Schistosomiasis and the impact on sexual and reproductive health

Genital Schistosomiasis. Part 1: Disease, HIV and Diagnostics

Urogenital schistosomiasis is a dangerous consequence of schistosome infections that drastically decreases quality of life, causes much misery and pain, leads to pelvic inflammation, infertility and can increase the likelihood of contracting other dangerous diseases such as HIV. Researchers are working to define genital schistosomiasis in women and men, to develop practical diagnostic tests and to improve treatment platforms and outcomes.

 

Schistosomes and Schistosomiasis

Schistosomes are tiny worms that live in the blood system of mammals, they produce hundred to thousands of eggs per day that break through the barrier between the blood system and the urinary or intestinal tract (depending on the schistosome species) to exit the body when the host urinates or defecates. But it is estimated that at least a third of the eggs do not make it out of the body and instead get washed up into organs. This is where the danger lies. The trapped eggs lead to damaged tissues, damaged organs and an increasing risk of severe and life-threatening conditions.

The damage caused by these parasites is severe but the chronic nature, spectrum of disease manifestations and complex disease settings presents challenges to its diagnoses, control and elimination in resource-poor settings where it is prevalent.

Genital Schistosomiasis

Schistosome eggs are dispersed through the blood system and can lodge in various organs, leading to tissue damage. A species of schistosome worms called S. haematobium infects people and the eggs often end up in the urinary and reproductive organs causing inflammation and lesions, hence the name ‘Urogenital schistosomiasis’.

When the eggs lodge in the genital tract they cause a form of the disease referred to as genital schistosomiasis. In women, where the impact is more apparent, this is called female genital schistosomiasis (FGS). In men it is called male genital schistosomiasis (MGS).

Symptoms of genital schistosomiasis include:

  • Blood in urine
  • Abdominal and pelvic pain
  • Pain and difficulty urinating
  • Pain and bleeding from intercourse and contact (e.g. from examination)
  • Vaginal discharge
  • Inflammation of the genitals
  • Painful erection and ejaculation
  • Blood in semen
  • Glandular tumours near the prostate

The World Health Organization (WHO) estimate that approximately 56 million women suffer from FGS. Potential complications from female genital schistosomiasis include miscarriages, ectopic pregnancy and infertility.  These not only carry huge risks to women but their impact on mental health and social status cannot be underestimated. Infertility can be a taboo subject in many cultures and can lead to a broader range of issues such as stigma, economic difficulties and social exclusion and isolation.

Sub-Saharan Africa has an ‘Infertility Belt’, a zone across the continent where subfertility levels are far higher than the global average. Explanations for this phenomenon are usually tide to infections such as TB and STIs however the overlap with S. haematobium infections is now being researched and there is a growing body of evidence linking early year infections with S. haematobium to sub/infertility later on in life.

The pathology of genital schistosomiasis mimics many sexually transmitted diseases and when patients present themselves at a local health facility with these symptoms they are often misdiagnosed by healthcare professionals due to the lack of awareness and clear diagnostics. Thus, patients often receive the wrong treatment and are said to be non-responsive to treatment or as having “chronic pain”. Either way their misery is not alleviated.

Link with HIV

The lesions and tissue damage caused by FGS can provide an easy route for STI infections, and one STI in particular seems to be strongly associated with FGS: Worryingly women with FGS are around 3 times more likely to have HIV than those without. And women with schistosome worm infections and with FGS are potentially far more susceptible and at an increased risk of becoming HIV positive.    There is also concern that schistosomiasis and other Neglected Tropical Diseases (NTDs) may lower the efficacy of anti-retroviral drugsClinical trials are being undertaken in South Africa to see if regular treatment with Praziquantel (PZQ), the drug used to treat schistosome infections, of pre-pubescent and post-pubescent young girls can prevent FGS and HIV infections.

The link between genital schistosomiasis and HIV is being researched in more detail but the evidence is getting stronger and stronger that FGS and schistosome infections increase the risk of acquiring HIV.

However, to make things a bit more muddled, researchers are also looking at the impact of schistosome infections in people who are already HIV positive and how quickly they progress to AIDS; here the picture is less clear with studies indicating a potential rapid progression to AIDS and others indicating a more complex effect of schistosome infections. More work needs to be done to understand the impact of schistosome infections on AIDS progression.

But if we want to prevent HIV acquisition in the first place, schistosomiasis control and elimination could be a huge boon to the global effort to stop HIV.

Diagnostic challenges

We rely on microscopic identification of schistosome eggs in urine and stool samples to diagnose someone with schistosome infections. We already know that this is not an ideal diagnostic since there is variability in egg production and excretion and light infections are often missed. A complication for genital schistosomiasis is that once established the lesions and tissue damage last after worm infections have been resolved, whether through treatment with PZQ or from the natural death of the worms themselves.

Thanks to researchers and the WHO we now have a WHO Atlas for FGS, an imaged based reference guide for the diagnosis of FGS in clinical settings.

However, this has to be used with other screening methods to make sure that other infections and diseases have been ruled out (STIs, urogenital TB, cancer screening). And this image-based atlas can only diagnose schistosomiasis in the lower genital region of the female reproductive tract and may miss damage to the fallopian tubes and upper reproductive tract. Another problem is that these clinical diagnostic methods require the use of specialised equipment such as a colposcope, and highly trained personnel which can be challenging in the resource poor settings where schistosomiasis thrives.

Another possibility is the use of molecular techniques based on the identification of schistosome DNA in the genital tract. A study currently being undertaken in Zambia is looking at a potential home-based self-screening test for the detection of S. haematobium DNA as a way of diagnosing FGS.  It is also testing the use of an affordable point-of-care colposcope the size of a smart phone that can be operated by non-highly skilled personnel.  This device is already being used for the diagnosis of cervical cancer in low resource settings.

Further research is needed to refine and develop practical and scalable diagnostic techniques for genital schistosomiasis in resource poor settings.

Genital Schistosomiasis. Part 2: Treatment and Prevention

Treatment

What if a clinician has diagnosed a woman with genital lesions as having Female Genital Schistosomiasis, what treatment could they give her? The clinician could prescribe her Praziquantel, the drug effective against all schistosome species. But here is the bad news. The evidence indicates that giving PZQ at it’s current recommended dosage of 40mg/kg is not an effective treatment for FGS. It can kill living adult worms still residing in the blood vessels and thus stop any additional damage, but it is not effective at reversing already established lesions and tissues damage. And as we know, FGS can last long after the worms have gone.

This is devastating news for the millions of women who already have FGS. We urgently need an effective treatment to reverse FGS lesions and tissue damage. A potential solution might be found in PZQ itself. It does after all have anti-inflammatory properties therefor perhaps at a higher concentration it might reverse some of the damage already established from FGS.

This surely needs to be pursued and quickly to provide some relief to those with genital schistosomiasis.

Prevention

The good news is we can prevent FGS and MGS from developing! And we do.

PZQ is distributed to school-aged children as a regular preventative treatment to kill off any worms and stop the build-up of eggs in their organs 16. This preventative treatment is repeated because infections are caught regularly through contact with contaminated freshwater. In poverty-stricken areas clean-safe water is often not accessible so avoiding contaminated water is not an option even if the local people are aware of schistosomiasis. Improving the water infrastructure and implementing behaviour change can take time, in the meantime the regular treatment of children will save then from sickness, improve their overall health and prevent much misery later in life. In fact studies have shown that women who received PZQ before the age of 20, through schistosomiasis control programmes using PZQ, are significantly less likely to have FGS!

So regular treatment of children is crucial to ensure the long-term damage of genital schistosomiasis is stamped out in the next generation!

We are also eagerly waiting for the results of the clinical trial underway in South Africa to see if regular PZQ treatment in pre-pubescent and post-pubescent young girls can prevent HIV infections. Should this prove successful then PZQ preventative treatment could be the cheapest complimentary tool for HIV prevention on the continent and has the potential to speed up the decrease of HIV acquisition in sub-Saharan Africa.

Male Genital Schistosomiasis

FGS currently gets a bit of attention, although in this author’s humble opinion not nearly as much as it should! However, MGS is severely neglected. Some studies have shown that schistosome eggs are present in semen indicating that there could be a high number of eggs lodged along the reproductive tract of men causing tissue damage and problems. More research is underway but we need more studies to better understand the impact of genital schistosomiasis on men.

Next steps

The WHO and Joint United Nations Programme on HIV/AIDS (UNAIDS) are calling for more research on the link between genital schistosomiasis and HIV as well as the uptake of large-scale coverage of schistosomiasis treatment. WHO & UNAIDS plan to discuss joint screening and testing of HIV, STIs, cervical cancer and FGS at the 22nd International AIDS conference in Amsterdam in July 2018.

Uniting to Combat NTDs, the advocacy group for all 10 NTDs targeted by the London declaration (http://unitingtocombatntds.org/) recently produced a policy document to raise awareness of FGS and how NTD control programmes can prevent this disease from developing.

But PZQ administration through preventative chemotherapy is currently focused on primary schools. What about secondary schools and adolescent children? What about mothers and pre-school aged children? How about distributing Praziquantel in sexual and reproductive health clinics?

To stop the blight of genital schistosomiasis we need to:

  • Strengthen the delivery of PZQ to those at risk of urogenital schistosomiasis.
  • Develop better practical diagnostics for female and male genital schistosomiasis.
  • Engage and advocate for the inclusion of schistosomiasis in already established HIV/AIDS and reproductive health programmes and clinics by strengthening the evidence of a causal link between FGS and HIV
  • Develop an effective treatment for the millions of women already suffering from established genital schistosomiasis and
  • Undertake and support research to better understand the impact of male genital schistosomiasis.

For more info on FGS read the International Society for NTDs briefing on FGS, FGS workshop presentations, a recent review on FGS and the BRIGHT website. This article was ammended from http://blogs.biomedcentral.com/bugbitten/2018/07/13/sexual-reproductive-health-schistosomiasis-endemic-areas/

19 Sep 2018