Postexposure Prophylaxis
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Recommendation:
Postexposure prophylaxis should be provided to selected
persons with exposures to Haemophilus influenzae type b
disease, meningococcal infection, hepatitis A, hepatitis B,
tuberculosis, and rabies (see Clinical Intervention).
Burden of Suffering
Secondary infection following exposure to persons with
certain infectious diseases may be preventable through the
prompt administration of prophylactic antibiotics or
immunobiologics. Although a complete discussion of each of
these diseases is beyond the scope of this report, certain
exposures deserve special emphasis. These include
Haemophilus influenzae type b disease, infection with
Neisseria meningitidis, hepatitis A and B, tuberculosis,
and rabies.
Systemic Haemophilus influenzae type b occurs in about 1
out of every 200 children born in the United States.1 Most
cases occur during infancy,2,3 but children remain
susceptible to infection until age 5. Children are at
especially increased risk if they are exposed to infected
persons at home or at day-care centers.2-4 Meningococcal
infections were reported in nearly 3000 persons in 1987.5
Infection with Neisseria meningitidis can lead to severe
meningitis and septicemia.6 Hepatitis A and hepatitis B
each accounted for over 25,000 new cases in 1987, and over
22,000 new cases of tuberculosis were reported in the same
year.5 Human rabies remains an uncommon disease in the
United States, with only nine cases diagnosed since 1980.7
In the absence of adequate postexposure prophylaxis,
however, infected persons often die from rabies
encephalitis.8
Efficacy of Prophylaxis
Rifampin prophylaxis can reduce the risk of secondary
infection in persons exposed to Haemophilus influenzae type
b (Hib) and Neisseria meningitidis. Studies have shown that
a four-day antibiotic regimen can reduce both the rate of
asymptomatic carriage of Hib and the incidence of secondary
infection in household and day-care contacts of infected
persons.3,9-11 Rifampin may also be effective in reducing
secondary infection in children exposed at day-care centers
to Hib-infected children.4,12 Similarly, rifampin
prophylaxis in contacts of patients with meningococcal
infection can reduce the rate of colonization and secondary
infection.13 Sulfonamides are preferred over rifampin if
the strain of Neisseria meningitidis is known to be
sensitive.14
Since the 1940s, passive immunization with immune globulin
has been shown to be an effective means of preventing
infection with hepatitis A in persons exposed to active
disease.15 Standard immunoglobulin (IG) must be
administered within two weeks of exposure. Hepatitis B
immune globulin (HBIG) is about 75% effective when
administered promptly to susceptible persons with
percutaneous, sexual, or mucosal exposure to hepatitis
B.16-18 Combined HBIG plus hepatitis B vaccine is over 90%
effective in preventing perinatal transmission (see Chapter
20) and is likely to be equally effective in other
circumstances. For passive prophylaxis, a second HBIG dose
is generally necessary after one month. This second dose
can be obviated through active immunization with hepatitis
B vaccine at the time of the first dose of HBIG.
Active-passive immunization has the advantage of providing
long-term protection against future exposure.19 Recombinant
DNA hepatitis B vaccine has recently become available in
the United States and appears to be more immunogenic (see
Chapter 57).
Bacille Calmette-Guerin (BCG), a live vaccine derived from
attenuated Mycobacterium bovis, has been used worldwide for
more than 50 years to prevent tuberculosis (TB). Clinical
trials of the efficacy of BCG have yielded inconsistent
results since the early 1930s, however, with reported
levels of protection ranging from -56% to 80%.20 In a
recent report, a large controlled trial in India reported
no significant reduction in the risk of sputum-positive
pulmonary TB in 15 years of follow-up.21 Observational
studies have shown that the incidence of the disease is
lower in vaccinated children than in unvaccinated
controls.22-27 Factors contributing to the wide variation
in results in BCG vaccine efficacy include genetic changes
in the bacterial strains as well as differences in
production techniques, methods of administration, and the
populations and environments in which the vaccine has been
studied.28 In the United States, where the risk of becoming
infected with TB is relatively low, the disease can be
controlled most successfully by periodic tuberculin skin
testing of high-risk groups and the administration of
preventive chemotherapy to those whose skin tests convert
from negative to positive (see Chapter 21). However, BCG
vaccination may have a role in the United States for
persons with special exposures to individuals with active
TB, such as uninfected children who are at high risk for
continuous or repeated exposure to infectious persons who
remain undetected or untreated.28
Combined active-passive immunization provides effective
postexposure prophylaxis against exposure to rabies. Two
vaccine preparations, human diploid cell vaccine and rabies
vaccine adsorbed, are licensed in the United States, but
only the former is widely available.29 All persons treated
with at least five doses of human diploid cell vaccine (or
rabies vaccine, adsorbed) and human rabies immune globulin
have developed adequate antibody titers.29 Since human
rabies is a rare disease, with less than five cases per
year having occurred in the United States since 1960,30 it
is difficult to measure the efficacy of postexposure
prophylaxis by the incidence of actual cases. No cases of
rabies were reported in over 500 persons given postexposure
therapy (human diploid cell vaccine and rabies immune
globulin) for bite exposures to rabid animals.31,32 Very
rarely, cases of fatal encephalitis have been reported in
individuals given human diploid cell vaccine; in one case
immune globulin was not administered, and in the other,
rabies vaccine was not administered as directed.14,33
Rabies vaccination is also recommended for preexposure
prophylaxis in persons at high risk of contact with rabies
virus, such as animal handlers, veterinarians, cave
explorers, and hunters exposed to rabid animals.31,34 A
three-dose series of human diploid cell vaccine (1 mL IM or
0.1 mL ID) on days 0, 7, and 28 provides adequate antibody
response in virtually all recipients.35,36
Recommendations of Others
The Immunization Practices Advisory Committee of the
Centers for Disease Control (CDC) and/or the American
College of Physicians have issued recommendations on
postexposure prophylaxis for Haemophilus influenzae type b
disease,37 meningococcal infection,38 hepatitis A and
B,39,40 rabies,36,41 and tuberculosis.28 The American
College of Obstetricians and Gynecologists has issued
detailed guidelines on the use of vaccines during
pregnancy.42
Clinical Intervention
Oral rifampin prophylaxis should be prescribed promptly for
all household contacts of patients with Haemophilus
influenzae type b, if at least one of the contacts is a
child less than 4 years old. Prophylaxis of infants and
young children (less than 2 years old) with day-care
exposure to infected cases may also be appropriate. The
dosage is 20 mg/kg, with a maximum of 600 mg, daily for
four days for children and adults. Infants less than 1
month old should receive 10 mg/kg.
Oral rifampin prophylaxis is also indicated for household
or day-care contacts of persons with meningococcal
infection, as well as for those with direct exposure to
oral secretions (e.g., kissing). Dosage is 600 mg for
adults, 10 mg/kg for children 1 month of age or older, and
5 mg/kg for children under 1 month of age, all given twice
daily for two days. Rifampin is contraindicated during
pregnancy. Sulfonamides should be used if the meningococcus
is adequately sensitive.
Hepatitis A immune globulin (0.02 mL/kg intramuscularly)
should be administered to close household and sexual
contacts of persons with hepatitis A, staff and children at
day-care centers where hepatitis A is occurring, staff and
patients of custodial institutions in which hepatitis A is
occurring, and co-workers of food handlers with hepatitis
A. Immune globulin should be given within two weeks of
exposure.
The recommended protocol for postexposure prophylaxis
against hepatitis B depends on the nature of the exposure
and the HB vaccination status of the exposed person. For
unvaccinated persons with percutaneous or mucous membrane
exposure to blood known to be hepatitis B surface antigen
(HBsAg) positive, or those bitten by a known carrier, a
single intramuscular dose of HBIG (0.06 mL/kg) should be
administered immediately, and a three-dose series of
hepatitis B vaccine should be initiated. The first dose
should accompany the dose of HBIG; the second and third
doses should be given one and six months later. If vaccine
is not administered, a second dose of HBIG should be given
after one month. The three-dose vaccine series should also
be initiated for persons with percutaneous or mucosal
exposure to bodily fluids of persons at high risk of being
infected. However, serologic confirmation of the HBsAg
status of the suspected person should be obtained within
seven days of exposure before administering HBIG. For
percutaneous exposure to bodily fluids of persons at low
risk, a three-dose vaccine series should be administered;
testing of the source person and HBIG administration are
not necessary.
Previously vaccinated persons exposed to infected bodily
fluids should receive serologic testing. If the exposed
person has inadequate antibody, one dose of HBIG should be
given along with a vaccine booster dose (1 mL or 20 mcg) at
a different site. If the source is at high risk of HB
infection but HBsAg status is unknown, serologic testing of
the source is indicated only if the exposed person is a
known vaccine nonresponder. If the source is
HBsAg-positive, the exposed person should receive one dose
of HBIG and a vaccine booster dose.
Persons with sexual exposure to HBsAg-positive persons
should receive serologic screening before treatment, unless
it will delay intervention to more than 14 days after
exposure. Seronegative persons should receive a single dose
of HBIG within 14 days of the last sexual contact. A second
dose should be given if the source remains HBsAg-positive
at three months and exposure continues. If the source
becomes a carrier (HBsAg-positive for six months), the
contact should receive a complete vaccine series. For
exposures among homosexual men, the HB vaccine series
should be initiated at the time HBIG is given; for
exposures among heterosexuals, the HB vaccine is optional.
If HB vaccine is given, additional doses of HBIG are
unnecessary.
See Chapter 20 for recommendations on prenatal screening
and neonatal vaccination against hepatitis B, as well as
for general information about HB vaccine. More details on
postexposure prophylaxis for HB are available from CDC
publications.39-40
Postexposure prophylaxis against rabies should be
instituted if a possible exposure to rabies virus has
occurred. Criteria for making this assessment, which
include the type of animal (e.g., carnivorous wild animals,
bats), the circumstances of the incident (e.g., unprovoked
attack), and the type of exposure (e.g., bite), are
available in published guidelines14 and from local health
departments. Rabies immune globulin is given at a dose of
20 IU/kg; half of the dose is infiltrated around the wound,
and the remainder is given intramuscularly at another site.
Rabies vaccine is administered in the deltoid area in five
1 mL intramuscular injections: days 0, 3, 7, 14, and 28.
Persons who were immunized before the incident require only
two 1 mL doses of vaccine (day of exposure and day 3) and
do not require immune globulin. Rabies vaccination is also
recommended for preexposure prophylaxis in persons at high
risk of contact with rabies virus, such as veterinarians,
animal handlers, cave explorers, and hunters exposed to
rabid animals.
BCG vaccination against TB should be considered only in
tuberculin-negative children who cannot be placed on
isoniazid (INH) and who have continuous exposure to persons
with active disease, those with continuous exposure to
patients with organisms resistant to INH or rifampin, and
those belonging to groups with a rate of new infections
greater than 1% per year and for whom the usual
surveillance and treatment programs may not be
operationally feasible. These groups may also include
persons with limited access to or willingness to use health
care services.
Note: See Appendix A for the U.S. Preventive Services Task
Force Table of Ratings for this topic. See also the
relevant Task Force background paper: LaForce MF.
Immunizations, immunoprophylaxis, and chemoprophylaxis to
prevent selected infections. JAMA 1987; 257:2464-70.
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