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

2

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

10

Strategies

11

Strategies always rely on:

• Immunizing susceptible population

• Conducting effective surveillance

• Sustaining the gains

Basic strategies for MR eradication

12

• 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

The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. ©WHO 2016. All rights reserved.

Introduced before 2012 (130 countries or 67%)

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

18

• 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

**

* **

*

LSP

INS

CDC

CARECINH

CHAGASLACEN

FIOCRUZ

MALBRAN

***

INCAP*

Polio Measles

Lab testing through EIA IgM serology

Reference Laboratories

Bacterial Meningitis & Pneumonia

Regional Reference CenterSub-regional Reference CenterNational Reference Laboratories

19

92 90 90

61

8378 77

61

8279 8188

55 57

7479

89

74

85 80

63

8687

59

86

0

20

40

60

80

100

% sitesreporting

% cases withadequate

investigation

% cases withadequatesample

% samples inlaboratories <=5

days

% lab resultsreported <=4

days

Per

cent

age

2003 2004 2005 2006 2007

Source: Country reports* Data reported until epidemiological week 10/2007

Integrated Measles-Rubella Surveillance Indicators, Region of the Americas, 2003-2007*

Measles Epidemiology

21

• Reservoir - Human• Transmission - Respiratory

Airborne• Temporal pattern - Peak in late

winter - spring• Communicability - 4 days before

to 4 days after rash onset

Rubella Epidemiology

22

• 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

25

• 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

28

• 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

Pertussis 285,000Neonatal tetanus 200,000Congenital rubella syndrome (1996) 110,000

Yellow fever 30,000Diphtheria 5,450Paralytic polio 1919

Catch up campaign

* MMR in children 1 year of age by vaccine introduction

Follow-up campaigns

% Vaccination coverage

Con

firm

ed c

ases

Speed up campaigns

Source: Country reports to FGL-IM/PAHO* Data as of February 25, 2013

Last endemic measles case Last endemic

rubella case

Measles Vaccination Coverage among Children <1 Year of Age* and Reported Measles and Rubella Cases, the Americas 1980-2013*

Catch up (<15years)

Follow-up(1-4 years)

Speed-up (adol/adult)

140 million 80 million 260 million

Risk of Virus Importations from Other Regions, including CRS Cases

~150 million tourists have arrived to the Americas in 2010, which is an increase of 6% compared with 2009.

Confirmed measles cases by epidemiological week, Pernambuco, Brazil - 2013/2014*

Source: National Surveillance Branch, Ministry of Health*Data as of February 11, 2014

1ª C

ampa

nha

vaci

nal d

o sa

ram

po

0 1 2 2 4 4 6 8 12 94 3 6 2 5 5 8

3 4 5 81 2 3 1 1 2 2 1 4 2 2 6 7 8 9 11 11

4 3 1 1 2 02 02

410 2

11

1516

8 76

8 3 6 27 2 2

6

36 8 5 9

5 7 5 5 56 9 7

1520

41

71

45 4245

30 38

23

8 62 00

10

20

30

40

50

60

70

80

90

100

10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 2 4 6

Confirmado Descartado Em investigação

2ª C

ampa

nha

vaci

nal d

o sa

ram

po

Suspected: 873Confirmed:185Discarded: 585Under investigation: 103

3ª C

ampa

nha

vaci

nal d

o sa

ram

po

Vaccination of men and women Vaccination of women only

82

98 98 99 99 97 99 99 98 99 969999

0

20

40

60

80

100

CAR COR HON ELS PAR COL NIC BOL PER DOR ARG* CHI BRA

Source: Country reportsAndrus JK, et al. Vaccine 2008 (In Print)

Cov

erag

e (%

)Rubella Vaccination Coverage in Selected

Countries of the Americas,1997-2006

35

Vaccination Campaign Phases for the Elimination of Rubella and CRS

Post partum and post abortion vaccination (X 9 months)

Weeks

Captive population House to house

In transit populations and places of high circulation

Fixed and mobile posts

Rapid Coverage MonitoringSchool Institutional Labor

Addi

tiona

l Opp

ortu

nity

“Cen

tral

Day

”

Laun

chin

g

Verif

icat

ion

of C

over

age

Anno

unce

men

t

21 3 4 5 6

Social Communication and MobilizationWeekends

Rubella elimination and primary health care

PAHO. Changing lives: The EHDI experience in Costa Rica. EPI Newsletter August 2007;29(4):1.

Castillo-Solorzano C, Andrus JK. Rubella elimination and improving health care for women. Emerging Infectious Diseases 2004;10(11):17-21.

Surveillance strengthening: 3 general priority areas

37

Field operations - logistics

Laboratory Data management

Global estimated measles mortality and measles deaths averted, 2000 - 2012

Source: MMWR http://www.cdc.gov/mmwr/pdf/wk/mm6305.pdf and WER http://www.who.int/entity/wer/2014/wer8906.pdf?ua=1 7 Feb 201438

Financial Facts• Measles vaccination costs: $2.3 billion/year • Treatment costs: $68 billion/year with 100,000

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

43

>1000 personnel>100 personnel>40 personnel>10 personnel

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.

Country-level Transition Planning | Transition Independent Monitoring Board

M&RI – 6 Gavi priority

Characteristics of the 16 Priority“Polio Transition” Countries

• Most of the world’s unvaccinated and under-vaccinated children (53% of 20.8 million infants who did not receive measles vaccine in

2015 are in the Big 6 priority measles countries)• Most of the world’s measles cases and deaths (88% of deaths)

• Most of the world’s rubella and congenital rubella syndrome(100,000 CRS cases)

Consequences of losing polio assets – risk that EPI progress in these countries and globally will be reversed !!

Polio-Funded Surveillance Officer Responsibilities

Polio

Other VPDs:• Measles/Rubella• Yellow Fever• Neonatal tetanus• Meningitis• Acute encephalitis

syndrome• Diphtheria• Cholera• Pertussis…and so on

Other VPDs

Other Communicable Diseases:• Bloody diarrhea • Neglected tropical diseases• Dengue• Viral hemorrhagic fevers• Rabies• Malaria….and so on

Thank you!

46

32

35

67

56

59

47

86% of WHO immunization personnel in Africa are polio-funded

40% of WHO AFRO’s workforce is polio-funded

Example: Polio funds 70% of WHO staff in DR Congo1

Kinshasa

Provinces

Total staff1

126

Other

383

# polio-funded personnel

88

1. 2013 DRC FRR data; excluding consultantsSource: GPEI FRR, WHO, UNICEF, BCG analysis

Polio funding plays a significant role in overall partner capacity in many regions

and countries

Country-level Transition Planning | Transition Independent Monitoring Board

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

50

Health Emergency and IHR Capacity: Building on the Polio/MR Lab and Surveillance Network (>700 labs)

50

Source: GPEI

Lessons Learned and Impact of Polio on Capacity Development

51

• 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