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T Fandeur

Publications and source records attributed to T Fandeur.

43 records · Page 3Linked to original sources

Extensive genetic diversity of Plasmodium falciparum isolates collected from patients with severe malaria in Dakar, Senegal.

While some genetic host factors are known to protect against severe Plasmodium falciparum malaria, little is known about parasite virulence factors. We have compared the genetic characteristics of P. falciparum isolates collected from 56 severe malaria patients and from 30 mild malaria patients recruited in Hôpital Principal, Dakar, Senegal. All isolates were typed using polymerase chain reaction amplification of polymorphic genetic loci (MSP-1, MSP-2, HRP1, GLURP, CSP, RESA, and the multigene family Pf60). The complexity of infections was lower in severe than in mild malaria and the parasite genetic diversity in both groups was very large. No specific genetic make-up was associated with severity; there were, however, marked differences in allele frequencies in both groups, with a prevalence up to 60% of MSP-2 alleles specifically observed in the severe malaria isolates. In addition, the presence of MSP-1/RO33 alleles was significantly associated with a higher plasma level of tumour necrosis factor alpha receptor 1 (P < 0.05), a reported indicator of severity in human malaria. These results point to potential differences in the genetic characteristics of parasites inducing severe versus mild pathology.

Adolescent↗

Opsonic activity of ascitic fluids from Plasmodium falciparum-infected Saimiri monkey: positive correlation with protection in passive transfer assay.

An investigation into the protective activity of ascitic fluids from Saimiri monkeys infected with Plasmodium falciparum and the role played by opsonins in that activity was undertaken. P. falciparum-parasitized blood was collected from splenectomized Saimiri (when parasitaemia reached at least 20% or more) and used in an in vitro phagocytic assay including ascitic fluid and cultures of peripheral blood monocytes from normal Saimiri. Under the conditions of this in vitro assay, we found that ascitic fluid phagocytosis-promoting factors were opsonic rather than cytophilic. The opsonic activity was highly specific for parasitized red blood cells and was effective against all stages of development of the parasite. A highly positive relationship between in vitro opsonizing activity and in vivo protective capacity of immune ascitic fluid was found.

Animals↗

Characterization by anti-Ig monoclonal antibodies of protective and non-protective antibodies against asexual forms of Plasmodium falciparum in the Saimiri monkey.

Four monoclonal antibodies (mAb) which recognize distinct epitopes on Saimiri immunoglobulins were successfully used to characterize the protective and non-protective antibodies developed by this experimental host in response to infection by the human malaria parasite Plasmodium falciparum. Two of these mAb, 3F11/G10 and 3E4/H8, were IgG-specific and directed against conformationally conserved epitopes on the intact molecule. mAb 3A2/G6 and 4G3/B5 were specific for epitopes on two distinct L chain types of all Ig. Radioimmunoassay and immunoblots indicated that L-chains defined by 3A2/G6 were present in IgG molecules of type 3F11/G10, while L chains defined by 4G3/B5 were associated with IgG of type 3E4/H8. The use of these four mAb as immunoadsorbents allowed the purification of two IgG and two Ig populations. When assayed in vivo by passive transfer experiments in recipient monkeys previously infected by P. falciparum, protection could be associated with the IgG or Ig populations of type 3F11/G10-3A2/G6. In contrast, recipient animals which received the IgG type 3E4/H8 or Ig type 4G3/B5 presented rapidly evolving parasitemia similar to that in animals which received non-immune IgG or protective immune sera depleted of the above Ig or IgG fractions. The identification of protective and non-protective Ig populations will help in the evaluation of vaccine candidates against P. falciparum.

Animals↗

Study of some parameters affecting the in vitro cultivation of Plasmodium falciparum within Saïmiri sciureus red blood cells.

The in vitro growth and multiplication of the erythrocytic stages of Plasmodium falciparum within Saïmiri sciureus (squirrel monkey) red blood cells have been studied. Various parameters, such as the origin of the red blood cells and serum supplement, nature of the buffer, influence of the final pH of the medium, role of proteose peptone and glucose addition, were investigated. The selection of the best culture conditions led to the obtention of a reproducible in vitro growth of two parasite cycles in Saïmiri erythrocytes, which is an useful achievement for in vitro studies. Our failure to establish a continuous culture line for longer than 19 days, could be explained by a dramatic increasing of osmotic fragility of the Saïmiri red blood cells related to their small size.

Animals↗

Immunogenicity of Plasmodium falciparum antigenic determinants produced by Escherichia coli recombinant clones.

The immunogenicity of two parasite antigens produced by Escherichia coli as proteins fused to beta-galactosidase was investigated in three animal species: mice, rabbits and squirrel monkeys. 2L protein carries 71 amino acids of a parasite antigen and 11.1 protein carries 23 repeats of a 9-amino-acid repetitive unit. The humoral response was studied using indirect immunofluorescence and immunoprecipitation. The results indicate that immunization of mice, rabbits and squirrel monkeys using SDS-denatured 2L fusion protein induced antibodies able to bind to parasite antigen 2L in the IFA or in the immunoprecipitation assays. Immunization using the native fusion protein did not induce antibodies able to immunoprecipitate the 2L parasite antigen. The same observation was made for the animals immunized with 11.1 recombinant protein. In this case, the antibody response was also measured by ELISA using synthetic dimers of the repeat as antigen. In mice and rabbits, high titres of anti-11.1 antibodies were found by ELISA. However, when the antigen produced by the parasite itself was used to evaluate the response, low titres were found. This indicates that the animals produced high levels of antibodies to a structure which is not exposed in the parasite. In squirrel monkeys, the same observation was made, but the overall levels of the response to 11.1 antigen were considerably lower than those observed in mice or rabbits.

Animals↗

Kinetics of the humoral immune response to blood-induced falciparum malaria in the squirrel monkey Saimiri sciureus.

Twenty squirrel monkeys were inoculated with the Palo Alto (FUP) strain of Plasmodium falciparum and treated with quinine one or two weeks after inoculation. Antibody production, measured by the IFA technique, closely followed the appearance of parasites in the blood, rose to a maximum in about two to three weeks, stayed at this level for one to two months and then declined progressively. IgM antibodies appeared faster than any other class of antibody and at two weeks of infection represented 50-80% of total malarial antibodies. IgM antibodies also declined more rapidly and reached barely detectable levels within two to three months. IgG antibodies rose slowly to a maximal level which was, however, maintained for a longer period. No significant differences were observed between intact and splenectomized monkeys. Challenge with virulent parasites two months after the initial infection showed that both groups of monkeys, particularly the intact ones, had acquired a strong protective immunity. The secondary IgG response was stronger when the challenge was performed more than two months after the primo-inoculation.

Animals↗