Vaccines used in the expanded program on immunization (EPI): indications and contradictions

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192 PAHO BULLETIN l vol. 18, no. 2, 1984

search on development of a vaccine that could be produced in cell cultures; this latter would greatly improve the speed and possibly the economy of vaccine production and allow for rapid expansion of production in the event of emergency situations.

In response to these recommendations, Brazil and Colombia have improved the phy- sical facilities of their vaccine proddction laboratories using national funds. In addition, both laboratories are modernizing their vac-

cine production methods with funds made available by Canada’s International Develop- ment Research Center and the Canadian In- ternational Development Agency. A portion of these latter funds has also been provided to conduct research on thermostabilizing media for yellow fever vaccine.

Source: Pan American Health Organization (Epidemi- ology Unit, Health Programs Development), PAHO Epi- demiological Bulletin 4(6):7-10, 1983.

VACCINES USED IN THE EXPANDED PROGRAM ON

IMMUNIZATION (EPI): INDICATIONS AND CONTRAINDICATIONS

Introduction

Immunization is one of the most powerful and cost-effective weapons of modern medicine. Immunization services, however, re- main tragically underutilized in the world to- day. In developing countries, it can be ex- pected that some 0.5% of all newborns will become crippled from poliomyelitis, 1% will die from neonatal tetanus, 2% will die of pertussis, and 3% will die from measles. In all, some five million children die from these diseases each year, 10 children with each passing minute.

These diseases are preventable with currently available vaccines if children ca.n be immunized early enough in childhood. There- fore, the decision to withhold the benefits of immunization from an eligible child, whatever the reason, should not be taken lightly. Unfor- tunately, health workers in many countries are faced with long lists of contraindications which, when followed scrupulously, result in many children remaining unimmunized. The problem resulting from deferring immunization is greatest where access to health services is limited and where the morbidity and mortality from vaccine-preventable diseases are

high. Immunization is frequently postponed if children are ill, malnourished, or about to be hospitalized; yet these are the very children for whom immunization services are most needed, for they are the ones most likely to die should they acquire a vaccine-preventable disease.

The purpose of this work is to review the benefits and risks of routine immunization of children with BCG, DPT, measles, and poliomyelitis vaccines, and (particularly for ill and malnourished children) to suggest circumstances in which immunization may be in the child’s best interest.

Adverse Reactions to Immunization

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. ABSTRACTS AND REPORTS 193

tally related to a child’s illness. Convulsions, for example, may follow DPT or measles immunization, but the background rate is high. At ages 3 to 15 months, the monthly incidence of convulsions ranges from 0.8 to 1.4 cases per 1,000 children (41-42).

BCG Immunization

The most serious complications of BCG immunization are disseminated infection with the BCG bacillus and BCG osteitis (Table 1). Both of these complications are rate. The former is usually associated with severe abnor- malities of cellular immunity (12, 43), while the latter has been reported mainly among infants immunized in the neonatal period in the Scandinavian countries (3-5). The most common complication, suppurative lymphade- nitis, has been reported in 0.1-4s of immunized children under two years of age. The risk of adverse reactions is related to the BCG strain used by different manufacturers, the dose, the age of the child, the method of immunization, and the skill of the vaccinator.

DPT Immunization

The most severe complications following DPT immunization are neurologic and are thought to be due primarily to the pertussis component of the vaccine. A recent large study in the United Kingdom, the National Childhood Encephalopathy Study, reviewed the immunization histories of children two months to three years of age who were hospi-

Table 1. Estimated rates of adverse reaction

following BCG immunization.

Adverse reaction

Disseminated BCG infection Osteitis

Suppurative adenitis (among children < 2 years old)

Estimated adverse References

reaction rate per providing

100,ooo vaccinees data

<O.l 1-3 <O.l-30 2-5

200-4,300 3, 6-12

talized with serious acute neurologic illnesses (encephalitis/encephalopathy, prolonged convulsions, infantile spasms, and Reye’s syndrome) and compared them with a control group (14, 44). It was estimated that a severe neurologic illness attributable to DPT occurred once in 110,000 DPT immunizations, and that lasting neurologic damage occurred once in 310,000 immunizati0ns.l The hazards of DPT immunization must, however, be bal- anced against the risks of remaining unimmunized. Convulsions, for example, occur 100 to 3,000 times more often during whooping cough than following DPT immunization, and pertussis frequently causes encephalopathy or death (Table 2).

Fever and mild local reactions following DPT immunization are common. It is estimated that 2-6% of the vaccinees develop a fever of 39% or higher, and that 5-10 % ex- perience swelling and induration or pain lasting more than 48 hours at the site of the injection. In studies in the United States and Australia, about 50% of the vaccinated children had local reactions (30, 31, 47, 48). Measles Immunization

Severe reactions following measles immunization are rare (Table 3). In the United States, neurologic disorders (including encephalitis and encephalopathy) have been reported once for approximately every million vaccine doses administered (33). However, the reported incidence of, encephalitis or encephalopathy following measles immunization is lower than the observed incidence of encephalitis of unknown etiology (two cases per milhon children in 28 days-34). This sug-

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194 PAHO BULLETIN l vol. 18, no. 2, 1984

Table 2. Estimated rates of adverse reaction following DPT immunization, compared to

complications of natural whooping cough.

Adverse reaction

Whoopmg cough DPT vaccme advene

complication rate reaction rate per

per 100,coo cases 100,000 immunizations

References pmwdrng data

Perr&nent brain damage

Death

Encephalopathy/enceph’alitis”

Convulsions

Shock

600-2,000 (0.6-2.0%)

loo-4,000

(O.l-4.0%)

go-4,000

(0.09-4.0%) 600-8,000 (0.6-8.0%)

-

0.3-0.6 13-18

0.2 16, 18-24

0.1-3.0 14, 16-19, 23, 25-29

0.3-90 16, 19, 22-32

0.5-30 25, 28

‘Including seizures, focal neurologic signs, coma, and Reye’s syndrome.

Table 3. Estimated rates of serious adverse reaction following measles immunization, compared to

complications of natural measles infection and the background rate of illness.

Adverse reaction

Measles complication rate per 100,ooo

case.5

Measles vaccine adverse reaction rate per 100,ooo vaccinees

Background rate of illness per 100,ooo persons

RCkWlC.3 providing data

Encephalitis/ encephalopatby Subacute sclerosing

panencephalitis Pneumonia

Convulsions

Death

50-400 0.1 0.1-0.3 33-35

(0.05-0.4%)

0.5-2.0 0.05-O. 1 - 16, 27, 36

3,800-7,300 - - 16, 35

(3.8-7.3%)

500-1,000 0.02-190 30 16, 27, 32, 34

(0.5-1.0%) 35, 37-39

lo-10,ooa 0.02-0.3 - 16, 20, 33, 35, 40

(O.Ol-10%)

gests that some of the reported severe neurologic disorders may not be caused by measles immunization, but instead may be related only in time. In the United Kingdom, however, the National Childhood Encephalopathy Study found a statistically significant association between the onset of acute neurologic illness and measles immunization given 7 to 14 days before the onset of illness, compared with controls. The relative risk for this period was estimated to be 2.5 times the background rate (19

Some 5- 15 % of measles vaccinees develop a temperature of 39.4’C or higher, beginning on the sixth day and usually lasting one or two days. Transient rash may occur in about 5% of the vaccinees (33).

Measles immunization, by preventing natural measles, reduces the risk of developing subacute sclerosing panencephalitis (SSPE) (33).

Poliomyelitis Immunization

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l ABSTRACTS AND REPORTS 195

the United States, the reported risk of paralysis among vaccinees or their close contacts has been one case per 3.2 million doses distributed PO)-

No serious adverse reactions to the inacti- vated poliomyelitis vaccines currently in use have been reported.

Immunization of I11 or Malnourished children

Health personnel are understandably cau- tious in offering immunization to any child who is not healthy. Nevertheless, as already noted, such children may be particularly benefited by immunization, and in most cases the immunization is safe and effective.

The most ample literature on this subject concerns measles immunization. Several studies have investigated measles immunization of malnourished or ill children. McMur- ray and coworkers (51) studied serum antibody responses and reaction rates to measles vaccine in normal and moderately malnourished ten-month-old Colombian children. The children were followed for more than a year. The malnourished children showed high measles antibody responses and had no more adverse reactions than well-nourished children. The authors concluded that measles vaccine was both safe and effective in moderately malnourished children.

Ifekwunigwe and coworkers (52) studied serum antibody responses and adverse reactions following measles immunization of malnourished Nigerian children five months to nine years old. They found that malnutrition did not impair the children’s serologic responses; of 111 children who were seronega- tive before immunization, 94% serocon- verted. There were no major adverse reactions to immunization during the eight-week followup period. The authors concluded that malnutrition should be a prime indication for measles immunization rather than a contraindication, because antibody responses are nor-

mal and because natural measles is often severe in malnourished children.

In most other studies, nutritional status appears to have had no significant effect on measles seroconversion rates when measles vaccine was administered alone (53-56) or simultaneously with DPT vaccine (56). In one investigation, however, children with severe kwashiorkor had impaired responses to measles immunization as compared to the responses of well children (57).

The results of three studies on measles immunization of ill hospitalized children (58-60) are shown in Table 4. The studies were con- ducted in hospital pediatric wards during ef- forts to control hospital-acquired measles, a cause of high morbidity and mortality. Chil- dren with a wide range of acute and chronic illnesses were included; reasons for exclusion were a terminal illness, a history of measles, steroid therapy, or an immunologic disorder. The authors concluded measles immunization of ill or malnourished children did not appear to adversely affect the course of the children’s illnesses, and that the risk of measles cross- infection in pediatric wards practicing measles immunization was diminished considerably.

In the Ivory Coast a policy of immunizing sick children was introduced in 1981 (61). All children between nine and 35 months of age visiting health centers because of illness other than measles were screened; if unimmunized against measles, they were immunized. The introduction of this new policy resulted in a near-doubling of the number or doses of measles vaccine administered, from 26,000 to 45,000 doses over comparable six-month periods.

Limited data are available concerning use of other EPI vaccines in malnourished or ill children. The use of DPT (62), BCG (9), and poliomyelitis (63) vaccines in moderately malnourished children appears to be safe.

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Table 4. Responses of ill African children to measles immunization, as indicated by three studies.

Children

Country and teference Agein

providing data NO. months

South Africa (70) 214 6-60

Subjects studied

Consecutive patients

admitted to hospital

Adverse reactions

Temperature 238.9”C (12%)

Koplik spot and rash (8 % )

Effects of immunization

Reduced nosocomial measles

compared to control wards

Zimbabwe (formerly

Rhodesia) (34)

Hospital patients with

gastmenteritis (4O%),

bronchopneumonia (30%), Temperature 138.9’C (13%) Reduced nosocomial measles

98 6-32 malnutrition (12%), other Rash (4%) compared to unimmunized

respiratory infections (6%), control group

meningitis (3%), or other

illnesses (9%)

south Africa (41)

Hospital patients with No nosocomial measles,

gastmenteritis (35%), compared to 9 cases and 3

654 7-36 cardiac or renal diseases deaths noted in the previous

(35%), bronchopneumonia (17%), year. Overall mortality

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Responses to tetanus toxoid of malnourished children also appear to be normal (62, 67, 68). Sick children with respiratory infections, gastroenteritis, or febrile illness (exclud- ing malaria) appear to respond like healthy controls to tetanus toxoid (69). Malaria has been shown in some studies to inhibit the antibody response to tetanus toxoid (67, 69, 70). In two of these studies, however, (69, 70), only one or two doses of unadsorbed tetanus toxoid (rather than adsorbed tetanus toxoid) were given. In more recent studies (71, 72), malaria was found to have no major effect on the serologic response to adsorbed tetanus toxoid, measles, or DPT vaccines. There is no evidence of increased rates of adverse reactions following immunization of children who have malaria.

Serum neutralizing antibody titers following a single dose of trivalent oral poliomyelitis vaccine have been found similar in malnourished and well-nourished children (54, 73). However, in malnourished children secretory IgA antibody was detected significantly less often, its appearance was delayed, and the observed levels were significantly lower.

Considerable evidence suggests that injec- tions, including immunizations, may provoke paralysis in the injected limbs of children who are in the incubation period of polio infection. This partly explains why authorities in some areas without poliomyelitis immunization programs have recommended that DPT be withheld from febrile children. Even though a small risk of injection-provoked paralysis may exist in polio-endemic areas, however, fever is neither a sensitive nor a specific sign of polio infection. It thus seems likely that withholding DPT immunization from febrile children would result in far more deaths from pertussis than prevented cases of injection-provoked poliomyelitis. However, concern about injection-provoked poliomyelitis does provide a strong argument in favor of providing polio immunization simultaneously with DPT at an early age, before infants are at high risk of ex- posure to wild polio virus.

National Policies Concerning Contraindications to Immunizzkm: Agreements and Disagreements

The countries of the world have adopted similar policies with respect to certain possible contraindications to immunization and different policies with respect to others. Policies are often based on theoretical concerns rather than facts, and needed data frequently are lacking. There is general agreement that immunization should be deferred in the presence of a severe febrile illness (14,74). The reasons are to avoid the risk of superimposing possible adverse effects from the vaccine on the under- lying febrile disease, and to avoid a manifesta- tion of the illness being attributed to the immunization.

There is also a consensus that vaccines re- quiring multiple doses, such as DPT, should not be repeated if a severe reaction occurred after a previous dose. Such reactions include collapse or a shock-like state, persistent screaming episodes, a temperature above 40.6%, convulsions, severe alterations in consciousness or other neurologic symptoms, and anaphylactic reactions. In the case of DPT, subsequent immunization with diphtheria and tetanus is recommended. Local reactions at the site of the injection or mild fever do not by themselves preclude the further use of DPT or other vaccines.

Also, live vaccines should not be administered to persons with immune deficiency diseases or to persons &hose immune response may be suppressed because of leukemia, lym- phoma, generalized malignancy, or therapy with corticosteroids, alkylating agents, anti- metabolic agents, or retardation.

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198 PAHO BULLETIN . vol. 18, no. 2, 1984

Kingdom, the Department of Health and Social Security includes untreated tuberculosis as a contraindication to measles immunization and recommends that children with a history of convulsions, epilepsy, or chronic heart or lung disease, as well aschildren who are seriously underdeveloped, be given measles vaccine only with the simultaneous administration of human immunoglobulin (14). The United States Public Health Service Advisory Committee on Immunization Prac- tices (ACIP), on the other hand, finds no con- vincing evidence that measles immunization exacerbates tuberculosis and concludes that the benefit of measles immunization far out- weighs the theoretical risk of such exacerba- tion (33). The ACIP recommends measles vaccine should never be administered simultaneously with immunoglobulin and does not recognize any neurologic contraindications to measles immunization.

Gastrointestinal disturbances, including diarrhea, are considered contraindications to oral poliomyelitis immunization in the United Kingdom but not in the United States (14, 50). Likewise, a family history of neurologic disease and developmental defects are considered contraindications to DPT immunization in the United Kingdom (14). In the United States an evolving neurologic disorder is considered a contraindication, but not a static neurologic disorder such as cerebral palsy or a family history of neurologic disease (25).

Recommendations of the Expanded Program on Immunization

A lack of resources-including personnel, supplies, and equipment-is the major factor constraining the delivery of effective immunization services in developing countries, while incomplete implementation of immunization policies is the main problem in in- dustrialized countries. Immunization policies that are needlessly restrictive can compound both of these problems.

It does not seem feasible or desirable to for-

mulate a universal set of recommendations for immunization of children. Each country should formulate its own policies, preferably based on the advice of a broadly constituted advisory group. The recommended national policy should reflect a practical appraisal of the disease risks, and of the benefits and potential risks of immunization. Important considerations include the availability and ac- cessibility of health care services, utilization patterns of these services, the ability to identi- fy and provide follow-up services for children who are not immunized, the likelihood that children will return for subsequent immunization, and the sociocultural acceptability of specific procedures and recommendations. A list of principal recommendations that can serve as a general guide is as follows:

l Health workers should use every opportunity to immunize eligible children,

l BCG can be given safely and effectively in the newborn period, while DPT and oral poliomyelitis vaccine can be given as early as six weeks after birth (or even earlier in certain circumstances). In countries where measles poses a major burden before the first birthday, measles vaccine should ordinarily be given at nine months of age.

l No vaccine is totally without adverse reactions, but the risks of serious complications arising from the EPI vaccines are much lower than the risks posed by the natural diseases they prevent.

l The decision to withhold immunization should be taken only after serious considera- tion of the potential consequences for the in- dividual child and the community.

l It is particularly important to immunize malnourished children. Low-grade fever, mild respiratory infections, diarrhea, and other minor illness should not be considered contraindications to immunizations.

l Immunization of children so ill as to re- quire hospitalization should be deferred for a decision by the hospital authorities.

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receive appropriate immunization before dis- charge. (In some cases they should be immunized on admission, because of the high risk of hospital-acquired measles.)

l A second or third DPT injection should not be given to a child who has suffered a severe adverse reaction to the previous dose. In such cases the pertussis component should be omitted, and the diphtheria and tetanus immunizations should be completed.

l Diarrhea should not be considered a contraindication to oral poliomyelitis vaccine; however, to ensure full protection, doses given to children with diarrhea should not be counted as part of the series, and each child should be given another dose at the first available opportunity.

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Source: World Health Organization, Indications and Contraindications for Vaccines Used in the Expanded Programme on Immunization, WHO Document EPII