Parasitic protozoan infections are a significant problem in many developing countries. Often a large proportion of the blood donor population is infected, and the prevention of transmission by transfusion is a problem. Conversely, protozoan infections in most industrialized countries are far fewer and are largely restricted to the potential risk of transmission of malaria by donations collected from donors who may have been infected while travelling in malarious areas on holiday or on business. In recent years, however, the risk in industrialialized countries has increased, in terms of both the number of donors potentially exposed to parasitic infections and the number of different organisms involved, as the number of individuals travelling abroad and variety of destinations have increased, and also as migrants from endemic areas move into nonendemic areas and donate blood.
Malaria is caused by the parasite species Plasmodium, four of which are recognized as the causative agents of human malaria: P. falciparum, P. malariae, P. ovale and P. vivax. It has long been recognized as a transmissible infection, and cases of transmission, and sometimes death, occur still. Malaria is carried by the Anopheles mosquito and is injected into humans through the bite of an infected feeding mosquito. There are two stages to the life cycle of the parasite, one in the mosquito host and one in the human host. The infective form (sporozoite) travels to the liver where it divides many times before being released back into the bloodstream (merozoite). This merozoite infects red cells in which another replication cycle then takes place, after which the red cell bursts, releasing more merozoites into the bloodstream to infect yet more red cells. After a number of such cycles some of the merozoites will form male and female forms (gametocytes) at which stage the human cycle finishes. The gametocytes are then ingested by a feeding Anopheles mosquito in which the mosquito stage of the organisms life cycle begins again.
Donations collected at the stage when the red cells are infected could contain potentially infectious red cells, or even free merozoites, which could result in transmission of infection to the patient. Because of the great variation in prevalence of malaria in different countries, approaches to minimizing any risks of transmission vary. In nonendemic countries the risk of malaria comes from donors who have travelled in malarious areas. In this case the use of standardized country risk groups (i.e. listing countries and their associated malaria risk) and donor questioning is generally sufficient to identify and defer any "at-risk" donors. In low prevalence endemic countries donor questioning may be effective if, for example, cases are usually symptomatic and therefore would not go unnoticed, or if malaria is restricted geographically. Failing this, however, many countries screen donations by preparing and looking at thick films. While this may identify a donor with a high parasitaemia, the technique is not sensitive enough to detect most infections and certainly is not suitable for mass screening. In highly endemic areas donor questioning and thick films may have some value, but whether there is any value to malaria screening at all has to be considered. If the prevalence is very high it is likely that most patients would already be infected, and it could therefore be argued that transfusing potentially infected blood would not have any serious sequelae. This is an ethical and moral dilemma, but in such a situation it is very likely that if all infected donors were deferred there would be no donors left and therefore no blood for transfusion.
Although malarial antibody tests are now available, their sensitivity and specificity are not optimal and therefore such tests not totally reliable. In addition, they would not be able to identify very recently infected parasitaemic individuals in whom specific antibody had not yet appeared. The cost of these tests is also high, and at present it would appear that their main value in donor screening would be in nonendemic countries, to screen donors who had travelled to endemic countries and been deferred, and so return them to active status as soon as possible.
4.3.3 Trypanosoma cruzi—Chagas disease
Chagas disease is caused by the parasite Trypanosoma cruzi. The disease is confined mainly to the American subcontinent, where it is endemic in Latin America and increasing its presence in the southern states of the USA as migrant workers from Latin America move north. This spread in migrant workers may also affect other industrialized countries as these migrant workers travel to these countries. However, it is likely that this spread is self-limiting; infected individuals may present with the disease in other countries but the living conditions are usually not the same and the insect carriers (reduviid bugs) are not present, so preventing the full life cycle of the organism from establishing.
The parasite is carried in the gut of members of the family of reduviid bugs (triatomids) and is excreted in the faeces. These bugs live in the cracks in the walls and ceilings of buildings and at night feed on human blood. The bug normally defecates while feeding, and the open feeding site acts as the site of entry for the parasite. The entry site, generally on the face, swells to produce the typical chagoma of the disease. However, while this route is generally the major route of infection, blood transfusion is now considered to be the second most important route of transmission in endemic areas. When ingested by the reduviid bug the organisms enter the midgut where they replicate to form epimastigotes, which are then converted into trypomastigotes before being excreted in the faeces. Once in the human bloodstream, the trypomastigotes develop into amastigotes which infect the regional lymph nodes and may eventually infect virtually every organ of the body. The organism multiplies in the cells of the infected organs and when these cells burst trypomastigotes are released into the bloodstream. However, these cannot multiply in the human. They need to be ingested by a feeding bug, enter its gut and then start the whole cycle again. Although the liver and spleen are usually infected, the most characteristically infected organ is the heart. The amastigote forms replicating in the heart appear to induce an inflammatory response which causes enlargement of the heart. Central nervous system (CNS) involvement is common, often leading to meningoencephalitis.
Identification of infected donors can be problematical as more than 20% of infected individuals may be asymptomatic. Donor selection can identify symptomatic individuals, but that is of limited value in endemic areas. In nonendemic areas, in a similar manner to malaria screening, donors who either come from or have visited endemic areas can be deferred to minimize any risks of transmission. There are now a number of screening tests available that detect specific antibody. In recent years these assays have improved greatly in both specificity and sensitivity. However, there is no real standardization of T. cruzi serology and currently no reliable confirmatory tests available. Lastly, there is an effective way of inactivating organisms in the actual blood donations. For at least 40 years some Latin American countries, mainly in hyperendemic areas, have used gentian violet at a final concentration of 125 mg/500 ml added to the primary blood pack as an apparently totally effective way of inactivating any organisms present in the donation. After 24 hours at 4 °C in the presence of gentian violet T. cruzi is killed. Although effective in killing T. cruzi the use of gentian violet is not without some problems. It is unsuitable when products are required within 24 hours of collection, and some recipients of donations containing gentian violet have ended up with purple staining of the skin and mucosa; rouleaux formation and microagglutination have also been reported.
Although still a significant problem in Latin America, a number of countries in the Eastern Mediterranean Region with more developed transfusion services have managed to control T. cruzi and minimize any risks of transmission without compromising the availability of blood and blood products.
4.3.4 Leishmania spp.—leishmaniasis
Leishmaniasis is an infection of the reticuloendothelial system but it exists in three main forms: cutaneous, mucocutaneous and visceral (kala-azar). Cutaneous leishmaniasis results in skin lesions, subcutaneous leishmaniasis results in ulcers on the oral and nasal mucosa, and visceral leishmaniasis results in infection of the reticuloendothelial system in the liver and spleen. It is thought that the basic differences between the three types of infection result from the differing ability of the parasites to invade the body. The disease is found in a broad band extending around the globe across central and south America, central Africa, the Middle East, Pakistan, China and south-east Asia. Although a number of leishmania species exist, morphologically they are almost identical; differences are apparent only when molecular techniques are used to examine their DNA. The parasites are transmitted through the bite of infected sandflies of the genus Phlebotomus, with each parasite species being restricted to a particular Phlebotomus species. The reservoirs for organism vary in different regions but invariably include rodents and other small wild mammals, although in urban areas dogs and even humans can serve as reservoirs.
The parasite is carried in the insect's gut where it develops into the motile promastigote which migrates to the pharynx from where it can be injected into a new host. In the human host these injected promastigotes invade the reticuloendothelial system where they develop into the amastigote forms which are eventually released into the bloodstream, and which may be ingested by a biting sandfly, so completing the cycle.
Identification of infected individuals is generally based upon clinical diagnosis, and, although more straightforward in cases of cutaneous and subcutaneous leishmaniasis, is complicated by the fact that a large percentage of cases are asymptomatic. Specific reliable diagnostic tests are not available widely, and not suitable for blood screening. Although potentially a threat to the blood supply in endemic areas, parasitaemia is generally transient and at a low level, consequently there is a low risk of transmission. This is supported by the lack of reports of transfusion transmission even in endemic areas.
4.3.5 Toxoplasma gondii—toxoplasmosis
Toxoplasma gondii is globally one of the most widespread vertebrate protozoan parasites; in some countries up to 95% of adults may have been infected with the parasite. Following resolution of acute infection, circulating antibodies appear but the organism persists latently in the circulating leukocytes. Reactivation of this latent infection has been reported, notably in immunocompromised individuals. The acute infection in healthy individuals is generally asymptomatic and not associated with any morbidity; however, in immunocompromised individuals infection is far more severe with the possibility of central nervous system involvement, myocarditis and pneumonia. Congenital infection can give rise to serious complications involving the liver and the central nervous system, and even abortion or stillbirth.
Members of the cat family are the hosts of T. gondii, and mice are thought to act as intermediate hosts helping to maintain the life cycle of the organism. It replicates in intestinal cells of cats resulting in the excretion of infectious oocysts, containing sporozoites, in the faeces. After ingestion by another animal, including by humans, these oocysts release the sporozoites which then infect and multiply in a wide variety of other cell types including the reticuloendothelial system, leukocytes, and eventually the central nervous system.
Transmission of the organism to humans is thought to be mainly through eating raw or undercooked meat or contact with the faeces of infected animals, notably domestic animals and especially pets. Transfusion transmission has occasionally been documented in immunosuppressed individuals, with sometimes fatal consequences. To minimize any risk of transfusion transmission, susceptible patients who are seronegative and immunosuppressed could be provided with blood screened for the presence of antibody to T. gondii or with blood leukodepleted, ideally by filtration, prior to transfusion.
4.3.6 Babesia microti and B. divergens—babesiosis
Babesiosis is due to infection with the tick-borne protozoan parasite Babesia (B. microti in north America and B. divergens in Europe) which infects red cells and causes a sometimes serious malaria-like illness. Details on the global spread of babesiosis are not known but at present it appears that it is restricted to parts of the USA and Europe. The organism can survive in red cells for at least one month under normal blood bank storage conditions and, like plasmodium, can be transmitted by transfusion of blood from an infected asymptomatic individual. There have been only a few cases of transfusion-transmitted babesiosis reported and no deaths have so far occurred, although it is likely that a number of cases have gone unreported following asymptomatic infection in the recipient. Laboratory screening is not possible at present, and donor selection procedures have to be relied upon to minimize any risks of transmission.