COUNTDOWN on diagnostics for soil-transmitted helminthiasis and schistosomiasis in Ghana

By Russell Stothard

Shortly before Christmas, I had the pleasure of visiting Accra and Dodowa to discuss with the COUNTDOWN teams our research on DNA diagnostics. Previously, the surveillance of soil-transmitted helminthiasis (STH) and schistosomiasis has relied upon traditional parasitological methods. This involves rather old-fashioned techniques to visualise worm eggs in stool or urine samples by light microscopy. Although pragmatic in field-based surveys, these parasitological methods are insensitive and do not precisely capture the true levels of infections.

Improving diagnostics by introduction of modern molecular methods is important for two reasons. First and at a population level, infected cases are better detected leading to more accurate reporting and subsequently better allocation of treatment. Second and at an individual level, the more cryptic associations between infection and disease are unveiled. For example, for the latter in better describing the relationship between growth stunting and STH in children or the gynaecological impact of female genital schistosomiasis in adolescent girls.

A major research theme in COUNTDOWN is to develop and strengthen the molecular diagnostic capacity within the laboratory of Dr Mike Osei-Atweneboana. Mike will also explore future synergies with the Ghanaian polio programme based in the Ngouchi Institute, Accra which regularly collects thousands of stool samples from children. Regular access to these samples and heightened scrutiny with molecular diagnostics could provide a wider platform to assess STH throughout the country.

Last September, Dr Emily Adams visited Mike’s laboratory to make a preliminary situation assessment of his equipment needs. I was there in December to assist him with further planning for a forthcoming training workshop in DNA diagnostics. This is to be held the week of 14th March in Accra and in liaison with colleagues from the Ngouchi Institute. I visited a primary school in New Abarim where ongoing deworming had just taken place. We also made a spot-check visit on the local health centre in Adausena. It is clear that future application of DNA diagnostics in these settings will shed new light on the true burden of disease.

Ahead of the workshop in March, Emily and I will be taking steps with Lucas Cunningham to develop a training manual and also assemble the necessary DNA reagents for transfer to Ghana. To make a success of the training course, I am delighted to report that Dr Jaco Verweij, the world’s expert on DNA diagnostics, will be visiting the LSTM in February to provide use with best technical advice and later also join us in Ghana to develop best clinical international standards.

 

From PK-PD to COUNTDOWN: Multidisciplinary studies on schistosomiasis in Africa

On Friday the 20 November Russell Stothard will be presenting at the London School of Hygiene and Tropical Medicine in one of the regular seminars of the Department of Immunology and Infection.

Russell will discuss contemporary research on schistosomiasis and draw attention to the pioneering early role of the London School’s first helminthologist, Robert Leiper, who uncovered the lifecycle of the African schistosome 100 years ago. Russell’s recent work in Uganda has drawn attention to a significant burden of disease in pre-school children, and he will present the case as to why expanded access to praziquantel treatment is needed now. Ongoing pharmacokinetic and pharmacodynamic (PK-PD) suggests that higher doses of praziquantel may be required.  Russ will close showing how implementation research, as framed within the DFID-funded COUNTDOWN consortium, is playing an important role in accelerating towards WHO 2020 NTD targets.

COUNTDOWN at WHO: The treatment gap in young children with schistosomiasis

By Russell Stothard

I was pleased to attend an informal WHO meeting (from the 29-30th September) where we reviewed and discussed the treatment needs of pre-school-aged children with schistosomiasis. Having chaired a similar meeting five years ago, it is now very clear that young children can catch schistosomiasis, even within the first few months of life, and can then go on to develop chronic disease even before reaching school-age. This highlights an important gap in current control strategies as children typically have their first access to praziquantel (PZQ), our only available drug treatment, once enrolled into primary school. School-based treatment campaigns operate under the auspices of national control programmes where school teachers administer PZQ treatment en masse each year. Access to PZQ aims to arrest later disease development but sadly for some children, there is already significant, perhaps irreversible damage, upon entry into school so their first treatment is already too late.

This raises two important questions with this donated medicine; why is PZQ not currently available to young children today and what can be done in future to redress this medical inequity or treatment gap? During the two-day meeting several studies were presented, including those undertaken by myself and colleagues in Uganda where intestinal schistosomiasis was shown to cause significant childhood anaemia and liver fibrosis. Later discussions framed and explored answers to these questions. The ‘why’ was relatively easy to explain; health surveillance systems have been woefully weak and failed to notice and report the occurrence of infection and disease in young children. Only after conducting targeted parasitological and epidemiological surveys, for which there are now several publications within the peer-review literature, has sufficient evidence now accrued to confidently ring that alarm bell.

This has firmly focused attention on this vulnerable paediatric group and the need to revise health policies but revealed disconnects and lack of effective dialogue between various influential stakeholders. For example, pregnant women can have schistosomiasis, and should be treated, yet even within high endemic areas PZQ is not embedded within routine antenatal care. Once the child is born, PZQ is not on the essential drug list within frontline primary child care whilst other drugs, such as mebendazole (used for treatment of soil-transmitted helminthiasis), are. This deficit is further compounded by major health players, e.g. UNICEF, continuing to overlook this disease or are simply unable to revise their stance.

About the ‘what’; well, I am glad to report that pharmaceutical sector has responded with the creation of the paediatric praziquantel initiative. Presently PZQ comes in large, unpalatable tablets for younger children. Hence a first step has been to develop an orally dispersible tablet (ODT) formulation with taste masking which will make administration easier. However, this formulation needs some clarification of its original drug licensing as children under four years old were not included in its formal clinical indication. Hence some new clinical trial data are required for this ODT, as well as, information concerning the stability of the ODT in tropical conditions e.g. sufficient resilience to high temperatures and humidity. The good news is that the project is set to deliver on its goals and is currently held on target to produce an ODT by late 2019 with an associated access plan.

But what about the children already infected – is it ethical to wait a further 4-5 years before expanded access to a paediatric formulation can begin? I don’t think so.  Therefore I was happy to see that an outcome from this meeting was to encourage the use of crushed and broken PZQ tablets. To do so is certainly within the remit of national control programmes but some further convincing may be needed for action in other health sectors, i.e. within maternal and child health clinics. To that end I firmly expect that our future studies on schistosomiasis in COUNTDOWN will pave a better way for access to PZQ in both young children and their mothers.

To ensure that a wider selection of international donors and agencies are fully aware of these issues and our intentions, we are hosting a break-out session within the COR-NTD this October where our future research uptake strategy will be honed.

Co-Infections: Impact on Neglected Tropical Diseases

By Kate Hawkins

Next week the 9th European Congress on Tropical Medicine and International Health will meet in Basel, Switzerland. We are delighted that our team member Margaret Gyapong will be there representing COUNTDOWN.

Margaret will speak in a satellite session on co-infections and their impact on Neglected Tropical Diseases. Panellists in this session will talk about female genital schistosomiasis and health systems, the association of the schistosome infection with inflammatory response profiles and the challenges of co-infections, in particular Visceral Leishmaniasis (VL) and HIV.

If you are going to the conference do pop along and give Margaret your support. The satellite is on Monday 7 September from 12:15 to 13:15 in the Sydney Meeting Room.

We look forward to reading your tweets!

A research update on schistosomiasis for COUNTDOWN

By Russell Stothard

It is important to ensure that COUNTDOWN’s implementation research is best guided by the latest information from other research groups and Neglected Tropical Disease (NTD) programmes.  Being invited to present my work, I found the 14th International Symposium on Schistosomiasis an exciting place to learn about research outputs from groups such as SCORE, the Brazilian National Control Programme and from individuals presenting their own state-of-the-art research. Much of this was captured by video interviews and posted on Facebook, a very valuable learning resource.

Amongst others, Phil LoVerde’s work on redeveloping oxaminquine to have activity against all schistosome species was the best example of how meticulous molecular studies breathe new life into older drugs. Having an alternative treatment that can synergise with praziquantel (PZQ), our only antischistosomal drug, is important to safeguard future options in chemotherapy.  That said and in terms of public health, several of us highlighted why better access and scale-up of PZQ treatment was needed now, especially if WHO 2020 targets are to be realised.

As part of a round table discussion addressing the needs of treatment of infants and preschool children, I presented our recent work in Uganda alongside colleagues from the paediatric praziquantel consortium  who are developing an orally dispersible tablet.  The need for better PZQ access now is very clear and next month WHO-Geneva will convene a two day meeting to review and revise their treatment guidelines as the magnitude of this problem in young children is exposed. This has important repercussions for progress towards the WHO 2020 targets.

The Question and Answer Panel on paediatric schistosomiasis

It is now widely accepted that young children develop overt disease in later childhood and also contribute to disease transmission. For these two reasons alone there is now sufficient international interest and momentum to provide treatment to them which our COUNTDOWN work will move towards changing national control policies in each of our supported countries.

Whilst we already know that schistosomiasis control goes beyond more traditional aspects of the health system, forging dialogue between the Ministries responsible for agriculture, water and sanitation and education is needed. The round table session sponsored by SCORE in the attempt to eliminate urogenital schistosomiasis from Zanzibar provided the latest information about these island-wide trials on Unguja and Pemba.

The challenges of bringing such high-level stakeholders together in a co-ordinated was discussed by David Rollinson. He also showed that provision of biannual PZQ treatment could depress infection prevalence but only so far, and not evenly across the studied communities (i.e. shehias). Furthermore, health education and sanitation initiatives did not yield the expected declines in transmission with infection prevalence even increasing in some shehias despite intensified control. These results show we are still a long way from breaking transmission on the island, and better strategies for elimination of hotspots are needed. The importance of snail control and the difficulties associated with it were discussed at length. Simply put, if we cannot prevent and contain infections in snails we will never eliminate schistosomiasis in people.

About access to PZQ treatment, other studies from SCORE in East and West Africa showed that ‘treatment holidays’ were not a good idea and should be abandoned. A ‘treatment holiday’ is defined as the intervening period between biennial rather than annual tablet administration. The original rationale was that in communities where prevalence was between 10-50% it was thought that biennial treatment alone was sufficient and cost-effective to bring the disease under control when PZQ was under much shorter supply. This is clearly not the case and PZQ treatment regimes, as per Zanzibar, are now favouring biannual as the only way forward as more PZQ is available globally. Future COUNTDOWN workplans will investigate more formally biannual treatment regimes in terms of its operational feasibility and health impact significance.

Lester Chitsulo receiving his award from Rosa SoaresDuring the conference, a major honour was bestowed on Lester Chitsulo in thanks of his long standing work on schistosomiasis control based from the WHO-Geneva office. For just over 15 years, Lester was the NTD (schistosomiasis) desk-officer and had recently retired, being succeeded by Amadou Garba. Other distinguished retired researchers included Zilton Andrade and Ronaldo Amaral.

One of the important aspects within this meeting was witnessing the close association of the National Control Programme of Brazil with the many researcher and research arms of academia. In Africa, it was noted that this research capacity was much lower and needed a significant boost.

Owing to recent financial fragility within Brazilian economy and associated health budget cuts, this meeting was nearly cancelled. I therefore very warmly congratulate Mitermayer Reis and the symposium organisers for their continued perseverance, welcoming this opportunity for up-to-date discussions which help frame our future COUNTDOWN research with best available information.

 

Work on Neglected Tropical Diseases in Brazil provides lessons for the Africa region

By Russell Stothard Brazil has a significant burden of Neglected Tropical Diseases (NTDs) but these often differ to those in sub-Saharan Africa. For example in Brazil, there are no tsetse flies and thus there can be no transmission of human sleeping sickness. However, other blood sucking insects abound and in rural areas, triatomine bugs act as the principal vectors of Chagas disease, a major blight throughout South America and is the leading cause of heart failure. Infection with this single-celled parasite is typically chronic and drug treatment is largely ineffective when the disease progresses towards its later stages, where nearly all muscle tissues can be parasitized. Several years ago when working at the London School of Hygiene of Tropical Medicine with Professor Michael Miles, we showed that the parasite Trypanosoma cruzi underwent sexual reproduction in such tissues highlighting its capacity for  rapid evolution within the body. Of the early leading names in tropical medicine, two researchers Oswaldo Cruz and Evandro Chagas, are not as well-known in Europe as they should be, both being eclipsed perhaps by Patrick Manson and Ronald Ross. Nonetheless, Cruz and Chagas have left a truly impressive legacy in Brazil with the FIOCRUZ which is celebrating its 115 anniversary. Today FIOCRUZ employs over 11,000 staff and maintains a highly-regarded hospital and conducts an impressive portfolio of applied health research from the production of vaccines, drugs, reagents and diagnostic kits to education and training and engagement with its many social programmes focused on disease control. Within the UK we have much to learn from the approach taken by the foundation on how integrated control can proceed across a range of areas of health.

Carlos Chagas and team

Charlos Chagas with his team (Fernando’s grandfather is in the middle row on the right-hand side)

Being a speaker at ARTHROMINT 2015 meant I had the good fortune to visit the FIOCRUZ castle and see first-hand the library where Cruz and Chagas once worked. The history really does seep from its walls as I learnt from my hosting colleague Dr Fernando Monteiro, who works on the molecular systematics of Triatomines, that his grandfather was part of Chagas’s team and that his family has maintained a long connection with the institute. Having also worked on triatomine bugs before, it was a pleasure to give my research seminar at the institute and highlight more recent work on schistosomiasis and the implementation research that COUNTDOWN will conduct on several other NTDs, that often parallels similar challenges in Chagas disease control.

Speaking about schistosomiasis in Brazil is highly appropriate, for intestinal schistosomiasis is a major health hazard in rural populations where water hygiene and sanitation is poor. There is also a longstanding national control programme also focused on curative treatment with praziquantel (PZQ), however, there are key differences in approach when compared to those in Africa. Foremost, PZQ treatment is given out on a selective basis rather than in community-wide programmes. Hence, for a child to receive treatment (s)he must be shown to have evidence of infection upon the occurrence of schistosome eggs, the frontline diagnostic being the Kato-Katz stool examination in a ‘test and treat’ strategy.

Whilst this classic parasitolological method is also used in Africa, the necessary man-power and resources within the health system to provide this service to each child annually is outside the reach and resources of many Ministries of Health. Hence only community-wide application is possible or recourse is needed to more field-friendly diagnostic methods such as rapid urine antigen tests. Discussions with Octavio Pieri, the Brazilian national control programme co-ordinator, demonstrated a range of experiences in the Brazilian programme which it is important to share across the Africa region. Themes emerged such as the need for better PZQ dosing, treatment of marginalised groups (e.g. pregnant women and preschool children) and cross-talk with health education and water sanitation sectors. ARTHROMINT 2015 was a great success and I now look forward to discussing further in August how schistosomiasis control programmes can be optimised, especially in promoting access to PZQ in young children, across the transition from control to elimination settings.

New article in Open Democracy #NTDs #schisto

By Kate Hawkins

It can cause bleeding and discharge from the vagina, genital lesions, nodules in the vulva, discomfort and pain during sex, sub-fertility, miscarriage and can effect vulnerability to HIV and the Human Papilloma Virus. Yet it is completely off the radar of most people working on sexual and reproductive health and Neglected Tropical Diseases.

If you haven’t read our latest article on urogenital schistosomiasis in Open Democracy it is worth a look.

The World Health Organization’s working definition of sexual health is:

“…a state of physical, emotional, mental and social well-being in relation to sexuality; it is not merely the absence of disease, dysfunction or infirmity. Sexual health requires a positive and respectful approach to sexuality and sexual relationships, as well as the possibility of having pleasurable and safe sexual experiences, free of coercion, discrimination and violence. For sexual health to be attained and maintained, the sexual rights of all persons must be respected, protected and fulfilled.”

We think that between 100 and 120 million people are living with urogenital schistosomiasis which is most likely causing damage to their urinary and reproductive systems. Why isn’t it on the radar of policy makers, activists and researchers? Why hasn’t more been done to explore the causes and the consequences of this illness?

Is it to do with a squeamishness when it comes to talking about sex and sexuality?

These are some questions that urgently need to be answered if we are serious about sexual health and rights for all.

Intestinal schistosomiasis in Uganda: Taking advanced diagnostics to the lakeshore

By Hajri Al-Shehri

Neglected Tropical Diseases (NTDs) are often a symptom of poverty and challenging living conditions. Those who are most affected are the poorest people living in remote rural areas, urban slums or in conflict zones. Schistosomiasis, for example, is often found in populations with very limited access to safe water and in environments poorly served by primary health outposts as typified by out-of-stock drugs and inadequate diagnostic testing. The lack of reliable statistics reporting on treatment and disease has kept the true burden of schistosomiasis in the shadows and failed to identify the inefficiencies of control programmes that are committed to reach those most in need of treatment.

I have just returned from a three-week epidemiological study on the shores of Lake Albert, Uganda. Working with Vector Control Division (VCD), Ministry of Health, Uganda we visited five rural primary schools in Hoima and Buliisa Districts, examining just over 50 children per school with a combination of diagnostic methods.

Performance of diagnostic tools in a high prevalence settings

urine antogen testsOur basic analysis revealed that in three schools on the immediate lakeshore, prevalence of active intestinal schistosomiasis was just over 85%. With such high levels detected, it is taken for granted that these children are in regular contact with contaminated water, remaining a daily way of life and mitigates the impact of the national control programme (NCP). The Uganda NCP started in 2003 and has been providing annual treatment of school children with praziquantel (PZQ) for over several years. But despite best intentions, it is clear that annual treatment is failing on the lakeshore and needs to be strengthened. Our clinical assessments showed substantial amounts of morbidity in these unfortunate children with swollen livers, numerous schistosome eggs and blood in stool as well as enlarged tummies.

My thoughts on successful fieldwork

Fieldwork is not just an important, stimulating and often challenging part of the research process I undertake; it also offers a wonderful way of seeing the world, and a chance for personal development. The key points are to understand theory, develop skills, integrate and build tacit knowledge, develop alternative solutions for the problems in certain places, and work cooperatively with a team. Despite our best efforts in preparations, fieldwork constantly offers surprises and ad hoc solutions that may fail miserably for many reasons: a sudden rainstorm reduces time at the study site, your way back to camp is blocked by a flood and you endure water-logged muddy roads that drain your energy, as does our intermittent camp electrical supply as our portable generator fails then you are hounded by irritating lake flies that dance around your head torch while you concentrate at the microscope. Conditions in the field are often unpredictable and can affect your aims in different ways sometimes being left frustrated but when you overcome these obstacles you have good reason to be proud and satisfied.

car in UgandaSo what are the ingredients for successful fieldwork? I now realise that fieldwork should have clear vision of what you want to accomplish but be flexible within a set of integrated goals and contingency plans that can be brought rapidly into action when needed. For example, assessing each day everyone’s workload, checking in-field logistics and sampling techniques is essential to adapt to local conditions, as well as having enough in reserve to put in extra effort when required. Before leaving to Uganda, my supervisor and I had many discussions during the planning process who explained the theory but I have now the practice. The key ingredient is that there is a small window of opportunity to get the survey right where all the necessary equipment, reagents and team’s skills are brought together at the right place and at the right time, ensuring that these remote communities can be well-attended. Only by doing so can the true burden of NTDs be brought out of the shadows and highlight today’s treatment needs. I am proud to have made an important contribution to the Uganda NCP with our colleagues from VCD.  

About the author

I was born in Asser, Saudi Arabia, and have worked there for several years as a specialist in molecular diagnosis of infectious diseases in Asser Central Hospital. Being based in this busy clinical laboratory, I have developed interests in Neglected Tropical Diseases, especially schistosomiasis, and completed an MSc degree in the UK in Biomolecular and Biomedical Sciences, Faculty of Life Sciences & Medicine, at Glasgow Caledonian University. To further extend my qualifications and broaden my experience, I started my PhD in June 2014 at the Liverpool School of Tropical Medicine with Professor Russell Stothard and decided to focus on the epidemiology and control of intestinal parasites. My project hopes to compare the performance of state-of-the-art diagnostic tools in high prevalence versus low prevalence settings and understand how these tools can be applied in my own country where schistosomiasis and soil-transmitted helminthiasis are nearing elimination. Writing a science blog helps me stay motivated and by sharing my recent fieldwork in Uganda, and highlights what I have learned.

 

Hot topics in schistosomiasis

COUNTDOWN has been busy this week at the mini-symposium on ‘hot topics’ in schistosomiasis at Leiden University Medical Center in the Netherlands. Russell Stothard represented the Consortium and says:

“I am delighted to present at Leiden amongst friends and colleagues who have contributed so much to the advancement of tropical parasitology. I will present our recent experiences in Uganda and Namibia where we have used the CCA test and also uncovered that there are still barriers to its effective deployment within the health system. This is something which we will hope to address more specifically in COUNTDOWN to ensure that preventive chemotherapy approaches against schistosomiasis have the future impact we expect of them.”

Read more…

The history of innovation in Neglected Tropical Diseases: Some useful points from Jürg Utzinger

By Rossely Paulo

Jürg Utzinger (Swiss Tropical and Public Health Institute) was one of the key note speakers at the recent meeting of the British Society for Parasitology. He gave a great overview of some of the history of Neglected Tropical Diseases (NTDs) and areas where innovation is needed.

NTDs: Where did the term come from?

Three of the eight Millennium Development Goals are health-related. Although NTDs were not specifically mentioned, Goal 6 is focussed on combating HIV, malaria, TB and other diseases. Jürg explained that the conceptual framework of the Neglected Tropical Diseases was formulated in the years following the 2000 launch of the Millenium Declaration. NTDs, as a concept, went on to be popularised in seminal papers written by David Molyneux, Peter Hotez, Alan Fenwick and David Rollinson. Many at this time were arguing that it is important to look across the spectrum of the diseases that particularly affect poorer people in low-income settings rather than singling out a few priority illnesses. An initial list of NTDs was drawn up that clustered together 15 complaints.

Innovation in work on NTDs

Jürg explained that large–scale, longitudinal, community-based surveys have provided a great opportunity to drive innovation in NTDs by allowing us to assess population risk and guiding interventions for control and elimination.

But challenges remain

For example the current anthelminthic drug – albendazol and mebendazole – have a low kill rate against Trichuris which lead us to the conclusion that there is an urgent need to develop new drugs. One alternative could be multiple dosing of existing drugs which decreases the Trichuris parasitemia rate, the hardest parasite to cure. Diagnosis of various NTDs such as S. mansoni are still largely dependent on stool examination based on the Kato-Katz thick smears technique. But this has become a big concern due to its low sensitivity particularly in low-endemicity areas. Therefore, more sophisticated diagnostic techniques are required such as the Point-of-Care urine assay for the detection of Circulating Cathodic Antigen (POC-CCA) and the multivalent faecal egg count (FLOTAC) methods which are three times more sensitive than Kato-Katz. There is a need for more integrated control programming which brings together different sectors. Jürg pointed to efforts in China and Zanzibar where work on schistosomasis control and elimination is based on working with stool samples, agricultural factors, Mass Drug Administration, snail control and vector behaviour as examples of interesting practice.

The future

NTDs are finally on the radar screen of policy makers but how do we sustain these positive developments. We have some tools for control and elimination but they are insufficient! We need constant innovation and validation of the tools and strategies. Jürg ended by stressing that innovation is crucial to prepare and be ready for the future and that collaboration, communication and partnership are the absolute keys to success.