Clinical trial NCT02764918: Cryptosporidiosis and Enteropathogens in Bangladesh
Official title: Field Studies of Cryptosporidiosis and Enteropathogens in Bangladesh
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Cryptosporidiosis
Lead sponsor: University of Virginia
Sponsor class: OTHER
Collaborators: name: International Centre for Diarrhoeal Disease Research, Bangladesh
name: National Institutes of Health (NIH)
First posted: 2016-05-06
Enrollment: 150
Sex: ALL
Minimum age (years): 1
Maximum age (years): 7
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Mother-child pairs from the Mirpur Neighborhood of Dhaka, Bangladesh

Brief summary: The purpose of this study is to explore the role of anti-parasite antibody in protection of children from the parasitic infection cryptosporidiosis. This work has the promise of identifying immune pathways important for protection from parasitic infections of the gut, and will help with designing a vaccine to prevent this infection estimated to cause, from diarrhea and malnutrition, an overall burden of 12 million disability-adjusted life-years in children.


Eligibility criteria: Inclusion Criteria:

* Mother willing to sign informed consent form.
* Healthy infant
* No obvious congenital abnormalities or birth defects.
* Stable household with no plans to leave the area for the next one year.

Exclusion Criteria:

* Parents are not willing to have child's blood drawn.
* Parents are planning to enroll child into another interventional clinical study during the time period of this trial that could affect the outcomes of this study.
* Mother not willing to have blood drawn and breast milk extracted.
* Parents not willing to have field research assistant in home two times per week.
* History of seizures or other apparent neurologic disorders.
* Infant has any sibling currently or previously enrolled in this study, including a twin.

Primary outcomes:
measure: Functional characterization of anti-Cryptosporidium antibodies associated with protection
timeFrame: Birth until 4 years
Secondary outcomes:
measure: In depth characterization of Cryptosporidium antigens recognized by the child humoral immune response
timeFrame: Birth until 4 years.
measure: Polymerase chain reaction (PCR) testing for diarrheal pathogens during acute infection
timeFrame: Birth to 4 years old
measure: Determine the role of circulating T follicular helper (cTfh) cells in induction of antibody response
timeFrame: Through collection of blood specimens on day 0, 14 and 28 during acute infection.
measure: Determination of maternal humoral response and impact on child infection/immunity
timeFrame: On enrollment (all) and 4 months (breast milk only).
measure: Surveillance polymerase chain reaction (PCR) testing for diarrheal pathogens
timeFrame: Birth until 4 years.
measure: Determine child anthropometric measures
timeFrame: Every 6 months until 4 years
measure: Socioeconomic status questionnaire
timeFrame: At enrollment
measure: Household sanitation questionnaire
timeFrame: At enrollment
Other outcomes:
Locations:
city: Dhaka
country: Bangladesh
facility: The International Centre for Diarrhoeal Disease Research, Bangladesh
Study officials:
References:
citation: Gilchrist CA, Cotton JA, Burkey C, Arju T, Gilmartin A, Lin Y, Ahmed E, Steiner K, Alam M, Ahmed S, Robinson G, Zaman SU, Kabir M, Sanders M, Chalmers RM, Ahmed T, Ma JZ, Haque R, Faruque ASG, Berriman M, Petri WA. Genetic Diversity of Cryptosporidium hominis in a Bangladeshi Community as Revealed by Whole-Genome Sequencing. J Infect Dis. 2018 Jun 20;218(2):259-264. doi: 10.1093/infdis/jiy121.
citation: Steiner KL, Ahmed S, Gilchrist CA, Burkey C, Cook H, Ma JZ, Korpe PS, Ahmed E, Alam M, Kabir M, Tofail F, Ahmed T, Haque R, Petri WA Jr, Faruque ASG. Species of Cryptosporidia Causing Subclinical Infection Associated With Growth Faltering in Rural and Urban Bangladesh: A Birth Cohort Study. Clin Infect Dis. 2018 Oct 15;67(9):1347-1355. doi: 10.1093/cid/ciy310.
citation: Steiner KL, Kabir M, Priest JW, Hossain B, Gilchrist CA, Cook H, Ma JZ, Korpe PS, Ahmed T, Faruque ASG, Haque R, Petri WA. Fecal Immunoglobulin A Against a Sporozoite Antigen at 12 Months Is Associated With Delayed Time to Subsequent Cryptosporidiosis in Urban Bangladesh: A Prospective Cohort Study. Clin Infect Dis. 2020 Jan 2;70(2):323-326. doi: 10.1093/cid/ciz430.
citation: Donowitz JR, Drew J, Taniuchi M, Platts-Mills JA, Alam M, Ferdous T, Shama T, Islam MO, Kabir M, Nayak U, Haque R, Petri WA. Diarrheal Pathogens Associated With Growth and Neurodevelopment. Clin Infect Dis. 2021 Aug 2;73(3):e683-e691. doi: 10.1093/cid/ciaa1938.
citation: Donowitz JR, Pu Z, Lin Y, Alam M, Ferdous T, Shama T, Taniuchi M, Islam MO, Kabir M, Nayak U, Faruque ASG, Haque R, Ma JZ, Petri WA Jr. Small Intestine Bacterial Overgrowth in Bangladeshi Infants Is Associated With Growth Stunting in a Longitudinal Cohort. Am J Gastroenterol. 2022 Jan 1;117(1):167-175. doi: 10.14309/ajg.0000000000001535.
citation: Kabir M, Alam M, Nayak U, Arju T, Hossain B, Tarannum R, Khatun A, White JA, Ma JZ, Haque R, Petri WA Jr, Gilchrist CA. Nonsterile immunity to cryptosporidiosis in infants is associated with mucosal IgA against the sporozoite and protection from malnutrition. PLoS Pathog. 2021 Jun 28;17(6):e1009445. doi: 10.1371/journal.ppat.1009445. eCollection 2021 Jun.
citation: Carey MA, Medlock GL, Alam M, Kabir M, Uddin MJ, Nayak U, Papin J, Faruque ASG, Haque R, Petri WA, Gilchrist CA. Megasphaera in the Stool Microbiota Is Negatively Associated With Diarrheal Cryptosporidiosis. Clin Infect Dis. 2021 Sep 15;73(6):e1242-e1251. doi: 10.1093/cid/ciab207.
citation: Gilchrist CA, Campo JJ, Pablo JV, Ma JZ, Teng A, Oberai A, Shandling AD, Alam M, Kabir M, Faruque ASG, Haque R, Petri WA Jr. Specific Cryptosporidium antigens associate with reinfection immunity and protection from cryptosporidiosis. J Clin Invest. 2023 Aug 15;133(16):e166814. doi: 10.1172/JCI166814.