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Plague Vaccine USP - Instructions for use

Author: Not Specified
Publication: Not Specified
Document Dated: Not Specified
Date Posted: January 15, 1997


This is a verbatim transcript of the "Directions for use" leaflet

14-7600-000(Rev. Dec. 1988)

Plague Vaccine USP

Description


Plague vaccine is a sterile, liquid vaccine for intramuscular injection. It contains at the time of manufacture 1.8-2.2 x 109 per mL of formaldehyde killed plague bacilli (Yersinia Pestis) in Sodium Chloride injection, USP. The product may also contain trace amounts of: beef heart extract, yeast extract, the peptones and peptides of soya and casein, agar and not more than 0.019% formaldehyde. It is preserved with 0.5% phenol.

CLINICAL PHARMACOLOGY

Plague vaccine is used to promote active immunity to plague in individuals considered at high risk of infection. Inactivated bacilli present in plague vaccine promote the production of plague antibody; plague antibody neutralizes the bacilli so that the incidence and severity of infection are reduced.

Plague is caused by the bacterium, Yersinia Pestis, an organism which occurs naturally in rodents and their ectoparasites. Plague may develop in humans following exposure to or handling of infected wild rodents or their fleas and, less commonly, following exposure to or handling of other infected wild animals (eg., bobcats, coyotes, rabbits) or domestic animals (eg., cats, dogs). In the US, plague has been found in ground squirrels, prairie dogs, jack rabbits, and pack rats. Worldwide, camels, goats, sheep, coyotes, deer, dogs, and cats may be exposed to infection either by feeding on infected carcasses or by becoming infested with infected fleas.

Transmission of plague from rodent to rodent or rodent to human is generally mediated by bite(s) of an infected flea(s). Human infection from an infected flea bite(s) most frequently results in bubonic plague with an incubation period of 2-8 days. Bubonic plague may rarely progress to pneumonic plague by haematogenous (septicemic) transport of Y. Pestis to the lungs. Virulent encapsulated droplets of Y. Pestis can then be transmitted from individual to individual by the respiratory route without insect vectors. The incubation period for pneumonic plague is 2-5 days.

Y. Pestis contains at least 19 antigenic components. Five components (ie., Fraction 1 capsular antigen, the V and W antigens, exotoxin and endotoxin) correlate immunogenic activity and virulence, whereas the remaining components have not been demonstrated to correlate with plague immunity or infection. Fraction 1 capsular antigen is the principal antigen involved with both virulence and immunity. Antibody to Fraction 1 capsular antigen, determined by passive hemagglutination (PHA) test, correlates with protection against Y. Pestis infection in experimental animals; a comparable correlation between the titer for antibody to Fraction 1 capsular antigen (determined by PHA) and immunity appears to exist in humans. Although some experts consider a titer of antibody to Fraction 1 capsular antigen (determined by PHA) of at least 1:32 to be indicative of protection, the US Public Health Service Immunization Practices Advisory Committee (ACIP) states that the minimum titer of antibody to Fraction 1 capsular antigen (determined by PHA) indicative of adequate protection against plague is 1:128 in animals.

The presumptive protective titer of antibody to Fraction 1 capsular antigen (1:128) is generally reached following IM administration of an initial 1mL dose of Plague Vaccine followed by a second dose of 0.2mL. The titer increases following administration of a third dose of 0.2mL of vaccine, and persist for about 6-12 months. In one study in 29 adult male volunteers,1 following IM administration of Plague Vaccine in doses of 1, 0.2 and 0.2mL on days 0, 90, and 270, respectively, the mean titer of antibody to Fraction 1 capsular antigen determined by passive hemagglutination (PHA) test, was 1:25, 1:140, and 1:576 at 15, 105, and 285 days respectively. However, in this study, 7% of the individuals failed to produce detectable antibodies even after the second booster dose. Thus individual variation in the response to vaccine does exist.

It is generally believed that the use of plague vaccine greatly increases the chances of recovery in those vaccinated individuals who may develop the insect borne (bubonic) form of the infection.2 The degree of protection afforded against the pneumonic form is unknown and vaccinated persons exposed to pneumonic form should be given daily, adequate doses of a suitable antibiotic over a 7-10 day period.

The duration of protection against infection following administration of the primary series of these injections of Plague vaccine is brief (ie., 6-12 months) and booster doses in approximate 6 month intervals are required for continued protection.

INDICATION AND USAGE

Immunisation with this vaccine is recommended for those persons at particularly high risk of exposure to plague. High risk areas include rural mountains or upland areas of South America, Asia and Africa.

Routine vaccination is not necessary for persons residing in plague enzootic areas (such as those living in the western United States) nor for travellers in countries where cases have been reported particularly if travel is limited to urban areas.3 Use of the vaccine is recommended in the following situations:3

1. Following natural disaster and/or at times when regular sanitary practices are interrupted;

2. All laboratory and field personnel who are working with Y. Pestis organisms resistant to antimicrobics;

3. Persons engaged in aerosol experiments with Y. Pestis;

4. Persons engaged in field operations in plague enzootic areas where prevention of exposure is not possible (such as some disaster areas).

Selective vaccination might be considered for:

1. Laboratory personnel regularly working with Y. Pestis or plague infected rodents;

2. Workers (for example, Peace Corps volunteers or agricultural advisors) who reside in plague enzootic areas or plague epidemic rural areas where avoidance of rodents or fleas is impossible;

3. Persons whose vocation brings them into regular contact with wild rodents or rabbits in plague enzootic areas.

CONTRAINDICATIONS

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

Plague vaccinations should not be administered to patients who have severe thrombocytopenia or any coagulation disorder that would contraindicate intramuscular injections.

WARNINGS

Immunization of individuals with severe febrile illness should generally be deferred until they have recovered to avoid superimposing adverse effects of the vaccine on the underlying illness or to avoid mistakenly concluding that manifestation of the underlying illness resulted from vaccination. Public health officials should be consulted regarding the need for prophylaxis in these individuals. Administration of plague vaccine to individuals with minor illnesses (eg., mild upper respiratory infections) should not be postponed.

PRECAUTIONS

General

Epinephrine should be available for immediate treatment of any anaphylactic reaction if it occurs.

Drug Interactions

When practical, Plague Vaccine should not be given on the same occasion as typhoid or cholera vaccines to avoid the possibility of accentuated side effects.4

Pregnancy Category C

Animal reproduction studies have not been conducted with Plague Vaccine. It is not known whether Plague Vaccine can cause fetal harm when administered to pregnant women or can affect reproduction capacity. Plague Vaccine should be given to a pregnant woman only if clearly needed.

Paediatric Use

Although clinical studies have not been conducted in children, the Immunization Practices Advisory Committee (ACIP) recommends immunization of children who are at risk.3

ADVERSE REACTIONS

Adverse reactions are usually mild following Immunization with Plague Vaccine. Adverse reactions may occur more frequently and with more severity following repeated doses of the vaccine. The increased frequency and severity of adverse reactions following repeated doses appears to depend on the number of doses received, the method by which the doses are administered, and the reactivity of the individual.

Local Effects

Erythema and induration at the site of injection occur in about 10% of patients receiving Plague Vaccine but may occur more frequently following repeated injections. Other adverse local reactions to the vaccine include tenderness and edema. Most local adverse reactions to the vaccine subside within 2 days. Sterile abscesses occur rarely.

Systemic Effects

Malaise, headache, lymphadenopathy, and fever occur in about 10% of patients receiving Plague Vaccine but may occur more frequently following repeated doses. Other adverse systemic reactions to the vaccine include arthralgia, myalgia, leucocytosis, nausea and vomiting. Adverse systemic effects to the vaccine usually only persist for a few days.

Sensitivity reactions, manifested by anaphylactic shock, tachycardia, urticaria, asthma and/or hypotension, have occurred rarely following administration of Plague Vaccine.

DOSAGE AND ADMINISTRATION

Plague Vaccine is administered by intramuscular injection preferably into the deltoid muscle. It may be used with a jet injector gun. The product should be well shaken before use.

Adults and Children Over 10 Years Old:

Primary immunization consists of a series of two to three injections. The first injection consists of 1.0mL of Plague Vaccine followed after one to three months by a second injection of 0.2mL.5 This series of two injections will adequate protection in the vast majority of human beings who have never received this vaccine.1 Generally, plague antibody titers are increased by a third injection. Some individuals not responding to the first two injections may produce adequate response following the third injection. A third injection of 0.2mL three to six months after the second injection is recommended.

Booster injections of 0.1 to 0.2mL should be administered at six month intervals to individuals remaining in a known plague area. The smaller doses should be approached as the total number of such injections increases. It should be noted, however, that booster doses at intervals of greater than six months, eg., 1-2 years, may be appropriate for persons who have received 3 or more booster doses at six month intervals. In persons who have an unusually high risk of infection or who have a history of serious reactions to the vaccine, passive hemagglutination titers (PHA) should be determined in order to determine the frequency of booster doses.3

Children Less Than Ten Years Old

The same technique and time schedule holds true for primary and booster injections in children; however, in both primary and booster injections the following dosage formula should be used:

Under 1 year 1/5 adult primary or booster dose

1-4 years 2/5 adult primary or booster dose

5-10 years 3/5 adult primary or booster dose

11 years and over adult primary or booster dose

Table 1 summarizes the recommended doses for primary and booster vaccinations:

Table 1

Recommended doses, by volume (mL), for immunization against plague:

Age in years
Dose Number less than 1 1 to 4 5 to 10 over 10
1 0.2mL 0.04mL 0.6mL 1.0mL
2&3 0.04mL 0.08mL 0.12mL 0.2mL
booster 0.02-0.04mL 0.04-0.08mL 0.06--.12mL 0.1-0.2mL

Parental drug products should be inspected visually for particulate matter and discolouration prior to administration, whenever solution and container permit.

HOW SUPPLIED

Plague Vaccine is supplied in a 20mL vial.

STORAGE

Store at 2-8oC (35-46oF). Do not freeze. Do not use after expiration date.

CAUTION

US FEDERAL LAW PROHIBITS DISPENSING WITHOUT A PRESCRIPTION.

LIMITED WARRANTY

A number of factors beyond our control could reduce the efficacy of this product or even result in an ill effect following its use. These include improper storage and handling of the product after it leaves our hands, diagnosis, dosage, method of administration, and biological differences in individual patients. Because of these factors, it is important that this product be stored properly and that the directions be followed carefully during use.

The forgoing statement is made in lieu of any other warranty, express or implied, including any warranty of merchantability or fitness. Representatives of the Company are not authorised to vary the terms of this warranty or the contents of any printed labelling for this product except by printed notice from the Companies headquarters. The prescriber and user of this product must accept the terms hereof.

REFERENCES

1.Bartelloni PJ, Marshall JD Jr, Cananaugh DC: Clinical and serological responses to plague vaccine USP.Milit.Med 138:720-2, 1978

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

3.Plague vaccine. Morbidity Mortality Weekly Report 31(22):301-4,1982

4.General recommendation on immunisation. Morbidity Mortality Weekly Report 32(1):1-18, 1983

5.Meyer KF: Effectiveness of live or killed plague vaccines in man Bull WHO 42:653-66, 1970

US License No 8 Canadian License No 24

Miles Inc, Cutter Biological, Elkhart, IN 46515 USA (Mfr) Miles Canada Inc,Etobicoke, Ontario, M9W 1G6, Canada.


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