The new england journal of medicine

review article

current concepts

Amebiasis
Rashidul Haque, M.B., Ph.D., Christopher D. Huston, M.D.,
Molly Hughes, M.D., Ph.D., Eric Houpt, M.D., and William A. Petri, Jr., M.D., Ph.D.

d iarrheal diseases continue to be major causes of morbidity

and mortality in children in developing countries. For example, in Bangladesh
1 in 30 children dies of diarrhea or dysentery by his or her fifth birthday.1 In
developed countries the microorganisms that cause diarrheal disease remain of concern
because of their potential use as bioterrorist agents. Bacillary dysentery is most com-
From the International Centre for Diarrhoe-
al Disease Research, Dhaka, Bangladesh
(R.H.); the University of Vermont, Burling-
ton (C.D.H.); and the University of Virgin-
ia, Charlottesville (M.H., E.H., W.A.P.). Ad-
dress reprint requests to Dr. Petri at the
Division of Infectious Diseases and Interna-
monly caused by microorganisms belonging to the genus shigella, whereas amebic dys- tional Health, University of Virginia Health
entery is caused by the protozoan parasite Entamoeba histolytica. The annual number of System, Rm. 2115, MR4 Bldg., P.O. Box
shigella infections throughout the world is believed to be approximately 164 million.2 801340, Charlottesville, VA 22908-1340, or
at [email protected].
Estimates of E. histolytica infections have primarily been based on examinations of stool
for ova and parasites, but these tests are insensitive and cannot differentiate E. histolytica N Engl J Med 2003;348:1565-73.
Copyright 2003 Massachusetts Medical Society.
from morphologically identical species that are nonpathogenic, such as E. dispar and
E. moshkovskii.3,4
Specific and sensitive means to detect E. histolytica in stool are now available and in-
clude antigen detection and the polymerase chain reaction (PCR).5 Two recent studies
in developing countries used these modern diagnostic tests. A three-year study in Dhaka,
Bangladesh, showed that preschool children had a 2.2 percent frequency of amebic
dysentery, as compared with a 5.3 percent frequency of shigella dysentery6 (and unpub-
lished data). The annual incidence of amebic liver abscess was reported to be 21 cases
per 100,000 inhabitants in Hue City, Vietnam.7 In the United States, where fecaloral
transmission is unusual, amebiasis is most commonly seen in immigrants from and
travelers to developing countries. The disease is more severe in the very young and old
and in patients receiving corticosteroids.

entamoeba histolytica
Molecular phylogeny places entamoeba on one of the lowermost branches of the eu-
karyotic tree, closest to dictyostelium. Although the organism was originally thought to
lack mitochondria, nuclear-encoded mitochondrial genes and a remnant organelle have
now been identified.8,9 Unusual features of entamoeba include polyploid chromosomes
that vary in length; multiple origins of DNA replication; abundant, repetitive DNA; close-
ly spaced genes that largely lack introns; a novel GAAC element controlling the expres-
sion of messenger RNA; and unique endocytic pathways.10-13

pathogenesis
Ingestion of the quadrinucleate cyst of E. histolytica from fecally contaminated food or
water initiates infection (Fig. 1). This is a daily occurrence among the poor in developing
countries and is a threat to inhabitants of developed countries, as the epidemic linked to
contaminated municipal water supplies in Tbilisi, Republic of Georgia, demonstrates.14
Excystation in the intestinal lumen produces trophozoites that use the galactose and

n engl j med 348;16 www.nejm.org april 17, 2003 1565

The New England Journal of Medicine

Downloaded from nejm.org on February 18, 2014. For personal use only. No other uses without permission.
Copyright 2003 Massachusetts Medical Society. All rights reserved.
 The new england journal of medicine

N-acetyl-d-galactosamine (Gal/GalNAc)specific cysteine proteinases also degrade secretory IgA

lectin to adhere to colonic mucins and thereby colo- and serum IgG, possibly protecting amebae from
nize the large intestine.15 The reproduction of opsonization. Finally, amebae appear to suppress
trophozoites has no sexual cycle, and the overall both the macrophage respiratory burst and antigen
population of E. histolytica appears to be clonal.16 presentation by class II major-histocompatibility-
Aggregation of amebae in the mucin layer most complex (MHC) molecules.
likely triggers encystation by means of the Gal/Gal-
NAc-specific lectin.17 Cysts excreted in stool per-
immunity
petuate the life cycle by further fecaloral spread.
Colitis results when the trophozoite penetrates Immunity to infection with E. histolytica is associat-
the intestinal mucous layer, which otherwise acts ed with a mucosal IgA response against the car-
as a barrier to invasion by inhibiting amebic adher- bohydrate-recognition domain of the Gal/GalNAc
ence to the underlying epithelium and by slowing lectin. Over a one-year period, children with this re-
trophozoite motility.18 Invasion is mediated by the sponse had 86 percent fewer new infections than
killing of epithelial cells, neutrophils, and lympho- children without this response.6 Cell-mediated
cytes by trophozoites, which occurs only after the responses have been described in patients with ame-
parasite lectin engages host N-acetyl-d-galactos- bic liver abscess, characterized by lymphocyte pro-
amine on O-linked cell-surface oligosaccharides.15 liferation and lymphokine secretion that is amebi-
The interaction of the lectin with glycoconjugates cidal in vitro.29 One study found that in patients
is stereospecific and multivalent.19 The identity of with liver abscess, the prevalence of the class II MHC
the high-affinity intestinal epithelial-cell receptor is haplotype HLA-DR3 is increased by a factor of more
unknown. Secretion by the ameba of amoebapore, than three, suggesting a role of CD4+ T-cell func-
a 5-kD pore-forming protein, may contribute to kill- tion in the outcome of the disease.30 It is notewor-
ing.20 Activation of human caspase 3, a distal effec- thy, however, that the acquired immunodeficiency
tor molecule in the apoptotic pathway, occurs rapid- syndrome pandemic has not led to increases in inva-
ly after amebic contact, and caspases are required sive amebiasis, although asymptomatic intestinal
for cell killing in vitro and for the formation of ame- colonization is undoubtedly common.31 In fact, in
bic liver abscesses in vivo.21,22 the murine model of amebic colitis, the depletion of
Interaction of the parasite with the intestinal ep- CD4+ T cells decreases the severity of the disease.32
ithelium causes an inflammatory response marked
by the activation of nuclear factor kB and the se-
cretion of lymphokines.23,24 The development of
this epithelial response may depend on trophozo- Figure 1 (facing page). Life Cycle of Entamoeba histolytica.
ite virulence factors such as cysteine proteinase and Infection is normally initiated by the ingestion of fecally
contaminated water or food containing E. histolytica
leads to intestinal abnormalities through neutro-
cysts. The infective cyst form of the parasite survives pas-
phil-mediated damage. Neutrophils can also be pro- sage through the stomach and small intestine. Excysta-
tective, however, in that activation of neutrophils or tion occurs in the bowel lumen, where motile and
macrophages by tumor necrosis factor a or inter- potentially invasive trophozoites are formed. In most in-
feron g kills amebae in vitro and limits the size of fections the trophozoites aggregate in the intestinal mu-
amebic liver abscesses.25 In contrast to the intense cin layer and form new cysts, resulting in a self-limited
inflammatory response typical of early invasive ame- and asymptomatic infection. In some cases, however,
adherence to and lysis of the colonic epithelium, medi-
biasis, inflammation surrounding well-established
ated by the galactose and N-acetyl-D-galactosamine
colonic ulcers and liver abscesses is minimal, given (Gal/GalNAc)specific lectin, initiates invasion of the colon
the degree of tissue damage.26 by trophozoites. Neutrophils responding to the invasion
During chronic infection, E. histolytica evades contribute to cellular damage at the site of invasion.
the host immune response in several ways. The Once the intestinal epithelium is invaded, extraintestinal
Gal/GalNAc-specific lectin has sequence similarity spread to the peritoneum, liver, and other sites may fol-
and antigenic cross-reactivity to CD59, a human leu- low. Factors controlling invasion, as opposed to encysta-
tion, most likely include parasite quorum sensing
kocyte antigen that prevents the assembly of the
signaled by the Gal/GalNAc-specific lectin, interactions
complement C5bC9 membrane attack complex.27 of amebae with the bacterial flora of the intestine, and in-
Amebic cysteine proteinases rapidly degrade the nate and acquired immune responses of the host.
complement anaphylatoxins C3a and C5a.28 The

1566 n engl j med 348;16 www.nejm.org april 17 , 2003

The New England Journal of Medicine

Downloaded from nejm.org on February 18, 2014. For personal use only. No other uses without permission.
Copyright 2003 Massachusetts Medical Society. All rights reserved.
 current concepts

Ingestion of fecally contaminated Brain

water or food containing
Entamoeba histolytica cysts

Invasive disease
10% of cases

Pleural and
pericardial effusions
Mucin
layer
Self-limiting, Extraintestinal
asymptomatic infection disease
90% of cases <1% of cases

Liver
abscess
Mucin
layer Hematogenous
dissemination

Colon
Invasion of
colon by Colitis
trophozoites
Excystation
in lumen of
small intestine
Multiplication
of trophozoites
by binary Invasion of mucosa
fission and submucosa
by trophozoites
Colonic
epithelium

Neutrophil-
Colonization induced
damage
Amebic
cytotoxicity

Encystation

Gal/GalNAc-specific Neutrophils
lectin
Excretion
of cyst

n engl j med 348;16 www.nejm.org april 17, 2003 1567

The New England Journal of Medicine

Downloaded from nejm.org on February 18, 2014. For personal use only. No other uses without permission.
Copyright 2003 Massachusetts Medical Society. All rights reserved.
 The new england journal of medicine

intestinal amebiasis
A B
Infection with E. histolytica may be asymptomatic or
may cause dysentery or extraintestinal disease (Fig.
2 and 3). Asymptomatic infection should be treated
because of its potential to progress to invasive dis-
ease. Patients with amebic colitis typically present
C with a several-week history of cramping abdominal
pain, weight loss, and watery or bloody diarrhea.
The insidious onset and variable signs and symp-
toms make diagnosis difficult, with fever and gross-
ly bloody stool absent in most cases.33-35 The dif-
D ferential diagnosis of a diarrheal illness with occult
or grossly bloody stools should include infection
with shigella, salmonella, campylobacter, and en-
teroinvasive and enterohemorrhagic Escherichia coli.
Noninfectious causes include inflammatory bowel
disease, ischemic colitis, diverticulitis, and arterio-
venous malformation.
Unusual manifestations of amebic colitis include
acute necrotizing colitis, toxic megacolon, amebo-
ma (Fig. 3B), and perianal ulceration with potential
formation of a fistula. Acute necrotizing colitis is
rare (occurring in less than 0.5 percent of cases)
and is associated with a mortality rate of more than
40 percent.35 Patients with acute necrotizing colitis
typically appear very ill, with fever, bloody mucoid
diarrhea, abdominal pain with rebound tenderness,
E F G and signs of peritoneal irritation. Surgical interven-
tion is indicated if there is bowel perforation or if
the patient has no response to antiamebic therapy.
Toxic megacolon is rare (occurring in approximately
0.5 percent of cases) and is typically associated with
the use of corticosteroids. Early recognition and
H I surgical intervention are important, since patients
with toxic megacolon usually have no response to
antiamebic therapy alone. Ameboma results from
the formation of annular colonic granulation tissue
at a single site or multiple sites, usually in the cecum
or ascending colon. An ameboma may mimic carci-
noma of the colon (Fig. 3B).
In developing countries, intestinal amebiasis is
Figure 2. Endoscopic and Pathological Features of Intestinal Amebiasis. most commonly diagnosed by identifying cysts or
Panel A shows the appearance of intestinal amebiasis on colonoscopy. Panel motile trophozoites on a saline wet mount of a stool
B shows colonic ulcers averaging 1 to 2 mm in diameter on gross pathological specimen (Fig. 2E, 2F, and 2H). The drawbacks of
examination. Panel C shows a cross-section of a flasked-shaped colonic ulcer
(hematoxylin and eosin, 20). Panel D shows an inflammatory response to in-
this method include its low sensitivity and false pos-
testinal invasion by Entamoeba histolytica (hematoxylin and eosin, 100). Ar- itive results owing to the presence of E. dispar or
rows indicate E. histolytica trophozoites. Panels E and F show E. histolytica E. moshkovskii infection. The diagnosis should ide-
cysts in a saline preparation (1000), and Panel G shows an iodine-stained ally be based on the detection in stool of E. histoly-
cyst from stool (1000). Panel H shows an E. histolytica trophozoite with an
ingested erythrocyte in a saline preparation from stool (1000), and Panel I
ticaspecific antigen or DNA and by the presence
shows a trophozoite from stool stained with trichrome (1000). (Panels B, C, of antiamebic antibodies in serum (Table 1). Field
and D are from the slide collection of the late Dr. Harrison Juniper.) studies that directly compared PCR with stool cul-
ture or antigen-detection tests for the diagnosis of

1568 n engl j med 348;16 www.nejm.org april 17 , 2003

The New England Journal of Medicine

Downloaded from nejm.org on February 18, 2014. For personal use only. No other uses without permission.
Copyright 2003 Massachusetts Medical Society. All rights reserved.
 current concepts

A B

C D

Figure 3. Radiographic and Pathological Features of Extraintestinal Amebiasis.

Panel A shows a posteroanterior (left-hand side) and lateral (right-hand side) chest radiograph in a patient with amebic
liver abscess. The findings include elevated right hemidiaphragm and evidence of atelectasis. Panel B shows luminal
narrowing (arrow) on a barium-enema examination in a patient with ameboma. Panel C shows two abscesses in the
right lobe and one abscess in the left lobe in a patient with amebic liver abscess. In Panel D, abdominal computed to-
mography in a patient with amebic liver abscess shows one abscess in the right lobe and one abscess in the left lobe.

E. histolytica infection suggest that these three meth- shaped lesions (Fig. 2C) with ulceration extending
ods perform equally well.5,36 An important aid to through the mucosa and muscularis mucosa into
antigen-detection and PCR-based tests is the de- the submucosa; and necrosis and perforation of the
tection of serum antibodies against amebae, which intestinal wall.41 Staining with periodic acidSchiff
are present in 70 to more than 90 percent of pa- or immunoperoxidase and antilectin antibodies aids
tients with symptomatic E. histolytica infection.37-40 in the visualization of amebae.42
A drawback of current serologic tests is that patients
remain positive for years after infection, making it
amebic liver abscess
difficult to distinguish new from past infection in
regions of the world where the seroprevalence is Amebic liver abscess is 10 times as common in men
high. Examination of colonic mucosal biopsy spec- as in women and is a rare disease in children.37,43,44
imens and exudates can reveal a wide range of his- Approximately 80 percent of patients with amebic
topathological findings associated with amebic liver abscess present with symptoms that develop
colitis, including diffuse, nonspecific mucosal thick- relatively quickly (typically within two to four weeks),
ening with or without ulceration and, in rare cases, including fever, cough, and a constant, dull, aching
the presence of amebae in the mucinous exudate; abdominal pain in the right upper quadrant or epi-
focal ulcerations (Fig. 2B) with or without amebae gastrium. Involvement of the diaphragmatic surface
in a diffusely inflamed mucosal layer; classic flask- of the liver may lead to right-sided pleural pain or

n engl j med 348;16 www.nejm.org april 17, 2003 1569

The New England Journal of Medicine

Downloaded from nejm.org on February 18, 2014. For personal use only. No other uses without permission.
Copyright 2003 Massachusetts Medical Society. All rights reserved.
 The new england journal of medicine

of presentation) (Table 1). Preliminary studies in-

Table 1. Sensitivity of Tests for the Diagnosis of Amebiasis.* dicate that the detection of serum amebic antigens
Test Colitis Liver Abscess
is a sensitive, noninvasive means of diagnosis.5 Oc-
casionally, aspiration of the abscess is required to
percent rule out a pyogenic abscess. Amebae are visualized
Microscopy in the abscess fluid in a minority of patients with
Stool 2560 1040 amebic liver abscess.
Abscess fluid NA 20
Complications of amebic liver abscess may arise
Antigen detection from rupture of the abscess with extension into the
Stool 90 40 peritoneum, pleural cavity, or pericardium. Extrahe-
Serum 65 (early) 100
(before treatment) patic amebic abscesses have occasionally been de-
Abscess fluid NA 40 scribed in the lung, brain, and skin and presumably
Indirect hemagglutination (antibody) result from hematogenous spread.
Serum obtained during acute illness 70 7080
Serum obtained during convalescence >90 >90
therapy
* NA denotes not applicable.
Therapy for invasive infection differs from therapy
for noninvasive infection. Noninvasive infections
may be treated with paromomycin. Nitroimidazoles,
referred shoulder pain. Associated gastrointestinal particularly metronidazole, are the mainstay of ther-
symptoms, which occur in 10 to 35 percent of pa- apy for invasive amebiasis45 (Table 2). Nitroimida-
tients, include nausea, vomiting, abdominal cramp- zoles with longer half-lives (namely, tinidazole, sec-
ing, abdominal distention, diarrhea, and constipa- nidazole, and ornidazole) are better tolerated and
tion. Hepatomegaly with point tenderness over the allow shorter periods of treatment but are not avail-
liver, below the ribs, or in the intercostal spaces is a able in the United States. Approximately 90 percent
typical finding.43,44 of patients who present with mild-to-moderate ame-
Laboratory studies may reveal a mild-to-moder- bic dysentery have a response to nitroimidazole ther-
ate leukocytosis and anemia. Patients with acute apy. In the rare case of fulminant amebic colitis, it
amebic liver abscess tend to have a normal alkaline is prudent to add broad-spectrum antibiotics to treat
phosphatase level and an elevated alanine amino- intestinal bacteria that may spill into the peritone-
transferase level; the opposite is true of patients um; surgical intervention is occasionally required
with chronic disease.44 Ultrasonography, abdom- for acute abdomen, gastrointestinal bleeding, or
inal computed tomography, and magnetic reso- toxic megacolon. Parasites persist in the intestine
nance imaging are all excellent for detecting liver le- in as many as 40 to 60 percent of patients who re-
sions (usually single lesions in the right lobe) but ceive nitroimidazole. Therefore, nitroimidazole
are not specific for amebic liver abscess (Fig. 3). treatment should be followed with paromomycin
The differential diagnosis of a liver mass should or the second-line agent diloxanide furoate to cure
include pyogenic liver abscess, necrotic hepatoma, luminal infection. Metronidazole and paromomy-
and echinococcal cyst (usually an incidental finding cin should not be given at the same time, since the
that is not the cause of fever and abdominal pain). diarrhea that is a common side effect of paromomy-
Patients with amebic liver abscess are more likely cin may make it difficult to assess the patients re-
than patients with pyogenic liver abscess to be male, sponse to therapy.46-48
to be younger than 50 years of age, to have immi- Therapeutic aspiration of an amebic liver abscess
grated from or traveled to a country where the dis- is occasionally required as an adjunct to antipara-
ease is endemic, and not to have jaundice, biliary sitic therapy. Drainage of the abscess should be con-
disease, or diabetes mellitus. Less than half of pa- sidered in patients who have no clinical response to
tients with amebic liver abscess have parasites de- drug therapy within five to seven days or those with
tected in their stool by antigen detection. a high risk of abscess rupture, as defined by a cavity
Helpful clues to the diagnosis include the pres- with a diameter of more than 5 cm or by the pres-
ence of epidemiologic risk factors for amebiasis ence of lesions in the left lobe.49 Bacterial coinfec-
and the presence of serum antiamebic antibodies tion of amebic liver abscess has occasionally been
(present in 70 to 80 percent of patients at the time observed (both before and as a complication of

1570 n engl j med 348;16 www.nejm.org april 17 , 2003

The New England Journal of Medicine

Downloaded from nejm.org on February 18, 2014. For personal use only. No other uses without permission.
Copyright 2003 Massachusetts Medical Society. All rights reserved.
 current concepts

Table 2. Drug Therapy for the Treatment of Amebiasis.*

Drug Adult Dosage Pediatric Dosage Side Effects

Amebic liver abscess

give

Metronidazole 750 mg orally 3 times 3550 mg/kg of body weight/ Primarily gastrointestinal: anorexia, nausea,
a day for 710 days day in 3 divided doses vomiting, diarrhea, abdominal discomfort,
for 710 days or unpleasant metallic taste; disulfuram-like
intolerance reaction with alcohol; rarely,
neurotoxicity, including seizures, peripheral
neuropathy, dizziness, confusion, irritability

or

Tinidazole 800 mg orally 3 times 60 mg/kg/day (maximum, Primarily gastrointestinal and disulfuram-like
a day for 5 days 2 g) for 5 days intolerance reaction as for metronidazole

followed by a luminal agent

Paromomycin 2535 mg/kg/day in 2535 mg/kg/day in 3 divided Primarily gastrointestinal: diarrhea, gastrointes-
3 divided doses for 7 days doses for 7 days tinal upset

or second-line agent

Diloxanide furoate 500 mg orally 3 times 20 mg/kg/day in 3 divided Primarily gastrointestinal: flatulence, nausea,
a day for 10 days doses for 10 days vomiting, pruritus, urticaria

Amebic colitis

give

Metronidazole 750 mg orally 3 times 3550 mg/kg/day in 3 divided As for amebic liver abscess
a day for 710 days doses for 710 days

followed by a luminal agent (as for amebic liver abscess)

Asymptomatic intestinal
colonization

give

Paromomycin 2535 mg/kg/day in 2535 mg/kg/day in 3 divided Primarily gastrointestinal: diarrhea,

3 divided doses for 7 days doses for 7 days gastrointestinal upset

or second-line agent

Diloxanide furoate 500 mg orally 3 times 20 mg/kg/day in 3 divided Primarily gastrointestinal: flatulence, nausea,
a day for 10 days doses for 10 days vomiting, pruritus, urticaria

* The information is updated annually by the Medical Letter on Drugs and Therapeutics at http://www.medletter.com/html/prm.htm#Parasitic.
This drug is not yet available in the United States.
This drug is not available in the United States.

drainage), and it is reasonable to add antibiotics,

the need for a vaccine
drainage, or both to the treatment regimen in the
absence of a prompt response to nitroimidazole In a perfect world amebiasis would be prevented by
therapy. Imaging-guided percutaneous treatment eradicating fecal contamination of food and water.
(needle aspiration or catheter drainage) has replaced However, providing safe food and water for all chil-
surgical intervention as the procedure of choice for dren in developing countries would require massive
reducing the size of an abscess.49 societal changes and monetary investments. An ef-

n engl j med 348;16 www.nejm.org april 17, 2003 1571

The New England Journal of Medicine

Downloaded from nejm.org on February 18, 2014. For personal use only. No other uses without permission.
Copyright 2003 Massachusetts Medical Society. All rights reserved.
 The new england journal of medicine

fective vaccine would be much less costly, and there a vaccine could be broadly protective.50 Finally, the
are several reasons to indicate that a vaccine is a de- absence of epidemiologically significant animal res-
sirable and feasible goal. The high incidence of ame- ervoirs suggests that herd immunity could interrupt
biasis in recent community-based studies suggests fecaloral transmission in humans. The challeng-
that an effective vaccine would improve child health es will be to design vaccines capable of eliciting du-
in developing countries. That humans naturally ac- rable mucosal immunity, to understand the corre-
quire partial immunity against intestinal infection lates of acquired immunity, and most important, to
indicates that there should not be insurmountable enlist the continued support of industrialized na-
barriers to stimulating an effective acquired immune tions to combat diarrheal diseases of children in
response. Aiding vaccine design is the demonstra- developing countries.
tion that several recombinant antigens, including Supported in part by grants from the Howard Hughes Medical In-
stitute (to Drs. Haque and Houston) and from the Burroughs
the Gal/GalNAc-specific lectin, provide protection Wellcome Fund, the Lucille P. Markey Trust, and the National Insti-
in animal models of amebiasis and that human im- tutes of Health (to Dr. Petri).
munity is linked to intestinal IgA against the lectin. Dr. Petri has reported receiving royalties from a patent license
agreement with TechLab for a diagnostic test for amebiasis; these
The clonal-population structure of E. histolytica and, royalties accrue to the American Society of Tropical Medicine and
specifically, the high degree of sequence conserva- Hygiene without benefit to Dr. Petri.
tion of the Gal/GalNAc-specific lectin suggest that

refer enc es
1. Petri WA Jr, Haque R, Lyerly D, Vines Biochem Parasitol 1999;99:41-53. recognition by the Entamoeba histolytica and
RR. Estimating the impact of amebiasis on 11. Dhar SK, Choudhury NR, Mittal V, Bhat- rat hepatic N-acetylgalactosamine/galactose
health. Parasitol Today 2000;16:320-1. tacharya A, Bhattacharya S. Replication ini- lectins. Glycobiology 1998;8:1037-43.
2. Kotloff KL, Winickoff JP, Ivanoff B, et al. tiates at multiple dispersed sites in the ribo- 20. Leippe M, Ebel S, Schoenberger OL,
Global burden of Shigella infections: impli- somal DNA plasmid of the protozoan parasite Horstmann RD, Muller-Eberhard HJ. Pore-
cations for vaccine development and imple- Entamoeba histolytica. Mol Cell Biol 1996;16: forming peptide of pathogenic Entamoeba
mentation of control strategies. Bull World 2314-24. histolytica. Proc Natl Acad Sci U S A 1991;88:
Health Organ 1999;77:651-66. 12. Singh U, Rogers JB, Mann BJ, Petri WA 7659-63.
3. Diamond LS, Clark CG. A redescrip- Jr. Transcription initiation is controlled by 21. Huston CD, Houpt ER, Mann BJ, Hahn
tion of Entamoeba histolytica Shaudinn, 1903 three core promoter elements in the hgl5 CS, Petri WA Jr. Caspase 3-dependent killing
(amended Walker, 1911) separating it from gene of the protozoan parasite Entamoeba of host cells by the parasite Entamoeba histo-
Entamoeba dispar Brumpt, 1925. J Eukaryot histolytica. Proc Natl Acad Sci U S A 1997; lytica. Cell Microbiol 2000;2:617-25.
Microbiol 1993;40:340-4. 94:8812-7. 22. Yan L, Stanley SL Jr. Blockade of caspases
4. Ali IKM, Hossain MB, Roy S, et al. Enta- 13. Saito-Nakano Y, Nakazawa M, Shigeta inhibits amebic liver abscess formation in a
moeba moshkovskii infections in children in Y, Takeuchi T, Nozaki T. Identification and mouse model of disease. Infect Immun 2001;
Bangladesh. Emerg Infect Dis (in press). characterization of genes encoding novel 69:7911-4.
5. Haque R, Mollah NU, Ali IKM, et al. Diag- Rab proteins from Entamoeba histolytica. Mol 23. Eckmann L, Reed SL, Smith JR, Kagnoff
nosis of amebic liver abscess and intestinal Biochem Parasitol 2001;116:219-22. MF. Entamoeba histolytica trophozoites induce
infection with the TechLab Entamoeba histo- 14. Barwick R, Uzicanin A, Lareau S, et al. an inflammatory cytokine response by cul-
lytica II antigen detection and antibody tests. Outbreak of amebiasis in Tbilisi, Republic tured human cells through the paracrine
J Clin Microbiol 2000;38:3235-9. of Georgia, 1998. Am J Trop Med Hyg 2002; action of cytolytically released interleukin-1
6. Haque R, Duggal P, Ali IM, et al. Innate 67:623-31. alpha. J Clin Invest 1995;96:1269-79.
and acquired resistance to amebiasis in Bang- 15. Petri WA Jr, Mann BJ, Haque R. The bit- 24. Seydel KB, Li E, Zhang Z, Stanley SL Jr.
ladeshi children. J Infect Dis 2002;186:547- tersweet interface of parasite and host: lec- Epithelial cell-initiated inflammation plays
52. tin-carbohydrate interactions during human a crucial role in early tissue damage in ame-
7. Blessmann J, Van Linh P, Nu PA, et al. invasion by the parasite Entamoeba histolytica. bic infection of human intestine. Gastroen-
Epidemiology of amebiasis in a region of high Annu Rev Microbiol 2002;56:39-64. terology 1998;115:1446-53.
incidence of amebic liver abscess in central 16. Ghosh S, Frisardi M, Ramirez-Avila L, 25. Denis M, Chadee K. Human neutrophils
Vietnam. Am J Trop Med Hyg 2002;66:578- et al. Molecular epidemiology of Entamoeba activated by interferon-gamma and tumour
83. spp.: evidence of a bottleneck (demographic necrosis factor-alpha kill Entamoeba histolyt-
8. Mai Z, Ghosh S, Frisardi M, Rosenthal sweep) and transcontinental spread of dip- ica trophozoites in vitro. J Leukoc Biol 1989;
B, Rogers R, Samuelson J. Hsp60 is targeted loid parasites. J Clin Microbiol 2000;38: 46:270-4.
to a cryptic mitochondrion-derived organelle 3815-21. 26. Brandt H, Tamayo RP. Pathology of
(crypton) in the microaerophilic protozoan 17. Eichinger D. A role for a galactose lectin human amebiasis. Hum Pathol 1970;1:351-
parasite Entamoeba histolytica. Mol Cell Biol and its ligands during encystment of Enta- 85.
1999;19:2198-205. moeba. J Eukaryot Microbiol 2001;48:17-21. 27. Braga LL, Ninomiya H, McCoy JJ, et al.
9. Tovar J, Fischer A, Clark CG. The mito- 18. Chadee K, Petri WA Jr, Innes DJ, Ravdin Inhibition of the complement membrane
some, a novel organelle related to mitochon- JI. Rat and human colonic mucins bind to attack complex by the galactose-specific
dria in the amitochondriate parasite Enta- and inhibit the adherence lectin of Enta- adhesion of Entamoeba histolytica. J Clin Invest
moeba histolytica. Mol Microbiol 1999;32: moeba histolytica. J Clin Invest 1987;80: 1992;90:1131-7.
1013-21. 1245-54. 28. Reed SL, Ember JA, Herdman DS, Di-
10. Willhoeft U, Tannich E. The electropho- 19. Yi D, Lee RT, Longo P, et al. Substruc- Scipio RG, Hugli TE, Gigli I. The extracellu-
retic karyotype of Entamoeba histolytica. Mol tural specificity and polyvalent carbohydrate lar neutral cysteine proteinase of Entamoeba

1572 n engl j med 348;16 www.nejm.org april 17 , 2003

The New England Journal of Medicine

Downloaded from nejm.org on February 18, 2014. For personal use only. No other uses without permission.
Copyright 2003 Massachusetts Medical Society. All rights reserved.
 current concepts

histolytica degrades anaphylatoxins C3a and N. Microscopy, PCR and ELISA applied to 44. Katzenstein D, Rickerson V, Braude A.
C5a. J Immunol 1995;155:266-74. the epidemiology of amoebiasis in Greece. New concepts of amebic liver abscess derived
29. Salata RA, Martinez-Palomo A, Murray Parasitol Int 2001;50:185-9. from hepatic imaging, serodiagnosis and
HW, et al. Patients treated for amebic liver 37. Haque R, Ali IKM, Akther S, Petri WA Jr. hepatic enzymes in 67 consecutive cases in
abscess develop cell-mediated immune Comparison of PCR, isoenzyme analysis, and San Diego. Medicine (Baltimore) 1982;61:
responses effective in vitro against Entamoeba antigen detection for diagnosis of Entamoeba 237-46.
histolytica. J Immunol 1986;136:2633-9. histolytica infection. J Clin Microbiol 1998; 45. Powell SJ, MacLeod I, Wilmot AL, Els-
30. Arellano J, Perez-Rodriguez M, Lopez- 36:449-52. don-Dew E. Metronidazole in amoebic dys-
Osuna M, et al. Increased frequency of HLA- 38. Krogstad DJ, Spencer HC Jr, Healy GR, entery and amoebic liver abscess. Lancet
DR3 and complotype SCO1 in Mexican mes- Gleason NN, Sexton DJ, Herron CA. Amebi- 1966;2:1329-31.
tizo children with amoebic abscess of the asis: epidemiologic studies in the United 46. Blessmann J, Tannich E. Treatment of
liver. Parasite Immunol 1996;18:491-8. States, 1971-1974. Ann Intern Med 1978;88: asymptomatic intestinal Entamoeba histoly-
31. Fontanet AL, Sahlu T, Rinke de Wit T, et 89-97. tica infection. N Engl J Med 2002;347:1384.
al. Epidemiology of infections with intes- 39. Pillai DR, Keystone JS, Sheppard DC, 47. McAuley JB, Herwaldt BL, Stokes SL, et
tinal parasites and human immunodeficiency MacLean JD, MacPherson DW, Kain KC. Enta- al. Diloxanide furoate for treating asympto-
virus (HIV) among sugar-estate residents in moeba histolytica and Entamoeba dispar: epide- matic Entamoeba histolytica cyst passers: 14
Ethiopia. Ann Trop Med Parsitol 2000;94: miology and comparison of diagnostic meth- years experience in the United States. Clin
269-78. ods in a setting of nonendemicity. Clin Infect Infect Dis 1992;15:464-8.
32. Houpt ER, Glembocki DJ, Obrig TG, et Dis 1999;29:1315-8. 48. McAuley JB, Juranek DD. Paromomycin
al. The mouse model of amebic colitis reveals 40. Krupp IM, Powell SJ. Comparative study in the treatment of mild-to-moderate intes-
mouse strain susceptibility to infection and of the antibody response in amebiasis: per- tinal amebiasis. Clin Infect Dis 1992;15:
exacerbation of disease by CD4+ T cells. sistence after successful treatment. Am J Trop 551-2.
J Immunol 2002;169:4496-503. Med Hyg 1971;20:421-4. 49. vanSonnenberg E, Mueller PR, Schiff-
33. Adams EB, MacLeod IN. Invasive ame- 41. Prathap K, Gilman R. The histopathol- man HR, et al. Intrahepatic amebic abscesses:
biasis. I. Amebic dysentery and its complica- ogy of acute intestinal amebiasis: a rectal indications for and results of percutaneous
tions. Medicine (Baltimore) 1977;56:315-23. biopsy study. Am J Pathol 1970;60:229-46. catheter drainage. Radiology 1985;156:
34. Aristizabal H, Acevedo J, Botero M. Ful- 42. McCarthy JS, Peacock D, Trown KP, Bade 631-5.
minant amebic colitis. World J Surg 1991; P, Petri WA Jr, Currie BJ. Endemic invasive 50. Beck DL, Tanyuksel M, Mackey AJ, et al.
15:216-21. amoebiasis in northern Australia. Med J Aust Sequence conservation of the Gal/GalNAc
35. Ellyson JH, Bezmalinovic Z, Parks SN, 2002;177:570. lectin from clinical isolates. Exp Parasitol
Lewis FR Jr. Necrotizing amebic colitis: a 43. Adams EB, MacLeod IN. Invasive ame- 2002;101:157-63.
frequently fatal complication. Am J Surg biasis. II. Amebic liver abscess and its com- Copyright 2003 Massachusetts Medical Society.
1986;152:21-6. plications. Medicine (Baltimore) 1977;56:
36. Evangelopoulos A, Legakis N, Vakalis 325-34.

electronic access to the journals cumulative index

At the Journals site on the World Wide Web (http://www.nejm.org) you can search
an index of all articles published since January 1975 (abstracts 19751992, full-text
1993present). You can search by author, key word, title, type of article, and date.
The results will include the citations for the articles plus links to the abstracts of
articles published since 1993. For nonsubscribers, time-limited access to single
articles and 24-hour site access can also be ordered for a fee through the Internet
(http://www.nejm.org).

n engl j med 348;16 www.nejm.org april 17, 2003 1573

The New England Journal of Medicine

Downloaded from nejm.org on February 18, 2014. For personal use only. No other uses without permission.
Copyright 2003 Massachusetts Medical Society. All rights reserved.