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Plotkin SA, Orenstein WA, editors. Vaccines. 3rd edition. Philadelphia: Saunders; 1999.

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Vaccines. 3rd edition.

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Vaccine Strains

Strains of Vaccine and Their Passage

Many strains of vaccinia, known by different names, have been used by different producers during this and the past century, but little is known about their origins or passage histories. Characterization of strains is further complicated by the fact that a seed lot system for vaccine production was not used until the 1960s. Thus, even those strains with common names and ancestors have different passage histories, having been passed sequentially through a variety of vaccinifers, such as cows, sheep, and water buffalo, with periodic passages through rabbits, horses, and even humans. Indicative of the ignorance of vaccine technology until recent decades is a statement of the Ministry of Health of Great Britain, which, in 1928, 74 advised that seed lymph could be obtained from (1) “smallpox direct”; (2) cowpox; (3) horsepox, sheep-pox, or goatpox; and (4) vaccinia in the human body.

Jenner is believed to have used cowpox in vaccination, but the vaccinia virus strains used most recently are a different species of orthopoxvirus with distinctive DNA maps that are similar to each other but different from both cowpox and variola. That the vaccinia strains are not mutants of variola virus seems certain, 75 but where the present vaccinia species arose is unknown. It may have arisen either as a hybrid of cowpox and another orthopoxvirus or through thousands of serial passages under artificial conditions of culture. It is also possible that the species represents a laboratory survivor of a now naturally extinct species of orthopoxvirus. 76

In 1958, a World Health Organization (WHO) Study Group first recommended that a seed lot system be employed in vaccine manufacture. Beginning in 1967, an increasing number of vaccine producers, encouraged by the WHO, began to use one of two strains. Most common was the Lister strain from the Lister Institute, England, which was propagated as seed virus by the National Public Health Institute of the Netherlands for distribution by the WHO. The second strain was the New York City Board of Health strain, propagated by Wyeth Laboratories, Radnor, Pennsylvania, United States. Two of the largest countries, China and India, used other strains called, respectively, the Temple of Heaven strain and the Patwadanger strain.

During the 1930s, vaccinia strains began to be attenuated by serial passages in an effort to diminish the incidence of complications; the first was the Rivers strain, which was derived from the New York City Board of Health strain. 77 Three principal variants were developed that had been passed repeatedly through rabbit testis, chick embryo explants, and chorioallantoic membranes of embryonated hens' eggs. 78 Rivers and colleagues 79, 80 showed that the “second revived strain” produced less severe reactions in rabbits and humans than did the New York City Board of Health strain, especially if it was inoculated intradermally. This strain, administered with 2 mL of vaccinia immunoglobulin, was used for primary vaccination of 60,000 Dutch army recruits by van der Noordaa and colleagues. 81 One mild case of postvaccinal encephalitis occurred, but this was a lower incidence than that noted after administration of other strains. The resultant neutralizing antibody titers, however, were lower than those usually observed. This called into question the level of protection provided against smallpox, and the strain was not further employed.

Another variant of the Rivers vaccine, the CVI-78 also found to produce less severe local reactions, and although used to vaccinate children with eczema, 82 it was not thought likely to provide adequate protection against smallpox. 83 A large-scale comparative trial sponsored by the National Institutes of Health 84, 85 showed that the CVI-78 strain was 10-fold less infectious than the Lister strain and New York City Board of Health strains and produced smaller skin lesions and fewer febrile responses. Only 30% of children, however, exhibited neutralizing antibody, and after challenge vaccination with a standard strain, 25% still did not respond with neutralizing antibody.

Another attenuated vaccine, the modified vaccinia virus Ankara (MVA) strain produced by Stickl and collaborators 86 through passage in chick embryo fibroblast cells, had characteristics similar to those of the CVI-78 strain 87 . Some workers believed that a sequential vaccination schedule using the CVI-78 or MVA strain, followed after some months by application of a conventional strain, offered prospects for protection against smallpox with fewer complications. However, whether persons without neutralizing antibody response would be protected against natural challenge remained an unanswered question.

A more satisfactory attenuated strain, LC 16m8, was produced by Hashizume 88– 90 through passage at low temperature in rabbit kidney cells. This strain produced a satisfactory immune response in humans (HI and neutralizing antibodies), and in a field trial of 50,000 persons, it was found to produce a markedly lower frequency of reactions than that noted for other strains. 91 However, the achievement of smallpox eradication precluded use of this vaccine under circumstances of natural challenge.

Dosage and Route

The vaccine is inoculated intradermally with use of a bifurcated needle. Vaccine, as reconstituted for use with the bifurcated needle, is required to have a titer of not less than 108 pock-forming units per milliliter when it is assayed on the chorioallantoic membranes of 12-day-old chick embryos. Approximately 0.0025 mL of vaccine adheres by capillarity to the tines of the needle when it is dipped into the vaccine. The needle is positioned vertically to the skin surface, usually the lateral surface of the upper arm (Fig. 6-4), and 5 to 15 rapid strokes are made. These strokes are sufficiently vigorous that within 20 to 30 seconds, a trace of blood appears at the vaccination site.

Figure 6-4. The bifurcated needle positioned to begin multiple puncture vaccination.

Figure 6-4

The bifurcated needle positioned to begin multiple puncture vaccination. (Courtesy of the World Health Organization, Geneva, Switzerland.)

Constituents of Vaccine

Most vaccine now available for use is grown on the skin of a calf and harvested after sacrifice of the animal. The vaccine is purified by the addition of fluorocarbon and differential centrifugation, and its bacterial content is reduced by the addition of phenol. Peptone is added as a stabilizing agent, and the vaccine is freeze-dried. Because of its source, the vaccine inevitably contains some bacteria, but properly prepared, the number of bacteria is 10/mL or less. Microbiological examination must confirm that none is a human pathogen. For reconstitution of the vaccine for multiple puncture vaccination, a solution of 50% (volume per volume), glycerin in McIlvaine solution is used; for vaccine intended for jet injection, saline is used.

Laboratories in Brazil, New Zealand, Sweden, and the United States (e.g., Texas State Health Department) harvested vaccinia virus from the chorioallantoic membranes of chick embryos, a simple process that permits production of a bacteria-free vaccine. However, vaccine from this source proved difficult to produce in a satisfactory thermostabile freeze-dried form, and as far as is known, only Sweden produced the vaccine in eggs that were free of avian leukosis virus.

Vaccinia virus grown in tissue culture also prove difficult to produce as a thermostabile freeze-dried product, but Hekker and colleagues 92 eventually achieved this result using primary rabbit kidney cells. In field trials, the vaccine was comparable to vaccine grown on calf skin, 93, 94 but because of the approaching conclusion of the smallpox eradication program, the WHO made no effort to introduce the method for use in other laboratories.

Producers

Because of the eradication of smallpox and the cessation of routine vaccination, the number of production laboratories diminished from 76 in 1977 to 11 in 1985. The few remaining laboratories are in the industrialized countries and are engaged only in the preparation of finished vaccine from bulk preparations harvested in quantity some years ago and preserved by freezing. Virus grown in tissue culture is available in the Netherlands (Lister strain) and Japan (LC 16m8 strain); other countries use vaccine grown on calf skin (primarily Lister and New York City Board of Health strains).

Storage Conditions

Freeze-dried smallpox vaccine is the most stable of currently available vaccines. The vaccine can be preserved indefinitely at −20°C and most batches are equally well preserved at 4°C. International standards require that the vaccine in its freeze-dried form maintain full potency when it is incubated at 37°C for 1 month. Studies of vaccine produced at the Lister Institute, however, demonstrated that the vaccine retained full potency for 64 weeks when it was incubated at temperatures of up to 45°C and for 104 weeks at 37°C. 95 Not all vaccines were this stable, but assay of vaccines produced in India and the former USSR and retrieved from the field revealed batches of vaccine that met potency standards after 6 to 9 months of exposure at high ambient summer temperatures. After reconstitution, the vaccine is much more sensitive both to temperature and to exposure to direct light. During the eradication program, unused reconstituted vaccine was routinely discarded at the end of each day, although it can be preserved in this form for at least 1 week at 41°C.

Results of Vaccination

Immune Response

After primary vaccination, neutralizing and HI antibodies develop about the 10th day and are present in almost all persons by the end of 2 weeks; CF antibodies develop in less than half of the vacinees. 52 Because the antibody response after primary vaccination usually occurs 4 to 8 days earlier than the response after naturally acquired smallpox infection, 96 primary vaccination even after exposure sometimes modified or aborted an overt attack of smallpox. The neutralizing antibodies are most persistent and may be detected for 20 years or more; HI and CF antibodies, however, are usually not detectable beyond 6 months. Little is known about the cell-mediated immunity that is induced, although Pincus and Flick 97 demonstrated the beginning development of delayed hypersensitivity, an index of cell-mediated immunity, as early as 2 days after vaccination. Antibody response after revaccination is more rapid, usually within 7 days, and antibody titers are generally higher. However, some persons who exhibit a substantial rise in neutralizing antibody titer after revaccination fail to exhibit a rise in either HI or CF antibody levels.

Successful primary vaccination results in virus proliferation in the basal cells of the epidermis, producing the typical jennerian vesicle (Fig. 6-5). A papule with surrounding erythema develops in 3 to 5 days, rapidly becoming a vesicle and later a pustule. It reaches its maximum size after 8 to 12 days. A scab forms that separates at 14 to 21 days, leaving a typical vaccination scar. A low-grade fever usually accompanies the development of the pustule, and swelling of the draining lymph nodes, associated with tenderness, is often observed. Viremia may occasionally occur 98 between the third and tenth days, and vaccinia virus can sometimes be isolated from tonsillar swabs. 99

Figure 6-5. A primary vaccination response on the ninth day after inoculation shows erythema surrounding a pustular lesion.

Figure 6-5

A primary vaccination response on the ninth day after inoculation shows erythema surrounding a pustular lesion. Although the picture is from a colored drawing made by Captain C. Gold in 1801, the lesion shown is indistinguishable from contemporary responses (more...)

An individual's response to revaccination depends on the level of immunity. Erythema typically develops within 24 to 48 hours as a classic delayed hypersensitivity reaction. As Benenson 100 has shown, this reaction can be elicited with both live and inactivated vaccine. Persons with some residual cell-mediated immunity, but not enough to inhibit viral replication, develop erythema and sometimes a pustule at the site of a vesicle, both of which evolve in a sequence more rapid than that in a primary vaccination reaction. Those with substantial immunity may experience no more than the hypersensitivity reaction.

Because it is impossible to distinguish between a hypersensitivity reaction due to the use of impotent vaccine and a similar reaction due to a high level of immunity the WHO Expert Committee on Smallpox 101 recommended that such a response be termed an equivocal reaction. For persons with equivocal reactions, repeated vaccinations were advised. Others who exhibited evidence of virus proliferation at 6 to 8 days, as manifested by a pustular lesion or an area of induration surrounding a central lesion, were said to have experienced a major reaction.

Protection Afforded by Vaccination

Reliable data are surprisingly sparse as to the efficacy and durability of protection afforded by vaccination. Before 1967, when the intensified global eradication program began, revaccination every 3 to 10 years was considered essential to ensure protection. In part, this practice was based on early data largely from the United Kingdom, such as those provided by Hanna, 102 and on more recent data from India, 103 which compared the frequency of cases among those with and without vaccination scars. However, the vaccine in use in the populations studied was far lower in titer than that used after 1967; most of the vaccine was heavily contaminated with bacteria. In India, the vaccination instrument that was used (i.e., the rotary lancet) was found to produce localized sepsis and an apparent scar, even when only the diluent was applied. Estimates of protection after successful vaccination were therefore almost certainly understated in these as in other early studies. Another observation that suggested that protection might persist for no more than 3 to 5 years was the increasing proportion of persons who exhibited a major reaction to revaccination beginning about this time. Mistakenly, resistance to intradermal inoculation with vaccinia virus was equated with resistance to variola virus acquired by droplet inhalation.

From studies conducted after 1967, it became apparent that vaccinial immunity was far more durable than most investigators believed. It was found that with the available higher titer vaccines, major reactions could be induced in persons successfully vaccinated as recently as 3 to 6 months before and, indeed, in almost all of those who had experienced smallpox only 1 year previously. 104 Because natural infection effectively confers permanent immunity, it was apparent that the ability of vaccinia virus to proliferate on inoculation into the basal cells of the dermis correlated poorly with the level of protection afforded against natural infection. Moreover, in most countries, 90% or more of cases were among individuals without vaccination scars. This finding led to surveys in the endemic countries that disclosed vaccine-efficacy ratios of 80% or more among those vaccinated 20 years previously. Heiner and colleagues, 65 however, showed that this protection could not be attributed solely to the vaccine. They discovered that previously vaccinated persons often developed inapparent infection with substantial increases in antibody levels. Immunity in the endemic countries was thus a composite of past experiences with both vaccinia and variola infections. Data from countries where smallpox was introduced after an absence of many years provide insufficient information to permit calculation of vaccine-efficacy ratios, but they do indicate that the vaccine provides substantial long-term protection against a fatal outcome. 73 Among 680 cases of variola major occurring after importations of smallpox into Europe, the case-fatality rate was 52% among those who had never been vaccinated, 1.4% among those vaccinated up to 10 years before exposure, and 11.1% among those vaccinated more than 20 years before.

Simultaneous Administration with Other Antigens

It has been shown that smallpox vaccine can be administered at the same time as a number of other antigens, usually at a different site, with levels of safety and efficacy comparable to those observed when the vaccines are given separately. Simultaneous administration of oral poliovirus and smallpox vaccines became a routine practice in many countries beginning in the 1960s. 105, 106 Smallpox and bacille Calmette-Guerin (BCG) vaccines began to be administered to newborns in Hong Kong in the 1960s 107 ; this became a common practice in many African countries in the late 1960s. Yellow fever and smallpox vaccines were mixed and administered successfully in many French-speaking areas of western Africa, 108 and measles and smallpox vaccines were simultaneously administered in a program throughout western Africa from 1967 to 1972. 109 Mixing of smallpox, yellow fever, and measles vaccines for inoculation by jet injection resulted in a diminished immune response to yellow fever, 110 but responses were satisfactory when different sites of inoculation were used. Ruben and colleagues 111 extended the studies to the simultaneous administration by jet injection, but at different sites, of smallpox, yellow fever, measles, and diphtheria-pertussis-tetanus (DPT) vaccines. Systemic reactions were no more frequent or severe than those that occurred after measles or smallpox vaccination alone, but there was, in this study, a diminished immune response to measles. The last observation was not, however, confirmed in subsequent studies. From these and other observations, Foege and Foster 112 concluded that it was safe and efficacious to administer simultaneously all the vaccines (oral poliovirus, DPT, measles, and BCG) employed in the WHO Expanded Program of Immunization as well as smallpox and yellow fever vaccines.

Complications of Vaccination

Skin Infections

After vaccination, three types of abnormal skin reactions may occur as follows: (1) eczema vaccinatum and (2) progressive vaccinia, which are both associated with abnormal host reactions, and (3) generalized vaccinia. Vaccinia virus from a lesion may also be accidentally inoculated at other sites on the body or transferred to others. The approximate frequency of such complications and rates per million vaccinees are shown in Tables 6-2 and 6-3 based on a national survey by Lane and colleagues 113 in the United States, the only country in which comprehensive studies of this type were undertaken. More detailed prospective studies in 10 states 114 revealed higher rates for eczema vaccinatum, generalized vaccinia, and accidental infection as well as for other complications; the higher rates resulted from the detection of more minor complications.

Table 6-2. Complications of smallpox vaccination in the United States, 1968.

Table 6-2

Complications of smallpox vaccination in the United States, 1968.

Table 6-3. Complications per 1 million smallpox vaccinations in the United States during 1968.

Table 6-3

Complications per 1 million smallpox vaccinations in the United States during 1968.

Eczema vaccinatum occurs in both vaccinated persons and their unvaccinated contacts who have active or quiescent eczema. Either concurrently with or shortly after the development of the local vaccinial lesion or after an incubation period of 5 days in an unvaccinated eczematous contact, a vaccinial eruption occurs at sites that are eczematous or that had previously been so. The areas become intensely inflamed, and the eruption sometimes spreads to normal skin. Constitutional symptoms are usually severe, with high temperature and generalized lymphadenopathy. Treatment with vaccinia immune globulin appears to reduce mortality. 115

Progressive vaccinia occurs in persons who suffer from deficient immune mechanisms, such as agammaglobulinemia, defective cell-mediated immunity, or immune deficiency associated with tumors of the reticuloendothelial system or the use of immunosuppressive drugs. In such patients, the vaccinia lesion fails to heal; secondary lesions sometimes appear elsewhere on the body and then gradually spread. Methisazone (N-methylisatin β-thiosemicarbazone) is reported to be partially effective in treatment, 116 but one third of such patients die. 113

With generalized vaccinia, one to many lesions develop in 6 to 9 days after vaccination at locations other than the vaccination site in otherwise healthy persons. The evolution of these lesions follows the same temporal course as that of the vaccination lesion itself. Although patients may experience high fever and malaise, an uneventful recovery without the need for specific therapy is usual.

Accidental inoculation of vaccinia virus, transferred from the lesion at the vaccination site, is by far the most common, although innocuous, complication. The most common sites for inoculation are the eyelids, vulva, and perineum. Such lesions evolve rapidly and heal at the same time as the primary lesion. Accidental infection of normal contacts may also occur.

Postvaccinal Encephalopathy and Encephalitis

Among those without known contraindications to vaccination, postvaccinal encephalopathy and encephalitis are the most serious complications. The incidence of these related complications was substantially higher in Europe after the use of strains in common use at that time 117 than in the United States, where the New York City Board of Health strain was employed. Two pathological forms were distinguished by de Vries 118 : encephalopathy primarily in children younger than 2 years, and encephalitis or encephalomyelitis in those who were older. The encephalopathy is characterized by general hyperemia of the brain, lymphocytic infiltration of the meninges, widespread degenerative changes in ganglion cells, and perivascular hemorrhage. Severe symptoms begin abruptly within 6 to 10 days after vaccination, 119 with fever and convulsions, usually followed by hemiplegia and aphasia; death, when it occurs, follows within a few days. Recovery is seldom complete; the patient is left with mental impairment and some degree of paralysis. Postvaccinal encephalitis, characterized by perivenous, demyelination and microglial proliferation, primarily afflicts persons older than 2 years and is similar to the form of encephalitis observed after vaccination against rabies or after measles infection. Illness usually begins between 11 and 15 days after vaccination and is accompanied by fever, vomiting, headache, malaise, and anorexia followed by disorientation and drowsiness and sometimes convulsions and coma. Death occurs in 10 to 35% of cases, usually within a week. Some survivors have residual paralysis or mental impairment. Paralysis, when it is present, tends to be of the upper motor neuron type. Among those patients who recover fully, symptoms and signs resolve within 2 weeks. 120– 127

Many reports document the frequency of cases of postvaccinal encephalopathy and encephalitis in Europe and the United States, but comparison of rates is difficult because of differing criteria for diagnosis and variability in the completeness of reporting (Table 6-4). The usual levels of incidence, such as those reported from the Netherlands, Germany, and Austria, were higher than those in the United Kingdom, and these rates in turn were higher than those in the United States. 113, 114, 128 Whatever the criteria and methods, differences between the rates appeared to be real, and this fact caused a number of countries, during the 1960s, to begin using the Lister strain, then in use in the United Kingdom. A dramatic reduction in the incidence of postvaccinal encephalitis subsequently occurred. 120, 129 The incidence in the Netherlands between 1964 and 1971 appeared to approach that in the United States; 10 of the 16 cases were fatal, however, compared with only 4 of 16 cases reported in the United States in 1968. The differences are not statistically significant, but the results are consistent with other observations that suggest that the New York City Board of Health strain is somewhat less pathogenic than the Lister strain.

Table 6-4. Incidence of postvaccinal encephalopathy (in infants younger than 2 years) and postvaccinal encephalomyelitis (in persons older than 2 years) after primary vaccination, in various countries and at various times.

Table 6-4

Incidence of postvaccinal encephalopathy (in infants younger than 2 years) and postvaccinal encephalomyelitis (in persons older than 2 years) after primary vaccination, in various countries and at various times.

No single laboratory test correlates with strain virulence, but Marrenikova and colleagues, 130 as a result of a series of studies in mice and rats, provide a broad classification of a number of strains as follows: (1) least pathogenic: New York City Board of Health and EM-63 (a derivative of this strain); (2) moderately pathogenic: Lister, Berne, and Patwadanger (from India); and (3) highly pathogenic, Denmark, Tashkent (an older Russian strain), and Ikeda (an older Japanese strain).

Unusual Complications

In some laboratories, even during the present century, the vaccine was often contaminated with tetanus spores or other pyogenic bacteria that induced infections. With improved methods, however, such infections ceased to occur.

Vaccination during pregnancy did not appear to result in an increase in the incidence of abortions or still births. 131– 133 Fetal vaccinia is rare, having been documented on fewer than 20 occasions 134 ; no studies have implicated vaccinia virus as a teratogen. 135

A rare occurrence is the development of a malignant skin tumor, such as a melanoma, in the vaccination scar many years later, 136 and vaccinal osteomyelitis has occasionally been recorded and sometimes confirmed by recovery of vaccinia virus. 137

Indications for Vaccination

In endemic countries, which, until after World War I, consisted of most of the world, vaccination was recommended for everyone, with revaccination to occur every 3 to 10 years. The only exceptions were infants, for whom primary vaccination was customarily delayed until they were 3 to 12 months of age, mainly because of more frequent vaccination failures at an earlier age. As higher titer vaccines became available in the 1920s, French and then German physicians showed that a high proportion of successful vaccinations could be achieved in some hospitals, this became routine practice. 138 In at least one city in the United States, Detroit, neonatal vaccination was mandated in the mid-1920s. 139

As time passed and smallpox incidence declined, it became increasingly common for smallpox-free countries to delay primary vaccination until children were older. This resulted in part from the demonstration that maternal antibody inhibited virus proliferation 140 and in part from the belief that older children could better cope with the fever and systemic symptoms of vaccinial infection.

Vaccination at a later age was also less likely to be associated mistakenly with other events, such as sudden infant death syndrome, which might be temporally but not causally related. Some European countries recommended that vaccination be delayed until the second year of life to avoid postvaccinal encephalopathy, 119 and the United States adopted the practice of vaccinating at 12 months of age when studies suggested a higher frequency of postvaccinal encephalitis among those vaccinated before 1 year of age than among those vaccinated between 1 and 4 years of age. 113 What theses changes in policy may have achieved, however, is unknown, because no studies were performed to validate that complications were subsequently less frequent.

As a rule, most vaccination practices in the developing countries tended to parallel those in Europe and North America, and as of 1967, most countries, even those with endemic smallpox, delayed vaccination until the child was 3 to 9 months of age. Notable exceptions were Hong Kong, 107 where neonatal vaccination had been traditional at least since World War II, and Madras, India, 103 where neonatal vaccination was introduced in the late 1950s. During the late 1960s, it became apparent that vaccines that met international standards of potency consistently resulted in high levels of vaccination “takes” in newborns. Thus, newborn vaccination was recommended for all countries, although not all countries followed the practice. Unfortunately, there are no adequate studies that serve to compare the efficacy and durability of immunity provided at birth with that provided at older ages, nor is there information that permits a comparison to be made between the relative frequency of vaccination complications at this and older ages.

Primary vaccination was provided for adults if required, although many workers have considered it to be associated with a substantially higher incidence of postvaccinal encephalitis and other serious complications. Earlier European data suggest this to be the case, 117 but this was not borne out in studies conducted in the United States. 113, 128 Confirming this association was a review of United States military medical records between 1946 and 1962, conducted by the Centers for Disease Control and Prevention, which revealed no cases of central nervous system complications among an estimated 2 million recruits who were given primary vaccinations. The differences in experience in Europe and the United States almost certainly reflect differences in the pathogenicity of the strains employed.

Since 1980, routine vaccination has ceased in all countries, although a number of countries continue to provide vaccination to military forces as a protection in case variola virus is used as a biological warfare agent. Otherwise, vaccination is recommended only for those working in laboratories where orthopoxviruses are used.

Contraindications to Vaccination

During campaigns in areas that were endemic for smallpox, the WHO recognized no contraindications to vaccination for two reasons: first, the risk associated with smallpox infection was significantly greater than the risk of complications; second, most vaccinations were performed by individuals without medical training who could not be expected to recognize conditions such as eczema or to identify patients with immune deficiency syndromes. It was recommended that only those who were extremely sick not be vaccinated on the grounds that their subsequent death might be attributed mistakenly to vaccination.

In nonendemic areas, four conditions were generally accepted as contraindications.

Immune Disorders

Immune disorders included agammaglobulinemia, hypogammaglobulinemia, neoplasms affecting the reticuloendothelial system, and compromised immune status associated with the use of immunosuppressive drugs. Persons with such disorders, if vaccinated, were at substantial risk of developing the frequently fatal progressive vaccinia.

Eczema

Individuals with active eczema or a past history of eczema were at special risk of developing eczema vaccinatum, a serious and sometimes fatal complication. Because family members with eczema were also at risk from contact spread of vaccinia virus, it was recommended that either the healthy vaccinee or the eczematous family member live apart from the family until the lesion had fully scabbed over.

Pregnancy

Pregnant women were not vaccinated on the general principle that immunization of any sort should be avoided during pregnancy and because of the rare risk of fetal vaccinia.

Disorders of the Central Nervous System

Many countries recognized as contraindications disorders of the central nervous system in potential vaccinees and sometimes their families, hoping, in so doing, to minimize the risk of postvaccinal encephalitis. However, there is no evidence that the exclusion of such persons affected the incidence of that complication.

Some authorities recommended withholding vaccination from patients suffering from various acute or chronic illnesses of many other types, hypothesizing that the response to vaccination might be abnormal. There was no evidence for this occurrence except in the case of leprosy patients, some of whom developed erythema nodosum leprosum or neuritis after primary vaccination. 141, 142 In endemic areas, however, leprosy patients were vaccinated because the risk of smallpox substantially outweighed the risk of complications.

Copyright © 1999, W.B. Saunders Company.
Bookshelf ID: NBK7289

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