SaniVac Trial - Sanitation and Oral Rotavirus Vaccine Performance

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Rotavirus Infections, Environmental Enteric Dysfunction, Enteric Infections

Intervention / Treatment
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* Other: Sanitation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Mother being pregnant and having gestational age between 3 and 9 months or being puerperal (up to 40 days postpartum) Mother planning to use the prenatal care, delivery and vaccination services provided by the Ministry of Health of Mozambique Mother able to understand and complete the informed consent process and allow your newborn to participate in the study Mother at least 16 years of age Infant eligible to receive rotavirus vaccination Exclusion criteria: Infant whose medical team considers that they cannot be part of the study Infant with complications associated with gestation, childbirth or postpartum, including congenital malformations 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 Infant who has already received the rotavirus vaccine

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Historic intervention<br>Infants born into the historic intervention arm of sanitation trial (NCT02362932) | Other: Sanitation<br>* Improved sanitation facility<br>|
| Historic control<br>Infants born into the historic control arm of sanitation trial (NCT02362932) | |

What is the study measuring?
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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) |