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Human immunoglobulins can be given by IV or IM injection to confer passive (temporary) immunity.They provide immediate protection. The effects last weeks. They tend to be large-volume injections and should be given by deep IM injection into the thigh or buttock and, in children, should be divided and given in different sites. They are derived from plasma of non-UK blood donors - to avoid new Creutzfeldt-Jakob disease (nCJD) - and are safe from hepatitis B and C, HIV and syphilis (and can be tested for cytomegalovirus (CMV) and malaria if necessary).
There are two types of immunoglobulins
- Normal (nonspecific) - from unselected donors
- Hyperimmune (specific) - from selected donors
Side-effects of both types
- Malaise, chills, fever
- Headache, nausea, facial flushing
- Anaphylaxis (rarely)
Human normal immunoglobulin
Human normal immunoglobulin (HNIG) is made from the plasma of about 1,000 donors. This provides antibodies against hepatitis A, rubella, measles and other viruses prevalent in the general population. It is most effective within three days of contact (but has some effect up to six days); protection is immediate and lasts several weeks. They block the immune response to live vaccines (except yellow fever) for three months, and live vaccines should ideally be given at least three weeks before or three months after an injection of HNIG. This can, however, be ignored if there is insufficient time - eg, for travellers. It is contra-indicated in those with class-specific antibody to IgA.
HNIG is used for:
- Hepatitis A contact in immunocompromised patients, preferably given within 72 hours, together with hepatitis A vaccine (HAV) - in a different site because there may be a poor antibody response to the vaccine alone. HAV protects normal individuals if given within a week of contact (possibly even up to the day of travel).
- Rubella contact in non-immune pregnant women where termination is unacceptable - it does not prevent infection but reduces symptoms and the risks to the fetus. Give as soon as possible after exposure only when termination is not acceptable. Measles, mumps and rubella (MMR) and anti-D may be given in the postpartum period (separate syringes and into different limbs). Measure rubella antibodies after eight weeks and vaccinate if necessary. However, rubella vaccine is not effective for post-exposure prophylaxis.
- Measles contact, within 72 hours of exposure (some effect if given within six days) in:
- The immunocompromised.
- Non-immune pregnant women (but there is no evidence it prevents fetal loss).
- An infant aged under 9 months - if the mother is not immune
- An infant aged 6-8 months - if the mother is immune (because under 6 months the child is protected by maternal antibodies and after 9 months MMR can be given for prophylaxis following exposure to measles).
- Poliomyelitis - HNIG may reduce the risk of developing paralysis in the immunocompromised but there is no evidence to support this.
IV HNIG is also used to give broad-spectrum passive protection to premature babies, patients with congenital hypogammaglobulinaemia, immunoglobulin deficiencies, autoimmune disorders - eg, thrombocytopenic purpura (where temporary, rapid rise in platelets is needed, such as pregnancy, or pre-operatively), Kawasaki disease, following bone-marrow transplantation, children with HIV, Guillain-Barré syndrome, and myasthenia gravis (unlicensed use) when it can induce remission in severe relapse.
Note: For mumps contacts, neither HNIG nor MMR offers protection.
Human specific immunoglobulins
- Hepatitis B immunoglobulin:[5, 6]
This is used after needlestick or sexual exposure and in infants born to infected mothers (persistent carrier with detectable hepatitis e antigen or its antibody or in recent infection. It should also be given in hepatitis B mothers when the birth weight of the baby is <1500 g. The sexual contacts of acute hepatitis B sufferers and chronic hepatitis B sufferers (newly diagnosed) should also receive specific immunoglobulin if unprotected sexual contact occurred in the previous seven days. It should be given preferably within 12 hours and not later than one week after exposure. Hepatitis B vaccine should also be given. See separate article Hepatitis B Vaccination and Prevention.
- Human varicella-zoster immunoglobulin:
This given to the non-immune exposed to chickenpox or shingles if at risk of severe infection:
- Immunocompromised individuals.
- High-dose steroidal therapy (an adult who has received 40 mg daily for more than a week in the previous three months, or a child who has received a daily dose of 2 mg/kg for more than a week, or 1 mg/kg for more than a month, in the previous three months).
- Non-immune pregnant women (to protect the fetus).
- Neonates of women who develop chickenpox seven days before/after delivery.
- Significant exposure to the virus.
- Rabies immune globulin:
This is indicated for an unimmunised person exposed to a bite from an animal from a high-risk country. As much as possible is injected into or around the cleansed wound (after washing with soapy water). Rabies vaccine should also be given.
- Tetanus immunoglobulin:
Together with metronidazole and wound cleansing, this is given for tetanus-prone wounds, in the non-immune or those not up-to-date with boosters. Tetanus vaccine should also be given. IV immunoglobulins are also given for treatment of tetanus.
- Cytomegalovirus immune globulin:
On a named-patient basis, this is for patients receiving immunosuppressive treatment.
Rarer uses of immunoglobulins
- Aplastic anaemia - IV antilymphocytic globulin (50% respond).
- Diphtheria antitoxin - (from horses) for suspected diphtheria, adverse reactions are common. Diphtheria antitoxin does not provide any benefit when used prophylactically.
- Botulism antitoxin for suspected botulism; again, adverse reactions are common.
Further reading and references
Immunisation against infectious disease - the Green Book (latest edition); Public Health England
Hepatitis A - Immunoglobulin Handbook; Health Protection Agency, Dec 2009
Measles - Immunoglobulin Handbook; Health Protection Agency, May 2009
Polio - Immunoglobulin Handbook; Health Protection Agency, Oct 2008
Hepatitis B - Immunoglobulin Handbook; Health Protection Agency, Oct 2008
HBIG for infants - Immunoglobulin Handbook; Health Protection Agency, Aug 2008
Chickenpox - Immunoglobulin Handbook; Health Protection Agency, Oct 2008
Rabies - Immunological Handbook; Health Protection Agency, Aug 2010
Tetanus, Immunoglobulin Handbook; Health Protection Agency, Mar 2013
Diphtheria - Immunoglobulin Handbook; Health Protection Agency, Nov 2013
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