Prospective Studies ofAvian Influenza

Transmission in AsiaLaura 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 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

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

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

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

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

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

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

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

*As of November 12, 2007, WHO

http://www.pbs.org/wnet/wideangle/shows/vietnam/

map.html

http://www.pbs.org/wnet/wideangle/shows/vietnam/

map.html

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.

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

Kamphaeng Phet Province (KPP)

Bangkok

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

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)

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

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

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

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

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

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

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.

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

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