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Presentation of Quiz #69

A random urine specimen was submitted to the laboratory for review.  Unusual “organisms” were seen in Urinalysis; the specimen was then submitted to Clinical Microbiology for review.  In reviewing the patient’s chart and other laboratory results, the patient was noted to have hematuria over an extended period of time and was from the Sudan.
Routine examination of the urine sediment revealed the structures seen below:


quiz69_slide1 quiz69_slide2 quiz69_slide3
  • Can you identify these structures?
  • Do these structures explain the patient’s symptoms and history?  Why or why not?  What additional laboratory procedures could be performed?
  •  

Scroll Down for Answer and Discussion

 

 

 

 

Answer and Discussion of Quiz #69
The images presented in Diagnostic Quiz #69 represent (left to right) examples of Schistosoma haematobium eggs with the released miracidia larvae in the same field.  Note that the larvae expand considerably when released from the egg shells.  Humans are the only significant reservoir hosts of S. haematobium. Fully embryonated eggs without an operculum (112 to 170 µm by 40 to 70 µm) escape from the body in the urine. The eggs are light yellowish brown and contain a conspicuous terminal spine (See images below).  Images (hatching eggs) courtesy of Dr. Betty Forbes.

Answers to Questions:
These helminths belong to the Schistosoma genus, Schistosoma haematobium.  Since they are pathogenic and the eggs are viable (living miracidia larvae within the egg shells), the patient should be treated.
quiz69_slide4 quiz69_slide5
S. mansoni, S. haematobium, S. japonicum       Stained miracidium larva
quiz69_slide6  quiz69_slide7
S. haematobium eggs in bladder biopsy (Note the terminal spine and shrunk larvae within the egg shells.

Light infections with urinary schistosomiasis usually produce no symptoms; however, in early disease there may be dysuria and hematuria due to cystitis from deposited eggs. Depending on the worm burden, symptoms may include dysuria, frequency, and terminal or total hematuria. Hematuria is so common that in some areas of endemic infection this phenomenon was considered to be analogous to menarche in girls. Symptoms are usually not seen for 3 to 6 months and may take a year or more to develop. Physical examination is usually normal, but urinalysis may reveal many red blood cells and a few white blood cells on microscopic examination; reagent strip results may indicate hematuria and proteinuria. Chronic disease may lead to major diseases, including obstructive uropathy, chronic bacteriuria, bladder carcinoma, and bladder calcification.

Carcinoma of the bladder has been frequently noted in patients infected with S. -haematobium. Many factors have been suggested as agents promoting schistosome-associated bladder cancer. N-Nitroso compounds in association with secondary bacterial infections of the urinary tract may contribute to the high prevalence of bladder cancer. Bladder cancer is the most prevalent cancer in Egyptians. Many of the tumors involve the posterior wall of the bladder and are noted to occur more frequently in males than in females. The extent of S. haematobiuminfection plays a significant role in the induction of different types of carcinoma, since squamous cell carcinoma is usually associated with moderate and/or high worm burdens while transitional cell carcinoma occurs more frequently in areas associated with lighter parasite loads. The predominance of squamous cell carcinoma in urinary bladder tissues in patients with schistosomiasis is probably due to continuous exposure to the larger quantities of carcinogens (N-nitroso compounds) in urine in patients with the disease.
Since the eggs hatched in the urine, there is no need to perform a hatching test for confirmation of viable miracidia larvae.
                         
Comments on Diagnostic Methods:
S. haematobium eggs are usually detected in the urine, although in heavy infections they may also be found in the stools. The terminal hematuria portion of the urine specimen may contain numerous eggs trapped in the mucus and pus. Peak egg excretion occurs between noon and 3 p.m. Samples collected during this time, or during a 24-h urine collection without preservatives, may be used for examination. Urine can be examined under a microscope after sedimentation or centrifugation. It is important to use saline and not water for the concentration procedures; this will avoid premature hatching of the eggs. Nuclepore filtration is an excellent method for the concentration of eggs in urine. Some data indicate that egg output in urine is an accurate method of confirming the diagnosis and shows less day-to-day variation than in ELISA detection of schistosome circulating antigens in urine.

Use of reagent strips to detect hematuria and proteinuria in areas of endemic infection has proven to be an effective screening technique for S. haematobium infections. The assay correctly identified 87% of egg-negative controls and 98% of parasitologically confirmed cases, including those in six individuals who had been treated but not cured. Also, antigen was detected in the urine of three individuals from whom two specimens had to be examined microscopically to confirm the infection. This suggests that the test is more sensitive than microscopy. To increase the sensitivity of the reagent strip tests, the tests should be performed during the period of peak egg excretion in the urine (noon to 3 p.m.). Although the use of reagent strips allows one to rapidly screen a population at risk, other conditions can yield a positive result.  

Comments on the Infection:
Periportal fibrosis with hepatomegaly and splenomegaly has been noted in patients in areas where infections are endemic. Splenic enlargement has been correlated with the intensity of S. haematobium infection. Cardiopulmonary disease can develop in patients with hepatosplenic schistosomiasis; eggs are carried via the mesenteric veins to the lungs through systemic collateral veins. Schistosomal cor pulmonale tends to be rare in infections with S. haematobium; and eggs can be found in lung tissue at autopsy but are generally not clinically relevant. Although any Schistosoma species may involve the central nervous system, S. mansoni and S. haematobium more commonly involve the spinal cord than the brain. Severe disease presents as transverse myelitis.
As with S. mansoni, chronic bacteremic infections with Salmonella are seen, particularly in cases of chronic active schistosomiasis. Also, schistosomal appendicitis appears to be specific to infection with S. haematobium and is an uncommon cause of appendicitis in areas where schistosomiasis is not endemic. Therapy requires antischistosomal medication in addition to surgery.

Comments on Therapy:
Praziquantel is the drug of choice for treating infections with S. haematobium. It can be taken orally in a single dose and is well tolerated by the host. Side effects, which are usually mild and transient, include abdominal discomfort, dizziness, drowsiness, headache, fever, and loose stools. These effects usually disappear within 48 h. In heavily infected individuals, the side effects, although transient, may be very severe. Split doses have been recommended for treating heavy infections, but this may be a concern for population-based therapy, where individuals may not present themselves for follow-up therapy. Data suggest that a single dose of praziquantel (40 mg/kg of body weight) may have a longer-lasting effect than was previously thought: possibly more than 2.5 years. In certain population-based treatment programs, it appears that a 20-mg/kg dose of praziquantel may be sufficient to provide control of morbidity due to urinary schistosomiasis. Praziquantel has little effect on immature stages of the parasite, and this will affect the cure rates as the immature parasites develop to maturity and egg production.

References:

  1. Garcia, LS, 2016. Diagnostic Medical Parasitology, 6th Ed., ASM Press, Washington, DC.
  2. Garcia, L.S. 2009. Practical Guide to Diagnostic Parasitology, 2nd Ed., ASM Press, Washington, D.C.
  3. Garcia, L.S. (ed.). 2010. Clinical Microbiology Procedures Handbook, 3rd Ed., vol. 1, 2, and 3. ASM Press, Washington, D.C.
  4. Isenberg, H. D. (ed.). 2004. Clinical Microbiology Procedures Handbook, 2nd Ed, vol. 1, 2 and 3. ASM Press, Washington, D.C.
  5. Isenberg, H. D. (ed.). 1995. Essential Procedures for Clinical Microbiology, ASM Press, Washington, D.C.
  6. Mostafa, M. H., S. A. Sheweita, and P. J. O’Connor. 1999. Relationship between schistosomiasis and bladder cancer. Clin. Microbiol. Rev. 12:97–111.