A novel de novo variant in the RUNX2 gene causes cleidocranial dysplasia in a Malian girl.

Key Clinical Message: Cleidocranial dysplasia (CCD) is a rare genetic skeletal disorder with only few cases reported in Africa, mostly based on clinical and radiological findings. We report the first case in Mali, caused by a novel de novo variant in the RUNX2 gene. Abstract: Cleidocranial dysplasia (CCD) is a rare autosomal dominant skeletal dysplasia characterized by an aplastic/hypoplastic clavicles, patent sutures and fontanels, dental abnormalities and a variety of other skeletal changes. We report a novel de novo variant in the RUNX2 gene causing a severe phenotype of CCD in a Malian girl.

Metabolic and Immune Consequences of Antibiotic Related Microbiome Alterations during first-line Tuberculosis Treatment in Bamako, Mali.

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.

Dynamics of SARS-CoV-2 variants characterized during different COVID-19 waves in Mali.

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.

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.

Relationships between gut microbiota, red meat consumption and colorectal cancer.

Excessive consumption of red and processed meat has been associated with a higher risk of developing colorectal cancer. There are many attempts to explain the risk of colorectal cancer associated with the consumption of red and processed meat: The temperature cooking of meat such as grilling and smoking contribute to the formation of mutagenic compounds including heterocyclic amines and polycyclic aromatic hydrocarbons.Heme iron in red meat is involved in the formation of N-nitroso compounds and lipid peroxidation products in the digestive tract.Fatty red meat is involved in the production of secondary bile acids by the bacteria of the gut microbiota. Many of the products formed are genotoxic and can cause DNA damage and initiate carcinogenesis of colorectal cancer. Various mechanisms contributing to their genotoxic role have been established in human and animal studies. In addition, there is increasing evidence that compounds formed from red and processed meat interact with the gut microbiota in colorectal cancer pathways. Although several early studies in animals and humans suggest a direct causal role of the gut microbiota in the development of colorectal cancer, the links between diet, gut microbiota, and colonic carcinogenesis are largely associations rather than proven causal relationships. Various biological mechanisms, including inflammation and oxidative stress can lead to DNA damage, gut dysbiosis, and therefore increase the risk of colorectal cancer. Dysbiosis of the gut microbiota may increase the risk of colorectal cancer through dietary component promotion of colonic carcinogenesis. In this paper, we review and update current knowledge about the relationships between red meat consumption, gut microbiota, and colorectal cancer.

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.

Performance Comparison of Xpert HIV-1 Viral Load Assay and Roche Taqman and Abbott M2000 RT in Bamako, Mali.

BACKGROUND: Routine monitoring of HIV-1 Viral Load (VL) is important in patients on Antiretroviral Therapy (ART) management. Access to HIV VL remains a challenge in resource-limited settings, especially in rural areas. Universal access to VL requires more simplified and less restrictive alternatives to current conventional VL methods. The objective of this study was to evaluate the performance of the new rapid (2-hour turnaround time) Xpert HIV-1VL technique compared to Roche TaqMan and Abbott RT m2000 for HIV-1 RNA quantification in HIV- infected patients. STUDY DESIGN: We conducted a cross-sectional study in patients seen for routine VL monitoring between August and November 2018 in a HIV care site in Bamako. The performance of the Xpert HIV-1 VL assay was evaluated against the Roche TaqMan assay and Abbott m2000 RT assay. Performance, utility and reliability/reproducibility were verified using accuracy, sensitivity, specificity, positive and negative predictive values, Diagnostic Odds Ratio (DOR), Kappa coefficient, Pearson correlation coefficient, and Bland-Altman analysis. RESULTS: The Xpert assay compared well with the two current referral assays (Roche TaqMan and Abbott m2000 RT assays). Compared to Roche TaqMan assay the sensitivity was 93.10%, specificity (97.01%) and accuracy (95.20%), the correlation coefficient of Pearson (r) was 0.98 (p <0.01). Bland-Altman analysis showed a mean difference of 0.18 log10 cp/mL; (Standard Deviation) SD=0.33. Compared to the Abbott m2000 RT, the sensitivity, the specificity and the accuracy were respectively 93.44%; 92% and 92.65%. The Xpert HIV-1 VL assay showed a good correlation with a correlation coefficient of Pearson, r=0.99 (p <0.001). The overall mean difference in the HIV-1 VL values obtained by Xpert HIV-1 VL and Abbott m2000 RT assays was 0.08 log10 cp/mL; SD=0.30. CONCLUSION: Xpert HIV-1 VL showed a good performance compared to Roche TaqMan and Abbott m2000 RT. With the rapid test results (less than 2 h) and ease of testing individual specimens, the Xpert HIV-1 VL assay could be an effective alternative for HIV VL monitoring in resource-limited settings.