Update in Immunization

by Eric Poon, M.D.

(Presented at the 1999CAMS Annual Scientific Meeting)

Vaccination, or immunization, is one of the most cost-effective, safest and most powerful tools of medicine for preventing disease, disability, and death. While variolation has been documented to have been practiced as early as the 10^th century in China, credit for the first vaccine goes to the English Country doctor, Edward Jenner, who made the observation that milkmaids who contracted "cowpox", a disease of cows that causes only mild illness in humans, rarely became victims of the devastating human illness, smallpox. In 1796, Jenner took the fluid from the pustule of a cowpox lesion on the hand of a milkmaid, and inoculated it into the skin of an eight year old boy, who then was protected against small pox despite exposure to the virus. This weakened form of "small pox" was called a "vaccine" from vacca, the Latin word for "cow".

It was Pasteur who suggested that in Jenner’s honor, all inoculations be called "vaccinations" even though, properly speaking, they have nothing to do with cows. Today, the more accurate term "immunization" is preferred.

In the past 50 years, some vaccine-preventable diseases were reduced by nearly 99% from their peak levels just a few decades earlier. The World Health Organization (WHO) estimated that in 1990, 80% of the world’s children were immunized against measles, diphtheria, pertussis, tetanus, tuberculosis and polio. In 1985, The Institute of Medicine (IOM) of the National Research Council commissioned by NIH to define priorities for vaccine research and development. Identified as the highest priorities were vaccines against Hemophilus Influenza type B (HIb), Hepatitis B, and Typhoid. Currently, HIb and Hepatitis B vaccines are being incorporated into global immunization programs.

Let us look at some of the controversies around some of the present vaccines. Polio has existed for thousands of years. The first recorded U.S. epidemic was in 1894. Paralytic cases peaked in the U.S. in 1952 (720,000). Inactivated Polio vaccine was introduced in 1955 by Jonas Salk. In 1960, Albert Sabin introduced the oral Polio vaccine (OPV). Global eradication was targeted for the year 2000. The last case of wild-type Polio virus was reported in 1979. Every year, there were 1-3 cases of Vaccine Acquired Paralytic Poliomyelitis (VAPP) reported because of mutation of the attenuated virus in the intestine. It was found that antibodies arising from the enhanced potency inactivated polio vaccine and OPV were comparable. It was recommended that as of January 1, 2000, no OPV is to be used in the United States. OPV continues to be used in underdeveloped countries where massive immunization is needed. Four separate doses of IPV are to be given at 2,4,15-18 months and 4-6 years olds.

Pertussis (whopping cough), an acute respiratory tract infection caused by B. Pertussis, is a highly infectious disease. Whooping can lead to choking, seizure, and even death. It affects more than 50 million people around the world annually and causes about 500,000 deaths. In the U.S., whole cell Pertussis vaccine (since 1948) have been responsible for reducing the infection from a peak of more than 260,000 cases in 1934 to about 4300 cases in 1995. Although whole cell Pertussis vaccines were used effectively for decades, they were occasionally associated with adverse reactions (e.g., fever, seizure, encephalopathy). For the past 15 years, the U.S. has focused on developing safer Pertussis vaccines. The new vaccines were made up with one or more inactivated, purified, or recombinant antigens. The first acellular Pertussis vaccine was licensed in 1991 and Tripedia was the first acellular DPT vaccine marketed in 1996. All acellular vaccines provide comparable antibodies response to that given by the whole cell vaccines, and are much less reactogenic, with low rates of fever, local reactions, and few if any episodes of seizures or other acute idiosyncratic events..

Over the past quarter century, the highly infectious viral diseases Measles, Mumps and Rubella have been largely controlled or nearly eliminated in the U.S. through the use of vaccines in a 2-dose vaccination program. The first dose is to be given after the first birthday and the 2^nd dose at 4-6 years, or any time after the first dose after at least 4 weeks have elapsed after the first dose. Those who have not received the 2^nd dose should have it by 11-12 years.

Hepatitis A and B are responsible for nearly 70% of the Hepatitis infections in the United States. Hepatitis C accounts for another 21% and hepatitis D, 4%.Hepatitis B virus is transmitted through blood and blood products, but the viral antigens have also been found in tears, saliva, breast milk, urine, semen, and vaginal secretions. Chronic infection with Hepatitis B virus is second only to tobacco among known tumor carcinogens. Therefore, immunization against Hepatitis B is equal to immunization against liver cancer.

Studies carried out by NYU Downtown Hospital and Chinatown Health Clinic in 1996-98 showed that seroprevalence of HBcAb increased in the Chinese immigrant children as they grow older. Thus, besides longitudinal transmission, horizontal transmission is also the cause. Therefore, the practicing physician should test all Asian adolescents before administering the hepatitis B vaccine.

Currently, vaccines can prevent 10 childhood diseases: polio, diphtheria, tetanus, pertussis, measles, mumps, rubella, hepatitis B, varicella and H. Influenza b. Federal and State governments are committed to immunize every single child or 98% of youngsters entering school. It is children under 2 years of age for whom nearly all basic vaccines are recommended that have the poorest immunization records. In 1993, some 37-56% of the nation’s 2 year old’s (about 4 million) were not immunized with the complete required series of vaccines. Unfortunately, the immunization schedule is not "user-friendly". To be fully compliant, a child must have 16 individual vaccines given in 5 or more years of life. Until combination vaccines become available, new and improved vaccines that will initially be licensed as single products will further complicate the childhood immunization schedule. For example, a safer vaccine against Pertussis and the recently recommended change from OPV to IPV will have the interim effect of increasing the number of injections and medical visits required to be fully compliant with recommended immunization schedule.

New vaccines forthcoming including new Pneumococal vaccines, Lyme disease vaccine, Meningococal vaccine, Rotavirus vaccine are expected to be introduced in the near future. A combination vaccine, COMVAX, with Hepatitis B and Hemophilus Influenza b may be an alternative to cut down the number of clinic visits and injections.

Immunization remains one of the most powerful tools that medical science has for disease prevention. To be fully effective in saving lives, especially those of children in less developed countries, the ultimate children’s vaccine will have to be one that is affordable for global use. "A children’s Vaccine" is beginning to take shape.

birth to 2 mos Hep B

2 mos DTaP, IPV + COMVAX or Hib, Hep B

4 mos DTaP, IPV + COMVAX or Hib, Hep B

6 mos DtaP, Hib, Hep B (there must be 4 wks. between 1^st & 2^nd dose

and 8 wks between 2^nd & 3^rd dose of Hep B)

12 mos 1^st MMR, or 3^rd dose of Hep B

15-18 mos 1^st booster DtaP, IPV

12-24 mos VARIVAX

4 yr. 2^nd MMR

4-6 yrs 2^nd booster DtaP, IVP

11-12 yrs adolescent’s 3 doses of Hep B

COMVAX: Hemophilus b conjugate and Hepatitis B (recombinant) vaccine

DtaP: Diphtheria, Tetanus, Pertussis vaccine

IPV: injected Polio vaccine

MMR: Measles, Mumps and Rubella virus vaccine (live)

VARIVAX: Varicella virus vaccine live (oral)

*updated by Dr. Poon in March, 2000

Dr. Poon is Chief of Pediatrics, NYU Downtown Hospital