Parasitology Research

https://doi.org/10.1007/s00436-021-07292-8

TREATMENT AND PROPHYLAXIS - ORIGINAL PAPER

Management of Entamoeba histolytica in the non‑human primates

at the Singapore Zoo
Yirui Heng1 · Shin Min Chong1 · Chia‑Da Hsu1 · Ali Anwar Ahmad1

Received: 22 June 2021 / Accepted: 13 August 2021

© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021

Abstract
Amebic dysentery caused by Entamoeba histolytica accounts for significant morbidity in the non-human primates (NHP) at
the Singapore Zoo. This includes the animals in the collection as well as a sizeable free-roaming wild crab-eating macaque
(Macaca fascicularis) population. The disease is of great concern because of its zoonotic potential. Passive surveillance,
both ante and post-mortem, of NHP displaying clinical symptoms and active surveillance of NHP assessed to be at a higher
risk of infection were carried out via fecal real-time polymerase chain reaction (PCR) testing for 4 years. Treatment of the
disease with 25 mg/kg metronidazole BID for 10 days followed by 15 mg/kg paromomycin BID for 7 days achieved good
clinical resolution in most cases that tested positive. Three diseased NHP with severe clinical signs of weight loss, lethargy,
and diarrhea were anesthetized for veterinary diagnostic investigation. Mesenteric lymphadenopathy was consistently seen
on ultrasound examination in these severe cases of entamoebiasis. Two animals eventually died of severe chronic enteritis
due to the disease. The eradication of entamoebiasis in the NHP at the Singapore Zoo may be complicated by the mainte-
nance of a disease reservoir in wildlife, but a combination of timely treatment and efforts at maintaining biosecurity can help
manage the disease in the collection.

Keywords Entamoeba histolytica · Entamoebiasis · Primates · Reservoir · Zoonotic disease

Introduction contaminated food or water. The cysts pass through the

stomach and small intestine where they excyst to invasive
Entamoeba histolytica is a zoonotic anaerobic parasitic trophozoites in the lumen of the intestine. Trophozoites
amoebozoan of the genus Entamoeba. The pathogen is part penetrate the mucus layer of the large intestine, causing
of the E. histolytica species complex, which comprises two clinical disease. Tissue damage in the intestines is a result
other pathogens, E. dispar and E. moshkovskii, all of which of parasite invasion, inflammation, and host cell death
are morphologically indistinguishable but have different viru- (Ghosh et al. 2019). Studies have shown E. histolytica
lence capabilities. E. histolytica is the only species definitely to also infect captive primates, causing symptomatic and
associated with pathological sequalae in humans and the rest non-symptomatic infections in Old World and New World
are considered non-pathogenic (Katzwinkel-Wladarsch et al. non-human primates (NHP). In a survey of 20 NHP in La
1996). Amebic dysentery caused by E. histolytica is respon- Vallée des Singes Primate Park, Romagne, France, 6 spe-
sible for 50 million human cases of hemorrhagic colitis and cies tested positive for the disease representing 45 out of
extra-intestinal abscessation, accounting for 100,000 deaths 192 (23.4%) individual NHP (Verweij et al. 2003). Stud-
annually (Bercu et al. 2007). The life cycle of E. histolytica ies in Twycross Zoo, Leiceistershire, UK, also revealed a
begins with the ingestion of the infectious cyst from fecal disease prevalence of 16.2%, with six NHP species testing
positive for Entamoeba histolytica complex. A nationwide
surveillance in the UK only showed a disease prevalence
Section Editor: Kevin S.W. Tan
of 0.3% (Regan et al. 2014). The zoonotic potential of the
* Yirui Heng disease in NHP in zoos poses a significant health risk to
[email protected] humans that work closely with the animals. The manage-
ment of the spread of the disease within the collection and to
1
Wildlife Reserves Singapore, 80 Mandai Lake Road,
Singapore 729826, Singapore

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humans is therefore of paramount importance to workplace In animals with severe signs of intestinal disease, addi-
health and safety. tional diagnostics were carried out, including routine blood
The laboratory testing capabilities at the Singapore Zoo hematology, biochemistry analyses, and radiographic and
expanded to include in-house real-time polymerase chain reac- ultrasonographic examination of the thoracic and abdominal
tion (PCR) tests for E. histolytica in 2017, which enabled quick cavities. Where indicated, further imaging with colonoscopy
and accurate confirmatory diagnosis of E. histolytica infec- and laparoscopy was carried out for biopsy collection and
tions. Active and passive surveillance programs were carried analysis.
out to estimate the disease prevalence in the collection and
wild crab-eating macaques (Macaca fascicularis) that roam Test result interpretation
around the grounds of the zoo, which could be potential dis-
ease reservoirs. The hypothesis is that E. histolytica infections All collection animals that tested positive on PCR under-
in NHPs are manageable in the Singapore Zoo with prompt went treatment with metronidazole (Unique Pharmaceuti-
detection and treatments but are difficult to eradicate com- cals, Gujarat, 393,002, India; 25 mg/kg PO, twice daily for
pletely due to the potential maintenance of disease reservoir 10 days) followed by paromomycin (Pfizer Italia, Latina,
in wildlife. 04,100, Italy; 15 mg/kg PO, twice a day for 7 days). The
exception to this was when the treatment course may be del-
eterious to the health of the animal, like in the gut-sensitive
Materials and methods leaf eating monkeys. All animals undergoing treatment
were retested for the disease until three consecutive nega-
Population and sampling tive results were obtained 2 weeks apart. These animals were
also retested for entamoebiasis if signs of enterocolitis were
Passive surveillance included ante-mortem analysis of NHP detected.
displaying clinical signs of colic, weight loss, hemorrhagic
diarrhea and dysentery, and post-mortem examination of Post‑mortem sampling
all animals with clinical signs suspicious of entamoebia-
sis. Active surveillance of the disease was targeted at NHP Post-mortem examinations were performed on all animals
populations held in enclosures or sections of the zoo where that died. Representative samples from all organs were col-
one or more animals had been confirmed to be positive for lected in 10% buffered formalin saline and processed rou-
the disease and was carried out once every 6 months. Fecal tinely for H&E staining for histopathology analysis. Fresh
samples that were collected as part of the active surveillance tissue from organs with pathologic lesions were collected
program were pooled in groups not more than five animals and stored at − 80 °C for molecular diagnostic tests includ-
and submitted for analyses. The wild crab-eating macaques ing PCR.
were also tested for the disease for a period of 6 months. A
researcher that followed the troops of macaques around the
park grounds collected fresh feces from the ground when- Results
ever any animal was observed to be defecating. Where more
than one animal was seen to be defecating at the same time, Entamoeba histolytica was detected in 10 of the 27 NHP
the fecal samples would be pooled for analyses. species sampled (Table 1). In a total of 158 samples from
collection animals, 50 (31.6%) samples were positive for
Test methods E. histolytica, of which 22 were detected as part of active
disease surveillance, 6 as part of clinical disease investi-
Confirmed cases of Entamoeba histolytica is diagnosed in gation, and 22 as part of recheck examinations. Fifteen
the laboratory at the Singapore Zoo via real-time polymerase samples from the wild free-ranging crab-eating macaques
chain reaction (real-time PCR). Fresh animal fecal samples were tested, of which 6 (40%) samples were positive for the
were submitted and kept chilled until processing on the same disease.
day. A total of 173 samples were analyzed from 27 NHP
species, of which 15 samples were from the wild crab-eat- Treatment outcomes
ing macaques. DNA was extracted with a commercial fecal
DNA extraction kit (QIAamp Fast Stool Mini Kit; Qiagen, Treatment was started for all collection animals except
Hilden, Germany) and amplified with the E. histolytica q16 for one proboscis monkey (Nasalis larvatus). Most cases
Genesig Easykit (Path-E.histolytica; Primer design Ltd, achieved complete clinical resolution after one round of
Southampton, UK) using a Genesig q16™ qPCR machine treatment. Only three groups of animals required multiple
following the manufacturer’s instructions. treatments: a lone black howler (case 1) and a group of 4

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Table 1  List of non-human Common name Scientific name Total number of Positive samples
primate species tested for samples
Entamoeba histolytica
Bearded emperor tamarin Sanguinus imperator 3 0
Black howler Alouatta caraya 33 18 (n* = 3)
Black-and-white ruffed lemur Varecia variegata 1 0
Black-handed spider monkey Ateles geoffroyi 2 0
Chimpanzee Pan troglodytes 1 0
Colombian black spider monkey Ateles fusciceps 7 1 (n = 3)
Common squirrel monkey Saimiri sciureus 7 2 (n = 12)
Cotton top tamarin Sanguinus oedipus 9 0
Crab-eating macaque Macaca fascicularis 13 5 (n = 9)
Wild crab-eating macaque Macaca fascicularis 30 4 (n = 4)
Eastern black-and-white colobus Colobus guereza 1 0
Golden-headed lion tamarin Leontopithecus chrysomelas 7 1 (n = 2)
Grey gibbon Hylobates muelleri 1 0
Guyanan red howler Alouatta macconnelli 11 1 (n = 5)
Javan langur Trachypithecus auratus 2 0
Lar gibbon Hylobates lar 4 0
Lion-tailed macaque Macaca Silenus 9 2 (n = 4)
Orangutan Pongo sp 1 0
Patas monkey Erythrocebus patas 1 0
Proboscis monkey Nasalis larvatus 4 3 (n = 1)
Red-backed bearded saki Chiropotes chiropotes 17 12 (n = 6)
Red-shanked douc langur Pygathrix nemaeus 2 0
Siamang Symphalangus syndactylus 5 0
Southern pig-tailed macaque Macaca nemestrina 1 0
Tufted capuchin Sapajus apella 2 0
Western purple-faced langur Semnopithecus vetulus 1 0
White-faced saki Pithecia pithecia 10 5 (n = 5)
White-lipped tamarin Sanguinus labiatus 3 0
*
n = total number of individual animals sampled

lion-tailed macaques (Macaca silenus) requiring just one initial examination of all three animals are summarized
repeated treatment, and a group of 9 crab-eating macaques in Table 2 and were generally within normal limits for all
requiring two repeated treatments. Most cases achieved three animals. Mild anemia was only detected in case 3,
long-term clinical resolution, with a recurrence of disease and a mild leukopenia and hypoproteinemia in case 2. On
seen only in the same lone black howler and the group of ultrasound examination, all three animals had diffusely
9 crab-eating macaques a year after the last negative test enlarged mesenteric lymph nodes (Fig. 1A). The proximal
result. One black howler (Alouatta caraya) did not respond gastrointestinal tract was also described to have normal
to treatment at all despite multiple attempts with persistently layering but a generalized moderate to severe increase in
positive results on follow up checks (case 2). thickness along the duodenum to the cecum. A fine-needle
aspirate of the lymph nodes revealed a heavy amount of
Clinical cases activated macrophages and degenerate neutrophils but no
bacteria.
Three animals (cases 1–3) were assessed to have severe Case 1 was the only case that achieved clinical resolution.
manifestations of the disease and all of them were black A follow-up examination at the end of the treatment showed
howlers. These animals had a history of weight loss and a normal blood profile and ultrasonographic findings, includ-
intermittent diarrhea and presented with lethargy, inap- ing normal sized mesenteric lymph nodes (Fig. 1B). E.
petence, profuse diarrhea, and abdominal colic. All ani- histolytica was detected again during active surveillance
mals had a history of weight loss and intermittent diar- 6 months after the case had resolved but the animal dis-
rhea. The hematology and biochemistry results at the played no signs of clinical disease.

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Table 2  Hematology and Parameter (Ref. interval)*/unit Case 1 14,268 Case 2 13,528 Case 3 12,976
biochemistry results of 5 year 1 month 6 year 0 month 7 year 9 month
three black howlers with Male Female Female
entamoebiasis on initial
examination HCT (27.7–50.8) 41 38 27
/%
HGB (90–170) 126 114 71
/g/L
RBC (2.95–5.60) 3.74 3.64 2.36
/ × ­1012 cells/L
MCV (79.8–105.1) 98.9 84.6 86.4
/fL
MCH (26.5–37.4) 33.7 31.3 30.1
/pg
MCHC (297–377) 341 370 348
/g/L
WBC (5.8–32.0) 12.57 3.11 12.08
/ × ­109 cells/L
Lymphocyte (0.00–7.15) 2.61 2.06 2.14
/ × ­109 cells/L
Monocyte (0.00–3.246) 0.99 0.95 0.52
/ × ­109 cells/L
Neutrophil (0.05–17.76) 8.89 0.09 9.29
/ × ­109 cells/L
Eosinophil (0.00–1.484) 0.08 0.00 0.13
/ × ­109 cells/L
Basophil (0.00–0.2) 0.00 0.01 0.00
/ × ­109 cells/L
Platelets (data deficient) 273 74 465
/ × ­109 cells/L
Total protein (37–89) 72 45 46
/g/L
Globulin (17–56) 33 32 29
/g/L
Albumin (8–56) 39 13 17
/g/L
ALT (6–62) 41 < 10 18
/U/L
ALKP (31–649) 31 12 69
/U/L
AST (56–277) 92 73 High
/U/L
Glucose (1.45–17.26) 4.7 6.65 7.89
/mmol/L
BUN (3.2–21.1) 4.9 15.7 10.8
/mmol/L
Creatinine (23–211) 114 45 80
/µmol/L
Sodium (131–147) 143 121 139
/mmol/L
Potassium (2.7–6.3) 4.3 3.9 3.8
/mmol/L
Chloride (94–110) 109 92 97
/mmol/L
Calcium (1.8–2.9) 2.19 1.77 2.0
/mmol/L
Phosphorous (0.68–3.15) 0.88 1.5 1.97
/ mmol/L
Amylase (31–462) 118 87 103
/U/L

*
Reference intervals for the species obtained on the Zoological Information Management System (Zims
Species360, Bloomington, MN, USA) database

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Fig. 1  A Abdominal ultrasonography of mesenteric lymph nodes of cases 1–3. B Abdominal ultrasonography of mesenteric lymph nodes and
cecum of case 1 before and after treatment

Cases 2 and 3 died. Case 2 was persistently positive for E. from cecal tissue samples and Salmonella and Mycobacte-
histolytica despite multiple treatment attempts over a period rium spp. DNA were not detected by conventional PCR.
of 6 months and succumbed to the disease. Post-mortem For case 3, E. histolytica DNA was never detected by
gross findings showed marked mesenteric lymphadenopa- real-time PCR but the animal displayed symptoms sugges-
thy and severe diffuse thickening and discoloration of the tive of entamoebiasis. Treatment of Entamoeba was started
cecal mucosa and submucosa. The cecal serosa contained over a period of 6 months but the animal was euthanized
few black lesions and fibrinous tags (Fig. 2). Histopathology due to its deteriorating condition and grave prognosis. Post-
showed a chronic, ongoing severe fibronecrotizing typhlitis mortem examination showed the animal was emaciated with
due to entamoebiasis with moderate lymphoplasmacytic sarcopenia. Mesenteric lymphadenopathy was diffuse and
enteritis. E. histolytica DNA was detected by real-time PCR marked at the ileocecal junction. The cecum and proximal

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disease prevalence in the parks is unknown and will require

further testing of the remaining 13 NHP species in the park.
This overall figure is however estimated to be lower than
37% because there has been no cause for clinical suspicion
of the disease in the remaining NHP picked from health
screenings and the regular microscopic fecal surveillance.
There is no clear risk factor for the spatial distribution of
the disease, occurring only in isolated enclosure or groups
of animals without infecting NHP in adjacent enclosures.
This is reassuring as it suggests that the disease can be con-
tained without a high risk of transmission between NHP
enclosures.
Of the positive E. histolytica cases in the zoo, 22 cases
were detected in asymptomatic animals, compared to 6 cases
that were first detected in symptomatic animals. The higher
number of asymptomatic cases is similar to the manifes-
tation of the disease in humans (Haque et al. 2003). The
Fig. 2  Case 2 ileum adhered to the cecum, which was found to be
thickened and doughy on palpation, with multifocal black lesions and
initial hematological assessment of the three severe cases
fibrinous tags was unremarkable, except for case 2 (leukopenia and hypo-
proteinemia). Abdominal ultrasonographic findings showed
evidence of severe disease in cases 1–3 and were an impor-
colonic mucosa showed diffuse thickening with multiple tant tool for diagnosis. Although normal mesenteric lymph
raised white necrotic materials (Fig. 3A). The duodenal node sizes and gastrointestinal wall thickness ranges have
mucosa was covered with a light yellow membrane on the not been established in this species, case 1 showed drastic
mucosal surface and the pancreas appeared atrophic with reduction in size of both parameters after treatment and clin-
multifocal white foci in the parenchyma. Histopathological ical resolution, suggesting that the initial measurements of
examination showed multifocal neutrophilic inflammation the lymph node and cecum thickness were indeed abnormal.
and necrosis in the cecal and colonic mucosa. Numerous The therapy of invasive and noninvasive amebiasis dif-
intra-lesional amebic organisms were noted (Fig. 3B). Fur- fers, with nitroimidazoles being the mainstay of therapy
ther testing by PCR and sequencing detected E. dispar. for invasive amebiasis (Petri 2003). The parasites however
persist in the intestine in as many as 40–60% of nitroim-
idazole-treated human patients. Paromomycin is therefore
Discussion required to cure luminal infections (Blessman and Tannich
2002). Despite this difference in therapeutic approaches
Entamoebiasis is a disease that has significant morbidity in to the different disease manifestations, a similar treatment
the collection of NHP at the Singapore Zoo, with 10 out regime was initiated for all positive cases. This treatment
of 27 (37%) of the species sampled testing positive for the regime followed published dosages for amoebic diseases,
disease. These 27 species of NHP were surveyed because the enteric protozoal disease, or Entamoeba infections in NHP
animals either had displayed clinical signs of the disease or (Calle and Joslin 2014; Masters 2010). This medication
had been in close proximity to confirmed cases. The overall regime achieved clinical resolution in all individuals, which

Fig. 3  A The cecum and

proximal colonic mucosa with
diffuse thickening and multiple
raised white necrotic materials
(Fig. 3A). B Histopathology of
colonic mucosa with numerous
intra-lesional amebic organisms

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suggests that the dosing is likely to be effective against E. including rubber gloves, face masks, and site-specific rubber
histolytica infections. It is possible case 2 remained refrac- boots before working in these areas. Hard surfaces were also
tory to treatment due to the chronicity and severity of the cleaned with Virkon™. In exhibits with organic flooring,
pathological lesions in the cecum. Fulminant or necrotizing 5 cm of additional substrate may be added, with or without
colitis is an unusual manifestation of the disease in humans, prior treatment of the topsoil with soda lime. Any work in
with most patients presenting with abdominal pain and dis- these areas was done only after work in areas without infec-
tension. The persistence of these signs while undergoing tion was completed. These processes were in place until the
antiamebic therapy is an indication for surgery such as par- animals were confirmed negative for the disease.
tial or total colectomy (Ellyson et al. 1986) for complete There are concerns that wild free-ranging crab-eating
resolution. The same surgical approach may have been con- macaques are a disease reservoir for E. histolytica. Although
sidered for case 2. E. histolytica DNA was detected in these animals, additional
Case 3 was a confounding case because it showed symp- advanced diagnostics such as genomic sequencing and typ-
toms highly suggestive of entamoebiasis but did not respond ing of E. histolytica strains in the wild animals are required
to treatment and did not have E. histolytica detected on to study the risk of transmission to collection animals. How-
repeated PCR tests. Post-mortem PCR tests on cecal tissue ever, we cannot rule out the possibility of spill-over trans-
showed that E. dispar was the causative organism, which has mission to collection animals from the wild macaques. Strict
been reported as non-pathogenic and responsible for asymp- biosecurity measures can be difficult to implement due to
tomatic infections only (Cantellano et al. 1997). Reviews by the free-ranging nature of these animals. Newly built den
Oliveira et al. (2015) showed that some strains of E. dispar blocks have hot wires in the perimeter to serve as a deterrent
have similar pathogenicity as E. histolytica and can produce to the macaques. NHP kept in all-round mesh exhibits have
the same severity of symptoms and lesions. Identifying the also been moved to other areas where wild macaques cannot
causative agent in case 3 during ante-mortem tests would not easily climb on and defecate in. Trash bins around the parks
have changed the treatment regime but could have helped have also been modified to make it difficult for macaques to
clinicians better prognose the disease and decide on humane access in an effort to make it less enticing for the macaques
euthanasia sooner. Future cases displaying symptoms of to stay within the park grounds. Despite these measures,
entamoebiasis should be screened for Entamoeba spp. with wild macaques are still present in the parks and have on
fecal PCR testing if tests for E. histolytica are negative. occasion been seen in close proximity to the collection NHP.
The group of 4 lion-tailed macaques and the group of Studying the various strains of E. histolytica in collection
9 crab-eating macaques were still positive for the disease animals has not been done and may be useful to determine
after one round of treatment, which could be due to drug the epidemiology of the disease in the park.
underdosing. This may be due to inaccurate weight estima-
tions in animals, challenges of accurately dosing individual
animals in groups, or inaccurate preparation of drugs. In
the lion-tailed macaques, the second round of treatment was Conclusion
dispensed for the animals at the higher end of their estimate
weight range, avoiding the splitting tablets or capsules. The E. histolytica is a parasite of significant morbidity in the
group of 9 crab-eating macaques were transferred to a sepa- NHP at the Singapore Zoo. Death resulting from the dis-
rate holding facility off exhibit, where they were anesthe- ease has however been rare. The zoonotic potential of E.
tized, weighed, and dosed according to their actual weights. histolytica also poses a concern to the humans that work
The new facility also offered separate compartments in a closely with NHP. A combination of disease surveillance
raceway where the medications could be administered indi- programs, accurate diagnostic methods, and prompt treat-
vidually. These measures were successful in treating E. ment can manage the disease within the collection. Com-
histolytica in these groups of NHP. For case 1, the authors plete disease eradication from the parks is complicated by
propose that the disease was too severe and required another the presence of a disease reservoir in the wild crab-eating
round of treatment for clinical resolution. macaques, but transmission can be mitigated with good bios-
The control of E. histolytica in the Singapore zoo relies ecurity practices.
on prompt and accurate disease detection, as well as the
Acknowledgements The authors would like to thank fellow veterinary
implementation of strict biosecurity measures whenever ani-
colleagues, laboratory technicians, and animal caretakers in the assis-
mals test positive for the disease. Exhibits and back of house tance rendered in data consolidation.
cages of diseased NHP were isolated, often with a single
point of entry and exit with a footbath containing Virkon™ Declarations
(Lanxess Deutschland GmbH, Cologne 50,569, Germany).
Animal caretakers put on personal protective equipment, Competing interest The authors declare no competing interests.

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Human and animal rights All work involving animals meet the Interna- Haque R, Huston CD, Hughes M, Houpt E, Petri WA Jr (2003) Ame-
tional Guiding Principles for Biomedical Research Involving Animals biasis. N Engl J Med 348(16):1565–1573. https://d​ oi.o​ rg/1​ 0.1​ 056/​
as issued by the Council for the International Organizations of Medical NEJMr​a0227​10
Sciences. The data in this research is from the diagnostic work and Katzwinkel-Wladarsch S, Lieb M, Heise W, Löscher T, Rinder H
treatment of veterinary cases in the Singapore Zoo and retrospectively (1996) Direct amplification and species determination of micro-
analyzed; no work was done on any animal where unrequired. sporidina DNA from stool specimens. Trop Med Int Health
1(3):373–378. https://d​ oi.o​ rg/1​ 0.1​ 046/j.1​ 365-3​ 156.1​ 996.d​ 01-5​ 1.x
Masters N (2010) Primates-callitrichids, cebids and lemurs. In: Mer-
edith A, Delaney CJ (eds) BSAVA manual of exotic pets, 5th edn.
References BSAVA, Gloucester, pp 148–66
Oliveira FMS, Neumann E, Gomes MA, Caliari MV (2015) Entamoeba
dispar: could it be pathogenic. Trop Parasitol 5(1):9. https://​doi.​
Bercu TE, Petri WA, Behm BW (2007) Amebic colitis: new insights
org/​10.​4103/​2229-​5070.​149887
into pathogenesis and treatment. Curr Gastroenterol Rep 9:429–
Petri WA Jr (2003) Therapy of intestinal protozoa. Trends Parasitol
433. https://​doi.​org/​10.​1007/​s11894-​007-​0054-8
19(11):523–526. https://​doi.​org/​10.​1016/j.​pt.​2003.​09.​003
Blessman J, Tannich E (2002) Treatment of asymptomatic intestinal
Regan CS, Yon L, Hossain M, Elsheikha HM (2014) Prevalence of
Entamoeba histolytica infection. N Engl J Med 347:1384. https://​
Entamoeba species in captive primates in zoological gardens in
doi.​org/​10.​1056/​NEJM2​00210​24347​1722
the UK. PeerJ 2:e492. https://​doi.​org/​10.​7717/​peerj.​492
Calle PP, Joslin JO (2014) New world and old world monkeys. In:
Verweij JJ, Vermeer J, Brienen EA, Blotkamp C, Laeijendecker D, van
Miller ER, Fowler ME (eds) Zoo and wild animal medicine, 8th
Lieshout L, Polderman AM (2003) Entamoeba histolytica infec-
edn. Elsevier Saunders, St Louis, pp 301–35
tions in captive primates. Parasitol Res 90:100–103. https://​doi.​
Cantellano ME, Gutiérrez GC, Martínez-Palomo A (1997) In vivo
org/​10.​1007/​s00436-​002-​0808-z
pathogenesis of Entamoeba dispar. Arch Med Res 28:204–206
Ellyson JH, Bezmalinovic Z, Parks SN, Lewis FR Jr (1986) Necrotiz-
Publisher’s note Springer Nature remains neutral with regard to
ing amebic colitis: a frequently fatal complication. Am J Surg
jurisdictional claims in published maps and institutional affiliations.
152(1):21–26. https://​doi.​org/​10.​1016/​0002-​9610(86)​90131-5
Ghosh S, Padalia J, Moonah S (2019) Tissue destruction caused by
Entamoeba histolytica parasite: cell death, inflammation, inva-
sion and the gut microbiome. Curr Clin Microbiol Rep 6:51–57

13