Immune Issues
Despite great success, stumbling blocks and controversies hound the immunization program
By Lucio Victor Jr.
The World Health Organization and the United Nations Children's Fund report that each year as many as two million children under five years can be saved from deaths with vaccines given free through the Expanded Program on Immunization (EPI). Since its launch in 1974, the EPI has been able to prevent an estimated three million deaths each year while reducing morbidity from vaccine preventable diseases.
The EPI addressed six target diseases initially-tuberculosis, diphteria, tetanus, whooping cough, polio, and measles. In 1992, the WHO recommended inclusion of hepatitis B into its string of free vaccines. In 1993, the EPI plus was conceived, adding hepatitis B vaccine and, in areas where endemic, the vaccine against yellow fever. The EPI plus also incorporated iodine and vitamin A supplements into the program. However with donor funding dwindling and lack of government support, not everyone can avail of hepatitis B and yellow fever vaccine.
Vaccines for All
The concept of giving vaccines free or at low-cost sounds very attractive. Realistically, however, the EPI can only offer vaccines against six diseases, those against hepatitis B and yellow fever only when funding makes it possible. Sadly, the WHO and UNICEF report that these two vaccines are not available in endemic countries.
Despite having very good EPI coverage, the Philippines still has a lot to do to ensure children get adequate immunization against other equally important diseases like Hepatitis B, Haemophilus influenza B, chicken pox, mumps, German measles, and Hepatitis A.
Says Dr. Nina Gloriani Barzaga, director of the Institute of Biotechnology and Molecular Biology at the University of the Philippines-Philippine General Hospital: "I tend to look at the positive side, and giving these vaccines will actually be for prevention. Though EPI is free. If [the patient] has enough money I don't mind giving the other vaccines as long as they get the protection."
Dr. Barzaga also suggests the use of combination vaccines when available. "It is better to give the vaccines in a combination at the same time. Although it is costly, it means less puncture marks, better compliance, and lesser syringes and needles used." She adds that the Childhood Immunization Schedule (CIS) formulated jointly by the Philippine Society of Microbiology and Infectious Diseases (PSMID), Philippine Pediatric Society (PPS) and Philippine Foundation for Vaccination (PFV) is similar to the EPI schedule in that the most important vaccines are given to newborns by the first year. However, unlike the EPI, the CIS also inform parents of the availability of other equally important vaccines that are not given free.
Dr. Barzaga recounts many first world countries are very particular about the schedule of vaccination. Ideally, the EPI should be completed by the time the child reaches one year old. "The Philippines has a good EPI coverage," says Dr. Barzaga, but she is saddened by the unavailability of Hepatitis B. "Hepatitis B should be given free, dapat 90 percent or more of the target population should [already] be receiving this."
The WHO estimates that over two billion people worldwide are infected with the Hepatitis B virus (HBV) with 350 million chronic carriers and about one million dying from HBV related liver diseases including hepatocellular carcinoma. Saudi Arabia, Thailand, and Taiwan are among the 90 countries that have successfully integrated Hepatitis B vaccination into their EPI and reported reduction in chronic carrier states and cases of acute Hepatitis B infections.
Dr. Barzaga admits that local government units that handle the immunization programs have other problems to deal with, and immunization ranks low on their list of priorities. But she stresses that the cost of treatment will be much greater than the cost of prevention. "The problem is logistics every time. It is very sad we have to reset our priorities and sometimes the budget gets cut or realigned. It would be nicer if we could at least maintain, if not improve, our immunization coverage."
OPV or IPV
One of the pressing issues on EPI involves which type of vaccine to use-inactivated injectable polio vaccine (IPV) or the live attenuated oral polio vaccine (OPV)-once polio is eradicated.
According to Dr. Michael Decker, associate professor of preventive medicine and infectious diseases at Vanderbilt University School of Medicine, 2,824 cases of wild polio were reported in 2000-50 percent less than in 1999. He also reports that as of 1999, there has been no reported isolation of the type 2 poliovirus, bringing the world closer to eradicating one of the three serotypes responsible for the disease.
Despite the markedly improved surveillance and the declaration of the Americas as polio-free in 1994 and the Western Pacific Region on October 29, 2000, 32 cases of wild poliovirus were still reported in India and Pakistan as of 2001. As of now, most cases of wild poliovirus are limited to the Indian subcontinent and Africa.
So what is the hoopla over OPV and IPV?
Dr. Ana Lisa Ong-Lim, assistant professor of pediatrics at the UP-PGH says: "The controversy between the use of IPV and OPV did not start in one era but has been going on for almost 40 to 50 years." She recalls that field trials of formalin-treated live attenuated polio virus prepared from monkey spinal cords were terminated because it led to paralysis in the limbs of some of the subjects inoculated with it. By the early 1950s results of the preliminary study of Dr. Jonas Salk's IPV were encouraging that its use became widespread by 1955. At about the same time, however, Dr. Albert Sabin was developing OPV, and by 1961, it became available.
Despite accumulated evidence on the safety and efficacy of the IPV, the OPV drew more favor for three reasons. It was cheaper to produce and market, easier and less painful to administer, and it induced local gut immunity and conferred herd immunity by inducing an immune response in persons who are in close contact with vaccinated individuals. Herd immunity, explains Dr. Ong-Lim, is caused when vaccine progeny viruses in OPV are abundantly excreted and infect close contacts through oral-fecal route.
In 1964, the Committee on the Control of Infectious Diseases of the American Academy of Pediatrics (AAP) expressed preference for the OPV, noting that 50 percent of recipients were immune to any of the three wild poliovirus strains after the first does and more than 95 percent were immune after the third dose. Plus, protection was persistent for an average of 35 years and, in epidemic situations, OPV can preempt sites of multiplication within the host population blocking implantation of the wild poliovirus. This would greatly explain why OPV is favored in most countries, especially in poor developing nations.
Changing Tides
Dr. Decker says that in June 1995, the US Advisory Committee on Immunization Practices drew up new guidelines on polio vaccination and suggested the combined use of IPV for first two doses and IPV for the remaining two. The committee explained that it removed the risk of vaccine associated paralytic polio (VAPP), the adverse reaction that occurs in one in three million doses of OPV caused by reversion of the vaccine virus to its virulent form. It afflicts five to 10 newly immunized American children each year. Unlike the wild poliovirus, the rouge virus responsible for VAPP is non-infective.
He explains that the two initial IPV doses can induce good seroconversion that can protect against VAPP. The latter two OPV doses, on the other hand, will cover both gut and herd immunity, which are not attainable with IPV alone. The new schedule meant an additional US$20 million immunization budget each year, a rather small amount the US government deemed in exchange for saving five to 10 children from VAPP each year.
Dr. Decker also expresses concern over the occurrence of vaccine derived paralytic polio (VDPP) which is caused by a mutation of the vaccine virus into a pathogen genetically distinct from the wild poliovirus and is more virulent than the original wild poliovirus. Like the wild poliovirus, the vaccine-derived poliovirus (VDPV) can replicate in the host, be transmitted from one person to the next, and has a significant paralytic attack rate.
First reported in 32 cases in Egypt between 1988 to 1993, it did not grab much attention until April 2001 when an outbreak occurred in Hispaniola, the Carribean island shared by the Dominican Republic and Haiti. So far there are eight confirmed cases in Haiti and 13 in the Dominican Republic. The Philippines reported three cases in September 2001.
Dr. Decker says the VDPV strains in Egypt were 93 to 96 percent homologous to the Sabin 2 vaccine virus, and regression analysis estimated the VDPV to have been in circulation since 1983. The Hispaniola and Philippine strains were between 95 to 98 percent homologous to the Sabin 1 vaccine virus.
The aberrant vaccine viruses, according to Dr. Decker, were associated with inadequate vaccination of the target population particularly in populations where the immunization rate fell below 50 percent. He also points to persons with immunocompromised states as likely sources of VDPV, noting that those with HIV or congenital immunodeficiencies have been shown to continually excrete VDPV. One of the longest cases, he said, was that of a British national who had been excreting VDPV for about 16 years.
Dr. Decker says that OPV has greatest use in populations where wild poliovirus circulates, but notes that a high level of immunity has to be maintained even after a population is declared polio-free. He endorses the use of sequential IPV-OPV or pure IPV alone, and though this is not currently covered by the EPI due to high cost, Dr. Decker warns that even if the whole world becomes polio-free, VDPV will remain in circulation unless polio vaccination is maintained. The Philippine CIS gives physicians and parents the option to choose sequential IPV-OPV or either IPV or OPV alone.
Dr. Barzaga who chairs the National Certification Committee in charge of declaring the Philippines polio-free, says despite the risk of VDPV from OPV, OPV must still be given to displace and control the spread of the vaccine variant.
She confirms talks on the discontinuation of OPV use once the wild poliovirus is globally eradicated. But polio immunizations will continue using IPV only. Dr. Decker supports a shift saying countries like France that shifted to pure IPV vaccinations in 1984 have shown no incidences of VAPP or polio even with migration of persons from endemic areas like Africa. Also, he notes that there has been no report of VDPV from France since then.
New Blood
Many developed countries have gone beyond the EPI and added more vaccines to their schedules, ensuring better immunization coverage. At the same time, research goes on to improve existing vaccines like the BCG.
Purified from Mycobacterium bovis components, BCG helps prevent pulmonary tuberculosis in its recipients. Dr. Barzaga says that its protection lies anywhere from zero to 70 percent, but it remains one of the most important EPI vaccines. She notes that researchers have tried to improve on the efficacy of the BCG vaccine but have not been successful yet.
Vaccines against malaria, dengue, schistosomiasis and leptospirosis have been in development in various parts of the globe, including the Philippines. Dr. Barzaga hopes the efforts will soon pay off.
Dr. Barzaga says that research efforts have been slackened by budget cuts and donor fatigue, they have also been stymied by the difficulty of establishing the possible antigens the human immune system would respond to. "Because many molecules come out as potential vaccine molecules, there are so many antigens we have to work on and study. [For example] parasites for malaria and schistosoma are very complicated. In dengue, the pathogenesis is not clearly explained so we do not know if antibodies from a dengue vaccine will actually protect [against] or enhance the illness. There may also be problems with host responses and virulence factors of the pathogenic organism. Is the vaccine molecule a strong or poor immunogen or can it have a mechanism to camouflage itself, like malaria which can somehow escape immune responses?"
Still, it all boils down to money, says Dr. Barzaga. Without monetary support, vaccination programs won't succeed, no new vaccines would come out of laboratories. And the world will remain at high risk for infectious diseases.
|
