This paper examines the social etiology of poverty-related infectious diseases prevalent in Spain and Italy in the first half of the twentieth century. Using an ecological model of health determinants, we analyze an explanatory framework consisting of the interaction between infectious agents, individuals vulnerable or susceptible to illness and unhealthy environments that facilitate contagion, on the one hand, and the action of fomites and vectors and high-risk practices and behaviors on the other. In addition, we discuss the bases of the intervention strategies and epidemiological and health surveillance measures that made it possible to improve hygienic conditions and mitigate the primary deficiencies responsible for the prevalence of these diseases.