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Why I’m adding my voice to David Beckham says: the campaign to end malaria “Please add your voice” A Nigerian doctor who lends his voice — literally — to the Malaria Must Die campaign fronted by David Beckham, tells his personal story about contracting and treating the disease.

s a boy growing up in Nigeria, Dr Elvis Eze contracted malaria not once, but four times. And those were just the times that were confirmed. “In Nigeria, malaria is normalised,” he explains. “People say: ‘I had malaria, but I’m well now.’” Yet the disease should not be dismissed so easily, he insists — because malaria kills. “Each time I had fever, my body ached and I felt as though I was going to die,” says Dr Eze. “However, thankfully, I never had severe malaria. With the extreme version of the disease — which is usually more common in children — patients can become unconscious and start convulsing.” If untreated, it can be fatal. I was lucky malaria didn’t kill me Looking back, Dr Eze — who now works in emergency medicine at Southend University Hospital — realises that he could easily have lost his life had the illness progressed to the severe stage. “And that messes with my head,” he admits. “As a kid, I never really grasped the severity of my situation.” Becoming a doctor, working in emergency rooms in Lagos and seeing people die from the disease changed all that. “That was when it dawned on me that malaria was a big problem and something had to be done about it,” he says. “Being on the frontline opened my eyes. That was my inspiration to tell my personal story and take part in the Malaria Must Die campaign.” Dr Eze’s voice appears in the Malaria Must Die campaign video, speaking Yoruba through David Beckham (using AI technology) and inviting people to sign up to the world’s first voice petition to help end the disease.

150 years ago, all countries (except in Antarctica) had endemic malaria within their borders. Since then, half have eliminated malaria. David Beckham is working to accelerate this progress through the latest phase of the Malaria Must Die campaign.

If we follow a two-pronged approach of preventing it and treating it appropriately, we will be able to eradicate malaria in our lifetime.”

knew who David Beckham was,” he says. “Many people in my country do because we watch football a lot. I was on social media yesterday and MPs were re-tweeting information about the campaign. So someone with David Beckham’s profile and reach can get the message out to the right people.” That’s important, but so is better collaboration between numerous stakeholders, notes Dr Eze. For example, if everyone from political leaders and medical researchers to organisations with innovative technologies talk to each other, the goal of halving malaria across the Commonwealth by 2023 is within our grasp. “We have to remember that this is a disease that is preventable and treatable,” he says. “If we follow a two-pronged approach of preventing it and treating it appropriately, we will be able to eradicate malaria in our lifetime.

David Beckham stars in global video to inspire support David Beckham is a founding member of Malaria No More UK Leadership Council and a committed champion in the fight against malaria with over a decade of support for Malaria No More UK. In his long-term role as a UNICEF Goodwill Ambassador he has seen the impact of malaria on people’s lives in countries such as Sierra Leone. This year, David Beckham is launching the world’s first voice petition to end malaria for the campaign Malaria Must Die, So Millions Can Live.

ince 2000, a combination of powerful new tools, increased investment and strengthened international political commitment has cut malaria deaths globally by more than 60%, saving almost seven million lives, mainly young children. Ending malaria is achievable with the right action. However, it will return if it is not controlled. Decisions made now by political leaders – backed by strong public support – will determine this trajectory.

Tony Greenway

Better collaboration is needed to defeat the disease “When I was growing up in Nigeria I followed the English Premier League and always DR ELVIS EZE NHS Doctor, Southend University Hospital and contributor to Malaria Must Die

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Instead of collecting signatures, the campaign asks people around the world to use the power of their voice to demand action by visiting malariamustdie.com and recording the message ‘Malaria Must Die’. “I have been working with Malaria No More UK for over 10 years and to be a part of this campaign and to help share some of the real stories behind malaria is really important to me,” says David. Global malaria survivors speak ‘through David’ In a short film, produced by Ridley Scott Associates and harnessing ground breaking AI technology, David appears to speak nine languages. But the voices are not all his own. Instead, using emerging AI video synthesis technology, we hear David speaking the voices of men and women from around the world, including malaria survivors and doctors fighting the disease. Each voice represents a part of the world affected by malaria, past or present; from the UK to China, a country on the brink of elimination, to Nigeria, where the malaria toll is the heaviest with close to 300 lives lost every day, mainly young children. David goes on to explain: “Dr Elvis Eze, who was with us on set, has suffered with malaria many times and as a doctor, he has seen how dangerous this disease can be. For me, it was so important to learn how he is using his experiences to raise awareness of malaria with young people in the UK and abroad.” The petition will contribute to a unique piece of audio art that will be delivered to world leaders ahead of critical funding decisions for the Global Fund to Fight AIDS, Tuberculosis and Malaria in six months’ time. “It’s unacceptable that malaria still kills a child every two minutes so please add your voice to the petition,” says David. DAVID BECKHAM Malaria No More, Leadership Council

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2019: a crucial year of action in the fight against malaria This World Malaria Day, Dr Abdourahmane Diallo, CEO of the RBM Partnership to End Malaria, discusses the urgent need to step up commitment and investment to end malaria.

istor y proves that continued commitment and investment in malaria elimination pays dividends. Since 2000, global progress has saved seven million lives and prevented more than one billion cases of ma la r ia, enabl i ng m i l l ion s of children to stay in school, parents to work, and economies to grow. Today, more countries than ever are close to elimination. Just last year, Paraguay and Uzbekistan were certified malaria-free, and Algeria and A rgent ina have requested malaria-free certification from the World Health Organization (WHO). The time for action is now But, after decades of progress, malaria cases have risen in high burden countries in the last two years. There were 3.5 million more cases among the 10 highest burden African countries in 2017 than in 2016. As the floods of Cyclone Idai come to a standstill, one of these

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countries – Mozambique – is now facing the threat of a malaria epidemic as stagnant water attracts breeding mosquitoes and the health services are under growing pressure. Accelerating progress Last year, Commonwealth Heads of G over n ment c om m it te d to halve malaria by 2023 across the 53 Commonwealth nations. One year on, leaders representing Frenchspeaking countries, where over 300 million people are at risk of malaria, are today gathering in Paris to discuss similar commitments to end malaria starting with Francophone Mayors, who will sign a declaration committing to integrate malaria in urban development strategies in support of global efforts towards a malaria-free world. Continued progress toward ending malaria requires greater investment in innovation and ensuring access to these innovations by affected populations. Today, new tools such

Leaders across the globe must now prioritise funding and programmes that will save more lives, continue to reduce the malaria burden, build stronger health systems, and reignite the pace of progress against the disease.” as innovative antimalarials, new methods for vector control, interventions to minimise insecticide and drug resistance, and better use of data to improve targeting of resources have great potential to accelerate progress. One important development we are watching closely this World Malaria Day is underway in Ghana, Malawi, and Kenya, where country leadership has resulted in t he roll-out of the first trial vaccine for malaria, RTS,S. Leaders across the globe must now prioritise funding and programmes

DR ABDOURAHMANE DIALLO CEO, RBM Partnership to End Malaria that will save more lives, continue to reduce the malaria burden, build stronger health systems, and reignite the pace of progress against the disease. Empowering communities Together, members of society can also have considerable impact. Last year, the African Union endorsed “Zero Malaria Starts with Me” – a new initiative seeking to empower communities to take ownership of malaria prevention and hold government and private sector leaders accountable for meeting malaria commitments. Already, Mozambique, Senegal, Uganda and Zambia have joined the Zero Malaria movement and today, several more countries, including Ghana and Sierra Leone, will also adopt the initiative. Supporting these efforts, a new coalition of civil society organisations – Civil Society for Malaria Elimination (CS4ME) – has also been created to empower

communities and civil society to advocate for more effective, sustainable and people-centred, malaria programmes. Stepping up the fight 2019 is a crucial year of action in the fight against malaria. In October, the Global Fund to Fight AIDS, Tuberculosis and Malaria calls on all countries to pledge at least US$14 billion in funding for these diseases. Accounting for approximately 60% of funding for anti-malaria programmes worldwide, the importance of reaching this target cannot be overestimated. This World Malaria Day, join us and global partners in calling on leaders to step up the fight to end malaria by following through on their commitments and investing the resources the Global Fund needs to save millions more lives. Read more at fightagainstmalaria.com MEDIAPLANET

Addressing the market failures in anti-malaria product development A lack of commercial perspectives has meant the marketable pipeline for interventions against malaria is too narrow. A new funding facility will bring innovative biotech to the domain by mediating its initial financial risk.

olm Keller doesn't pull his punches. Progress the world has made in responding to malaria has stalled, he says. Unacceptably, around 1,000 children a day are dying from the disease. Some unpalatable realities need to be confronted. “Quite simply, there is a market failure around the development of interventions against malaria,” says Keller, Executive Chairman of kENUP, a non-profit organisation. Together with public promotional banks, kENUP promotes innovative approaches to product development with the aim to control some of the world’s most lethal infectious diseases. "There is high risk in product development and little profit associated with diseases primarily affecting the global south, like malaria. So, once a project leaves academia, companies are usually not investing.” Moreover, many institutions have slowed down or halted their malaria

projects in anticipation of the highly-invested RTS,S vaccine - which is still work in progress and now in pilot programmes in two countries. In the therapeutic market, the world also holds many eggs in one basket: with artemisinin-based combination therapies (ACTs), reliance is on a single therapeutic intervention that really works - and which is procured in huge volumes from very few manufacturers. In parallel, mainly costdriven procurement procedures also lead to fewer and fewer suppliers being engaged in diagnostics. Incentivising commercial investment Plain ly, hea lt hcare compan ies need to be better incentivised to invest in this space if malaria prevention, diagnosis and treatment is to advance. “We need to enlarge the malaria vaccine and therapeutics pipeline,” says Keller. “Despite the seriousness of this disease, not enough companies are seriously engaged”.

We need to enlarge the malaria vaccine and therapeutics pipeline. Despite the seriousness of this disease, not enough companies are seriously engaged.” Alongside the European Investment Bank (EIB), kENUP is initiating a €240 million financing facility called the EU Malaria Fund. By providing funds to a portfolio of projects in commercial development, the EU Malaria Fund aims to balance the risk of failure, or, more optimistically, increase the chance of success. Supporting a risk-balanced portfolio of projects The f u nd bu i lds on a n i n it ia l portfolio of scientifically independent malaria projects not yet pursued by industry, run by leading companies including spin-offs from renowned research organisations, SMEs, and start-ups. Projects

HOLM KELLER Executive Chairman, kENUP Foundation

include vaccines, field test kits and therapeutics, including monoclonal antibodies and new drug targets. The projects will target different parts of the parasite life cycle and leverage progress in the scientific community through a variety of approaches and research platforms. Providing milestone-based venture loans Companies will receive funding in installments, only getting more if their project reaches the next stage of development. “Funds are given as venture loans, which only need to be paid back if a project is successful,” says Keller. “This is why it's only available to companies, and not universities or research institutions. If a potential product fails, the loan will be converted into a grant.” Fifty per cent of the money from the EU Malaria Fund is expected to be provided by public and charitable sources from Europe. The remaining i s b e i n g r a i s e d f r om i mp ac t investors, who will reasonably

expect their money back (although this is not guaranteed), potentially even with a modest return. “If the pilot of this financing facility is successful, it could be replicated for other areas where there are similar market failures, such as the field of antimicrobial resistance,” says Keller. “And even if the fund doesn't create a blockbuster intervention, we hope that will be a much more impactful response to malaria t han depending on academia alone: by engaging innovative biotechnology companies that otherwise couldn't bear the risk.” Tony Greenway

Read more at controlmalaria.eu

How we co-develop our new vector control tool for malaria My team in Mali is part of an international, not-for-profit research consortium called Target Malaria. We are part of an effort to combat malaria at its source, by targeting the mosquitoes themselves; the Anopheles gambiae complex.

ur aim is to develop and share an innovative vector control tool that reduces the population of malaria mosquitoes in sub-Saharan Africa and hopefully reduces the transmission of the disease. A vector refers to an organism – typically a biting insect or tick, that transmits a disease or parasite between humans or from animals to humans. This vector control tool would be complementary to the ones already existing and to any new ones under development. The success of ou r resea rch will not only be measured by our scientific achievements but also by the acceptance and involvement of affected com munities in our research. As a project, we a re c om m it te d to developi n g somet h i ng t hat i s u sef u l a nd responds to the expectations of communities living with the burden of malaria. MEDIAPLANET

We work closely with local communities Co-development is at the heart of our work. We want to make sure our new tool meets the needs of the affected populations and we can only do this by involving them in our efforts and research activities. Since the start of the project in Mali in 2012, Target Malaria has engaged various, in-country stakeholders with a specific focus on local communities where we conduct our research activities. In the communities where we work, we are ¬– at this stage – mainly focused on mosquito collections and engagement activities. Mosquito collections are necessary to gather baseline data on mosquito population and dynamics. Engagement is necessary to seek consent and/or acceptance for those activities. We engage the local communities by establishing an ongoing dialogue

Mosquito collections are necessary to gather baseline data on mosquito population and dynamics. Engagement is necessary to seek consent and/or acceptance for those activities.” to explain, in complete transparency, our research and inform them on our progress. This engagement is extended to the regional and the national level (including but not limited to national authorities, civil society and the media to disseminate information on several levels). Translating our scientific progress to local communities can be complex With the development of new technologies come new challenges. For our team in Mali, we had to ask

DR MAMADOU COULIBALY Head of Vector Genomics Lab and Principal Investigator, Target Malaria Mali

ourselves how to best communicate our advancements in science to local communities in the local language. Science can be complex to translate into easily understandable and accessible terms. All languages have their nuances and we wanted to make sure we had the right words to convey the right concepts. Our team worked w it h local communities and the National Di rec torate for Non-For ma l Education and National Languages (DNENF - LN) to develop a glossary, which has since become the basis of our engagement in local language. All the concepts and terms present in our glossary have been validated w ith the communities and we believe this has strengthened our relat ion sh ip a nd c om mu n ic ation with local stakeholders. We continue to work on translating scientific concepts to make our results dynamic as we move forward.

Responsible and ethical development to combat malaria We believe that the early commitment of Target Malaria to stakeholder engagement is key in the success of the co-development of our new tool for malaria control. We want to responsibly and ethically develop a new vector control tool that will hopefully contribute to the wider efforts of combatting this preventable disease that still kills half a million people across the world each year.

Read more at fightagainstmalaria.com FIGHTAGAINSTMALARIA.COM

Malaria resurgence is a very real risk Rates of malaria have dropped significantly in recent years, but the battle is far from over — and without investment and commitment we run the risk of reversing progress.

hat’s according to the team at the Global Fund to Fight A I D S, T ub erc u lo s i s a nd Malaria, which has invested more than $10 billion in malaria control since 2002. Dr Scott Filler, Malaria Team Leader at the Global Fund, says: “ There has been a sig n i f ica nt reduction in malaria mortality and morbidity since the fund started in 2002. The number of cases has come down and global death rates have decreased by about 60%. “It’s all incredibly exciting, but in the last two or three years we have reached an inflection point.” Progress is slowing, and, in some places, the number of cases and deaths are once again starting to rise. “Malaria is like a coiled spring. You can squeeze it really hard, but if you let go, if populations grow and

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don’t get access to prevention, or you do not treat it effectively, it can suddenly spring back, and return to baseline rates very quickly. It’s unforgiving,” said Dr Filler. Campaign to fight malaria: Step Up The Fight It is with this plea that the Global F u nd h a s l au nche d it s l ate s t triennial replenishment campaign, Step Up The Fight. As overseas development funding has plateaued, populations have continued to grow, meaning per capita expenditure has gone down, and more resources are needed to continue the fight. “With current funding levels we might not be able to maintain the progress we have made, and we are nervous that the number of cases and deaths will continue to increase,” says Dr Filler.

As many as 150 in every 1,000 children die before their fifth birthday.” The World Health Organization estimates malaria control will cost $6.5bn a year by 2020, compared to $2.8bn in 2015. An increasing global population, however, is not the only reason for this increase. Mosquitos are becoming resistant to insecticide Malaria carrying mosquitos have developed resistance to insecticides used on bed nets and human conflict and environmental disaster also take their toll. Recent unrest in Venezuela, for example, led to the collapse of the healthcare system, and cases have skyrocketed. Dr Filler says: “It was close to

SCOTT FILLER MD, DTM&H Malaria Team Leader, the Global Fund to Fight Aids, Tuberculosis and Malaria

eliminating malaria, and now there are one million cases a year. It shows how a country on the cusp of eliminating the disease can return to a highly deadly prevalence within just a couple of years.” Aggressive control, elimination and continuing R&D Explaining how the fund spends its money, Dr Filler says it had a threepart strategy but focused primarily on areas such as sub-Saharan Africa where 90% of all cases occur. In these high-burden areas, prevalence can be 40 or 50%, and as many as 150 in every 1,000 children die before their fifth birthday. Malaria, Dr Filler says, is deeply connected to poverty meaning high-burden areas lack the resources to tackle the problem alone. “We concentrate the bulk of our resources in those areas. But we also

work in the marginal countries so that when they have eliminated the disease, we can move the resources to those that haven’t,” he says, adding the organisation worked with research and development partners on projects such as new insecticides. Ultimately, the fight against malaria is about saving lives and improving quality of life in communities that often do not have a voice, he says. “ We s t r o n g l y b e l i e v e t h a t removing malaria from the equation of development can contribute to an upward spiral, to a place where countries can lift themselves out of poverty and sustain their own health programmes.” Amanda Barrell

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The life-saving benefits of pre-referral management

PIERRE HUGO Senior Director, Access and Product Management, MMV

In some countries, there is a — sometimes fatal — time lag before patients with severe malaria can start full treatment at health facilities. That is why ‘pre-referral’ medication is so critical.

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reat ing pat ients w it h severe ma lar ia is a race against the clock. “Severe malaria is the end stage of a terrible disease,” explains Pierre Hugo, Senior Director, Access and Product Management at MMV (Medicines for Malaria Venture), a leading product development partnership in the field of antimalarial drug research and development. “with severe malaria, if intravenous antimalarial treatment is not administered quickly, critically ill patients may d ie.” The v u l nerable a nd immune-compromised (children under five and pregnant women) are particularly at risk. Patients with severe malaria must immediately be referred to a health facility to be treated with injectable artesunate, which is administered into a vein or at least a muscle so it can work very quickly. Tragically, many patients are so ill they die before they get there. Patient access to health centres is limited In some countries, not everyone has immediate access to health facilities,” says Hugo. “Rural areas may be over 30km from the nearest health centre and it can take hours to get there. And when patients with the disease do get there, they may have

to wait.” Time, therefore, is of the essence — and studies have shown that if such patients are first given 'pre-referral' rectal artesunate (RAS) 100mg in their own community, ideally administered by community health workers, their risk of disability and death during the journey to a healthcare facility is halved. Pre-referral medication is a matter of life and death Administering R AS to children under six years old ‘buys patients time’ until a full course of treatment can begin at a health facility. Simply put, RAS could mean the difference between life and death. To ensure the availability of RAS at community level, more governments need to recognise its benefits and include it in their treatment guidelines. “RAS 100mg medication is now registered in 16 countries,” says Hugo. “It is a life-saving tool and should be implemented widely. The other critical piece of the puzzle is for those same countries to ensure they have a network of trained community health workers in order to administer it.” Tony Greenway Read more at fightagainstmalaria.com

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Oxford scientists could have malaria vaccine soon

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PROFESSOR SIMON J DRAPER Vaccinology and Translational Medicine, University of Oxford

The dawn of a new era in malaria prevention is coming, as scientists work on developing and trialling malaria vaccines. Here’s what’s happening now.

opes are high that malaria could be defeated soon, with malaria vaccines in clinical trials now. “We need effective vaccines as soon as possible,” says Simon Draper, Professor of Vaccinology and Translational Medicine who heads the Blood-Stage Malaria Vaccine Group at the Jenner Institute, University of Oxford. “In the year 2000, malaria was claiming about a million lives a year globally. By 2018, bed nets, insecticides and anti-malarial drugs had reduced that to around 450,000, but that improvement seems to be stalling.” Apart from the human toll, malaria control is costing the world US $ 2-3 billion a year. “The battle to develop a malaria vaccine is at a very exciting stage,” says Simon. “Trials of vaccines are happening now, and more start soon.” The nature of malaria makes vaccine development difficult. Simon explains: “When an infected Anopheles mosquito feeds on a human, it injects the Plasmodium parasite, which stays in the liver for a week before bursting into the bloodstream, at which point symptoms of malaria appear. When another mosquito feeds on an infected human, the Plasmodium parasite is passed on. “We now have methods to induce the production of antibodies to stop the Plasmodium in its tracks at three points: in the blood, the liver, and in the mosquito.”

A different vaccine is required for each, but vaccines developed at the institute are being trialled now. Phase I/II trials of a vaccine that targets the liver are already underway in both Oxford and Africa; a vaccine targeting the blood is undergoing Phase I trials in Africa, and a trial targeting the mosquito-stage starts soon. Oxford’s unique approach The Jenner Institute is the only place in the world that is working on all three approaches at once. “Our long-term goal is to develop a vaccine that will stop the Plasmodium in all three sites at the same time,” says Simon, who is working on the blood-stage vaccine. His colleagues, Professors Adrian Hill and Sumi Biswas, are working on the liver and mosquito stages. “Everyone is keen to produce safe and cost-effective vaccines as soon as we can, but careful, staged trials are essential to determine safety, dosages, and whether the vaccine works effectively,” says Simon. “We will not know for sure whether our vaccines reduce episodes of malaria until the trials in Africa are completed, but we are collaborating with academics, small biotech companies and big pharmaceutical companies, with the ultimate aim of getting safe, effective vaccines licensed as soon as possible.” Linda Whitney

Vaccines for Tomorrow Specialist Biotech company, based in Switzerland and the Netherlands, focused on R&D of safe preventative vaccines against human infectious and life disabling diseases. Unique and proven proprietary virosome technology platform with viral membrane proteins and ability to incorporate and anchor antigens and adjuvants on one enveloped virus like particle. Vaccine candidates in development: Infectious diseases: Malaria, HIV, Chikungunya, Influenza, RSV Immunotherapy partnerships in Oncology and Allergies For Malaria: Mymetics is actively working with academic partners on a multi-stage malaria virosome-based vaccine with a membrane anchored adjuvant for optimal immunogenicity in infants and children.

www.mymetics.com tel +41 21 653 4535 Mymetics is quoted on the OTCQB market under ticker symbol MYMX

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50% fewer malaria deaths since 2000, but we cannot relax our efforts PHILIP WELKHOFF Malaria Program Director, Bill & Melinda Gates Foundation

Insecticide-treated nets, better data and genetically-modified mosquitos can help end malaria. But endemic countries must make it a top health priority, and funding must not plateau.

his time last year, leaders from government, industry and philanthropy convened in London to spotlight and advance the global effort to end malaria. The Malaria Summit London was an unqualified success, resulting in financial commitments totaling £2.9 billion and a bold commitment by Commonwealth nations to halve the burden of malaria by 2023. This is aligned with the World Health Organization’s (WHO) global target to significantly reduce the burden of malaria by 2030, including a milestone to reduce burden by at least 75% compared to 2015 levels, by 2025. The summit captured the nature of malaria - we either move forward or we fall back. Since 2000, deaths from malaria have been reduced by half. This is the result of increased funding and scale-up of drugs, diagnostics and insecticide-treated bed nets and spraying. But the total number of malaria cases remains stubbornly high. Overall funding for the malaria response has plateaued, and the malaria parasite and mosquitoes that transmit it are growing resistance to our most effective drugs and insecticides. Continued process is possible, but not inevitable. The situation today requires us to evolve our approach and harness new learnings, technologies and partnerships to overcome the challenges we face. Steps being taken to drive progress: 1: Using data to save lives in high-burden countries More than two-thirds of malaria cases and deaths are concentrated

Since 2000, deaths from malaria have been reduced by half. This is the result of increased funding and scale-up of drugs, diagnostics and insecticidetreated bed nets and spraying.” in just 11 countries. And the rate of reduction in deaths per year has slowed. To meet ambitious milestones and more importantly save lives today, we need a more targeted, data-driven approach to fighting the disease. Encouragingly, that approach is the focus of a range of initiatives. A new initiative led by high-burden countries and supported by the WHO and RBM Partnership to End Malaria aims to strengthen malaria surveillance and case management, while using data to drive decision-making. The Global Fund and US President’s Malaria Initiative are collaborating for more accurate and timely data. Efforts like Visualize No Malaria are integrating technology, data and country programmes to bring real-time data to the frontlines of the fight against malaria. 2: Harnessing innovation to deliver impact A new generation of interventions are in development, which will enable us to stay ahead of resistance and tackle the disease in the most challenging places, including new insecticide-treated nets and insecticide sprays. Scaling innovation is critical to turning the tide on malaria infections and deaths. Investments in transformative tools are vital. We must advance research into innovative vector

control tools – such as attractive targeted sugar baits and genetically-modified mosquitos. 3: Elevating malaria on health agendas M a k i ng major st r ides aga i n st malaria is biologically and technically feasible today but will only be possible if donors and endemic countries make it a top health priority. This year, the world has an opportunity to signal its commitment by replenishing the Global Fund. Since its establishment in 2002, more than 27 million lives have been saved by health programmes supported by the Global Fund partnership. In 2017 alone, countries where the fund invests saw distribution of 197 million bed nets and treatment of 108 million malaria cases. The UK government has historically been a leading supporter of the Global Fund, pledging £1.1 billion during the last replenishment cycle. Stepped-up leadership from the UK and other donors will be vital to ensuring that Global Fund programmes continue to save and improve lives around the world. Some of the most striking recent successes, including elimination of the disease in Sri Lanka, were driven by dedicated health ministries and strong local malaria control programmes. Deepening collaboration with affected countries and supporting their efforts will be essential to translating global commitments into a world free of malaria. Reducing deaths now and eliminating the disease for good go hand in hand. Read more at fightagainstmalaria.com MEDIAPLANET

Detect, differentiate, defeat Effective diagnostic tools are essential to save the lives of malaria patients, break the cycle of transmission and stop the disease from spreading. More R&D is needed.

he global health community needs a range of tools at its disposal if it is to eliminate m a l a r i a i n re g ion s or ent i re countries. Effective diagnostics are crucial, says Dr Sabine Dittrich, Head of Malaria & Fever at FIND (the Foundation for Innovative New Diagnostics), a global non-profit accelerating the development, evaluation

and delivery of diagnostic tests for poverty-related diseases. As the parasites in a malaria patient's blood can infect mosquitoes — which then bite and infect other people — every single case of the disease must be found and treated if this deadly cycle of transmission is to be broken.

Different malaria parasites require different types of treatment Unfortunately, malaria is not a simple disease to diagnose or treat. It can be caused by several different Plasmodium parasites with different c h a r ac te r i s t ic s: for exa mple, P. vivax m a la r ia lies dormant in a person's liver, and can cause the infection to reoccur at a later Breaking the cycle of malaria transmission depends on every stage. A patient infection being identified and appropriately treated with this form of CREDIT: ©VISUALMEDIA 2013 the disease requires

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Diagnostic integration for fever and malaria enables us to start with the patient, not the disease.” ‘radical cure’ — that is, the complete eradication of P. vivax parasites from their body even if they are not causing active disease. Thankfully, progress is being made in malaria treatment, says Dr Dittrich. Radical cure of P. vivax malaria is now available as a single-dose drug. However, it may have potentially severe side-effects for patients with G6PD deficiency, a disorder affecting red blood cells. “Careful diagnosis is very important,” explains Dr Dittrich. “Before healthcare professionals can give patients this treatment, t hey have to be sure t hat t he infection is due to P. vivax, as well as to check their G6PD status and confirm that it will be safe to do so.” Finding P. vivax parasites hiding in the liver is only one of the many diagnostic challenges for malaria, says Dr Dittrich. “Early detection

DR SABINE DITTRICH Head of Malaria & Fever, FIND

and treatment of all forms of the disease are needed to break the cycle of transmission. Aside from diagnostics that can be used in health facilities, we also need better, sensitive rapid diagnostic tests that can identify asymptomatic patients in the community.” Integration of diagnostics for fever and malaria If a patient is found to have malaria, urgent treatment will be required in order to save their life and stop the spread of the disease. But not everyone who presents at a health facility with a fever will have malaria, particularly in low endemic countries — and this situation will only become more common as progress is made towards malaria elimination. What should clinicians do when the malaria test is negative? The default answer is often a course of broad-spectrum antibiotics, but if the fever is due to a virus, such a prescription will not only be ineffective, but may also contribute to the development of antimicrobial resistance. FIND is taking a holistic approach.

“Diagnostic integration for fever and malaria enables us to start with the patient, not the disease,” notes Dr Dittrich. “Yes, there must be a strong focus on breaking the cycle of malaria transmission. But healthcare professionals have a duty to diagnose and treat patients, whatever their illness.” Going forward, better R&D that delivers new diagnostic tools is required — including improved P. vivax diagnostics, as well as tests that can identify both malaria and other diseases at the same time, says Dr Dittrich. “Eliminating malaria is both an urgent priority and a golden opportunity. If we are smart about the diagnostic tools we use to support elimination, we can help all patients with fever to access the healthcare they need.” Tony Greenway

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Bone marrow studies are key to blocking malaria Bringing together scientists from various disciplines is helping to develop novel ways to tackle the parasites that cause malaria with new tools, drugs and vaccines.

cientists in Glasgow are aiming to halt the spread of malaria by tackling malaria-causing parasites in their human hiding places. “The parasite that causes malaria lodges in various tissue niches where it causes disease,” says Professor Marti, a parasitologist at the Wellcome Centre for Integrative Parasitology (WCIP) at The University of Glasgow Institute of Infection, Immunity and Inflammation. Marti is working mainly with Plasmodium falciparum, the human parasite that caused over 435,000 malaria-related deaths in 2017. Bone marrow is the headquarters for malaria infection and transmission “The parasite travels via the blood and binds to the walls of blood vessels (vasculature). Discovering that the extravascular niche of the human bone marrow was also a hiding place for Plasmodium parasites was a surprise," says Marti, lead author on the 2014 study that resulted in the discovery. “Even more intriguingly, we found that the bone marrow is also the major place where transmission stages mature until they are ready to be picked up by a mosquito. "Knowing that the bone marrow is MEDIAPLANET

the headquarters for parasite growth and transmission opens up a whole new field for research," says Marti. "Why does the parasite go to the bone marrow and how does it survive in this place without being attacked by the immune system?" Great success in malaria elimination amid warning signs Ongoing efforts for malaria elimination and eradication had brought down infections from 260 million to just over 200 million and fatal cases from one million to about 400,000 between 2000 and 2015. However, since then, progress has stalled and there is concern of a rebound. “This is a critical time to maintain the momentum. When the previous campaign was abandoned in the 1960s it resulted in a huge resurgence of cases.” "Our research focuses on closing a knowledge gap in the malaria transmission cycle, as a basis for efforts to reduce or completely block transmission from humans to mosquitos," says Marti. Multi disciplinary teams to understand parasites’ lifestyle Three years ago, Marti came to WCIP

“Bringing together people with state-of-the art skills, excellent technology, resources and collaboration opportunities means moving further, faster.” to continue his research. "With the combination of in vitro studies and field work, in particular in Malawi, we have started to understand the hidden stages of parasites' lives," he says. The WCIP has been essential to this. "It brings together a critical mass of people from multiple disciplines, and attracts the best researchers, students, collaborators and attention from funders," says Marti. "Here we have experts in clinical research, immunology and computational biology, epidemiology and vector biology. Access to bioengineering skills means we can develop a model of bone marrow on a chip to study the parasite interactions in the marrow under controlled in vitro conditions.” "Bringing together people with state-of-the art skills, excellent technology, resources and collaboration opportunities means moving further, faster."

PROFESSOR MATTHIAS MARTI Wellcome Centre for Integrative Parasitology (WCIP), The University of Glasgow Institute of Infection, Immunity and Inflammation

Targeting parasites in the bone marrow, or before it reaches it Marti identifies at least three ways that WCIP research could lead to new ways to tackle malaria - with drugs, vaccines, and earlier diagnosis. "If we can prevent the parasites going into the marrow, or trap them there, we can block the transmission cycle. Alternatively, if we can help the body flush the parasite-infected red blood cells out via the spleen, we will also have a way forward," he says. Old or otherwise altered blood cells are normally cleared from the body by the spleen, but this does not usually happen with those infected by malaria parasites. "If we can create a vaccine that acts against the proteins on the infected red blood cells then they could be cleared by the immune system, or they may be prevented from binding within the bone marrow," he says. "Also, we could possibly develop diagnostic markers that indicate the presence of the parasites in the marrow before they get detected in the blood and get to the next stage of the cycle," he says. Bone marrow studies may also identify ways to make anti-malarial drugs more effective.

"Cancer studies show that bone marrow is less accessible to drugs because of the low blood flow. If we can find a method of reaching the parasites in the bone marrow more efficiently, we could make the drugs more effective," says Marti. The future needs a funding pipeline "Malaria is far from eradication and maintaining a research and drug discovery pipeline is essential in our fight to get rid of this deadly disease. "Here we are among the world's leading places to do malaria research, and we are on our way towards creating new tools to tackle malaria."