Brief Title
Immunity to Human Cholera in Bangladesh
Official Title
Protective Immunity to Human Cholera in Bangladesh
Brief Summary
Cholera is a severe diarrhea illness caused by bacteria. The purpose of this study is to
better understand how the immune systems of people in Dhaka, Bangladesh, fight infection with
cholera. Understanding immune responses that influence the outcome of infection with cholera
can assist in the development of more effective cholera vaccines. The International Center
for Diarrheal Diseases Research, Bangladesh (ICDDR,B) will enroll in this study 75 patients
with acute cholera and 250 of their household contacts. Individuals ages 2-60 years are
eligible. Study participation will last 1 year for cholera patients and 30 days for household
contacts. Participants will come to the ICDDR,B for 3 (household contacts) or 4 (cholera
patients) study visits, and field workers will visit them at home at other times. For all
participants, blood samples will be taken at each of the ICDDR,B visits. Household contacts
will have rectal swabs taken at 2 ICDDR visits and during field worker visits.
Detailed Description
The purpose of this study is to investigate protective immunity to human cholera in Dhaka,
Bangladesh. Immune responses to Vibrio cholerae are poorly understood and have not been
extensively studied in an endemic setting such as Bangladesh. Understanding systemic and
mucosal immune responses that influence the outcome of infection with V cholerae can assist
in the development of more effective cholera vaccines. Identifying host factors, such as
human genetic variations or nutritional status, that affect the outcome of infection with V
cholerae can lead to an improved understanding of disease pathogenesis and better treatment
modalities. One of the likely key determinants of protection following either natural cholera
or vaccination is the duration of immune responses to key antigens, particularly at the
mucosal surface. This study proposes to assess the duration of immune responses in a group of
75 cholera study participants over the course of 1 year of follow-up and to correlate
baseline immune responses in 250 household contacts of the index patients, with protection
from disease over the subsequent 30 days. The researchers will assess the duration of
immunity in serum to known cholera virulence factors, including the serum vibriocidal
antibody and antibodies specific for LPS, cholera toxin, B subunit (CtxB), and TcpA. The
researchers will also measure antigen-specific memory B cells circulating in human blood,
which has previously been used to examine the longevity of B cell immunologic memory
following various infections and vaccinations. The objectives of this study are to determine
genes and proteins expressed by V. cholerae during human infection; determine which V.
cholerae proteins are immunogenic during human cholera infection in Bangladesh; assess the
duration of immune responses to V. cholerae antigens following an episode of cholera;
determine which anti-V. cholerae immune responses are protective on exposure to cholera in
household contacts; and evaluate selected host factors that influence the development of
immune responses following cholera, or susceptibility to symptomatic cholera following
exposure in household contacts. A total of 325 study participants (75 index patients with
acute cholera and 250 of their household contacts) will be enrolled. Index study participants
will be recruited from among patients presenting with acute cholera to the International
Center for Diarrheal Diseases Research, Bangladesh (ICDDR,B) hospital in Dhaka, Bangladesh.
Any individual with acute cholera between the ages of 2 to 60 years, inclusive, without a
severe complicating illness, and any household contact of the cholera patients between the
ages of 2 and 60 years, inclusive, is eligible for enrollment in this study. The length of
participation for each study participant will be 1 year for acute cholera index patients and
30 days for their household contacts. For cholera patients, study physicians will perform an
initial assessment and collect blood at various time points over 1 year. Study participants
(cases and household contacts) will come to the ICDDR,B for blood collection. On Study Days 3
through 6 and 8 through 10, a trained field worker will visit the household contacts to
collect information about symptoms and treatment of diarrhea and to obtain rectal swab
samples. Household contacts will come to the ICDDR,B on Days 2 or 3, and 7 (range 6-9) for a
questionnaire, rectal swab, and blood drawing. Questionnaires will be filled out upon
enrollment and at each study visit.
Study Type
Observational
Condition
Cholera
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Estimated Enrollment
400
Start Date
December 11, 2006
Completion Date
December 31, 2012
Primary Completion Date
January 4, 2012
Eligibility Criteria
Inclusion Criteria:
All Participants:
- Men or women age 2 to 60 years, inclusive.
- Provision of informed consent for enrollment in study by patient/parent or guardian,
as well as verbal assent for children age 7 to 17 years, inclusive.
- Expressed interest and availability to fulfill the study requirements (index patients
for up to 1 year; household contacts up to 30 days).
Index Patients:
- Any individual with cholera enrolled in the surveillance system at the International
Centre for Diarrhoeal Diseases Research, Bangladesh (ICDDR,B).
Household Contacts:
- Any household contact of the index patient (defined as sharing the same cooking pot for
longer than 3 days before the index patient presented to the ICDDR,B).
There is no upper limit on the number of household members that can enroll from a single
household.
Exclusion Criteria:
- Clinically apparent severe comorbid condition (meningitis, encephalitis, coma,
respiratory distress).
- Concurrent enrollment in an unrelated interventional study.
- For household contacts, living in the same place with an index patient for 3 or fewer
days before the index patient presented to the International Centre for Diarrhoeal
Diseases Research, Bangladesh.
Gender
All
Ages
2 Years - 60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Contacts
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Location Countries
Bangladesh
Location Countries
Bangladesh
Administrative Informations
NCT ID
NCT00401934
Organization ID
06-0045
Study Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Study Sponsor
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Verification Date
August 2011