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Household Transmission of Zoonotic Influenza Viruses in a Cohort of Egyptian Poultry Growers

Completed
Conditions
Influenza
Interventions
Other: Questionnaire
Other: Blood sample
Other: Nasal wash
Other: Throat swab
Registration Number
NCT02459171
Lead Sponsor
St. Jude Children's Research Hospital
Brief Summary

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.

Detailed Description

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
2400
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.

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
ParticipantsNasal washSubjects who meet eligibility requirements and consent to participate. Interventions: Blood sample, nasal wash, throat swab, questionnaire
ParticipantsBlood sampleSubjects who meet eligibility requirements and consent to participate. Interventions: Blood sample, nasal wash, throat swab, questionnaire
ParticipantsThroat swabSubjects who meet eligibility requirements and consent to participate. Interventions: Blood sample, nasal wash, throat swab, questionnaire
ParticipantsQuestionnaireSubjects who meet eligibility requirements and consent to participate. Interventions: Blood sample, nasal wash, throat swab, questionnaire
Primary Outcome Measures
NameTimeMethod
Incidence of avian influenza (AI) in poultry-exposed populationsUp to 6 years

New cases of avian influenza (AI) in poultry-exposed human populations will be detected using throat and nasal swabs and nasal washes obtained from subjects using rapid tests and molecular techniques.

Sero-prevalence rates of infection with AI virusesUp to 6 years

Prevalence rates will be measured by the presence of antibodies against AI viruses subtypes using a micro-neutralization assay. Incidence rates will be assessed based on molecular detection of AI infection annually with 95% confidence intervals. Risk or protective factors correlated with infection will be measured using the baseline enrollment questionnaire.

Secondary infection risk for household contactsUp to 6 years

Throat and nasal swabs, blood, and nasal washes will be obtained from household contacts of poultry-exposed individuals with a confirmed influenza A infection. These will be tested for the presence of influenza A viruses or antibodies against influenza A viruses.

Risk factors associated with AI human infections in poultry-exposed individualsUp to 6 years

A questionnaire will be used to collect specific occupational, environmental, and behavioral risk factors. These will be correlated to sero-prevalence and incidence of AI infections.

Secondary Outcome Measures
NameTimeMethod
Serologic response following confirmed influenza virus infectionUp to 6 years

Antibodies will be measured in acute and convalescent sera of confirmed influenza cases.

Pathogenicity and disease severity of AI viruses causing human infections and the associated immune responseUp to 6 years

Data will be collected on disease pathogenicity and severity of symptoms from subjects reporting ILI and blood samples will be obtained to isolate and study peripheral blood mononuclear cells (PBMCs). PBMCs will be used to study innate and adaptive cell phenotyping by flow cytometry and functional assays that will be read out by flow cytometry and ELISPOT.

Antigenic and genetic makeup of AI viruses infecting humansUp to 6 years

PCR, sequencing, culture and serological techniques will be used to characterize these viruses.

Trial Locations

Locations (1)

National Research Centre

🇪🇬

Cairo, Egypt

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