SPECIAL ARTICLES Indian J Pediatr 1989; 56 : 321-325

What is Wrong with Vaccine Literature Inserts ?

Ramesh Shrestha

Programme Officer (Health), UNICEF, Kathmandu

Immunization of children has become a programme of great priority in all developing countries of the world. If administered properly this programme could save millions of infants and children from unnecessary ill health and untimely death. Advocacy by UNICEF has resulted in an increase in financial contributions by the governments of Italy, United States, etc. In many developing countries, additional budget for EPI programmes is being given special priority. Special days have been declared for immunization of children on mass scale and national campaigns to immunize children against six target diseases.

With advances in biotechnology it has become increasingly possible to immunize all children with antigens against diphtheria, pertussis, tuberculosis, neonatal tetanus, poliomyelitis and measles. The process of antigen administration can be divided into three components; cold chain, vaccine and staff management. A slight disruption in any of these factors is a constant threat to programme success.

In this paper, I review a seemingly small component in the immunization system--

Reprint requests : Ramesh Shrestha, Programme Officer (Health), UNICEF, Kathmandu, Nepal.

the vaccine literature inserts. Inconsistent information and misinformation in these can contribute to the vulnerability of immunization programmes. While millions of dollars are spent globally one piece of misinformation or exaggeration can result in an ineffective programme. Administra- tion of vaccine in most developing countries is done by para-professionals with only high school education. Any information provided to them should be simple and straight-forward. The vaccine literature inserts may not be specifically intended for these vaccinators but they certainly have easy access to them. It is from their perspective that the information content of the inserts is reviewed here. The comparative study is limited to these insert headings; indications, contraindications, dosage and administration, storage, expiry dates and side reactions. The information which follows was collected from four of the six vaccines used in Nepal.

BCG VACCIN~

All BCG vaccine used in Nepal is imported from one manufacturer. This particular brand of freeze dried vaccine is known to have a longer shelf life than other BCG vaccine manufactured elsewhere.

The literature insert for this vaccine

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does not provide any information on indications, contraindications or side reactions! The opening phrase of the literature insert says "HEAT STABLE". By the laws of nature, nothing is totally heat stable. This is especially true for vaccines and drugs. The actual stability of this vaccine is indicated under the heading "Storage". When stored at +5~ the vaccine can remain potent upto 2 years while at 37~ the potency lasts only upto one month. Drugs requiring reconstitution are less stable than drugs for instant use. "The vaccine once reconstituted", says the insert, "should be used within a 'few' hours." How many hours is a few hours?

The information printed in bold-type (HEAT STABLE) may lead the vaccine transporters to keep the vaccine at ambient temperature for a considerable period of time at several transit points ultimately destroying the vaccine. In addition, if the vaccinator interprets "HEAT STABLE" as having no cold chain requirements he may be immunizing children with ineffective vaccine. This will certainly jeopardize the credibility of the programme.

It is necessary therefore that literature inserts of this nature should be revised and words like 'heat stable' be deleted. Important instruction like indications, constraindications, side effects, efficacy, etc. must be included.

ORAL eOUO VACCINE (S~ls)

The comparative information given here is on polio vaccine manufactured by two companies, A and B.

Indications and Contraindications. Manufacturer A indicates this vaccine is appropriate for "all children, susceptible adults, school entering children, school

leaving children and all individuals travelling to polio endemic areas". No specific mention of infants is made. However, the insert says "the schedule of routine vaccination varies slightly from country to country..."

Manufacturer B, in addition to the above recipients also specifically mentions infants. For adults and pregnant women at any age Salk polio vaccine (intramuscular) is recommended before the administration of Sabin vaccine.

Many of the conditions listed as contraindication are common in both literature inserts. These include impaired immune response, hypersensitivity to enomyciue, acute febrile illness, leukemia malignant neoplastic diseases, etc.

There is, however, contradictory information concerning the use of polio vaccine in pregnant women. Manufacturer A says ..... "in accordance with general principles, the vaccine should not be given to pregnant women unless they are at a definite risk from poliomyelitis". Manufacturer B writes " . . . . . and for pregnant women at any age, inactivated poliomyelitis vaccine (Salk) is recommended for primary immunization before administration of trivakmt Sabin vaccine".

In most countries polio vaccine is given only for infants and young children. So the abov~ remarks may not confuse the vaccinators. But, inconsistencies such as this should be avoided since the same vaccinators will have access to both manufacturers vaccines, depending on supplier.

Dosage and Administration. Manufacturer A recommends 2 to 3 drops at an interval of 4 to 8 weeks to be administered three

SHRESTHA : WHAT IS WRONG WITH VACCINE LITERATURE INSERTS ? 323

times for acquiring a satisfactory antibody level. Manufacturer B recommends 3 doses of 3 drops each at an interval of six weeks.

Manufacturer A makes no mention of the earliest age at which this vaccine may be administered. While manufacturer B recommends starting the first dose at an age of three months in endemic areas with an interval of 4 weeks between doses. The recommended dose should be specified and consistent at 2 drops or 3 drops for all manufacturers as it makes a considerable difference in estimating the vaccine requirement.

While in actual practice the minimum age for administering polio vaccine is six weeks, the interval between doses varies from four weeks to twelve weeks in different countries. The programmes in various countries perhaps need to standardize this. Accurate, consistent information from drug companies would facilitate standardization.

Storage and Expiry Dates. Manufacturer A under the title, "Stability", writes "the sucrose-stabilized vaccine will maintain adequate potency for 7 mo;~ths when kept in a refrigerator at +2~ to +8~ At + 25~ adequate potency is maintained for three weeks and at + 37~ for three days." The insert continues "the magnesium chloride stabilized vaccine will maintain adequate potency for 18 months when kept in a refrigerator at 2~ to +8~ Adequate potency is maintained for six weeks at + 25~ three days at + 37~ and one day at + 45~ '' However, under the title, "Expiry date", it says "When stored at +2~ to +8~ sucrose and magnesium chloride stabilized Polio Sabin (oral) vaccine has a shelf-life of 6 months and 12 months respectively" which is less than what was

presented in the stability section of the insert "Recommended storage and shipment conditions" it says " the vaccine should be stored in a refrigerator between +2~ and +8~ or at -20~

Manufacturer B is a little more specific on this issue. The insert reads, "Poliovirus vaccine, live, oral (Sabin) should always be stored in the frozen state at a temperature not higher than minus 20 ~ C." It also says that after thawing it may be kept in a refrigerator at a temperature not higher than --40~ for a period not exceeding 90 days. Whereas manufacturer A writes "Freezing and thawing up to ten times does no effect the titen of the vaccine.

D.P.T.

The literature inserts are available for three different manufacturers. The comparative information available shows the following features :

Indications and Contraindications. Manufactures X and Y indicate that this vaccine is for infants and young children upto 2 years, against diphtheria, pertussis and tetanus. No lower age limit is specified for giving the first dose. The third manufacturer, Z, however has specified the lower limit as 2 months, but the upper age limit is increased to preschool age which may mean upto five years.

Manufacturer X writes "the immunity conferred by a complete course of basic immunization lasts 5 to 10 years for diphtheria and tetanus and 2 to 3 years for pertussis." Booster immunization is indicated every 5 to 10 years using adsorbed diphtheria and tetanus vaccine. The other two manufacturers are not very specific on this issue. Dosage and Administration. The recommended dose is 0.5 ml. The

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recommended intervals between doses is 4 to 8 weeks by manufacturers Y and Z.

Manufacturers Y and Z warn not to give DPT vaccine after 11 years and 6 years respectively for fear of reaction to diphtheria toxoid or to the pertussis component. Manufacturer X gives no warning.

Storage and Expiry Date. The recommended temperature for storage is fairly uniform. Manufacturers Y and Z recommend + 2 ~ C - + 8 ~ C and give strict warning not to freeze. Vaccine once frozen should be discarded. However manufacturer X recommends storage upto +10~ and recommends against freezing but does not indicate that the vaccine should not be used once it has been frozen.

Side Reactions and Efficacy. Manufacturer X makes no mention of any possible side reactions. While manufacturers Y and Z list a few side reactions like transitory reddening of skin, swelling at the site of vaccination, occasional fever, etc. In a few cases muscular cramps also occur due to cerebral damage.

Most of the gaps between doses in DPT are due to the transitory reactions. If the vaccinators are well informed and careful enough to explain these to the mothers the coverage with 2nd and even 3rd doses of DTP may increase.

MmSLES

Three manufacturers have supplied measles vaccine to Nepal. The similarities and differences in the information provided in the literature inserts are as follows :

Indication and Contraindications. One manufacturer, P, indicates this vaccine for

all children above 9 months of age, especially to those, at risk of malnutrition, thos~ who live in institutions, etc. The other two manufacturers, Q and R, recommends not administering the vaccine under 9 months of age and suggest revaccination at about 15-18 months of age in a child who was vaccinated under 12 months. The upper age limit is not specified by any of the manufacturers. In actual practice most countries administer this vaccine after 9 months and before 12 months of age as recommended by WHO.

Storage and Expiry Date. Manufacturers P and R recommend storing the vaccine at + 2~ to 8~ and away from light. If stored under these conditions the vaccine has a shelf-life of upto 2 years. Manufacturer O also agrees with the above storage recommendation but also includes information that if the vaccine is stored at +25~ it can remain potent upto 6 months, at +37~ upto 4 weeks and at + 41~ for 8 days. Is this true h)r all other vaccines also?

Measles vaccine once reconstituted using cooled diluent loses its potency very quickly. R mentions that under experimental conditions the potency of reconstitutes measles vaccine deteriorated after 24 hours at + 4~ to + 8~ and after 3 hours at +37~ Manufacturer R recommends storing the vaccine in the refrigerator no longer than 8 hours once it has been reconstituted, while manufacturer P makes no mention of this vulnerability of reconstituted measles vaccine.

In general it can be observed that some manufacturers go into detail on all aspects of the vaccine, while others limit themselves only to very broad information guides. The manufacturers whose vaccine

SHRESTHA : WHAT IS WRONG WITH VACCINE LITERATURE INSERTS ? 325

literature is reviewed here are perhaps the biggest suppliers of vaccines to the third world countries. By virtue of the fact that a large proportion of these vaccine consumers live in developing countries most of the commercial gains are generated from these countries, no matter who pays for the vaccine.

It is, therefore, vital that all the manufactures should give uniform and precise information to the consumers in the developing countries. The marketing

strategy adopted for drugs, especially for vaccines should be noncommercial in nature. In the present group of vaccines the information provided with BCG vaccine is more commercially oriented than any other vaccine. Such practices should be discouraged by agencies like WHO, UNICEF, etc. WHO are the biggest purchasers of vaccine. It is suggested that WHO/UNICEF should supply accurate, standard and uniform inserts for various vaccines.

SPOILED CHILD SYNDROME

At birth, human infants are totally dependent on those around them for the gratification of their needs. These needs include food, warmth, shelter, and love. They are vocal in their demands that these needs be met and will not willingly wait for anything when a need is felt. The process of developing into a mature, well-adjusted child and adult involves learning that not all needs can be met immediately, that others have needs as well, and that there is a difference between "wanting" and "needing."

The spoiled child syndrome represents the failure of this process of socialization. Because of the failure of parents to teach the growing child age-appropriate limits, the child remains self-centered and immature, unable to delay gratification or to tolerate not having his or her way. There is no upper age limit on being a spoiled child. Guidance and reassurance from the health care provider can help parents teach the necessary limits effectively, avoiding both the short-and long-term adverse consequences of spoiling. At the same time, the health care provider's advice can free the parents from the unnecessary worry and help them to get full enjoyment from participating in their child's growth and development.

Abstracted from : Mclntosh BJ. Pediatrics 1989; 83 : 108-15.