Wrinkling and developable cones in centrally confined sheets.

Thin sheets respond to confinement by smoothly wrinkling or by focusing stress into small, sharp regions. From engineering to biology, geology, textiles, and art, thin sheets are packed and confined in a wide variety of ways, and yet fundamental questions remain about how stresses focus and patterns form in these structures. Using experiments and molecular dynamics simulations, we probe the confinement response of circular sheets, flattened in their central region and quasistatically drawn through a ring. Wrinkles develop in the outer, free region, then are replaced by a truncated cone, which forms in an abrupt transition to stress focusing. We explore how the force associated with this event, and the number of wrinkles, depend on geometry. Additional cones sequentially pattern the sheet until axisymmetry is recovered in most geometries. The cone size is sensitive to in-plane geometry. We uncover a coarse-grained description of this geometric dependence, which diverges depending on the proximity to the asymptotic d-cone limit, where the clamp size approaches zero. This paper contributes to the characterization of general confinement of thin sheets, while broadening the understanding of the d cone, a fundamental element of stress focusing, as it appears in realistic settings.

Hematological profiles of patients with tuberculosis and nontuberculous mycobacteria infections in Bamako, Mali.

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.

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.

Self-Ordering of Buckling, Bending, and Bumping Beams.

A collection of thin structures buckle, bend, and bump into each other when confined. This contact can lead to the formation of patterns: hair will self-organize in curls; DNA strands will layer into cell nuclei; paper, when crumpled, will fold in on itself, forming a maze of interleaved sheets. This pattern formation changes how densely the structures can pack, as well as the mechanical properties of the system. How and when these patterns form, as well as the force required to pack these structures is not currently understood. Here we study the emergence of order in a canonical example of packing in slender structures, i.e., a system of parallel confined elastic beams. Using tabletop experiments, simulations, and standard theory from statistical mechanics, we predict the amount of confinement (growth or compression) of the beams that will guarantee a global system order, which depends only on the initial geometry of the system. Furthermore, we find that the compressive stiffness and stored bending energy of this metamaterial are directly proportional to the number of beams that are geometrically frustrated at any given point. We expect these results to elucidate the mechanisms leading to pattern formation in these kinds of systems and to provide a new mechanical metamaterial, with a tunable resistance to compressive force.

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.

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.

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.

Exploring the usefulness of molecular epidemiology of tuberculosis in Africa: a systematic review.

BACKGROUND: Tuberculosis (TB) is caused by Mycobacterium tuberculosis complex (MTBC) and remains a serious global public health threat, especially in resource-limited settings such as the African region. Recent developments in molecular epidemiology tools have significantly improved our understanding of TB transmission patterns and revealed the high genetic diversity of TB isolates across geographical entities in Africa. This study reports the results of a systematic review of current knowledge about MTBC strain diversity and geographical distribution in African regions. METHODS: Search tools (PubMed, Embase, Popline, OVID and Africa Wide Information) were employed to identify the relevant literature about prevalence, strain diversity, and geographic distribution of MTBC infection in Africa. RESULTS: A total of 59 articles from 739 citations met our inclusion criteria. Most articles reported about patients with presumptive pulmonary TB (73%), fewer reports were on retreatment and treatment failure cases (12%), and presumptive drug resistance cases (3%). Spoligotyping was the most used, alone in 21 studies and in parallel with either the Mycobacterial Interspersed Repetitive Units Variable Number of Tandem Repeats or the Restriction Fragment Length Polymorphism. Various TB lineages were observed across the African continent, with the originally European lineage 4 spotted in all countries studied. CONCLUSION: TB molecular epidemiology tools have substantially improved our understanding of the MTBC circulating isolates, their evolution, and diversity in this highly endemic region of Africa. We found that only TB lineage 4 is present throughout all the continent and the clusters identified provides an extended insight into the disease transmission dynamics.

Dynamic buckling of an inextensible elastic ring: Linear and nonlinear analyses.

Slender elastic objects such as a column tend to buckle under loads. While static buckling is well understood as a bifurcation problem, the evolution of shapes during dynamic buckling is much harder to study. Elastic rings under normal pressure have emerged as a theoretical and experimental paradigm for the study of dynamic buckling with controlled loads. Experimentally, an elastic ring is placed within a soap film. When the film outside the ring is removed, surface tension pulls the ring inward, mimicking an external pressurization. Here we present a theoretical analysis of this process by performing a postbifurcation analysis of an elastic ring under pressure. This analysis allows us to understand how inertia, material properties, and loading affect the observed shape. In particular, we combine direct numerical solutions with a postbifurcation asymptotic analysis to show that inertia drives the system towards higher modes that cannot be selected in static buckling. Our theoretical results explain experimental observations that cannot be captured by a standard linear stability analysis.

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.

Dynamic Buckling of an Elastic Ring in a Soap Film.

Dynamic buckling may occur when a load is rapidly applied to, or removed from, an elastic object at rest. In contrast to its static counterpart, dynamic buckling offers a wide range of accessible patterns depending on the parameters of the system and the dynamics of the load. To study these effects, we consider experimentally the dynamics of an elastic ring in a soap film when part of the film is suddenly removed. The resulting change in tension applied to the ring creates a range of interesting patterns that cannot be easily accessed in static experiments. Depending on the aspect ratio of the ring's cross section, high-mode buckling patterns are found in the plane of the remaining soap film or out of the plane. Paradoxically, while inertia is required to observe these nontrivial modes, the selected pattern does not depend on inertia itself. The evolution of this pattern beyond the initial instability is studied experimentally and explained through theoretical arguments linking dynamics to pattern selection and mode growth. We also explore the influence of dynamic loading and show numerically that, by imposing a rate of loading that competes with the growth rate of instability, the observed pattern can be selected and controlled.

Association of Mycobacterium africanum Infection with Slower Disease Progression Compared with Mycobacterium tuberculosis in Malian Patients with Tuberculosis.

Mycobacterium africanum (MAF) is known to endemically cause up to 40-50% of all pulmonary TB in West Africa. The aim of this study was to compare MAF with Mycobacterium tuberculosis (MTB) with regard to time from symptom onset to TB diagnosis, and clinical and radiological characteristics. A cross-sectional study was conducted in Bamako, Mali, between August 2014 and July 2016. Seventy-seven newly diagnosed pulmonary TB patients who were naive to treatment were enrolled at Mali's University Clinical Research Center. Sputum cultures were performed to confirm the diagnosis and spoligotyping to identify the mycobacterial strain. Univariate and multivariate analyses were used to identify factors associated with disease progression. Overall, the frequency of female patients was 25% in MAF infection and only 10.0% in MTB infection (OR = 2.9), and MAF was more represented in patients aged ≥ 30 years (57.1% versus 36.7% [OR = 2.3]). More MAF- than MTB-infected patients had a history of a prior TB contact (32.1% versus 14.3% [OR = 2.8]). The mean duration between cough onset and TB diagnosis was 111 days (∼3.7 months) for MAF and 72 days (∼2.4 months) for MTB (P = 0.007). In a multivariate regression, weight loss (body mass index [BMI] < 18.5 kg/m2) and cough duration (> 4 months) were strongly associated with MAF infection (OR = 5.20 [1.49-18.26], P = 0.010, and 4.74 [1.2-18.58], P = 0.02), respectively. Our data show that MAF infection was significantly associated with lower BMI and a longer time between symptom onset and TB diagnosis than MTB. This supports the concept that MAF infection may have slower disease progression and less severe cough symptoms than MTB.

Use of sodium dodecyl sulfate to improve tuberculosis sputum smear microscopy.

Sputum smear microscopy (SSM), the most widely available tool for tuberculosis (TB) detection, has limited performance in paucibacillary patients and requires highly experienced technicians. The objective of this study was to determine whether the addition of sodium dodecyl sulfate (SDS), a detergent that thins sputum, at 4% and 10%, improves the detection of acid-fast bacilli (AFB), the clarity of slides, and the biosafety of the technique. Thirty participants with presumptive TB were enrolled. Three independent, blinded technicians examined the slides. Regular sputum concentrated AFB smear and sputum culture were used as standard control methods. Sputum culture was also performed before and after 10% SDS addition for safety analysis. We found that neither SSM with SDS 4% nor SSM with SDS 10% improved the test's performance. However, slides with 4% and 10% SDS, compared with slides prepared without SDS, had significantly better clarity scores. The 10% SDS-prepared sputum samples were all culture negative. While adding SDS detergent does not improve the performance of SSM slides, it does improve the clarity and biosafety. Where experienced technicians are scarce, especially in low resource settings, use of SDS may enhance the ease of slide reading in sputum smear microscopy.

Dynamics of wrinkling in ultrathin elastic sheets.

The wrinkling of thin elastic objects provides a means of generating regular patterning at small scales in applications ranging from photovoltaics to microfluidic devices. Static wrinkle patterns are known to be governed by an energetic balance between the object's bending stiffness and an effective substrate stiffness, which may originate from a true substrate stiffness or from tension and curvature along the wrinkles. Here, we investigate dynamic wrinkling induced by the impact of a solid sphere onto an ultrathin polymer sheet floating on water. The vertical deflection of the sheet's center induced by impact draws material radially inward, resulting in an azimuthal compression that is relieved by the wrinkling of the entire sheet. We show that this wrinkling is truly dynamic, exhibiting features that are qualitatively different to those seen in quasistatic wrinkling experiments. Moreover, we show that the wrinkles coarsen dynamically because of the inhibiting effect of the fluid inertia. This dynamic coarsening can be understood heuristically as the result of a dynamic stiffness, which dominates the static stiffnesses reported thus far, and allows control of wrinkle wavelength.

Competitive fitness of Mycobacterium tuberculosis in vitro.

Background: While, bacteria resistance mutations can affect competitive fitness, given our multidrug-resistant (MDR) prevalence, we conducted this study to determine the impact of MDR on the competitive fitness of Mycobacterium tuberculosis (MTB) complex MDR strains. We conducted a cross-sectional study at the University Clinical Research Center (UCRC) from January to December 2017. New TB patients over aged of 18 were recruited at University teaching hospital and health reference centers of Bamako in USTTB Ethical committee approved protocols. Methods: MDR and drug-susceptible (wild-type [WT]) MTB strains (T1 and Beijing) and MTB H37Rv were competed on solid media in UCRC's Tuberculosis Laboratory. Competitive and individual cultures were incubated for 14 days at 37°C with 7% CO2. Number of generation, generation time, and relative competitive fitness (W) of the strains were calculated. Data were analyzed with Epi-Info 7.1.5.2 software (CDC). P value was considered significant when it was <0.05. Scientific calculator (CS-82TL) was used for competitive fitness parameters calculations. Results: We performed 24 competitive cultures and 10 individual cultures. In individual cultures, strains' generation number was for Beijing (WT: 4.60 and mutant MR: 4.40), T1 (WT: 2.69 and MR: 2.37), and H37Rv: 2.91. Generation number of WT strains was less than those of MDR strains in both individual and competitive culture. Relative competitive fitness was below 1 (W<1) in 83.3%. Conclusion: MDR strains were less competitive than WT strains in 83.3% of cases. Resistant mutation impacts bacteria fitness.

On the figure of elastic planets I: gravitational collapse and infinitely many equilibria.

A classic problem of elasticity is to determine the possible equilibria of an elastic planet modelled as a homogeneous compressible spherical elastic body subject to its own gravitational field. In the absence of gravity, the initial radius is given and the density is constant. With gravity and for small planets, the elastic deformations are small enough so that the spherical equilibria can be readily obtained by using the theory of linear elasticity. For larger or denser planets, large deformations occur and the general theory of nonlinear elasticity is required to obtain the solution. Depending on the elastic model, we show that there may be parameter regimes where there exist no equilibrium or arbitrarily many equilibria. Yet, at most two of them are dynamically stable with respect to radial disturbances. In some of these models, there is a critical initial radius at which spherical solutions cease to exist. For planets with larger initial radii, there is no spherical solution as the elastic forces are not sufficient to balance the gravitational force. Therefore, the system undergoes gravitational collapse, an unexpected phenomenon within the framework of classical continuum mechanics.

Diagnostic Performances of Three Rapid Diagnostic Tests for Detecting HIV Infections in Mali.

Diagnosis of HIV infections in resource-limited countries like Mali is based on Rapid Diagnostic Tests (RDTs). The RDTs are diagnostic assays designed for use at the Point-Of-Care (POC), which is quick, cost-effective and easy to perform. However, in these countries, the tests are commonly used without any initial evaluation or monitoring of their performance despite high levels of HIV strain diversity and rapid evolution of the virus. In this study, the reliability and accuracy of HIV RDTs (Determine™, Multispot™, SD Bioline™) used in Mali, where HIV-1 and HIV-2 co-exist, were evaluated from August 2004 to November 2017. A total of 1303 samples from new HIV-suspect patients in Bamako were tested for HIV-1 and HIV-2 using the RDT Determine™, followed by ELISA and Western Blot (WB). The Determine™ test showed a robust diagnostic sensitivity of 98.7% [CI 95: 97.59-99.37] and a diagnostic specificity of 99.2% [CI 95: 98.22-99.67]. The Multispot™ assay showed a diagnostic sensitivity of 98.77% [CI 95: 97.59-99.37] and a diagnostic specificity of 99.2% [CI 95: 98.22-99.67]. The diagnostic sensitivity and specificity of SD Bioline™ HIV-1/2 were 100% [CI 95:72.25-100] and 88.89% [CI 95: 56.50- 98.71], respectively. These data indicate excellent performance for HIV RDTs in Mali and we recommend the use of Determine™ HIV-1/2 for HIV screening and Multispot™ for discriminating HIV-2 from HIV-1 infections.

Differential HLA allele frequency in Mycobacterium africanum vs Mycobacterium tuberculosis in Mali.

Tuberculosis (TB) is caused by Mycobacterium tuberculosis complex (MTBC), however, the distribution and frequency of MTBC lineages and sublineages vary in different parts of the globe. Mycobacterium africanum, a member of MTBC is responsible for a large percentage of TB cases in West Africa, however, it is rarely identified outside of this part of the World. Whether or not differential HLA polymorphism (an important host factor) is contributing to the geographic restriction of M. africanum to West Africa is unknown. Here, we conducted a cohort study in Mali of newly diagnosed individuals with active pulmonary TB and normal healthy controls. The MTBC isolates were spoligotyped to determine the TB study groups (M. tuberculosis sensu stricto LAM10 and M. africanum), and HLA typing was performed on peripheral blood. Unlike previous reports on other populations, we found that HLA class-I alleles were significantly associated with active TB disease in this population. HLA-B alleles (B*07:02, B*08:01, B*14:02, B*15:03, B*15:10, B*18:01, B*42:01, B*42:02, B*51:01 and B*81:01) were significantly associated with M. africanum (40%-45%) and M. tuberculosis (75%) compared with healthy controls. Many HLA-A alleles (A*02:05, A*34:02, A*66:01 and A*68:02) were also associated with both TB groups (65%-70%). However, many class II HLA-DR variants were found to be associated with M. tuberculosis but not M. africanum with the exception of the DRB1*03:01, which was associated with both groups. The differential HLA distribution observed in this study might be at least partially responsible for the geographical restriction of M. africanum infections to West Africa.

Mycobacterium africanum (Lineage 6) shows slower sputum smear conversion on tuberculosis treatment than Mycobacterium tuberculosis (Lineage 4) in Bamako, Mali.

OBJECTIVE: Ancestral M. tuberculosis complex lineages such as M. africanum are underrepresented among retreatment patients and those with drug resistance. To test the hypothesis that they respond faster to TB treatment, we determined the rate of smear conversion of new pulmonary tuberculosis patients in Bamako, Mali by the main MTBc lineages. METHODS: Between 2015 and 2017, we conducted a prospective cohort study of new smear positive pulmonary tuberculosis patients in Bamako. Confirmed MTBc isolates underwent genotyping by spoligotyping for lineage classification. Patients were followed at 1 month (M), 2M and 5M to measure smear conversion in auramine (AR) and Fluorescein DiAcetate (FDA) vital stain microscopy. RESULT: All the first six human MTBc lineages were represented in the population, plus M. bovis in 0.8% of the patients. The most widely represented lineage was the modern Euro-American lineage (L) 4, 57%, predominantly the T family, followed by L6 (M. africanum type 2) in 22.9%. Ancestral lineages 1, 5, 6 and M. bovis combined amounted to 28.8%. Excluding 25 patients with rifampicin resistance, smear conversion, both by AR and FDA, occurred later in L6 compared to L4 (HR 0.80 (95% CI 0.66-0.97) for AR, and HR 0.81 (95%CI 0.68-0.97) for FDA). In addition we found that HIV negative status, higher BMI at day 0, and patients with smear grade at baseline ≤ 1+ were associated with earlier smear conversion. CONCLUSION: The six major human lineages of the MTBc all circulate in Bamako. Counter to our hypothesis, we found that patients diseased with modern M. tuberculosis complex L4 respond faster to TB treatment than those with M. africanum L6.

Simultaneous diagnosis of tuberculous and non-tuberculous mycobacterial diseases: Time for a better patient management.

Tuberculosis (TB) is the deadliest infectious disease in the world which disproportionately affects low-and-middle-income countries (LMICs) where diagnostic resources and treatment options are limited. The incidence of pulmonary non-tuberculous mycobacteria (NTM) disease is also rapidly increasing in these regions traditionally dominated by TB infections. This poses significant diagnostic and treatment challenges, since these two diseases are often indistinguishable clinically or by sputum smear microscopy (SSM), the most commonly used TB diagnostic tool in LMICs. Consequently, NTM-infected patients usually receive unnecessary TB treatment for months. TB patients with NTM co-infections may also be treated incorrectly due to inaccurate SSM and Xpert™ MTB/RIF (M. tuberculosis./rifampin) results. These issues complicate the management of patients and contribute to the worsening of the current TB and NTM epidemiological features including development of drug resistant strains. It is therefore critical to develop improved diagnostic tools to accurately distinguish these two different pathogens that have many similar clinical and epidemiological features but have different treatment regimens. In this review, we will discuss limitations with current diagnostic tools and the need to develop novel techniques that can accurately and simultaneously diagnose TB and NTM disease._.