Humoral responses to defined malaria antigens in children living since birth under insecticide treated curtains in Burkina Faso
Introduction
During the last decade, the impact of insecticide treated materials (ITM) on child mortality has been studied in The Gambia, Ghana, Kenya and Burkina Faso, with reductions in mortality ranging from 15% in Burkina Faso to 33% in Kenya observed (Alonso et al., 1991, D'Alessandro et al., 1995, Binka et al., 1996, Nevill et al., 1996, Habluetzel et al., 1997).
However, it has been hypothesised that this benefit, interpreted as the consequence of a reduction in human–vector contacts, might not be sustained in the longer term because of a possible loss (or delay in the acquisition) of resistance to malaria subsequent to this reduced exposure (Snow and Marsh, 1995, Trape and Rogier, 1996).
Some degree of protection from the worst consequences of Plasmodium falciparum malaria is acquired after repeated exposure to infection and is achieved in early childhood in high transmission areas. The effective components of this ‘immunity’ have not been individually identified, although the classic immune repertoire, i.e. collaboration between B-cells, T-cells, antigens presenting cells and macrophages, seems to be implicated (Taylor-Robinson, 1998, Plebanski and Hill, 2000).
Several studies have investigated associations between naturally acquired protection against malaria in endemic populations and immune responses to particular malaria antigens, determining antibody and isotype titres or cell proliferation in response to these antigens. A high prevalence of circulating antibodies against recombinant glutamate-rich-protein (GLURP) fragments was found in Liberian adults and these IgG antibodies were associated with low parasite densities and absence of clinical malaria (Hogh et al., 1992, Theisen et al., 1995). Other investigations suggest that the levels of some malaria-specific antibodies vary with the level of malaria transmission. In Burkina Faso, the prevalence and levels of antibodies to the P. falciparum circumsporozoite protein (CSP) repetitive sequence (NANP)3 showed a marked difference between three localities (two rural areas and one urban district) characterised by different transmission intensities and clear seasonal variation, higher antibody levels being associated with higher transmission levels (Esposito et al., 1988). Jakobsen and co-workers found that IgG and IgM reactivity to malaria peptides of GLURP and acidic–basic repeat antigen (ABRA), in plasma from donors living in areas of different malaria endemicity, increased with the level of malaria transmission (Jakobsen et al., 1996). As to the impact of vector control on antibody responses, in Papua New Guinea the prevalence of antibody to the ring erythrocyte surface antigen (RESA) and the major merozoite surface antigen 2 (MSA-2) were lower in bednet users than in non-users (Genton et al., 1994). Implementation of insecticide treated curtains (ITC) in a rural village in Burkina Faso was followed by a reduction in the level of antibodies to the repetitive sequence of CSP (Lombardi et al., 1988). However, in a recent study also conducted in Burkina Faso, no difference in antibody levels to the C-terminal domain of the P. falciparum exported protein 1 (PfExp1) was observed between individuals in villages protected with ITC compared with unprotected controls (Meraldi et al., 2002).
In this paper, we examine the impact of ITCs on children's humoral immune responses to the P. falciparum CSP repetitive sequence, using five repeats of NANP (Asn–Asp–Asn–Pro)5, to the C-terminal part of the P. falciparum exported protein 1 (Cter-PfExp1, amino acids 73–165), to the GLURP fragments R0 (nonrepeat region, amino acids 94–489), R1 (central repeat region, amino acids 489–705) and R2 (repeat region, amino acids 705–1178) and to the merozoite surface protein 3 (MSP3, amino acids 181–276). The repetitive sequence of CSP has been reported to be related to the level of malaria transmission (Webster et al., 1987, Esposito et al., 1988). GLURP and MSP3 antibodies appear to promote a strong monocyte-dependent inhibition of P. falciparum growth in vitro (Oeuvray et al., 1994, Theisen et al., 1998), while monoclonal antibodies directed against PfExp1 inhibit parasite growth in vivo and in vitro (Kara et al., 1988). The GLURP and MSP3 antigens selected for inclusion in this investigation are components of candidate malaria vaccines undergoing testing for protection in humans, while NANP and PfExp1 as components of RTS′S/SBAS2 and 5.1-(NANP)19, respectively, two malaria vaccines candidate already went in field trials (Sturchler et al., 1992, Bojang et al., 2001).
We also investigate whether these humoral responses are associated with the presence or absence of P. falciparum infection, the parasite density and malaria-associated fever (malaria morbidity). In addition, a larger parasitological study was also conducted in children aged 6 months to 5 years during the peak period of malaria transmission (September) in the same area to investigate whether ITC were associated with alterations in prevalence or intensity of infection or risk of malaria morbidity.
Section snippets
Study area
The study area, the site of a large trial to evaluate the impact of ITC on all cause child mortality, has been described in detail elsewhere (Habluetzel et al., 1997). It is located in the central Mossi Plateau, Burkina Faso, 15–50 km north of the capital Ouagadougou, in the provinces of Oubritenga and Koulwéogo. The climate is characteristic of areas of Sudanese savannah, with a dry season from November to May and a rainy season from June to October. In 1999, the year of fieldwork for this
Immunological and parasitological studies in ten villages
Children living in five ITC and five non-ITC villages were of similar age (mean age 4.5 years in both groups), with similar proportions of males and females (female: 53.1 vs. 51.1% in non-ITC and ITC areas, respectively; P=0.7). Table 1 shows the geometric means for the AU of antibodies against (NANP)5, Cter-PfExp1, GLURP (R0, R1, R2) and MSP3 antigens in children aged 3–6 years living with or without ITC protection. Antibody levels against (NANP)5 among children living under ITC were about
Discussion
In this paper, we examined whether ITC might have induced a change in humoral responses to malaria specific antigens in children living since their birth in villages where this vector control measure had been implemented for 6 years. Results from a seroepidemiological cross-sectional survey conducted in November 1999, at the end of the malaria transmission season in rural Burkina Faso, show that the levels of antibodies against the P. falciparum circumsporozoite repeats (NANP)5 in children from
Acknowledgements
We thank the population of the study villages for their cooperation and the Ministry of Health, Burkina Faso. We are grateful to the staff of CNRFP, without whom this study would not have been possible. This investigation received financial support from the UNDP/World Bank/WHO Special programme for Research and Training in Tropical Diseases (TDR). It formed part of a programme of activities run by CNRFP, under the bilateral cooperation agreement between Burkina Faso and Italian Direzione
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