Human immunoglobulins can be given by IV or IM injection to confer passive (temporary) immunity.¹ 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 2 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 3 days of contact (but has some effect up to 6 days); protection is immediate and lasts several weeks. They block the immune response to live vaccines (except yellow fever) for 3 months, and live vaccines should ideally be given at least 3 weeks before or 3 months after an injection of HNIG, although this can be ignored if there is insufficient time, e.g. 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 vaccine protects normal individuals if given within a week of contact (possibly even up to the day of travel).²
• Rubella contact in nonimmune pregnant women where termination is unacceptable³ - it does not prevent infection but reduces symptoms and the risks to the fetus. Give as soon as possible after exposure. Serological follow-up is essential. 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 8 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 6 days) if:⁴
  • Immunocompromised
  • Nonimmune pregnant women (but no evidence it prevents fetal loss)
  • Infant under 9 months - if mother not immune
  • Infant 6-8 months - if mother 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 this⁵

Intravenous HNIG is also used to give broad-spectrum passive protection to premature babies, patients with congenital hypogammaglobulinaemia, immunoglobulin deficiencies, autoimmune disorders, e.g. thrombocytopenic purpura (where temporary, rapid rise in platelets is needed, such as pregnancy, or preoperatively), Kawasaki syndrome, 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 offer protection.

Human specific immunoglobulins

These solutions are made from plasma containing high levels of certain antibodies.


1. Anti-D (Rho) immunoglobulin (see separate article Anti-D (Rho) Immunoglobulin) 500 units, can be given at 28 weeks, 34 weeks and at birth to rhesus-negative mothers to block fetal RhD-cells from stimulating antibodies (which could cause haemolytic disease of the newborn in future babies). Anti-D is given within 72 hours of abortion, miscarriage or birth, and after any potentially sensitising situations, e.g. amniocentesis, antepartum haemorrhage and abdominal trauma. Anti-D can be safely repeated as many times as needed during one pregnancy.⁶
2. Hepatitis B immunoglobulin^7,8 (see separate article Hepatitis B Vaccination and Prevention) 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 1 week after exposure. Hepatitis B vaccine should also be given.
3. Human varicella-zoster immunoglobulin is given to the nonimmune exposed to chickenpox or shingles if at risk of severe infection:⁹
   • Immunocompromised individuals
   • High-dose steroidal therapy (adult who has received 40 mg daily for more than a week in the previous 3 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 3 months)
   • Nonimmune pregnant women (to protect the fetus)
   • Neonates of women who develop chickenpox 7 days before/after delivery
   • Significant exposure to the virus
4. Rabies immune globulin¹⁰ 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.
5. Tetanus immunoglobulin¹¹ (together with metronidazole and wound cleansing) is given for tetanus-prone wounds, in the nonimmune or those not up-to-date with boosters. Tetanus vaccine should also be given. IV immunoglobulins are also given for treatment of tetanus).
6. Cytomegalovirus immune globulin (on a named-patient basis) for patients receiving immunosuppressive treatment.

Rarer uses of immunoglobulins

• Aplastic anaemia - IV antilymphocytic globulin (50% respond).
• Diphtheria anti-toxin - (from horses) for suspected diphtheria, adverse reactions are common. Diphtheria antitoxin does not provide any benefit when used prophylactically.¹²
• Botulism antitoxin for suspected botulism; again, adverse reactions are common.

Availability

Immunoglobulins are available from NHS microbiology laboratories and, in Scotland, from the Blood Transfusion Service - they are prepared by Bio Products Laboratory (BPL), and are issued by the Health Protection Agency.

Document references

1. Department of Health; Immunisation against infectious disease - 'The Green Book' (various dates).
2. HPA Hepatitis A; Immunoglobulin handbook; Dec 2009.
3. HPA Rubella; Imuunological handbook; Apr 2009.
4. HPA Measles; Immunoglobulin handbook; May 2009.
5. HPA Polio; Immunoglobulin handbook; Oct 2008.
6. The clinical effectiveness and cost effectiveness of routine anti-D prophylaxis for RhD-negative women in pregnancy, NICE Technology appraisal (2002)
7. HPA Hepatitis B; Imuunoglobulin handbook; Oct 2008.
8. HPA HBIG for infants; Immunoglobulin handbook; Aug 2008.
9. HPA VZIG; Immunoglobulin handbook; Oct 2008.
10. HPA Rabies; Immunological handbook; May 2009.
11. HPA Tetanus; Immunoglobulin handbook; Jan 2007.
12. HPA Diptheria; Immunoglobulin handbook; Apr 2009.

Internet and further reading

• HPA - 24 hour advice is available from the Health Protection Agency. Central Office in London,Tel 020 7759 2700 / 2701, Fax: 020 7759 2733 Email: webteam@hpa.org.uk

Acknowledgements