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Prospective Studies of Avian 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 . Abstract. May - August 2007

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Prospective Studies of Avian Influenza Transmission in Asia

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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

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  • 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

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  • 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

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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

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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

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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

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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

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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

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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

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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.

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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

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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



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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)

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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

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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

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  • 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

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  • 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

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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

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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

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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.

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  • 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

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  • University of Iowa, 2006- Center for Emerging Infectious Diseases.

  • Council on Linkages Between Academia and Public Health Practice.

  • The World Health Organization. Avian Influenza fact sheet.

  • The Armed Forces of Research Institute of Medical Sciences.

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