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Plague Vaccine


SUMMARY

These revised ACIP recommendations on plague vaccine represent an update of the previous recommendations (MMWR 1978;27:255-8) to include current information and practices.

INTRODUCTION

Plague is a natural infection of rodents and their ectoparasites and occurs in many parts of the world, including the western United States. In this country, a few human cases develop each year following exposure to infected wild rodents or their fleas and, less commonly, to other infected wild animals (bobcats, coyotes, rabbits) and domestic animals (cats, dogs). Epidemic plague may result when domestic rat populations and their fleas become infected. Recently, the areas of the most intensive epidemic and epizootic infection have been some countries in Africa, Asia, and South America.

General Recommendations

Because human plague is rare in most parts of the world, there is no need to vaccinate persons other than those at particularly high risk of exposure. Routine vaccination is not necessary for persons living in areas with enzootic plague such as the western United States. It is not indicated for most travelers to countries reporting cases, * particularly if their travel is limited to urban areas with modern hotel accommodations.

Many plague patients in the western United States are infected as a direct result of wild-rodent plague in the immediate vicinity of their homes. Recommended risk-reduction measures include eliminating wild-rodent harborage and food sources near homes, ridding pet dogs and cats of fleas at least weekly, and avoiding direct contact with sick or dead rodents.

In most countries of Africa, Asia, and South America where plague is reported, the risk of exposure exists primarily in rural mountainous or upland areas. Following natural disasters and at times when regular sanitary practices are interrupted, plague can extend from its usual areas of endemicity into urban centers. Rarely, pneumonic plague has been reported in conjunction with outbreaks of bubonic plague, and tourist travel to areas with reported cases of plague should be avoided.

Routine bacteriologic precautions, including the use of a biological safety cabinet to isolate procedures that may produce aerosols, are sufficient to prevent accidental infection with plague among clinical laboratory workers. Few laboratory-associated cases have ever been reported, and these almost exclusively occurred at plague research laboratories or involved unusual exposures. Vaccination of clinical laboratory workers is not indicated.

Ecologists and other field workers who might come in contact with wild animals and their ectoparasites in areas where plague has been known to occur should be made aware of the potential risks of plague and told how to minimize direct contact with potentially infective animals and their tissues or parasites. These precautionary measures are generally sufficient to prevent infection.

PLAGUE VACCINE

Plague vaccines ** have been used since the late 19th century, but their effectiveness has never been measured precisely. Field experience indicates that vaccination with plague vaccine reduces the incidence and severity of disease resulting from the bite of infected fleas. The degree of protection afforded against primary pneumonic infection is not known. Persons exposed to plague patients who have pneumonia or to Yersinia pestis *** aerosols in the laboratory should be given a 7- to 10-day course of antimicrobic therapy regardless of vaccination history. Recommended antimicrobials include tetracyclines, chloramphenicol, or streptomycin.

The plague vaccine licensed for use in the United States is prepared from Y. pestis organisms grown in artificial media, inactivated with formaldehyde, and preserved in 0.5% phenol. The vaccine contains trace amounts of beef-heart extract, yeast extract, agar, and peptones and peptides of soya and casein.

Serum antibody to Fraction I capsular antigen, as measured by the passive hemagglutination (PHA) test, is correlated with resistance to Y. pestis infection in experimental animals. A comparable correlation between PHA titer and immunity probably occurs in humans.

Following the primary series of 3 injections, about 7% of individuals do not produce PHA antibody, and a few fail to develop a titer of 128, the level correlated with immunity in experimental animals. PHA titers should be determined for individuals who have an unusually high risk of infection or who have a history of serious reactions to the vaccine in order to govern the frequency of booster doses. Such testing can be arranged through state health departments. Since plague vaccination may only ameliorate illness, whenever a vaccinated person has a definite exposure, prophylactic antibiotics may be indicated whether or not an antibody response has been demonstrated.

Vaccine Recipients

Vaccination is recommended for:

  1. All laboratory and field personnel who are working with Y. pestis

organisms resistant to antimicrobics, 2) Persons engaged in aerosol experiments with Y. pestis and 3) Persons engaged in field operations in areas with enzootic plague where preventing exposure is not possible (such as some disaster areas).

Selective plague vaccination should be considered for:

  1. Laboratory personnel regularly working with Y. pestis or

plague-infected rodents, 2) Workers (for example, Peace Corps volunteers and agricultural advisors) who reside in rural areas with enzootic or epidemic plague where avoidance of rodents and fleas is impossible, and 3) Persons whose vocation brings them into regular contact with wild rodents or rabbits in areas with enzootic plague.

Primary Vaccination

All injections should be given intramuscularly.

Adults and children greater than or equal to 11 years old: The primary series consists of 3 doses of vaccine. The first dose, 1.0 ml, is followed by the second dose, 0.2 ml, 4 weeks later. The third dose, 0.2 ml, is administered 6 months after the first dose. If an accelerated schedule is essential, 3 doses of 0.5 ml each, administered at least 1 week apart, may be given. The efficacy of this schedule has not been determined.

Children less than or equal to 10 years old: The primary series is also 3 doses of vaccine, but the doses are smaller (Table_1). The intervals between injections are the same as for adults.

Booster Doses

When needed because of continuing exposure, 3 booster doses should be given at approximately 6-month intervals. Thereafter, antibody levels decline slowly and booster doses at 1- to 2-year intervals, depending on the degree of continuing exposure, should provide good protection.

The recommended booster dosages for children and adults are the same as the second and third doses in the primary series. However, if serious side effects to the vaccine occur, their severity may be reduced by using half the usual dose. The primary series need never be repeated for booster doses to be effective (Table_1).

SIDE EFFECTS OF VACCINE

Primary vaccination may result in general malaise, headache, fever, mild lymphadenopathy, and erythema and induration at the injection site in about 10% of recipients. These reactions occur more commonly with repeated injections. Sterile abscesses occur rarely. Rare cases of sensitivity reactions manifested by urticarial and asthmatic phenomena have been reported.

PRECAUTIONS AND CONTRAINDICATIONS

Plague vaccine should not be administered to anyone with a known hypersensitivity to any of the constituents, such as beef protein, soya, casein, and phenol. Patients who have had severe local or systemic reactions to plague vaccine should not be revaccinated.

The safety or efficacy of vaccination with plague vaccine during pregnancy has not been determined, and therefore it should not be used unless there is a substantial risk of infection.

  • For a current listing, consult the most recent issue of the World Health Organization's Weekly Epidemiological Record; current information is also available from the Quarantine Division, Center for Prevention Services, Centers for Disease Control, Atlanta, Georgia 30333. ** Official name: Plague Vaccine *** The designation Yersinia pestis is used advisedly since there is reportedly a recommendation by the International Committee on Systematic Bacteriology to reclassify this organism as Yersinia pseudotuberculosis ssp. pestis (WHO. Weekly Epidemiological Record 1981;56:399).

SELECTED BIBLIOGRAPHY

Bartelloni PJ, Marshall JD Jr, Cavanaugh DC. Clinical and serological responses to plague vaccine. U.S.P. Mills Med 1973;138:720-2.

Burmeister RW, Tigertt WD, Overholt EL. Laboratory-acquired pneumonic plague. Ann Intern Med 1962;56:789-800.

Cavanaugh DC, Elisberg BL, Llewellyn CH, et al. Plague immunization. V. Indirect evidence for the efficacy of plague vaccine. J Infect Dis 1974;129 (Suppl):S37-S40.

Chen TH, Meyer KF. An evaluation of Pasteurella pestis fraction-1-specific antibody for the confirmation of plague infections. Bull WHO 1966;34:911-8.

Marshall JD, Jr, Bartelloni PJ, Cavanaugh DC, et al. Plague immunization. II. Relation of adverse clinical reactions to multiple immunizations with killed virus. J Infect Dis 1974;129(Suppl):S19-S25.

Marshall JD, Jr, Cavanaugh DC, Bartelloni PJ, et al. Plague immunization. III. Serologic response to multiple inoculations of vaccine. J Infect Dis 1974; 129(Suppl):S26-S29.

Meyer KF. Effectiveness of live or killed plague vaccines in man. Bull WHO 1970;42:653-66.
Table_1
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Table 1. Plague vaccine doses (in milliliters), by age group (in years),
for primary and booster vaccinations *
========================================================================
Dose number       <1 1-4 5-10>10
----------------------------------------------------------------
     1            0.2           0.4           0.6          1.0
   2 & 3         0.04          0.08          0.12          0.2
Boosters +     0.02-0.04     0.04-0.08     0.06-0.12     0.1-0.2
----------------------------------------------------------------
* Important details are in the text.
+ Smaller dose volume may be used if severe side effects are expected.
========================================================================

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