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Free-living

amebas
Warayuwadee Amornpinyo
April’4 2011
•  Protozoan parasites.
•  "free-living” à survive and replicate in the
environment without requiring a host.
•  Naegleria, Acanthamoeba, Balamuthia, Sappinia

Introduction
(1) Primary amebic meningoencephalitis (PAM)
(2) Granulomatous amebic encephalitis (GAE)
(3) Amebic keratitis (AK)
(4) Disseminated granulomatous amebic disease
(e.g., skin, pulmonary, and sinus infection)

Naegleria(1), Acanthamoeba(2,3), Balamuthia(4)

Clinical syndrome
•  N.fowleri 3 life cycle stages:
Cyst trophozoites flagellates

single-walled, 10-15 µm in diameter,


spherical and 8-12 broadly rounded
µm in diameter lobopodia

Naegleria
•  A. castellanii, A. polyphaga, A. culbertsoni, A. palestinensis, A. astronyxis,
A. hatchetti, A. healyi, A. rhysodes, A. divionesis, and A. griffini

double-walled,
25 -40 µm in
polygonal,
diameter ,spine-
spherical, 15- 20
µm in diameter. Cyst Trophozoite like pseudopodia.

Acanthamoeba spp
(Courtesy Division of Parasitic Diseases/Centers for Disease Control and Prevention, with permission.)
Balamuthia
NAEGLERIA FOWLERI
•  Worldwide
•  Soil and warm fresh water
•  Host defense : unknown
•  Child, young adult

Epidermiology
Pathogenesis
•  PAM : diffuse meningoencephalitis, which affects
the cortical gray matter most severely.
•  cortical hemorrhage & edema
•  olfactory bulbs are hemorrhagic & necrotic
•  Naegleria trophozoites found in :
•  olfactory nerves
•  adventitia & perivascular spaces of small to midsize arteries
•  CSF in acute meningoencephalitis
•  No cysts are seen in the brain
•  Onset : 2-5 d
•  IP : 2wks
•  Changes in taste / smell ,abrupt fever à N/V,
headache & meningismus (86-100%)
•  Mental change(66%)
•  Rapidly coma à death in 1 wk without focal
neuro sign

Clinical manifestations
•  Leukocytosis ; PMN
•  CSF : WBC 400-26,000, PMN predominating,
low-normal Glucose, elevated protein,
•  wet smear : motile trophozoites
•  G/S negative
•  Serology

Laboratory diagnosis
Imaging : CT brain
•  Optimum Rx : not well defined
•  High-dose systemic and IT amphotericin B
•  Part of empirical anti-infective regimen
•  Additional drugs systemic and IT miconazole,
fluconazole, rifampin, and sulfisoxazole

Treatment
ACANTHAMOEBA
•  Soil, water, and air in diverse geographic locations
•  Growth is inhibited by 35°-39° C , IP unknown
•  Immunocompromised
•  Healthy à Contact lens

Epidermiology
Histology :
1. Parenchymatous necrosis,
infiltration c
PMN,Lymph,Macrophage
2. Perivascular Trophozoite

Pathogenesis Hematogenous
Spreading
Granuloma

Amoebic skin

Amoebic keratosis Sinusitis

Clinical Manifestation
Figure 274-8 Acanthamoeba keratitis with the characteristic ring infiltrate.
(Reproduced with permission from J Comm Eye Health. 1999; 12(30): 21, Figure 1.)
•  Insidious onset of focal neurologic deficitsàGAE
•  mental change(86%); seizures (66%); fever,
headache,hemiparesis (53%); meningismus (40%); visual
disturbances (26%); and ataxia (20%)
•  Acanthamoeba skin ulcers : mo before CNS
•  Pneumonitis,Adrenalitis,LCV,osteomyelitis,sinusitis
•  Death 7-120 days

Clinical Manifestations
•  Brain autopsy, rarely biopsy & CSF wet smear
•  Skin biosy
•  Serum Ab : not useful
•  Corneal scraping for G/S,C/S
•  associated with coninfection with S. epidermidis, S. aureus, β-
hemolytic streptococcus, or Propionibacterium.
•  Contact lens C/S

Labaratory
GAE, Disseminated dz
•  Combination regimens
•  pentamidine,azole,sulfonamide, and possibly
flucytosine. McBride J, Ingram PR, Henriquez FL, et al: Development of colorimetric
microtiter plate assay for

AK
assessment of antimicrobials against Acanthamoeba. J Clin Microbiol 2005;
43:629-634.

•  Topical chlorhexidine or PHMB with or without


adjuvant diamidine q hr for first several days.
•  Adjunctive surgical therapy
Perez-Santonja JJ, Kilvington S, Hughes R, et al: Persistently culture positive
Acanthamoeba keratitis: In

Treatment :
vivo resistance and in vitro sensitivity. Ophthalmology 2003; 110:1593-1600.
BALAMUTHIA
MANDRILLARIS
•  Soil, water
•  Worldwide, 150 cases : 55 in US
•  High mortality rate
•  Both immunocompetent, immunocompromised
•  In cohort, preexisting medical conditions (diabetes,
splenectomy, nephrotic syndrome, lymphoma)

Epidermiology
•  Subacute or chronic meningoencephalitis
•  Histopathology : brain parenchyma or meninges
•  range from acute or neutrophilic immune response à
primarily chronic or granulomatous response.
•  Cysts&trophozoites in perivascularàangiitis &
hemorrhagic necrosis
•  Skin, Adrenal, Kidney

Pathogenesis
•  Subacute or chronic granulomatous
meningoencephalitis ** most common
•  Death from 1wk – mo
•  Fever with focal neurologic signs
•  Concurrent illnesses
•  Diabetes, renal failure, alcoholism, IVDU

Clinical menifestations
•  In Peruvian
•  Skin lesion : solitary,
nodular
•  on the central face, lower
face, abdomen,extremities

Clinical manifestations
•  Autopsy : cyst, Trophozoite
•  Tissue stained Balamuthia specific Ab à definitive
•  A multiplex real-time PCR assay

Laboratory
•  Not well defined
•  In the United States, 4 survivors reported.
•  ¾ à flucytosine, pentamidine, fluconazole, sulfadiazine,
and a macrolide (azithromycin or clarithromycin)
•  ¼ à unknown regimen
•  Multidrug therapy

Treatment
Centers for Disease Control and Prevention: Balamuthia amebic encephalitis—
California, 1999-2007. MMWR 2008; 57:768-771.
•  N. fowleri in public swimming areas
•  Adequate chlorination
•  AK à Contact lens
•  No use while swimming/showering
•  cleaning solution every night
•  air dry case each day
•  Avoid orthokeratology
•  Daily disposable lens
•  Disposing contact lens case q 3 mo, or microwaving the
lens case for 3 minutes on high power.
•  Disinfectant solutions effecrively

Prevention
Comparative Table
As attachment
Amebiasis
Warayuwadee Amornpinyo
April,4 2011
•  Worldwide, esp. in developing country :
India, Africa, Mexico and parts of Central
and South America
•  In developed countries via travelers, MSM

Epidemiology
•  First described by Fedor Losch in 1875 in St.
Petersburg, Russia.
•  The species name E histolytica was first coined
by Fritz Schaudin in 1903.
•  In 1913, in the Philippines, Walker and Sellards
documented the cyst as the infective form of E
histolytica.
•  The life cycle was then established by Dobell in
1925.
The genus of Entamoeba
•  E histolytica, E dispar, E moshkovskii, E polecki, E
coli, Entamoeba hartmanni) à in human interstitial
lumen
•  E histolytica à Disease; the others à Nonpathogenic
•  In homosexual males
•  In US and Europe : E. dispar
•  In Japan and Taiwan : E. histolytica
•  HIV+ve : risk factor for invasive extraintestinal
amebiasis
Invasive and
Non-invasive
Amebiasis
Pathogenesis
: Amoebiasis
Invasion
Transmission
1.  Cyst stage : infective form
Viable wk-mo in
environment
2.  Trophozoite : invasive form
Via contaminated food, water,
fecal-oral contact
•  Intestinal Entamoeba histolytica
•  Extraintestinal Entamoeba histolytica
•  Amebic liver abscess
•  pleuropulmonary, cardiac, cerebral, renal,
genitourinary, and cutaneous sites

Amebiasis
Intestinal Entamoeba
histolytica amebiasis
Amoebic Colitis
•  E. dispar ,E. moshkovskii ,90 %E. histolytica
infections are asymptomatic .
•  The strain of E. histolytica & host factors (genetic
susceptibility, age and immunocompetence ) leads to
asymptomatic or invasive

Clinical
•  Young age
•  Pregnancy
•  Corticosteroid
•  Malignancy
•  Malnutrition
•  Alcoholism

Risk for fulminant colitis


•  Subacute onset, 1-3 weeks.
•  Mild diarrhea - severe dysentery producing
abdominal pain (12-80 %), bloody stools
diarrhea (94 -100 %). Weight lost (<50%).
•  Fever (8-38%)
•  Fulminant colitis with bowel necrosis à
perforation and peritonitis (0.5%/case) à
Mortality rate >40%
•  Toxic megacolon can also develop.

Intestinal amebiasis
probably also present as

•  Chronic, nondysenteric diarrhea, weight loss,


abdominal pain (Mimic IBD)
•  Localized colonic infection à Granulation
tissue mass “Amoeboma” (Mimic colon cancer)
Amoebic extension
•  Antigen testing
•  Serology
•  Stool examination
•  Other methods
•  Visual inspection of colon

diagnosis
•  Fecal and serum antigen detection assays
(ELISA,immunofluorescence)
•  Use monoclonal antibodies to bind to epitopes
•  Specific (>90%) ,Sensitivity (87%)for E.histolytica
•  Useful for early detection, defind strain

1. Antigen testing
•  Ab à detectable within 5-7 days of acute
infection and persist for years.
•  -ve à exclude disease
•  +ve à acute infection and past exposure
•  IHA (90% +ve in symptomatic intestinal
infection)
•  Agar gel diffustion & Counterimmunophoresis
•  (Less but lasting 6-12 mo +ve)

2. Serology
•  Less sensitive, indifferentiate between species
•  Cysts / trophozoites in the stool
•  Findings ; Positive blood, Ingested erythrocytes
with E.dispar, rarely seen leukocytes
•  At least 3 specimens separate days detect 85-95%

3. Stool examination
Technique

•  Saline wet smear


•  Fresh smear stained with
•  Iron hematoxylin
•  Wheatley’s trichrome
•  Fixation with polyvinyl
alcohol à delayed staining
•  Detection of parasitic DNA or RNA in feces via
probes
•  Fecal culture
•  Research tools

4. Other methods
•  Scrapings or biopsy from the edge of ulcers,
•  positive for cysts or trophozoites on microscopy, and antigen
testing for E. histolytica may be positive
•  Colonic lesions : nonspecific mucosal thickening and
inflammation to classic flask-shaped amebic ulcers.
•  Not recommend à Perforation

5. sigmoidoscopy/Colonoscopy
Extraintestinal
Entamoeba histolytica
Amebiasis
•  Amebic liver abscess
•  Pleuropulmonary infection
•  Cardiac infection
•  Cerebral amebiasis
•  Cutaneous infection
•  Vaginal or uterine involvement, Rectovaginal fistula

Findings
•  Most common
•  Via : Ascending portal venous system, Travelers
exposure
•  CMIR defect (such as extremes of age,
pregnancy, corticosteroid, malignancy, and
malnutrition) à increase invasive E. histolytica
infection with liver involvement.
•  Increase risk in HIV

Amebic liver abscess


•  Acute fever (38.5-39.5ºC) with RUQ pain
Concurrent diarrhea <1/3
•  Chronic : fever, wt loss, abdominal pain,
hepatomegaly, anemia
•  For travelers returning from endemic area :
8-20wk à yr
•  Jaundice <10%

Clinical : Amebic liver abscess


•  Peritonitis
•  Hepatic vein and IVC thrombosis

Complications
•  Leukocytosis >10,000 without eosinophilia
•  Elevated ALP(80%), may elevated transminase
•  Fecal microscopy positive Amebae Only 18% ,
Culture 80%
•  Imaging : U/S , CT or MRI
•  Serologic testing : Serum Ab (92-95%) but –ve
in 1st 7day

diagnosis
•  Single subcapsular abscess
•  Maybe multiple
•  Gallium scan : cold+bright rim
•  No repeat imaging
•  Complete Radiologic à 2yr
•  Calcified,anechoic,cystic

Amoebic liver abscess


•  Amebiasis
•  Pyogenic abscess
•  Echinococcal abscess
•  Hepatoma

Differential diagnosis
Mortality : Uncomplicated <1%, Mortality 20%
Factor increase Mortality
•  bilirubin level >3.5 mg/dL,
•  serum albumin <2.0 g/dL,
•  large volume or multiple abscesses
•  encephalopathy

Prognosis
Developing :
•  Ruptured amebic hepatic abscess àdiaphragm**
•  pleural space à amebic empyema
•  lung à consolidation, abscess, hepatobronchial
fistula
•  Lymphatic spread from the liver
•  Hematogenous embolic spread from the liver/
colon

2. Pleuropulmonary amebiasis
•  Pain : pleuritic, RUQ
•  Cough : nonproductive, amebic pus
•  Hemoptysis, and dyspnea
•  If hepatobronchial fistula àcopious amounts of
reddish brown or anchovy sauce appearance

Clinical
•  Metronidazole (750 mg PO TID 7days)
•  Alternative : Tinidazole (2 g/day 3-5days)
•  Amebic pleural effusions à aspiration

treatment
•  Lt lobe liver à pericardium
•  Severe chest pain, CHF, and cardiac tamponade
•  High mortality

3. Cardiac infection
•  Hematogenous
•  Abrupt onset , rapid death if untreated.
•  CT scan : non-enhancing irregular foci
•  Treatment : Metronidazole , Surgical intervention
for decompression and/or tissue biopsy

4. Brain abscess
In case of :
• Impending rupture, Lt lobe
• No response to ATBafter 3-5 day
• Exclusion of other diagnoses
• Mass > 5 cm
Acellular, proteinaceous debris and an "anchovy
paste", chocolate colored fluid, consisting
predominantly of necrotic hepatocytes.
Trophozoite in peripheral part of abscess

Aspiration
•  Prevention of fecal contamination of food and water
•  Safe sexual practices in men who have sex with men

Prevention
THANKS FOR ATTENTION