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The Lancet. Respiratory Medicine May 2024Tuberculosis is a preventable disease. However, there is debate regarding which individuals would benefit most from tuberculosis preventive treatment and whether these...
Effectiveness of preventive treatment among different age groups and Mycobacterium tuberculosis infection status: a systematic review and individual-participant data meta-analysis of contact tracing studies.
BACKGROUND
Tuberculosis is a preventable disease. However, there is debate regarding which individuals would benefit most from tuberculosis preventive treatment and whether these benefits vary in settings with a high burden and low burden of tuberculosis. We aimed to compare the effectiveness of tuberculosis preventive treatment in exposed individuals of differing ages and Mycobacterium tuberculosis infection status while considering tuberculosis burden of the settings.
METHODS
In this systematic review and individual-participant meta-analysis, we investigated the development of incident tuberculosis in people closely exposed to individuals with tuberculosis. We searched for studies published between Jan 1, 1998, and April 6, 2018, in MEDLINE, Web of Science, BIOSIS, and Embase. We restricted our search to cohort studies; case-control studies and outbreak reports were excluded. Two reviewers evaluated titles, abstracts, and full text articles for eligibility. At each stage, two reviewers discussed discrepancies and re-evaluated articles until a consensus was reached. Individual-participant data and a pre-specified list of variables, including characteristics of the exposed contact, the index patient, and environmental characteristics, were requested from authors of all eligible studies; contacts exposed to a drug-resistant tuberculosis index patient were excluded. The primary study outcome was incident tuberculosis. We estimated adjusted hazard ratios (aHRs) for incident tuberculosis with mixed-effects Cox regression models with a study-level random effect. We estimated the number-needed-to-treat (NNT) to prevent one person developing tuberculosis. Propensity score matching procedures were used in all analyses. This study is registered with PROSPERO (CRD42018087022).
FINDINGS
After screening 25 358 records for eligibility, 439 644 participants from 32 cohort studies were included in the individual-participant data meta-analysis. Participants were followed for 1 396 413 person-years (median of 2·7 years [IQR 1·3-4.4]), during which 2496 people were diagnosed with incident tuberculosis. Overall, effectiveness of preventive treatment was 49% (aHR 0·51 [95% CI 0·44-0·60]). Participants with a positive tuberculin-skin-test (TST) or IFNγ release assay (IGRA) result at baseline benefitted from greater protection, regardless of age (0·09 [0·05-0·17] in children younger than 5 years, 0·20 [0·15-0·28] in individuals aged 5-17 years, and 0·17 [0·13-0·22] in adults aged 18 years and older). The effectiveness of preventive treatment was greater in high-burden (0·31 [0·23-0·40]) versus low-burden (0·58 [0·47-0·72]) settings. The NNT ranged from 9 to 34 depending on age among participants with a positive TST or IGRA in both high-burden and low-burden settings; among all contacts (regardless of TST or IGRA test result), the NNT ranged from 29 to 43 in high-burden settings and 213 to 455 in low-burden settings.
INTERPRETATION
Our findings suggest that a risk-targeted strategy prioritising contacts with evidence of M tuberculosis infection might be indicated in low-burden settings, and a broad approach including all contacts should be considered in high-burden settings. Preventive treatment was similarly effective among contacts of all ages.
FUNDING
None.
PubMed: 38734022
DOI: 10.1016/S2213-2600(24)00083-3 -
Journal of Clinical Medicine Apr 2024It is unclear whether patients with basal ganglia calcifications (BGC) should undergo infectious disease testing as part of their diagnostic work-up. We investigated... (Review)
Review
It is unclear whether patients with basal ganglia calcifications (BGC) should undergo infectious disease testing as part of their diagnostic work-up. We investigated the occurrence of possibly associated infections in patients with BGC diagnosed with Fahr's disease or syndrome and consecutively performed a systematic review of published infectious diseases associated with BGC. In a cross-sectional study, we evaluated infections in non-immunocompromised patients aged ≥ 18 years with BGC in the Netherlands, who were diagnosed with Fahr's disease or syndrome after an extensive multidisciplinary diagnostic work-up. Pathogens that were assessed included the following: sp., cytomegalovirus, human herpesvirus type 6/8, human immunodeficiency virus (HIV), , rubella virus, and . Next, a systematic review was performed using MEDLINE and Embase (2002-2023). The cross-sectional study included 54 patients (median age 65 years). We did not observe any possible related infections to the BGC in this population. Prior infection with occurred in 28%, and in 94%, IgG rubella antibodies were present. The positive tests were considered to be incidental findings by the multidisciplinary team since these infections are only associated with BGC when congenitally contracted and all patients presented with adult-onset symptoms. The systematic search yielded 47 articles, including 24 narrative reviews/textbooks and 23 original studies (11 case series, 6 cross-sectional and 4 cohort studies, and 2 systematic reviews). Most studies reported congenital infections associated with BGC (cytomegalovirus, HIV, rubella virus, Zika virus). Only two studies reported acquired pathogens (chronic active Epstein-Barr virus and ). The quality of evidence was low. In our cross-sectional study and systematic review, we found no convincing evidence that acquired infections are causing BGC in adults. Therefore, we argue against routine testing for infections in non-immunocompromised adults with BGC in Western countries.
PubMed: 38673641
DOI: 10.3390/jcm13082365 -
The American Journal of Tropical... Jun 2024Substantial tuberculosis transmission occurs outside of households, and tuberculosis surveillance in schools has recently been proposed. However, the yield of... (Meta-Analysis)
Meta-Analysis
Substantial tuberculosis transmission occurs outside of households, and tuberculosis surveillance in schools has recently been proposed. However, the yield of tuberculosis outcomes from school contacts is not well characterized. We assessed the prevalence of Mycobacterium tuberculosis infection among close school contacts by performing a systematic review. We searched PubMed, Elsevier, China National Knowledge Infrastructure, and Wanfang databases. Studies reporting the number of children who were tested overall and who tested positive were included. Subgroup analyses were performed by study location, index case bacteriological status, type of school, and other relevant factors. In total, 28 studies including 54,707 school contacts screened for M. tuberculosis infection were eligible and included in the analysis. Overall, the prevalence of M. tuberculosis infection determined by the QuantiFERON Gold in-tube test was 33.2% (95% CI, 0.0-73.0%). The prevalences of M. tuberculosis infection based on the tuberculin skin test (TST) using 5 mm, 10 mm, and 15 mm as cutoffs were 27.2% (95% CI, 15.1-39.3%), 24.3% (95% CI, 15.3-33.4%), and 12.7% (95% CI, 6.3-19.0%), respectively. The pooled prevalence of M. tuberculosis infection (using a TST ≥5-mm cutoff) was lower in studies from China (22.8%; 95% CI, 16.8-28.8%) than other regions (36.7%; 95% CI, 18.1-55.2%). The pooled prevalence of M. tuberculosis infection was higher when the index was bacteriologically positive (43.6% [95% CI, 16.5-70.8%] versus 23.8% [95% CI, 16.2-31.4%]). These results suggest that contact investigation and general surveillance in schools from high-burden settings merit consideration as means to improve early case detection in children.
Topics: Humans; Schools; Mycobacterium tuberculosis; Tuberculosis; Prevalence; Tuberculin Test; Contact Tracing; Child; China
PubMed: 38653232
DOI: 10.4269/ajtmh.23-0038 -
Cureus Mar 2024Bacillus Calmette-Guérin (BCG) vaccination remains a cornerstone in global efforts to combat tuberculosis (TB), a persistent public health threat worldwide. The purpose... (Review)
Review
Bacillus Calmette-Guérin (BCG) vaccination remains a cornerstone in global efforts to combat tuberculosis (TB), a persistent public health threat worldwide. The purpose of this systematic review is to find out how well BCG revaccination protects against TB. This systematic review synthesized recent studies investigating the efficacy of BCG vaccination in preventing TB infection and disease. A total of 15 relevant publications were identified through a comprehensive search across multiple databases, including Cochrane Library, PubMed, Medline, and Scopus. The inclusion criteria encompassed studies involving humans, written in English, and categorized as case-control, cohort, meta-analysis, or full-text. Studies were selected based on their relevance to BCG revaccination and protection against TB, and a standardized data extraction form was used to gather pertinent information from each study. Quality assessment was conducted using established tools to evaluate the rigor, study design, and risk of bias in each included study. The findings revealed significant insights into BCG's effectiveness across different populations and age groups. Several studies demonstrated a substantial reduction in latent TB infection (LTBI) and incidence rates of TB following BCG vaccination. However, the protective efficacy of BCG revaccination varied across studies and populations, with some indicating modest protection against TB disease development, particularly in high-risk populations like healthcare workers. Furthermore, investigations into the immunological mechanisms underlying BCG's protective efficacy provided valuable insights into cytokine/chemokine profiles and immunomodulatory properties.
PubMed: 38646352
DOI: 10.7759/cureus.56643 -
PLoS Pathogens Apr 2024Drug-resistant tuberculosis (DR-TB) threatens progress in the control of TB. Mathematical models are increasingly being used to guide public health decisions on managing...
Drug-resistant tuberculosis (DR-TB) threatens progress in the control of TB. Mathematical models are increasingly being used to guide public health decisions on managing both antimicrobial resistance (AMR) and TB. It is important to consider bacterial heterogeneity in models as it can have consequences for predictions of resistance prevalence, which may affect decision-making. We conducted a systematic review of published mathematical models to determine the modelling landscape and to explore methods for including bacterial heterogeneity. Our first objective was to identify and analyse the general characteristics of mathematical models of DR-mycobacteria, including M. tuberculosis. The second objective was to analyse methods of including bacterial heterogeneity in these models. We had different definitions of heterogeneity depending on the model level. For between-host models of mycobacterium, heterogeneity was defined as any model where bacteria of the same resistance level were further differentiated. For bacterial population models, heterogeneity was defined as having multiple distinct resistant populations. The search was conducted following PRISMA guidelines in five databases, with studies included if they were mechanistic or simulation models of DR-mycobacteria. We identified 195 studies modelling DR-mycobacteria, with most being dynamic transmission models of non-treatment intervention impact in M. tuberculosis (n = 58). Studies were set in a limited number of specific countries, and 44% of models (n = 85) included only a single level of "multidrug-resistance (MDR)". Only 23 models (8 between-host) included any bacterial heterogeneity. Most of these also captured multiple antibiotic-resistant classes (n = 17), but six models included heterogeneity in bacterial populations resistant to a single antibiotic. Heterogeneity was usually represented by different fitness values for bacteria resistant to the same antibiotic (61%, n = 14). A large and growing body of mathematical models of DR-mycobacterium is being used to explore intervention impact to support policy as well as theoretical explorations of resistance dynamics. However, the majority lack bacterial heterogeneity, suggesting that important evolutionary effects may be missed.
Topics: Humans; Mycobacterium tuberculosis; Tuberculosis, Multidrug-Resistant; Models, Theoretical; Antitubercular Agents
PubMed: 38598556
DOI: 10.1371/journal.ppat.1011574 -
Diagnostic Microbiology and Infectious... Jul 2024Increasing evidence has indicated dysbiosis of the gut microbiota in patients with pulmonary tuberculosis (PTB). However, the change in the intestinal microbiota varies... (Review)
Review
Increasing evidence has indicated dysbiosis of the gut microbiota in patients with pulmonary tuberculosis (PTB). However, the change in the intestinal microbiota varies between different studies. This systematic review was conducted to investigate the characteristics of the gut microbiota in PTB patients. The MBASE, MEDLINE, Web of Science, and Cochrane Library electronic databases were systematically searched, and the quality of the retrieved studies was evaluated using the Newcastle-Ottawa scale. A total of 12 studies were finally included in the systematic review. Compared with healthy controls, the index reflecting α-diversity including the richness and/or diversity index decreased in 6 studies, while β-diversity presented significant differences in PTB patients in 10 studies. Although the specific gut microbiota alterations were inconsistent, short-chain fatty acid-producing bacteria (including Lachnospiraceae, Ruminococcus, Blautia, Dorea, and Faecalibacterium), bacteria associated with an inflammatory state (e.g., Prevotellaceae and Prevotella), and beneficial bacteria (e.g., Bifidobacteriaceae and Bifidobacterium) were commonly noted. Our systematic review identifies key evidence for gut microbiota alterations in PTB patients, in comparison with healthy controls; however, no consistent conclusion could be drawn, due to the inconsistent results and heterogeneous methodologies of the enrolled studies. Therefore, more well-designed research with standard methodologies and large sample sizes is required.
Topics: Humans; Gastrointestinal Microbiome; Tuberculosis, Pulmonary; Dysbiosis; Bacteria
PubMed: 38581928
DOI: 10.1016/j.diagmicrobio.2024.116291 -
Preventive Veterinary Medicine May 2024Bovine tuberculosis (bovine TB) is a chronic wasting disease of cattle caused primarily by Mycobacterium bovis. Controlling bovine TB requires highly sensitive,... (Meta-Analysis)
Meta-Analysis
Bovine tuberculosis (bovine TB) is a chronic wasting disease of cattle caused primarily by Mycobacterium bovis. Controlling bovine TB requires highly sensitive, specific, quick, and reliable diagnostic methods. This systematic review and meta-analysis evaluated molecular diagnostic tests for M. bovis detection to inform the selection of the most viable assay. On a per-test basis, loop-mediated isothermal amplification (LAMP) showed the highest overall sensitivity of 99.0% [95% CI: 86.2%-99.9%] and specificity of 99.8% [95% CI: 96.2%-100.00%]. Quantitative real-time polymerase chain reaction (qPCR) outperformed conventional PCR and nested PCR (nPCR) with a diagnostic specificity of 96.6% [95% CI: 88.9%-99.0%], while the diagnostic sensitivity of 70.8% [95% CI: 58.6-80.5%] was comparable to that of nPCR at 71.4% [95% CI: 60.7-80.2%]. Test sensitivity was higher with the input of milk samples (90.9% [95% CI: 56.0%-98.7%]), while specificity improved with tests based on major M. bovis antigens (97.8% [95% CI: 92.3%-99.4%]), the IS6110 insertion sequence (95.4% [95% CI: 87.6%-98.4%]), and the RD4 gene (90.7% [95% CI: 52.2%-98.9%]). The design of the currently available molecular diagnostic assays, while mostly based on nonspecific gene targets, prevents them from being accurate enough to diagnose M. bovis infections in cattle, despite their promise. Future assay development should focus on the RD4 region since it is the only target identified by genome sequence data as being distinctive for detecting M. bovis. The availability of a sufficiently accurate diagnostic test combined with the routine screening of milk samples can decrease the risk of zoonotic transmissions of M. bovis.
Topics: Cattle; Animals; Mycobacterium bovis; Tuberculosis, Bovine; Pathology, Molecular; Sensitivity and Specificity; Real-Time Polymerase Chain Reaction; Cattle Diseases
PubMed: 38574490
DOI: 10.1016/j.prevetmed.2024.106190 -
Journal of Global Antimicrobial... Jun 2024This study aims to estimate the overall in vitro activity of bedaquiline (BDQ) against clinical isolates of Mycobacterium abscessus complex (MABS) and M. avium complex... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study aims to estimate the overall in vitro activity of bedaquiline (BDQ) against clinical isolates of Mycobacterium abscessus complex (MABS) and M. avium complex (MAC), considering BDQ as a repurposed drug for non-tuberculous mycobacteria (NTM) infections.
METHODS
We conducted a systematic review of publications in PubMed/ MEDLINE, Web of Science, and Embase up to 15 April 2023. Studies were included if they followed the Clinical and Laboratory Standards Institute (CLSI) criteria for drug susceptibility testing (DST). Using a random effects model, we assessed the overall in vitro BDQ resistance rate in clinical isolates of MABS and MAC. Sources of heterogeneity were analysed using Cochran's Q and the I statistic. All analyses were performed using CMA V3.0.
RESULTS
A total of 24 publications (19 reports for MABS and 11 for MAC) were included. Using 1 µg/mL and 2 µg/mL as the breakpoint for BDQ resistance, the pooled rates of in vitro BDQ resistance in clinical isolates of MABS were found to be 1.8% (95% confidence interval [CI], 0.7-4.6%) and 1.7% (95% CI, 0.6-4.4%), respectively. In the case of MAC, the pooled rates were 1.7% (95% CI, 0.4-6.9%) and 1.6% (95% CI, 0.4-6.8%) for 1 µg/mL and 2 µg/mL, respectively.
CONCLUSION
This study reports the prevalence of BDQ resistance in clinical isolates of MABS and MAC. The findings suggest that BDQ holds potential as a repurposed drug for treating MABS and MAC infections.
Topics: Diarylquinolines; Humans; Microbial Sensitivity Tests; Mycobacterium abscessus; Mycobacterium avium Complex; Mycobacterium Infections, Nontuberculous; Antitubercular Agents; Drug Resistance, Bacterial; Mycobacterium avium-intracellulare Infection
PubMed: 38561143
DOI: 10.1016/j.jgar.2024.03.009 -
Journal of Clinical Tuberculosis and... May 2024Drug resistance among (MTB) strains is a growing concern in developing countries. We conducted a comprehensive search for relevant studies in Iran on PubMed, Scopus,... (Review)
Review
Drug resistance among (MTB) strains is a growing concern in developing countries. We conducted a comprehensive search for relevant studies in Iran on PubMed, Scopus, and Embase until June 12, 2020. Our study focused on determining the prevalence of antibiotic resistance in MTB isolates, with subgroup analyses based on year, location, and drug susceptibility testing (DST) methods. Statistical analyses were performed using STATA software. Our meta-analysis included a total of 47 articles. Among new TB cases, we found the following prevalence rates: Any-resistance to first-line drugs: 31 % (95 % CI, 24-38), mono-drug resistance: 15 % (95 % CI, 10-22), and multidrug resistance to first-line drugs: 6 % (95 % CI, 4-8). There was a significant variation in the rate of MDR among new TB cases based on the year of publication, location, and DST methods ( < 0.0001). We observed substantial variability in multidrug-resistant TB rates among new cases across the studies. Stratified analyses revealed that publication years and DST methods significantly affected resistance rates. Studies from southern and central Iran reported higher any-drug resistance rates, suggesting regional differences. Among retreatment cases, the prevalence rates were as follows: Any resistance: 68 % (95 % CI 58-78), mono-resistance: 19 % (95 % CI 7-34), multidrug resistance: 28 % (95 % CI 15-43). Our study revealed that the prevalence of drug-resistant TB (DR-TB) among TB cases in Iran is higher than the global average. Particularly, MDR-TB among retreatment TB cases is a significant public health issue.
PubMed: 38560029
DOI: 10.1016/j.jctube.2024.100430 -
Scientific Reports Mar 2024The seasonal outbreaks of Mpox continue in most parts of West and Central Africa. In the past year, Nigeria had the highest number of reported cases. Here, we used the... (Meta-Analysis)
Meta-Analysis
The seasonal outbreaks of Mpox continue in most parts of West and Central Africa. In the past year, Nigeria had the highest number of reported cases. Here, we used the PRISMA guidelines to carry out a systematic review and meta-analysis of available evidence on Mpox in Nigeria to assess the prevalence, transmission pattern, diagnostic approach, and other associated factors useful for mitigating the transmission of the disease. All relevant observational studies in PubMed/MEDLINE, Embase, AJOL, Web of Science, Scopus and Google Scholar on Mpox in Nigeria were assessed within the last fifty years (1972 to 2022). In all, 92 relevant articles were retrieved, out of which 23 were included in the final qualitative analysis. Notably, most of the cases of Mpox in Nigeria were from the southern part of the country. Our findings showed a progressive spread from the southern to the northern region of the country. We identified the following factors as important in the transmission of Mpox in Nigeria; poverty, lack of basic healthcare facilities, and risk of exposure through unsafe sexual practices. Our findings reiterate the need to strengthen and expand existing efforts as well as establish robust multi-sectoral collaboration to understand the dynamics of Mpox Nigeria.
Topics: Humans; Mpox (monkeypox); Nigeria; Disease Outbreaks; Health Facilities; MEDLINE
PubMed: 38548826
DOI: 10.1038/s41598-024-58147-y