Silver nanoparticle biosynthesis utilizing Ocimum kilimandscharicum leaf extract and assessment of its antibacterial activity against certain chosen bacteria.

The use of plants in the biological production of silver nanoparticles for antibacterial applications is a growing field of research. In the current work, we formulated Ocimum kilimandscharicum extracts using silver nanoparticles, and evaluated its potential antibacterial activity. Aqueous and methanol plant extracts were used to reduce silver nitrate at different time intervals (30 to 150 minutes) and pH (2 to 11). The UV-visible absorption spectrum recorded for methanol and aqueous extracts revealed a successful synthesis of AgNPs for methanol and aqueous extracts. The antimicrobial activity of the AgNPs was evaluated against Escherichia coli ATCC 25922, Salmonella choleraesuius ATCC 10708, and Staphylococcus aureus ATCC 25923 The best inhibition zone for the methanol and aqueous-mediated AgNPs, ranging from 12 ± 1 to 16 ± 1mm. Additionally, the methanol and aqueous extract silver nanoparticles had the same Minimum Inhibitory Concentration (6.25 ± 0.00 mg/ml), whereas the Minimum Bactericidal Concentrations were 12.5 ± 0.00 and 25 ± 0.00 mg/ml, respectively. The highest inhibition zone of 16 ± 1 mm was observed against Salmonella choleraesuius with 50 ± 0.00 mg/ml aqueous silver nanoparticles. The results show that the silver nanoparticles made with Ocimum kilimandscharicum have antibacterial action against those microorganisms.

Genomic characterization of SARS-CoV-2 in Guinea, West Africa.

SARS-CoV-2 has claimed several million lives since its emergence in late 2019. The ongoing evolution of the virus has resulted in the periodic emergence of new viral variants with distinct fitness advantages, including enhanced transmission and immune escape. While several SARS-CoV-2 variants of concern trace their origins back to the African continent-including Beta, Eta, and Omicron-most countries in Africa remain under-sampled in global genomic surveillance efforts. In an effort to begin filling these knowledge gaps, we conducted retrospective viral genomic surveillance in Guinea from October 2020 to August 2021. We found that SARS-CoV-2 clades 20A, 20B, and 20C dominated throughout 2020 until the coincident emergence of the Alpha and Eta variants of concern in January 2021. The Alpha variant remained dominant throughout early 2021 until the arrival of the Delta variant in July. Surprisingly, despite the small sample size of our study, we also found the persistence of the early SARS-CoV-2 clade 19B as late as April 2021. Together, these data help fill in our understanding of the SARS-CoV-2 population dynamics in West Africa early in the COVID-19 pandemic.

Phytochemical Screening and GC-MS Analysis of Methanolic and Aqueous Extracts of Ocimum kilimandscharicum Leaves.

Kenyans have long utilized Ocimum kilimandscharicum, an East African permanent evergreen plant, to treat measles, stomachaches, diarrhea, mosquito bites (anti-insect), congested chest, cough, and colds. Using conventional qualitative and quantitative techniques, this study was done to identify the secondary metabolites in O. kilimandscharicum leaf extracts. The chemical content of the crude extracts from the leaves of O. kilimandscharicum has also been investigated and characterized using gas chromatography-mass spectrometry (GC-MS). By using a 1:20 dilution in methanol, in cold maceration, a fine powder of O. kilimandscharicum was first extracted then filtered and concentrated after 72 h utilizing a rotary evaporator. By using also a 1:20 dilution in water at 80 °C, a fine powder of O. kilimandscharicum was extracted and then filtrated and lyophilized 1 h later. Each extract underwent further gas chromatography-mass spectrometry testing. We found that both extracts contain secondary metabolites such as alkaloids, phenolics, flavonoids, saponins, and tannins. However, the overall amount of phytochemicals in each solvent varied significantly. Total phenolics contents (TPCs) were 5.6 ± 1.20 and 10.8 ± 1.00 mg, total flavonoid contents (TFCs) were 8.2 ± 0.4 and 39.6 ± 2.2 mg, total tannin contents (TTCs) were 0 ± 0.00 and 10.5 ± 0.4 mg, the total alkaloid content (TAC) was 49.2 ± 0.40%, and the total saponin content (TSC) was 38 ± 2.00%. Additionally the gas chromatography-mass spectrometry, revealed a number of high- and low-molecular-weight bioactive molecules at various concentrations for each extract. We also found an inhibitory effect on adhP and chbR gene expression of Staphylococcus aureus and Salmonella choleraesuius, respectively. Hence, these chemicals could potentially have a biological and pharmacological significance. Therefore, the discovery of many physiologically active chemicals in the leaf extracts of O. kilimandscharicum justifies future biological and pharmaceutical research.

Current clinical presentations of AIDS dementia in a tropical environment: study of 26 observations in the neurology department of the University Hospital of Conakry.

INTRODUCTION: In sub-Saharan Africa (SSA), the clinical and progressive diagnostic certainty of AIDS dementia is difficult to establish due to under-medicalization and delays in consultation and especially the diversity of etiologies of demented states. MATERIAL AND METHODS: We carried out a retrospective study of 196 patients hospitalized for dementia syndrome between 2016 and 2021 in the neurology department of the University Hospital of Conakry. The criteria labeled in this study are those retained by the DSM-IV and the classification of the American Academy of Neurology (AAN) developed in accordance with the WHO. RESULTS: HIV etiology was identified in patients aged 44-67 years (17 women and 19 men). The clinical picture was dominated by severe cognitive disorders, slowed ideation, memory disorders and reduced motor skills associated with personality changes. Neurological examination revealed dysphoric disorders in most patients, sphincter abnormalities in 13 cases and labio-lingual tremor in 11 cases. Diagnosis was based on positive serological tests for HIV1 antibodies (25 cases) and HIV2 antibodies (1 case) using the Elisa and Western blot techniques, and the presence of discretely hypercellular CSF. Magnetic resonance imaging contributed to the diagnosis, showing diffuse white matter abnormalities with hyper signals on T2-weighted or FLAIR sequences. CONCLUSION: This study shows a non-stereotype clinical picture of AIDS dementia requiring a differential diagnosis with other infectious dementias. These results are important for the therapeutic and prognostic discussion.

Relationship between patient sex and anatomical sites of extrapulmonary tuberculosis in Mali.

Background: Contribution of host factors in mediating susceptibility to extrapulmonary tuberculosis is not well understood. Objective: To examine the influence of patient sex on anatomical localization of extrapulmonary tuberculosis. Methods: We conducted a retrospective cross-sectional study in Mali, West Africa. Hospital records of 1,304 suspected cases of extrapulmonary tuberculosis, available in TB Registry of a tertiary tuberculosis referral center from 2019 to 2021, were examined. Results: A total of 1,012 (77.6%) were confirmed to have extrapulmonary tuberculosis with a male to female ratio of 1.59:1. Four clinical forms of EPTB predominated, namely pleural (40.4%), osteoarticular (29.8%), lymph node (12.5%), and abdominal TB (10.3%). We found sex-based differences in anatomical localization of extrapulmonary tuberculosis, with males more likely than females to have pleural TB (OR: 1.51; 95% CI [1.16 to 1.98]). Conversely, being male was associated with 43% and 41% lower odds of having lymph node and abdominal TB, respectively (OR: 0.57 and 0.59). Conclusion: Anatomical sites of extrapulmonary tuberculosis differ by sex with pleural TB being associated with male sex while lymph node and abdominal TB are predominately associated with female sex. Future studies are warranted to understand the role of sex in mediating anatomical site preference of tuberculosis.

Use of light-emitting diode fluorescence microscopy to detect acid-fast bacilli in sputum as proficient alternative tool in the diagnosis of pulmonary tuberculosis in countries with limited resource settings.

Background: Despite recent advances in the development of more sensitive technologies for the diagnosis of tuberculosis (TB), in resource-limited settings, the diagnosis continues to rely on sputum smear microscopy. This is because smear microscopy is simple, cost-efficient and the most accessible tool for the diagnosis of TB. Our study evaluated the performance of light-emitting diode fluorescence microscopy (LED-FM) using auramine/rhodamine (auramine) and the fluorescein di-acetate (FDA) vital stain in the diagnostic of pulmonary TB in Bamako, Mali. Methods: Sputum smear microscopy was conducted using the FDA and auramine/rhodamine staining procedures on fresh samples using LED-FM to evaluate the Mycobacterium TB (MTB) metabolic activity and to predict contagiousness. Mycobacterial culture assay was utilized as a gold standard method. Results: Out of 1401 TB suspected patients, 1354 (96.65%) were retrieved from database, which were MTB complex culture positive, and 47 (3.40%) were culture negative (no mycobacterial growth observed). Out of the 1354 included patients, 1343 (95.86%), were acid-fast bacillus (AFB) positive after direct FDA staining, 1352 (96.50%) AFB positive after direct Auramine, and 1354 (96.65%) AFB positive with indirect auramine after digestion and centrifugation. Overall, the FDA staining method has a sensitivity of 98.82%, while the sensitivity of Auramine with direct observation was 99.48%, and 99.56% with the indirect examination. Conclusion: This study showed that, using fresh sputum both auramine/rhodamine and FDA are highly sensitive methods in diagnosing pulmonary TB and could be easily used in countries with limited resource settings.

Prevalence and Clinical Relevance of Schistosoma mansoni Co-Infection with Mycobacterium tuberculosis: A Systematic Literature Review.

Tuberculosis disease stands for the second leading cause of death worldwide after COVID-19, most active tuberculosis cases result from the reactivation of latent TB infection through impairment of immune response. Several factors are known to sustain that process. Schistosoma mansoni, a parasite of the helminth genus that possesses switching power from an immune profile type Th1 to Th2 that favors reactivation of latent TB bacteria. The aim of the study was to assess the prevalence of the co-infection between the two endemic infections. Systematic literature was contacted at the University Clinical Research Center at the University of Sciences, Techniques, and Technologies of Bamako in Mali. Original articles were included, and full texts were reviewed to assess the prevalence and better understand the immunological changes that occur during the co-infection. In total, 3530 original articles were retrieved through database search, 53 were included in the qualitative analysis, and data from 10 were included in the meta-analysis. Prevalence of the co-infection ranged from 4% to 34% in the literature. Most of the articles reported that immunity against infection with helminth parasite and more specifically Schistosoma mansoni infection enhances latent TB reactivation through Th1/Th2. In sum, the impact of Schistosoma mansoni co-infection with Mycobacterium tuberculosis is under-investigated. Understanding the role of this endemic tropical parasite as a contributing factor to TB epidemiology and burden could help integrate its elimination as one of the strategies to achieve the END-TB objectives by the year 2035.

Sex Differences in Active Pulmonary Tuberculosis Outcomes in Mali, West Africa.

Men and women often respond differently to infectious diseases and their treatments. Tuberculosis (TB) is a life-threatening communicable disease that affects more men than women globally. Whether male sex is an independent risk factor for unfavorable TB outcomes, however, has not been rigorously investigated in an African context, where individuals are likely exposed to different microbial and environmental factors. We analyzed data collected from a cohort study in Mali by focusing on newly diagnosed active pulmonary TB individuals who were treatment naive. We gathered baseline demographic, clinical, and microbiologic characteristics before treatment initiation and also at three time points during treatment. More males than females were affected with TB, as evidenced by a male-to-female ratio of 2.4:1. In addition, at baseline, males had a significantly higher bacterial count and shorter time to culture positivity as compared with females. Male sex was associated with lower smear negativity rate after 2 months of treatment also known as the intensive phase of treatment, but not at later time points. There was no relationship between patients' sex and mortality from any cause during treatment. This study suggests that sex-based differences in TB outcomes exist, with sex-specific effects on disease outcomes being more pronounced before treatment initiation and during the intensive phase of treatment rather than at later phases of treatment.

The G Protein-Coupled Serotonin 1A Receptor Augments Protein Kinase Cε-Mediated Neurogenesis in Neonatal Mouse Hippocampus-PKCε-Mediated Signaling in the Early Hippocampus.

The neurotransmitter serotonin (5-HT) plays an important role in mood disorders. It has been demonstrated that 5-HT signaling through 5-HT1A receptors (5-HT1A-R) is crucial for early postnatal hippocampal development and later-life behavior. Although this suggests that 5-HT1A-R signaling regulates early brain development, the mechanistic underpinnings of this process have remained unclear. Here we show that stimulation of the 5-HT1A-R at postnatal day 6 (P6) by intrahippocampal infusion of the agonist 8-OH-DPAT (D) causes signaling through protein kinase Cε (PKCε) and extracellular receptor activated kinase ½ (ERK1/2) to boost neuroblast proliferation in the dentate gyrus (DG), as displayed by an increase in bromodeoxy-uridine (BrdU), doublecortin (DCX) double-positive cells. This boost in neuroproliferation was eliminated in mice treated with D in the presence of a 5-HT1A-R antagonist (WAY100635), a selective PKCε inhibitor, or an ERK1/2-kinase (MEK) inhibitor (U0126). It is believed that hippocampal neuro-progenitors undergoing neonatal proliferation subsequently become postmitotic and enter the synaptogenesis phase. Double-staining with antibodies against bromodeoxyuridine (BrdU) and neuronal nuclear protein (NeuN) confirmed that 5-HT1A-R → PKCε → ERK1/2-mediated boosted neuroproliferation at P6 also leads to an increase in BrdU-labeled granular neurons at P36. This 5-HT1A-R-mediated increase in mature neurons was unlikely due to suppressed apoptosis, because terminal deoxynucleotidyl transferase dUTP nick-end labeling analysis showed no difference in DNA terminal labeling between vehicle and 8-OH-DPAT-infused mice. Therefore, 5-HT1A-R signaling through PKCε may play an important role in micro-neurogenesis in the DG at P6, following which many of these new-born neuroprogenitors develop into mature neurons.

Molecular epidemiology and genetic diversity of Mycobacterium tuberculosis complex in referral health centers of Bamako, Mali: What is new?

BACKGROUND AND AIMS: Tuberculosis (TB) remains an important global health issue worldwide. Despite this scourge threatening many human lives, especially in developing countries, thus far, no advanced molecular epidemiology study using recent and more accurate tools has been conducted in Mali. Therefore, this study aimed to use variable-number tandem repeats of mycobacterial interspersed repetitive units (MIRU-VNTR) technology coupled with the spoligotyping method to accurately determine the hot spots and establish the epidemiological transmission links of TB in Bamako, Mali. METHODS: In a cross-sectional study, 245 isolates of Mycobacterium tuberculosis complex (MTBC) were characterized using spoligotyping and MIRU-VNTR, and an epidemiological investigation was conducted. RESULTS: Of the 245 isolates, 184 (75.1%) were formally identified. The most widespread strain was the Cameroon strain (83; 45.1%). Eight major clusters were identified: Ghana (27; 14.7%), West African 2 (22; 12%), Haarlem (13; 7.1%), H37Rv (t) (8; 4.3%), Latin American Mediterranean (8; 4.3%), and Uganda I and II (6; 3.3%). Statistical analysis showed a significant difference between lineages from the respective referral health centers of Bamako, Mali (P = 0.01). CONCLUSION: This study establishes, for the first time, an accurate spatial distribution of circulating MTB strains in Bamako, Mali. The data was used to identify strains and "hot spots" causing TB infection and can also be used for more targeted public health responses, particularly for hot spots of drug-resistant strains.

Nasopharyngeal Viral and Bacterial Co-Detection among Children from Low- and Middle-Income Countries with and without Pneumonia.

The role of microbial coinfection in the pathogenesis of pneumonia in children is not well known. The aim of this work was to describe the prevalence of microorganism co-detection in nasopharyngeal samples (NPS) of pneumonia cases and control subjects and to study the potential association between nasopharyngeal microorganism co-detection and pneumonia. A case-control study was carried out from 2010 to 2014 in nine study sites located in low- or middle-income countries. The data from 888 children under 5 years of age with pneumonia (cases) and 870 children under 5 without pneumonia (controls) were analyzed. Nasopharyngeal samples were collected; reverse transcription polymerase chain reaction (RT-PCR) enabled the detection of five bacteria and 19 viruses. Multiple, mixed-effects logistic regression modeling was undertaken to evaluate the association between microorganism co-detection and pneumonia. A single Streptococcus pneumoniae colonization was observed in 15.2% of the controls and 10.1% of the cases (P = 0.001), whereas S. pneumoniae and a single virus co-detection was observed in 33.3% of the cases and in 14.6% of the controls (P < 0.001). Co-detections with rhinovirus, respiratory syncytial virus, parainfluenza virus, human metapneumovirus, and influenza virus were more frequent in the cases compared with the controls (P < 0.001) and were significantly associated with pneumonia in multiple regression analysis. The proportion of single virus detection without bacterial co-detection was not different between cases and controls (13.6% versus 11.3%, P = 0.13). This study suggests that coinfection of S. pneumoniae and certain viruses may play a role in the pathophysiology of pneumonia in children.

High SARS-CoV-2 Seroprevalence among Healthcare Workers in Bamako, Mali.

In Mali, a country in West Africa, cumulative confirmed COVID-19 cases and deaths among healthcare workers (HCWs) remain enigmatically low, despite a series of waves, circulation of SARS-CoV-2 variants, the country's weak healthcare system, and a general lack of adherence to public health mitigation measures. The goal of the study was to determine whether exposure is important by assessing the seroprevalence of anti-SARS-CoV-2 IgG antibodies in HCWs. The study was conducted between November 2020 and June 2021. HCWs in the major hospitals where COVID-19 cases were being cared for in the capital city, Bamako, Mali, were recruited. During the study period, vaccinations were not yet available. The ELISA of the IgG against the spike protein was optimized and quantitatively measured. A total of 240 HCWs were enrolled in the study, of which seropositivity was observed in 147 cases (61.8%). A continuous increase in the seropositivity was observed, over time, during the study period, from 50% at the beginning to 70% at the end of the study. HCWs who provided direct care to COVID-19 patients and were potentially highly exposed did not have the highest seropositivity rate. Vulnerable HCWs with comorbidities such as obesity, diabetes, and asthma had even higher seropositivity rates at 77.8%, 75.0%, and 66.7%, respectively. Overall, HCWs had high SARS-CoV-2 seroprevalence, likely reflecting a "herd" immunity level, which could be protective at some degrees. These data suggest that the low number of cases and deaths among HCWs in Mali is not due to a lack of occupational exposure to the virus but rather related to other factors that need to be investigated.

Antituberculosis Therapy and Gut Microbiota: Review of Potential Host Microbiota Directed-Therapies.

Tuberculosis (TB) remains a major public health concern with millions of deaths every year. The overlap with HIV infections, long treatment duration, and the emergence of drug resistance are significant obstacles to the control of the disease. Indeed, the standard first-line regimen TB treatment takes at least six months and even longer for the second-line therapy, resulting in relapses, drug resistance and re-infections. Many recent reports have also shown prolonged and significant damage of the gut microbial community (dysbiosis) from anti-TB drugs that can detrimentally persist several months after the cessation of treatment and could lead to the impairment of the immune response, and thus re-infections and drug resistance. A proposed strategy for shortening the treatment duration is thus to apply corrective measures to the dysbiosis for a faster bacterial clearance and a better treatment outcome. In this review, we will study the role of the gut microbiota in both TB infection and treatment, and its potential link with treatment duration. We will also discuss, the new concept of "Host Microbiota Directed-Therapies (HMDT)" as a potential adjunctive strategy to improve the treatment effectiveness, reduce its duration and or prevent relapses. These strategies include the use of probiotics, prebiotics, gut microbiota transfer, and other strategies. Application of this innovative solution could lead to HMDT as an adjunctive tool to shorten TB treatment, which will have enormous public health impacts for the End TB Strategy worldwide.

Development and clinical evaluation of a new multiplex PCR assay for a simultaneous diagnosis of tuberculous and nontuberculous mycobacteria.

BACKGROUND: The prevalence of non-tuberculous mycobacteria (NTM) has been increasing worldwide in both developed and developing countries. NTM infection is clinically indistinguishable from tuberculosis and therefore poses significant challenges in patient management, especially in patients chronically treated for pulmonary TB. In this study, we evaluated a new highly sensitive Multiplex MTB/NTM assay that can differentiate M. tuberculosis complex (MTBC) from all NTM, including the treatable and most common NTM, M. avium complex (MAC). METHODS: We developed and optimized a new open- Multiplex MTB/NTM assay with two gene-targets for MTBC (IS6110/senX3-regX3) and two targets for MAC (IS1311/DT1) with samples spiked with stored strains and testing 20 replicates. Patients with presumptive TB and NTM were enrolled at the Respiratory Disease Department of The University Teaching Hospital of Point G, in Mali. FINDINGS: In the development stage, the new assay showed a high analytic performance with 100% detections of MTBC and MAC at only 5 colony forming units (CFUs). Overall, without the treatment failure cases, the Multiplex assay and the Xpert showed a sensitivity, specificity, PPV and NPV of 83·3% [66·4-92·6], 96·6% [88·6-99·0], 92·5% [82·3-96·5] and 92·2% [82·7-96·5] and the Xpert had values of 96·7% [83·3-99·4], 80·0% [68·2-88·1], 70·7 [55·5-82·3] and 97·9% [89·3-99·6], respectively. The Multiplex assay successfully detected all (5/5) the MAC cases. INTERPRETATION: Our new Multiplex assay demonstrates better specificity than Xpert for all group studied, in addition to detecting potential NTM cases. The assay could therefore complement the widely used Xpert assay and enhance discrimination of TB and NTM infections. FUNDING: This work was supported by the National Institutes of Health (R03AI137674, U54EB027049, D43TW010350 and UM1AI069471) and Northwestern University's Institute for Global Health Catalyzer Fund.

An oral history of medical laboratory development in francophone West African countries.

BACKGROUND: Underdeveloped and underused medical laboratories in sub-Saharan Africa negatively affect the diagnosis and appropriate treatment of ailments. OBJECTIVE: We identified political, disease-related and socio-economic factors that have shaped the laboratory sector in Senegal, Mali and Burkina Faso to inform laboratory-strengthening programmes. METHODS: We searched peer-reviewed and grey literature from February 2015 to December 2018 on laboratory and health systems development from colonial times to the present and conducted in-depth interviews with 73 key informants involved in (inter)national health or laboratory policy, organisation, practice or training. This article depended on the key informants' accounts due to the paucity of literature on laboratory development in francophone West African countries. Literature and interview findings were triangulated and are presented chronologically. RESULTS: Until around 1990 there were a few disease-specific research laboratories; only the larger hospitals and district health facilities housed a rudimentary laboratory. The 1990s brought the advent of donor-dictated, vertical, endemic and epidemic disease programmes and laboratories. Despite decentralising from the national level to the regional and district levels, these vertical laboratory programmes biased national health resource allocation deleteriously neglecting the development of the horizontal, general-health laboratory. After the year 2000, the general-health laboratory system received more attention when, influenced by the World Health Organization, national networks and (sub-)directorates of laboratories were installed. CONCLUSION: To advance national general healthcare, as opposed to disease-specific healthcare, national laboratory directors and experts in general laboratory development should be consulted when national policies are made with potential laboratory donors.

Antennal Enriched Odorant Binding Proteins Are Required for Odor Communication in Glossina f. fuscipes.

Olfaction is orchestrated at different stages and involves various proteins at each step. For example, odorant-binding proteins (OBPs) are soluble proteins found in sensillum lymph that might encounter odorants before reaching the odorant receptors. In tsetse flies, the function of OBPs in olfaction is less understood. Here, we investigated the role of OBPs in Glossina fuscipes fuscipes olfaction, the main vector of sleeping sickness, using multidisciplinary approaches. Our tissue expression study demonstrated that GffLush was conserved in legs and antenna in both sexes, whereas GffObp44 and GffObp69 were expressed in the legs but absent in the antenna. GffObp99 was absent in the female antenna but expressed in the male antenna. Short odorant exposure induced a fast alteration in the transcription of OBP genes. Furthermore, we successfully silenced a specific OBP expressed in the antenna via dsRNAi feeding to decipher its function. We found that silencing OBPs that interact with 1-octen-3-ol significantly abolished flies' attraction to 1-octen-3-ol, a known attractant for tsetse fly. However, OBPs that demonstrated a weak interaction with 1-octen-3-ol did not affect the behavioral response, even though it was successfully silenced. Thus, OBPs' selective interaction with ligands, their expression in the antenna and their significant impact on behavior when silenced demonstrated their direct involvement in olfaction.

Short Communication: Genetic Variation in Human IL10 Proximal Promoter and Susceptibility to HIV-1 Infection in Mali, West Africa.

It is now recognized that to fully understand the role of host genetic variation on susceptibility to HIV-1 infection, investigations must be extended to African populations. We sought to determine if genetic variation in IL10 are associated with HIV-1 infection in a West African cohort in Mali. HIV-infected and -uninfected individuals were genotyped for three common single nucleotide polymorphisms (SNPs) located at positions -592 (C/A), -819 (C/T), and -1082 (G/A) of the IL10 promoter. We found that the ATA haplotype, which has been previously associated with low IL-10 expression, was the most represented in the cohort. Although we observed a trend toward an increased frequency of ATA/ATA carriage in HIV-infected compared with -uninfected individuals, the difference was not statistically significant. Similarly, individual IL10 SNPs were not significantly enriched in the HIV-infected group, suggesting that IL10 genetic variants are not associated with HIV-1 in this West African cohort from Mali.

Cellular and Molecular Targets of Waterbuck Repellent Blend Odors in Antennae of Glossina fuscipes fuscipes Newstead, 1910.

Insects that transmit many of the world's deadliest animal diseases, for instance trypanosomosis, find their suitable hosts and avoid non-preferred hosts mostly through olfactory cues. The waterbuck repellent blend (WRB) comprising geranylacetone, guaiacol, pentanoic acid, and δ-octalactone derived from waterbuck skin odor is a repellent to some savannah-adapted tsetse flies and reduces trap catches of riverine species. However, the cellular and molecular mechanisms associated with detection and coding of the repellent odors remain to be elucidated. Here, we demonstrated that WRB inhibited blood feeding in both Glossina pallidipes Austen, 1903 and Glossina fuscipes fuscipes Newstead, 1910. Using the DREAM (Deorphanization of Receptors based on Expression Alterations in odorant receptor mRNA levels) technique, combined with ortholog comparison and molecular docking, we predicted the putative odorant receptors (ORs) for the WRB in G. f. fuscipes, a non-model insect. We show that exposure of G. f. fuscipes in vivo to WRB odorant resulted in up- and downregulation of mRNA transcript of several ORs. The WRB component with strong feeding inhibition altered mRNA transcript differently as compared to an attractant odor, showing these two odors of opposing valence already segregate at the cellular and molecular levels. Furthermore, molecular dynamics simulations demonstrated that the predicted ligand-OR binding pockets consisted mostly of hydrophobic residues with a few hydrogen bonds but a stable interaction. Finally, our electrophysiological response showed the olfactory sensory neurons of G. f. fuscipes tuned to the tsetse repellent components in different sensitivity and selectivity.

Patients infected with Mycobacterium africanum versus Mycobacterium tuberculosis possess distinct intestinal microbiota.

BACKGROUND: Mycobacterium tuberculosis complex (MTBC), the causative agent of tuberculosis (TB), is composed of eight subspecies. TB in West Africa, in contrast to other geographical regions, is caused by Mycobacterium africanum (MAF) in addition to M. tuberculosis (MTB), with both infections presenting similar symptoms. Nevertheless, MAF is considered to be hypovirulent in comparison with MTB and less likely to progress to active disease. In this study, we asked whether MAF and MTB infected patients possess distinct intestinal microbiomes and characterized how these microbiota communities are affected by anti-tuberculosis therapy (ATT). Additionally, we assessed if the changes in microbiota composition following infection correlate with pathogen induced alterations in host blood-gene expression. METHODS: A longitudinal, clinical study of MAF infected, MTB infected patients assessed at diagnosis and two months after start of ATT, and healthy, endemic controls was conducted to compare compositions of the fecal microbiome as determined by 16S rRNA sequencing. A blood transcriptome analysis was also performed on a subset of subjects in each group by microarray and the results cross-compared with the same individual's microbiota composition. FINDINGS: MAF participants have distinct microbiomes compared with MTB patients, displaying decreased diversity and increases in Enterobacteriaceae with respect to healthy participants not observed in the latter patient group. Interestingly, this observed elevation in Enterobacteriaceae positively correlated with enhanced inflammatory gene expression in peripheral blood and was reversed after initiation of ATT. INTERPRETATION: Our findings indicate that MAF and MTB have distinct associations with the gut microbiome that may be reflective of the differential susceptibility of West Africans to these two co-endemic infections either as biomarkers or as a contributing determinant.