This study seeks to determine the incidence and transmission of avian influenza viruses in humans exposed to poultry. Enrolled subjects will be selected from five different rural areas (villages) in the Nile delta region in Egypt where poultry are commonly raised. From those study sites, 2400 healthy subjects will be monitored for 6 years with annual follow up visits to measure sero-prevalence and exposure variables, and more importantly, biweekly or weekly visits to measure incidence of infection, measure secondary transmission rates, monitor symptoms, and assess immunological response.

Primary Objectives:

• To estimate the incidence of avian influenza (AI) in poultry-exposed human populations.
• To estimate sero-prevalent of AI in poultry-exposed human populations.
• To investigate potential risk factors associated with AI human infections in poultry-exposed individuals.
• To investigate secondary infection risk for household contacts.

Secondary Objectives:

• To characterize the antigenic and genetic makeup of AI viruses infecting humans.
• To monitor the pathogenicity and disease severity of AI viruses causing human infections and the associated immune response.
• To investigate the serologic response following confirmed influenza virus infection.

All residents of a household will be invited to participate. After study enrollment, participants will complete a questionnaire to collect data on the demographics and health status of the subjects and the poultry kept at the household. A 3-ml blood sample will be obtained from each subject for serological testing.

Field nurses or physicians will visit each household biweekly (October through March) or weekly (April through September) to determine if any subject has influenza-like illness (ILI), defined according to Centers for Disease Control (CDC) criteria as having measured fever of ≥38ºC. and cough and/or sore throat. Subjects with confirmed ILI (index case) will provide two nasal swabs for a point-of-care rapid influenza A test and PCR. For those who test positive for influenza A by rapid test or PCR on nasal swab (day 1), two 3-ml blood samples will be obtained. In addition, nasal washes, throat swabs, and blood samples will be obtained from all household contacts.

Cloacal swabs will also be collected from the poultry in the household on day 1.

The index case and household contacts will be re-sampled by nasal wash and throat swab on days 3, 6, 9 and 14 post initial diagnosis data, and an additional 3-ml blood sample will be obtained on day 14 for serological testing.

Household contacts who report ILI symptoms during follow-up visits to the index case will then be followed with the same follow-up regimen as the original index case.

At annual follow-up and final visits, questionnaire data will be updated if needed, and a 3-ml blood sample will be obtained from each subject for serological testing.

Inclusion Criteria:

• Poultry-exposed individuals with poultry in the household willing to participate by signing a consent or assent form as appropriate for age, completing the study questionnaire, and permitting the withdrawal of blood, nasal washes, nasal swabs, and throat swabs.

Exclusion Criteria:

• Any known immunosuppressive condition or immune deficiency disease (including HIV infection), or ongoing receipt of any immunosuppressive therapy. (Note that we have chosen to exclude such populations because of their increased risk of acquiring infections, they are relatively few, and are not representative of a national sample.)
• Terminally ill individuals.
• Children who are less than 2 years old when baseline enrollment is performed.

This study will be conducted on rural Egyptian poultry growers in areas where avian influenza is endemic in Egypt. The study sample is expected to have the same composition as the general population in that area.