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Liver damages caused by Bilharzia in Uganda, feedback from a gastroenterologist

Dr Christopher Opio is a gastroenterologist in Kampala. Many of the patients whom he treats at the hospital suffer from portal hypertension and ascites caused by Schistosoma or the hepatitis B or C virus. As the on-site doctor, he has been working with our teams along the banks of Lake Albert for several years. We would like to let him speak, in order to have a better understanding of the destruction caused by these hepatic illnesses, which affect communities in Uganda.

Dr Opio, how do you know about BILHI Genetics?

I met Professor Dessein, from the Aix-Marseille university Medical School, at the Vector Disease Control. It was the previous Director who put us in touch. Professor Dessein’s work was based by the banks of Lake Albert. He would visit on-site and, like me, would be witness to the devastation caused by the illness, and the limited control programs in place. Together we have a common desire to “push the agenda forward” in the fight against Bilharzia.

What are the characteristics of this disease?

There is a high prevalence of bilharzia in Northern Uganda and along other water bodies in Uganda. This disease has the characteristic of being asymptomatic, which would explain the number of my patients reaching the advanced stages of their disease. They didn’t know they were ill until they started bleeding. I’m sure you can imagine their distress. For some, they considered themselves to be in good health, until they started vomiting blood. When I asked them how they felt at that moment, their response was explicit: “I thought I was going to die”.

How do you treat Bleeding due to Bilharzia?

Initially the aim is to stabilise the patients with bleeding, at the same time attempt to stop the bleeding, and prevent future re-bleeding. We do this by drugs, bands, and shunts. These treatments aim to reduce blood pressure in the portal veins. Once we manage to stop the bleeding and stabilise the patient, we will then treat the cause. We are quickly able to determine if the bleeding has been caused by a hepatitis virus, or by the presence of the Schistosoma worm infection in the liver. We treat Bilharzia by administering Praziquantel. However, we must be extremely careful because this medicine has been linked to worrying side effects in patients with severe or extensive fibrosis. In this group of patients it is advised to give praziquantel in a hospital under close monitoring.

What is the biggest problem about Bilharzia?

The problem is that when we talk about Bilharzia, we rarely talk about bleeding, even though it is the most frequent cause of hospitalization and death.

It has been identified as such in numerous cases: in Tanzania, in Malawi, in South Sudan…There are many cases in South Sudan. You can find articles about it. People do not always make the connection with Bilharzia, which leads me to say that the prevalence of this disease is even higher than people say.

In your opinion, how can we combat Bilharzia?

Only those having seriously suffered from Bilharzia can truly understand the disease and talk about it. This is why we must work with patients and let them speak up to raise awareness. It is very complex because Bilharzia is a “poor person’s illness”. For example, Water represents 20% of the territory in Uganda. People enter the water daily because it is their key resource livelyhood. If I need to wash my child, fish, feed my family, wash my clothes…I’ll go back in. I can’t worry about getting Bilharzia when I am starving, and my first concern is to feed myself and my family. You cannot stop people entering into the water, because the water is part of their life. And it only takes one person to contaminate the water. Treating people is a good thing, but it does not solve the problem. The core solution is to raise the country’s economic standards.

Kampala, December 2017.

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June 27 & 28, 2019 - 5ème congrès de la SFMPP

Le 5ème congrès de la SFMPP took place on June 27th and 28th, 2019 at the Institut des Cordeliers, Paris.Major players in precision medicine have come together to discuss genomic and oncogenomic medicine.

On June 27th, BILHI Genetics presented predictive genetic test of cirrhosis and liver cancer.

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July 7, 2018 - Rencontres Economiques d'Aix-en-Provence

Le 7 juillet 2018, Pierre Dessein participait à la table ronde "Quel principe de Précaution dans un monde imprévisible " aux rencontres Economiques d'Aix-en-Provence / Les métamorphoses du monde.

Alors que l’interprétation juridique du principe de précaution reste difficile et controversée, son poids économique est tout aussi difficile à mesurer que le coût des externalités néfastes qu’il est censé prévenir. Face à cette double incertitude, nombreux sont ceux qui critiquent sa tendance à freiner l’innovation, la créativité et donc, plus généralement, la marche de l’économie. C’est peut-être vrai à court terme mais, devant la prégnance des scandales écologiques et sanitaires, il semble difficile de contester totalement son bien-fondé. D’un autre côté, l’existence même de ces évènements parfois tragiques démontre que ce système juridique, sous sa forme actuelle, ne suffit pas pour prévenir les risques.

Face à l’émergence de nouvelles technologies qui soulèvent de nouvelles questions éthiques, il convient de relancer un débat constructif sur ce que serait un principe de précaution compatible avec l’innovation du futur. Le principe d’invention devrait-il primer ? Prudence, prévention ou précaution : où faut-il placer le curseur ? Le principe de précaution doit-il être assoupli ou au contraire renforcé ? L’expertise doit- elle venir des régulateurs ?

Pierre Dessein intervient aux côtés de Loraine DONNEDIEU de VABRES-TRANIÉ (Jeantet); Saeb EIGNER (Autorité des services financiers deDubaï); Suet-Fern LEE (Morgan Lewis); Armando MANUEL (Ancien Ministre des Finances, Angola); Nicolas MOREAU (Deutsche Asset Management)Emmanuelle WARGON (Danone). Coordinateur : Augustin TAUFFLIEB (La Parole aux Étudiants). Modérateur : Anne-Laure JUMET (Europe 1).

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April 29, 2018 - Never getting ill again?

Cette médecine permettant notamment grâce à la génétique de "prévoir l'apparition de certaines maladies avant même l'expression de leurs symptômes" - et donc de pouvoir agir préventivement pour éviter le développement de ces pathologies - se démocratise de plus en plus. Vantée par certains et honnie par d'autres, elle pose plusieurs questions, qu'elles soient économiques, sociales ou éthiques.

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April 17, 2018 - The rapid development of predictive medicine

La médecine prédictive se développe à grande vitesse. Il est désormais possible de prédire les chances d'être atteints d'une maladie en analysant le code génétique. Une pratique encore très encadrée en France pour les dérives.

De l'avis des scientifiques, une révolution est en cours : la médecine prédictive. Grâce à une analyse génétique, nous sommes aujourd'hui capables de connaître les risques de développer une maladie au cours de sa vie alors même que nous sommes en bonne santé. Plus de 500 000 Français y ont eu recours ces trois dernières années. Actuellement, les conditions sont très précises pour faire un test génétique : trois membres de la famille doivent être atteints du même cancer ou le cancer doit avoir été développé jeune. Des conditions trop restrictives pour certains qui réclament une plus large utilisation de ces tests.

Les spécialistes craignent des dérives

En matière de médecine prédictive, les progrès sont spectaculaires. "Nous avons aujourd'hui des algorithmes capables de lire le code génétique et d'identifier des mutations génétiques qui prédisposent les patients à développer certaines maladies graves", affirme Pierre Dessein, fondateur de GenePred, une start-up capable de lire un génome en quelques heures. Ces mêmes tests pourraient être également appliqués aux futurs enfants. C'est ce qu'on appelle les tests préconceptionnels. Mais certains tirent la sonnette d'alarme : cette méthode pourrait conduire à dire "on élimine tout ce qui n'est pas normal, même si on peut éventuellement apporter une solution", prévient une spécialiste. Aujourd'hui en France, entre 5 et 10% des cancers sont d'origine génétique.

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Press

March, 2018 - Innovation in health - BILHI Genetics heard by The Montaigne Institute

BILHI GENETICS a été auditionné par l'Institut Montaigne dans le cadre de son rapport : Innovation en santé : soignons nos talents !
Science

Professor Alain DESSEIN short selection of Scientific publications

[1] Dessein AJ, Parker WL, James SL, David JR. IgE antibody and resistance to infection. I. Selective suppression of the IgE antibody response in rats diminishes the resistance and the eosinophil response to Trichinella spiralis infection. J Exp Med 1981;153:423-436.

[2] Kigoni EP, Elsas PP, Lenzi HL, Dessein AJ. IgE antibody and resistance to infection. II. Effect of IgE suppression on the early and late skin reaction and resistance of rats to Schistosoma mansoni infection. Eur J Immunol 1986;16:589-595.

[3] Rihet P, Demeure CE, Bourgois A, Prata A, Dessein AJ. Evidence for an association between human resistance to Schistosoma mansoni and high anti-larval IgE levels. Eur J Immunol 1991;21:2679-2686.

[4] Rihet P, Demeure CE, Dessein AJ, Bourgois A. Strong serum inhibition of specific IgE correlated to competing IgG4, revealed by a new methodology in subjects from a S. mansoni endemic area. Eur J Immunol 1992;22:2063-2070.

[5] Demeure CE, Rihet P, Abel L, Ouattara M, Bourgois A, Dessein AJ. Resistance to Schistosoma mansoni in humans: influence of the IgE/IgG4 balance and IgG2 in immunity to reinfection after chemotherapy. J Infect Dis 1993;168:1000-1008.

[6] Dessein AJ, Vadas MA, Nicola NA, Metcalf D, David JR. Enhancement of human blood eosinophil cytotoxicity by semi-purified eosinophil colony-stimulating factor(s). J Exp Med 1982;156:90-103.

[8] Dessein AJ, Lenzi HL, Bina JC, Carvalho EM, Weiser WY, Andrade ZA, et al. Modulation of eosinophil cytotoxicity by blood mononuclear cells from healthy subjects and patients with chronic schistosomiasis mansoni. Cell Immunol 1984;85:100-113.

[9] Pincus SH, Dessein A, Lenzi H, Vadas MA, David J. Eosinophil-mediated killing of schistosomula of Schistosoma mansoni: oxidative requirement for enhancement by eosinophil colony stimulating factor (CSF-alpha) and supernatants with eosinophil cytotoxicity enhancing activity (E-CEA). Cell Immunol 1984;87:424-433.

[10] Lenzi HL, Mednis AD, Dessein AJ. Activation of human eosinophils by monokines and lymphokines: source and biochemical characteristics of the eosinophil cytotoxicity-enhancing activity produced by blood mononuclear cells. Cell Immunol 1985;94:333-346.

[11] Dessein AJ, Begley M, Demeure C, Caillol D, Fueri J, dos Reis MG, et al. Human resistance to Schistosoma mansoni is associated with IgG reactivity to a 37-kDa larval surface antigen. J Immunol 1988;140:2727-2736.

[12] Goudot-Crozel V, Caillol D, Djabali M, Dessein AJ. The major parasite surface antigen associated with human resistance to schistosomiasis is a 37-kD glyceraldehyde-3P-dehydrogenase. J Exp Med 1989;170:2065-2080.

[13] Couissinier-Paris P, Bourgois A, Dessein H, Bacellar O, Rodrigues V, Kohlstädt S, et al. Identification of a major T cell immunogen in the anti-schistosome response of adult residents in an area endemic for Schistosoma mansoni. Eur J Immunol 1995;25:903-910.

[14] Argiro L, Henri S, Dessein H, Dessein AJ, Bourgois A. Induction of a protective immunity against Schistosoma mansoni with ovalbumin-coupled Sm37-5 coadsorbed with granulocyte-macrophage colony stimulating factor (GM-CSF) or IL-12 on alum. Vaccine 1999;17:13-18.

[15] Argiro LL, Kohlstädt SS, Henri SS, Dessein HH, Matabiau VV, Paris PP, et al. Identification of a candidate vaccine peptide on the 37 kDa Schistosoma mansoni GAPDH. Vaccine 2000;18:2039-2048.

[16] Argiro L, Henri S, Dessein H, Kouriba B, Dessein AJ, Bourgois A. Induction of a protection against S. mansoni with a MAP containing epitopes of Sm37-GAPDH and Sm10-DLC. Effect of coadsorption with GM-CSF on alum. Vaccine 2000;18:2033-2038.

[17] Abel L, Demenais F, Prata A, Souza AE, Dessein A. Evidence for the segregation of a major gene in human susceptibility/resistance to infection by Schistosoma mansoni. Am J Hum Genet 1991;48:959-970.

[18] Marquet S, Abel L, Hillaire D, Dessein H, Kalil J, Feingold J, et al. Genetic localization of a locus controlling the intensity of infection by Schistosoma mansoni on chromosome 5q31-q33. Nat Genet 1996;14:181-184.

[19] Mohamed-Ali Q, Elwali NE, Abdelhameed AA, Mergani A, Rahoud S, Elagib KE, et al. Susceptibility to periportal (Symmers) fibrosis in human schistosoma mansoni infections: evidence that intensity and duration of infection, gender, and inherited factors are critical in disease progression. J Infect Dis 1999;180:1298-1306.

[20] Garcia A, Marquet S, Bucheton B, Hillaire D, Cot M, Fievet N, et al. Linkage analysis of blood Plasmodium falciparum levels: interest of the 5q31-q33 chromosome region. Am J Trop Med Hyg 1998;58:705-709.

[21] Dessein A, Chevillard C, Arnaud V, Hou X, Hamdoun AA, Dessein H, et al. Variants of CTGF are associated with hepatic fibrosis in Chinese, Sudanese, and Brazilians infected with schistosomes. J Exp Med 2009;206:2321-2328.

[22] Sertorio M, Hou X, Carmo RF, Dessein H, Cabantous S, Abdelwahed M, et al. IL-22 and IL-22 binding protein (IL-22BP) regulate fibrosis and cirrhosis in hepatitis C virus and schistosome infections. Hepatology 2015;61:1321-1331.

[23] Bucheton B, Abel L, El-Safi S, Kheir MM, Pavek S, Lemainque A, et al. A major susceptibility locus on chromosome 22q12 plays a critical role in the control of kala-azar. Am J Hum Genet 2003;73:1052-1060.

[24] Bucheton B, Argiro L, Chevillard C, Marquet S, Kheir MM, Mergani A, et al. Identification of a novel G245R polymorphism in the IL-2 receptor beta membrane proximal domain associated with human visceral leishmaniasis. Genes Immun 2007;8:79-83.

[25] Bucheton B, Abel L, Kheir MM, Mirgani A, El-Safi SH, Chevillard C, et al. Genetic control of visceral leishmaniasis in a Sudanese population: candidate gene testing indicates a linkage to the NRAMP1 region. Genes Immun 2003;4:104-109.

[26] Salhi A, Rodrigues V, Santoro F, Dessein H, Romano A, Castellano LR, et al. Immunological and genetic evidence for a crucial role of IL-10 in cutaneous lesions in humans infected with Leishmania braziliensis. J Immunol 2008;180:6139-6148.

[27] Pitta MG, Romano A, Cabantous S, Henri S, Hammad A, Kouriba B, et al. IL-17 and IL-22 are associated with protection against human kala azar caused by Leishmania donovani. J Clin Invest 2009;119:2379-2387.

[28] Dessein H, Duflot N, Romano A, Opio C, Pereira V, Mola C, et al. Genetic algorithms identify individuals with high risk of severe liver disease caused by schistosomes. Hum Genet 2020;139:821-831.

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December 12, 2017 - France Biotech Grants Genepred best 2017 eHealth Entrepreneur Awards

The best eHealth Entrepreneur award goes to Pierre Dessein Co-founder and CEO of Genepred.

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Bilharzia, “a silent killer”. The poignant witness of Robert K, 24-year-old, Uganda.

Robert Kabu* is a 24-year-old student from Makerere University in Kampala, Uganda. 10 years ago, he got infected by schistosomiasis in the Victoria Lake, where he used to go and play with his schoolmates. After many years of fear and pain, Robert is now cured and has decided to get involved in the fight against schistosomiasis, liver cirrhosis and varices in the region. Through his experience, he is in a better position to raise awareness about the damaging effect of schistosomiasis on the liver and the importance of prevention.

Hello Robert, please could you explain to us how you got infected and how you felt at that time?

I got schistosomiasis back between 2008 and 2011 when I was studying in a school near Lake Victoria, where I used to go for recreation and games. I’d been infected for more than 6 years without any specific signs and symptoms, until I started vomiting blood. This is when doctors found out that I had chronic schistosomiasis and was bleeding due to oesophageal varices! This meant that I had reached the last, and most damaging, stage of the disease. Before that, I used to get upsetting stomach-aches, which I thought were ulcers, and had an enlarged spleen, which was nothing relevant for the health workers I used to consult. All these years I always felt normal and healthy, although I had constant complications with my stomach, which I think I got used to until the fateful day I got unconscious from vomiting blood.

What kind of care and treatment did you receive?

I was given immediate first aid at Nakasero Hospital in Uganda to reduce my bleeding and tests started immediately to find out the cause of the bleeding. Upon discovery it was oesophageal varices, I had to undergo endoscopy band litigation 3 times. The doctor kept me strong. He was always there to attend to me in times of emergency when I would bleed to unconsciousness. As for my family and friends, they gave me financial support and stayed close to me during this trying period, as well as advising me on what lifestyle to adopt.

What were the main difficulties you had to overcome in terms of healthcare?

There were so many difficulties I had to overcome, the most frustrating one being failure to find out exactly what the problem is since most of the tests could not be done in Uganda. Difficulties like lack of drugs to stop bleeding in hospitals and pharmacies, lack of kits for banding and also the fact that there’s only one specialist in this field is scary too.

According to your own experience, what are the biggest stakes doctors and patients have to deal with?

Schistosomiasis is a silent killer that is all over the country, since the fresh water bodies and swamps as well as dams are all over the country. However due to its affiliation with the poorest communities on top of being illiterate, many people actually don’t understand it as they think its just worms; some even believe its sorcery which is absurd. According to my experience I think doctors must work to raise awareness about the disease first, as many don’t know how deadly it can be, and also train more health workers on how to handle chronic schistosomiasis aside from participating in Mass Drug Administration only. Vector control has also a key role to play through sanitation drives and provision of safe water to avoid people relying on infested water bodies like lakes and wetlands. Much more advocacy and awareness are also needed about this disease, as it’s the 2nd most deadly killer after malaria in Uganda.

Would you like to add something? To emphasize on some specific points on Bilharzia?

Bilharzia is not only for the poor communities as many people believe so. Anybody can get Bilharzia. It is a silent killer with little or unnoticed signs and symptoms until it gets chronic, very serious and irreversible. We must take on a severe fight against bilharzia.*not his real name.

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April 26, 2017 - Genepred, at the intersection of digital technology and biology

L’homme est sur le point de vivre sa plus importante mutation, depuis des centaines de milliers d’années. Alors que la biologie atteint ses limites, c’est le numérique qui est en passe de prendre le relais pour améliorer l’humanité. Rencontre avec Pierre Dessein, fondateur de Genepred, startup française qui mise sur un algorithme pour prédire et soigner les maladies.

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January 2, 2017 - Genepred wants to tackle cirrhosis with its predictive algorithm

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