Discussion

The two trematode species Fasciola hepatica and F. gigantica cause a vector-borne zoonotic disease distributed worldwide. This parasitic disease is included in the group of Foodborne Trematodiases among the list of Neglected Tropical Diseases considered by the World Health Organization. Fasciolid flukes parasitize herbivore mammals (mainly livestock) and are transmitted by freshwater lymnaeid snail vectors. The origins and geographical spread of these two fasciolid digeneans were analysed in both the ruminant predomestication times and the livestock postdomestication period. The ancestor may be found in an ancient fasciolid form infecting old Artiodactyla in Africa during the early Oligocene when the first pecoran radiation occurred. The origin of F. gigantica was probably the result of an adaptation of this ancient fasciolid to bovids, such as ancestors of Alcelaphinae, Reduncinae and Bovinae, during the second pecoran episode, resulting in an explosive radiation during the early Miocene. This origin was probably in the warm, eastern Africa, where the lymnaeid snail Radix natalensis assured the transmission. The origin of F. hepatica was probably in the Eurasian Near East, as a derivation from the same ancient fasciolid or a F. gigantica&hypen;close old form introduced with ruminants from Africa during a major sea level lowering in the early Miocene. The origin of F. hepatica is likely the result of colonization of and subsequent adaptation to a new, more northern and temperate-colder region, as well as the result of two host capture phenomena to smaller lymnaeid species of another lineage such as Galba truncatula and to mid-sized ruminants. At present, the geographical distribution of the human fascioliasis endemic areas in Europe, Asia, Africa and the Americas pose a question mark. None of the many different epidemiological characteristics analysed, nor any combination of them, is able to explain such a surprising distribution including highly heterogeneous scenarios. This fact runs, moreover, parallel to the genetic differences shown by the molecular markers of Fasciola hepatica worldwide and by F. gigantica in Africa and Asia, which are too low for such wide distributions. Paleontological, archeological and historical records, together with genetic data on recent dispersal of livestock species are considered to establish an evolutionary framework for the fasciolids across all continents on the baseline furnished by selected markers of the nuclear ribosomal DNA and mitochondrial DNA of both fasciolid flukes and lymnaeid vectors, without forgetting herbivore mammal host preferences and immunological interactions. The puzzle reconstruction indicates that crucial events of the history of humanity played a important role in fascioliasis spread. Thus, human fascioliasis endemic areas appears to correlate with the following mankind's phases: initially the Fertile Crescent and Old Egypt in the Near East, and later the Phoenicians and Romans in the Mediterranean, the Bantu radiation and Proto-Khoisan spread in Africa, the Silk Road in Asia, and the Spanish colonization in the New World, just to mention the most important ones. This evolutionary framework is expected to greatly help in designing global control measures, local interventions and forecast initiatives to fight against human fascioliasis in the different regions of the world.
Studies funded by Proyecto de Investigación en Salud No. PI16/00520 (MINECO, Madrid, Spain), Red de Investigación Cooperativa en Enfermedades Tropicales RICET No. RD16/0027/0023