COMPLEXITY AND BIOSECURITY: Molecular Detection of Emerging Threats

Transcription

1 COMPLEXITY AND BIOSECURITY: Molecular Detection of Emerging Threats Herawati Sudoyo Eijkman Institute for Molecular Biology Presented at Workshop on Complexity and Governance, Singapore, July 2013

2 MEGATRENDS - Societal Increasing wealth and urbanisation Low tolerance for risk Environmental Climate change Financial Economic crisis? Energy costs Biological GM technology Antibiotic resistance Emergence of zoonotics 21 st CENTURY THE CENTURY OF COMPLEXITY AND FEAR

3 Mission - To advance fundamental knowledge in the field of molecular cell biology, and to apply such knowledge to the understanding, prevention and treatment of human diseases

4 SCIENCE AT THE EIJKMAN INSTITUTE SUPPORTED THE DEVELOPMENT OF DISEASE MANAGEMENT SYSTEM Human Genome Diversity and Disease. Taking advantage of the huge human genetic resource of Indonesia, as reflected by its many ethnic populations - as the basis for disease genes discovery, with their medical and biotechnological applications.

5 EIJKMAN INSTITUTE and STRATEGIC RESEARCH The peopling of the Indonesian archipelago - population markers DNA Barcoding for speciation has been used in most animal for nonforensic context - fish and its larvae, insects, primates, marine organisms, parasites and others Forensic DNA laboratory has established its credibility since 2004 dealing with terrorism cases Application of forensics to wildlife crime investigation involves genetic species identification

6 Indonesia and Infectious Diseases a Great Challenge to Mitigate Biorisk Problems with emerging and reemerging infectious diseases Most caused mainly by environmental, ecological or demographic factors spread by travel and trade Indonesia is a maritime country with islands, 700 languages, 33 provinces, 220 million population Problems with people movement Recognize the need to develop, strengthen and maintained the capacity to detect, report and respond to public health events

7 National Actions to Promote Capacity Building WHAT ARE WE FACING? Indonesia a very diverse populations vast genome diversity disease management complex Indonesia - a rapidly developing country with serious challenges in infectious (emerging and reemerging) and zoonotic diseases

8 Indonesia A Rapidly Developing Country With Serious Problems In Infectious Disease Malaria: 15 million cases and 42,000 deaths/year (2005) - highest case number and fatality rate in the world; increasing drug resistant parasites Tuberculosis: ranked third in TB burden following India and China - TB is third major causes of mortality increasing drug resistant Estimation: 269 TB cases/100,000 Dengue: 123,174 cases,1,251 deaths (2007) Hepatitis B: 10% of population are carriers Moderate-to-high endemic (WHO) Avian Influenza: highest case number and fatality rate in the world Anthrax, Chickenpox, HIV-AIDS, Meningitis, Plaque, Hantaan and Nipah, Ricketsiosis

9 NOT ONLY BIRD THAT CAN SPREAD THE FLU

10 THE WORLD WITHOUT BORDERS

11 INTRODUCTION TO BIOSAFETY AND BIOSECURITY Terms are relatively new in the region - have not been emphasized until the introduction of anthrax powder as a bioterrorism tool Biosecurity encompasses minimizing risk through biological harm, not least being the economic impact from spread of alien species. The ability to implement risk management strategies through early detection system which allow prediction of species, and also monitoring is necessary.

12 BIORISK SPECTRUM (BIOLOGICAL RISK) Natural Accidental Intentional Outbreak Epidemic Pandemic Laboratory acquired infection Containment failure Negligence Sabotage Biocriminal Bioterorism Biosafety Biosecurity

13 WHAT DO WE MEAN BY BIOSECURITY? WHO sets out a limited definition of laboratory biosecurity and describes it as the "protection, control and accountability for valuable biological materials within laboratories in order to prevent their unauthorized access, loss, theft, misuse, diversion or intentional release"

14 BIOSECURITY Biosecurity - recent concept that appeared in parallel with discussions about the growing bioterrorist threat. Its meaning has expanded in scope. Biosecurity is the objective of the whole range of policies, mechanisms, regulations, and initiatives that also includes export controls, biodefense, GLP, GMP, national implementation of the BTWC including the obligation to create national legislation relating to biosecurity, and diplomacy etc that together minimise the possibility that the life sciences will be misused for hostile purposes.

15 Reducing risk of natural infection, accident and misuse need complex and good management

16 MOLECULAR DETECTION OF EMERGING THREATS: DNA BAR CODES FOR BIOSECURITY COI pb Molecular diagnostic tools - rapid and accurate identification of morphologically indistinct alien species DNA barcoding use information within a single gene region common across all taxa and to access that information by DNA sequencing under universal conditions. Provide standardization and efficiency needs lacking in international biosecurity community

17 HATARI! Danger (Swahili) The Effort to Mitigate Emerging Infectious Pathogens of Wildlife

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20 The long road to Tesso Nilo

21 Palm oil tree plantation along the way

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24 From Uryu et al. 2007

25 Tesso Nilo, Riau August 2012 (Doc. WWF ID) - Elephant s habitat replaced by palm oil plantation WHERE DO THE WILDLIFE LIVE NOW?

26 ELEPHANT POPULATION ESTIMATE IN RIAU FROM From: Uryu et al. 2007

27 Sumatran Elephant Population BUKIT TIGAPULUH Analysis using Genetic Approach NATIONAL PARK, JAMBI TESSO NILO NATIONAL PARK, RIAU -249 fecal sample -Multiplex PCR -13 microsatellite markers - 3 sex-associated markers -Ongoing analysis on 108 sample 64 female, 19 male -357 fecal samples -Multiplex PCR -14 microsatellite markers - 3 sex-associated markers -Latest results: 101 individuals 74 female, 29 male, 1 ND WAY KAMBAS NATIONAL PARK, LAMPUNG fecal samples -Multiplex PCR -13 microsatellite markers - 3 sex-associated markers -Latest results: 139 individuals 117 female, 21 male 1 ND

28 Aim : 1. Best-practice for the extraction and genetic analysis of DNA from dung samples. 2. The use of genetic markers (mtdna, microsatelite, sex determination) for capture-recapture analyses and the estimation of population size provide scientific basis for conservation purposes 3. Provide estimates of genetic diversity for each of 6 sampled populations.

29 June 8 th 2013 HOW MANY OF THEM LEFT?

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31 Exploitation of forest area without respect reduce the size of natural habitat IUCN 2007: Sumatran orang utan critically endangered; Bornean endangered

32 Geographically Origin of Borneo Orang Utan Based on Taxonomy Sumatra (Pongo pygmaeus abelii) Borneo (Pongo pygmaeus pygmaeus) Based on cranial and dental morphologies; and MtDNA control region- Borneo Orangutan further classification: Serawak and Northwest Kalimantan (P. pygmaeus pygmaeus) Central and Southwest Kalimantan (P. pygmaeus wurmbii) East Kalimantan and Sabah (P. pygmaeus morio) Conservation = Rescue + Release

33 Rehabilitation and reintroduction of orangutan need a specific attention related to genetic, health, behavioral contamination and geography. Samboja Lestari Nyaru Menteng Sample Collection (blood): 1. ORC Nyaru Menteng, Central Kalimantan (94) 2. ORC Samboja Lestari, East Kalimantan (6) Result 6 distinct subpopulations within Bornean orangutans Sequence motif to differentiate between Sumatran and Borneo orangutan subspecies Specific motif: East (8) Central A (2) Central B (1) Central and Southwest (89) Kalimantan The orangutan subpopulations should be protected in each geographic region to ensure their genetic diversity and survival

34 PHYLOGENETIC TREE AND BARCODE DIAGRAM INDICATE COI GENE CAN DIFFERENTIATE SPECIES OF MALARIA PARASITE 0.05 CONSENSUS PvivaxEI 100 Psimium 36 Pvivax Pknowlesi PknowlesiEI Psimiovale Pfieldi 18 Pcynomolgi 16 PcynomolgiEI 98 Pfragile 28 Pcoatneyi 97 Pinui Phylobati Pgonderi 90 Pmalariae 100 PmalariaeEI Povale PovaleEI 100 Pchabaudi PchabaudiEI 100 Pyoelli PyoeliEI 100 Pberghei 100 PbergheiEI Pmexicanum 81 Pjuxtanucleare 56 Pfloridense 80 Pgalinnaceum 100 PgallinaceumEI 100 Pfalciparum PfalciparumEI 100 Preichinowi 100 PreichinowiEI Theileria prava Human Malaria Parasites Primate Malaria Parasites b p Reptile Malaria Parasites Rodent Malaria Parasites Avian Malaria Parasites Theileria prava - Outgroup

35 Phylogenetic tree of 19 orangutan s malaria parasite showing 3 different clusters of ovale, malaria and falciparum-types PvivaxNC PsimiumNC PvivaxAF PvivaxAY PsimiumAY PvivaxY17721 PknowlesiAY PknowlesiAY PknowlesiNC PcoatneyiAB PfragileAY PcynomolgiAY PfieldiAB PsimiovaleAY Valent-12 Kejutan-48 KetutSatrio-6 PhylobatiAB PinuiAB Mayfalica-14 Bulan-13 Eropa-1 Lomon-5 Dogie-2 Eka-8 Shiba-41 Asapa-9 Puput-49 Yuyu-11 Pink-4 Susi-42 MissTut-3 Gilang-47 Romeo-50 PgonderiAY PovaleAB PmalariaeAB PmalariaeAF PreichinowiAJ PreichinowiNC Sisil-17 PfalciparumAY PfalciparumAJ PfalciparumNC PfalciparumM76611 PfalciparumAJ PfalciparumAJ PfalciparumAJ PfalciparumM99416 Theileria prava 3 Ovale-type 15 Malariae-type parasite Falciparumtype

36 Reported Cases Of Plasmodium Knowlesi Infection In Human Host Jumping Naturally acquired human Plasmodium knowlesi infection, Singapore Tek Ng et al, Emerg Infec Dis 14:814 Human infections with Plasmodium knowlesi, the Philippines Luchavez et al. Emerg Infect Dis 14:811 Swedish traveller with Plasmodium knowlesi malaria after visiting Malaysian Borneo Bronner et al. BMC 8:15 Human Plasmodium knowlesi infections in young children in central Vietnam Van den Eede et al, BMC 8:249 Plasmodium knowlesi in human, Indonesian Borneo Figtree et al, Emerg Infect Dis 16:4 First case of detection of Plasmodium knowlesi in Spain by Real time PCR in a traveller from Southeast Asia Tang et al, Malaria J 9:219

37 Parasite, Bakteria and Viruses Zoonosis Animal Animal Human Human Anthroponosis Human Animal Michalak et al, Emerg Infect Dis,1998: Mycobacterium tuberculosis infection as a zoonotic disease: Transmission between humans and elephants. Three elephants from an exotic animal farm in Illinois died of pulmonary disease due to M. tuberculosis. A fourth living elephant was culturepositive for M. tuberculosis. Twenty two handlers were screened for TB; One culture positive active TB. Molecular diagnosis showed that the isolates from the four elephants and the handler were the same strain. The investigation indicates transmission of M.tuberculosis between humans and elephants

38 MEDIA COVERAGE - EBOLA AND AVIAN FLU (Not Mutation but man made)

39 Bioterrorism is an act of bioterrorist to deliberately release of biological agents, in order to cause death or disease in humans, animals, or plants The motif of the bioterrorist is mostly to create fear and/or intimidate government or societies in the pursuit of political, religious, or ideological goals.

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41 353 healthy Pongo pygmaeus from central and east Kalimantan 65/353 (18.4%) and 6/353 (1.7%) seropositive for EBOV and MARV Majority of sera showed specificity to Zaire, Sudan, Ivory coast or Bundibugyo virus found in Africa Result suggest the existence of multiple species of filoviruses or unknown filoviruses-related in Indonesia and transmission from unidentified reservoir hosts into the orang utan populations

42 TOWARDS ONE HEALTH CAPACITY BUILDING IN IDENTIFICATION AND SURVEILLANCE through EMERGING PANDEMIC THREATS (EPT) PROGRAM

43 PREDICT ANIMAL STUDY Pathogen Detection - identification of novel wildlife pathogens that pose a significant public health threat: Capacity building - Wildlife surveillance at humananimal interfaces; non-invasive sampling; Technology development and pathogen discovery/ diagnostics - PREDICT viral family (14) Coordination with National Committee of Zoonoses and related government partners: Ministry of Agriculture, Ministry of Forestry, and Ministry of Health

44 PREDICT - HUMAN STUDY To detect new and known zoonotic pathogens that are spilling over from wildlife into humans. Better understand the presence/prevalence of emerging pandemic threats circulating in people Begin providing updated information to clinicians to improve diagnosis and treatment protocols

45 WILDLIFE SURVEILLANCE AT HUMAN ANIMAL INTERFACE: wet markets, wild macaque colonies, national parks on bats, rodents and primates

46 BUILDING CULTURE OF RESPONSIBILITY Biosecurity in Indonesia - a multi sector issue with unique priorities and challenges Coordination between MFA. MOH, MOA/DGLSAHS, MST, MOTI, MOD and private sector Best practices of biorisk management system Accountability and oversight Awareness and Education

47 Building Biorisk Culture in Indonesia Challenge that We Should Face Together unconscious competent culture conscious competent heard understood applied conscious Incompetent heard understood not applied unconscious incompetent heard not understood Geneva WHERE ARE WE NOW?

48 WHAT TO OFFER TO COMPLEXITY SCIENCE? The Population Dynamics of Emerging pathogens? Emergence due to anthropogenic change, Emergence of pathogen in an introduced species (alien), Emergence of a potential human pathogen from transportation of a wildlife pathogen The environmental and social influences on emerging infectious diseases: past, present and future? Travel and trade, land use and environmental change

49 Thank you for your kind attention