Plasmodium falciparum merozoite surface antigen-specific cytophilic IgG and control of malaria infection in a Beninese birth cohort.

BACKGROUND: Substantial evidence indicates that cytophilic IgG responses to Plasmodium falciparum merozoite antigens play a role in protection from malaria. The specific targets mediating immunity remain unclear. Evaluating antibody responses in infants naturally-exposed to malaria will allow to better understand the establishment of anti-malarial immunity and to contribute to a vaccine development by identifying the most appropriate merozoite candidate antigens. METHODS: The study was based on parasitological and clinical active follow-up of infants from birth to 18 months of age conducted in the Tori Bossito area of southern Benin. For 399 infants, plasma levels of cytophilic IgG antibodies with specificity for five asexual stage malaria vaccine candidate antigens were determined by ELISA in infants' peripheral blood at 6, 9, 12 and 15 months of age. Multivariate mixed logistic model was used to investigate the association between antibody levels and anti-malarial protection in the trimester following the IgG quantification. Moreover, the concentrations of merozoite antigen-specific IgG were compared between a group of infants apparently able to control asymptomatic malaria infection (CAIG) and a group of infants with no control of malaria infection (Control group (NCIG)). Protective effect of antibodies was also assessed after 15 months of malaria exposure with a Cox regression model adjusted on environmental risk. RESULTS: Cytophilic IgG responses to AMA1, MSP1, MSP2-3D7, MSP2-FC27, MSP3 and GLURP R2 were associated with increasing malarial infection risk in univariate analysis. The multivariate mixed model showed that IgG1 and IgG3 to AMA1 were associated with an increased risk of malarial infection. However infants from CAIG (n = 53) had significantly higher AMA1-, MSP2-FC27-, MSP3-specific IgG1 and AMA1-, MSP1-, MSP2-FC27-, MSP3 and GLURP-R2-specific IgG3 than those from NCIG (n = 183). The latter IgG responses were not associated with protection against clinical malaria in the whole cohort when protective effect is assessed after 15 months of malaria exposition. CONCLUSION: In this cohort, merozoite antigen-specific cytophilic IgG levels represent a marker of malaria exposure in infants from 6 to 18 months of age. However, infants with resolution of asymptomatic infection (CAIG) seem to have acquired naturally immunity against P. falciparum. This observation is encouraging in the context of the development of multitarget P. falciparum vaccines.

BRIP1 coding variants are associated with a high risk of hepatocellular carcinoma occurrence in patients with HCV- or HBV-related liver disease.

The molecular mechanisms of hepatocellular carcinoma (HCC) carcinogenesis are still not fully understood. DNA repair defects may influence HCC risk. The aim of the study was to look for potential genetic variants of DNA repair genes associated with HCC risk among patients with alcohol- or viral-induced liver disease. We performed four case-control studies on 2,006 European- (Derivation#1 and #2 studies) and African-ancestry (Validation#1 and #2 studies) patients originating from several cohorts in order to assess the association between genetic variants on DNA repair genes and HCC risk using a custom array encompassing 94 genes. In the Derivation#1 study, the BRIP1 locus reached array-wide significance (Chi-squared SV-Perm, P=5.00×10-4) among the 253 haplotype blocks tested for their association with HCC risk, in patients with viral cirrhosis but not among those with alcoholic cirrhosis. The BRIP1 haplotype block included three exonic variants (rs4986763, rs4986764, rs4986765). The BRIP1 'AAA' haplotype was significantly associated with an increased HCC risk [odds ratio (OR), 2.01 (1.19-3.39); false discovery rate (FDR)-P=1.31×10-2]. In the Derivation#2 study, results were confirmed for the BRIP1 'GGG' haplotype [OR, 0.53 (0.36-0.79); FDR-P=3.90×10-3]. In both Validation#1 and #2 studies, BRIP1 'AAA' haplotype was significantly associated with an increased risk of HCC [OR, 1.71 (1.09-2.68); FDR-P=7.30×10-2; and OR, 6.45 (4.17-9.99); FDR-P=2.33×10-19, respectively]. Association between the BRIP1 locus and HCC risk suggests that impaired DNA mismatch repair might play a role in liver carcinogenesis, among patients with HCV- or HBV-related liver disease.

Exhaled carbon monoxide: a non-invasive biomarker of short-term exposure to outdoor air pollution.

BACKGROUND: In urban settings of Africa with rapidly increasing population, traffic-related air pollution is a major contributor to outdoor air pollution (OAP). Although OAP has been identified as a leading cause of global morbidity and mortality, there is however, lack of a simple biomarker to assess levels of exposure to OAP in resource-poor settings. This study evaluated the role of exhaled carbon monoxide (exhCO) as a potential biomarker of exposure to ambient carbon monoxide (ambCO) from OAP. METHODS: This was a descriptive study conducted among male commercial motorcycle riders in Cotonou - the economic capital of Benin. The participants' AmbCO was measured using a portable carbon monoxide (CO) data logger for 8 h during the period of their shift. ExhCO was measured just before and immediately after their shift (8-h) Participants were asked not to cook or to smoke during the day of the measurements. Linear regression analysis was used to assess the association between ambCO and exhCO for the last 2, 4 and 6 h of their shift. RESULTS: Of 170 participants who completed the study, their mean ± SD age was 42.2 ± 8.4 years, and their mean ± SD daily income was 7.3 ± 2.7$. Also, 95% of the participants' used solid fuels for cooking and only 2% had ever smoked. Average exhCO increased by 5.1 ppm at the end of the shift (p = 0.004). Post-shift exhCO was significantly associated to ambCO, this association was strongest for the last 2 h of OAP exposure before exhCO measurement (ß = 0.34, p < 0.001). CONCLUSION: ExhCO level was associated with recent exposure to ambCO from OAP with measurable increase after 8 h of exposure. These findings suggest that ExhCO may be a potential biomarker of short-term exposure to OAP.

Acthaside: a new chromone derivative from Acacia ataxacantha and its biological activities.

BACKGROUND: Acacia ataxacantha (Fabaceae), used in traditional medicine grows in the South-West of Bénin. Ethyl acetate extract of the barks of this species was previously reported to display various bioactivities, including antibacterial, antifungal and antioxidant activities. In the present study, we investigate the antimicrobial and antioxidant activities of compound isolated from ethyl acetate extract of Acacia ataxacantha. METHODS: Purification, isolation and structural identification of isolated compound were done using various chromatographic and spectroscopic methods. Antimicrobial activity was investigated using a two-fold serial microdilution method. The inhibitory potency of isolated compound was evaluated by kinetic experiments. The antioxidant activity was also determined using 2, 2-diphenyl-1-picrylhydrazyl. RESULTS: The isolated compound was identified as 7-hydroxy-2-methyl-6-[ß-galactopyranosyl-propyl]-4H-chromen-4-one. As far as we know, this compound, named "acthaside", reported for the first time, was active against all tested microorganisms with minimal inhibitory concentration ranging from 25 to 50 µg/ml. At 50 µl/ml, no growth was observed in almost all tested microbial after 24 h of exposure. The isolated compound had significant antioxidant activity with an IC50 value of 3.61 ± 0.12 µg/ml compared to quercetin (IC50 1.04 ± 0.01 µg/ml). CONCLUSION: The present work demonstrates that the new chromen derivative isolated from A. ataxacantha may help treat bacterial and yeast infections. However, further studies are required to clarify the mechanism of action of this compound.

The hide and seek of Plasmodium vivax in West Africa: report from a large-scale study in Beninese asymptomatic subjects.

BACKGROUND: Plasmodium vivax is considered to be absent from western Africa, where the prevalence of Duffy-negative red blood cell phenotype proves to be high. Several studies have, however, detected P. vivax infection cases in this part of Africa, raising the question of what is the actual prevalence of P. vivax in local populations. METHODS: The presence of P. vivax was investigated in a large population of healthy blood donors in Benin using microscopy, serology and molecular detection. The seroprevalence was measured with species-specific ELISA using two recombinant P. vivax proteins, namely rPvMSP1 and rPvCSP1. Specific molecular diagnosis of P. vivax infection was carried out using nested-PCR. The performances and cut-off values of both rPvCSP1 and rPvMSP1 ELISA were first assessed using sera from P. vivax-infected patients and from non-exposed subjects. RESULTS: Among 1234 Beninese blood donors, no parasites were detected when using microscopy, whereas 28.7% (354/1234) of patients exhibited had antibodies against rPvMSP1, 21.6% (266/1234) against rPvCSP1, and 15.2% (187/1234) against both. Eighty-four samples were selected for nested-PCR analyses, of which 13 were positive for P. vivax nested-PCR and all Duffy negative. CONCLUSION: The results of the present study highlight an unexpectedly high exposure of Beninese subjects to P. vivax, resulting in sub-microscopic infections. This suggests a probably underestimated and insidious parasite presence in western Africa. While the vaccination campaigns and therapeutic efforts are all focused on Plasmodium falciparum, it is also essential to consider the epidemiological impact of P. vivax.

Diversity of high risk human papilloma viruses in women treated with antiretroviral and in healthy controls and discordance with cervical dysplasia in the South of Benin.

BACKGROUND: High risk oncologic Human Papilloma Virus (HPV) is one of the leading causes of cervical cancer worldwide. We investigated HPV genotypes among women living or not with Human Immuno-deficiency Virus (HIV) in two major hospitals in the south of the republic of BENIN in the city of Cotonou. Our objective is to investigate the association of high risk-HPV to cervical dysplasia among women under stringent anti-retroviral (ARV) treatment and in controls without HIV. METHODS: The investigation was carried out within 1 year period in two groups of adult women: one group with HIV1 infection and under ARV therapy in the National University Hospital (CNHU-HKM) designated as CH group (n = 86); and one control group without HIV infection and attending the hospital Mènontin for routine gynecologic checkup and designated as ME group (n = 86). Cells derived from cervical uterine smears (CUS) were used for this investigation. The samples in ME group were selected to have similar lamin A/C profile with CH group. HPV genotypes were assessed by polymerase chain reaction (PCR) while lamin A/C expression profile was assessed by western blotting to corroborate the risk of cervical dysplasia. RESULTS: HPV56 is dominant in CH group while HPV66 is dominant in ME group. 31 % of women in CH group are infected with HPV compared to 23 % in ME group. Quadruple and quintuple HPV infections are more observed among CH group but not in ME group making HPV counts of 43 in CH group and 27 in ME group. Cervical dysplasia are present in 5 % (4/86) of women in CH group and in 1 % (1/86) of women in ME group at the time of CUS collection. The adjustment of the risk to develop cervical cancer in the future related to HPV infection and the total loss of lamin A/C is not significantly different in both groups. CONCLUSION: Women living with HIV are more sensitive to multiple HPV infection but not all HPV infections generated cervical dysplasia. The effectiveness of antiretroviral therapy in CH group may reduce significantly the frequency of cervical dysplasia.

Triterpenoids from Acacia ataxacantha DC: antimicrobial and antioxidant activities.

BACKGROUND: Acacia ataxacantha is a medicinal specie used extensively in traditional medicine of Benin republic to treat infectious diseases. Our previous study showed interesting antibacterial and antifungal activities against six strains of bacteria and six strains of fungi. The aim of this study was to investigate the antimicrobial and antioxidant activities of compounds isolated from A. ataxacantha. METHODS: Chromatographic and spectroscopic methods were used to isolate and identify three compounds (1-3) from the bark of A. ataxacantha. Phytochemical investigation of A. ataxacantha (Fabaceae) led to the isolation of three triterpenoids (1-3). The structure of isolated compounds was established by differents spectroscopic methods such as UV, (1)H NMR, (13)C NMR, 2D NMR and Mass. All isolated compounds were tested for antimicrobial activity using agar disc-diffusion and microdilution methods. The radical scavenging activity of isolated compounds was assessed using 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. RESULTS: Phytochemical investigation led to the isolation and identification of lupeol (1), betulinic acid (2) and betulinic acid-3-trans-caffeate (3). Moderate antimicrobial activity was obtained with compound 3 against methicillin-resitant Staphylococcus aureus, Enterococcus feacalis and Pseudomonas aeruginosa with MIC value of 25 µg/ml and Staphylococcus aureus (MIC of 50 µg/ml). Compounds 3 was more active against Staphylococcus epidermidis and Candida albicans with a MIC value of 12.5 µg/ml in boths cases. Compounds 3 had also interesting antioxidant activity with an IC50 of 3.57 µg/ml compared to quercetin (1.04 µg/ml). CONCLUSION: The overall results of this study provide evidence that the compound 3, isolated from A. ataxacantha, exhibit antimicrobial activity against Gram-positive and Gram-negative bacteria and yeast, especially against C. albicans.

Identification of novel major and minor QTLs associated with Xanthomonas oryzae pv. oryzae (African strains) resistance in rice (Oryza sativa L.).

BACKGROUND: Xanthomonas oryzae pv. oryzae (Xoo) is the causal agent of Bacterial Leaf Blight (BB), an emerging disease in rice in West-Africa which can induce up to 50 % of yield losses. So far, no specific resistance gene or QTL to African Xoo were mapped. The objectives of this study were to identify and map novels and specific resistance QTLs to African Xoo strains. RESULTS: The reference recombinant inbred lines (RIL) mapping population derived from the cross between IR64 and Azucena was used to investigate Xoo resistance. Resistance to African and Philippine Xoo strains representing different races was assessed on the RIL population under greenhouse conditions. Five major quantitative trait loci (QTL) for resistance against African Xoo were located on different chromosomes. Loci on chromosomes 1, 7, 9, 10 and 11 explained as much as 13 %, 37 %, 13 %, 11 % and 15 % of resistance variation, respectively. A major novel QTL located on chromosome 7 explained 37 % of the phenotypic variance to the African Xoo corresponding to race A3 whereas that on chromosome 11 is effective to all African races tested. Together with genes and QTLs for resistance to bacterial blight previously described, the QTLs described here were mapped onto the reference O. sativa subs japonica (var. Nipponbare) physical map. CONCLUSION: We characterized new resistance QTLs. While some co-localize with known resistance genes/QTLs to Asian strains, others are specific to African strains. We result with new information on genes and QTLs for resistance to bacterial blight that will be useful for controlling the disease.

Plasmodium falciparum infection and age influence parasite growth inhibition mediated by IgG in Beninese infants.

Antibodies that impede the invasion of Plasmodium falciparum (P. falciparum) merozoites into erythrocytes play a critical role in anti-malarial immunity. The Growth Inhibition Assay (GIA) is an in vitro measure of the functional capacity of such antibodies to limit erythrocyte invasion and/or parasite growth. Up to now, it is unclear whether growth-inhibitory activity correlates with protection from clinical disease and there are inconsistent results from studies performed with GIA. Studies that have focused on the relationship between IgGs and their in vitro parasite Growth Inhibition Activity (GIAc) in infants aged less than two years old are rare. Here, we used clinical and parasitological data to precisely define symptomatic or asymptomatic infection with P. falciparum in groups of infants followed-up actively for 18 months post-natally. We quantified the levels of IgG1 and IgG3 directed to a panel of candidate P. falciparum vaccine antigens (AMA-1, MSP1, 2, 3 and GLURP) using ELISA and the functional activity of IgG was quantified using GIA. Data were then correlated with individuals' infection status. At 18 months of age, infants harbouring infections at the time of blood sampling had an average 19% less GIAc than those not infected (p=0.004, multivariate linear regression). GIAc decreased from 12 to 18 months of age (p=0.003, Wilcoxon matched pairs test). Antibody levels quantified at 18 months in infants were strongly correlated with their exposure to malarial infection, however GIAc was not correlated with malaria infectious status (asymptomatic and symptomatic groups). In conclusion, both infection status at blood draw and age influence parasite growth inhibition mediated by IgG in the GIA. Both factors must be taken into account when correlations between GIAc and anti-malarial protection or vaccine efficacy have to be made.

Comparative Analysis of Iron Homeostasis in Sub-Saharan African Children with Sickle Cell Disease and Their Unaffected Siblings.

Iron is an essential trace element subject to tight regulation to ensure adequate running of biological processes. In sub-Saharan Africa where hemoglobinopathies are common, iron homeostasis is likely to be impaired by these conditions. Here, we assessed and compared key serum proteins associated with iron metabolism between sub-Saharan African children with sickle cell disease (SCD) and their unaffected siblings. Complete blood counts and serum concentrations of four key proteins involved in iron regulation (ferritin, transferrin, sTfR, and hepcidin) were measured for 73 children with SCD and 68 healthy siblings in Benin, West Africa. We found significant differences in concentration of transferrin, sTfR, and ferritin between the two groups. Hepcidin concentrations were found at unusually high concentrations but did not differ among the two groups. We found a significant negative correlation between hepcidin levels and both MCH and MCV in the SCD group and report that sTfR concentrations show a correlation with MCV and MHC in opposite directions in the two groups. These results highlight the unusually high levels of hepcidin in the Beninese population and the patterns of differential iron homeostasis taking place under SCD status. These results lay the foundation for a systematic evaluation of the underlying mechanisms deregulating iron homeostasis in populations with SCD or high prevalence of iron deficiency.

Antimicrobial, antioxidant, toxicity and phytochemical assessment of extracts from Acmella uliginosa, a leafy-vegetable consumed in Bénin, West Africa.

BACKGROUND: Acmella uliginosa (Asteraceae) is a flowering plant whose leaves are consumed as a vegetable in Benin. They are also traditionally used as an antibiotic in the treatment of infectious diseases. To evaluate the therapeutic potential and toxicity effect of this leafy-vegetable, the antibacterial, antifungal, antioxidant activities and, toxicity and phytochemical constituents were investigated. METHODS: Dichloromethane, methanol and aqueous extracts of Acmella uliginosa were evaluated for their antimicrobial activity against six bacterial and six fungi strains. Antibacterial and antifungal activities were investigated by microdilution method and agar diffusion method respectively. Antioxidant activity was assessed using the 2,2-diphenyl-1-picryl-hydrazyl assay and phytochemical screening was carried out using standard procedures. Finally, oral acute toxicity at a dose of 2000 mg/kg was done according to the Organization for Economic Co-operation and Development guideline n° 423. RESULTS: The antibacterial activity was broad spectrum, inhibiting both Gram-positive and Gram-negative bacteria. The minimum inhibitory concentration ranged from 0.625 to 5 mg/ml. The antifungal evaluation show that all the extracts inhibited mycelial growth and sporulation of fungi with percentages of inhibition ranging from 9.39 to 75.67% and 22.04 to 99.77%, respectively. In DPPH radical scavenging assay, the effect on reducing free radicals increased in a dose dependent manner. The percentage of inhibition of DPPH ranged from 0.94 to 73.07%. Phytochemical screening revealed the presence of coumarin, flavonoid, naphtoquinone, anthracene derivative, saponin, lignan, triterpene and tannin. The dichloromethane and methanol extracts showed the best biological activities; they were also shown as the best extraction solvents of phytochemicals. In the acute toxicity evaluation, all animals were physically active and no deaths of rats were observed during the test. However, the aqueous extract promoted biochemical, hematological and histopathological alterations of treated rats at 2000 mg/kg body weight. CONCLUSION: A. uliginosa extracts contains antimicrobial, antioxidant agents and was not lethal for rats when ingested. However, according to the results obtained for biochemical, hematological, and histopathological analysis, caution is required regarding its consumption.

Lamin A/C deficiency is an independent risk factor for cervical cancer.

BACKGROUND: In the past, cervical cancer has been linked to Human Papilloma Virus (HPV) infection. Previously, we found that pre-neoplastic breast and ovarian lesions may be associated with lamin A/C deficiency, resulting in abnormal nuclear morphologies and chromosomal instability. Ultimately, these phenomena are thought to lead to cancer. Here, we assessed lamin A/C deficiency as an indicator for the risk to develop cervical cancer. METHODS: The expression of lamin A/C was assessed by Western blotting in cervical uterine smears (CUS) of 76 adult women from Benin concomitant with nuclear morphology assessment and HPV genotyping using microscopy and PCR-based assays, respectively. In vitro analyses were performed to uncover the mechanism underlying lamin A/C expression alterations observed in vivo. The presence of cervical intra-epithelial neoplasia (CIN) was assessed by colposcopy. RESULTS: Normal lamin A/C expression (group A) was observed in 39% of the CUS, weak lamin A/C expression (group B) was observed in 28% of the CUS and no lamin A/C expression (group C) was observed in 33% of the CUS tested. Infection with oncogenic HPV was found to be significantly higher in group C (36%) than in groups A (17%) and B (14%). Two years after our first assessment, CIN was observed in 20% of the women in group C. The in vitro application of either a histone deacetylase inhibitor (trichostatin) or a protein kinase inhibitor (staurosporine) was found to restore lamin A/C expression in cervical cancer-derived cells. CONCLUSION: Lamin A/C deficiency may serve as an independent risk factor for CIN development and as an indicator for preventive therapy in cervical cancer.

Diversity, Physicochemical and Technological Characterization of Elite Cassava (Manihot esculenta Crantz) Cultivars of Bantè, a District of Central Benin.

Cassava is one of the staple food crops contributing significantly to food and nutrition security in Benin. This study aimed to assess the diversity of the elite cassava cultivars of Bantè district, determine the physicochemical properties of the most preferred ones as well as the sensory attributes of their major derived products (gari and tapioca), and compare them with the farmers' and processors' perception on their technological qualities. The ethnobotanical investigation revealed existence of 40 cultivars including 9 elites that were further classified into three groups based on agronomics and technological and culinary properties. Clustered together, cultivars Idilèrou, Monlèkangan, and Odohoungbo characterized by low fiber content, high yield of gari and tapioca, and good in-ground postmaturity storage were the most preferred ones. Their physicochemical analysis revealed good rate of dry matters (39.8% to 41.13%), starch (24.47% to 25.5%) and total sugars (39.46% to 41.13%), low fiber (0.80% to 1.02%), and cyanide (50 mg/kg) contents. The sensory analysis of their gari and tapioca revealed very well appreciated (taste, color, and texture) products by the consumers. The confirmation by scientific analysis of the farmers' perception on qualities of the most preferred cultivars indicated that they have good knowledge of their materials.

Genetic divergence in northern Benin sorghum (Sorghum bicolor L. Moench) landraces as revealed by agromorphological traits and selection of candidate genotypes.

Sorghum [Sorghum bicolor (L.) Moench] is an important staple food crop in northern Benin. In order to assess its diversity in Benin, 142 accessions of landraces collected from Northern Benin were grown in Central Benin and characterised using 10 qualitative and 14 quantitative agromorphological traits. High variability among both qualitative and quantitative traits was observed. Grain yield (0.72-10.57 tons/ha), panicle weight (15-215.95 g), days to 50% flowering (57-200 days), and plant height (153.27-636.5 cm) were among traits that exhibited broader variability. Correlations between quantitative traits were determined. Grain yield for instance exhibited highly positive association with panicle weight (r = 0.901, P = 0.000) and 100 seed weight (r = 0.247, P = 0.000). UPGMA cluster analysis classified the 142 accessions into 89 morphotypes. Based on multivariate analysis, twenty promising sorghum genotypes were selected. Among them, AT41, AT14, and AT29 showed early maturity (57 to 66 days to 50% flowering), high grain yields (4.85 to 7.85 tons/ha), and shorter plant height (153.27 to 180.37 cm). The results obtained will help enhancing sorghum production and diversity and developing new varieties that will be better adapted to the current soil and climate conditions in Benin.

Antibiotic resistance and genotype of beta-lactamase producing Escherichia coli in nosocomial infections in Cotonou, Benin.

BACKGROUND: Beta lactams are the most commonly used group of antimicrobials worldwide. The presence of extended-spectrum lactamases (ESBL) affects significantly the treatment of infections due to multidrug resistant strains of gram-negative bacilli. The aim of this study was to characterize the beta-lactamase resistance genes in Escherichia coli isolated from nosocomial infections in Cotonou, Benin. METHODS: Escherichia coli strains were isolated from various biological samples such as urine, pus, vaginal swab, sperm, blood, spinal fluid and catheter. Isolated bacteria were submitted to eleven usual antibiotics, using disc diffusion method according to NCCLS criteria, for resistance analysis. Beta-lactamase production was determined by an acidimetric method with benzylpenicillin. Microbiological characterization of ESBL enzymes was done by double disc synergy test and the resistance genes TEM and SHV were screened by specific PCR. RESULTS: ESBL phenotype was detected in 29 isolates (35.5%). The most active antibiotic was imipenem (96.4% as susceptibility rate) followed by ceftriaxone (58.3%) and gentamicin (54.8%). High resistance rates were observed with amoxicillin (92.8%), ampicillin (94%) and trimethoprim/sulfamethoxazole (85.7%). The genotype TEM was predominant in ESBL and non ESBL isolates with respectively 72.4% and 80%. SHV-type beta-lactamase genes occurred in 24.1% ESBL strains and in 18.1% of non ESBL isolates. CONCLUSION: This study revealed the presence of ESBL producing Eschericiha coli in Cotonou. It demonstrated also high resistance rate to antibiotics commonly used for infections treatment. Continuous monitoring and judicious antibiotic usage are required.

The ears of the African elephant: unexpected high seroprevalence of Plasmodium ovale and Plasmodium malariae in healthy populations in Western Africa.

BACKGROUND: Malaria Is A Life-Threatening Pathology In Africa. Plasmodium Falciparum And Plasmodium Vivax Attract The Most Focus Because Of Their High Prevalence And Mortality. Knowledge About The Prevalence Of The Cryptic Pathogens Plasmodium Ovale And Plasmodium Malariae Is Limited. Thanks To Recombinant Tools, Their Seroprevalence Was Measured For The First Time, As Well As The Prevalence Of Mixed Infections In A Malaria-Asymptomatic Population In Benin, A Malaria-Endemic Country. METHODS: A Panel Of 1,235 Blood Donations Collected Over Ten Months In Benin Was Used For Validation Of The Recombinant Tools. Recombinant P. Falciparum, P. Malariae, P. Ovale MSP1, And P. Falciparum AMA1 Were Engineered And Validated On A Biobank With Malaria-Infected Patients (N = 144) Using A Species-Speific ELISA Test (Recelisa). Results Were Compared To An ELISA Using A Native P. Falciparum Antigen (NatELISA). RESULTS: Among Microscopically Negative African Blood Donors, 85% (1,050/1,235) Present Antibodies Directed To Native P. Falciparum, 94.4% (1,166/1,235) To rPfMSP1 And rPfAMA1, 56.8% (702/1,235) To rPoMSP1, 67.5% (834/1235) To rPmMSP1 And 45.3% Of The Malaria Seropositive Population Had Antibodies Recognizing The Three Species. CONCLUSION: A High Rate Of Antibodies Against P. Ovale And P. Malariae Was Found In Asymptomatic Blood Donors. The Proportion Of Mixed Infections Involving Three Species Was Also Unexpected. These Data Suggest That Determining Seroprevalence For These Cryptic Species Is An Appropriate Tool To Estimate Their Incidence, At The Eve Of Upcoming Anti-P. Falciparum Vaccination Campaigns.

Genomic architecture of sickle cell disease in West African children.

Sickle cell disease (SCD) is a congenital blood disease, affecting predominantly children from sub-Saharan Africa, but also populations world-wide. Although the causal mutation of SCD is known, the sources of clinical variability of SCD remain poorly understood, with only a few highly heritable traits associated with SCD having been identified. Phenotypic heterogeneity in the clinical expression of SCD is problematic for follow-up (FU), management, and treatment of patients. Here we used the joint analysis of gene expression and whole genome genotyping data to identify the genetic regulatory effects contributing to gene expression variation among groups of patients exhibiting clinical variability, as well as unaffected siblings, in Benin, West Africa. We characterized and replicated patterns of whole blood gene expression variation within and between SCD patients at entry to clinic, as well as in follow-up programs. We present a global map of genes involved in the disease through analysis of whole blood sampled from the cohort. Genome-wide association mapping of gene expression revealed 390 peak genome-wide significant expression SNPs (eSNPs) and 6 significant eSNP-by-clinical status interaction effects. The strong modulation of the transcriptome implicates pathways affecting core circulating cell functions and shows how genotypic regulatory variation likely contributes to the clinical variation observed in SCD.

Proinflammatory effects and oxidative stress within human bronchial epithelial cells exposed to atmospheric particulate matter (PM(2.5) and PM(>2.5)) collected from Cotonou, Benin.

After particulate matter (PM) collection in Cotonou (Benin), a complete physicochemical characterization of PM2.5 and PM>2.5 was led. Then, their adverse health effects were evaluated by using in vitro culture of human lung cells. BEAS-2B (bronchial epithelial cells) were intoxicated during short-term exposure at increasing PM concentrations (1.5-96 µg/cm(2)) to determine global cytotoxicity. Hence, cells were exposed to 3 and 12 µg/cm(2) to investigate the potential biological imbalance generated by PM toxicity. Our findings showed the ability of both PM to induce oxidative stress and to cause inflammatory cytokines/chemokines gene expression and secretion. Furthermore, PM were able to induce gene expression of enzymes involved in the xenobiotic metabolism pathway. Strong correlations between gene expression of metabolizing enzymes, proinflammatory responses and cell cycle alteration were found, as well as between proinflammatory responses and cell viability. Stress oxidant parameters were highly correlated with expression and protein secretion of inflammatory mediators.

Is a Plasmodium lactate dehydrogenase (pLDH) enzyme-linked immunosorbent (ELISA)-based assay a valid tool for detecting risky malaria blood donations in Africa?

BACKGROUND: Malaria is a leading cause of mortality in southern Benin. The main causative agent, Plasmodium falciparum, poses a threat on critical transfusions in pregnant women and children. This study's objective was to compare the performance of different malaria screening methods in blood donors in southern Benin, a malaria-endemic country. METHODS: Blood from 2,515 voluntary blood donors in Benin was collected over a period of 10 months in ethylenediaminetetraacetic acid (EDTA) tubes, which were then classified according to extraction time: long rainy season, short dry season, short rainy season, and long dry season. Microscopic examination was used to count parasites. Parasite density (PD) was expressed as the number of parasites per µL of blood. Pan Plasmodium pLDH detection was assessed by an ELISA-malaria antigen test. Using crude soluble P. falciparum antigens, an ELISA-malaria antibody test detected anti-Plasmodium antibodies. RESULTS: Among the 2,515 blood donors (2,025 males and 488 females) screened, the rate of asymptomatic Plasmodium carriage was 295/2,515 (11.72%, 95% CI: 10.5-13.1%). Males had a higher infection rate (12.4%) than did females (8.8%). Parasite density was very low: between seven and100 parasites per µL of blood was reported in 80% of donors with parasitaemia. Three Plasmodium species were diagnosed: P. falciparum in 280/295 patients (95.0%), Plasmodium malariae in 14/295 (5.0%), and Plasmodium ovale in 1/295 (0.34%). Malaria prevalence in donors was higher during the rainy seasons (13.7%) compared with the dry seasons (9.9%). The use of a highly sensitive assay enabled pan Plasmodium pLDH detection in 966/2,515 (38.4%, 95% CI: 36.5%-40.3%). Malaria antibody prevalence was 1,859/2,515 (73.9%, 95% CI: 72.16-75.6%). Donors' antigenaemia and antibody levels varied significantly (P <0.05) over the course of the four seasons. The highest antigenaemia rate 323/630 (51.3%), was observed during the short rainy season, while the highest antibody prevalence, 751/886 (84.7%), was recorded during the long dry season. CONCLUSION: Blood donations infected with Plasmodium can transmit malaria to donation recipients. Malaria diagnostic methods are currently available, but the feasibility criteria for mass screening in endemic areas become preponderant. Detection of the pLDH antigen seems to be an adequate screening tool in endemic areas, for this antigen indicates parasite presence. Routine screening of all donated blood would prevent infected blood donations and reduce P. falciparum transmission in critical patients, such as children and pregnant women. This tool would also decrease medical prophylaxis in donation recipients and contribute to lower Plasmodium resistance.

Evidence for additive and interaction effects of host genotype and infection in malaria.

The host mechanisms responsible for protection against malaria remain poorly understood, with only a few protective genetic effects mapped in humans. Here, we characterize a host-specific genome-wide signature in whole-blood transcriptomes of Plasmodium falciparum-infected West African children and report a demonstration of genotype-by-infection interactions in vivo. Several associations involve transcripts sensitive to infection and implicate complement system, antigen processing and presentation, and T-cell activation (i.e., SLC39A8, C3AR1, FCGR3B, RAD21, RETN, LRRC25, SLC3A2, and TAPBP), including one association that validated a genome-wide association candidate gene (SCO1), implicating binding variation within a noncoding regulatory element. Gene expression profiles in mice infected with Plasmodium chabaudi revealed and validated similar responses and highlighted specific pathways and genes that are likely important responders in both hosts. These results suggest that host variation and its interplay with infection affect children's ability to cope with infection and suggest a polygenic model mounted at the transcriptional level for susceptibility.