Department of Virology: Research Projects

Influenza Surveillance Service

Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand is undertaking influenza surveillance with regional U.S. Embassy Medical Units. During the current novel influenza A (H1N1) outbreak, we will continue to conduct this influenza surveillance in which you can send respiratory samples to AFRIMS for influenza testing.

Click here for more info on Influenza Surveillance Service

Title of the Study: Prospective, Randomized, Double blind, Placebo Controlled Field Efficacy Trial of Candidate Hepatitis E Vaccine

Principal Investigators: Robert McNair Scott, M.D., former Head of Station, WARUN; Mrigendra P. Shrestha, M.B.B.S., Chief Medical Officer, WARUN

Location: Shree Birendra Hospital, Chaun, Kathmandu, Nepal (administered by WARUN)

Collaborating Institutions: United States Army Medical Material Development
Activity (USAMMDA); Glaxo Smith Kline Beecham Biologicals (GSK Bio);
Royal Nepalese Army, Chauni, Kathmandu, Nepal.

Description: This efficacy trial is designed to assess whether a candidate HEV vaccine affords protection against Hepatitis E disease so as to ensure that the large investment required for a manufacturing establishment is warranted.

Status: Unblinding completed; results to be released shortly; long-term immunogenicity plan under development.

Title of the Study: A Phase I/II Trial of a Tetravalent Live Attenuated Dengue Vaccine in Flavivirus Antibody Naive Children

Principal Investigators: Stephen J. Thomas, M.D., MAJ, Medical Corps, USAMC-AFRIMS; Sriluck Simasathien M.D., Infectious Disease Consultant, Department of Pediatrics, Pramongkutklao Hospital, Bangkok

Location: Watsamiannaree School and Phramongkutklao Hospital, Bangkok

Collaborating Institutions: Department of Pediatrics, Phramongkutklao Hospital; the Thai Ministry of Public Health (MOPH); U.S. Army Medical Materiel Development Activity (USAMMDA); the Walter Reed Army Institute of Research (WRAIR); GlaxoSmithKline Biological (GSK Bio); Office of the Surgeon General of the Army, Department of Defense (DoD).

Description: Phase I/II, opened-label dengue vaccine trial in Thai children enrolled to receive two doses of dengue vaccine.

Status of the Study: The study ended in May 2004. Immunogenicity testing on-going. Data to be presented at World Health Organization (WHO) meeting, in Bangkok in October 2004.

Title of the study: A Phase I/II Trial of Tetravalent Live Attenuated Dengue Vaccine in Flavivirus Antibody Na?ve Infants

Principal Investigators: Mammen P. Mammen Jr., M.D., LTC, Medical Corps, Chief , Department of Virology, USAMC-AFRIMS; Sriluck Simasathien , M.D., Infectious Disease Consultant, Department of Pediatrics, Pramongkutklao Hospital, Bangkok, Thailand

Location: Phramongkutklao Hospital, Bangkok

Collaborating Institutions: Department of Pediatrics, Phramongkutklao Hospital; the Thai Ministry of Public Health (MOPH); U.S. Army Medical Materiel Development Activity (USAMMDA); the Walter Reed Army Institute of Research (WRAIR); GlaxoSmithKline Biological (GSK Bio); Office of the Surgeon General of the Army, Department of Defense (DoD).

Description: Phase I/II randomized, open-blinded, controlled study of dengue vaccine in infants.

Status: On-going

Title of the Study: Prospective Study of Dengue Virus Transmission and Disease in Primary School and Village Children in Kamphaeng Phet, Thailand

Principal Investigators: Mammen P. Mammen, Jr., M.D., LTC, Medical Corps, Chief, Virology Department, USAMC-AFRIMS; Dr. Suwich Thammapalo, M.D., M.P.H.& T.M., Chief, Dengue Section, Bureau of Vector-Borne Diseases, Thai Ministry of Public Health

Location: 11 primary schools and more than 20 villages in Kamphaeng Phet, Lower Northern Thailand (administered by KAVRU)

Collaborating Institutions: Thai Ministry of Public Health (MOPH); Institute of Urology and Nephrology, University College London; the Middlesex Hospital, London, Great Britain; Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School (UMMS); Department of Entomology, University of California, Davis, California; Department of Geography, San Diego State University, San Diego, California

Description: The goal of the study is to identify those factors (host-specific factors, virus-specific factors and environmental-specific factors) that have the strongest influence in determining the early events in acute dengue virus infections, and the eventual clinical manifestations of disease. An improved understanding of the correlations between the host, viral, and environmental factors and dengue disease severity will contribute to dengue virus vaccine development and testing.

Status: A total of 2,176 school children were enrolled. Active surveillance will be done during the months of June-mid December. Cluster studies in selected villages are done during the active surveillance.

Title of the Study: The Dengue Hemorrhagic Fever Project III: Continued Prospective Observational Studies of Children with Suspected Dengue

Principal Investigator: Siripen Kalayanorooj, M.D.; Robert V. Gibbons, M.D., LTC, Medical Corps, USAMC-AFRIMS

Location: Queen Sirikit National Institute of Child Health (QSNICH), Bangkok, Thailand

Collaborating Institutions: Queen Sirikit National Institute of Child Health (QSNICH); Institute of Urology and Nephrology, University College London; Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School (UMMS)

Description: A study to identify the most likely targets for pharmacology therapies, and provide a benchmark of immune responses, which induce dengue hemorrhagic fever (DHF). Further understanding of cross-reactive T and B cell responses and virus-host interaction are crucial for the design of future field studies for candidate dengue virus vaccines.

Status: The study will end in December 2008.

Title of the Study: A Randomized, Placebo-controlled, Study of Non-pegylated and Pegylated Forms of Recombinant Human Interferon-alpha-2a for Suppression of Dengue Viremia in Rhesus Macaques

Principal Investigator: Chuanpis Ajariyakhajorn, DVM, MS., Department of Virology, USAMC-AFRIMS, Bangkok, Thailand

Location: Bangkok

Collaborating Institutions: University of Massachusetts, Roche

Description: Study of using recombinant human interferon-alpha-2a (rhIFNa-2a) and long acting form of rhIFNa-2a for treatment of dengue-2 infected rhesus monkeys. Serial daily blood collecting was done to determine viremia level and neutralizing antibody titer after treatment. Recombinant human interferon-alpha-2a temporarily suppressed dengue-2 virus replication and delayed time to peak viremia by a median of 2 days. Pegylated rhIFNa-2a produced a 1-log drop in mean daily viremia level over 4 days compared to placebo.

Status: Clinical aspect of study has been closed. Abstract has been accepted for presentation at the American Society of Tropical Medicine and Hygiene meeting in Miami, Florida in November 2004. Manuscript is under development.

Title of the Study: Japanese Encephalitis Surveillance in NEPAL

Principal Investigators: Sanjaya Shrestha, M.D., Head of Station, WARUN

Location: Nepal (to be administered by WARUN)

Collaborating Institutions: Program for Appropriate Technology in Health (PATH); AMDA Hospital, Damak, Jhapa, Nepal (The Association of Medical Doctors of Asia-Nepal); Koshi Zonal Hospital, Biratnagar, Morang, Nepal; B.P. Koirala Institute of Health Sciences Hospital, Dharan, Nepal; Lumbhini Zonal Hospital, Butwal, Nepal; Bhim Hospital, Bhairawa, Rupandehi, Nepal; Universal College of Medical Science Hospital, Siddarthanagar, Nepal

Description: This study plans to enroll 500-1000 encephalitis cases from different hospitals of the Terai region in Nepal with the objective to charactrize the burden of Japanese Encephalitis among the encephalitis cases reporting to selected collaborating hospitals.

Status: Protocol under scientific/ethical review.

Title of the Study: The Study of Febrile Illness in NEPAL

Principal Investigators: Sanjaya Shrestha, M.D., Head of Station, WARUN

Location: Nepal (administered by WARUN)

Collaborating Institutions: Multiple AFRIMS Departments; Sheer Memorial Hospital, Banepa, Nepal; Dhulikhel Hospital, Dhulikhel, Kavre, Nepal; Sukra Raj Tropical Infectious Disease Hospital, Teku, Kahtmandu, Nepal.

Description: This is a multi-departmental study planned to identify and characterize different etiologies of febrile illness in Nepal.

Status: Protocol scientific/ethical review.

Title of the study: Characterization of dengue tetravalent vaccine formulations in rhesus monkeys. PN04-08

Principal Investigator: Robert V. Gibbons, M.D., M. PH., LTC, Department of Virology, USAMC-AFRIMS, Bangkok, Thailand

Location: Bangkok

Collaborating Institutions: GlaxoSmithKline (GSK)

Description: WRAIR dengue vaccines have been tested in monkeys and humans. To ensure compliance with the highest standards, the vaccine strains were extracted, RNA purified, and used to transfect GMP-grade FRhL cells. Viruses produced need to be compared phenotypically with viruses that were used as starting material. This will be done using the rhesus monkey measuring infection levels by titrating virus in blood following inoculation and measuring neutralizing antibodies. Additionally, a group of vaccinated monkeys receiving one dose of tetravalent vaccine will be challenged at 60 days post vaccination.

Status: Approved for implementation; team preparation

Title of the Study: Selective Molecular Characterization of Banked Dengue Virus Isolates for Determination of Virological Correlates of Disease Severity.

Principal Investigators: Chunlin Zhang, Ph.D., MAJ, Chief of Laboratory Operation, Department of Virology, USAMC-AFRIMS, Bangkok, Thailand

Location: Bangkok, Thailand

Collaborating Institutions: Queen Sirikit National Institution of Child Health (QSNICH), Bangkok, Thailand; Department of Zoology, University of Oxford, UK

Description: To select dengue virus isolates from children with dengue fever and DHF caused by the same serotype in the same year to: 1)ascertain potential molecular determinants of symptomatic dengue disease not only associated with E-protein but across the entire genome and to sequence, and 2) sequence dengue virus strains circulating in Thailand in preparation for a potential future phase 3 vaccine study.

Status: Sixty DEN-3 and fifty-three DEN-4 virus isolates from children in Bangkok, Thailand, admitted with varying degrees of DEN severity DF/DHF/DSS from 1974 to 2002 were selected to sequence the envelope (E) gene for identifying specific sequence patterns which may correlate with disease severity and for ascertaining the intra-serotypic genetic variation; molecular evolution and epidemiology history in Bangkok for past 30 years; and potential trends in molecular evolution and epidemiology of circulating DEN-3 and -4 viruses.

Title of the Study: Safety and Immunogenicity of Molecularly Derived Live-Attenuated Candidate Monovalent Dengue Vaccines in Rhesus Macaques

Principle Investigator: Mammen P. Mammen, Jr., M.D., LTC, Medical Corps, Chief, Department of Virology, USAMC-AFRIMS

Location: Bangkok

Collaborating Institutions: Department of Viral Research, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration (FDA), Bethesda, Maryland; Department of Biologicals Research, Walter Reed Army Institute of Research (WRAIR), Silver Spring, Maryland; Department of Virus Diseases, WRAIR; U.S. Army Medical Research and Materiel Command, Fort Detrick, Maryland

Description: This study is the prospective, randomized, placebo-controlled trial to compare the safety, immunogenicity and viremia profiles in flavivirus-na?ve Rhesus macaques following vaccination with varying live dengue vaccines. The primary objective is to facilitate down-selection of dengue virus vaccines to advance to GMP production for Phase I testing in volunteers.

Status: The study has been completed, the manuscript is being prepared.

Project Quality Assurance (QA) Program Development

QA Manager: Michael Charles Van Hoven, CPT, MS

Description:
The AFRIMS Department of Virology now has initiated a Quality Assurance Program to support the conduct of regulated AFRIMS Virology studies. The program entails the following Quality Systems Essentials (QSE):

1. Organizational Issues.
2. Standard Operating Procedures (SOP).
3. Personnel Training/Education/Competency Evaluation/Proficiency Testing.
4. Deviation/Incident Reporting.
5. Qualification/Validation/Calibration/Preventive Maintenance.
6. Document/Record-keeping/Record Review.
7. Supplier Qualification.
8. Process Control.
9. Internal Quality Assurance Audits.
10. Process Improvement.

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