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      Early-Onset Neonatal Sepsis in Low- and Middle-Income Countries: Current Challenges and Future Opportunities

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          Abstract

          Neonatal sepsis is defined as a systemic infection within the first 28 days of life, with early-onset sepsis (EOS) occurring within the first 72h, although the definition of EOS varies in literature. Whilst the global incidence has dramatically reduced over the last decade, neonatal sepsis remains an important cause of neonatal mortality, highest in low- and middle-income countries (LMICs). Symptoms at the onset of neonatal sepsis can be subtle, and therefore EOS is often difficult to diagnose from clinical presentation and laboratory testing and blood cultures are not always conclusive or accessible, especially in resource limited countries. Although the World Health Organisation (WHO) currently advocates a ß-lactam, and gentamicin for first line treatment, availability and cost influence the empirical antibiotic therapy administered. Antibiotic treatment of neonatal sepsis in LMICs is highly variable, partially caused by factors such as cost of antibiotics (and who pays for them) and access to certain antibiotics. Antimicrobial resistance (AMR) has increased considerably over the past decade and this review discusses current microbiology data available in the context of the diagnosis, and treatment for EOS. Importantly, this review highlights a large variability in data availability, methodology, availability of diagnostics, and aetiology of sepsis pathogens.

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          Most cited references127

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          The microbiome in early life: implications for health outcomes.

          Recent studies have characterized how host genetics, prenatal environment and delivery mode can shape the newborn microbiome at birth. Following this, postnatal factors, such as antibiotic treatment, diet or environmental exposure, further modulate the development of the infant's microbiome and immune system, and exposure to a variety of microbial organisms during early life has long been hypothesized to exert a protective effect in the newborn. Furthermore, epidemiological studies have shown that factors that alter bacterial communities in infants during childhood increase the risk for several diseases, highlighting the importance of understanding early-life microbiome composition. In this review, we describe how prenatal and postnatal factors shape the development of both the microbiome and the immune system. We also discuss the prospects of microbiome-mediated therapeutics and the need for more effective approaches that can reconfigure bacterial communities from pathogenic to homeostatic configurations.
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            Neonatal sepsis.

            Neonatal sepsis is the cause of substantial morbidity and mortality. Precise estimates of neonatal sepsis burden vary by setting. Differing estimates of disease burden have been reported from high-income countries compared with reports from low-income and middle-income countries. The clinical manifestations range from subclinical infection to severe manifestations of focal or systemic disease. The source of the pathogen might be attributed to an in-utero infection, acquisition from maternal flora, or postnatal acquisition from the hospital or community. The timing of exposure, inoculum size, immune status of the infant, and virulence of the causative agent influence the clinical expression of neonatal sepsis. Immunological immaturity of the neonate might result in an impaired response to infectious agents. This is especially evident in premature infants whose prolonged stays in hospital and need for invasive procedures place them at increased risk for hospital-acquired infections. Clinically, there is often little difference between sepsis that is caused by an identified pathogen and sepsis that is caused by an unknown pathogen. Culture-independent diagnostics, the use of sepsis prediction scores, judicious antimicrobial use, and the development of preventive measures including maternal vaccines are ongoing efforts designed to reduce the burden of neonatal sepsis.
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              The global burden of paediatric and neonatal sepsis: a systematic review

              The incidence of sepsis is highest in neonates and children, yet the global burden of sepsis in these age groups has not been assessed. We reviewed available evidence from observational epidemiological studies to estimate the global burden and mortality of sepsis in neonates and children. We did a systematic review and meta-analysis of studies reporting population-based sepsis incidence in neonates and children, published between 1979 and 2016. Our search yielded 1270 studies, 23 of which met the inclusion criteria; 16 were from high-income countries and seven from middle-income countries. 15 studies from 12 countries reported complete data and were included in the meta-analysis. We found an aggregate estimate of 48 (95% CI 27-86) sepsis cases and 22 (14-33) severe sepsis cases in children per 100 000 person-years. Mortality ranged from 1% to 5% for sepsis and 9% to 20% for severe sepsis. The population-level estimate for neonatal sepsis was 2202 (95% CI 1099-4360) per 100 000 livebirths, with mortality between 11% and 19%. Extrapolating these figures on a global scale, we estimate an incidence of 3·0 million cases of sepsis in neonates and 1·2 million cases in children. Although these results confirm that sepsis is a common and frequently fatal condition affecting neonates and children globally, few population-based data are available from low-income settings and the lack of standardisation of diagnostic criteria and definition of sepsis in the reviewed studies are obstacles to the accurate estimation of global burden. Robust epidemiological monitoring to define global sepsis incidence and mortality in children is urgently needed.
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                Author and article information

                Journal
                Infect Drug Resist
                Infect Drug Resist
                idr
                Infection and Drug Resistance
                Dove
                1178-6973
                09 March 2022
                2022
                : 15
                : 933-946
                Affiliations
                [1 ]Ineos Institute of Antimicrobial Research, Department of Zoology, University of Oxford , Oxford, UK
                [2 ]Division of Infection and Immunity, Cardiff University , Cardiff, UK
                [3 ]National Hospital Abuja , Abuja, Nigeria
                Author notes
                Correspondence: Kirsty Sands, Email kirsty.sands@zoo.ox.ac.uk
                Article
                294156
                10.2147/IDR.S294156
                8921667
                35299860
                c8e43655-15be-4db5-95f9-a41a4d43b3b6
                © 2022 Sands et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 19 November 2021
                : 17 February 2022
                Page count
                Figures: 0, References: 129, Pages: 14
                Funding
                Funded by: was not funded;
                This work was not funded.
                Categories
                Review

                Infectious disease & Microbiology
                early-onset neonatal sepsis,low- and middle-income countries,antimicrobial resistance,diagnosis,treatment

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