Beyond 2020: A discussion on Neglected Tropical Diseases at the Bill and Melinda Gates Foundation, London

By Russell Stothard Liverpool School of Tropical Medicine

I was fortunate today to be invited to attend this discussion arranged by the strategic policy group within Bill and Melinda Gates Foundation. I was representing COUNTDOWN, along with my two colleagues Lorenzo Savioli and David Molyneux. This meeting followed on from the launch of the World Health Organisation’s 3rd Report on Neglected Tropical Diseases.

The WHO’s report is today’s foremost Neglected Tropical Disease (NTD) policy document. It reviews progress towards control and elimination of several diseases and calls for increased financial support and mobilisation of resources within the health system to secure progress towards control and elimination targets up to 2020.

Today’s meeting addressed a different agenda – tomorrow’s health policies. More specifically, those that take us towards 2030 and address the Sustainable Development Goals (SDGs). It is without doubt that this coming year is very important within the global health policy arena and we hope to see a fruitful marriage between the WHO’s report and the soon-to-be-released 17 SDGs. Dove-tailing these two projections and policies, however, is complex and brought to my mind the often quoted Yogi Berra who once said “The future ain’t what it used to be”.

The meeting’s objectives were introduced by Don Bundy, who has recently joined the Bill and Melinda Gates Foundation from the World Bank. These were then elaborated by Richard Horton, the editor of the Lancet, who went on to expertly chair the meeting and drew out many observations, questions and answers from the 40 or so delegates.

We were joined by video link to the WHO-AFRO offices in Democratic Republic of Congo and to the newly installed regional director Matshidiso Moeti. She confirmed her strong commitment to the control and elimination of NTDs within the Africa region and was supported in local discussions by Julie Jacobson from the Gates Foundation and by Ifeoma Anagbogu, Federal Ministry of Health, Nigeria. Both Julie and Ifeoma were visiting Brazzaville and it is by good fortune that I will meet with Ifeoma next week in Abuja. Once there we will discuss future activities of COUNTDOWN within her country, being able to quickly follow-up on many of the points being raised today.

How will the SDGs take NTDs into account?

I must admit I am not very familiar with the SDGs and their 169 associated targets but I am more aware of the Millennium Development Goals (MDGs), especially how ‘other diseases’ in MDG 6 made scant reference to NTDs. As introduced by Dominic Haslam of Sightsavers, it is clear that NTDs are now specifically mentioned in SDGs as part of promoting universal healthy lives and fostering general well-being.

As the SDGs are currently being formulated, as well as development of indicators to record and track progress, Christopher Fitzpatrick, WHO outlined the current NTD-specific indicator. This will attempt to encapsulate progress in control and elimination of NTDs by 2030 within a simple metric. Obviously this metric will be quite complicated in its calculation and will be discussed at length but it will help to unify efforts within the international health agenda to highlight activities against NTD across the world.

During discussions, it was felt that the NTD community should be proud to have achieved so much in the past decade. This ranged from forming equitable public-private-partnerships to the mobilisation of the pharmaceutical sector to donate millions of tablets of essential medicines to national NTD control programmes. Indeed, NTD programmes are cost-effective and are addressing very real health inequities in many impoverished regions of the world.

Addressing present and future hurdles

As might be expected, such large-scale deployment of medicines at the coal-face of control, which often operates outside the final level of primary health care infrastructure, has some unique challenges. Foremost, is the realisation that even with donated medicine there still needs to be considerable financial outlay and manpower to cover costs and delivery of medications to affected communities.

Moreover, developing methods to sustain this and promote the equitable administration of drugs to those in need with regard to age, gender and marginalisation is not trivial. Although these issues were not specifically addressed during the presentations, they were raised during discussions and how inter-sectoral dialogue between, health, education and water/sanitation was needed. The latter might consider using NTDs as ‘tracers’ of progress toward this end.

We should not lose sight of the efforts needed to achieve WHO 2020 targets. During the meeting it became increasingly clear that placing NTDs explicitly within the SDGs, with an associated specific indicator, is a tremendously important step. To conclude I therefore very warmly congratulate those philanthropic organisations and individual NTD advocates who have taken us to this point with a clearer vision towards 2030.

“The final mile is often the most difficult one”: Launch of the third WHO report on Neglected Tropical Diseases

By Kate Hawkins, Pamoja Communications The WHO report on Neglected Tropical Diseases (NTDs) was launched yesterday with a simultaneous live feed that linked Addis Ababa and London.  Here are four issues that dominated the conversation:

  1. Money, money, money

The report outlines a business case for the control of NTDs both on cost effectiveness and equity grounds. It was suggested that meeting NTD Road Map targets for 2015-2020 requires $750 million a year (not counting vector control). Maintaining progress from 2020-2030 requires an additional $460 million a year as programmes are scaled down.  There was agreement that endemic countries will need to do more to raise the revenue required to fund this push and Baroness Northover (UK Parliamentary Under Secretary of State, Department for International Development) suggested that parliamentarians have a key role to pay in lobbying Ministries of Finance to allocate more to health budgets.

  1. NTDs as a litmus test for universal health coverage?

At the meeting we were reminded that universal health coverage is also about equity and ‘ensuring that nobody is left behind.’ In the case of NTDs this includes the poor in middle income countries.  The report describes them as a litmus test for universal health coverage, and Margaret Chan is quoted: “We are moving ahead towards achieving universal health coverage with essential health interventions for neglected tropical diseases, the ultimate expression of fairness. This will be a powerful equalizer that abolishes distinctions between the rich and the poor, the privileged and the marginalized, the young and the old, ethnic groups, and women and men.” Strong words…although presumably this will be part of a larger social and political project of tackling the norms, institutions, and structures which create and maintain such divides.

  1. Equity

Andrew Jack of the Financial Times described NTDs as conditions that effect, rural, remote, neglected, and abandoned people. They effect poorer people and because they effect physical development, educational attainment and are often disabling they can also have an impact on people’s ability to generate a livelihood. The report states, “The inclusion of an equity focus in policy-making will become more and more important the closer countries get for achieving the targets for the Roadmap. Such a focus will help justify sustained efforts in the remaining number of NTD hot spots where unit costs begin to increase just as the scale of operations begin to decrease.”

We heard little about gender at the launch, although Baroness Northover mentioned that NTDs disproportionately affect or impact upon women and girls. If this is an area you are interested in you might like to check out this review of gender and NTDs that our colleague Margaret Gyapong co-authored way back in 2005 for some background.

  1. Integration

There was consensus that collaboration is necessary if we are to make impact on NTDs. To tackle NTDs will require the health sector to work with their colleagues in water and sanitation, the environment, vector control and the veterinary sciences. A task made more tricky by climate change, urganisation, and increasing migration in many settings. It was noted that governments, the private sector, researchers, multi-lateral and bilateral donors, and non-governmental organisations all have complimentary roles to play. People were hopeful: Nigel Crisp (Chair of Sight Savers among many other roles) described the area of NTDs as ‘global solidarity actually working.’ The perennial issue of vertical versus horizontal approaches to health programming and system support raised its, now very familiar, head. Some argued that NTD programmes were a shining example of integration at its best. Others that these diseases occur in settings where there is little existing infrastructure and that there is an argument for kick starting action through vertical programmes and moving to an integrated and comprehensive approach over time. Tim Evans (World Bank) pointed to the success of Ivermectin programmes in creating community systems and structures that provide a host of other services to the poor, and poorly served. I left the meeting with the feeling that there have been many positive developments in the world of NTDs. There is much to be hopeful about and maintaining a positive sense that change is possible is important. However, I also heard talk of growing inequality, Ebola, environmental fragility, civil unrest, and conflict – all of which make real world action on NTDs all the more challenging and complicated than it at first appears.

An introduction to Rossely Paulo

I’m a microbiologist from Angola and I’ve just started my PhD on understanding of the spatial and temporal micro-epidemiology on Neglected Tropical Diseases in the province of Bengo, Angola. The aim of my research is to be focused on vector prevalence based on the molecular, geographic information system mapping and spatial analysis where it will confirm the endemicity of filariasis and schistosomiasis and how their co-endemicity can affect the mass drug administration of albendazol and ivermectin respectively. This will develop my long term interest on parasitic conditions – very important diseases in my country.

I’m from the e-generation, I realise that writing scientific blogs is important, not only to enhance my research while doing my PhD, but also to share my personal experiences and increase the awareness of Neglected Tropical Diseases. So, on my first day of the PhD programme I was lucky to attend the lecture by Russell Stothard, my supervisor, to the Wilderness Medical Association, a student group in University of Liverpool, “Tips in field epidemiology: Just get out there and be well prepared”.

Expeditions in medicine give you a little bit of wilderness, especially when you go to the tropics, and this lecture aimed to inspire the audience how to practice proper medical research outside the hospital. It also emphasized that this is a strength of the type of study at Liverpool School of Tropical Medicine.

Learning more about schistosomiasis

To set the scene we heard an introduction to schistosomiasis, including its life cycle, its pathology, and a cultural analysis of the impact of the disease. Even after 150 years of research, there’s always something new to be learnt from archives. For example, in the seminal observations by Professor Robert Thomson Leiper in Egypt which he wrote while seconded to the Royal Army Medical Corps which bring together the best principles of wilderness and tropical medicine.

Today, 90% of the cases of schistosomiasis occur in Africa, and it is vital to put this disease on the global radar and to increase efforts to control it. The interesting bit about studying schistosomiasis is that you can actually become a gastroenterologist, a urologist, or even a neuroscientist (if you want to study its rarer neurological conditions)!

Schistosomiasis is a major health concern. In countries such as Tanzania, where urogenital schistosomiasis is highly endemic, some people in rural areas think that boys also have a type of menstruation. In reality their children urinate blood due to the presence of the parasite. Blood in the urine is a classic sign of urogenital schistosomiasis and is not always completely understood.

The three skills vital for those interested in conducting an expedition are: Patience, practice and perseverance

At the lecture we learnt that is important to be meticulously organized for an expedition, which means having a contingency plan, materials double-checked, carefully plotting a route, and having research documents ready. One week in the field usually takes about five or six weeks of prior organisation. All this can be found fully explained in the excellent field manual by Sheppard, the Vehicle-dependent Expedition Guide. It is also important to be very precise with communications, especially dealing in complex local languages.

Russell reported on his experiences in Lake Victoria during an expedition in 2010 with the aim of mapping schistosomiasis across the Sesse Islands. A video about the survey was shown, where freshwater snail and parasite collection methods could be seen and the techniques used to take GPS points and pH measurements. These surveys revealed a large burden of the disease which was previously unreported.

This lecture provided the taste of my future research and I’ll be joining the annual conference of the British Society of Parasitology in April on malaria, Neglected Tropical Diseases and vectors. Would you join me? If yes, please register and help place these issues on the global health agenda.

Schisto-so-what? The importance of careful language when talking across sectors

By Kate Hawkins, Pamoja Communications

I am a real newcomer to the world of Neglected Tropical Diseases (NTDs) and so it was a great privilege to attend the recent meeting on Female Genital Schistosomiasis and HIV. Research on, and control of ,schistosomiasis goes back to 1851 with its discovery by Theodor Bilharz. So like many people I left the meeting somewhat horrified that a list of the existing studies which look at HIV and schistosomiasis together could practically fit on the back of an envelope.

But I am also excited that such a disparate group of knowledgeable people had the chance to come together and try and make sense of what we already know and what a future research, policy and implementation agenda might look like. We need more of these types of conversations which cross geographical, health issue, and disciplinary areas if we are going to make progress.

Are we talking the same language?

I was amused when I came across this Tweet on the difficulty of communicating about NTDs.

Many researchers share James’s frustration about the seemingly impenetrable language employed in the sector.

I am immersed in a world of academics and not so easy to understand acronyms. When we are passionate about our own particular field of study it is easy to fall back on technical language and jargon. Overcoming this first barrier is a part of better communicating across the potential divide between the diverse stakeholders who need to work together on HIV and schistosomiasis.

With talk of haematospermia, eosinophils, cytokines, sandy patches, qPCR, anodic antigens, R-PZQ, plexus rectalis, uterus-vesicalis, schistosomula, IgG antibody concentration, NK-cells, interleukin-2, Neopterin, petechial, eosinophils and more, my Internet search engine was working overtime at this meeting as I tried to figure out what was going on! This is despite my helpful colleague Russell giving me a copy of Bambo has Bilharzia in advance of the meeting!

Technical language is fine at a meeting of health practitioners and researchers but it will take some effort to put some of the evidence we were talking about into formats that speak to others. The Female Genital Schistosomiasis Atlas, is one such tool for clinicians but we are going to need many more for all the other target audiences that we need to help understand this information.

Beyond the technical

When you talk across different areas of health it isn’t only the technicality of language that can be a barrier to understanding.

Much of my previous work has been on sexuality and HIV. At the HIV and schistosomiasis meeting I heard terms like ‘prostitute’ and ‘promiscuity’ being used, and that was a bit of a shock. There has been a great deal of work on how language can (re)enforce notions of stigma, blame and shame which are detrimental to the HIV response. When I hear words that I find insulting, my brain immediately stops processing information. So even if the point that was being made was intellectually brilliant it is lost to me.

Debates about language and HIV are not new, and as this UNAIDS article points out, “Words are not neutral against HIV”.

UNAIDS makes the following recommendations on the use of the words prostitute or prostitution, “These words should not be used. For adults, use terms such as sex work, sex worker, commercial sex, transactional sex, or the sale of sexual services.” The term ‘sex work’ was coined by Carol Leigh in 1978 and it is widely used in public health. This language guide from InterNews in Kenya points out that the word ‘promiscuous’ is both “judgmental and accusatory.”

When it comes to my ideas about language you may think that I am an uptight, politically correct Brit. You would be absolutely correct in that assumption. However, if the schistosomiasis and HIV worlds are going to interact in a fruitful and mutually supportive way then we need to establish a more correct cross-talk. A first step will be to understand and appreciate each other’s language. In the words of Maya Angelou,

“If you want what you’re saying heard, then take your time and say it so that the listener will actually hear it. You might save somebody’s life. Your own, first.”

Neglected Tropical Diseases: Influence, impact and engagement

By Julie Irving, Sally Theobald, and Kate Hawkins

It has been great to be at the ResUpMeetUp symposium in Nairobi. The different sessions provided excellent opportunities to share perspectives and experiences. There is clear leadership from AFIDEP on research uptake with excellent presentations by Eliya Zulu and Rose Oronje, energising sessions led by Jeff Knezovich and IDS providing interesting content and keeping the buzz alive on social media.

An eclectic and growing research uptake field

Kate Hawkins (Pamoja Communications and partner on COUNTDOWN) said, “I was involved in the first round of health systems Research Programme Consortia, and at that time there was little guidance and academics were often not very supportive. It’s great to see how the field has developed and the sharing between different approaches and sectors, and I look forward to keeping the dialogue and experience sharing alive as we move forward in COUNTDOWN.”

What have we learnt and how we will apply it?

Julie Irving, soon to start as Programme Officer (Research Uptake) for COUNTDOWN explained, “The meeting provided a strategic and timely opportunity to reflect on my skills and experience in research uptake and how to apply these as we move forward with the project. I did a multimedia degree and in this meeting I was able to see how the concepts I’d been working with can be creatively applied to research uptake.  A lot of people at the meeting were struggling with the notions of impact and how to measure it; we have lots of learning here from the processes we went through in developing the Liverpool School of Tropical Medicine impact case studies for the Research Excellence Framework. There are also lots of debates on the challenges and time scales for achieving influence that we need to be mindful of and I’m looking forward to thinking creatively about this, and what evidence and indicators we require as we develop our COUNTDOWN research uptake strategy.”

Research uptake: questions for the future?           

Nicholas Benequista raised the important point, what does research uptake look like in difficult, challenging or neglected environments? This is clearly relevant to us, Neglected Tropical Diseases are a very low policy priority in many settings and we will need to ensure we move carefully and sensitively in our work in Ebola-affected Liberia. Sally Theobald, (Social Scientist, COUNTDOWN) said “I enjoyed the discussions that related to the ethics, power and positionality in research uptake. We need to ensure we think critically and creatively here in COUNTDOWN. Currently there is limited literature or resources that share the lived experiences and priorities of communities affected by or living with Neglected Tropical Diseases or the close-to-community providers – community based drug distributors – who delivery Mass Drug Administration. In COUNTDOWN we will be using photo-voice and will seek other opportunities to ensure the experience of neglected communities shape priorities for policy and delivery.”

COUNTDOWN in WHO: Discussing new diagnostics for schistosomiasis control

Russell Stothard, Liverpool School of Tropical Medicine

Last week I was in very interesting discussions with a panel of around 40 international technical experts, brought together by WHO-Geneva to review and revise the application of new diagnostics for the control of schistosomiasis. The meeting was expertly chaired by my longstanding colleague and friend Narcis Kabatereine, and, from the outset it was clear that discussions would be complex.

We covered many diagnostic nuances that ranged from the biomarkers and mechanics of the tests themselves to how these tests might be deployed and used appropriately to guide treatment decisions in the large-scale use of praziquantel. Some of these issues were covered in our special issue of Parasitology which is useful background reading.

Complexities in diagnosis

To me, it was hardly a surprise that consensus was difficult to reach as we all often want different things. It is the subtle distinction between active infection versus chronic disease that causes so much confusion and blurring in schistosomiasis diagnosis. Without wishing to digress too much, it hangs on the distinction between schistosomiasis versus schistosomosis. The later terminology was adopted in veterinary helminthology as an attempt to resolve the tensions in disconnect between infection and disease, but it was never accepted by the medical community. Perhaps, this was a mistake as an imprecise terminology begets confusion and mixed objectives.

In short; infection (schistosomiasis) is caught by exposure to water infected by larval stages, these larval stages mature to adult male and female worms that pair and mate. The fertilised female sheds numerous eggs each day into the blood stream which are either voided in the urine/faeces or become trapped in internal organs. As the eggs secrete potent toxins, trapped eggs induce a very strong inflammatory reaction and with it the gradual accumulation of lesions, these then conglomerate into fibrotic masses that irreversibly disease the body (schistosomosis).

The worms themselves are relatively benign but their laid eggs, however, are not. Also the numbers of voided eggs in urine/stool versus those accumulating in tissues is not clear, especially when exit sites of the eggs become progressively blocked.

The relationship between the numbers of adult worms, excreted egg tallies in stool or urine, and the trapped eggs accumulating in tissues reacting with the immune system is complex and not straightforward. Typically in advanced disease, adult worms may not be present having died or excreted eggs fall below detection thresholds, however, the long-lasting lesions around trapped eggs remain causing mischief. All this can have the rather perverse consequence that rampant late-stage clinical signs of diseases, like in Female Genital Schistosomiasis, may be misinterpreted by those who place too much importance on diagnostic tests of active infection (i.e. eggs in stool).

This is like inspecting the damage of a crashed car by looking at its current speedometer reading, where you would be mistaken to think it never moved, but you can of course check its milometer. Unfortunately for schistosomiasis no such cross-check is possible and by analogy not all crashed cars have the same mileage, thus like schistosomiasis (or rather schistosomosis), advanced disease may have completely different presentations following from different durations and rates of the accumulation of trapped eggs.

In areas where there is high transmission and reinfection, treatments with praziquantel slows down the milometer and in so doing averts severe disease.

Point of care diagnosis?

The main thrust of the WHO-Geneva discussion was the acceptance of a point-of-care dipstick which detects schistosome circulating cathodic antigen (CCA). Several of us have shown it to be proven useful for detection of Schistosoma mansoni infection. The advantages of this test are that it is quick, low cost (about $1.5), easy to perform, rapid and with high diagnostic sensitivity. Above all it uses urine samples rather than faecal samples which is easier to collect.

Faecal samples are used for the Kato-Katz test which is the backbone diagnostic method for nearly all faecal helminths, and it was delightful to see Naftale Katz, one of the originators of the test, at the meeting. Naftale is still going strong after 50 years of research and control into intestinal schistosomiasis in Brazil.

Switching from Kato-Katz to the CCA test raises a whole raft of related questions: how can it be used in disease mapping and surveillance; can it be produced in sufficient supply to fulfil future demand; how will its use change the treatment algorithms for praziquantel etc.?

The long road to the WHO

Ten years ago I was the first to evaluate the test for its use in control programmes in East and West Africa. Even then I was convinced that it had an important future role to play in guiding control, especially when you had small teams working in remote areas where it was difficult to carry in equipment. I remember very vividly taking boats to distant islands in Lake Victoria and uncovering alarming levels of disease on those island communities simply because we were the very first to travel there with field-based diagnostic tools. Using the CCA in combination with Kato-Katz and ELISA testing in later work, we also mapped the disease on the Sesse Islands, proving it to be much more extensive there than previously thought.  However, it has taken several more papers, large-scale funding by Bill & Melinda Gates Foundation via SCORE and several years of advocacy to place the test in front of the eyes of WHO-Geneva for their reconsideration of current diagnostic guidelines.

It was a long journey indeed, and we should not be proud of taking such a prolonged time to put operational research into revised control actions. Had the CCA test been used several years ago in large-scale control programmes we would likely have seen increased use of praziquantel because the Kato-Katz test tends to underestimate the ‘true’ prevalence of schistosomiasis. I ask myself in this elapsed time period how many thousands of children and adults who could have been treated that weren’t? It disappoints me that international advocacy does not quantify these deficits. If we did it might prompt swifter decisions.

One of the major tasks ahead in COUNTDOWN is to turn best evidence into best practice as quickly as possible. This is our driving rationale if we are to be successful in the scale-up of praziquantel treatment and in acceleration towards NTD control targets…so watch this space.

Photo courtesy of the United States Mission Geneva

Schistosomiasis: We need to treat younger and better

By Amaya Bustinduy, St George’s University

Currently millions of praziquantel tablets are being delivered to school age children across sub-Saharan Africa for the treatment of schistosomiasis.  Although this is itself is a fantastic achievement thanks to the relentless efforts of a very dedicated community of researchers, policy makers at WHO and on-the ground personnel from in country national health programmes, there is still much we need to know about this drug. For one, praziquantel dosing is being delivered to children but using adult dosing since there were no studies conducted in children.  As it becomes more and more apparent that young children less than five years of age should also be included in control efforts, this becomes a potentially dangerous problem.

To tackle this issue, I joined Russell Stothard at Liverpool School of Tropical Medicine to lead the first praziquantel study in young African children.  This was carried out in Lake Albert, Uganda, an area known to be particularly a ‘hot spot’ for the transmission of schistosomiasis. The breathtaking beauty of a lake that is swarming with larval stages of the parasite contrast with the clinical manifestations that are found in most of the children living along the lake shore.  As the paediatrician on the ground, I documented extensive morbidity related to schistosomiasis that ranged from anaemia, growth retardation as well as liver fibrosis seen in very young children.

The work was intense, as we had to keep the children in our research facilities for over a day.  We asked the mothers to stay with them and sometimes some young babies as well, so our study site was a family camp where we performed the delicate work of measuring praziquantel in young children’s blood every few  hours for 24 hours.  The side effects of praziquantel are particularly unpleasant and this is worse if the child is heavily infected.  An important part of the team’s work was to keep children as comfortable as possible.  At the same time we were keeping our facilities organized and well kept which is a challenge when power is dependent on a noisy generator always thirsty for fuel. We had to take care of parallel housekeeping activities such as food, lodging and entertainment. Evening songs and dances kept the spirits high for both families and staff members.

And the efforts led to meaningful results.  Our analysis showed that children younger than five years of age may need almost double the WHO recommended dose of praziquantel.  As we integrate preschool children in mass drug administration programmes, getting the dose right is essential. In parallel, there is a paediatric praziquantel formulation in development that will help deliver the adequate dose without the risk of choking that the large current praziquantel tablet has.  Repeating doses at six weeks would also be something to consider to target more immature forms of the parasite that would get untreated after the first dose.  Also in hot spots, treatment more than once a year would allow us to target reinfection.

There is a perceived momentum in getting treatment for children of all ages on the international agenda. As we get the praziquantel dose right and the adequate formulation there can be no more excuses for excluding the very young from a treatment they deserve.

Ed: The image used above was taken by Amaya at the study site. Please credit her if you reuse it.

How can learning from Lymphatic Filariasis help guide advocacy for Female Genital Schistosomiasis?

By Margaret Gyapong (Ghana Health Service)

It was really useful for me to attend the recent meeting in South Africa on Female Genital Schistosomiasis. I have never worked on Schistosomiasis before. Most of my work has been on Lymphatic Filariasis and Neglected Tropical Disease but I moved about a decade or so into malaria, Demographic Surveillance, maternal health and other areas of research. In recent times however, I find that I am being drawn back into Neglected Tropical Diseases. Hence my attendance at this all important meeting on Female Genital Schistosomiasis, and I find the emerging discussions intriguing. Clearly there are many research questions that still need to be answered on the relationship between schistosomiasis, reproductive health and HIV. Work needs to be done to get this issue on the radar of decision makers and scientists. To support this there is a lot that we can learn from the journey we took in Ghana to put Lymphatic Filariasis on the national and international health agenda.

Early days

There is evidence that more than a decade ago scientists were drawing attention to Female Genital Schistosomiasis so why is it not on the agenda? 25 years ago there was no Lymphatic Filariasis programme in Ghana and a lot of effort had to go into convincing the decision makers in the health sector that the disease was a problem and needed attention.

Work on Lymphatic Filariasis  started kind of by mistake when in the early 1990’s some of us were posted to the north of the country to work on a Vitamin A supplementation trial. During field work we noticed a lot of people walking around with big legs and baggy pants (that were clearly disguising scrotal swelling, technically known as hydrocele).  Coming from the South of Ghana, this was unusual and we decided to explore the issue in more depth.

Gathering the evidence

A survey we conducted  in 1995 with lay field workers using local terms for the disease showed  that over 12% of households reported at least one person with a big leg (lymphoedema (tissue swelling) or elephantiasis (skin/tissue thickening) of limbs). We spoke to the powers that be in the Ministry of Health at the time but the response was very much, “The disease doesn’t kill and there are many more burning issues such as malaria that needed urgent attention.”

Luckily for us the World Health Organisation’s TDR, the Special Programme for Research and Training in Tropical Diseases, was putting out calls for proposals at that time and we linked up with other countries and scientists to gather further evidence.  From 1996-2001 we aggressively collected evidence on the epidemiology of the disease in the entire country and showed the highest prevalence in the north of the country, the number of working days lost due to disability from the acute phase of the disease, and varying cultural beliefs and practices about Lymphatic Filariasis. This enabled us present a much more complete picture to national policy makers.


But evidence alone wasn’t enough to provoke change, and we also engaged in activities which could more accurately be classed as advocacy. We realised that at the international level there were many people doing disease modelling who had probably never met a person with the condition. So we showed photos of people from the field – and to be honest many of them were pretty gory. But they got people’s attention. We also thought it was important for people affected by the condition to tell their story. Photovoice methodologies enabled community members to describe their lives before and after becoming disabled by Lymphatic Filariasis. We took one woman with us to a meeting in Geneva. This had a personal impact on scientists and policy makers. The photovoice stories on Lymphatic Filariasis moved some of the female policy makers almost to tears because they could relate to the way that women described their relationships with their bodies and the impact of Lymphatic Filariasis on their family and intimate relationships.

Why hasn’t their been more action on Female Genital Schistosomiasis

In 2005 my colleague and I did a review on gender and Neglected Tropical Diseases and I realised from the document (when I was preparing for the Female Genital Schistosomiasis conference) that as far back as 1992 issues related to Female Genital Schistomiasis  had been documented. Scientists had indicated that sequelae from Female Genital Schistosomiasis such as infertility have an important social and pathological impact.  They had also indicated that conditions may be undiagnosed because women would be more likely to present to a gynaecologist than an infectious disease specialist probably because Female Genital Schistosomiasis is not well recognised. Another interesting observation at the time was that Female Genital Schistosomiasis increases the risk of HIV infection because the lesion provides easier access to deeper vaginal cell layers during intercourse with an infected partner.

Why are we still talking about it today rather than acting?

Like Lymphatic Filariasis, schistosomiasis is a disease of poverty. It effects people living around rivers – people earning a living through their interaction with water, their children playing in water bodies and households rely on this water in their domestic lives. I think that if schistosomiasis was a disease like Ebola which anyone could get then perhaps something would have been done about it.

We also have to think about the social-cultural context. The people suffering are marginalised and find it hard to speak about issues related to their sexuality. Who can they talk to? How does a child have the words to describe what is wrong? We need to start listening to their stories. They will be graphic, but they are necessary.

Blood in the urine in certain cultures means you are a strong man and mature. Women may just think that they are bleeding between periods and that it is not important. When women bleed after sex because they have schistosomiasis (that is if they know it is schistosomiasis related)  can they talk about it with their partners? What about when it causes infertility? In many cases the woman will be the one who is blamed and she will go through unnecessary tests. Then when she remains undiagnosed and unable to conceive she may well suffer stigma and possibly be abandoned. There are major gaps in our understanding of the genital manifestations of schistosomiasis including a lack of data on the possible psychological effects of dyspareunia and post coital bleeding in women with genital lesions.

Rolling out and scaling up

It is time to act on what we know and skill up health workers so that they can diagnose Female Genital Schistosomiasis either in the clinical context or during Mass Drug Administration. We need to think carefully about how and when integration into other services occurs. Integration at community level can only occur with joined up thinking at the top. Our task now is to ensure that an approach is taken that takes account of the health system as a whole rather than bombarding communities with a host of new vertical interventions.

And in all of this we need to remember that we are dealing not just with blood or urine samples, but with people who have names and faces and their suffering is unnecessary.

Female Genital Schistosomiasis and its impact on HIV: Round up of Day Two

By Kate Hawkins

The second day of the South Africa meeting on Female Genital Schistosomiasis was as engaging as the first with a host of keynote speakers who were diverse in terms of their discipline, approach, and geographical and institutional locations. If you missed our notes on the first day you can find them here…

First up was Charles King, of the Center for Global Health and Diseases, Case Western Reserve University and the Schistosomiasis Consortium for Operational Research and Elimination (SCORE). He explained the methodology behind the disability-adjusted life year (DALY) system which calculates years of life lost and years lost to disability. DALYS are often used to prioritise health interventions and are important in terms of getting particular health conditions onto the global policy agenda and stimulating action. He told us,

“If you are at the bottom of the DALY league table you are out in terms of the priority given to your health issue.”

But is this the DALY the right measure in a world where multiple infections are the rule? There is evidence that schistosomiasis interacts with HIV and that helminths effect people with TB, and malaria. Helminths during pregnancy impair infant HIB vaccine response in the child. In older children (5-18 years) there is an impact of combined infections: children with Schistosoma haematobium infection, hook worm and malaria are more likely to have anaemia and growth retardation. They are shorter, less able to do active physical activity, experience more school absence, worse cognitive scores, and worse performance at school and none of these are presently factored into the DALY score.

Simply put, the DALY calculations are based on the assumption that people can only have one condition at a time. Furthermore if your condition goes undiagnosed (as it currently does in the case of Female Genital Schistosomiasis) you will not get it counted. Under the DALY system if there is comorbidity and someone dies the death is attributed to the ‘most important’ disease. But the decision about what disease is important is made by a small group of people in the US rather than by consensus among researchers and clinicians from low- and middle-income countries. So often this decision does not take into account the context of disease nor fallibilities of the health reporting system in sub-Africa where cause of death is often enigmatic. Furthermore, it also does not appropriately measure the often distressing effects of infertility in terms of mental ill health and family breakdown.

Amadou Garba, World Health Organisation, gave us an overview of the current state of play in terms of Neglected Tropical Diseases. Looking at the data reported in the WHO preventive chemotherapy databank, he explained that there was 12.7% global coverage for schistosomiasis treatments with praziquantel  in 2013.  In Africa, this is just 14.2%, a mere fraction of what should be expected. He argued that more countries need to introduce preventive chemotherapy and expand coverage at country level to all districts that require it. Merck donations of praziquantel have increased from 26.9 million in 2012 to 104 million in 2015. The biggest part of this donation goes to the Africa region which is the most endemic area in the world. So whilst insufficient medicines used to be the barrier to scale up this is no longer the case. This then, however, raises the question of how the low-level distribution of donated drugs will be sustained so they do not become stalled within the health system, something which COUNTDOWN will hope to address.

Multiple sessions in the meeting touched upon the need to begin schistosomiasis treatment programmes before children begin school. Amaya Bustinduy, of St George’s University, provided more evidence on the need to increase access to praziquantel at an earlier age, starting from six months of age. She explained how pediatric doses of praziquantel are currently extrapolated from adult data which, as typical of other medicines, is a flawed assumption. To formally test this her  work in Uganda clearly showed that  a 60 mg/kg dose gave a better egg reduction and cure rates against Schistosoma mansoni. Egg counts were supplemented by antigen testing (urine) which  also favoured higher dosing as well. Amaya posed the question, are we giving the right dose for the right outcome? Typical of pharmacokinetic/dynamics studies which are very technically demanding, she extrapolated her findings  using a simulated data set of 5000 children. This modelling showed that they only approach a target of 90% parasitological cure in 3 year old girls when they have a dose of 80 mg/kg. In school age children it is only when they get to 80mg/kg that we get acceptable cure rates. There are gendered differences, in that boys needed higher doses than girls. This is ground-breaking research showing how mis-leading the direct extrapolation of dosing from adults to children was. As a take home message, if you treat schistosomiasis before school age you can prevent up to 6 years of ill health in children which drew importance to the need of a suitable pediatric formulation of the drug and rapid deployment.

As Herman Feldmeier was unable to attend his lecture was presented by Peter Leutcher, on potential therapies for Female Genital Schistosomiasis and future clinical studies. He outlined how previous studies have shown that schistosomiasis haematobium is already present in girls, persists in women of reproductive age and may affect genital, urinary and intestinal tract simultaneously or subsequently. Taken together this means Female Genital Schistosomiasis is a multi-organ disease. So far the only drug used for the treatment of Female Genital Schistosomiasis is praziquantel. However, praziquantel’s efficacy depends on the response of the individual to treatment, the developmental stage of schistosome worms (praziquantel has limited efficacy on immature adult worms), where the worms are in your body (larval stages in the lungs often have insufficient drug exposure), and other medicines you might be taking. In review, it is safe to assume that a single dose of praziqunatel (40mg/kg) cures less than 50% of patients with schistosomiasis highlighting that multiple praziquantel treatments with higher dosing need to be investigated.

The clinical pathology of Female Genital Schistosomiasis reflects local inflammatory responses in the vulva, vagina or cervix; inflammation-related abnormalities account for ≥ 80% of all abnormalities; inflammation occurs in all layers of epithelium including blood vessels; inflammation is the result of a complex immune response; inflammation is associated with presence of viable eggs and worms. In a study in selected patients with Female Genital Schistosomiasis Richter et al. observed that after a single treatment with praziquantel some types of lesions resolved and others remained unchanged demonstrating a complex patho-physiology.

Many different kinds of outcome measures were used to assess the efficacy of praziquantel. This ranged from infertility to complaints and signs such as sandy patches or contact bleeding. Outcomes were assessed at very different intervals from 2 weeks to 12 months. In one study there was no reduction at all and in other studies it was up to 73%.

So we can conclude that none of the previous treatment studies was appropriately designed; there was not a single randomized controlled trial. The true efficacy of praziquantel in treating Female Genital Schistosomiasis has never been formally assessed as there has been no control of reinfection, which is of course difficult to rule out in out-patient settings. Different outcome measures were used and, therefore, no conclusion about the efficacy of praziquantel is possible.

To address this deficiency, Peter  outlined how an expert group has conceived a randomized controlled trial with three treatment arms. In group A patients will receive the standard treatment, that means a single dose of praziquantel. In group B patients receive three doses of praziquantel. Dose one is given immediately after diagnosis. Dose two is given one day later and dose three is given two days later. In group C patients receive an identical treatment as those in group B. In addition, they receive another dose of praziquantel after five weeks and a final dose after 10 weeks. These additional doses are foreseen to kill schistosomula which have developed in the meantime to adult worms and to prevent reinfection to establish. Patients are followed up 5, 10 and 16 weeks after initial treatment. He suggested that this study would arm us with the type of information that we need to respond adequately to Female Genital Schistosomiasis.

But how can we can take action on the diagnosis of Female Genital Schistosomiasis now rather than later? Part of this solution  requires  tools so that health workers recognise Female Genital Schistosomiasis when they see it. Sibone Mocumbi, Head of Gynecology, Hospital Central de Maputo, presented on the deployment of one exciting new tool, the Female Genital Schistosomiasis Pocket Atlas.

Sibone explained that lesions in Female Genital Schistosomiasis may mimic any neoplastic infection in the female genital tract. Health care workers know very little about it and so they don’t take the opportunities that they have to treat it. Women are often misclassified as having Sexually Transmitted Infections (STIs) and lab diagnosis is not sufficient.

The Pocket Atlas is a tool for low-resource settings to enable health care professionals to identify Female Genital Schistosomiasis and avoid unnecessary radical surgery and misdiagnosis of STIs. It contains pictures and outlines the methods for examining patients and the symptoms to expect.  It will be disseminated for free especially in the rural areas where schistosomiasis is endemic. It was put together in concert with gynaecologists, doctors, nurses, and clinicians. It will be available in English, French and Portuguese. They will also be creating a poster, online versions of the Atlas, a PowerPoint presentation, video, and a website. Watch this space!

To further clarify the action of praziquantel the final presentation of the day, by Collen Masimirembwa (African Institute of Biomedical Science and Technology, Zimbabwe) addressed our lack of knowledge about the pharmacological effects of this drug. Pharmacokinetics is the absorption, distribution, metabolism and excretion of drug as it metabolises in the body. If you understand this it helps you understand how often to give the drug and how much you should give. At the moment our practice is driven by observation. But we don’t know how much of the drug should be in the blood and that is important. With drugs like praziquantel you can lose a lot of the active ingredients in the gut and that which is absorbed is quickly metabolised by the liver by a complex set of cytochrome P450 oxidases. Understanding this will allow us to better understand the differences between individuals when it comes to efficacy. Currently we know very little about the distribution across the body so we don’t know if it is exactly restricted to the blood or if it goes into other tissues and lasts there much longer.  If we are eager to push forward with paediatric formulations we need better data on this following along the lines of the seminal data presented earlier by Amaya. It would also assist us with understanding drug interactions – such as with those of other NTDs or HIV. Collen cautioned that there may be serious interactions with TB drugs. During questions, Russ Stothard raised pointed out that the unusual position of the adult schistosome population in the body, largely residing in the hepatic portal vein, which means the schistosome has a very different surrounding drug environment to that which we can measure within the peripheral blood stream.

After the final break-out session the workshop reconvened in a plenary session led by Eryun Kjetland which was a brainstorming and question and answer session with the audience about where to go next and how to do it. It was remarked at how supportive, refreshing and collegiate this symposium was and so the meeting finished on a real high. Many people pledged to take forward action at home based on what they had heard either in informing their local Ministries of Health, revising their teaching content or providing access to samples for further testing. The conference organisers will be arranging some official communications on lessons learned and next steps via the conference website and a working group on Female Genital Schistosomiasis/HIV will be formed to ensure the network is sustained. COUNTDOWN will be sure to advertise them here and on other social media. If you have any questions about the meeting feel free to leave a comment below and we will get back to you. Thank you for reading.

Photo courtesy of Trygve Utstumo under a Creative Commons License. You can view more images here…