1. Emerging diseases Nguyen Tien Dung DVM, PhD. Head of Virology National Institute for Veterinary Research 86, Truong Chinh, Dong Da, Hanoi

2. EMERGING DISEASE WHO’s definition: An emerging disease is one that has appeared in a population for the first time, or that may have existed previously but is rapidly increasing in incidence or geographic range

3. Which are they? GROUP II - RE-EMERGING PATHOGENS (human only) Enterovirus 71 Clostridium difficile Coccidioides immitis Mumps virus Prion diseases Streptococcus, group A Staphylococcus Aureus Coccidioides immitis GROUP III – AGENTS WITH BIOTERRORISM POTENTIAL - NIAID – Category A - NIAID - Category B - NIAID - Category C GROUP I – PATHOGENS NEWLY RECOGNIZED IN THE PAST TWO DECADES (humans only) Acanthamebiasis Australian bat lyssavirus Babesia, atypical Bartonella henselae Ehrlichiosis Encephalitozoon cuniculi Encephalitozoon hellem Enterocytozoon bieneusi Helicobacter pylori Hendra or equine morbilli virus Hepatitis C Hepatitis E Human herpesvirus 8 Human herpesvirus 6 Lyme borreliosis Parvovirus B19 Nipah virus

4. J Clin Invest. 2004 March 15; 113(6): 796–798.

5. http://www.who.int/csr/don/archive/disease/en/

6. WHAT ABOUT VIETNAM? Human: Sars (2003) AI (2003) Rubella (2005) Foot, hand and mouth (2006) Str. suis (2007) Cholera (2007) Animal: Foot & Mouth (1995) AI (2003) Capripox (2004) PRRS (blue ear disease - 2007)

7. WHY ARE THEY EMERGING? Pathogen nature: RNA virus is prone to mutation Environment degradation (deforestation, chemical, vectors, wild animals, land use…) Population displacement (more contact, rapidity) World population increase (food need, hygiene…) Resistance to drugs (malaria) Industries: prions. Food-born …

8. Virus nature (example) RNA viruses: spontaneous mutation 1/1,000 as compared to 1/100,000,000 in DNA Mutation due to chemicals Adaptive evolution (vaccine, new host…) Re-assortment: AI Recombination

9. Phylogenetic relationship of 19 PRRSV CAVs. Letters (A, B, and C) represent the lines of pig passages in which the variant was detected during 367 days of in vivo replication. Lines represent the distances of sequence divergence from the ancestor (CC-01). J Virol. 2002 May; 76(10): 4750–4763.

10. Emergence of the AIVH5N1 (1997) Hång K«ng

11. H9N2 H6N1 H5N1 G1 w312 Gs/Gd H5N1/97 H?N? H5N1/2001 H?N? Y280 H9N2 A B C H9N2 H6N1A B C D E H9N2 (Y280) Virus cóm HK N¨m 2001 N¨m 1997 stop Qu¸ tr×nh TiÕn Hãa vi rót Cóm gia CÇm t¹i Hång K«ng (theo Guam et al, 2002) PB2 PB1 PA HA NP NA M NS

12. PB2 PB1 PA HA NP NA M NS H5N1 g©y bÖnh t¹i ViÖt Nam (ViÖn Thó y, ViÖn VSDT vµ §H Hèng k«ng) A/Gs/Gd/96 (H5N1) 1996 - Do tæ hîp tõ mét vi rót sinh ra nhiÒu vi rót míi

13. - Newly identified viruses - Advances in virology - Urban migration - Population displacement - Quality of environment New viruses in global village 2000 1900 1600 1700 1800 - World population While the world population soars and the quality of the environment degrades, the number of the newly identified viruses increases. These viruses are the cause of emerging diseases in humans, animals and plants that may have a devastating impact on the world’s health. Source: Havard University Press, 1992

14. When, where & how? More and more frequent. Vietnam: AI, PRRS, Cholera, Dengue, FHMD… only in 2006-2007. Where: – Every where e.g. AI, HIV/AID – West Nile in USA – FHMD in Vietnam 2006 – ASF in Georgia 2007 – … How: from a regular basis to a more randomness.

15. http://www.who.int/csr/don/archive/disease/en/

16. Summary What: Emerging and re-emerging diseases When and where: Appear each day more and more frequently (in time) and in any place and few days it can be spread all over the world (in space). For ex. : SARS Why: Convergence theory (it is not due to a single reason). It may be the paying back for the development. How: unpredictable.

17. WHAT WE ARE DOING Concept of emerging diseases: 1990’s Institutional level : three main tasks have been worked out: – Preparedness Strategies of fighting. – Emerging disease centers – Information network Scientist level: – Mathematic modeling – Computer based simulation of the disease (outbreak) – Statistic: to test hypothesis.

18. Emerging Disease Centers Only in industrialized countries In the developing countries: hindered by the endemic diseases and resources The development is a irreversible process (world population, transport…); few factors can be recovered (environment); Emergence disease apparition is so a going on process; efforts are now focused on monitoring, early detection and control measures.

19. THE CENTRES New techniques of diagnosis and screening (molecular and computer techniques combined) : Real-time PCR, sequencing… (simple & easy to use device + results to satellite and to the centers). Systematic surveillance (modern epidemiological approaches) Objective: gathering all the data for a prompt processing for an early alerting.

20. Influenza Diagnostic Technologies Nucleic Acid Detection: Nucleic Acid Arrays Flow-through arrays Microarrays,GeneChips Nucleic Acid-targeted Liquid Arrays www.combimatrix.com BioTrove.com

21. Influenza Diagnostic Technologies Nucleic Acid Detection: RT-PCR and qRT-PCR Single Target and Multiplex Single tube and 96-well Wet reagent, lyophilized Commercial kits (AI, H5) Fully-integrated technologies (extraction to result)

22. Objectives New techniques: early detection, pathogen identification and comparison with the previously existed ones. Epidemiology: measuring the disease (in time and space), understanding the disease (transmission, reservoir, immunity, treatment…), GIS +environment data. Hence, work out effective measures

23. The Genomics Program of the Division of Microbiology and Infectious Diseases at NIAID, USA established in 2004. http://www3.niaid.nih.gov/research/topics/pathogen/default.htm. http://www3.niaid.nih.gov/research/topics/pathogen/default.htm Infect. Immun. 2007 July; 75(7): 3212–3219

24. NIAID BRCs (8 Bioinformatic Resource Centres) BRC name (URL), principal investigator (institution) Organisms assigned (no. of genomes in the BRC as of March 2007) Institutions ApiDB (http://www.apidb.org), David Roos (University of Pennsylvania), Apicomplexan species, including Toxoplasma gondii (1), Cryptosporidium spp. (2), Theileria spp. (2), and Plasmodium spp. (8) University of Pennsylvania, University of Georgiahttp://www.apidb.org BioHealthBase (http://www.biohealthbase.org), Richard Scheuermann (University of Texas Southwestern Medical Center) Giardia lamblia (*), Mycobacterium spp. (10), influenza virus (10,880), Francisella tularensis (5), Encephalitozoon cuniculi (1), and Ricinus communis (*) Northrop Grumman Information Technology, University of Texas Southwestern Medical Center, Vecna Technologies, Amar Internationalhttp://www.biohealthbase.org ERIC (http://www.ericbrc.org), John Greene (SRA International, Inc.) Diarrheagenic Escherichia coli (10), Shigella spp. (9), Salmonella spp. (6), Yersinia enterocolitica (0), and Yersinia pestis (7) SRA International, Inc., University of Wisconsin—Madisonhttp://www.ericbrc.org NMPDR (http://www.nmpdr.org), Rick Stevens (University of Chicago) Staphylococcus aureus (11), pathogenic Vibrio spp. (11), Listeria monocytogenes (15), Campylobacter jejuni (10), Streptococcus pyogenes (12), and Streptococcus pneumoniae (2) University of Chicago; FIG; University of Illinois, Urbana-Champaignhttp://www.nmpdr.org Pathema (http://pathema.tigr.org), Owen White (TIGR) Bacillus anthracis (10), Clostridium botulinum (1), Burkholderia mallei (7), Burkholderia pseudomallei (7), Clostridium perfringens (3), and Entamoeba histolytica (1) TIGR, University of Marylandhttp://pathema.tigr.org PATRIC (http://patric.vbi.vt.edu), Bruno Sobral (VBI) Brucella sp. (4), Coxiella burnetii (4), Rickettsia sp. (10), caliciviruses (77), coronaviruses (217), hepatitis A virus (47), hepatitis E virus (65), and lyssaviruses (15) VBI, Loyola University Medical Center, Social and Scientific Systems, University of Maryland, Swiss Institute of Bioinformaticshttp://patric.vbi.vt.edu VBRC (http://www.vbrc.org), Elliott Lefkowitz (University of Alabama—Birmingham) Viral pathogens belonging to the following families: Arenaviridae (106), Bunyaviridae (857), Filoviridae (27), Flaviviridae (498), Paramyxoviridae (169), Poxviridae (106), Togaviridae (83), and hepatitis C virus (*)University of Alabama—Birmingham; University of Victoria, British Columbia, Canada; Columbia Universityhttp://www.vbrc.org VectorBase (Invertebrate Vectors of Human Pathogens [http://www.vectorbase.org]), Frank Collins (University of Notre Dame) Anopheles gambiae (1), Aedes aegypti (1), Culex pipiens (1), Pediculus humanus (1), and Ixodes scapularis (1)University of Notre Dame; European Bioinformatics Institute; Imperial College of London; Institute of Molecular Biology and Biotechnology, Crete; Harvard University; Purdue University; University of California—Riversidehttp://www.vectorbase.org J.Virol. 2004 April; 78(7): 3684–3703.

25. AN EXAMPLE: H5N1 BIRD FLU Two main concerns (among many others): Virus: is it changed; how much is the change; what does the change mean? Which one is good for vaccine production? Epidemiology: Is there human to human transmission? How is it distributed?

26. Probability of AI Outbreaks based on Logistic Regression Model for 1 st AI Epidemic Courtesy: DAH -Vietnam

27. INFORMATION NETWORKS Much more in progress due to IT as compared to the establishment of Centres. ProMedmail was established in 1993 (ProMED-mail, www.promedmail.org). Disease information in the world is hourly updated.www.promedmail.org

28. Summary Emerging diseases continue to appear in the world and become a risk for the humans, animals and plants. The preparedness to fight the disease is a stake of future of the earth

29. Xin cám ơ n