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Schistosomiasis: An urine test to help millions in the developing world

Schistosomiasis is a parasitic disease that infects 243 million people worldwide, and kills about 200 thousand every year. The infection is contracted through contaminated waters, and in the developing world is 2nd only to malaria in rates of infection and public health impact. To make things worse, women already one of the most vulnerable groups in these regions, often develop infertility secondary to the infection. This in places where female role remains centred on being a mother, and gynaecological medical care is next to inexistent.

But there is good news from a new study by scientists in Portugal and Angola: Julio Santos, Monica Botelho and colleagues have discovered catechols (molecules similar to oestrogen, the female sex hormone) in the urine of infected females that seem to be produced by the parasite and associated to infertility problems. If these results are confirmed – and catechols have already been seen in the blood of schistosomiasis patients – testing for these molecules in the urine, could be an easy and non-intrusive way to identify infected women in risk of infertility to fast track towards urgent medical care. But not only that as catechols have been linked to cancer development and another complication of schistosomiasis is bladder cancer.

In fact, this suggests that the same urine test could be used to detect a higher risk for bladder cancer in schistosomiasis-infected patients too. The development of such tests would have important implications for global health: not only there are millions infected in risk of cancer and/or infertility, but also urine tests are easy and cheap to do (crucial in poor countries) and they do not clash with cultural believes, like gynaecological or even blood assessments can.

And with schistosomiasis already endemic in 76 of the poorer countries in the world, we do need all the help we can gather to detect and control the infection and its complications. The work from the Department of Health Promotion and Chronic Diseases of the National Institute of Health at Porto will be published in the journal PLOS ONE.

Schistosomiasis is caught on contact with contaminated waters, when the parasite larva released by infected snails enters the skin. The larvae can live in our blood vessels up to 5 years releasing eggs, which once excreted to the outside will again infect snails restarting a new parasite’s life cycle. The problem is that many eggs never make it out. Instead, they get stuck on the patient’s tissues and organs triggering an immune attack that cause destruction of the tissues nearby. When the parasite is Schistosoma haematobium (S. haematobium), which is most often, the organs affected are part of the urogenital (urinary and gynaecological) system.

In women, the cervix and the uterus are often affected causing female genital schistosomiasis, which produces infertility as well as bleeding and pain during sex. And in countries with restricted access to information, this type of problems results in abuse, stigmatization and other negative social consequences to women, as fertility remains central to their identity and discussion of sexual problems taboo.

Until very recently, both bladder cancer and female infertility of infected patients were believed to result from the tissue destruction caused by the immune response against the trapped eggs. But Botelho’s group, which has been working in S. haematobium for many years, have recently challenged this idea when they discovered that the blood of schistosomiasis patients contained oestrogen-like molecules produced by the parasite, with characteristics that could help the cancer emergence as well. So can the infertility seen in infected females be associated to these catechols too?

To investigate Santos, Botelho and colleagues, in collaboration with fertility specialists Mário Sousa and Alberto Barros, and the clinic of Sagrada Esperança in Angola that supplied the samples, analysed the urine of 93 women from an Angolan region endemic for S haematobium. They looked for parasite eggs and oestrogen-like molecules, trying to correlate these with information on urinary and genital problems (including fertility issues)

What they discovered was that the urine of infected females (positive for parasite eggs), but not of healthy ones (negative for eggs) often had catechols, and that these were associated with infertility, whether this meant less children or no children at all.

So what do catechols do? Botelho had shown that catechols can down-regulate oestrogen receptors blocking the action of the body’s natural oestrogens, which act through these receptors. In addition, catechols can trigger DNA mutations. Botelho explains: “Oestrogen metabolism/ degradation is a normal body process – oestrogens are degraded into catechols and these into quinones. But if there are too many quinones (due to an excessive oestrogen production or altered metabolism) this can cause DNA damage, because they tend to bind to DNA disturbing it. Now we detect these molecules not only in the serum, but also the urine of patients infected with Schistosoma, while uninfected patients do not have them. They have been linked before to cancer (thyroid, breast and prostate) and auto-immunity (when the immune system attacks the own body). Now we see them in infertility associated with schistosomiasis infection.”

So whether by affecting the hormonal environment (and hormones are known to affect the immune response too), and/or by increasing the chance of mutations, the catechols produced by S. haematobium are no doubt contributing for the bladder cancer and the infertility seen in these patients.

“From the estimated 70 million children currently infected with S. haematobium, approximately 19 million will develop female genital schistosomiasis in the coming decade, and most of these will be affected by eggs trapped in their reproductive organs” say the researchers. Bladder cancer on the other hand, is often the most common type among men, and the second in women just behind breast cancer in regions where S. haematobium is endemic. To make things worse, the number of S. haematobium cases is probably much greater than estimated – perhaps as much as three times more.

So even if Botelho’s results need confirmation, the possibility that catechols in the urine of schistosomiasis-infected patients could be used as a prognostic tool for high risk of bladder cancer and/or infertility is great news.

As the researchers put:” development of non-invasive tests especially for female genital schistosomiasis with its potential for infertility if accomplished, should improve the public health in under-resourced and under-served populations.”

A question remains though – why does the parasite produce estrogenic molecules? A possibility is that the aim is to reduce the density of the bladder wall (a known effect of increased estrogens) to help the eggs excretion. Another option is that manipulation of the host’s hormonal environment improves somehow the parasite’s living conditions.

Source

Urinary Estrogen Metabolites and Self-Reported Infertility in Women Infected with Schistosoma haematobium, Júlio Santos, Maria João Gouveia, Nuno Vale, Maria de Lurdes Delgado, Ana Gonçalves, José M. Teixeira. da Silva, Cristiano Oliveira, Pedro Xavier, Paula Gomes, Lúcio L. Santos, Carlos Lopes, Alberto Barros, Gabriel Rinaldi, Paul J. Brindley, José M. Correia da Costa, Mário Sousa, Mónica C. Botelho, PLOS One, DOI: 10.1371/journal.pone.0096774, Published 21 May 2014.

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