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      Antibodies to malaria vaccine candidates are associated with chloroquine or sulphadoxine/pyrimethamine treatment efficacy in children in an endemic area of Burkina Faso

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          Abstract

          Background

          Patient immune status is thought to affect the efficacy of anti-malarial chemotherapy. This is a subject of some importance, since evidence of immunity-related interactions may influence our use of chemotherapy in populations with drug resistance, as well as assessment of the value of suboptimal vaccines. The study aim was to investigate relationship between antibodies and anti-malarial drug treatment outcomes.

          Methods

          Some 248 children aged 0.5 and 15 years were recruited prior to the high malaria transmission season. Venous blood (5 ml) was obtained from each child to measure antibody levels to selected malaria antigens, using ELISA. Blood smears were also performed to assess drug efficacy and malaria infection prevalence. Children were actively followed up to record clinical malaria cases.

          Results

          IgG levels to MSP3 were always higher in the successfully treated group than in the group with treatment failure. The same observation was made for GLURP but the reverse observation was noticed for MSP1-19. Cytophilic and non-cytophilic antibodies were significantly associated with protection against all three antigens, except for IgG4 to MSP1-19 and GLURP.

          Conclusion

          Acquired anti-malarial antibodies may play an important role in the efficacy of anti-malarial drugs in younger children more susceptible to the disease.

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          Most cited references20

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          Medical need, scientific opportunity and the drive for antimalarial drugs.

          Continued and sustainable improvements in antimalarial medicines through focused research and development are essential for the world's future ability to treat and control malaria. Unfortunately, malaria is a disease of poverty, and despite a wealth of scientific knowledge there is insufficient market incentive to generate the competitive, business-driven industrial antimalarial drug research and development that is normally needed to deliver new products. Mechanisms of partnering with industry have been established to overcome this obstacle and to open up and build on scientific opportunities for improved chemotherapy in the future.
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            Mechanisms underlying the monocyte-mediated antibody-dependent killing of Plasmodium falciparum asexual blood stages

            The relevance of the antibody-dependent cellular inhibition (ADCI) of Plasmodium falciparum to clinical protection has been previously established by in vitro studies of material obtained during passive transfer of protection by immunoglobulin G in humans. We here report further in vitro investigations aimed at elucidating the mechanisms underlying this ADCI effect. Results obtained so far suggest that (a) merozoite uptake by monocytes (MN) as well as by polymorphonuclear cells has little influence on the course of parasitemia; (b) the ADCI effect is mediated by a soluble factor released by MN; (c) this or these factors are able to block the division of surrounding intraerythrocytic parasites at the one nucleus stage; (d) the critical triggering antigen(s) targeted by effective Abs would appear to be associated with the surface of merozoites, as opposed to that of infected red blood cells; (e) the MN receptor for Abs effective in ADCI is apparently Fc gamma RII, and not RI; (f) MN function is up- and down- regulated by interferon-gamma and interleukin 4, respectively; and (g) of several potential mediators released by MN, only tumor necrosis factor (TNF) proved of relevance. The involvement of TNF in defense may explain the recently described increased frequency of the TNF-2 high- expression promoter in individuals living in endemic regions despite its compromising role in severe malaria.
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              Humoral responses to Plasmodium falciparum blood-stage antigens and association with incidence of clinical malaria in children living in an area of seasonal malaria transmission in Burkina Faso, West Africa.

              There is longstanding evidence that immunoglobulin G (IgG) has a role in protection against clinical malaria, and human antibodies of the cytophilic subclasses are thought to be particularly critical in this respect. In this cohort study, 286 Burkinabè children 6 months to 15 years old were kept under malaria surveillance in order to assess the protective role of antibody responses against four antigens which are currently being evaluated as vaccine candidates: apical membrane antigen 1 (AMA1), merozoite surface protein 1-19 (MSP1-19), MSP3, and glutamate-rich protein (GLURP). Total IgG, IgM, and IgG subclass responses were measured just before the malaria transmission season. The incidence of malaria was 2.4 episodes per child year of risk. After adjusting for the confounding effects of age, the level of total IgG to GLURP was strongly associated with reduced malaria incidence (incidence rate ratio associated with a doubling of total IgG, 0.79; 95% confidence interval, 0.66 to 0.94; P = 0.009.); there was a borderline statistically significant association between the level of total IgG to MSP3 and malaria incidence and no evidence of an association for total IgG to AMA1 and to MSP1-19. Of the IgG subclass responses studied, only IgG3 and IgG4 against GLURP and IgG1 against AMA1 were associated with reduced risk of clinical malaria. There was no evidence of an interaction between responses to AMA1 and baseline parasitemia in their effects on malaria incidence. Currently included in malaria vaccine formulations for clinical trials in humans, these blood-stage antigens, AMA1 and GLURP, offer good prospects for malaria vaccine development.
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                Author and article information

                Journal
                Malar J
                Malar. J
                Malaria Journal
                BioMed Central
                1475-2875
                2012
                22 March 2012
                : 11
                : 79
                Affiliations
                [1 ]Centre National de Recherche et de Formation sur le paludisme, o1 BP 2208 Ouagadougou 01, Burkina Faso
                [2 ]Department of Clinical Biochemistry, Statens Serum, 5, Orestads Boulevard, DK-2300 Copenhagen, Denmark
                [3 ]Noguchi Memorial Institute for Medical Research, Legon, P.O. Box M44, Accra, Ghana
                [4 ]UFR Sciences de la Vie et de la Terre (SVT), Université de Ouagadougou, Ouagadougou, Burkina Faso
                [5 ]Groupe de Recherche Action en Santé, 06 BP 10248 Ouagadougou 06, Burkina Faso
                Article
                1475-2875-11-79
                10.1186/1475-2875-11-79
                3338389
                22439695
                16d5cb99-5e48-4ce6-808d-ebbbb84c166f
                Copyright ©2012 Diarra et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 23 November 2011
                : 22 March 2012
                Categories
                Research

                Infectious disease & Microbiology
                msp3,glurp,chloroquine,msp1-19,sulphadoxine/pyrimethamine,antibodies
                Infectious disease & Microbiology
                msp3, glurp, chloroquine, msp1-19, sulphadoxine/pyrimethamine, antibodies

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