Author:
- Introduction
- Methods
- Results
- Higher peaks are more likely to be followed by undetectable parasitemia.
- Simulating liver- and blood-stage infection.
- High peak parasitemias are followed by low nadir levels of parasitemia and a delay until subsequent peaks.
- Patterns of parasitemia in adults are consistent with simulation results.
- Variable infection rate is not a cause of delayed peaks.
- Discussion
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
Simpson JA, Aarons L, Collins WE, Jeffery GM, White NJ, 2002. Population dynamics of untreated Plasmodium falciparum malaria within the adult human host during the expansion phase of the infection. Parasitology 124: 247–263.
-
2.
Murphy JR, Baqar S, Davis JR, Herrington DA, Clyde DF, 1989. Evidence for a 6.5-day minimum exoerythrocytic cycle for Plasmodium falciparum in humans and confirmation that immunization with a synthetic peptide representative of a region of the circumsporozoite protein retards infection. J Clin Microbiol 27: 1434–1437.
-
3.
Juliano JJ, Porter K, Mwapasa V, Sem R, Rogers WO, Ariey F, Wongsrichanalai C, Read A, Meshnick SR, 2010. Exposing malaria in-host diversity and estimating population diversity by capture-recapture using massively parallel pyrosequencing. Proc Natl Acad Sci USA 107: 20138–20143.
-
4.
Nussler AK, Renia L, Pasquetto V, Miltgen F, Matile H, Mazier D, 1993. In vivo induction of the nitric oxide pathway in hepatocytes after injection with irradiated malaria sporozoites, malaria blood parasites or adjuvants. Eur J Immunol 23: 882–887.
-
5.
Mazier D, Goma J, Pied S, Renia L, Nussler A, Miltgen F, Mattei D, Grau G, 1990. Hepatic phase of malaria: a crucial role as “go-between” with other stages. Bull World Health Organ 68 (Suppl): 126–131.
-
6.
Portugal S, Carret C, Recker M, Armitage AE, Gonçalves LA, Epiphanio S, Sullivan D, Roy C, Newbold CI, Drakesmith H, Mota MM, 2011. Host-mediated regulation of superinfection in malaria. Nat Med 17: 732–737.
-
7.
van Santen S, de Mast Q, Swinkels DW, van der Ven AJ, 2011. Hepcidin in malaria superinfection: can findings be translated to humans? Nat Med 17: 1341, author reply 1341–1342.
-
8.
Moorman AM, Sumba PO, Chelimo K, Fang H, Tisch DJ, Dent AE, John CC, Long CA, Vulule J, Kazura JW, 2013. Humoral and cellular immunity to Plasmodium falciparum merozoite surface protein 1 and protection from infection with blood-stage parasites. J Infect Dis 208: 149–158.
-
9.
Bloland PB, Boriga DA, Ruebush TK, McCormick JB, Roberts JM, Oloo AJ, Hawley W, Lal A, Nahlen B, Campbell CC, 1999. Longitudinal cohort study of the epidemiology of malaria infections in an area of intense malaria transmission II. Descriptive epidemiology of malaria infection and disease among children. Am J Trop Med Hyg 60: 641–648.
-
10.
Golenser J, Waknine JH, Krugliak M, Hunt NH, Grau GE, 2006. Current perspectives on the mechanism of action of artemisinins. Int J Parasitol 36: 1427–1441.
-
11.
Britton NF, 2003. Essential Mathematical Biology. London: Springer-Verlag, 370.
-
12.
Andrews L, Andersen RF, Webster D, Dunachie S, Walther RM, Bejon P, Hunt-Cooke A, Bergson G, Sanderson F, Hill AV, Gilbert SC, 2005. Quantitative real-time polymerase chain reaction for malaria diagnosis and its use in malaria vaccine clinical trials. Am J Trop Med Hyg 73: 191–198.
-
13.
Bejon P, Andrews L, Andersen RF, Dunachie S, Webster D, Walther M, Gilbert SC, Peto T, Hill AVS, 2005. Calculation of liver-to-blood inocula, parasite growth rates, and preerythrocytic vaccine efficacy, from serial quantitative polymerase chain reaction studies of volunteers challenged with malaria sporozoites. J Infect Dis 191: 619–626.
-
14.
Deans AM, Lyke KE, Thera MA, Plowe CV, Kone A, Doumbo OK, Kai O, Marsh K, Mackinnon MJ, Raza A, Rowe JA, 2006. Low multiplication rates of African Plasmodium falciparum isolates and lack of association of multiplication rate and red blood cell selectivity with malaria virulence. Am J Trop Med Hyg 74: 554–563.
-
15.
Douglas AD, Andrews L, Draper SJ, Bojang K, Milligan P, Gilbert SC, Imoukhuede EB, Hill AV, 2011. Substantially reduced pre-patent parasite multiplication rates are associated with naturally acquired immunity to Plasmodium falciparum. J Infect Dis 203: 1337–1340.
-
16.
Sokhna CS, Rogier C, Dieye A, Trape JF, 2000. Host factors affecting the delay of reappearance of Plasmodium falciparum after radical treatment among a semi-immune population exposed to intense perennial transmission. Am J Trop Med Hyg 62: 266–270.
-
17.
Beier JC, Oster CN, Onyango FK, Bales JD, Sherwood JA, Perkins PV, Chumo DK, Koech DV, Whitmire RE, Roberts CR et al., 1994. Plasmodium falciparum incidence relative to entomologic inoculation rates at a site proposed for testing malaria vaccines in western Kenya. Am J Trop Med Hyg 50: 529–536.
-
18.
Bloland PB, Boriga DA, Ruebush TK, McCormick JB, Roberts JM, Oloo AJ, Hawley W, Lal A, Nahlen B, Campbell CC, 1999. Longitudinal cohort study of the epidemiology of malaria infections in an area of intense malaria transmission II. Descriptive epidemiology of malaria infection and disease among children. Am J Trop Med Hyg 60: 641–648.
-
19.
Pinkevych M, Petravic J, Chelimo K, Kazura JW, Moormann AM, Davenport MP, 2012. The dynamics of naturally acquired immunity to Plasmodium falciparum infection. PLOS Comput Biol 8: e1002729.
-
20.
Smith TA, Leuenberger R, Lengeler C, 2001. Child mortality and malaria transmission intensity in Africa. Trends Parasitol 17: 145–149.
-
21.
Walther M, Tongren JE, Andrews L, Korbel D, King E, Fletcher H, Andersen RF, Bejon P, Thompson F, Dunachie SJ, Edele F, de Souza JB, Sinden RE, Gilbert SC, Riley EM, Hill AV, 2005. Upregulation of TGF-beta, FOXP3, and CD4+CD25+ regulatory T cells correlates with more rapid parasite growth in human malaria infection. Immunity 23: 287–296.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 111 | 111 | 3 |
| Full Text Views | 303 | 98 | 0 |
| PDF Downloads | 71 | 18 | 0 |
Density-Dependent Blood Stage Plasmodium falciparum Suppresses Malaria Super-Infection in a Malaria Holoendemic Population
Mykola Pinkevych
Mykola Pinkevych
Centre for Vascular Research, University of New South Wales, Sydney, NSW, Australia; Kenya Medical Research Institute, Kisumu, Kenya; Case Western Reserve University, Cleveland, Ohio; University of Massachusetts Medical School, Worcester, Massachusetts
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Janka Petravic
Janka Petravic
Centre for Vascular Research, University of New South Wales, Sydney, NSW, Australia; Kenya Medical Research Institute, Kisumu, Kenya; Case Western Reserve University, Cleveland, Ohio; University of Massachusetts Medical School, Worcester, Massachusetts
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Kiprotich Chelimo
Kiprotich Chelimo
Centre for Vascular Research, University of New South Wales, Sydney, NSW, Australia; Kenya Medical Research Institute, Kisumu, Kenya; Case Western Reserve University, Cleveland, Ohio; University of Massachusetts Medical School, Worcester, Massachusetts
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John Vulule
John Vulule
Centre for Vascular Research, University of New South Wales, Sydney, NSW, Australia; Kenya Medical Research Institute, Kisumu, Kenya; Case Western Reserve University, Cleveland, Ohio; University of Massachusetts Medical School, Worcester, Massachusetts
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James W. Kazura
James W. Kazura
Centre for Vascular Research, University of New South Wales, Sydney, NSW, Australia; Kenya Medical Research Institute, Kisumu, Kenya; Case Western Reserve University, Cleveland, Ohio; University of Massachusetts Medical School, Worcester, Massachusetts
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Ann M. Moormann
Ann M. Moormann
Centre for Vascular Research, University of New South Wales, Sydney, NSW, Australia; Kenya Medical Research Institute, Kisumu, Kenya; Case Western Reserve University, Cleveland, Ohio; University of Massachusetts Medical School, Worcester, Massachusetts
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Miles P. Davenport
Miles P. Davenport
Centre for Vascular Research, University of New South Wales, Sydney, NSW, Australia; Kenya Medical Research Institute, Kisumu, Kenya; Case Western Reserve University, Cleveland, Ohio; University of Massachusetts Medical School, Worcester, Massachusetts
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Recent studies of Plasmodium berghei malaria in mice show that high blood-stage parasitemia levels inhibit the development of subsequent liver-stage infections. Whether a similar inhibitory effect on liver-stage Plasmodium falciparum by blood-stage infection occurs in humans is unknown. We have analyzed data from a treatment-time-to-infection cohort of children < 10 years of age residing in a malaria holoendemic area of Kenya where people experience a new blood-stage infection approximately every 2 weeks. We hypothesized that if high parasitemia blocked the liver stage, then high levels of parasitemia should be followed by a “skipped” peak of parasitemia. Statistical analysis of “natural infection” field data and stochastic simulation of infection dynamics show that the data are consistent with high P. falciparum parasitemia inhibiting liver-stage parasite development in humans.
Author Notes
Financial support: This work was funded by the National Health and Medical Research Council (NHMRC, Australia), the Australian Research Council, and National Institutes of Health (NIH, USA), National Institute of Allergy and Infectious Diseases, R01 AI043906 (JK and AMM), and Fogarty International Center (FIC) 1D43TW006576 (KC).
Disclosure: MPD is an NHMRC Senior Research Fellow. This study is published with permission from the Director, Kenya Medical Research Institute.
Authors' addresses: Mykola Pinkevych, Janka Petravic, and Miles P. Davenport, Centre for Vascular Research, University of New South Wales, Kensington, Australia, E-mails: pinkevych@student.unsw.edu.au, j.petravic@unsw.edu.au, and m.davenport@unsw.edu.au. Kiprotich Chelimo and John Vulule, Medical Research Institute, Kisumu, Kenya, E-mails: chelimokip@yahoo.co.uk and jvulule@kisian.mimcom.net. James W. Kazura, Case Western Reserve University, Cleveland, OH, E-mail: jxk14@po.cwru.edu. Ann M. Moormann, University of Massachusetts Medical School, Worcester, MA, E-mail: ann.moormann@umassmed.edu.
- Introduction
- Methods
- Results
- Higher peaks are more likely to be followed by undetectable parasitemia.
- Simulating liver- and blood-stage infection.
- High peak parasitemias are followed by low nadir levels of parasitemia and a delay until subsequent peaks.
- Patterns of parasitemia in adults are consistent with simulation results.
- Variable infection rate is not a cause of delayed peaks.
- Discussion
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
Simpson JA, Aarons L, Collins WE, Jeffery GM, White NJ, 2002. Population dynamics of untreated Plasmodium falciparum malaria within the adult human host during the expansion phase of the infection. Parasitology 124: 247–263.
-
2.
Murphy JR, Baqar S, Davis JR, Herrington DA, Clyde DF, 1989. Evidence for a 6.5-day minimum exoerythrocytic cycle for Plasmodium falciparum in humans and confirmation that immunization with a synthetic peptide representative of a region of the circumsporozoite protein retards infection. J Clin Microbiol 27: 1434–1437.
-
3.
Juliano JJ, Porter K, Mwapasa V, Sem R, Rogers WO, Ariey F, Wongsrichanalai C, Read A, Meshnick SR, 2010. Exposing malaria in-host diversity and estimating population diversity by capture-recapture using massively parallel pyrosequencing. Proc Natl Acad Sci USA 107: 20138–20143.
-
4.
Nussler AK, Renia L, Pasquetto V, Miltgen F, Matile H, Mazier D, 1993. In vivo induction of the nitric oxide pathway in hepatocytes after injection with irradiated malaria sporozoites, malaria blood parasites or adjuvants. Eur J Immunol 23: 882–887.
-
5.
Mazier D, Goma J, Pied S, Renia L, Nussler A, Miltgen F, Mattei D, Grau G, 1990. Hepatic phase of malaria: a crucial role as “go-between” with other stages. Bull World Health Organ 68 (Suppl): 126–131.
-
6.
Portugal S, Carret C, Recker M, Armitage AE, Gonçalves LA, Epiphanio S, Sullivan D, Roy C, Newbold CI, Drakesmith H, Mota MM, 2011. Host-mediated regulation of superinfection in malaria. Nat Med 17: 732–737.
-
7.
van Santen S, de Mast Q, Swinkels DW, van der Ven AJ, 2011. Hepcidin in malaria superinfection: can findings be translated to humans? Nat Med 17: 1341, author reply 1341–1342.
-
8.
Moorman AM, Sumba PO, Chelimo K, Fang H, Tisch DJ, Dent AE, John CC, Long CA, Vulule J, Kazura JW, 2013. Humoral and cellular immunity to Plasmodium falciparum merozoite surface protein 1 and protection from infection with blood-stage parasites. J Infect Dis 208: 149–158.
-
9.
Bloland PB, Boriga DA, Ruebush TK, McCormick JB, Roberts JM, Oloo AJ, Hawley W, Lal A, Nahlen B, Campbell CC, 1999. Longitudinal cohort study of the epidemiology of malaria infections in an area of intense malaria transmission II. Descriptive epidemiology of malaria infection and disease among children. Am J Trop Med Hyg 60: 641–648.
-
10.
Golenser J, Waknine JH, Krugliak M, Hunt NH, Grau GE, 2006. Current perspectives on the mechanism of action of artemisinins. Int J Parasitol 36: 1427–1441.
-
11.
Britton NF, 2003. Essential Mathematical Biology. London: Springer-Verlag, 370.
-
12.
Andrews L, Andersen RF, Webster D, Dunachie S, Walther RM, Bejon P, Hunt-Cooke A, Bergson G, Sanderson F, Hill AV, Gilbert SC, 2005. Quantitative real-time polymerase chain reaction for malaria diagnosis and its use in malaria vaccine clinical trials. Am J Trop Med Hyg 73: 191–198.
-
13.
Bejon P, Andrews L, Andersen RF, Dunachie S, Webster D, Walther M, Gilbert SC, Peto T, Hill AVS, 2005. Calculation of liver-to-blood inocula, parasite growth rates, and preerythrocytic vaccine efficacy, from serial quantitative polymerase chain reaction studies of volunteers challenged with malaria sporozoites. J Infect Dis 191: 619–626.
-
14.
Deans AM, Lyke KE, Thera MA, Plowe CV, Kone A, Doumbo OK, Kai O, Marsh K, Mackinnon MJ, Raza A, Rowe JA, 2006. Low multiplication rates of African Plasmodium falciparum isolates and lack of association of multiplication rate and red blood cell selectivity with malaria virulence. Am J Trop Med Hyg 74: 554–563.
-
15.
Douglas AD, Andrews L, Draper SJ, Bojang K, Milligan P, Gilbert SC, Imoukhuede EB, Hill AV, 2011. Substantially reduced pre-patent parasite multiplication rates are associated with naturally acquired immunity to Plasmodium falciparum. J Infect Dis 203: 1337–1340.
-
16.
Sokhna CS, Rogier C, Dieye A, Trape JF, 2000. Host factors affecting the delay of reappearance of Plasmodium falciparum after radical treatment among a semi-immune population exposed to intense perennial transmission. Am J Trop Med Hyg 62: 266–270.
-
17.
Beier JC, Oster CN, Onyango FK, Bales JD, Sherwood JA, Perkins PV, Chumo DK, Koech DV, Whitmire RE, Roberts CR et al., 1994. Plasmodium falciparum incidence relative to entomologic inoculation rates at a site proposed for testing malaria vaccines in western Kenya. Am J Trop Med Hyg 50: 529–536.
-
18.
Bloland PB, Boriga DA, Ruebush TK, McCormick JB, Roberts JM, Oloo AJ, Hawley W, Lal A, Nahlen B, Campbell CC, 1999. Longitudinal cohort study of the epidemiology of malaria infections in an area of intense malaria transmission II. Descriptive epidemiology of malaria infection and disease among children. Am J Trop Med Hyg 60: 641–648.
-
19.
Pinkevych M, Petravic J, Chelimo K, Kazura JW, Moormann AM, Davenport MP, 2012. The dynamics of naturally acquired immunity to Plasmodium falciparum infection. PLOS Comput Biol 8: e1002729.
-
20.
Smith TA, Leuenberger R, Lengeler C, 2001. Child mortality and malaria transmission intensity in Africa. Trends Parasitol 17: 145–149.
-
21.
Walther M, Tongren JE, Andrews L, Korbel D, King E, Fletcher H, Andersen RF, Bejon P, Thompson F, Dunachie SJ, Edele F, de Souza JB, Sinden RE, Gilbert SC, Riley EM, Hill AV, 2005. Upregulation of TGF-beta, FOXP3, and CD4+CD25+ regulatory T cells correlates with more rapid parasite growth in human malaria infection. Immunity 23: 287–296.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 111 | 111 | 3 |
| Full Text Views | 303 | 98 | 0 |
| PDF Downloads | 71 | 18 | 0 |