entamoeba histolytica by nuhman10

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									                             Intestinal Protozoa
      Entamoeba Histolytica:
a.         Strains
         For this protozoa , there are two strains. One pathogenic , the other non-pathogenic. The
      Pathogenic form is called Entamoeba Histolytica, meaning cell lysis due to ameobiasis. The non-
      pathogenic strain is called Entamoeba Dispar, both strains are morphologically indistinguishable.


b.         Identification
       Cyst form :
             Round in shape ~10 to 20 m in diameter
             They have smooth reflective coating
             Immature cysts contain dark sausage shaped bodies known as chromatin bodies which
       disappear as the cyst matures
             Immature cysts have less than four nuclei, and four up on maturity
       Trophozoite form:
             Amoeboid shape ~10 to 60 m
             Reflectile hyaline ectoplasm, sharply separated from the endoplasm
             The granulated cytoplasm contain no bacteria , but sometimes RBCs in different stages of
       breakdown
             Single eccentric nucleus
             Chromatin evenly lines the inner wall of the nucleus
             A central dark karyosome is present from which a linin network of fine fibrils radiate to
       the periphery

c.         Life Cycle
         Infection takes place when the cyst form of the parasite is ingested. The cyst is the resistant
      infective form of the parasite. They are formed in the intestinal lumen of the definitive host (man),
      and are passed out on the stool, there are reservoir hosts but are negligible. Upon ingestion of the
      cyst , it is immediately infective. Only mature cysts are able to withstand the acidity of the gastric
      juices of the stomach, which will start to act upon the cyst coating. Upon passage to the upper part of
      the small intestine, and due to the change in acidity of the environment, the cyst wall disintegrates
      liberating four metacystic amoeba, which eventually divide into eight trophozoites. The parasites
      move from the small intestine to the large bowels, and they rely on intestinal stasis in the cecal
      region to establish a site of infection. Sometimes this is done in the sigmoidorectal region. In cases of
      hyper intestinal motility , the trophozoite might be passed out of the body completely. Cyst
      formation takes place in the lumen, and is passed out with the stool.
d.            Epidemiology
             World Wide Distribution (WWD) – since this is an intestinal disease- it is highest in
       developing countries, due to lack of hygiene , and contaminated water and food supply
             Infection spread is due to low hygiene, and takes place by contamination of water and
       food supplies. Mechanical transmission of the disease is also done by insects.
             The ratio of Dispar to Histolytica is about 10:1 respectively
             10% of cases develop extraintestinal complications
             There is no gender bias regarding intestinal ameobiasis, but complications are higher in
       men , children, and pregnant women.

e.            Pathogenesis

            The pathogenesis of E. Histolytica is primarily intestinal, and secondarily extraintestinal , and is
         associated with ulceration of the colonic mucosa. The parasite is invasive . With superficial ulcers
         damage is contained with in the mucosa muscularis. As the parasite digs deeper into the colonic wall,
         and into the submucosa, it extend laterally from its point of penetration, thus widening the ulcer ,
         and giving rise to the classic flask ulcer shape(pathogonomic). The severity of the ulcerations depend
         on a number of factors such as : Number of parasites present, immunity status of mucosa (ie. IgA
         gamma globulin), condition of the IG tract at point of penetration, and later on the cellular mediated
         immunity if and when the parasite gains access to the blood.
            The reason of the flask shaped ulcer seen in E. Histolytica infection is due to the remaining of the
         parasite on the lateral wall of the ulcer. As it penetrates laterally, the center of the ulcer fills up with
         necrotic tissue, while the parasite keeps going laterally, this is a hallmark of invasive ameobiasis.
         Examination of the necrotic tissue will result in absence of the trophozoite due to it staying on the
         perimeter of the ulcer. The conditions favoring the invasive nature of the parasite is thought to be
         provided by the intestinal flora.
            Mechanical damage caused by the parasite suckers , as it tries to hold to the colon wall cause
         destruction of the epithelium and blunting of the mircovilli, and removal of the Lactase and
         Galactase enzymes present on the boundaries of the micro villi. Since both Galactose and Lactose are
         osmotically active molecules, water is drawn into the lumen of the intestine, and hence we get the
         clinical manifestation of diarrhea. Malabsorption , and toxin translocation is also possible due to
         mucosal damage.
            Finally , E. Histolytica is a phagocytic parasite, ingesting RBCs and to a lesser extent bacteria, is
         indicative of the invasive phase.

f.            Clinical Manifestations
         Acute Case:

            Classic Dysentery ( inflammation of the colon + abdominal pain) : Abdominal pain –
      Straining and pain upon defecation (Tenesmus) – Bloody diarrhea – Constipation
            In sharply acute cases fulminant colitis my develop with sever bloody diarrhea
            Fibroblast buildup may occur and project into the lumen. Usually mistaken for carcinoma

         Asymptomatic Case:
            No clinical signs , and the DH is unaware of the parasite
            The DH is a silent cyst carrier
            May persist or turn to acute ameobiasis

      Chronic Case:

            Recurrent attacks of dysentery
            Intervening periods of moderate constipation
            Localized abdominal tenderness
            Usually secondary complication symptoms are present

g.          Complications

      Complications arise when Extraintestinal ameobiasis occurs.

             Amebic Liver Abscess (ALA) : by gaining access to the portal circulation , the parasite
       maybe transported to the liver, usually it infects the posterior aspect of the right lobe.
       Enlargement and tenderness of the liver arises. Pain maybe referred to the right shoulder due to
       common origin of the phrenic nerve and the brachial nerves. As in the intestine , the parasite
       would tend to form an abscess in the liver tissue, with necrotic cell in the center and the parasite
       on the parameter. This is important to distinguish ALA from Pyogenic liver infection, where
       bacteria would form an abscess, but will be through out the necrotic tissue. Patients suffering
       from ALA show the following manifestations:
             Hepatomegally and tenderness
             Remittent fever (40˚ C ) with chills
             Recurrent diarrhea
             Pain in the right hypochondrium
             Most patients show leucocytosis, (increased numbers of polymorphonuclear neutrophils
       distinguish Amebic hepatitis from viral hepatitis.
             Liver functions will be abnormal with high Alkaline Phosphatase reading, but unlike
       pyogenic liver abscess, no hyperbilirubineamia
             Jaundice can occur in cases of super bacterial infection with ALA
             ALA may develop more complications such as rupture into the pleural cavity and lung, in
       such a case a bronchopleural fistula can develop . The patient will cough up sputum which will
       be dark brown due to necrotic liver tissue. Rupture may occur into the peritoneum , and in very
       few cases the pericardium in involved.
             ALA has less then 1% mortality if uncomplicated and treated in time.
             ALA present in the left lobe maybe very difficult to detect since, right lobe functions
       normally and no signs are detected

            Peritonitis and diverticulitis are both a common complication of invasive ameobiasis, due
      the parasite eroding the bowel wall and getting access to the peritoneal cavity. This is usually
      accompanied by bacterial leakage into the peritoneum from the intestinal flora, causing local or
      general peritonitis
            Cutaneous Ameobiasis is rare
            Abscesses in the brain , kidney, spleen as well as ulcers and lesions in the rectum, uterus,
      vagina, cervix, and testes are extremely uncommon.
h.        Diagnosis Key
1.      Clinical examination
        No symptoms                                                                 Go to 14
        Symptoms of intestinal Ameobiasis                                           Go to 2

     2. Immediate stool Examination
        E. Histolytica cyst present                                                 Confirm intestinal
                                                                                    histolytica . Go to 6
       E. Histolytica trophozoite present                                           Confirm intestinal
                                                                                    histolytica. Go to 6
       Nothing can be seen                                                          Go to 3 ; If done more
                                                                                    than 3 times Go to 4 for
                                                                                    confirmation

     3. Take stool examination three times due to acyclic or uneven                 Go to 2
     production of cysts

     4. Endoscopy
        Flask shaped ulcer seen                                                     95% confirm intestinal
                                                                                    histolytica. Go to 5
       Other shaped ulcer or no ulcer                                               Unlikely Histolytica

     5. Biopsy from ulcer edges and exudate
        Trophozoite identified by mircoscopy and clean exudate                      Confirm intestinal
                                                                                    histolytica. Go to 6
       Exudate contain viable organism                                              Histolytica unlikely

     6. Symptoms of extraintestinal ameobiasis
       Symptoms present                                                             Go to 7
       Symptoms not present                                                         Extraintestinal
                                                                                    ameobiasis unlikely . Go
                                                                                    to 15 ,but confirm with
                                                                                    serology . Go to 7

     7. Serum examination
        +ve for histolytica antibodies                                              Go to 8
        -‘ve for histolytica antibodies                                             Go to 9

     8. Check past infections and dates
        If past infection present , and recent, with correlation of endemic areas   Serum test unreliable,
                                                                                    due to antibody masking
                                                                                    from previous infection.
                                                                                    Go to 10


       If no past infections are noted                                              Extra intestinal
                                                                                    histolytica confirmed. Go
                                                                                    to 10
9. Retake serum test after 5-7 days to confirm –‘ve result
   Confirmation +’ve                                                       Parasite in early
                                                                           extraintestinal phase. Go
                                                                           to 10
  Confirmation –‘ve                                                        No extraintestinal
                                                                           ameobiasis confirmed Go
                                                                           to 15

10. CT or Sonography imaging of upper right abdominal quadrant
    Abscess found                                                          Go to 11
    No Abscess present                                                     No ALA , but may be too
                                                                           small to see, because still
                                                                           in initial stages

11. Aspirate collected from abscess using CT guided needle (not to be
done if hydatid cyst is suspected due to risk of spillage & anaphylaxis)
    Clean aspirate                                                         Confirm histolytica liver
                                                                           ameobiasis confirmed Go
                                                                           to 12 & 13
    Other organism found in aspirate                                       Abscess unlikely due to
                                                                           histolytica, most likely
                                                                           caused due to other super
                                                                           infection Go to 12

12. Liver functions test
    Functions abnormal                                                     Go to 13
    Functions normal                                                       Histolytica unlikely to be
                                                                           cause of liver abscess,
                                                                           but maybe secondary
                                                                           infection

13. Blood chemistry panel
    High bilirubin                                                         Histolytica unlikely to be
                                                                           cause of liver abscess
   Normal bilirubin                                                        Go to 16

14. Diagnosis: Healthy or E. Dispar infected person, confirm with stool
exam.
15. Diagnosis: Patient is suffering from intestinal ameobiasis only , no
extraintestinal complications have been seen.
16. Diagnosis: Patient is suffering from ALA and intestinal ameobiasis.
i.         Treatment
          Antibiotic therapy is usually effective against invasive intestinal, and extraintestinal ameobiasis.
       However consideration of secondary complications may require treatment modification, to allow best
       result of recovery.
          Treatment of invasive ameobiasis is done in two stages: Invasive disease treatment, and removal
       and eradication of the intestinal carriage of the organism
             Stage 1:
             The drug of choice is Metronidazole , given over a 5-10 day period ,effective in 90% of
       cases.
             This is also the drug of choice for treatment of ALA
             Critically ill patient , with fulminating colitis, should be given Metronidazole and
       Dehydroemetine ( this is a rapid amoebicidal agent) for the 1st three days, then only
       Metronidazole for the next week or so.
             In some cases Metronidazole will not have an appreciable effect. In such a case Tinidazole
       should be administered, and it has been reported to be effective in a single dose.
             In cases of peritonitis , the above treatment should be administered with antibacterial
       therapy and antidiarrheal drugs for relief of dysentery
             Stage 2:
             After the above treatment is complete, the patient should be treated with luminal drugs to
       eradicate the parasite. The drugs of choice are Paromomycine or Iodoquinol
             In cases of peritonitis the same treatment is advised
             In cases of pregnant patients , only the nonabsorbable Paromomycin should be given

         Usually medical treatment is enough to recover full health for such a parasitic infection. However
      severe complications may warrant surgical intervention. Cases in which toxic megacolon develops or
      severe ulcerative destruction of a large section of the colon , which may lead to massive hemorrhage,
      may need resectioning operations to be performed.

								
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