MASTER OF GLOBAL HEALTH 2016-2017 UNIVERSITY OF BARCELONA- ISGLOBAL Tackling Plasmodium knowlesi malaria Landscape of current research in Plasmodium knowlesi Maria Tusell Rabassa Supervisor: Kate Whitfield; Coordinator of the Malaria Eradication Scientific Alliance, ISGlobal Word count: 10119 June 2017 Tackling Plasmodium knowlesi malaria Table of contents List of abbreviations ....................................................................................................................... i Executive summary ....................................................................................................................... 1 1. Background............................................................................................................................ 2 1.1. Malaria .......................................................................................................................... 2 1.2. Plasmodium knowlesi .................................................................................................... 2 1.2.1. Transmission .......................................................................................................... 3 1.2.2. Risk of infection ..................................................................................................... 5 1.2.3. Diagnostics ............................................................................................................ 5 1.2.4. Clinical outcomes and pathophysiology ................................................................ 6 1.2.5. Drugs ..................................................................................................................... 6 1.2.6. Vaccines ................................................................................................................. 7 1.2.7. Parasite genetic diversity ...................................................................................... 7 1.3. Malaria Policy Advisory Committee (MPAC) ................................................................. 7 1.4. MESA Track database .................................................................................................... 8 2. Problem statement ............................................................................................................... 8 3. Objectives .............................................................................................................................. 8 4. Methods ................................................................................................................................ 8 4.1. Creation of a database of the current research in P. knowlesi ..................................... 8 4.1.1. Inclusion/ exclusion criteria .................................................................................. 9 4.1.2. Systematic data collection .................................................................................... 9 4.1.3. Expert validation ................................................................................................. 10 4.2. Publication in the MESA Track database ..................................................................... 10 4.3. Design of an online mapping tool ............................................................................... 11 4.4. Presentation of the landscape analysis to the WHO ERG on P. knowlesi ................... 11 4.5. Analysis of the determined needs as stated in the literature ..................................... 11 5. Study results ........................................................................................................................ 11 5.1. Database of the current research in P. knowlesi ........................................................ 11 5.1.1. Inclusion/ exclusion criteria ................................................................................ 11 5.1.2. Systematic data collection .................................................................................. 12 5.1.3. Expert validation ................................................................................................. 12 5.1.4. Publication in the MESA Track database ............................................................. 14 5.2. Data analysis ................................................................................................................ 14 5.2.1. Landscape analysis .............................................................................................. 19 Tackling Plasmodium knowlesi malaria 5.3. Design of an online mapping tool ............................................................................... 22 5.4. Research gaps .............................................................................................................. 23 5.4.1. Transmission ........................................................................................................ 23 5.4.2. Risk of infection ................................................................................................... 24 5.4.3. Diagnostics .......................................................................................................... 24 5.4.4. Clinical outcomes and pathophysiology .............................................................. 24 5.4.5. Drugs ................................................................................................................... 25 5.4.6. Parasite genetic diversity .................................................................................... 25 5.4.7. Outcomes from the MPAC .................................................................................. 25 6. Discussion ............................................................................................................................ 26 7. Conclusions and recommendations .................................................................................... 28 8. References ........................................................................................................................... 30 9. Acknowledgements ............................................................................................................. 34 10. Annexes ........................................................................................................................... 35 10.1. Annex 1. Expert researchers contacted .................................................................. 35 10.2. Annex 2. Validated and published projects ............................................................. 36 10.3. Annex 3. Ongoing data collection ........................................................................... 53 10.4. Annex 4. Summary of ongoing research grants in P. knowlesi ............................... 61 Tackling Plasmodium knowlesi malaria List of abbreviations ACT Artemisinin-based Combination Therapies APMEN Asia Pacific Malaria Elimination Network ASTMH American Society of Tropical Medicine and Hygiene ERG Evidence Review Group FISH Fluorescent In Situ Hybridization GMP Global Malaria Programme HSPH Harvard T. H. Chan School of Public Health IRS Indoor Residual Spraying LAMP Loop-mediated amplification LLINs Long Lasting Insecticidal Nets LSHTM London School of Hygiene and Tropical Medicine M Macaca malERA malaria Eradication Research Agenda MESA Malaria Eradication Scientific Alliance MOE Ministry of Education MOH Ministry of Health MPAC Malaria Policy Advisory Committee MRCUK Medical Research Council of the United Kingdom NHMRC National Health and Medical Research Council Australia NIH National Institutes of Health P Plasmodium PCR Polymerase Chain Reaction PDP Product Development Partnership PI Principal Investigator RBC Red Blood Cells RCUK Research Councils United Kingdom RDT Rapid Diagnostic Test UI Uncertainty Interval UK United Kingdom USA United States of America WHO World Health Organization i Tackling Plasmodium knowlesi malaria Executive summary Plasmodium knowlesi is the fifth species that can cause malaria in humans and was declared an emerging public health threat in 2004. 13 years later, this species still holds many unanswered questions, such as its transmission mechanism or its complete geographic distribution; threatening the effectiveness of malaria control and elimination strategies. In the last years, the number of cases reported has increased in South-East Asia and P. knowlesi is the first cause of malaria in Malaysia. The aim of this report was to describe the landscape of current research in P. knowlesi, compare it to determined needs and identify the main research gaps. Information related to ongoing research activities was collected, quality checked and validated through systematically searching online databases of grants and through direct contact with expert researchers. 20 projects have been validated and 41 experts have been contacted. The main knowledge gap is determining whether humans are always infected through the natural host or if human to human transmission is taking place in some cases. Being this the case, control and elimination strategies should be adapted in order to be effective. Current research priorities are effective vector control strategies, clinical management guidelines and new diagnostic methods. Unless more research is carried out to fulfil these gaps, we will not have the knowledge and the tools to properly fight against P. knowlesi. 1 Tackling Plasmodium knowlesi malaria 1. Background 1.1. Malaria The World Health Organization (WHO) in its latest World Malaria Report[1] estimated that 91 countries and