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PloS One 2018Bacterial meningitis is a global public health concern, with several responsible etiologic agents that vary by age group and geographical area. The aim of this... (Meta-Analysis)
Meta-Analysis
Bacterial meningitis is a global public health concern, with several responsible etiologic agents that vary by age group and geographical area. The aim of this systematic review and meta-analysis was to assess the etiology of bacterial meningitis in different age groups across global regions. PubMed and EMBASE were systematically searched for English language studies on bacterial meningitis, limited to articles published in the last five years. The methodological quality of the studies was assessed using a customized scoring system. Meta-analyses were conducted to determine the frequency (percentages) of seven bacterial types known to cause meningitis: Escherichia coli, Haemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae, group B Streptococcus agalactiae, Staphylococcus aureus, and Listeria monocytogenes, with results being stratified by six geographical regions as determined by the World Health Organization, and seven age groups. Of the 3227 studies retrieved, 56 were eligible for the final analysis. In all age groups, S. pneumoniae and N. meningitidis were the predominant pathogens in all regions, accounting for 25.1-41.2% and 9.1-36.2% of bacterial meningitis cases, respectively. S. pneumoniae infection was the most common cause of bacterial meningitis in the 'all children' group, ranging from 22.5% (Europe) to 41.1% (Africa), and in all adults ranging from 9.6% (Western Pacific) to 75.2% (Africa). E. coli and S. pneumoniae were the most common pathogens that caused bacterial meningitis in neonates in Africa (17.7% and 20.4%, respectively). N. meningitidis was the most common in children aged ±1-5 years in Europe (47.0%). Due to paucity of data, meta-analyses could not be performed in all age groups for all regions. A clear difference in the weighted frequency of bacterial meningitis cases caused by the different etiological agents was observed between age groups and between geographic regions. These findings may facilitate bacterial meningitis prevention and treatment strategies.
Topics: Age Factors; Databases, Factual; Humans; Meningitis, Bacterial; Neisseria meningitidis; Risk Factors; Streptococcus pneumoniae
PubMed: 29889859
DOI: 10.1371/journal.pone.0198772 -
The Cochrane Database of Systematic... Sep 2015In experimental studies, the outcome of bacterial meningitis has been related to the severity of inflammation in the subarachnoid space. Corticosteroids reduce this... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In experimental studies, the outcome of bacterial meningitis has been related to the severity of inflammation in the subarachnoid space. Corticosteroids reduce this inflammatory response.
OBJECTIVES
To examine the effect of adjuvant corticosteroid therapy versus placebo on mortality, hearing loss and neurological sequelae in people of all ages with acute bacterial meningitis.
SEARCH METHODS
We searched CENTRAL (2015, Issue 1), MEDLINE (1966 to January week 4, 2015), EMBASE (1974 to February 2015), Web of Science (2010 to February 2015), CINAHL (2010 to February 2015) and LILACS (2010 to February 2015).
SELECTION CRITERIA
Randomised controlled trials (RCTs) of corticosteroids for acute bacterial meningitis.
DATA COLLECTION AND ANALYSIS
We scored RCTs for methodological quality. We collected outcomes and adverse effects. We performed subgroup analyses for children and adults, causative organisms, low-income versus high-income countries, time of steroid administration and study quality.
MAIN RESULTS
We included 25 studies involving 4121 participants (2511 children and 1517 adults; 93 mixed population). Four studies were of high quality with no risk of bias, 14 of medium quality and seven of low quality, indicating a moderate risk of bias for the total analysis. Nine studies were performed in low-income countries and 16 in high-income countries.Corticosteroids were associated with a non-significant reduction in mortality (17.8% versus 19.9%; risk ratio (RR) 0.90, 95% confidence interval (CI) 0.80 to 1.01, P value = 0.07). A similar non-significant reduction in mortality was observed in adults receiving corticosteroids (RR 0.74, 95% CI 0.53 to 1.05, P value = 0.09). Corticosteroids were associated with lower rates of severe hearing loss (RR 0.67, 95% CI 0.51 to 0.88), any hearing loss (RR 0.74, 95% CI 0.63 to 0.87) and neurological sequelae (RR 0.83, 95% CI 0.69 to 1.00).Subgroup analyses for causative organisms showed that corticosteroids reduced mortality in Streptococcus pneumoniae (S. pneumoniae) meningitis (RR 0.84, 95% CI 0.72 to 0.98), but not in Haemophilus influenzae (H. influenzae) orNeisseria meningitidis (N. meningitidis) meningitis. Corticosteroids reduced severe hearing loss in children with H. influenzae meningitis (RR 0.34, 95% CI 0.20 to 0.59) but not in children with meningitis due to non-Haemophilus species.In high-income countries, corticosteroids reduced severe hearing loss (RR 0.51, 95% CI 0.35 to 0.73), any hearing loss (RR 0.58, 95% CI 0.45 to 0.73) and short-term neurological sequelae (RR 0.64, 95% CI 0.48 to 0.85). There was no beneficial effect of corticosteroid therapy in low-income countries.Subgroup analysis for study quality showed no effect of corticosteroids on severe hearing loss in high-quality studies.Corticosteroid treatment was associated with an increase in recurrent fever (RR 1.27, 95% CI 1.09 to 1.47), but not with other adverse events.
AUTHORS' CONCLUSIONS
Corticosteroids significantly reduced hearing loss and neurological sequelae, but did not reduce overall mortality. Data support the use of corticosteroids in patients with bacterial meningitis in high-income countries. We found no beneficial effect in low-income countries.
Topics: Acute Disease; Adolescent; Adult; Anti-Inflammatory Agents; Child; Developed Countries; Developing Countries; Dexamethasone; Glucocorticoids; Hearing Loss; Humans; Hydrocortisone; Meningitis, Bacterial; Prednisolone; Randomized Controlled Trials as Topic
PubMed: 26362566
DOI: 10.1002/14651858.CD004405.pub5 -
The Cochrane Database of Systematic... Apr 2016Tuberculous meningitis is a serious form of tuberculosis (TB) that affects the meninges that cover a person's brain and spinal cord. It is associated with high death... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tuberculous meningitis is a serious form of tuberculosis (TB) that affects the meninges that cover a person's brain and spinal cord. It is associated with high death rates and with disability in people who survive. Corticosteroids have been used as an adjunct to antituberculous drugs to treat people with tuberculous meningitis, but their role has been controversial.
OBJECTIVES
To evaluate the effects of corticosteroids as an adjunct to antituberculous treatment on death and severe disability in people with tuberculous meningitis.
SEARCH METHODS
We searched the Cochrane Infectious Diseases Group Specialized Register up to the 18 March 2016; CENTRAL; MEDLINE; EMBASE; LILACS; and Current Controlled Trials. We also contacted researchers and organizations working in the field, and checked reference lists.
SELECTION CRITERIA
Randomized controlled trials that compared corticosteroid plus antituberculous treatment with antituberculous treatment alone in people with clinically diagnosed tuberculous meningitis and included death or disability as outcome measures.
DATA COLLECTION AND ANALYSIS
We independently assessed search results and methodological quality, and extracted data from the included trials. We analysed the data using risk ratios (RR) with 95% confidence intervals (CIs) and used a fixed-effect model. We performed an intention-to-treat analysis, where we included all participants randomized to treatment in the denominator. This analysis assumes that all participants who were lost to follow-up have good outcomes. We carried out a sensitivity analysis to explore the impact of the missing data.
MAIN RESULTS
Nine trials that included 1337 participants (with 469 deaths) met the inclusion criteria.At follow-up from three to 18 months, steroids reduce deaths by almost one quarter (RR 0.75, 95% CI 0.65 to 0.87; nine trials, 1337 participants, high quality evidence). Disabling neurological deficit is not common in survivors, and steroids may have little or no effect on this outcome (RR 0.92, 95% CI 0.71 to 1.20; eight trials, 1314 participants, low quality evidence). There was no difference between groups in the incidence of adverse events, which included gastrointestinal bleeding, invasive bacterial infections, hyperglycaemia, and liver dysfunction.One trial followed up participants for five years. The effect on death was no longer apparent at this time-point (RR 0.93, 95% CI 0.78 to 1.12; one trial, 545 participants, moderate quality evidence); and there was no difference in disabling neurological deficit detected (RR 0.91, 95% CI 0.49 to 1.69; one trial, 545 participants, low quality evidence).One trial included human immunodeficiency virus (HIV)-positive people. The stratified analysis by HIV status in this trial showed no heterogeneity, with point estimates for death (RR 0.90, 95% CI 0.67 to 1.20; one trial, 98 participants) and disability (RR 1.23, 95% CI 0.08 to 19.07; one trial, 98 participants) similar to HIV-negative participants in the same trial.
AUTHORS' CONCLUSIONS
Corticosteroids reduce mortality from tuberculous meningitis, at least in the short term.Corticosteroids may have no effect on the number of people who survive tuberculous meningitis with disabling neurological deficit, but this outcome is less common than death, and the CI for the relative effect includes possible harm. However, this small possible harm is unlikely to be quantitatively important when compared to the reduction in mortality.The number of HIV-positive people included in the review is small, so we are not sure if the benefits in terms of reduced mortality are preserved in this group of patients.
Topics: Adult; Antitubercular Agents; Chemotherapy, Adjuvant; Child; Dexamethasone; Glucocorticoids; Humans; Hydrocortisone; Intention to Treat Analysis; Prednisolone; Randomized Controlled Trials as Topic; Tuberculosis, Meningeal
PubMed: 27121755
DOI: 10.1002/14651858.CD002244.pub4 -
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 -
PloS One 2017Bacterial meningitis persists in being a substantial cause of high mortality and severe neurological morbidity, despite the advances in antimicrobial therapy. Accurate... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Bacterial meningitis persists in being a substantial cause of high mortality and severe neurological morbidity, despite the advances in antimicrobial therapy. Accurate data has not been available regarding the epidemiology of bacterial meningitis particularly in developing countries, yet. Indeed, the present systematic review provides a comprehensive data analysis on the prevalence and epidemiology of bacterial meningitis in Iran.
METHODS
We systematically reviewed articles from 1994 to 2015. The reports which contained the prevalence and etiology of acute bacterial meningitis by valid clinical and laboratory diagnosis were comprised in the present study.
RESULTS
Our analysis indicated that Streptococcus pneumoniae (30% [I2 = 56% p < 0.01]), Haemophilus influenza type b (15% [I2 = 82.75% p < 0.001]), coagulase negative staphylococci (CoNS) (14% [I2 = 60.5% p < 0.06]), and Neisseria meningitidis (13% [I2 = 74.16% p < 0.001]) were the most common cause of acute bacterial meningitis among meningitis cases in Iran. Notably, high frequency rates of nosocomial meningitis pathogens were detected in the present analysis.
CONCLUSIONS
It was magnificently attained that the majority of cases for bacterial meningitis in Iran could be avertable by public immunization schemes and by preventive care to inhibit the broadening of hospital acquired pathogens.
Topics: Biomarkers; History, 20th Century; History, 21st Century; Iran; Meningitis, Bacterial; Phenotype; Population Surveillance; Prevalence
PubMed: 28170400
DOI: 10.1371/journal.pone.0169617 -
The Journal of Antimicrobial... Feb 2015Antibiotics are commonly classified into bactericidal and bacteriostatic agents based on their antimicrobial action. We aimed to assess whether this distinction is... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Antibiotics are commonly classified into bactericidal and bacteriostatic agents based on their antimicrobial action. We aimed to assess whether this distinction is clinically relevant.
METHODS
OVID MEDLINE, EMBASE, The Cochrane Central Register of Controlled Trials (CENTRAL) and relevant references and conference proceedings using the Web of Science and Scopus databases were searched for randomized controlled trials comparing bactericidal with bacteriostatic antibiotics for treatment of severe infections. Main outcome measures were clinical cure rates and overall mortality. Abstracts of studies selected in the database search were screened by one reviewer; full-text screening and data extraction were performed by three independent reviewers.
RESULTS
Thirty-three studies were included. Approximately half of patients were treated with bacteriostatic monotherapy. Infections covered were pneumonia (n=13), skin and soft tissue infections (n=8), intra-abdominal infections (n=4) and others (n=8). Neither clinical cure rates [risk ratio (RR), 0.99; 95% CI, 0.97-1.01; P=0.11] nor mortality rates (RR, 0.91; 95% CI, 0.76-1.08; P=0.28) were different between patients treated with bactericidal drugs and those treated with bacteriostatic drugs. Subgroup analyses showed a benefit for clinical cure rates associated with linezolid and increased mortality associated with tigecycline. In meta-regression, clinical cure rates remained higher in patients treated with linezolid (P=0.01); tigecycline displayed a close to significant association with increased mortality (P=0.05) if compared with other bacteriostatic agents.
CONCLUSIONS
The categorization of antibiotics into bacteriostatic and bactericidal is unlikely to be relevant in clinical practice if used for abdominal infections, skin and soft tissue infections and pneumonia. Because we were not able to include studies on meningitis, endocarditis or neutropenia, no conclusion regarding these diseases can be drawn.
Topics: Anti-Bacterial Agents; Bacterial Infections; Humans; Odds Ratio; Randomized Controlled Trials as Topic; Recurrence; Severity of Illness Index; Treatment Outcome
PubMed: 25266070
DOI: 10.1093/jac/dku379 -
The Cochrane Database of Systematic... May 2021Neonatal sepsis is a major cause of morbidity and mortality. It is the third leading cause of neonatal mortality globally constituting 13% of overall neonatal mortality....
BACKGROUND
Neonatal sepsis is a major cause of morbidity and mortality. It is the third leading cause of neonatal mortality globally constituting 13% of overall neonatal mortality. Despite the high burden of neonatal sepsis, high-quality evidence in diagnosis and treatment is scarce. Due to the diagnostic challenges of sepsis and the relative immunosuppression of the newborn, many neonates receive antibiotics for suspected sepsis. Antibiotics have become the most used therapeutics in neonatal intensive care units, and observational studies in high-income countries suggest that 83% to 94% of newborns treated with antibiotics for suspected sepsis have negative blood cultures. The last Cochrane Review was updated in 2005. There is a need for an updated systematic review assessing the effects of different antibiotic regimens for late-onset neonatal sepsis.
OBJECTIVES
To assess the beneficial and harmful effects of different antibiotic regimens for late-onset neonatal sepsis.
SEARCH METHODS
We searched the following electronic databases: CENTRAL (2021, Issue 3); Ovid MEDLINE; Embase Ovid; CINAHL; LILACS; Science Citation Index EXPANDED and Conference Proceedings Citation Index - Science on 12 March 2021. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-RCTs.
SELECTION CRITERIA
We included RCTs comparing different antibiotic regimens for late-onset neonatal sepsis. We included participants older than 72 hours of life at randomisation, suspected or diagnosed with neonatal sepsis, meningitis, osteomyelitis, endocarditis, or necrotising enterocolitis. We excluded trials that assessed treatment of fungal infections.
DATA COLLECTION AND ANALYSIS
Three review authors independently assessed studies for inclusion, extracted data, and assessed risk of bias. We used the GRADE approach to assess the certainty of evidence. Our primary outcome was all-cause mortality, and our secondary outcomes were: serious adverse events, respiratory support, circulatory support, nephrotoxicity, neurological developmental impairment, necrotising enterocolitis, and ototoxicity. Our primary time point of interest was at maximum follow-up.
MAIN RESULTS
We included five RCTs (580 participants). All trials were at high risk of bias, and had very low-certainty evidence. The five included trials assessed five different comparisons of antibiotics. We did not conduct a meta-analysis due to lack of relevant data. Of the five included trials one trial compared cefazolin plus amikacin with vancomycin plus amikacin; one trial compared ticarcillin plus clavulanic acid with flucloxacillin plus gentamicin; one trial compared cloxacillin plus amikacin with cefotaxime plus gentamicin; one trial compared meropenem with standard care (ampicillin plus gentamicin or cefotaxime plus gentamicin); and one trial compared vancomycin plus gentamicin with vancomycin plus aztreonam. None of the five comparisons found any evidence of a difference when assessing all-cause mortality, serious adverse events, circulatory support, nephrotoxicity, neurological developmental impairment, or necrotising enterocolitis; however, none of the trials were near an information size that could contribute significantly to the evidence of the comparative benefits and risks of any particular antibiotic regimen. None of the trials assessed respiratory support or ototoxicity. The benefits and harms of different antibiotic regimens remain unclear due to the lack of well-powered trials and the high risk of systematic errors.
AUTHORS' CONCLUSIONS
Current evidence is insufficient to support any antibiotic regimen being superior to another. RCTs assessing different antibiotic regimens in late-onset neonatal sepsis with low risks of bias are warranted.
Topics: Amikacin; Ampicillin; Anti-Bacterial Agents; Aztreonam; Bias; Cefazolin; Clavulanic Acid; Drug Therapy, Combination; Floxacillin; Gentamicins; Humans; Infant, Newborn; Neonatal Sepsis; Randomized Controlled Trials as Topic; Ticarcillin; Vancomycin
PubMed: 33998665
DOI: 10.1002/14651858.CD013836.pub2 -
Neonatology 2021The diagnosis of neonatal meningitis often rests on microscopic and biochemical findings in the cerebrospinal fluid (CSF). There is ongoing uncertainty about age-related...
BACKGROUND
The diagnosis of neonatal meningitis often rests on microscopic and biochemical findings in the cerebrospinal fluid (CSF). There is ongoing uncertainty about age-related normal values for CSF findings in neonates, and many previous studies have included infants in whom antibiotics were administered before lumbar puncture or in whom viral meningitis was not excluded.
METHODS
A systematic search was done using MEDLINE and EMBASE to identify original studies which investigated CSF normal values in either healthy neonates or febrile neonates in whom bacterial and viral meningitis were reliably excluded.
RESULTS
We identified seven studies investigating 270 term and 96 preterm neonates. There were minimal differences between preterm and term neonates in the CSF white blood cell (WBC) count and glucose concentration. In contrast, the CSF neutrophil count and protein concentration were influenced by gestational and chronological age. In the four studies that reported individual patient data, in 95% of cases the CSF WBC count was <12 cells/μL in preterm and <10 cells/μL in term neonates, the neutrophil count was <16 and 8 cells/μL, and the protein concentration was <210 and 110 mg/dL, respectively.
CONCLUSION
The normal range for CSF parameters in neonates is different to that in older infants, and some parameters are influenced by gestational and chronological age. CSF parameters alone are not sufficiently reliable to exclude meningitis.
Topics: Aged; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Leukocyte Count; Meningitis; Reference Values; Retrospective Studies; Spinal Puncture
PubMed: 34818234
DOI: 10.1159/000517630 -
The Cochrane Database of Systematic... Nov 2021Measles, mumps, rubella, and varicella (chickenpox) are serious diseases that can lead to serious complications, disability, and death. However, public debate over the... (Review)
Review
BACKGROUND
Measles, mumps, rubella, and varicella (chickenpox) are serious diseases that can lead to serious complications, disability, and death. However, public debate over the safety of the trivalent MMR vaccine and the resultant drop in vaccination coverage in several countries persists, despite its almost universal use and accepted effectiveness. This is an update of a review published in 2005 and updated in 2012.
OBJECTIVES
To assess the effectiveness, safety, and long- and short-term adverse effects associated with the trivalent vaccine, containing measles, rubella, mumps strains (MMR), or concurrent administration of MMR vaccine and varicella vaccine (MMR+V), or tetravalent vaccine containing measles, rubella, mumps, and varicella strains (MMRV), given to children aged up to 15 years.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2019, Issue 5), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to 2 May 2019), Embase (1974 to 2 May 2019), the WHO International Clinical Trials Registry Platform (2 May 2019), and ClinicalTrials.gov (2 May 2019).
SELECTION CRITERIA
We included randomised controlled trials (RCTs), controlled clinical trials (CCTs), prospective and retrospective cohort studies (PCS/RCS), case-control studies (CCS), interrupted time-series (ITS) studies, case cross-over (CCO) studies, case-only ecological method (COEM) studies, self-controlled case series (SCCS) studies, person-time cohort (PTC) studies, and case-coverage design/screening methods (CCD/SM) studies, assessing any combined MMR or MMRV / MMR+V vaccine given in any dose, preparation or time schedule compared with no intervention or placebo, on healthy children up to 15 years of age.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed the methodological quality of the included studies. We grouped studies for quantitative analysis according to study design, vaccine type (MMR, MMRV, MMR+V), virus strain, and study settings. Outcomes of interest were cases of measles, mumps, rubella, and varicella, and harms. Certainty of evidence of was rated using GRADE.
MAIN RESULTS
We included 138 studies (23,480,668 participants). Fifty-one studies (10,248,159 children) assessed vaccine effectiveness and 87 studies (13,232,509 children) assessed the association between vaccines and a variety of harms. We included 74 new studies to this 2019 version of the review. Effectiveness Vaccine effectiveness in preventing measles was 95% after one dose (relative risk (RR) 0.05, 95% CI 0.02 to 0.13; 7 cohort studies; 12,039 children; moderate certainty evidence) and 96% after two doses (RR 0.04, 95% CI 0.01 to 0.28; 5 cohort studies; 21,604 children; moderate certainty evidence). The effectiveness in preventing cases among household contacts or preventing transmission to others the children were in contact with after one dose was 81% (RR 0.19, 95% CI 0.04 to 0.89; 3 cohort studies; 151 children; low certainty evidence), after two doses 85% (RR 0.15, 95% CI 0.03 to 0.75; 3 cohort studies; 378 children; low certainty evidence), and after three doses was 96% (RR 0.04, 95% CI 0.01 to 0.23; 2 cohort studies; 151 children; low certainty evidence). The effectiveness (at least one dose) in preventing measles after exposure (post-exposure prophylaxis) was 74% (RR 0.26, 95% CI 0.14 to 0.50; 2 cohort studies; 283 children; low certainty evidence). The effectiveness of Jeryl Lynn containing MMR vaccine in preventing mumps was 72% after one dose (RR 0.24, 95% CI 0.08 to 0.76; 6 cohort studies; 9915 children; moderate certainty evidence), 86% after two doses (RR 0.12, 95% CI 0.04 to 0.35; 5 cohort studies; 7792 children; moderate certainty evidence). Effectiveness in preventing cases among household contacts was 74% (RR 0.26, 95% CI 0.13 to 0.49; 3 cohort studies; 1036 children; moderate certainty evidence). Vaccine effectiveness against rubella, using a vaccine with the BRD2 strain which is only used in China, is 89% (RR 0.11, 95% CI 0.03 to 0.42; 1 cohort study; 1621 children; moderate certainty evidence). Vaccine effectiveness against varicella (any severity) after two doses in children aged 11 to 22 months is 95% in a 10 years follow-up (rate ratio (rr) 0.05, 95% CI 0.03 to 0.08; 1 RCT; 2279 children; high certainty evidence). Safety There is evidence supporting an association between aseptic meningitis and MMR vaccines containing Urabe and Leningrad-Zagreb mumps strains, but no evidence supporting this association for MMR vaccines containing Jeryl Lynn mumps strains (rr 1.30, 95% CI 0.66 to 2.56; low certainty evidence). The analyses provide evidence supporting an association between MMR/MMR+V/MMRV vaccines (Jeryl Lynn strain) and febrile seizures. Febrile seizures normally occur in 2% to 4% of healthy children at least once before the age of 5. The attributable risk febrile seizures vaccine-induced is estimated to be from 1 per 1700 to 1 per 1150 administered doses. The analyses provide evidence supporting an association between MMR vaccination and idiopathic thrombocytopaenic purpura (ITP). However, the risk of ITP after vaccination is smaller than after natural infection with these viruses. Natural infection of ITP occur in 5 cases per 100,000 (1 case per 20,000) per year. The attributable risk is estimated about 1 case of ITP per 40,000 administered MMR doses. There is no evidence of an association between MMR immunisation and encephalitis or encephalopathy (rate ratio 0.90, 95% CI 0.50 to 1.61; 2 observational studies; 1,071,088 children; low certainty evidence), and autistic spectrum disorders (rate ratio 0.93, 95% CI 0.85 to 1.01; 2 observational studies; 1,194,764 children; moderate certainty). There is insufficient evidence to determine the association between MMR immunisation and inflammatory bowel disease (odds ratio 1.42, 95% CI 0.93 to 2.16; 3 observational studies; 409 cases and 1416 controls; moderate certainty evidence). Additionally, there is no evidence supporting an association between MMR immunisation and cognitive delay, type 1 diabetes, asthma, dermatitis/eczema, hay fever, leukaemia, multiple sclerosis, gait disturbance, and bacterial or viral infections. AUTHORS' CONCLUSIONS: Existing evidence on the safety and effectiveness of MMR/MMRV vaccines support their use for mass immunisation. Campaigns aimed at global eradication should assess epidemiological and socioeconomic situations of the countries as well as the capacity to achieve high vaccination coverage. More evidence is needed to assess whether the protective effect of MMR/MMRV could wane with time since immunisation.
Topics: Chickenpox; Child; Humans; Infant; Measles; Measles-Mumps-Rubella Vaccine; Mumps; Rubella
PubMed: 34806766
DOI: 10.1002/14651858.CD004407.pub5 -
The Cochrane Database of Systematic... Aug 2018Tuberculosis (TB) is the world's leading infectious cause of death. Extrapulmonary TB accounts for 15% of TB cases, but the proportion is increasing, and over half a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tuberculosis (TB) is the world's leading infectious cause of death. Extrapulmonary TB accounts for 15% of TB cases, but the proportion is increasing, and over half a million people were newly diagnosed with rifampicin-resistant TB in 2016. Xpert MTB/RIF (Xpert) is a World Health Organization (WHO)-recommended, rapid, automated, nucleic acid amplification assay that is used widely for simultaneous detection of Mycobacterium tuberculosis complex and rifampicin resistance in sputum specimens. This Cochrane Review assessed the accuracy of Xpert in extrapulmonary specimens.
OBJECTIVES
To determine the diagnostic accuracy of Xpert a) for extrapulmonary TB by site of disease in people presumed to have extrapulmonary TB; and b) for rifampicin resistance in people presumed to have extrapulmonary TB.
SEARCH METHODS
We searched the Cochrane Infectious Diseases Group Specialized Register, MEDLINE, Embase, Science Citation Index, Web of Science, Latin American Caribbean Health Sciences Literature (LILACS), Scopus, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform, the International Standard Randomized Controlled Trial Number (ISRCTN) Registry, and ProQuest up to 7 August 2017 without language restriction.
SELECTION CRITERIA
We included diagnostic accuracy studies of Xpert in people presumed to have extrapulmonary TB. We included TB meningitis and pleural, lymph node, bone or joint, genitourinary, peritoneal, pericardial, and disseminated TB. We used culture as the reference standard. For pleural TB, we also included a composite reference standard, which defined a positive result as the presence of granulomatous inflammation or a positive culture result. For rifampicin resistance, we used culture-based drug susceptibility testing or MTBDRplus as the reference standard.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data, assessed risk of bias and applicability using the QUADAS-2 tool. We determined pooled predicted sensitivity and specificity for TB, grouped by type of extrapulmonary specimen, and for rifampicin resistance. For TB detection, we used a bivariate random-effects model. Recognizing that use of culture may lead to misclassification of cases of extrapulmonary TB as 'not TB' owing to the paucibacillary nature of the disease, we adjusted accuracy estimates by applying a latent class meta-analysis model. For rifampicin resistance detection, we performed univariate meta-analyses for sensitivity and specificity separately to include studies in which no rifampicin resistance was detected. We used theoretical populations with an assumed prevalence to provide illustrative numbers of patients with false positive and false negative results.
MAIN RESULTS
We included 66 unique studies that evaluated 16,213 specimens for detection of extrapulmonary TB and rifampicin resistance. We identified only one study that evaluated the newest test version, Xpert MTB/RIF Ultra (Ultra), for TB meningitis. Fifty studies (76%) took place in low- or middle-income countries. Risk of bias was low for patient selection, index test, and flow and timing domains and was high or unclear for the reference standard domain (most of these studies decontaminated sterile specimens before culture inoculation). Regarding applicability, in the patient selection domain, we scored high or unclear concern for most studies because either patients were evaluated exclusively as inpatients at tertiary care centres, or we were not sure about the clinical settings.Pooled Xpert sensitivity (defined by culture) varied across different types of specimens (31% in pleural tissue to 97% in bone or joint fluid); Xpert sensitivity was > 80% in urine and bone or joint fluid and tissue. Pooled Xpert specificity (defined by culture) varied less than sensitivity (82% in bone or joint tissue to 99% in pleural fluid and urine). Xpert specificity was ≥ 98% in cerebrospinal fluid, pleural fluid, urine, and peritoneal fluid.Xpert testing in cerebrospinal fluidXpert pooled sensitivity and specificity (95% credible interval (CrI)) against culture were 71.1% (60.9% to 80.4%) and 98.0% (97.0% to 98.8%), respectively (29 studies, 3774 specimens; moderate-certainty evidence).For a population of 1000 people where 100 have TB meningitis on culture, 89 would be Xpert-positive: of these, 18 (20%) would not have TB (false-positives); and 911 would be Xpert-negative: of these, 29 (3%) would have TB (false-negatives).For TB meningitis, ultra sensitivity and specificity against culture (95% confidence interval (CI)) were 90% (55% to 100%) and 90% (83% to 95%), respectively (one study, 129 participants).Xpert testing in pleural fluidXpert pooled sensitivity and specificity (95% CrI) against culture were 50.9% (39.7% to 62.8%) and 99.2% (98.2% to 99.7%), respectively (27 studies, 4006 specimens; low-certainty evidence).For a population of 1000 people where 150 have pleural TB on culture, 83 would be Xpert-positive: of these, seven (8%) would not have TB (false-positives); and 917 would be Xpert-negative: of these, 74 (8%) would have TB (false-negatives).Xpert testing in urineXpert pooled sensitivity and specificity (95% CrI) against culture were 82.7% (69.6% to 91.1%) and 98.7% (94.8% to 99.7%), respectively (13 studies, 1199 specimens; moderate-certainty evidence).For a population of 1000 people where 70 have genitourinary TB on culture, 70 would be Xpert-positive: of these, 12 (17%) would not have TB (false-positives); and 930 would be Xpert-negative: of these, 12 (1%) would have TB (false-negatives).Xpert testing for rifampicin resistanceXpert pooled sensitivity (20 studies, 148 specimens) and specificity (39 studies, 1088 specimens) were 95.0% (89.7% to 97.9%) and 98.7% (97.8% to 99.4%), respectively (high-certainty evidence).For a population of 1000 people where 120 have rifampicin-resistant TB, 125 would be positive for rifampicin-resistant TB: of these, 11 (9%) would not have rifampicin resistance (false-positives); and 875 would be negative for rifampicin-resistant TB: of these, 6 (1%) would have rifampicin resistance (false-negatives).For lymph node TB, the accuracy of culture, the reference standard used, presented a greater concern for bias than in other forms of extrapulmonary TB.
AUTHORS' CONCLUSIONS
In people presumed to have extrapulmonary TB, Xpert may be helpful in confirming the diagnosis. Xpert sensitivity varies across different extrapulmonary specimens, while for most specimens, specificity is high, the test rarely yielding a positive result for people without TB (defined by culture). Xpert is accurate for detection of rifampicin resistance. For people with presumed TB meningitis, treatment should be based on clinical judgement, and not withheld solely on an Xpert result, as is common practice when culture results are negative.
Topics: Antibiotics, Antitubercular; Bacterial Proteins; DNA-Directed RNA Polymerases; Drug Resistance, Bacterial; False Negative Reactions; False Positive Reactions; Humans; Mycobacterium tuberculosis; Reagent Kits, Diagnostic; Reference Standards; Rifampin; Sensitivity and Specificity; Tuberculosis; Tuberculosis, Meningeal
PubMed: 30148542
DOI: 10.1002/14651858.CD012768.pub2