Multiplicity of Plasmodium falciparum infection following intermittent preventive treatment in infants.
BACKGROUND
Intermittent preventive treatment in infants with sulphadoxine-pyrimethamine (IPTi-SP) reduces malaria morbidity by 20% to 33%. Potentially, however, this intervention may compromise the acquisition of immunity, including the tolerance towards multiple infections with Plasmodium falciparum.


METHODS
Plasmodium falciparum isolates were obtained from children participating in two Ghanaian IPTi-SP trials (Tamale, Afigya Sekyere) at 15 months of age, i.e., six months after they had received the second dose of IPTi-SP or placebo. By typing the polymorphic merozoite surface protein 1 (msp1) and msp2 genes, multiplicity of infection (MOI) was assessed in 389 isolates. A total of additional 133 samples were collected in Tamale at 3, 6, 9, and 12 months of age. Comparisons of MOI between groups were done by non-parametric statistical tests.


RESULTS
The number of distinguishable P. falciparum clones (MOI) ranged between one and six. Mean MOI in Tamale was stable at 2.13 - 2.17 during the first year of life, and increased to 2.57 at age 15 months (P = 0.01). At no age did MOI differ between the IPTi-SP and placebo groups (each, P ≥ 0.5). At 15 months of age, i.e., six months after the second dose, MOI was very similar for children who had received IPTi or placebo (means, 2.25 vs. 2.33; P = 0.55) as was the proportion of polyclonal infections (69.6% vs. 69.7%; P = 0.99). Adjusting for study site, current and prior malaria, parasite density, and season did not change this finding.


CONCLUSIONS
IPTi-SP appears to have no impact on the multiplicity of infection during infancy and thereafter. This suggests that tolerance of multiple infections, a component of protective immunity in highly endemic areas, is not affected by this intervention.
Buchholz
Ulrike
U
Institute of Tropical Medicine and International Health, Charité - University Medicine, Berlin, Germany.
Kobbe
Robin
R
Danquah
Ina
I
Zanger
Philipp
P
Reither
Klaus
K
Abruquah
Harry H
HH
Grobusch
Martin P
MP
Ziniel
Peter
P
May
Jürgen
J
Mockenhaupt
Frank P
FP
D000953:Antigens, Protozoan / Q000235:genetics; D000962:Antimalarials / Q000008:administration & dosage*; D018890:Chemoprevention / Q000379:methods*; D004338:Drug Combinations; D005260:Female; D005869:Ghana; D006801:Humans; D007223:Infant; D008288:Malaria / Q000469:parasitology* / Q000517:prevention & control*; D008297:Male; D020066:Merozoite Surface Protein 1 / Q000235:genetics; D010919:Placebos / Q000008:administration & dosage; D010963:Plasmodium falciparum / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification*; D015800:Protozoan Proteins / Q000235:genetics; D011739:Pyrimethamine / Q000008:administration & dosage; D013413:Sulfadoxine / Q000008:administration & dosage; D016896:Treatment Outcome
D000953:Antigens, Protozoan; D000962:Antimalarials; D004338:Drug Combinations; D020066:Merozoite Surface Protein 1; D010919:Placebos; D015800:Protozoan Proteins; C065974:merozoite surface protein 2, Plasmodium; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D011739:Pyrimethamine
Trans R Soc Trop Med Hyg. 2001 Mar-Apr;95(2):143-8
11355544
J Infect Dis. 2005 Dec 1;192(11):1962-5
16267768
J Infect Dis. 2007 Dec 1;196(11):1595-602
18008242
J Infect Dis. 2006 Aug 1;194(3):276-85
16826474
Am J Trop Med Hyg. 2010 May;82(5):755-6
20439949
Lancet. 1997 Sep 20;350(9081):844-50
9310602
Acta Trop. 2002 Nov;84(2):83-92
12429425
Mol Biochem Parasitol. 1993 Apr;58(2):283-92
8479452
PLoS Clin Trials. 2006 May;1(1):e5
16871327
Trans R Soc Trop Med Hyg. 1999 Feb;93 Suppl 1:29-34
10450423
PLoS One. 2008 May 21;3(5):e2227
18493597
Microbes Infect. 2007 Jan;9(1):103-10
17194613
PLoS One. 2010 Apr 02;5(4):e10016
20368815
Trends Parasitol. 2008 Aug;24(8):340-4
18617441
Malar J. 2008 Jan 23;7:17
18215251
J Infect Dis. 2008 Aug 1;198(3):393-400
18522503
BMJ. 2005 Oct 1;331(7519):727-33
16195288
Res Immunol. 1991 Oct;142(8):707-12
1817300
Lancet. 2008 Oct 18;372(9647):1383-4
18940461
Trans R Soc Trop Med Hyg. 1999 Feb;93 Suppl 1:59-64
10450428
Parasitology. 2001 Aug;123(Pt 2):113-23
11510676
Lancet. 2009 Oct 31;374(9700):1521-32
19765815
PLoS Med. 2005 Dec;2(12):e340
16259530
Trans R Soc Trop Med Hyg. 2004 Dec;98(12):687-94
15485698
Trop Med Int Health. 2003 Jan;8(1):3-11
12535242
Exp Parasitol. 2004 Jan-Feb;106(1-2):22-9
15013785
Lancet. 2001 May 12;357(9267):1471-7
11377597
Antimicrob Agents Chemother. 2007 Sep;51(9):3273-81
17638703
Clin Infect Dis. 2007 Jul 1;45(1):16-25
17554695
Parasitology. 1998 Jun;116 ( Pt 6):501-10
9651932
J Infect Dis. 2009 Oct 1;200(7):1166-75
19702508
Trans R Soc Trop Med Hyg. 1997 Sep-Oct;91(5):602-5
9463681
J Infect Dis. 1997 Apr;175(4):921-6
9086150
Lancet. 2009 Oct 31;374(9700):1533-42
19765816
Trans R Soc Trop Med Hyg. 2001 Mar-Apr;95(2):225-32
11355566
J Infect Dis. 1999 Apr;179(4):989-95
10068596
Trans R Soc Trop Med Hyg. 1995 Nov-Dec;89(6):629-33
8594677
Lancet. 1997 Jun 7;349(9066):1650-4
9186382
Trans R Soc Trop Med Hyg. 1999 Feb;93 Suppl 1:41-5
10450425
Trop Med Int Health. 2006 May;11(5):613-9
16640613
PLoS One. 2009 Nov 17;4(11):e7849
19924281
Acta Trop. 2001 Feb 23;78(2):155-62
11230825
Trans R Soc Trop Med Hyg. 1999 Feb;93 Suppl 1:35-9
10450424
Trans R Soc Trop Med Hyg. 1999 Feb;93 Suppl 1:47-51
10450426
Trans R Soc Trop Med Hyg. 1999 Jul-Aug;93(4):369-74
10674079