Antimicrobial Resistance in Outpatient Escherichia coli Urinary Isolates in Dakar; Senegal

Background: Data regarding the evolution of antimicrobial resistance are needed to suggest appropriate empirical treatment of urinary tract infections (UTI) in developing countries. To assess the antimicrobial susceptibility of Escherichia coli; the predominant pathogen in community-acquired UTI; a prospective multicenter study was carried out in Dakar; Senegal. Methodology: From February 2004 to October 2006; 1010 non-duplicate E. coli strains were collected from four centres. Antimicrobial susceptibility testing was performed using disk diffusion method according to the recommendations of the CA-SFM (2004). Results: Most of the isolates were resistant to amoxicillin (73.1); amoxicillin- clavulanic acid (67.5); cephalothin (55.8); and trimethoprim/sulfamethoxazole (68.1). Extended spectrum beta-lactamase was detected in 38 strains. The overall resistance rates to nalidixic acid; norfloxacin and ciprofloxacin were 23.9; 16.4and 15.5; respectively. Most of the strains were susceptible to gentamicin; nitrofurantoin and fosfomycin (respective susceptibility rates; 93.8; 89.9; and 99.3). During this period; a significant decrease in sensitivity was observed for cephalothin; fluoroquinolones and trimethoprim/sulfamethoxazole (p0.001). Conclusions: These data suggest that trimethoprim/sulfamethoxazole may no longer be used as empirical treatment for community- acquired UTI in Dakar. In order to preserve the activity of fluoroquinolones for future years; alternatives such as fosfomycin or nitrofurantoin should be considered

Environmental lead exposure and its relationship to traffic density among Senegalese children: a pilot study.

In Senegal, as in many developing countries, traffic density is increasing in urban areas; in Dakar more than 50% of vehicles use gasoline. Yet the extent and real magnitude of the problem has neither been recognized nor assessed in these countries. Systemic data assessment of lead pollution and people's exposure are not well known in Senegal. This study was also designed to determine the impregnation levels of the lead released by the exhaust of cars and the changes of some early biological markers in Senegalese children. Blood lead (BPb) levels showed that all the children enrolled were exposed. However, lead exposure levels (from 34.7 to 145.8 microg/L) were less important for children living in rural areas (60.9+/-18.3 microg/L) than for those living in urban areas (106.7+/-16.9 microg/L). These changes could be correlated to the difference in the automobile traffic between both these regions (P < 0.001). BPb mean levels found in boys were higher than those in girls (P < 0.05). Despite elevated BPb levels, all values for blood zinc protoporphyrin and urine delta-aminolevulinic acid were within physiological ranges. In addition, variations in some biological markers of oxidative stress and renal disorders were seen; however, they must be confirmed by a future epidemiological study.

[Hairy cell leukemia revealed by an isolated neutropenia]. / Leucémie a tricholeucocytes révélée par une neutropénie isolée.

Hairy cell leukemia is a rare lymphoproliferative disorder which affect predominantly older males. Typical presentation includes pancytopenia, splenomegaly, presence of malignant cells with hairy projections, and some difficulty to perform a bone marrow aspiration. Reported is a 78 year - old female patient, who presented only neutropenia. There was no splenomegaly and the bone marrow aspiration was easy. Diagnosis was based on the presence of characteristic cells in a second bone marrow aspiration, whereas a treatment by recombinant human G-CSF was introduced for a suspicion of an idiopathic neutropenia. Confirmation was done with immunostaining by DBA 44 monoclonal antibody. This is the first case of hairy cell leukemia reported in Dakar, and with an uncommon clinical presentation making it difficult to be recognized.

[Toxocological study of Guiera senegalensis Lam (Combretaceae)]. / Etude toxicologique de Guiera senegalensis Lam (Combretaceae).

The study was based on an aqueous extract derived from a 60 degrees ethanolic tincture containing 0.032 g of dry matter per ml. The leaves of Guiera senegalensis Lam (Combretaceae) were collected in December 1991 at Nguekhokh a village within 20 km from Mbour (Senegal). The extract was administered for six months through daily forced-feeling at 2 g/kg to Wistar male and female rats whose weight at the beginning of the experiment tanged between 140 g and 180 g. The urine was analysed during the study and the animals were weighed every four weeks. At the end of the experiment, the animals were slaughtered and various analyses carried out. Haematological features in relation with erythropoiesis, haemoglobinogenesis and leucopoiesis, were studied in relation with renal and hepatic functions; biochemical features too. Some organs (heart, lungs, kidneys, brain, cerebellum, spleen and liver) were removed and examined in order to detect possible lesions following the experiment. Judging by the results, Guiera senegalensis Lam (Combretaceae), as used in the experiment, did not show any significant toxicity.

Relation between HIV-2 proviral load and CD4+ lymphocyte count differs in monotypic and dual HIV infections.

OBJECTIVE: To explore and compare the relations between proviral DNA load and CD4+ lymphocyte counts in both HIV-2 monotypic and HIV dual infection. STUDY DESIGN/METHODS: In Dakar, Senegal, where the HIV-1 and HIV-2 epidemics overlap, serum and peripheral blood mononuclear cell (PBMC) DNA samples were collected from registered female sex workers and hospitalized patients. Sera were evaluated for reactivity to antigens of HIV-1 and HIV-2 by immunoblot; dual reactivity was confirmed with recombinant envelope peptides for HIV-1 and HIV-2. These samples were then subjected to HIV-1 and HIV-2 proviral DNA polymerase chain reaction (PCR). To evaluate the HIV-2 cellular proviral DNA loads, a quantitative competitive PCR (QC-PCR) was developed using nested primers to amplify the gag region of HIV-2. This assay used an internal competitor generated by inserting 25 bp in the first-round PCR target sequence. T-lymphocyte subset counts were estimated by flow cytometry for both HIV-2 monotypic and dually infected persons. RESULTS: 35 HIV-2-infected and 33 dually seroreactive samples were evaluated in this study. The CD4+ lymphocyte counts were similar in both groups, with mean values of 449 +/- 390 cells/mm3 for the HIV-2 monotypic infected persons and 476 +/- 308 cells/mm3 among the dually infected persons. However, the median proviral loads differed significantly, with those in the HIV-2 group ranging from 63.2 to 669.8 copies/10(5) CD4+ cells and demonstrating an inverse correlation with CD4+ lymphocyte count. The HIV dually infected persons showed less variation in viral load, ranging from 9.9 to 43.3 copies/10(5) CD4+ cells. Among the HIV dually infected persons, low HIV-2 proviral load was correlated with low CD4+ lymphocyte counts. CONCLUSIONS: The HIV-2 proviral loads in HIV dually infected persons were significantly lower than those in HIV-2 monotypically infected individuals (P < .0001), despite comparable CD4+ lymphocyte counts. These results suggest that different HIV-2 proviral dynamics prevail in HIV dual infection.

Human immunodeficiency virus type 1 subtypes differ in disease progression.

At least 10 different genetic human immunodeficiency virus type 1 (HIV-1) subtypes (A-J) are responsible for the AIDS pandemic. Much of the understanding of HIV-1 disease progression derives from studies in the developed world where HIV infection is almost exclusively subtype B. This has led many to question whether the properties and consequences of HIV-1 infection can be generalized across subtypes that afflict the majority of infected persons in the developing world. From 1985 to 1997, a prospective study of registered female sex workers in Senegal tracked the introduction and spread of HIV-1 subtypes A, C, D, and G. In clinical follow-up, the AIDS-free survival curves differed by HIV-1 subtype. Women infected with a non-A subtype were 8 times more likely to develop AIDS than were those infected with subtype A (hazard ratio=8.23; P=. 009), the predominant subtype in the study. These data suggest that HIV-1 subtypes may differ in rates of progression to AIDS.

Antibodies to the HIV type 2 core protein p26 and Vpx: association with disease progression.

A longitudinal cohort study was conducted to define the prevalence and temporal pattern of antibody response to the HIV-2 virion-associated proteins p26gag and Vpx. One hundred and forty-one asymptomatic HIV-2-infected women were enrolled, and followed for up to 11 years. Eighty-one percent of the subjects had antibodies to p26, and 51% to Vpx; response to these two antigens was not correlated. The response to both proteins was determined early in infection, and remained stable over time. The absence of antibodies to p26 was a highly significant predictor of CDC category IV HIV-related disease (p < 0.01) in both univariate and multivariate analysis. Antibody response to Vpx alone was not associated with disease progression. However, those individuals lacking anti-p26 antibodies, and with anti-Vpx antibodies, were six times more likely to be classified as CDC category IV by the end of the study (p < 0.01). This represents the first identification of virus-specific serological markers for HIV-2-related disease progression.

HIV-1 and HIV-2 dual infection: lack of HIV-2 provirus correlates with low CD4+ lymphocyte counts.

OBJECTIVE: We conducted this study to genetically characterize dual infection in individuals demonstrating a dual serological profile. METHODS: All subjects were first evaluated by immunoblot for antibody reactivity to the major viral antigens for HIV-1 and HIV-2. Sera were judged to be dual-seropositive if they reacted with strong and equal intensity with the envelope antigens of both HIV-1 and HIV-2 and were confirmed with type-specific recombinant env peptides. We used nested polymerase chain reaction (PCR) to amplify proviral gag and env sequence from peripheral blood mononuclear cell (PBMC) DNA from HIV-1- and HIV-2-infected individuals. Positive amplification was detected after Southern blot hybridization. RESULTS: Plasmid dilution and mixing showed equivalent sensitivity of HIV-1 and HIV-2 primers that was not altered by heterologous target sequences. The DNA PCR showed 100% sensitivity and specificity for detection of monotypic HIV infection. Serologically defined HIV-dual reactives were evaluated by this assay, with 100% detection in female sex workers (21 out of 21), but only 38.5% detection (five out of 13) in hospitalized patients; all being HIV-1 positive only. The lack of HIV-2 proviral signal was significantly correlated with low CD4+ lymphocyte counts (Pvalue = 0.04). CONCLUSION: The results suggest that HIV dual infection may not be a static condition. Levels of HIV-2 may decrease with disease progression or sequester in tissue reservoirs; our results may also suggest that HIV-1 effectively overgrows HIV-2 in the dually exposed host individual.

Natural protection against HIV-1 infection provided by HIV-2.

Significant differences have been observed in the rates of transmission and disease development in human immunodeficiency virus (HIV) types 1 and 2. Because many HIV-2-infected people remain asymptomatic for prolonged periods, the hypothesis that HIV-2 might protect against subsequent infection by HIV-1 was considered. During a 9-year period in Dakar, Senegal, the seroincidence of both HIV types was measured in a cohort of commercial sex workers. Despite a higher incidence of other sexually transmitted diseases (STDs), HIV-2-infected women had a lower incidence of HIV-1 than did HIV-seronegative women, with a relative risk of 0.32 (P = 0.008). An understanding of the cross-protective mechanisms involved may be directly relevant to HIV-1 vaccine development.

Intrapatient variability of the human immunodeficiency virus type 2 envelope V3 loop.

Studies of HIV-2 infection have shown lower rates of sexual and perinatal transmission and a prolonged incubation period to AIDS as compared to HIV-1. To evaluate the role of genetic variation in HIV pathogenesis, we studied intrapatient variability in the V3 loop of the HIV-2 envelope gene over time in five seropositive individuals. Proviral sequences derived from uncultured PBMC DNA (n = 102) demonstrated an average sequence heterogeneity within a sample of 1.4% (0-4.1%). This was significantly lower than the V3 sequence heterogeneity observed in HIV-1, which can be as high as 6.1%. In HIV-2-seropositive healthy patients the average intrapatient nucleotide variability rate was 0.6% compared to 2.0% in patients with clinical AIDS. The lower rate of variability between HIV-2 and HIV-1 is compatible with differences in transmission and pathogenesis of these two related viruses.

Reduced rate of disease development after HIV-2 infection as compared to HIV-1.

Human immunodeficiency virus type-2 (HIV-2) is a close relative of the prototype acquired immunodeficiency syndrome (AIDS) virus, HIV-1. HIV-2 is biologically similar to HIV-1, but information is lacking concerning clinical outcomes of HIV-2-infected individuals. From 1985 to 1993, a prospective clinical study was conducted in women with HIV-2 and HIV-1 infection to determine and compare rates of disease development. HIV-1-infected women had a 67% probability of AIDS-free survival 5 years after seroconversion in contrast with 100% for HIV-2-infected women. In addition to having significantly less HIV-related disease outcome in HIV-2 enrollees compared to HIV-1 enrollees, the rate of developing abnormal CD4+ lymphocyte counts with HIV-2 infection was also significantly reduced. This natural history study demonstrates that HIV-2 has a reduced virulence compared to HIV-1.

Slower heterosexual spread of HIV-2 than HIV-1.

Because of the similar virological properties of HIV types 1 and 2, HIV-2 was assumed to be as infectious and capable of inducing AIDS as HIV-1. Seroepidemiological studies have shown significant rates of HIV-2 infection in West Africa, and surveys from other regions of the world indicate that the spread of HIV-2 infection continues. However the pathogenic potential of HIV-2 is considered to be lower than that of HIV-1. It is therefore important to understand the transmission properties of HIV-2 and its contribution to the AIDS pandemic. Since 1985, we have prospectively studied 1452 registered female prostitutes in Dakar, Senegal, with sequential evaluation of their antibody status to HIV-1 and HIV-2. During the study the overall incidence of HIV-1 and HIV-2 was the same (1.11 per 100 person-years of observation [pyo]). However, the annual incidence of HIV-1 increased substantially: there was a 1.4-fold increased risk per year and thus a 12-fold increase in risk over the entire study period. The incidence of HIV-2 remained stable, despite higher HIV-2 prevalence. In our population the heterosexual spread of HIV-2 is significantly slower than that of HIV-1, which strongly suggests differences in the viruses' infectivity potential.

PIP: Between February 1985 and February 1993 in Dakar, Senegal, the Social Hygiene Clinic screened 1452 registered female prostitutes (5608 samples) for sexually transmitted diseases, including HIV-1 and HIV-2. The overall prevalence rate stood at 11.3% for HIV-2 while it was 6.2% for HIV-1. 12 women (0.8%) tested positive for HIV-1 and HIV-2. Health workers followed the 1277 women who were initially HIV seronegative to determine seroconversion. 46 of these women seroconverted to HIV-2 and another 46 seroconverted to HIV-1. Overall incidence of HIV-2 and HIV-1 was 1.11 per person years of observation (pyo). Eight women (incidence = 0.19 per 100 pyo) seroconverted to both HIV-2 and HIV-1. When the researchers controlled for age, nationality, years of registered prostitution, calendar year, and time in study, the relative risk for HIV-2 infection each year did not change. On the other hand, there was a significant 1.43 annual increase in the risk for HIV-1 infection (p .002), indicating a 12-fold increase in the risk of HIV-1 infection over the study period. These findings suggest that the 2 viruses have a distinctly different in-vivo biology and that HIV-2 has a lower infectivity than does HIV-1.