Metabolic Profile of Individuals with and without Type 2 Diabetes from Sub-Saharan Africa.

Epidemiological data predicts that sub-Saharan Africa will have the largest increase in type 2 diabetes (T2D) prevalence over the next two decades. Metabolomics studies have identified biomarkers that could improve T2D diagnosis and follow-up. However, no studies have characterized the metabolome of people from sub-Saharan Africa. Plasma samples from Senegalese individuals with T2D (n = 31) or without T2D (n = 34) were compared using measures of oxidative stress damage and plasma antioxidant enzyme activity and mass-spectrometry-based metabolomics analyses. Results showed that glucose, lactate, and tricarboxylic acid metabolites (fumarate, malate, and succinate) were increased in the T2D group, suggesting alterations in glycolysis and mitochondrial dysfunction. Several amino acids (leucine, isoleucine, valine, and tryptophan) and long-to-very-long-chain fatty acids were higher in the T2D group. Finally, elevated levels of ketone bodies and acylcarnitines were observed along with increased levels of oxidative stress damage and antioxidant activity. In conclusion, the T2D group exhibited modifications in metabolites previously shown to be associated with T2D risk in populations from other areas of the world. Future studies should seek to test whether these metabolites could be used as predictors for T2D-related complications in people from sub-Saharan Africa.

Widespread Bradyrhizobium distribution of diverse Type III effectors that trigger legume nodulation in the absence of Nod factor.

The establishment of the rhizobium-legume symbiosis is generally based on plant perception of Nod factors (NFs) synthesized by the bacteria. However, some Bradyrhizobium strains can nodulate certain legume species, such as Aeschynomene spp. or Glycine max, independently of NFs, and via two different processes that are distinguished by the necessity or not of a type III secretion system (T3SS). ErnA is the first known type III effector (T3E) triggering nodulation in Aeschynomene indica. In this study, a collection of 196 sequenced Bradyrhizobium strains was tested on A. indica. Only strains belonging to the photosynthetic supergroup can develop a NF-T3SS-independent symbiosis, while the ability to use a T3SS-dependent process is found in multiple supergroups. Of these, 14 strains lacking ernA were tested by mutagenesis to identify new T3Es triggering nodulation. We discovered a novel T3E, Sup3, a putative SUMO-protease without similarity to ErnA. Its mutation in Bradyrhizobium strains NAS96.2 and WSM1744 abolishes nodulation and its introduction in an ernA mutant of strain ORS3257 restores nodulation. Moreover, ectopic expression of sup3 in A. indica roots led to the formation of spontaneous nodules. We also report three other new T3Es, Ubi1, Ubi2 and Ubi3, which each contribute to the nodulation capacity of strain LMTR13. These T3Es have no homology to known proteins but share with ErnA three motifs necessary for ErnA activity. Together, our results highlight an unsuspected distribution and diversity of T3Es within the Bradyrhizobium genus that may contribute to their symbiotic efficiency by participating in triggering legume nodulation.

Incidence and determinants of new AIDS-defining illnesses after HAART initiation in a Senegalese cohort.

BACKGROUND: Although a dramatic decrease in AIDS progression has been observed after Highly Active Anti Retroviral Therapy (HAART) in both low- and high-resource settings, few data support that fact in low-resource settings.This study describes the incidence of AIDS-defining illnesses (ADI) after HAART initiation and analyzes their risk factors in a low-resource setting. A focus was put on CD4 cell counts and viral load measurements. METHODS: 404 HIV-1-infected Senegalese adult patients were enrolled in a prospective observational cohort and data censored as of April 2008. A Poisson regression was used to model the incidence of ADIs over two periods and to assess its association with baseline variables, current CD4, current viral load, CD4 response, and virological response. RESULTS: ADI incidence declined from 20.5 ADIs per 100 person-years, 95% CI = [16.3;25.8] during the first year to 4.3, 95% CI = [2.3;8.1] during the fourth year but increased afterwards. Before 42 months, the decrease was greater in patients with clinical stage CDC-C at baseline and with a viral load remaining below 1000 cp/mL but was uniform across CD4 strata (p = 0.1). After 42 months, 293 patients were still at risk. The current CD4 and viral load were associated with ADI incidence (decrease of 21% per 50 CD4/mm3 and of 61% for patients with a viral load < 1000 cp/mL). CONCLUSIONS: During the first four years, a uniform decline of ADI incidence was observed even in patients with low CD4-cell counts at HAART initiation as long as the viral load remained undetectable. An increase was noted later in patients with immunologic and virological failures but also in patients with only virological failure.

Increased Prevalence of Type 2 Diabetes-Related Complications in Combined Type 2 Diabetes and Sickle Cell Trait.

OBJECTIVE: The prevalence of type 2 diabetes (T2D) is rapidly increasing in sub-Saharan Africa, where sickle cell trait (SCT) is also frequent. Although SCT is generally considered a benign condition, evidence suggests that SCT could exaggerate vascular dysfunction in T2D. However, it remains unclear whether SCT could increase the risk of the development of T2D complications. Therefore, this study was conducted to determine whether T2D complications were more prevalent among Senegalese individuals with SCT and T2D than among those with T2D only. RESEARCH DESIGN AND METHODS: Rates of hypertension, retinopathy, peripheral neuropathy, peripheral artery disease, and impaired renal function as well as arterial stiffness, blood rheology, and concentrations of plasma advanced glycation end products (AGEs) and cytokines were compared between groups of Senegalese individuals with combined SCT and T2D (T2D-SCT) (n = 60), T2D (n = 52), SCT (n = 53), and neither T2D nor SCT (control) (n = 56). Human aortic endothelial cell (HAEC) expression of inflammatory and adhesion factors was measured after treatment with tumor necrosis factor-α and subjects' plasma. Effects of AGE inhibition or tiron on HAEC expression of E-selectin were measured. RESULTS: Retinopathy, hypertension, and reduced renal function were more prevalent, and arterial stiffness, blood viscosity at high shear rates, and thixotropic index were higher, in the SCT group compared with the other groups. Multivariable analysis showed that plasma AGE concentration was significantly associated with arterial stiffness. E-selectin expression was elevated in HAECs treated with T2D-SCT plasma compared with the other groups, but AGE inhibition reversed this. CONCLUSIONS: SCT could potentially augment the risk of the development of T2D-related complications, including retinopathy, nephropathy, and hypertension.

Antimicrobial susceptibility of select respiratory tract pathogens in Dakar, Senegal.

BACKGROUND: Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pyogenes, and Streptococcus pneumoniae are the most common causative agents of respiratory tract infections (RTIs). The increase in resistance to current antibacterial agents highlights the need to monitor the resistance pattern of these bacterial pathogens. METHODOLOGY: In this study, we assessed the antibacterial susceptibility of these pathogens causing respiratory tract infections in Dakar, Senegal, during 2007-2008. A total of 290 bacterial isolates (75 H. influenzae, 10 M. catarrhalis, 105 S. pneumoniae, and 100 S. pyogenes) were collected. RESULTS AND CONCLUSIONS: All H. influenzae isolates were susceptible to amoxicillin/clavulanic acid, ofloxacin, clarithromycin, cephalosporins, and macrolides. Overall, 26.7% of H. influenzae isolates were completely resistant to ampicillin. Among the M. catarrhalis isolates, 30% were resistant to ampicillin. All the isolates of H. influenzae and M. catarrhalis that were resistant to ampicillin were beta-lactamase producing strains. Among the S. pneumoniae isolates, 33.3% isolates exhibited intermediate susceptibility to penicillin G, and one isolate was completely resistant. All five isolates that were resistant to erythromycin expressed the M phenotype. S. pyogenes exhibited high susceptibility to all other antibiotics, except tetracycline. Our study suggests that except for M. catarrhalis, all other bacterial isolates are susceptible to cephalosporins, macrolides, and fluroquinolones.

Long-term efficacy and tolerance of efavirenz- and nevirapine-containing regimens in adult HIV type 1 Senegalese patients.

Owing to their low toxicity, low price, and ease of use, efavirenz (EFV) and nevirapine (NVP) are frequently used as part of antiretroviral regimens for AIDS treatment. Several clinical trials have already studied their efficacy and tolerance. However, long-term observations of the effects of these drugs in patients are limited. We used data from a prospective Senegalese cohort to analyze long-term tolerance and efficacy of these two drugs in a low-resources setting. Patients were included if they started their therapy with EFV or NVP. They were censored after treatment discontinuation. The primary endpoint was the time to treatment discontinuation. Secondary endpoints included time to death, time to disease progression, occurrence of severe adverse effects, CD4 cell recovery, and virological response. Confounding factors were controlled using marginal structural models. The median follow-up time in both EFV and NVP arms was 48 months. The hazard ratio (HR) of drug discontinuation in the EFV arm vs. the NVP arm was 0.84 (0.34; 1.87). There was a borderline difference in virological response [HR 1.38 (0.999; 1.89)] but no differences in time to death [HR 1.15 (0.41; 3.24)], time to AIDS progression [HR 1.25 (0.61; 2.58)], or time to increase in CD4 cell count above 500 cells/mm3. Adverse effects were different between NVP and EFV, but long-term tolerance was good for both. This analysis provided further information on long-term tolerance and efficacy of EFV and NVP in a resource-limited setting.

Time-resolved Fourier transform intracavity spectroscopy with a Cr2+:ZnSe laser.

Intracavity laser absorption spectroscopy (ICLAS) with an evacuated Cr2+:ZnSe laser is performed with a high-resolution time-resolved Fourier transform interferometer with a minimum detectable absorption coefficient equal to 4 x 10(-9) cm(-1) Hz(-1/2) in the 2.5 microm region. This represents the extreme limit currently reached in the infrared by ICLAS with Doppler-limited resolution. The broad gain band of the crystal allows a spectral coverage at most equal to 125 nm, wide enough to see entire vibration bands. Weak CO2 bands observed up to now only in the Venusian atmosphere are recorded for the first time, to our knowledge, in a laboratory. An H2O detection limit down to 0.9 parts per billion by volume is also demonstrated.