Background Men who have sex with men living with HIV (MSMLWHIV) have a high risk of persistent high-risk HPV infection, and rapid tools like Xpert HPV can help expand screening in low-resource settings. Objectives This study aimed to assess the feasibility of using self-collected anal swabs for detecting high-risk human papillomavirus (HR-HPV) infections in MSMLWHIV, using the Xpert® HPV assay. Additionally, we investigated factors associated with HR-HPV positivity. Design This was a single-center cross-sectional study conducted from 22 nd May 2024 to 31 st July 2024 among MSMLWHIV in Bamako. Methods Participants were recruited from the Soutoura NGO in Bamako, Mali. To be eligible, individuals had to be HIV-1 positive, on antiretroviral therapy, 18 years or older, and self-identified as MSM. The prevalence of HR-HPV was reported by sociodemographic characteristics and sexual behaviors. We used a penalized logistic regression model using Firth’s method to identify sociodemographic and behavioral factors associated with HR-HPV positivity. Results A total of 245 MSMLWHIV were initially tested. Of these, 170 yielded successful results and were subsequently included in the study analysis. The participants had a median age of 26 years (IQR 24-29) with the median age of first anal intercourse at 16 years (IQR 16-18). Among the participants, 29% (49/170) identified as bisexual, 42% (72/170) reported never using condoms, 16% (27/170) participated in group intercourse, and 42% (71/170) had at least two different sexual partners in the past six months. Among those successfully tested, 65% (110/170) were positive for HR-HPV, with HPV16 detected in 12% (21/170) of participants. No or primary education and consistent condom use were associated with lower odds of HR-HPV positivity, while the unexpected association observed with smoking should be interpreted with caution. Conclusion The high HR-HPV prevalence among MSMLWHIV calls for targeted screening and prevention. Although Xpert HPV shows promise, the 31% failure rate with self-collected samples underscores the need for improvements in sample collection procedures and technical performance.

Introduction:Like many other countries, Mali, a West African country, has encountered various obstacles in the fight against the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite resource constraints, however, the country implemented containment strategies. Therefore, in early 2021, Mali initiated a vaccination campaign as a tangible defense against COVID-19, prioritizing the administration of the first vaccine doses to healthcare personnel. Consequently, we found assessing anti-SARS-CoV-2 IgG antibody levels important to gauge the efficacy of vaccines administered to frontline healthcare workers in Bamako, Mali. Methods:The study enrolled 172 vaccinated front-line healthcare workers from referral hospitals in Bamako, Mali, between March and June 2022. Serum samples were subjected to enzyme-linked immunosorbent assay (ELISA) to assess the levels of anti-SARS-CoV-2 IgG antibodies. Prevaccination serum samples served as controls. Chi-square and Mann-Whitney tests were used to compare proportions and means. Results:Among the 172 participants, 98.2% had high levels of anti-SARS-CoV-2 spike protein antibodies; only 1.6% (n=2) were seronegative. The majority, 62.2% (n=107), received a two-dose vaccination schedule, and the Astra Zeneca® vaccine was the most widely used (52.3%). The average level of postvaccine antibodies was significantly greater in participants who received two doses of vaccine than in those who received one dose (33.7 index vs. 29.1 index; p=0.02). Conclusions:Most healthcare workers exhibited favorable vaccine responses, as indicated by their positive reactivity to anti-SARS-CoV-2 IgG spike proteins. The nature and dosage of the vaccines influenced the antibody response, with a notable advantage observed for individuals who received a two-dose regimen. These findings underscore the importance of continuous research and evaluation to understand and enhance vaccine effectiveness.

Aim To conduct a case-control study (pilot study) in Africa (Mali) in comparing the gut microbiota of patients with stage III colorectal cancer (CRC) using next-generation sequencing. Methods Shotgun sequencing was performed to characterize participants’ fecal microbiota using Illumina’s HiSeq platform. This case-control study involved newly diagnosed CRC patients (n = 23) prior to any treatment initiation, and unrelated healthy controls (n = 24) to elucidate their microbial diversity and relative abundance. Results The findings revealed that the gut microbiota in CRC and in healthy were significantly distinctive according to the PERMANOVA test (R2 = 0.132, P = 0.001), and the alpha-diversity was significantly lower in CRC. Beta-diversity, based on principal coordinate analysis, showed a distinct taxonomy between the CRC and the healthy.Levels of Pseudomonadota, Escherichia, Citrobacter freundii, Klebsiella sp. LTGPAF-6F, Escherichia albertii, Escherichia coli, Caudovirales, Apicomplexa, and Verrucomicrobiota populations were significantly elevated in CRC. The major metabolic pathways with higher relative abundance levels found in CRC compared to healthy were related to HEMESYN2-PWY: heme biosynthesis II (anaerobic), PWY-5154:L-arginine biosynthesis III (via N-acetyl-L-citrulline), FUC-RHAMCAT-PWY: superpathway of fucose and rhamnose degradation, ECASYN-PWY: enterobacterial common antigen biosynthesis, ENTBACSYN-PWY: enterobactin biosynthesis, and AEROBACTINSYN-PWY: aerobactin biosynthesis. Conclusion Distinct gut microbiome profiles between healthy and CRC were observed. In particular, the findings showed a significant reduction in microbial diversity in stage III CRC. This study provides initial metagenomic data on Malian patients with CRC. It will be used to create a larger cohort to better understand the relationship between CRC and the gut microbiota in the Malian CRC population.

Tuberculosis (TB) remains a major global health challenge, affecting approximately 10 million people annually. Susceptibility to infection by Mycobacterium tuberculosis, progression to TB, response to antimycobacterial chemotherapy, and the propensity to develop post-infectious sequelae have all been linked to a complex interplay of host and pathogen factors. Studies have revealed that communities of microorganisms colonize the human respiratory and gastrointestinal tracts and regulate regional immunity, with consequent effects on TB acquisition, progression, and resolution. An in-depth understanding of the multifaceted determinants of host susceptibility to TB, including the cross-talk between the host immune system and gut and lung microbiomes, could provide new insights into TB pathogenesis, treatment response, sequelae, and recurrence dynamics. This review explores the role of the gut-lung microbiome axis across the spectrum of TB pathogenesis, including microbial changes during and beyond TB treatment, and assesses their potential effect on treatment outcomes and the risk of TB recurrence.

BackgroundIndividuals with a history of tuberculosis (TB) treatment are at a higher risk of experiencing a recurrent episode of the disease. Previous cross-sectional studies identified a connection between dysbiosis (alterations) in the gut microbiota composition and the administration of first-line TB antibiotics. However, these studies have not successfully elucidated this dysbiosis’s resulting metabolic and immune consequences.MethodsIn a longitudinal assessment, we studied the antituberculosis drug-related changes in the gut microbiota’s composition and the resulting functional consequences. Sputum for TB culture, peripheral blood for metabolomics and cytokines analysis, and stool for shotgun metagenomics were collected from TB participants at Month-0, Month-2, Month-6 of treatment, and 9 Months after treatment (Month-15). Healthy controls were sampled at Month-0 and Month-6.FindingsWe found notable differences in gut microbiota between individuals with TB and healthy controls. While gut microbiota tended to resemble healthy controls at the end of TB treatment, significant differences for many taxa persisted up to Month-15. Concurrently, disturbances in plasma metabolites, including tryptophan, tricarboxylic acids, and cytokine levels were observed. Certain fatty acids associated with inflammation pathways negatively correlated with the abundance of several taxa.ConclusionWe observed alterations in the gut microbiota composition and function during treatment and at Month-15. Numerous changes in bacterial taxa abundances and inflammation-linked metabolites did not reverse at Month-15. This study suggests potential influences of anti-TB drugs and the gut microbiome on the disease outcome, response to treatment, and resistance to future TB infections.

The human gut microbiome consists of highly complex microbial populations that play important roles in disease pathogenesis. Changes in the gut microbiome are associated with HIV infection. However, it is unclear whether gut microbiome dysbiosis is causally linked to disease or whether it simply reflects disease-induced changes in the host immune and metabolic systems. This study aims to describe and compare intestinal microbial compositions and derived metabolic pathways in people living with HIV (PL-HIV) from prior to antiretroviral therapy (ART) to 6 and 12 months after ART initiation, compared to HIV-negative individuals. Whole-genome microbiome sequencing coupled with bioinformatics analysis was used to characterize participants' intestinal microbial structures and derived metabolic pathways. Pre- and post-ART gut microbiota characterization of PL-HIV revealed substantial dysbiosis compared to HIV-negative people. An enrichment of pro-inflammatory microorganisms was the hallmark of dysbiosis in the PL-HIV pre-ART, with a decline in Proteobacteria at 6 months of ART, continuing until 12 months of ART. Lower proportions of Bacteroidetes were noted pre-ART, but they increased slightly at 6 months of ART before decreasing again at 12 months of ART. Additionally, we reported metabolic changes that are particularly important for health and are associated with dysbiosis both before and post-ART. Alteration of the pyruvate fermentation to the isobutanol metabolic pathway persisted in PL-HIV after 12 months of ART, and this mechanism was correlated with a decrease in Ruminococcus bromii species. ART initiation appears to lead to changes in several crucial metabolic pathways and may not entirely restore the dysbiosis of the gut microbiota caused by HIV.IMPORTANCEResearchers are facing a major challenge in the treatment of HIV infection due to the continuous use of antiretroviral (ARV) molecules. However, regularly monitoring these molecules is necessary because they are not without consequences. They have toxicity and side effects and could also destabilize the intestinal microbiota, which could harm the metabolic pathways essential to good health. This study reveals that ARV treatment only partially restores gut microbiota dysbiosis and alters metabolic pathways due to pathogenic taxa. This provides additional insights into the relationship between antiretroviral therapy and the microbiome, potentially leading to new prevention and treatment strategies such as probiotic/prebiotic or microbiota transplants.

SARS-CoV-2 geno-surveillance has been challenging in West Africa. Despite the multiple challenges encountered, particularly in West Africa during the COVID-19 pandemic, efforts were made to circumscribe the spread of the disease and to provide methods and resources for surveillance. We aim to describe the dynamic of SARS-CoV-2 variants and highlight the efforts made in genomic surveillance in West Africa. Therefore, we proceeded to retrieve West African countries' SARS-CoV-2 data from public repository (GISAID) and then ensued to a descriptive statistical analysis. From the start of the pandemic till December 2023, we found less than a million COVID-19 cases notified within the West African region. Overall, the study population was 50.21 % Males with a median age of 37. Regarding genomic data, only 3.02 % of cases were sequenced and deposited in GISAID. Of the available sequence, we noted that most of the variants have circulated in West Africa before the official notification of the variants. Nigeria, Ghana, and Senegal provided together more than half of West Africa's originating sequences when Omicron and Delta variants were the most sequenced in 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.

Global tuberculosis (TB) eradication is undermined by increasing prevalence of emerging resistance to available drugs, fuelling ongoing demand for more complex diagnostic and treatment strategies. Early detection of TB drug resistance coupled with therapeutic decision making guided by rapid characterisation of pre-treatment and treatment emergent resistance remains the most effective strategy for averting Drug-Resistant TB (DR-TB) transmission, reducing DR-TB associated mortality, and improving patient outcomes. Solid- and liquid-based mycobacterial culture methods remain the gold standard for Mycobacterium tuberculosis (MTB) detection and drug susceptibility testing (DST). Unfortunately, delays to result return, and associated technical challenges from requirements for specialised resource and capacity, have limited DST use and availability in many high TB burden resource-limited countries. There is increasing availability of a variety of rapid nucleic acid-based diagnostic assays with adequate sensitivity and specificity to detect gene mutations associated with resistance to one or more drugs. While a few of these assays produce comprehensive calls for resistance to several first- and second-line drugs, there is still no endorsed genotypic drug susceptibility test assay for bedaquiline, pretomanid, and delamanid. The global implementation of regimens comprising these novel drugs in the absence of rapid phenotypic drug resistance profiling has generated a new set of diagnostic challenges and heralded a return to culture-based phenotypic DST. In this review, we describe the available tools for rapid diagnosis of drug-resistant tuberculosis and discuss the associated opportunities and challenges.

Introduction: Human immunodeficiency virus (HIV) infection remains a major public health concern despite a significant decline in HIV-related mortality and morbidity. These significant advances are linked mostly to effective antiretroviral therapy (ART). However, these treatments are not without consequences on other microorganisms in our body, especially when they must be used for life. Balanced gut microbiota is essential for maintaining human health through symbiotic relationship with the host cells. Aims and methodology: This review focuses on ART and its potential impact on the intestinal microbial population of HIV-infected individuals. Therefore, we retrieved studies focusing on the impact of HIV ART on the gut microbiota, that were published from 2010 to 2021. Results: It was observed that most studies on HIV ART and associated gut microbiota have been cross-sectional, and the findings, in general, showed significant damages caused by the ART to the gut microbial community (dysbiosis), with the impact varying in different studies. These changes also revealed dysfunction in microbial translocation and some immune markers, including T lymphocyte rates and the overall inflammation balance. Conclusions: There are significant gaps in our understanding of the impact of HIV ART on gut microbiota. Thus, a longitudinal study is likely needed with a considerable sample size from different settings and classes of ART to better understand the impact of HIV ART on the gut microbiota, and develop remedial (restorative) and adjunctive host-directed strategies during HIV ART.

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.

Background: Pulmonary tuberculosis (TB) remains one of the main causes of morbidity and mortality in Mali. Nontuberculous mycobacteria (NTM) infections are very common but are often cofounded with TB because of the similarity of symptoms, which makes the diagnosis difficult. Hematological abnormalities associated with TB have been described, but not with NTM. Therefore, the goal of this study was to compare the hematological parameters of patients infected with TB and NTM infections. Methods: A cross-sectional study enrolling TB and NTM participants was conducted in 2018–2020. Five milliliters of venous blood and sputum samples were collected from each participant to determine the hematological parameters using the RUBY CELL-DYN Ruby Version 2.2 ML. A BACTEC MGIT 960 and multiplex reverse transcription–polymerase chain reaction were used to distinguish Mycobacterium tuberculosis from NTM, respectively. Results: Of the total 90 patients enrolled, there was a decrease in hemoglobin and hematocrit levels in both the groups (P = 0.05). In addition, we found that the percentages of basophil cells (P = 0.01) and mean values of platelets (P = 0.04) were significantly higher in TB patients than those of NTMs. Moreover, the mean of absolute values of eosinophil cells of TB patients was significantly lower than those of NTMs (P = 0.03). Conclusion: We found significant statistical differences in basophils, platelets, and eosinophils in differentiating TB and NTM in this pilot study. Future studies with patients at different clinical stages are needed to confirm the hematological profiles of TB and NTM patients.

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.

Au Mali, les racines de Securidaca longipedunculata sont fortement utilisées et les peuplements de l’espèce se font de plus en plus rares. Ce travail visait à effectuer une étude comparative des paramètres pharmacognosiques des feuilles, écorces de tronc, écorces de racine et de la racine entière. Les échantillons ont été analysés pour déterminer les caractéristiques botaniques et physicochimiques. Des extraits aqueux et organiques ont été préparés pour caractériser les principaux constituants bioactifs par des techniques colorimétriques et chromatographiques. Les composés majoritaires ont été extraits par ultrasons et quantifiés. Les éléments botaniques communs étaient des fibres, cristaux d’oxalate de calcium, xylèmes et parenchymes. Des sclérites et fragments d’épiderme étaient seulement dans les feuilles. Le meilleur rendement d’extraction a été obtenu avec l’éthanol. Les principaux constituants étaient des tanins, flavonoïdes, coumarines, anthraquinones et saponines dans les feuilles ; des coumarines et saponines dans les écorces de tronc, écorces de racine et la racine entière. Les constituants majoritaires étaient des saponines triterpéniques dont 1,51 g de précipités enrichis ont été extraits à partir des écorces de racine. Les feuilles ont qualitativement présenté le plus de constituants bioactifs. Des investigations sont nécessaires pour évaluer leur efficacité afin de diminuer la pression sur les racines. English title: Pharmacognostic study of the leaves, root bark, trunk bark and whole root of Securidaca longipeduncultata Fresen (Polygalaceae), harvested in Mali In Mali, the roots of Securidaca longipedunculata are used extensively, and stands of the species are becoming increasingly are becoming increasingly rare. The aim of this work was to carry out a comparative study of the pharmacognosic parameters of leaves, trunk bark, root bark and the whole root. Samples were analyzed for botanical and physicochemical characteristics. Aqueous and organic extracts were prepared to characterize the main bioactive constituents using colorimetric and chromatographic techniques. Major compounds were ultrasonically extracted and quantified. Common botanical elements were fibers, calcium oxalate crystals, xylem and parenchyma. Sclerites and epidermal fragments were only found in leaves. The best extraction yield was obtained with ethanol. The main constituents were tannins, flavonoids, coumarins, anthraquinones and saponins in the leaves; coumarins and saponins in the trunk bark, root bark and whole root. The main constituents were triterpene saponins, of which 1.51 g of enriched precipitates were extracted from root barks. Leaves qualitatively presented the most bioactive constituents. Further investigations are needed to assess their effectiveness in reducing pressure on the roots.

Background: The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants may have contributed to prolonging the pandemic, and increasing morbidity and mortality related to coronavirus disease 2019 (COVID-19). This article describes the dynamics of circulating SARS-CoV-2 variants identified during the different COVID-19 waves in Mali between April and October 2021. Methods: The respiratory SARS-CoV-2 complete spike (S) gene from positive samples was sequenced. Generated sequences were aligned by Variant Reporter v3.0 using the Wuhan-1 strain as the reference. Mutations were noted using the GISAID and Nextclade platforms. Results: Of 16,797 nasopharyngeal swab samples tested, 6.0% (1008/16,797) tested positive for SARS-CoV-2 on quantitative reverse transcription polymerase chain reaction. Of these, 16.07% (162/1008) had a cycle threshold value <= 28 and were amplified and sequenced. The complete S gene sequence was recovered from 80 of 162 (49.8%) samples. Seven distinct variants were identified: Delta (62.5%), Alpha (1.2%), Beta (1.2%), Eta (30.0%), 20B (2.5%), 19B (1.2%) and 20A (1.2%). Conclusions and perspectives: Several SARS-CoV-2 variants were present during the COVID-19 waves in Mali between April and October 2021. The continued emergence of new variants highlights the need to strengthen local real-time sequencing capacity and genomic surveillance for better and coordinated national responses to SARS-CoV-2.

While Hepatitis B virus (HBV) and the human immunodeficiency virus (HIV) are endemic in West Africa, the prevalence of HBV/HIV coinfection and their associated risk factors in children remains unclear. In this review, we sought to assess HBsAg seroprevalence among 0- to 16-year-olds with and without HIV in West African countries and the risk factors associated with HBV infection in this population. Research articles between 2000 and 2021 that reported the prevalence of HBV and associated risk factors in children in West Africa were retrieved from the literature using the Africa Journals Online (AJOL), PubMed, Google Scholar, and Web of Science databases as search tools. StatsDirect, a statistical software, was used to perform a meta-analysis of the retained studies. HBV prevalence and heterogeneity were then assessed with a 95% confidence interval (CI). Publication bias was evaluated using funnel plot asymmetry and Egger’s test. Twenty-seven articles conducted across seven West African countries were included in this review. HBV prevalence among persons aged 0 to 16 years was 5%, based on the random analysis, given the great heterogeneity of the studies. By country, the highest prevalence was observed in Benin (10%), followed by Nigeria (7%), and Ivory Coast (5%), with Togo (1%) having the lowest. HBV prevalence in an HIV-infected population of children was (9%). Vaccinated children had lower HBV prevalence (2%) than unvaccinated children (6%). HBV prevalence with a defined risk factor such as HIV co-infection, maternal HBsAg positivity, undergoing surgery, scarification, or being unvaccinated ranged from 3–9%. The study highlights the need to reinforce vaccination of newborns, screening for HBV, and HBV prophylaxis among pregnant women in Africa, particularly in West Africa, to achieve the WHO goal of HBV elimination, particularly in children.

Background:Tuberculosis (TB) infection is known to lead to the unbalance of the gut microbiota and act synergistically on the decline of the host immune response, when untreated. Moreover, previous work has found a correlation between dysbiosis in the gut microbiota composition and the use of antibiotics. However, there is a need for an in-depth understanding of the metabolic and immune consequences of antibiotic-related microbiome alterations during first-line TB treatment. Methods:In a longitudinal cohort study, which included TB-infected cohorts and healthy individuals (control group), we studied the anti-TB-related changes in the gut microbiota composition and related functional consequences. Sputum, whole blood and stool samples were collected from participants at four time-points including before (Month-0), during (Month-2), at the end of drug treatment (Month-6) and 9 months after treatment (Month-15). Controls were sampled at inclusion and Month-6. We analyzed the microbiota composition and microbial functional pathways with shotgun metagenomics, analyzed the blood metabolomics using high-performance liquid chromatography (HPLC), and measured the levels of metabolites and cytokines with cytometric bead array. Results:We found that the gut microbiota of patients infected with TB was different from that of the healthy controls. The gut microbiota became similar to healthy controls after treatment but was still significantly different after 6 months treatment and at the follow up 9 months after treatment. Our data also showed disturbance in the plasma metabolites such as tryptophan and tricarboxylic acids components of patients during TB treatment. Levels of IL-4, IL-6, IL-10, and IFN-γ decreased during treatment and levels were maintained after treatment completion, while IL-17A known to have a strong link with the gut microbiota was highly expressed during treatment period and longer than the 9-month post treatment completion. We found that some fatty acids were negatively correlated with the abundance of taxa. For example, Roseburia, Megasphaera, and alpha proteobacterium HIMB5 species were negatively correlated (rho = -0.6) with the quinolinate production. Conclusion:Changes in the composition and function of gut microbiota was observed in TB patients before and after treatment compared to healthy controls. The differences persisted at nine months after treatment completion. Alterations in some bacterial taxa were correlated to the changes in metabolite levels in peripheral blood, thus the altered microbial community might lead to changes in immune status that influence the disease outcome and future resistance to infections.

The 3C protease is distinguished from most proteases due to the presence of cysteine nucleophile that plays an essential role in viral replication. This peculiar structure encompassed with its role in viral replication has promoted 3C protease as an interesting target for therapeutic agents in the treatment of diseases caused by human rhinovirus (HRV). Herein we present a comprehensive molecular dynamics study of the comparison of two potent inhibitors, sg85 and rupintrivir complexed with HRV-3C protease. The binding free energy studies revealed a higher binding affinity for sg85 −58.853 kcal/mol than for rupintrivir −54.0873 kcal/mol and this was found to be in correlation with the experimental data. The energy decomposition analysis showed that, residues Leu 127, Thr 142, Ser 144, Gly 145, Tyr 146, Cys 147, His 161, Val 162, Gly 163, Gly 164, Asn 165, Phe 170 largely contributed to the binding of sg85, whereas His 40, Leu 127 and Gly 163 impacted the binding of rupintrivir. It further showed that His 40, Glu 71, Leu 127, Cys 147 Gly 163 and Gyl 164 are crucial residues that play a key role in ligand-enzyme binding; amongst these residues are residues of the conserved active site (His 40, Glu 71 and Cys 147). These findings provide a comprehensive understanding of the dynamics and structural features and will serve as guidance in the design and development of potent novel inhibitors of HRV. ![Figure][1]</img> ### Competing Interest Statement The authors have declared no competing interest. [1]: pending:yes

In light of the rapid rise of an influenza pandemic, the constant genetic mutations of H5N1 influenza viruses pose a threat. Mutations at the sialic site are often responsible for multiple drug resistance. To design effective new inhibitors, it is necessary to undertake research into the mechanism of resistance of influenza viruses and their rapid mutations. The molecular dynamic simulation technique has been an instrumental tool in understanding how proteins function from an atomic perspective. A thorough investigation has not been conducted using molecular dynamics to examine the impact of these mutations (I222K, H274Y, and H274Y-I222K) on Peramivir. This study investigates the effects of I222K, H274Y, H274Y-I222K substitution on the neuraminidase–Peramivir complex and identifies responsible residues for complex conformations. The mutations caused distorted Peramivir orientation in the enzyme active site, which affected the inhibitor’s binding. In the presence of various mutations, interaction between protein and ligand became less thermodynamically favorable. We observed the following trend in binding free energy difference: WT<I222<H274Y<H274Y-I222K. As a result of the thermodynamic instability of the mutant complexes, Peramivir’s potency is reduced due to impaired binding interactions. Wild type complex displays thermodynamic stability and strong protein-ligand interactions due to their high total energy contributions and low residue flexibility. Based on the energy decomposition analysis, Arg117, Arg224, and Arg292 contributed the largest residual energy for the binding of Peramivir to wild type and mutants. These residues are thought to play a key role in the formation of the binding pocket between Peramivir and neuraminidase. This study provides a basis for investigating the effects of other mutations on Peramivir’s efficacy against the H5N1 virus.

The presence of the zoonotic pathogen Salmonella in the food supply chain poses a serious public health threat. This study describes the prevalence, susceptibility profiles, virulence patterns, and clonality of Salmonella from a poultry flock monitored over six weeks, using the farm-to-fork approach. Salmonella was isolated using selective media and confirmed to the genus and species level by real-time polymerase chain reaction (RT-PCR) of the invA and iroB genes, respectively. Antimicrobial susceptibility profiles were determined using Vitek-2 and the Kirby–Bauer disk diffusion method against a panel of 21 antibiotics recommended by the World Health Organisation Advisory Group on Integrated Surveillance of Antimicrobial Resistance (WHO-AGISAR). Selected virulence genes were identified by conventional PCR, and clonality was determined using enterobacterial repetitive intergenic consensus PCR (ERIC-PCR). Salmonella was present in 32.1% of the samples: on the farm (30.9%), at the abattoir (0.6%), and during house decontamination (0.6%). A total of 210 isolates contained the invA and iroB genes. Litter, faeces, and carcass rinsate isolates were classified as resistant to cefuroxime (45.2%), cefoxitin (1.9%), chloramphenicol (1.9%), nitrofurantoin (0.4%), pefloxacin (11.4%), and azithromycin (11%). Multidrug resistance (MDR) was observed among 3.8% of the isolates. All wastewater and 72.4% of carcass rinsate isolates were fully susceptible. All isolates harboured the misL, orfL, pipD, stn, spiC, hilA, and sopB virulence genes, while pefA, spvA, spvB, and spvC were absent. In addition, fliC was only present among the wastewater isolates. Various ERIC-PCR patterns were observed throughout the continuum with different subtypes, indicating the unrelated spread of Salmonella. This study concluded that poultry and the poultry environment serve as reservoirs for resistant and pathogenic Salmonella. However, there was no evidence of transmission along the farm-to-fork continuum.