*Corresponding author:Elham Ahmed Hassan, MD, Department of Gastroenterology and Tropical Medicine, Al-Rajhi liver center, Assiut University Hospital, Assiut 71515, Egypt
How to cite this article:Elham A H, Amany M A-H, Saad Z M, Mohamed E M, Asmaa O A, et al. Amoebiasis in Active Ulcerative Colitis: Epidemiological
Aspects, Association and Impact of Anti-Amoebic Therapy on Disease Severity. Adv Res Gastroentero Hepatol, 2020;15(1): 555899.
Background and Aim: the incidence of ulcerative colitis (UC) is increasing worldwide. Several enteropathogens may be implicated in its pathogenesis. Amoebiasis is a common infection but it is overlooked or neglected especially in endemic regions. The study aimed to assess the frequency of Entamoeba (E.) histolytica in patients with active UC and evaluate the impact of the parasite and its therapy on disease severity.
Patients and Methods: Fresh fecal samples of 30 patients with active UC were examined for direct detection of E. histolytica cysts or trophozoites and its specific Ag (E. histolytica II) using ELISA. Colonoscopy and assessment of UC severity based on Mayo score and Montreal Classification were done. Patients with amoebiasis received anti-amoebic therapy and were followed up for 2 weeks.
Results: About 36.7% of those patients had amoebiasis. Amoebic infection was significantly higher in older age (P=0.048) and those with co-morbidities (P=0.001). Amoebiasis significantly associated with severe course (P=0.041, OR=1.2, 95%CI:0.2–2.1). Ten of eleven cases with amoebiasis had moderate/severe UC. On receiving anti-amoebic therapy, those patients showed clinical improvement with absent parasite in feces and mucosal healing in some cases.
Conclusion: Searching for amoebiasis in patients with active UC is important as it may be a trigger for UC exacerbation in endemic regions. Anti-amoebic therapy could be indicated for patients with persistent UC to avoid serious complications.
Keywords: Ulcerative colitis; Amoebiasis; E. histolytica; Exacerbation; Activity flare
Ulcerative colitis (UC) is a chronic, idiopathic inflammatory condition of the colonic mucosa characterized by a relapsing course that often requires long-term therapy to maintain remission . A complex of genetic, immune and environmental factors may be implicated in UC pathogenesis. Additionally, the possibility of enteric pathogens in initiation or reactivation of the quiescent disease had been reported . Management of UC is a significant clinical challenge as its active phase is associated with bloody diarrhea with mucus simulating infectious colitis also its treatment with immunomodulators and biological agents increases the risk of opportunistic infections and exacerbates
concomitant infections [3-5]. The frequency of these infections in UC patients is underestimated probably due to low index of suspicion or problems in their detection.
Amoebiasis is a common parasitic infection and globally about 50 million people are affected by Entamoeba (E.) histolytica, primarily in developing countries, with high annual fatality rate (over 100,000 deaths a year) [6,7]. It has been associated with autoimmune phenomena including antibodies to colonic epithelial cells and UC development . Both amoebic colitis and UC constitute major health problems particularly in endemic areas for amoebiasis. Amoebic colitis can mimic acute phase of UC causing misdiagnosis or coexist with UC causing missed diagnosis
. Missed or misdiagnosis of amoebic infection in UC patients
receiving immunosuppressive agents may cause Fulminant
colitis, bowel perforation and peritonitis with a high mortality
rate . Furthermore, Amoebiasis can exacerbate symptoms and
adversely affect the course of UC . So, screening for amoebiasis
is crucial in patients with UC flares for accurate diagnosis and
Earlier studies assessed the frequency and participation of
several enteropathogens including amoebiasis in UC flares [3-
5], however, these studies are deficient in our region. Egypt is
endemic for amoebiasis with a high prevalence of 38% and it has
an increasing incidence of UC in the last years so, distinguishing UC
from amoebic colitis is important [6,7,10]. Therefore, we aimed to
assess the epidemiological aspects of amoebiasis in patients with
active UC, and the impact of the parasite and its therapy on the
This cohort study was carried out prospectively at Assiut
University Hospital, Assiut, Egypt between January 2019 and June
2019. The study was approved by the Local Ethics Committee
of Assiut University Hospital (The ethical approval code was
17100958) and was conducted in accordance with the previsions
of the Declaration of Helsinki. Informed consent was obtained
from all the participants before enrollment.
During the study period, patients with well-defined active UC
admitted to Gastroenterology and Tropical Medicine Department,
Assiut University Hospital, Assiut, Egypt were consecutively
included in the study. The diagnosis of UC and its activity was
based on clinical, colonoscopic and histopathological findings
[11,12], and the severity of UC activity was assessed by Mayo
and Partial Mayo scores and Montreal classification [13,14].
Amoebiasis was diagnosed by the presence of the parasite and its
specific antigen in stool. Patients known to have IBD other than
UC or colorectal malignancies were excluded.
At study entry, thorough medical history and physical
examination were taken for data collection e.g., age, sex, comorbidities,
rectal bleeding, bloody diarrhea and its daily
frequency and severity of disease. Laboratory investigations
including complete blood picture, serum albumin, serum
C-reactive protein (CRP) and erythrocyte sedimentation rate
(ESR) were done. Stool analysis for the presence of E. histolytica
(trophozoites and/or cysts) and for detection of E. Histolytica Ag
was one. In addition, colonoscopy and assessment of Mayo score
were done for all participants.
With universal safety precautions and standard laboratory
protocols, fresh faecal samples were collected from each patient
in a dry, clean, leak-proof plastic container to be examined for E.
histolytica. Fresh and Formol-ether concentrated stool specimens
were examined as saline and Lugol’s iodine wet mount to detect
motile trophozites and cysts respectively. If Entamoeba parasite
was identified in stool, ELISA detection of faecal E. histolytica
adhesion antigen was used to confirm diagnosis using E. histolytica
II assay “TechLab, Blacksburg, VA, USA” that was performed
according to the manufacturer’s instructions.
Steroids were stopped for those patients with amoebic
infection then they received a single oral dose of 500 mg of
Secnidazole, anti-amoebic drug, and followed by oral diloxanide
furoate (500 mg) three times daily for 10 days. Their response
was evaluated within 2 weeks by clinical history and examination,
assessment of Partial Mayo score and stool analysis for detection
of the parasite and colonoscopy in some cases.
Statistical analyses were conducted using SPSS for windows
version 16 (IBM Corp., Armonk, NY, USA) and Microsoft Excel
2010. The continuous data was expressed as means ± standard
deviation (SD) or median and range and was compared using
Student’s t test or Mann-Whitney U test. Categorical variables
were expressed as a percentage and compared using chi-squared
(χ2) or Fisher’s exact probability test. Multiple regression analysis
was used to study the influence of independent variables on
amoebic infection. Wilcoxon (two –related samples) test was used
to compare the partial Mayo score in UC patients with positive
E. histolytica Ag in response to anti-amoebic treatment. For all
analyses, P value < 0.05 is statistically significant.
A total of 30 patients with active UC were consecutively
included in the study between January and June 2019. Their
mean age was 34 ± 9.5 years and 53.3% were females. The
extent of disease was extensive colitis (46.7%), left-sided colitis
(36.7%) and proctitis (16.6%). Regarding severity of activity, 20
of the patients (66.7%) had moderate activity, 7 (23.3%) had mild
activity, and 3 (10%) had severe disease. Apart from one patient
who treated with infliximab, participated patients treated with
conventional treatment (5-aminosalicylic acid with or without
immunotherapy) for their disease. Detailed clinical and laboratory
and endoscopic findings of the studied patients were summarized
in Table 1.
On fecal examination, amoebic infection was identified in
36.7% of patients (6 females and 5 males with mean age of 38.5
± 8.8 years), where, trophozites were detected in two cases, cysts
in seven cases and both trophozites and cysts in further two
cases. Furthermore, the presence of E. histolytica was confirmed
with fecal detection of its specific Ag in these cases. Details of
characteristics of ulcerative colitis patients with E. histolytica Ag
were shown in Table 2.
Compared to those without amoebiasis, patients with
amoebiasis were significantly older age where 45.5% of these
cases were older than 40 years. In addition, co-morbidities,
frequency of diarrheal attacks per day, severity of the disease
based on Montreal classification, Mayo and partial Mayo scores
were significantly higher in patients with amoebic infection
compared to those without infection. However, gender and other
clinical and laboratory parameters had no significant differences
between two groups (Table 1).
The presence of amoebiasis was significantly associated with
moderate/severe UC (0.041). Ten out of eleven cases (90.9%) with
E. histolytica had moderate/severe UC, while 13 out of 19 cases
(68.4 %) without E. histolytica had moderate/severe UC (Table 3).
Detection of E. histolytica in stool was associated with a relative
risk for moderate/severe UC of 1.2 (95% CI: 0.2 to 2.1) compared
to patients without detectable E. histolytica.
On receiving the anti-amoebic therapy, those patients clinically
improved e.g., decrease the frequency of daily diarrheal attacks,
decrease blood amount in stool, improved their general condition
and absence of fecal parasite with colonoscopic mucosal healing
in some cases (Figure 1). In addition, those patients receiving
anti-amoebic treatment showed significant improvement in
their partial Mayo scores [pre-treatment score 7 (3 - 9) vs. posttreatment
5 (2 -7), P < 0.001] as shown in Figure 2.
This study aimed to highlight the epidemiological aspects
of amoebiasis in patients with active UC, and the impact of the
parasite and its therapy on disease severity. Egypt has a high
prevalence of amoebic infection [4,7], and a limited published
data on amoebiasis and its relation to UC activity coexist so,
it was encouraged to be carried out on that special population.
Infection may contribute in the ethiopathogenesis of UC affecting
the colonic mucosa with disarrangement in its immunity .
Amoebic infection is usually overlooked or underestimated due to diverse clinical and colonoscopic presentations of amoebic
colitis confusing with other types of colitis including UC in
addition to difficulty in its definitive diagnosis with absence of
fecal trophozoites and cysts in some cases [4,15]. Detection of E.
histolytica by identifying both the parasite and its specific Ag in
stool, as in our cases, supports the diagnostic utility and enhances
the sensitivity to definite detection of amoebic infection .
Our analysis identified amoebiasis in 36.7% of thirty patients
with active UC. Our result was higher than that mentioned in
previous studies in Mexico (5%), Turkey (17.2%), and Bosnia and
Herzegovina (14.3%) owing to its endemicity in our area along
with various environmental and socioeconomic factors .
This study corroborates that age, co-morbidities and disease
severity were independently associated with amoebiasis in those
patients that were in agreement with previous studies [16-18].
We found that UC patients with amoebiasis were significantly
older than those without, where 45.5% of cases were over 40
years old because of their poor health and higher frequency of comorbidities
that increased their susceptibility to infection. These
findings were consistent with earlier reports that showed that the
peak rate of amoebiasis occurred between 40 and 49 years . In
line with previous studies [4,19], in those UC patients, amoebiasis
were significantly associated with severe course that can be
explained by mucosal disruption facilitating mucosal invasion of
trophozoites and worsening the clinical and endoscopic conditions
. Babic et al.,  documented that hyperactivity of the mucosal
immune system to the intraluminal antigens e.g., E. histolytica can
initiate or reactivate quiescent disease in IBD. Schulzke et al., 
reported that infectious gastroenteritis (IGE) may exacerbate IBD
increasing its risk (OR= 1.40, 95% CI: 1.19 - 1.66). In addition, the
increased use of immunomodulators and biological agents can
increase the risk of enteropathogens including amoebiasis among
those patients . These data indicate that stools from UC patients
should be examined before planning optimal medical therapy.
Contrary to our finding, Vukobrat-Bijedic et al.,  found that
disease severity was not associated with amoebic infection in UC
Consistent with the earlier series [21-23], in this study,
treatment of infected patients with anti-amoebic therapy showed
symptomatic improvement and colonic mucosal healing in
some cases. Collins and Bynum , treated four UC patients
with amoebiasis by medications for both diseases and observed
a good response. However, Brown & Winkelman , treated
two UC patients with amoebiasis with anti-amoebic therapy
resulting in clinical and endoscopic improvement with abolition
of colectomy decision in one of those two patients. Underwood
 and Shirley & Moonah  concluded that this concomitant
amoebiasis should always be considered before administrating
corticosteroids and/or immunosuppressive therapy especially
in UC patients residing in endemic areas or with a travel history.
Therefore, an empirical trial of anti-amoebic therapy should
be recommended in persistent or relapsing IBD, especially in
endemic areas that may reduce or prevent serious complications
or unneeded critical management as colectomy. In this study,
secnidazole was administrated in a single oral dose that was
better tolerated with a high cure rate making it a suitable option
to other single-dose treatments and an attractive alternative to
multiple dose regimens with other drugs in this class [15,26]. This
study has certain strengths and limitations. This is one of the very
few studies that have searched for amoebic infection as a trigger
for UC exacerbations and the effect of its treatment on disease
severity in this endemic area where the majority of previous
studies discussed amoebiasis in patients who lived in developed
countries and had a travel history. In addition, amoebic infection
was diagnosed by detecting the parasite and its specific Ag in stool
to differentiate it from non-pathogenic organisms e.g., E. dispar
or E. moshkovskiis and to distinguish new from past infection
in our region where seroprevalence is high. Single dose of antiamoebic
drug “secnidazole” was highly effective and tolerated in
those patients who were exhausted by frequent medications. On
the other hand, there were some limitations to this work. It was a
small sample sized and single-centre study however, it carried out
in Assiut University Hospital; a tertiary care centre, where cases
of persistent or relapsing UC is more possible to be admitted.
Colonoscopic mucosal biopsies for detection of the parasite were
not taken for fear of perforation during air insufflations to expand
the colon in those patients with UC flares. So, large multicenter
cohort studies will be emphasized to confirm these findings.
Intestinal amoebiasis was presented in 36.7% of patients
with active UC that may contribute to in its activity flare or
persistence despite optimal medical treatment of UC. Searching
for E. histolytica is recommended in every patient with UC to rule
out missed or misdiagnosis. A trial of anti-amoebic therapy may
be indicated for any patient with persistent UC to avoid serious