Infectious diseases in the 21st century: old challenges and new opportunities.
Infectious diseases are the confrontation of two worlds, the microbial world and the world of human physiology. Although these two worlds are as a whole governed by the same laws of nature, they show substantial differences: the microbiological world is 1000 times older, and was initiated by the development of the archaea, the 'living organisms of the extreme': its biomass and its diversity are immense - two to three billion species or 60% of the total biomass of the planet. The number of pathogens that adapted to man, however, is extremely limited - barely 1000. Thus, over billions of years, an evolution of the microbial world took place from 'early life', characterized by chemosynthesis, to the 'modern pathogens', and entailed a dramatic 'concentration' of life conditions and an adaptation towards a narrow range of requirements - those allowing survival in the human body. Within the last two centuries, these two slowly evolving systems, microbial life and human life, were profoundly modified in an unprecedented manner by a third player, human civilization, with its global impact on the environment through physical, chemical, societal, and climatic determinants. An appreciation of the evolution of infectious diseases in the 21st century and of the development of new diagnostic and therapeutic strategies therefore requires a full understanding of these three domains: human physiology, microbiology, and the environment. This review will put major emphasis on the environmental role of civilization on infectious diseases before considering new opportunities to combat them through novel and creative solutions.