HIV-1 specific CD4+ T cell activity in clade C infected subjects has not been studied. CD4+ T cells play a vital role in controlling infectious diseases and there is a need to augment our knowledge of HIV immunology to aid vaccine design. We therefore embarked on a study to characterize HIV-1 specific CD4+ T cell activity in both adults and infants; assess the relationship between CD4+ and CD8+ immune responses; and the relationship between CD4+ T cell activity and markers of disease progression (viral loads and CD4 counts). Our study revealed that the magnitude of CD8+ T cell responses correlated significantly with CD4+ T cell responses, but that the percentage of CD8+ T cells directed against HIV-1 was always greater than that of CD4+ T cells. Gag was the frequently targeted HIV-1 protein by CD4+ T cells and had the highest density of epitopes targeted by CD4+ T cells. Patients with either a dominant CD4 or CD8 T cell response against Gag had significantly lower viral loads than patients in whom non-Gag proteins were the main target (p< 0.0001 for CD4 activity and p= 0.007 for CD8 responses). Single IFN- producing CD4+ T cells were present in significantly higher numbers than cells producing both IFN- and IL-2 simultaneously (p=0.009). Gag also dominated the CD4+ T cell response in acutely infected infants with IFN- production detected more frequently than IL-2 or TNF- . Longitudinal analysis of infants receiving early ARV treatment and then ceasing after 12 months revealed that early treatment conferred no protection against increasing viremia and disease progression. CD4+ T cell responses were detected sporadically in untreated infants indicating a dysfunctional immune response in the face of constant exposure to high levels of viremia. Taken together, the data reveal that a vaccine inducing Gag specific CD4+ T cell responses has the potential to confer some degree of protection, but other immunological parameters need to be investigated especially in infants. / Thesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2011.

Background: Despite years of implementation, the program for PMTCT is not reaching the HIV positive pregnant women. Poor documentation as well as poor monitoring and evaluation for the program has contributed to the poor performance. This has led to South Africa being one of the 12 countries in the world with an increasing child mortality rate which is related to HIV/AIDS. Multi-steps and the complexity of the program and poor documentation have resulted in gaps in the provision of care. Objective: The aim of the study was to assess the documentation of the core activities of Prevention of Mother-to-Child Transmission of HIV program provided to pregnant women from antenatal, maternity and post-natal care at a selected Regional hospital in Ethekwini District. Methods: A non-experimental retrospective descriptive exploratory design informs the study. Provides a description of whether the activities of PMTCT are perfomed through the use of documented activities on patient’s charts. A data extraction tool was used to extract information, with the demographic information as well as the key activities of PMTCT. One hundred and thirty charts of women who had delivered in the hospital of study were sampled. Results: The study revealed gaps in the documentation of some activities, with dual therapy initiated at antenatal clinic documented to be n=98(75%), whilst NVP to the baby was 105/130 (80%). The results are in contrast with Horwood’s (2010) study which reported 91% receiving the Nevirapine prophylaxis. Although there are children missed by the program, it is interesting to note that more babies are receiving prophylaxis compared to women receiving NVP. The cd4 count, n=78(60%) uptake, seems not to be doing well, with only n=45(35%) , which is supported by Horwood’s (2010) study that showed much improvement in the cd4 uptake (70%) compared to the study results of 60%, but less cd4 results documented were reported by Horwood (2010), showing 33% respectively. Conclusion: The National strategic Plan’s (SADOH, 2007- 2011/2013) for South Africa, as well as the global Millennium Development Goals can only be achieved if all the activities for the PMTCT are improved. Documentation of activities remains the key to improved care. / Thesis (M.N.)-University of KwaZulu-Natal, Durban, 2011.

Actualmente es posible el alta precoz del prematuro si va acompañada de atención domiciliaria. Nuestro PROPÓSITO es demostrar que la Atención Domiciliaria de Enfermería (ADE) del prematuro, tras su alta precoz, es beneficiosa y segura. OBJETIVOS. Comparar, en los casos y controles, la evolución del peso desde una semana prealta (de los casos), durante la ADE y al finalizarla, analizando sus posibles causas, y la morbilidad. METODOLOGÍA. Estudio caso-control (1:1), observacional y preferentemente prospectivo, de los recién nacidos del Hospital Clínic de Barcelona durante los años 2007 a 2009, prematuros (edad gestacional entre 25-36 semanas), de procedencia interna, con peso de nacimiento superior a 750 g, que cumplían las siguientes condiciones en el momento del alta (o apareamiento de los controles): ausencia de cromosomopatías o malformaciones mayores, edad postmenstrual corregida ³ 30 semanas, estabilidad térmica, alimentación por boca sin dificultad, peso superior a 1500 g e inferior a 2100 g con curva ascendente, buen estado clínico y consentimiento familiar. Se incluyeron 65 casos y 65 controles. La ADE fue administrada por un pediatra neonatólogo y dos enfermeras especializadas en neonatología, dependientes del Hospital. El programa se inició con una sesión de educación sanitaria a los padres de los prematuros tributarios de ADE. Tras el alta, la ENFERMERA realizó la primera visita en los dos días siguientes y las consecutivas dos veces por semana hasta los 2100 g. Se desplazó al domicilio en taxi. Controló el estado general, incremento de peso, alimentación, temperatura, deposiciones, medidas higiénicas, ritmo de sueño, cuidados especiales y cualquier aspecto que preocupara a la familia. Completó la educación sanitaria, comprobó la situación familiar y coordinó los horarios de las siguientes visitas domiciliarias y en el hospital. Los PADRES dispusieron de contacto telefónico con el hospital mediante el teléfono móvil asignado, visita pediátrica el día del alta y reingreso en el Hospital si fuese necesario. El/la PEDIATRA coordinador/a del programa, el día del alta realizó la visita médica y redactó un informe final complementario del alta hospitalaria. RESULTADOS. El apareamiento fue satisfactorio. En el período neonatal destacó una menor utilización de corticoides prenatales en los casos. Los prematuros de ambos grupos no estuvieron muy enfermos. La estancia total del grupo con ADE fue 10 días inferior. Las familias del grupo con ADE fueron de un nivel social superior con más trabajo por cuenta propia y estuvieron más adaptadas. Tanto los pesos de la semana previa al alta como los pesos iniciales fueron similares en los casos y controles, condición indispensable. Respecto a los cambios de peso en g/kg/día en la semana previa al alta y en la semana del estudio, los casos partieron de una cifra similar a los controles, pero terminaron el estudio con una cifra muy superior. En la semana previa al alta, en el grupo control se seguía con nutrición por sonda nasogástrica, mientras que en el grupo de ADE se retiraba antes, para facilitar su ida a casa. Durante el periodo de estudio, los casos recibieron más lactancia materna. El estudio multivariante demostró que el “incremento en g/kg/d durante el estudio” aumentaba al estar en casa (ADE) o en los varones y disminuía al recibir lactancia materna o presentar hemorragia peri-intraventricular. Durante la ADE no hubo mayor morbilidad en los casos. Sólo un 9% de las familias llamaron por teléfono. El total de visitas a domicilio osciló entre 3 y 5. Las principales incidencias fueron infecciones respiratorias. CONCLUSIÓN. La ADE es segura e implica un mayor aumento de peso del prematuro, siendo los factores que lo favorecen la ADE, la lactancia artificial, la ausencia de hemorragia peri-intraventricular y el sexo masculino. / INFLUENCE OF NURSING HOME CARE IN THE EVOLUTION OF PREMATURE INFANTS WITH EARLY DISCHARGE The purpose is to demonstrate that the Nursing Home Care (NHC) of premature infants with early discharge is safe and beneficial. OBJECTIVES: To compare the evolution of weight, analyzing their causes, and morbidity in cases and controls. METHODOLOGY: Case-control (1:1) and observational study, preferably prospective, of newborns at the Hospital Clínic of Barcelona during the years 2007 to 2009, premature, with birth weight over 750 g, which at discharge (or matching of controls) had: corrected postmenstrual age <30 weeks, thermal stability, food by mouth, weight over 1500 g and below 2100 g with upward curve, good clinical evolution and family consent obtained. 65 cases and 65 controls were included. The NHC was administered by a neonatologist pediatrician and two nurses in neonatology, dependent on the Hospital. The nurse made the first visit in two days after discharge, and afterwards twice weekly until 2100 g, by taxi. She supervised the general state, weight gain, food tolerance, temperature, deposition, hygiene and sleep rhythm of the infant. Parents arranged exclusive telephone contact with the hospital and readmission if necessary. The doctor performed the medical examination at the end of NHC and issued a supplemental final report. RESULTS: The total stay of NHC group was 10 days less. Families in the NHC group were of a higher social level. The initial weights were similar in both groups. Regarding changes in weight in g/kg/day in the week prior to discharge and during the week of the study, cases were based on a figure similar to controls, but ended the study with a higher figure. The multivariate analysis showed that the "increase in g/kg/d during the study" increased in NHC group or in males and decreased in case of breastfeeding or peri-intraventricular hemorrhage. During the NHC no major morbidity existed. Only 9% of families did a phone call. CONCLUSION: The NHC is safe and carries a greater weight gain, being the positive factors the NHC group, artificial feeding, the absence of peri-intraventricular hemorrhage and male sex.

Antibiotics are among the most commonly prescribed drugs. Although the majority of these drugs were developed several decades ago, optimal dosage (dose, dosing interval and treatment duration) have still not been well defined. This thesis focuses on the development and evaluation of pharmacometric models that can be used as tools in the establishment of improved dosing strategies for novel and already clinically available antibacterial drugs. Infectious diseases are common causes of death in preterm and term newborn infants. A population pharmacokinetic (PK) model for gentamicin was developed based on data from a prospective study. Body-weight and age (gestational and post-natal age) were found to be major factors contributing to variability in gentamicin clearance and therefore important patient characteristics to consider for improved dosing regimens. A semi-mechanistic pharmacokinetic-pharmacodynamic (PKPD) model was also developed, to characterize in vitro bacterial growth and killing kinetics following exposure to six antibacterial drugs, representing a broad selection of mechanisms of action and PK as well as PD characteristics. The model performed well in describing a wide range of static and dynamic drug exposures and was easily applied to other bacterial strains and antibiotics. It is, therefore, likely to find application in early drug development programs. Dosing of antibiotics is usually based on summary endpoints such as the PK/PD indices. Predictions based on the PKPD model showed that the commonly used PK/PD indices were well identified for all investigated drugs, supporting that models based on in vitro data can be predictive of antibacterial effects observed in vivo. However, the PK/PD indices were sensitive to the study conditions and were not always consistent between patient populations. The PK/PD indices may therefore extrapolate poorly across sub-populations. A semi-mechanistic modeling approach, utilizing the type of models described here, may thus have higher predictive value in a dose optimization tailored to specific patient populations.

[Truncated abstract] Pneumococcal exposure is high and life-long in developing countries including Papua New Guinea (PNG), with children under 2 years of age being at most risk for early upper respiratory tract pneumococcal carriage and infection. Deaths from pneumococcal diseases such as pneumonia and meningitis are common and likely the result of an absence of vaccination programmes. The need for effective and affordable pneumococcal vaccines has led to the testing of protein antigens including pneumolysin (Ply) and pneumococcal surface protein A (PspA) as novel vaccine antigens. Little is known on the immune responses to these proteins in humans, particularly in high-risk populations where such vaccines will be of most benefit. In this study, we examined the roles of naturally acquired antibody and cellular immune responses in mothers and newborns to Ply and PspA family 1 (PspA1) and family 2 (PspA2) in protection against or risk for early carriage in a high-risk PNG population. Antibodies to Ply, PspA1 and PspA2 were measured in plasmas of 241 mothers and 115 newborns (cords) from PNG, and 50 Australian mothers using an enzyme-linked immunosorbent assay (ELISA). Pernasal swabs were collected from PNG mothers at the time of delivery, one month post-partum, and weekly within the first month of life from their newborns to determine pneumococcal carriage. Cellular immune responses to Ply, PspA1 and PspA2, the TLR2/TLR4 ligands, LTA and LPS and to PHA were measured in cord blood mononuclear cells (CBMC) of 84 PNG versus 33 Australian newborns. Innate and T-cell cytokine responses in the PNG newborns were then analysed to determine their effect on infant pneumococcal carriage. ... No protective effect against infant pneumococcal carriage was observed with maternal and cord IgG levels for all antigens. Maternal carriage at time of delivery increased the risk for infant pneumococcal carriage in the first month of life (HR: 1.93, 95% CI 1.36 – 2.73, p = 0.001) with 70% of infants being colonised. Papua New Guinean newborns produced higher innate IL-10 and IFN-¿ (p = 0.003) and TNF-a (p < 0.001) to Ply compared to Australian newborns with no significant differences observed for IL-6 or IL-12. IFN-¿ responses to LPS and LTA (p = 0.005 and p < 0.001) were higher in PNG than Australian newborns, while IL-6, IL-10 (p < 0.001) and TNF-a (p = 0.002) to LPS with LTA-induced IL-6 and IL-10 (p < 0.001) were higher in Australian newborns. T-cell IL-5, IL-10, IL-13, IFN-¿, IL-6 and TNF-a response levels to PspA and PHA stimulation were significantly high in PNG newborns. No differences were observed for cytokine responses to Ply and PspA between PNG infant pneumococci carriers and non-carriers. Papua New Guinean infants are colonised by pneumococci very early in life and this may be influenced by high maternal carriage rates. PspA- and Ply-IgG levels are high in PNG mothers and undergo cross placental transfer but do not appear to be protective against early pneumococcal carriage. In PNG newborns, PspA elicits T-cell responses, while Ply drives more innate cellular responses, neither were demonstrated to have a protective effect against early carriage though further work is required to better define these and their relation to immune development in early childhood.

Thesis (M.S.W.)--Smith College School for Social Work, Northampton, Mass., 2009. / Includes bibliographical references (p. 70-72).

Les enfants nés prématurément, et plus particulièrement les grands prématurés nés avant<p>31 semaines d’âge gestationnel, sont à haut risque de contracter des infections. La<p>vaccination peut prévenir certaines infections, dont la coqueluche qui est causée par la<p>bactérie Bordetella pertussis (Bp). Cependant, cette maladie infectieuse hautement<p>contagieuse est en recrudescence depuis plusieurs années malgré une bonne couverture<p>vaccinale. La morbidité et surtout la mortalité de la coqueluche affectent plus<p>particulièrement les jeunes enfants, incomplètement ou non encore vaccinés.<p>Il existe deux types de vaccins contre B. pertussis :les vaccins de première génération à<p>cellules entières et les vaccins acellulaires, plus récents. Suite à l’apparition d’effets<p>secondaires causés par le vaccin à cellules entières, les vaccins acellulaires, comprenant<p>seulement un certain nombre d’antigènes purifiés de B. pertussis, sont utilisés en Belgique<p>comme dans de nombreux autres pays industrialisés.<p>L’immunité protectrice contre B. pertussis fait appel tant à l’immunité cellulaire qu‘à<p>l’immunité humorale. De nombreuses études ont démontré une production d’anticorps<p>spécifiques aux antigènes de B. pertussis suite à l’administration des différents types de<p>vaccins. Par contre, peu d’entre elles ont analysé la réponse d’immunité cellulaire spécifique<p>caractérisée, entre autres, par une sécrétion d’Interféron-gamma (IFN-& / Doctorat en Sciences médicales / info:eu-repo/semantics/nonPublished

Thesis (M. Diac. (Spelterapie)) / Die navorser het met hierdie intervensiestudie hanteringsriglyne vanuit ʼn Gestaltperspektief vir ouers met ʼn eiesinnige kleuter ontwikkel. Om bogenoemde te bereik, is slegs die eerste drie fases, asook Stap 1 van Fase 4 van Rothman en Thomas se Design & Development-model voltooi. Fase 1, naamlik die probleemanalise en projekbeplanning, het gefokus op die identifisering en betrek van respondente, die verkryging van toegang tot en samewerking van respondente, ʼn behoeftebepaling van die populasie, die analisering van die geïdentifiseerde probleem en die bepaling van die doelstellings en doelwitte. Deur die bestudering van bestaande literatuur en natuurlike voorbeelde, sowel as die identifisering van funksionele elemente van suksesvolle modelle is Fase 2, naamlik die insameling en sintese van data, suksesvol voltooi. Tydens Fase 3, naamlik die ontwerpfase, is ʼn waarnemingsisteem ontwikkel en prosedures vir die intervensie gespesifiseer. Deur die ontwikkeling van ʼn prototipe is Stap 1 van Fase 4, naamlik vroeë ontwerp en ontwikkeling, voltooi. Gevolgtrekkings en aanbevelings is vanuit die bevindinge gemaak. / Social Work

Thesis (M.Med. (Paediatrics and Child Health)) -- University of Limpopo, 2019 / Objectives To determine the prevalence and survival rate; and to assess the maternal risk factors as well as complications of prematurity, associated with the mortality of very low and extremely low birth weight infants in the Neonatal Intensive Care Unit (NICU) of Mankweng Hospital. Materials and Methods A retrospective descriptive study was conducted at the NICU of Mankweng Hospital for a 7-month period from 1st January to 31st July 2015. The patient medical records and the Perinatal Problem Identification Programme (PPIP) data were used for the study. Results Prevalence of prematurity was 23%, Infants weighing between 500g-1499g represented 6.3% of the total live births and 25% of the admissions to the NICU; of which 4.9% were classified as extremely low birth weight (ELBW). Overall 77% of the study population survived until discharge. From the medical records, the survival to discharge of infants with weight 500g - 999g was 52%; and 84% for those with weight 1000g-1499g. Multivariable analysis found that improved survival was associated with an increase in gestational age (p <0.001), as well as birth weight (p <0.001) and prolonged length of stay. Variables associated with poor survival were spontaneous preterm labour (p = 0.031), low Apgar score at 1 and 5 minutes (p <0.001), sepsis (p = 0.001), respiratory distress syndrome (p <0.001), pulmonary hemorrhage (p <0.001), hypothermia (P = 0.005), resuscitation at birth (p = 0.002) and necrotising enterocolitis (p =0.044). Antenatal steroids were not associated with survival (p =0.111), however this was not documented in 53%(134/252) of the records, so the non-significance to outcome in this study may not be a true reflection. The use of NCPAP or SiPAP only was associated with improved survival of up to 69% and high mortality rates were recorded in babies who required invasive ventilator support. Multi-organ immaturity was found to be the most common cause of death, followed by sepsis. Conclusion: The prevalence and survival rates of very low and extremely low birth weight, found in this study are comparable to those found in other tertiary hospitals in South Africa. The survival rate of ELBW babies is low and must be improved. Reliable data and further research should address effective steps to prevent preterm labour, extreme prematurity and hypothermia. The documentation and provision of antenatal steroids is encouraged. KEY CONCEPTS: Prematurity, Extremely low and Very low birth weight, Risk factors, Prevalence, Survival, Neonatal mortality rate.

Research has shown that children born low birth weight (i.e., ≤2500 grams) and/or premature (i.e., birth prior to 37 weeks gestation) are at increased risk of experiencing developmental delays, as well as long-standing executive functioning and academic challenges. Despite these well-known risks, children born low birth weight are under-enrolled nationally in Part C Early Intervention (EI) services intended to support developmentally vulnerable children. Little is known regarding why EI enrollment is low in this high risk population, especially given children born LBW are readily identifiable as at increased risk of delays at birth. This study explored EI referral outcomes from a high risk infant follow up program serving children with complex early medical histories that place them at increased risk of experiencing developmental delays to determine how many children referred to EI were ultimately evaluated and enrolled in the program. This explanatory sequential mixed methods study included a quantitative phase characterizing the EI referral outcome and a qualitative phase consisting of interviews with families to explore the parent/caregiver's experience of the EI referral process. Data analysis included descriptive statistics to characterize the sample and Pearson Chi Square and independent samples t-tests to investigate child characteristics associated with successful referral. Qualitative interviews were transcribed and coded for themes in an iterative and cyclical fashion. Results indicate that only 62% of the children who were referred for EI services were evaluated by the program, with about the same percentage of those evaluated being found eligible (67%). Of those who were not found eligible, about a third of children should have qualified based on previous testing and/or medical conditions. However, these qualifying medical conditions were often not clearly documented on the referral form, and not all forms included documentation of the scores from developmental testing. There were also a significant number (71%) of Oregon children referred to EI but never evaluated who were likely to have qualified based on medical history and/or results from developmental testing. There were several key themes identified following analysis of the qualitative interviews. Most critically, the parent/caregiver's perception of the need for the EI referral was identified as an essential factor in facilitating a successful connection to EI. Other key themes included the need to honor the many different demands placed on the caregivers of these high risk children, as well as the necessity of providing clear explanation of the purpose of both the visit to the high risk infant follow up program and the EI referral. The Chronic Care Model is used as a framework for discussing implications for practice.