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Biomedical subjects

A Tall

Publications and source records attributed to A Tall.

At least 37 records · Page 2Linked to original sources

[Differential changes in IgG1 and IgG3 against a major antigen of blood stage Plasmodium falciparum (MSP1(19)) as a function of the parasite transmission period: study among immune Senegalese adults].

This study examined the evolution of P. falciparum specific IgG1 and IgG3 antibodies "before" and "after" the highest transmission period in clinically immune Senegalese adults settle in Dielmo, a holoendemic area for P. falciparum transmission. Plasma was tested for antibodies to an antigen (Q-KNG- MSP1(19)) known to react with IgG1 and/or IgG3 in the majority of these individuals. There was a decrease in titers in individuals with low, but not high titer IgG1 whereas specific IgG3 remained unchanged following the highest transmission period. These results raise the question of the differential role of anti-MSP1(19)g-IgG1 antibody fractions in the maintenance of immunity to P. falciparum.

Adult↗

Bayesian analysis of an epidemiologic model of Plasmodium falciparum malaria infection in Ndiop, Senegal.

Plasmodium falciparum has a complex transmission cycle. Public health planning and research would benefit from the ability of a calibrated model to predict the epidemiologic characteristics of populations living in areas of malaria endemicity. This paper describes the application of Bayesian calibration to a malaria transmission model using longitudinal data gathered from 176 subjects in Ndiop, Senegal, from July 1, 1993, to July 31, 1994. The model was able to adequately predict P. falciparum parasitemia prevalence in the study population. Further insight into the dynamics of malaria in Ndiop was provided. During the dry season, the estimated fraction of nonimmune subjects goes down to 20% and then increases up to 80%. The model-predicted time-weighted average incidences contributed by nonimmune and immune individuals are 0.52 cases per day and 0.47 cases per day, respectively. The median times needed to acquire infection (conversion delay) for nonimmune and immune individuals are estimated at 39 days and 285 days, respectively.

Adolescent↗

Perspectives for vascular genomics.

Diseases of the vascular system result from a complex mixture of genetic and environmental factors. Data sets, technologies and strategies emanating from the human genome programme have been applied to the analysis of both rare single-gene and common multigenic vascular disorders. Genomic approaches including inter- and intraspecies sequence comparisons, genotyping with dense marker sets spanning the genome, large-scale mutagenesis screens of model organisms, and genome-wide expression profiling have all begun to contribute to the identification of new genes and mechanisms that are central to cardiovascular disease processes.

Animals↗

Increased susceptibility to malaria during the early postpartum period.

BACKGROUND: Pregnancy is associated with increased susceptibility to malaria. It is generally agreed that this increased risk ends with delivery, but the possible persistence of increased susceptibility during the puerperium had not been investigated. METHODS: From June 1, 1990, to December 31, 1998, we monitored exposure to malaria, parasitemia, and morbidity among the residents of a village in Senegal in which the rate of transmission of malaria was high. In this population we analyzed 71 pregnancies in 38 women from the year before conception and through one year after delivery. RESULTS: Among the 38 women, there were 58 episodes of clinical Plasmodium falciparum malaria during 61,081 person-days of observation. The incidence of malaria was 20.2 episodes per 1000 person-months during the year preceding conception and 12.0 episodes per 1000 person-months during the period from 91 to 365 days after delivery. The incidence of episodes of malaria increased significantly during the second and third trimesters of pregnancy and reached a maximum of 75.1 episodes per 1000 person-months during the first 60 days after delivery. The adjusted relative risk of an episode of malaria was 4.1 (95 percent confidence interval, 1.8 to 9.5) during the first 60 days post partum, as compared with the year preceding pregnancy. The duration of fever during the episodes of malaria was longer and the prevalence and density of asymptomatic malarial parasitemia were significantly higher during pregnancy and the early postpartum period than during the other periods. CONCLUSIONS: Among women who live in areas with high rates of transmission of malaria, the susceptibility to malaria is highest during the second and third trimesters of pregnancy and the early postpartum period.

Adolescent↗

[Laryngeal foreign bodies: management in children in Senegal].

UNLABELLED: Inhalation of foreign bodies is a frequent accident in children. It remains severe in the case of laryngeal foreign bodies. PATIENTS AND METHODS: Retrospectively, for a 16-year period, 65 laryngeal foreign bodies have been treated (44.8%), among 145 cases of airway foreign bodies, in the ENT department of Dakar University hospital. Etiological, clinical and therapeutic aspects were reviewed. RESULTS: Average age was 36 months, with a sex-ratio of 2.42 in favour of males. The time lag (time between the accident and admission to the department) was particularly long; 73.33% of the children were admitted more than 24 hours after the event. Eighty-three percent of the patients presented greater or lesser laryngeal dyspnea. Tracheostomy was performed in 55.4% of the patients. Average duration for abiation of the canula was ten days. Three cases of death were recorded (4.16%). DISCUSSION: The frequency of 44.8% for laryngeal localization of foreign bodies appears to be the highest in the literature. If the appropriate treatment for foreign bodies in the respiratory tract is endoscopic removal, the tracheostomy nevertheless occupies a central place in the management of the disease. This procedure may be recommended to all ENT specialists working in similar conditions. In spite of its inherent complications, tracheostomy allows reduction of mortality in relation to laryngeal foreign bodies. Improvement of prognosis requires prevention based on widespread public information and improving technical infrastructures.

Adolescent↗

Apoptosis modulation in mononuclear cells recovered from individuals exposed to Plasmodium falciparum infection.

In endemic areas, asymptomatic infection by the malaria parasite Plasmodium falciparum was found associated with elevated percentages of human host's mononuclear cell spontaneous in-vitro apoptosis. In Dielmo, a village where malaria is holoendemic, apoptosis was age-and parasite-dependent. In-vitro exposure of peripheral blood mononuclear cells (PBMC) to the parasite extract induced a marked increase in the mononuclear cell membrane expression of functional CD95 antigen: a 3-h exposure of the mononuclear cells to anti-CD95 antibodies led to a detectable increase in the mean percentage of apoptotic nuclei found in the cultures carried out in the presence of P. falciparum extracts compared to control cultures. IL-2, IL-4, IL-6 and IL-10 promoted the viability of PBMC in cultures while IL-1alpha or IFN-gamma had no obvious impact and TNFalpha gave conflicting results. IL-2 was the most efficient cytokine at rescuing PBMC from cell death and this effect was associated with a strong increase in T cell activation. In contrast, IL-4 and IL-10 had no such effect on T cell activation, hence they acted as survival factors and not through their mitogenic activity. Taken together, these different observations suggested that the levels of in-vitro apoptosis observed were not only associated with parasite infection, but also potentially modulated by the human host through different pathways.

Animals↗

Seasonal fluctuation of antibody levels to Plasmodium falciparum parasitized red blood cell-associated antigens in two Senegalese villages with different transmission conditions.

The recombinant R23, PfEB200, and GST-5 antigens derive from conserved antigens associated with the Plasmodium falciparum-infected erythrocyte membrane. They were identified as targets of protective antibodies in the Saimiri sciureus model. We have assessed here the humoral response to these antigens in humans. Cross-sectional surveys were conducted in two Senegalese villages with different levels of endemicity. The prevalence of specific IgG and IgM was similar and influenced by age in both localities. The anti-R23 antibodies decreased after the rainy season, particularly in the children less than ten years old. The anti-PfEB200 response did not show significant seasonal variation. The anti-GST-5 response increased in both the less-than 10-year-old and the greater-than 10-year-old groups after the rainy season in Dielmo, but only in the Ndiop villagers who were more than 10-years-old. Thus, antigen-specific seasonal variations of antibody levels were influenced differently by age in both villages. The isotype distribution was antigen-specific and differed for both seasons.

Adolescent↗

Antibiotics for prophylaxis of Plasmodium falciparum infections: in vitro activity of doxycycline against Senegalese isolates.

The in vitro activities of doxycycline, chloroquine, quinine, amodiaquine, artemether, pyrimethamine, and cycloguanil were evaluated against Plasmodium falciparum isolates from Senegal (Dielmo and Ndiop), using an isotopic, micro, drug susceptibility test. The 71-50% inhibitory concentration (IC50) values for doxycycline ranged from 0.7 to 108.0 microM and the geometric mean IC50 for the 71 isolates was 11.3 microM (95% confidence interval = 9.5-13.4 microM). The activity of doxycycline did not differ significantly (P = 0.0858) between the chloroquine-susceptible isolates and the chloroquine-resistant isolates. There was no in vitro correlation between the responses to doxycycline and those to artemether, chloroquine, quinine, amodiaquine, pyrimethamine, and cycloguanil, suggesting no in vitro cross-resistance among these drugs. Potency was increased by prolonged exposure. In 96-hr incubations, the activity of doxycycline was 4-5-fold more increased than in 48-hr incubations. The in vitro activity of doxycycline against intraerythrocytic stages of multidrug-resistant P. falciparum, its action against the preerythrocytic forms, the lack of correlation between the responses in vitro of P. falciparum to doxycycline and the other antimalarial drugs, and its original potential site of action are factors that favor its use as antimalarial drug.

Amodiaquine↗

[Partial laryngectomies at the University Hospital Center of Dakar].

Our experience on partial laryngectomies stretched on a period of 16 years. In an unfavorable medical environment, we issue our indicative criteria throughout this experience. From January 1st 1981 to December, 31st 1996, 14 patients have had a partial laryngectomy in University Hospital Center of Dakar. The average year was 56 and the sex-ratio was 1 woman out of 13 men. There were 13 carcinomas and 1 cas of acute dysplasia. 4 patients have had vertical partial laryngectomy, 5 have had a horizontal partial laryngectomy and 5 a partial laryngectomy on the upper out of the cricoid cartilage with the ganglia. After a 3 years close look, on 10 patients, we noted that 1 died, 1 disappeared, and 8 still were living. Carcinological failures consisted in 3 development by stages and 1 cas of a 2nd localisation. As for as functional results, the removal of the nozzle and the elimination of the nasogastric grohe of supply, were effective for respective average allotted time of 11 and 12 days. This laryngeal partial surgery seem scarce in our practice (12% of the patient who have had it). The improvement of results go to the choice of indications, the information the formation and the acquisition of technical stools more efficient.

Academic Medical Centers↗

[Protein-energy malnutrition in children less than five years old in a rural zone in Senegal (Khombole)].

A survey on 400 children less than five years old living in three villages of the sanitary district of Khombole has been realized from 17th to 25th April 1997 in order to evaluate the existence of malnutrition and the hazard factor linked to it. All children have been weighed and measured. The paraclinic assessment made up by a rate of haemoglobin and a parasitical test of the, motions have been realized on 275 children. The emaciation concerns 8% of the children and the statural backwardness 34.7% of them. The malnutrition is variable from one village to another. The percentage of children suffering from a severe malnutrition according to the classification of Gomez concerns 4.5%. Geophagy, intestinal parasitosis, and anaemia are closely related to chronic malnutrition. The results show the existence of a precarious nutritional situation in rural area requiring new policies of struggle against malnutrition.

Acute Disease↗

[Specific antibodies to Plasmodium falciparum antigens in immune patients: IV--Cross-sectional analysis of anti-P. falciparum Ab responses in a mesoendemic zone of transmission in Sine-Saloum region].

We report here a comparative study of specific antibody responses to blood stages of P. falciparum in 100 individuals aged from 3 to 76 years, living in the village of Ndiop (an area where parasite transmission is approximately 20 infective bites per year). We have used 2 antigen preparations: crude merozoites and infected erythrocyte ghosts (GRp). High specific antibody responses were found in the villagers' sera, with IgG levels being significantly higher than those directed to the whole P. falciparum schizont Ag preparation; the reverse was found for IgM responses. An imbalanced IgG subclass Ab response was evidenced towards cytophilic IgG1+/gG3+ responses rather than to IgG2+/lgG4+. Mean levels of antibodies increased significantly with age and a strong relationship was evidenced in individual levels of Ab responses towards all the Ag studied. Investigation of the morbidity, recorded as the number of confirmed clinical accesses, underlined a significant inverse relationship only with the levels of IgG to GRp. Taken together, these results proved usefullness of crude P. falciparum Ags for immuno-epidemiological related studies and underlined GRp as a particular target of Ab responses.

Adolescent↗

Variation of Plasmodium falciparum msp1 block 2 and msp2 allele prevalence and of infection complexity in two neighbouring Senegalese villages with different transmission conditions.

To investigate the impact of transmission on the development of immunity to malaria and on parasite diversity, longitudinal surveys have been conducted for several years in Dielmo and Ndiop, 2 neighbouring Senegalese villages with holo- and mesoendemic transmission conditions, respectively. We analysed Plasmodium falciparum msp1 block 2 and msp2 genotypes of isolates collected from 58% of the Dielmo villagers during the same week as those studied recently from Ndiop. Allele frequencies differed in both villages, indicating considerable microgeographical heterogeneity of parasite populations. The complexity of the infections, estimated using individual or combined msp1 and msp2 genotyping, in Dielmo was more than double that in Ndiop and it was age-dependent in Dielmo but not in Ndiop. Thus, this study confirmed the influence of age on the complexity of asymptomatic malaria infections in a holoendemic area. The age distribution of complexity in Dielmo substantiates the interpretation that the number of parasite types per isolate reflects acquired antiparasite immunity. This cross-sectional survey also confirms that the sickle cell trait has no impact on complexity but influences the distribution of P. falciparum genotypes.

Adolescent↗

Different Plasmodium falciparum recombinant MSP1(19) antigens differ in their capacities to stimulate in vitro peripheral blood T lymphocytes in individuals from various endemic areas.

This study reports on T-cell proliferative responses to the 19-kDa C-terminal domain of the Plasmodium falciparum merozoite surface protein (MSP1(19)). Three different recombinant proteins were used: an Escherichia coli product expressing the first EGF-like domain and Saccharomyces cerevisiae and baculovirus/insect-cell-produced proteins containing both EGF-like domains, the latter protein being produced with or without N-glycosylation. Cell donors were P. falciparum-immune adults with no recent history of clinical malaria and recruited from three Senegalese settings with different epidemiological parasite transmission. Each mononuclear-blood-cell preparation was stimulated with a range of concentrations of the three proteins. Most subjects' mononuclear cells were reactive to at least one protein, but significant differences in lymphoproliferation were seen between the settings and within individual cultures depending on the protein source and concentration. Importantly, lymphoproliferation indices correlated inversely with the intensity of P. falciparum malaria transmission. When purified T lymphocytes were cultured in the presence of MSP1(19) plus autologous monocytes, B lymphocytes or a proposed CD1+ dendritic-cell population as costimulatory cells, significant differences were observed depending on the individual's previous exposure to parasites. This study shows that the stimulation of lymphocyte proliferation in vitro with MSP1(19) depends on several factors, including epidemiological conditions and protein preparations.

Adult↗

In vitro activities of benflumetol against 158 Senegalese isolates of Plasmodium falciparum in comparison with those of standard antimalarial drugs.

The 50% inhibitory concentration (IC50s) of benflumetol (range, 12.5 to 240 nM; mean, 55.1 nM) for 158 Senegalese isolates were evaluated. Ten isolates (6%) showed decreased susceptibility to benflumetol. Benflumetol was slightly more potent against chloroquine-resistant isolates (P < 0.025). No correlation or weak correlations in the responses to benflumetol and pyrimethamine, chloroquine, amodiaquine, artemether, quinine, and pyronaridine were observed, and these correlations are insufficient to suggest cross-resistance. Benflumetol may be an important alternative drug for the treatment of chloroquine-resistant malaria.

Animals↗

Plasmodium falciparum clinical malaria in Dielmo, a holoendemic area in Senegal: no influence of acquired immunity on initial symptomatology and severity of malaria attacks.

Six hundred eighty-nine Plasmodium falciparum malaria attacks were observed during a three-year period among 226 inhabitants of the village of Dielmo, Senegal, an area of high malaria transmission. Malaria attacks were defined as clinical episodes with fever (body temperature > or = 38.0 degrees C) or reporting of fever or headache or vomiting, associated with a parasite:leukocyte ratio above an age-dependent pyrogenic threshold identified in this population. The symptom frequencies were tested against age, gender, and parasite density using a random-effect logistic regression model and the study of distinguishable clinical presentations was carried out by multi-correspondence analysis. There was little difference between the severity of symptoms during the initial course of attacks in young children and adults, and this severity was not correlated with the duration of the pathologic episode. It was not possible to distinguish objectively different malaria attack types according to the severity of clinical manifestations. In contrast, the duration of fever, symptoms, and parasite clearance were significantly longer among the youngest children than among the oldest children and adults. These findings suggest that of the two components of protective immunity, anti-parasite immunity and anti-toxic immunity, only the first would play a major role as age increases. They suggest also that the initial clinical presentation of malaria attacks is not predictive of the level of protective immunity.

Adolescent↗

Human immune responses to the highly repetitive Plasmodium falciparum antigen Pf332.

The B and T cell responses to EB200, a repetitive part of the Plasmodium falciparum antigen Pf332, were examined in malaria-exposed Senegalese adults. Most donors had high levels of antibodies to recombinant EB200 and 17 overlapping peptides spanning EB200. Taking proliferation and/or cytokine (interferon-gamma and interleukin-4) production as a measure of T cell activation, eight of the EB200-derived peptides induced responses in > 40% of the donors tested. There was no general association between the different types of T cell responses measured, emphasizing the importance of including multiple parameters when analyzing T cell responses and suggesting that EB200 induces functionally distinct T cell responses. The most efficient peptide for induction of proliferative responses was one previously shown to induce T cell responses in five different H-2 congenic mouse strains primed with EB200, suggesting that this is a universal T cell epitope. The presence of multiple B and T cell epitopes in EB200, widely recognized by humans, is important since EB200 has been shown to elicit protective antibody responses in monkeys and may be considered for inclusion in malaria subunit vaccines.

Adolescent↗

ApoA-II maintains HDL levels in part by inhibition of hepatic lipase. Studies In apoA-II and hepatic lipase double knockout mice.

High density lipoprotein (HDL) cholesterol levels are inversely related to the risk of developing coronary heart disease. Apolipoprotein (apo) A-II is the second most abundant HDL apolipoprotein and apoA-II knockout mice show a 70% reduction in HDL cholesterol levels. There is also evidence, using human apoA-II transgenic mice, that apoA-II can prevent hepatic lipase-mediated HDL triglyceride hydrolysis and reduction in HDL size. These observations suggest the hypothesis that apoA-II maintains HDL levels, at least in part, by inhibiting hepatic lipase. To evaluate this, apoA-II knockout mice were crossbred with hepatic lipase knockout mice. Compared to apoA-II-deficient mice, in double knockout mice there were increased HDL cholesterol levels (57% in males and 60% in females), increased HDL size, and decreased HDL cholesteryl ester fractional catabolic rate. In vitro incubation studies of plasma from apoA-II knockout mice, which contains largely apoA-I HDL particles, showed active lipolysis of HDL triglyceride, whereas similar studies of plasma from apoA-I knockout mice, which contains largely apoA-II particles, did not. In summary, these results strongly suggest that apoA-II is a physiological inhibitor of hepatic lipase and that this is at least part of the mechanism whereby apoA-II maintains HDL cholesterol levels.

Animals↗