09 December 2014

The threat from genital schistosomiasis

We look at the experiences and viewpoints of three experts working with the Pediatric Praziquantel Consortium to help eliminate the genital form of schistosomiasis: Eyrun Kjetland, Jutta Reinhard-Rupp and Peter Hotez.

Female genital schistosomiasis (FGS), a common complication of the urinary tract schistosome,Schistosoma haematobium, has been known since the 19th century. Yet it has been largely overlooked as a major neglected tropical disease, and is a major gynecologic affliction of girls and women living on the African continent. Occasional reports of FGS have come to light, but the condition has always been ignored again shortly afterwards.

Prompting action is proving to be a major challenge. The effects of genital schistosomiasis are not widely acknowledged or understood, and could be more significant than suspected until now – with some as-yet unexplored associations with high HIV rates.

Eyrun Kjetland from Oslo University Hospital heads the Otimati team working on FGS in South Africa. From early on in her career, she has seen the serious effects of the disease first-hand: “Women infected with FGS have many problems as a result. Sometimes the vaginal walls and cervix can be covered in schistosome eggs, causing the kind of inflammation you would see if there were thousands of tiny thorns there. Simply touching the area can cause bleeding, and the eggs cause calcification with crust-like protrusions on the surface. Women experience spot bleeding, burning sensations, discharge and infertility. The condition is often misdiagnosed, and specialists from all areas are unaware of what to look for or exactly where to find it.”

The results of an infection are permanent, as Eyrun discovered when she was working in Zimbabwe: “I was horrified when I first saw that lesions were unchanged by curing the underlying condition – it wasn’t what I had anticipated: even when I used the maximum praziquantel dose of 60mg/kg, the lesions were still there after 9 months, and in fact even five years later. I had to tell patients that I didn’t know what to do next.”

Eyrun also suspects a strong link with HIV: “This is a difficult disease to study, because you can’t conduct routine gynecological exams in young girls. However, it makes sense to suspect that it might be implicated in high HIV rates in some geographical areas, and we are certainly seeing some associations between HIV and FGS infection rates. We now know that teenagers show the same kind of lesions as adult women, both in Zimbabwe and Madagascar, but data are at an early stage. We’ll be looking at whether or not the lesions are reversible in teenagers, and if regular treatment in early teenage years can prevent FGS. We are currently working with schools and Departments of Health to explore treated and untreated schools.”

Jutta Reinhard-Rupp is Head of the Translational Innovation Platform Global Health at Merck, the company responsible for a major donations program for the ‘gold standard’ drug, praziquantel. Merck also leads the Pediatric Praziquantel Consortium and Jutta says that treating pre-school children is likely to be a very significant factor in preventing FGS: “We cannot routinely diagnose invasively with young girls, but it is clear that very young children can be infected. By the age of 6, some girls will have been infected for five years and the damage can only get worse as they get older.

“The Pediatric Praziquantel Consortium was established to provide for the first time a formulation suitable for treating children below 6 years of age, and this will be a very important new tool. However, we know that we need to do more, and raising awareness has always been a Consortium priority. Not only is schistosomiasis itself a huge problem, but links with HIV have to be investigated too. Many other diseases are treated with the goal of reducing HIV rates, but schisto remains inexplicably excluded from the potential risk factors.

Jutta sees awareness and new guidelines working hand in hand: “Even in affected communities, this disease is often not recognized – for example, young boys with bloody urine can be seen as going through a normal part of adolescence. We need action from the grass roots and from the top down and the Consortium is working on this. Just recently we talked in Geneva with regulators from endemic countries and some had not heard of schistosomiasis being such a problem in their country. The Merck donation program is helping, a Global Schistosomiasis Alliance is in preparation and the London Declaration to Combat Neglected Tropical Diseases has put schistosomiasis on the list of their 10 priority diseases.”

Peter Hotez has been in contact with Eyrun and Jutta on the FGS challenge. Among many other roles, Peter is Dean of the US National School of Tropical Medicine and President of the Sabin Vaccine Institute. He sees progress towards taking FGS seriously as slow but gaining in momentum: “This issue is beginning to be more visible at last. This year saw the New York Times publishing a ‘deep dive’ article on Eyrun’s Otimati team’s work in South Africa. It explained the need for cheap drug treatments and/or a schistosomiasis vaccine of the kind we are developing ourselves at the Sabin Vaccine Institute.

“Because so few people know about FGS as a major public health threat to African girls and women, or the role of FGS as a major co-factor in Africa’s AIDS epidemic, it was clear that we needed a big awareness campaign about the condition – in order to raise the issue to the level of elected leaders in the United States and Europe. Congressman Chris Smith from New Jersey, a senior member on the House Committee on Foreign Affairs, has been doing some great work, and he invited me to give public testimony on FGS in Congress last year. This opened the door to engage in dialogue with leaders of the Global Fund to Fight AIDS, Tuberculosis, and Malaria (GFATM), and to explore the potential for adding mass treatments for schistosomiasis and other neglected tropical diseases to existing initiatives for HIV/AIDS. In the coming months I hope to see FGS having a prominent role on the agenda of the GFATM as well as that of the US President’s Emergency Plan for AIDS Relief (PEPFAR). Debate on the forthcoming End Neglected Tropical Disease Act gives us a further opportunity to raise awareness.

“We have a lot of interest across the globe in the circumstances of girls and women, and we need to make FGS visible alongside the major health and social challenges affecting girls and women living in extreme poverty, including safe pregnancies, female genital mutilation (FGM) violence against women, and other key gender equality issues.”

Together with the University of Kwazulu-Natal (Durban, South Africa), the Oslo University Hospital (Oslo, Norway) and the Liverpool School of Tropical Medicine (Liverpool, UK), Merck is toco- organizing an international scientific workshop on “Female Genital Schistosomiasis (FGS) and its Impact on HIV/AIDS” on January 28-29, 2015 in Johannesburg (South Africa). About 80 international experts in schistosomiasis, HIV and pediatrics, and governmental representatives will join the event.

The objectives of the workshop are to present the latest findings on genital schistosomiasis, develop a new research agenda on interactions between HIV and schistosomiasis, promote agendas on best diagnosis and future treatment as well as advocate for scaled-up interventions against Neglected Tropical Diseases.