TYPHOID FEVER AND AMOEBIASIS

DR A.O. OLUWASOLA

Epidemiology

• Typhoid is a pyrexial systemic disease caused by intestinal infection with certain Salmonella species viz.

• S. typhi, S. paratyphi A, B and C. • Humans are the only host of S typhi, which is

shed in the feaces, urine, vomitus and oral secretions of acutely ill persons and feaces of chronic carriers.

• S.typhi is transmitted through food, water, diary products and flies,

• While others species are via commercial meats.

Epidemiology ctd.

• Typhoid has a worldwide distribution• Endemic only in communities (Developing

countries) where the standards of sanitations and personal hygiene are low.

• All ages and both sexes are susceptible.• About 2-4% of typhoid patients become

chronic carriers of the infection- • Mostly feacal carriers while some are urinary

carriers.

PATHOGENESIS

• Following ingestion; • The bacilli multiply in the second part of the

duodenum; • Salmonellae invade non-phagocytic intestinal

epithelial cells & tissue macrophages;• Invasion of intestinal epithelial cells is

controlled by different invasion genes: -ity genes• It occurs via adhesion and internalisation

processes.

Phases of infection

• I. Incubation period (10-14 days): • Transcytosis in peyer’s patches; • Then lymphatic dissemination via thoracic

duct and transient bactaraemia; • Clearance and multiplication in MPS; • II. Septicemia – Ist week of clinical disease:• Parasitized MPS cells undergo necrosis; • Blood is flooded with bacilli;• Diagnosis depends on obtaining positive

blood culture.

• III. 2nd week of clinical dx:-• Via the liver they pass into bile,• Multiply rapidly, • Enter intestinal tract for the second time. • Heavy reinfection of the lymphoid tissue

occurs; • Local Ab production occurs. • Stages involve Hyperemia, Necrosis,

Ulceration, Haemorrhage and perforation or healing of Peyer’s patches.

• 2nd and 3rd weeks- Diagnosis depends on culture of feaces.

• 3rd –4th wks- Diagnosis is by urine culture.• After about the tenth day the widal test. • (O & H agglutinin) becomes positive and

rises progressively.• Vi reaction is of no value either in the

diagnosis of acute attack or forecasting clinical relapse but of help in detection of carrier state.

Clinical course

• Onset may be insidious• Wk1. Malaise, headache, fever, stepladder

temperature pattern, chills.• Wk 2. Abdominal Symptoms esp. cramps

constipation and then diarrhea, prostration,• Rose red spots (hyperemic macules in lower

chest and upper abdomen).• Disappears after 2nd wk.• Hyperplasia of MPS.- • Hepatosplenomegally (mild to moderate).

The typical ‘Face of Typhoid’

•

• Wk 3: Ulcer, Bleeding – shock; & perforation• Other signs include- Bradycardia &

Leucopenia, relative lymphocytosis.• As toxaemia increases delirium, Coma &

death.• In those who recover, temperature falls by

lysis, and appetite returns etc.• Diagnosis:–• As above i.e. B. F.U. culture and widal test. 

Complications:

• Haemorrhages and perforation at end of 2nd wk or during third wk.

• Pneumonia,

• Thrombophlebitis,

• Myocarditis, myositis, arthritis, osteomyelitis, meningitis, and cholecystitis.

Morphology

• I GIT:- Macro: • Shows hyperplasia of lymphoid tissue in the

small and large intestine. • Especially terminal ileum + jejunum or

ascending colon.• Paratyphoid B infection may cause ulcers in

stomach & rectum. • Longitudinal as in yersinia enterocolitica. • Four stages occur – hyperaemia, necrosis,

ulceration and healing

LONGITUDINAL ULCERS

Microscopically:

• There is infiltration of large monocytes with pale eosinophilic cytoplasm,

• Eccentric nucleus with erythrophagocytosis + bacilli, lymphocytes and cellular debris in cytoplasm called mallory cells or typhoid cells;

• Monocytes; lymphocytes; plasma cells and rarely neutrophils.

• Mesenteric lymphadentis occurs, • Healing is without fibrosis + fibrinous

exudates; haemorrhage; perforation; ileus; intussusception.

TYPHOID CELLS

II.LIVER & GALLBLADDER

• Hepatomegally: • Striking feature is the presence of typhoid

nodules in the liver- • Consists of collection of macrophages,

lymphocytes + central necrosis + bacilli, • Also seen in Bone marrow and lymph nodes.• + Typhoid abscesses, • Cholangitis is rarer; • Gall bladder is the usual seat of carrier +

chronic cholecystitis + Gall stone.

TYPHOID NODULES IN ILEUM

• III. SPLEEN –• Enlarged, Soft, pale red pulp,• Sinus histiocytosis; reticulo-endothelial

proliferation (prominent malpighian corpuscles) + typhoid nodules.

• IV. GENITOURINARY SYSTEM.• Toxic nephrosis + typhoid nodules; • Orchitis –typhoid nodules.• V. RESPIRATORY SYSTEM – • Ulceration and oedema of the larynx, Pneumonitis +

lung abscesses, & mild bronchitis,

• VI. CVS- • Pericarditis, Fatty degeneration of myofibrils

due to toxaemia.• VII. CNS• Meningism, (N) CSF due to toxaemia• VIII. SKIN:• Rose Spots- hyperaemia of dermis with an

associated monocytic infiltration + bacilli.

• 8. MUSCULOSKELETAL SYSTEM• Osteomyelitis of long bones in SCD- SS &SC.• Typhoid osteitis – typhoid nodules in

marrow.• Zenkers degeneration in Skeletal muscle e.g.• Rectus abdominis,• -A focal hyaline degeneration with

fragmentation of the muscle fibres caused by the toxaemia.

AMOEBIASIS

• Agent:- Protozoan Entamoeba histolytica. • It has a world wide distribution but clinical

disease occurs most frequently in tropical and sub-tropical regions.

• E. histolytica cyst is the infectious form of the parasite because they are resistant to gastric acid.

• In the colonic lumen, cysts release trophozoites,

• When there is no diarhoea the amoebae cease feeding and encyst.

PATHOGENIC MECHANISM

• Amoebae cause dysentery – bloody diarrhoea, intestinal pain, fever –

• When they attach to the colonic epithelium, they lyse colonic epithelial cells and invade the bowel wall.

• Amoebae proteins involved in tissue invasion include:-

• Lectins on parasite bind carbohydrate on colonic epithelium and RBC

• Channel forming proteins (amoebopore) form holes on colonic epithelial cells- plasma membrane and lyse them.

• Cysteine proteinases, -break down proteins of extracellular matrix.

Figure 17-35 Entamoeba histolytica in colon. High-power view of the organisms. Note some of the organisms ingesting red blood cells.

Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 9 December 2005 06:39 PM)

© 2005 Elsevier

AMOEBIC TROPHOZOITES

EPIDEMIOLOGY

• Only 10% of persons infected develop diarrhea, possibly non virulent strains exist (e.g. E. dispar is avirulent).

• Trophozoites containing ingested red cells- a virulent strain.

• Diseases spread by cyst passers, either in the convalescent period or much later after attacks. -directly through contaminated hands or indirectly through foods or flies or water large outbreaks.

• The disease appears in fulminating forms in pregnant and peuperal women and may be severe in mal-nourished children.

Life Cycle of Entamoeba histolytica:

Clinical Features

• Depends on site; intensity of lesion produced; host immune competence and protozoal virulence.

• a. Intestinal -fever, malaise, nausea, vomiting, diarrhea, cramps, abdominal tenderness, dehydration and incapacitation & weight loss.

• OR asymptomatic until immunity falls or malnutrition ensues.

• b. Extra intestinal –Liver: tender hepatomegally; more than half give no hx of intestinal infection. Others - abscesses in brain, lung, & spleen. +Discharging sinus- draining through body wall.

DISCHARGING SINUS FROM AMOEBIC LIVER ABSCESS

DIAGNOSIS

1. Fresh and warm fluid feaces can be taken for immediate examn. for motile trophozoites- staining with iodine reveals 1-4 nuclei and glycogen mass, & cysts.

2. Scrapings and biopsies obtained by sigmoidoscopy

3. Liver abscess aspirate for trophozoites4. Blood for serologic tests- complement fixation

& indirect haemaglutination tests, indirect fluorescent antibody test (IFAT), counter immunoelectrophoresis (CIEP) and (ELISA)

MORPHOLOGY

• Amoebiasis most frequently involves the ceacum and ascending colon.

• In severe cases the entire colon is affected and rarely ileum.– Trophozoites resemble macrophages; contain

vacuoles, have smaller nucleus and stain +ve with PAS stain.

– Amoebae invade through the crypts of lieberkuhn; burrow through the lamina propia and are halted by the muscularis mucosa.

Morphology ctd.– Fan out laterally to create small pin point flask shaped

ulcers with a narrow neck, and broad base and over hanging edges.

– Overlying mucosa sloughs off. – Usually a low-grade inflammatory reaction initially

neutrophilic then with lymphocytes and macrophages predominating.

– + Amoebae in submucosa and muscularis propia. Neutrophils are rare.

– Trophozoites may penetrate muscle coat and cause perforation(rarely) with:

– Haemorrhage , amoebic & bacterial peritonitis and paralytic ileus & abscesses.

– Rectal and anal fistulae may follow penetrating deeper lesions + stricture.

FLASK SHAPED ULCERS

PAS+VE TROPHOZOITES

Amoeboma

• An uncommon lesion seen in areas of stasis in the large bowel viz – ceacum, rectum, sigmoid & trans colon –

• A napkin-like constrictive lesion which consists of a core of necrosis with acute and chronic inflammatory cells surrounded by granulation tissue.

• It can be mistaken for a colonic tumour.

Amoebic Liver Abscess

– In about 40% of cases amoebae embolize through portal circulation to liver.

– To produce usually solitary or less often multiple, discrete abscesses, usually in the right lobe,

– Liver abscess is the most common extra-intestinal complication of intestinal amoebiasis.

– It has scant inflammatory reaction and shaggy fibrinous linning. –contains a chocolate colour/anchovy sauce material.

– usually sterile, but 20 infection purulent material. Amoebae may be present in the periphery.

AMOEBIC LIVER ABSCESS

• Rare complications include:• empyema thoracis, broncho-pleural fistulas,

pericardial abscesses, and perianal skin infection (amoebiasis cutis)

• Metastatic abscesses in kidney and brain.• There is risk of systemic spread and

widespread dissemination when patients with underlying amoebiasis or carriers undergo surgical procedures e.g.

appendisectomy.