Transgenic animal models for the production of human immunocompounds in milk to prevent diarrhea, malnourishment and child mortality: perspectives for the Brazilian Semi-Arid region

Abstract

Diarrhea is one of the most significant issues for global health in children under the age of five. Close to 60% of mortality in this risk group is caused by pneumonia, diarrhea or measles, which is usually associated with malnutrition. In Brazil, this scenario is no different, with the Northeast semi-arid region having alarming rates of child mortality, almost twice that of the current national mortality rate, with some cities being three times higher, placing child mortality rates in the Northeast of Brazil among those of the most problematic in the world. The oral rehydration solution, introduced by the World Health Organization (WHO), is seen as one of the major medical advances in the past 50 years, and is believed to save the lives of 1 to 2 million children each year. However, the oral rehydration solution simply restores body fluid normality, treating the consequences and not the causes of diarrheas. Other means to effectively address worldwide diarrheic ailments still need to be devised or improved, focusing more on preventive rather than curative approaches, to prevent or shorten the course of disease and to minimize recurrences. A great example is breast-feeding. A series of studies documented the reduction of diarrhea episodes in breast-fed children and, also, noted a faster recovery time following an infection in these children. The positive benefit of breast milk is attributed to the antimicrobial actions of human milk proteins, such as lysozyme and lactoferrin that can enhance intestinal and systemic immunological functions. Unfortunately, breast-feeding is not always an option, especially for toddlers, which is usually aggravated by undernourishment and low standard of living, reinforcing the need for alternative strategies. Consequently, to successfully combat childhood undernourishment, morbidity and mortality in the Northeast region of Brazil, the investment in approaches and models that are more suitable to the local semi-arid adapted agriculture-base is required. The goat is an important economic asset to the Northeast region, providing milk, meat and leather, with the number of goats in the Northeast region representing more than 90% of the Brazilian herd. Historically, goats have been used as a model in biotechnological studies involving the expression of specific proteins in the milk of lactating animals. In this way, the use of goats expressing recombinant human lysozyme (rhLZ) and lactoferrin (rhLF) in milk is a proven reality that can be employed for the reduction of malnutrition, infectious diseases and diarrhea in children in the Brazilian semi-arid region with an extraordinary potential for success. Due to the protective nature of human milk imparted, in part, by the presence of lysozyme and lactoferrin, the generation of transgenic lines for the production of these important antimicrobial compounds in the milk of the local goat population is a unique approach for delivering the potential protective benefits of human milk. In addition, the use of rhLZ and rhLF transgenic animals can be used as a research tool for studying and elucidating the individual roles of these antimicrobial proteins in gut development and their synergistic in vivo effects. The proposed research was designed with the rational that the transgenic approach can be used to modify the milk composition of dairy animals to supply milk-borne human immunocompounds (rhLZ, rhLF) and nutrients University of Fortaleza, UNIFOR, Fortaleza, Brazil Full list of author information is available at the end of the article Bertolini et al. BMC Proceedings 2014, 8(Suppl 4):O30 http://www.biomedcentral.com/1753-6561/8/S4/O30