Yersinia pestis infection primary prevention

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2]

Overview

The plague may be prevented by the administration of prophylactic therapy and implementation of hospital and public risk reduction measures. Post-exposure prophylaxis is indicated in persons with known exposure to plague, such as close contact with a pneumonic plague patient or direct contact with infected body fluids or tissues. There is a vaccine available for professionals who work in laboratories with the bacteria, or who study infected rodents.

Primary Prevention

Prophylactic Therapy

• Post-exposure prophylaxis (PEP) is indicated in persons who, in the previous six days:
  • Have had close contact with pneumonic plague patients
  • Are likely to have been exposed to Y. pestis-infected fleas
  • Are likely to have had direct contact with body fluids or tissues of a Y. pestis-infected mammal
  • Were exposed during a laboratory accident to known infectious materials
• The preferred antimicrobials for preventive or abortive therapy are the tetracyclines, chloramphenicol, or one of the effective sulfonamides.
• True prophylaxis, meaning the administration of an antibiotic prior to exposure, may be indicated when persons must be present for short periods in plague-active areas under circumstances in which exposure to plague sources (fleas, pneumonic cases) is difficult or impossible to prevent.
• Duration of post-exposure prophylaxis to prevent plague is 7 days.
• Shown below is a table summarizing the recommended antibiotic regimens for PEP.

▸ Click on the following categories to expand treatment regimens.

Plague Treatment   ▸  Adult Patients   ▸  Children   ▸  Pregnant Patients

Adult Patients Preferred Regimen ▸ Doxycycline 100 mg PO q12h OR ▸ Ciprofloxacin 500 mg PO q12h Children Preferred Regimen ▸ Doxycycline (for children ≥8 years) if <45Kg: 2.2 mg/Kg PO q12h (max 200mg/day); if ≥45Kg: 100 mg PO q12h or 200 mg IV q24h OR ▸ Ciprofloxacin 20 mg/Kg PO q12h (maximum dose, 1g) Pregnant Patients Preferred Regimen ▸ Doxycycline 100 mg PO q12h OR ▸ Ciprofloxacin 500 mg PO q12h

Hospital Precautions

Standard patient-care precautions should be applied for the management of all suspected plague patients. These include prescribed procedures for:

• Handwashing
• Wearing of latex gloves and gowns
• Wearing protective devices to protect mucous membranes of the eye, nose and mouth during those procedures and patient-care activities likely to generate splashes or sprays of blood, body fluids, secretions and excretions.

Additionally, a patient with suspected respiratory plague infection should be specifically managed under respiratory droplet precautions, including:

• Management in an individual room
• Restriction of movement of the patient outside the room
• Masking of the patient as well as persons caring for the patient until the he/she is no longer infectious

Vaccination

Worldwide, live attenuated and formalin-killed Y. pestis vaccines are variously available for human use.

The vaccines are variably immunogenic and moderately to highly reactogenic. They do not protect against primary pneumonic plague.

In general, vaccinating communities against epizootic and enzootic exposures is not feasible; further, vaccination is of little use during human plague outbreaks, since a month or more is required to develop a protective immune response.

The production of the vaccine in the United States was stopped in 1999.

The vaccine is indicated for persons whose work routinely brings them into close contact with Y. pestis, such as:

• Laboratory technicians in plague reference research laboratories
• Persons studying infected rodent colonies

Primary Vaccination

• All injections should be administered intramuscularly, preferably in a deltoid muscle.
• Primary vaccination consists of a series of three injections.
• The simultaneous administration of plague vaccine with other vaccines that are likely to be reactogenic should be avoided.

Booster Doses and Monitoring Antibody Levels

• PHA antibody titers decrease soon after vaccination and could drop below the presumably protective level of 128 within a few months.
• Booster doses of 0.2 mL each can be administered three times at approximately 6-month intervals when vaccines have continuing high risk for exposure, especially for those persons who have passive haemagglutination test (PHA) titers of less than 128.
• Additional booster doses can be administered at 1- to 2-year intervals to persons who remain at risk for infection.
• Persons considering being vaccinated should be advised that they may have difficulty having their PHA titers evaluated because only a few public health and research laboratories routinely perform this test.

Adverse Reactions

• Adverse reactions following injection of the first dose of plague vaccine are generally mild, but the frequency and severity of such events can increase with repeated doses.
• Common adverse reactions include:
  • Local erythema and induration at the site of injection
  • Malaise
  • Headache
  • Fever
  • Lymphadenopathy

These reactions do not usually persist for greater than 48 hours.

Precautions and Contraindications

• Precautions to prevent adverse reactions should include review of the vaccine's history of hypersensitivity to plague vaccine and its components. Epinephrine should be available for immediate use in the event of anaphylaxis or other allergic reactions to the vaccine.
• The safety and immunogenicity of the vaccine for persons less than 18 years of age have not been evaluated. The effects of plague vaccine on the developing fetus also are unknown. Pregnant women who cannot avoid high-risk situations should be advised of risk-reduction practices and should be vaccinated only if the potential benefits of vaccination outweigh potential risks to the fetus.
• Persons who are immunocompromised or who are receiving immunosuppressive therapy may not develop protective levels of antibodies following vaccination. Whenever possible, antibody levels determined by PHA should be obtained to determine whether additional doses beyond the primary series should be administered.

• Plague vaccine should not be administered to persons who have a history of hypersensitivity to the vaccine or its components. Persons who have an acute febrile illness (e.g., influenza) should not be vaccinated until they have recovered fully.

Risk Reduction Measures

Attempts to eliminate fleas and wild rodents from the natural environment in plague-infected areas are impractical. However, controlling rodents and their fleas around places where people live, work, and play is very important in preventing human disease. Therefore, preventive measures are directed to home, work, and recreational settings where the risk of acquiring plague is high. A combined approach using the following methods is recommended:

• Environmental sanitation
• Educating the public on ways to prevent plague exposures
• Preventive antibiotic therapy

Environmental Sanitation

• Effective environmental sanitation reduces the risk of persons being bitten by infectious fleas, of rodents and other animals in places where people live, work, and recreate.
• It is important to remove food sources used by rodents and make homes, buildings, warehouses, or feed sheds rodent-proof.
• Applying chemicals that kill fleas and rodents is effective but should usually be done by trained professionals.
• Rats that inhabit ships and docks should also be controlled by trained professionals who can inspect and, if necessary, fumigate cargoes.

Public Health Education

In the western United States, where plague is widespread in wild rodents, people living, working, or playing where the infection is active face the greatest threat. Educating the general public and the medical community about how to avoid exposure to disease-bearing animals and their fleas is very important and should include the following preventive recommendations:

• Watch for plague activity in rodent populations where plague is known to occur. Report any observations of sick or dead animals to the local health department or law enforcement officials.
• Eliminate sources of food and nesting places for rodents around homes, work places, and recreation areas; remove brush, rock piles, junk, cluttered firewood, and potential-food supplies, such as pet and wild animal food. Make your home rodent-proof.
• If you anticipate being exposed to rodent fleas, apply insect repellents to clothing and skin, according to label instructions, to prevent flea bites. Wear gloves when handling potentially infected animals.
• If you live in areas where rodent plague occurs, treat pet dogs and cats for flea control regularly and don't allow these animals to roam freely.
• Health authorities may use appropriate chemicals to kill fleas at selected sites during animal plague outbreaks.