Bilharzia(Schistosomiasis)

It is estimated that more than 80% of all the people infected with schistosomiasis are in sub-Saharan Africa.

Schistosomiasis is associated with:

  • poverty and poor living conditions
  • inadequate sanitation and water supply
  • unplanned water resource development

1. Epidemiology

  • Worldwide in tropical and sub-tropical areas.
  • In SA east flowing rivers are mostly contaminated
  • Import from Mozambique is very troublesome

2. Definition

A parasitic disease caused by 5 species trematodes (flukes) of the genus

shistosoma.

Only two are of importance in Southern Africa-

S. mansoni responsible for intestinal bilharzia and

S. heamatobium the causative agent of urinary bilharzia.

3. Aetiology and life cycle

  • Humans become infected after contact with water containing the infective stage of the parasite, called cercaria (forked-tailed larvae).
  • Cercariae penetrates the unbroken skin (within a few seconds) and transform into Schistosomes.
  • Within 30 to 45 days, the parasite is transformed into a long worm - either male or female.
  • A localized dermatitis may occur at the site of entry.
  • After 2-3 days they migrate to the lungs and then to the portal vein.
  • In the portal vein the maturing male and female schistosomes pair and migrate to the venules of the mesentery, bladder, or ureters, depending on the species, and begin to deposit eggs.
  • Adult worms may remain for many years (2-10 years) in the body, and produce huge numbers of ova (200 –2000 eggs per day).
  • Some eggs remain in the tissues, causing a local inflammatory reaction (granulomatuous) to form "pseudotubercule".
  • Eventually, these ova degenerate or calcify (fibrotic response).
  • A portion of the ova are extruded into the lumen of the intestines (mansoni), or bladder wall (haematobium).
  • After contact with water, ova hatch, releasing a miracidium, which infect a snail of the particular species.
  • After some weeks of developmental stages in the snail, cercariae are produced in the surrounding water, which again can infect humans.

4. Immunity

  • It has not been clearly established that protective immunity develops in humans; however, reinfection rates in previously treated humans are reduced in older populations.

5. Pathogenesis

  • A number of factors govern the disease manifestations:
  1. duration and intensity of infection (worm burden of the host)
  2. location of egg deposition
  3. host genetics
  4. concurrent infections and
  5. other unidentified factors
  • Initial infection with schitosomes is most likely a manifestation of the immune response to the schistosomes and eggs, and results in an acute febrile illness (Katayama fever or acute schistosomiasis).
  • Most of the morbidity and mortality of the disease are determined by the inflammatory and fibrotic response to these eggs.
  • All schistosome eggs elicit a granulomatous response. After years of continued infection, with S. Mansoni, some heavily infected individuals develop fibrosis, mainly portal fibrosis, resulting in portal hypertension.
  • After development of portal fibrosis, eggs are shunted to the lungs via portal-systemic collateral veins, resulting in cor pulmonale.
  • Immune complexes shunted to the systemic circulation cause glomerulonephritis.
  • Continued infection of S. haematobium result in fibrosis of the ureters and bladder.

6. Clinical manifestations

a.) Immediately following exposure, patients frequently complain of intense transient itching (within hours). "SWIMMERS ITCH" (the eruption usually disappears in 2-3 days)

- Cercaria penetration of skin.

b.)ACUTE SCHISTOSOMIASIS OR KATAYAMA FEVER:

  • encountered principally in previously unexposed individuals, and those exposed to sudden intense infection.
  • the etiology of this syndrome is uncertain
  • 2 to 8 weeks after initial exposure (and infection with S. mansoni and S.

japonica, rarely with S. heamatobium), an acute febrile illness may develop.

  • Variety of symptoms including fever, chills, anorexia, headache, urticaria or

angioedema, weakness, myalgias, weight loss, non-productive cough, abdominal pain with enlarged tender liver and diarrhea.

  • Common reason for FUO in endemic areas.
  • Acute schistosomiasis is self-limited, resolving over 1 to 2 months.
  • These symptoms gradually diminish but may last as long as 2-3 months.
  • Central nervous system lesions may occur.
  • Presence of eosinophilia (30-5O% of total WCC).
  • Leukocytosis, increased immune complexes and elevated immunoglobulins.
  • The course can be abbreviated by treatment with corticosteroids, followed by specific antischistosomal therapy with praziquantel. The recommended praziquantel dose is 40 mg/kg per day in two doses for one day for S. haematobium and S. mansoni (and 60 mg/kg /d, t.d.s.,1day for S. japonicum).

c.)LIVER FIBROSIS WITH PORTAL HYPERTENSION: (S. Mansoni)

  • After 10-15 years of prolonged exposure and infection.
  • Liver may be enlarged, nodular with "pipe-stem" fibrosis.
  • Portal venous tracts are replaced with fibrous tissues, sometimes leading to presinusoidal blockage, portal hypertension, splenomegaly, ascites and

oesophageal and gastric varices. (haematemesis)

  • Finally hepatocellular failure may occur.
  • In the past the diagnosis required a wedge biopsy of the liver.
  • Ultrasonograms of the liver show characteristic findings. (Specificity

and sensitivity of 100%).

  • Patients with periportal fibrosis may not have schistosome eggs in the

feces.

d.)PULMONARY MANIFESTATIONS OF SCHISTOSOMIASIS

  • Exclusively in patients with periportal fibrosis and portal hypertension.
  • Pulmonary involvement with schistosomiasis may occur in three settings:

• Acute schistosomiasis

• As a complication of chronic hepatosplenic disease

• As a result of antischistosomal therapy.

d.1) ACUTE SCHISTOSOMIASIS – (Katayama fever)

  • 2 to 8 weeks after exposure to the organism, affected patients may experience fever, chills, anorexia, weight loss, abdominal pain, diarrhea, urticaria, myalgias, and a dry cough.
  • the severity of symptoms reflects the intensity of infection.
  • Typical findings during the acute phase include hepatosplenomegaly, lymphadenopathy, and blood eosinophilia.
  • Bronchospasm may occur in addition to the frequent dry cough.
  • Chest x-rays have recorded basilar and midzone infiltrates, miliary mottling, and beaded micronodulation.

d.2) HEPATOSPLENIC DISEASE

  • occurs in those with heavy infection, particularly with S. mansoni and S. japonicum.
  • travel of schistosome eggs through the portal circulation into the liver, thereby causing the development of hepatic granulomata and fibrosis.
  • The resulting presinusoidal portal hypertension fosters the development of portosystemic collateral vessels that allow schistosome eggs to embolize into the pulmonary circulation.
  • Eggs lodge in pulmonary arterioles of 50 to 100 µm diameter and produce a granulomatous pulmonary endarteritis
  • Pulmonary hypertension and cor pulmonale ensue gradually.
  • Dyspnea is the principal symptom attributable to this pulmonary process .
  • The chest x-ray initially shows fine miliary nodules.
  • As the disease evolves, the heart enlarges and the pulmonary arteries dilate to aneurysmal proportions [12].

Severe cardiopulmonary schistosomiasis does not develop in patients without marked hepatic involvement . Thus, the diagnosis can be confirmed by liver biopsy, which demonstrates a very characteristic form of fibrosis known as Symmer's pipestem fibrosis.

Detection of eggs in bronchoscopic washings or transbronchial biopsies can also establish the diagnosis.

The pulmonary changes represent end-stage alterations. Thus, the course of this illness may be only minimally reversible with antischistosomal therapy.

d.3) POSTSCHISTOSOMAL THERAPY

  • Initiation of antischistosomal therapy for established infections may result in embolization of adult worms to the liver or lungs.
  • Coughing and wheezing can result, accompanied by new infiltrates on chest x-ray and a rise in the peripheral eosinophil count.

These changes are self-limited and do not necessitate cessation of antischistosomal therapy. The mechanism probably involves an immunologic response to exposed or released antigens from dead worms.

e.) SCHISTOSOMIASIS AND GLOMERULAR DISEASE

  • Chronic infection with Schistosoma mansoni (and to a lesser degree other schistosomal species) is associated with glomerular disease in 10 to 15 percent of patients
  • antibodies against schistosomal antigens can often be eluted from the glomeruli
  • schistosomal antigens have been detected in the glomeruli by indirect immunofluorescence
  • initial glomerular injury: direct deposition of schistosomal antigens
  • subsequent disease progression: hepatic fibrosis
  • Circulating schistosomal immune complexes are normally removed by the Kupffer cells in the liver; in the presence of portal hypertension, however, the hepatic circulation is partially bypassed resulting in increased delivery to and deposition in the glomeruli.

Histologic evaluation most often reveals membranoproliferative glomerulonephritis (MPGN). As with idiopathic MPGN, most patients present with the nephrotic syndrome, hypertension, and a plasma creatinine concentration between 88 and 176 µmol/L. [mesangial proliferation, membranous nephropathy, focal glomerulosclerosis, and secondary amyloidosis is also possible].

f.) GRANULOMATOUS CHANGES IN THE LARGE INTESTINE (S. mansoni):

  • 3 months - years later, eggs are laid in the inferior mesenteric veins, with colonic symtoms related to the intensity of infection.
  • Focal deposits of eggs in large intestines results in the formation of tubercles, ulceration and inflammatory polyps. (mostly rectosigmoid colon)
  • Major clinical presentation is bloody diarrhea, sometimes associated

with protein-losing enteropathy and anaemia.

  • Less commonly of S. heamatobium.

g.) CENTRAL NERVOUS SYSTEM

  • Eggs may lodge ectopically in the CNS with a predilection for the spinal cord, causing transverse myelitis (S. mansoni and rarely haematobium).

h.) BLADDER AND URETERS: (S. heamatobium)

  • Dysuria and hematuria are frequently noted 2 to 3 months after infection.
  • Intense inflammatory and granulomatous response evoked by the eggs may cause anatomic and/or functional obstruction, hydro-ureter and hydronephrosis, and masses in the bladder or ureters.
  • Mostly the lower 1/3 of the ureters are involved
  • Cystoscopic examination may reveal friable masses extending into the bladder, ulceration, petechiae, and granulomas ("sandy patches").
  • These early lesions are reversible after anti-schistosomal chemotherapy.

-if untreated fibrosis increases, and the bladder may become contracted.

-squamous cell cancer of bladder.

-Significant cause of morbidity and mortality.

7. Diagnosis

  • Identification of ova in the feces, urine or tissues, rectal biopsies.
  • Laterally spined eggs for mansoni and terminally spined for haematobium.
  • Urine must be collected in the middle of the day 12h00 to 14H00 when egg output is maximal.
  • Serologic tests:
  1. not 100% sensitive
  2. non specific (can’t distinguish between different species)
  3. False positive: avian schistosomiasis, other helminth infections)
  4. Do not distinguish between past and present infection.
  5. Do not revert to negative after treatment even though there may be a drop in antibody titre.
  6. Time consuming and expensive.
  • Radiology

bladder calcification on AXR

characteristic IVP

polypoid lesions in the distal ureters and bladder are evidence of active infection and show up as filling defects

postmicturition film show a shaggy “moth-eaten” bladder

calcifications of the bladder and or ureters indicates an old infection

curvilinear calcifications of the bladder is pathogomonic

  • Cystoscopy will visualize bladder abnormalities.
  • Sigmoidoscopy may reveal rectal and sigmoid colon involvement.
  • Ultrasonogram of the liver (portal fibrosis).
  • Wedge biopsy of liver (portal fibrosis).
  • Immunofluorescent antibody test.

8. Treatment

  1. Prevention: Health information

Protection against contamination

b.Medication:

S. heamatobium:Praziquantel (Bilttricide) 4O mg/kg single dose

Not < 1 year or

First trimester

or Metrifonate (Bilharcil) – Not registered in SA

S. Mansoni: Praziquantel 4Omg/kg single dose

or Oxamiquine (Vancil) 20-30 mg/kg over 3 days

Treatment can only be considered ineffective if the patient still excrete viable ova

6 to 8 months after treatment and if reinfection is ruled out.

Acute disease may require steroid treatment to control fever and toxaemia.

Coexisting Neurocystisercosis !!

may result in acute brain oedema and raised intracranial pressure if treated with Praziquantel.