Bacterial pathogens and resistance causing community acquired paediatric bloodstream infections in low- and middle-income countries: a systematic review and meta-analysis

Background Despite a high mortality rate in childhood, there is limited evidence on the causes and outcomes of paediatric bloodstream infections from low- and middle-income countries (LMICs). We conducted a systematic review and meta-analysis to characterize the bacterial causes of paediatric bloodstream infections in LMICs and their resistance profile. Methods We searched Pubmed and Embase databases between January 1st 1990 and October 30th 2019, combining MeSH and free-text terms for “sepsis” and “low-middle-income countries” in children. Two reviewers screened articles and performed data extraction to identify studies investigating children (1 month-18 years), with at least one blood culture. The main outcomes of interests were the rate of positive blood cultures, the distribution of bacterial pathogens, the resistance patterns and the case-fatality rate. The proportions obtained from each study were pooled using the Freeman-Tukey double arcsine transformation, and a random-effect meta-analysis model was used. Results We identified 2403 eligible studies, 17 were included in the final review including 52,915 children (11 in Africa and 6 in Asia). The overall percentage of positive blood culture was 19.1% [95% CI: 12.0–27.5%]; 15.5% [8.4–24.4%] in Africa and 28.0% [13.2–45.8%] in Asia. A total of 4836 bacterial isolates were included in the studies; 2974 were Gram-negative (63.9% [52.2–74.9]) and 1858 were Gram-positive (35.8% [24.9–47.5]). In Asia, Salmonella typhi (26.2%) was the most commonly isolated pathogen, followed by Staphylococcus aureus (7.7%) whereas in Africa, S. aureus (17.8%) and Streptococcus pneumoniae (16.8%) were predominant followed by Escherichia coli (10.7%). S. aureus was more likely resistant to methicillin in Africa (29.5% vs. 7.9%), whereas E. coli was more frequently resistant to third-generation cephalosporins (31.2% vs. 21.2%), amikacin (29.6% vs. 0%) and ciprofloxacin (36.7% vs. 0%) in Asia. The overall estimate for case-fatality rate among 8 studies was 12.7% [6.6–20.2%]. Underlying conditions, such as malnutrition or HIV infection were assessed as a factor associated with bacteraemia in 4 studies each. Conclusions We observed a marked variation in pathogen distribution and their resistance profiles between Asia and Africa. Very limited data is available on underlying risk factors for bacteraemia, patterns of treatment of multidrug-resistant infections and predictors of adverse outcomes

Measuring antibiotic availability and use in 20 low- and middle-income countries

Objective To assess antibiotic availability and use in health facilities in low- and middle-income countries, using the service provision assessment and service availability and readiness assessment surveys. Methods We obtained data on antibiotic availability at 13 561 health facilities in 13 service provision assessment and 8 service availability and readiness assessment surveys. In 10 service provision assessment surveys, child consultations with health-care providers were observed, giving data on antibiotic use in 22 699 children. Antibiotics were classified as access, watch or reserve, according to the World Health Organization’s AWaRe categories. The percentage of health-care facilities across countries with specific antibiotics available and the proportion of children receiving antibiotics for key clinical syndromes were estimated. Findings The surveys assessed the availability of 27 antibiotics (19 access, 7 watch, 1 unclassified). Co-trimoxazole and metronidazole were most widely available, being in stock at 89.5% (interquartile range, IQR: 11.6%) and 87.1% (IQR: 15.9%) of health facilities, respectively. In contrast, 17 other access and watch antibiotics were stocked, by fewer than a median of 50% of facilities. Of the 22 699 children observed, 60.1% (13 638) were prescribed antibiotics (mostly co-trimoxazole or amoxicillin). Children with respiratory conditions were most often prescribed antibiotics (76.1%; 8972/11 796) followed by undifferentiated fever (50.1%; 760/1518), diarrhoea (45.7%; 1293/2832) and malaria (30.3%; 352/1160). Conclusion Routine health facility surveys provided a valuable data source on the availability and use of antibiotics in low- and middle-income countries. Many access antibiotics were unavailable in a majority of most health-care facilities

Planetary nebulae detected in the Spitzer Space Telescope GLIMPSE 3D Legacy Survey

Due to interstellar extinction, optical census of Galactic planetary nebulae (PNs) is highly incomplete, and some compact H ii regions might have been mis-classified as PNs. The problem is particularly severe in the Galactic plane where the extinction in the optical is significant and hampers the detections of PNs. Unlike optical observations, infrared (IR) observations are hardly affected by interstellar extinction, and provide a good opportunity to study highly obscured PNs. In this study, we use the data from the Spitzer Legacy Infrared Mid-Plane Survey Extraordinaire 3D (GLIMPSE 3D) to investigate the mid-infrared (MIR) properties of PNs and PN candidates. © 2012 International Astronomical Union.published_or_final_versionThe IAU Symposium No. 283: 'Planetary Nebulae: an Eye to the Future', Puerto de la Cruz, Tenerife, Spain, 25-29 July 2011. In International Astronomical Union Proceedings, 2011, v. 7 n. S283, p. 528-52

Consumption of oral antibiotic formulations for young children according to the WHO Access, Watch, Reserve (AWaRe) antibiotic groups: an analysis of sales data from 70 middle-income and high-income countries

Background The 2017 WHO Model List of Essential Medicines for Children (EMLc) groups antibiotics as Access, Watch, or Reserve, based on recommendations of their use as first-choice and second-choice empirical treatment for the most common infections. This grouping provides an opportunity to review country-level antibiotic consumption and a potential for stewardship. Therefore, we aimed to review 2015 levels of oral antibiotic consumption by young children globally. Methods We analysed wholesale antibiotic sales in 70 middle-income and high-income countries in 2015. We identified oral antibiotic formulations appropriate for use in young children (defined as child-appropriate formulations [CAFs]) using wholesale data from the IQVIA-Multinational Integrated Data Analysis System database, and we estimated 2015 antibiotic consumption in reference to the 2017 WHO EMLc Access, Watch, Reserve (AWaRe) antibiotic groups. We used three metrics for assessment of intra-country patterns: access percentage, defined as the number of CAF standard units of Access antibiotics divided by the total number of CAF standard units; amoxicillin index, defined as the number of amoxicillin CAF standard units divided by the total number of CAF standard units; and access-to-watch index, defined as the ratio of Access-to-Watch CAF standard units. Findings The overall median volume of CAF antibiotic standard units sold in 2015 per country was 74·5 million (IQR 12·4–210·7 million). The median access percentage among the 70 countries was 76·3% (IQR 62·6–84·2). The amoxicillin index was low (median 30·7%, IQR 14·3–47·3). The median access-to-watch index was 6·0 (IQR 3·1–9·8). CAF antibiotic consumption patterns were highly variable between the 70 countries, without a clear difference between high-income and middle-income countries. Interpretation Antibiotics in the Access group have a key role in treating young children globally. A simple combination of metrics based on the AWaRe groups can be informative on individual countries' patterns of antibiotic consumption and stewardship opportunities. These metrics could support countries in the development of programmes to improve access to core Access antibiotics, particularly amoxicillin. Funding Global Antibiotic R&D Partnership (German Federal Ministry of Health, Médecins Sans Frontières, Netherlands Ministry of Health, Welfare and Sport, and UK Department for International Development)

Separating Beads and Cells in Multi-channel Microfluidic Devices Using Dielectrophoresis and Laminar Flow

Microfluidic devices have advanced cell studies by providing a dynamic fluidic environment on the scale of the cell for studying, manipulating, sorting and counting cells. However, manipulating the cell within the fluidic domain remains a challenge and requires complicated fabrication protocols for forming valves and electrodes, or demands specialty equipment like optical tweezers. Here, we demonstrate that conventional printed circuit boards (PCB) can be used for the non-contact manipulation of cells by employing dielectrophoresis (DEP) for bead and cell manipulation in laminar flow fields for bioactuation, and for cell and bead separation in multichannel microfluidic devices. First, we present the protocol for assembling the DEP electrodes and microfluidic devices, and preparing the cells for DEP. Then, we characterize the DEP operation with polystyrene beads. Lastly, we show representative results of bead and cell separation in a multichannel microfluidic device. In summary, DEP is an effective method for manipulating particles (beads or cells) within microfluidic devices

Haemodynamic consequences of targeted single- and dual-site right ventricular pacing in adults with congenital heart disease undergoing surgical pulmonary valve replacement

Aims The purpose of this study was to create an epicardial electroanatomic map of the right ventricle (RV) and then apply post-operative-targeted single- and dual-site RV temporary pacing with measurement of haemodynamic parameters. Cardiac resynchronization therapy is an established treatment for symptomatic left ventricular (LV) dysfunction. In congenital heart disease, RV dysfunction is a common cause of morbidity—little is known regarding the potential benefits of CRT in this setting. Methods and results Sixteen adults (age = 32 ± 8 years; 6 M, 10 F) with right bundle branch block (RBBB) and repaired tetralogy of Fallot (n = 8) or corrected congenital pulmonary stenosis (n = 8) undergoing surgical pulmonary valve replacement (PVR) for pulmonary regurgitation underwent epicardial RV mapping and haemodynamic assessment of random pacing configurations including the site of latest RV activation. The pre-operative pulmonary regurgitant fraction was 49 ± 10%; mean LV end-diastolic volume (EDV) 85 ± 19 mL/min/m2 and RVEDV 183 ± 89 mL/min/m2 on cardiac magnetic resonance imaging. The mean pre-operative QRS duration is 136 ± 26 ms. The commonest site of latest activation was the RV free wall and DDD pacing here alone or combined with RV apical pacing resulted in significant increases in cardiac output (CO) vs. AAI pacing (P < 0.01 all measures). DDDRV alternative site pacing significantly improved CO by 16% vs. AAI (P = 0.018), and 8.5% vs. DDDRV apical pacing (P = 0.02). Conclusion Single-site RV pacing targeted to the region of latest activation in patients with RBBB undergoing PVR induces acute improvements in haemodynamics and supports the concept of ‘RV CRT’. Targeted pacing in such patients has therapeutic potential both post-operatively and in the long term

Systematic Review and Meta-Analyses of Incidence for Group B Streptococcus Disease in Infants and Antimicrobial Resistance, China.

We performed a systematic review and meta-analysis of the incidence, case-fatality rate (CFR), isolate antimicrobial resistance patterns, and serotype and sequence type distributions for invasive group B Streptococcus (GBS) disease in infants <1-89 days of age in China. We searched the PubMed/Medline, Embase, Wanfang, and China National Knowledge Infrastructure databases for research published during January 1, 2000-March 16, 2018, and identified 64 studies. Quality of included studies was assessed by using Cochrane tools. Incidence and CFR were estimated by using random-effects meta-analyses. Overall incidence was 0.55 (95% CI 0.35-0.74) cases/1,000 live births, and the CFR was 5% (95% CI 3%-6%). Incidence of GBS in young infants in China was higher than the estimated global incidence (0.49 cases/1,000 live births) and higher than previous estimates for Asia (0.3 cases/1,000 live births). Our findings suggest that implementation of additional GBS prevention efforts in China, including maternal vaccination, could be beneficial

A statistical shape modelling framework to extract 3D shape biomarkers from medical imaging data: assessing arch morphology of repaired coarctation of the aorta

Background Medical image analysis in clinical practice is commonly carried out on 2D image data, without fully exploiting the detailed 3D anatomical information that is provided by modern non-invasive medical imaging techniques. In this paper, a statistical shape analysis method is presented, which enables the extraction of 3D anatomical shape features from cardiovascular magnetic resonance (CMR) image data, with no need for manual landmarking. The method was applied to repaired aortic coarctation arches that present complex shapes, with the aim of capturing shape features as biomarkers of potential functional relevance. The method is presented from the user-perspective and is evaluated by comparing results with traditional morphometric measurements. Methods Steps required to set up the statistical shape modelling analyses, from pre-processing of the CMR images to parameter setting and strategies to account for size differences and outliers, are described in detail. The anatomical mean shape of 20 aortic arches post-aortic coarctation repair (CoA) was computed based on surface models reconstructed from CMR data. By analysing transformations that deform the mean shape towards each of the individual patient’s anatomy, shape patterns related to differences in body surface area (BSA) and ejection fraction (EF) were extracted. The resulting shape vectors, describing shape features in 3D, were compared with traditionally measured 2D and 3D morphometric parameters. Results The computed 3D mean shape was close to population mean values of geometric shape descriptors and visually integrated characteristic shape features associated with our population of CoA shapes. After removing size effects due to differences in body surface area (BSA) between patients, distinct 3D shape features of the aortic arch correlated significantly with EF (r = 0.521, p = .022) and were well in agreement with trends as shown by traditional shape descriptors. Conclusions The suggested method has the potential to discover previously unknown 3D shape biomarkers from medical imaging data. Thus, it could contribute to improving diagnosis and risk stratification in complex cardiac disease