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Vaccine-Preventable Diseases PUBHLTH 350 Matthew L. Boulton, MD, MPH University of Michigan December 2, 2015

Immunizations One of the most successful and cost- effective public health interventions Successes: –Global eradication of smallpox –Regional elimination of polio and measles –Reduction in morbidity and mortality from diphtheria, tetanus, and pertussis (whooping cough) WHO estimates 2 million child deaths are prevented through vaccination each year

MMWR (29). Available at

Principles of Vaccination Active Immunity Protection produced by the person’s own immune system In response to disease or vaccination Usually permanent Passive Immunity Protection transferred from another person or animal as antibody Transplacental or through immunobiologics Transient protection

Another Principle of Vaccination The more similar a vaccine is to the disease- causing form of the organism, the better the immune response to the vaccine. CDC. Pink Book

Vaccine Classification Live attenuated vaccine Viral Bacterial Inactivated / killed vaccine Whole –Viral –Bacterial Fractional –Protein-based Subunit Toxoid –Polysaccharide-based Pure Conjugate Recombinant vaccine USAID. Immunization Essentials

Live Attenuated Vaccine Attenuated (weakened) form of wild type virus or bacteria Must replicate in the host to be effective In a few cases, vaccine strain can spread beyond host (e.g., polio) Immune response similar to natural infection Effective with relatively few doses Long-lasting immunity

Live Attenuated Vaccines Drawbacks Severe reactions possible (i.e., adverse event) Interference from circulating antibody –maternal antibodies –immune globulin Unstable, must maintain cold chain chain-box/vaccine-cold-chain-box-HTLL1080A jpg

Inactivated Vaccines Cannot replicate Minimal interference from circulating antibodies Generally not as effective as live vaccines Generally need 3-5 doses Antibody titer falls over time so periodic booster doses are required

Immunization Schedule Becoming more complex Requires multiple visits over many years Recent additions of adolescent and adult vaccinations –e.g., HPV, Tdap, Pneumococcal Polysaccharide vaccine (PPSV), Herpes-Zoster Not all vaccines are recommended for all countries –e.g., US does not use BCG (TB vaccine) Fewer vaccines used in developing countries –e.g., Haemophilus influenzae type b (Hib), Pneumococcal conjugate vaccine (PCV), Hepatitis B vaccine (HBV), rotavirus Some vaccines are highly reactogenic with low efficacy –e.g., cholera

US Pediatric Immunization Schedule 1940s1950s1960s1970s Smallpox Diphtheria, Tetanus, Pertussis Polio Measles, Mumps, Rubella Hib HepB Varicella HepA Pneumococcus Influenza Rotavirus Offit PA

Recommended immunization schedule for persons aged 0-18 years Schedules available at

Vaccination Assessment for the 4:3:1:3:3:1:4 series NumberRefers to 4Four doses of diphtheria, tetanus, & pertussis/acellular pertussis vaccine (DTP/DTaP) or diphtheria & tetanus vaccine (DT) 3Three doses of poliovirus vaccine (IPV or OPV) 1One dose of measles, mumps, & rubella vaccine (MMR) or measles containing vaccine (MCV) 3Three doses of Haemophilus influenza type b vaccine (Hib) 3Three doses of hepatitis B vaccine (Hep B) 1One dose of varicella (chicken pox) vaccine (Var) 4Four doses of pneumococcal conjugate vaccine (PCV) U.S. Department of Health and Human Services, Health Resources and Services Administration, Maternal and Child Health Bureau. Child Health USA 2010

Comparison of US and Chinese vaccination schedule before 12 months ChinaUS BirthHepatitis B BCG (Tuberculosis) Hepatitis B 1 monthHepatitis B 2-3 months DTP Polio Rotavirus DTP Hib PCV Polio 4-5 months DTP Polio Rotavirus DTP Hib PCV Polio 6 monthsHepatitis B DTP Polio Hepatitis B Rotavirus DTP Hib PCV Polio Influenza 8-9 monthsMeasles Japanese Encephalitis

Vaccine-Preventable Diseases Based on 2009 WHO estimates: Annually, 2.5 million deaths worldwide are caused by vaccine-preventable diseases in all age groups 1.8 million of these deaths are among children under 5 years due to diseases preventable by routine vaccination especially pneumococcal disease, measles, rotavirus, Haemophilus influenzae type b (Hib), pertussis, and tetanus VPD deaths represent 20% of total global mortality in children under 5 years of age

Global number of deaths in children, and percentage of total VPD deaths (2008) Pneumococcal 476,000 31% Rotavirus 453,000 29% Hib 199,000 13% Pertussis 195,000 13% Measles 118,000 8% Tetanus 61,000 4% Other 35,000 2% WHO. Global Immunization Data Available from

Vaccination Coverage Indicators By convention, the success of routine immunization programs in reaching children has been measured by the vaccination coverage achieved with the 3 rd dose of diphtheria-tetanus- pertussis (DTP3) in children aged months. Global Immunization Vision and Strategy (GIVS) goal of 90% DTP3 coverage by age 12 months in all countries by 2010 In addition, coverage with first dose of Measles- containing Vaccine (MCV1) is used to monitor progress toward 4 th Millennium Development goal of reducing age <5 mortality Coverage difficult to ascertain for all vaccines

DTP3-unvaccinated children by country in 2014 MMWR (44);

61% live in 1 of 10 countries: India, Nigeria, Pakistan, Indonesia, Ethiopia, DR Congo, Philippines, Iraq, Uganda, South Africa 40% live in India (22%), Nigeria (12%), and Pakistan (6%) DTP3-unvaccinated children by country in 2014 MMWR (44);

Global pediatric vaccine coverage, Coverage in 1990 Coverage in 2013 Change in coverage DTP376%84%+8% Polio376%84%+8% Measles-containing vaccine 173%84%+11% HepB31%81%+80% WHO. Global Immunization Data Available at

Hepatitis B Vaccine 600,000 estimated deaths in 2002, the majority of infections acquired in childhood 81% estimated HepB3 coverage in 2013 (increased from 1% in 1990 & 48% in 2004) 92% of countries (179) have integrated in routine immunization services by 2010 (increased from 80% in 2004)

HepB 3-dose coverage,

HepB3 Global Coverage

Immunization Program Services Administrative limits to effective services Vaccine shortages Lack of cold chain equipment Irregular or infrequent immunization clinics Shortages of clinic staff Inadequate mobilization and use of staff Lack of micro-planning at the primary health care level

Immunization Program Services Why people don’t use or return to use services Lack of information on when to have vaccination Expectation of poor service Time constraints Social, cultural, religious, political, and financial barriers Improper contraindications Distance USAID. Immunization Field Guide

Vaccine Strategies Improve program monitoring –Improve cold chain logistics Improve routine immunization services –Outsource services to NGOs in underserved areas –Provide incentives to health care workers and families of children Implement supplementary immunization activities –Large-scale catch-up campaigns –Mop-up campaigns to target hard-to-reach areas –National Immunization Days

Reaching Every District (RED) strategy Introduced in 2002 by WHO, UNICEF, and GAVI (Global Alliance for Vaccines and Immunizations) Successful strategies for improving vaccine coverage in rural Africa and India 5 Operational Components 1.Re-establishment of regular outreach services 2.Supervision and onsite training of health workers 3.Community links with service delivery 4.Planning and management of resources 5.Monitoring and use of data for action

New vaccines on the horizon? TargetChallenges HIVMutation of key surface proteins TBExisting vaccine has limited usefulness PneumococcusImmunization is strain specific InfluenzaNew strains emerge from antigenic shift and drift Enteric infections (cholera, rotavirus) Vaccinations typically not as immunogenic Cancer therapyTargets are patient-specific NicotinePotentially harmful collateral effects Greenwood. Phil. Trans. R. Soc. B (2011) 366, 2733–2742

Questions of the day How should countries decide which childhood vaccines to provide for free? Should childhood vaccinations be publicly funded through government sponsorship like the US Vaccine for Children (VFC) program or privately funded through individual health insurance plans?