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

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.

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.

• 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.