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Zoonoses and Public Health Nov 2021Tuberculosis (TB) is a chronic communicable bacterial disease caused by Mycobacterium tuberculosis complex (MTBC) species. M. tuberculosis is the main causative agent... (Meta-Analysis)
Meta-Analysis Review
Tuberculosis (TB) is a chronic communicable bacterial disease caused by Mycobacterium tuberculosis complex (MTBC) species. M. tuberculosis is the main causative agent of human TB, and cattle are the primary host of Mycobacterium bovis; due to close interaction between cattle and humans, M. bovis poses a zoonotic risk. This review summarizes and estimates the prevalence of M. bovis infection among human cases. Studies reporting TB prevalence data that were published in English during 10 years from 20 April 2009 to 17 April 2019 were identified through search of PubMed and other sources. Quality of studies and risk of bias were assessed using standard tools for prevalence study reports. Characteristics of included studies and their main findings were summarized in tables and discussed with narrative syntheses. Meta-analysis was performed on 19 included studies, with a total of 7,185 MTBC isolates identified; 702 (9.7%) of them were characterized as of subspecies M. bovis, but there was a large prevalence difference between the studies, ranging from 0.4% to 76.7%. The genotyping-based studies reported significantly lower prevalence of zoonotic TB than did the studies based on older techniques. The overall pooled prevalence of M. bovis aggregated from all included studies was 12.1% of the total MTBC isolates, while the corresponding pooled figure from the 14 genotyping-based studies was only 1.4%. Generally, human M. bovis cases reported from different countries of the world suggest that the impact of zoonotic TB is still important in all regions. However, it was difficult to understand the true picture of the disease prevalence because of methodological differences. Future investigations on zoonotic TB should carefully consider these differences when evaluating prevalence results.
Topics: Animals; Cattle; Cattle Diseases; Humans; Mycobacterium bovis; Mycobacterium tuberculosis; Prevalence; Tuberculosis
PubMed: 34169644
DOI: 10.1111/zph.12868 -
Saudi Journal of Gastroenterology :... 2021Tuberculosis (TB) once considered a disease of the developing world is infrequent in the developing world too. Its worldwide prevalence with a huge impact on the... (Review)
Review
Tuberculosis (TB) once considered a disease of the developing world is infrequent in the developing world too. Its worldwide prevalence with a huge impact on the healthcare system both in economic and health terms has prompted the World Health Organization to make it a top priority infectious disease. Tuberculous infection of the pulmonary system is the most common form of this disease, however, extrapulmonary TB is being increasingly recognized and more often seen in immunocompromised situations. Gastrointestinal TB is a leading extrapulmonary TB manifestation that can defy diagnosis. Overlap of symptoms with other gastrointestinal diseases and limited accuracy of diagnostic tests demands more awareness of this disease. Untreated gastrointestinal TB can cause significant morbidity leading to prolonged hospitalization and surgery. Prompt diagnosis with early initiation of therapy can avoid this. This timely review discusses the epidemiology, risk factors, pathogenesis, clinical presentation, current diagnostic tools and therapy.
Topics: Humans; Mycobacterium tuberculosis; Prevalence; Tuberculosis, Gastrointestinal
PubMed: 34213424
DOI: 10.4103/sjg.sjg_148_21 -
Journal of Neurology Jul 2022Tuberculosis (TB) is the second most common cause of death due to a single infectious agent worldwide after COVID-19. Up to 15% of the cases are extrapulmonary, and if... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tuberculosis (TB) is the second most common cause of death due to a single infectious agent worldwide after COVID-19. Up to 15% of the cases are extrapulmonary, and if it is located in the central nervous system (CNS-TB), it presents high morbidity and mortality. Still, the global epidemiology of CNS-TB remains unknown.
AIM
To estimate the global prevalence and incidence of CNS-TB based on the available literature.
METHODS
We systematically searched in MEDLINE, Cochrane Central, Scopus, and LILACS databases (April 2020) and included observational studies evaluating the epidemiology of CNS-TB. Two independent researchers selected and assessed the quality of the studies and extracted relevant data. We performed random-effects model meta-analysis of proportions to estimate the pooled prevalence. The protocol of this study was registered in PROSPERO (CRD 42018103946).
RESULTS
We included 53 studies from 28 countries, representing 12,621 patients with CNS-TB. The prevalence of CNS-TB was 2 per 100,000 inhabitants. According to the clinical setting, the prevalence of CNS-TB represented the 13.91% of all cases of meningitis and 4.55% of all cases of TB. The mortality was calculated by tuberculous meningitis due to the lack of data of other presentation, and it rose up to 42.12% in hospitalized patients. The burden of countries' TB, Human Development Index (HDI), and the prevalence of HIV were the most important prevalence moderators, especially in patients with TB. No data on incidence were found.
CONCLUSION
The prevalence and mortality of CNS-TB remain high, and TB meningitis is the most frequent presentation. The highest prevalence was reported in developing countries, and its main moderators were the countries' HDI and HIV infection. Our study was limited by high heterogeneity, risk of bias, and potential data under registration from developing countries. The integration of CNS-TB early detection and management into national TB programs and population-based studies from developing countries are needed for better global estimation and response.
Topics: COVID-19; HIV Infections; Humans; Morbidity; Mycobacterium tuberculosis; Sensitivity and Specificity; Tuberculosis, Central Nervous System; Tuberculosis, Meningeal
PubMed: 35288778
DOI: 10.1007/s00415-022-11052-8 -
The Journal of Antimicrobial... Aug 2020Improved genetic understanding of Mycobacterium tuberculosis (MTB) resistance to novel and repurposed anti-tubercular agents can aid the development of rapid molecular...
Systematic review of mutations associated with resistance to the new and repurposed Mycobacterium tuberculosis drugs bedaquiline, clofazimine, linezolid, delamanid and pretomanid.
BACKGROUND
Improved genetic understanding of Mycobacterium tuberculosis (MTB) resistance to novel and repurposed anti-tubercular agents can aid the development of rapid molecular diagnostics.
METHODS
Adhering to PRISMA guidelines, in March 2018, we performed a systematic review of studies implicating mutations in resistance through sequencing and phenotyping before and/or after spontaneous resistance evolution, as well as allelic exchange experiments. We focused on the novel drugs bedaquiline, delamanid, pretomanid and the repurposed drugs clofazimine and linezolid. A database of 1373 diverse control MTB whole genomes, isolated from patients not exposed to these drugs, was used to further assess genotype-phenotype associations.
RESULTS
Of 2112 papers, 54 met the inclusion criteria. These studies characterized 277 mutations in the genes atpE, mmpR, pepQ, Rv1979c, fgd1, fbiABC and ddn and their association with resistance to one or more of the five drugs. The most frequent mutations for bedaquiline, clofazimine, linezolid, delamanid and pretomanid resistance were atpE A63P, mmpR frameshifts at nucleotides 192-198, rplC C154R, ddn W88* and ddn S11*, respectively. Frameshifts in the mmpR homopolymer region nucleotides 192-198 were identified in 52/1373 (4%) of the control isolates without prior exposure to bedaquiline or clofazimine. Of isolates resistant to one or more of the five drugs, 59/519 (11%) lacked a mutation explaining phenotypic resistance.
CONCLUSIONS
This systematic review supports the use of molecular methods for linezolid resistance detection. Resistance mechanisms involving non-essential genes show a diversity of mutations that will challenge molecular diagnosis of bedaquiline and nitroimidazole resistance. Combined phenotypic and genotypic surveillance is needed for these drugs in the short term.
Topics: Antitubercular Agents; Clofazimine; Diarylquinolines; Humans; Linezolid; Microbial Sensitivity Tests; Mutation; Mycobacterium tuberculosis; Nitroimidazoles; Oxazoles; Pharmaceutical Preparations; Tuberculosis, Multidrug-Resistant
PubMed: 32361756
DOI: 10.1093/jac/dkaa136 -
PLoS Neglected Tropical Diseases Apr 2020Leprosy is a chronic infectious disease caused by Mycobacterium leprae (M. leprae) and the more recently discovered Mycobacterium lepromatosis (M. lepromatosis). The two...
Leprosy is a chronic infectious disease caused by Mycobacterium leprae (M. leprae) and the more recently discovered Mycobacterium lepromatosis (M. lepromatosis). The two leprosy bacilli cause similar pathologic conditions. They primarily target the skin and the peripheral nervous system. Currently it is considered a Neglected Tropical Disease, being endemic in specific locations within countries of the Americas, Asia, and Africa, while in Europe it is only rarely reported. The reason for a spatial inequality in the prevalence of leprosy in so-called endemic pockets within a country is still largely unexplained. A systematic review was conducted targeting leprosy transmission research data, using PubMed and Scopus as sources. Publications between January 1, 1945 and July 1, 2019 were included. The transmission pathways of M. leprae are not fully understood. Solid evidence exists of an increased risk for individuals living in close contact with leprosy patients, most likely through infectious aerosols, created by coughing and sneezing, but possibly also through direct contact. However, this systematic review underscores that human-to-human transmission is not the only way leprosy can be acquired. The transmission of this disease is probably much more complicated than was thought before. In the Americas, the nine-banded armadillo (Dasypus novemcinctus) has been established as another natural host and reservoir of M. leprae. Anthroponotic and zoonotic transmission have both been proposed as modes of contracting the disease, based on data showing identical M. leprae strains shared between humans and armadillos. More recently, in red squirrels (Sciurus vulgaris) with leprosy-like lesions in the British Isles M. leprae and M. lepromatosis DNA was detected. This finding was unexpected, because leprosy is considered a disease of humans (with the exception of the armadillo), and because it was thought that leprosy (and M. leprae) had disappeared from the United Kingdom. Furthermore, animals can be affected by other leprosy-like diseases, caused by pathogens phylogenetically closely related to M. leprae. These mycobacteria have been proposed to be grouped as a M. leprae-complex. We argue that insights from the transmission and reservoirs of members of the M. leprae-complex might be relevant for leprosy research. A better understanding of possible animal or environmental reservoirs is needed, because transmission from such reservoirs may partly explain the steady global incidence of leprosy despite effective and widespread multidrug therapy. A reduction in transmission cannot be expected to be accomplished by actions or interventions from the human healthcare domain alone, as the mechanisms involved are complex. Therefore, to increase our understanding of the intricate picture of leprosy transmission, we propose a One Health transdisciplinary research approach.
Topics: Animals; Armadillos; Disease Reservoirs; Disease Transmission, Infectious; Global Health; Humans; Incidence; Leprosy; Mycobacterium; Mycobacterium leprae; Prevalence; Sciuridae
PubMed: 32339201
DOI: 10.1371/journal.pntd.0008276 -
International Journal of Molecular... Oct 2022Dapsone (DDS), Rifampicin (RIF) and Ofloxacin (OFL) are drugs recommended by the World Health Organization (WHO) for the treatment of leprosy. In the context of leprosy,... (Meta-Analysis)
Meta-Analysis Review
Dapsone (DDS), Rifampicin (RIF) and Ofloxacin (OFL) are drugs recommended by the World Health Organization (WHO) for the treatment of leprosy. In the context of leprosy, resistance to these drugs occurs mainly due to mutations in the target genes (Folp1, RpoB and GyrA). It is important to monitor antimicrobial resistance in patients with leprosy. Therefore, we performed a meta-analysis of drug resistance in Mycobacterium leprae and the mutational profile of the target genes. In this paper, we limited the study period to May 2022 and searched PubMed, Web of Science (WOS), Scopus, and Embase databases for identified studies. Two independent reviewers extracted the study data. Mutation and drug-resistance rates were estimated in Stata 16.0. The results demonstrated that the drug-resistance rate was 10.18% (95% CI: 7.85-12.51). Subgroup analysis showed the highest resistance rate was in the Western Pacific region (17.05%, 95% CI:1.80 to 13.78), and it was higher after 2009 than before [(11.39%, 7.46-15.33) vs. 6.59% (3.66-9.53)]. We can conclude that the rate among new cases (7.25%, 95% CI: 4.65-9.84) was lower than the relapsed (14.26%, 95 CI%: 9.82-18.71). Mutation rates of Folp1, RpoB and GyrA were 4.40% (95% CI: 3.02-5.77), 3.66% (95% CI: 2.41-4.90) and 1.28% (95% CI: 0.87-1.71) respectively, while the rate for polygenes mutation was 1.73% (0.83-2.63). For further analysis, we used 368 drug-resistant strains as research subjects and found that codons (Ser, Pro, Ala) on RpoB, Folp1 and GyrA are the most common mutation sites in the determining region (DRDR). In addition, the most common substitution patterns of Folp1, RpoB, and GyrA are Pro→Leu, Ser→Leu, and Ala→Val. This study found that a higher proportion of patients has developed resistance to these drugs, and the rate has increased since 2009, which continue to pose a challenge to clinicians. In addition, the amino acid alterations in the sequence of the DRDR regions and the substitution patterns mentioned in the study also provide new ideas for clinical treatment options.
Topics: Humans; Rifampin; Dapsone; Leprostatic Agents; Ofloxacin; Drug Resistance, Bacterial; Mycobacterium leprae; Leprosy; Mutation; Amino Acids; Microbial Sensitivity Tests
PubMed: 36293307
DOI: 10.3390/ijms232012443 -
Chest Nov 2023Nontuberculous mycobacterial pulmonary disease (NTM-PD) is widely underdiagnosed, and certain patient groups, such as those with underlying respiratory diseases, are at... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Nontuberculous mycobacterial pulmonary disease (NTM-PD) is widely underdiagnosed, and certain patient groups, such as those with underlying respiratory diseases, are at increased risk of developing the disease. Understanding patients at risk is essential to allow for prompt testing and diagnosis and appropriate management to prevent disease progression.
RESEARCH QUESTION
What are the risk factors for NTM-PD that should prompt a physician to consider NTM testing and diagnosis?
STUDY DESIGN AND METHODS
Electronic searches of PubMed and EMBASE were conducted in July 2021 for the period 2011-2021. Inclusion criteria were studies of patients with NTM-PD with associated risk factors. Data were extracted and assessed using the Newcastle-Ottawa Scale. Data analysis was conducted using the R-based "meta" package. Only studies that reported association outcomes for cases with NTM-PD compared with control participants (healthy populations or participants without NTM-PD) were considered for the meta-analysis.
RESULTS
Of the 9,530 searched publications, 99 met the criteria for the study. Of these, 24 formally reported an association between possible risk factors and the presence of NTM-PD against a control population and were included in the meta-analysis. Comorbid respiratory disease was associated with a significant increase in the OR for NTM-PD (bronchiectasis [OR, 21.43; 95% CI, 5.90-77.82], history of TB [OR, 12.69; 95% CI, 2.39-67.26], interstitial lung disease [OR, 6.39; 95% CI, 2.65-15.37], COPD [OR, 6.63; 95% CI, 4.57-9.63], and asthma [OR, 4.15; 95% CI, 2.81-6.14]). Other factors noted to be associated with an increased risk of NTM-PD were the use of inhaled corticosteroids (OR 4.46; 95% CI, 2.13-9.35), solid tumors (OR, 4.66; 95% CI, 1.04-20.94) and the presence of pneumonia (OR, 5.54; 95% CI, 2.72-11.26).
INTERPRETATION
The greatest risk for NTM-PD is conferred by comorbid respiratory diseases such as bronchiectasis. These findings could help with identification of patient populations at risk for NTM-PD to drive prompt testing and appropriate initiation of therapy.
Topics: Humans; Mycobacterium Infections, Nontuberculous; Risk Factors; Bronchiectasis; Asthma; Respiratory Tract Diseases; Nontuberculous Mycobacteria; Lung Diseases; Retrospective Studies
PubMed: 37429481
DOI: 10.1016/j.chest.2023.06.014 -
International Journal of Infectious... Dec 2022To describe the global trends of pulmonary nontuberculous mycobacteria (NTM) infection and disease. (Review)
Review
OBJECTIVES
To describe the global trends of pulmonary nontuberculous mycobacteria (NTM) infection and disease.
METHODS
A systematic review of studies including culture-based NTM data over time. Studies reporting on pulmonary NTM infection and/or disease were included. Information on the use of guideline-based criteria for disease were collected, in which, infection is defined as the absence of symptoms and radiological findings compatible with NTM pulmonary disease. The trends of change for incidence/prevalence were evaluated using linear regressions, and the corresponding pooled estimates were calculated.
RESULTS
Most studies reported increasing pulmonary NTM infection (82.1%) and disease (66.7%) trends. The overall annual rate of change for NTM infection and disease per 100,000 persons/year was 4.0% (95% confidence interval [CI]: 3.2-4.8) and 4.1% (95% CI: 3.2-5.0), respectively. For absolute numbers of NTM infection and disease, the overall annual change was 2.0 (95% CI: 1.6-2.3) and 0.5 (95% CI: 0.3-0.7), respectively. An increasing trend was also seen for Mycobacterium avium complex infection (n = 15/19, 78.9%) and disease (n = 10/12, 83.9%) and for Mycobacterium abscessus complex (n = 15/23, 65.2%) infection (n = 11/17, 64.7%) but less so for disease (n = 2/8, 25.0%).
CONCLUSION
Our data indicate an overall increase in NTM worldwide for both infection and disease. The explanation to this phenomenon warrants further investigation.
Topics: Humans; Nontuberculous Mycobacteria; Mycobacterium Infections, Nontuberculous; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Mycobacterium abscessus; Lung Diseases; Pneumonia
PubMed: 36244600
DOI: 10.1016/j.ijid.2022.10.013 -
Lancet (London, England) Mar 2020Tens of millions of children are exposed to Mycobacterium tuberculosis globally every year; however, there are no contemporary estimates of the risk of developing... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Tens of millions of children are exposed to Mycobacterium tuberculosis globally every year; however, there are no contemporary estimates of the risk of developing tuberculosis in exposed children. The effectiveness of contact investigations and preventive therapy remains poorly understood.
METHODS
In this systematic review and meta-analysis, we investigated the development of tuberculosis in children closely exposed to a tuberculosis case and followed for incident disease. We restricted our search to cohort studies published between Jan 1, 1998, and April 6, 2018, in MEDLINE, Web of Science, BIOSIS, and Embase electronic databases. Individual-participant data and a pre-specified list of variables were requested from authors of all eligible studies. These included characteristics of the exposed child, the index case, and environmental characteristics. To be eligible for inclusion in the final analysis, a dataset needed to include: (1) individuals below 19 years of age; (2) follow-up for tuberculosis for a minimum of 6 months; (3) individuals with household or close exposure to an individual with tuberculosis; (4) information on the age and sex of the child; and (5) start and end follow-up dates. Studies assessing incident tuberculosis but without dates or time of follow-up were excluded. Our analysis had two primary aims: (1) estimating the risk of developing tuberculosis by time-period of follow-up, demographics (age, region), and clinical attributes (HIV, tuberculosis infection status, previous tuberculosis); and (2) estimating the effectiveness of preventive therapy and BCG vaccination on the risk of developing tuberculosis. We estimated the odds of prevalent tuberculosis with mixed-effects logistic models and estimated adjusted hazard ratios (HRs) for incident tuberculosis with mixed-effects Poisson regression models. The effectiveness of preventive therapy against incident tuberculosis was estimated through propensity score matching. The study protocol is registered with PROSPERO (CRD42018087022).
FINDINGS
In total, study groups from 46 cohort studies in 34 countries-29 (63%) prospective studies and 17 (37%) retrospective-agreed to share their data and were included in the final analysis. 137 647 tuberculosis-exposed children were evaluated at baseline and 130 512 children were followed for 429 538 person-years, during which 1299 prevalent and 999 incident tuberculosis cases were diagnosed. Children not receiving preventive therapy with a positive result for tuberculosis infection had significantly higher 2-year cumulative tuberculosis incidence than children with a negative result for tuberculosis infection, and this incidence was greatest among children below 5 years of age (19·0% [95% CI 8·4-37·4]). The effectiveness of preventive therapy was 63% (adjusted HR 0·37 [95% CI 0·30-0·47]) among all exposed children, and 91% (adjusted HR 0·09 [0·05-0·15]) among those with a positive result for tuberculosis infection. Among all children <5 years of age who developed tuberculosis, 83% were diagnosed within 90 days of the baseline visit.
INTERPRETATION
The risk of developing tuberculosis among exposed infants and young children is very high. Most cases occurred within weeks of contact investigation initiation and might not be preventable through prophylaxis. This suggests that alternative strategies for prevention are needed, such as earlier initiation of preventive therapy through rapid diagnosis of adult cases or community-wide screening approaches.
FUNDING
National Institutes of Health.
Topics: Adolescent; Age Factors; Child; Child, Preschool; Contact Tracing; Disease Transmission, Infectious; Family Characteristics; Female; Global Health; Humans; Incidence; Male; Mycobacterium tuberculosis; Risk Assessment; Sex Factors; Tuberculosis, Pulmonary
PubMed: 32199484
DOI: 10.1016/S0140-6736(20)30166-5 -
The Lancet. Infectious Diseases Jan 2017Mycobacterium tuberculosis is recognised as the primary cause of human tuberculosis worldwide. However, substantial evidence suggests that the burden of Mycobacterium... (Review)
Review
Mycobacterium tuberculosis is recognised as the primary cause of human tuberculosis worldwide. However, substantial evidence suggests that the burden of Mycobacterium bovis, the cause of bovine tuberculosis, might be underestimated in human beings as the cause of zoonotic tuberculosis. In 2013, results from a systematic review and meta-analysis of global zoonotic tuberculosis showed that the same challenges and concerns expressed 15 years ago remain valid. These challenges faced by people with zoonotic tuberculosis might not be proportional to the scientific attention and resources allocated in recent years to other diseases. The burden of zoonotic tuberculosis in people needs important reassessment, especially in areas where bovine tuberculosis is endemic and where people live in conditions that favour direct contact with infected animals or animal products. As countries move towards detecting the 3 million tuberculosis cases estimated to be missed annually, and in view of WHO's end TB strategy endorsed by the health authorities of WHO Member States in 2014 to achieve a world free of tuberculosis by 2035, we call on all tuberculosis stakeholders to act to accurately diagnose and treat tuberculosis caused by M bovis in human beings.
Topics: Animals; Cattle; Humans; Mycobacterium bovis; Mycobacterium tuberculosis; Tuberculosis; Tuberculosis, Bovine; Zoonoses
PubMed: 27697390
DOI: 10.1016/S1473-3099(16)30139-6