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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/121993
Understanding different opportunities to prevent severe disease and reduce mortality in African infants and children: From vertical transmission prevention to enhanced diagnosis of life-threatening conditions of childhood = Oportunidades para prevenir enfermedades graves y reducir la mortalidad en lactantes y niños africanos. Prevención de la transmisión vertical y mejora del diagnóstico de enfermedades que amenazan la vida de los niños
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[eng] Infant and child mortality have played a crucial role in health transition patterns and both have been considered as good indicators of development and demographic modernization. The establishment of the Millennium Development Goals (MDGs) meant a significant injection of funds and resources for health, and a national and international commitment to child health, which led to an unprecedented progress in the reduction of child mortality worldwide. In terms of neonatal infections, neonatal sepsis and meningitis are well- known leading causes of mortality and severe sequelae in term and preterm babies in industrialized countries but information about them and their burden in LIC is more limited. Early-onset disease (EOD, 0-6 days), is usually vertically transmitted, and mainly caused by Group B streptococcus (GBS) and Escherichia coli (E. coli). Late-onset disease (LOD, 7-89 days) is generally due to horizontal infections (either community-acquired or hospital-acquired) and most frequently associated pathogens include E. coli, Klebsiella spp, GBS and other Gram-positive organisms (Staphylococcus aureus and Coagulase-negative staphylococci). Maternal colonization by these pathogens is crucial for transmission from mother to child to occur, presenting in such cases generally as EOD. Prevalence of maternal colonization may be affected by Human Immunodeficiency Virus (HIV), maternal nutritional status and other maternal risk factors. Prevention strategies such as maternal screening of GBS at the end of the pregnancy and intrapartum antibiotic prophylaxis (IAP) for those mothers found to be carriers have demonstrated their efficacy in dramatically reducing EOD. However, IAP as we know it is not currently reaching all women in need in poor settings, possibly in relation to the fragility of health systems, precariousness of laboratory infrastructures, or more simply because a significant proportion of deliveries in these settings still occurs at home. In addition, other preventive strategies against E. coli or those bacterial causing LOD have yet to be developed. Other infectious diseases also considered as important contributors to neonatal, infant and even child morbidity and mortality include infections encompassed under the TORCH syndrome. The HIV pandemic and the Zika virus outbreak have raised great concern across the world and have highlighted the importance of other pathogens for infants, including viruses, parasites or fungi. Screening of some of these diseases such as syphilis or HIV is routinely offered to women attending antenatal care (ANC) clinics of LIC. However, further screening of other potential vertically transmitted pathogens, such as cytomegalovirus (CMV), rubella, toxoplasma gondii (T. gondii), enterovirus (EV), parvovirus B19 (B19V), herpes simplex virus (HSV) or hepatitis B virus (HBV), among others is not offered. Congenital CMV infection (cCMV) is the most prevalent and principal cause of deafness in developed countries. However, and similarly to other congenital infections, it remains fundamentally unnoticed and therefore largely neglected in resource-constrained settings, thus also hindering the characterization of its real burden and impact in these settings. An interesting approach to prevent many of these congenital and neonatal infections now includes maternal vaccination during pregnancy under the assumption that maternal transfer of antibodies to the newborn will be more feasible, effective and rapidly protective than waiting for the generation of neonatal immune responses to vaccines administered directly to them. This “vertical vaccination” strategy has already been successfully implemented for tetanus and pertussis control, and is being explored against other pathogens. There are other well-known causes of severe disease and mortality in children, although not usually listed as direct CoD and therefore often forgotten in global estimates. Malnourished children, neonates born with a low weight or small for their gestational age, may be prone to suffering life-threating conditions or developing significant sequelae. In many cases, the fatal outcome is determined by the underlying condition rather than the acute disease. On the other hand, the emergence of certain complications such as for instance hypoglycaemia, relatively common in the evolution of many different diseases or conditions (malaria, sepsis, diarrhoea cases, malnutrition or neonates in general), may also adversely determine the prognosis of these cases, although the real incidence and significance of such complications remains to be described and addressed as part of their management strategies. In many LMIC, at least half the child deaths occur at home, often without having been seen by a clinician. In some cases, though, deaths occur also at home, but soon after a contact with the health system. Inpatient mortality is a well-understood portion of the global overall child mortality estimates, and interventions to reduce it have been developed and successfully implemented. However, post-discharge mortality (PDM) could be as high as inpatient mortality in those constrained-resource settings, but is clearly a neglected and understudied phenomenon. Indeed, no guidelines, recommendations or further strategies have been developed to address the care of patients during the days immediately following discharge, a critical period for child survival. The fragility of the health systems and scarcity of the health force in LIC, the unaffordable high costs to provide care for acute illness and the generalised lack of awareness about the burden and implications of PDM by health workers and policy makers partly explain this neglect. This thesis aims to address issues related with those severe diseases that cause the majority of morbidity and deaths among neonates, infants and children under five and for which no specific interventions have yet been implemented. Most of the studies conforming this thesis have been conducted in Manhiça, a semi-rural area in Southern Mozambique, and a paradigmatic example of a resource-constrained setting.
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MADRID CASTILLO, María dolores. Understanding different opportunities to prevent severe disease and reduce mortality in African infants and children: From vertical transmission prevention to enhanced diagnosis of life-threatening conditions of childhood = Oportunidades para prevenir enfermedades graves y reducir la mortalidad en lactantes y niños africanos. Prevención de la transmisión vertical y mejora del diagnóstico de enfermedades que amenazan la vida de los niños. [consulta: 11 de desembre de 2025]. [Disponible a: https://hdl.handle.net/2445/121993]