Biomedical subjects

S Mboup

Publications and source records attributed to S Mboup.

At least 19 recordsLinked to original sources

PubMed2006

Defining the origin of Plasmodium falciparum resistant dhfr isolates in Senegal.

We previously reported a high baseline prevalence of mutations in the dhfr and dhps genes of Plasmodium falciparum throughout Senegal. The highest prevalence of the triple dhfr pyrimethamine associated mutations were found in isolates obtained in the western part of the country near the capital city of Dakar. In this study, we sought out to determine the relatedness of dhfr wild type and mutated strains by analyzing three microsatellite regions upstream of the dhfr locus. Twenty-six of the 31 wild type strains had a unique microsatellite pattern. In contrast, of the 17 isolates containing the triple mutation in dhfr, 11 had an identical microsatellite pattern. Diverse geographical isolates in Senegal containing the triple dhfr mutation have arisen from a limited number of ancestral strains. In addition, we demonstrate that these isolates have shared ancestry with the previously reported triple mutation haplotype found in Tanzania, South Africa, and southeast Asia. This common ancestry may have implications for the malaria control strategy for reducing the spread of sulfadoxine-pyrimethamine resistance in Senegal and elsewhere in Africa.

Animals↗

PubMed2006

[Prevalence of the HIV infection and five other sexually-transmitted infections among sex workers in Niamey, Niger].

We performed a systematic screening of HIV infection and five other sexually transmitted infections on a consecutive sample of 529 female sex workers from Niamey. HIV seroprevalence rate was 30.1%, with HIV-1 profile in 93.1% of the cases. For curable STI, 4.7% of women had treponematosis, 7% gonorrhoea, 16.8% Gardnerella vaginalis, 36.9% Mycoplasma hominis and 68.2% Chlamydia trachomatis infection. The percentage of women with at least one STI was significantly higher in HIV positive's: 95.6% against 87.9%. Only 7.9% of women were free of any infection.

Adolescent↗

PubMed2005

Mutations in Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase genes in Senegal.

Senegal recently (2004) switched to sulfadoxine-pyrimethamine (SP) with amodiaquine as first line therapy for malaria in response to increasing chloroquine resistance. In anticipation of emerging resistance to SP as a result of this change in drug pressure, we set out to define the baseline prevalence of SP-associated mutations in the dhfr and dhps genes in Plasmodium falciparum using geographically diverse and longitudinally collected samples. A total of 153 blood samples were analysed from patients (5 years or older) with mild malaria after informed consent was obtained. Longitudinal samples were collected between 2000 and 2003 in Pikine, a suburb of Dakar. Geographically diverse site sampling was carried out in 2003. The mutation prevalence in DHFR codons 51, 59 and 108 is 65%, 61% and 78% in Pikine, 2003. The overall prevalence of the triple mutation that is associated with high-level pyrimethamine resistance is 61%. The mutation prevalence rate in DHPS codons 436 and 437 is 21% and 40%, respectively. There is significant geographic variation in genotypic resistance, as samples from Pikine in 2003 had higher mutation prevalence in the pfdhfr and pfdhps genes compared to samples from Tambacounda (P < 0.015). In summary, this study demonstrates a high background prevalence of SP resistance mutations already present in P. falciparum in Senegal.

Animals↗

PubMed2005

[In vitro evaluation of the sensitivity of Plasmodium falciparum to chloroquine using the deli-microtest in region of Dakar, Senegal].

This study was carried out between 2000 and 2001 in the peri-urban Pikine area located 15 km from Dakar, Senegal. The purpose was to evaluate the in vitro sensitivity of Plasmodium falciparum isolates to chloroquine, which was the recommended first-line drug for uncomplicated malaria treatment in Senegal. Testing was carried out using the double-site enzyme-linked lactate dehydrogenase imnunosorbent (DELI) microtest. The DELI-microtest is an ELISA method using 2 monoclonal antibodies against 2 antigenic sites of the specific P. falciparum lactate dehydrogenase (LDH) enzyme. The level of LDH is proportional to the extent of parasite growth. P. falciparum isolates were cultured in 96-well plates in RPMI 1640 medium supplemented with hypoxanthine and albumax, in the presence of chloroquine sulphate concentrations ranging from 5.6 nM/L to 2870.8 nM/L. Plates were incubated in a candle-jar for 48 hours at 37 degrees C and frozen at -20 degrees C. The DELI-microtest was performed using the supernatant of hemolysed cultures. The amount of pLDH released was evaluated based on optical density. The chloroquine sensitivity of the isolate was estimated based on IC50 with a cut-off of <100 nM/L. Geometric mean IC50 values were 41 nM/L (range: 4.8 nM/L to 1435 nM/L) and 135 nM/L (range: 8.63 nM/L to 2153 nM/L) in 2000 and 2001 respectively. This study demonstrated a dramatic increase in the in vitro resistance of P. falciparum to chloroquine from 30% in 2000 to 59.6% in 2001. These findings suggest that regular surveillance of in vitro drug resistance is important to predict in vivo drug resistance and allow timely changes in public health recommendations.

Animals↗

PubMed2004

Monitoring of didanosine and stavudine intracellular trisphosphorylated anabolite concentrations in HIV-infected patients.

OBJECTIVE: To determine the concentrations of intracellular active anabolites of stavudine (d4T) and didanosine (DDI) and their interpatient variability in HIV-infected patients and to explore relationships between plasma and intracellular forms. METHODS: This pilot study included 28 antiretroviral-naive HIV-infected patients who received d4T (40/30 mg twice daily), ddI (400/250 mg daily) and efavirenz (600 mg daily). After 6 months of therapy, 7 ml of blood was collected between 0.5 and 16.2 h and 2.5 and 28.5 h after the last dose of d4T and ddI, respectively. Plasma samples were obtained for the determination of d4T and ddI concentrations. Peripheral blood mononuclear cells were prepared for measuring intracellular d4T and ddI triphosphates (d4T-TP and ddA-TP, respectively). RESULTS: d4T-TP and ddA-TP concentrations were above the limit of quantification in 25 of 26 compliant patients: median d4T-TP was 31 fmol/10(6) cells (range, 0-99) and median ddA-TP was 8 fmol/10(6) cells (range, 0-23). The half-life of d4T-TP was calculated as 7 h. Interpatient variability in d4T-TP and ddA-TP concentrations was 48% and 58%, respectively. A significant relationship was observed between plasma d4T and intracellular d4T-TP. No relation was found between ddI and ddA-TP. A linear relation was observed between the intracellular concentrations of d4T-TP and ddA-TP. CONCLUSION: This is the first time that data have been obtained on intracellular concentrations of d4T-TP and ddA-TP, their intracellular pharmacokinetics and interpatient variability. Other similar studies with more patients are needed to enhance knowledge of the intracellular pharmacology of the nucleoside reverse transcriptase inhibitors.

Anti-HIV Agents↗

PubMed2004

CCR5 receptor expression is down-regulated in HIV type 2 infection: implication for viral control and protection.

HIV-2 is known to display an attenuated phenotype in vivo with prolonged time to disease and decreased rate of transmission. Observational studies in Senegal have demonstrated protection from HIV-1 infection, although the putative mechanism for immunoprotection remains undefined. We evaluated HIV-2-seropositive women from a cohort of commercial sex workers in Dakar, Senegal and identified individuals with very low surface CCR5 receptor expression on CD4+ T cells. In vitro up-regulation of the CCR5 receptor was readily achieved. Down-regulation of the CCR5 was not correlated with activation markers (HLA-DR), beta-chemokine levels, or plasma viral loads. A correlation was observed with HIV-2-specific CD8+ T cell activity as measured by intracellular cytokine production. We postulate that down-regulation of the CCR5 receptor in HIV-2 infection contributes to slower disease course and to the protective mechanism against HIV-1 superinfection, mediated in part by HIV-2-specific cellular immune responses.

CD4-Positive T-Lymphocytes↗

PubMed2003

Prevalence of Plasmodium falciparum pfcrt polymorphisms and in vitro chloroquine sensitivity in Senegal.

Mutations in pfcrt K76T are associated with chloroquine resistance in Plasmodium falciparum. Previous studies of K76T mutations in Senegal reported the association of T76 with in vitro-resistant isolates, but this mutation was also prevalent in chloroquine-sensitive isolates. This suggests involvement of additional genetic loci in modulating chloroquine resistance. Additional pfcrt polymorphisms at codons A220S, Q271E, N326S and R371I have been found in chloroquine-resistant isolates. We wanted to test if sequential acquisition of mutations at these codons leads to in vitro chloroquine resistance. Stepwise accumulation of mutations was not detected, rather there was almost complete linkage between the pfcrt K76T mutation and polymorphisms in these codons. Therefore these additional polymorphisms do not enhance the correlation between pfcrt T76 and chloroquine resistance in Senegal. These data suggest that in vitro chloroquine resistance requires the genetic background of the pfcrt K76T mutation and additional mutations in genetic loci outside the pfcrt gene.

Adolescent↗

PubMed2003

[Gastroduodenal peptic ulcer: descriptive study].

Our goals were to describe the epidemiological, clinical and endoscopic aspects of gastrointestinal ulcer and to determine the frequency of H. pylori, we included 140 gastrointestinal peptic ulcers from January 1999 to June 2000. Diagnosis of ulcerous disease delt with the presence of an ulcer discovered during a high digestive endoscopy. Gastro-duodenal ulcers bleeding or with stenosis have been excluded as well as patients who were under anticoagulant treatment or antibiotics or under pump of protons inhibitors during the previous month. Data were collected from a unique questionnaire specifying the sociodemographic characteristic, the history of the ulcerous disease, the antecedents, the style of life, and the endoscopic findings. Five biopsies were done using sterile grips and a fast urease test and the direct exam of the smear. The prevalence of gastro-duodenal ulcers in our population of survey was 6.2%. One hundred twenty eight duodenal ulcers (91.4%), and 12 gastric ulcers (8.6%) were found. The average of age was of 37.1 years +/- 15.3. The sex ratio was 2.9. The gastro-duodenal disease had begun for more than 5 years at 40.8%. No difference in the characters of the pain and signs has been found between duodenal and gastric localization of the ulcer. Hp was associated in 91.4% (91.4% when duodenal ulcers, 88.9% when gastric ulcers and all gastric and duodenal ulcers). We conclude that gastrointestinal ulcers occupies an important place in our gastroenterological practice and the infection rate with H. pylori infection is so high during gastro-duodenal ulcers in our country that the eradication of Hp could be proposed in any case of gastro-duodenal ulcer diagnosed by endoscopy.

Adult↗

PubMed2002

[An association of HIV infection and noma in Niger].

We report a case of noma having occurred in an adult female patient with HIV. The strain was characterized as HIV-1 group M subtype G. In order to explore the interactions between HIV/AIDS and this disease, we purpose systematic HIV screening for any case of noma, especially for adult patients.

Adult↗

PubMed2001

Immunologic and virologic response after tetanus toxoid booster among HIV-1- and HIV-2-infected Senegalese individuals.

Twelve HIV-1-infected, nine HIV-2-infected patients and eight HIV-negative subjects were given a 40IU booster dose of tetanus toxoid (TT). Blood was collected on days 0, 7 and 30 after immunization. Changes in HIV-1 or HIV-2 RNA load were evaluated by nested PCR. TT-IgG antibody levels were quantified by ELISA. CD4 cell counts as well as activation, memory and maturation markers of T lymphocyte subsets were determined by flow cytometry. The induction of apoptosis was investigated using 7-aminoactinomycin D (AAD) and propidium iodide (PI) staining. Proliferative responses to TT and pokeweed mitogen (PWM) were determined by the level of [(3)H] thymidine incorporation. Seven and 30 days after immunization, there was no detectable increase in HIV-1 or HIV-2 plasma load. There were also no changes in CD4 cell counts, CD69, HLA-DR and memory CD45RO or naive CD45RA antigens. Immunization did not increase the spontaneous apoptosis of peripheral blood mononuclear cells (PBMCs), CD4+ and CD8+ T cells subsets neither in controls nor in HIV-infected patients. Similarly, apoptosis induced in vitro by PWM or by the specific TT recall antigen did not vary during the study period. The proliferative response to PWM and to the TT recall antigen was decreased both in HIV-1- and HIV-2-infected patients compared to HIV-negative controls. Immunization significantly increased the TT-IgG levels in healthy controls and in HIV-infected patients. However, the anti-TT-IgG response, as measured by the fold-increase index between days 0 and 30, was significantly higher in healthy controls than in HIV-1- (P=0.036) and HIV-2-infected patients (P=0.003). In conclusion, we found no deleterious immunologic or virologic effect was detected in healthy HIV-1- and HIV-2-infected individuals after antigenic challenge with a TT booster. However, the response to TT vaccination was lower in HIV-1- and in HIV-2-infected individuals than in healthy HIV-negative controls.

Adult↗

PubMed2001

Robust HIV type 2 cellular immune response measured by a modified anthrax toxin-based enzyme-linked immunospot assay.

Evaluation of immune mechanisms responsible for control of viral replication is critical to understanding HIV-2 attenuated biological characteristics in pathogenesis and transmission. Evaluation of the cellular immune response is often based on labor-intensive techniques that limit the scope of most studies performed. A simple and rapid anthrax toxin-based ELISPOT method to assess HIV-2 cellular immune response was developed. The modified anthrax toxin-based antigen presentation process performed better than a recombinant vaccinia system and the ELISPOT method significantly enhanced the ease and simplicity of the assay. Using this method, a robust HIV-2 cellular immune response directed toward the p26 core protein was exhibited in 21 of 24 (87.5%) infected women, and all 8 seronegative subjects were negative in both assays. Cellular immune responses were associated with low HIV-2 viral load. This simple and rapid modified anthrax toxin-based ELISPOT method allowed us to demonstrate, strong cellular immune responses that may be critical determinants in the HIV-2 attenuated phenotype.

Antigen Presentation↗

PubMed2001

Full-length genome sequencing of HIV type 1 group O viruses isolated from a heterosexual transmission cluster in Senegal.

In a polygamous marriage in Senegal, the husband and his two spouses were infected with HIV-1 group O. This study provides new full-length genome sequences for the two spouses (99SE-MP1299 and 99SE-MP1300) and the 3'-end LTR-tat fragment (6084 bp) for the husband (98SE-42HALD). Phylogenetic tree and diversity plot analysis revealed that the new viruses belong to HIV-1 group O and that they are closely related to each other in a cluster around ANT-70. The intrafamilial transmission occurred at most 6 years ago. The interpatient variability was highest in the envelope region, and in some regions of the envelope the strains from the two spouses do not cluster together anymore. The source of infection was in Cameroon and confirms a slow but continuous spread of HIV-1 group O viruses.

Female↗

PubMed2001

Prevalence and risk factors of cervicovaginal HIV shedding among HIV-1 and HIV-2 infected women in Dakar, Senegal.

OBJECTIVES: To assess the risk determinants and prevalence of cervicovaginal shedding of HIV-1 and HIV-2 among women in Dakar, Senegal. METHODS: We conducted a cross sectional study of 153 HIV seropositive female sex workers (FSW) and another 142 HIV seropositive women attending an infectious diseases unit, based on an interview, physical examination, and laboratory screening for major sexually transmitted infections (STI). Cervicovaginal lavage fluid was tested for HIV-RNA by means of nested PCR. Links between cervicovaginal shedding of HIV-1 and HIV-2 and sociodemographic, clinical, and laboratory variables were identified by using odd ratios and 95% confidence intervals. Logistic regression analysis was used to identify independent links with HIV shedding. RESULTS: The detection rate of HIV-RNA in cervicovaginal lavage fluid was low among FSW, with no difference between HIV-1 (7/90: 8%) and HIV-2 (3/48: 6%). The rate was far higher among the other women (41%, 48/117; 33%, 7/21 for HIV-1 and HIV-2, respectively). In multivariate analysis, high plasma viral load (>40 000 copies/ml) (AOR = 2.4 (1.0-5.6) p = 0.04) and basic vaginal pH (AOR = 2.2 (1.3-3.7) p = 0.002) were independently associated with HIV-1 shedding. For HIV-2 a CD4 count < 200 cells x 10(6)/l was the only factor associated with the shedding of HIV-2 (AOR = 9.0 (0.9-93)). The genital shedding rate was higher with HIV-1 than with HIV-2 (OR = 2.1 (0.9-4.8), but this difference disappeared after adjustment for the CD4+ cell count (AOR = 1.2 (0.5-2.9)). CONCLUSION: Advanced disease stage and immunosuppression are the major risk determinants for shedding of both HIV-1 and HIV-2. Basic vaginal pH is also a risk determinant for HIV-1 shedding.

Adult↗

PubMed2001

[Preliminary study of human Herpesvirus type 8 infection in pregnant women in Dakar (Senegal)].

HHV8 was discovered in 1994 and few studies on this virus have been conducted in Africa. The virus is related to Kaposi sarcoma, an opportunistic affection occurring during HIV infection. No studies have been carried out on this subject in Senegal, a country known for its low KS prevalence even among people living with HIV/AIDS. Thus it will be interesting to explore this field. The aim of our study has been first, to demonstrate the presence of HHV8; second, to evaluate sero-prevalence of the infection in Senegal and third, to determine the specificities of HHV8 infection in our country. We performed our study on 407 pregnant women whose average age was 29.24 years, the majority of whom were Senegalese. HIV serology was done by dot blot for the screening and western blot for the confirmation. For the diagnosis of HHV8 infection, we used the indirect immunofluorescence kit of ABI. HIV infection was low among this study population; 0.5% and no HIV1 infection was mentioned. Among the 407 women, 58 or 14.3% were HHV8 positive and there was no HHV8/HIVco-infection. Regarding marital status, no significant difference was found between HHV8 positive and HHV8 negative among unmarried, monogamous or polygamous women. However, women having had 4 to 5 children were more likely to test positive for HHV8. The difference is significant and a relationship has been established with a p value of 0.02. Regarding pregnancy, HHV8 infection is more closely related to abortion: 17.2% of women who had aborted were HHV8 positive versus 4.9% seronegative. The odds ratio calculation shows a strong correlation with a p value of 0.01. No correlation was found between HHV8 infection of the mother and neonate mortality or Apgar score. However, a relationship did show up between HHV8 infection of the mother and low birth weight. 29.2% of seropositive women had had a child with a birth weight under 2600 g whereas only 16.3% of seronegative women had had babies with low birth weight. We determined that HHV8 is indeed present in Senegal. Further studies should focus on transmission routes as well as the molecular epidemiology of this virus and diseases related to HHV8 infection in Senegal.

Abortion, Spontaneous↗

PubMed2001

[Infective etiology of diarrhea in adults with HIV infection in Dakar: a case-control study on 594 patients].

A survey was conducted in Dakar, Senegal from May 1997 to May 1999, to identify major types and prevalences of bacteria, parasites, fungi and Rotaviruses associated with diarrhea in relation to human immunodeficiency virus serostatus with the aim to provide guidance to physicians for case management. Etiologic agents were identified in a case-control study: cases were HIV-infected patients with diarrhea (HIV+ D+) and HIV seronegative patients with diarrhea (HIV- D+); controls were HIV-infected patients without diarrhea (HIV+ D-) and seronegative controls without diarrhea (HIV- D-). Strict enteric pathogens were identified by conventional methods. Different E. coli pathotypes were characterized by PCR. Opportunistic parasites such as Cryptosporidium and Microsporidium were identified by the Kinyoun method and trichromic stain of Weber respectively. Rotaviruses were identified with a commercial latex agglutination kit. Antimicrobial susceptibility testing was carried out by the disk diffusion method. A total of 594 patients were examined (158 HIV+D+, 121 HIV- D+, 160 HIV+ D- and 155 HIV- D-). In immunocompetent adults the main causes of diarrhea were: Shigella sp. (12.4%), Entamoeba histolytica (10.7%), Salmonella enterica (6,6%) and Giardia lamblia (4.9%). In the immunocompromised host the more frequent pathogens were: enteroaggregative E.coli (19,6%), Microsporidium(9.4%), Cryptosporidium sp.(8.2%), Rotavirus (8.2%), Shigella sp. (7.6%), Candida albicans (7.6%), Entamoeba histolytica (5,1%), Salmonella enterica (4.4%), Isospora belli (4.4%) and Blastocystis hominis (2,5%). Isolated enteropathogenic strains displayed high resistance to most antibiotics used in Senegal for treating diarrhea (tetracycline, cotrimoxazole); they were susceptible to quinolons and cephalosporins III .

Adult↗

PubMed2000

Dating the common ancestor of SIVcpz and HIV-1 group M and the origin of HIV-1 subtypes using a new method to uncover clock-like molecular evolution.

Attempts to estimate the time of origin of human immunodeficiency virus (HIV)-1 by using phylogenetic analysis are seriously flawed because of the unequal evolutionary rates among different viral lineages. Here, we report a new method of molecular clock analysis, called Site Stripping for Clock Detection (SSCD), which allows selection of nucleotide sites evolving at an equal rate in different lineages. The method was validated on a dataset of patients all infected with hepatitis C virus in 1977 by the same donor, and it was able to date exactly the known origin of the infection. Using the same method, we calculated that the origin of HIV-1 group M radiation was in the 1930s. In addition, we show that the coalescence time of the simian ancestor of HIV-1 group M and its closest related cpz strains occurred around the end of the XVII century, a date that could be considered the upper limit to the time of simian-to-human transmission of HIV-1 group M. The results show also that SSCD is an easy-to-use method of general applicability in molecular evolution to calibrate clock-like phylogenetic trees.

Animals↗

PubMed2000

Religion and protective behaviours towards AIDS in rural Senegal.

OBJECTIVES: To describe the association between religion and factors related to sexually transmitted diseases (STD)/AIDS in a country where religious leaders were involved early in prevention. DESIGN: A cross-sectional study conducted in a rural area in central Senegal. METHODS: Questionnaire-based interviews of a random sample of 858 adults from the general population aged 15-59 years and in-depth interviews of four religious leaders and 50 people. RESULTS: Seventy-six per cent of the respondents were Muslim, 24% Catholic, 1% Animist and 0.2% Protestant. A total of 86% of men and 87% of women reported religion to be very important to them. Important prevention-related variables were inversely associated with the importance of religion. Men who considered religion to be very important were less likely to cite AIDS as a major health problem [odds ratio (OR) 0.4, P = 0.008] and were less likely to feel at risk of getting HIV (OR 0.5, P = 0.0005). Women who considered religion to be very important were less likely to report an intention to change to protect themselves from AIDS (OR 0.2, P = 0.0001), less likely to report having discussed AIDS with others (OR 0.4, P = 0.01) and much more likely to feel at risk of getting HIV (OR 9.3, P = 10(-4)). Individuals who considered religion to be very important were not more likely to report intending to or actually having become faithful to protect themselves from AIDS. CONCLUSION: These findings stress the need to intensify the involvement of religious authorities in HIV/STD prevention at the local level.

Adolescent↗

PubMed2000

High levels of tumor necrosis factor-alpha and interleukin-1beta in bacterial vaginosis may increase susceptibility to human immunodeficiency virus.

Bacterial vaginosis (BV) was identified recently as a cofactor that promotes sexual transmission of human immunodeficiency virus (HIV). This study was done to determine if interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha could be measured consistently in cervical secretions and if high levels of these cytokines were associated with BV. Secretions were obtained from 209 study subjects; most samples had detectable levels of TNF-alpha (84.2%) and IL-1beta (79.8%). BV was detected in 53 (27.0%) of 196 women. High cytokine levels were significantly associated with BV (adjusted odds ratio [AOR], 4.17; 95% confidence interval [CI], 1.69-10.30), oral contraceptive use (AOR, 2.78; 95% CI, 1.04-7.48), and high leukocyte counts on vaginal smear (AOR, 1.18; 95% CI, 1.03-1.36). Since these cytokines could up-regulate local HIV replication through activation of the long terminal repeat promoter region, the association of BV with high levels of IL-1beta or TNF-alpha may partly explain the mechanism by which this risk factor enhances HIV transmission.

Adolescent↗