قراءة
عرض

cvcv

cvcv
cvcv
cvcv
cvcv
Amoebiasis
Professor dr. ali abid saadoon
Clinical
Summary
Introduction
Epidemiology
Disease biology

cvcv

cvcv
cvcv
cvcv
cvcv
Introduction Amoebiasis is a parasitic protozoan disease that affects the gut mucosa and liver, resulting in dysentery, colitis and liver abscess. The causative agent, Entamoeba histolytica, is a potent pathogen that is spread via ingestion of contaminated food and water. Globally, amoebiasis is highly prevalent, and is the second leading cause of death to parasitic disease. This resource will outline the disease biology, epidemiology and clinical principles of amoebiasis.
Introduction
Disease biology
Epidemiology
Clinical
Summary

cvcv

cvcv
cvcv
cvcv
cvcv
The causitive orgainism is parasitic protazoan, called Entamoeba histolytica. What was once thought to be a single entity, is now recognised as two morphologically identical but genetically distinct forms; E. histolytica (pathogen) and E. dispar (commensal). This has affected our understanding of amoeba distribution. Many suspected cases of E. histolytica carrier, may simply have been E. dispar colonisation The WHO recommendes that E. histolytica colonisation should be treated, however, treatment is unnecessary for E. dispar colonisation
Causative Organism
Pathogenesis 1
Life Cycle and transmission 1
Causative Organism
Life Cycle and transmission 2
Self Assessment
Pathogenesis 2
E. Histolytica
Introduction
Disease biology
Epidemiology
Clinical
Summary

cvcv

cvcv
cvcv
cvcv
cvcv
Entammoeba histolytica has a biphasic life cycle, existing in two forms; as an infectious cyst and an amoeboid trophozoite
Life cycle and transmission 1
Mouth - Cyst ingested
Invades gut mucosa – cyst formation Cyst
Passed in stool
Excyst to trophozoite
Trophozoite
Amoebic disease
Introduction
Disease biology
Epidemiology
Clinical
Summary
Pathogenesis 1
Life Cycle and transmission 1
Causative Organism
Life Cycle and transmission 2
Self Assessment
Pathogenesis 2

Life cycle

Life cycle

Epidemiology

Prevalence of amebic infection varies with level of sanitation and generally higher in tropics and subtropics than in tempearate climates. *Worldwide prevalence is about 10% to 50% *Cyst passers are important source of infection The true estimated prevalence of E. histolytica is close to 1% worldwide. Entamoeba histolytica is the second leading cause of mortality due to parasitic disease in humans. (The first being malaria). Amebiasis is the cause of an estimated 50,000-100,000 deaths each year.

cvcv

cvcv
cvcv
cvcv
cvcv
Susceptibility
Amoebiasis is found primarily in developing tropical and subtropical countries where sanitation is poor, leading to a direct link between faeces and ingestion (see Box-1). Occasionally cases are reported in non-endemic areas e.g. UK and USA. Usually due to travel and immigration from endemic areas. There are an estimated 40,000-100,000 deaths due to amoebiasis worldwide each year.
Epidemiology
Box-1. Amoebiasis rates/figures in endemic regions -Egypt: accounts for 38% of patients presenting with acute diarrhoea in outpatient clinic. -Mexico:1.3 million cases reported in 1996. -Hue, Vietnam: 1500 of a 1million population over 5 years
Self Assessment
Epidemiology
Introduction
Disease biology
Epidemiology
Clinical
Summary

cvcv

cvcv
cvcv
cvcv
cvcv
Susceptibility
Generally considered to affect children and adults, of both sexes equally. However, some data and anecdotal evidence suggests a male predominance. Amoebic liver abscesses are most common in males, 18-55. Susceptibility to liver abscess conferred by HLA-DR3 and complotype SC01 in the Mexican populations Other risk factors include oral and anal sex, and contact with contaminated enema apparatus.
Susceptibility
Self assessment
Epidemiology
Introduction
Disease biology
Epidemiology
Clinical
Summary

Transmission

1-driect contact of person to person( fecal-oral) 2- Veneral transmission among homosexual for both gender ( oro-anal) 3- Food or drink contaminated with feces containing the E.his. cyst 4- Use of human feces (night soil) for soil fertilizer 5- contamination of foodstuffs by flies, and possibly cockroaches

Pathogenesis

Effective factores: 1- strain virulence: - classic strain - non-classic strain; Laredo , Huff, …. - pathogen zymodemes 2- susceptibility of the host; nutrition status, immune-sys. 3- breakdown of immunologic barrier (tissue invasion)

Pathogenicity mechanisms

1- secreting proteolytic enzymes( histolysine ) and cytotoxic substances. 2 - contact-dependent cell killing 3 – cytophagocytosisAmebic killing target cell: 1- receptor-mediated adherence of amebae to target cell ( adherence lectin)2- amebic cytolysis of target cell 3- amebic phagocytosis of killed target cell

cvcv

cvcv
cvcv
cvcv
cvcv
Cysts (10-15μm) are ingested via contaminated food or water. A refractile wall containing chitin, allows the cyst to survive stomach acid. In the terminal ileum or colon, the parasite excysts and begins the trophozoite stage. Trophozoites (10-50μm) are highly motile and pleomorphic. They are unable to survive outside the human gut. Energy is derived from the ingestion of bacteria and food particles. No mitochondria are present in trophozoites. Respiration enzymes are prokaryotic in origin and are anaerobic, converting: glucose + pyruvate ethanolTrophozoites reproduce by binary fission and encyst in the colonic wall. Cysts are passed in the stool where they become infectious. The signal for encystation is thought to be via epithelial galactose/N-acetylgalactosamine specific lectin (gal-lectin) binding protein. Life cycle and transmission -details
Introduction
Disease biology
Epidemiology
Clinical
Summary
Pathogenesis 1
Life Cycle and transmission 1
Causative Organism
Life Cycle and transmission 2
Self Assessment
Pathogenesis 2

cvcv

cvcv
cvcv
cvcv
cvcv
Amoebic trophozoites invade the colon causing colitis. They may also invade the portal circulation and travel to the liver, causing liver abscess. Gastrointestinal Pathology The spectrum of colitis in amoebiasis ranges from mucosal thickening, to multiple cyst formation, to diffuse Inflammation / oedema, to necrosis and perforation of colonic wall. Binding of E. histolytica to epithelial cells via gal-lectin. This molecule shows homologous to human CD59, conferring resistance to complement . A change in the epithelial permeability is induced, probably via the inter-cellular tight junctions. .

Pathogenesis 1

Introduction
Disease biology
Epidemiology
Clinical
Summary
Pathogenesis 1
Life Cycle and transmission 1
Causative Organism
Life Cycle and transmission 2
Self Assessment
Pathogenesis 2



Cell lysis and apoptosis of mucosa are thought to be mediated by amoebapores, peptides capable of forming pores in lipid bi-layers. Trophozoites invade through to the submucosa causing flask shaped cysts . Cysteine proteases released by trophozoites digest extracellular matrix in liver and colon, and induce interleukin-1 mediated inflammation. Proteases also cleave IgA and IgG antibodies. Neutrophils and macrophages are drawn to invasion sites. E. histolytica can lyse neutrophils leading to further tissue damage, and contributing towards the induction of diarrhoea. Inflammation is a significant cause of tissue damage, however, innate immunity may be the main combatant against the disease

cvcv

cvcv
cvcv
cvcv
cvcv
Pathogenesis 2
Hepatic Pathology Trophozoites invading the colonic mucosa may enter the hepatic circulation and reach the liver

Histological cross section of classical flask shaped amoebic ulcer in colonic mucosa.

Amoebic colitis with multiple ulcer formation
Amoebic liver abscess
Well circumscribed abscesses are formed in the liver containing liquefied cells surrounded by inflammatory cells and trophozoites Adjacent parenchyma is usually unaffected
Introduction
Disease biology
Epidemiology
Clinical
Summary
Pathogenesis 1
Life Cycle and transmission 1
Causative Organism
Life Cycle and transmission 2
Self Assessment
Pathogenesis 2

Clinical symptoms

Asymptomatic infection Symptomatic infection Intestinal Amebiasis Extraintestinal Amebiasis Dysenteric Non-Dysenteric colitis Hepatic Pulmonary The extra foci Liver abscces Acut nonsupprative Intestinal Amebiasis symptoms: Diarrhea or dysentery, abdominal pain, cramping , anorexia, weight loss, chronic fatigue

cvcv

cvcv
cvcv
cvcv
cvcv
Some individuals carry E. histolytica asymptomatically. 4 -10% will go on to develop the disease within a year. Gastroenterological Gradual onset (weeks) of bloody diarrhoea, occasionally with small volumes of mucoid stool. If blood is not visible, stool is usually ‘haem’ positive due to the breach of the mucosa. Abdominal pain and tenderness. Leucocytes and pus may be present in stool. Fever present in <40% of patients. Weight loss and anorexia can be present. In more severe cases fulminant amoebic colitis develops. Liver involvement is more common in these cases, along with paralytic ileus, toxic megacolon and mucosal sloughing. Over 75% of patients with fulminant colitis develop intestinal perforation. Presentation
Diagnosis
Treatment and Management
Presentation
Vaccine Development 1
Self Assessment
Vaccine Development 2
Vaccine Development 3
Introduction
Disease biology
Epidemiology
Clinical
Summary



Local inflammatory masses, amoebomas, may cause obstructive symptoms. Hepatic More common in men Liver abscess pan present in conjunction with bowel symptoms (10% of cases), or in isolation. Sudden onset of upper abdominal pain with fever. Pain may radiate to right shoulder or be exacerbated by repiratory movements. Hepatic tenderness may be present. Jaundice is unusual. Complicated liver abscess may develop if abscess ruptures into the peritoneal, pericardial or pleural cavity. Morbidity and mortality is high. Rarely, trophozoites may also invade the respiratory tract, brain and GU tract

Pathology of Amebiasis

Flask-like Ulcer

Extra-ntestinalAmebiasis

Pyogenic- Liver Abscess

Liver abscess

This is an amebic abscess of liver. Abscesses may arise in liver when there is seeding of infection from the bowel, because the infectious agents are carried to the liver from the portal venous circulation.

Diagnosis

Paraclinical Diagnosis: Sigmoidoscopic examination: precence of a grossly normal mucosa between the ulcers serves to differentiate amebic from bacillary dysentery,( the entire mucosa being involvoed in bacillary dysentery). Hepatomegally C.B.C. : leukocytosis in Amebic dys. rises above 12000 per microliter, but counts may reach 16000 to 20000 per microliter.


Laboratory Diagnosis
Entamoeba histolytica must be differentiated from other intestinal protozoa including: E. coli, E. hartmanni, E. dispare,……Differentiation is possible, but not always easy, based on morphologic characteristics of the cysts and trophozoites. The nonpathogenic Entamoeba dispar, however, is morphologically identical to E. histolytica, and differentiation must be based on isoenzymatic or immunologic analysis. Molecular methods are also useful in distinguishing between E. histolytica and E. dispar and can also be used to identify E. polecki.

Microscopy

Trophozoites of Entamoeba histolytica /E. dispar ( trichrome stain )


A

Trophozoites of Entamoeba histolytica with ingested erythrocytes (trichrome stain)

F
E

Cysts of Entamoeba histolytica /E. dispar

GHI

I
H
G


Immunodiagnosis (Antibody Detection)

Antigen Detection

Molecular diagnosis
In reference diagnosis laboratories, PCR is the method of choice for discriminating between the pathogenic species (E. histolytica) from the (nonpathogenic species (E. dispar.

Treatment

Intestinal Amebiasis: *Asymptomatic amebiasis(cyst passer): Diloxanide furoate ( furamide) 500 mg 3 times daily / 10 days *Symptomatic amebiasis ( troph. & cyst): - Iodoquinol , 650 mg 3 times daily/ 20 days or Metronidazole (Flagyl) , 750 mg 3 times daily/ 10 days *Amebic colitis: Chloroquine, 250 mg 2 times daily * Acute amebic dysentery: Emetine hydrochloride, 1mg/kg daily IM or SC

Treatment

Extraintestinal Amebiasis:*Amebic liver abscess, ameboma: Metronidazole, as above plus dehydroemetine / 10 days or Metronidazole or dehydroemetine as above plus Chloroquine , 500 mg 2 times daily / 2 days,…..

cvcv

cvcv
cvcv
cvcv
cvcv
Clinical history is important. In low resource settings this may be the means of diagnosis. A good travel history is important as disease may develop years after a visit to an endemic area. Demonstration of E. histolytica in stool by microscopy (old), or ELISA assay for antigen detection. Trophozoites only survive for short periods of time, therefore, fresh stool samples should be used Colonoscopy to confirm colitis and tissue biopsy for amoeba Liver abscess; space occupying lesion on CT/USS with positive amoebic serology
Diagnosis
Introduction
Disease biology
Epidemiology
Clinical
Summary
Diagnosis
Treatment and Management
Presentation
Vaccine Development 1
Self Assessment
Vaccine Development 2
Vaccine Development 3

cvcv

cvcv
cvcv
cvcv
cvcv
References
Summary
Amoebiasis is a major global cause of mortality and morbidity, due to dysentery. The causative organism, E. histolytica. E. histolytica has a biphasic life cycle and exists as an infective cyst and pathological trophozoite. The disease is spread via contaminated food and water, usually due to poor sanitation. The disease is found in tropical and sub-tropical parts of the world.
Summary
Introduction
Disease biology
Epidemiology
Clinical
Summary


Every year, 40,000-100,000 people die from amoebiasis Certain genetic traits pre-dispose to certain pathologies. Patients usually present with abdominal pain, bloody stools and fever. Hepatic symptoms are more acute with upper abdominal pain and radiation to the right shoulder. Treatment is with Nitroimidazole (e.g.metronidazole) and a luminal agent. Spread can be prevented by boiling water. A potential gal-lectin vaccine is currently in development. Good results have been yielded with native gal-lectin vaccines, and moderate results with a DNA based vaccine. Immunity appears to be mainly via a Th1 cell medicated response and secretory IgA

cvcv

cvcv
cvcv
cvcv
cvcv
Amoebiasis, in particular with liver involvement, can be fatal if not treated. Chemotherapy can effectively cure ameobiasis. Nitroimidazole (e.g.metronidazole) is used to treat the invasive pathogens – 800mg t.d.s for 10 days. This is followed by a luminal agent (e.g.diloxanide furoate) to eliminate colonisation – 500mg t.d.s for 10 days. This is also suitable for asymptomatic individuals. Complicated liver abscesses should be drained surgically.PreventionBoiling water for at least ten minutes kills amoebic cysts effectively. Chlorine and iodine tablets are not thought to be 100% effective. Treatment and Management
Introduction
Disease biology
Epidemiology
Clinical
Summary
Diagnosis
Treatment and Management
Presentation
Vaccine Development 1
Self Assessment
Vaccine Development 2
Vaccine Development 3

cvcv

cvcv
cvcv
cvcv
cvcv
Questions
Reveal Answer
What are the symptoms of gastrointestinal amoebiasis?What are the symptoms of hepatic amoebiasis?Why is a good travel history important in diagnosis of amoebiasis?What investigations can be performed to confirm a diagnosis? Name two drugs and dosage regimes that can be used to treat amoebiasis.Is the following statement true or false?“chlorine and iodine can be used to decontaminate water of E.histolytica with 100% effectiveness”7) Does Gal-lectin induce a Th1 or Th2 cell mediated immune response? Introduction
Disease biology
Epidemiology
Clinical
Summary
Diagnosis
Treatment and Management
Presentation
Vaccine Development 1
Self Assessment
Vaccine Development 2
Vaccine Development 3

cvcv

cvcv
cvcv
cvcv
cvcv
Answers
What are the symptoms of gastrointestinal amoebiasis? Gradual onset (weeks) of bloody diarrhoea, abdominal pain and tenderness, fever present in <40% of patients, weight loss and anorexia, amoebomas, may cause obstructive symptoms. What are the symptoms of hepatic amoebiasis?Sudden onset of upper abdominal pain with fever. Pain may radiate to right shoulder or be exacerbated by repiratory movements. Hepatic tenderness may be present. Jaundice is unusual3) Why is a good travel history important in diagnosis of amoebiasis? A good travel history is vital to ascertain whether a patient has visited an endemic area. The disease may develop over a year after travel.What investigations can be performed to confirm a diagnosis?Demonstration of E. histolytica in stool by microscopy (old), or ELISA assay for antigen detection. Colonoscopy may be performed to check for colitis and biopsy. Check for liver abscess with USS or CT.Name two drugs and dosage regimes that can be used to treat amoebiasis.Nitroimidazole (e.g.metronidazole)– 800mg t.d.s for 10 days. This is followed by a luminal agent (e.g.diloxanide furoate) 500mg t.d.s for 10 days. 6) Is the following statement true or false?“chlorine and iodine can be used to decontaminate water of E.histolytica with 100% effectiveness”Boiling is the most effective methos for water decontaminationDoes Gal-lectin induce a Th1 or Th2 cell mediated immune response?Th1 cell mediated response Introduction
Disease biology
Epidemiology
Clinical
Summary
Diagnosis
Treatment and Management
Presentation
Vaccine Development 1
Self Assessment
Vaccine Development 2
Vaccine Development 3






رفعت المحاضرة من قبل: حيدر عبدالله الحربي
المشاهدات: لقد قام 0 عضواً و 243 زائراً بقراءة هذه المحاضرة








تسجيل دخول

أو
عبر الحساب الاعتيادي
الرجاء كتابة البريد الالكتروني بشكل صحيح
الرجاء كتابة كلمة المرور
لست عضواً في موقع محاضراتي؟
اضغط هنا للتسجيل