Host Genetic Susceptibility to Avian Influenza A/H5N1

• ClinicalTrials.gov Identifier: NCT01074736
• Recruitment Status: Completed
• First Posted: February 24, 2010
• Last Update Posted: November 4, 2010
• Sponsor: South East Asia Infectious Disease Clinical Research Network
• Collaborators: University of Oxford; Wellcome Trust
• Information provided by: South East Asia Infectious Disease Clinical Research Network

Study Description

Brief Summary:

The identification and characterization of susceptibility loci for H5N1 infection in humans could have profound implications. The detection of host genetic factors may shed light on key pathogenic interactions between H5N1 and human cells, assisting in identifying the viral characteristics determining pandemic potential. In addition, the identification and verification of susceptibility loci would be followed by functional studies which might point the way to new therapeutic and preventive options.

The objective of this study is to investigate if host genetic factors are associated with susceptibility to influenza H5N1 illness

Condition or disease
Influenza A Virus/H5N1 Subtype

Detailed Description:

This is primarily an hypothesis screening exercise and while guesses based on biological plausibility are possible, a comprehensive analysis of genetic susceptibility can only be achieved by a whole genome approach. Therefore we will test for genetic linkage and association using a large number of Single Nucleotide Polymorphisms (SNPs) spanning the whole genome.

Principal Investigators have access to information on all surviving and deceased laboratory confirmed H5N1 cases. These cases will form the study base. The epidemiologist will attempt to make telephone contact with either the recovered patient or,if the patient died, the closest relative of the deceased patient. The proposed study will be explained and permission will be sought for the epidemiologist and a study nurse to visit the household to explain the study in greater detail, to offer an opportunity for questions and, if the subject agrees, to obtain informed consent for participation. If the epidemiologist has difficulty in making contact with the case or their family the local public authorities will be asked to assist in making contact. Eligible family members of H5N1 cases will be identified by face-to-face interviews with the surviving confirmed cases or close family members of deceased cases.

Study Design

• Study Type: Observational
• Actual Enrollment: 500 participants
• Observational Model: Family-Based
• Time Perspective: Cross-Sectional
• Official Title: Host Genetic Susceptibility to Avian Influenza A/H5N1 in Vietnam, Thailand, Indonesia and Singapore
• Study Start Date: July 2008
• Actual Primary Completion Date: August 2010
• Actual Study Completion Date: October 2010

Groups and Cohorts

Outcome Measures

Biospecimen Retention:   Samples With DNA

• whole blood in tubes containing EDTA
• mouth wash.
• buffy coat; cell pellet from centrifuged blood, nucleic acid extracted for diagnostic purposes, serum, throat, nose or endotracheal swabs

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

• symptomatic cases with laboratory confirmed H5N1 infection will be eligible for inclusion.
• Priority for recruitment will be given to cases from multi-case families in order tomaximize the probability of including cases with a genetic etiology.

Criteria

Inclusion Criteria:

• The individual had a clinically compatible illness (defined as respiratory symptoms and an abnormal chest x-ray or encephalitis), AND
• Influenza A/H5 RNA identified in a clinical sample by reverse transcription-polymerase chain reaction [RT-PCR], OR
• Influenza A/H5 cultured from a clinical sample, OR
• High titres (1:80 or higher) of anti-H5 antibodies by microneutralization in convalescent samples of patients who had a compatible illness but no or negative RT-PCR, AND
• The patient survived or if they died an archived biological specimen is available for potential DNA extraction, AND
• Valid, written consent is obtained.
• The biological parents and biological siblings of all the cases and any other family members linking two cases, AND
• Valid, written consent is obtained.

Contacts and Locations

Locations

Vietnam

Oxford University Clinical Research Unit

Hanoi, Vietnam

Sponsors and Collaborators

South East Asia Infectious Disease Clinical Research Network

University of Oxford

Wellcome Trust

Investigators

• Principal Investigator: Tawee Chotpitayasunond, Professor; Queen Sirikit National Institute of Child Health, Bangkok, Thailand
• Principal Investigator: Herawati Sudoyo, Dr.; Eijkman Institute for Molecular Biology
• Principal Investigator: Tran Hien Nguyen, Professor; National Institute of Hygiene and Epidemiology, Hanoi, Vietnam
• Principal Investigator: Martin Hibberd, Dr.; Genome Institute of Singapore, Singapore

More Information

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• Responsible Party: Peter Horby, NCC Oxford University Clinical Research Unit - The Hospital for Tropical Diseases, Vietnam
• ClinicalTrials.gov Identifier: NCT01074736
• Other Study ID Numbers: SEA 007
• First Posted: February 24, 2010
• Last Update Posted: November 4, 2010
• Last Verified: November 2010

Keywords provided by South East Asia Infectious Disease Clinical Research Network:

influenza A/H5N1; host genetic susceptibility; genotyping

Additional relevant MeSH terms:

Influenza, Human; Influenza in Birds; Disease Susceptibility; Genetic Predisposition to Disease; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Disease Attributes; Pathologic Processes