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Published in: Malaria Journal 1/2009

Open Access 01-12-2009 | Research

Three different Plasmodium species show similar patterns of clinical tolerance of malaria infection

Authors: Ivo Müller, Blaise Genton, Lawrence Rare, Benson Kiniboro, Will Kastens, Peter Zimmerman, James Kazura, Michael Alpers, Thomas A Smith

Published in: Malaria Journal | Issue 1/2009

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Abstract

Background

In areas where malaria endemicity is high, many people harbour blood stage parasites without acute febrile illness, complicating the estimation of disease burden from infection data. For Plasmodium falciparum the density of parasitaemia that can be tolerated is low in the youngest children, but reaches a maximum in the age groups at highest risk of infection. There is little data on the age dependence of tolerance in other species of human malaria.

Methods

Parasite densities measured in 24,386 presumptive malaria cases at two local health centres in the Wosera area of Papua New Guinea were compared with the distributions of parasite densities recorded in community surveys in the same area. We then analyse the proportions of cases attributable to each of Plasmodium falciparum, P. vivax, and P. malariae as functions of parasite density and age using a latent class model. These attributable fractions are then used to compute the incidence of attributable disease.

Results

Overall 33.3%, 6.1%, and 0.1% of the presumptive cases were attributable to P. falciparum, P. vivax, and P. malariae respectively. The incidence of attributable disease and parasite density broadly follow similar age patterns. The logarithm of the incidence of acute illness is approximately proportion to the logarithm of the parasite density for all three malaria species, with little age variation in the relationship for P. vivax or P. malariae. P. falciparum shows more age variation in disease incidence at given levels of parasitaemia than the other species.

Conclusion

The similarities between Plasmodium species in the relationships between parasite density and risk of attributable disease are compatible with the hypothesis that pan-specific mechanisms may regulate tolerance to different human Plasmodia. A straightforward mathematical expression might be used to project disease burden from parasite density distributions assessed in community-based parasitological surveys.
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Literature
1.
go back to reference Rogier C, Commenges D, Trape JF: Evidence for an age-dependent pyrogenic threshold of Plasmodium falciparum parasitemia in highly endemic populations. Am J Trop Med Hyg. 1996, 54: 613-619.PubMed Rogier C, Commenges D, Trape JF: Evidence for an age-dependent pyrogenic threshold of Plasmodium falciparum parasitemia in highly endemic populations. Am J Trop Med Hyg. 1996, 54: 613-619.PubMed
2.
go back to reference Smith T, Genton B, Baea K, Gibson N, Taime J, Narara A, Al Yaman F, Beck HP, Hii J, Alpers M: Relationships between Plasmodium falciparum infection and morbidity in a highly endemic area. Parasitology. 1994, 109 (Pt 5): 539-549. 10.1017/S0031182000076411.CrossRefPubMed Smith T, Genton B, Baea K, Gibson N, Taime J, Narara A, Al Yaman F, Beck HP, Hii J, Alpers M: Relationships between Plasmodium falciparum infection and morbidity in a highly endemic area. Parasitology. 1994, 109 (Pt 5): 539-549. 10.1017/S0031182000076411.CrossRefPubMed
3.
go back to reference Dicko A, Mantel C, Kouriba B, Sagara I, Thera MA, Doumbia S, Diallo M, Poudiougou B, Diakite M, Doumbo OK: Season, fever prevalence and pyrogenic threshold for malaria disease definition in an endemic area of Mali. Trop Med Int Health. 2005, 10: 550-556. 10.1111/j.1365-3156.2005.01418.x.CrossRefPubMed Dicko A, Mantel C, Kouriba B, Sagara I, Thera MA, Doumbia S, Diallo M, Poudiougou B, Diakite M, Doumbo OK: Season, fever prevalence and pyrogenic threshold for malaria disease definition in an endemic area of Mali. Trop Med Int Health. 2005, 10: 550-556. 10.1111/j.1365-3156.2005.01418.x.CrossRefPubMed
4.
go back to reference Mwangi TW, Ross A, Snow RW, Marsh K: Case definitions of clinical malaria under different transmission conditions in Kilifi district, Kenya. J Infect Dis. 2005, 191: 1932-1939. 10.1086/430006.PubMedCentralCrossRefPubMed Mwangi TW, Ross A, Snow RW, Marsh K: Case definitions of clinical malaria under different transmission conditions in Kilifi district, Kenya. J Infect Dis. 2005, 191: 1932-1939. 10.1086/430006.PubMedCentralCrossRefPubMed
5.
go back to reference Prybylski D, Khaliq A, Fox E, Sarwari AR, Strickland GT: Parasite density and malaria morbidity in the Pakistani Punjab. Am J Trop Med Hyg. 1999, 61 (5): 791-801.PubMed Prybylski D, Khaliq A, Fox E, Sarwari AR, Strickland GT: Parasite density and malaria morbidity in the Pakistani Punjab. Am J Trop Med Hyg. 1999, 61 (5): 791-801.PubMed
6.
go back to reference Faye FB, Spiegel A, Tall A, Sokhna C, Fontenille D, Rogier C, Trape JF: Diagnostic criteria and risk factors for Plasmodium ovale malaria. J Infect Dis. 2002, 186 (5): 690-695. 10.1086/342395.CrossRefPubMed Faye FB, Spiegel A, Tall A, Sokhna C, Fontenille D, Rogier C, Trape JF: Diagnostic criteria and risk factors for Plasmodium ovale malaria. J Infect Dis. 2002, 186 (5): 690-695. 10.1086/342395.CrossRefPubMed
7.
go back to reference Miller MJ: Observations on the natural history of malaria in the semi-resistant West African. Trans R Soc Trop Med Hyg. 1958, 52: 152-168. 10.1016/0035-9203(58)90036-1.CrossRefPubMed Miller MJ: Observations on the natural history of malaria in the semi-resistant West African. Trans R Soc Trop Med Hyg. 1958, 52: 152-168. 10.1016/0035-9203(58)90036-1.CrossRefPubMed
8.
go back to reference Clark IA, Al-Yaman FM, Cowden WB, Rockett KA: Does malarial tolerance, through nitric oxide, explain the low incidence of autoimmune disease in tropical Africa?. Lancet. 1996, 348: 1492-1494. 10.1016/S0140-6736(96)07342-4.CrossRefPubMed Clark IA, Al-Yaman FM, Cowden WB, Rockett KA: Does malarial tolerance, through nitric oxide, explain the low incidence of autoimmune disease in tropical Africa?. Lancet. 1996, 348: 1492-1494. 10.1016/S0140-6736(96)07342-4.CrossRefPubMed
9.
10.
go back to reference Dondorp AM, Desakorn V, Pongtavornpinyo W, Sahassananda D, Silamut K, Chotivanich K, Newton PN, Pitisuttithum P, Smithyman AM, White NJ, Day NP: Estimation of the total parasite biomass in acute falciparum malaria from plasma PfHRP2. PLoS Medicine. 2005, 2: e204-10.1371/journal.pmed.0020204.PubMedCentralCrossRefPubMed Dondorp AM, Desakorn V, Pongtavornpinyo W, Sahassananda D, Silamut K, Chotivanich K, Newton PN, Pitisuttithum P, Smithyman AM, White NJ, Day NP: Estimation of the total parasite biomass in acute falciparum malaria from plasma PfHRP2. PLoS Medicine. 2005, 2: e204-10.1371/journal.pmed.0020204.PubMedCentralCrossRefPubMed
11.
go back to reference Ochola LB, Marsh K, Lowe B, Gal S, Pluschke G, Smith T: Estimation of the sequestered parasite load in severe malaria patients using both host and parasite markers. Parasitology. 2005, 131: 449-458. 10.1017/S0031182005008085.CrossRefPubMed Ochola LB, Marsh K, Lowe B, Gal S, Pluschke G, Smith T: Estimation of the sequestered parasite load in severe malaria patients using both host and parasite markers. Parasitology. 2005, 131: 449-458. 10.1017/S0031182005008085.CrossRefPubMed
12.
go back to reference Smith T, Hii JL, Genton B, Muller I, Booth M, Gibson N, Narara A, Alpers MP: Associations of peak shifts in age – prevalence for human malarias with bednet coverage. Trans R Soc Trop Med Hyg. 2001, 95 (1): 1-6. 10.1016/S0035-9203(01)90314-1.CrossRefPubMed Smith T, Hii JL, Genton B, Muller I, Booth M, Gibson N, Narara A, Alpers MP: Associations of peak shifts in age – prevalence for human malarias with bednet coverage. Trans R Soc Trop Med Hyg. 2001, 95 (1): 1-6. 10.1016/S0035-9203(01)90314-1.CrossRefPubMed
13.
go back to reference Genton B, Al Yaman F, Beck HP, Hii J, Mellor S, Narara A, Gibson N, Smith T, Alpers MP: The epidemiology of malaria in the Wosera area, East Sepik Province, Papua New Guinea, in preparation for vaccine trials. I. Malariometric indices and immunity. Ann Trop Med Parasitol. 1995, 89 (4): 359-376.PubMed Genton B, Al Yaman F, Beck HP, Hii J, Mellor S, Narara A, Gibson N, Smith T, Alpers MP: The epidemiology of malaria in the Wosera area, East Sepik Province, Papua New Guinea, in preparation for vaccine trials. I. Malariometric indices and immunity. Ann Trop Med Parasitol. 1995, 89 (4): 359-376.PubMed
14.
go back to reference Genton B, Al Yaman F, Beck HP, Hii J, Mellor S, Rare L, Ginny M, Smith T, Alpers MP: The epidemiology of malaria in the Wosera area, East Sepik Province, Papua New Guinea, in preparation for vaccine trials. II. Mortality and morbidity. Ann Trop Med Parasitol. 1995, 89 (4): 377-390.PubMed Genton B, Al Yaman F, Beck HP, Hii J, Mellor S, Rare L, Ginny M, Smith T, Alpers MP: The epidemiology of malaria in the Wosera area, East Sepik Province, Papua New Guinea, in preparation for vaccine trials. II. Mortality and morbidity. Ann Trop Med Parasitol. 1995, 89 (4): 377-390.PubMed
15.
go back to reference Kasehagen LJ, Mueller I, McNamara DT, Bockarie MJ, Kiniboro B, Rare L, Lorry K, Kastens W, Reeder JC, Kazura JW: Changing patterns of Plasmodium blood-stage infections in the Wosera region of Papua New Guinea monitored by light microscopy and high throughput PCR diagnosis. Am J Trop Med Hyg. 2006, 75 (4): 588-596.PubMedCentralPubMed Kasehagen LJ, Mueller I, McNamara DT, Bockarie MJ, Kiniboro B, Rare L, Lorry K, Kastens W, Reeder JC, Kazura JW: Changing patterns of Plasmodium blood-stage infections in the Wosera region of Papua New Guinea monitored by light microscopy and high throughput PCR diagnosis. Am J Trop Med Hyg. 2006, 75 (4): 588-596.PubMedCentralPubMed
16.
go back to reference Health PNGDoP: Standard Treatment for Common Illnesses of Children in Papua New Guinea. 1993, Port Moresby: Department of Health Health PNGDoP: Standard Treatment for Common Illnesses of Children in Papua New Guinea. 1993, Port Moresby: Department of Health
17.
go back to reference Genton B, Smith T, Baea K, Narara A, Al Yaman F, Beck HP, Hii J, Alpers M: Malaria: how useful are clinical criteria for improving the diagnosis in a highly endemic area?. Trans R Soc Trop Med Hyg. 1994, 88 (5): 537-541. 10.1016/0035-9203(94)90152-X.CrossRefPubMed Genton B, Smith T, Baea K, Narara A, Al Yaman F, Beck HP, Hii J, Alpers M: Malaria: how useful are clinical criteria for improving the diagnosis in a highly endemic area?. Trans R Soc Trop Med Hyg. 1994, 88 (5): 537-541. 10.1016/0035-9203(94)90152-X.CrossRefPubMed
18.
go back to reference Muller I, Smith T, Mellor S, Rare L, Genton B: The effect of distance from home on attendance at a small rural health centre in Papua New Guinea. Int J Epidemiol. 1998, 27 (5): 878-884. 10.1093/ije/27.5.878.CrossRefPubMed Muller I, Smith T, Mellor S, Rare L, Genton B: The effect of distance from home on attendance at a small rural health centre in Papua New Guinea. Int J Epidemiol. 1998, 27 (5): 878-884. 10.1093/ije/27.5.878.CrossRefPubMed
19.
go back to reference Genton B, D'Acremont V, Rare L, Baea K, Reeder JC, Alpers M, Muller I: Plasmodium vivax and Misex Infections Are Associated with Severe Malaria in Children: A Prospective Study from Papua New Guinea. PLOS Medicine. 2008, 5: e127-10.1371/journal.pmed.0050127.PubMedCentralCrossRefPubMed Genton B, D'Acremont V, Rare L, Baea K, Reeder JC, Alpers M, Muller I: Plasmodium vivax and Misex Infections Are Associated with Severe Malaria in Children: A Prospective Study from Papua New Guinea. PLOS Medicine. 2008, 5: e127-10.1371/journal.pmed.0050127.PubMedCentralCrossRefPubMed
20.
go back to reference Kasehagen LJ, Mueller I, Kiniboro B, Bockarie MJ, Reeder JC, Kazura JW, Kastens W, McNamara DT, King CH, Whalen CC: Reduced Plasmodium vivax erythrocyte infection in PNG Duffy-negative heterozygotes. PLoS ONE. 2007, 2 (3): e336-10.1371/journal.pone.0000336.PubMedCentralCrossRefPubMed Kasehagen LJ, Mueller I, Kiniboro B, Bockarie MJ, Reeder JC, Kazura JW, Kastens W, McNamara DT, King CH, Whalen CC: Reduced Plasmodium vivax erythrocyte infection in PNG Duffy-negative heterozygotes. PLoS ONE. 2007, 2 (3): e336-10.1371/journal.pone.0000336.PubMedCentralCrossRefPubMed
21.
go back to reference Vounatsou P, Smith T, Smith AF: Bayesian analysis of two-component mixture distributions applied to estimating malaria attributable fractions. J Roy Stat Soc C-Applied Statistics. 1998, 47 (4): 575-587. 10.1111/1467-9876.00129.CrossRef Vounatsou P, Smith T, Smith AF: Bayesian analysis of two-component mixture distributions applied to estimating malaria attributable fractions. J Roy Stat Soc C-Applied Statistics. 1998, 47 (4): 575-587. 10.1111/1467-9876.00129.CrossRef
22.
go back to reference Spiegelhalter DJ, Thomas A, Best N, Lunn D: Winbugs Version 1.4. 2003, Cambridge, England: MRC-BSU Spiegelhalter DJ, Thomas A, Best N, Lunn D: Winbugs Version 1.4. 2003, Cambridge, England: MRC-BSU
23.
go back to reference Trape JF, Peelman P, Morault-Peelman B: Criteria for diagnosing clinical malaria among a semi-immune population exposed to intense and perennial transmission. Trans R Soc Trop Med Hyg. 1985, 79: 435-442. 10.1016/0035-9203(85)90054-9.CrossRefPubMed Trape JF, Peelman P, Morault-Peelman B: Criteria for diagnosing clinical malaria among a semi-immune population exposed to intense and perennial transmission. Trans R Soc Trop Med Hyg. 1985, 79: 435-442. 10.1016/0035-9203(85)90054-9.CrossRefPubMed
24.
go back to reference Greenwood BM, Bradley AK, Greenwood AM, Byass P, Jammeh K, Marsh K, Tulloch S, Oldfield FS, Hayes R: Mortality and morbidity from malaria among children in a rural area of The Gambia, West Africa. Trans R Soc Trop Med Hyg. 1987, 81: 478-486. 10.1016/0035-9203(87)90170-2.CrossRefPubMed Greenwood BM, Bradley AK, Greenwood AM, Byass P, Jammeh K, Marsh K, Tulloch S, Oldfield FS, Hayes R: Mortality and morbidity from malaria among children in a rural area of The Gambia, West Africa. Trans R Soc Trop Med Hyg. 1987, 81: 478-486. 10.1016/0035-9203(87)90170-2.CrossRefPubMed
25.
go back to reference Snow RW, Lindsay SW, Hayes RJ, Greenwood BM: Permethrin-treated bed nets (mosquito nets) prevent malaria in Gambian children. Trans R Soc Trop Med Hyg. 1988, 82 (6): 838-842. 10.1016/0035-9203(88)90011-9.CrossRefPubMed Snow RW, Lindsay SW, Hayes RJ, Greenwood BM: Permethrin-treated bed nets (mosquito nets) prevent malaria in Gambian children. Trans R Soc Trop Med Hyg. 1988, 82 (6): 838-842. 10.1016/0035-9203(88)90011-9.CrossRefPubMed
26.
go back to reference Smith T, Schellenberg JA, Hayes R: Attributable fraction estimates and case definitions for malaria in endemic areas. Stat Med. 1994, 13 (22): 2345-2358. 10.1002/sim.4780132206.CrossRefPubMed Smith T, Schellenberg JA, Hayes R: Attributable fraction estimates and case definitions for malaria in endemic areas. Stat Med. 1994, 13 (22): 2345-2358. 10.1002/sim.4780132206.CrossRefPubMed
27.
go back to reference NETWORK I: Population, Health and Survival at INDEPTH Sites. 2002, Ottawa: IDRC NETWORK I: Population, Health and Survival at INDEPTH Sites. 2002, Ottawa: IDRC
28.
go back to reference Heyman A, Beeson PB: Influence of various disease states upon the febrile response to intravenous injection of typhoid bacterial pyrogen; with particular reference to malaria and cirrhosis of the liver. J Lab Clin Med. 1949, 34 (10): 1400-1403.PubMed Heyman A, Beeson PB: Influence of various disease states upon the febrile response to intravenous injection of typhoid bacterial pyrogen; with particular reference to malaria and cirrhosis of the liver. J Lab Clin Med. 1949, 34 (10): 1400-1403.PubMed
29.
go back to reference Rubenstein M, Mulholland JH, Jeffery GM, Wolff SM: Malaria Induced Endotoxin Tolerance. Proc Soc Exp Biol Med. 1965, 118: 283-287.CrossRefPubMed Rubenstein M, Mulholland JH, Jeffery GM, Wolff SM: Malaria Induced Endotoxin Tolerance. Proc Soc Exp Biol Med. 1965, 118: 283-287.CrossRefPubMed
30.
go back to reference Sehgal VM, Siddjiqui WA, Alpers MP: A seroepidemiological study to evaluate the role of passive maternal immunity to malaria in infants. Trans R Soc Trop Med Hyg. 1989, 83 (Suppl): 105-106. 10.1016/0035-9203(89)90616-0.CrossRefPubMed Sehgal VM, Siddjiqui WA, Alpers MP: A seroepidemiological study to evaluate the role of passive maternal immunity to malaria in infants. Trans R Soc Trop Med Hyg. 1989, 83 (Suppl): 105-106. 10.1016/0035-9203(89)90616-0.CrossRefPubMed
31.
go back to reference Desowitz RS: Prenatal immune priming in malaria: antigen-specific blastogenesis of cord blood lymphocytes from neonates born in a setting of holoendemic malaria. Ann Trop Med Parasitol. 1988, 82 (2): 121-125.PubMed Desowitz RS: Prenatal immune priming in malaria: antigen-specific blastogenesis of cord blood lymphocytes from neonates born in a setting of holoendemic malaria. Ann Trop Med Parasitol. 1988, 82 (2): 121-125.PubMed
32.
go back to reference Garner PA: The epidemiology of maternal and neonatal health in Papua New Guinea. MD thesis. 1989, University of London Garner PA: The epidemiology of maternal and neonatal health in Papua New Guinea. MD thesis. 1989, University of London
33.
go back to reference Vounatsou P, Smith T, Kitua AY, Alonso PL, Tanner M: Apparent tolerance of Plasmodium falciparum in infants in a highly endemic area. Parasitology. 2000, 120 (Pt 1): 1-9. 10.1017/S0031182099005211.CrossRefPubMed Vounatsou P, Smith T, Kitua AY, Alonso PL, Tanner M: Apparent tolerance of Plasmodium falciparum in infants in a highly endemic area. Parasitology. 2000, 120 (Pt 1): 1-9. 10.1017/S0031182099005211.CrossRefPubMed
Metadata
Title
Three different Plasmodium species show similar patterns of clinical tolerance of malaria infection
Authors
Ivo Müller
Blaise Genton
Lawrence Rare
Benson Kiniboro
Will Kastens
Peter Zimmerman
James Kazura
Michael Alpers
Thomas A Smith
Publication date
01-12-2009
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2009
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/1475-2875-8-158

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