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Field Studies of Amebiasis in Bangladesh

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ClinicalTrials.gov Identifier: NCT02734264
Recruitment Status : Completed
First Posted : April 12, 2016
Last Update Posted : October 26, 2017
Sponsor:
Collaborator:
International Centre for Diarrhoeal Disease Research, Bangladesh
Information provided by (Responsible Party):
William Petri, MD, University of Virginia

Brief 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.

Condition or disease
Amebiasis Cryptosporidium

Detailed 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.


Study Type : Observational
Actual Enrollment : 629 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Field Studies of Human Immunity to Amebiasis in Bangladesh: A Prospective Study of Children Ages 0-17 Years
Study Start Date : January 2008
Actual Primary Completion Date : December 2014
Actual Study Completion Date : December 2014

Resource links provided by the National Library of Medicine

U.S. FDA Resources




Primary Outcome Measures :
  1. Incidence of Amebiasis and Cryptosporidium infection [ Time Frame: Birth to 5 years ]

Secondary Outcome Measures :
  1. Peripheral blood mononuclear cell Interleukin (IL)-1β stimulation studies [ Time Frame: Birth to 5 years ]
    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.

  2. Peripheral blood mononuclear cell IL-2 stimulation studies [ Time Frame: Birth to 5 years ]
    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.

  3. Peripheral blood mononuclear cell IL-4 stimulation studies [ Time Frame: Birth to 5 years ]
    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.

  4. Peripheral blood mononuclear cell IL-5 stimulation studies [ Time Frame: Birth to 5 years ]
    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.

  5. Peripheral blood mononuclear cell IL-6 stimulation studies [ Time Frame: Birth to 5 years ]
    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.

  6. Peripheral blood mononuclear cell IL-7 stimulation studies [ Time Frame: Birth to 5 years ]
    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.

  7. Peripheral blood mononuclear cell IL-8 stimulation studies [ Time Frame: Birth to 5 years ]
    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.

  8. Peripheral blood mononuclear cell IL-10 stimulation studies [ Time Frame: Birth to 5 years ]
    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.

  9. Peripheral blood mononuclear cell IL-12(p70) stimulation studies [ Time Frame: Birth to 5 years ]
    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.

  10. Peripheral blood mononuclear cell IL-12(p40) stimulation studies [ Time Frame: Birth to 5 years ]
    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.

  11. Peripheral blood mononuclear cell IL-13 stimulation studies [ Time Frame: Birth to 5 years ]
    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.

  12. Peripheral blood mononuclear cell IL-17 stimulation studies [ Time Frame: Birth to 5 years ]
    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.

  13. Peripheral blood mononuclear cell interferon-γ stimulation studies [ Time Frame: Birth to 5 years ]
    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.

  14. Peripheral blood mononuclear cell granulocyte-macrophage colony-stimulating factor stimulation studies [ Time Frame: Birth to 5 years ]
    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.

  15. Peripheral blood mononuclear cell tumor necrosis factor-α stimulation studies [ Time Frame: Birth to 5 years ]
    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.

  16. Peripheral blood mononuclear cell tumor necrosis factor-β stimulation studies [ Time Frame: Birth to 5 years ]
    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.

  17. Peripheral blood mononuclear cell granulocyte-colony stimulating factor stimulation studies [ Time Frame: Birth to 5 years ]
    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.

  18. Peripheral blood mononuclear cell macrophage inflammatory protein (MIP)-1 β stimulation studies [ Time Frame: Birth to 5 years ]
    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.

  19. Peripheral blood mononuclear cell MIP-1 α stimulation studies [ Time Frame: Birth to 5 years ]
    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.

  20. Peripheral blood mononuclear cell monocyte chemotactic protein-1 stimulation studies [ Time Frame: Birth to 5 years ]
    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.

  21. Peripheral blood mononuclear cell eotaxin stimulation studies [ Time Frame: Birth to 5 years ]
    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.

  22. Peripheral blood mononuclear cell fibroblast growth factor basic stimulation studies [ Time Frame: Birth to 5 years ]
    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.

  23. Peripheral blood mononuclear cell vascular endothelial growth factor stimulation studies [ Time Frame: Birth to 5 years ]
    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.

  24. Peripheral blood mononuclear cell "regulated on activation, normal T expressed and secreted" (RANTES) stimulation studies [ Time Frame: Birth to 5 years ]
    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.

  25. Peripheral blood mononuclear cell leptin stimulation studies [ Time Frame: Birth to 5 years ]
    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.

  26. Peripheral blood mononuclear cell epithelial neutrophil activating peptide (ENA)-78 stimulation studies [ Time Frame: Birth to 5 years ]
    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.

  27. Peripheral blood mononuclear cell nerve growth factor stimulation studies [ Time Frame: Birth to 5 years ]
    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.

  28. Peripheral blood mononuclear cell inducible protein-10 stimulation studies [ Time Frame: Birth to 5 years ]
    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.

  29. Fecal immunoglobulin-A [ Time Frame: Birth to 5 years ]
    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.

  30. Fecal immunoglobulin-G anti-cross-reacting determinant [ Time Frame: Birth to 5 years ]
    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.

  31. Single nucleotide polymorphism analysis of innate and adaptive immunity [ Time Frame: Once; between birth and day 7 of life. ]
  32. Genome wide association scan [ Time Frame: Once, at 5 years of age ]
  33. Fecal microbiome determination via 16s ribosomal deoxyribonucleic acid (rDNA) [ Time Frame: Birth to 5 years ]
  34. Length/Height in centimeters [ Time Frame: Birth to 5 years ]
  35. Weight in grams [ Time Frame: Birth to 5 years ]

Biospecimen Retention:   Samples With DNA
Serum and feces


Information from the National Library of Medicine

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Ages Eligible for Study:   up to 7 Days   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Newborn children in the Mirpur neighborhood of Dhaka, Bangladesh.
Criteria

Inclusion Criteria:

  • Resident of Mirpur, Dhaka, Bangladesh

Exclusion Criteria:

  • Mother under 65 years old

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02734264


Locations
Bangladesh
The International Centre for Diarrhoeal Disease Research, Bangladesh
Dhaka, Bangladesh
Sponsors and Collaborators
University of Virginia
International Centre for Diarrhoeal Disease Research, Bangladesh
Investigators
Principal Investigator: William A Petri, M.D., PhD University of Virginia

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: William Petri, MD, Division Chief, Infectious Disease, University of Virginia
ClinicalTrials.gov Identifier: NCT02734264     History of Changes
Other Study ID Numbers: 7563
First Posted: April 12, 2016    Key Record Dates
Last Update Posted: October 26, 2017
Last Verified: April 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Additional relevant MeSH terms:
Amebiasis
Dysentery, Amebic
Protozoan Infections
Parasitic Diseases
Intestinal Diseases, Parasitic
Dysentery
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases