01/01/2014 - 31/12/2017
Instituto de Salud Carlos III
A path towards new diagnostic and prevention tools for severe infectious pathologies
In pediatrics, and especially in developing countries where diagnostic methods are scarce, some severe infectious diseases
such as pneumonia (bacterial or viral) and severe malaria (SM) are difficult to distinguish clinically because of the lack of specifity
of their symptoms.
The discovery of biomarkers specific for these severe pathologies is important for the development of new methods for the early identification of critically ill patients and their adequate therapeutic management. This is therefore a research area with a high potential for translation to clinical practice able to place Spain in a leading scenario in the fight against diseases of global impact.
Sequestration of Plasmodium falciparum in host organs through cytoadhesion of infected erythrocytes (IEs) to host receptors is a central pathogenic event mediated by parasite proteins expressed on the surface of the IEs (P. falciparum erythrocyte membrane protein 1 [PfEMP1]). The hypothesis of this project is that host tissues damaged by the sequestration of P. falciparum secrete microRNAs (a class of small endogenous RNAs that can regulate genes posttranscriptionally) different to the ones secreted during uncomplicated malaria or pneumonia.
The aim is therefore to identify a) microRNAs suitable to predict pathologies associated with SM or pneumonia that can be developed into diagnostic/ prognostic biomarkers and b) PfEMP1s involved in the sequestration of P. falciparum during SM which constitute targets for the prevention/treatment of SM. To achieve these objectives, miRNAs in plasma of African children with different clinical phenotypes (severe and uncomplicated malaria, bacterial or viral pneumonia; n=50/group) and in postmortem tissue biopsies will be detected by massive parallel sequencing, as well as clinically relevant PfEMP1s expressed by P. falciparum field isolates (n=100).
This research will allow the development of new methods for early diagnosis of diseases such as malaria and pneumonia, as well as innovative tools to prevent the sequestration of the malaria parasite and its adverse consequences.