Mortality In Young Infants Research Articles

Predictive Accuracy of Infant Clinical Sign Algorithms for Mortality in Young Infants Aged 0 to 59 Days: A Systematic Review.

Clinical sign algorithms are a key strategy to identify young infants at risk of mortality. Synthesize the evidence on the accuracy of clinical sign algorithms to predict all-cause mortality in young infants 0-59 days. MEDLINE, Embase, CINAHL, Global Index Medicus, and Cochrane CENTRAL Registry of Trials. Studies evaluating the accuracy of infant clinical sign algorithms to predict mortality. We used Cochrane methods for study screening, data extraction, and risk of bias assessment. We determined certainty of evidence using Grading of Recommendations Assessment Development and Evaluation. We included 11 studies examining 26 algorithms. Three studies from non-hospital/community settings examined sign-based checklists (n = 13). Eight hospital-based studies validated regression models (n = 13), which were administered as weighted scores (n = 8), regression formulas (n = 4), and a nomogram (n = 1). One checklist from India had a sensitivity of 98% (95% CI: 88%-100%) and specificity of 94% (93%-95%) for predicting sepsis-related deaths. However, external validation in Bangladesh showed very low sensitivity of 3% (0%-10%) with specificity of 99% (99%-99%) for all-cause mortality (ages 0-9 days). For hospital-based prediction models, area under the curve (AUC) ranged from 0.76-0.93 (n = 13). The Score for Essential Neonatal Symptoms and Signs had an AUC of 0.89 (0.84-0.93) in the derivation cohort for mortality, and external validation showed an AUC of 0.83 (0.83-0.84). Heterogeneity of algorithms and lack of external validation limited the evidence. Clinical sign algorithms may help identify at-risk young infants, particularly in hospital settings; however, overall certainty of evidence is low with limited external validation.

Efficacy of Antibiotic Regimens for Sepsis or Possible Serious Bacterial Infection in Young Infants Aged 0 to 59 Days: A Systematic Review and Meta-analysis.

Sepsis is a leading cause of young infant mortality. To evaluate the efficacy of different antibiotic regimens to treat young infant sepsis or possible serious bacterial infection (PSBI) on clinical outcomes. MEDLINE, Embase, CINAHL, World Health Organization Global Index Medicus, Cochrane Central Registry of Trials. We included randomized controlled trials (RCTs) of young infants 0 to 59 days with sepsis or PBSI (population) comparing the efficacy of antibiotic regimens (intervention) with alternate regimens or management (control) on clinical outcomes. We extracted data and assessed risk of bias in duplicate. We performed random-effects meta-analysis, and used Grading of Recommendations, Assessment, Development, and Evaluation to assess certainty of evidence. Of 2390 publications, we included 41 RCTs (n = 18 054). Thirty-five trials were hospital-based and 6 were nonhospital-based. Meta-analysis of 4 trials demonstrated similar rates of treatment success with intramuscular/intravenous third generation cephalosporins versus intramuscular/intravenous penicillin or ampicillin + gentamicin (RR 1.03, 95% CI 0.93-1.13]; n = 1083; moderate certainty of evidence). Meta-analysis of 3 trials demonstrated similar rates of treatment failure with oral amoxicillin + intramuscular gentamicin versus intramuscular penicillin + gentamicin for nonhospital treatment of clinical severe illness (RR 0.86, 95% CI 0.72-1.02]; n = 5054; low certainty of evidence). Other studies were heterogeneous. RCTs evaluated heterogeneous regimens, limiting our ability to pool data. We found limited evidence to support any single antibiotic regimen as superior to alternate regimens to treat young infant sepsis or PSBI.

Comparison of Bordetella pertussis Antibody Levels in Pregnant Women and Umbilical Cord Blood: A Multicenter Study.

In countries where pertussis vaccination is not administered during pregnancy, the determination of pertussis antibody levels in pregnant women is very important in terms of knowing the current seroepidemiology and potential strategies for immunizations. We included 396 pregnant women who were admitted to 4 different obstetrics and gynecology clinics. Anti-Bordetella pertussis toxin (PT) IgG and anti-Bordetella pertussis filamentous hemagglutinin IgG levels in maternal and cord blood pairs were determined by the ELISA method. Venous blood serum anti-PT level was below 5 IU/mL in 58.8%, 5-40 IU/mL in 34.8%, 40-100 IU/mL in 5.1% and >100 IU/mL in 1.3% of pregnant women. Cord blood serum anti-PT level was below 5 IU/mL in 47.7%, 5-40 IU/mL in 44.5%, 40-100 IU/mL in 6.8% and >100 IU/mL in 1% of pregnant women. In our study, the anti-PT level was found below 40 IU/mL in 93.6% of pregnant women and 92.2% of cord blood. Our study found the anti-filamentous hemagglutinin level below 40 IU/mL in 81% of pregnant women and 66.2% of cord blood. Although it is known that pertussis causes serious morbidity and mortality in young infants all over the world and that the most effective and reliable way to prevent it is vaccination of pregnant women, it is a remarkable contradiction that pertussis vaccination rates and therefore seropositivity rates in pregnant women are very low.

Young Infant Mortality Associated with Preterm and Small-for-Gestational-Age Births in Rural Bangladesh: A Prospective Cohort Study

ObjectiveTo assess the relative risk of mortality in preterm and small-for-gestational-age (SGA) infants during the first and second months of life in rural Bangladesh. Study designWe analyzed data from a cohort of pregnant women and their babies in Sylhet, Bangladesh, assembled between 2011 and 2014. Community health workers visited enrolled babies up to 10 times from birth to age 59 days. Survival status was recorded at each visit. Gestational age was estimated from mother’s reported last menstrual period. Birth weights were measured within 72 hours of delivery. SGA was defined using the INTERGROWTH-21st standard. We estimated unadjusted and adjusted hazard ratios and corresponding 95% confidence intervals for preterm and SGA babies separately for the first and second month of life using bivariate and multivariable weighted Cox regression models. ResultsThe analysis included 17,643 singleton live birth babies. Compared with term-AGA infants, in both unadjusted and adjusted analyses, preterm-SGA infants had the highest risk of death in the first (HR 13.25, 95% CI 8.65 - 20.31; AHR 12.05, 95% CI 7.82 - 18.57) and second month of life (HR 4.65; 95% CI 1.93 - 11.23; AHR 4.1, 95% CI 1.66 - 10.15), followed by preterm-AGA infants, and term-SGA. ConclusionsThe risk of mortality in preterm and/or SGA is increased for newborns and extends through the second month of life. Appropriate interventions to prevent and manage complications due to prematurity and SGA could improve survival during and beyond the neonatal period.

Invasive bacterial disease in young infants in rural Gambia: Population-based surveillance.

Invasive bacterial diseases (IBD) cause significant mortality in young infants. There are limited population-based data on IBD in young infants in Sub-Saharan Africa. We conducted population-based surveillance for IBD among infants aged 0-90 days in a demographic surveillance area in rural Gambia between 1 March 2011 and 31 December 2017. Infants admitted to health facilities within the study area had standardised clinical evaluation plus conventional microbiological investigation. We defined IBD as isolation of pathogenic bacteria from blood, cerebrospinal fluid, lung, or pleural aspirate. We determined incidence, aetiology and case-fatality of IBD. A total of 3794 infants were admitted and 3605 (95%) had at least one sample collected for culture. We detected 254 (8.0%) episodes of IBD (bacteraemia 241; meningitis 14; pneumonia seven). The incidence of IBD in infants aged 0-90 days was 25 episodes/1000 person-years (95% confidence interval (CI) = 22-28), the incidence in neonates was 50 episodes/1000 person-years (95% CI = 43-58) and the incidence in infants aged 29-90 days was 12 episodes/1000 person-years (95% CI = 9-15). The most common pathogens causing IBD were Staphylococcus aureus (n = 102, 40%), Escherichia coli (n = 37, 15%), Streptococcus pneumoniae (n = 24, 9%) and Klebsiella pneumoniae (n = 12, 5%). Case-fatality was 29% (95% CI = 23-37) in neonates and 19% (95% CI = 11-29) in infants aged 29-90 days. A minimum of 7.3% of all young infant deaths in the population were caused by IBD. IBD are common in young infants in rural Gambia and have a high case-fatality. Strategies are needed to prevent IBD in young infants. Overcoming barriers to widespread implementation of existing vaccines and developing new vaccines against the most common pathogens causing IBD should be among top priorities for reducing the high mortality rate in young infants.

Devolved health system capacity in the provision of care for sick newborns and young infants in four counties serving vulnerable populations in Kenya.

Possible severe bacterial infections (PSBI) is one of the three leading causes of newborn and young infant mortality globally that can be prevented by timely diagnosis and treatment using suitable antibiotics. High impact interventions such as use of out-patient injectable gentamicin and dispersible Amoxicillin with community-based follow up have been shown to reduce mortality in clinical trials. The objective of this study was to assess the health systems' preparedness and organizational gaps that may impact execution in providing care for newborns and sick young infants. This formative research study was embedded within a three-year implementation research project in 4 Counties in Kenya. The indicators were based on facility audits for existing capacity to care for newborns and young infants as well as County organizational capacity assessment. The organizational capacity assessment domains were derived from the World Health Organization's Health Systems Building blocks for health service delivery. The scores were computed by adding average scores in each domain and calculated against the total possible scores to generate a percentage outcome. Statistical analyses were descriptive with adjustment for clustering of data. Overall, the Counties have inadequate organizational capacity for management of sick young infants with Organizational Capacity Index scores of between 61-64%. Among the domains, the highest score was in Health Management Information System and service delivery. The lowest scores were in monitoring and evaluation (M&E). Counties scored relatively low scores in human resources for health and health products and commodities with one scoring poorly for both areas while the rest scored average performance. The four counties revealed varying levels of organizational capacity deficit to effectively manage sick young infants. The key underlying issues for the below par performance include poor coordination, low funding, inadequate supportive supervision, and M&E to enable data utilisation for quality improvement. It was evident that newborn and young infant health services suffer from inadequate infrastructure, equipment, staffing, and coordination. As Kenya, continuously rolls out the guidelines on management of sick young infants, there is need to focus attention to these challenges to enhance sustainable adoption and reduction of young infant morbidity and mortality.

Etiology and outcome of neonatal cholestasis: an experience in a tertiary center of Bangladesh

BackgroundNeonatal cholestasis (NC) is a major cause of morbidity and mortality in young infants. This study examines the etiology of NC and its outcome during 2 years of follow-up at a tertiary referral center in Bangladesh.ResultsOut of 80 cholestatic infants, 60% had intrahepatic cholestasis with a mean age of onset of 12.4±2.8 days and a mean age of admission of 82.4±29.0 days. The remaining 40% were extrahepatic with a mean age of onset of 6.7±2.3 days and a mean age of admission of 94.6±50.4 days. Biliary atresia (BA), idiopathic neonatal hepatitis (INH), and TORCH (Toxoplasma, rubella, cytomegalovirus, and herpes simplex) infection except rubella were the most common causes. After receiving treatment, 46.2% of the cases improved, 23.8% deteriorated with morbidity, and 30% died. The majority of the children with INH, TORCH, choledochal cyst, hypothyroidism, galactosemia, and urinary tract infection (UTI) with sepsis were improved. Significant mortality was found in BA (56.6%), intrahepatic bile duct paucity (PIBD) (100%), and progressive familial intrahepatic cholestasis (PFIC) (100%) whereas the rest of BA (43.4%) live with persistent morbidity. Significant clinical improvement was observed in 37 (46.2%) cases of cholestasis evidenced by decreasing jaundice, change of color of urine from dark to normal color, change of stool color from pale to yellow, and gradual decrease in liver size from hepatomegaly state. In addition, decreasing median total bilirubin, direct bilirubin, alanine transaminase, gamma-glutamyl transferase, and alkaline phosphatase showed biochemical improvement at 2 years follow-up. The age of admission, etiology, and presence of ascites are the predictors of outcomes.ConclusionBA was the most common cause of extrahepatic while INH and TORCH infection were the most common cause of intrahepatic cholestasis. Majority of children with intrahepatic cholestasis improved but deteriorated with BA and genetic causes. Prompt referral and early diagnosis as well as the etiology of NC were the main determinants of the favorable outcome.

Validation of Pediatric Index of Mortality 3 in a Single Referral Pediatric Intensive Care Unit in Iran

Objectives: The research aimed to evaluate the Pediatric Index of Mortality 3 (PIM-3) for determining the risk of mortality among pediatric intensive care unit patients. Methods: A retrospective analysis was conducted on case records, as well as patient data from all admissions to the PICU of Mofid Children’s Hospital, Tehran, from October 2017 to February 2018. Employing an android calculator application, the PIM-3 score was estimated early within the first PICU admission. Then, the PIM-3 score and mortality rate were analyzed using the Mann-Whitney U test. In addition, calibration and discrimination were assessed by the Hosmer-Lemeshow goodness-of-fit test and a receiver operating characteristic curve method, respectively. Finally, the Standardized Mortality Ratio (SMR) was calculated. Results: In this study, 365 young infants, ranging from 10 to 29-months-old, were included. The overall mortality rate was 10.4%. Further, the patients’ PIM-3 scores ranged from 0.06% to 2.37% (95% confidence interval), with a mean of 1.45% (4.16% in non-survivors and 1.14% in survivors). The SMR was estimated at 7.18, demonstrating the underprediction of the death rate. The AUC of 0.714 (95% CI: 0.626 to 0.801) demonstrated a fair to good discrimination power of PIM-3 as an international standard risk-adjusted mortality indicator. Moreover, this score underpredicted the risk of mortality in young infants admitted to our ICU in 2017. Generally, the prediction was weak among low-risk patients. Therefore, the Pediatric Index of Mortality-3 score has the potential to be implemented in our PICU by modifying the expected probability of death by multiplying the original PIM-3 score by 7.12.

Role of astroglial Connexin 43 in pneumolysin cytotoxicity and during pneumococcal meningitis.

Streptococcus pneumoniae or pneumococcus (PN) is a major causative agent of bacterial meningitis with high mortality in young infants and elderly people worldwide. The mechanism underlying PN crossing of the blood brain barrier (BBB) and specifically, the role of non-endothelial cells of the neurovascular unit that control the BBB function, remains poorly understood. Here, we show that the astroglial connexin 43 (aCx43), a major gap junctional component expressed in astrocytes, plays a predominant role during PN meningitis. Following intravenous PN challenge, mice deficient for aCx43 developed milder symptoms and showed severely reduced bacterial counts in the brain. Immunofluorescence analysis of brain slices indicated that PN induces the aCx43–dependent destruction of the network of glial fibrillary acid protein (GFAP), an intermediate filament protein specifically expressed in astrocytes and up-regulated in response to brain injury. PN also induced nuclear shrinkage in astrocytes associated with the loss of BBB integrity, bacterial translocation across endothelial vessels and replication in the brain cortex. We found that aCx4-dependent astrocyte damages could be recapitulated using in vitro cultured cells upon challenge with wild-type PN but not with a ply mutant deficient for the pore-forming toxin pneumolysin (Ply). Consistently, we showed that purified Ply requires Cx43 to promote host cell plasma membrane permeabilization in a process involving the Cx43-dependent release of extracellular ATP and prolonged increase of cytosolic Ca2+ in host cells. These results point to a critical role for astrocytes during PN meningitis and suggest that the cytolytic activity of the major virulence factor Ply at concentrations relevant to bacterial infection requires co-opting of connexin plasma membrane channels.

Group B Streptococcal Disease in England (1998 – 2017): A Population-based Observational Study

Group B Streptococcus (GBS) is the leading cause of sepsis and meningitis in infants <90 days. In this study, the burden of GBS disease and mortality in young infants in England was assessed. Using linked hospitalization records from every National Health Service (NHS) hospital from April 1, 1998 to March 31, 2017, we calculated annual GBS incidence in infants aged <90 days and, using regression models, compared their perinatal factors, rates of hospital-recorded disease outcomes, and all-cause infant mortality rates with those of the general infant population. 15 429 infants aged <90 days had a hospital-recorded diagnosis of GBS, giving an average annual incidence of 1.28 per 1000 live births (95% CI 1.26-1.30) with no significant trend over time. GBS-attributable mortality declined significantly from 0.044 (95% CI .029-.065) per 1000 live births in 2001 to 0.014 (95% CI .010-.026) in 2017 (annual percentage change -6.6, 95% CI -9.1 to -4.0). Infants with GBS had higher relative rates of visual impairment (HR 7.0 95% CI 4.1-12.1), cerebral palsy (HR 9.3 95% CI 6.6-13.3), hydrocephalus (HR 17.3 95% CI 13.8-21.6), and necrotizing enterocolitis (HR 18.8 95% CI 16.7-21.2) compared with those without GBS. Annual rates of GBS disease in infants have not changed over 19 years. The reduction in mortality is likely multifactorial and due to widespread implementation of antibiotics in at-risk mothers and babies, as well as advances in managing acutely unwell infants. New methods for prevention, such as maternal vaccination, must be prioritized.

Effect of home-based newborn care on neonatal and infant mortality: a cluster randomised trial in India

BackgroundHome-based newborn care has been found to reduce neonatal mortality in rural areas. Study evaluated effectiveness of home-based care delivered by specially recruited newborn care workers- Shishu Rakshak (SR) and...

Neurodevelopmental Impairment at 1 Year of Age in Infants With Previous Invasive Group B Streptococcal Sepsis and Meningitis.

Invasive group B streptococcal (GBS) disease causes considerable morbidity and mortality in young infants, and 18% of GBS-meningitis survivors have moderate-to-severe neurodevelopmental impairment. However, there is a paucity of data regarding neurologic impairment following GBS sepsis. A case-control study was undertaken in infants at 3 secondary-tertiary hospitals in Johannesburg, South Africa. Neurodevelopmental assessments were done at 1 year of age using the Denver II Developmental screening tool. A case was defined as isolation of GBS from blood or cerebrospinal fluid in infants less than 90 days of age. Three healthy controls (range: 1-6) were matched to maternal age, maternal HIV-infection status, gestational age and timing of enrollment. Of 122 invasive GBS cases, 78 (63.9%) had sepsis and 44 (36.1%) meningitis. Twenty-two (18%) invasive GBS cases (17 of 78; 21.8% with sepsis and 5 of 44; 11.4% with meningitis) died during the course of hospitalization, and a further 2 (1.6%; 1 sepsis and 1 meningitis case) died by 1 year of age. Five (1.1%) of 449 controls died by 1 year of age. Of the 45 GBS sepsis cases and 141 matched controls followed through to 1 year of age, 11 (24.4%) cases (3 with moderate-to-severe impairment) and 10 (7.1%) controls had an abnormal Denver score with an adjusted (for gender) odds ratio of 3.51; 95% confidence interval (CI): 1.23-10.04; P = 0.019. Four (20%) of the 20 GBS meningitis cases compared with 1 (1.5%) control had neurologic impairment at 1-year of age (aOR: 8.29; 95% CI: 0.88-78.3; P = 0.065) CONCLUSION:: In this setting, invasive GBS disease is associated with a high mortality. Infant survivors of invasive GBS sepsis compared with controls had 3.5-fold greater odds of neurologic impairment by 1 year of age. This corroborates the need for strategies to prevent invasive GBS disease.

Pregnancy has a minimal impact on the acute transcriptional signature to vaccination

Vaccination in pregnancy is an effective tool to protect both the mother and infant; vaccines against influenza, pertussis and tetanus are currently recommended. A number of vaccines with a specific indication for use in pregnancy are in development, with the specific aim of providing passive humoral immunity to the newborn child against pathogens responsible for morbidity and mortality in young infants. However, the current understanding about the immune response to vaccination in pregnancy is incomplete. We analysed the effect of pregnancy on early transcriptional responses to vaccination. This type of systems vaccinology approach identifies genes and pathways that are altered in response to vaccination and can be used to understand both the acute inflammation in response to the vaccine and to predict immunogenicity. Pregnant women and mice were immunised with Boostrix-IPV, a multivalent vaccine, which contains three pertussis antigens. Blood was collected from women before and after vaccination and RNA extracted for analysis by microarray. While there were baseline differences between pregnant and non-pregnant women, vaccination induced characteristic patterns of gene expression, with upregulation in interferon response and innate immunity gene modules, independent of pregnancy. We saw similar patterns of responses in both women and mice, supporting the use of mice for preclinical screening of novel maternal vaccines. Using a systems vaccinology approach in pregnancy demonstrated that pregnancy does not affect the initial response to vaccination and that studies in non-pregnant women can provide information about vaccine immunogenicity and potentially safety.

Implementation of the WHO guideline on treatment of young infants with signs of possible serious bacterial infection when hospital referral is not feasible in rural Zaria, Nigeria: Challenges and solutions.

Bacterial infection is one of the leading causes of mortality in young infants globally. The standard practice to manage young infants with any sign of possible serious bacterial infection (PSBI) is in a hospital setting with parenteral antibiotics, which may not be feasible for majority of cases in most low resource settings. The World Health Organization developed a guideline on management of PSBI in young infants when referral is not feasible in 2016. We conducted implementation research in selected communities in Zaria Local Government Areas of Kaduna State with an estimated population of 50,000 with the aim of understanding how to implement the WHO PSBI treatment guideline to achieve high coverage with low case fatality and treatment failure rates. Implementation was within the programmatic settings using existing health structure. We conducted policy dialogue with decision makers to adapt the recommendations to their social, cultural and programmatic context in Nigeria, held orientation meetings with program managers, built capacity of the health workers and supported the implementation within the health system. We supported a non-government organization to conduct community sensitization to promote care seeking and adherence to treatment advice. The research team collected data systematically on all young infants identified to have PSBI, the treatment they received and the clinical outcome. Between April 2016 and March 2017, we identified 347 young infants up to 2 months of age with signs of PSBI who received treatment either as an outpatient or in a hospital among 2,154 births in the study population. The coverage of PSBI treatment in the study area was 95.5% assuming that 10% of all births have an episode of PSBI in the first two months of life. Most (89%) sick young infants with PSBI were identified by the community-oriented resource persons and sent to the Primary Health Care Centres (PHCs). Most families (97%) refused referral and were treated at a primary health care centre on outpatient basis. There were 12 deaths (3.5%) and 17 non-death treatment failures (4.9%) in 343 infants in whom an outcome could be ascertained. While non-death treatment failure rate was highest in 0-6-day infants with fast breathing (14.4%), case fatality was highest in those with signs of critical illness (20%). We have demonstrated that outpatient treatment strategy for young infants with PSBI when referral is not feasible is implementable within the programmatic settings, achieving very high population coverage and relatively low treatment failure and case fatality rates. Implementation at scale will require government's commitment to strengthen the health system with trained, motivated health care providers and necessary commodities.

Effectiveness of birthing kits for clean childbirth: a systematic review.

Poor infection control practices during childbirth are recognised as a critical factor leading to life-threatening maternal and newborn sepsis. Therefore, this paper assesses the effectiveness of clean birth kits (CBKs) to ensure a safe birthing environment. We searched PubMed, Cochrane Library and CINAHL, as well as Google Scholar, to identify both qualitative and quantitative studies on CBKs published in English up to November 2018. Studies were included if the pregnant women or women giving birth intended to use or used a CBK. The methodological quality of included papers was assessed. A total of 37 studies, 26 quantitative and 11 qualitative studies, were included. Quantitative studies showed a positive impact of CBKs on reducing the incidence of puerperal sepsis and neonatal tetanus. The review also identified CBK use to be associated with a reduction in perinatal, neonatal and young infant mortality. Qualitative studies suggested that a lack of awareness of the importance of CBKs and clean delivery practices, unavailability of CBKs and financial constraints to purchase CBKs were the potential barriers. CBKs appear to be a promising strategy to reduce maternal and neonatal morbidity and mortality. However, the current evidence is limited and further large-scale trials are required.

Biomarkers of endothelial dysfunction predict sepsis mortality in young infants: a matched\xa0case-control study

BackgroundReducing death due to neonatal sepsis is a global health priority, however there are limited tools to facilitate early recognition and treatment. We hypothesized that measuring circulating biomarkers of endothelial function and integrity (i.e. Angiopoietin-Tie2 axis) would identify young infants with sepsis and predict their clinical outcome.MethodsWe conducted a matched case-control (1:3) study of 98 young infants aged 0–59 days of life presenting to a referral hospital in Bangladesh with suspected sepsis. Plasma levels of Ang-1, Ang-2, sICAM-1, and sVCAM-1 concentrations were measured at admission. The primary outcome was mortality (n = 18); the secondary outcome was bacteremia (n = 10).ResultsAng-2 concentrations at presentation were higher among infants who subsequently died of sepsis compared to survivors (aOR 2.50, p = 0.024). Compared to surviving control infants, the Ang-2:Ang-1 ratio was higher among infants who died (aOR 2.29, p = 0.016) and in infants with bacteremia (aOR 5.72, p = 0.041), and there was an increased odds of death across Ang-2:Ang-1 ratio tertiles (aOR 4.82, p = 0.013).ConclusionsThis study provides new evidence linking the Angiopoietin-Tie2 pathway with mortality and bacteremia in young infants with suspected sepsis. If validated in additional studies, markers of the angiopoietin-Tie2 axis may have clinical utility in risk stratification of infants with suspected sepsis.

Incidence of laboratory-confirmed influenza disease among infants under 6 months of age: a systematic review

ObjectivesThe aim of this systematic review was to assess incidence rates of laboratory-confirmed influenza (LCI) outcomes among infants under 6 months of age.DesignSystematic literature search and review of indexed studies...

Host-immune responses to RSV infection and associated lung injury is modulated by Osteopontin (OPN) in age-dependent fashion

Abstract RSV bronchiolitis and pneumonia causes significant mortality in young infants every year. The survivors become susceptible to asthma. In our present study, using a mouse model of BALB/C and NKT−/− mice, we examined the pulmonary responses to RSV infection in the very young hosts as opposed to relatively older hosts. We also examined the effects of exogenous osteopontin (OPN) administration on the alveolar cellular constitution by direct microscopy and flowcytometry and the role of NKT cells in this process. Pulmonary damage was assessed by measuring the Lactic Dehydrogenase (LDH) levels in the BALF by ELISA and histopathological examination by microscopy. Microscopy revealed a decreased lymphocyte response in the bronchoalevolar lavage fluid (BALF) of RSV-infected-4-day- old pups as compared to that of -14- and -20-day-old mice; but an enhanced neutrophil response, which was associated with increased LDH levels. Flowcytometry revealed that administration of OPN had downregulatory effects on lung lymphocyte (CD4+ and CD8+) responses in all age groups with proportional upregulation of lung macrophage (CD11bmed/hi, CD11Clo/−) responses. This effect was less pronounced in the older age groups. Additionally, activation of macrophages, as indicated by MHCII expression, was NKT dependent. Moreover, RSV- infection significantly inhibited lung CD8+ T cell activation as indicated by decreased CD44 expression, which was recovered by OPN administration. Understanding the underlying mechanisms of RSV-infection induced differential immune responses and OPN-mediated differential immunomodulation in different age groups may help develop newer therapeutic strategies.

Impact of a maternal immunization program against pertussis in a developing country

BackgroundPertussis disease is a growing concern for developing countries. In Argentina, rates of illness and death peaked in 2011. More than 50% of fatalities due to pertussis occurred in infants younger than two months of age, too young for vaccination. In 2012, the government offered immunization with a vaccine containing Tdap to all pregnant women after 20weeks of gestation with the intent of reducing morbidity and mortality in young infants. MethodsMaternal acellular pertussis vaccine impact on reducing infant disease burden was estimated based on data from the Argentinean Health Surveillance System. We divided Argentinean states in two groups experiencing high (>50) and low (⩽50) Tdap vaccine coverage and compared these two groups using a Bayesian structural time-series model. Low coverage regions were used as a control group, and the time series were compared before and after the implementation of the Tdap program. FindingsWe observed a relative reduction of 51% (95% CI [−67%, −35%]; p=0.001) in pertussis cases in high coverage states in comparison with the low coverage areas. Analysis of infants between two and six months showed a 44% (95% CI [−66%, −24%]; p=0.001) reduction in illness. Number of deaths was highest in 2011 with 76 fatalities, for an incidence rate of 2.9 per 100,000. Comparing with 2011, rates decreased by 87% to 10 subjects, or 0.9 per 100,000 in 2013. InterpretationWe show an age-dependent protective effect of maternal Tdap immunization in a developing country for infants younger than six months.

High Prevalence of Antimicrobial-resistant Gram-negative Colonization in Hospitalized Cambodian Infants.

Antimicrobial-resistant Gram-negative infections are a significant cause of mortality in young infants. We aimed to determine characteristics of, and risk factors for, colonization and invasive infection caused by 3rd generation cephalosporin (3GC) or carbapenem-resistant organisms in outborn infants admitted to a neonatal unit (NU) in Cambodia. During the first year of operation, patients admitted to the Angkor Hospital for Children NU, Siem Reap, Cambodia, underwent rectal swabbing on admission and twice weekly until discharge. Swabs were taken also from 7 environmental sites. Swabs were cultured to identify 3GC or carbapenem-resistant Acinetobacter sp., Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. The study included 333 infants with a median age at NU admission of 10 days (range, 0-43). Colonization by ≥1 3GC-resistant organism was detected in 85.9% (286/333). Admission swabs were collected in 289 infants: 61.9% were colonized by a 3GC-resistant organism at the time of admission, and a further 23.2% were colonized during hospitalization, at a median of 4 days [95% confidence interval: 3-5]. Probiotic treatment (hazard ratio: 0.58; 95% confidence interval: 0.35-0.98) was associated with delayed colonization. Colonization by a carbapenem-resistant organism occurred in 25 (7.5%) infants. Six infants had NU-associated K. pneumoniae bacteremia; phenotypically identical colonizing strains were found in 3 infants. Environmental colonization occurred early. Colonization by antimicrobial-resistant Gram-negative organisms occurred early in hospitalized Cambodian infants and was associated with subsequent invasive infection. Trials of potential interventions such as probiotics are needed.