SaniVac Trial - Sanitation and Oral Rotavirus Vaccine Performance

SaniVac Trial: An Assessment of Oral Rotavirus Vaccine Performance Among Infants Enrolled in a Controlled Before-after Study in Low-income Neighbourhoods of Maputo, Mozambique

This is a controlled cohort study to assess the effect of improved sanitation on oral rotavirus vaccine performance in low-income urban neighbourhoods of Maputo, Mozambique. The specific hypotheses are that: (1) access to improved sanitation is associated with increased oral rotavirus vaccine immunogenicity; (2) enteric infection concurrent to oral rotavirus vaccination is associated with reduced oral rotavirus vaccine immunogenicity; and (3) Environmental Enteric Dysfunction is associated with reduced oral rotavirus vaccine immunogenicity.

Pregnant women will be enrolled from the intervention and control arms of a previous sanitation trial (NCT02362932) post-intervention and will be enrolled at no later than eight months' gestation and then followed to 4 months of age of the infant. Blood samples and faeces will be taken from the infant at the time of administration of the first dose of the oral rotavirus vaccine and four weeks after the second dose of the vaccine.

The primary outcome of interest in the study is oral rotavirus vaccine immunogenicity among participating vaccinated infants. Seroconversion is defined as a ≥ fourfold rise in serum anti-rotavirus IgA titers between first dose of oral RV vaccine and 4 weeks (+/- 1 week) after second dose of oral RV vaccine. Enteric infections are defined as the presence of ≥ 1 of the following enteric infections in stool: adenovirus 40/41, rotavirus A, norovirus GI/GII, Salmonella spp. (including serovars Typhi and Paratyphi), Campylobacter spp. (C. jejuni, C. coli, C. lari), Shigella spp. (S. boydii, S. sonnei, S. flexneri, S. dysenteriae), Clostridium difficile Toxin A/B, enterotoxigenic Escherichia coli (ETEC) LT/ST, E. coli O157, Shiga-like toxin-producing E. coli (STEC) stx1/stx2, Yersinia enterocolitica, Vibrio cholerae, Giardia lamblia, Entamoeba histolytica, and Cryptosporidium spp. (C. parvum, C. hominis). Environmental Enteric Dysfunction is measured via a combined disease activity score including faecal markers of intestinal inflammation and permeability: neopterin, α-1 antitrypsin, and myeloperoxidase in stool.

Study Overview

• Status: Recruiting
• Conditions: Environmental Enteric Dysfunction; Rotavirus Infections; Enteric Infections
• Intervention / Treatment: Other: Sanitation

• Study Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

• Study Contact: Name: Oliver D Cumming, MSc; Phone Number: +442076368636; Email: oliver.cumming@lshtm.ac.uk

Study Locations

• Mozambique
  • Maputo, Mozambique, 264
    • Recruiting
    • Centro de Investigação em Saúde da Polana Caniço (CISPOC)
    • Contact: Edna Viegas, MD; Phone Number: +258 21 43 08 14; Email: ednaviegas@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

• Sampling Method: Probability Sample

Study Population

Pregnant women of gestational age between 3-9 months (and postpartum) residing in the historic intervention and control compounds of a previous sanitation trial (NCT02362932) and their descendant(s) [infant(s)] of that pregnancy.

Description

Inclusion Criteria:

1. Mother residing in an intervention or control compound of a previous sanitation trial (NCT02362932) for at least 6 months prior to recruitment and not intending to switch study compound over the next 9 months
2. Mother being pregnant and having gestational age between 3 and 9 months or being puerperal (up to 40 days postpartum)
3. Mother planning to use the prenatal care, delivery and vaccination services provided by the Ministry of Health of Mozambique
4. Mother able to understand and complete the informed consent process and allow your newborn to participate in the study
5. Mother at least 16 years of age
6. Infant eligible to receive rotavirus vaccination

Exclusion criteria:

1. Infant whose medical team considers that they cannot be part of the study
2. Infant with complications associated with gestation, childbirth or postpartum, including congenital malformations
3. Infant with any medical, psychiatric or social condition, occupational reason, or other responsibility on the part of the pregnant woman, which, in the opinion of the investigator, is a contraindication to protocol compliance or impedes the participant's ability to give informed consent
4. Infant who has already received the rotavirus vaccine

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Historic intervention; Infants born into the historic intervention arm of sanitation trial (NCT02362932)	Other: Sanitation; Improved sanitation facility
Historic control; Infants born into the historic control arm of sanitation trial (NCT02362932)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oral rotavirus vaccine seroconversion	Seroconversion is defined as a ≥ fourfold rise in serum anti-rotavirus IgA titers between first dose of oral RV vaccine and 4 weeks (+/- 1 week) after second dose of oral RV vaccine	Approx. 16 weeks age of infant (4 weeks after second dose of oral rotavirus vaccine)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Enteric infection	Enteric infections are defined as the presence of ≥ 1 of the following enteric infections in stool: adenovirus 40/41, rotavirus A, norovirus GI/GII, Salmonella spp. (including serovars Typhi and Paratyphi), Campylobacter spp. (C. jejuni, C. coli, C. lari), Shigella spp. (S. boydii, S. sonnei, S. flexneri, S. dysenteriae), Clostridium difficile Toxin A/B, enterotoxigenic Escherichia coli (ETEC) LT/ST, E. coli O157, Shiga-like toxin-producing E. coli (STEC) stx1/stx2, Yersinia enterocolitica, Vibrio cholerae, Giardia lamblia, Entamoeba histolytica, and Cryptosporidium spp. (C. parvum, C. hominis).	Approx. 8 weeks age of infant (date of first dose of oral rotavirus vaccine)
Environmental Enteric Dysfunction	EED is measured via a combined disease activity score including faecal markers of intestinal inflammation and permeability: neopterin, α-1-antitrypsin, and myeloperoxidase in stool.	Approx. 8 weeks age of infant (date of first dose of oral rotavirus vaccine)

Collaborators and Investigators

• Sponsor: London School of Hygiene and Tropical Medicine
• Collaborators: Centers for Disease Control and Prevention; Georgia Institute of Technology; Instituto Nacional de Saúde, Mozambique
• Investigators: Principal Investigator: Oliver D Cumming, MSc, London School of Hygiene and Tropical Medicine; Principal Investigator: Edna Viegas, MD, Centro de Investigação em Saúde da Polana Caniço (CISPOC)

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2017
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: October 6, 2017
• First Submitted That Met QC Criteria: October 17, 2017
• First Posted (Actual): October 18, 2017

Study Record Updates

• Last Update Posted (Actual): March 30, 2023
• Last Update Submitted That Met QC Criteria: March 29, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; RNA Virus Infections; Virus Diseases; Disease Attributes; Reoviridae Infections; Infections; Communicable Diseases; Rotavirus Infections
• Other Study ID Numbers: QA919

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No