INFLAMMATORY RESPONSE STATUS IN INFANTS WITH INTRAUTERINE INFECTION FROM MOTHERS WITH IDENTIFIED TORCH INFECTION.

OBJECTIVE: The aim: To investigate the status and possibilities of markers of the inflammatory response of organism in infants with identified IUI born to mothers diagnosed with TORCH infection. PATIENTS AND METHODS: Materials and methods: The study group included: infants diagnosed with IUI (n = 40), born to mothers (age 31.31 ± 2.08 years) with the diagnosis of TORCH infection and a control group (n = 25 infants). Childbirth in all newborns was physiological. The average weight of newborns was 1877.69 ± 981.78 g (min - 600 g; max - 4000 g). Gestational age: 32.25 ± 5.15 weeks. Observation and treatment of newborns lasted up to 7 days (included stay in the emergency department of the Uzhhorod maternity hospital in the Zakarpattia region). Cytokine profile, γ-IFN, TNF-α, Pg E2, serum neopterin and procalcitonin levels were studied. RESULTS: Results: The values of the parameters of the cytokine profile (IL-1, IL-6, IL-8, IL-10) varied within the reference values, but with significant differences with the values of the control group, which was 1,2; 4; 10; 6 times, respectively. The levels of inflammatory mediators (γ-IFN Procalcitonin Neopterin TNF-α Pg E2) differed significantly from the data of the control group of infants and exceeded the upper limit of the reference values by 1,3; 3; 25; 4 times, respectively. According to the correlation analysis, there are positive correlations of medium level: IL 1 and procalcitonin (r = 0.33); IL 6 and IL10 (r = 0.44); IL 10 and prostaglandin E2 (r = 0.44); neopterin and prostaglandin E2 (r = 0.39), which indicates synergism in the performance of biologically active processes. Negative correlations of moderate degree were observed between the following parameters: IL 1 and gestational age of infants (r = -0.36); IL 6 and IL 8 (r = -0.34); γ-IFN and TNF-α (r = -0.43), which indicates the diversity of interactions between participants in the inflammatory response of the organism. CONCLUSION: Conclusions: Various infectious agents can act as «primary affect¼ of sepsis as a complex pathological process involving the organism, and each of the infections has its own characteristics of the pathological process, therefore curent changes in infectious circumstances make new demands on research. It has been proven that intrauterine infection has a negative effect on the homeostatic parameters of infants, in particular, on the indicators of the inflammatory response of the child's organism. Symptomatic inflammatory biomarkers can be used to identify the pathological condition of the infant, in addition to routine laboratory tests, for early correction of VUI. This delay in identifying affected infants can lead to long and unnecessary therapy, the emergence of resistant strains of microorganisms, increased treatment costs and, in particular, a higher risk of complications such as cerebral palsy or intraventricular hemorrhage.

Congenital infections in Hong Kong: beyond TORCH.

Congenital infections refer to a group of perinatal infections that are caused by pathogens transmitted from mother to child during pregnancy (transplacentally) or delivery (peripartum) which may have similar clinical presentations, including rash and ocular findings. TORCH is the acronym that covers these infections (toxoplasmosis, other [syphilis], rubella, cytomegalovirus, herpes simplex virus). Other important causes of intrauterine/perinatal infection include human immunodeficiency virus, varicella-zoster virus, Treponema pallidum, Zika virus, and parvovirus B19. This overview aims to describe various congenital infections beyond TORCH with a Hong Kong perspective. Intrauterine and perinatal infections are a major cause of in utero death and neonatal mortality, and an important contributor to childhood morbidity. A high index of suspicion for congenital infections and awareness of the prominent features of the most common congenital infections can help to facilitate early diagnosis, tailor appropriate diagnostic evaluation, and initiate appropriate early treatment. Intrauterine infections should be suspected in newborns with clinical features including microcephaly, seizures, cataract, hearing loss, congenital heart disease, hepatosplenomegaly, small for gestational age, and/or rash. Primary prevention of maternal infections during pregnancy is key to the prevention of congenital infection, and resources (if available) should focus on public health promotion and pre-marital counselling.

Role of Regulatory T Cells in Infection and Vaccination During Early Infancy.

Reducing infant mortality due to infectious diseases is one of the most important public health goals worldwide. Several approaches have been implemented to reach this goal and vaccination has been an effective strategy for reducing infant and newborn mortality. However, the immunological features of neonates and infants represent a significant barrier to the effectiveness of vaccination. Since regulatory T cells (Treg cells) are known to play an active role in contributing to various mechanisms of suppression of the immune cell function. It has been proposed that these immune cells could decrease the immunogenicity of vaccines administered in newborns and infants. In this article, we discuss the various types of Treg cells, along with their suppressing and inhibitory mechanisms, which are used by these cells in the context of infectious and immunization processes in newborns and infants.

The effectiveness of e-learning in pediatric medical student education.

BACKGROUND: Electronic learning allows individualized education and may improve student performance. This study assessed the impact of e-modules about infection control and congenital infections on medical knowledge. METHODS: A descriptive study was conducted involving third-year medical students on pediatric clerkship. e-Module content in three different formats was developed: a text monograph, a PowerPoint presentation, and a narrated PowerPoint lecture. Students' use of the e-modules was tracked, as was participation in the infectious disease rotation and the order of pediatric rotation. Pre- and posttests specific to the e-module content and National Board of Medical Examiners (NBME) pediatric exam scores were recorded. RESULTS: Among 67 participants, 63% of them visited at least one e-module. Neither accessing any e-modules, timing of pediatric clerkship, nor assignment to ID rotation resulted in improved posttest nor NBME scores. Seventy percent of students rated the e-modules as satisfactory and reported usage improved their confidence with the congenital infections topic. DISCUSSION: e-Modules did not improve student performance on NBME or posttest; however, they were perceived as satisfactory and to have improved confidence among those who used them. This study underscores the importance of formally evaluating electronic and other innovative curricula when implemented within existing medical education frameworks.

[Serological diagnosis of congenital infections and algorithms to improve diagnostic efficacy]. / Diagnóstico serológico de las infecciones congénitas y algoritmos para mejorar la eficacia diagnóstica.

Congenital infection is those transmitted by the mother to the fetus before delivery. It can occur transplacentally or by direct contact with the pathogen during birth or in the immediate postnatal period. Congenital infection can be due to viruses (rubella, cytomegalovirus, herpes simplex, varicella-zoster, hepatitis B and C virus, human inunodeficiencia, erythrovirus B19) as bacteria (Treponema pallidum) and parasites (Toxoplasma gondii and Trypanosoma cruzi). Serological diagnosis of congenital infection is based on both the knowledge of infectious serology in the mother, including the systematic serological screening and diagnostic aspects of the determination of IgM and confirmatory methods, IgG avidity tests, establishment of antibody profiles, and in the diagnosis the neonate. Serological diagnosis of congenital infection in the newborn is mainly based on the detection of specific IgM usually by immunoenzymatic assays or immunochemiluminescence techniques. In some instances it is important to perform the serological follow up of the newborn to confirm the congenital infection.

Long-term neurodevelopmental outcome in high-risk newborns in resource-limited settings: a systematic review of the literature.

BACKGROUND: Improving outcomes beyond survival for high-risk newborns in resource-limited settings is an emerging challenge. Global estimates demonstrate the scale of this challenge and significant gaps in morbidity outcome data in high mortality contexts. A systematic review was conducted to document the prevalence of neurodevelopmental impairment in high-risk newborns who were followed up into childhood in low- and middle-income countries. METHODS: High-risk newborns were defined as low, very or extremely low birthweight, preterm infants or those surviving birth asphyxia or serious infections. Electronic databases were searched and articles screened for eligibility. Included articles were appraised according to STROBE criteria. Narrative review was performed and median prevalence of key neurodevelopmental outcomes was calculated where data quality allowed. RESULTS: 6959 articles were identified with sixty included in final review. At follow-up in early childhood, median estimated prevalence (inter-quartile range) of overall neurodevelopmental impairment, cognitive impairment and cerebral palsy were: for survivors of prematurity/very low birthweight 21.4% (11.6-30.8), 16.3% (6.3-29.6) and 11.2% (5.9-16.1), respectively, and for survivors of birth asphyxia 34.6% (25.4-51.5), 11.3% (7.7-11.8) and 22.8% (15.7-31.4), respectively. Only three studies reporting outcomes following newborn serious bacterial infections were identified. There was limited reporting of important outcomes such as vision and hearing impairment. Major challenges with standardised reporting of key exposure and developmental outcome variables and lack of control data were identified. CONCLUSION: Understanding the limitations of the available data on neurodevelopmental outcome in newborns in resource-limited settings provides clear direction for research and efforts to improve long-term outcome in high-risk newborns in these settings.

Overview of congenital infections: the prominence of cytomegalovirus.

Congenital infections are those that are acquired transplacentally by the fetus from an infected mother. They constitute a major public health burden, affecting millions of infants and children worldwide. Despite significant advances in medical diagnostics, the majority of newborns with congenital infections are not recognized, since many of these infections may not cause clinically - apparent disease in the newborn period. Nonetheless, these infections - whether they are apparent or silent - have the potential to adversely impact the neurodevelopmental outcomes of these vulnerable children.

[Diagnosis of congenital infection]. / Diagnóstico de infección congénita.

In general, congenital diagnosis is based on: a) maternal serologic assays; b) microbiologic study of amniotic fluid or fetal blood sampling; and c) serology in children and microorganism detection by polymerase chain reaction (PCR) or culture. Congenital infections due to cytomegalovirus, herpes simplex, varicella, B19 erythrovirus and toxoplasmosis are usually the result of primary infection in the mother. Therefore, when IgG antibodies are detected before pregnancy, these infections are ruled out. Definitive serologic diagnosis of acute infection in pregnant women requires the demonstration of seroconversion (i.e., from seronegative to seropositive). In these cases, amniotic fluid or fetal blood sampling should be performed to determine the presence of intrauterine congenital infection. Cytomegalovirus, rubella and toxoplasmosis can be diagnosed by detection of specific IgM antibodies in fetal blood. However, PCR in amniotic fluid has replaced conventional prenatal diagnostic techniques, including fetal blood sampling, in the diagnosis of these infections. In the newborn, these infections may be confirmed by measuring IgM specific antibodies. B19 erythrovirus can be detected by PCR in amniotic fluid or fetal blood. Congenital varicella-zoster infection may be diagnosed on the basis of persistence of IgG antibodies after birth. Definitive diagnosis of herpes simplex virus infection requires viral isolation. Swabs or scraping from clinical specimens can be inoculated into susceptible cell lines for isolation.

Nonimmune hydrops fetalis part II: does etiology influence mortality?

Hydrops fetalis is a condition in which there is an excess of total body fluid, primarily within the fetal interstitial spaces. Etymologically, hydrops fetalis is a Latin term meaning "edema of the fetus." In addition to generalized edema, the fetus has at least one of the following: ascites, pericardial effusion, pleural effusion(s), and an abnormally thick (>6 cm) placenta. Hydrops is classified as nonimmune hydrops fetalis (NIHF) when it occurs without evidence of isoimmunization.

Documento de consenso de la Sociedad Española de Infectología Pediátrica sobre el diagnóstico y el tratamiento de la infección congénita por citomegalovirus / Consensus document from the Spanish Society of Paediatric Infectious Diseases (SEIP) on the diagnosis and treatment of congenital cytomegalovirus infection

El citomegalovirus (CMV) es la causa más frecuente de infección congénita en los países desarrollados y aparece entre un 0,3 y un 0,6% de los recién nacidos en Europa. La primoinfección durante el embarazo ocurre entre el 1 y el 4% de las gestantes seronegativas. En este caso, el 40% de los fetos se infecta y un 10% presenta síntomas al nacimiento. La mitad de estos niños y el 13% de los que nacen asintomáticos desarrollan secuelas permanentes, especialmente hipoacusia neurosensorial y retraso mental. En la actualidad, la determinación de la avidez de los anticuerpos IgG maternos y la detección del virus en líquido amniótico por cultivo o reacción en cadena de la polimerasa (PCR) permiten el diagnóstico de la primoinfección en la embarazada y el diagnóstico de la infección en el feto. Además, existe cierta evidencia sobre la posibilidad de prevención de la infección sintomática en el recién nacido mediante el empleo en el embarazo de gammaglobulina hiperinmune frente a CMV. El diagnóstico de la infección congénita en el recién nacido debe realizarse mediante el cultivo del virus en shell vial o mediante la identificación del genoma viral por PCR en una muestra de orina recogida en las 2 primeras semanas de vida. La infección también puede diagnosticarse retrospectivamente mediante PCR para CMV en la sangre seca de papel de filtro (Guthrie card) que se utiliza para la prueba del talón en el recién nacido. Actualmente se dispone de 2 fármacos para el tratamiento del CMV congénito: ganciclovir y su profármaco valganciclovir. El tratamiento con ganciclovir intravenoso durante 6 semanas previene el desarrollo de hipoacusia progresiva en los niños con infección congénita sintomática por CMV y afectación del sistema nervioso central. El tratamiento con valganciclovir oral puede ser excelente alternativa debido a su buena biodisponibilidad, lo que le permite conseguir niveles plasmáticos similares a los alcanzados con ganciclovir intravenoso (AU)

Cytomegalovirus (CMV) is the leading cause of congenital infection in developed countries, affecting 0.3 to 0.6% of all live births in Europe. Primary CMV infection occurs in 1 to 4% of seronegative women during pregnancy and may be transmitted to the fetus in 40% of cases. Up to 10% of intrauterine CMV infections result in symptomatic congenital disease at birth. Half of these children and 13% of those born with asymptomatic infection will develop long-term sequelae, especially neurosensory hearing loss and mental retardation. Accurate diagnosis of primary maternal and fetal infection is now possible using the avidity index of anti-CMV IgG and virological testing to detect the virus in amniotic fluid. Symptomatic congenital infection may be preventable using CMV hyperimmune globulin during pregnancy. The gold standard for diagnosis of congenital CMV infection is the detection of the virus in urine within the first 2 weeks of life by rapid cell culture techniques (shell vial) or nucleic acid amplification of viral DNA (PCR). Retrospective diagnosis can be achieved by detection of viral DNA by PCR in dried blood spots (Guthrie card) collected on filter paper in the first days of life. Currently available drugs for the treatment of congenital CMV include ganciclovir and its oral prodrug valganciclovir. Treatment with intravenous ganciclovir for six weeks may prevent hearing deterioration in children with symptomatic congenital CMV infection and central nervous system involvement. Valganciclovir may be an excellent alternative because of its good bio-availability, providing plasma concentrations similar to those achieved with intravenous ganciclovir (AU)

Evaluation of the Role of FMLF chemotaxic peptide receptors in umbilical cord blood granulocytes from newborns at risk of infectious inflammatory diseases.

We studied the role of receptors with high and low affinity for fMLF chemotaxic peptide in the generation of active oxygen species by umbilical cord blood granulocytes from newborns with normal neonatal period, born after normal or complicated gestation, in children with manifestations of bacterial infection born after complicated pregnancy, and in granulocytes of non-pregnant women with normal reproductive function. Granulocytes of children born after complicated pregnancy exhibited high reactivity in induction of respiratory burst in a wide range of fMLF concentrations. The presentation of receptors with high and low affinity on granulocytes during initiation of the respiratory burst differs in children born after complicated pregnancy and in healthy babies born after normal gestation. Presumably, the detected differences result from high expression of receptors with low affinity for fMLF and disorders or immaturity of mechanisms responsible for receptor inactivation.

Disminución de la transmisión materno infantil del VIH-1 en Cuba utilizando quimioprofilaxis con Zidovudina / s. t

La transmisión del virus de la Inmunodeficiencia Humana (VIH) ha devenido como la pandemia de este siglo. Las formas de transmisión universalmente aceptadas son, sexual, sangre y hemoderivados y transmisión perinatal. La transmisión materno infantil (TMI) es la principal fuente de infección por el VIH en los niños, se estima que actualmente viven con el virus 380 000 menores de 15 años. Se realizó un estudio observacional, prospectivo, de cohortes no concurrentes en gestantes VIH/SIDA (Síndrome de Inmunodeficiencia Adquirida) que recibieron dos esquemas de un mismo tratamiento profiláctico con Zidovudina (AZT) según el Pediatrics AIDS Clinical Trials Group protocol 076 (PACTG 076). Un grupo recibió el tratamiento modificado a dos etapas en el período comprendido entre 1996 y marzo de 2005 y el otro recibió el esquema profiláctico en tres etapas a partir de abril de 2005 hasta octubre de 2006, donde se incluye el uso de AZT endovenoso. Se comparó a través de los resultados de la Reacción en Cadena de la Polimerasa (PCR) realizadas a los niños, el por ciento de ellos nacidos sanos por uno y otro esquema de tratamiento. Se tomó como muestra las gestantes VIH/SIDA de Cuba, excluyendo las que por diversas causas abandonaron tratamiento. Se aplicó pruebas de proporciones múltiples para muestras de tamaño grande (n >30). De los 140 niños nacidos de las gestantes que recibieron quimioprofilaxis antirretroviral con AZT en dos etapas, 11 resultaron positivos para un 7,86 porciento de TMI. Del total de 69 niños de las embarazadas seropositivas al VIH que recibieron el esquema en sus tres etapas, solo 1 niño resultó positivo lo que disminuyó la TMI en 1,45 porciento. Existiendo diferencias significativas estadísticamente probada, con un nivel de confianza de 95 porciento para ambos tratamientos...(AU)

Festschrift for Professor Margaret Burgess AO.

In honour of the retirement of our director Margaret Burgess, National Centre for Immunisation Research and Surveillance (NCIRS) held a Festschrift on 5th to 6th February 2004. The themes of the event were Vaccines for the 21st Century and Congenital and Neonatal Infections. International guests attended the Festschrift, as well as over 180 colleagues and co-workers from across Australia. A summary of the presentations over these two fascinating days is provided herein.

Investigating intellectual disability: a genetic perspective.

Intellectual disability (ID) is a common paediatric problem. Investigation focused on determining the aetiology of ID is warranted because a specific diagnosis may assist in prognostication, recurrence risk counselling, and identification of therapeutic and educational interventions. Three groups of screening investigations can be justified on the basis of expert opinion, common sense and the small body of published evidence-based medicine. First, investigations where current evidence justifies routine use in the investigation of ID; second, investigations which should be considered in all children with ID, although there is insufficient current evidence to support routine use; and finally, investigations which currently have an unclear role in children with ID and should be restricted to specific clinical situations unless further evidence suggesting otherwise emerges. There is a great need for systematic evaluation of the diagnostic yield of investigation templates based on this proposed stratification of investigations.

Analysis of spiral ganglion cell populations in children with normal and pathological ears.

This study analyzed features of total and segmental spiral ganglion cell populations in children with normal ears and those with various pathological conditions. Sixty-three human temporal bone specimens, obtained from 43 children 4 days to 9 years of age, were studied histopathologically. These specimens were divided into 5 diagnostic groups: group 1, normal ears (13 ears); group 2, congenital infectious diseases (13 ears); group 3, chromosomal aberrations (11 ears); group 4, multiple craniofacial anomalies with hereditary or genetic causes (21 ears); and group 5, perinatal and postnatal asphyxia (5 ears). Eighteen of the 63 ears had documented profound deafness. In either normal ears (group 1) or those with various pathological conditions (groups 2 through 5), the total number of ganglion cells did not change as a function of age during the first 10 years. The total number of ganglion cells was significantly larger in group 1 (33,702) than in each of groups 2, 3, 4, and 5 (p < .01), and the number was significantly larger in group 2 than in each of groups 4 and 5 (p < .01 and p < .05, respectively). The ratio of basal to apical ganglion cell populations remained constant in both normal and pathological ears. Each ratio of the number of basal and apical ganglion cells in groups 2, 3, 4, and 5 to the mean number in group 1 (basal and apical survival ratios) was at least approximately 40%. There was no statistical difference between these two ratios in groups 2, 3, 4, and 5. The mean (+/-SD) total number of ganglion cells in ears with documented profound deafness was 15,417 +/- 5,944, which is approximately 40% of those present in normal ears. Our results suggest that normally, cochlear neurons are completely present at birth and minimally regress during the first decade of life. In addition, although intergroup differences among various pathological groups were present, the majority of pathological ears had more than 10,000 spiral ganglion cells present. Cochlear implantation has gradually been recognized as an effective and reliable tool for rehabilitation of children who have profound deafness, even congenitally or prelingually deafened children. On the basis of the results obtained in this study, we discuss the implications for cochlear implantation in children.

Exposición prenatal a drogas y efectosen el neonato / Prenatal drug exposure and neonatal outcome

Objetivo: el consumo de sustancias de abuso por parte de la madre gestante puede ocasionar al feto un variado grupo de patología: aborto, malformaciones, bajo peso, prematuridad, sufrimiento fetal, síndrome agudo de abstinencia, síndrome subagudo o crónico, infecciones verticales, etc. Material y métodos: analizar la clínica y el tratamiento en casos de exposición prenatal a drogas, y en particular del síndrome de abstinencia neonatal agudo. Resultados: de toda esta patología destaca por su frecuencia el síndrome de abstinencia neonatal agudo. Clínicamente se presenta como un cuadro de signos y síntomas neurológicos (irritabilidad, temblores, hipertonía,...), digestivos (vómitos, diarrea, succión alterada, escaso apetito,...) y autonómicos (sudoración, piel moteada,...). Su tratamiento consiste en medidas de soporte y tratamiento farmacológico. Conclusiones: la decisión de iniciar el tratamiento farmacológico debe ser individualizada. Los hijos de madre toxicómana deben ser ingresados a su nacimiento en una unidad neonatal donde se les mantenga controlados y donde se valore la posibilidad de otros problemas asociados (AU)