new approaches to preventing diagnosing and treating neonatal sepsis CORD-Papers-2022-06-02 (Version 1)

Title: New Approaches to Preventing Diagnosing and Treating Neonatal Sepsis
Abstract: Karen Edmond and Anita Zaidi highlight new approaches that could reduce the burden of neonatal sepsis worldwide.
Published: 2010-03-09
Journal: PLoS Med
DOI: 10.1371/journal.pmed.1000213
DOI_URL: http://doi.org/10.1371/journal.pmed.1000213
Author Name: Edmond Karen
Author link: https://covid19-data.nist.gov/pid/rest/local/author/edmond_karen
Author Name: Zaidi Anita
Author link: https://covid19-data.nist.gov/pid/rest/local/author/zaidi_anita
sha: 9fdb08f94d250800ca69a84cb21c110adbe1476b
license: cc-by
license_url: https://creativecommons.org/licenses/by/4.0/
source_x: Medline; PMC
source_x_url: https://www.medline.com/https://www.ncbi.nlm.nih.gov/pubmed/
pubmed_id: 20231868
pubmed_id_url: https://www.ncbi.nlm.nih.gov/pubmed/20231868
pmcid: PMC2834705
pmcid_url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2834705
url: https://doi.org/10.1371/journal.pmed.1000213 https://www.ncbi.nlm.nih.gov/pubmed/20231868/
has_full_text: TRUE
Keywords Extracted from Text Content: lysozymes Protein antigen vaccines Ciprofloxacin Clostridium tetani penicillin/ US preterm births E. coli vitamin A human DNA secretory IgA granulocyte/ monocyte colony stimulating factor amniotic fluid IgG tetanus toxoid ribosomal CRP antigen leucocyte cephalosporins trimester gentamicin S. agalactiae vaccine 23S lactoferrin LOCs S. agalactiae Oral liver India [42] TLR cell blood specimens human blood cocci placenta mononuclear cells S. agalactiae type III conjugate lactobacilli CRP [66] [6] [7] [8] monocytes preterms women IL8 GM-CSF cefadroxil saliva oral law hyaline membrane immunoglobulin interleukin 6 Toll-like receptors parenteral vitamin A [46] immune stimulants latex Bordetella pertussis Parenteral anti-inflammatory Th2-polarizing cytokines Escherichia coli utero DNA neutrophils vaginal tract patient cells pregnancy-induced cell wall antigens infants blood cells cefotaxime mother's blood 5%-10 concentra- oral cotrimoxazole cord micro-volume peripheral fluids [3] [4] [5] Th1-polarizing cytokines tumour necrosis factor-alpha bloodstream cytomegalovirus neutrophil left cotrimoxazole cefuroxime intravenous hepatitis B vaccines Streptococcus spp sunflower seed oil anti-Staphylococcus influenza immunisations T cell muscular TLRs serotypes ampicillin n-IMCI parenteral intramuscular hepatitis B virus TNF-a conjugate vaccines skin staphylococci Treponema pallidum KE AZ herpes simplex virus ceftriaxone KE polio 5-7 cell wall blood vessel preterm labour membranes IL6 US gastrointestinal fluids umbilical stump chlorhexidine rubella virus blood cultures vaginal chlorhexidine procalcitonin tetanus chlorhexidine APPs Ig surface interferon-gamma Streptococcus pneumoniae vaccines measles vaccine vaginal umbilical cord
Extracted Text Content in Record: First 5000 Characters:Neonatal sepsis or septicaemia is a clinical syndrome characterized by systemic signs of circulatory compromise (e.g., poor peripheral perfusion, pallor, hypotonia, poor responsiveness) caused by invasion of the bloodstream by bacteria in the first month of life. In the pre-antibiotic era neonatal sepsis was usually fatal. Case fatality rates in antibiotic treated infants now range between 5% and 60% with the highest rates reported from the lowestincome countries [1] . The World Health Organization (WHO) estimates that 1 million deaths per year (10% of all under-five mortality) are due to neonatal sepsis and that 42% of these deaths occur in the first week of life [2] . There are wide disparities in neonatal care between highand low-income countries. In high-income countries the major concern is the increasing numbers of extremely premature infants with high nosocomial infection rates due to multiresistant organisms in intensive care units. Health facility infections are also a major problem in lowincome countries, but the more pressing issues are the high proportion of home deliveries in unclean environments predisposing to sepsis and ensuring that all neonates have access to effective interventions from health care providers in the first days of life 2 . Indeed, new strategies that can prevent, diagnose, and treat neonates with sepsis are needed in both low-and high-income settings. Distal risk factors for neonatal sepsis include poverty and poor environmental conditions. Proximate factors include prolonged rupture of membranes, preterm labour, maternal pyrexia, unhygienic intrapartum and postnatal care, low birth weight, and prelacteal feeding of contaminated foods and fluids [3] [4] [5] . The bacteria that cause neonatal sepsis are acquired shortly before, during, and after delivery (Figure 1 ). They can be obtained directly from mother's blood, skin, or vaginal tract before or during delivery or from the environment during and after delivery. Streptococcus agalactiae (Group B streptococcus, GBS) is the most common cause of neonatal sepsis in many countries, though low rates are reported from many low-income countries, especially those in south Asia. [6] [7] [8] ; gramnegative bacilli (Escherichia coli, Klebsiella spp., Pseudomonas spp., Acinetobacter spp.) and gram-positive cocci (such as Staphylococcus aureus and Staphylococcus epidermidis) are other important causes [6] [7] [8] . However, there are many difficulties in interpreting aetiological neonatal sepsis data, because many studies report selected populations of high-risk infants. Specimens from infants in the first 24 hours of life are also seriously under-represented, especially those from low birth-weight babies and babies born outside health facilities [6, [9] [10] [11] . Intrapartum antibiotic prophylaxis against S. agalactiae has also led to a substantial change in the bacteria responsible for early onset neonatal sepsis; gramnegative bacilli and Staphylococcus spp. predominate in countries implementing these programs [12] . There are also many other important neonatal infectious disease pathogens that are not associated with the sepsis syndrome including: Treponema pallidum, rubella virus, herpes simplex virus, cytomegalovirus, toxoplasmosis, Clostridium tetani, HIV, hepatitis B virus, and Bordetella pertussis ( Figure 1 ) [1, 7, 13] . These infectious pathogens cause serious morbidities in young infants and multifaceted disease syndromes including congenital anomalies, developmental disabilities, chronic liver disease, neonatal tetanus, and apnoea. They are also important causes of morbidity and mortality in older age groups. However, only pathogens that cause neonatal sepsis are discussed in this paper. Neonates have a functionally immature immune system. They have extremely low immunoglobulin (Ig) levels except for IgG to specific maternal antigens transferred passively across the placenta during the last trimester of pregnancy [14, 15] . T cell function is relatively unimpaired but complement activity is half that of healthy adults. Neonates have a low neutrophil storage pool, and their existing neutrophils have impaired capacity to migrate from the blood to sites of infection [16] . The basal expression of Toll-like receptors (TLRs, receptors that detect the presence of microbes) is similar in the neonate and adult [17] . However, innate immune responses of neonatal mononuclear cells are characterised by markedly reduced release of the proinflammatory Th1-polarizing cytokines tumour necrosis factor-alpha (TNF-a) and interferon-gamma (IFN-c) with relative preservation of anti-inflammatory Th2-polarizing cytokines such as interleukin 6 (IL6) [18] . These findings may reflect in utero requirements, including the avoidance of harmful inflammatory immune reactions [19] . These immunological problems are reflected in the clinical presentation of neonatal sepsis. Neonates have a rapid and fulminant progression of septicaemic disease, nonspe
Keywords Extracted from PMC Text: low- cefadroxil IFN-γ parenteral vitamin A [46] vaginal tract saliva serotypes surface [8],[71 CRP preterm labour penicillin/ampicillin Protein antigen vaccines Streptococcus spp ampicillin tetanus US preterm placenta ribosomal [6]–[8] polio cell wall antigens LOC (Figure 2 Clostridium tetani Th1-polarizing cytokines tumour necrosis factor-alpha LOCs chlorhexidine cells skin liver women blood cells conjugate vaccines [22],[26 S. agalactiae type III conjugate fluids [65],[66 2-month-old infants neutrophils interleukin 6 procalcitonin mother's blood IL6 oral cotrimoxazole mononuclear cells infants intramuscular human blood [62],[68 granulocyte/monocyte colony stimulating factor cytomegalovirus cell hepatitis B virus cephalosporins vitamin A TLR immune stimulants cell wall interferon-gamma staphylococci [27]–[29] anti-Staphylococcus IgG Ciprofloxacin [30],[31 GM-CSF cotrimoxazole blood oral S. agalactiae ceftriaxone amniotic fluid E. coli Oral n-IMCI Bordetella pertussis anti-inflammatory Th2-polarizing cytokines herpes simplex virus Ig 5%–10 neutrophil lysozymes 5–7 IL8 micro-volume vaginal Cytokines latex Escherichia coli left lactobacilli TLRs blood vessel gastrointestinal blood cultures membranes rubella virus tetanus toxoid intravenous cefotaxime Streptococcus pneumoniae vaccines T cell parenteral lactoferrin antigen US specimens [60],[61] measles vaccine trimester umbilical cord immunoglobulin DNA India [42] gentamicin patient " 23S [14],[15] S. agalactiae vaccine cord human DNA [39],[40] vaginal chlorhexidine monocytes pregnancy-induced leucocyte secretory IgA CRP [66] muscular hyaline membrane Parenteral APPs Treponema pallidum cefuroxime TNF-α umbilical stump chlorhexidine utero [6],[9]–[11 hepatitis B vaccines Toll-like receptors sunflower seed oil preterms
Extracted PMC Text Content in Record: First 5000 Characters:Distal risk factors for neonatal sepsis include poverty and poor environmental conditions. Proximate factors include prolonged rupture of membranes, preterm labour, maternal pyrexia, unhygienic intrapartum and postnatal care, low birth weight, and prelacteal feeding of contaminated foods and fluids [3]–[5]. The bacteria that cause neonatal sepsis are acquired shortly before, during, and after delivery (Figure 1). They can be obtained directly from mother's blood, skin, or vaginal tract before or during delivery or from the environment during and after delivery. Streptococcus agalactiae (Group B streptococcus, GBS) is the most common cause of neonatal sepsis in many countries, though low rates are reported from many low-income countries, especially those in south Asia.[6]–[8]; gram-negative bacilli (Escherichia coli, Klebsiella spp., Pseudomonas spp., Acinetobacter spp.) and gram-positive cocci (such as Staphylococcus aureus and Staphylococcus epidermidis) are other important causes [6]–[8]. However, there are many difficulties in interpreting aetiological neonatal sepsis data, because many studies report selected populations of high-risk infants. Specimens from infants in the first 24 hours of life are also seriously under-represented, especially those from low birth-weight babies and babies born outside health facilities [6],[9]–[11]. Intrapartum antibiotic prophylaxis against S. agalactiae has also led to a substantial change in the bacteria responsible for early onset neonatal sepsis; gram-negative bacilli and Staphylococcus spp. predominate in countries implementing these programs [12]. There are also many other important neonatal infectious disease pathogens that are not associated with the sepsis syndrome including: Treponema pallidum, rubella virus, herpes simplex virus, cytomegalovirus, toxoplasmosis, Clostridium tetani, HIV, hepatitis B virus, and Bordetella pertussis (Figure 1) [1],[7],[13]. These infectious pathogens cause serious morbidities in young infants and multifaceted disease syndromes including congenital anomalies, developmental disabilities, chronic liver disease, neonatal tetanus, and apnoea. They are also important causes of morbidity and mortality in older age groups. However, only pathogens that cause neonatal sepsis are discussed in this paper. Neonates have a functionally immature immune system. They have extremely low immunoglobulin (Ig) levels except for IgG to specific maternal antigens transferred passively across the placenta during the last trimester of pregnancy [14],[15]. T cell function is relatively unimpaired but complement activity is half that of healthy adults. Neonates have a low neutrophil storage pool, and their existing neutrophils have impaired capacity to migrate from the blood to sites of infection [16]. The basal expression of Toll-like receptors (TLRs, receptors that detect the presence of microbes) is similar in the neonate and adult [17]. However, innate immune responses of neonatal mononuclear cells are characterised by markedly reduced release of the proinflammatory Th1-polarizing cytokines tumour necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) with relative preservation of anti-inflammatory Th2-polarizing cytokines such as interleukin 6 (IL6) [18]. These findings may reflect in utero requirements, including the avoidance of harmful inflammatory immune reactions [19]. These immunological problems are reflected in the clinical presentation of neonatal sepsis. Neonates have a rapid and fulminant progression of septicaemic disease, nonspecific clinical signs of infection, and difficult-to-interpret laboratory results including haematological and immunological biomarkers of infection and inflammation. Low birth-weight (preterm and small for gestational age) infants have even poorer functional immunity, and are especially at risk of sepsis [19]. However, neonates do have well-functioning cationic membrane-active antimicrobial proteins and peptides (APPs) which have microbicidal properties [15],[19]. These APPs can be found in the vernix caseosa covering the skin at birth, and in the neonatal gastrointestinal and respiratory tracts. Many older studies have demonstrated that improving maternal health and nutrition before delivery is directly associated with improved neonatal health outcomes [3]. Randomised controlled trials (RCTs) of maternal protein-calorie and multiple micronutrient and supplementation have demonstrated significant improvements in rates of prematurity and birth weight and variable impact on mortality; but no studies have examined their impact on rates of neonatal sepsis [20],[21]. Maternal immunisation is an important method of providing neonates with appropriate antibodies as soon as they are born [22]. This approach is less sensitive to obstacles in accessing the health care system than are other approaches, and examples of successful interventions include maternal tetanus toxoid and influenza immunisations [23],[24]. Studies of
PDF JSON Files: document_parses/pdf_json/9fdb08f94d250800ca69a84cb21c110adbe1476b.json
PMC JSON Files: document_parses/pmc_json/PMC2834705.xml.json
G_ID: new_approaches_to_preventing_diagnosing_and_treating_neonatal_sepsis