Old dog, New Tricks? Assessing the Potential of Integrating Focal Vector Suppression with Drug Cure to Control and Eliminate River Blindness

By Louise Hamill

Onchocerciasis, also known as river blindness, is one of the vector-borne neglected tropical diseases (NTDs); in this case, transmitted by many different species of black fly. The majority of infections (99%) occur in sub-Saharan Africa. The disease was previously also found in South America but is now thankfully close to total elimination; with only a few isolated, extremely remote areas still to be verified disease-free. The aim for Africa is to achieve continent-wide interruption of transmission by 2025.  Current control of river blindness in Africa, which, as well as blindness, leads to debilitating, disfiguring skin pathology, is based upon the mass delivery of ivermectin to entire populations in endemic areas. Ivermectin kills microfilariae in the skin, but has no significant effects on adult worms. This necessitates repeated rounds of ivermectin mass delivery for a period of 12 – 15 years, with sustained high coverage of the at-risk population essential for successful disease control and eventual elimination.

This approach has had notable successes in several areas, led by the efforts of the African Programme for Onchocerciasis Control (APOC). However in other areas, the impact of sustained delivery of ivermectin for fifteen years, and in some areas more than two decades, has yet to result in the predicted interruption of transmission. Furthermore, where the eye worm Loa loa and onchocerciasis occur together, mass delivery of ivermectin cannot be easily rolled out. Ivermectin causes unwanted side effects, and in rare cases death, in individuals infected with L. loa as the drug rapidly kills this parasite. L. loa is common in large swathes of West and Central Africa, allowing onchocerciasis to endure in these areas, where many people are still infected and transmission of both pathogens is actively taking place, despite ongoing control efforts. Clearly there is no one-size-fits-all approach to curtail river blindness, and there is a need to seek alternative strategies to ivermectin-based control in areas where river blindness and L. loa overlap.

In the nineteen seventies and eighties the WHO onchocerciasis control programme, OCP, ran an extremely successful vector control strategy against onchocerciasis in savannah areas of West Africa. This programme relied exclusively on aerial application of larvicide to kill black fly larval as they resided in rivers and streams. It is estimated this past use of vector control prevented 600,000 cases of blindness and prevented 40 million people being infected. The scale of this undertaking, including the huge financial cost and human resource needed, means that the use of mass vector elimination as a tool for onchocerciasis control is very much consigned to the history books. Before turning the page completely on this chapter of onchocerciasis control, are there any lessons to be learnt from this “old dog”?

The COUNTDOWN meeting on Focal black fly Control in Cameroon

This is exactly the question we set out to debate when COUNTDOWN convened a technical advisory panel at the Liverpool School of Tropical Medicine on 22nd of July 2016. Although mass vector control is out of the question, is there any way in which short-term, localised approaches can be used to augment and complement existing strategies?

Vector Meeting

Attendees at the COUNTDOWN meeting on Focal Black fly Control, from Left to Right: Professor Graham Matthews, Professor Rory Post, Dr Frank Walsh, Didier Bakajika, Dr John B. Davies, Dr Louise Hamill, Dr Hans Dobson, Dr Joseph Turner, Professor María-Gloria Basáñez, Professor Mark Taylor, Isobel Routledge, Professor Russell Stothard, Professor Robert Cheke. Not pictured; Professor Janet Hemingway, Dr Lisa Reimer.

Previous work in South West Cameroon by members of the COUNTDOWN consortium indicates that ten years of ivermectin delivery in our study area has not had the expected impact on disease prevalence. The average community-level of skin microfilaria prevalence stands at 52.7 percent, with the infection intense even in children under ten years of age. Additional work in South West Cameroon found current adherence to ivermectin mass delivery by local residents is not adequate to achieve onchocerciasis control. This is an area where alternative and complementary strategies are urgently needed.

The COUNTDOWN consortium has proposed that larvicidal treatment of vector breeding sites at the same time as testing and treating the human population with doxycycline could offer a complementary onchocerciasis control strategy. This two-pronged approach, it is hoped, will have a greater impact on disease transmission than using either technique in isolation. Doxycycline targets “friendly” bacteria living within the adult onchocerciasis worms, resulting in a significant shortening of their lifespans and giving doxycycline a very different mode of action to ivermectin. Since L. loa does not harbour the same bacteria, individuals co-infected with L. loa who take doxycycline will not suffer the same side effects as can happen with ivermectin. From the evidence above, it is clear to see ivermectin mass delivery has not had the desired impact on disease prevalence over the past ten years in this area of South West Cameroon; could targeted vector suppression jump start the path to onchocerciasis control?

At the meeting, debate revolved around the factors influencing choice of larvicide; when, how often & for how long the larvicide should be applied; the most suitable sampling methods to monitor impact of the larviciding on adult and larval black fly; and how best to undertake monitoring of the impact of insecticide application on non-target organisms. The optimal timing of any vector suppression to best amplify the impact of the community test-and-treat strategy is crucial. The way ahead is far from straight forward, highlighting the importance of rigorously assessing the evidence and our proposed strategy in this way. Although the use of localised vector control against black flies is not a new proposal, there is little information on how this could be implemented against free-living black fly larvae.

Where next?

The control and elimination of NTDs in Africa has repeatedly been in the post-millennium development goals policy spotlight, with (among others) the WHO roadmap to elimination, the London Declaration on NTDs and recently the launch of the Expanded Special Programme for Elimination of NTDS (ESPEN). Similar to the situation for lymphatic filariasis, scale-up of mass delivery of ivermectin will not be enough to achieve the London Declaration 2020 targets for onchocerciasis control and elimination. The use of both doxycycline and focal vector suppression are separately recommended by WHO and APOC as alternative onchocerciasis control strategies, to accelerate progress towards onchocerciasis control, however as relatively new control strategies evidence on their implementation is scarce and evidence on integrated, dual-strategy implementation is wholly absent. The specific contexts in which these tools could be successfully implemented together are unclear.  Going forward with our onchocerciasis work in Cameroon, COUNTDOWN’s focus is consolidation of the evidence gathered at the vector control meeting to assess the possibility of implementing localised vector suppression as an adjunct to existing and alternative control and elimination strategies. This will bridge vital evidence gaps and provide clarity on if and where these techniques can be used, and the optimal conditions in which to implement them.

 

 

 

A Bed Net to Rule Them All: Accelerating Lymphatic Filariasis Elimination Through Malaria Control Programmes

by Corrado Minetti

In rural areas of Africa, Lymphatic Filariasis (LF) is primarily transmitted by night-biting Anopheles mosquitoes, which also transmit malaria. Currently, the two major ways of controlling malaria vectors are the indoor residual spraying (IRS) of insecticides and the use of bed nets. It has been estimated that the combination of these two interventions, in the decade 2000-2010, has prevented  more than 200 million new cases and more than 1 million deaths due to malaria.

In areas where both LF and malaria occur and are transmitted by the same mosquitoes, should we then promote vector control alongside mass drug administration (MDA) to accelerate the elimination of LF through a better and more cost-effective integration of LF and malaria control programmes at the national level?

The answer is yes.

The importance of vector control for lymphatic filariasis elimination

Reducing mosquito numbers and preventing people being bitten has a significant impact in reducing the burden of LF and, ultimately, pushing towards its elimination. As it has been reported in various countries around the world the use of bed nets, IRS and/or reducing the mosquito breeding sites can all result in a significant reduction of LF transmission even in the absence of MDA. For example, in Papua New Guinea the deployment of insecticidal bed nets in communities where MDA was stopped 10 years before resulted in a reduction of the LF transmission potential down to zero within only 11 months following distribution.

Corrado - Pic 1

A long-lasting insecticidal net (LLIN) in Agyan (Ghana) (Photo: Corrado Minetti)

Mathematical models have clearly shown the strategic impact of implementing vector control alongside MDA for LF: reducing the human-mosquito exposure allows reaching the community and vector infection thresholds below which LF transmission will be interrupted faster and earlier compared with using MDA alone. As a result less rounds of MDA may be needed to reach elimination if vector control is in place, with important savings for the programme.  Furthermore, sustained vector control may avoid the resurgence of LF in treated communities in a post-elimination setting (after MDA has been stopped) due to the potential re-introduction of the disease through human movement.

The way forward: integration of lymphatic filariasis and malaria control programmes

Corrad Pic 2

Mass distribution of ivermectin for LF elimination (on the left, source: www.mectizan.og) and bed nets for malaria control (on the right, source: www.usaid.org)

Given the importance of vector control for LF elimination; with LF and malaria being transmitted by the same mosquito vectors in West and rural Africa, integrated vector management (IVM) becomes crucial. There is a tremendous opportunity to effectively integrate the LF and the malaria control programmes, making both more efficient and cost-effective.

Establishing a synergy between MDA for LF and bed nets distribution/indoor insecticide spraying for malaria can have two major effects which will be extremely beneficial for the fight of both diseases. Firstly, a more efficient use of resources: the same community distributors delivering the drugs can distribute bed nets at the same time leading to important savings in terms of time and human resources. Secondly, a higher impact on the burden of both diseases: MDA campaigns can facilitate the distribution and penetration of bed nets in the community and vice-versa.

The beneficial effects of an integration of MDA and bed nets distribution has been clearly shown in Nigeria, where the concomitant delivery of nets alongside MDA resulted in a significant improvement in insecticide-treated bed net ownership and use (up to 9-fold) and it did not negatively affect the MDA coverage.

Following the above evidence, in 2014 Nigeria has been the first country in Africa to launch a Nationwide Malaria and LF elimination Co-Implementation Plan alongside specific guidelines.

We now have the tremendous opportunity to promote a better cross-talk between the vector borne disease-specific communities, stakeholders and policy-makers in order to raise awareness on the importance of a sustained and better planned vector control leading to a more cost-effective and effective use of resources across disease control programmes.

Within the COUNTDOWN research consortium, we recognize that the scale-up of MDA won’t be enough to achieve the London Declaration 2020 targets for the elimination of lymphatic filariasis. In particular, following the example of Nigeria, we are seeking opportunities in Ghana for an integration of the national LF elimination and malaria control programmes to co-ordinate MDA distribution and delivery of vector control interventions and to evaluate the impact of such synergy on service delivery, community participation and cost-effectiveness.

Find more information on COUNTDOWN’s activities here.

Future directions in Neglected Tropical Diseases

By Eleanor MacPherson, Liverpool School of Tropical Medicine

On the 14th June I attended a meeting of the All-Party Parliamentary Group (APPG) on Malaria and Neglected Tropical Diseases (NTDs). It brought together a panel of four men to discuss Neglected Tropical Diseases and the Sustainable Development Goals. The panel included three members from the World Health Organisation: Dirk Engels (Director of NTDs), Christopher Fitzpatrick (Economist for NTDs), Bruce Gordon (NTD-WASH strategy) and Mr Andy Wright from GSK Uniting to Combat NTDs. The meeting was chaired by Jeremy Lefroy the MP for Stafford and coordinator for the APPG on Malaria and Neglected Tropical Diseases.

Here are five reflections on our discussions:

  1. Including women in community led mass drug administration can improve women’s standing within communities. Dirk Engles talked about the different ways that tackling NTDs could help meet the 17 Sustainable Development Goals but this one stood out. He described how including women as community drug distributors could be empowering for women because by taking a leadership role they were challenging gender norms. However, I would love to broaden this out to highlight the multiple ways gender shapes women and girls’ experiences of NTDs. These include the way social norms within communities often mean that women and girls are expected to interact with infected water sources on a near constant basis. Women can experience greater stigma from living with the clinical manifestations of NTDs. For instance, women living with swelling in their legs can lead to greater stigmatisation both within their families and in the communities more broadly. Expectations around who provides care in households can also mean that women and girls care for those living with the symptoms of NTDs. Making sure we highlight the diverse ways gender power relations shape vulnerability and experiences of living with the diseases is vital. One step to doing this would be the inclusion of women and girls voices in the design health and social programmes to ensure their needs are not overlooked.
  2. Despite free drugs being available not all countries request them: Understanding why countries do not request free drugs is important. Health systems in resource limited settings are often overburdened. Provision of free drugs is only part of a health programme. Many bottlenecks obviously exist that prevent countries from requesting and delivering these programmes. Taking a health systems approach that asks stakeholders what challenges governments face that stops them from requesting drugs could provide important insights.
  3. We need to look beyond just giving drugs: Where people live, whether they have access to safe water, whether they have access to health care, and what they do for a living can all affect their vulnerability to NTDs. Giving preventative chemotherapy has to be seen as a strategy that goes hand in hand with other interventions that aim to prevent people becoming infected in the first place. These include vector controls as well as Water, Sanitation and Hygiene (WASH).
  4. WASH is not always easy but it is necessary: WASH’s start-up and maintenance costs can be expensive but given the very real ways it can prevent illness and suffering investment should be made.
  5. Let’s not leave anyone behind: Millions of people, and their families, continue to be affected by NTDs. Making sure that these people’s health and social needs are considered and addressed within NTD programmes is of the upmost importance.

It was heartening to see the successes of NTD interventions such as the lymphatic filariasis programme from the last decade. However, it is clear that many challenges still remain if we are to live in a world free of NTDs.

Photo credit: Lake Malawi by Eleanor MacPherson

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.

The Neglected Tropical Disease hotspot puzzle requires multidisciplinary investigation

Sally Theobald, Margaret Gyapong, Mike Osei-Atweneboano, Sheila Addei, Alexander Adjei, Adriana Opong, Samantha Page and Kate Hawkins Dr Benjamin Kofi Marfo, Deputy Director of the Neglected Tropical Disease (NTD) programme in Ghana, is fizzing with energy as he explains the NTD hotspot conundrum in Ghana. Hotspots, or areas with persistent NTD prevalence above a threshold set by the World Health Organisation, present the final hurdle to elimination of certain NTDs. The COUNTDOWN team meeting in Accra brought together the Ghana Health Service (GHS) NTD team, colleagues from Dodowa Health Research Centre, the Council for Scientific and Industrial Research, Liverpool School of Tropical Medicine and Pamoja Communications. Together we discussed the map of hotspots for Lymphatic Filariasis (LF) in Ghana – bringing to mind a detective story – we debated different explanatory possibilities:

  • Border areas: All but four of the 22 hotspot areas are either on the border or next to a border district – with the Cote D’Ivoire (West of Ghana), and Burkina Faso (North of Ghana), but intriguingly not Togo (East of Ghana). These borders, carved up by colonial powers, separate families and communities and in reality are porous with regular movement and trade across them. Could it be that people here are missing Mass Drug Administration as they move from one country to the other? Dr Marfo and his team discussed the importance and challenge of cross border NTD collaboration and the possibility of synchronising approaches to MDA to minimise losing people from the process.
  • Genetic variation in human population: Why is it that in some families people get LF and others don’t although their exposure is arguably similar. Are there some genetic factors at play which predispose certain individuals or communities to LF?
  • Genetic variation in parasite or vector population that we don’t understand: Are there some genetic changes in some population of parasites and/or vectors and some geographically specific adaptation going on that needs further investigation?
  • Context specific socio-cultural beliefs or practices: Or is there something specific about the understanding, livelihoods and socio-cultural realities of these communities that lead to additional vulnerability or challenges in accessing and adhering to drugs (or in NTD language are there more persistent non-compliers in hotspots?)
  • Health system challenges: Or could it be that there are some health systems challenges and bottle necks within the hotspots? Challenges relating to distribution or possibly community based drug distributors feeling under motivated and undervalued?

Or does the explanation lie in a mixture of some or all of the factors above? Trachoma is on the road to elimination in Ghana. However, with the exception of the Upper East Region, it is more problematic in the Northern and Upper West Regions of Ghana. Why is the Upper East Region less affected? Dr Marfo explained how this district has benefitted from different Non-Governmental Organisations conducting water, sanitation and hygiene programmes, which have supported access to fresh water and the construction of latrines. There is also an eye hospital in the Region which has enabled earlier access to treatment. The trachoma story highlights the importance of understanding the context and historical evolution of the Regions when looking at NTDs. It also illustrates the positive legacy of interventions in water and sanitation and the importance of multisectoral partnership in efforts to address the debilitating and disabling effects of NTDs. The tricky conundrum presented by hotspots demands multidisciplinary investigation and multi-sectoral engagement to understand which factors play out in different contexts to shape hotspots. COUNTDOWN brings together social scientists, health systems researchers, health communication experts, health economists, parasitologists, molecular biologists and modellers to work in partnership with NTD programmes in Ghana, Cameroon and Liberia to support NTD programmes. Watch this space as we bring different disciplines to bear to understand and address hotspots.

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.

Tailoring Mass Drug Administration to at risk communities

By Alan Fenwick (Schistosomiasis Control Initiative (SCI) Imperial College London)

In terms of schistosomiasis control with Mass Drug Administration (MDA) of the drug praziquantel there is a need to target those who are most vulnerable to infection – those people who come into the greatest contact with infested water. The profile of treatment should be driven by its health consequences which can include: malnutrition and anemia; growth retardation; cognitive impairment; increased susceptibility to other infections; chronic health problems such as inflammation and fibrosis of the bladder wall, colon, liver, spleen, lungs; and life threatening consequences such as bladder cancer, portal hypertension, and hematemesis. In the case of some of these life threatening consequences it can be quite challenging to trace the cause back to swimming in a pond 20 years ago, especially in communities that have an incomplete understanding of the disease.

In 2000 there were no MDA programmes for schistosomiasis, now look at where we are!

We currently target our programmes in the manner which is simplest – by administering drugs to children in schools. Children tend to be responsive to their teachers who deliver treatments against schistosomiasis and intestinal helminths in settings where governments don’t stipulate that medical attendance is mandatory. Administering the medicine is fairly simple as they are taken orally – although praziquantel tastes quite bitter and children sometimes vomit if they chew the tablet when they take it. With sufficient training MDA is easy to establish as the front line method of control in resource poor areas, but we need to ensure that the delivery of drugs is best targeted and sustained  within at risk populations.

We know that pre-school children are often bathed in infected water and are therefore also vulnerable. But as a rule we don’t treat them, because of the large bitter tablet. But emerging research shows that more and more younger children are getting infected, and because of the small size of their bodies immense damage can be done by the worms and their eggs to the children’s internal organs, and some may never recover from it. Expanding treatment coverage to younger children is becoming more feasible with the development of paediatric formulations by Merck so there is now good reason to expect change for the better

In 2012 only 14.4% of the people worldwide who needed praziquantel treatment actually received the drug. That amounts to 42.1 million people. However, until quite recently one of the barriers to scale up was the accessibility of treatment. That argument no longer holds as we estimate that by 2016 we will have enough donated drugs from Merck, DFID, USAID and World Vision to treat 165 million people.  Now we have a new problem, we face financial constraints to fund delivery – the UK and the US are currently the only bilateral donors that are funding the delivery of drugs and the main financing burden falls on the governments of low- and middle-income countries who don’t always prioritise NTDs. That being said we are in a better position than ever before and are optimistic in future expansion of our operations

Scaling-up control to those who need treatment, however, will depend on a number of factors: on improving country political will and resources; on praziquantel availability; and on accurate geographical and epidemiological mapping that enables the development of evidence based national plans. To make this a reality advocacy needs to occur at the national and district level, and this work needs to be done well in advance. It can take up to six months for WHO to fulfil requests for drug donations, but creating systems and the training of those who will deliver the programmes takes time, so these tasks need to go in parallel. Other tasks may include ensuring that there is ethical clearance from the parents and caregivers of those who will be treated and we need to be ready in case there are any adverse events, however mild, with sufficient supporting community dialogue and assurance.Today we are poised to expand coverage of praziquantel treatments and improve the present and future quality of life of hundreds of millions of children in Africa, but we have only a small window of opportunity to get it right so we have to rise to the challenge.