Search PubMed⌕ Search

Biomedical subjects

C Rogier

Publications and source records attributed to C Rogier.

At least 91 records · Page 5Linked to original sources

High prevalence of natural antibodies against Plasmodium falciparum 83-kilodalton apical membrane antigen (PF83/AMA-1) as detected by capture-enzyme-linked immunosorbent assay using full-length baculovirus recombinant PF83/AMA-1.

The 83-kilodalton (kD) apical membrane antigen of Plasmodium falciparum (PF83/AMA-1) is a potential asexual blood stage vaccine component. This antigen has been expressed as a full-length, nonfusion, recombinant baculovirus protein (PF83-7G8-1) using the authentic predicted signal peptide for appropriate postsynthetic routing. When purified by a novel high-performance, ion exchange chromatography (HPIEC) method, PF83-7G8-1 induced polyclonal antibodies in rats that immunoprecipitated both 83- and 66-kD forms of PF83/AMA-1 from 35S-methionine metabolically labeled parasite extracts. Using HPIEC-purified PF83-7G8-1 in combination with a rat monoclonal antibody against the highly conserved carboxy-terminal (CT) region of PF83/AMA-1, we developed a CT-capture-enzyme-linked immunosorbent assay to measure naturally acquired responses against the entire PF83/AMA-1 molecule. Analysis of populations from villages in Guinea-Bissau and in an area of high malarial transmission in Senegal demonstrated a very high prevalence (94-100%) of naturally acquired serum IgG responses to PF83/AMA-1. Analysis of these natural responses showed that PF83/AMA-1 may be a well-recognized asexual parasite antigen. A statistically significant age-related change in antibody levels to PF83/AMA-1 was observed in Guinea-Bissau. No such correlation was observed in the Senegalese population, although an age-related antibody response was seen for total parasite antigen. No significant correlation was observed between PF83/AMA-1 responses and the parameters of parasite load and malaria-related fever.

Adolescent↗

Immune response in mouse and malaria-exposed humans to peptides derived from Pf11-1, a highly repetitive megadalton protein of Plasmodium falciparum.

We have investigated the immune response against the Plasmodium falciparum gametocyte-specific antigen Pf11-1. This megadalton parasite molecule has been implicated in the process of erythrocyte rupture during gametogenesis. The molecule is composed in great part of degenerated nonapeptide motifs which are tandemly repeated several hundred times. A computer algorithm searching for T sites predicted that the entire repeat region of the Pf11-1 represents potential T cell antigenic major histocompatibility complex class II-binding sites. To test this hypothesis, synthetic peptides corresponding to two nonamer subtype repeats, differing only at two amino acid positions, were used to immunize congenic mouse strains. Both peptides were shown to contain both B and T cell epitopes. The immune response is restricted to the H-2d and H-2k haplotypes. The T cell response against the peptides appeared to be highly specific, clearly discriminating between the two similar nonamer repeat sequences, whereas the humoral response produced cross-reacting antibodies. We also investigated the humoral and T cell reactivities of P. falciparum-primed individuals in West Africa against the synthetic Pf11-1 peptides. Among 51 individuals 35 had antibodies to at least one of the two peptides and a majority of them (28) had antibodies reacting with both peptides. The cellular response was analyzed by [3H]thymidine incorporation or interferon-gamma release. There was considerable variation in the response to the two peptides. Among the human samples 36% responded to one repeat subtype, while only 13% responded to the second subtype. Interestingly, in individual donors the T cell response to both peptides are associated, suggesting that, as shown for mice, the response is restricted by a genetic element. The data obtained on the two subtypes of the nonamer repeat region suggest that the entire Pf11-1 molecule might induce an unusually heterogenous B and T cell response during natural infection in man.

Adolescent↗

Lymphocyte response in vitro to Plasmodium falciparum merozoite antigens in donors from a holoendemic area.

Crude merozoite antigens from Plasmodium falciparum were used to evaluate the proliferative response of peripheral mononuclear cells (PBMCs) from 114 inhabitants of the village of Dielmo (Senegal, West Africa) exposed continuously to malaria transmission. The high or low responses to merozoite antigens obtained in lymphocyte stimulation assays were correlated with the presence or absence of parasites, IFN-gamma production and HLA phenotype. The high responders produced high levels of IFN-gamma, in contrast to the low responders, most of whom did not secrete IFN-gamma (23/27). Among others, the two HLA phenotypes HLA-B51 and HLA-DR1 were significantly associated with a high response (P < 0.05).

Adolescent↗

Malaria morbidity among children exposed to low seasonal transmission in Dakar, Senegal and its implications for malaria control in tropical Africa.

To measure morbidity due to malaria and to study its relationship with transmission and parasitemia in children living in an area of low malaria endemicity, a cohort study of 343 schoolchildren was undertaken during a one-year period in Dakar, Senegal. From parallel investigations on transmission and the frequency of malaria as a cause for outpatient visits, three different seasons were chosen for close monitoring of different clinical parasitologic, and sero-immunologic parameters. The daily incidence rates of malaria parasitemia and primary attacks were at a maximum level during the high transmission season (0.00198 and 0.00185 new cases/person/day, respectively) and decreased considerably during the season of low transmission. For each given period, the values of these two rates were close to each other, suggesting that each new infection was followed by a clinical attack. During the period of maximum transmission, clinical malaria prevalence was 1.36% and malaria was responsible for 36% of school absences due to medical reasons. At the end of the period of minimum transmission, clinical malaria prevalence was 0.15% and malaria was responsible for 3% of school absences due to medical reasons. In contrast, parasite prevalence hardly varied with the season (minimum 3.6%, maximum 7.5%). In a one-year period, the total number of new malarial infections was estimated between 173 and 230. Because of the existence of a vector density gradient in the area concerned, the annual malaria incidence varied considerably according to the children's place of residence.(ABSTRACT TRUNCATED AT 250 WORDS)

Absenteeism↗

[Analysis of the antibody response to merozoite antigens in a malaria holoendemic area].

In the aim to determine the possible role of HLA-antigens in malaria infection, sera from 50 HLA-typed donors from Dielmo (Senegal) were tested in immunoblotting (using crude merozoites as antigen) and immunoprecipitation (using detergent-extracts from surface-iodinated merozoite as antigen). The donors were previously tested on lymphocyte proliferation in vitro and gamma-interferon production and grouped into two classes: high responders and low responders. In immunoblotting and immunoprecipitation experiments, no specific differences were found in the antibody reactivity with native merozoite antigen in individuals with high (HR) or low (LR) in vitro proliferative T cell responses. In other words, both groups of responders, high and low, showed antibodies in their sera against a wide range of different parasite antigens; although between individual donors striking differences were found. Individual donors had developed different levels of antibodies, or no antibodies at all, against individual natural antigens. These differences, however, could not be correlated with HR or LR. The band patterns obtained were compared with HLA-antigens of donors phenotypes. Results showed that there was no correlation found between the different merozoite antigens recognized by sera of the different donors or groups of donors (HR and LR) and the donors' HLA-phenotypes. The fact that donors with HLA-B51 all recognized (MSP1(42) and donors with DR1 recognized MSP1(19), was not a convincing correlation.

Animals↗

[Bacterial, viral and parasitic etiologies of acute infantile diarrhea in a rural Senegal].

We have studied the incidence of parasites, viruses and bacteria associated with acute infantile diarrhea in rural Senegal. Among parasitoses, Cryptosporidium parvum (7.7%) is the most frequent, followed by Entamoeba histolytica (5.1%). The first bacteriological etiologic agent is Escherichia coli (20.9%). Rotavirus are also frequently isolated (14.7%). Prevalence of pathogens is higher: among children over 6 months and under two years old, among children either with mixed feeding or weaned, during the raining season, except for rotaviruses. Breast feeding seems to be a good protective factor against bacterial and parasitological infections but not against rotavirus contaminations.

Acute Disease↗

Lymphocyte response in vitro to Plasmodium falciparum merozoite antigens in donors from a holoendemic area.

Crude merozoite antigens from P. falciparum were used to analyse the proliferative response of peripheral blood mononuclear cells from 114 inhabitants of the village of Dielmo (Senegal, West Africa), who are exposed continuously to malaria transmission. The high or low responses to merozoite antigens obtained in lymphocyte stimulation assays were correlated to the presence or absence of parasites, to the IFN-gamma production and to the HLA-phenotype. High responders produced high levels of IFN-gamma while low responders did not secrete IFN-gamma (23/27). The two HLA phenotypes HLA-B51 and HLA-DR1 were significantly associated with high response (p < 0.05).

Adolescent↗

Antibodies and reactive T cells against the malaria heat-shock protein Pf72/Hsp70-1 and derived peptides in individuals continuously exposed to Plasmodium falciparum.

Pf72/Hsp70-1, a heat-shock protein of m.w. 72 kDa from Plasmodium falciparum is one of the Ag of interest to be included in a polyvalent vaccine against malaria. It is one of the major immunogens present in a fraction of purified blood stage parasites that elicited protection against experimental infection of Saimiri monkeys with blood stages of P. falciparum. It is present at all blood stages and one of its B cell epitopes is also detected on the surface of the infected hepatocyte. Moreover, Pf72 appears to be well conserved among different isolates of P. falciparum. We have examined the immune response against Pf72/Hsp70-1 in individuals from different age groups living in a holoendemic area (West Africa). The immune response against the native Ag (purified from schizonts and called Pf/Hsp70) was analyzed both at the humoral level by ELISA and at the cellular level by assessing in vitro proliferation and IFN-gamma production of PBMC. Of the individuals studied 52% had a statistically significant level of anti-Pf/Hsp70 antibodies as compared with unexposed individuals. These positive individuals showed a heterogeneous distribution because significant levels of antibodies were found in 70% of the adults but in only 26% of the children. The presence of Pf/Hsp70-specific reactive T cells in the blood was detected in 32% of the individuals. The total anti-Pf/Hsp70 antibody level (IgG+IgM) appeared strongly age related and correlated positively with parasite exposure, whereas the T cell response failed to correlate either with the antibody level or with age. Moreover, PBMC of donors responded to the Pf/Hsp70 in a dissociated way, namely, by either T cell proliferation or IFN-gamma production. Ten synthetic peptides based on sequences found in the C-terminal part of Pf72/Hsp70-1 were further tested as potential T cell epitopes. The proliferative response of PBMC from individuals continuously exposed to the parasite showed that three peptides more frequently trigger significant T cell proliferation (in 21% to 27% of the individuals) and three others less frequently (10%). None of these peptides allowed detection of reactive T cells in PBMC of Europeans with no previous exposure to malaria. Some of the stimulating peptides are highly similar to human heat-shock Hsc and Hsp70 with large stretches of identical amino acids.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

[In vitro T cell response to merozoite antigens in the area of continuous malaria transmission].

T CELL response in vitro to merozoite extracts of P falciparum was tested in holoendémic area (Dielmo, Region of Fatick). 58 individuals (29 adults and 29 children) were sampled. Mononuclear cells from peripheral blood were cultured with the presence of merozoites antigens during 7 days. Cells were pulsed at day 6 and 3H-thymidine incorporation was measured 16h later. T Cell response high or low was evaluated by Stimulation Index (SI). This is defined as mean cpm expérimental cells/mean cpm control cells. Two groups of Responders have been identified: High Résponders: SI > or = 5 48% of subjects Low Responders: SI < 5 52% of subjects. A microparasitaemia have been found in 19 donnors without illness. 14 of these are Low Responders (89%). It was found that SI increased with the number year of exposure.

Adolescent↗

[Platelet antibody activity in malaria thrombocytopenia].

To assess immune responses to malaria-induced thrombocytopenia, an haematologic and immunologic study was performed on 25 patients with imported malaria upon admission and 8 days after treatment. Thrombocytopenia (150 x 10(9)/litre) was detected in 19 cases (P. falciparum: 11 cases, P. ovale: 6 cases, P. vivax: 2 cases). No laboratory evidence of disseminated intravascular coagulation impairment was found in any of the patients. Bone marrow examination performed in 9 cases showed no abnormality in the megakaryocyte series. Platelet count was independent of circulating parasite levels (r = 0.27) and inversely related to the number of antibody binding sites (ABS) on platelets (r = -0.6, p. less than 0.01). The indirect Coombs test (r = -0.54; p less than 0.01) and IgG and IgE levels (p less than 0.02) gave similar findings. A statistical correlation was observed between the level of circulating immune complex and the number of ABS (r = 0.525, p less than 0.01). Thus malaria-induced thrombocytopenia seems to mainly involve IgG type antiplatelet antibody activity. Although they may be implicated in the binding of antibodies to platelets, circulating immune complexes do not appear to mediate thrombocytopenia.

Adolescent↗

[What role do smoking and air conditioning play in the occurrence of otorhinolaryngological and upper respiratory symptoms in the personnel of a hospital center?].

A cross-sectional study of the risk factors of upper respiratory symptoms has been carried out in September 1987 among the 220 employees of the Dax General Hospital. The study was not able to prove that air conditioning contributed to the occurrence of this symptomatology, but showed that smoking was associated with the disease. Prevalence of symptoms was 34% among the employees who were smokers (32% of the personnel) and only 19% among the non-smokers (p less than 0.025). In the context of the national campaign against smoking, reducing the tobacco consumption at work in buildings with air conditioning systems is likely to decrease substantially the frequency of building sickness among the personnel. This recommendation seems particularly relevant to hospital settings.

Adult↗

A French double-blind crossover study (danazol versus placebo) in the treatment of severe fibrocystic breast disease.

The Authors report their experience in a double-blind, crossover study (danazol versus placebo) in 38 patients suffering from severe benign mastopathy. The results were evaluated with regard to clinical data (mastodynia, breast nodularity) and data from comparative infrared thermography. Danazol was given in a dose of 400 mg/day for 3 months. Placebo, in identical packing, was also given for a three month period. In 32 cases out of 38, there was an improvement with Danazol treatment. For some patients, thermography was more precise than clinical part. Side effects consisted predominantly of menstrual disorders recorded in 30 cases and a generally moderate weight gain in 23 cases. In the light of these results it appears that danazol constitutes a powerful agent in the treatment of severe benign mastopathy of the breast. The best dosage and best duration of treatment remain to be specified. Finally, the original contribution of the thermographic document deserves to be underlined.

Adult↗

Malaria attacks in children exposed to high transmission: who is protected?

In persons naturally exposed to high transmission, how significant, in terms of immune protection, is the occurrence or non-occurrence of a malaria attack during a given observation period? This question was studied in a West African village where Plasmodium falciparum malaria is holoendemic with intense and perennial transmission. A cohort of 94 children aged 4 months-14 years from Dielmo village, Sénégal, was studied over 4 months, June-September 1990. 41 children had no malaria attack and 53 children suffered between one and 6 attacks. The average number of attacks was 1.80, 2.25, 1.87, 0.29 and 0.07, respectively, in children aged 4-11 months, 1-2, 3-6, 7-10 and 11-14 years. The transmission level was 75 infective bites per person. Analysis of the distribution of the number of attacks in individual children suggested that all children within the same age group had either the same, or a very similar, level of protection. This suggests that the acquisition of clinical protection in areas where malaria is highly endemic involves a progressive and homogeneous decrease of the probability of having a malaria attack (attacks occur less frequently as age increases, in all children), rather than the acquisition of complete protection by an increasing number of children. The differences between the number of clinical attacks observed in young children and their presumed exposure suggest that protective mechanisms become effective from the first reinfection onwards, and are independent of the cumulative exposure to a great variety of antigens.

Adolescent↗

A comparative study of three methods of detection of Borrelia crocidurae in wild rodents in Senegal.

In a rural area in Sénégal with a high incidence of tick-borne relapsing fever in humans, Borrelia crocidurae was studied in the blood and brain of wild rodents (Mastomys erythroleucus, Arvicanthis niloticus and Rattus rattus) using 3 methods: (i) direct examination of thick blood films; (ii) intraperitoneal inoculation of blood into white mice; (iii) intraperitoneal inoculation of homogenized cerebral tissue into white mice. Of the 82 rodents examined, the proportion of infected animals was respectively 2.4%, 7.3% and 14.6% for each method, and 18.3% for all 3 methods combined. Of the 12 animals with infected cerebral tissue, only 3 were found to have infected blood. These results suggest that isolated infections of the brain occur frequently in Senegalese wild rodents. Measurement of the real prevalence of B. crocidurae should therefore take into account these infections in addition to blood infections.

Animals↗