Researchers explain why fascioliasis patients have increased risk for neurological diseases

Fascioliasis is a parasitic disease caused by two species that are present in the liver: Hepatic Fasciola, which is present worldwide, and Fasciola gigantica, which is in Asia and Africa. The high pathogenicity of this disease has led the World Health Organisation (WHO) to include it in the list of the great diseases of humanity. The two Fasciola species cause varied clinical pictures, from cases without symptoms, to other severe ones that can cause death. Among the severe cases there is a broad range of neurological diseases, from the paralysis of limbs, motor and speech disorders and the loss of senses, to seizures, epilepsy and entering coma. Spain is the country with the second largest number of cases of diagnosed neurological fascioliasis, after France.

In an article published in the journal Parasitology, María Adela Valero and María Dolores Bargues, professors at the Department of Pharmacy and Pharmacy Technology and Parasitology of the UV, along with professor Santiago Mas-Coma and his collaborators, show that Fasciola excretes and/or secretes a large number of proteins that induce the transformation of a plasma protein called plasminogen, into the enzyme plasmin, which has the ability to decompose clots or thrombi. This transformation of plasminogen into plasmin is part of the fibrinolytic and contact systems, whose end product is a strong proinflammatory peptide called bradykinin, which increases the vasodilation of arteries and veins, as well as vascular permeability.

This is how Fasciola ends up generating the bradykinin capable of opening the hematoencephalic barrier, a small impermeable layer of cells that acts as a protector of the brain. This barrier is located in the capillaries that irrigate the brain and works as a filter between the blood and nervous systems, blocking a large number of substances from going from the blood to the brain. The opening of the hematoencephalic barrier by bradykinin makes it possible for different Fasciola secretion/excretion products to access the brain, as well as other toxic substances derived from the pathogenic action of this parasite, with the resulting neurological effects.

Santiago Mas-Coma, WHO expert in tropical diseases and study director, highlights the importance of these findings, when referring to "the door that opens to develop markers that allow us to diagnose the risk of patients infected by fascioliasis of suffering neurological diseases, as one of the main problems that these patients with neurological symptoms have is that the medical specialists who tend to these patients, as is logical, rarely think of fascioliasis as the source, due to the infrequent nature of these cases."

The UV professor highlights that "it has taken us many years of work, because nobody had any idea of the path or paths that a parasite present in the liver of patients could use to open the hematoencephalic barrier at a distance. There were many varied hypotheses that different teams had considered, but they had not been confirmed. Clarifying how the parasite causes these diseases and explaining all the clinical complexity and heterogeneity of these cases has undoubtedly been the most important challenge."

María Adela stresses:

The problems inherent in the necessary experimental part in order to obtain the fresh biological materials to appropriately extract and analyse the excretion/secretion proteins in a parasite of vectoral transmission by way of a freshwater snail and the subsequent experimental infecting of laboratory animals. They are lengthy experiments where many aspects can go wrong. Fortunately, we had the expected success."

Furthermore, María Dolores Bargues, president of the Spanish Tropical Medicine and International Health Society (SEMTSI), highlights "the success that an entirely Spanish collaboration has had in this research, with two teams from Valencia University and one from Salamanca University."

The initial dissemination of this article took place in the oral presentation of professor Mas-Coma in the symposium of the International Federation for Tropical Medicine held in Korea last year. The work has been financed by the Spanish International Cooperation Agency for Development (AECID), by the FIS and the RICET Network of the Ministry of Health, by the PROMETEO program of Valencia's regional government, and by a Development Cooperation Project of the UV.

Source:
Journal reference:

González-Miguel, J. et al. (2019) Numerous Fasciola plasminogen-binding proteins may underlie blood-brain barrier leakage and explain neurological disorder complexity and heterogeneity in the acute and chronic phases of human fascioliasis. Parasitology. doi.org/10.1017/S0031182018001464.

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