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Pasteur Paris 2019
Context
Nowadays, worldwide, infectious diseases account for 40% of the total 50 million annual estimated deaths. 700,000 of these deaths are due to infections caused by resistant bacteria, with up to 25,000 in Europe alone [1]. Concerning sepsis, someone dies every 5 seconds in the world.
SEPSIS - CAUSE & IMPACT
Sepsis occurs when the immune system develops a very strong response against a bacterial infection, causing widespread (systemic) inflammation throughout the entire body that can lead to tissue damage, organ failure, and death. When sepsis occurs, the body undergoes a cascade of changes, including the formation of blood clots and greater permeability of blood vessels that impede blood flow to the organs. Blood pressure decreases, several organs may be insufficient, the heart is affected, and death may result.
In the United States, there are approximately 750,000 sepsis cases per year and 75,000 cases in Canada. Mortality varies between 18% and 30% depending on the study, or 215,000 deaths per year, while it is in the order of 40% to 70% in patients with septic shock[1]. In France, there are about 70,000 cases of sepsis per year and nearly 30,000 deaths, Inserm reported in 2015. Mortality in people with sepsis is 27%, but mortality in the most severe form (septic shock) can reach 50%. Sepsis causes as many deaths as myocardial infarction[2].
TREAT QUICKLY ...
One minute.
A single minute could truly make a difference in the management of
patients with sepsis in the Emergency Department (ED). The
management of the patients affected by an infection is impacted by
a time factor. In that way, diagnostic tests could help to
identify high-risk patients, isolate patients as needed, and
rapidly initiate treatment. In the most serious cases,
particularly in sepsis cases, the need for a rapid and accurate
diagnosis then becomes absolute to provide first aid : each second
being crucial.
… AND EFFICIENTLY
In such a context, the urgency of the treatment and its vital nature may lead to the prescription of non-targeted treatments. This practice contributes to antibiotic resistance. Antimicrobial resistance is a major concern as the excessive use of antimicrobial drugs is not only making the microorganisms resistant, but also causing severe infections, which are becoming harder to treat.
No new antibiotics with a new mechanism of action have been developed for 20 years
158,000 multi-resistant bacterial infections in France
12,500 deaths are linked to multi-resistant bacterial infection in France
Between 71 and 441 million euros of overconsumption of antibiotics in France
If providing quick and safe treatment in the short term is necessary, providing the right treatment is life-saving in the long term is better
Then we should act on both.
How ?
Our Solution
Our project aims to create a portable, precise and rapid device for diagnosis, in order to detect pathogens through the use of an aptamer-based sensing electrode. Current diagnostic methods often require bacterial culture, implying at least 24 hours of incubation, which is not ideal for time sensitive clinical cases. In this context, improving the speed, sensitivity, and specificity of bacterial detection is crucial.
Given the emergency of the antibiotic resistance issues, research is
dense and diverse in the field of infectious diseases diagnosis.
Existing and future techniques can be focused on pathogen
identification (ID) and antibiotic susceptibility testing (AST).
Today, a lot of methods are still culture based. They are manual and
highly time-consuming since the first bacterial identification
results are revealed in at least 24 hours. Molecular based
techniques, using DNA amplification by PCR, require knowledge of the
primers in advance. Mass spectrometry methods and flow cytometry are
certainly faster since they allow a diagnostic in about 10 hours,
but not cheaper than the previous methods. When we look at the
techniques in development and the future techniques, we can observe
that they are more and more sophisticated. For example,
imaging-based methods will use microscopy to scan a population of
bacterial cells and to analyze a multitude of parameters to
discriminate resistance from susceptible strains. On another side,
microfluidics techniques will allow the isolation of each cell to
measure its metabolically activity in the presence of antibiotics.
Other futuristic methods involve next generation sequencing, or
e-noses to detect volatile compounds as an electronic aroma
signature to identify bacteria. These latest technologies, in the
research or development phase use state-of-the-art technologies and
require a large package of scientific expertise. They often allow
the analysis of a large mass of samples and they reduce the
diagnostic time to few hours. But they are expensive and applied in
machines that are imposing in size and that require expertise and
material to manage. Therefore, they cannot be transportable on more
"uneven" terrain, in humanitarian missions for example.
For more information about our project click here!
Design
Integrating product design
into our project has helped us create a real, working, simple and
efficient solution for customers to use in bedside medicine and in
humanitarian context. Using the methodology of product design, by
performing user research, sketches, model making and prototyping, we
have assessed the different needs and expectations of potential
users. Working with a professional from industrial design has helped
us achieve our main goal : design a working product from scratch,
using interviews and experiments to get answers on hypotheses we
have made on our way to our final device. Working with a
professional business in medical devices automation has allowed us
to step up our device and fully automate the use of DIANE using
pumps and valves. Finally, designing a scenario for our users has
helped us understand all the challenges users might face during
their daily work, allowing us to try and solve those problems to
facilitate the use of DIANE.
For more information about the design of the device click here!
Team
DIANE was led by a team of
ten students from different Parisian schools and universities. Among
them, Sup’Biotech (biology), ESPCI Paris (physics and chemistry),
AgroParisTech (engineering), ENS Cachan (chemistry), Chimie ParisTech
(chemistry), and Faculté Jean Monnet (intellectual property law). The team was
accompanied by a project director, Dr. Deshmukh Gopaul (Director of
Research at the Institut Pasteur) and three coaches (PhD students at
the Institut Pasteur). For more information about our team click
here!
For more information about our team click here!
References :
[1] INSERM, “Résistance
aux antibiotiques”, INSERM, online since the 22/03/18,
available on : www.inserm.fr/information-en-sante/dossiers-information/resistance-antibiotiques, visited the 11/04/19
[2] Martin GS, Mannino DM, Eaton S et al. The Epidemiology of Sepsis
in the United States from 1979 through. NEJM 2003 ; 348 (16):
1546-1554; O’Brien JM, Ali NA, Aberegg SK, Abraham Edward. Sepsis.
The American Journal of Medicine. 2007; 120 (12): 1012-1022.
[3] https://www.pasteur.fr/fr/centre-medical/fiches-maladies/sepsis-septicemie