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Antibody responses in Plasmodium falciparum malaria and their relation to protection against the disease
Stockholm University, Faculty of Science, Wenner-Gren Institute for Experimental Biology.
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Protective immunity against Plasmodium falciparum may be obtained after repeated exposure to infection. Several studies indicate that immunity against the blood stages of the P. Falciparum infection is mainly antibody mediated. Protective antibodies may act either on their own, mediate antibody-dependent phagocytosis and/or cell-mediated neutralization of parasites. This thesis describes several aspects of humoral immune responses to P. falciparum infection in individuals of different age groups, different genetic background and with different degrees of malaria exposure.

Several target antigens for antibody-mediated inhibition of parasite growth or invasion have been identified. One such antigen is Pf332, which appears on the surface of parasitized erythrocytes at late trophozoite and schizont stage. This surface exposure makes the antigen a possible target for opsonizing antibodies. We optimized an in vitro assay for studying cellmediated parasite neutralization in the presence of Pf332-reactive antibodies. Our data demonstrate that, Pf332 specific antibodies are able to inhibit parasite growth on their own and in cooperation with human monocytes.

The P. falciparum parasites have evolved several mechanisms to evade the host neutralizing immune responses. In this thesis, we show that freshly isolated P. falciparum parasites from children living in a malaria endemic area of Burkina Faso were less sensitive for growth inhibition in vitro by autologous immunoglobulins (Ig) compared with heterologous ones. Analyses of two consecutive isolates taken 14 days apart, with regard to genotypes and sensitivity to growth inhibition in vitro, did not give any clear-cut indications on possible mechanisms leading to a reduced inhibitory activity in autologous parasite/antibody combinations. The frequent presence of persisting parasite clones in asymptomatic children indicates that the parasite possesses as yet undefined mechanisms to evade neutralizing immune responses.

Transmission reducing measures such insecticide treated nets (ITNs) have been shown to be effective in reducing morbidity and mortality from malaria. However, concerns have been raised that ITNs usage could affect the acquisition of malaria immunity. We studied the effect of the use of insecticide treated curtains (ITC) on anti-malarial immune responses of children living in villages with ITC since birth. The use of ITC did neither affect the levels of parasite neutralizing immune responses nor the multiplicity of infection. These results indicate that the use of ITC does not interfere with the acquisition of anti-malarial immunity in children living in a malaria hyperendemic area.

There is substantial evidence that the African Fulani tribe is markedly less susceptible to malaria infection compared to other sympatrically living ethnic tribes. We investigated the isotypic humoral responses against P. falciparum asexual blood stages in different ethnic groups living in sympatry in two countries exhibiting different malaria transmission intensities, Burkina Faso and Mali. We observed higher levels of the total malaria-specific-IgG and its cytophilic subclasses in individuals of the Fulani tribe as compared to non-Fulani individuals. Fulani individuals also showed higher levels of antibodies to measles antigen, indicating that the intertribal differences are not specific for malaria and might reflect a generally activated immune system in the Fulani.

Place, publisher, year, edition, pages
Stockholm: Wenner-Grens institut för experimentell biologi , 2004. , 94 p.
Keyword [en]
immunity, parasital immunology, Plasmodium falciparum malaria, antibody mediated invasion/growth inhibition
National Category
Immunology in the medical area
Identifiers
URN: urn:nbn:se:su:diva-37ISBN: 91-7265-811-8 (print)OAI: oai:DiVA.org:su-37DiVA: diva2:193058
Public defence
2004-02-26, Nordenskiöldsalen, Geovetenskapens hus, Svante Arrnhenius väg 8 C, Stockholm, 10:00
Opponent
Supervisors
Available from: 2004-02-05 Created: 2004-02-05Bibliographically approved
List of papers
1. Antibodies to the Plasmodium falciparum antigen Pf332 inhibit parasite growth in vitro on their own and in cooperation with monocytes
Open this publication in new window or tab >>Antibodies to the Plasmodium falciparum antigen Pf332 inhibit parasite growth in vitro on their own and in cooperation with monocytes
Article in journal (Refereed) Submitted
Identifiers
urn:nbn:se:su:diva-23589 (URN)
Note
Part of urn:nbn:se:su:diva-37Available from: 2004-02-05 Created: 2004-02-05Bibliographically approved
2. Antibody-mediated in vitro growth inhibition of field isolates of plasmodium falciparum from asymptomatic children in Burkina Faso
Open this publication in new window or tab >>Antibody-mediated in vitro growth inhibition of field isolates of plasmodium falciparum from asymptomatic children in Burkina Faso
Show others...
2003 In: American Journal of tropical medicine and hygiene, ISSN 0569-6062, Vol. 68, no 6, 728-733 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:su:diva-23590 (URN)
Note
Part of urn:nbn:se:su:diva-37Available from: 2004-02-05 Created: 2004-02-05Bibliographically approved
3. The use of impregnated curtains does not affect antibody responses against Plasmodium falciparum and complexity of infecting parasite populations in children from Burkina Faso
Open this publication in new window or tab >>The use of impregnated curtains does not affect antibody responses against Plasmodium falciparum and complexity of infecting parasite populations in children from Burkina Faso
2004 (English)In: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 90, no 3, 237-247 p.Article in journal (Refereed) Published
Abstract [en]

In Burkina Faso, where malaria is hyper-endemic and transmission intensity is very high, the majority of malaria-related morbidity and mortality occurs in children less than 5 years of age. A control measure such as the use of insecticide-treated curtains (ITC) significantly reduces transmission of malaria infection. Concerns remain whether reduced transmission intensity may lead to a delay in the development of immunity in younger children and even to a partial loss of already acquired immunity. In this study, the levels of P. falciparum-specific IgG subclasses, the number of infecting parasite clones determined by PCR-based genotyping of the msp2 gene and the parasite density were analysed in 154 asymptomatic children (3–6 years) living in 16 villages (8 with and 8 without ITC) in the vicinity of Ouagadougou, the capital of Burkina Faso. In addition, the parasite inhibitory effects of Ig fractions, prepared from selected children, in co-operation with normal human monocytes were studied. Blood samples from asymptomatic ITC-users showed a significant decrease in P. falciparum prevalence as well as in parasite density. However, no significant difference was observed in P. falciparum-specific antibodies or in parasite multiplicity of infection between the two groups. Furthermore, Ig fractions from children of both groups showed similar levels of inhibitory activity against autologous parasite growth both on their own and in co-operation with monocytes.

Place, publisher, year, edition, pages
Elsevier B.V., 2004
Keyword
Wild isolate of P. falciparum; Insecticide-treated curtains; Immunity
National Category
Immunology
Identifiers
urn:nbn:se:su:diva-23591 (URN)10.1016/j.actatropica.2003.12.004 (DOI)
Note
Part of urn:nbn:se:su:diva-37Available from: 2004-02-05 Created: 2004-02-05 Last updated: 2017-12-13Bibliographically approved
4. Analyses of antibody responses to asexual blood stages of Plasmodium falciparum in ethnic tribes living in sympatry
Open this publication in new window or tab >>Analyses of antibody responses to asexual blood stages of Plasmodium falciparum in ethnic tribes living in sympatry
Show others...
Manuscript (Other academic)
Identifiers
urn:nbn:se:su:diva-23592 (URN)
Note
Part of urn:nbn:se:su:diva-37Available from: 2004-02-05 Created: 2004-02-05 Last updated: 2010-01-13Bibliographically approved

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