Immunological consequences of intermittent preventive treatment against malaria in Senegalese preschool children

Abstract

Background: Intermittent preventive treatment in children (IPTc) is a promising strategy to control malaria morbidity. A significant concern is whether IPTc increases children's susceptibility to subsequent malaria infection by altering their anti-Plasmodium acquired immunity.

Methods: To investigate this concern, IgG antibody (Ab) responses to Plasmodium falciparum schizont extract were measured in Senegalese children (6 months-5 years old) who had received three rounds of IPTc with artesunate + sulphadoxine-pyrimethamine (or placebo) at monthly intervals eight months earlier. Potential confounding factors, such as asexual malaria parasitaemia and nutritional status were also evaluated.

Results: Firstly, a bivariate analysis showed that children who had received IPTc had lower anti-Plasmodium IgG Ab levels than the non-treated controls. When epidemiological parameters were incorporated into a multivariate regression, gender, nutritional status and haemoglobin concentration did not have any significant influence. In contrast, parasitaemia, past malaria morbidity and increasing age were strongly associated with a higher specific IgG response.

Conclusions: The intensity of the contacts with P. falciparum seems to represent the main factor influencing anti-schizont IgG responses. Previous IPTc does not seem to interfere with this parasite-dependent acquired humoral response eight months after the last drug administration.

Figure 1

IgG antibodies against Plasmodium falciparum schizont extract measured in July 2003. Children received, in September-October-November 2002, either intermittent preventive treatment (IPTc) with artesunate + sulphadoxine-pyrimethamine or placebo (controls). Bars indicate the median value for each group. The two groups were compared using a bivariate Mann-Whitney test.

Figure 2

Anti-Plasmodium falciparum schizont IgG levels in July 2003. Anti-Plasmodium falciparum schizont IgG antibodies in 338 children presented according to their age class and to the treatment they received in September-October-November 2002 (IPT or placebo). Bars indicate the median value for each sub-group. P values drawn for comparisons between the age groups obtained using multivariate analysis (see Table 1) are displayed above the frame. P values obtained by comparing the IPT and control groups using bivariate analysis (Mann-Whitney test) are displayed within the frame. yo: years old

Figure 3

Anti-Plasmodium falciparum schizont IgG levels in July 2003. A comparison of anti-Plasmodium falciparum schizont IgG antibodies in 290 children surveyed in December 2002 (panel A) and in 305 children surveyed in July 2003 (panel B) by parasite status. All children had received IPT or placebo in September, October and November. The P value between the IPT and the control groups originates from a multivariate analysis (see Table 1) whereas Mann-Whitney tests were used to compare Plasmodium carriers to non-carriers. Bars indicate the median value for each sub-group.