Imunogen – Division

There are five immunoglobulin classes (isotypes) of antibody molecules found in serum: IgG, IgM, IgA, IgE and IgD.

• IgA (immunoglobin A)
• IgD (immunoglobin D)
• IgE (immunoglobin E)
• IgG (immunoglobin G)
• IgM (immunoglobin M)

Types of Collagen Fibers They help identify and destroy foreign substances such as microbes (e.g., bacteria, protozoan parasites and viruses). Immunoglobulins are classified into five categories: IgA, IgD, IgE, IgG and IgM.

Immunoglobulins

Passive immunity

Immunity with immediate protection against certain infective organisms can be obtained by injecting preparations made from the plasma of immune individuals with adequate levels of antibody to the disease for which protection is sought. The duration of this passive immunity varies according to the dose and the type of immunoglobulin. Passive immunity may last only a few weeks; when necessary, passive immunisation can be repeated. Antibodies of human origin are usually termed immunoglobulins. The term antiserum is applied to material prepared in animals. Because of serum sickness and other allergic-type reactions that may follow injections of antisera, this therapy has been replaced wherever possible by the use of immunoglobulins. Reactions are theoretically possible after injection of human immunoglobulins but reports of such reactions are very rare.

Two types of human immunoglobulin preparation are available, normal immunoglobulin and disease-specific immunoglobulins.

Human immunoglobulin is a sterile preparation of concentrated antibodies (immune globulins) recovered from pooled human plasma or serum obtained from outside the UK, tested and found non-reactive for hepatitis B surface antigen and for antibodies against hepatitis C virus and human immunodeficiency virus (types 1 and 2). A global shortage of human immunoglobulin and the rapidly increasing range of clinical indications for treatment with immunoglobulins has resulted in the need for a Demand Management programme in the UK.

Availability

Normal immunoglobulin for intramuscular administration is available from some regional Public Health laboratories for protection of contacts and the control of outbreaks of hepatitis A, measles, and rubella only. For other indications, subcutaneous or intravenous normal immunoglobulin should be purchased from the manufacturer.

Disease-specific immunoglobulins are available from some regional Public Health laboratories, with the exception of tetanus immunoglobulin which is available from BPL, hospital pharmacies, or blood transfusion departments. Rabies immunoglobulin is available from the Specialist and Reference Microbiology Division, Public Health England, Colindale. Hepatitis B immunoglobulin required by transplant centres should be obtained commercially.

In Scotland all immunoglobulins are available from the Scottish National Blood Transfusion Service (SNBTS).

In Wales all immunoglobulins are available from the Welsh Blood Service (WBS).

In Northern Ireland all immunoglobulins are available from the Northern Ireland Blood Transfusion Service (NIBTS).

Normal immunoglobulin

Human normal immunoglobulin (‘HNIG’) is prepared from pools of at least 1000 donations of human plasma; it contains immunoglobulin G (IgG) and antibodies to hepatitis A, measles, mumps, rubella, varicella, and other viruses that are currently prevalent in the general population.

Uses

Normal immunoglobulin (containing 10%–18% protein) is administered by intramuscular injection for the protection of susceptible contacts against hepatitis A virus (infectious hepatitis), measles and, to a lesser extent, rubella. Injection of immunoglobulin produces immediate protection lasting several weeks.

Normal immunoglobulin (containing 3%–12% protein) for intravenous administration is used as replacement therapy for patients with congenital agammaglobulinaemia and hypogammaglobulinaemia, and for the short-term treatment of idiopathic thrombocytopenic purpura and Kawasaki disease; it is also used for the prophylaxis of infection following bone-marrow transplantation and in children with symptomatic HIV infection who have recurrent bacterial infections. Normal immunoglobulin for replacement therapy may also be given intramuscularly or subcutaneously, but intravenous formulations are normally preferred. Intravenous immunoglobulin is also used in the treatment of Guillain-Barré syndrome as an alternative to plasma exchange.

Hepatitis A

Hepatitis A vaccine is recommended for individuals at risk of infection including those visiting areas where the disease is highly endemic (all countries excluding Northern and Western Europe, North America, Japan, Australia, and New Zealand). In unimmunised individuals, transmission of hepatitis A is reduced by good hygiene. Intramuscular normal immunoglobulin is no longer recommended for prophylaxis in travellers.

Public Health England recommends the use of normal immunoglobulin in addition to hepatitis A vaccine for prevention of infection in close contacts (of confirmed cases of hepatitis A) who are 60 years of age or over, have chronic liver disease (including chronic hepatitis B or C infection), or HIV infection (with a CD4 count < 200 cells per microlitre), or who are immunosuppressed; normal immunoglobulin should be given as soon as possible, preferably within 14 days of exposure to the primary case. However, normal immunoglobulin can still be given to contacts with chronic liver disease up to 28 days after exposure to the primary case. Hepatitis A vaccine can be given at the same time, but it should be given at a separate injection site.

Measles

Intravenous or subcutaneous normal immunoglobulin may be given to prevent or attenuate an attack of measles in individuals who do not have adequate immunity. Patients with compromised immunity who have come into contact with measles should receive intravenous or subcutaneous normal immunoglobulin as soon as possible after exposure. It is most effective if given within 72 hours but can be effective if given within 6 days.

Subcutaneous or intramuscular normal immunoglobulin should also be considered for the following individuals if they have been in contact with a confirmed case of measles or with a person associated with a local outbreak:

• non-immune pregnant women
• infants under 9 months

Further advice should be sought from the Centre for Infections, Public Health England (tel. (020) 8200 6868).

Individuals with normal immunity who are not in the above categories and who have not been fully immunised against measles, can be given measles, mumps and rubella vaccine, live for prophylaxis following exposure to measles.

Rubella

Intramuscular immunoglobulin after exposure to rubella does not prevent infection in non-immune contacts and is not recommended for protection of pregnant women exposed to rubella. It may, however, reduce the likelihood of a clinical attack which may possibly reduce the risk to the fetus. Risk of intrauterine transmission is greatest in the first 11 weeks of pregnancy, between 16 and 20 weeks there is minimal risk of deafness only, after 20 weeks there is no increased risk. Intramuscular normal immunoglobulin should be used only if termination of pregnancy would be unacceptable to the pregnant woman—it should be given as soon as possible after exposure. Serological follow-up of recipients is essential to determine if the woman has become infected despite receiving immunoglobulin.

For routine prophylaxis against Rubella, see measles, mumps and rubella vaccine, live.

Disease-specific immunoglobulins

Specific immunoglobulins are prepared by pooling the plasma of selected human donors with high levels of the specific antibody required. For further information, see Immunoglobulin Handbook (www.gov.uk/phe).

There are no specific immunoglobulins for hepatitis A, measles, or rubella—normal immunoglobulin is used in certain circumstances. There is no specific immunoglobulin for mumps; neither normal immunoglobulin nor measles, mumps and rubella vaccine, live is effective as post-exposure prophylaxis.

Hepatitis B immunoglobulin

Disease-specific hepatitis B immunoglobulin (‘HBIG’) is available for use in association with hepatitis B vaccine for the prevention of infection in laboratory and other personnel who have been accidentally inoculated with hepatitis B virus, and in infants born to mothers who have become infected with this virus in pregnancy or who are high-risk carriers. Hepatitis B immunoglobulin will not inhibit the antibody response when given at the same time as hepatitis B vaccine but should be given at different sites.

An intravenous and subcutaneous preparation of hepatitis B immunoglobulin is licensed for the prevention of hepatitis B recurrence in HBV-DNA negative patients who have undergone liver transplantation for liver failure caused by the virus.

Rabies immunoglobulin

Following exposure of an unimmunised individual to an animal in or from a country where the risk of rabies is high the site of the bite should be washed with soapy water and specific rabies immunoglobulin of human origin administered. All of the dose should be injected around the site of the wound; if this is difficult or the wound has completely healed it can be given in the anterolateral thigh (remote from the site used for vaccination).

Rabies vaccine should also be given intramuscularly at a different site (for details see rabies vaccine). If there is delay in giving the rabies immunoglobulin, it should be given within 7 days of starting the course of rabies vaccine.

Tetanus immunoglobulin

For the management of tetanus-prone wounds, tetanus immunoglobulin should be used in addition to wound cleansing and, where appropriate, antibacterial prophylaxis and a tetanus-containing vaccine. Tetanus immunoglobulin, together with metronidazole and wound cleansing, should also be used for the treatment of established cases of tetanus.

Varicella–zoster immunoglobulin

Varicella-zoster immunoglobulin (VZIG) is recommended for individuals who are at increased risk of severe varicella (neonates, pregnant women and immunosuppressed individuals with varicella-zoster virus immunoglobulin G antibody less than 150 mIU/mL) and who have no antibodies to varicella–zoster virus and who have significant exposure to chickenpox (varicella) or shingles (herpes zoster) during the infectious period.

Immunosuppressed patients receiving regular intravenous immunoglobulin replacement therapy only require varicella-zoster immunoglobulin if the most recent dose was administered more than 3 weeks before exposure.

Immunosuppressed patients on long term aciclovir or valaciclovir prophylaxis will require a temporary increase in their dose following exposure; for patients within 12 months of a stem cell transplant, varicella-zoster immunoglobulin should also be considered.

Important: for full details consult Guidance for issuing varicella-zoster immunoglobulin (VZIG) and Immunisation against infectious disease from Public Health England (www.gov.uk).

Anti-D (Rh₀) immunoglobulin

anti-D (Rh0) immunoglobulin is prepared from plasma taken from rhesus-negative donors who have been immunised against the anti-D-antigen. anti-D (Rh0) immunoglobulin is used to prevent a rhesus-negative mother from forming antibodies to fetal rhesus-positive cells which may pass into the maternal circulation. The objective is to protect any subsequent child from the hazard of haemolytic disease of the newborn.

anti-D (Rh0) immunoglobulin should be administered to the mother following any sensitising episode (e.g. abortion, miscarriage and birth); it should be injected within 72 hours of the episode but even if a longer period has elapsed it may still give protection and should be administered. anti-D (Rh0) immunoglobulin is also given when significant feto-maternal haemorrhage occurs in rhesus-negative women during delivery. The dose of anti-D (Rh0) immunoglobulin is determined according to the level of exposure to rhesus-positive blood.

Use of routine antenatal anti-D prophylaxis should be given irrespective of previous anti-D prophylaxis for a sensitising event early in the same pregnancy. Similarly, postpartum anti-D prophylaxis should be given irrespective of previous routine antenatal anti-D prophylaxis or antenatal anti-D prophylaxis for a sensitising event in the same pregnancy.

anti-D (Rh0) immunoglobulin is also given to women of child-bearing potential after the inadvertent transfusion of rhesus-incompatible blood components and is used for the treatment of idiopathic thrombocytopenia purpura.

MMR vaccine

Measles, mumps and rubella vaccine, live may be given in the postpartum period with anti-D (Rh0) immunoglobulin injection provided that separate syringes are used and the products are administered into different limbs. If blood is transfused, the antibody response to the vaccine may be inhibited—measure rubella antibodies after 6–8 weeks and revaccinate if necessary.

Taj Pharma As A Health Care Provider