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IDDEAA : Improving Detection and Discovery of Emerging Arboviruses in Amazon

Because of the characteristics of this project (short duration and limited funds), we have built a pilot project, proposing the implementation of a new and unique technology to capture, concentrate and cleans viruses present in complex human samples (urine, feces, blood, sera, plasma, cerebrospinal fluids, tissues, etc). To improve the detection of viruses in sample from “suspected-of-infection individuals” (possible false negative diagnosis with current methods) this unique technology will be transferred to virology labs from both the Hospital of FMT-HVD in Manaus and to the French National Reference Center for Arbovirus at the Pasteur Institute in the French Guiana.

This technology is based upon the capacity of the activated protein from the acute phase, Apolipoprotein H (ApoHa) to capture, with high affinity, pernicious microorganisms that for their detection need to be further processed with current or new sensitive detection methods, thus increasing their efficiency. Thus, ApoHa-coated nano-¬magnetic beads (ACnMB)-captured single or mixed viruses are associated to different PCR-derived methodologies (ACnMB-PCR system). Using this innovative technology will also strongly enhance the sensitivity of virus (from different viruses including DENV, YFV, OROV, MAYV, CHIKV EEEV, WNV, etc) detection allowing a surveillance of low-noise circulating viruses or unexplained acute febrile syndromes from different origins, (neurologic, respiratory and hemorrhagic fevers). Possible co-infections, and improve the therapeutic management of patients with low undetected infection. It should be also possible to use this technology to try to isolate, in appropriated target cells, those viruses difficult to cultivate and when needed use downstream the next generation sequencing (NGS) and metagenomic (mostly at the Instituto Evandro Chagas, Belem and at the Sao Paulo University NGS facilities) analysis to accelerate the discovery of new viruses. 

In addition, at the LIMPC, will improve the scaling up of the production of ACnMB using chemical synthetic structure mimicking ApoH. This will open new lines of research based on new diagnostic tools for viruses promoting the training of students, researchers (post--doctorates), and teachers, of both places in Manaus, Brazil and Cayenne, French Guiana. The previous large experience using the ApoH technology to capture divers viruses and bacteria, including some Arboviruses like DENV, WNV, JEV, from different origins, it makes possible to consider that ApoH technology is reliably and efficient assist in the ultrasensitive diagnosis of Arboviruses, permitting the healthcare improvement with appropriate management and treatment of patients. In addition, ApoH could be very useful to improve the control of those epidemics that are disseminated by asymptomatic or low symptomatic carriers. 

A part of this experience was acquired during a true “success story” that took place within the USDEP (Ultrasensitive detection of Emerging Pathogens) project that was funded by the European Commission realized between the end of 2006 and 2010 (FP6). 

Taking in consideration the abundance and biodiversity of already presents and potentially (re)-emerging microorganisms in Amazon, this ambitious pilot project will begin by transferring a unique and innovative technology that should reduce the major diagnostic present and future unmet needs of the Amazonian clinical settings. To this, we have planned in situ trainings; as well as international exchanges for students, researchers, and technicians. With the support of different Brazilian partners (FMT-HVD in Manaus, IEC in Belem & LVFMRP de Sao Paulo University), we have already started with the contribution and support of FAPEAM, FMT-HVD and CNPq not only for a “Ciencia sin Frontera” fellowship for a post-doctoral position Mario Luis Figueiredo at the LIPMC Montpellier in 2013, but also for a visit and the First Virology International Workshop in Manaus where one of the concluding remarks of the expert round table was to develop as soon as possible opportunities for international cooperation on virus research. In addition to this our Brazilian partners are willing to fund the organization of 2 additional workshops and our colleagues from the IPG are ready to go to share experiences and know-how. From LIPMC, researchers or PhD students will participate each year to an in situ training and optimization of ACnMB-PCR system.

• Coordinateurs : Francisco Veas, IRD, Maria Paula Mourao UEA/FMT HVD, Mario Luis Garcia de Figueiredo

• Autres institutions impliquées :  Institut Pasteur Guyane, IEC, USP, cnra, IEC, LV FMRP USP