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Biomedical subjects

A Tall

Publications and source records attributed to A Tall.

At least 55 records · Page 3Linked to original sources
PubMed1999

Plasmodium falciparum clinical malaria: lessons from longitudinal studies in Senegal.

Development of new antimalaria strategies and particularly vaccines, needs an in-depth understanding of the relationships between transmission, infection, immunity, morbidity and mortality. The intensive and longitudinal collection of entomological, parasitological and clinical data from the Senegalese populations of Dielmo (250-300 inhabitants), exposed to a perennial and intense transmission (about 200 infective bites/person/year) and of Ndiop (300-350 inhabitants) exposed to a seasonal transmission (about 20 infective bites/person/year), allows to respond to many questions about this subject. The acquisition of an antimalaria immunity as one gets older appears to reduce parasite density, complexity of infection, risk of new patent infection after a suppressive treatment but does not reduce the prevalence (as assessed by PCR) of infection which is commonly chronic and asymptomatic. The existence of a pyrogenic threshold effect of parasitaemia allows the individual diagnosis of malaria attacks. P. falciparum genotyping suggests that successive malaria attacks are due to distinct recently inoculated parasite populations that multiply initially without restriction, a dominant population is generally responsible of the clinical manifestations and all new populations do not trigger systematically attacks. The initial intensity of clinical manifestations does not differ perceptibly among children and adults, is not related to the duration of the attacks, does not allow the distinction between several types of attacks, is not predictive of their severity, and the clearance of parasites and manifestations is longer among youngest persons. The risk of malaria attacks is lower as one gets older and among carriers of AS haemoglobin, is higher when transmission increases and during pregnancy up to three months after delivery, and vary between children. The risk of malaria attack per infective bite is negatively related to the intensity of transmission. Because of their high sensitivity in malaria case detection, this type of small community-based studies are powerful and useful for the identification of protective immunological mechanisms as well as for testing rapidly and cheaply the clinical efficacy of any intervention such as antimalarial vaccines and drug therapy or prophylaxis. As a lot of vaccine candidates and drug combinations will be screened or tested in the perspective of the 'Roll-Back Malaria' programme, more attention must be given to longitudinal studies of this type.

Adult↗
PubMed1999

[HLA-DQ allele typing in a Senegalese population: comparative study of serology and PCR-SSP].

In this study, we compared the serological standard typing method and the DNA genotyping PCR-SSP for the characterization of HLA-DQ alleles in a senegalese population. For this purpose, 120 individuals leaving in Dielmo were typed using the microlymphocytotoxicity assay and the PCR-SSP DQ low Resolution method. A discordance of 42.5% (51/120) was found between these two methods. Thirty % (36/120) of serological typed persons failed to be typed by PCR-SSP method whereas 1% (1/120) assigned by PCR-SSP failed to be characterized by serology. Advantages and limits of these two typing methods and also the genetic background of our study population were valid arguments to comment our findings. The PCR-SSP, as suggested by several authors, is reliable, accurate and fast for HLA class II alleles characterization. Nevertheless, it needs, to become an alternative HLA typing method, available primers adapted to genetic background of study population.

Alleles↗
PubMed1999

[Antibodies specific to Plasmodium falciparum antigens in immune individuals: III. Seasonal course of the response to a major antigen of the asexual blood forms in two sites of different malaria exposure].

Specific IgG1 and IgG3 antibody responses to a major Plasmodium falciparum blood stage antigen i.e. MSP1 have been measured in plasma obtained from immune individuals living in areas with different endemicities and sampled at different periods corresponding to different levels of parasite transmission. The study shows a significant imbalance between IgG1 and IgG3 antibody responses in Dielmo vs. Ndiop, and a differential regulation of IgG1 and IgG3 responses both in subclasses and in titers (low: 1/200, and high: 1/2,000) depending upon intensity of parasite exposure.

Animals↗
PubMed1999

[Fibrodysplasia ossificans progressiva or Munchmeyer disease apropos of 2 cases].

Fibrodysplasia ossificans progressiva or myositis ossificans progessiva or still Munchmeyer disease is a genetic ailment with dominant autosomic transmission. It includes a high rate of change and doesn't appear any race. The authors gave an account of two remarks about it on a causal and late discovery upon two young black Africans. The first observation is a nine year-old-boy, without any similar family previous history and who has been hospitalized in maxillo-facial milieu for a mandible osteitis staphiloccocus. It showed some muscular ossifications of paravertebral, cervical, dorsal and lumbar nature--from a spontaneous appearance and evolving progressively since the age of three months. The radiographic results displayed some specific bones disorders which enable to retain the diagnosis above. The second observation is the case of a twenty four-year-old-woman who has previously benefitted from a surgical exploration a non-inflammatory muscular tumefication at the right arm which occurred at the age of twenty one. Three years later, she took surgery for the restriction of the oral gap and a right hand side lumbar paravertebral tumefaction which was thus restricting the mobility of the rachis. The radiological results have found some specific bone disorder++ at the hands and the feet which enable to link the paravertebral ossifications to their fibrodysplasic origin. Munchmeyer disease remains a affection of easy radio-clinical diagnosis. The essential point is to precociously think of it before the specific osseous anomalies occurring at the level of the feet and the hands. The functional or even vital prognosis remains closely linked to both the important and the topography of conjunctivo-muscular ossifications.

Adult↗
PubMed1999

[Cancers of the larynx: what therapeutic strategy to use in Senegal?].

The technical method's deficiency limits the respect of therapeutic principles of cervico-facial oncology in our practice. In a period of 16 years, 116 patients, aged of 24 to 81 years, sex male in a majority have had laryngectomy for extended cancer. In 88% of cases total laryngectomy has been realized and in 12% of cases a partial laryngectomy has been realized. In 101 patients, 87%, a neck dissection have been associated to the laryngectomy. The post operative radiotherapy have been realized in 51 patients. The immediate results are marked by the unexpected arrival of pharyngeal fistula in 34 patients. 7 cases of death have been noticed. The global survival have been 35% in 3 years and 30% in 5 years. The fatal cases have been loco-regional cases and occur during the 18 first months. The surgery option, which is our choice, must be maintained and the neck dissection more vigorous.

Adult↗
PubMed1998

In-vitro activity of pyronaridine and amodiaquine against African isolates (Senegal) of Plasmodium falciparum in comparison with standard antimalarial agents.

The in-vitro activities of pyronaridine, amodiaquine, chloroquine and quinine were evaluated against 161 isolates of Plasmodium falciparum from Senegal (Dielmo, Ndiop and Pikine), using an isotopic, micro, drug susceptibility test. The mean IC50 values (50% inhibitory concentration) for pyronaridine and amodiaquine were 3.8 nM (95% confidence interval (95% CI), 3.1-4.4) and 12.0 nM (95% CI, 10.0-14.0 nM), respectively. Pyronaridine and amodiaquine were more active than chloroquine against susceptible parasites. However, both drugs were significantly less active (P < 0.002 and P < 0.025) against chloroquine-resistant isolates than against chloroquine-susceptible isolates. Based on statistical calculation using the present data (mean IC50 + 2 S.D.), the cut-off value for in-vitro susceptibility to pyronaridine is IC50 < 15 nM; for eight isolates (5%) the IC50 was > 15 nM. No isolates tested showed resistance to amodiaquine (IC50 > 80 nM). Significant positive correlations, suggesting cross-resistance among these drugs in vitro, were found between pyronaridine and chloroquine (r2 = 0.19, P < 0.001), pyronaridine and quinine (r2 = 0.44, P < 0.001), pyronaridine and amodiaquine (r2 = 0.34, P < 0.001), amodiaquine and chloroquine (r2 = 0.14, P < 0.001), and amodiaquine and quinine (r2 = 0.21, P < 0.001). The present in-vitro findings require comparison with clinical studies.

Africa↗
PubMed1998

In vitro activity of artemether against African isolates (Senegal) of Plasmodium falciparum in comparison with standard antimalarial drugs.

The in vitro activity of artemether against 56 African isolates of Plasmodium falciparum from Senegal was evaluated using an isotope-based drug susceptibility semi-microtest. The 50% inhibitory concentration (IC50) values for artemether were in a narrow range from 0.8 to 15.2 nM (mean IC50 = 3.43 nM) and the 95% confidence interval (CI) was 2.50-4.36 nM. Artemether was equally effective on chloroquine-sensitive and chloroquine-resistant isolates (mean IC50 = 346 nM, 95% CI = 2.08-4.84 nM versus mean IC50 = 2.80 nM, 95% CI = 2.00-3.60 nM). There was a significant positive correlation between responses to artemether and mefloquine (r2 = 0.36, P < 0.001), artemether and quinine (r2 = 0.085, P < 0.05), artemether and halofantrine (r2 = 0.075, P < 0.05), quinine and mefloquine (r2 = 0.205, P < 0.01), quinine and halofantrine (r2 = 0.124, P < 0.05), and mefloquine and halofantrine (r2 = 0.801, P < 0.001). A positive correlation between these drugs suggests in vitro cross-resistance or at least in vitro cross-susceptibility.

Animals↗
PubMed1998

Re-emergence of yellow fever in Senegal in 1995.

An outbreak of yellow fever (YF) occurred in the central part of Senegal during October 1995. Thirty-one probable cases were detected and 79 cases were confirmed either by IgM ELISA or by virus isolation (30 strains isolated). The case fatality rate was 18.9%. Incidence of the infection was evaluated by a serosurvey in the area. Males 10-29 years old belonging to the Peul ethnic group were more affected. Moreover, 28 YF virus strains were isolated from mosquitoes and larvae pools and vertical transmission of YF virus by Aedes aegypti was also demonstrated for the first time in the field. This outbreak occurred after the major amplification of the wild cycle of YF virus in 1993 in West Africa. This epidemic represented a typical example of intermediate transmission of YF: both humans and wild vertebrates are involved in the virus cycle through wild mosquitoes with semidomestic habits, mainly Ae. furcifer, Ae. luteocephalus, and domestic vector Ae. aegypti. It was controlled by a prompt immunization campaign. The impact of inclusion of YF vaccine in the Expanded Program of Immunization, which has been conducted in Senegal for eight years, is discussed.

Adolescent↗
PubMed1998

No influence of age on infection complexity and allelic distribution in Plasmodium falciparum infections in Ndiop, a Senegalese village with seasonal, mesoendemic malaria.

We have shown previously that in Dielmo, a Senegalese village with intense perennial Plasmodium falciparum transmission, the infection complexity and the distribution of some allelic types harbored by asymptomatic carriers was age-dependent. We report here an investigation of these parameters in Ndiop, a village located 5 km from Dielmo, where malaria is mesoendemic and seasonal, and where immunity is acquired at a very low rate, as indicated by the lifelong distribution of P. falciparum clinical attacks. Blood was collected from 143 and 125 inhabitants, including 122 individuals sampled in both surveys, during two cross-sectional surveys at one-month intervals during the 1994 transmission season. Plasmodium falciparum parasites were genotyped for three polymorphic single copy genes. Genetic diversity was very large, with 17, 43, and nine distinct alleles detected for the merozoite surface protein-1 (MSP-1), MSP-2, and glutamate-rich protein loci, respectively. These figures, similar to those previously observed in Dielmo, indicate that the parasite genetic diversity is not directly related to the inoculation rate, at least in the range of transmission intensity studied here. The complexity of the asymptomatic infections (average number of distinct genotypes per isolate) was more than two-fold lower in Ndiop than in Dielmo and importantly, did not decrease with age. Likewise, the allele distribution was not influenced by age, contrasting with the observations made in Dielmo. This indicates that the number of parasite types per isolate and the influence of age on complexity and allele distribution depend on the level of endemicity, consistent with the interpretation that they reflect acquired anti-parasite immunity.

Adolescent↗
PubMed1998

[Ethmoid tumors. Experience of the otorhinolaryngologic clinic of the University Hospital Center of Dakar, 20 cases].

24 cases of ethmoid tumors collected between January 1st, 1990 and June 30th, 1996 were reported. The analysis of epidemiological, clinical and therapeutic aspects showed the following elements: the average age was 25 years with an equal repartition between men and women, a delay in consultation with an average of 2 years, 41.7% of patients consulted mostly for non rhinological signs, on the therapeutic aspect, surgery was performed on 95.8% of the patients with ethmoidectomy by external way. In 50% of cases, the removal was extended to one or many sinuses, 61.2% of tumors were benign to the histological analysis, one patient died immediately after operations. In the short run, we observed 2 cases of persistence of the carcinoma. In the long run, a recurrence of mucocele was noticed. Because of late consultation, limits of preoperative assessment notably for radiology, therapeutic approach is difficult, the improvement of technical infrastructures, the use of scanner in particular, should allow a better codification of the therapeutic indications.

Academic Medical Centers↗
PubMed1997

T- and B-cell responses of malaria immune individuals to synthetic peptides corresponding to non-repeat sequences in the N-terminal region of the Plasmodium falciparum antigen Pf155/RESA.

While the C-terminal repeat region of Pf155/RESA, a Plasmodium falciparum vaccine candidate has been extensively studied for B- and T-cell reactivities, little is so far known about the non-repeat region in this respect. The present study aimed at investigating the non-repeat sequence 171-227 of Pf155/RESA for T- and B-cell epitopes. Eight overlapping peptides were synthesised and assayed for their ability to stimulate peripheral blood mononuclear cells obtained from P. falciparum-immune donors to proliferate and to induce secretion of interferon-gamma (IFN-gamma) and/or interleukin 4 (IL-4) using the ELISPOT assay. The plasmas of the corresponding donors were tested for antibody reactivity with the same peptides in ELISA. The individual cellular responses to the different peptides varied and in general they were not correlated, emphasising the importance of including several parameters for T-cell activation. The most frequent T-cell responses (proliferation, IFN-gamma and/or IL-4) were seen with two partially overlapping peptides corresponding to the sequences 171-185 and 181-195 that induced responses in 71 and 62% of the donors, respectively. Although, the frequency of responders was high, the magnitude of the responses was generally low. Two overlapping peptides corresponding to the sequence 186-206 bound antibodies from a large number of plasma samples. IL-4 producing cells were frequently found in donors whose sera contained antibodies to the corresponding peptide. However, there was no absolute correlation and many donors having anti-peptide antibodies could also be induced to produce IFN-gamma. In conclusion, the non-repeat region of Pf155/RESA contains several epitopes inducing functionally distinct T-cell responses. The sequence 171-206 was found to contain both B- and T-cell epitopes recognised by almost all individuals naturally primed to malaria. Thus, this sequence should be a useful tool in future immuno-epidemiological studies and/or for inclusion into a subunit vaccine against the asexual blood stages of the P. falciparum parasite.

Adolescent↗
PubMed1997

Plasmodium falciparum- and merozoite surface protein 1-specific antibody isotype balance in immune Senegalese adults.

This study shows markedly different isotype distributions of antibodies to asexual blood stages of Plasmodium falciparum and to merozoite surface protein 1 in clinically immune Senegalese adults depending on the study site. The relationships between immunoglobulin M (IgM) and IgG and between IgG3 and IgG1 antibodies differed in settings where transmission is perennial compared to settings where it is seasonal. This suggests a role for antibody class and/or subclass production and utilization in the regulation of protective immunity to such antigens.

Adult↗
PubMed1997

Interaction of diet and genes in atherogenesis. Report of an NHLBI working group.

Recent advances in genetics and information emerging from the Human Genome Project make it feasible to examine the importance of dietary-genetic interactions in the development of atherosclerosis. In the opinion of the Working Group, three approaches are necessary to examine this concern. The first approach utilizes animal models to map and identify candidate genes involved in dietary responsiveness and atherogenesis. The second approach involves the evaluation of these genes in specific physiological processes involved in dietary responsiveness and atherogenesis. Finally, the third approach is to extend the studies performed in animal models to human populations using linkage or association studies.

Animals↗
PubMed1997

ApoA-I knockout mice: characterization of HDL metabolism in homozygotes and identification of a post-RNA mechanism of apoA-I up-regulation in heterozygotes.

The major high density lipoprotein (HDL) apolipoprotein, apoA-I, was knocked out by gene targeting in ES cells to provide a model for the study of HDL metabolism and its relationship to plasma and tissue cholesterol metabolism. HDL and non-HDL cholesterol (HDL-C) were reduced in apoA-I-deficient mice. Feeding a high fat-high cholesterol diet raised HDL-C minimally in apoA-I knockout compared to the large increase seen in control mice, suggesting an interaction between diet and apoA-I genotype. In apoA-I-deficient mice, HDL was normal in size but altered in composition. Compared to control mice there was more triglyceride and free cholesterol and less cholesteryl ester (CE), suggesting that apoA-I-deficient HDL is a poor substrate for hepatic lipase and lecithin:cholesterol acyltransferase (LCAT). The metabolic basis of the low HDL-C levels in the apoA-I knockout mice was decreased flux into the HDL CE pool. The absolute delivery of HDL CE to both peripheral tissues and liver was also decreased. As tissue cholesterol levels and synthesis were unchanged, the decreased flux of cholesterol into the HDL CE pool was most likely due to decreased efflux of cholesterol from the peripheral tissues and decreased functional LCAT activity. The low HDL-C state in the apoA-I-deficient mouse was associated with an absolute decrease in unidirectional transport of cholesterol from peripheral tissues to the liver but this did not lead to cholesterol accumulation in the periphery or a cholesterol deficit in the liver; nor was there altered peripheral tissue HMG-CoA reductase activity. The only sign of decreased cholesterol flux to the liver was a 2.3-fold decrease in liver cholesterol 7 alpha-hydroxylase mRNA, suggesting decreased bile acid synthesis. In the apoA-I knockout mouse model it appears that low HDL levels create a new steady state in which decreased cholesterol is delivered to both peripheral tissues and the liver.

Animals↗
PubMed1997

[Profile of cancers of the hypopharynx in Senegal].

A retrospective study of carcinomas of the hypopharynx was conducted to examine the epidemiological and clinical features of this cancer in Senegal. An analysis of 66 cases showed a very particular distribution in Senegal with more female (57.6%) than male cases. Average age at diagnosis was 33 years. Advanced cancer (T3-T4) was noted in 65% of the cases, but the first physical examination noted the absence of cervical nodes in 53.6% of the cases. Location at the piriform sinus was observed in 41% of the cases, followed by the posterior wall of the hypopharynx (25.7%). Chronic anemia with iron deficiency was seen in 30% of the cases, probably an important etiological factor of the cancer in Senegal. This point would be the goal of a future prospective study.

Adolescent↗
PubMed1997

[Specific antibodies against Plasmodium falciparum antigens in immune subjects: I. Comparison of detection/titration methods].

We report a comparative study of specific antibody levels to the blood stages of P. falciparum in individuals living in two different areas with different transmission levels of malaria. We have compared 2 techniques for the detection/titration of antibodies i.e. ELISA and IFI, ELISA being particularly suitable for immuno-epidemiological related studies. A schizont lysate from P. falciparum infected red blood cells from FUP/CB Marburg strain as antigen proved usefullness, as compared with an antigen extracted from a local strain recently adapted to in vitro culture. Using these techniques, high specific antibody responses were found in the villagers' sera and mean levels of antibodies increased with age. Levels of specific IgG were comparable between those two locations, in spite of a ten fold higher level of transmission between the two villages. In contrast, a significantly higher level of IgM in adults living in holoendemic.

Adolescent↗
PubMed1997

[Specific antibodies against Plasmodium falciparum antigens in immune subjects: II. Screening of responses against the merozoite major surface antigen (MSP!)].

Specific immune responses to asexual blood stages of P. falciparum antigens (a lysate of parasitized red blood cells and a characterized vaccine candidate i.e. MSP1 p19) were analyzed in plasma samples from immune adult individuals living in three different areas of Senegal, where malaria transmission is different. Most individuals in the three sites had specific IgG and IgM to total P. falciparum antigens, whereas approximately 50% had either IgG or IgM specific to MSP1 p19. Further, no anti-MSP1 p19 IgG2 and IgG4 antibody was noticed in any individual whereas the distribution of anti-MSP1 p19 IgG1 and IgG3 was different upon the epidemiological context. In addition, no relationship was found between antibody responses and in vitro T cell responses against P. falciparum antigens upon those experimental conditions. These data stress on the relatively elevated distribution of specific antibodies to MSP1 p19 in P. falciparum hyperendemic areas and suggest a differential regulation of isotypes depending on individual parasite exposure.

Adolescent↗