Field Studies of Amebiasis in Bangladesh
关键词
抽象
描述
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.
日期
最后验证: | 03/31/2016 |
首次提交: | 03/21/2016 |
提交的预估入学人数: | 04/04/2016 |
首次发布: | 04/11/2016 |
上次提交的更新: | 10/23/2017 |
最近更新发布: | 10/25/2017 |
实际学习开始日期: | 12/31/2007 |
预计主要完成日期: | 11/30/2014 |
预计完成日期: | 11/30/2014 |
状况或疾病
相
资格标准
有资格学习的性别 | All |
取样方式 | Non-Probability Sample |
接受健康志愿者 | 是 |
标准 | Inclusion Criteria: - Resident of Mirpur, Dhaka, Bangladesh Exclusion Criteria: - Mother under 65 years old |
结果
主要结果指标
1. Incidence of Amebiasis and Cryptosporidium infection [Birth to 5 years]
次要成果指标
1. Peripheral blood mononuclear cell Interleukin (IL)-1β stimulation studies [Birth to 5 years]
2. Peripheral blood mononuclear cell IL-2 stimulation studies [Birth to 5 years]
3. Peripheral blood mononuclear cell IL-4 stimulation studies [Birth to 5 years]
4. Peripheral blood mononuclear cell IL-5 stimulation studies [Birth to 5 years]
5. Peripheral blood mononuclear cell IL-6 stimulation studies [Birth to 5 years]
6. Peripheral blood mononuclear cell IL-7 stimulation studies [Birth to 5 years]
7. Peripheral blood mononuclear cell IL-8 stimulation studies [Birth to 5 years]
8. Peripheral blood mononuclear cell IL-10 stimulation studies [Birth to 5 years]
9. Peripheral blood mononuclear cell IL-12(p70) stimulation studies [Birth to 5 years]
10. Peripheral blood mononuclear cell IL-12(p40) stimulation studies [Birth to 5 years]
11. Peripheral blood mononuclear cell IL-13 stimulation studies [Birth to 5 years]
12. Peripheral blood mononuclear cell IL-17 stimulation studies [Birth to 5 years]
13. Peripheral blood mononuclear cell interferon-γ stimulation studies [Birth to 5 years]
14. Peripheral blood mononuclear cell granulocyte-macrophage colony-stimulating factor stimulation studies [Birth to 5 years]
15. Peripheral blood mononuclear cell tumor necrosis factor-α stimulation studies [Birth to 5 years]
16. Peripheral blood mononuclear cell tumor necrosis factor-β stimulation studies [Birth to 5 years]
17. Peripheral blood mononuclear cell granulocyte-colony stimulating factor stimulation studies [Birth to 5 years]
18. Peripheral blood mononuclear cell macrophage inflammatory protein (MIP)-1 β stimulation studies [Birth to 5 years]
19. Peripheral blood mononuclear cell MIP-1 α stimulation studies [Birth to 5 years]
20. Peripheral blood mononuclear cell monocyte chemotactic protein-1 stimulation studies [Birth to 5 years]
21. Peripheral blood mononuclear cell eotaxin stimulation studies [Birth to 5 years]
22. Peripheral blood mononuclear cell fibroblast growth factor basic stimulation studies [Birth to 5 years]
23. Peripheral blood mononuclear cell vascular endothelial growth factor stimulation studies [Birth to 5 years]
24. Peripheral blood mononuclear cell "regulated on activation, normal T expressed and secreted" (RANTES) stimulation studies [Birth to 5 years]
25. Peripheral blood mononuclear cell leptin stimulation studies [Birth to 5 years]
26. Peripheral blood mononuclear cell epithelial neutrophil activating peptide (ENA)-78 stimulation studies [Birth to 5 years]
27. Peripheral blood mononuclear cell nerve growth factor stimulation studies [Birth to 5 years]
28. Peripheral blood mononuclear cell inducible protein-10 stimulation studies [Birth to 5 years]
29. Fecal immunoglobulin-A [Birth to 5 years]
30. Fecal immunoglobulin-G anti-cross-reacting determinant [Birth to 5 years]
31. Single nucleotide polymorphism analysis of innate and adaptive immunity [Once; between birth and day 7 of life.]
32. Genome wide association scan [Once, at 5 years of age]
33. Fecal microbiome determination via 16s ribosomal deoxyribonucleic acid (rDNA) [Birth to 5 years]
34. Length/Height in centimeters [Birth to 5 years]
35. Weight in grams [Birth to 5 years]