-
Lancet (London, England) Feb 2022Antimicrobial resistance (AMR) poses a major threat to human health around the world. Previous publications have estimated the effect of AMR on incidence, deaths,...
BACKGROUND
Antimicrobial resistance (AMR) poses a major threat to human health around the world. Previous publications have estimated the effect of AMR on incidence, deaths, hospital length of stay, and health-care costs for specific pathogen-drug combinations in select locations. To our knowledge, this study presents the most comprehensive estimates of AMR burden to date.
METHODS
We estimated deaths and disability-adjusted life-years (DALYs) attributable to and associated with bacterial AMR for 23 pathogens and 88 pathogen-drug combinations in 204 countries and territories in 2019. We obtained data from systematic literature reviews, hospital systems, surveillance systems, and other sources, covering 471 million individual records or isolates and 7585 study-location-years. We used predictive statistical modelling to produce estimates of AMR burden for all locations, including for locations with no data. Our approach can be divided into five broad components: number of deaths where infection played a role, proportion of infectious deaths attributable to a given infectious syndrome, proportion of infectious syndrome deaths attributable to a given pathogen, the percentage of a given pathogen resistant to an antibiotic of interest, and the excess risk of death or duration of an infection associated with this resistance. Using these components, we estimated disease burden based on two counterfactuals: deaths attributable to AMR (based on an alternative scenario in which all drug-resistant infections were replaced by drug-susceptible infections), and deaths associated with AMR (based on an alternative scenario in which all drug-resistant infections were replaced by no infection). We generated 95% uncertainty intervals (UIs) for final estimates as the 25th and 975th ordered values across 1000 posterior draws, and models were cross-validated for out-of-sample predictive validity. We present final estimates aggregated to the global and regional level.
FINDINGS
On the basis of our predictive statistical models, there were an estimated 4·95 million (3·62-6·57) deaths associated with bacterial AMR in 2019, including 1·27 million (95% UI 0·911-1·71) deaths attributable to bacterial AMR. At the regional level, we estimated the all-age death rate attributable to resistance to be highest in western sub-Saharan Africa, at 27·3 deaths per 100 000 (20·9-35·3), and lowest in Australasia, at 6·5 deaths (4·3-9·4) per 100 000. Lower respiratory infections accounted for more than 1·5 million deaths associated with resistance in 2019, making it the most burdensome infectious syndrome. The six leading pathogens for deaths associated with resistance (Escherichia coli, followed by Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa) were responsible for 929 000 (660 000-1 270 000) deaths attributable to AMR and 3·57 million (2·62-4·78) deaths associated with AMR in 2019. One pathogen-drug combination, meticillin-resistant S aureus, caused more than 100 000 deaths attributable to AMR in 2019, while six more each caused 50 000-100 000 deaths: multidrug-resistant excluding extensively drug-resistant tuberculosis, third-generation cephalosporin-resistant E coli, carbapenem-resistant A baumannii, fluoroquinolone-resistant E coli, carbapenem-resistant K pneumoniae, and third-generation cephalosporin-resistant K pneumoniae.
INTERPRETATION
To our knowledge, this study provides the first comprehensive assessment of the global burden of AMR, as well as an evaluation of the availability of data. AMR is a leading cause of death around the world, with the highest burdens in low-resource settings. Understanding the burden of AMR and the leading pathogen-drug combinations contributing to it is crucial to making informed and location-specific policy decisions, particularly about infection prevention and control programmes, access to essential antibiotics, and research and development of new vaccines and antibiotics. There are serious data gaps in many low-income settings, emphasising the need to expand microbiology laboratory capacity and data collection systems to improve our understanding of this important human health threat.
FUNDING
Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care using UK aid funding managed by the Fleming Fund.
Topics: Anti-Bacterial Agents; Bacterial Infections; Drug Resistance, Bacterial; Global Burden of Disease; Global Health; Humans; Models, Statistical
PubMed: 35065702
DOI: 10.1016/S0140-6736(21)02724-0 -
Clinical Microbiology and Infection :... Sep 2021Bacteria colonizing the upper respiratory tract (URT) of young children play a key role in the pathogenesis of lower respiratory tract infection (LRTI). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Bacteria colonizing the upper respiratory tract (URT) of young children play a key role in the pathogenesis of lower respiratory tract infection (LRTI).
OBJECTIVES
To systematically review the literature on the association between bacteria colonizing the URT and LRTI among young children.
DATA SOURCES
MEDLINE, Academic Search Premier, Africa-Wide Information and CINAHL, Scopus and Web of Science.
STUDY ELIGIBILITY CRITERIA
Studies published between 1923 and 2020, investigating URT bacteria from LRTI cases and controls.
PARTICIPANTS
Children under 5 years with and without acute LRTI.
METHODS
Three reviewers independently screened titles, abstracts and full texts. Meta-analysis was done using Mantel-Haenszel fixed- or random-effects models.
RESULTS
Most eligible studies (41/50) tested nasopharyngeal specimens when investigating URT bacteria. Most studies were of cross-sectional design (44/50). Twenty-four studies were performed in children in lower- or lower-middle-income countries (LMICs). There was higher prevalence of Haemophilus influenzae (pooled OR 1.60; 95% CI 1.23-2.07) and Klebsiella spp. (pooled OR 2.04; 95% CI 1.17-3.55) from URT specimens of cases versus controls. We observed a positive association between the detection of Streptococcus pneumoniae from URT specimens and LRTI after excluding studies where there was more antibiotic treatment prior to sampling in cases vs. controls (pooled OR 1.41; 95% CI 1.04-1.90). High density colonization with S. pneumoniae (>6.9 log copies/mL) was associated with an increased risk for LRTI. The associations between both Streptococcus and Haemophilus URT detection and LRTI were supported, at genus level, by 16S rRNA sequencing. Evidence for the role of Moraxella catarrhalis and Staphylococcus aureus was inconclusive.
CONCLUSIONS
Detection of H. influenzae or Klebsiella spp. in the URT was associated with LRTI, while evidence for association with S. pneumoniae was less conclusive. Longitudinal studies assessing URT microbial communities, together with environmental and host factors are needed to better understand pathogenesis of childhood LRTI.
Topics: Bacteria; Child; Child, Preschool; Cross-Sectional Studies; Humans; RNA, Ribosomal, 16S; Respiratory Tract Infections
PubMed: 34111578
DOI: 10.1016/j.cmi.2021.05.034 -
Clinical Microbiology and Infection :... Jan 2022Point-of-care tests could be essential in differentiating bacterial and viral acute community-acquired lower respiratory tract infections and driving antibiotic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Point-of-care tests could be essential in differentiating bacterial and viral acute community-acquired lower respiratory tract infections and driving antibiotic stewardship in the community.
OBJECTIVES
To assess diagnostic test accuracy of point-of-care tests in community settings for acute community-acquired lower respiratory tract infections.
DATA SOURCES
Multiple databases (MEDLINE, EMBASE, Web of Science, Cochrane Library, Open Gray) from inception to 31 May 2021, without language restrictions.
STUDY ELIGIBILITY CRITERIA
Diagnostic test accuracy studies involving patients at primary care, outpatient clinic, emergency department and long-term care facilities with a clinical suspicion of acute community-acquired lower respiratory tract infections. The comparator was any test used as a comparison to the index test. In order not to limit the study inclusion, the comparator was not defined a priori.
ASSESSMENT OF RISK OF BIAS
Four investigators independently extracted data, rated risk of bias, and assessed the quality using QUADAS-2.
METHODS OF DATA SYNTHESIS
The measures of diagnostic test accuracy were calculated with 95% CI.
RESULTS
A total of 421 studies addressed at least one point-of-care test. The diagnostic performance of molecular tests was higher compared with that of rapid diagnostic tests for all the pathogens studied. The accuracy of stand-alone signs and symptoms or biomarkers was poor. Lung ultrasound showed high sensitivity and specificity (90% for both) for the diagnosis of bacterial pneumonia. Rapid antigen-based diagnostic tests for influenza, respiratory syncytial virus, human metapneumovirus, and Streptococcus pneumoniae had sub-optimal sensitivity (range 49%-84%) but high specificity (>80%).
DISCUSSION
Physical examination and host biomarkers are not sufficiently reliable as stand-alone tests to differentiate between bacterial and viral pneumonia. Lung ultrasound shows higher accuracy than chest X-ray for bacterial pneumonia at emergency department. Rapid antigen-based diagnostic tests cannot be considered fully reliable because of high false-negative rates. Overall, molecular tests for all the pathogens considered were found to be the most accurate.
Topics: Bias; Biomarkers; Diagnosis, Differential; Humans; Pneumonia, Bacterial; Pneumonia, Viral; Point-of-Care Testing; Sensitivity and Specificity; Ultrasonography
PubMed: 34601148
DOI: 10.1016/j.cmi.2021.09.025 -
The Lancet. Neurology Aug 2023Although meningitis is largely preventable, it still causes hundreds of thousands of deaths globally each year. WHO set ambitious goals to reduce meningitis cases by...
BACKGROUND
Although meningitis is largely preventable, it still causes hundreds of thousands of deaths globally each year. WHO set ambitious goals to reduce meningitis cases by 2030, and assessing trends in the global meningitis burden can help track progress and identify gaps in achieving these goals. Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we aimed to assess incident cases and deaths due to acute infectious meningitis by aetiology and age from 1990 to 2019, for 204 countries and territories.
METHODS
We modelled meningitis mortality using vital registration, verbal autopsy, sample-based vital registration, and mortality surveillance data. Meningitis morbidity was modelled with a Bayesian compartmental model, using data from the published literature identified by a systematic review, as well as surveillance data, inpatient hospital admissions, health insurance claims, and cause-specific meningitis mortality estimates. For aetiology estimation, data from multiple causes of death, vital registration, hospital discharge, microbial laboratory, and literature studies were analysed by use of a network analysis model to estimate the proportion of meningitis deaths and cases attributable to the following aetiologies: Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae, group B Streptococcus, Escherichia coli, Klebsiella pneumoniae, Listeria monocytogenes, Staphylococcus aureus, viruses, and a residual other pathogen category.
FINDINGS
In 2019, there were an estimated 236 000 deaths (95% uncertainty interval [UI] 204 000-277 000) and 2·51 million (2·11-2·99) incident cases due to meningitis globally. The burden was greatest in children younger than 5 years, with 112 000 deaths (87 400-145 000) and 1·28 million incident cases (0·947-1·71) in 2019. Age-standardised mortality rates decreased from 7·5 (6·6-8·4) per 100 000 population in 1990 to 3·3 (2·8-3·9) per 100 000 population in 2019. The highest proportion of total all-age meningitis deaths in 2019 was attributable to S pneumoniae (18·1% [17·1-19·2]), followed by N meningitidis (13·6% [12·7-14·4]) and K pneumoniae (12·2% [10·2-14·3]). Between 1990 and 2019, H influenzae showed the largest reduction in the number of deaths among children younger than 5 years (76·5% [69·5-81·8]), followed by N meningitidis (72·3% [64·4-78·5]) and viruses (58·2% [47·1-67·3]).
INTERPRETATION
Substantial progress has been made in reducing meningitis mortality over the past three decades. However, more meningitis-related deaths might be prevented by quickly scaling up immunisation and expanding access to health services. Further reduction in the global meningitis burden should be possible through low-cost multivalent vaccines, increased access to accurate and rapid diagnostic assays, enhanced surveillance, and early treatment.
FUNDING
Bill & Melinda Gates Foundation.
Topics: Child; Humans; Global Burden of Disease; Bayes Theorem; Meningitis; Risk Factors; Global Health
PubMed: 37479374
DOI: 10.1016/S1474-4422(23)00195-3 -
Clinical Microbiology and Infection :... Mar 2020The FilmArray® meningitis/encephalitis (ME) panel is a multiplex PCR assay which can detect the most commonly identified pathogens in central nervous system infections.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The FilmArray® meningitis/encephalitis (ME) panel is a multiplex PCR assay which can detect the most commonly identified pathogens in central nervous system infections. It significantly decreases the time to diagnosis of ME and data has yielded several positive outcomes. However, in part, reports of both false positive and false negative detections have resulted in concerns about adoption.
OBJECTIVES
The aim was to evaluate the ME panel in a diagnostic test accuracy review.
DATA SOURCES
The PubMed and EMBASE databases were systematically searched through May 2019.
STUDY ELIGIBILITY CRITERIA
Eligible studies were those providing sensitivity and specificity data for the ME panel compared with a reference standard. Studies providing details on false positive and false negative results of the panel as well as further investigation (adjudication) of the discordant results between the panel and comparator assays were included and assessed separately.
PARTICIPANTS
Patients with suspected ME for whom a panel was ordered were included.
METHODS
The ME panel was compared to reference standard methods for diagnosing community-acquired ME. We performed a meta-analysis and calculated the summary sensitivity and specificity of the ME panel. Moreover, we evaluated the false positive and false negative results of the panel.
RESULTS
Thirteen studies (3764 patients) were included in the review and 8 of them (3059 patients) were pooled in a meta-analysis. The summary estimates of sensitivity and specificity with 95% confidence intervals (CI) was 90% (95% CI 86-93%) and 97% (95% CI 94-99%), respectively. When we looked specifically at studies that assessed further the false positive and false negative results, false positive detections were 11.4% and 4% before and after adjudication, respectively. The highest proportion of false positive was observed for Streptococcus pneumoniae followed by Streptococcus agalactiae. False negative isolates were 2.2% and 1.5% before and after adjudication, respectively. Herpes simplex virus 1 and 2, enterovirus and Cryptococcus neoformans/gattii had the highest proportions of false negative determinations. False negative C. neoformans/gattii were mostly patients with positive antigen titres, on treatment or cleared disease.
CONCLUSIONS
The currently available literature suggests that the ME panel has high diagnostic accuracy. However, the decision for implementation should be individualized based on the needs of the patient population, the capabilities of the laboratory, and the knowledge of the healthcare providers that will utilize the test.
Topics: Encephalitis; Humans; Meningitis; Multiplex Polymerase Chain Reaction; Publication Bias; ROC Curve; Reagent Kits, Diagnostic; Reproducibility of Results; Sensitivity and Specificity
PubMed: 31760115
DOI: 10.1016/j.cmi.2019.11.016 -
Pneumonia (Nathan Qld.) 2020The etiology of community-acquired pneumonia (CAP) has evolved since the beginning of the antibiotic era. Recent guidelines encourage immediate empiric antibiotic... (Review)
Review
BACKGROUND
The etiology of community-acquired pneumonia (CAP) has evolved since the beginning of the antibiotic era. Recent guidelines encourage immediate empiric antibiotic treatment once a diagnosis of CAP is made. Concerns about treatment recommendations, on the one hand, and antibiotic stewardship, on the other, motivated this review of the medical literature on the etiology of CAP.
METHODS
We conducted a systematic review of English-language literature on the etiology of CAP using methods defined by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched PubMed using a combination of the keywords 'pneumonia', 'CAP', 'etiology', 'microbiology', 'bacteriology', and 'pathogen'. We examined articles on antibiotics that were develop to treat pneumonia. We reviewed all 'related articles' as well as studies referenced by those that came up in the search. After we excluded articles that did not give sufficient microbiological data or failed to meet other predetermined criteria, 146 studies remained. Data were stratified into diagnostic categories according to the microbiologic studies that were done; results are presented as the percentage in each category of all cases in which an etiology was established.
RESULTS
remains the most common cause of CAP although declining in incidence; this decline has been greater in the US than elsewhere. is the second most common cause of CAP, followed by and Gram negative bacilli. The incidence of all bacteria as causes of CAP has declined because, with routine use of PCR for viruses, the denominator, cases with an established etiology, has increased. Viruses were reported on average in about 10% of cases, but recent PCR-based studies identified a respiratory virus in about 30% of cases of CAP, with substantial rates of viral/bacterial coinfection.
CONCLUSION
The results of this study justify current guidelines for initial empiric treatment of CAP. With pneumococcus and continuing to predominate, efforts at antibiotic stewardship might be enhanced by greater attention to the routine use of sputum Gram stain and culture. Because viral/bacterial coinfection is relatively common, the identification of a virus by PCR does not, by itself, allow for discontinuation of the antibiotic therapy.
PubMed: 33024653
DOI: 10.1186/s41479-020-00074-3 -
Journal of Global Antimicrobial... Dec 2020Epidemiological surveillance is one critical approach to estimate and fight the burden of antibiotic resistance (AR). Here we summarise the characteristics of... (Review)
Review
OBJECTIVES
Epidemiological surveillance is one critical approach to estimate and fight the burden of antibiotic resistance (AR). Here we summarise the characteristics of surveillance systems devoted to the surveillance of AR worldwide and published in the literature.
METHODS
We performed a systematic review of the literature available on PubMed from January 2007 to July 2019 (12.5 years). The keywords ('surveillance system' OR 'laboratory-based surveillance' OR 'syndromic surveillance' OR 'sentinel surveillance' OR 'integrated surveillance' OR 'population-based surveillance') AND ('antibiotic resistance' OR 'antimicrobial resistance') were used. This research was completed with AR monitoring systems available on websites.
RESULTS
We identified 71 AR surveillance systems described by 90 publications from 35 countries, including 64 (90.1%) national and 7 (9.9%) multinational surveillance systems. Two regions accounted for ∼72% of systems: European region (37; 52.1%) and Region of the Americas (14; 19.7%). Fifty-three focused on AR surveillance in humans, 12 studied both humans and animals, and 6 focused only on animals. The two most common bacterial species reported were Staphylococcus aureus (42; 59.2%) and Escherichia coli (39; 54.9%). Of the 71 AR surveillance systems, 20 (28.2%) used prevalence as an indicator, 3 (4.2%) used incidence and 7 (9.9%) used both. Methicillin-resistant S. aureus (MRSA), vancomycin-resistant Enterococcus spp., S. aureus and Streptococcus pneumoniae, penicillin-resistant S. pneumoniae, and extended-spectrum β-lactamase (ESBL)-producing and carbapenem-resistant E. coli and Klebsiella pneumoniae were monitored.
CONCLUSIONS
Our results showed heterogeneous surveillance systems. A 'One Health' approach is needed to monitor AR, with reference to the WHO Global Action Plan.
Topics: Anti-Bacterial Agents; Escherichia coli; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Staphylococcus aureus
PubMed: 33176216
DOI: 10.1016/j.jgar.2020.10.009 -
Value in Health : the Journal of the... Apr 2023Pneumococcal conjugate vaccines (PCVs) have significantly reduced disease burden caused by Streptococcus pneumoniae, a leading cause of childhood morbidity and mortality... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Pneumococcal conjugate vaccines (PCVs) have significantly reduced disease burden caused by Streptococcus pneumoniae, a leading cause of childhood morbidity and mortality globally. This systematic review and meta-analysis aimed to assess the incremental net benefit (INB) of the 13-valent PCV (PCV13) and 10-valent PCV (PCV10) in children.
METHODS
We performed a comprehensive search in several databases published before May 2022. Studies were included if they were cost-effectiveness or cost-utility analyses of PCV13 or PCV10 compared with no vaccination or with each other in children. Various monetary units were converted to purchasing power parity, adjusted to 2021 US dollars. The INBs were calculated and then pooled across studies stratified by country income level, perspective, and consideration of herd effects, using a random-effect model.
RESULTS
Seventy studies were included. When herd effects were considered, PCV13 was cost-effective compared with PCV10 from the payer perspective in both high-income countries (HICs) (INB, $103.94; 95% confidence interval, $75.28-$132.60) and low- and middle-income countries (LMICs) (INB, $53.49; 95% confidence interval, $30.42-$76.55) with statistical significance. These findings were robust across a series of sensitivity analyses. PCV13 was cost-effective compared with no vaccination across perspectives and consideration of herd effects in both HICs and LMICs, whereas findings were less consistent for PCV10.
CONCLUSION
PCVs were generally cost-effective compared with no vaccination in HICs and LMICs. Our study found that PCV13 was cost-effective compared with PCV10 when herd effects were considered from the payer perspective in both HICs and LMICs. The results are sensitive to the consideration of herd effects.
Topics: Child; Humans; Infant; Pneumococcal Infections; Cost-Benefit Analysis; Immunization Programs; Vaccination; Pneumococcal Vaccines; Vaccines, Conjugate
PubMed: 36328324
DOI: 10.1016/j.jval.2022.10.006 -
The Cochrane Database of Systematic... Sep 2019Trachoma is the world's leading infectious cause of blindness. In 1996, WHO launched the Alliance for the Global Elimination of Trachoma by the year 2020, based on the...
BACKGROUND
Trachoma is the world's leading infectious cause of blindness. In 1996, WHO launched the Alliance for the Global Elimination of Trachoma by the year 2020, based on the 'SAFE' strategy (surgery, antibiotics, facial cleanliness, and environmental improvement).
OBJECTIVES
To assess the evidence supporting the antibiotic arm of the SAFE strategy by assessing the effects of antibiotics on both active trachoma (primary objective), Chlamydia trachomatis infection of the conjunctiva, antibiotic resistance, and adverse effects (secondary objectives).
SEARCH METHODS
We searched relevant electronic databases and trials registers. The date of the last search was 4 January 2019.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that satisfied either of two criteria: (a) trials in which topical or oral administration of an antibiotic was compared to placebo or no treatment in people or communities with trachoma, (b) trials in which a topical antibiotic was compared with an oral antibiotic in people or communities with trachoma. We also included studies addressing different dosing strategies in the population. DATA COLLECTION AND ANALYSIS: We used standard methods expected by Cochrane. We assessed the certainty of the evidence using the GRADE approach.
MAIN RESULTS
We identified 14 studies where individuals with trachoma were randomised and 12 cluster-randomised studies. Any antibiotic versus control (individuals)Nine studies (1961 participants) randomised individuals with trachoma to antibiotic or control (no treatment or placebo). All of these studies enrolled children and young people with active trachoma. The antibiotics used in these studies included topical (oxy)tetracycline (5 studies), doxycycline (2 studies), and sulfonamides (4 studies). Four studies had more than two study arms. In general these studies were poorly reported, and it was difficult to judge risk of bias.These studies provided low-certainty evidence that people with active trachoma treated with antibiotics experienced a reduction in active trachoma at three months (risk ratio (RR) 0.78, 95% confidence interval (CI) 0.69 to 0.89; 1961 people; 9 RCTs; I = 73%) and 12 months (RR 0.74, 95% CI 0.55 to 1.00; 1035 people; 4 RCTs; I = 90%). Low-certainty evidence was available for ocular infection at three months (RR 0.81, 95% CI 0.63 to 1.04; 297 people; 4 RCTs; I = 0%) and 12 months (RR 0.25, 95% CI 0.08 to 0.78; 129 people; 1 RCT). None of these studies assessed antimicrobial resistance. In those studies that reported harms, no serious adverse effects were reported (low-certainty evidence).Oral versus topical antibiotics (individuals)Eight studies (1583 participants) compared oral and topical antibiotics. Only one study included people older than 21 years of age. Oral antibiotics included azithromycin (5 studies), sulfonamides (2 studies), and doxycycline (1 study). Topical antibiotics included (oxy)tetracycline (6 studies), azithromycin (1 study), and sulfonamide (1 study). These studies were poorly reported, and it was difficult to judge risk of bias.There was low-certainty evidence of little or no difference in effect between oral and topical antibiotics on active trachoma at three months (RR 0.97, 95% CI 0.81 to 1.16; 953 people; 6 RCTs; I = 63%) and 12 months (RR 0.93, 95% CI 0.75 to 1.15; 886 people; 5 RCTs; I = 56%). There was very low-certainty evidence for ocular infection at three or 12 months. Antimicrobial resistance was not assessed. In those studies that reported adverse effects, no serious adverse effects were reported; one study reported abdominal pain with azithromycin; one study reported a couple of cases of nausea with azithromycin; and one study reported three cases of reaction to sulfonamides (low-certainty evidence).Oral azithromycin versus control (communities)Four cluster-randomised studies compared antibiotic with no or delayed treatment. Data were available on active trachoma at 12 months from two studies but could not be pooled because of reporting differences. One study at low risk of bias found a reduced prevalence of active trachoma 12 months after a single dose of azithromycin in communities with a high prevalence of infection (RR 0.58, 95% CI 0.52 to 0.65; 1247 people). The other, lower quality, study in low-prevalence communities reported similar median prevalences of infection at 12 months: 9.3% in communities treated with azithromycin and 8.2% in untreated communities. We judged this moderate-certainty evidence for a reduction in active trachoma with treatment, downgrading one level for inconsistency between the two studies. Two studies reported ocular infection at 12 months and data could be pooled. There was a reduction in ocular infection (RR 0.36, 0.31 to 0.43; 2139 people) 12 months after mass treatment with a single dose compared with no treatment (moderate-certainty evidence). There was high-certainty evidence of an increased risk of resistance of Streptococcus pneumoniae, Staphylococcus aureus, and Escherichia coli to azithromycin, tetracycline, and clindamycin in communities treated with azithromycin, with approximately 5-fold risk ratios at 12 months. The evidence did not support increased resistance to penicillin or trimethoprim-sulfamethoxazole. None of the studies measured resistance to C trachomatis. No serious adverse events were reported. The main adverse effect noted for azithromycin (˜10%) was abdominal pain, vomiting, and nausea.Oral azithromycin versus topical tetracycline (communities)Three cluster-randomised studies compared oral azithromycin with topical tetracycline. The evidence was inconsistent for active trachoma and ocular infection at three and 12 months (low-certainty evidence) and was not pooled due to considerable heterogeneity. Antimicrobial resistance and adverse effects were not reported.Different dosing strategiesSix studies compared different strategies for dosing. There were: mass treatment at different dosing intervals; applying cessation or stopping rules to mass treatment; strategies to increase mass treatment coverage. There was no strong evidence to support any variation in the recommended annual mass treatment.
AUTHORS' CONCLUSIONS
Antibiotic treatment may reduce the risk of active trachoma and ocular infection in people infected with C trachomatis, compared to no treatment/placebo, but the size of the treatment effect in individuals is uncertain. Mass antibiotic treatment with single dose oral azithromycin reduces the prevalence of active trachoma and ocular infection in communities. There is no strong evidence to support any variation in the recommended periodicity of annual mass treatment. There is evidence of an increased risk of antibiotic resistance at 12 months in communities treated with antibiotics.
Topics: Administration, Oral; Administration, Topical; Anti-Bacterial Agents; Chlamydia trachomatis; Drug Resistance, Bacterial; Humans; Randomized Controlled Trials as Topic; Trachoma; Treatment Outcome
PubMed: 31554017
DOI: 10.1002/14651858.CD001860.pub4 -
Infectious Diseases and Therapy Nov 2023Streptococcus pneumoniae is the leading cause of meningitis, with a case fatality of up to about 50%. Children younger than 5 years are at greater risk for pneumococcal... (Review)
Review
INTRODUCTION
Streptococcus pneumoniae is the leading cause of meningitis, with a case fatality of up to about 50%. Children younger than 5 years are at greater risk for pneumococcal meningitis compared with other populations. It is of significant importance to provide a comprehensive understanding of the burden of pneumococcal meningitis among under-fives in the low pneumococcal conjugate vaccine (PCV) coverage period in China.
METHODS
A systematic review was conducted. We searched both English (PubMed, Ovid-EMBASE, Biosis, Web of Science, and Cochrane) and Chinese (CNKI, Wanfang, and ViP) databases for studies on bacterial meningitis in China published between January 1980 and July 2022. Ineligible studies were excluded based on study design and data integrity. Heterogeneity was assessed with I and estimates of bacterial meningitis morbidity and mortality were pooled using random-effects models. Subgroup analysis was conducted to trace the source of the heterogeneity and summarize average estimates.
RESULTS
A total of 13,082 studies were identified in the literature, and 56 studies were finally included for data analysis. The estimated incidence of pneumococcal meningitis was 2.10 cases per 100,000 children younger than 5 years each year (95% CI: 0.59-7.46), with a pooled case fatality rate of 24.59% (95%CI: 19.35-30.28%) in China. It was estimated that 1617.16 (95% CI: 454.35-5744.78) pneumococcal meningitis cases and 548.86 (95% CI: 474.80-627.62) deaths occurred among under-fives in China in 2020. Streptococcus pneumoniae played an important role in the etiology of confirmed bacterial meningitis cases, with a pooled proportion of 22.05% (95% CI: 17.83-26.27%). The most prevalent serotypes were 6B, 14, 19F, 19A, and 23F, which were preventable with a vaccine.
CONCLUSIONS
Pneumococcal meningitis remains one of the most important health problems among children younger than 5 years in China. Immunization programs should be promoted to avoid preventable cases and deaths.
PubMed: 37837523
DOI: 10.1007/s40121-023-00878-y