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| Preparing for the inevitable: how do we tackle drug resistant malaria? | Preparing for the inevitable: how do we tackle drug resistant malaria? |
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| Tamara Bugembe, paediatric registrar, Bamenda Regional Hospital, Bamenda, Cameroon. @tbugembe | Tamara Bugembe, paediatric registrar, Bamenda Regional Hospital, Bamenda, Cameroon. @tbugembe |
| Improving diagnostics is key to preventing further resistance: This should include not just improving facilities at health centres. We need to educate pharmacists to stop treating patients without a positive test, and educate the public to request a test before treatment. | Improving diagnostics is key to preventing further resistance: This should include not just improving facilities at health centres. We need to educate pharmacists to stop treating patients without a positive test, and educate the public to request a test before treatment. |
| Jörg Möhrle, head of translational medicine, Medicines for Malaria Venture, Geneva, Switzerland | Jörg Möhrle, head of translational medicine, Medicines for Malaria Venture, Geneva, Switzerland |
| We should expect that all drugs will at some time face resistance: When discussing antimalarial drug resistance we have to acknowledge the fact that all drugs will at some stage face resistance. The situation we are facing now is that there are indications that artemisinins, which have been a cornerstone of combination therapy, are losing some of their effects in southeast Asia and that the time until patients are parasite-free is getting longer. There are also indications that cure rates after combination treatment are smaller and that resistance to the non-artemisinin partner drugs might increase. | We should expect that all drugs will at some time face resistance: When discussing antimalarial drug resistance we have to acknowledge the fact that all drugs will at some stage face resistance. The situation we are facing now is that there are indications that artemisinins, which have been a cornerstone of combination therapy, are losing some of their effects in southeast Asia and that the time until patients are parasite-free is getting longer. There are also indications that cure rates after combination treatment are smaller and that resistance to the non-artemisinin partner drugs might increase. |
| Slow supply chains are a barrier: Some of the anti-malaria drugs have short shelf lives (counting from production). If the supply chain into - and in - the countries is slow, patients will receive drugs which may be beyond their shelf life and contain lower drug amounts than required to effectively eliminate all parasites in the body, increasing their risk to select for resistance. | Slow supply chains are a barrier: Some of the anti-malaria drugs have short shelf lives (counting from production). If the supply chain into - and in - the countries is slow, patients will receive drugs which may be beyond their shelf life and contain lower drug amounts than required to effectively eliminate all parasites in the body, increasing their risk to select for resistance. |
| We need to look beyond current partner drugs to artemisinins: Most partner drugs have been met with resistance when used as monotherapy: the drug dose is large and the therapeutic windows are not very large. All this limits our space to move or to add something. As we are still in a situation where in the majority of malaria cases ACT work, we should use the opportunity to look for 'new combinations' instead of adding something. | We need to look beyond current partner drugs to artemisinins: Most partner drugs have been met with resistance when used as monotherapy: the drug dose is large and the therapeutic windows are not very large. All this limits our space to move or to add something. As we are still in a situation where in the majority of malaria cases ACT work, we should use the opportunity to look for 'new combinations' instead of adding something. |
| Kefas Mugittu, director and senior consultant, Muvek Development Solutions Ltd, Dar es Salaam, Tanzania. @kmugittu | Kefas Mugittu, director and senior consultant, Muvek Development Solutions Ltd, Dar es Salaam, Tanzania. @kmugittu |
| We need simple and sensitive diagnostic tools: Malaria transmission has decreased substantially. We are also now observing lower prevalence and densities. Prior to 2005, one would recruit 120 patients meeting study criteria in just 30 days but today that number can be achieved only after 5 months working in the field. As we move towards eradication we need simple and sensitive diagnostic tools to be able to detect asymptomatic and sub-microscopic parasites. To the best of my knowledge molecular tools are so far the most sensitive and best suited ones. | We need simple and sensitive diagnostic tools: Malaria transmission has decreased substantially. We are also now observing lower prevalence and densities. Prior to 2005, one would recruit 120 patients meeting study criteria in just 30 days but today that number can be achieved only after 5 months working in the field. As we move towards eradication we need simple and sensitive diagnostic tools to be able to detect asymptomatic and sub-microscopic parasites. To the best of my knowledge molecular tools are so far the most sensitive and best suited ones. |
| Regulatory authorities need to be supported to tackle fake drugs: The prevalence of fake drugs is one of the major problems that needs more attention as one of the cornerstones in the fight against diseases. These drugs are cheap and therefore attractive to the majority of the poor segments of society. There is a need to support regulatory authorities to be able to quickly and efficiently detect and withdrawal fake drugs or ban their importation. | Regulatory authorities need to be supported to tackle fake drugs: The prevalence of fake drugs is one of the major problems that needs more attention as one of the cornerstones in the fight against diseases. These drugs are cheap and therefore attractive to the majority of the poor segments of society. There is a need to support regulatory authorities to be able to quickly and efficiently detect and withdrawal fake drugs or ban their importation. |
| Prudence Hamade, senior technical adviser, Malaria Consortium, London UK. @fightingmalaria | Prudence Hamade, senior technical adviser, Malaria Consortium, London UK. @fightingmalaria |
| We need better determinants of resistance: Artemisinin-combination therapies (ACTs) still cure patients with malaria but they are taking longer to do so, allowing the resistant parasite which remains when all the non-resistant parasites are cleared to be transmitted to others. Being positive 72 hours after treatment is only a proxy measure of resistance. We need better determinants of resistance and after this is achieved, the ability to make sure the resistant parasites are not passed on to others. | We need better determinants of resistance: Artemisinin-combination therapies (ACTs) still cure patients with malaria but they are taking longer to do so, allowing the resistant parasite which remains when all the non-resistant parasites are cleared to be transmitted to others. Being positive 72 hours after treatment is only a proxy measure of resistance. We need better determinants of resistance and after this is achieved, the ability to make sure the resistant parasites are not passed on to others. |
| New approaches to prevention are needed: Malaria Consortium is looking at impregnated clothing such as impregnated wrist and ankle bands as used by the US military for migrant workers. | New approaches to prevention are needed: Malaria Consortium is looking at impregnated clothing such as impregnated wrist and ankle bands as used by the US military for migrant workers. |
| Accessing migrant groups is a big challenge to resistance containment: Africa and Asia are undergoing very rapid development which attracts workers to infrastructure and agricultural development projects. As drug usage goes up in Africa (although use of ACTs to treat malaria remains low in many countries) spontaneous resistant parasites may develop as well as those imported by migrants. I think the international community needs to have a clear plan of how to detect and manage these parasites and strong advocacy to tell the world that malaria will come back with a vengeance if control efforts are relaxed. | Accessing migrant groups is a big challenge to resistance containment: Africa and Asia are undergoing very rapid development which attracts workers to infrastructure and agricultural development projects. As drug usage goes up in Africa (although use of ACTs to treat malaria remains low in many countries) spontaneous resistant parasites may develop as well as those imported by migrants. I think the international community needs to have a clear plan of how to detect and manage these parasites and strong advocacy to tell the world that malaria will come back with a vengeance if control efforts are relaxed. |
| Georgina Humphreys, researcher, World Wide Antimalarial Resistance Network (WWarn), Oxford, UK. @WWARN | Georgina Humphreys, researcher, World Wide Antimalarial Resistance Network (WWarn), Oxford, UK. @WWARN |
| Getting the correct dosage is crucial: It is also important to get the correct dosing of each drug specific for the patient's body weight. This will prevent under or over dosing which we know has taken place in the past. | Getting the correct dosage is crucial: It is also important to get the correct dosing of each drug specific for the patient's body weight. This will prevent under or over dosing which we know has taken place in the past. |
| Resource: | Resource: |
| WWarn have launched a parasite clearance estimator which standardises the method to assess the clearance of parasites from the blood. Data collected from patients treated with any drugs can be run through our tool. However, comparisons between patients treated with different drugs cannot be made, and it is difficult to distinguish which drug is related to slow clearance unless monotherapy is used. | WWarn have launched a parasite clearance estimator which standardises the method to assess the clearance of parasites from the blood. Data collected from patients treated with any drugs can be run through our tool. However, comparisons between patients treated with different drugs cannot be made, and it is difficult to distinguish which drug is related to slow clearance unless monotherapy is used. |
| WWarn's antimalarial quality surveyor displays published data on drug quality and may serve as a useful source of the information the community has to date. | WWarn's antimalarial quality surveyor displays published data on drug quality and may serve as a useful source of the information the community has to date. |
| Sanjeev Krishna, professor of molecular parasitology and medicine, St George's, University of London, England. @Nanomal | Sanjeev Krishna, professor of molecular parasitology and medicine, St George's, University of London, England. @Nanomal |
| We need a more precise way to confirm resistance: The current view is that prolonged parasite clearance times seen with ACTs in certain parts of the world are sufficient to define resistance. We know that many factors influence parasite clearance times in patients, so I would argue that we need much more than this to confirm resistance. We need measures of resistance in the parasites themselves, as well as seeing treatment failures with artemisinins on their own. Otherwise, what we are seeing is the treatment failure of ACTs but not pure artemisinin resistance. | We need a more precise way to confirm resistance: The current view is that prolonged parasite clearance times seen with ACTs in certain parts of the world are sufficient to define resistance. We know that many factors influence parasite clearance times in patients, so I would argue that we need much more than this to confirm resistance. We need measures of resistance in the parasites themselves, as well as seeing treatment failures with artemisinins on their own. Otherwise, what we are seeing is the treatment failure of ACTs but not pure artemisinin resistance. |
| Artemisinin monotherapy trials are important: Artemisinin monotherapy trials for research should be key components in the tool box for evaluating and identifying true artemisinin resistance. | Artemisinin monotherapy trials are important: Artemisinin monotherapy trials for research should be key components in the tool box for evaluating and identifying true artemisinin resistance. |
| Angus Spiers, deputy director, malaria and child survival department, Population Services International (PSI), Washington DC, USA. @PSIimpact | Angus Spiers, deputy director, malaria and child survival department, Population Services International (PSI), Washington DC, USA. @PSIimpact |
| Having an informed patient is the goal: ACTwatch data suggests practitioners are extremely influential in treatment outcome, probably because the patient is usually uninformed and trusts their judgement. Raising patient awareness of the issues of diagnosis and effective treatment (eg not all fevers are malaria) as well as looking at the incentives for the provider (be they financial, supervisory, regulatory) are key to effective case management, particularly in the private sector. | Having an informed patient is the goal: ACTwatch data suggests practitioners are extremely influential in treatment outcome, probably because the patient is usually uninformed and trusts their judgement. Raising patient awareness of the issues of diagnosis and effective treatment (eg not all fevers are malaria) as well as looking at the incentives for the provider (be they financial, supervisory, regulatory) are key to effective case management, particularly in the private sector. |
| The next frontier is increasing the role of the private sector: Many people access treatment from private providers but the availability of quality diagnosis and treatment (for malaria or anything else) is not consistent. I think our Unitaid programme will significantly help to build evidence for implementation of rapid diagnostic tests at scale in the private sector that can be used by WHO to develop evidence based policy recommendations. | The next frontier is increasing the role of the private sector: Many people access treatment from private providers but the availability of quality diagnosis and treatment (for malaria or anything else) is not consistent. I think our Unitaid programme will significantly help to build evidence for implementation of rapid diagnostic tests at scale in the private sector that can be used by WHO to develop evidence based policy recommendations. |
| Colin James Sutherland, reader in parasitology, London School of Hygiene and Tropical Medicine, London, UK | Colin James Sutherland, reader in parasitology, London School of Hygiene and Tropical Medicine, London, UK |
| ACTs afford us more time, but not much: Our experience tells us that the speed with which parasite populations develop the new gene variants needed to evade drugs has led to eventual failure of all single drug agents. We have not yet seen major collapse of efficacy of any two drug combination for malaria treatment, where neither drug has been previously used alone. We probably have a little time with the ACTs, but may see bonafide combination failure quite soon with artemether-lumefantrine and probably artesunate mefloquine in Asia. | ACTs afford us more time, but not much: Our experience tells us that the speed with which parasite populations develop the new gene variants needed to evade drugs has led to eventual failure of all single drug agents. We have not yet seen major collapse of efficacy of any two drug combination for malaria treatment, where neither drug has been previously used alone. We probably have a little time with the ACTs, but may see bonafide combination failure quite soon with artemether-lumefantrine and probably artesunate mefloquine in Asia. |
| The three key challenges are diagnostics, logistics and politics: I remain optimistic that we will find ways to keep ACT efficacy up in Africa for some time to come, and that, with continued support for MMV and other pipeline pushing initiatives, the newer compounds may just make it to the field in time. The three key challenges remain in diagnostics, logistics and politics. | The three key challenges are diagnostics, logistics and politics: I remain optimistic that we will find ways to keep ACT efficacy up in Africa for some time to come, and that, with continued support for MMV and other pipeline pushing initiatives, the newer compounds may just make it to the field in time. The three key challenges remain in diagnostics, logistics and politics. |
| Jasson Urbach, director, Africa Fighting Malaria, Durban, South Africa | Jasson Urbach, director, Africa Fighting Malaria, Durban, South Africa |
| Several treatment options should be available at the same time: We should assume that resistance is inevitable, therefore several treatment options should be available at the same time (and even same place) and we should continue to look for novel drugs not affected by existing resistances. | Several treatment options should be available at the same time: We should assume that resistance is inevitable, therefore several treatment options should be available at the same time (and even same place) and we should continue to look for novel drugs not affected by existing resistances. |
| Resource: | Resource: |
| My organisation Africa Fighting Malaria (AFM), have released a report entitled Antimalarial drug quality in the most severely malarious parts of Africa – a six country study . We conducted tests to check the efficacy of drugs collected in Ghana, Nigeria, Tanzania, Rwanda, Kenya and Uganda. Over 200 samples of antimalarial treatments were collected and tested to see if they met international standards. Overall, 35% of the samples were substandard and failed the test. It was also found that 33% of the treatments tested were artemisinin monotherapy drugs – 42% of these failed the test. At least 78% of the monotherapy drugs collected were manufactured after the WHO appealed for monotherapy production to stop. | My organisation Africa Fighting Malaria (AFM), have released a report entitled Antimalarial drug quality in the most severely malarious parts of Africa – a six country study . We conducted tests to check the efficacy of drugs collected in Ghana, Nigeria, Tanzania, Rwanda, Kenya and Uganda. Over 200 samples of antimalarial treatments were collected and tested to see if they met international standards. Overall, 35% of the samples were substandard and failed the test. It was also found that 33% of the treatments tested were artemisinin monotherapy drugs – 42% of these failed the test. At least 78% of the monotherapy drugs collected were manufactured after the WHO appealed for monotherapy production to stop. |
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