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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02734264
Other study ID # 7563
Secondary ID
Status Completed
Phase N/A
First received March 22, 2016
Last updated October 24, 2017
Start date January 2008
Est. completion date December 2014

Study information

Verified date April 2016
Source University of Virginia
Contact n/a
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial Summary

The purpose of this study will be to investigate the incidence of both Amebiasis and cryptosporidiosis in Bangladeshi children and examine genetic variation in innate and adaptive immunity with respect to these infections. Novel diagnostics to these infections will also be investigated.


Description:

Entamoeba histolytica infection results from ingestion of the cyst of Entamoeba histolytica from fecally-contaminated food or water. Local invasion results in amebic dysentery and metastasis to amebic liver abscess. The diagnosis of intestinal amebiasis is ideally made using an E. histolytica-specific stool antigen detection test or using real-time polymerase chain reaction (PCR). The two major clinical syndromes of amebiasis are amebic colitis and amebic liver abscess. Together they are estimated to result in 50 million cases of colitis and liver abscess and 100,000 deaths worldwide each year. In developing countries, colonization with E. histolytica has been observed in 5% or more of poor children. Patients with amebic colitis typically present with a several week history of gradual onset of abdominal pain and tenderness, diarrhea and bloody stools (dysentery). The pathological lesions in the colon include ulceration of the intestinal epithelium and invasion into the lamina propria by trophozoites. Inflammation, with infiltrating neutrophils and mononuclear lymphocytes is pronounced, but inflammatory cells near the amebae are killed with pyknotic nuclei characteristic of apoptotic death. Amebic liver abscess is a rare form of the disease that is almost exclusively limited to adult males.

Cryptosporidiosis in humans is caused primarily by two species, Cryptosporidium parvum and C. hominis. There are annually approximately 1.4 cases/100,000 in the United States reported to the Centers for Disease Control. Infection results from ingestion of fecally contaminated water or food containing the infectious oocyst form. Sporozoites are released from the oocyst in the small intestine and attach to the epithelial cell surface. Upon invasion of the epithelial cells the parasite undergoes both the sexual and asexual stages of the life cycle. Infection with C. parvum in a normal host leads to days to several weeks of non-bloody diarrhea.

In many people E. histolytica and Cryptosporidia infections resolve without symptoms. A major emphasis of this study will be to study the host, environment, and parasite factors controlling susceptibility to E. histolytica and Cryptosporidia infection and disease, to begin to answer the question of why all infections do not cause disease. At the same time, want to improve diagnostic techniques for these diseases.

This study will continue a cohort of 420 children (average age now 10.5 years) that the research team has been following since birth and measure the incidence of amebiasis and cryptosporidiosis prospectively. In addition, 500 live births will be enrolled into an existing cohort.

This work has several objectives. The first objective is to compare current "gold-standard" diagnostic techniques for these diseases with newer antigen detection and polymerase chain reaction techniques. The second objective is to delineate the protective role of innate and acquired immunity to E. histolytica. The investigators hypothesize that protective immunity is mediated both by innate immune responses initiated via Toll-like Receptor stimulation and acquired responses including mucosal immunoglobulin A (IgA) and systemic Interferon-γ. Acquired immune responses (peripheral blood mononuclear cell cytokine production and fecal IgA anti-cross reacting determinant) during amebic and cryptosporidial infection and disease will be determined in the children in the cohort. The third objective is to test for the association of genetic polymorphisms in innate and acquired immune genes with incidence of amebiasis. The investigators hypothesize that common genetic polymorphisms in genes of the innate and acquired immune system influence susceptibility to E. histolytica and Cryptosporidia infection or disease. The final objective is to test the role of human genetic polymorphisms and microbiome in protection from undernutrition. Genome wide scans and microbiome compositional analyses will be performed on children to determine if the nutritional status of the child correlates with these measurements.


Recruitment information / eligibility

Status Completed
Enrollment 629
Est. completion date December 2014
Est. primary completion date December 2014
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group N/A to 7 Days
Eligibility Inclusion Criteria:

- Resident of Mirpur, Dhaka, Bangladesh

Exclusion Criteria:

- Mother under 65 years old

Study Design


Related Conditions & MeSH terms


Locations

Country Name City State
Bangladesh The International Centre for Diarrhoeal Disease Research, Bangladesh Dhaka

Sponsors (2)

Lead Sponsor Collaborator
University of Virginia International Centre for Diarrhoeal Disease Research, Bangladesh

Country where clinical trial is conducted

Bangladesh, 

Outcome

Type Measure Description Time frame Safety issue
Primary Incidence of Amebiasis and Cryptosporidium infection Birth to 5 years
Secondary Peripheral blood mononuclear cell Interleukin (IL)-1ß stimulation studies Investigators plan to obtain blood for cytokine analysis from children when they do not have E. histolytica infection and are free of diarrheal disease. Investigators also plan to obtain blood for cytokine analysis from children within 48 hours of the diagnosis of E. histolytica infection or disease. Birth to 5 years
Secondary Peripheral blood mononuclear cell IL-2 stimulation studies Investigators plan to obtain blood for cytokine analysis from children when they do not have E. histolytica infection and are free of diarrheal disease. Investigators also plan to obtain blood for cytokine analysis from children within 48 hours of the diagnosis of E. histolytica infection or disease. Birth to 5 years
Secondary Peripheral blood mononuclear cell IL-4 stimulation studies Investigators plan to obtain blood for cytokine analysis from children when they do not have E. histolytica infection and are free of diarrheal disease. Investigators also plan to obtain blood for cytokine analysis from children within 48 hours of the diagnosis of E. histolytica infection or disease. Birth to 5 years
Secondary Peripheral blood mononuclear cell IL-5 stimulation studies Investigators plan to obtain blood for cytokine analysis from children when they do not have E. histolytica infection and are free of diarrheal disease. Investigators also plan to obtain blood for cytokine analysis from children within 48 hours of the diagnosis of E. histolytica infection or disease. Birth to 5 years
Secondary Peripheral blood mononuclear cell IL-6 stimulation studies Investigators plan to obtain blood for cytokine analysis from children when they do not have E. histolytica infection and are free of diarrheal disease. Investigators also plan to obtain blood for cytokine analysis from children within 48 hours of the diagnosis of E. histolytica infection or disease. Birth to 5 years
Secondary Peripheral blood mononuclear cell IL-7 stimulation studies Investigators plan to obtain blood for cytokine analysis from children when they do not have E. histolytica infection and are free of diarrheal disease. Investigators also plan to obtain blood for cytokine analysis from children within 48 hours of the diagnosis of E. histolytica infection or disease. Birth to 5 years
Secondary Peripheral blood mononuclear cell IL-8 stimulation studies Investigators plan to obtain blood for cytokine analysis from children when they do not have E. histolytica infection and are free of diarrheal disease. Investigators also plan to obtain blood for cytokine analysis from children within 48 hours of the diagnosis of E. histolytica infection or disease. Birth to 5 years
Secondary Peripheral blood mononuclear cell IL-10 stimulation studies Investigators plan to obtain blood for cytokine analysis from children when they do not have E. histolytica infection and are free of diarrheal disease. Investigators also plan to obtain blood for cytokine analysis from children within 48 hours of the diagnosis of E. histolytica infection or disease. Birth to 5 years
Secondary Peripheral blood mononuclear cell IL-12(p70) stimulation studies Investigators plan to obtain blood for cytokine analysis from children when they do not have E. histolytica infection and are free of diarrheal disease. Investigators also plan to obtain blood for cytokine analysis from children within 48 hours of the diagnosis of E. histolytica infection or disease. Birth to 5 years
Secondary Peripheral blood mononuclear cell IL-12(p40) stimulation studies Investigators plan to obtain blood for cytokine analysis from children when they do not have E. histolytica infection and are free of diarrheal disease. Investigators also plan to obtain blood for cytokine analysis from children within 48 hours of the diagnosis of E. histolytica infection or disease. Birth to 5 years
Secondary Peripheral blood mononuclear cell IL-13 stimulation studies Investigators plan to obtain blood for cytokine analysis from children when they do not have E. histolytica infection and are free of diarrheal disease. Investigators also plan to obtain blood for cytokine analysis from children within 48 hours of the diagnosis of E. histolytica infection or disease. Birth to 5 years
Secondary Peripheral blood mononuclear cell IL-17 stimulation studies Investigators plan to obtain blood for cytokine analysis from children when they do not have E. histolytica infection and are free of diarrheal disease. Investigators also plan to obtain blood for cytokine analysis from children within 48 hours of the diagnosis of E. histolytica infection or disease. Birth to 5 years
Secondary Peripheral blood mononuclear cell interferon-? stimulation studies Investigators plan to obtain blood for cytokine analysis from children when they do not have E. histolytica infection and are free of diarrheal disease. Investigators also plan to obtain blood for cytokine analysis from children within 48 hours of the diagnosis of E. histolytica infection or disease. Birth to 5 years
Secondary Peripheral blood mononuclear cell granulocyte-macrophage colony-stimulating factor stimulation studies Investigators plan to obtain blood for cytokine analysis from children when they do not have E. histolytica infection and are free of diarrheal disease. Investigators also plan to obtain blood for cytokine analysis from children within 48 hours of the diagnosis of E. histolytica infection or disease. Birth to 5 years
Secondary Peripheral blood mononuclear cell tumor necrosis factor-a stimulation studies Investigators plan to obtain blood for cytokine analysis from children when they do not have E. histolytica infection and are free of diarrheal disease. Investigators also plan to obtain blood for cytokine analysis from children within 48 hours of the diagnosis of E. histolytica infection or disease. Birth to 5 years
Secondary Peripheral blood mononuclear cell tumor necrosis factor-ß stimulation studies Investigators plan to obtain blood for cytokine analysis from children when they do not have E. histolytica infection and are free of diarrheal disease. Investigators also plan to obtain blood for cytokine analysis from children within 48 hours of the diagnosis of E. histolytica infection or disease. Birth to 5 years
Secondary Peripheral blood mononuclear cell granulocyte-colony stimulating factor stimulation studies Investigators plan to obtain blood for cytokine analysis from children when they do not have E. histolytica infection and are free of diarrheal disease. Investigators also plan to obtain blood for cytokine analysis from children within 48 hours of the diagnosis of E. histolytica infection or disease. Birth to 5 years
Secondary Peripheral blood mononuclear cell macrophage inflammatory protein (MIP)-1 ß stimulation studies Investigators plan to obtain blood for cytokine analysis from children when they do not have E. histolytica infection and are free of diarrheal disease. Investigators also plan to obtain blood for cytokine analysis from children within 48 hours of the diagnosis of E. histolytica infection or disease. Birth to 5 years
Secondary Peripheral blood mononuclear cell MIP-1 a stimulation studies Investigators plan to obtain blood for cytokine analysis from children when they do not have E. histolytica infection and are free of diarrheal disease. Investigators also plan to obtain blood for cytokine analysis from children within 48 hours of the diagnosis of E. histolytica infection or disease. Birth to 5 years
Secondary Peripheral blood mononuclear cell monocyte chemotactic protein-1 stimulation studies Investigators plan to obtain blood for cytokine analysis from children when they do not have E. histolytica infection and are free of diarrheal disease. Investigators also plan to obtain blood for cytokine analysis from children within 48 hours of the diagnosis of E. histolytica infection or disease. Birth to 5 years
Secondary Peripheral blood mononuclear cell eotaxin stimulation studies Investigators plan to obtain blood for cytokine analysis from children when they do not have E. histolytica infection and are free of diarrheal disease. Investigators also plan to obtain blood for cytokine analysis from children within 48 hours of the diagnosis of E. histolytica infection or disease. Birth to 5 years
Secondary Peripheral blood mononuclear cell fibroblast growth factor basic stimulation studies Investigators plan to obtain blood for cytokine analysis from children when they do not have E. histolytica infection and are free of diarrheal disease. Investigators also plan to obtain blood for cytokine analysis from children within 48 hours of the diagnosis of E. histolytica infection or disease. Birth to 5 years
Secondary Peripheral blood mononuclear cell vascular endothelial growth factor stimulation studies Investigators plan to obtain blood for cytokine analysis from children when they do not have E. histolytica infection and are free of diarrheal disease. Investigators also plan to obtain blood for cytokine analysis from children within 48 hours of the diagnosis of E. histolytica infection or disease. Birth to 5 years
Secondary Peripheral blood mononuclear cell "regulated on activation, normal T expressed and secreted" (RANTES) stimulation studies Investigators plan to obtain blood for cytokine analysis from children when they do not have E. histolytica infection and are free of diarrheal disease. Investigators also plan to obtain blood for cytokine analysis from children within 48 hours of the diagnosis of E. histolytica infection or disease. Birth to 5 years
Secondary Peripheral blood mononuclear cell leptin stimulation studies Investigators plan to obtain blood for cytokine analysis from children when they do not have E. histolytica infection and are free of diarrheal disease. Investigators also plan to obtain blood for cytokine analysis from children within 48 hours of the diagnosis of E. histolytica infection or disease. Birth to 5 years
Secondary Peripheral blood mononuclear cell epithelial neutrophil activating peptide (ENA)-78 stimulation studies Investigators plan to obtain blood for cytokine analysis from children when they do not have E. histolytica infection and are free of diarrheal disease. Investigators also plan to obtain blood for cytokine analysis from children within 48 hours of the diagnosis of E. histolytica infection or disease. Birth to 5 years
Secondary Peripheral blood mononuclear cell nerve growth factor stimulation studies Investigators plan to obtain blood for cytokine analysis from children when they do not have E. histolytica infection and are free of diarrheal disease. Investigators also plan to obtain blood for cytokine analysis from children within 48 hours of the diagnosis of E. histolytica infection or disease. Birth to 5 years
Secondary Peripheral blood mononuclear cell inducible protein-10 stimulation studies Investigators plan to obtain blood for cytokine analysis from children when they do not have E. histolytica infection and are free of diarrheal disease. Investigators also plan to obtain blood for cytokine analysis from children within 48 hours of the diagnosis of E. histolytica infection or disease. Birth to 5 years
Secondary Fecal immunoglobulin-A This will be collected as paired samples. One sample will be from each episode of Amebiasis diarrhea and will paired with a stool from that child when they have no Amebiasis detected in the stool and are without acute diarrhea. Birth to 5 years
Secondary Fecal immunoglobulin-G anti-cross-reacting determinant This will be collected as paired samples. One sample will be from each episode of Amebiasis diarrhea and will paired with a stool from that child when they have no Amebiasis detected in the stool and are without acute diarrhea. Birth to 5 years
Secondary Single nucleotide polymorphism analysis of innate and adaptive immunity Once; between birth and day 7 of life.
Secondary Genome wide association scan Once, at 5 years of age
Secondary Fecal microbiome determination via 16s ribosomal deoxyribonucleic acid (rDNA) Birth to 5 years
Secondary Length/Height in centimeters Birth to 5 years
Secondary Weight in grams Birth to 5 years
See also
  Status Clinical Trial Phase
Terminated NCT00001162 - Parasitic Infections of the Gastrointestinal Tract N/A
Completed NCT00366730 - Study of Nitazoxanide in the Treatment of Amebiasis in Children Phase 3
Completed NCT00366236 - Study of Nitazoxanide in the Treatment of Amebiasis in Adults and Adolescents Phase 3