Thematic areas and Case Studies
1. Drug resistance
2. Insecticide resistance
3. Driving innovation (Google Earth, mobile technology, AI, drones)
4. Medical innovation
5. Malaria in complex settings
1. Drug resistance
Anti-malarial drug resistance is a threat to malaria control and has significant implications for global public health. Resistance has a major impact on the cost of global malaria control due to the need for new drugs and the costs of treatment failures.
ACT efficacy is threatened by the emergence of both artemisinin and partner drug resistance, typically resulting in less effective treatment. While there is evidence of artemisinin resistance in the Greater Mekong Sub region including Myanmar and Thailand, increased surveillance systems and improvements to health systems are minimizing the impact.
Developing new medicines to address drug-resistance
In partnership with various organisations, MMV is developing new combination therapies aiming to address the challenge of drug resistance by identifying molecules with novel mechanisms of action and antimalarial activity against all-known resistant parasite strains.
The goal is also to have simpler dosing regimens to improve patient compliance to treatment, which will in turn protect against the development of drug resistance in the future.
Last year, Novartis launched a patient trial for KAF156, a next-generation antimalarial compound with the potential to treat drug-resistant strains of the malaria parasite. This work is done with scientific and financial support from MMV (in collaboration with the Bill & Melinda Gates Foundation).
KAF156 is currently being tested with a new formulation of lumefantrine in a Phase IIb trial. Trial centers are operational in Gabon, Gambia, Kenya, Mali, Mozambique, Uganda, Thailand, and Vietnam with Burkina Faso to be added in June. The trial will be run in a total of 15 sites across nine countries in Africa and Asia.
In partnership with MMV, GSK researches potential therapies to address two pressing needs in malaria drug research: treatments for drug-resistant strains of the malaria parasite and treatments for Plasmodium vivax, the strain of malaria that is predominant in Asia and Latin America.
Low adherence to current standard of care along with emerging resistances to ACTs, mainly observed in the Mekong region, have been identified as primary concerns. To contribute to address these needs, Sanofi is co-developing two compounds with MMV - OZ/Ferroquin (PhIIb): a single dose for uncomplicated Malaria Falciparum, active on resistant strains, and SAR441121 (pre-clinical). To pursue its contribution in achieving a world free of malaria, Sanofi continues investments to bring to market new drugs that meet WHO requirements.
2. Insecticide Resistance
Evidence of resistance to four of the most commonly used insecticide classes used in long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS), has been found in all affected regions except Europe, with the majority being reported in the African region.
Of the 76 malaria endemic countries that reported standard monitoring data for 2010 to 2016, resistance was detected in 61 countries to at least one insecticide in one malaria vector from one collection site. In 50 countries there was resistance to two or more insecticide classes.1
Resistance to pyrethroids – the insecticide class used in all ITNs – is widespread. The proportion of malaria endemic countries that reported pyrethroid resistance (of those that monitored for it) increased from 71% in 2010 to 81% in 2016; 16 of the 72 countries that monitored throughout this period did not detect pyrethroid resistance.2
The prevalence of confirmed pyrethroid resistance differed between regions and was highest in the WHO African and Eastern Mediterranean regions, where it was detected in malaria vectors in over two thirds of all sites monitored.
Case studies
IVCC NgenIRS, shaping markets & saving lives
Addition of new product allows for improved resistance management through rotation while increasing competition
SumiShield® 50WG, the second 3rd generation indoor residual spraying (3GIRS) insecticide was added to the IVCC NgenIRS project, after WHO prequalification (PQ) listing in Oct 2017. This addition created much needed competition in the marketplace.
Competition leads to lower prices and makes it possible for countries to implement sub-national rotation with a new class of chemistry for vector control, in line with the Global Plan for Insecticide Resistance Management in malaria vectors (GPIRM) and national insecticide resistance management (IRM) strategies.
In 2018 half of NgenIRS partner countries will begin rotation with SumiShield® 50WG. Actellic® 300CS was the first 3GIRS product introduced and will now form part of the sub-national rotation strategies in African partner countries.
In addition to the currently available products Bayer's 3GIRS product, Fludora™ Fusion is currently undergoing the final stage of trials required for WHO prequalification and evaluation by the PQ team will follow shortly after. BASF's Sylando® 240SC is under WHO-evaluation.
In partnership NgenIRS delivers on its mission
The NgenIRS project, a 4-year $65.1 million Unitaid-funded market shaping initiative, launched in early 2016 to expand the use 3GIRS products. IVCC is working in partnership with the U.S. President's Malaria Initiative (PMI), The Global Fund, Abt Associates, PATH and African Malaria Control/Elimination Programmes and multiple insecticide manufacturers to deliver on this mission.
Since 2016 NgenIRS has expanded the number of countries it supports from 4 to 14. As a result of co-payments and volume guarantees, malaria programmes in partner countries have been able to procure over 4 million units of 3GIRS at $15, a significant reduction from the $23.50 starting price in 2016. Over 1 million additional units have been procured by partners outside of the co-payment mechanism at a significant discount, in return for volume guarantees to manufacturers. As a result, implementing partners have been able to procure approximately 1.7 million additional units of 3GIRS and protect an estimated 15 million more people than would have been possible if they had been paying full price.
Demonstrating the impact and cost-effectiveness of 3GIRS
For products to be accepted by countries and implementation partners, evidence on their cost effectiveness and impact is imperative. A cluster randomized control trial, co-funded by the President's Malaria Initiative (PMI), is underway in Zambezia province, Mozambique. In addition, retrospective evaluations of the impact of IRS are being supported in Zambia, Mali, Ghana, and Uganda and will shed more light on the incremental cost and impact of IRS in these settings.
Results from Mali show that in 2014, 3GIRS with Actellic® 300CS was a good public health investment. In Barouéli District more than 250,000 people were protected and over 76,000 cases of malaria were prevented. In neighbouring Bla District, where both IRS and seasonal malaria chemoprevention interventions were rolled out simultaneously, preliminary analysis suggests a combined impact of these complimentary strategies. After suspending IRS in 2015 in Bla District, an area with high access to LLINs, a 70% increase in under-5-years-old malaria incidence rates was observed from 2014 -2015. This was significantly greater than the change reported from Barouéli District, where incidence rates remained the same.
Planning for transition and sustainability
The project is now in the process of planning with its partners for the transition of key NgenIRS-funded activities such as country-level and Africa-wide forecast consolidation, establishment of volume guarantees to manufacturers in exchange for reduced prices and the ongoing collection of data to evaluate the impact and cost-effectiveness of 3GIRS in order to ensure continued expansion of use within a competitive and sustainable market. (Source: IVCC)
3. Driving innovation
Using Google Earth and smartphones to track malaria outbreaks
DiSARM is a unique web application that uses Google Earth. Health workers in Botswana and Namibia are using it on tablets and smartphones to predict where malaria outbreaks will happen next.
They can upload their own data on where and when malaria cases have been occurring and combine it with real-time satellite data on weather and other environmental conditions within Google Earth to pinpoint where new cases are most likely to occur.
That way, they can get lifesaving tools to those who need them most -- spray insecticide, distribute bed nets or give antimalarial drugs just to the people who still need them, instead of blanketing the entire country. Pilots are planned for Zimbabwe and South Africa.
Mobile phones improving community health care in Mozambique
In Mozambique, Malaria Consortium is running a programme called upSCALE, which involves using an interactive mobile phone app that covers all community health services. The app supports community health workers to screen new-borns and children for signs of childhood illnesses (malaria, diarrhoea and pneumonia), prompts them to check the child's vaccination status, and offers them treatment and referral recommendations as appropriate. Data is reported in near-real time to health officials, informing them of disease outbreaks and low stock levels.
Alongside this, Malaria Consortium is working in collaboration with the Mozambican Ministry of Health and UNICEF to develop a digital strategy to strengthen health systems and community health delivery, which is to be scaled up in all provinces to create a national mHealth system led by the Ministry of Health. By doing so, Mozambique will be the first country to scale up a digital health strategy to this extent.
Data mapping transforming the fight against malaria in Zambia
Visualize No Malaria is an initiative of the Government of Zambia, PATH, the Tableau Foundation, and a number of other technology partners. Together, this coalition of tech companies are each applying their tools, resources and expertise in a united pursuit of malaria elimination. The result? Front line health workers are being armed with data visualization tools and analytical skills to improve reporting and to make informed decisions on managing malaria and deploying appropriate resources in their area.
Using Artificial Intelligence to reduce malaria burden
Zenysis Technologies, a Big Data and Artificial Intelligence software company headquartered in San Francisco, has developed a powerful analytics platform that allows governments of malaria endemic countries unprecedented insight into the best ways to reduce the malaria burden, to effectively allocate resources and ultimately save lives.
The platform can be used to help governments identify areas of high risk with unprecedented precision, identify potential outbreaks months ahead of time, and save millions of pounds by intelligently allocating resources in a targeted, data-driven way.
Zenysis is working with the Federal Ministry of Health in Ethiopia (FMOH) which can now generate insights on malaria control for all +800 districts individually within seconds. The platform also leverages Artificial Intelligence to generate district-level forecasts of malaria incidence in Ethiopia with single-digit accuracy, a significant new breakthrough with the potential to transform malaria control in Ethiopia and beyond.
Zenysis is expanding its work into other malaria endemic countries in Africa
Using drones to target insecticide spraying in Zanzibar
Wales' Aberystwyth University and Zanzibar's Malaria Elimination Programme have partnered on an initiative that uses drones to survey malaria hot spots and identify the water-laden areas where malaria-carrying mosquitoes are likely to breed.
A popular off-the-shelf drone, the DJI Phantom, captures images of the water bodies over a large area which are then used to create precise and accurate maps of potential habitats. The imagery can be processed and analysed on the same afternoon to locate and map water bodies.
The next step is to bring the drone imagery to smartphones to both guide the insecticide spraying teams and track their progress. Instead of having only a general idea of where to go, sprayers can make a beeline for affected areas and report back when they're done.
Drones, monkey behaviour and malaria
London School of Hygiene and Tropical Medicine researchers are pioneering the use of drones for health and ecological research. They are being used to provide highly accurate information on changes to land, such as deforestation or changing types of agriculture to help understand the impact on the movement and distribution of people, animals and insects that carry disease.
This is a significant innovation as drones can repeatedly collect detailed information in real time at relatively low cost. The Monkey Bar project in Malaysia is a large multi-disciplinary study into a malaria parasite which was previously thought to only affect macaque monkeys and is now increasingly found to be affecting people. The research, funded by The UK Research Council Living with Environmental Change Initiative, involves using a drone to map changes in human, mosquito and monkey habits and correlating how those changes affect human infection.
Data gathered by the drone is being used alongside hospital cases, data on mosquito abundance and monkey and human movement to understand risks. In addition to Monkeybar, researchers are also exploring opportunities to map public health emergencies and estimating population sizes in hard to reach places. (more info https://www.lshtm.ac.uk/newsevents/news/2014/drones%20monkeys%20malaria.html
Innovative financing partnership for malaria elimination in Asia Pacific, M2030
Eliminating malaria in Asia by 2030 is possible and M2030 is envisioned as a movement contributing to this goal. Launched by the Asia Pacific Leaders Malaria Alliance (APLMA), M2030 is a groundbreaking partnership that raises funds and inspires corporate action to end malaria in Asia.
For the first time ever, consumers and some of the largest businesses in Asia are joining forces. By combatting malaria in their own countries, they address the regional problem posed by drug-resistant malaria before it becomes a global issue.
M2030 partners include a select group of Asia's leading business, including Dentsu Aegis Network, the DT Group of Companies (Thailand), Shopee (the leading e-commerce platform in Southeast Asia and Taiwan), Tahir Foundation (Indonesia), Yoma Strategic Holdings (Myanmar) and The Global Fund.
More M2030 partners are joining the movement. Partners gain the right to use the M2030 trademark and develop M2030 products and services. In return, they run consumer-focused campaigns and raise funds to end malaria in Asia. 100 per cent of funds raised by M2030 will go to The Global Fund to finance malaria programmes in the region.
With M2030 partners and influencers, this initiative will raise millions of dollars for malaria programmes and reach at least 46 million people with M2030 campaigns.
Source: M2030 campaign. For more information, visit www.m2030.org
Web-based scorecard for African leaders
The African Leaders Malaria Alliance (ALMA) was launched in September 2009 and comprises 49 African heads of state and government working to end malaria by 2030. The ALMA Scorecard for Accountability & Action is a mechanism through which ALMA Heads of State and Government track progress on malaria control and tracer maternal, newborn and child health interventions within their own countries and across the African continent. It was developed at their request for a management tool to increase transparency and accountability around national action. In 2018, ALMA added neglected tropical diseases (NTDs) to the ALMA Scorecard.
Following the success of the ALMA Scorecard for Accountability & Action, ALMA was requested by countries to support the development of country-owned, country-led accountability and action management scorecards for malaria control and elimination.
Country Malaria Scorecards enhance accountability and drive action to improve performance for malaria, providing a tool to easily track and compare performance sub-nationally for key interventions, while enhancing performance transparency, strengthening accountability and encouraging action. With Head of State and Government, as well as Ministerial leadership, the scorecards at national, and subnational level help ensure African countries meet their targets.
Hosted on a web platform and integrated in health management information systems, the scorecard is updated quarterly and gathers readily available data, identifies bottlenecks and captures action. This scorecard mechanism also supports country and partner collaboration and coordination to accelerate efforts to eliminate malaria.
Performance is reviewed at the highest levels, including Head of State and Ministerial, and is increasingly disseminated to the public. For more details, please logon to www.alma2030.org.
4. Medical innovation
Rectal artesunate product for children with severe malaria receives WHO approval
Indian pharmaceutical company, Cipla Ltd, has received approval from WHO's Prequalification Programme for their 100mg rectal artesunate suppositories (RAS), for the pre-referral management of severe malaria. The approval will expand access to the drug and help save the lives of thousands of children who contract severe malaria.
This much-awaited approval, achieved with support from Medicines from Malaria Venture and funding from Unitaid, will enable countries to procure the life-saving suppository with donor funds and distribute it to rural areas, where it is most needed.
Severe malaria can kill within 24 hours if left untreated, and travel times to hospital can be long, particularly for children from remote rural communities.
A single dose of RAS 100mg, given as soon as a presumptive diagnosis of severe malaria has been made, can halve the likelihood of disability and death for young patients living 6 hours or more from a health facility where they can receive recommended severe malaria treatment (WHO TDR 2009 study). This is life changing for children who do not have quick access to injectable artesunate.
To date, Cipla has registered RAS in two high-burden countries and the dossier is under review in a further 14 countries. Close to 150,000 treatments have been distributed to countries by the company. For 2018, orders for RAS have been placed to supply close to a dozen high-burden malaria countries.
First malaria vaccine to be piloted in Ghana, Kenya and Malawi
A malaria vaccine, RTS,S, shown in clinical trials to reduce the risk of developing malaria in young children, will move into pilot implementation in selected areas of Ghana, Kenya and Malawi, starting later this year.
The three countries have achieved significant reductions in malaria mortality through the deployment of currently available prevention and control measures, but still face a substantial disease burden from malaria. They were also involved in the Phase 3 efficacy and safety trial of the vaccine.
The country-led implementation programme is coordinated by the World Health Organization (WHO). Ministries of Health in each of the pilot countries will lead the vaccine introduction, supported by WHO and in collaboration with in-country and international partners, including PATH, a non-profit organization that also supported the development of the vaccine. GSK, which developed and manufactures the vaccine, is donating up to 10 million doses of RTS,S for use in the programme.
Implementation plans call for RTS,S to be administrated to approximately 360 000 children annually in selected areas of Ghana, Kenya and Malawi, through their immunization programmes. WHO recommended pilot implementation to evaluate the feasibility of delivering the required four doses of RTS,S, the vaccine's potential role in reducing childhood mortality, and its safety in the context of routine use, before considering wider-scale introduction.
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Pilot implementation will be complemented by additional studies, led by GSK, to continue monitoring the vaccine's safety and effectiveness in routine use. PATH is providing technical and project management support for the programme and is leading studies on healthcare utilization and the economics of vaccine implementation.
First conceived in the 1980s, the RTS,S malaria vaccine has undergone a series of studies, including a Phase 3 efficacy and safety trial that involved approximately 15,000 infants and young children at 11 sites in seven African countries.
Since the end of the Phase 3 trial in early 2014, the data generated on the vaccine have been reviewed by two leading health authorities. First, RTS,S received a positive scientific opinion from the European Medicines Agency, Europe's regulatory authority, in July 2015. Then, WHO issued a position paper in January 2016, recommending pilot implementation of the vaccine in selected areas of sub-Saharan Africa.
RTS,S is the only malaria vaccine that has shown a protective effect against malaria among young children in Phase 3 clinical trials. The pilot in sub-Saharan Africa is an important step towards a vaccine being available alongside the tools currently recommended for prevention, diagnosis, and treatment of malaria.
5. Malaria in complex situations
Complex situations, whether as a result of natural factors such as excessive rains, flooding or earthquakes, or human-made ones such as conflict and political crises, often disrupt service delivery, and the implementation of interventions. Where the ecological conditions are suitable for malaria, such situations often result in increased malaria transmission, disease and deaths. The burden of disease can be exceptionally high among the most vulnerable, such as children and pregnant women, especially when worsening nutritional conditions impair their capacity to fight the disease.
Fears for malaria outbreak in Rohingya camps as Monsoon rains approach
As the Monsoon season in Bangladesh is just weeks away, there are fears of a malaria outbreak amongst the estimated 650,000 Rohingya Muslims living in makeshift refugee camps in the Chittagong Hills and Cox Bazaar area of Bangladesh, who have crossed the border from Rakhine state in Myanmar. The combination of poor sanitation, emergency sub-standard housing and approaching rains provide the perfect conditions for a significant outbreak, especially amongst the large population of pregnant women and children under five. (Source: Malaria Consortium)
Malaria and conflict in Borno State
The eight-year conflict in Borno State in north-eastern Nigeria has had a huge impact on malaria in the country, destroying and damaging 60% of the health facilities and leading to the displacement of 3.7 million people, all of whom are at risk of malaria.
In 2017 WHO estimated that half of the deaths in Borno state were due to malaria, more than all other causes of death combined.
In collaboration with the Borno State Ministry of Health, WHO is now aiming to dramatically reduce malaria mortality in the region, particularly among children under five, by:
- Strengthening surveillance systems to monitor cases and outbreaks of malaria;
- Increasing people's access to care in clinics and to health facilities;
- Spraying insecticides and distributing bed nets as part of vector control; and
- Administering malaria drugs to children under 5 every month.
Effective surveillance of malaria cases and deaths is essential for identifying which areas or population groups are most affected by malaria, and for targeting resources to communities most in need and ensuring smart investments. Such surveillance also alerts ministries of health to epidemics, enabling control measures to be intensified when necessary.
Cases and deaths from the surveillance system reported by countries are often from the public health sector, predominantly through passive case detection. In elimination settings, data on cases may also be recorded during active case detection. Often, data from the private sector remain sparse, and in countries with moderate to high transmission it is possible that a substantial proportion of patients who do not seek care remain undocumented by the surveillance system.
A strong surveillance system therefore requires high levels of access to care and case detection, and complete reporting by all health sectors.
Innovative methods are now being employed to gather information, using mobile phones, software mapping and drones. See below for some examples. (Source: WHO)
