Infections transmissible by transfusion

Frequency of transfusion transmitted infections in tested donations − estimated and observed (Table 24 and Table 25)

On very rare occasions screening fails to detect the target infection in a donation. The risk of this can be estimated by calculation and also from the actual reported number of infections associated with transfusion. The estimated frequency of HBV, HCV and HIV infectious donations entering the UK blood supply in 2002−2003 is shown in Table 24. About three million blood component units are supplied (though all are not necessarily transfused) each year in the UK, so these estimates would predict that about one donation per two years could transmit HIV, seven donations per year could transmit hepatitis B, and one donation per seven years could transmit hepatitis C. The number of transfusion-transmitted infections reported to SHOT is shown in Table 25.

Hepatitis B

Hepatitis B can cause severe disease, and although most infected patients recover without serious complications, in some cases infection persists as a chronic carrier state. Patients who are immunosuppressed (e.g. those with leukaemia, cancer or transplant recipients) are more likely to go on to become carriers, often with high levels of infection. Tests for hepatitis B surface antigen (HBsAg) are extremely effective; there are very rare instances, however, in which HBsAg may be undetectable in a donor who is actually infectious. The role of tests for HBV DNA is still uncertain.

Hepatitis C

Although many people infected with hepatitis C are asymptomatic, some develop chronic liver disease and some will eventually progress to cirrhosis or hepatocellular carcinoma. Serological tests to detect hepatitis C virus infection were introduced in 1991. An additional test for hepatitis C RNA was introduced in 1999. It is estimated that the current risk of a blood unit infected with hepatitis C entering the UK blood supply is about 0.05 per million (or 1 in 22 million).

Human T-cell lymphotropic virus types I and II

HTLV infection is occasionally detected in blood donors in the UK; usually these are individuals from countries where the infection is endemic or the female sexual partners of men from these areas. Only a small proportion (less than 5%) of those infected become ill, but infection has been associated with a chronic neurological disorder (tropical spastic paraparesis) and a rare, aggressive malignancy adult T-cell leukaemia/lymphoma (ATLL). These conditions may develop many years after infection. All blood donations in the UK have been tested for antibody to HTLV I and II since 2002. Four HTLV-transmitted infections have been identified in the UK since 1991, all of which received transfusions prior to the introduction of leucodepletion of all components in 1999.

Cytomegalovirus (CMV)

see prevention of cytomegalovirus transmission.

Hepatitis A

Hepatitis A is caused by a non-enveloped virus that is resistant to current methods of pathogen inactivation of blood components. Transfusion transmission of hepatitis A is extremely rare. In the UK, there have been four reports of transmission over the past 25 years.

Human parvovirus B19

Human parvovirus B19 is a prevalent, seasonal, non-enveloped virus that is quite resistant to current methods for pathogen inactivation of blood components. It can be transmitted via transfusion. Clinically, infection is generally asymptomatic or causes mild symptoms, but it can cause aplastic crisis in patients with sickle-cell disease, thalassaemia, chronic haemolytic anaemia or red cell membrane defects. Infection in the second trimester can lead to fetal anaemia, death or malformation.

West Nile virus

A mosquito-borne flavivirus infection causing encephalitis. Recent seasonal epidemics have occurred in North America. West Nile virus can be transmitted by blood donated during the viraemic phase. During the epidemic season, donors may not give blood in the UK for 28 days after returning from an affected area unless a test for viral RNA is negative. There have been no cases transmitted by transfusion in the UK and no infected donors have been detected to date.

Treponemal infections (syphilis)

There have been no reports of transfusion-transmitted syphilis in the UK in recent years. All donations are screened for serological evidence of Treponema pallidum infection.

Other bacterial infections

Despite all precautions, bacteria may occasionally enter a blood component pack, for example in skin fragments arising from the venepuncture. To reduce this risk, the first 20 ml of the donation is diverted from the collection pack and used for all the screening tests. Bacterial culture of platelet units is also being introduced, because a transfusion contaminated with bacteria can result in fatal transfusion reactions. Platelets are more likely to be associated with bacterial complications than red cells. Skin contaminants such as staphylococci may proliferate in platelet concentrates stored at 22°C. Bacteria identified in contaminated red cell transfusions are usually strains that can grow in red cells stored at 4°C. Examples are Pseudomonas fluorescens, an environmental contaminant, and Yersinia enterocolitica, which may contaminate a donation taken during an episode of asymptomatic bacteraemia.

Malaria

Only five cases of transfusion-transmitted malaria (all due to Plasmodium falciparum) have been reported in the UK in the past 25 years. In the US between 1993 and 1998, transfusion transmitted malaria (by several species of plasmodium) occurred with a frequency between zero and 0.18/million units collected. Blood donor selection procedures, and in some cases tests for malaria antibody, are used to identify and exclude individuals whose blood could transmit malaria.

Chagas’ disease

This is a serious chronic multi-organ disease caused by Trypanosoma cruzi, and is transmissible by transfusion. In the UK no cases transmitted by transfusion have been reported; a small number of such cases have been reported in North America. It is an important problem in parts of South America where the infection is endemic. A negative test for antibody to T. cruzi allows the acceptance of donors at risk of infection.

Variant CJD

Clinical features and epidemiology

Variant CJD (vCJD) was identified in 1996. It is a transmissible spongiform encephalopathy (TSE) that is thought to be caused by the same agent as bovine spongiform encephalopathy (BSE). This is an altered form of a normal protein called prion protein. During the period of the BSE epidemic, the UK population was exposed to the agent through consumption of beef. It is possible that there are healthy individuals who could be carriers of the agent. vCJD affects younger people (median age 29 years) than the long-recognised sporadic form of CJD. It also differs clinically, presenting with behaviour disorders, depression and anxiety, followed by sensory and coordination problems and progressive dementia. Survival from diagnosis is 6−24 months. To date about 160 definite and probable cases of vCJD have been reported in the UK, 14 in France, three in Ireland and single cases in a number of other countries. The eventual number of cases that can be expected in the UK is uncertain. Three possible transmissions of vCJD by blood transfusion have been reported. One of the patients died of unrelated causes.

vCJD precautionary measures taken by the UK blood and tissue services

Measures to minimise transmission by blood or tissues have been introduced as new information has become available. It can be expected that further precautions will be introduced. The measures summarised below have an important impact on both cost and availability of blood for transfusion.

• Withdrawal and recall of any blood components, plasma derivatives, cells or tissues obtained from any individual who later develops variant CJD (announced December 1997).
• Importation of plasma from countries other than the UK for fractionation to manufacture plasma derivatives (announced May 1998, fully implemented October 1999).
• Leucodepletion of all blood components (decision announced July 1998, fully implemented Autumn 1999).
• Importation of clinical FFP for patients born after January 1996, announced on 16 August 2003 and implemented by the end of June 2004, and extended to all patients under the age of 16 by July 2005.
• Exclusion of whole blood donors who state that they have received a blood component transfusion in the UK since 1 January 1980 (April 2004). Extended to whole blood and apheresis donors who may have received a blood component transfusion in th e UK since 1 January 1980 (August 2004) and to any donors who have been treated with intravenous immunoglobulin prepared from UK plasma, or who have undergone plasma exchange procedures anywhere in the world.
• Exclusion of live bone donors who have been transfused since 1 January 1980 (July 2005).
• Exclusion of blood donors whose blood has been transfused to recipients who later developed vCJD, where blood transfusion cannot be excluded as a source of the vCJD infection and where no infected donor has been identified (July 2005).
• Further measures may include the use of processes intended to remove any infectivity that may be present in blood and the use of donor screening tests.

The single most effective way of protecting patients against both known and unrecognised blood-borne infections is to avoid the use of blood products or tissues unless there is a well-founded reason. This handbook and the associated website reflects the importance placed by the Chief Medical Officers of the UK on the appropriate use of blood and tissues.

Pathogen reduction and leucodepletion

The production of plasma derivatives includes physical, chemical and thermal processes to inactivate and remove pathogens. Chemical (e.g. solvent detergent) and thermal processes have reduced the risk of transmitting HIV, HTLV, hepatitis B or hepatitis C. Sterile filtration can eliminate bacteria and parasites. Cell-associated viruses such as CMV and HTLV do not pose a risk to plasma-derived products. Both plasma and cryoprecipitate may be subject to pathogen inactivation (see Pathogen-reduced plasma components). Cellular blood components are not currently pathogen inactivated, but processes to inactivate microbial agents in platelet concentrates (using psoralen amotosalen-HCI combined with UVA light) have recently become available. These are not yet used in the UK. Leucodepletion reduces, but may not eliminate, the risk of transmission of pathogens that are carried by white cells.(PMID15852240)