IHU 2010 POLMIT SUMMARY A. INTRODUCTION 2 1. Why an Institute of University Hospital (IHU) on infectious diseases? 2 2. The institutional resources involved in Marseille and their skills 3 3. The coordinator of the project: Didier Raoult 13 B. PROJECT 14 1. The building 16 2. Care 18 3. Diagnosis 25 4. Epidemiology 33 5. Research 39 6. Valorization and transfer 43 7. Teaching 51 C. WORK PACKAGES (WP) 58 1. WP1. Contagion management in the hospital: Construction of a building 58 2. WP2. Monitoring the emergence of vectors and vector‐borne diseases 63 3. WP3. Microbiogenomics 67 4. WP4. Emerging pathogens detection and studies of microbiota 71 5. WP5. Point‐of‐Care (POC) 76 6. WP6. Physiopathology 80 7. WP7. Organization of collections 83 8. WP8. Valorization and Transfer 87 9. WP9. Life of the IHU 89 D. MANAGEMENT OF THE IHU 90 E. BUDGET OF THE IHU 94 F. EXPECTED RESULTS 95 G. APPENDIXES 97 1 IHU 2010 POLMIT A. INTRODUCTION 1. Why an Institute of University Hospital (IHU) on Infectious Diseases? In the 21st century, infectious diseases (ID) are a challenge that requires the coordination of research forces, epidemiological surveillance, diagnosis and care all at a single site. Major challenges include contagiousness, including intra‐hospital dissemination of disease; ID related to travel, outbreaks in the South and their risk of spread to the North; the treatment of chronic infections, including those that associated with major pathologies such as cancers; the discovery and monitoring of emerging pathogens and the detection of future human pathogens in the environment (including potential vectors and animal reservoirs). Finally, we face the challenge of the capacity of health systems (in the North and in the South) to manage the outbreaks, obtain public support for policies of prevention and fight against these risks at acceptable costs to the community. To meet these challenges, we propose to bring together important resources in the fields of basic research (not only in bacteriology, virology, parasitology, immunology and cell biology but also in epidemiology and human and social sciences) as well as infectious and tropical diseases (ITD), with the creation of a physical hub for ID, a building of 20,000 m2 dedicated to ID care and research. The building will have an area of hospitalization whose capacity should be within a range of 90 beds and include an extensive Biological Safety Level (BSL) 3 unit. The departments of ID as well as the laboratories of Nimes and Nice are already grouped in the Infectiopôle Sud foundation and will join in partnership. ITD continue to remain the leading cause of death worldwide, with 17 million deaths per year, or more than a quarter (27%) of all deaths. This infectious mortality disproportionately affects the poorest countries, which are predominately located in Sub‐Saharan Africa and South East Asia. The 43 poorest countries in the world (per capita incomes of less than 976 U.S. dollars) continue to suffer from massive premature death (less than a quarter of their population reach the age of 70), which is predominately caused by ID. This is why WHO (World Health Organization) lists the three most serious killers in the world as HIV (3 million/year), tuberculosis (1.6 million/year) and malaria (1.2 million/year). Additionally, lower respiratory tract infections cause 4 million deaths per year, diarrheal diseases cause 2 million deaths per year, and there are 3 million deaths annually from diseases that are preventable by vaccines (Morens DM et al. 2010 Nature 463:122). Due to a lack of research, more than one billion human beings currently suffer from one or more of the «neglected tropical diseases», which are characterized by the lack of diagnostic tools, vaccines and medicines to meet the specific needs of patients in poor countries. In the last 30 years, the globalization of trade, the migratory flow and the transport of travelers (international traffic increases by 6% per year), as well as climate change, have increased the movement of infectious agents and heightened the risk of global pandemics affecting, or likely to affect, our country. Several phenomena have been added to pandemic risks that call for a global response to «emerging» or «re‐emerging » ID: the chronicity of 2 IHU 2010 POLMIT certain viral infections, such as HIV and hepatitis; the prevalence of care‐associated or nosocomial infections, which affect nearly 5% of hospitalized patients in developed countries; the increasing capacity of microorganisms to resist the anti‐infective drugs available (antibiotics, tuberculosis drugs, antivirals, antifungals and antiparasitics)1; the discovery of the involvement of viral agents in the genesis of several chronic pathologies, including more than a quarter of cancers2; and even terrorist threats that include the danger of biological weapons. For 50 years, medicine has relied mainly on drugs to control infections. However, it appears that antibiotics were over prescribed, and resistance has developed rapidly. This resulted from the fact that therapeutic strategies are primarily empirical and that etiological diagnoses are rarely effective. An important goal of the 21st century is to standardize and apply at the clinical level the etiological diagnosis of ID to optimize ID management (Raoult D. et al. 2004 Nature Rev Microbiol 2,151‐9). The fight against contagious disease has decreased significantly, as the isolation of patients presumed contagious is no longer practiced or inefficient for both respiratory infections and nosocomial infections. Recent alerts have focused attention on potential epidemics, and in response, countries such as Italy, China and the USA have proposed the regrouping all medical and scientific resources for ID in one centralized location. The considerable increase in life expectancy of humans is one of the highlights of the last 10 years. Although there are multiple reasons, it is mainly a reflection of the progress made in the fight against ID. These changes are in turn responsible for an upheaval in the hierarchy of infectious medical problems in our country. The increase in life expectancy and hospital care has resulted in growth in population sensibility facing ID. Also, longer life can unmask the role of chronic viral infections such as etiology of certain cancers. ID are the result of interactions between people and their environment and the conflict between humans and microorganisms. For 20 years, many acute emerging infections have been identified. Marseille is particularly vulnerable to infectious agents; it is the European city that hosts the largest proportion of people of foreign origin. Thus, tropical diseases are common among people living in Marseille and the possibility of disease dissemination concerns the populations of inter‐region PACA/Languedoc Roussillon. 2. The institutional resources involved in Marseille and their skills Marseille, due to its geographic and demographic characteristics, has always been a gateway for migrants in the surrounding areas of the Mediterranean and the African continent. It is the oldest city in France and remains an important port for the South. It was founded by Greeks from Phocaea 1While 1 in 3 people in the world are infected with dormant Mycobacterium tuberculosis the emergence of strains of multidrug resistant M. tuberculosis (MDR‐TB) that are refractory to treatment with the main TB drugs (isoniazid and rifampicin) is worrisome. According to WHO, about 5% of new TB cases diagnosed each year are MDR; the 13 countries with the highest prevalence of MDR‐TB are all in Europe, in Eastern Europe in particular. Worse still, these last 3 years, the number of countries reporting cases of Extensively drug resistant TB (or XDR‐TB), a generally incurable disease in developing countries, has increased by almost 25%. 2The example of human papillomavirus (HPV) is very significant as it affects 3/4 of sexually active people. It predisposes women to cervical cancer. Helicobacter pylori, a bacterium that infects the gastric mucosa, is responsible for 80% of peptic ulcers. 3 IHU 2010 POLMIT (now a Turkish city in the vicinity of Izmir). Demographically, Marseille has a population that is naturally connected to the tropics. Thus, every year there are about 150 recorded cases of malaria in residents of Marseille returning to their home countries for short stays; this is especially true for residents visiting Comoros. The geographic position of Marseille explains why the city is especially specifically exposed to contagious agents. History records three outbreaks of plague that were spread from the city; the first outbreak occurred from 1347 to 1353, the second in 1580 and the last but most important in 1720. The last outbreak decimated the city and spread to the entire Provence, killing between 90,000 and 120,000 people out of a population of approximately 400,000. These epidemics strongly marked the history of the city, and they are the reason that care facilities (diagnostics, research and teaching of ID) were established in the city and its immediate surroundings. Marseille had a unique historical evolution, and its detachment from the French royal dynamic has prevented the creation of university structures that would have allowed a better development of medical schools. However, medicine has always been practiced at a very high level, as evidenced by the creation of the Bonaparte Internat des Hôpitaux of Marseille immediately following the creation of the Internat des Hôpitaux of Paris. This created a chasm between medical practice recognized for excellence and the lack of formal institutions for medical education. Ultimately, the creation of a Medical School in Marseille was carried out during the 19th century thanks to the "colonial" vocation of the city. In 1905, the French army established its training, expertise and research in tropical medicine at Pharo in Marseille for geographical and historical reasons. Over the last 15 years, Marseille has become a major place of ITD research with over 400 publications per year in international scientific journals; studies have been predominately focused on clinical microbiology and ID.