Passive Immunization

Hepatitis A

A major use of IM standard IG is for preexposure and postexposure prophylaxis of hepatitis A virus (HAV) in a susceptible person. When administered within 14 days of exposure, IG is 80%–90% effective in preventing clinical hepatitis. IG is most effective when administered early in the incubation period. When administered later in the incubation period, IG still may attenuate HAV disease. The usual dose of IM IG varies by age and should be administered as soon as possible after exposure. For persons 12 months–40 years of age, HAV vaccine is preferred for postexposure prophylaxis. IG is recommended for people >40 years of age because of the absence of data regarding vaccine use in adults >40 years of age and the severity of HAV infection in older adults. Children <12 months of age, immunocompromised people, people with chronic liver disease, and others who may have a diminished response to vaccine should receive IG.

IG may be effective for preexposure prophylaxis in travelers to areas where HAV is prevalent. However, for travelers who are ≥1 year old and whose departure is not imminent, HAV vaccine largely has replaced IG. Due to concern that preexposure prophylaxis with IG may decrease the effectiveness of measles, mumps, and rubella (MMR) vaccine (which is recommended for infants aged 6 months–11 months who are traveling internationally), an off-label dose of HAV vaccine instead of IG is recommended. The dose of IG depends on the age of the traveler and the length of stay. For a child <1 year old, the dose is 0.01–0.02 mL/kg if the anticipated stay is ≤2 months and 0.06 mL/kg if longer. In older persons whose departure is imminent, the dose of IG is 0.01–0.02 mL/kg, concomitant with the first dose of vaccine, for a stay of up to 5 months, and 0.06 mL/kg, concomitant with the first dose of vaccine, for a longer stay.

For people ≥12 months of age for whom IG is given for preexposure or postexposure prophylaxis, hepatitis A vaccine is given simultaneously, at a separate site and using a separate syringe.

Measles

Vaccination is the major strategy for achieving protection against measles. More than 98% of persons who receive 2 doses of measles vaccine (with the first dose administered no earlier than the first birthday and the second dose administered at least 28 days after the first dose) develop serologic evidence of immunity. Nonetheless, measles postexposure prophylaxis with IG is important for children <12 months of age (for age 6–11 months, MMR vaccine can be substituted for IG if within 72 hours of exposure), seronegative persons who cannot be vaccinated within 72 hours of exposure, seronegative pregnant women, and immunocompromised children not receiving routine immunoglobulin replacement therapy. Prophylaxis is indicated for susceptible household or hospital contacts of a case. A single dose of 0.5 mL/kg administered within 6 days of exposure may prevent or modify disease and provide temporary protection. No more than 15 mL should be injected; small children should be given no more than 3 mL at any single site. Manufacturer instructions should be consulted for maximum volume injected into a single muscle. A child receiving routine IgG replacement therapy is likely to have a protective concentration of measles-neutralizing antibody. If the child is ≥12 months of age, live measles vaccine should be administered ~6 months after IG administration if no contraindication exists. For children 6–11 months of age who are traveling to areas where measles is endemic, MMR vaccine (rather than IG) should be administered; this dose is not counted in the required 2-dose series at ≥12 months of age. IGIV is recommended for seronegative pregnant woman and for severely immunocompromised persons.

Rubella

IG can be considered for prophylaxis of rubella-susceptible women who are exposed to rubella early in pregnancy. As many as 85% of infants born to mothers who are infected in the first trimester of pregnancy will have signs of congenital rubella syndrome. The IG option is recommended only for women if termination of pregnancy is declined. Limited data indicate that IM IG in a dose of 0.55 mL/kg may decrease clinically apparent infection, virus shedding, and rates of viremia in infected susceptible people. Theoretically, the reduction in viral replication may decrease the likelihood of fetal infection. The absence of clinical signs in a woman who has received IG does not guarantee that fetal infection has been prevented. Infants with congenital rubella have been born to mothers who received IG shortly after exposure.

Hepatitis B Immune Globulin

All pregnant women should be tested for circulating hepatitis B surface antigen (HBsAg). Infants born to women who are HBsAg positive (either acutely or chronically infected with hepatitis B virus [HBV]) are at high risk of developing acute and chronic HBV infection. The HBV vaccination series accompanied by a single dose of HBIG is 85%–95% effective in preventing HBV infection in the infant. Infants born to an HBsAg-positive mother should receive HBIG (0.5 mL) within 12 hours of birth. The first of 3 doses of HBV vaccine should be given at the same time as HBIG but at a different site.

In general, HBIG is not recommended if the mother’s HBsAg status is not known, but HBV vaccination series should be begun within 12 hours of birth. Ideally, in such a case, the mother should be tested for HBsAg as soon as possible after delivery. If the test result is positive, the infant should receive 0.5 mL of HBIG IM as soon as possible (within 12–24 hours) and if delay is unavoidable, at least within 7 days of birth; vaccination series should be completed according to schedule. Preterm infants (<2 kg) constitute a special class. If the mother’s HBsAg status is unknown and cannot be determined within 12 hours, the neonate should be given 0.5 mL of HBIG as well as vaccine to provide passive antibody before onset of the active immune response to the vaccine.

After a percutaneous (needlestick, laceration, or bite) or mucosal exposure that contains or may contain HBV, blood should be obtained from the person who was the source of the exposure (if possible) to determine his or her HBsAg status. Management of the exposed person depends on the HBsAg status of the source and the vaccination and antibody to HBsAg response status of the exposed person. Recommended postexposure prophylaxis for different situations has been outlined by the Centers for Disease Control and Prevention (CDC).

Human Rabies Immune Globulin

Rabies IG (human) (HRIG) is always used in association with rabies vaccine for postexposure prophylaxis. ^, HRIG is administered to previously unvaccinated persons to provide rabies virus-neutralizing antibody until the patient responds to vaccination by actively producing virus-neutralizing antibodies. HRIG is administered once, at the same time postexposure prophylaxis is initiated with the human rabies vaccine.

The dose of HRIG is 20 IU/kg. If anatomically feasible, the dose should be infiltrated around the wound, and any remaining dose should be administered by the IM route at an anatomic site distant from the vaccine administration. HRIG is supplied in 2-mL (300 IU) and 10-mL (1500 IU) vials with an average potency of 150 IU/mL. Thus the contents of a 2-mL vial can be used to treat a child of up to 15 kg; for larger children, additional vials are required. A 10-mL vial is sufficient to treat a 75-kg adult and as a result is less suitable for pediatric use. However, if the smaller vials are not available, an appropriate portion can be withdrawn to treat a child. The product contains no preservative; once a vial has been entered, the contents should be administered promptly, and the remainder should be discarded.

Tetanus Immune Globulin

TIG was one of the first specific IG products. TIG is recommended for the treatment of tetanus and for prophylaxis in certain circumstances. A patient with tetanus should receive a single dose of TIG, although the optimal dose has not been determined. For postexposure prophylaxis, the need for active immunization with or without passive immunization depends on the condition of the wound and the patient’s immunization history. Specific guidance has been provided by the Advisory Committee on Immunization Practices. Persons with wounds that are neither clean nor minor and who have had 0–2 previous doses of tetanus toxoid or have an uncertain history of previous doses should receive TIG, as well as diphtheria and tetanus toxoids (DTs), tetanus and diphtheria toxoids (Td), diphtheria and tetanus toxoids and acellular pertussis (DTaP), or tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap), depending on age and other needed vaccines. TIG can neutralize only unbound tetanus toxin; it cannot affect toxin bound to nerve endings. A single IM dose of 3000–5000 units TIG is generally recommended for treatment of children and adults, with part of the dose infiltrated around the wound (250 units is maximum used for prophylaxis). IGIV contains tetanus antitoxin and can be used if TIG is not available.

Varicella-Zoster Immune Globulin

Postexposure prophylaxis should be targeted toward patients without evidence of immunity to varicella who are at high risk for severe disease and complications and who have been exposed to and likely infected by VZV. Such persons include the following: (1) immunocompromised people; (2) nonimmune pregnant women; (3) neonates whose mothers develop signs and symptoms of varicella within 5 days before delivery to 48 hours after delivery; (4) premature infants born at 28 weeks of gestation or later who are exposed in the neonatal period and whose mothers do not have evidence of immunity; and (5) premature infants born before 28 weeks of gestation or who weigh <1000 g at birth and are exposed during the neonatal period regardless of maternal history of varicella disease or vaccination (because transfer of maternal antibody may not have occurred). Significant exposure can occur through residence in the same household, close contact with a playmate, proximity to a contagious patient, or contact with a contagious visitor or hospital staff member.

In December 2012, the FDA approved VariZIG, a varicella-zoster IG preparation (Cangene Corporation, Winnipeg, Canada) for postexposure prophylaxis for persons at high risk of severe disease who lack evidence of immunity to varicella and for whom varicella vaccine is contraindicated. VariZIG is a lyophilized product and, after reconstitution, is administered IM. VariZIG is approved for administration as soon as possible following VZV exposure, ideally within 96 hours (4 days) for greatest effectiveness, but if it is administered within 10 days, it may result in disease attenuation. The dose is 125 U (1 vial)/10 kg body weight up to a maximum of 625 IU (5 vials). The minimum dose is 125 IU, or 62.5 IU if weight is ≤2 kg.

If VariZIG cannot be obtained within 96 hours after exposure, IGIV can be substituted at a dose of 400 mg/kg. Although licensed IGIV preparations are known to contain varicella antibody, the titer of any specific lot is uncertain. An alternative to postexposure prophylaxis with VariZIG or IGIV is administration of oral acyclovir or valacyclovir, which should be started 7–10 days after exposure and continued for a total of 7 days. This approach can be considered in immunocompetent, seronegative people with significant exposure who cannot be vaccinated. The oral acyclovir dose for adults is 800 mg given 4 times a day. If a child requires acyclovir preemptively, the dose is 40–80 mg/kg/day, divided into 4 doses (maximum daily dose 3200 mg) or valacyclovir 60 mg/kg/day divided into 3 doses (maximum daily dose 3000 mg). As an alternative, exposed immunocompetent children and adults can be given varicella vaccine within 3–5 days of exposure if they have not previously received 2 doses of vaccine and have no contraindication.