Transcript Introduction and Comments on Measles Genotype Distribution and

Session 3: Molecular Epidemiology
Introduction
Paul Rota
Centers for Disease Control
Accelerating Progress towards Measles and Rubella Elimination
Hotel Royal, Geneva, Switzerland, 21-23 June 2016
*The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and
Prevention.
National Center for Immunization & Respiratory Diseases
Division of Viral Diseases
Lessons Learned from > 20 years of Genetic Characterization of
Measles Viruses: 1
• All vaccines strains are in genotype A
• Wild-type viruses in genotype A no longer circulate
• Sequence information allowed development of RT-PCR based
assays for rapid confirmation of vaccines reactions
National Center for Immunization & Respiratory Diseases
Division of Viral Diseases
Lessons Learned from > 20 years of Genetic Characterization of
Measles Viruses: 2
• No evidence for selective pressure on the H protein based on
measurement of rates on nonsynonymous/synonymous amino acid
substitutions
• Site directed mutagenesis of the measles H protein shows structural
constraints needed for binding to SLAM and nectin-4
• Unlikely that antigenic drift will compromise vaccine efficacy
National Center for Immunization & Respiratory Diseases
Division of Viral Diseases
Lessons Learned from > 20 years of Genetic Characterization of
Measles Viruses: 3
• Genetic characterization allows tracking of viral transmission pathways
• Extended sequencing windows will be needed to increase the
resolution of molecular epidemiologic studies
• Change in apparent geographic restriction of some genotypes
• Genotype B3, once restricted to African countries, now has a
global distribution
• Genotype D8, endemic in India, now has a global distribution
• Genotype H1, still endemic only in China
National Center for Immunization & Respiratory Diseases
Division of Viral Diseases
Lessons Learned from > 20 years of Genetic Characterization of
Measles Viruses: 4
• In countries that have eliminated measles, the pattern of genotypes
reflects the sources of imported virus
• Lack of endemic genotype is an essential criterion for verification
of elimination
• Countries with endemic measles have multiple, co circulating lineages
of measles virus
• In countries where measles has been reintroduced, often only a single
lineage is detected
National Center for Immunization & Respiratory Diseases
Division of Viral Diseases
11 Wild-type Genotypes Detected Since 2005: 6 Still
Circulating
Genotype 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014
B2
B3
D11
D4
D5
D6
D7
D8
D9
G3
H1
National Center for Immunization & Respiratory Diseases
Division of Viral Diseases
Lessons Learned from > 20 years of Genetic Characterization of
Measles Viruses: 5
• There is an apparent decrease in genetic diversity of circulating
measles viruses based on a decrease in the number of genotypes
detected
• Shift in genotypes over time in various regions
National Center for Immunization & Respiratory Diseases
Division of Viral Diseases
What Does the Decreasing Genetic Diversity of Measles Viruses Tell Us?
• As the incidence of measles decreases the number of co-circulating
lineages decreases.
• Can this decrease be used to measure the effectiveness of
vaccination programs?
• The shift of genotypes and decrease in number of circulating genotypes
suggests that measles transmission is interrupted frequently. However, as
the number of measles susceptible individuals in increases, the
country/region is reseeded by imported viruses.
• Though interruption of transmission has been suggested by epidemiologic
data in the past, the more recent application of molecular epidemiology has
helped to document these interruptions. Examples:
• Europe (C2, D6, D4, now D8 and B3)
• The Philippines, 2000-2015, interruption of genotype D3
National Center for Immunization & Respiratory Diseases
Division of Viral Diseases
Measles Genotypes In the Philippines
2014-2015
Genotype B3
introduced,
genotype B3 and D9
continues to
circulate and cause
outbreaks
Measles cases by year, Philippines, 2000-2014
70000
Number of measles cases
60000
50000
40000
30000
2000-2004
Genotype D3 is the
endemic genotype in
the Philippines and
D3 imports to other
countries are traced
to the Philippines
2007-2009
Genotypes D9 and
G3 introduced and
detected in
outbreaks
2004-2005
Measles
campaign in 2004,
no measles
detected in 2005
20000
10000
0
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
2011
Genotype D3 not detected globally after 2004
National Center for Immunization & Respiratory Diseases
Division of Viral Diseases
2012
2013
2014
Short Summary
• Genetic characterization of measles virus by the GMRLN has
made substantial contributions to both the biology and
evolution of measles viruses, and has become and integral
prat of routine laboratory surveillance for measles
• The GMRLN needs to continue to build capacity for genetic
characterization of both measles and rubella and to integrate
new testing schemes and new technologies