Amebiasis Clinical Trial
Official title:
Field Studies of Human Immunity to Amebiasis in Bangladesh: A Prospective Study of Children Ages 0-17 Years
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.
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.
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Terminated |
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Completed |
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