Hostname: page-component-848d4c4894-wg55d Total loading time: 0 Render date: 2024-05-12T05:52:17.582Z Has data issue: false hasContentIssue false
  • English
  • Français

Commit, hide and escape: the story of Plasmodium gametocytes

Published online by Cambridge University Press:  16 July 2018

Divya Beri ,
Balu Balan  and
Utpal Tatu Open the ORCID record for Utpal Tatu [Opens in a new window]
Divya Beri
Affiliation:
Department of Biochemistry, Indian Institute of Science, Bangalore, 560012, India
Balu Balan
Affiliation:
Department of Biochemistry, Indian Institute of Science, Bangalore, 560012, India
Utpal Tatu*
Affiliation:
Department of Biochemistry, Indian Institute of Science, Bangalore, 560012, India
*
Author for correspondence: Utpal Tatu, E-mail: tatu@biochem.iisc.ernet.in and tatu@iisc.ac.in
Get access Rights & Permissions [Opens in a new window]

Abstract

Malaria is the major cause of mortality and morbidity in tropical countries. The causative agent, Plasmodium sp., has a complex life cycle and is armed with various mechanisms which ensure its continuous transmission. Gametocytes represent the sexual stage of the parasite and are indispensable for the transmission of the parasite from the human host to the mosquito. Despite its vital role in the parasite's success, it is the least understood stage in the parasite's life cycle. The presence of gametocytes in asymptomatic populations and induction of gametocytogenesis by most antimalarial drugs warrants further investigation into its biology. With a renewed focus on malaria elimination and advent of modern technology available to biologists today, the field of gametocyte biology has developed swiftly, providing crucial insights into the molecular mechanisms driving sexual commitment. This review will summarise key current findings in the field of gametocyte biology and address the associated challenges faced in malaria detection, control and elimination.

Keywords

GametocytemalariaPlasmodiumsexual commitment
Type
Special Issue Review
Information
Parasitology , Volume 145 , Special Issue 13: 2017 Autumn Symposium of the British Society for Parasitology The multi-disciplinarity of parasitology: Host-parasite evolution in an ever changing world , November 2018 , pp. 1772 - 1782
Check for updates
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

Aguilar, R, Magallon-Tejada, A, Achtman, AH, Moraleda, C, Joice, R, Cistero, P, Li, WAI, Suen, CS, Nhabomba, A, Macete, E, Mueller, I, Marti, M, Alonso, PL, Menendez, C, Schofield, L and Mayor, A (2014) Molecular evidence for the localization of Plasmodium falciparum immature gametocytes in bone marrow. Blood 123, 959–966.Google Scholar
Alano, P (2014) The sound of sexual commitment breaks the silencing of malaria parasites. Trends in Parasitology 30, 509–510.Google Scholar
Arai, M, Billker, O, Morris, HR, Panico, M, Delcroix, M, Dixon, D, Ley, SV and Sinden, RE (2001) Both mosquito-derived xanthurenic acid and a host blood-derived factor regulate gametogenesis of Plasmodium in the midgut of the mosquito. Molecular and Biochemical Parasitology 116, 17–24.Google Scholar
Bannister, L and Mitchell, G (2003) The ins, outs and roundabouts of malaria. Trends in Parasitology 19, 209–213.Google Scholar
Becker, K, Tilley, L, Vennerstrom, JL, Roberts, D, Rogerson, S and Ginsburg, H (2004) Oxidative stress in malaria parasite-infected erythrocytes: host-parasite interactions. International Journal for Parasitology 34, 163–189.Google Scholar
Beri, D, Balan, B, Chaubey, S, Subramaniam, S, Surendra, B and Tatu, U (2017) A disrupted transsulphuration pathway results in accumulation of redox metabolites and induction of gametocytogenesis in malaria. Scientific Reports 7, 40213.Google Scholar
Billker, O, Lindo, V, Panico, M, Etienne, AE, Paxton, T, Dell, A, Rogers, M, Sinden, RE and Morris, HR (1998) Identification of xanthurenic acid as the putative inducer of malaria development in the mosquito. Nature 392, 289–292.Google Scholar
Billker, O, Dechamps, S, Tewari, R, Wenig, G, Franke-Fayard, B and Brinkmann, V (2004) Calcium and a calcium-dependent protein kinase regulate gamete formation and mosquito transmission in a malaria parasite. Cell 117, 503–514.Google Scholar
Bousema, T and Drakeley, C (2011) Epidemiology and infectivity of Plasmodium falciparum and Plasmodium vivax gametocytes in relation to malaria control and elimination. Clinical Microbiology Reviews 24, 377–410.Google Scholar
Bousema, T, Okell, L, Felger, I and Drakeley, C (2014) Asymptomatic malaria infections: detectability, transmissibility and public health relevance. Nature Reviews Microbiology 12, 833–840.Google Scholar
Brancucci, NM, Bertschi, NL, Zhu, L, Niederwieser, I, Chin, WH, Wampfler, R, Freymond, C, Rottmann, M, Felger, I, Bozdech, Z and Voss, TS (2014) Heterochromatin protein 1 secures survival and transmission of malaria parasites. Cell Host & Microbe 16, 165–176.Google Scholar
Brancucci, NM, Goldowitz, I, Buchholz, K, Werling, K and Marti, M (2015) An assay to probe Plasmodium falciparum growth, transmission stage formation and early gametocyte development. Nature Protocols 10, 1131–1142.Google Scholar
Brancucci, NMB, Gerdt, JP, Wang, C, de Niz, M, Philip, N, Adapa, SR, Zhang, M, Hitz, E, Niederwieser, I, Boltryk, SD, Laffitte, MC, Clark, MA, Gruring, C, Ravel, D, Blancke Soares, A, Demas, A, Bopp, S, Rubio-Ruiz, B, Conejo-Garcia, A, Wirth, DF, Gendaszewska-Darmach, E, Duraisingh, MT, Adams, JH, Voss, TS, Waters, AP, Jiang, RHY, Clardy, J and Marti, M (2017) Lysophosphatidylcholine regulates sexual stage differentiation in the human malaria parasite Plasmodium falciparum. Cell 171, 1532–1544.e15.Google Scholar
Bright, AT, Manary, MJ, Tewhey, R, Arango, EM, Wang, T, Schork, NJ, Yanow, SK and Winzeler, EA (2014) A high resolution case study of a patient with recurrent Plasmodium vivax infections shows that relapses were caused by meiotic siblings. PLoS Neglected Tropical Diseases 8, e2882.Google Scholar
Bruce, MC, Alano, P, Duthie, S and Carter, R (1990) Commitment of the malaria parasite Plasmodium falciparum to sexual and asexual development. Parasitology 100(Pt 2), 191–200.Google Scholar
Buckling, A, Ranford-Cartwright, LC, Miles, A and Read, AF (1999) Chloroquine increases Plasmodium falciparum gametocytogenesis in vitro. Parasitology 118(Pt 4), 339–346.Google Scholar
Cai, H, Zhou, Z, Gu, J and Wang, Y (2012) Comparative genomics and systems biology of malaria parasites Plasmodium. Current Bioinformatics 7, 478–489.Google Scholar
Campino, S, Benavente, ED, Assefa, S, Thompson, E, Drought, LG, Taylor, CJ, Gorvett, Z, Carret, CK, Flueck, C, Ivens, AC, Kwiatkowski, DP, Alano, P, Baker, DA and Clark, TG (2016) Genomic variation in two gametocyte non-producing Plasmodium falciparum clonal lines. Malaria Journal 15, 229.Google Scholar
Carlton, JM, Adams, JH, Silva, JC, Bidwell, SL, Lorenzi, H, Caler, E, Crabtree, J, Angiuoli, SV, Merino, EF, Amedeo, P, Cheng, Q, Coulson, RM, Crabb, BS, del Portillo, HA, Essien, K, Feldblyum, TV, Fernandez-Becerra, C, Gilson, PR, Gueye, AH, Guo, X, Kang'a, S, Kooij, TW, Korsinczky, M, Meyer, EV, Nene, V, Paulsen, I, White, O, Ralph, SA, Ren, Q, Sargeant, TJ, Salzberg, SL, Stoeckert, CJ, Sullivan, SA, Yamamoto, MM, Hoffman, SL, Wortman, JR, Gardner, MJ, Galinski, MR, Barnwell, JW and Fraser-Liggett, CM (2008) Comparative genomics of the neglected human malaria parasite Plasmodium vivax. Nature 455, 757–763.Google Scholar
Carter, LM, Kafsack, BF, Llinas, M, Mideo, N, Pollitt, LC and Reece, SE (2013) Stress and sex in malaria parasites: why does commitment vary? Evolution, Medicine, and Public Health 2013, 135–147.Google Scholar
Carter, R (2001) Transmission blocking malaria vaccines. Vaccine 19, 2309–2314.Google Scholar
Carter, R and Miller, LH (1979) Evidence for environmental modulation of gametocytogenesis in Plasmodium falciparum in continuous culture. Bulletin of the World Health Organization 57(Suppl. 1), 37–52.Google Scholar
Carter, R, Mendis, KN, Miller, LH, Molineaux, L and Saul, A (2000) Malaria transmission-blocking vaccines--how can their development be supported? Nature Medicine 6, 241–244.Google Scholar
Chaubey, S, Grover, M and Tatu, U (2014) Endoplasmic reticulum stress triggers gametocytogenesis in the malaria parasite. Journal of Biological Chemistry 289, 16662–16674.Google Scholar
Chen, I, Clarke, SE, Gosling, R, Hamainza, B, Killeen, G, Magill, A, O'meara, W, Price, RN and Riley, EM (2016) “Asymptomatic” malaria: a chronic and debilitating infection that should be treated. PLoS Medicine 13, e1001942.Google Scholar
Chillemi, R, Zappacosta, B, Simpore, J, Persichilli, S, Musumeci, M and Musumeci, S (2004) Hyperhomocysteinemia in acute Plasmodium falciparum malaria: an effect of host-parasite interaction. Clinica Chimica Acta 348, 113–120.Google Scholar
Church, LW, Le, TP, Bryan, JP, Gordon, DM, Edelman, R, Fries, L, Davis, JR, Herrington, DA, Clyde, DF, Shmuklarsky, MJ, Schneider, I, Mcgovern, TW, Chulay, JD, Ballou, WR and Hoffman, SL (1997) Clinical manifestations of Plasmodium falciparum malaria experimentally induced by mosquito challenge. Journal of Infectious Diseases 175, 915–920.Google Scholar
Coalson, JE, Walldorf, JA, Cohee, LM, Ismail, MD, Mathanga, D, Cordy, RJ, Marti, M, Taylor, TE, Seydel, KB, Laufer, MK and Wilson, ML (2016) High prevalence of Plasmodium falciparum gametocyte infections in school-age children using molecular detection: patterns and predictors of risk from a cross-sectional study in southern Malawi. Malaria Journal 15, 527.Google Scholar
Coleman, BI, Skillman, KM, Jiang, RHY, Childs, LM, Altenhofen, LM, Ganter, M, Leung, Y, Goldowitz, I, Kafsack, BFC, Marti, M, Llinas, M, Buckee, CO and Duraisingh, MT (2014) A Plasmodium falciparum histone deacetylase regulates antigenic variation and gametocyte conversion. Cell Host & Microbe 16, 177–186.Google Scholar
Conway, DJ, Roper, C, Oduola, AM, Arnot, DE, Kremsner, PG, Grobusch, MP, Curtis, CF and Greenwood, BM (1999) High recombination rate in natural populations of Plasmodium falciparum. Proceedings of the National Academy of Sciences of the United States of America 96, 4506–4511.Google Scholar
de Koning-Ward, TF, Olivieri, A, Bertuccini, L, Hood, A, Silvestrini, F, Charvalias, K, Berzosa Diaz, P, Camarda, G, Mcelwain, TF, Papenfuss, T, Healer, J, Baldassarri, L, Crabb, BS, Alano, P and Ranford-Cartwright, LC (2008) The role of osmiophilic bodies and Pfg377 expression in female gametocyte emergence and mosquito infectivity in the human malaria parasite Plasmodium falciparum. Molecular Microbiology 67, 278–290.Google Scholar
Dearnley, MK, Yeoman, JA, Hanssen, E, Kenny, S, Turnbull, L, Whitchurch, CB, Tilley, L and Dixon, MW (2012) Origin, composition, organization and function of the inner membrane complex of Plasmodium falciparum gametocytes. Journal of Cell Science 125, 2053–2063.Google Scholar
Del Portillo, HA and Chitnis, CE (2013) Talking to each other to initiate sexual differentiation. Cell 153, 945–947.Google Scholar
Delves, MJ, Ruecker, A, Straschil, U, Lelievre, J, Marques, S, Lopez-Barragan, MJ, Herreros, E and Sinden, RE (2013) Male and female Plasmodium falciparum mature gametocytes show different responses to antimalarial drugs. Antimicrobial Agents and Chemotherapy 57, 3268–3274.Google Scholar
Doerig, C, Rayner, JC, Scherf, A and Tobin, AB (2015) Post-translational protein modifications in malaria parasites. Nature Reviews Microbiology 13, 160–172.Google Scholar
Drakeley, C, Sutherland, C, Bousema, JT, Sauerwein, RW and Targett, GA (2006) The epidemiology of Plasmodium falciparum gametocytes: weapons of mass dispersion. Trends in Parasitology 22, 424–430.Google Scholar
Drakeley, CJ, Akim, NI, Sauerwein, RW, Greenwood, BM and Targett, GA (2000) Estimates of the infectious reservoir of Plasmodium falciparum malaria in The Gambia and in Tanzania. Transactions of the Royal Society of Tropical Medicine and Hygiene 94, 472–476.Google Scholar
Duffy, S and Avery, VM (2013) Identification of inhibitors of Plasmodium falciparum gametocyte development. Malaria Journal 12, 408.Google Scholar
Dyer, M and Day, K (2000) Expression of Plasmodium falciparum trimeric G proteins and their involvement in switching to sexual development. Molecular and Biochemical Parasitology 110, 437–448.Google Scholar
Eichner, M, Diebner, HH, Molineaux, L, Collins, WE, Jeffery, GM and Dietz, K (2001) Genesis, sequestration and survival of Plasmodium falciparum gametocytes: parameter estimates from fitting a model to malariatherapy data. Transactions of the Royal Society of Tropical Medicine and Hygiene 95, 497–501.Google Scholar
Farid, R, Dixon, MW, Tilley, L and Mccarthy, JS (2017) Initiation of gametocytogenesis at very low parasite density in Plasmodium falciparum infection. Journal of Infectious Diseases 215, 1167–1174.Google Scholar
Fivelman, QL, Mcrobert, L, Sharp, S, Taylor, CJ, Saeed, M, Swales, CA, Sutherland, CJ and Baker, DA (2007) Improved synchronous production of Plasmodium falciparum gametocytes in vitro. Molecular and Biochemical Parasitology 154, 119–123.Google Scholar
Florens, L, Washburn, MP, Raine, JD, Anthony, RM, Grainger, M, Haynes, JD, Moch, JK, Muster, N, Sacci, JB, Tabb, DL, Witney, AA, Wolters, D, Wu, Y, Gardner, MJ, Holder, AA, Sinden, RE, Yates, JR and Carucci, DJ (2002) A proteomic view of the Plasmodium falciparum life cycle. Nature 419, 520–526.Google Scholar
Ganesan, S, Chaurasiya, ND, Sahu, R, Walker, LA and Tekwani, BL (2012) Understanding the mechanisms for metabolism-linked hemolytic toxicity of primaquine against glucose 6-phosphate dehydrogenase deficient human erythrocytes: evaluation of eryptotic pathway. Toxicology 294, 54–60.Google Scholar
Gardner, MJ, Hall, N, Fung, E, White, O, Berriman, M, Hyman, RW, Carlton, JM, Pain, A, Nelson, KE, Bowman, S, Paulsen, IT, James, K, Eisen, JA, Rutherford, K, Salzberg, SL, Craig, A, Kyes, S, Chan, MS, Nene, V, Shallom, SJ, Suh, B, Peterson, J, Angiuoli, S, Pertea, M, Allen, J, Selengut, J, Haft, D, Mather, MW, Vaidya, AB, Martin, DM, Fairlamb, AH, Fraunholz, MJ, Roos, DS, Ralph, SA, Mcfadden, GI, Cummings, LM, Subramanian, GM, Mungall, C, Venter, JC, Carucci, DJ, Hoffman, SL, Newbold, C, Davis, RW, Fraser, CM and Barrell, B (2002) Genome sequence of the human malaria parasite Plasmodium falciparum. Nature 419, 498–511.Google Scholar
Gbotosho, GO, Sowunmi, A, Happi, CT and Okuboyejo, TM (2011) Plasmodium falciparum gametocyte carriage, sex ratios and asexual parasite rates in Nigerian children before and after a treatment protocol policy change instituting the use of artemisinin-based combination therapies. Memorias do Instituto Oswaldo Cruz 106, 685–690.Google Scholar
Gething, PW, Elyazar, IR, Moyes, CL, Smith, DL, Battle, KE, Guerra, CA, Patil, AP, Tatem, AJ, Howes, RE, Myers, MF, George, DB, Horby, P, Wertheim, HF, Price, RN, Mueller, I, Baird, JK and Hay, SI (2012) A long neglected world malaria map: Plasmodium vivax endemicity in 2010. Plos Neglected Tropical Diseases 6, e1814.Google Scholar
Goncalves, LA, Cravo, P and Ferreira, MU (2014) Emerging Plasmodium vivax resistance to chloroquine in South America: an overview. Memorias do Instituto Oswaldo Cruz 109, 534–539.Google Scholar
Gouagna, LC, Ferguson, HM, Okech, BA, Killeen, GF, Kabiru, EW, Beier, JC, Githure, JI and Yan, G (2004) Plasmodium falciparum malaria disease manifestations in humans and transmission to Anopheles gambiae: a field study in Western Kenya. Parasitology 128, 235–243.Google Scholar
Greenwood, BM (2008) Control to elimination: implications for malaria research. Trends in Parasitology 24, 449–454.Google Scholar
Guerra, CA, Snow, RW and Hay, SI (2006) Defining the global spatial limits of malaria transmission in 2005. Advances in Parasitology 62, 157–179.Google Scholar
Guinet, F, Dvorak, JA, Fujioka, H, Keister, DB, Muratova, O, Kaslow, DC, Aikawa, M, Vaidya, AB and Wellems, TE (1996) A developmental defect in Plasmodium falciparum male gametogenesis. Journal of Cell Biology 135, 269–278.Google Scholar
Gupta, AP, Chin, WH, Zhu, L, Mok, S, Luah, YH, Lim, EH and Bozdech, Z (2013) Dynamic epigenetic regulation of gene expression during the life cycle of malaria parasite Plasmodium falciparum. PLoS Pathogens 9, e1003170.Google Scholar
Hallett, RL, Dunyo, S, Ord, R, Jawara, M, Pinder, M, Randall, A, Alloueche, A, Walraven, G, Targett, GA, Alexander, N and Sutherland, CJ (2006) Chloroquine/sulphadoxine-pyrimethamine for Gambian children with malaria: transmission to mosquitoes of multidrug-resistant Plasmodium falciparum. Plos Clinical Trials 1, e15.Google Scholar
Handunnetti, SM, Gunewardena, DM, Pathirana, PP, Ekanayake, K, Weerasinghe, S and Mendis, KN (1996) Features of recrudescent chloroquine-resistant Plasmodium falciparum infections confer a survival advantage on parasites and have implications for disease control. Transactions of the Royal Society of Tropical Medicine and Hygiene 90, 563–567.Google Scholar
Hodson, N, Invergo, B, Rayner, JC and Choudhary, JS (2015) Palmitoylation and palmitoyl-transferases in Plasmodium parasites. Biochemical Society Transactions 43, 240–245.Google Scholar
Hulden, L (2011) Activation of the hypnozoite: a part of Plasmodium vivax life cycle and survival. Malaria Journal 10, 90.Google Scholar
Ikadai, H, Shaw Saliba, K, Kanzok, SM, Mclean, KJ, Tanaka, TQ, Cao, J, Williamson, KC and Jacobs-Lorena, M (2013) Transposon mutagenesis identifies genes essential for Plasmodium falciparum gametocytogenesis. Proceedings of the National Academy of Sciences of the United States of America 110, E1676–E1684.Google Scholar
Jeffery, GM and Eyles, DE (1955) Infectivity to mosquitoes of Plasmodium falciparum as related to gametocyte density and duration of infection. American Journal of Tropical Medicine and Hygiene 4, 781–789.Google Scholar
John, CC, Mchugh, MM, Moormann, AM, Sumba, PO and Ofulla, AV (2005) Low prevalence of Plasmodium falciparum infection among asymptomatic individuals in a highland area of Kenya. Transactions of the Royal Society of Tropical Medicine and Hygiene 99, 780–786.Google Scholar
Joice, R, Nilsson, SK, Montgomery, J, Dankwa, S, Egan, E, Morahan, B, Seydel, KB, Bertuccini, L, Alano, P, Williamson, KC, Duraisingh, MT, Taylor, TE, Milner, DA and Marti, M (2014) Plasmodium falciparum transmission stages accumulate in the human bone marrow. Science Translational Medicine 6, 244re245.Google Scholar
Josling, GA and Llinas, M (2015) Sexual development in Plasmodium parasites: knowing when it's time to commit. Nature Reviews Microbiology 13, 573–587.Google Scholar
Kafsack, BF, Rovira-Graells, N, Clark, TG, Bancells, C, Crowley, VM, Campino, SG, Williams, AE, Drought, LG, Kwiatkowski, DP, Baker, DA, Cortes, A and Llinas, M (2014) A transcriptional switch underlies commitment to sexual development in malaria parasites. Nature 507, 248–252.Google Scholar
Kehr, S, Jortzik, E, Delahunty, C, Yates, JR 3rd, Rahlfs, S and Becker, K (2011) Protein S-glutathionylation in malaria parasites. Antioxidants & Redox Signaling 15, 2855–2865.Google Scholar
Khan, SM, Franke-Fayard, B, Mair, GR, Lasonder, E, Janse, CJ, Mann, M and Waters, AP (2005) Proteome analysis of separated male and female gametocytes reveals novel sex-specific Plasmodium biology. Cell 121, 675–687.Google Scholar
Klemola, T (1988) Immunohistochemical findings in the intestine of IgA-deficient persons: number of intraepithelial T lymphocytes is increased. Journal of Pediatric Gastroenterology and Nutrition 7, 537–543.Google Scholar
Kono, M, Herrmann, S, Loughran, NB, Cabrera, A, Engelberg, K, Lehmann, C, Sinha, D, Prinz, B, Ruch, U, Heussler, V, Spielmann, T, Parkinson, J and Gilberger, TW (2012) Evolution and architecture of the inner membrane complex in asexual and sexual stages of the malaria parasite. Molecular Biology and Evolution 29, 2113–2132.Google Scholar
Krampa, F, Aniweh, Y, Awandare, G and Kanyong, P (2017) Recent progress in the development of diagnostic tests for malaria. Diagnostics (Basel) 7, 54. doi:10.3390/diagnostics7030054.Google Scholar
Lasonder, E, Ishihama, Y, Andersen, JS, Vermunt, AM, Pain, A, Sauerwein, RW, Eling, WM, Hall, N, Waters, AP, Stunnenberg, HG and Mann, M (2002) Analysis of the Plasmodium falciparum proteome by high-accuracy mass spectrometry. Nature 419, 537–542.Google Scholar
Lasonder, E, Rijpma, SR, van schaijk, BC, Hoeijmakers, WA, Kensche, PR, Gresnigt, MS, Italiaander, A, Vos, MW, Woestenenk, R, Bousema, T, Mair, GR, Khan, SM, Janse, CJ, Bartfai, R and Sauerwein, RW (2016) Integrated transcriptomic and proteomic analyses of P. falciparum gametocytes: molecular insight into sex-specific processes and translational repression. Nucleic Acids Research 44, 6087–6101.Google Scholar
Lee, S-M, Wu, C-K, Plieskatt, JL, Miura, K, Hickey, JM and King, CR (2017) An N-terminal Pfs230 domain produced in baculovirus as a biological active transmission-blocking vaccine candidate. Clinical and Vaccine Immunology.Google Scholar
Lindblade, KA, Steinhardt, L, Samuels, A, Kachur, SP and Slutsker, L (2013) The silent threat: asymptomatic parasitemia and malaria transmission. Expert Review of Anti-Infective Therapy 11, 623–639.Google Scholar
Mair, GR, Braks, JA, Garver, LS, Wiegant, JC, Hall, N, Dirks, RW, Khan, SM, Dimopoulos, G, Janse, CJ and Waters, AP (2006) Regulation of sexual development of Plasmodium by translational repression. Science 313, 667–669.Google Scholar
Maswoswe, SM, Peters, W and Warhurst, DC (1985) Corticosteroid stimulation of the growth of Plasmodium falciparum gametocytes in vitro. Annals of Tropical Medicine & Parasitology 79, 607–616.Google Scholar
Mawili-Mboumba, DP, Nikiema, R, Bouyou-Akotet, MK, Bahamontes-Rosa, N, Traore, A and Kombila, M (2013) Sub-microscopic gametocyte carriage in febrile children living in different areas of Gabon. Malaria Journal 12, 375.Google Scholar
Mcrobert, L, Taylor, CJ, Deng, W, Fivelman, QL, Cummings, RM, Polley, SD, Billker, O and Baker, DA (2008) Gametogenesis in malaria parasites is mediated by the cGMP-dependent protein kinase. PLoS Biology 6, e139.Google Scholar
Mens, P, Spieker, N, Omar, S, Heijnen, M, Schallig, H and Kager, PA (2007) Is molecular biology the best alternative for diagnosis of malaria to microscopy? A comparison between microscopy, antigen detection and molecular tests in rural Kenya and urban Tanzania. Tropical Medicine & International Health 12, 238–244.Google Scholar
Metselaar, D (1960) Relative increase in the prevalence of Plasmodium falciparum some years after the beginning of a house-spraying campaign in Netherlands New Guinea. Transactions of the Royal Society of Tropical Medicine and Hygiene 54, 523–528.Google Scholar
Miao, J, Chen, Z, Wang, Z, Shrestha, S, Li, X, Li, R and Cui, L (2017) Sex-specific biology of the human malaria parasite revealed from the proteomes of mature male and female gametocytes. Molecular and Cellular Proteomics 16, 537–551.Google Scholar
Miles, A, Iqbal, Z, Vauterin, P, Pearson, R, Campino, S, Theron, M, Gould, K, Mead, D, Drury, E, O'brien, J, Ruano Rubio, V, Macinnis, B, Mwangi, J, Samarakoon, U, Ranford-Cartwright, L, Ferdig, M, Hayton, K, Su, XZ, Wellems, T, Rayner, J, Mcvean, G and Kwiatkowski, D (2016) Indels, structural variation, and recombination drive genomic diversity in Plasmodium falciparum. Genome Research 26, 1288–1299.Google Scholar
Modrzynska, K, Pfander, C, Chappell, L, Yu, L, Suarez, C, Dundas, K, Gomes, AR, Goulding, D, Rayner, JC, Choudhary, J and Billker, O (2017) A knockout screen of ApiAP2 genes reveals networks of interacting transcriptional regulators controlling the Plasmodium life cycle. Cell Host & Microbe 21, 11–22.Google Scholar
Molineaux, L, Storey, J, Cohen, JE and Thomas, A (1980) A longitudinal study of human malaria in the West African Savanna in the absence of control measures: relationships between different Plasmodium species, in particular P. falciparum and P. malariae. American Journal of Tropical Medicine and Hygiene 29, 725–737.Google Scholar
Moreira, CM, Abo-Shehada, M, Price, RN and Drakeley, CJ (2015) A systematic review of sub-microscopic Plasmodium vivax infection. Malaria Journal 14, 360.Google Scholar
Mu, J, Awadalla, P, Duan, J, Mcgee, KM, Joy, DA, Mcvean, GA and Su, XZ (2005) Recombination hotspots and population structure in Plasmodium falciparum. PLoS Biology 3, e335.Google Scholar
Naotunne, TS, Karunaweera, ND, Del Giudice, G, Kularatne, MU, Grau, GE, Carter, R and Mendis, KN (1991) Cytokines kill malaria parasites during infection crisis: extracellular complementary factors are essential. Journal of Experimental Medicine 173, 523–529.Google Scholar
Ngwa, CJ, Scheuermayer, M, Mair, GR, Kern, S, Brugl, T, Wirth, CC, Aminake, MN, Wiesner, J, Fischer, R, Vilcinskas, A and Pradel, G (2013) Changes in the transcriptome of the malaria parasite Plasmodium falciparum during the initial phase of transmission from the human to the mosquito. BMC Genomics 14, 256.Google Scholar
Nunes, JK, Woods, C, Carter, T, Raphael, T, Morin, MJ, Diallo, D, Leboulleux, D, Jain, S, Loucq, C, Kaslow, DC and Birkett, AJ (2014) Development of a transmission-blocking malaria vaccine: progress, challenges, and the path forward. Vaccine 32, 5531–5539.Google Scholar
Okell, LC, Drakeley, CJ, Ghani, AC, Bousema, T and Sutherland, CJ (2008) Reduction of transmission from malaria patients by artemisinin combination therapies: a pooled analysis of six randomized trials. Malaria Journal 7, 125.Google Scholar
Okell, LC, Ghani, AC, Lyons, E and Drakeley, CJ (2009) Submicroscopic infection in Plasmodium falciparum-endemic populations: a systematic review and meta-analysis. Journal of Infectious Diseases 200, 1509–1517.Google Scholar
Okell, LC, Bousema, T, Griffin, JT, Ouedraogo, AL, Ghani, AC and Drakeley, CJ (2012) Factors determining the occurrence of submicroscopic malaria infections and their relevance for control. Nature Communications 3, 1237.Google Scholar
Ono, T, Nakai, T and Nakabayashi, T (1986) Induction of gametocytogenesis in Plasmodium falciparum by the culture supernatant of hybridoma cells producing anti-P. falciparum antibody. Biken Journal 29, 77–81.Google Scholar
Ono, T, Ohnishi, Y, Nagamune, K and Kano, M (1993) Gametocytogenesis induction by Berenil in cultured Plasmodium falciparum. Experimental Parasitology 77, 74–78.Google Scholar
Ouedraogo, AL, De Vlas, SJ, Nebie, I, Ilboudo-Sanogo, E, Bousema, JT, Ouattara, AS, Verhave, JP, Cuzin-Ouattara, N and Sauerwein, RW (2008) Seasonal patterns of Plasmodium falciparum gametocyte prevalence and density in a rural population of Burkina Faso. Acta Tropica 105, 28–34.Google Scholar
Peatey, CL, Skinner-Adams, TS, Dixon, MW, Mccarthy, JS, Gardiner, DL and Trenholme, KR (2009) Effect of antimalarial drugs on Plasmodium falciparum gametocytes. Journal of Infectious Diseases 200, 1518–1521.Google Scholar
Peatey, CL, Watson, JA, Trenholme, KR, Brown, CL, Nielson, L, Guenther, M, Timmins, N, Watson, GS and Gardiner, DL (2013) Enhanced gametocyte formation in erythrocyte progenitor cells: a site-specific adaptation by Plasmodium falciparum. Journal of Infectious Diseases 208, 1170–1174.Google Scholar
Pett, H, Goncalves, BP, Dicko, A, Nebie, I, Tiono, AB, Lanke, K, Bradley, J, Chen, I, Diawara, H, Mahamar, A, Soumare, HM, Traore, SF, Baber, I, Sirima, SB, Sauerwein, R, Brown, J, Gosling, R, Felger, I, Drakeley, C and Bousema, T (2016) Comparison of molecular quantification of Plasmodium falciparum gametocytes by Pfs25 qRT-PCR and QT-NASBA in relation to mosquito infectivity. Malaria Journal 15, 539.Google Scholar
Poran, A, Notzel, C, Aly, O, Mencia-Trinchant, N, Harris, CT, Guzman, ML, Hassane, DC, Elemento, O and Kafsack, BFC (2017) Single-cell RNA sequencing reveals a signature of sexual commitment in malaria parasites. Nature 551, 95–99.Google Scholar
Price, R, Nosten, F, Simpson, JA, Luxemburger, C, Phaipun, L, ter kuile, F, van Vugt, M, Chongsuphajaisiddhi, T and White, NJ (1999) Risk factors for gametocyte carriage in uncomplicated falciparum malaria. American Journal of Tropical Medicine and Hygiene 60, 1019–1023.Google Scholar
Pukrittayakamee, S, Imwong, M, Singhasivanon, P, Stepniewska, K, Day, NJ and White, NJ (2008) Effects of different antimalarial drugs on gametocyte carriage in P. vivax malaria. American Journal of Tropical Medicine and Hygiene 79, 378–384.Google Scholar
Puta, C and Manyando, C (1997) Enhanced gametocyte production in Fansidar-treated Plasmodium falciparum malaria patients: implications for malaria transmission control programmes. Tropical Medicine & International Health 2, 227–229.Google Scholar
Ramdani, G, Naissant, B, Thompson, E, Breil, F, Lorthiois, A, Dupuy, F, Cummings, R, Duffier, Y, Corbett, Y, Mercereau-Puijalon, O, Vernick, K, Taramelli, D, Baker, DA, Langsley, G and Lavazec, C (2015) cAMP-signalling regulates gametocyte-infected erythrocyte deformability required for malaria parasite transmission. PLoS Pathogens 11, e1004815.Google Scholar
Rantala, AM, Taylor, SM, Trottman, PA, Luntamo, M, Mbewe, B, Maleta, K, Kulmala, T, Ashorn, P and Meshnick, SR (2010) Comparison of real-time PCR and microscopy for malaria parasite detection in Malawian pregnant women. Malaria Journal 9, 269.Google Scholar
Roth, JM, Korevaar, DA, Leeflang, MM and Mens, PF (2016) Molecular malaria diagnostics: a systematic review and meta-analysis. Critical Reviews in Clinical Laboratory Sciences 53, 87–105.Google Scholar
Rovira-Vallbona, E, Contreras-Mancilla, JJ, Ramirez, R, Guzman-Guzman, M, Carrasco-Escobar, G, Llanos-Cuentas, A, Vinetz, JM, Gamboa, D and Rosanas-Urgell, A (2017) Predominance of asymptomatic and sub-microscopic infections characterizes the Plasmodium gametocyte reservoir in the Peruvian Amazon. PLoS Neglected Tropical Diseases 11, e0005674.Google Scholar
Sauerwein, RW and Bousema, T (2015) Transmission blocking malaria vaccines: assays and candidates in clinical development. Vaccine 33, 7476–7482.Google Scholar
Schall, JJ (1989) The sex ratio of Plasmodium gametocytes. Parasitology 98(Pt 3), 343–350.Google Scholar
Schoone, GJ, Oskam, L, Kroon, NC, Schallig, HD and Omar, SA (2000) Detection and quantification of Plasmodium falciparum in blood samples using quantitative nucleic acid sequence-based amplification. Journal of Clinical Microbiology 38, 4072–4075.Google Scholar
Shekalaghe, SA, Bousema, JT, Kunei, KK, Lushino, P, Masokoto, A, Wolters, LR, Mwakalinga, S, Mosha, FW, Sauerwein, RW and Drakeley, CJ (2007) Submicroscopic Plasmodium falciparum gametocyte carriage is common in an area of low and seasonal transmission in Tanzania. Tropical Medicine & International Health 12, 547–553.Google Scholar
Silvestrini, F, Lasonder, E, Olivieri, A, Camarda, G, van Schaijk, B, Sanchez, M, Younis younis, S, Sauerwein, R and Alano, P (2010) Protein export marks the early phase of gametocytogenesis of the human malaria parasite Plasmodium falciparum. Molecular and Cellular Proteomics 9, 1437–1448.Google Scholar
Sinden, RE (1991) Mitosis and meiosis in malarial parasites. Acta Leidensia 60, 19–27.Google Scholar
Sinha, A, Hughes, KR, Modrzynska, KK, Otto, TD, Pfander, C, Dickens, NJ, Religa, AA, Bushell, E, Graham, AL, Cameron, R, Kafsack, BFC, Williams, AE, Llinas, M, Berriman, M, Billker, O and Waters, AP (2014) A cascade of DNA-binding proteins for sexual commitment and development in Plasmodium. Nature 507, 253–257.Google Scholar
Smalley, ME and Brown, J (1981) Plasmodium falciparum gametocytogenesis stimulated by lymphocytes and serum from infected Gambian children. Transactions of the Royal Society of Tropical Medicine and Hygiene 75, 316–317.Google Scholar
Smith, TG, Lourenco, P, Carter, R, Walliker, D and Ranford-Cartwright, LC (2000) Commitment to sexual differentiation in the human malaria parasite, Plasmodium falciparum. Parasitology 121(Pt 2), 127–133.Google Scholar
Srivastava, A, Creek, DJ, Evans, KJ, de Souza, D, Schofield, L, Muller, S, Barrett, MP, Mcconville, MJ and Waters, AP (2015) Host reticulocytes provide metabolic reservoirs that can be exploited by malaria parasites. PLoS Pathogens 11, e1004882.Google Scholar
Stepniewska, K, Price, RN, Sutherland, CJ, Drakeley, CJ, von Seidlein, L, Nosten, F and White, NJ (2008) Plasmodium falciparum gametocyte dynamics in areas of different malaria endemicity. Malaria Journal 7, 249.Google Scholar
Sumari, D, Mwingira, F, Selemani, M, Mugasa, J, Mugittu, K and Gwakisa, P (2017) Malaria prevalence in asymptomatic and symptomatic children in Kiwangwa, Bagamoyo district, Tanzania. Malaria Journal 16, 222.Google Scholar
Tao, D, Ubaida-Mohien, C, Mathias, DK, King, JG, Pastrana-Mena, R, Tripathi, A, Goldowitz, I, Graham, DR, Moss, E, Marti, M and Dinglasan, RR (2014) Sex-partitioning of the Plasmodium falciparum stage V gametocyte proteome provides insight into falciparum-specific cell biology. Molecular and Cellular Proteomics 13, 2705–2724.Google Scholar
Taylor, LH, Walliker, D and Read, AF (1997) Mixed-genotype infections of the rodent malaria Plasmodium chabaudi are more infectious to mosquitoes than single-genotype infections. Parasitology 115(Pt 2), 121–132.Google Scholar
Tiburcio, M, Dixon, MW, Looker, O, Younis, SY, Tilley, L and Alano, P (2015) Specific expression and export of the Plasmodium falciparum gametocyte EXported protein-5 marks the gametocyte ring stage. Malaria Journal 14, 334.Google Scholar
Trager, W (2005) What triggers the gametocyte pathway in Plasmodium falciparum? Trends in Parasitology 21, 262–264.Google Scholar
Trager, W and Gill, GS (1992) Enhanced gametocyte formation in young erythrocytes by Plasmodium falciparum in vitro. The Journal of Protozoology 39, 429–432.Google Scholar
Trager, W, Gill, GS, Lawrence, C and Nagel, RL (1999) Plasmodium falciparum: enhanced gametocyte formation in vitro in reticulocyte-rich blood. Experimental Parasitology 91, 115–118.Google Scholar
Vallejo, AF, Garcia, J, Amado-Garavito, AB, Arevalo-Herrera, M and Herrera, S (2016) Plasmodium vivax gametocyte infectivity in sub-microscopic infections. Malaria Journal 15, 48.Google Scholar
von Seidlein, L, Jawara, M, Coleman, R, Doherty, T, Walraven, G and Targett, G (2001) Parasitaemia and gametocytaemia after treatment with chloroquine, pyrimethamine/sulfadoxine, and pyrimethamine/sulfadoxine combined with artesunate in young Gambians with uncomplicated malaria. Tropical Medicine & International Health 6, 92–98.Google Scholar
Waheed, AA, Ghanchi, NK, Rehman, KA, Raza, A, Mahmood, SF and Beg, MA (2015) Vivax malaria and chloroquine resistance: a neglected disease as an emerging threat. Malaria Journal 14, 146.Google Scholar
Walliker, D, Quakyi, IA, Wellems, TE, Mccutchan, TF, Szarfman, A, London, WT, Corcoran, LM, Burkot, TR and Carter, R (1987) Genetic analysis of the human malaria parasite Plasmodium falciparum. Science 236, 1661–1666.Google Scholar
Wangai, LN, Karau, MG, Njiruh, PN, Sabah, O, Kimani, FT, Magoma, G and Kiambo, N (2011) Sensitivity of microscopy compared to molecular diagnosis of P. falciparum: implications on malaria treatment in epidemic areas in Kenya. African Journal of Infectious Diseases 5, 1–6.Google Scholar
Waters, AP (2016) Epigenetic roulette in blood stream Plasmodium: gambling on sex. PLoS Pathogens 12, e1005353.Google Scholar
Werstuck, GH, Lentz, SR, Dayal, S, Hossain, GS, Sood, SK, Shi, YY, Zhou, J, Maeda, N, Krisans, SK, Malinow, MR and Austin, RC (2001) Homocysteine-induced endoplasmic reticulum stress causes dysregulation of the cholesterol and triglyceride biosynthetic pathways. Journal of Clinical Investigation 107, 1263–1273.Google Scholar
WHO (2015) Global malaria Programme, World Malaria Report, 2015. ISBN 978 92 4 156515 8.Google Scholar
Williams, JL (1999) Stimulation of Plasmodium falciparum gametocytogenesis by conditioned medium from parasite cultures. American Journal of Tropical Medicine and Hygiene 60, 7–13.Google Scholar
Zhang, M, Joyce, BR, Sullivan, WJ Jr and Nussenzweig, V (2013) Translational control in Plasmodium and toxoplasma parasites. Eukaryotic Cell 12, 161–167.Google Scholar
Zhou, Z, Mitchell, RM, Kariuki, S, Odero, C, Otieno, P, Otieno, K, Onyona, P, Were, V, Wiegand, RE, Gimnig, JE, Walker, ED, Desai, M and Shi, YP (2016) Assessment of submicroscopic infections and gametocyte carriage of Plasmodium falciparum during peak malaria transmission season in a community-based cross-sectional survey in western Kenya, 2012. Malaria Journal 15, 421.Google Scholar