1/17/2017 Malaria elimination will require… … New tools Science and politics of malaria elimination in the Greater Mekong Subregion …New partnerships Chris Plowe MD MPH FASTMH Frank M. Calia MD Professor of Medicine Founding Director, Institute for Global Health Past President, American Society of Tropical Medicine & Hygiene ~~~ Joint International Tropical Medicine Meeting …New ways of thinking ~~~ Bangkok 7 December 2016 “This artemisinin resistance—is it popping, or is it jumping?” Professor Pe Thet Khin, former Minister of Health, Myanmar Nay Pyi Taw ACT treatment failure 46% April 2014 in Western Cambodia Amaratunga et al. Lancet Inf Dis 2016 A wave of Artemisinin resistance “paternity testing” artemisinin resistance? using K13 molecular marker K13 molecular marker map Woodrow et al. Lancet Inf Dis 2015 1
1/17/2017 Need better tools to stratify and K13 migration: Implications forecast malaria risk Many different K13 mutations arose • independently on many different • Myanmar National genetic backgrounds Malaria Control Several resistance mutations have Program seeks to • spread between countries in the “microstratify” malaria Greater Mekong Subregion (GMS) risk at village level Based on this result, 2015 WHO • recommendation: • Local transmission vs. – Containment is not importation? possible • Sources vs. sinks of – Falciparum elimination is transmission? imperative for the GMS WHO recommendations: Mass drug administration (MDA) for GMS …but not screen ‐ and ‐ treat (need better diagnostic tests) http://www.who.int/malaria/publications/atoz/role ‐ of ‐ mda ‐ for ‐ malaria.pdf Limits of detection usPCR PCR RDT Mapping the subclinical malaria reservoir Parasites/mL 16 1000 100K Ultrasensitive low ‐ volume Reverse Transcriptase PCR • Sensitivity: 16 parasites/mL & can detect both Pf & Pv simultaneously – P. falciparum and P. vivax in human + blood samples Transport to lab 0.3mL finger prick Mix with DNA ‐ Ultrasensitive blood in cap tube Extract DNA/RNA RNA shield qPCR Field scalable: No sample processing, no cold chain x 14 days • High throughput pipeline in Yangon: >20,000 samples since 2015 • Concordant with high volume PCR from frozen venous blood • Now achieving same lower limit of detection from dried blood spots • – Better, cheaper, faster Adams et al. Malaria Journal 2015 Zainabadi et al. in preparation 2
1/17/2017 >30,000 samples analyzed in 2016 Serology Department of Medical Research, Myanmar Ministry of Health Antibodies to diverse malaria antigens Serology for malaria surveillance • Extremely high throughput – Thousands of antibody assays on a single microarray the size of a microscope slide • Cost of equipment decreasing ten ‐ fold Array Cam microarray reader 3
1/17/2017 Rangoon University medical students 1987 Burma 1988 Rangoon University medical students 1989 Rangoon University medical students 1988 Myanmar 2011 4
1/17/2017 Building political will and ownership through capacity strengthening in the lab and the field First ever NIH grant in Myanmar Malaria as a catalyst for social change Gates Foundation Partners Meeting Nay Pyi Taw, Myanmar December 2014 Washington DC August 2015 Nay Pyi Taw 2016 Science Science Peace Health 5
1/17/2017 Thanks to Shannon Takala ‐ Harrison Chris Jacob Department of Medical Research ARC3 Collaborators Jason Bailey Myanmar Ministry of Health Andrew Pike Zayar Han ARCE Collaborators Alexa Machikis Hnin Hnin Wai Lwin Sonia Agarwal Kay Thwe Han TRAC Collaborators Andrea Berry Myat Phone Kyaw Mark Travassos Kyaw Zin Thant Matthew Adams Shay Roemmich Defence Services Military Academy Christina Shehata Myanmar Ministry of Defence Cheron Jones Khine Zaw Oo Nicole Eddington Johnson Ye Myat Kyaw Gillian Mbambo Tin Maung Hlaing Biraj Shrestha Sudhaunshu Joshi National Institute of Parasitic Diseases Kayvan Zainabadi Chinese CDC Myaing Nyunt Huang Fang Xiao ‐ Nong Zhou Institute for Genome Sciences University of Maryland Global Malaria Program Joana Silva World Health Organization Amol Shetty Pascal Ringwald Tim O’Connor Community Partners International Department of Geographical Sciences Si Thura University of Maryland College Park Phyo Maung Maung Demian Rybock Aye Aye Khaing Kathleen Stewart Tatiana Loboda Roche Innovation Technology John Tan 6
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