View the slides of a tribute to the late Alan Magill by ASTMH Past President Christopher V. Plowe, MD, MPH, FASTMH, during WRAIR's inaugural Magill Symposium on June 23 in Silver Spring, MD.

1. Fulfilling the Legacy and Vision of Alan Magill:
Malaria Delenda Est
Chris Plowe MD MPH FASTMH
Institute for Global Health, University of Maryland School of Medicine
Baltimore, Maryland USA
~~~
Alan Magill Malaria Symposium
~~~
WRAIR, Silver Spring, MD
23 June 2016

4. Malaria can be eliminated
COL John Boyd Coates, Jr., MC, USA
http://history.amedd.army.mil/booksdocs/wwii/Malaria/default.htm

5. • Control – reduction of disease incidence and burden to the
point where it is no longer a public health priority
• Elimination – interruption of transmission of the pathogen
and a fall in disease incidence to zero in a defined
geographical area
• Eradication – interruption of pathogen transmission
worldwide & fall in disease incidence to zero
• Extinction – disappearance of the pathogen from the planet
Definitions

6. 100 years
pre-eradication
Source:
Global malaria control and elimination
WHO 2008

7. Eradication era
1945 - 1977
Source:
Global malaria control and elimination
WHO 2008

8. Control era
1977 - 2007
Source:
Global malaria control and elimination
WHO 2008

9. Shrinking the
malaria map
• 62 countries have
eliminated malaria
• 96 countries still have
malaria
• 35 countries now
actively committed to
eliminating malaria
• 9 countries are close
to elimination

10. Today’s tools for malaria control,
elimination, eradication:
• LLIN = Long-lasting insecticide-treated nets
• IRS = Indoor residual spraying (DDT)
• IPT = Intermittent preventive treatment for pregnant women, infants,children
• ACT = Artemisinin-based combination therapy
~~~ Tomorrow’s tools?~~~
• SERCaP = Single Encounter Radical Cure & Prophylaxis
– (Targeted) Mass Drug Administration
– Focal/Mass Screening and Treatment
• VIMT = Vaccines that interrupt malaria transmission
• New surveillance tools?
• Transgenic mosquitoes?
• …?

12. Current tools:
Long-lasting insecticide-impregnated nets
WHO/S. Hollyman
C. Plowe

13. Elimination  eradication

14. Can malaria be eradicated?
Yes…
…eventually
…with an end to poverty and strife.
and/or
with new and better tools that can be
implemented everywhere.

15. What has worked for eradicating
other diseases?

16. Eradication programs
• Failure
Hookworm
Yellow fever
Yaws
Malaria
• Success
Smallpox
Polio (Americas)
Measles (Americas)
• Near success
Polio
Guinea worm
Rinderpest
Rubella (Americas)
DA Henderson, malERA Zenith Week, March 2010

17. Eradication programs
• Failure
Hookworm
Yellow fever
Yaws
Malaria
• Success
Smallpox
Polio (Americas)
Measles (Americas)
• Near success
Polio
Guinea worm
Rinderpest
Rubella (Americas)
DA Henderson, malERA Zenith Week, March 2010
Vaccines: Principal tool

18. Breman and Plowe J Inf Dis 2009
Modified from PATH Malaria Vaccine Initiative
Malaria vaccines

19. Is RTS,S an
elimination
vaccine?

22. R A Seder et al. Science 2013;341:1359-1365
Published by AAAS
IV PfSPZ Vaccine had 100% protective
efficacy in highest dose group

23. Snowden “The Conquest of Malaria”
2006
Malaria elimination in Italy 1900-1962
The logistical challenges are considerable…
Mali 2012

24. …but a frozen live sporozoite vaccine is already
being delivered in liquid nitrogen in Africa
International Livestock Research Institute, Kenya
Theileria parva (East Coast Fever)

26. “This artemisinin resistance—is it popping, or is it jumping?”
Professor Pe Thet Khin, former Minister of Health, Myanmar
April 2014

27. K13 molecular marker map
Woodrow et al. Lancet Inf Dis 2015
A wave of
artemisinin resistance?

28. Artemisinin resistance “paternity testing”
using K13 molecular marker

29. Most common resistance mutation has both
emerged independently (popped) and spread

30. K13 migration: Implications
• Many different K13 mutations arose
independently on many different
genetic backgrounds
• Several resistance mutations have
spread between countries in the
Greater Mekong Subregion (GMS)
• Based on this result, new WHO
recommendation:
– Containment is not possible
– Elimination is imperative for the GMS

31. Malaria as a catalyst
for social change

32. Washington DC August 2015

33. Surveillance & response:
Stratification of malaria risk to guide
elimination interventions
• Myanmar NMCP: Malaria risk stratification at
the township level is inadequate
– Ecological risks of vector exposure, reported clinical
cases
• Goal: Microstratification of malaria risk at village
level
• Identify sources and sinks of migrating parasites
to guide elimination interventions?

34. Gene flow:
Parasite migration patterns
• SNP chip: Genome-wide genotyping
• Coalescent theory to estimate gene
flow magnitude and direction
• 19 sites across Greater Mekong
Subregion
• Aim to identify sources, sinks,
pathways of malaria transmission to
target interventions
Chris Jacob PhD thesis

35. Molecular evolution methods may
provide new tools for mapping
contemporary parasite migration
• Next step: Move from regional to local
mapping to identify sources and sinks of
malaria transmission
• Useful for mapping transmission and spread
patterns of other parasites?

36. Subclinical, submicroscopic malaria reservoir
Malaria elimination may require elimination of all parasites
Demanding more sensitive tools to detect and map low density malaria

37. New WHO recommendations:
MDA is OK, but FSAT & MSAT need better diagnostic tests
http://www.who.int/malaria/publications/atoz/role-of-mda-for-malaria.pdf

39. Hunting for low density
malaria
• 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
• RDT: 100,000 parasites/mL; conventional PCR 1000-5000 parasites/mL)
• Ultrasensitive low-volume Reverse Transcriptase PCR
– Sensitivity: 16 parasites/mL & can detect both Pf & Pv simultaneously
0.3mL finger prick
blood in cap tube
+
Mix with DNA-
RNA shield
Transport to lab
Extract DNA/RNA Ultrasensitive
qPCR
Adams et al. Malaria Journal 2015

40. Mapping subclinical malaria in Myanmar

41. Simply increasing access to diagnosis
and treatment reduces malaria
• Village malaria workers
• Need for integration
especially as burden falls
• Will this be enough to
eliminate?
• Need tools to stratify and
forecast malaria risk and
target interventions

42. Alan Magill, February 2015
Siem Reap, Cambodia

45. Thanks to
Shannon Takala-Harrison
Chris Jacob
Jason Bailey
Andrew Pike
Alexa Machikis
Sonia Agarwal
Andrea Berry
Mark Travassos
Matthew Adams
Nicole Eddington Johnson
Gillian Mbambo
Biraj Shrestha
Kayvan Zainabadi
Myaing Nyunt
Institute for Genome Sciences
University of Maryland
Joana Silva
Amol Shetty
Tim O’Connor
Department of Geographical Sciences
University of Maryland College Park
Demian Rybock
Kathleen Stewart
Tatiana Loboda
Department of Medical Research
Myanmar Ministry of Health
Zayar Han
Hnin Hnin Wai Lwin
Kay Thwe Han
Myat Phone Kyaw
Kyaw Zin Thant
Defence Services Military Academy
Myanmar Ministry of Defence
Khine Zaw Oo
Ye Myat Kyaw
Tin Maung Hlaing
National Institute of Parasitic Diseases
Chinese CDC
Huang Fang
Xiao-Nong Zhou
Global Malaria Program
World Health Organization
Pascal Ringwald
Roche Innovation Technology
John Tan
TRAC, ARC3 & ARCE investigators
Arjen Dondorp, Mark Fukuda, Francois Nosten,
Harald Noedl, Mallika Imwong, Delia Bethell, Youry
Se, Chanthap Lon, Stuart Tyner, David L Saunders,
Charlotte Lanteri, Frederic Ariey, Aung Pyae Phyo,
Peter Starzengruber, Hans-Peter Fuehrer, Paul
Swododa, Nicholas White, Odile Mercereau-
Puijalon, Didier Menard, Paul Newton, Maniphone
Khanthavong, Bouasy Hongvanthong, Wasif A.
Khan