Disease Eradication: Past Successes and Struggles Case Study: Measles, Rubella, and CRS University of Colorado Jon Kim Andrus, MD Adjoint Professor and Director Vaccines and Immunization Center for Global Health Colorado School of Public Health University of Colorado, Denver Denver, Colorado October 2017
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Disease Eradication: Past Successes and Struggles · Important Facts • Vaccines are considered one of the most cost - effective interventions in medicine • The hardest stage of
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Disease Eradication: Past Successes and Struggles
Case Study: Measles, Rubella, and CRS
University of Colorado
Jon Kim Andrus, MDAdjoint Professor and Director Vaccines and ImmunizationCenter for Global HealthColorado School of Public HealthUniversity of Colorado, Denver
Denver, Colorado October 2017
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Published work on definitions
• Task Force for Disease Eradication– Don Hopkins et al
• Dahlem/Strugman formum and conferences– Steve Cochi, Walter Dowdle et al
Eradication - StrungmannForum 2010
Global eradication – the worldwide absence of a specific disease agent in nature as a result of deliberate control efforts that may be discontinued where the agent is judged no longer to present a significant risk from extrinsic sources (e.g., smallpox).
Regional or national eradication – the absence of a specific disease agent in a defined geographic area as a result of deliberate control efforts that must be continued to prevent reestablished endemic transmission (e.g., polio, measles, rubella, guinea worm).
Cochi & Dowdle
Important Facts• Vaccines are considered one of the most cost-
effective interventions in medicine• The hardest stage of eradication is often the last
stage• Eradication initiatives contribute greatly to the
development of infrastructure and capacity to implement strong national immunization programs
• Combining vaccine introduction with strategies that ensure rapid deployment and access will save more lives, faster
• Controlling an infectious disease regionally or globally may often be the best national prevention strategy
Key Issues
• Resources and political commitment must be upfront at the beginning and be sustained until the goal is achieved
• Short cuts on key technical strategies cannot be tolerated because of financial constraints
• Eradication must be time bound, resources will be diverted, so all efforts must mitigate risk of long, drawn out process
• Program resilience and agility is fundamental in order to able to respond to the unexpected as rapidly as possible
• Strong leadership is absolutely critical• Programs must be horizonal• Human resources and local capacity development
should be the matra of the program
Measles
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Strategies
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Strategies always rely on:
• Immunizing susceptible population
• Conducting effective surveillance
• Sustaining the gains
Basic strategies for MR eradication
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• Strong routine immunization program achieving high coverage
• Campaigns• MR Catch-up Campaign once• Follow-up Campaigns every 4 years• Rubella elimination mass vaccination
campaign ONCE, targeting population aged <40 years
• High quality surveillance• Sustain the gainsAndrus JK, de Quadros, Castillo, Roses, Henderson. Measles and rubellaeradication in the Americas. Vaccine 2011:29S;D91-D96.
Political Will
Measles and Rubella Elimination Goalsby WHO Region
20152015
2015 2012
2020
All 6 WHO Regions have measles elimination goalsAmericas and Europe have rubella elimination goals
2020
2000 2010
Recent increase in countries using rubella vaccine Countries with rubella vaccine in the national immunization programme, by year of vaccine introduction
Data source: WHO/IVB Database, as of 17 October 2016Map production Immunization Vaccines and Biologicals (IVB),World Health Organization
Planned introductions in 2016-2018 (17 countries or 8.8%)
Not Available/ Not Introduced/ No Plans (30 countries or 15.4%)
Not applicable
Introduced between 2012 and 2015 (17 countries or 8.8%)
17 countries introduced rubella vaccine during 2012-201517 countries planning introduction in 2016-2018
Global measles deaths
• Before measles vaccine >3 million deaths/year• 2015 – 134,200 deaths
• ~15 deaths/hour• 79% reduction in deaths 2000-2015• ~20 million deaths prevented 2000-2015• Measles no longer in the top 5 causes of childhood
mortality, but still causes 100,000 deaths per year
Source: Hinman keynote address to ARC Sep 2017
Strategic plan - Guiding principles
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• Provides vision for future work• Operationalizes the scientific components• Prioritizes targets• Utilizes lessons learned• Produces results and is product oriented• Develops direction with accountability• Promotes partnerships and collaboration• Remains focused & promotes quality of work• Expect the unexpected• “Disease eradication fights inequities and
creates social justice”
Network of Reference Laboratories
Viral Isolation and CharacterizationIntratypic Differentiation
Source: Country reports* Data reported until epidemiological week 10/2007
Integrated Measles-Rubella Surveillance Indicators, Region of the Americas, 2003-2007*
Measles Epidemiology
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• Reservoir - Human• Transmission - Respiratory
Airborne• Temporal pattern - Peak in late
winter - spring• Communicability - 4 days before
to 4 days after rash onset
Rubella Epidemiology
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• Reservoir - Human• Transmission - Respiratory• Subclinical cases may transmit• Temporal pattern - Peak in late
winter and spring• Communicability - 7 days before to
5-7 days after rash onset• Infants with CRS may shed virus for a
year or more
Large respiratory droplets
Source: Photo from the slide collection, Department of Medical Microbiology, Edinburgh University. From The Microbial World: Airborne Microorganisms, by Jim Deacon, Institute of Cell and Molecular Biology, The University of Edinburgh, at http://helios.bto.ed.ac.uk/bto/microbes/airborne.htm
Fergenson et al:
Ro Influenza A(h1N1) = 1.2 to 1.6Seasonal = 1.3
CFR = 0.4% (0.3-1.5%)
Opportunities
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• Prevent measles and measles-related deaths (estimated that 100,000 deaths still occurring globally)
• Prevent congenital rubella syndrome
Congenital Rubella Syndrome
Rubella Project for Multihandicapped; Bellevue Hospital – 1968Courtesy Dr. L. Cooper
Autistic boy
Autistic
Deaf-blind, retarded
Spastic, deaf
High morbidity rationale for immunization interventions
Congenital Rubella Syndrome
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• Infection may affect all organs• May lead to fetal death or
premature delivery• Severity of damage to fetus
depends on gestational age• Up to 85% of infants affected if
infected during first trimester
Incidence of viral excretion per month of age in infants and children with CRS
0
20
40
60
80
100
0 0-1 1-4 5-8 9-12 13-20 3-15Months
% w
ith p
ositi
ve c
ultu
re 71/85=84%
50/81=62%
26/80=33%
11/98=11%4/115=3% 0/20=0%
Age of Infants and Children
Source: Arch. Ophth. 71:434,1967
years
High mortality rationale for immunization interventions
Source: WHO 2004; Cutts & Vynnycky, 1999
Conditions Vaccine-preventable deathsamong children worldwide
Measles 610,000Haemophilus influenzae type B 450,000
children still dying every year• Return on investment: phenomenal both for investing
in a well performing immunization program ($56 for every $1) and for elimination of measles ($16 for every $1)
• In Americas: every dollar spent on the elimination of congenital rubella syndrome, the MOH would save approximately $13. These results were similar in several countries.
• Bottom line: no matter how you cut it, MR vaccination is still a best buy in global health
Measles outbreaks are not cheap.
The United States declared itself measles, rubella, and congenital rubella syndrome free, but continues to have recurring and expensive outbreaks of measles imported from Europe and other parts of the world.
In the United States such costs consume local public health budgets and overwhelm already fully stretched local public health authorities.
Developing countries pay too. The outbreak in Ecuador in 2011 from an imported “European” measles virus likely cost the country millions of dollars to contain and stop transmission.
Andrus JK, Cooper LZ. Measles and rubella elimination: Why now? Cultures 2015;2:42-49.
Summary• Collective impact
• 79% reduction in mortality from 2000 to 2015• >20 million deaths have been averted• Measles in no longer in the top 5 killers
• 100,000 children still die annually• MR vaccination still is the best buy in public health• In 2005 there were 11 genotypes circulating
globally, now there are 6• $2.3 billion/year – cost of measles vaccination.
Treatment costs are $68 billion/year• Countries recognize the PAHO success story with a
growing consensus that it needs to be replicated more extensively
Unfinished Agenda• 100,000 deaths still occurring globally per year,
despite a cheap vaccine available for >50 years• 100,000 CRS cases still occurring globally per
year• GVAP goals provide a roadmap for
immunization and systems strengthening• Some countries are experiencing a double
whammy with the polio transition and GAVI transition processes
• Measles and rubella elimination will require a diagonal approach as demonstrated in LAC
Note: Philippines, Haiti also have between 1-10 polio funded personnel but are not displayed; no headquarters staff displayedSource: GPEI partner HR databases, 2014
1+ personnel
GPEI presence in over 70 countries, but 95% of personnel footprint in 16 countries
Includes social mobilizers. Does not include national government staff, vaccinators or regional/headquarters personnel.
Why It Makes Sense to Pivot from Polio Eradication to Measles-Rubella Elimination1. Strategies are similar
– Surveillance and lab network– Outbreak preparedness and response– Importance of achieving/maintaining high routine coverage– Need for periodic SIAs to reach inaccessible children– Use of communications/social mobilization network
2. Polio infrastructure concentrated in the lowest-performing countries with highest measles-rubella disease burden
3. Polio and measles-rubella already working together and interconnected including human resources
4. Measles still major cause of <5 child deaths5. Rubella is the leading infectious cause of birth defects
GPEI Lessons Learned That Can Be Appliedto Measles-Rubella Elimination
• Using a targeted disease initiative for broader health communication
• Value of advanced state-of-the-art global lab network and real-time disease surveillance
• Experience with reaching every child• Outstanding program monitoring and use of accountability
frameworks for performance assessment• Partnership coordination, advocacy, resource mobilization
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Health Emergency and IHR Capacity: Building on the Polio/MR Lab and Surveillance Network (>700 labs)
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Source: GPEI
Lessons Learned and Impact of Polio on Capacity Development
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• General lessons learned – Political commitment, technical and operational excellence
• Partnerships• Lessons for capacity development
– Positive impact does not happen automatically, people have to look actively for linkages
– Mistakes will happen, is there sufficient capacity to react to extraordinary circumstances
• Report of the Taylor Commission– Culture of prevention– Increased community awareness– Multi-sectoral coordination