As we near the Passover holiday, I thought it appropriate to write about another new plague for Egypt that arises out of the Nile River.
We have come to recognize the fact that approximately 20% of cancer is causally related to infectious agents. When we think of what agents this statement represents, we generally recognize the role of viruses—human papillomavirus (HPV), hepatitis B and C, Epstein-Barr Virus (EBV), various retroviruses, KSHV8, etc. Another contributor to this collection of infectious agents is the only known cancer-causing bacterium, Helicobacter pylori, a major etiologic source for gastric cancer.
Luckily for us, as residents of the West and developed world, we do not have to cope as a rule with the world of parasites. When I was a medical student, I had a wonderful course on parasitology, highlighted by a textbook by Harold Brown (OK, yes, the name did generate jokes!), which described such diseases as malaria and various worms; we would examine stool specimens under the microscope to see the worms themselves or their eggs. Within the world of medicine, this is now mostly relegated to my infectious disease colleagues.
Schistosomiasis is the second most common form of parasitic infection worldwide (after malaria) with 250 million infections. The parasite is a flatworm for which the intermediate host is water-borne snails, which are found usually in shallow rivers or streams, and which obtain access to the bloodstream of those who are working in the waterway. There are three common varieties of schistosome. The worms S. Mansoni and S. Japonicum, after getting into the bloodstream, usually migrate to the GI tract—the liver or the intestines—and cause various acute and chronic infections and difficulties that are not our concern in this column devoted to cancer.
Our concern is S. Haematobium, a worm that is highly endemic to the Middle East and North Africa, and especially to the Nile River valley. Evidence of this parasite has been discovered in mummies and in the remains of Egyptians dating back over 6,000 years. If we were still slaves in Egypt today and washing our clothes in the river or working as agricultural workers standing barefooted while working in the river, the snails would release and inject the worms into the host through the skin. This can cause an acute rash and an infection at the site of injection which can last for multiple weeks. For S. Haematobium, the worms migrate through the bloodstream to the urinary tract and to the urinary bladder in particular, and the worms will ultimately lay their eggs there. This will lead to a chronic infection in the bladder as well as cause blood in the urine or urinary hematuria (hence the name of the parasite). One can diagnose the infection by the finding of eggs in the urine.
The typical cancer of the bladder that we see in the U.S. is histologically a transitional cell carcinoma. However, the cancer that is associated with S. Haematobium is a squamous cell carcinoma of the bladder. A review of 217 cases of carcinoma of the bladder that were diagnosed in Zambia over a five-year period, published in 1976, found that 75% of them were well differentiated squamous cell carcinomas rather than transitional cell cancers. The study found that two-thirds of these cases were infected with S. Haematobium. Another study in Tanzania, published in 1986, looked at 172 cases of bladder cancer that were identified over a nine-year period. Of these, 72% were squamous cell carcinomas and 46% had S. Haematobium eggs in the pathology specimens.
The theory is that the S. Haematobium eggs produce fibrosis in the bladder. This leads to proliferation, hyperplasia and metaplasia, all of which can be precursors of carcinogenesis. Another theory is that chronic urinary infections can lead to the production of nitrosamines which are known bladder carcinogens. It has also been reported that there is an interaction between S. Haematobium infection and cigarette smoking, another known bladder carcinogen.
Carcinoma of the urinary bladder is now the most common cancer in the parts of the Middle East where schistosomiasis is endemic. In a study published in CA Cancer J Clin in 1977, of 11,626 cancer cases seen at the Cairo Cancer Institute from 1970 to 1974, 27.6% were bladder cancer cases associated with S. Haematobium.
Efforts have been made in endemic regions of Africa and the Middle East to reduce the rates of infection and this has had some limited degree of success. Bladder cancer rates are declining as the rates of schistosomiasis decrease.
Alfred I. Neugut, MD, PhD, is a medical oncologist and cancer epidemiologist at Columbia University Irving Medical Center/New York Presbyterian and Mailman School of Public Health in New York. Email: [email protected].
This article is for educational purposes only and is not intended to be a substitute for professional medical advice, diagnosis, or treatment, and does not constitute medical or other professional advice. Always seek the advice of your qualified health provider with any questions you may have regarding a medical condition or treatment.
