title: Transmission-dependent tolerance to multiclonal Plasmodium falciparum infection.
abstract: Whether the number of concurrent clones in asymptomatic Plasmodium falciparum infections reflects the degree of host protection was investigated in children living in areas with different levels of transmission on the coast of Kenya. The number of concurrent clones was determined on the basis of polymorphism in msp2, which encodes the vaccine candidate antigen merozoite surface protein 2. In a low-transmission area, most children had monoclonal infections, and diversity did not predict a risk of clinical malaria. In an area of moderate transmission, asymptomatic infections with 2 clones were, compared with 1 clone, associated with an increased risk of subsequent malaria. In a comparative assessment in a high-transmission area in Tanzania, multiclonal infections conferred a reduced risk. The different nonlinear associations between the number of clones and malaria morbidity suggest that levels of tolerance to multiclonal infections are transmission dependent as a result of cumulative exposure to antigenically diverse P. falciparum infections.
authors.affiliation: Infectious Diseases Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden. anna.farnert@ki.se
authors.forename: Anna
authors.initials: A
authors.lastname: Färnert
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Williams
authors.forename: Tabitha W
authors.initials: TW
authors.lastname: Mwangi
authors.forename: Anna
authors.initials: A
authors.lastname: Ehlin
authors.forename: Greg
authors.initials: G
authors.lastname: Fegan
authors.forename: Alex
authors.initials: A
authors.lastname: Macharia
authors.forename: Brett S
authors.initials: BS
authors.lastname: Lowe
authors.forename: Scott M
authors.initials: SM
authors.lastname: Montgomery
authors.forename: Kevin
authors.initials: K
authors.lastname: Marsh
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005786:Gene Expression Regulation; D005838:Genotype; D006801:Humans; D007223:Infant; D007630:Kenya / Q000453:epidemiology; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000276:immunology* / Q000469:parasitology*; D010963:Plasmodium falciparum / Q000145:classification / Q000235:genetics* / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
chemical_list: D000953:Antigens, Protozoan; D015800:Protozoan Proteins; C065974:merozoite surface protein 2, Plasmodium
references.citation: Microbes Infect. 2007 Jan;9(1):103-10
references.pmid: 17194613
references.citation: Trends Parasitol. 2008 Aug;24(8):340-4
references.pmid: 18617441
references.citation: Am J Trop Med Hyg. 1996 Jun;54(6):632-43
references.pmid: 8686784
references.citation: Trans R Soc Trop Med Hyg. 2004 Dec;98(12):687-94
references.pmid: 15485698
references.citation: Trop Med Int Health. 2003 Jan;8(1):3-11
references.pmid: 12535242
references.citation: Am J Trop Med Hyg. 1997 Feb;56(2):141-7
references.pmid: 9080871
references.citation: J Infect Dis. 1997 Apr;175(4):921-6
references.pmid: 9086150
references.citation: J Infect Dis. 1999 Apr;179(4):989-95
references.pmid: 10068596
references.citation: Am J Trop Med Hyg. 2002 Jun;66(6):653-8
references.pmid: 12224569
references.citation: Vaccine. 2006 May 8;24(19):4233-46
references.pmid: 16111789
references.citation: Infect Immun. 2001 Dec;69(12):7783-92
references.pmid: 11705960
references.citation: Trans R Soc Trop Med Hyg. 1999 Feb;93 Suppl 1:15-20
references.pmid: 10450421
references.citation: Trans R Soc Trop Med Hyg. 1999 Feb;93 Suppl 1:29-34
references.pmid: 10450423
references.citation: Trans R Soc Trop Med Hyg. 1999 Feb;93 Suppl 1:21-8
references.pmid: 10450422
references.citation: Trans R Soc Trop Med Hyg. 2001 Mar-Apr;95(2):143-8
references.pmid: 11355544
references.citation: Parasitology. 1994 Nov;109 ( Pt 4):413-21
references.pmid: 7800409
references.citation: Am J Trop Med Hyg. 1995 Mar;52(3):201-6
references.pmid: 7694959
references.citation: Parasitology. 2001 Aug;123(Pt 2):113-23
references.pmid: 11510676
references.citation: Am J Trop Med Hyg. 1995 Jan;52(1):81-8
references.pmid: 7856831
references.citation: Parasitology. 1998 Jun;116 ( Pt 6):501-10
references.pmid: 9651932
references.citation: Int J Parasitol. 2004 Jul;34(8):935-42
references.pmid: 15217732
references.citation: Trans R Soc Trop Med Hyg. 1997 Sep-Oct;91(5):602-5
references.pmid: 9463681
references.citation: J Infect Dis. 2005 Jun 1;191(11):1932-9
references.pmid: 15871128
references.citation: Lancet. 1997 Jun 7;349(9066):1650-4
references.pmid: 9186382
references.citation: Acta Trop. 2001 Feb 23;78(2):155-62
references.pmid: 11230825
references.citation: Ann Trop Med Parasitol. 2001 Mar;95(2):117-32
references.pmid: 11299119
references.citation: Trans R Soc Trop Med Hyg. 1999 Feb;93 Suppl 1:47-51
references.pmid: 10450426
references.citation: Trans R Soc Trop Med Hyg. 1999 Jul-Aug;93(4):369-74
references.pmid: 10674079
references.citation: Trans R Soc Trop Med Hyg. 1998 Nov-Dec;92(6):580-5
references.pmid: 10326095
references.citation: Am J Trop Med Hyg. 2002 Dec;67(6):604-10
references.pmid: 12518850
references.citation: Am J Trop Med Hyg. 2003 Jun;68(6):734-42
references.pmid: 12887036