Multidrug-resistant tuberculosis: latest opinions on epidemiology, rapid diagnosis and management.

PURPOSE OF REVIEW: This review addresses the escalating global challenge of multidrug-resistant tuberculosis (MDR-TB) in Sub-Saharan Africa, with a focus on its complex comorbidity with HIV/AIDS. Emphasizing the urgency of the issue, the review aims to shed light on the unique healthcare landscape shaped by the convergence of high prevalence rates and intersecting complexities with HIV/AIDS in the region. RECENT FINDINGS: A notable increase in MDR-TB cases across Sub-Saharan Africa is attributed to challenges in timely diagnoses, treatment initiation, and patient treatment defaulting. The literature underscores the critical need for proactive measures to address diagnostic and treatment gaps associated with MDR-TB, particularly concerning its comorbidity with HIV/AIDS. SUMMARY: To effectively manage MDR-TB and its co-morbidity with HIV/AIDS, proactive screening programs are imperative. The review highlights the necessity of active follow-up strategies to ensure treatment adherence and reduce default rates, offering evidence-based insights for improved disease management in the region.

Diagnostic accuracy of Xpert MTB/RIF Ultra for childhood tuberculosis in West Africa - a multicenter pragmatic study.

OBJECTIVE: To evaluate the performance of Xpert Mycobacterium Tuberculosis/rifampicin (MTB/RIF) Ultra (Ultra) for diagnosis of childhood tuberculosis (TB) within public health systems. METHODS: In this cross-sectional study, children aged <15 years with presumptive pulmonary TB were consecutively recruited and evaluated for TB at tertiary-level hospitals in Benin, Mali, and Ghana. Bivariate random-effects models were used to determine the pooled sensitivity and specificity of Ultra against culture. We also estimated its diagnostic yield against a composite microbiological reference standard (cMRS) of positive culture or Ultra. RESULTS: Overall, 193 children were included in the analyses with a median (interquartile range) age of 4.0 (1.1-9.2) years, 88 (45.6%) were female, and 36 (18.7%) were HIV-positive. Thirty-one (16.1%) children had confirmed TB, 39 (20.2%) had unconfirmed TB, and 123 (63.7%) had unlikely TB. The pooled sensitivity and specificity of Ultra verified by culture were 55.0% (95% confidence interval [CI]: 28.0-79.0%) and 95.0% (95% CI: 88.0-98.0%), respectively. Against the cMRS, the diagnostic yield of Ultra and culture were 67.7% (95% CI: 48.6-83.3%) and 70.9% (95% CI: 51.9-85.8%), respectively. CONCLUSION: Ultra has suboptimal sensitivity in children with TB that were investigated under routine conditions in tertiary-level hospitals in three West African countries.

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.

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.

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.

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.

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.

Healthcare-Associated Infection in Surgery Department: A Big Challenge for African Surgical Teams.

Background: Healthcare-associated infections (HAIs) are increasing in health facilities in Mali, due to health disparities and growing costs. Twenty to fifty percent of HAIs in the surgery department can be prevented with appropriate measures. Objectives: This study aimed to determine the burden of HAI and its risk factors. Materials and Methods: This was a prospective cohort study from January to June 2021 at the CHU Gabriel TOURE, Bamako, Mali. The sample size was determined based on the CDC Atlanta criteria, used to confirm HAI in surgical settings. Demographic, clinical, and biological parameters were determined. For the confirmed case of infection, the incriminated bacteria were isolated and tests were performed for the choice of drugs. Results: Of the total 1001 patients included in this study, 195 patients (19.48%) have HAIs. The types of infections were as follows: 70 cases of surgical site infections, 54 infections on burns victims, 40 urinary tract infections, and 31 cases of bacteraemia. Germs such as Escherichia Coli, Klebsiella pneumoniae, and Acinetobacter were often isolated. We found increasing hospital stays as well as some postoperative mortality related to infections. At the end of this study, corrective efforts were implemented to prevent HAI. Among them are improvements in sterilisation techniques as far as surgical materials were concerned. In addition to a surgical checklist, locally used drapes were replaced with single-use surgical supplies. Advanced training of the surgical team on things such as bladder catheterisation was also conducted in the department. It is important to put in place a committee, to prevent nosocomial infection in our hospital. The selected committee will be responsible for planning and implementing diverse strategies to prevent infections. Conclusions: The prevention of HAIs will reduce health costs and improve the quality of surgical care.

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 evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance.

Investment in Africa over the past year with regards to SARS-CoV-2 genotyping has led to a massive increase in the number of sequences, exceeding 100,000 genomes generated to track the pandemic on the continent. Our results show an increase in the number of African countries able to sequence within their own borders, coupled with a decrease in sequencing turnaround time. Findings from this genomic surveillance underscores the heterogeneous nature of the pandemic but we observe repeated dissemination of SARS-CoV-2 variants within the continent. Sustained investment for genomic surveillance in Africa is needed as the virus continues to evolve, particularly in the low vaccination landscape. These investments are very crucial for preparedness and response for future pathogen outbreaks. One-Sentence SummaryExpanding Africa SARS-CoV-2 sequencing capacity in a fast evolving pandemic.

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.

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.

Epidemiology and microscopic diagnosis of tuberculosis in pigs and small ruminants slaughtered at Bobo-Dioulasso abattoir, Burkina Faso.

Bovine tuberculosis (bTB) is a zoonotic, infectious, chronic and contagious disease, caused by Mycobacterium bovis that mainly affects cattle. This pathology has a negative impact on animals and animal products trade. Unfortunately, in Burkina Faso where agriculture and livestock sectors represent around 80% of the socio-economic activities, the real situation of the disease is not well known especially in small ruminants and swine. Thus, our study focused on both the epidemiology and the microbiological diagnosis of tuberculosis (TB) in small ruminants and pigs slaughtered at Bobo-Dioulasso abattoir. A prospective study was conducted between August 2017 and December 2017. Epidemiological data collection was performed during routine meat inspection; moreover, samples were taken and transported to the Bacteriology laboratory of Centre Muraz for microbiological analyses. This diagnosis consisted in search of Acid Fast Bacilli (AFB) using the hot Ziehl-Neelsen staining. Out of a total of 14 648 small ruminants and 2430 pigs slaughtered during the study period, 156 and 17 had lesions suggestive of bTB with prevalence of 1.07% and 0.7%, respectively. Females and those between 2 and 4 years old were mainly infected. The most affected organs were: lungs, liver, spleen and lymph nodes. Finally, microscopy revealed 43.35% (75/173) of positive cases for AFB. These results confirm the presence of bTB in small ruminants and pigs in Burkina Faso. Efforts must still be made in the fight against this zoonosis in order to limit its economic and public health impacts.

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.

PREVALENCE OF PARASITIC INFECTIONS IN CHILDREN OF BOKE, GUINEA.

Helminthic and intestinal protozoan infections and malaria infections are common in children less than 15 yr old in sub-Saharan Africa, but little is known about these infections in Guinea. The aim of this study was to determine the prevalence of parasitic infections in children aged less than 15 yr and the relationship of these infections with anemia. The cross-sectional study was done in Dabbis sub-prefecture in the Boke region of Guinea from 18 to 26 March 2017. A simple random sampling at the household level was performed, and 1 child under the age of 15 was included per eligible household. A total of 392 children were included in the analysis. Clinical and parasitological information were assessed, including anthropometric measures (weight and height), disease symptoms, hemoglobin level, and malaria parasitemia. Helminthic and protozoan intestinal infections were present in 59.7% of the children surveyed. Malaria infection prevalence was 45.5% when assessed by microscopy and 43.6% when assessed by a rapid diagnostic test. Plasmodium falciparum, accounting for 84.2% of malaria infections, was the main malaria species infection. Gastrointestinal parasites were present in 19.1% of children. The main gastrointestinal parasites present included Entamoeba coli (5.4%) and Giardia intestinalis (5.1%). There was no association between the presence of anemia and the parasitic status of the children. Parasitic screening and mass treatment in this age group, as well as household awareness raising, would reduce cases of parasitic infections in rural Guinea.

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.

A year of genomic surveillance reveals how the SARS-CoV-2 pandemic unfolded in Africa

The progression of the SARS-CoV-2 pandemic in Africa has so far been heterogeneous and the full impact is not yet well understood. Here, we describe the genomic epidemiology using a dataset of 8746 genomes from 33 African countries and two overseas territories. We show that the epidemics in most countries were initiated by importations, predominantly from Europe, which diminished following the early introduction of international travel restrictions. As the pandemic progressed, ongoing transmission in many countries and increasing mobility led to the emergence and spread within the continent of many variants of concern and interest, such as B.1.351, B.1.525, A.23.1 and C.1.1. Although distorted by low sampling numbers and blind-spots, the findings highlight that Africa must not be left behind in the global pandemic response, otherwise it could become a breeding ground for new variants.

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.

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.