Biomedical subjects

Saadou Issifou

Publications and source records attributed to Saadou Issifou.

8 recordsLinked to original sources

PubMed2004

Depressed natural killer cell cytotoxicity against Plasmodium falciparum-infected erythrocytes during first pregnancies.

We measured natural killer (NK) cell cytotoxicity and cortisol and prolactin concentrations in peripheral venous blood samples obtained from pregnant Gabonese women at the time of delivery. The NK cell-mediated cytotoxicity against Plasmodium falciparum-infected erythrocytes in vitro was lower in samples obtained from primiparous women than in samples obtained from multiparous women; cortisol concentrations were significantly higher in primiparous women than in multiparous women, and prolactin concentrations were significantly lower. The highest cortisol concentrations were found in the plasma of P. falciparum-infected primiparous women. A positive correlation was found between cortisol concentration and parasite load; an inverse correlation was found between the magnitude of the NK cell cytolytic effect and cortisol production. A positive correlation was found between this effect and prolactin production. Thus, depressed NK cell cytotoxicity against P. falciparum-infected erythrocytes is correlated with high cortisol concentrations and may contribute to increased susceptibility to malaria during pregnancy.

Adult↗

PubMed2003

Complexity and genetic diversity of Plasmodium falciparum infections in young children living in urban areas of Central and West Africa.

A site-based characterization of Plasmodium falciparum infections in children living in two malaria hyperendemic urban areas from West and Central Africa was undertaken. A total of 58 and 46 children with either asymptomatic infections or uncomplicated (symptomatic) malaria were recruited in Gabon and Benin, respectively. Parasite density, hematological factors, the genetic diversity of P. falciparum merozoite surface protein 2 (msp2) and the complexity of infections (mean number of P. falciparum genotypes per infected child) were used for this characterization. Gabonese children with uncomplicated malaria presented a higher mean axillary temperature (39.2 vs 38.6, P=0.004) and a higher geometric mean parasite density (30,538 vs 18,921, P<0.001) associated with a significantly lower hemoglobin level ( P<0.01). A higher degree of msp2 polymorphism and the complexity of P. falciparum infections were also observed in children from Gabon ( P<0.05). With a similar level of malaria transmission in both urban sites, these results suggest an impact of malaria control interventions on the dynamics of concurrent P. falciparum infections.

Alleles↗

PubMed2003

Severe malaria in a splenectomised Gabonese woman.

BACKGROUND: The intact splenic function is of utmost importance for the host's defence capacity against Plasmodium spp. not only by limiting the acute infection through the removal of parasites from the blood stream, but also by modulating parasite antigen expression on the surface of infected red blood cells as well as cellular and humoral immune response. Splenectomised individuals are at high risk to develop a more severe and prolonged disease, even if they had acquired semi-immunity prior to their loss of splenic tissue. CASE REPORT: We report on a 37 year old splenectomised Gabonese woman who developed severe falciparum malaria with hyperparasitaemia, profound anaemia, and an overwhelming gametocytaemia, recovering very slowly following quinine therapy. Whereas the clinical course is not at odds with previous descriptions, the massive occurrence of mature gametocytes as documented here has not been reported before. Whether the high gametocyte count observed in our patient was primarily due to the impaired clearance of asexual forms or to the induction of gametocytogenesis remains unclear. Regarding the optimal drug regimen for treating malaria in splenectomized patients, a combination of an aminoquinoline with an artemisinin derivative might be the optimal choice.

Adult↗

PubMed2003

Short-course artesunate treatment of uncomplicated Plasmodium falciparum malaria in Gabon.

Artesunate is one of the most important antimalarial agents available, since it is effective against parasites that have developed resistance to conventional antimalarials in sub-Saharan Africa. Antimalarial combination chemotherapies with artesunate (4 mg/kg of body weight once daily for 3 days) as one partner have been proposed. However, the efficacy of a 3-day course of artesunate alone has never been evaluated in individuals in Africa (which has 90% of the worldwide malaria burden) living in regions of hyperendemicity, where a considerable degree of immunity might substantially enhance the efficacy of short courses of artesunate compared to those in regions where the levels of endemicity are low. This lack of information does not permit a systematic assessment of the value of artesunate-based combination chemotherapies in Africa. Therefore, we studied the efficacy and safety of a 3-day course of artesunate (4 mg/kg of body weight, orally, once daily) for the treatment of uncomplicated Plasmodium falciparum malaria in Gabonese patients aged 4 to 15 years (n = 50). Artesunate was well tolerated, and no severe adverse event was reported. Parasite elimination was rapid and was achieved in all patients within < or =72 h (geometric mean time to elimination, 34 h). The PCR-corrected cure rate by day 14 was 92% (46 of 50 patients), but it dropped to 72% (36 of 50 patients) by day 28. We conclude that a 3-day course of artesunate fails to achieve sufficiently high cure rates for uncomplicated falciparum malaria in Gabonese children.

Adolescent↗

PubMed2003

Antibodies to Plasmodium falciparum rifin proteins are associated with rapid parasite clearance and asymptomatic infections.

Plasmodium falciparum rifin proteins, belonging to the largest known family of variable infected-erythrocyte surface-expressed proteins encoded by rif genes, were recently shown to be capable of inducing a strong immune response in P. falciparum-infected adults living in an area in Gabon where malaria is endemic. In the present study, the levels of antirifin antibodies were analyzed in serum obtained from 60 children from the same area who were admitted to hospital and diagnosed with severe malaria. High antirifin antibody concentrations in these individuals correlated significantly with their capacity to rapidly clear their parasites from the circulation after the start of chemotherapy. A doubling of antirifin antibody concentrations reduced the clearance time by 5 h (95% confidence interval, 4.1 to 6.9 h). In the same group of children, who were followed up for 2 years, antirifin antibody levels did not correlate with a reduced rate of reinfection or with a delay in the time to the first reinfection. However, the initial antirifin antibody levels were sustained over the study period. The likelihood that these antibodies could confer a certain degree of protection against malaria is supported by our findings of statistically higher levels of antirifin antibodies to all four rifin proteins in a group of 42 asymptomatic parasitemic children.

Age Factors↗

PubMed2002

Fosmidomycin for malaria.

Safe and effective antimalarial drugs with new methods of action are urgently needed. Fosmidomycin inhibits the synthesis of isoprenoid by Plasmodium falciparum, and suppresses the growth of multidrug-resistant strains in vitro. Our aim was to assess the efficacy and tolerability of fosmidomycin in adults with malaria in Gabon. We administered the drug for 5, 4, or 3 days (1.2 g every 8 h), in nine, eight, and ten evaluable patients, respectively. All treatment regimens were well tolerated. Cure rates by day 14 were 89% (eight of nine), 88% (seven of eight), and 60% (six of ten), for treatment durations of 5, 4, and 3 days, respectively. These data suggest that fosmidomycin is a safe and effective treatment for uncomplicated malaria if given for 4 days or more.

Adult↗

PubMed2002

Plasmodium falciparum merozoite surface protein 1 (MSP1): genotyping and humoral responses to allele-specific variants.

The present study is the first to investigate Plasmodium falciparum merozoite surface protein 1 (MSP1) allele-specific humoral responses in residents of central Africa. In endemic areas, acquired immune responses to malaria are assumed to reflect the need to be infected with a large number of antigenically diverse parasite populations. In the work presented here, the relationship between antibody specificity and the infecting parasite genotype was investigated in asymptomatic subjects and patients with uncomplicated malaria in order to possibly clarify the relationship between anti-MSP1 block2 antibodies and clinical malaria. Overall isolates were typed by nested PCR using allele-specific primers of the P. falciparum MSP1 gene to identify the infecting parasite genotype. The K1 type was the predominant allelic family in both clinical groups. Polyinfection (number of isolates with more than one parasite genotype) and the complexity of infections (mean number of parasite genotype per infected subject) were higher in isolates from asymptomatic individuals. Total immunoglobulins G (IgG) responses to schizont crude extract antigens and to MSP1 variant-specific peptides were assessed by ELISA test. More than 90% of the sera reacted against schizont extract, whatever the clinical group and the K1 seroprevalence was the highest in both clinical groups. Our results showed an age-dependence in the number of different variants of MSP1 block2 recognised by serum. Indeed, isolates from older (>14 years) subjects showed lower multiplicity of infection and higher was the mean number of different MSP1 variants recognised by their serum. This corresponded to the age reported for the acquisition of anti-parasite immunity under high malaria endemicity. The contribution of variant-specific immunity in asymptomatic malaria infections is discussed.

Adolescent↗

PubMedDate not supplied

Severe malarial anemia associated with increased soluble Fas ligand (sFasL) concentrations in Gabonese children.

To investigate if severe malarial anemia is associated with specific cytokine overproduction, we evaluated serum levels of soluble Fas ligand (sFasL), tumor necrosis factor (TNF-alpha) and interleukin-10 (IL-10) from three groups of young children with Plasmodium falciparum infection (asymptomatic cases, uncomplicated malaria cases and severe malarial anemia cases), in a hyperendemic area of Gabon. In uncomplicated cases, only TNF levels were significantly (p < 0.001) increased in comparison to asymptomatic cases with P. falciparum infection. High levels of sFasL, TNF-alpha and IL-10 were associated with low hemoglobin concentrations, sFasL levels were significantly higher in children with severe malarial anemia (p < 0.001) as compared to both other groups. The parasite density was positively correlated with IL-10, TNF-alpha and sFasL levels. TNF-alpha and sFasL, but not IL-10 or parasitemia, were independent predictors of hemoglobin concentrations. These results suggest that, in malaria, a specific dysregulation of the cytokine balance may lead to complications such as severe anemia.

Acute Disease↗