Epilepsy in a cohort of Senegalese children

Epilepsy is a significant health public problem in Senegal with an estimated prevalence of 8 to 14%. The aim of this study was to determine the clinical and electroencephalographic features of epilepsy in a cohort of Senegalese infants, search for etiological factors and determine the impact of disease on school life. This retrospective study concerned 459 children who attended the neurological outpatients clinic at the Fann hospital, Dakar, Senegal, between July 2003 and December 2006. All were aged under 19 years. Among the 135 children with idiopathic epilepsy, 23.7% had parental consanguinity and 37.77 % familial epilepsy. Rolandic epilepsy and epilepsy with absences were more frequent but several infants with idiopathic epilepsy were not classified. Non-idiopathic epilepsy was noted in 312 children. In this group, estimates of parental consanguinity and familial epilepsy were of 21.79 and 17.94%, respectively. Etiological factors were predominantly pregnancy and birth abnormalities (28.84%) and central nervous system infection (20.19%). Twelve children had febrile seizures. Of patients with idiopathic epilepsy, 65.18% were attending school versus only 9.29 with non-idiopathic epilepsy.     

Combination of tumor site-located CTL-associated antigen-4 blockade and systemic regulatory T-cell depletion induces tumor-destructive immune responses

Accumulating data indicate that tumor-infiltrating regulatory T cells (Treg) are present in human tumors and locally suppress antitumor immune cells. In this study, we found an increased Treg/CD8 ratio in human breast and cervical cancers. A similar intratumoral lymphocyte pattern was observed in a mouse model for cervical cancer (TC-1 cells). In this model, systemic Treg depletion was inefficient in controlling tumor growth. Furthermore, systemic CTL-associated antigen-4 (CTLA-4) blockade, an approach that can induce tumor immunity in other tumor models, did not result in TC-1 tumor regression but led to spontaneous development of autoimmune hepatitis. We hypothesized that continuous expression of an anti-CTLA-4 antibody localized to the tumor site could overcome Treg-mediated immunosuppression and locally activate tumor-reactive CD8+ cells, without induction of autoimmunity. To test this hypothesis, we created TC-1 cells that secrete a functional anti-CTLA-4 antibody (TC-1/alphaCTLA-4-gamma1 cells). When injected into immunocompetent mice, the growth of TC-1/alphaCTLA-4-gamma1 tumors was delayed compared with control TC-1 cells and accompanied by a reversion of the intratumoral Treg/CD8 ratio due to an increase in tumor-infiltrating IFNgamma-producing CD8+ cells. When local anti-CTLA-4 antibody production was combined with Treg inhibition, permanent TC-1 tumor regression and immunity was induced. Importantly, no signs of autoimmunity were detected in mice that received local CTLA-4 blockade alone or in combination with Treg depletion.     

Epidemiological and clinical features of HIV-2 infection in Dakar

OBJECTIVE: The aim of this article was to describe the epidemiological and clinical aspects of HIV-2 infection in Dakar. DESIGN AND METHODS: This retrospective study was made on 217 HIV-2 infected patients hospitalized between 1986 and 2003; the epidemiological, clinical, and paraclinical data was collected and analyzed using the Epi-Info software version 6.04. RESULTS: The mean age was 40 years+/-9.6 and the male to female sex ratio was 1.33. The mode of transmission was primarily heterosexual. Some risk factors (travel abroad, heterosexual multi-partners, and unprotected sexual intercourse) were more frequently observed in men while others (blood transfusion, HIV positive partners) were noted among HIV-2 infected women. The most frequent symptoms were weight loss (88%), diarrhea (77%), fever (72.4%), asthenia (70.5%), chronic cough, and dermatosis (50.7%). The main opportunistic infections were oral candidiasis (61.8%), tuberculosis (26.3%), intestinal parasitosis (20.3%). The lethality rate was 33.2% and it was correlated with a low CD4 rate. Meningoencephalitis and bacterial infections were associated with a high lethality rate. CONCLUSIONS: The epidemiological and clinical aspects of HIV-2 infection were the same as in HIV-1 infected patients. However the lethality rate remained high among patients hospitalized with a low CD4 cell count. Early HIV testing and improving the diagnostic approach for opportunistic infections remains a high priority.     

Détection fortuite de <Emphasis Type="Italic">cmy</Emphasis>-2 et <Emphasis Type="Italic">dha</Emphasis>-1 chez des isolats d’<Emphasis Type="Italic">Escherichia coli</Emphasis> producteurs de BLSE au Sénégal

Cephalosporinases, which are naturally present in some enterobacterial species, can be mobilized by transposons, migrate to plasmids, and spread into other species such as Escherichia coli. The aim of this study was to characterize genes responsible for the production of extended-spectrum β-lactamases (ESBL) in E. coli isolates from urinary origin isolated in two hospitals in Senegal. Thus, a fortuitous discovery of plasmidic cephalosporinase in two isolates was noted. One of the isolates produced dha-1 associated with ESBL CTX-M-14, the other produced cmy-2, ESBL CTXM-15, tem-1 penicillinase, and oxa-1. This confirms the circulation of multidrug-resistant bacteria producing plasmidic cephalosporinase in Senegal. However, a large study is needed to better understand the prevalence and the nature of the genes involved.     

Tuberculosis-associated severe CD4+ T-lymphocytopenia in HIV-seronegative patients from Dakar. SIDAK Research Group

OBJECTIVES: To determine the frequency and associated features of severe CD4+ T-lymphocytopenia (<300 cells/mm(3)) in HIV-seronegative patients with tuberculosis. METHODS: Statistical analysis of 430 consecutively enrolled HIV-seronegative inpatients with tuberculosis in two teaching hospitals in Dakar, Senegal. RESULTS: The mean CD4 + cell count was 602+/-318.3 cells/mm(3). CD4 + cell counts were below 300 cells/mm(3)in 62 patients (14.4%). Patients with fewer than 300 CD4+ cells/mm(3)differed from those with higher counts in being less likely to have a positive smear for acid-fast bacilli; in having a higher frequency of extrapulmonary involvement (pleural effusion, adenopathy and miliary disease) and oral candidiasis; and in having smaller tuberculin reactions, lower haemoglobin levels, less cavitation and less patchy infiltration. After adjustment for gender and age, all differences remained except miliary disease. CONCLUSIONS: A substantial percentage (14.4%) of HIV-seronegative hospitalized patients for tuberculosis in a West African country presented with severe CD4 + T-lymphocyte depletion and had clinical and radiographic features indicative of more advanced disease and accompanying immunodepression. These results and those already published suggest that tuberculosis should be regarded as one of the diseases associated with a subgroup of patients with "idiopathic CD4 + T-lymphocytopenia".     

Molecular epidemiology of dual HIV-1/HIV-2 seropositive adults from Senegal,West Africa

Dual infection with HIV-1 and HIV-2 can occur in locales where these viruses co-circulate, most commonly in West Africa. Although dual seropositivity is common in this region, the true rate of dual infection remains unclear. In addition, whether unique HIV-1 subtypes are circulating in dually infected individuals is unknown. A cohort of 47 HIV-1 and HIV-2 dually seropositive individuals from Senegal, West Africa was screened for the presence of HIV-1 and HIV-2 gag and env PBMC viral DNA sequences using PCR. Of the 47 dual HIV-1/HIV-2 seropositive individuals tested, 19 (40.4%) had infection with both HIV-1 and HIV-2 confirmed by genetic sequence analysis, whereas only HIV-1 or HIV-2 was confirmed in 17 (36.2%) or 9 (19.1%), respectively. The majority of HIV-1 subtypes found were CRF-02 and A, although subtypes D, C, G, J and B were also found, reflecting the subtypes known to be circulating in Senegal. There was no significant difference in HIV-1 subtype distribution between individuals with confirmed dual infection and patients in this study with dual seropositivity but lacking HIV-2, or with HIV-1 infected patients within the general population in Senegal, although the study was underpowered to detect anything but large differences. The prevalence of HIV-1/HIV-2 dual infection appears to be significantly less than that of dually seropositive individuals and this likely reflects cross-reactive serology. The common HIV-1 subtypes prevalent in West Africa (CRF-02 and subtype A) have a similar distribution to those found in our cohort of dually infected and dually seropositive subjects.