1921
Volume 99, Issue 1
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Abstract.

gametocytes develop over 9–12 days while sequestered in deep tissues. On emergence into the bloodstream, they circulate for varied amounts of time during which certain host factors might influence their further development. We aimed to evaluate the potential association of patient clinical parameters with gametocyte development and carriage via in vivo methods. Seventy-two patients were enrolled from three hospitals in the Volta region of Ghana in 2016. Clinical parameters were documented for all patients, and gametocyte prevalence by microscopy was estimated at 12.5%. By measuring RNA transcripts representing two distinct gametocyte developmental stages using reverse transcriptase quantitative polymerase chain reaction (RT-qPCR), we obtained a more precise estimate of gametocyte carriage while also inferring gametocyte maturation. Fifty-three percent of the study participants harbored parasites expressing transcripts of the immature gametocyte-specific gene (), whereas 36% harbored RNA-positive parasites, which is enriched in mid and mature gametocytes, suggesting the presence of more immature stages. Linear logistic regression showed that patients older than 5 years but less than 16 years were more likely to carry gametocytes expressing both and compared with younger participants, and gametocytemia was more likely in mildly anemic individuals compared with those with severe/moderate anemia. These data provide further evidence that a greater number of malaria patients harbor gametocytes than typically estimated by microscopy and suggest a possible association between age, fever, anemia, and gametocytemia.

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References

  1. WHO, 2017. World Malaria Report 2017. Geneva, Switzerland: World Health Organization. Available at: http://www.who.int/malaria/media/world-malaria-report-2017/en/. Accessed February 19, 2018.
  2. Dinko B, Ayivor-Djanie R, Abugri J, Agboli E, Kye-Duodu G, Tagboto S, Tampuori J, Adzaku F, Binka FN, Awandare GA, , 2016. Comparison of malaria diagnostic methods in four hospitals in the Volta region of Ghana. MalariaWorld J 7: 5. [Google Scholar]
  3. Smalley ME, Abdalla S, Brown J, , 1981. The distribution of Plasmodium falciparum in the peripheral blood and bone marrow of Gambian children. Trans R Soc Trop Med Hyg 75: 103105. [Google Scholar]
  4. Carter R, Graves PM, , 1988. Gametocytes. Wernsdorfer WH, McGregor I, eds. Malaria: Principles and Practice of Malariology. London, United Kingdom: Churchill Livingstone, 253–320.
  5. Alano P, , 2007. Plasmodium falciparum gametocytes: still many secrets of a hidden life. Mol Microbiol 66: 291302. [Google Scholar]
  6. Joice R, 2014. Plasmodium falciparum transmission stages accumulate in the human bone marrow. Sci Transl Med 6: 244re5. [Google Scholar]
  7. Hawking F, Wilson ME, Gammage K, , 1971. Evidence for cyclic development and short-lived maturity in the gametocytes of Plasmodium falciparum. Trans R Soc Trop Med Hyg 65: 549559. [Google Scholar]
  8. Sinden RE, Carter R, Drakeley C, Leroy D, , 2012. The biology of sexual development of Plasmodium: the design and implementation of transmission-blocking strategies. Malar J 11: 70. [Google Scholar]
  9. Gebru T, Lalremruata A, Kremsner PG, Mordmüller B, Held J, , 2017. Life-span of in vitro differentiated Plasmodium falciparum gametocytes. Malar J 16: 330. [Google Scholar]
  10. Eichner M, Diebner HH, Molineaux L, Collins WE, Jeffery GM, Dietz K, , 2001. Genesis, sequestration and survival of Plasmodium falciparum gametocytes: parameter estimates from fitting a model to malaria therapy data. Trans R Soc Trop Med Hyg 95: 497501. [Google Scholar]
  11. Price R, Nosten F, Simpson JA, Luxemburger C, Phaipun L, ter Kuile F, van Vugt M, Chongsuphajaisiddhi T, White NJ, , 1999. Risk factors for gametocyte carriage in uncomplicated falciparum malaria. Am J Trop Med Hyg 60: 10191023. [Google Scholar]
  12. Gouagna LC, Bancone G, Yao F, Yameogo B, Dabiré KR, Costantini C, Simporé J, Ouedraogo JB, Modiano D, , 2010. Genetic variation in human HBB is associated with Plasmodium falciparum transmission. Nat Genet 42: 328331. [Google Scholar]
  13. Bousema T, Drakeley C, , 2011. Epidemiology and infectivity of Plasmodium falciparum and Plasmodium vivax gametocytes in relation to malaria control and elimination. Clin Microbiol Rev 24: 377410. [Google Scholar]
  14. Drakeley CJ, Secka I, Correa S, Greenwood BM, Targett GA, , 1999. Host haematological factors influencing the transmission of Plasmodium falciparum gametocytes to Anopheles gambiae s.s. mosquitoes. Trop Med Int Health 4: 131138. [Google Scholar]
  15. Barnes KI, Little F, Mabuza A, Mngomezulu N, Govere J, Durrheim D, Roper C, Watkins B, White NJ, , 2008. Increased gametocytemia after treatment: an early parasitological indicator of emerging sulfadoxine-pyrimethamine resistance in falciparum malaria. J Infect Dis 197: 16051613. [Google Scholar]
  16. Drakeley C, Sutherland C, Bousema JT, Sauerwein RW, Targett GA, , 2006. The epidemiology of Plasmodium falciparum gametocytes: weapons of mass dispersion. Trends Parasitol 22: 424430. [Google Scholar]
  17. Lobo CA, Kumar K, , 1998. Sexual differentiation and development in the malaria parasite. Parasitol Today 14: 146150. [Google Scholar]
  18. Nantakomol D, 2011. Circulating red cell-derived microparticles in human malaria. J Infect Dis 203: 700706. [Google Scholar]
  19. Mantel PY, 2013. Malaria-infected erythrocyte-derived microvesicles mediate cellular communication within the parasite population and with the host immune system. Cell Host Microbe 13: 521534. [Google Scholar]
  20. Regev-Rudzki N, 2013. Cell-cell communication between malaria-infected red blood cells via exosome-like vesicles. Cell 153: 11201133. [Google Scholar]
  21. Brancucci NMB, 2017. Lysophosphatidylcholine regulates sexual stage differentiation in the human malaria parasite Plasmodium falciparum. Cell 171: 15321544.e15. [Google Scholar]
  22. Eksi S, Haile Y, Furuya T, Ma L, Su X, Williamson KC, , 2005. Identification of a subtelomeric gene family expressed during the asexual-sexual stage transition in Plasmodium falciparum. Mol Biochem Parasitol 143: 9099. [Google Scholar]
  23. Eksi S, 2012. Plasmodium falciparum gametocyte development 1 (Pfgdv1) and gametocytogenesis early gene identification and commitment to sexual development. PLoS Pathog 8: e1002964. [Google Scholar]
  24. Kafsack BF, 2014. A transcriptional switch underlies commitment to sexual development in malaria parasites. Nature 507: 248252. [Google Scholar]
  25. Sinha A, 2014. A cascade of DNA-binding proteins for sexual commitment and development in Plasmodium. Nature 507: 253257. [Google Scholar]
  26. Joice R, 2013. Inferring developmental stage composition from gene expression in human malaria. PLoS Comput Biol 9: e1003392. [Google Scholar]
  27. Plasmo DB, , 2018. The Plasmodium Genome Resources. Available at: http://plasmodb.org/plasmo/. Accessed January 12, 2018.
  28. Kweku M, Liu D, Adjuik M, Binka F, Seidu M, Greenwood B, Chandramohan D, , 2008. Seasonal intermittent preventive treatment for the prevention of anaemia and malaria in Ghanaian children: a randomized, placebo controlled trial. PLoS One 3: e4000. [Google Scholar]
  29. Greenwood BM, Armstrong JR, , 1991. Comparison of two simple methods for determining malaria parasite density. Trans R Soc Trop Med Hyg 85: 186188. [Google Scholar]
  30. Drakeley CJ, Eling W, Teelen K, Bousema JT, Sauerwein R, Greenwood BM, Targett GA, , 2004. Parasite infectivity and immunity to Plasmodium falciparum gametocytes in Gambian children. Parasite Immunol 26: 159165. [Google Scholar]
  31. Chomczynski P, , 1993. A reagent for the single-step simultaneous isolation of RNA, DNA and proteins from cell and tissue samples. Biotechniques 15: 532537. [Google Scholar]
  32. Djimdé A, 2001. A molecular marker for chloroquine-resistant falciparum malaria. N Engl J Med 344: 257263. [Google Scholar]
  33. Duraisingh MT, Curtis J, Warhurst DC, , 1998. Plasmodium falciparum: detection of polymorphisms in the dihydrofolate reductase and dihydropteroate synthetase genes by PCR and restriction digestion. Exp Parasitol 89: 18. [Google Scholar]
  34. Chang HH, 2016. Persistence of Plasmodium falciparum parasitemia after artemisinin combination therapy: evidence from a randomized trial in Uganda. Sci Rep 6: 26330. [Google Scholar]
  35. WHO, 2011. Haemoglobin Concentrations for the Diagnosis of Anaemia and Assessment of Severity, Report, 2011. Available at: http://www.who.int/vmnis/indicators/haemoglobin.pdf. Accessed August 14, 2017.
  36. Schneider P, Bousema JT, Gouagna LC, Otieno S, van de Vegte-Bolmer M, Omar SA, Sauerwein RW, , 2007. Submicroscopic Plasmodium falciparum gametocyte densities frequently result in mosquito infection. Am J Trop Med Hyg 76: 470474. [Google Scholar]
  37. Bousema JT, 2006. Moderate effect of artemisinin-based combination therapy on transmission of Plasmodium falciparum. J Infect Dis 193: 11511159. [Google Scholar]
  38. Churcher TS, Bousema T, Walker M, Drakeley C, Schneider P, Ouédraogo AL, Basáñez MG, , 2013. Predicting mosquito infection from Plasmodium falciparum gametocyte density and estimating the reservoir of infection. Elife 2: e00626. [Google Scholar]
  39. Targett G, 2001. Artesunate reduces but does not prevent posttreatment transmission of Plasmodium falciparum to Anopheles gambiae. J Infect Dis 183: 12541259. [Google Scholar]
  40. Carter R, Miller LH, , 1979. Evidence for environmental modulation of gametocytogenesis in Plasmodium falciparum in continuous culture. Bull World Health Organ 57 (Suppl 1): 3752. [Google Scholar]
  41. Graves PM, Carter R, McNeill KM, , 1984. Gametocyte production in cloned lines of Plasmodium falciparum. Am J Trop Med Hyg 33: 10451050. [Google Scholar]
  42. Dyer M, Day KP, , 2000. Commitment to gametocytogenesis in Plasmodium falciparum. Parasitol Today 16: 102107. [Google Scholar]
  43. Smalley ME, Brown J, , 1981. Plasmodium falciparum gametocytogenesis stimulated by lymphocytes and serum from infected Gambian children. Trans R Soc Trop Med Hyg 75: 316317. [Google Scholar]
  44. Meerman L, Ord R, Bousema JT, van Niekerk M, Osman E, Hallett R, Pinder M, Walraven G, Sutherland CJ, , 2005. Carriage of chloroquine-resistant parasites and delay of effective treatment increase the risk of severe malaria in Gambian children. J Infect Dis 192: 16511657. [Google Scholar]
  45. Dunyo S, Milligan P, Edwards T, Sutherland C, Targett G, Pinder M, , 2006. Gametocytaemia after drug treatment of asymptomatic Plasmodium falciparum. PLoS Clin Trials 1: e20. [Google Scholar]
  46. WWARN Gametocyte Study Group, 2016. Gametocyte carriage in uncomplicated Plasmodium falciparum malaria following treatment with artemisinin combination therapy: a systematic review and meta-analysis of individual patient data. BMC Med 14: 79. [Google Scholar]
  47. Rieckmann KH, McNamara JV, Kass L, Powell RD, , 1969. Gametocytocidal and sporontocidal effects of primaquine upon two strains of Plasmodium falciparum. Mil Med 134: 802819. [Google Scholar]
  48. Ashley EA, Tracking Resistance to Artemisinin Collaboration (TRAC) , 2014. Spread of artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med 371: 411423. [Google Scholar]
  49. Beshir KB, 2013. Residual Plasmodium falciparum parasitemia in Kenyan children after artemisinin-combination therapy is associated with increased transmission to mosquitoes and parasite recurrence. J Infect Dis 208: 20172024. [Google Scholar]
  50. Venkatesan M, Alifrangis M, Roper C, Plowe CV, , 2013. Monitoring antifolate resistance in intermittent preventive therapy for malaria. Trends Parasitol 29: 497504. [Google Scholar]
  51. Kiarie WC, Wangai L, Agola E, Kimani FT, Hungu C, , 2015. Chloroquine sensitivity: diminished prevalence of chloroquine-resistant gene marker pfcrt-76 13 years after cessation of chloroquine use in Msambweni, Kenya. Malar J 14: 328. [Google Scholar]
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  • Received : 29 Jan 2018
  • Accepted : 23 Feb 2018
  • Published online : 05 Jul 2018

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