Vaccines: Barriers in the Developing World

Edwin J. Asturias, MD

Associate Professor of Pediatrics and EpidemiologyDirector for Latin America

Center for Global Health, Colorado School of Public Health

Global Health and Disasters CourseUniversity of Colorado, November, 2015

Objectives

• Vaccines and their impact in global health for children and women

• Vaccine effectiveness in the developing world (e.g. rotavirus, polio)

• Logistical barriers to delivering vaccines (e.g. yellow fever, polio)

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1800 1900 1910 1920 1940 1990 20101850 20001930 1950 1960 1970 1980 2020

PertussisTetanus

DiphtheriaYellow fever

Polio (IPV)Polio (OPV)Measles

Rubella

Hepatitis BHiB conjugate

Typhoid

Meningitis C conjugate

Pneumococcus conjugate

Rotavirus

HPV

Meningitis A conjugateJapanese encephalitis

PneumococcusInfluenza

RabiesTyphoidCholeraPlague

Tuberculosis

Smallpox

Mumps

InfluenzaMeningococcus (ACWY)

HiB polysaccharidePertussis acellular

[Hepatitis B]

Hepatitis A

Varicella

TyphoidMeningococcus ACWY conjugate

Influenza*

ZosterProstate cancer

Rotavirus**Meningitis C conjugate

Rotatshield

~40 human vaccines in the world to dateconsidered one of the most cost effective ways of advancing global health

EPI program success around the world as of 2015

http://www.who.int/immunization_monitoring/diseases/en/

Prepared by E. Asturias

§ children not receiving

Childhood deaths reducing worldwide!Impact of vaccines, malaria prevention and neonatal health

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80818283848586878889909192939495969798990001020304050607080910111213Measles cases Rubella cases Coverage Measles Coverage MMR

Catch up campaign for measles

Follow-up campaigns for measles

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over

age

Con

firm

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Speed-up campaigns for Rubella

The Comprehensive Family Immunization Unit (FGL/IM) – Pan American Health Organization

Last endemic measles

case

Last endemic rubella case

PAHO Measles and Rubella Strategy

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MCV

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Number of cases MCV1 Coverage* MCV2 Coverage*

Global Measles: 94% Reduction in Reported CasesAnnual reported cases and MCV1* and MCV2** coverage, 1980-2014

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* MCV1 coverage: coverage with first dose of measles-containing vaccine as estimated by WHO and UNICEF.

**MCV2 estimates is only available from 2000 when global data collection started, however some countries have introduced the vaccine earlier.

Campaigns

Source: WHO/IVB database, 2015194 WHO Member States. Updated on 15 July 2015

Endemic country1Excludes viruses detected from environmental surveillance2Onset of paralysis 10 November 2016 – 09 May 2017

Global Wild Poliovirus & cVDPV Cases1, Previous 6 Months2

Wild poliovirus type 1cVDPV type 22

Data in WHO HQ as of 09 May 2017

Number and location of wild polio cases around the world as of Oct 3, 2017

www.polioeradication.org

New Polio Vaccine Schedules

Status of Global IPV Introduction 2016

84% of children in the world now reached with DTP3 vaccine

* Based on data officially reported to WHO and UNICEF by current member states. Note: Includes DTP-containing vaccines, such as pentavalent vaccine.Source: WHO/UNICEF vaccine coverage estimates (July 2014).

Immunisation coverage rate (%)

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Mission and strategic goals 2011–2015

The vaccine goalAccelerate the uptake and use of underused and new vaccines

The health systems goalContribute to strengthening the capacity of integrated health systems to deliver immunisation

The financing goalIncrease the predictability of global financing and improve the sustainability of national financing for immunisation

The market shaping goalShape vaccine markets to ensure adequate supply of appropriate, quality vaccines at low and sustainable prices

1 2

3 4

To save children’s lives and protect people’s health by increasing access to immunisation in poor countries

Uptake of Hib and pneumococcal vaccines in high-income versus low-income countries

Hib= Haemophilus influenzae type b. PCV=pneumococcal vaccine. Dashed line=projected uptake. Solid line=actual uptake

Levine O, Bloom DE, et al .Lancet 2011; 378 (9789) 439 - 448

Board meeting2-3 December 2015

GAVI 20 priority countries as of 2017

Representing 75% of the world’s under-immunised

10 countriesmost under-immunised

children10 countrieshigh inequities1 or conflict

1 High inequity is defined as >20%

coverage difference between highest and lowest

wealth quintile in DHS surveys after

2010.N/A

How to deliver vaccines to the whole world?• Data on disease burden• Immunization systems ready

• Health workforce• Adequate cold chain• Vaccine schedule platform

• Financing for sustainability• Overcome political and social barriers

Immunization financing per infant through time and by WHO region Notes: *= Baseline years.

Lidija Kamara et al. Health Policy Plan. 2013;28:11-19

181 dot = 100 deaths

The Vast Majority of the ~200,000 Annual Deaths from Rotavirus Occur in Developing Countries

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Moderate Efficacy of Rotavirus Vaccines in Low Income African and Asian Countries

Vaccine Region Countries Efficacy (95%CI)

RotaTeq Africa Ghana, Kenya, Mali 64% (40%-79%)

RotaTeq Asia Bangladesh, Vietnam 51% (13%-73%)

Rotarix Africa South Africa, Malawi 62% (44%-73%)

Armah et al. Lancet 2010Zaman et al. Lancet 2010Madhi et al NEJM 2010

Efficacy of rotavirus vaccine by country and economic status 2007

Nelson & Glass, 2010 Lancet

Reasons for lower efficacy• Competing microbiome• Malnutrition• Higher maternal Ab titer• Co-pathogens causing diarrhea

What does 50% efficacy mean?

Would you rather have 99% of my salary or 1% of Bill Gates’?

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Malawi South Africa

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Placebo Vaccine

6.6 episodes prevented

4.2 episodes prevented

50% vaccine efficacy

77% vaccine efficacy

Madhi, NEJM 2010

Despite lower efficacy, rotavirus vaccines prevent more disease in high burden settings

Rotavirus vaccine introduction globally as of April 2017

Rates of Pneumococcal invasive diseases death around the world 2012

Progress in Introduction of Pneumococcal Conjugate Vaccine Worldwide, 2000–2012

MMWR April 26, 2013 / 62(16);308-311

• 36 (73%) of 50 high-income countries introduced PCV• 13 (37%) of 36 low-income• 18 (35%) of 52 lower-middle income

Countries that have introduced pneumococcal conjugate vaccines in their national Immunization programs, by income status* — worldwide, 2012

MMWR April 26, 2013 / 62(16);308-311

Worldwide HPV-Related Disease Burden5% of all cancers HPV related

Male FemalePenile cancer1 11,000

21,000 Vulvar & vaginal cancer1

530,000 Cervical cancer1

9,000,000 High-grade cervical dysplasia2,3,*

21,900,000

17,300,000 14,700,000

Oropharyngeal cancer1 Oropharyngeal cancer14,40017,000

Anal cancer1 Anal cancer111,000 13,000

*Estimated 90% of high-grade cervical lesions are HPV related3; †Estimated 73% of low-grade cervical lesions are HPV related3; ‡Estimated gender ratio of genital warts: 54% males; 46% females6

1. Forman D, et al. Vaccine. 2012;30:F12-F23; 2. World Health Organization; 3. Guan P, et al. Int J Cancer. 2012;131:2349-2359; 4. World Health Organization; 5. Greer CE, et al. J Clin Microbiol. 1995;33:2058-2063; 6. Public Health England.

Low-grade cervical dysplasia2,3,†

Genital warts4,5,‡ Genital warts4,5,‡

Cervical cancer burden of disease world map 2014

Countries With HPV Vaccine in the National Immunization Program1

Introduceda to date (63 countries or 32.5%)

Not available, not introduced/no plans

(131 countries or 67.5%)

Not applicable

aIncludes partial introduction.

1. Vaccine in National Immunization Programme Update. Map production Immunization Vaccines and Biologicals (IVB), WHO/IVB Database, World Health Organization website. http://www.who.int/immunization/monitoring_surveillance/VaccineIntroStatus.pptx?ua=1. Accessed July 28, 2015.

World Female population pyramid by income and vaccination in 2014

Bruni et al. 2016 Lancet Global Health

1.4 M13 M32 M

47 million vaccinated girls

Knowledge on HPV Vaccine and Cervical Cancer Facilitates Vaccine Acceptability among School Teachers in Kitui County, Kenya.

0% 20% 40% 60% 80% 100%

School Based Vaccination ShouldContinue

School girls should receive sex ed

HPV vaccine Safe

HPV infection common Kenya

Agree Neutral Disagree

Masika MM. PLoS One. 2015 Aug 12;10(8):

Barriers to use of existing childhood vaccines in LMICs

•Lack of disease burden data •Need of cold chain•Poor transportation and storage systems•Inadequate and poorly motivated HCW•Budget constraints•Lack of political will

Obaro et al. Vaccine 2003

Improving vaccine use in developing countriesAdvocate its use

•Generation of local burden of disease data (disease surveillance systems, regional sentinel sites)

•Demonstration of immunogenicity, efficacy and safety in the local population

•Cost effectiveness data (1 vaccine or comparisons?)

• Inform policy makers, opinion leaders and HCW

•Inform the community through mass media

Effect of vaccine prevention on earnings and wealth

•Fewer missed school days (better attendance)•Less long term disability•Changes in household behavior after survival•Better cognitive development

•Philippines: vaccination effect on scores in math, language and cognition

•Estimated return on investment of 21%

Beyond preventing 426 million cases of illness and averting 6.4 million deaths in the next 10 years…

Stack et al. and Ozawa et al. Health Affairs – June 2011

How we close the gap on under immunization globally in the next decade• Identify factors associated with under-

immunization (timeliness)• Maternal education, # child in family, distance

• Disrupt traditional immunization delivery• eHealth and mobile technology, consumer

based strategies

• Increase HCW numbers and education• Mid-level practitioners, on-line training

Obaro et al. Vaccine 2003

Perception of Safety of Vaccines according to the Program Effectiveness

Robert T. Chen, CDC

Parental Vaccine Preferences in Guatemala 2009

Asturias EJ, Submitted for publication 2015

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Rural Public Urban Public Urban PrivateProp

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IPV OPV DNK

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Rural Public Urban Public Urban PrivateProp

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DTaP DTwP DNK(b)

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• Urban areas more concerned with safety

• Safety overrides decision of number of injections

What is next on vaccines?

• Reduce infectious mortality in children

• Reduce morbidity in young children

• Reduce disability and perinatal infections

• Emerging infections

Global RSV Disease BurdenLozano, R et al. The Lancet. 2012; 380:2095-2128.

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• RSV kills more children <1 year of age than any other single pathogen except malaria

• Leading cause of hospitalization in children under 5 years of age in the

28-364 days of life0-27 days of life Malaria (11.3%)

RSV (2.3%)

RSV (6.7%)

Madhi SA et al. N Engl J Med 2014;371:918-931.

Effect of Maternal Influenza vaccination on confirmed cases of Influenza According to Cohort and Study Group in South Africa

Facts to remember

1 in 5 children do not have access to life-saving immunizations

Vaccines prevent 2 to 3 million deaths annually around the world

$20 can fully vaccinate a child against pneumonia, diarrhea, polio and measles

Over 18 million infants remain unimmunized in the world each year