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Quiz 26

Presentation of Quiz #26

A 56 year old male from Los Angeles had toured numerous areas throughout the world for approximately 5 months. His travels included stops in Japan, Hong Kong, Thailand, Singapore, Cambodia, India, Pakistan, Egypt, Turkey, Greece, Spain, England, France, and Italy. His expenses were minimal, and he often stayed at hostels. Water for bathing and drinking was often unfiltered and obtained from rivers and canals, and general living conditions (with the exceptions of the hostels) were often quite primitive.

During his trip, he complained of diarrhea, fatigue, weight loss, occasional fever, and general malaise. Although he saw several physicians during his trip, no specific diagnoses were made. Several months after he returned, he developed terminal pain on urination, which was thought to be caused by prostatitis.

Approximately 30+ months after his trip, he developed frequency of urination, nocturia, and dark, grossly bloody urine. After cystoscopy, he was referred because of an apparent bladder tumor. Laboratory findings included a urinalysis with few RBCs and WBCs; cytologic examination of the urine revealed no tumor cells.

A bladder biopsy was performed, and numerous, small lesions were seen, which appeared to be below the mucosa. There were also some discolored areas that were seen, but which did not appear specific to any particular condition. The following image was seen on biopsy.

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Answer and Discussion of Quiz #26

Comment: The image shows a Schistosoma haematobium egg from the bladder biopsy. Schistosomiasis affects between 200 and 300 million people in 77 countries throughout the world and is a significant cause of disease in areas of endemic infections. In Egypt, approximately 20% of the population is infected; prevalence rates in some villages have been estimated to be 85%. Although only about 10% of infected people have serious disease, this represents 20 to 30 million individuals worldwide. Approximately half of the remaining 180 to 270 million infected individuals will have symptoms. S. haematobium is found throughout Africa, portions of the Arab peninsula, the Middle East, parts of India, and southern Portugal. It is not found in the rest of Europe, Asia or the Americas. Obviously, the patient came in contact with contaminated water during his travels, the most likely geographic area being Egypt. After additional discussions, he indicated his water exposure in Egypt had been more extensive, with bathing directly in some of the rivers and canals.

Schistosomes are somewhat different from other human trematodes by (1) having two sexes, (2) living in the blood vessels, (3) having nonoperculated eggs, (4) and having no encysted metacercarial stage in the life cycle. The human is the definitive host for S. mansoni, S. japonicum, and S. haematobium; S. mekongi and S. malayi (both similar to S. japonicum); and S. intercalatum. S. mattheei, which causes infections in sheep, cattle, and horses, also infects humans and can cause disease. Other schistosomes have been found in humans, but do not tend to cause any pathology. Also, cercariae from birds and mammals can penetrate human skin, but cannot complete the life cycle and tend to die without migration or maturation; however, they do produce cercarial dermatitis.

Life Cycle: S. haematobium adults reside in the vesicle and pelvic plexuses of the venous circulation. The adult female can contain from 20 to 100 eggs in the uterus at one time. In addition to the vesicle and pelvic plexuses, oviposition may occur in the rectal venules. To maintain the life cycle, the miracidium must find a suitable snail host (Bulinus sp.) when it is released from the egg in fresh water. The immature larval worms after reaching the liver may migrate via the inferior mesenteric veins to the rectal vein to mature. However, they most commonly migrate through the hemorrhoidal and pudenda veins to the vesicle and pelvic plexuses. Within 3 months of exposure to cercariae, egg production will begin.

Clinical Disease: Light infections with urinary schistosomiasis usually produce no symptoms. 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 infections 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 (RBCs) and a few white blood cells (WBCs) on microscopic examination; reagent strip results may indicate hematuria and proteinuria. Chronic disease may lead to major disease pictures, including obstructive uropathy, chronic bacteriuria, bladder carcinoma, and bladder calcification.

Eggs are most concentrated in the tissues of the bladder and lower ureter. As the eggs become trapped in the tissues, granulomas and pseudoabscesses form, leading to fibrosis and ulceration. With extensive fibrosis, the bladder loses its contractility. The urethra frequently is occluded because of hyperplasia, polyp formation, and the discharge of purulent debris plugs from the bladder. The ureters are also frequently involved, and obstruction can cause urine reflux, hydronephrosis, retrograde infections, and renal failure.

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 malignancy 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. haematobium infection plays a significant role in the induction of different types of carcinoma, since squamous cell carcinoma (SSC) is usually associated with moderate and/or high worm burdens while transitional cell carcinoma (TCC) occurs more frequently in areas associated with lighter parasite loads. The predominance of SCC in urinary bladder tissues in patients with schistosomiasis is probably due to continuous exposure to the carcinogens (N-nitroso compounds) found in larger quantities in urine from patients with the disease.

Diagnosis: 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 obtained for examination. Urine can be examined with a microscope after sedimentation or centrifugation.

Key Points – Laboratory Diagnosis:

  1. Eggs cannot be detected in urine until the worms mature (may take from 5 to 13 weeks after initial infection).
  2. In very light or chronic infections, eggs may be very difficult to detect in urine; therefore, multiple urine examinations may be required.
  3. Biopsy and/or serologic tests may be helpful in these patients.
  4. Both 24 h and spot urines should be examined; remember to collect the urine specimens with no preservatives; these eggs can also occasionally be recovered in stool, so both urine and stool specimens should be examined.
  5. The membrane filtration technique using the Nuclepore filters can be very helpful in diagnosing infection with S. haematobium.
  6. Patients who have been treated should have follow-up ova and parasite examinations for up to 1 year to evaluate treatment.
  7. In active infections, the eggs should contain live or mature miracidia. Remember that examination for the confirmation of flame cell activity must be performed on fresh specimens; no preservatives can be used prior to this test or the hatching test.
  8. When performing the hatching test, do not get the light too close to the surface of the water; excess heat can kill the liberated larvae. Also, remember to examine the water about every 30 min for up to 4 hours.
  9. It is important to remember that the small and less commonly seen miracidium larva of S. haematobium may be present in the urine; motility in unpreserved specimens or stained morphology could confirm this diagnosis.
  10. It is also possible to see S. haematobium eggs in semen specimens, even when repeated urinary and fecal examinations and serologies are negative.

Epidemiology and Control: Humans appear to be the only important reservoir hosts, although naturally infected monkeys, baboons, and chimpanzees have been found. The intermediate snail host, Bulinus sp., can survive in the mud when the water dries up. The snails retain their infectivity and resume shedding cercariae when the rainy season begins. In some areas, cercariae are found in areas where infected snails are absent and sometimes cercariae are absent in the present of infected snails.

Data suggests that less than 1 in 100 contacts results in infection and less than 1 in 1,000 result in egg contact. This suggests that there may be substantial attrition of invading cercariae even in naïve individuals.

In many endemic areas, awareness of urinary schistosomiasis and its symptom of blood in the urine are high, but specific knowledge about the parasite, its vector and the interaction between the parasite and vector in the life cycle are extremely low. Activities that require behavior and attitude modification can be identified and encouraged as components in the control of schistosomiasis. Certainly snail control and contaminated water exposure modifications are key factors in control of this disease.

Treatment: Praziquantel is the drug of choice for treating infections with S. haematobium. Praziquantel 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, 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 show up for follow-up therapy.

These images demonstrate S. haematobium eggs: (left) eggs seen in a "squash" preparation of bladder biopsy material; (middle) egg seen in wet preparation; (right) egg seen in wet preparation.

Schistosome eggs: (left) S. mansoni; (middle) S. haematobium; (right) S. japonicum.

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. Hassan, M.M., A. Medhat, M.M. Makhlouf, T. Shata, M.A. Nafeh, O.A. Osman, E.A. Deaf, N. Galal, and Y.M. Fouad. 1998. Detection of circulating antigens in patients with active Schistosoma haematobium infection. Am. J. Trop. Med. Hyg. 59:295-301.
  4. Kahama, A.I., A.E. Odek, R.W. Kihara, B.J. Vennervald, Y. Kombe, T. Nkulila, C.F. Hatz, J.H. Ouma, and A.M. Deelder. 1999. Urine circulating soluble egg antigen in relation to egg counts, hematuria, and urinary tract pathology before and after treatment in children infected with Schistosoma haematobiumin Kenya. Am. J. Trop. Med. Hyg. 61:215-219.
  5. Mostafa, M.H., S.A. Sheweita, and P.J. O’Connor. 1999. Relationship between schistosomiasis and bladder cancer. Clin. Microbiol. Rev 12:97-111.
  6. Strickland, G.T. and B.L. Ramirez. 2000. Schistosomiasis, In:Strickland, G.T. (ed). Hunter’s Tropical Medicine and Emerging Infectious Diseases, 8th ed. W.B. Saunders Company, Philadelphia.

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The content within this site is made possible through the extensive contribution of Lynne S. Garcia, M.S., MT(ASCP), CLS(NCA), BLM(AAB), F(AAM), Director, Consultantation and Training Services (Diagnostic Medical Parasitology and Health Care Administration). For additional information, she can be contacted at LynneGarcia2@verizon.net.

Reference: Garcia, L.S. 2015. Diagnostic Medical Parasitology, 6th Ed., ASM Press, Washington, D.C.