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Journal of Infection in Developing... Jul 2015The varieties of infections caused by Helicobacter pylori may be due to differences in bacterial genotypes and virulence factors as well as environmental and... (Meta-Analysis)
Meta-Analysis Review
The varieties of infections caused by Helicobacter pylori may be due to differences in bacterial genotypes and virulence factors as well as environmental and host-related factors. This study aimed to investigate the prevalence of cagA and vacA genes among H. pylori-infected patients in Iran and analyze their relevance to the disease status between two clinical groups via a meta-analysis method. Different databases including PubMed, ISI, Scopus, SID, Magiran, Science Direct, and Medlib were investigated, and 23 relevant articles from the period between 2001 and 2012 were finally analyzed. The relevant data obtained from these papers were analyzed by a random-effects model. Data were analyzed using R software and STATA. The prevalence of cagA and vacA genes among H. pylori-infected patients was 70% (95% CI, 64-75) and 41% (95% CI, 24.3-57.7), respectively. The prevalence of duodenal ulcers, peptic ulcers, and gastritis among cagA+ individuals was 53% (95% CI, 20-86), 65% (95% CI, 34-97), and 71% (95% CI, 59-84), respectively. Odds ratio (OR) between cagA-positive compared with cagA-negative patients showed a 1.89 (95% CI, 1.38-2.57) risk of ulcers. In conclusion, the frequency of cagA gene among H. pylori strains is elevated in Iran and it seems to be more frequently associated with gastritis. Therefore, any information about cagA and vacA prevalence among different H. pylori-infected clinical groups in the country can help public health authorities to plan preventive policies to reduce the prevalence of diseases associated with H. pylori infection.
Topics: Antigens, Bacterial; Bacterial Proteins; Gastritis; Genotype; Helicobacter Infections; Helicobacter pylori; Humans; Iran; Peptic Ulcer; Prevalence
PubMed: 26230117
DOI: 10.3855/jidc.5970 -
Antimicrobial Agents and Chemotherapy Jan 2015Recently, there has been a renewed interest in the development of new drugs for the treatment of leishmaniasis. This has spurred the need for pharmacodynamic markers to... (Review)
Review
Recently, there has been a renewed interest in the development of new drugs for the treatment of leishmaniasis. This has spurred the need for pharmacodynamic markers to monitor and compare therapies specifically for visceral leishmaniasis, in which the primary recrudescence of parasites is a particularly long-term event that remains difficult to predict. We performed a systematic review of studies evaluating biomarkers in human patients with visceral, cutaneous, and post-kala-azar dermal leishmaniasis, which yielded a total of 170 studies in which 53 potential pharmacodynamic biomarkers were identified. In conclusion, the large majority of these biomarkers constituted universal indirect markers of activation and subsequent waning of cellular immunity and therefore lacked specificity. Macrophage-related markers demonstrate favorable sensitivity and times to normalcy, but more evidence is required to establish a link between these markers and clinical outcome. Most promising are the markers directly related to the parasite burden, but future effort should be focused on optimization of molecular or antigenic targets to increase the sensitivity of these markers. In general, future research should focus on the longitudinal evaluation of the pharmacodynamic biomarkers during treatment, with an emphasis on the correlation of studied biomarkers and clinical parameters.
Topics: Acute-Phase Proteins; Adenosine Deaminase; Antibodies, Protozoan; Antigens, Protozoan; Biomarkers; Cytokines; Humans; Immunity, Cellular; Leishmania donovani; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral; Macrophages; Membrane Proteins; Treatment Outcome
PubMed: 25367913
DOI: 10.1128/AAC.04298-14 -
PLoS Neglected Tropical Diseases Apr 2020Buruli ulcer (BU) is a subcutaneous necrotic infection of the skin caused by Mycobacterium ulcerans. It is the third most common human mycobacterial disease after... (Meta-Analysis)
Meta-Analysis
Buruli ulcer (BU) is a subcutaneous necrotic infection of the skin caused by Mycobacterium ulcerans. It is the third most common human mycobacterial disease after tuberculosis (TB) and leprosy. The available methods for detection of the bacilli in lesions are microscopic detection, isolation and cultivation of the bacterium, histopathology, and polymerase chain reaction (PCR). These methods, although approved by the World Health Organization (WHO), have infrastructural and resource challenges in medical centres and cell-mediated immunity (CMI) and/or serology-based tests have been suggested as easier and more appropriate for accurate assessment of the disease, especially in remote or underdeveloped areas. This study systematically reviewed and conducted a meta-analysis for all research aimed at developing cell-mediated immunity (CMI) and/or serology-based tests for M. ulcerans disease. Information for this review was searched through PubMed and Web of Science databases and identified up to June 2019. References from relevant articles and reports from the WHO Annual Meeting of the Global Buruli Ulcer Initiative were also used. Twelve studies beginning in 1952, that attempted to develop CMI and/or serology-based tests for the disease were identified. These studies addressed issues of specificity and sensitivity in context of antigen composition as well as study heterogeneity and bias. The two main types of antigenic preparations considered were pathogen-derived and recombinant protein preparations. There was slight difference in test performance when M. ulcerans recombinant proteins [positivity: 67.5%; 32.5%] or pathogen-derived [positivity: 76.0%; 24.0%] preparations were used as test antigens among BU patients. However, pathogen-derived preparations were better at differentiating between patients and control groups [odds ratio (OR) of 27.92, 95%CI: 5.05-154.28]. This was followed by tests with the recombinant proteins [OR = 1.23, 95%CI: 0.27-5.62]. Overall, study heterogeneity index, I2 was 92.4% (p = 0.000). It is apparent from this review that standardisation is needed in any future CMI and/or serology-based tests used for M. ulcerans disease.
Topics: Buruli Ulcer; Databases, Factual; Humans; Immunity, Cellular; Leprosy; Mycobacterium ulcerans; Polymerase Chain Reaction; Serologic Tests
PubMed: 32251470
DOI: 10.1371/journal.pntd.0008172 -
Journal of Clinical Microbiology Nov 2015Treponema pallidum PCR (Tp-PCR) testing now is recommended as a valid tool for the diagnosis of primary or secondary syphilis. The objectives were to systematically... (Comparative Study)
Comparative Study Meta-Analysis Review
Comparison of Diagnostic Accuracy of PCR Targeting the 47-Kilodalton Protein Membrane Gene of Treponema pallidum and PCR Targeting the DNA Polymerase I Gene: Systematic Review and Meta-analysis.
Treponema pallidum PCR (Tp-PCR) testing now is recommended as a valid tool for the diagnosis of primary or secondary syphilis. The objectives were to systematically review and determine the optimal specific target gene to be used for Tp-PCR. Comparisons of the performance of the two main targets are tpp47 and polA genes were done using meta-analysis. Three electronic bibliographic databases, representing abstract books from five conferences specialized in infectious diseases from January 1990 to March 2015, were searched. Search keywords included ("syphilis" OR "Treponema pallidum" OR "neurosyphilis") AND ("PCR" OR "PCR" OR "molecular amplification"). We included diagnostic studies assessing the performance of Tp-PCR targeting tpp47 (tpp47-Tp-PCR) or the polA gene (polA-Tp-PCR) in ulcers from early syphilis. All studies were assessed against quality criteria using the QUADAS-2 tool. Of 37 studies identified, 62.2% were judged at low risk of bias or applicability. Most used the U.S. Centers for Disease Control and Prevention (CDC) case definitions for primary or secondary (early) syphilis (89.2%; n = 33); 15 (40.5%) used darkfield microscopy (DFM). We did not find differences in sensitivity and specificity between the two Tp-PCR methods in the subgroup of studies using adequate reference tests. Among studies using DFM as the reference test, sensitivities were 79.8% (95% confidence intervals [CI], 72.7 to 85.4%) and 71.4% (46.0 to 88.0%) for tpp47-Tp-PCR and polA-Tp-PCR (P = 0.217), respectively; respective specificities were 95.3% (93.5 to 96.6%) and 93.7% (91.8 to 95.2%) (P = 0.304). Our findings suggest that the two Tp-PCR methods have similar accuracy and could be used interchangeably.
Topics: Carrier Proteins; DNA Polymerase I; Humans; Lipoproteins; Polymerase Chain Reaction; Sensitivity and Specificity; Syphilis; Treponema pallidum
PubMed: 26311859
DOI: 10.1128/JCM.01619-15 -
Health Technology Assessment... Jun 2004To determine the role of autoantibody tests for autoimmune diseases in children with newly diagnosed type 1 diabetes mellitus. (Review)
Review
OBJECTIVES
To determine the role of autoantibody tests for autoimmune diseases in children with newly diagnosed type 1 diabetes mellitus.
DATA SOURCES
MEDLINE, EMBASE and the Cochrane Library. Citation lists of included studies were scanned and relevant professional and patient websites reviewed. Laboratories and manufacturers were contacted to identify ongoing or unpublished research.
REVIEW METHODS
Following scoping searches on thyroid and coeliac autoantibodies, a systematic review of autoantibody tests for diagnosis of coeliac disease was carried out. Studies were included where cohorts of untreated patients with unknown disease status were included, all patients had undergone the reference test (biopsy) and antibody tests, and sensitivity and specificity were reported or calculable. Selected studies were then evaluated against a quality checklist. Summary statistics of diagnostic accuracy, i.e. sensitivity, specificity, positive and negative likelihood ratios and diagnostic odds ratios, were calculated for all studies. A decision analytic model was developed to evaluate the cost utility of screening for coeliac disease at diagnosis of diabetes.
RESULTS
All antibody tests for diagnosis of coeliac disease showed reasonably good diagnostic test accuracy. Studies reported variable measures of test accuracy, which may be due to aspects of study quality, differences in the tests and their execution in the laboratories, different populations and reference standards. The decision analytic model indicated screening for coeliac disease at diagnosis of diabetes was cost-effective. Sensitivity analyses exploring variations in the cost and disutility of gluten-free diet, the utilities attached to treated and untreated coeliac disease and the decrease in life expectancy associated with treated and untreated coeliac disease did substantially affect the cost-effectiveness of the screening strategies considered.
CONCLUSIONS
In terms of test accuracy in testing for coeliac disease, immunoglobulin A (IgA) anti-endomysium is the most accurate test. If an enzyme-linked immunoassay test was required, which may be more suitable for screening purposes as it can be semi-automated, testing for IgA tissue transglutaminase is likely to be most accurate. The decision analytic model shows that the most accurate tests combined with confirmatory biopsy are the most cost-effective, whilst combinations of tests add little or no further value. There is limited information regarding test accuracy in screening populations with diabetes, and there is some uncertainty over whether the test characteristics would remain the same. Further research is required regarding the role of screening in silent coeliac disease and regarding long-term outcomes and complications of untreated coeliac disease.
Topics: Adolescent; Adult; Autoantibodies; Celiac Disease; Child; Child, Preschool; Cohort Studies; Cost-Benefit Analysis; Diabetes Mellitus, Type 1; Enzyme-Linked Immunosorbent Assay; Humans; Infant; Thyroid Gland; United Kingdom
PubMed: 15191683
DOI: 10.3310/hta8220 -
PloS One 2015The detection of mutations in the gyrA and gyrB genes in the Mycobacterium tuberculosis genome that have been demonstrated to confer phenotypic resistance to... (Review)
Review
Frequency and geographic distribution of gyrA and gyrB mutations associated with fluoroquinolone resistance in clinical Mycobacterium tuberculosis isolates: a systematic review.
BACKGROUND
The detection of mutations in the gyrA and gyrB genes in the Mycobacterium tuberculosis genome that have been demonstrated to confer phenotypic resistance to fluoroquinolones is the most promising technology for rapid diagnosis of fluoroquinolone resistance.
METHODS
In order to characterize the diversity and frequency of gyrA and gyrB mutations and to describe the global distribution of these mutations, we conducted a systematic review, from May 1996 to April 2013, of all published studies evaluating Mycobacterium tuberculosis mutations associated with resistance to fluoroquinolones. The overall goal of the study was to determine the potential utility and reliability of these mutations as diagnostic markers to detect phenotypic fluoroquinolone resistance in Mycobacterium tuberculosis and to describe their geographic distribution.
RESULTS
Forty-six studies, covering four continents and 18 countries, provided mutation data for 3,846 unique clinical isolates with phenotypic resistance profiles to fluoroquinolones. The gyrA mutations occurring most frequently in fluoroquinolone-resistant isolates, ranged from 21-32% for D94G and 13-20% for A90V, by drug. Eighty seven percent of all strains that were phenotypically resistant to moxifloxacin and 83% of ofloxacin resistant isolates contained mutations in gyrA. Additionally we found that 83% and 80% of moxifloxacin and ofloxacin resistant strains respectively, were observed to have mutations in the gyrA codons interrogated by the existing MTBDRsl line probe assay. In China and Russia, 83% and 84% of fluoroquinolone resistant strains respectively, were observed to have gyrA mutations in the gene regions covered by the MTBDRsl assay.
CONCLUSIONS
Molecular diagnostics, specifically the Genotype MTBDRsl assay, focusing on codons 88-94 should have moderate to high sensitivity in most countries. While we did observe geographic differences in the frequencies of single gyrA mutations across countries, molecular diagnostics based on detection of all gyrA mutations demonstrated to confer resistance should have broad and global utility.
Topics: Anti-Bacterial Agents; DNA Gyrase; Drug Resistance, Bacterial; Fluoroquinolones; Humans; Meta-Analysis as Topic; Mutation; Mycobacterium tuberculosis; Tuberculosis, Pulmonary
PubMed: 25816236
DOI: 10.1371/journal.pone.0120470 -
Antimicrobial Agents and Chemotherapy Oct 2011Standard culture-based testing of the susceptibility of Mycobacterium tuberculosis to pyrazinamide is difficult to perform. This systematic review with meta-analyses... (Meta-Analysis)
Meta-Analysis Review
Standard culture-based testing of the susceptibility of Mycobacterium tuberculosis to pyrazinamide is difficult to perform. This systematic review with meta-analyses evaluated the roles of molecular assays targeting pncA and of pyrazinamidase assays. PubMed and Embase were searched for relevant publications in English. Sensitivity and specificity were estimated in bivariate random-effects models. Of 128 articles identified, 73 sets of data involving culture isolates were initially included in meta-analyses. Summary estimates of sensitivity and specificity, respectively, were 87% and 93% for PCR-DNA sequencing (n = 29), 75% and 95% for PCR-single-stranded conformation polymorphism (SSCP) (n = 5), 96% and 97% for a mixture of other molecular assays (n = 6), and 89% and 97% for pyrazinamidase assays using the Wayne method (n = 33). The median prevalence (range) of pyrazinamide resistance was 51% (31% to 89%) in multidrug-resistant M. tuberculosis isolates and 5% (0% to 9%) in non-multidrug-resistant isolates. Excluding studies with possibly considerable false resistance in the reference assay gave the following estimates of sensitivity and specificity, respectively: 92% and 93% for PCR-DNA sequencing (n = 20), 98% and 96% for other molecular assays (n = 5), and 91% and 97% for the Wayne assay (n = 27). The Wayne assay had significant funnel plot asymmetry, so the test performance might have been overestimated. Considering the prevalence of pyrazinamide resistance in different clinical settings, PCR-DNA sequencing, and possibly other molecular assays targeting pncA, can detect pyrazinamide resistance in multidrug-resistant M. tuberculosis isolates, with predictive values largely exceeding 90%, and rule out pyrazinamide resistance in non-multidrug-resistant isolates, with predictive values exceeding 99%. Molecular assays are probably the way forward for detecting pyrazinamide resistance.
Topics: Amidohydrolases; Antitubercular Agents; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Polymerase Chain Reaction; Pyrazinamide; Sequence Analysis, DNA
PubMed: 21768515
DOI: 10.1128/AAC.00630-11 -
European Respiratory Review : An... Dec 2013This systematic review evaluated evidence for two dry powder formulations, colistimethate sodium and tobramycin, for the treatment of chronic Pseudomonas aeruginosa in... (Review)
Review
This systematic review evaluated evidence for two dry powder formulations, colistimethate sodium and tobramycin, for the treatment of chronic Pseudomonas aeruginosa in cystic fibrosis, as part of the UK national recommendation process for new technologies. Electronic bibliographic databases were searched in May 2012 (MEDLINE, MEDLINE in-Process, EMBASE, Cochrane Library databases, CINAHL, Web of Science, Conference Proceedings Citation Index and BIOSIS Previews). Relevant outcomes included rate and extent of microbial response (e.g. sputum density of P. aeruginosa), lung function (e.g. forced expiratory volume in 1 s (FEV1)), frequency, severity of acute exacerbations and adverse events. Three trials were included, and both dry powder formulations were reported to be non-inferior in the short term to nebulised tobramycin for FEV1. However, long-term follow-up data were missing and the effect on exacerbation rates was not always reported. Whilst short-term results showed that both dry powder drugs were non-inferior to nebulised tobramycin, there was no long-term follow-up and no phase 3 trials compared nebulised and dry powder colistimethate sodium. The use of FEV1 as the primary end-point may not accurately represent changes in lung health. This review illustrates the difficulty in assessing new technologies where the evidence base is poor.
Topics: Administration, Inhalation; Anti-Bacterial Agents; Colistin; Cystic Fibrosis; Disease Progression; Dry Powder Inhalers; Evidence-Based Medicine; Forced Expiratory Volume; Humans; Lung; Powders; Pseudomonas Infections; Pseudomonas aeruginosa; Research Design; Time Factors; Tobramycin; Treatment Outcome
PubMed: 24293463
DOI: 10.1183/09059180.00001513 -
Parasites & Vectors Nov 2012Toxoplasmosis is a disease caused by Toxoplasma gondii and at least one-third of the world's population has detectable T. gondii antibodies. The seroprevalence of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Toxoplasmosis is a disease caused by Toxoplasma gondii and at least one-third of the world's population has detectable T. gondii antibodies. The seroprevalence of T.gondii ranges from 15% to 50% among the Mexican general population. The aim of this work was to determine the mean prevalence and weighted mean prevalence of T. gondii infection, and to evaluate the epidemiological transition of infection in Mexico.
METHODS
Pub Med, Lilacs, Medline, Latindex, Google Scholar data bases were searched to retrieve reports from 1951 up to 2012 regarding prevalence data, diagnostic tests and risk factors of infection among the adult population. Data collection and criteria eligibility was established in order to determine the crude prevalence (proportion of positive cases) of each study, together with weighted population prevalence according to individual research group categories to limit the bias that may impose the heterogeneous nature of the reports. A Forest Plot chart and linear regression analysis were performed by plotting the prevalence of infection reported from each study over a period of sixty years.
RESULTS
A total of 132 studies were collected from 41 publications that included 70,123 individuals. The average mean prevalence was 27.97%, and weighted mean prevalence was 19.27%. Comparisons among different risk groups showed that the weighted prevalence was higher in women with miscarriages (36.03%), immunocompromised patients (28.54%), mentally-ill patients (38.52%) and other risk groups (35.13%). Toxoplasma infection among the Mexican population showed a downward trend of 0.1%/year over a period of sixty years that represents a 5.8% reduction in prevalence.
CONCLUSIONS
This analysis showed a downward trend of infection; however, there are individuals at high risk for infection such as immunocompromised patients, mentally-ill patients and pregnant women. Further research is required to provide better prevention strategies, effective diagnostic testing and medical management of patients. Educational efforts are required to avoid the transmission of infection in populations that cannot be controlled by drugs alone.
Topics: Abortion, Spontaneous; Antibodies, Protozoan; Databases, Factual; Female; Humans; Immunocompromised Host; Male; Mental Disorders; Mexico; Pregnancy; Pregnancy Complications, Parasitic; Prevalence; Risk Factors; Seroepidemiologic Studies; Toxoplasma; Toxoplasmosis
PubMed: 23181616
DOI: 10.1186/1756-3305-5-271 -
PLoS Neglected Tropical Diseases Feb 2022A substantial amount of epidemiological data has been reported on Enterovirus D68 (EV-D68) infections after the 2014 outbreak. Our goal was to map the case fatality rate... (Meta-Analysis)
Meta-Analysis
A substantial amount of epidemiological data has been reported on Enterovirus D68 (EV-D68) infections after the 2014 outbreak. Our goal was to map the case fatality rate (CFR) and prevalence of current and past EV-D68 infections. We conducted a systematic review (PROSPERO, CRD42021229255) with published articles on EV-68 infections in PubMed, Embase, Web of Science and Global Index Medicus up to January 2021. We determined prevalences using a model random effect. Of the 4,329 articles retrieved from the databases, 89 studies that met the inclusion criteria were from 39 different countries with apparently healthy individuals and patients with acute respiratory infections, acute flaccid myelitis and asthma-related diseases. The CFR estimate revealed occasional deaths (7/1353) related to EV-D68 infections in patients with severe acute respiratory infections. Analyses showed that the combined prevalence of current and past EV-D68 infections was 4% (95% CI = 3.1-5.0) and 66.3% (95% CI = 40.0-88.2), respectively. The highest prevalences were in hospital outbreaks, developed countries, children under 5, after 2014, and in patients with acute flaccid myelitis and asthma-related diseases. The present study shows sporadic deaths linked to severe respiratory EV-D68 infections. The study also highlights a low prevalence of current EV-D68 infections as opposed to the existence of EV-D68 antibodies in almost all participants of the included studies. These findings therefore highlight the need to implement and/or strengthen continuous surveillance of EV-D68 infections in hospitals and in the community for the anticipation of the response to future epidemics.
Topics: Antibodies, Viral; Asthma; Central Nervous System Viral Diseases; Enterovirus D, Human; Enterovirus Infections; Humans; Myelitis; Neuromuscular Diseases; Prevalence; Respiratory Tract Infections
PubMed: 35134062
DOI: 10.1371/journal.pntd.0010073