Host Genetic Susceptibility to Avian Influenza A/H5N1
Host Genetic Susceptibility to Avian Influenza A/H5N1
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.