, J.M., Adams, J.H., Silva, J.C., Bidwell, S.L., Lorenzi, H., Caler, E., Crabtree, J., Fraser-Liggett, C.M., Comparative genomics of the neglected human malaria parasite Plasmodium vivax (2008) Nature, 455, pp. 757-763Carvalho, B.O., Lopes, S.C.P., Nogueira, P.A., Orlandi, P.P., Bargieri, D.Y., Blanco, Y.C., Mamoni, R., Costa, F.T.M., On the cytoadhesion of Plasmodium vivax-infected erythrocytes (2010) J. Infect. Dis., 202, pp. 638-647Chitnis, C.E., Sharma, A., Targeting the Plasmodium vivax Duffy-binding protein (2008) Trends Parasitol., 24, pp. 29-34Chotivanich, K., Udomsangpetch, R., Chierakul, W., Newton, P.N., Ruangveerayuth, R., Pukrittayakamee, S., Looareesuwan, S., White, N.J., In vitro efficacy of antimalarial drugs against Plasmodium vivax on the western border of Thailand (2004) Am. J. Trop. Med. Hyg., 70, pp. 395-397Chotivanich, K., Udomsangpetch, R., Suwanarusk, R., Pukrittayakamee, S., Wilairatana, P., Beeson, J.G., Day, N.P., White, N.J., Plasmodium vivax adherence to placental glycosaminoglycans (2012) PLoS ONE, 7, pp. e34509Congpuong, K., Na-Bangchang, K., Thimasarn, K., Tasanor, U., Wernsdorfer, W.H., Sensitivity of Plasmodium vivax to chloroquine in Sa Kaeo Province, Thailand (2002) Acta Trop., 83, pp. 117-121del Portillo, H.A., Longacre, S., Khouri, E., David, P.H., Primary structure of the merozoite surface antigen 1 of Plasmodium vivax reveals sequences conserved between different Plasmodium species (1991) Proc. Natl. Acad. Sci. USA, 88, pp. 4030-4034Deplaine, G., Safeukui, I., Jeddi, F., Lacoste, F., Brousse, V., Perrot, S., Biligui, S., Buffet, P.A., The sensing of poorly deformable red blood cells by the human spleen can be mimicked in vitro (2011) Blood, 117, pp. e88-95Druilhe, P., Brasseur, P., Blanc, C., Makler, M., Improved assessment of Plasmodium vivax response to antimalarial drugs by a colorimetric double-site Plasmodium lactate dehydrogenase antigen capture enzyme-linked immunosorbent assay (2007) Antimicrob. Agents Chemother., 51, pp. 2112-2116Fang, X.D., Kaslow, D.C., Adams, J.H., Miller, L.H., Cloning of the Plasmodium vivax Duffy receptor (1991) Mol. Biochem. Parasitol., 44, pp. 125-132Field, J.W., (1938) Notes on the Chemotherapy of Malaria, , Morris & Walker, MelbourneGalinski, M.R., Medina, C.C., Ingravallo, P., Barnwell, J.W., A reticulocyte-binding protein complex of Plasmodium vivax merozoites (1992) Cell, 69, pp. 1213-1226Galinski, M.R., Ingravallo, P., Corredor-Medina, C., Al-Khedery, B., Povoa, M., Barnwell, J.W., Plasmodium vivax merozoite surface proteins-3beta and -3gamma share structural similarities with P. vivax merozoite surface protein-3alpha and define a new gene family (2001) Mol. Biochem. Parasitol., 115, pp. 41-53Galinski, M.R., Barnwell, J.W., Plasmodium vivax: who cares? (2008) Malar. J., 7 (SUPPL. 1), pp. S9Grimberg, B.T., Udomsangpetch, R., Xainli, J., McHenry, A., Panichakul, T., Sattabongkot, J., Cui, L., King, C.L., Plasmodium vivax invasion of human erythrocytes inhibited by antibodies directed against the Duffy binding protein (2007) PLoS Med., 4, pp. e337Hamedi, Y., Nateghpour, M., Tan-ariya, P., Tiensuwan, M., Silachamroon, U., Looareesuwan, S., Plasmodium vivax malaria in Southeast Iran in 1999-2001: establishing the response to chloroquine in vitro and in vivo (2002) Southeast Asian J. Trop. Med. Public Health, 33, pp. 512-518Hamedi, Y., Nateghpour, M., Soonthornsata, B., Tan-ariya, P., Kojima, S., Chindanond, D., Looareesuwan, S., Monitoring of Plasmodium vivax sensitivity to chloroquine in vitro in Thailand (2003) Trans. R. Soc. Trop. Med. Hyg., 97, pp. 435-437Handayani, S., Chiu, D.T., Tjitra, E., Kuo, J.S., Lampah, D., Kenangalem, E., Renia, L., Russell, B., High deformability of Plasmodium vivax-infected red blood cells under microfluidic conditions (2009) J. Infect. Dis., 199, pp. 445-450Hasugian, A.R., Tjitra, E., Ratcliff, A., Siswantoro, H., Kenangalem, E., Wuwung, R.M., Purba, H.L.E., Price, R.N., In vivo and in vitro efficacy of amodiaquine monotherapy for treatment of infection by chloroquine-resistant Plasmodium vivax (2009) Antimicrob. Agents Chemother., 53, pp. 1094-1099Imwong, M., Russell, B., Suwanarusk, R., Nzila, A., Leimanis, M.L., Sriprawat, K., Kaewpongsri, S., Renia, L., Methotrexate is highly potent against pyrimethamine-resistant Plasmodium vivax (2011) J. Infect. Dis., 203, pp. 207-210Iyer, J., Gruner, A.C., Renia, L., Snounou, G., Preiser, P.R., Invasion of host cells by malaria parasites: a tale of two protein families (2007) Mol. Microbiol., 65, pp. 231-249Kaewpongsri, S., Sriprawat, K., Suwanarusk, R., Kyle, D.E., Lek-Uthai, U., Leimanis, M., Lwin, K.M., Renia, L., The presence of leukocytes in ex vivo assays significantly increases the 50-percent inhibitory concentrations of artesunate and chloroquine against Plasmodium vivax and P. falciparum (2011) Antimicrob. Agents Chemother., 55, pp. 1300-1304Kocken, C.H.M., Dubbeld, M.A., Van Der Wel, A., Pronk, J.T., Waters, A.P., Langermans, J.A., Thomas, A.W., High-level expression of Plasmodium vivax apical membrane antigen 1 (AMA-1) in Pichia pastoris: strong immunogenicity in Macaca mulatta immunized with P. vivax AMA-1 and adjuvant SBAS2 (1999) Infect. Immun., 67, pp. 43-49Kosaisavee, V., Suwanarusk, R., Nosten, F., Kyle, D.E., Barrends, M., Jones, J., Price, R., Lek-Uthai, U., Plasmodium vivax: isotopic, PicoGreen, and microscopic assays for measuring chloroquine sensitivity in fresh and cryopreserved isolates (2006) Exp. Parasitol., 114, pp. 34-39Kosaisavee, V., Lek-Uthai, U., Suwanarusk, R., Gruner, A.C., Russell, B., Nosten, F., Renia, L., Snounou, G., Genetic diversity in new members of the reticulocyte binding protein family in Thai Plasmodium vivax isolates (2012) PLoS ONE, 7, pp. e32105Lam, N.Y., Rainer, T.H., Chiu, R.W., Lo, Y.M., EDTA is a better anticoagulant than heparin or citrate for delayed blood processing for plasma DNA analysis (2004) Clin. Chem., 50, pp. 256-257Leimanis, M.L., Jaidee, A., Sriprawat, K., Kaewpongsri, S., Suwanarusk, R., Barends, M., Phyo, A.P., Nosten, F., Plasmodium vivax susceptibility to ferroquine (2010) Antimicrob. Agents Chemother., 54, pp. 2228-2230Lek-Uthai, U., Suwanarusk, R., Ruengweerayut, R., Skinner-Adams, T.S., Nosten, F., Gardiner, D.L., Boonma, P., Russell, B., Stronger activity of human immunodeficiency virus type 1 protease inhibitors against clinical isolates of Plasmodium vivax than against those of P. falciparum (2008) Antimicrob. Agents Chemother., 52, pp. 2435-2441Lux, D., Prajakwong, S., Kollaritsch, H., Wernsdorfer, G., Wernsdorfer, W.H., In-vitro sensitivity testing of Plasmodium vivax: response to lumefantrine and chloroquine in northwestern Thailand (2003) Wien. Klin. Wochenschr., 115 (SUPPL. 3), pp. 50-54Malleret, B., Claser, C., Ong, A.S., Suwanarusk, R., Sriprawat, K., Howland, S.W., Russell, B., Renia, L., A rapid and robust tri-color flow cytometry assay for monitoring malaria parasite development (2011) Sci. Rep., 1, p. 118Marfurt, J., Chalfein, F., Prayoga, P., Wabiser, F., Kenangalem, E., Piera, K.A., Machunter, B., Price, R.N., Ex vivo drug susceptibility of ferroquine against chloroquine-resistant isolates of Plasmodium falciparum and P. vivax (2011) Antimicrob. Agents Chemother., 55, pp. 4461-4464Mons, B., Collins, W.E., Skinner, J.C., van der Star, W., Croon, J.J., van der Kaay, H.J., Plasmodium vivax: in vitro growth and reinvasion in red blood cells of Aotus nancymai (1988) Exp. Parasitol., 66, pp. 183-188Mons, B., Croon, J.J., van der Star, W., van der Kaay, H.J., Erythrocytic schizogony and invasion of Plasmodium vivax in vitro (1988) Int. J. Parasitol., 18, pp. 307-311Mueller, I., Galinski, M.R., Baird, J.K., Carlton, J.M., Kochar, D.K., Alonso, P.L., del Portillo, H.A., Key gaps in the knowledge of Plasmodium vivax, a neglected human malaria parasite (2009) Lancet Infect. Dis., 9, pp. 555-566Nichols, M.E., Rubinstein, P., Barnwell, J., Rodriguez de Cordoba, S., Rosenfield, R.E., A new human Duffy blood group specificity defined by a murine monoclonal antibody. Immunogenetics and association with susceptibility to Plasmodium vivax (1987) J. Exp. Med., 166, pp. 776-785Phyo, A.P., Lwin, K.M., Price, R.N., Ashley, E.A., Russell, B., Sriprawat, K., Lindegardh, N., Nosten, F., Dihydroartemisinin-piperaquine versus chloroquine in the treatment of Plasmodium vivax malaria in Thailand: a randomized controlled trial (2011) Clin. Infect. Dis., 53, pp. 977-984Powell, R.D., Berglund, E.M., Effects of chloroquine upon the maturation of asexual erythrocytic forms of Plasmodium vivax in vitro (1974) Am. J. Trop. Med. Hyg., 23, pp. 1007-1014Price, R.N., Tjitra, E., Guerra, C.A., Yeung, S., White, N.J., Anstey, N.M., Vivax malaria: neglected and not benign (2007) Am. J. Trop. Med. Hyg., 77, pp. 79-87Rayner, J.C., Tran, T.M., Corredor, V., Huber, C.S., Barnwell, J.W., Galinski, M.R., Dramatic difference in diversity between Plasmodium falciparum and P. vivax reticulocyte binding-like genes (2005) Am. J. Trop. Med. Hyg., 72, pp. 666-674Renapurkar, D.M., Pradhan, V.R., Sutar, N.K., Deshmukh, R.A., Pandit, C.H., Marathe, S.N., Micro test for assaying sensitivity of Plasmodium vivax in vitro (1989) Chemotherapy, 35, pp. 160-163Rieckmann, K.H., Campbell, G.H., Sax, L.J., Mrema, J.E., Drug sensitivity of Plasmodium falciparum. An in-vitro microtechnique (1978) Lancet, 1, pp. 22-23Rijken, M.J., Boel, M.E., Russell, B., Imwong, M., Leimanis, M.L., Phyo, A.P., Muehlenbachs, A., Nosten, F., Chloroquine resistant vivax malaria in a pregnant woman on the western border of Thailand (2011) Malar. J., 10, p. 113Rossan, R.N., Cryopreservation of the blood stages of Plasmodium falciparum and P. vivax for in vivo studies (1985) Am. J. Trop. Med. Hyg., 34, pp. 207-208Rottmann, M., McNamara, C., Yeung, B.K.S., Lee, M.C.S., Zou, B., Russell, B., Seitz, P., Diagana, T.T., Spiroindolones, a potent compound class for the treatment of malaria (2010) Science, 329, pp. 1175-1180Russell, B., Chalfein, F., Prasetyorini, B., Kenangalem, E., Piera, K., Suwanarusk, R., Brockman, A., Price, R.N., Determinants of in vitro drug susceptibility testing of Plasmodium vivax (2008) Antimicrob. Agents Chemother., 52, pp. 1040-1045Russell, B., Li, A., Lim, C.T., Atomic force microscopy as a nanotool to investigate malaria-infected erythrocytes (2011) Bionanotechnology II: Global Prospects, pp. 287-295. , CRC Press, D. Reisner (Ed.)Russell, B., Suwanarusk, R., Borlon, C., Costa, F.T., Chu, C.S., Rijken, M.J., Sriprawat, K., Rénia, L., A reliable ex vivo invasion assay of human reticulocytes by Plasmodium vivax (2011) Blood, 118, pp. e74-81Russell, B.M., Udomsangpetch, R., Rieckmann, K.H., Kotecka, B.A., Coleman, R.E., Sattabongkot, J., Simple in vitro assay for determining the sensitivity of Plasmodium vivax isolates from fresh human blood to antimalarials in areas where P. vivax is endemic (2003) Antimicrob. Agents Chemother., 47, pp. 170-173Safeukui, I., Correas, J.M., Brousse, V., Hirt, D., Deplaine, G., Mule, S., Lesurtel, M., Buffet, P.A., Retention of Plasmodium falciparum ring-infected erythrocytes in the slow, open microcirculation of the human spleen (2008) Blood, 112, pp. 2520-2528Sharrock, W.W., Suwanarusk, R., Lek-Uthai, U., Edstein, M.D., Kosaisavee, V., Travers, T., Jaidee, A., Russell, B., Plasmodium vivax trophozoites insensitive to chloroquine (2008) Malar. J., 7, p. 94Sriprawat, K., Kaewpongsri, S., Suwanarusk, R., Leimanis, M.L., Lek-Uthai, U., Phyo, A.P., Snounou, G., Nosten, F., Effective and cheap removal of leukocytes and platelets from Plasmodium vivax-infected blood (2009) Malar. J., 8, p. 115Stewart, V.A., Plasmodium vivax under the microscope: the Aotus model (2003) Trends Parasitol., 19, pp. 589-594Suwanarusk, R., Cooke, B.M., Dondorp, A.M., Silamut, K., Sattabongkot, J., White, N.J., Udomsangpetch, R., The deformability of red blood cells parasitized by Plasmodium falciparum and P. vivax (2004) J. Infect. Dis., 189, pp. 190-194Suwanarusk, R., Russell, B., Chavchich, M., Chalfein, F., Kenangalem, E., Kosaisavee, V., Prasetyorini, B., Price, R.N., Chloroquine resistant Plasmodium vivax: in vitro characterisation and association with molecular polymorphisms (2007) PLoS ONE, 2, pp. e1089Suwanarusk, R., Chavchich, M., Russell, B., Jaidee, A., Chalfein, F., Barends, M., Prasetyorini, B., Price, R.N., Amplification of pvmdr1 associated with multidrug-resistant Plasmodium vivax (2008) J. Infect. Dis., 198, pp. 1558-1564Tan-ariya, P., Na-Bangchang, K., Tin, T., Limpaibul, L., Brockelman, C.R., Karbwang, J., Clinical response and susceptibility in vitro of Plasmodium vivax to the standard regimen of chloroquine in Thailand (1995) Trans. R. Soc. Trop. Med. Hyg., 89, pp. 426-429Tao, Z.Y., Xia, H., Cao, J., Gao, Q., Development and evaluation of a prototype non-woven fabric filter for purification of malaria-infected blood (2011) Malar. J., 10, p. 251Tasanor, O., Noedl, H., Na-Bangchang, K., Congpuong, K., Sirichaisinthop, J., Wernsdorfer, W.H., An in vitro system for assessing the sensitivity of Plasmodium vivax to chloroquine (2002) Acta Trop., 83, pp. 49-61Tasanor, O., Ruengweerayut, R., Sirichaisinthop, J., Congpuong, K., Wernsdorfer, W.H., Na-Bangchang, K., Clinical-parasitological response and in-vitro sensitivity of Plasmodium vivax to chloroquine and quinine on the western border of Thailand (2006) Trans. R. Soc. Trop. Med. Hyg., 100, pp. 410-418Udomsangpetch, R., Thanikkul, K., Pukrittayakamee, S., White, N.J., Rosette formation by Plasmodium vivax (1995) Trans. R. Soc. Trop. Med. Hyg., 89, pp. 635-637Udomsangpetch, R., Somsri, S., Panichakul, T., Chotivanich, K., Sirichaisinthop, J., Yang, Z., Cui, L., Sattabongkot, J., Short-term in vitro culture of field isolates of Plasmodium vivax using umbilical cord blood (2007) Parasitol. Int., 56, pp. 65-69Weed, R.I., LaCelle, P.L., Merrill, E.W., Metabolic dependence of red cell deformability (1969) J. Clin. Invest., 48, pp. 795-809Westenberger, S.J., McClean, C.M., Chattopadhyay, R., Dharia, N.V., Carlton, J.M., Barnwell, J.W., Collins, W.E., Winzeler, E.A., A systems-based analysis of Plasmodium vivax lifecycle transcription from human to mosquito (2010) PLoS Negl. Trop. Dis., 4, pp. e65

Generation, Characterization And Immunogenicity Of A Novel Chimeric Recombinant Protein Based On Plasmodium Vivax Ama-1 And Msp119

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Plasmodium vivax is the most widely distributed malaria species and the most prevalent species of malaria in America and Asia. Vaccine development against P. vivax is considered a priority in the global program for the eradication of malaria. Earlier studies have characterized the Apical Membrane Antigen 1 (AMA-1) ectodomain and the C-terminal region (19 kDa) of the Merozoite Surface Protein 1 (MSP-1) of P. vivax as immunodominant antigens. Based on this characterization, we designed a chimeric recombinant protein containing both merozoite immunodominant domains (PvAMA166-MSP119). The recombinant PvAMA166-MSP119 was successfully expressed in Pichia pastoris and used to immunize two different mouse strains (BALB/c and C57BL/6) in the presence of the Poly (I:C) as an adjuvant. Immunization with the chimeric protein induced high antibody titers against both proteins in both strains of mice as detected by ELISA. Antisera also recognized the native proteins expressed on the merozoites of mature P. vivax schizonts. Moreover, this antigen was able to induce IFN-gamma-secreting cells in C57BL/6 mice. These findings indicate that this novel yeast recombinant protein containing PvAMA166 and PvMSP119 is advantageous, because of improved antibody titers and cellular immune response. Therefore, this formulation should be further developed for pre-clinical trials in non-human primates as a potential candidate for a P. vivax vaccine. © 2017 Elsevier Ltd3518246324722011/23278-9, FAPESP, Fundação de Amparo à Pesquisa do Estado de São Paulo2013/01487-0, FAPESP, Fundação de Amparo à Pesquisa do Estado de São PauloCNPq 475500/2012-1, CNPq, Conselho Nacional de Desenvolvimento Científico e TecnológicoFAPESP 2012/13032-5, FAPESP, Fundação de Amparo à Pesquisa do Estado de São PauloFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP