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Exploring the role of wastewater-based epidemiology in understanding tuberculosis burdens in Africa.Environmental Research Aug 2023Tuberculosis (TB) remains a persistent challenge to public health and presents a substantial menace, especially in developing nations of sub-Saharan Africa. It exerts a...
Tuberculosis (TB) remains a persistent challenge to public health and presents a substantial menace, especially in developing nations of sub-Saharan Africa. It exerts a considerable strain on healthcare systems in these regions. Effective control requires reliable surveillance, which can be improved by incorporating environmental data alongside clinical data. Molecular advances have led to the development of alternative surveillance methods, such as wastewater-based epidemiology. This studyinvestigated the presence, concentration, and diversity of Mycobacterium tuberculosis complex, the cause of TB, in from six African countries: Ghana, Nigeria, Kenya, Uganda, Cameroon, and South Africa. Samples were collected from wastewater treatment plants. All samples were found to contain Mycobacterium species that have been linked to TB in both humans and animals, including Mycobacterium tuberculosis complex, Mycobacterium tuberculosis, Mycobacterium bovis, Mycobacterium africanum, and Mycobacterium caprae, at varying concentrations. The highest median concentration was found in Ghana, reaching up to 4.7 Log copies/ml for MTBC, 4.6 Log copies/ml for M. bovis, and 3.4 Log copies/ml for M. africanum. The presence of M. africanum outside of West Africa was found in South Africa, Kenya, and Uganda and could indicate the spread of the pathogen. The study underscores the usefulness of wastewater-based epidemiology for tracking TB and shows that even treated wastewater may contain these pathogens, posing potential public health risks.
Topics: Animals; Humans; Wastewater-Based Epidemiological Monitoring; Phylogeny; Tuberculosis; Mycobacterium tuberculosis; Ghana
PubMed: 37105295
DOI: 10.1016/j.envres.2023.115911 -
BMC Infectious Diseases Mar 2024Nontuberculous mycobacteria (NTM) are environmental bacteria which may cause chronic lung disease. The prevalence of NTM pulmonary infection and disease has been...
BACKGROUND
Nontuberculous mycobacteria (NTM) are environmental bacteria which may cause chronic lung disease. The prevalence of NTM pulmonary infection and disease has been increasing in the United States and globally. The predominant clinically relevant species of NTM in the United States are Mycobacterium avium complex (MAC) species and Mycobacterium abscessus. With the development of rapid species identification methods for NTM (e.g. PCR probes), more testing for NTM is being conducted through commercial labs, such as Laboratory Corporation of America (Labcorp), which provides deidentified real-time testing data to the Centers for Disease Control (CDC) pursuant to a data sharing agreement. Because NTM lung infections are not reportable in most states, other data sources are key to understanding NTM testing patterns, positivity rates, and species distributions to track infection trends and identify clinical care needs.
METHODS
We obtained national Labcorp data for the period January 2019 through mid-April 2022. We subset the data to only respiratory samples sent for Acid Fast Bacilli (AFB) cultures. NTM positive results were defined as those which identified an NTM species and are not Mycobacterium tuberculosis, Mycobacterium bovis, or Mycobacterium gordonae.
RESULTS
Overall, 112,528 respiratory samples were sent for AFB testing during the study period; 26.3% were from the Southeast U.S., identified as HSS Region IV in the Labcorp dataset, and 23.0% were from the Pacific and South Pacific region (Region IX). The culture positive prevalence ranged from 20.2% in the Southeast to 9.2% in the East North Central region (Region V). In the Southeast US, M. abscessus prevalence was 4.0%. For MAC, the highest prevalence was observed in the Mountain region (Region VII) (13.5%) and the lowest proportion was in the East South Central region (7.3%, Region III). Among positive tests, the proportion which was MAC varied from 61.8% to 88.9% and was highest in the Northeast U.S. The proportion of positive samples which were M. abscessus ranged from 3.8% to 19.7% and was highest in the Southeast.
CONCLUSIONS
The Southeastern region of the U.S. has the highest rate of culture positivity in Labcorp tests for total NTM and, of all positive tests, the highest proportion of M. abscessus. These estimates may underrepresent the true number of M. abscessus infections because M. absesscus-specific probes are not commercially available and not all NTM testing in the United States is done by Labcorp. Analysis of real-time testing data from commercial laboratories may provide insights into risk factors for NTM culture positivity in 'hotspot' areas.
Topics: United States; Humans; Nontuberculous Mycobacteria; Mycobacterium avium Complex; Mycobacterium abscessus; Laboratories; Mycobacterium bovis; Opportunistic Infections
PubMed: 38448840
DOI: 10.1186/s12879-024-09059-9 -
PLoS Neglected Tropical Diseases Oct 2023In this article, we provide an in-depth analysis on the drug-resistance phenotypic characteristics of a cohort of 325 tuberculosis and characterize by Whole Genome... (Review)
Review
In this article, we provide an in-depth analysis on the drug-resistance phenotypic characteristics of a cohort of 325 tuberculosis and characterize by Whole Genome Sequencing 24 isolates from Nigeria belonging to L4, L5 and L6. Our results suggest an alarming rate of drug-resistance of the L4.6.2.2 Mycobacterium tuberculosis complex (MTBC) lineage and a high diversity of L5. We compiled these new Sequence Read Archives (SRAs) to previously published ones from available Bioprojects run in Nigeria. We performed RAxML phylogenetic reconstructions of larger samples that include public NCBI SRAs from some neighboring countries (Cameroon, Ghana). To confront phylogenetic reconstruction to metadata, we used a new proprietary database named TB-Annotator. We show that L5 genomes in Northern Nigeria belong to new clades as the ones described until now and allow an update of the taxonomy of L5. In addition, we describe the L4.6.2.2 lineage in Nigeria, Cameroon and Ghana. We provide computations on the likely divergence time of L4.6.2.2 and suggest a new hypothesis concerning its origin. Finally we provide a short overview on M. bovis diversity in Nigeria. This study constitutes a baseline knowledge on the global genomic diversity, phylogeography and phylodynamics of MTBC in Nigeria, as well as on the natural history of this largely ignored but densely populated country of Africa. These results highlight the need of sequencing additional MTBC genomes in Nigeria and more generally in West-Africa, both for public health and for academic reasons. The likelihood of replacement of L5-L6 by L4.6.2.2 isolates, leave potentially little time to gather historical knowledge informative on the ancient history of tuberculosis in West-Africa.
Topics: Humans; Cameroon; Genotype; Ghana; Mycobacterium tuberculosis; Nigeria; Phylogeny; Tuberculosis
PubMed: 37824575
DOI: 10.1371/journal.pntd.0011619 -
Frontiers in Public Health 2023Tuberculosis (TB) is a major cause of ill health and one of the leading causes of death worldwide, caused by species of the complex (MTBC), with being the dominant...
BACKGROUND
Tuberculosis (TB) is a major cause of ill health and one of the leading causes of death worldwide, caused by species of the complex (MTBC), with being the dominant pathogen in humans and in cattle. Zoonotic transmission of TB (zTB) to humans is frequent particularly where TB prevalence is high in cattle. In this study, we explored the prevalence of zTB in central Ethiopia, an area highly affected by bovine TB (bTB) in cattle.
METHOD
A convenient sample of 385 patients with pulmonary tuberculosis (PTB, = 287) and tuberculous lymphadenitis (TBLN, = 98) were included in this cross-sectional study in central Ethiopia. Sputum and fine needle aspirate (FNA) samples were obtained from patients with PTB and TBLN, respectively, and cultures were performed using BACTEC MGIT 960. All culture positive samples were subjected to quantitative PCR (qPCR) assays, targeting IS, RD9 and RD4 genomic regions for detection of MTBC, and , respectively.
RESULTS
Two hundred and fifty-five out of 385 sampled patients were culture positive and all were isolates identified as MTBC by being positive for the IS assay. Among them, 249 (97.6%) samples had also a positive RD9 result (intact RD9 locus) and were consequently classified as . The remaining six (2.4%) isolates were RD4 deficient and thereby classified as . Five out of these six strains originated from PTB patients whereas one was isolated from a TBLN patient. Occupational risk and the widespread consumption of raw animal products were identified as potential sources of infection in humans, and the isolation of from PTB patients suggests the possibility of human-to-human transmission, particularly in patients with no known contact history with animals.
CONCLUSION
The detected proportion of culture positive cases of 2.4% being from this region was higher zTB rate than previously reported for the general population of Ethiopia. Patients with infection are more likely to get less efficient TB treatment because is inherently resistant to pyrazinamide. MTBC species identification should be performed where is common in cattle, especially in patients who have a history of recurrence or treatment failure.
Topics: Animals; Cattle; Humans; Tuberculosis, Bovine; Ethiopia; Cross-Sectional Studies; Mycobacterium bovis; Mycobacterium tuberculosis; Tuberculosis, Lymph Node
PubMed: 37771833
DOI: 10.3389/fpubh.2023.1204525 -
Minerva Urology and Nephrology Oct 2023The existence and prognosis of T1LG (T1 low-grade) bladder cancer is controversial. Also, because of data paucity, it remains unclear what is the clinical history of...
BACKGROUND
The existence and prognosis of T1LG (T1 low-grade) bladder cancer is controversial. Also, because of data paucity, it remains unclear what is the clinical history of bacillus Calmette-Guérin (BCG) treated T1LG tumors and if it differs from other NMIBC (non-muscle-invasive bladder cancer) representatives. The aim of this study was to analyse recurrence-free survival (RFS) and progression-free survival (PFS) in patients with T1LG bladder cancers treated with BCG immunotherapy.
METHODS
A multi-institutional and retrospective study of 2510 patients with Ta/T1 NMIBC with or without carcinoma in situ (CIS) treated with BCG (205 T1LG patients) was performed. Kaplan-Meier estimates and log-rank test for RFS and PFS to compare the survival between TaLG, TaHG, T1LG, and T1HG NMIBC were used. Also, T1LG tumors were categorized into EAU2021 risk groups and PFS analysis was performed, and Cox multivariate model for both RFS and PFS were constructed.
RESULTS
The median follow-up was 52 months. For the T1LG cohort, the estimated RFS and PFS rates at 5-year were 59.3% and 89.2%, respectively. While there were no differences in RFS between NMIBC subpopulations, a slightly better PFS was found in T1LG NMIBC compared to T1HG (5-year PFS; T1LG vs. T1HG: 82% vs. 89%; P<0.001). A heterogeneous classification of patients with T1LG NMIBC was observed when EAU 2021 prognostic model was applied, finding a statistically significant worse PFS in patients classified as high-risk T1LG (5-year PFS; 81.8%) compared to those in intermediate (5-year PFS; 93,4%), and low-risk T1LG tumors (5-year PFS; 98,1%).
CONCLUSIONS
The RFS of T1LG was comparable to other NMIBC subpopulations. The PFS of T1LG tumors was significantly better than of T1HG NMIBC. The EAU2021 scoring model heterogeneously categorized the risk of progression in T1LG tumors and the high-risk T1LG had the worst PFS.
Topics: Humans; BCG Vaccine; Carcinoma, Transitional Cell; Immunotherapy; Mycobacterium bovis; Prognosis; Retrospective Studies; Urinary Bladder Neoplasms
PubMed: 37728495
DOI: 10.23736/S2724-6051.23.05418-6 -
Preventive Veterinary Medicine Nov 2023Despite control and surveillance programmes, Mycobacterium bovis, the main aetiologic agent of bovine tuberculosis (bTB), is still detected on cattle farms and in...
Despite control and surveillance programmes, Mycobacterium bovis, the main aetiologic agent of bovine tuberculosis (bTB), is still detected on cattle farms and in wildlife populations in France, especially in badgers in the French Côte-d'Or département. The aim of our study was to find out if infected badgers were trapped significantly closer to pastures of infected farms than non-infected badgers and, if so, to determine the most efficient distance around those pastures for badger trapping, particularly for surveillance purposes. We studied two subareas (southern and northern), chosen based on natural barriers to badger movements and according to the presence of pastures belonging to infected farms (POIFs) and infected or non-infected badgers. In each subarea, we computed the shortest distances D and D between badgers trapped a given year n between 2015 and 2019 (n = 59 infected and n = 1535 non-infected badgers for D; n = 53 infected and n = 1476 non-infected badgers for D) and POIFs designated as infected between the year n - 4 and n + 1 (respectively n = 373 and n = 388 POIFs). D was calculated without considering spoligotypes, while D was calculated considering the possible epidemiological link between infected badgers and POIFs by using bTB spoligotype information. Then, we computed the observed mean and median of the D and D distances and used a bootstrap analysis to test if infected badgers were found significantly closer to POIFs than non-infected badgers. We observed that infection of badgers was not independent of distance from POIF in both subareas but distances (D or D) were different between the northern and southern subarea. In the northern subarea, which displays a mosaic landscape (mean and median D distances were respectively 612 m and 303 m for infected badgers), infected badgers indeed were trapped closer to POIFs, considering D and D. In the southern subarea, predominantly forested, infected badgers were significantly closer to POIFs than non-infected badgers when considering D but not for D (mean and median D distances were respectively 7148 m and 4831 m for infected badgers). These results will help to determine the most efficient distance from POIFs to trap badgers to determine their infection status in countryside landscapes. They also highlight the need to better understand the epidemiological systems at play in more forested landscapes where badgers may behave differently or other susceptible sympatric wild species might play a more important role in the circulation of M. bovis, both phenomena contributing to badger infection at greater distances from POIFs.
Topics: Cattle; Animals; Mycobacterium bovis; Mustelidae; Tuberculosis, Bovine; Animals, Wild; France; Cattle Diseases
PubMed: 37865009
DOI: 10.1016/j.prevetmed.2023.106044 -
Frontiers in Cellular and Infection... 2023Tuberculosis (TB), attributed to the complex, is one of the most serious zoonotic diseases worldwide. Nevertheless, the host mechanisms preferentially leveraged by...
Tuberculosis (TB), attributed to the complex, is one of the most serious zoonotic diseases worldwide. Nevertheless, the host mechanisms preferentially leveraged by Mycobacterium remain unclear. After infection, both (MTB) and (MB) bacteria exhibit intimate interactions with host alveolar macrophages; however, the specific mechanisms underlying these macrophage responses remain ambiguous. In our study, we performed a comparative proteomic analysis of bovine alveolar macrophages (BAMs) infected with MTB or MB to elucidate the differential responses of BAMs to each pathogen at the protein level. Our findings revealed heightened TB infection susceptibility of BAMs that had been previously infected with MTB or MB. Moreover, we observed that both types of mycobacteria triggered significant changes in BAM energy metabolism. A variety of proteins and signalling pathways associated with autophagy and inflammation-related progression were highly activated in BAMs following MB infection. Additionally, proteins linked to energy metabolism were highly expressed in BAMs following MTB infection. In summary, we propose that BAMs may resist MTB and MB infections via different mechanisms. Our findings provide critical insights into TB pathogenesis, unveiling potential biomarkers to facilitate more effective TB treatment strategies. Additionally, our data lend support to the hypothesis that MTB may be transmitted via cross-species infection.
Topics: Animals; Cattle; Mycobacterium tuberculosis; Mycobacterium bovis; Macrophages, Alveolar; Proteome; Proteomics; Tuberculosis
PubMed: 38029268
DOI: 10.3389/fcimb.2023.1266884 -
Frontiers in Veterinary Science 2024Deer tuberculosis is a chronic zoonotic infectious disease, despite the existence of socio-economic and zoonotic risk factors, but at present, there has been no...
BACKGROUND
Deer tuberculosis is a chronic zoonotic infectious disease, despite the existence of socio-economic and zoonotic risk factors, but at present, there has been no systematic review of deer tuberculosis prevalence in mainland China. The aim of this meta-analysis was to estimate the overall prevalence of deer TB in mainland China and to assess possible associations between potential risk factors and the prevalence of deer tuberculosis.
METHODOLOGY
This study was searched in six databases in Chinese and English, respectively (1981 to December 2023). Four authors independently reviewed the titles and abstracts of all retrieved articles to establish the inclusion exclusion criteria. Using the meta-analysis package estimated the combined effects. Cochran's Q-statistic was used to analyze heterogeneity. Funnel plots (symmetry) and used the Egger's test identifying publication bias. Trim-and-fill analysis methods were used for validation and sensitivity analysis. we also performed subgroup and meta-regression analyses.
RESULTS
In this study, we obtained 4,400 studies, 20 cross-sectional studies were screened and conducted a systematic review and meta-analysis. Results show: The overall prevalence of tuberculosis in deer in mainland China was 16.1% (95% confidence interval (CI):10.5 24.6; (Deer tuberculosis infected 5,367 out of 22,215 deer in mainland China) 5,367/22215; 1981 to 2023). The prevalence in Central China was the highest 17.5% (95% CI:14.0-21.9; 63/362), and among provinces, the prevalence in Heilongjiang was the highest at 26.5% (95% CI:13.2-53.0; 1557/4291). was the most commonly infected species, with a prevalence of 35.3% (95% CI:18.5-67.2; 6/17). We also assessed the association between geographic risk factors and the incidence of deer tuberculosis.
CONCLUSION
Deer tuberculosis is still present in some areas of China. Assessing the association between risk factors and the prevalence of deer tuberculosis showed that reasonable and scientific-based breeding methods, a suitable breeding environment, and rapid and accurate detection methods could effectively reduce the prevalence of deer tuberculosis. In addition, in the management and operation of the breeding base, improving the scientific feed nutrition standards and establishing comprehensive standards for disease prevention, immunization, quarantine, treatment, and disinfection according to the breeding varieties and scale, are suggested as ways to reduce the prevalence of deer tuberculosis.
PubMed: 38440384
DOI: 10.3389/fvets.2024.1333975 -
Microbiology Spectrum Sep 2023Zinc excess is toxic to bacteria and, thus, represents an important innate defense mechanism of host cells, especially against mycobacterial infections. However, the...
Zinc excess is toxic to bacteria and, thus, represents an important innate defense mechanism of host cells, especially against mycobacterial infections. However, the signaling pathway triggered by zinc excess and its relationship with iron homeostasis remain poorly understood in mycobacteria. Here, we characterize a novel Zur-IdeR-iron homeostasis signaling pathway that modulates the growth of under zinc toxicity. We found that the regulator Zur interacts with the iron-homeostasis regulator IdeR, enhancing the DNA-binding ability of IdeR. Excess zinc disrupts this interaction and represses transcription through Zur, which promotes the expression of iron uptake genes and leads to the accumulation of intracellular iron in . The elevated iron levels lower the bacterial survival ability under excess zinc stress. Consistently, deleting hinders intracellular iron accumulation of and enhances bacterial growth under stress, while silencing impairs the growth of the wild-type and -deleted strains under the same conditions. Interestingly, both Zur and IdeR are conserved in bacteria facing zinc toxicity. Overall, our work uncovers a novel antimicrobial signal pathway whereby zinc excess disrupts iron homeostasis, which may deepen our understanding of the crosstalk mechanism between iron and zinc homeostasis in bacteria.IMPORTANCEAs a catalytic and structural cofactor of proteins, zinc is essential for almost all living organisms. However, zinc excess is toxic and represents a vital innate immunity strategy of macrophages to combat intracellular pathogens, especially against mycobacterial pathogens such as , the causative agent of tuberculosis. Here, we first characterize an antibacterial signaling pathway of zinc excess and its relationship with iron homeostasis in . We found that excess zinc inhibits the transcription of and its DNA-binding activity through Zur, which, in turn, promotes the expression of iron uptake genes, causes intracellular iron accumulation, and finally impairs the bacterial growth. This study reveals the existence of the Zur-IdeR-iron homeostasis pathway triggered by zinc excess in , which will shed light on the crosstalk mechanisms between zinc and iron homeostasis in bacteria and the antimicrobial mechanisms of host-mediated zinc toxicity.
PubMed: 37668384
DOI: 10.1128/spectrum.01069-23 -
Frontiers in Immunology 2023Tuberculosis (TB) in the bovine is one of the most predominant chronic debilitating infectious diseases primarily caused by . Besides, the incidence of TB in humans due...
Tuberculosis (TB) in the bovine is one of the most predominant chronic debilitating infectious diseases primarily caused by . Besides, the incidence of TB in humans due to , and that in bovines (bovine TB, bTB) due to - indicates cattle as a major reservoir of zoonotic TB. While India accounts for the highest global burden of both TB and multidrug-resistant TB in humans, systematic evaluation of bTB prevalence in India is largely lacking. Recent reports emphasized markedly greater bTB prevalence in exotic and crossbred cattle compared to indigenous cattle breeds that represent more than one-third of the total cattle population in India, which is the largest globally. This study aimed at elucidating the immune responses underlying the differential bTB incidence in prominent indigenous (Sahiwal), and crossbred (Sahiwal x Holstein Friesian) cattle reared in India. Employing the standard Single Intradermal Tuberculin Test (SITT), and mycobacterial gene-targeting single as well as multiplex-PCR-based screening revealed higher incidences of bovine tuberculin reactors as well as Complex specific PCR positivity amongst the crossbred cattle. Further, mycobacterial infection in cultures of bovine peripheral blood mononuclear cells (PBMC) from SITT, and myco-PCR negative healthy cattle exhibited significantly higher intracellular growth of BCG, and H37Ra in the crossbred cattle PBMCs compared to native cattle. In addition, native cattle PBMCs induced higher pro-inflammatory cytokines and signaling pathways, such as interferon-gamma (IFN-γ), interleukin-17 (IL-17), tank binding kinase-1 (TBK-1), and nitric oxide (NO) upon exposure to live mycobacterial infection in comparison to PBMCs from crossbred cattle that exhibited higher expression of IL-1β transcripts. Together, these findings highlight that differences in the innate immune responses of these cattle breeds might be contributing to the differential susceptibility to bTB infection, and the resultant disparity in bTB incidence amongst indigenous, and crossbred cattle.
Topics: Humans; Animals; Cattle; Leukocytes, Mononuclear; Tuberculosis; Tuberculosis, Bovine; Mycobacterium bovis; Mycobacterium tuberculosis; Tuberculin; Immunity, Innate
PubMed: 37795082
DOI: 10.3389/fimmu.2023.1199092