Prospective Studies of Avian Influenza Transmission in Asia

1. Prospective Studies ofAvian Influenza Transmission in Asia Laura Lee MPH Candidate The University of Iowa Mentor: Dr. Gregory Gray Preceptor: Dr. Robert Gibbons The Armed Forces Research Institute of Medical Sciences

2. Abstract • May - August 2007 • Worked as a local study coordinator at the KAVRU, Kamphaeng Phet, Thailand • Prospective Studies of Avian Influenza Transmission in Asia • PI: Dr. Gregory Gray • Follow 1600 adults with exposure to poultry in Cambodia and Thailand for the evidence of avian influenza infection for over three years • Collaboration with the United States Department of Defense overseas laboratories and Ministry of Health officials in Thailand and Cambodia

3. Interventions/Activities • Assisting a local staff obtain an Institutional Review Board (IRB) approval from the Thai Ministry of Health (MOH) • Selecting field sites by compiling and updating demographic and animal-related data from local public health offices and villages • Assisting in writing a Standard of Operating Procedures (SOP) • Designing a log number system for specimen collection and processing • Planning for village enrollment

4. Collaborating Research Centers • The Center for Emerging Infectious Disease (CEID) • Research center in the College of Public Health at the University of Iowa, Iowa City, Iowa • Focuses in researching emerging infectious diseases with special interest in emerging respiratory viruses such as adenoviruses, human metapneumovirus, and influenza • U.S. Naval Medical Research Unit No. 2 (NAMRU-2) • Department of Defense overseas laboratory located in Jakarta, Indonesia • Its primary mission is to study infectious diseases of military importance in Asia • A satellite laboratory in Phnom Penh, Cambodia http://www.public-health.uiowa.edu/CEID

5. Armed Forces Research Institute of Medical Sciences (AFRIMS) • Located in Bangkok, Thailand • Established in 1958 to study cholera epidemic in Thailand • Current research interests include vector-borne diseases, malaria, emerging infections, and enteric diseases of military importance in Asia • Over 40 field sites and research laboratories in Southeast Asia • Funded by the US Department of Defense www.afrims.org

6. AFRIMS - Mission & Objectives • Monitor and assess potential disease threats - especially emerging infectious diseases • Evaluate new drugs and vaccines for prophylaxis and treatment of militarily important infectious diseases • Develop and test new forward-deployable rapid diagnostic methods • Investigate and test new control measures against infectious disease vectors to interrupt disease transmission • Define the epidemiology of militarily-important diseases endemic to tropical regions • Advise the Commander-in-Chief (CINC), Pacific Command and the U.S. Ambassador, Thailand on tropical disease threats • Develop infrastructure and continue proactive training, development and technology transfer to Thai medical research for Thai control and responsibility www.afrims.org

7. Kamphaeng Phet-AFRIMS Virology Research Unit (KAVRU) • One of AFRIMS’ satellite research laboratory • Has been involved with vaccine developments and field testing of new vaccines • Current project: Prospective Study of Dengue Virus Transmission and Disease in Primary School and Village Children in KPP (2003-07) • As of 2007, finished collecting 4-year-surveillance data • Planning a vaccine trial involving 2000 school children

8. Avian Influenza (“bird flu”) • AI is an infectious disease of birds caused by type A strain of the influenza virus, which causes a wide range of symptoms in birds • AI do not normally infect humans. Highly pathogenic strains such as H5N1 may cause severe respiratory illness in humans • Most of human cases have occurred among those in close contact with infected birds or objects contaminated with their feces • However, a virus may mutate and be easily transmissible between humans leading an influenza pandemic World Health Organization

9. AI in Southeast Asia • H5N1 outbreaks in many Asian countries since late 2003 • Among poultry (5): Bangladesh, Indonesia, India, Myanmar, and Thailand • Human cases (2): Indonesia and Thailand • 25 human cases in Thailand* • 17 cases have been fatal • Most cases occurring in 2004 • Last reported case in Sept 2006 • A need for good epidemiological collection and surveillance system *As of November 12, 2007, WHO http://www.pbs.org/wnet/wideangle/shows/vietnam/map.html

10. Study Objectives/Hypothesis • Design: • A three-year prospective study of H5N1 transmission among 1600 adults with exposure to poultry in Asia: 800 subjects from KPP, Thailand and 800 subjects from Kampong Cham Province, Cambodia. • Objectives: • To monitor adults with poultry contact for evidence of H5N1 infection • To determine risk factors for H5N1 infection among people with close poultry exposure • To characterize H5N1 isolates associated with human infections • Hypothesis: • Prevalence and incidence of H5N1 infection will be higher for those with more hours of exposure to poultry per week than those with less hours.

11. Study Components • Enrolling subjects • Sera and questionnaires collected • Weekly home & annual follow-up visits • Report any Influenza-Like Illnesses (ILI) • Village health workers • Investigation of ILI • 24-hour on-call staff • Serum & throat swabs collected • Family study of influenza transmission • Family members asked to participated • Specimen processing • KAVRU, CEID, Thai MOH

12. Kamphaeng Phet Province (KPP) • One of the 76 provinces in Thailand • Mainly rural • Total population: 728,000 • Male: 362,000 • Female: 366,000 • Region most affected by an outbreak of H5N1 in 2004-05 • Extensive culling occurred to control the outbreak, which lead to significant depopulation of poultry • Since, culling has been discouraged due to decreasing reports of large poultry die-offs • Many have repopulated their poultry • Caging of poultry encouraged yet poorly enforced KPP Bangkok

13. Field Site Selection • Source of information: • Ministry of agriculture and Livestock office provided animal-related data • Local public health offices provided specific info on housing layout and population demographics • Selection criteria: • Distance to healthcare facility • Distance to KAVRU • Density of poultry in sub-district • Population • Number of households • Density of animals such as fighting-cocks, ducks, pigs, wild birds, and cats • Recent outbreak of AI (2004 or 2005)

14. Field Site Selection (cont.) • Eight sites selected in the Meung District, KPP • Accessibility • All sites are within 35 km from the KAVRU • Villages are within 10 min drive of a local PH office • Villages are near a major road unless otherwise specified • Exposure • Moderate to high animal-animal cross-interaction and human-animal interaction • Caging encouraged yet poorly enforced • Some villages have many fighting-cock breeders • Confirmed outbreak of AI in 2004-05

15. Log Number System • A multi-site study that involved collecting multiple numbers and types of specimens • Designed a log system for specimen collection/processing • Each site assigned a site code that every label will start with • Each subject assigned a unique number during enrollment • During family ILI-investigation, the number assigned to each family member will contain matching cohort number • Three family members with a subject number 089 at site T4 • T408900 (cohort), T408901 (family #1), T408902 (family #2) • A letter at the end will indicate type of specimen

16. Results/Lessons • I developed skills and knowledge to work well in a diverse public health setting and dealt with challenging situations involving an international study involving multiple sites • Learned to effectively communicate both in writing and orally to accurately relay information to public health professionals • I had the rare opportunity to interact and work with many public health professionals from various international organization. • I observed at first hand how the PH professionals were dealing with current challenges of emerging global PH threat

17. Recommendations • Working closely with the Thai Ministry of Health (MOH) to obtain the IRB approval • Before an enrollment can begin, • Pilot testing questionnaires to a selected group of villagers • Conducting a village-wide meetings to inform villagers and local PH officials about the aims of the study • Creating a system for selecting houses so the research nurses will know exactly which houses to visit • Hiring more staff • A need of 24-hour on-call team for ILI investigation • Laboratory technicians, and research nurses

18. Communication Skills • Participated in weekly teleconference calls with the PI and other collaborating researchers • Wrote weekly reports to inform the PI of daily activities • Kept in regular correspondence through emails • Relayed scientific information between the local staff and other researchers • Informed local staff about specifics about the study and relayed concerns of the PI

19. Analytical/Assessment Skills • Collected and updated information on animal-related and demographic data in order to select eight field sites • Identified relevant and appropriate data and info source • Visited villages and discussed the info with the local staff to attach meaning to the collected data • Identified gaps and discrepancies in sources of the data • Designing a log number system for specimen collection • Assessed and analyze the main components of the study • Worked closely with the statistician and the local administrative team to identify and fix the problems of the system

20. Cultural Competency Skills • All-Nets • Three months of Thai tutoring lessons to learn about the culture and the language • Working with the local staff • Only foreigner in the laboratory • Learned to communicate with the staff who were at different levels of English • Consulted the local staff on site selection and log number system so that they also felt comfortable with the information and that the info applied to the local setting • Participated in several activities outside the work in order to learn about their culture and to share mine. • Playing sports, cooking, taking weekend trips, etc.

21. Acknowledgements • Dr. Gregory Gray and the staff; The Center for Emerging Infectious Disease (CEID) • Drs. Robert Gibbons,In-Kyu Yoon, and the staff; The Armed Forces Research Institue of Medical Sciences (AFRIMS) • Dr. Thomas Cook and Kristina Venzke; The Minority Health International Research Training (MHIRT) program • The University of Iowa College of Public Health

22. References • University of Iowa, 2006- Center for Emerging Infectious Diseases. http://www.public-health.uiowa.edu/CEID • Council on Linkages Between Academia and Public Health Practice. http://www.trainingfinder.org/competencies/list_nolevels.htm • The World Health Organization. Avian Influenza fact sheet. http://www.who.int/topics/avian_influenza/en/ • The Armed Forces of Research Institute of Medical Sciences. www.afrims.org