Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase I/II Dose-escalation Study to Evaluate Safety, Tolerability and Immunogenicity of '2-dose Primary Series' Single Strain (Hikojima Serotype) Inactivated Oral Cholera Vaccine Formulations (Two Formulations Based on Total O1 LPS Content), in Sequential Age Descending Population of Healthy Adults and Children
Brief Summary: Cholera, a rapidly dehydrating watery diarrheal disease transmitted through water or food contaminated with the bacterium, Vibrio cholerae, is a major cause of morbidity and mortality in low income countries like Bangladesh. In our country, Cholera disease burden consists of both cholera outbreaks and endemic cholera comprising at least 300,000 severe cases and 1.2 million infections each year. To combat this situation, Vaccination against cholera has been proved effective both in endemic and epidemic settings. But, the WHO recommended Dukoral and Prequalified Shanchol are quite expensive for our country perspective. Therefore, locally manufactured OCV can improve the cost effectiveness and make it affordable for all. The hypothesis of this proposal is that Locally produced orally administered whole cell inactivated HL-OCV test formulations A and B are safe and immunogenic in adults and children in Bangladesh as compared to ShancholTM. The results of the study will allow us to understand the safety and immunogenicity outcome of the HL-OCV compared to Shanchol vaccine. The total sample size will be 840 healthy participants. 840 healthy participants (360 adults, 240 Children and Adolescent and 240 young children) of 18-45 years, 5- less than 18 years and 1 year to less than 5 years will be enrolled in the study. Children whose parents/guardians give voluntary consent will be enrolled in the study. The investigators will provide 2 dose of vaccine for three groups in 14 days interval. Test formulations will be locally manufactured and the comparator group will get Shanchol. The Investigators propose to collect three blood samples (Day 0, 14 and 28).


Options:
A: Inclusion Criteria:

Healthy subjects \> 1 year of age and above Living in high risk area for cholera Provision of Informed consent for participating in the study by participant /parent or guardian as well as verbal assent for children 11-17 years.

Exclusion Criteria:

Pregnant women Aged less than 1 year History of taking cholera vaccine
B: Inclusion Criteria:

1. Age ≥1 year, stratified into different age groups
2. Living in the Waya Clinic Catchment Area
3. Good health condition, without clinically significant medical history (by participant or guardian, in case of minor)
4. Not pregnant for female subjects.
5. Available to participate for the study duration, including all planned follow-up visits for up to 9 months from screening.
6. Signed informed consent

Exclusion Criteria:

1. Presence of a significant medical or psychiatric condition (Examples include: Diagnosis and treatment of tuberculosis (TB) or HIV; renal insufficiency; hepatic disease; oral or parenteral medication known to affect the immune function, such as corticosteroids, other immunosuppressant drugs; or behavioural or memory issues)
2. Ever having received oral cholera vaccine.
3. Receipt of an investigational product (within 30 days before vaccination).
4. History of diarrhoea in 7 days prior to first dose of vaccine (defined as ≥3 unformed loose stools in 24 hours).
5. History of chronic diarrhea (lasting for more than 2 weeks in the past 6 months)
6. Current use of laxatives, antacids, or other agents to lower stomach acidity?
7. Planning to become pregnant in the next 2 years.
C: Inclusion Criteria:

1. Age: 1-45 Years.
2. Informed consent from study participants and guardian in case of children (1-17 years) and assent from children aged 11-17 years.
3. Participation in the study at least for next 6 months
4. Considered healthy as per medical judgment of the investigator

Exclusion Criteria:

1. Suffering from diarrhea or abdominal pain or vomiting in the past 24 hours or diarrhea lasting for more than 2 weeks in the past 6 months
2. History of taking oral cholera vaccine and history of confirmed cholera.
3. History of taking any other live or killed enteric vaccine in the last 8 weeks.
4. History of anaphylaxis or serious vaccine reaction.
5. Currently use of any immunosuppressive or immune-modifying drugs. 6.100.4 0 F (38℃) or higher body temperature measured prior to investigational product dosing.

7.Receipt of blood or blood products or parenteral immunoglobulin preparation in the past 3 months.

8.Currently on antimicrobial therapy. 9.Severe malnutrition or chornic disease based on the jugement of the investigator.

10.Stool sample at screening positive for V. cholerae. 11.Pregnant women or plans to become pregnant during the study period .
D: Inclusion Criteria:

1. Age: 1years to less than 5 years for the younger children group; 5- less than18 years for older children and adolescent group and 18- 45 years (inclusive) for the adult group.
2. Sex: Male, Female, Transgender.
3. Consent: Informed consent from study participants and guardian in case of children along with assent in children 11-17 years (inclusive) of age.
4. Apparently healthy.

Exclusion Criteria:

1. Suffering from diarrhoea or abdominal pain or vomiting in the past 24 hours or diarrhoea lasting for more than 2 weeks in the past 6 months
2. History of taking oral cholera vaccine.
3. History of taking any other live or killed enteric vaccine in the last 8 weeks.
4. History of anaphylaxis or serious vaccine reaction.
5. Currently use of any immunosuppressive or immune-modifying drugs.
6. Receipt of blood or blood products or parenteral immunoglobulin preparation in the past 3 months.
7. Currently on antimicrobial therapy (taking antibiotics within 24 hours during screening and vaccination).
8. Severe malnutrition defined as wt-for-ht z-score \<-3.0 with or without oedema.
9. For married females pregnancy or plans to become pregnant during the study period (as determined by verbal screening) will be excluded. In addition, pregnancy test will be done by pregnancy strip test before each day of vaccination (Day 0 and day 14) for married female.
10. Culture positive V. cholerae, ETEC, Salmonella and Shigella in stool.

Answer: D