Blutspenden-zh.ch

Vox Sanguinis (2006) 90, 77–84
Malaria and blood transfusion
A. D. Kitchen1 & P. L. Chiodini2
1National Blood Service, London, UK 2The Hospital for Tropical Diseases, London, UK The transmission of malaria by blood transfusion was one of the first recorded inci-dents of transfusion-transmitted infection. Although a number of different infectionshave been reported to be transmitted by transfusion since then, on a global scalemalaria remains one of the most common transfusion-transmitted infections.
Transfusion-transmitted malaria can have serious consequences, as infection withPlasmodium falciparum may prove rapidly fatal. Ensuring that, in non-endemiccountries, the blood supply is free from malaria is problematical, especially as travelto malarious areas is increasing and there is some spread of the disease into newareas, as well as a resurgence of malaria in areas where previously it had been eradi-cated. In non-endemic countries, donor deferral can be effective, but clear guidelinesare needed. In endemic countries the problem is far greater as the majority of donorsmay be potentially infected with malaria parasites. In both situations, the simpledeferral of donors may be wasteful and can eventually erode the donor base. Thus,other strategies are needed to ensure safety with sufficiency. However, the screeningof donations for evidence of malaria is not without its problems. Although the exam-ination of blood films is still the basis for diagnosing acute malaria, in most situationsit is not sufficiently sensitive for blood bank screening. In non-endemic countries,donor deferral in combination with screening for specific antimalarial immunoglobulinprovides an effective means of minimizing the risk of transmission. In endemic countries,more specific donor questioning, consideration of seasonal variation and geographicaldistribution may help to identify the population of donors who are most likely to beinfected. In addition, the administration of antimalarials to transfusion recipientsmay help to prevent transmission. Nonetheless, no matter what strategy is adopted, it is likely that cases of transfusion-transmitted malaria may still occur, so malaria must always be considered in any patient with a febrile illness post-transfusion.
Key words: antibody, blood transfusion, deferral, malaria.
political forces, there is no part of the world that is not accessible. With this freedom to travel, however, comes the The first case of transfusion-transmitted malaria (TTM) risk of exposure to the diseases endemic in different parts was reported in 1911, when intercontinental travel was an of the world. The major one of these is malaria. Globally, unattainable dream for most of the world’s population, and malaria presents a significant disease burden with estimates well before commercial air travel became established. Since of up to 150 million infections annually with 1–2 million deaths that time, international travel has become commonplace, and per year, mainly in sub-Saharan Africa. Although vast sums effectively, ignoring any restrictions caused by conflict or of time and money have been spent in trying to controlmalaria, the results of this have been variable, with instancesof control programmes failing as a result of the breakdown Correspondence: A. D. Kitchen, National Blood Service, North London, of public health systems, caused, for example, by conflict, the general lack of resources needed to sustain them, or the migration of populations. Furthermore, the spread of chloroquine- (and, later, multidrug-) resistant Plasmodium falciparum malaria, countries; and differences in the approaches taken between coupled with an ever-increasing number of travellers to its areas of endemicity, has led to an increasing proportion ofmalaria caused by P. falciparum among international travel- Endemic countries
lers returning from trips to malarious areas. In 2004 therewere five reported deaths in a total of 1660 cases of imported Differentiation of cases of TTM from natural infections is very malaria in the UK (HPA Malaria Reference Laboratory, difficult in endemic areas as malaria occurring post-transfusion can be the result of natural infection via a mosquito bite, Review of worldwide data recorded from 1911 to 1979 by rather than from the transfusion received. Furthermore, in Bruce-Chwatt [1,2] found that the reported incidence of TTM endemic areas, many of the donors and patients are already increased from six to 145 cases per year. In the early years, infected with, or are at high risk of, malaria infection.
P. vivax was the most frequently reported species, but by the Identifying low-risk individuals is virtually impossible.
1950s P. malariae predominated, followed by P. vivax, One approach is to use Giemsa-stained thick films or rapid P. falciparum, mixed infections and P. ovale. In the 1970s, diagnostic tests (RDTs) for malarial antigen to identify those P. vivax was again the commonest, followed by P. malariae donors with higher levels of parasitaemia. However, it is clear and P. falciparum, although, ominously, the proportion of that this approach only identifies the proportion of individ- uals with a parasitaemia above the detection limit for these To reinforce this, the last five cases of TTM reported by the techniques. It does not, however, prevent transmission from UK Blood Services (all in the southeast of England) were units of blood with parasitaemia too low to detect by micro- caused by P. falciparum [3–5]. This can be seen directly scopy or RDTs. There are additional strategies that can be in the figures for malaria imported into the UK in recent implemented, depending upon the geography of the country, years. Before 1986, there were more cases of P. vivax than the periodicity of malaria (seasonal or year round), the type P. falciparum, but since then P. falciparum has been the and age of the donors, and the age, gender and underlying single most common imported species. Indeed, the total for condition of the patients, together with their existing malaria P. falciparum now exceeds that of the other three species status. For example, the segregation of donations collected combined. In 2004, 74% of imported malaria was caused by from low- and high-risk localities (e.g. lowlands and high- P. falciparum (HPA Malaria Reference Laboratory). The fig- lands), with specific targeting of the donations from low-risk ures for imported malaria from 1985 to 1995 reported by donor groups to low risk and the most vulnerable recipients.
other European centres also show a substantial proportion Routine antimalarial treatment of transfusion recipients is caused by P. falciparum – 82·2% in France and 59·4% in Italy also performed in some areas. Such strategies are pragmatic – compared with 38·5% in the USA over the same period [6].
approaches that are not absolute in their effectiveness, but can In the USA, there are ≈ 1000 reported cases of imported help to lessen the risk of TTM in such situations. It has been malaria per annum, compared with ≈ 2000 in the UK [6]. In argued that many recipients in endemic areas will be immune 1990–1999, the USA reported 14 cases of TTM, 10 (71%) of to the plasmodium species present where they live, and therefore which were caused by P. falciparum [7].
less likely to be adversely affected if they are transfused Transmission of malaria has been reported to occur mainly with blood from an infected donor [9]. However, it must be from single-donor products [8]: red cells, platelets, white cell remembered that, paradoxically, many transfusions in these concentrates, cryoprecipitate and from frozen red cells after countries are to children with acute severe anaemia caused by thawing and washing. Transmission from single-donor malaria. These children are unlikely to have yet become semi- fresh-frozen plasma has not been reported. Transmission immune, and thus must be considered to be susceptible to TTM.
from cryoprecipitate is rare and likely to reflect the prepara- However, there remains the fact that, despite the different tion method and the degree to which the starting plasma is strategies adopted, it is virtually impossible to safeguard the blood supply from malaria in endemic countries [10,11], andoften the transfusion of blood, together with the judicial use Malarial risk-reduction strategies
of antimalarial drugs, is necessary to minimize the occur-rence of TTM in the recipient. In addition, promoting the There are two main aspects to bear in mind when considering appropriate clinical use of blood also has a role in minimizing malaria risk and transfusion: first, the malaria risk associated TTM, by ensuring that patients are not exposed unnecessarily.
with any individual donor; and, second, the ability of thesystems to identify and manage the donor and any donation.
Non-endemic countries
It is here that there are fundamentally different approachestaken by different blood transfusion services: differences in the Whilst overall, at any one time, the number of individuals overall approaches taken between endemic and non-endemic with any malaria risk represents only a small proportion of 2006 Blackwell Publishing Ltd. Vox Sanguinis (2006) 90, 77– 84
the overall number of donors, the number of these donors is cases of TTM. Aside from cases where errors allowed clearly cumulative as, year-on-year, donors either visit malarious identifiable ‘malaria-risk’ donations to be released for clini- areas for the first time or individuals originally from malar- cal use, the analysis of cases of TTM has facilitated the iden- ious areas present as donors for the first time. Thus, there is tification of specific ‘high risk’ donor groups and weaknesses a high reliance upon appropriate donor-deferral guidelines, in guidelines, and the subsequent amendment of the deferral and on the accuracy and clarity of the information gleaned from the donors about their travel and any consequentmalaria risk.
One simple approach taken by many countries is to iden- The main risk of introducing malaria parasites into the blood tify and defer permanently any ‘malaria-risk’ individuals.
supply in most non-endemic countries comes from semi- This approach has the advantage of clarity in action, but immune individuals. Semi-immunity develops in those indi- poses a number of problems – one is that of identifying viduals who generally live in areas with high entomological reliably the ‘malaria-risk’ individuals and another is the inoculation rates (EIR), and are thus multiply exposed to cumulative nature of malaria in a world where people are malaria. The EIR is an indication of the daily infectious bite travelling further and more frequently, and malaria is spread- rate over a period of time, expressed as the average number ing into countries previously considered malaria free. Perma- of infective bites per person per unit time, a factor of impor- nent deferral of an increasing donor group may very quickly tance when assessing risk in both residents and travellers. In reduce the overall donor base. Few countries can afford to Africa, for example, the EIR ranges from 1 to 1000, and even lose donors in such numbers and on a continual basis, espe- in areas with a low EIR, the prevalence of P. falciparum can cially when most of these donors have not been infected and exceed 40%; in the majority of areas with an EIR of 200 or could be reinstated as active donors.
more, the prevalence rate is at least 80%. A dynamic balance Thus, an increasing number of non-endemic countries, develops in the individual, whereby they are generally and indeed some endemic countries, are implementing selec- well and asymptomatic despite the simultaneous presence of tive screening strategies for ‘malaria-risk’ donors, utilizing both high-titre antibody and low-level parasitaemia in their specific in vitro screening to look for any evidence of malar- peripheral blood. Whilst those who are semi-immune were ial infection. This approach still relies upon specific donor- often born in and former residents of malaria-endemic areas, selection criteria and the use of a limited deferral period, but it is important to note that expatriates resident for long does then enable the reinstatement of those donors who have periods of time in malarious areas can also become semi- no evidence of infection. In both approaches, the need for a immune. For example, a case of TTM caused by P. falciparum set of clear and reliable donor-deferral criteria is paramount.
was thought to have arisen from blood donated by a person These criteria are the same regardless of whether there is to who had worked in Africa for 10 years, had a history of be permanent deferral or screening and reinstatement; the falciparum malaria, and failed to give a history of malaria most important aspect is that all donors with any malarial or foreign residence when they donated [3,13]. In contrast, risk are identified at the point of donation and the appropri- those donors without significant malarial immunity are likely to be symptomatic if they have malaria parasites intheir blood and thus are unlikely to attend a donor clinic or,should they attend, be rejected when questioned about their Donor and donation screening
health [4,13]. The potential role of semi-immune individualsas a source of TTM is further illustrated by Mungai et al. [14] Screening of donors
who analysed the characteristics of donors implicated in Screening of donors by questionnaire is thus the first, and in cases of TTM in the USA from 1963 to 1999. Whereas from many countries the only, step in the prevention of TTM. The 1963 to 1969, 45% of the 11 donors, and from 1970 to 1979, development of donor-deferral criteria that are appropriate 38% of the 24 donors, were former residents of malarious to the country and to the donor population is central to donor areas or recent visitors to their country of origin (itself malar- screening. It must be understood, however, that complete ious), these figures increased to 100% of the 17 donors from prevention of TTM may not be possible [12]. Any strategy 1980 to 1989, and to 91% of the 12 donors from 1990 to developed must focus on minimizing the risk of introducing malaria parasites into the blood supply, but without exclud-ing unnecessarily any potential donors, especially as many donors deferred for any significant period of time do not Although cases of acute malarial infections in travellers from non-endemic countries are not uncommon, such cases tend Determining reliable deferral guidelines is an area of some to be symptomatic, medical advice would normally be sought debate, but there is a lot that can be learnt from any reported and the donors would be identified by history taking prior to 2006 Blackwell Publishing Ltd. Vox Sanguinis (2006) 90, 77– 84
donation. Furthermore, the vast majority of P. falciparum prospective donors who have had a diagnosis of malaria are infections in such individuals present within 6 months of permanently excluded from donation in the absence of a leaving a malarious area, a time period during which these validated malaria antibody test, but can be reinstated if individuals would be excluded from donation.
malarial antibody negative for at least 6 months after thecessation of treatment or symptoms [15].
It is recognized that any such policies will invariably result The primary approach to donor screening is therefore that of in some unnecessary deferrals in some donor groups. It is history taking to identify any possible malaria risk associated common to find a ‘history of malaria’ in individuals from with travel or residency. Important questions to be answered malaria-endemic areas, as fevers are often labelled as malaria are the geographical location (i.e. whether or not a potential on clinical grounds without laboratory confirmation [12].
donor has visited or lived in a malarious area), the length of Nevertheless, permanent deferral, in the absence of any time in any malarious area, the length of time since last being donation screening, does provide a useful margin of safety in a malarious area, and any previous history of malaria.
as this group of potential donors is likely to contain the • Location. In general, countries are identified as being semi-immune individuals. Furthermore, a 3- or even a 5-year malaria risk or not. However, some transfusion services deferral would not totally exclude semi-immune individuals, subdivide countries according to geographical zones as cases of TTM have been linked to donations taken more within each of them, but this results in a substantial than 5 years after the last potential exposure of the donor to increase in the complexity of the assessment and in the malaria. For example, in a United States series covering risk of errors being made. Similarly for seasonality, such 1963–1999 [14], the longest interval between travel to a distinctions are not absolute, and even in the ‘non-malarial’ malarious area and transmission of malaria via a blood trans- season there may still be some residual transmission, fusion was 5 years for P. falciparum, 2·5 years for P. vivax, albeit at a significantly lower level, but nonetheless the 7 years for P. ovale and 44 years for P. malariae. In the UK, a recent case of P. falciparum transmission involved a semi- • Period of residence in a malarial area. The longer the immune donor who had last been in a malarious area 8 years period of residence, the greater the risk of an individual becoming semi-immune and thus asymptomatic whilst It must also be recognized that cases of TTM will still occur, parasitaemic. The residency status applies regardless of albeit rarely. Although no set of guidelines is perfect, appro- whether the individual was resident as a child or as an priate deferral strategies will reduce risk to a minimum, pro- adult, because long-term exposure as an adult can also viding that they are properly applied. However, given the fact result in an individual becoming semi-immune to that donor deferral relies heavily on questionnaire and inter- view techniques, significant failures can still occur. Donors • Period since last in a malarial area. Any visit to a malari- may give inaccurate information intentionally or uninten- ous area could result in infection, and sufficient time must tionally, because they misunderstand the question posed, or be allowed to elapse both for the malarial infection to because they are unaware or have forgotten that they pre- become clinically evident in non-immunes and for any viously have had malaria [12]. Furthermore, the interviewing immune response to an acute infection to develop. Defer- staff may have failed to implement the guidelines as ral for at least 6 months following the last visit to a risk intended. In a series of cases of TTM from the USA, it was area will allow sufficient time for either symptoms or an found that the guidelines had only been applied correctly in 23 out of 60 (38%) cases, four of them caused by • History of malaria. Although permanent deferral is com- P. falciparum and 15 by P. malariae [14]. In contrast, among monly adopted, alternative strategies may be appropriate the 37 cases in which the guidelines had not been correctly depending upon the time since the last symptoms/treatment.
implemented, 22 were caused by P. falciparum but only three Donor deferral is thus based upon the risk factors identified by P. malariae. This suggests that the potentially very long in relation to the four key factors identified above, with dif- persistence of P. malariae at low levels in the blood makes ferent countries developing their own specific criteria based it a more difficult species to exclude, but that correctly upon their specific needs, resources and the numbers of followed time-exclusion guidelines, even in the absence of donors involved. For example, since July 1995, the guide- antibody screening, are more effective in excluding lines operating in Canada have required that donors report- P. falciparum as a source of TTM.
ing a history of diagnosis or treatment of malaria at any timein the past be permanently deferred from donating compo- Screening of donations
nents for direct transfusion [12]. In the USA, prospectivedonors who have had a diagnosis of malaria are deferred for The ability to screen the donations, as well as the donors, can 3 years after becoming asymptomatic [14]. In the UK, decrease significantly any risk of TTM. The overall effectiveness 2006 Blackwell Publishing Ltd. Vox Sanguinis (2006) 90, 77– 84
of any donation-screening programme does, however, depend effective indicator of infection [22], although it does not on the correct application of the donor-deferral criteria.
necessarily indicate that the person is harbouring malaria There are four specific targets for donation screening: parasites. However, a negative malarial antibody test intracellular parasites; plasmodial antibodies; plasmodial cannot guarantee that the donor is not infected with malaria antigen; and plasmodial DNA. Although there has been parasites, as antibody may not be detectable in the first some debate over which is the most effective, donor deferral few days of malarial illness, and infection with P. ovale plus malarial antibody screening provides the most effective and P. malariae may not be detected by P. falciparum and strategy in non-endemic countries. In endemic countries it is P. vivax antigen-based assays.
clear that different strategies are needed, and that these need Draper & Sirr examined sera from 415 known cases of to be developed locally according to needs and resources.
malaria diagnosed in the UK [23]. Eighty-eight were fromUK residents who had travelled abroad and were suffering from their first attack of malaria, whilst 327 were from The most widely applied diagnostic test for malaria is exam- immigrants, who showed a wide range of malaria histories.
ination of Giemsa- or Wright’s-stained thick and thin blood One week after the onset of clinical symptoms 78% of UK films [16]. The worldwide application of this method as a residents had antibodies against P. falciparum, as determined ‘gold standard’ diagnostic assay is primarily a result of its by the indirect fluorescent antibody test (IFAT), but 100% of ability to allow speciation, quantification of parasitaemia the immigrants were already seropositive. Furthermore, the and assessment of the distribution of parasite forms. These immigrant patients also showed higher mean titres, longer latter two functions can help in the assessment of disease persistence of antibodies and greater cross-reactions with severity and sometimes influence the choice of therapy. The other (non-falciparum) malarial antigens. Draper & Sirr went sensitivity of the method varies, depending on the expertise on to observe that individuals from hyperendemic areas in of the microscopist. In experienced hands, sensitivities of Africa may have high titres of antibodies reactive to all anti- between 5 and 50 parasites/µl can be achieved, but in routine gens, which may be associated with a low-grade asympto- situations most laboratories achieve a lower sensitivity of matic infection that is undetectable microscopically – the around 500 parasites/µl [17,18]. The time required to read scenario now referred to as semi-immune and described individual films (20 min for a negative thick film), plus the lack of sensitivity, makes this approach non-viable for blood Given the potential for malaria parasites to persist in cer- tain patients for some years, it is important to note that in Fluorescence microscopy techniques based on dyes (e.g.
individuals who have suffered repeated attacks of malaria, acridine orange) with affinity for parasite nucleic acids have antimalarial immunoglobulin may be detectable for several also been applied as diagnostic assays [19–21], but difficulty years. Although the persistence of antibodies long after cure in discriminating between fluorescence-stained parasites of the malarial infection would lead to some individuals, who and other nucleic acid-containing cellular debris have are no longer parasitaemic, being excluded as potential limited the sensitivity of such techniques to more than 100 donors, it does provide a useful margin of safety if candidate parasites/µl. Although the processing time is reduced by donors, who are malaria antibody positive, are excluded from comparison with routine microscopy, specialized equipment is needed. Species differentiation is often difficult and Although for many years the IFAT was still regarded as the requires confirmation by alternative methods. For these rea- ‘Gold Standard’ for malarial serology, the more recent arrival sons, fluorescent methods offer little, if any, improvement of enzyme immunoassays (EIAs) using native and recom- binant antigens has provided a more sensitive and practical Despite their continued application as key diagnostic tests, alternative to IFAT [4,24]. Overall, EIAs demonstrated suffi- microscopic techniques have several key limitations that ciently high sensitivity and specificity to screen at-risk render them inappropriate for universal or targeted donor donors, and the authors estimated that use of the EIA could screening. Specifically, they lack the required sensitivity to safely retrieve up to 50 000 red cell donations each year that detect all infected units, are too time-consuming (generally may otherwise be lost to the English blood service. It is requiring 1 h or more for preparation and detailed examina- important to note that the use of antibody-detection enzyme- tion), and require significant expertise and specialized equip- linked immunosorbent assay (ELISA) is not recommended ment when fluorescence methods are used.
for the diagnosis of acute malaria, blood films still being themost sensitive method for malaria diagnosis in a clinical Following infection with plasmodial species, the immune Slinger et al. commented that malaria antibody-detection response results in the formation of specific antibody.
tests lack both sensitivity and specificity [12], and that Although not necessarily protective, it is nonetheless an although technically useful where the prevalence of malaria 2006 Blackwell Publishing Ltd. Vox Sanguinis (2006) 90, 77– 84
in donors is high, these tests would probably have a poor performed [27,28], the validity of this strategy in a donor positive predictive value in the Canadian setting, resulting screening context is not clear as the assay combinations and in the unnecessary rejection of donors with false-positive samples used are not representative of blood screening.
test results. However, although antibody from past infections Although a combination of IFAT and antigen assay [26] would indeed lead to, arguably, unnecessary donor exclusion would improve sensitivity over IFAT alone, IFAT has been in non-endemic areas, the absolute numbers would be low – shown to be less sensitive than a new recombinant EIA for 1·5–3% of the ‘malaria-risk donors’ [4,24] – an acceptable antibody detection [24]. Furthermore, the Australian study level for blood transfusion services in the context of malaria [28] used acute-phase samples, and thus studied individuals screening to reinstate donors and collect donations other- who would not have been eligible to donate until 6 months wise ‘lost’ because of a possible malaria risk. Additionally, after their return from a malarious area.
antibody-detection assays demonstrate high antibody levelsand good sensitivity in semi-immune individuals, the very donors who are potentially at high risk of acting as a source The detection of plasmodial DNA by molecular techniques of TTM by being asymptomatic but parasitaemic [13].
is now well established in diagnostic situations. Polymerase In New Zealand, only the plasma was used from donors chain reaction (PCR)-based amplification techniques have who had visited a malarious area within the last 3 years [22], been developed that have been quoted to provide relatively resulting in the ‘loss’ of 4% of all collected blood in the Auck- high levels of sensitivity in a diagnostic situation [28–30], land region alone. Using the same commercial EIA assessed offering a rapid and sensitive means of detection of plasmo- by Chiodini et al. [4], Davidson et al. then investigated the dial DNA in clinical samples. However, the use of molecular prevalence of malarial antibodies in these ‘malarial-risk’ techniques to detect malarial parasites in donated blood has, donors [22]. Of a group of 530 donors, 1·7% were found to for some time, been an area of debate. Although PCR sensi- be malarial antibody positive, a figure similar to that found tivities as low as 0·004 parasites/µl have been quoted [31,32], by Chiodini et al. Thus, antibody testing, with the appropriate the key issue is whether any of the current molecular tests time interval after the last possible exposure episode, pro- can detect parasites at the low level at which they may be vides an effective means of identifying donors who have had present and still transmit malaria, bearing in mind the size of malaria at some time and may still represent a risk of TTM.
the inoculum [33]. To illustrate whether an individual is par-asitaemic at a low level, for example one parasite per ml of whole blood (below the quoted sensitivity of current PCR Current malaria antigen-detection assays are not sufficiently tests), a unit of red cells would need to contain at least 200 sensitive to exclude totally the presence of malaria parasites parasites, a level at which transmission could clearly occur.
in a unit of blood destined for transfusion.
However, this level would be undetectable unless the initialextraction volume for the genomic test was at least 1 ml of blood and the whole extract was then used for the PCR of The detection of malarial antigen was originally intended as blood. Using this volume of sample starts to become prob- a more rapid and objective alternative to direct microscopy.
lematic as large sample volumes are not ideal for routine However, although rapid and reasonably objective, their sen- screening tests where sample numbers are relatively high and sitivity is not sufficient for use in a screening context, as their simple streamlined and automated techniques are required.
overall sensitivity is still less than that of blood films. The When the size of the inoculum is factored into the consider- assays are generally based on the detection of major specific ations, it is clear that the level of parasitaemia in any dona- proteins – histidine rich protein 2 (HRP-2), plasmodial lactate tion could actually be quite a lot lower, and yet the red cell dehydrogenase (pLDH) or aldolase – using various rapid products could still transmit malaria. Experiments involving immunochromatographic formats, and using whole blood as the infection of mice with P. chabaudi demonstrated infec- the sample of choice. Assay sensitivities range from 100 to tivity at a dose of 100 parasites [34]. Thus, in non-endemic 1000 parasites/µl, depending on the species and method, in countries the use of even the most sensitive techniques for general comparable with routine microscopy, except when the detection of malarial DNA would not be sufficient to this is performed by experienced staff [25]. Most of these ensure that a donation was free of parasites. Although it has assays are in a ‘dipstick’ format that can be used with mini- been suggested that a combination of PCR and donor ques- mal training and provide a result within 10–20 min. Expense tioning is an effective way of minimizing the risk of malaria and relative insensitivity have restricted their application as transmission by transfusion [31], a combination of question- ing, deferral and antibody screening is a far more effective Although some authors have proposed the combination and reliable, and in fact cheaper, strategy [24,35].
of malarial antibody screening with antigen detection as In endemic countries, however, PCR has been suggested a means of increasing the sensitivity of any screening as a way in which infectious donations, with parasitaemia 2006 Blackwell Publishing Ltd. Vox Sanguinis (2006) 90, 77– 84
below that detectable by standard thick films, can be identi- 5 Kitchen A, Mijovic A, Hewitt P: Transfusion transmitted fied. In comparison with thick films there is no doubt that a malaria: current donor selection guidelines are not sufficient.
well-designed PCR can be more sensitive [36,37]. Moreover, Vox Sang 2005; 88:200–201
routine PCR screening is not widely available in the majority 6 Schlagenhauf P, Mueutener P: Imported malaria; in Schlagen- hauf P (ed.): Travellers’ Malaria. Hamilton, BC Decker Inc., of malaria-endemic countries, the cost is almost always prohibitive and the infrastructure needed is not normally 7 Mungai M, Tegtmeier G, Chamberland M, Parise M: Transfusion- available. Therefore, in malaria-endemic countries, PCR is transmitted malaria in the United States from 1963 through not currently, or in the foreseeable future, a viable alternative 1999. N Engl J Med 2001; 344:1973–1978
to Giemsa-stained thick films for the screening of blood 8 Wylie BR: Transfusion transmitted infection: viral and exotic diseases. Anaesth Intensive Care 1993; 21:24–30
9 Tegtmeier GE: Infectious diseases transmitted by transfusion: a miscellanea. Vox Sang 1994; 67:179–181
Conclusions
10 Dodd RY: Transmission of parasites by blood transfusion. Vox Although cases of TTM are not common in non-endemic Sang 1998; 74:161–163
countries, malaria is nonetheless a significant problem in a 11 Dodd RY: Transmission of parasites and bacteria by blood components. Vox Sang 2000; 78:239–242
number of these countries and a potential problem in most 12 Slinger R, Giulivi A, Bodice-Collins M, Hindieh F, St John F, others. This is because malaria is a disease that is gradually Sher G, Goldman M, Ricketts M, Kain K: Transfusion-transmitted spreading in terms of the numbers of individuals exposed to malaria in Canada. Can Med Assoc J 2001; 164:377–379
it. The disease itself is encroaching into new areas and back 13 Kitchen AD, Barabara JA, Hewitt PE: Documented cases of into areas from which it was previously eradicated, and there post-transfusion malaria occurring in England: a review in is increasing travel into malarious areas. Thus, the number of relation to current and proposed donor selection guidelines.
donors who have a potential ‘malaria risk’ is increasing, and Vox Sang 2005; 89:77–80
there is corresponding pressure on the collection teams to 14 Mungai M, Tegtmeier G, Chamberland M, Parise M: Transfusion- correctly and effectively identify all such ‘malaria-risk’ indi- transmitted malaria in the United States from 1963 through viduals, and pressure on the recruitment staff to replace the 1999. N Engl J Med 2001; 344:1973–1978
donations lost, even if deferral is only temporary. Lengthy 15 Current UK donor selection guidelines: deferral increases the risk of donors not returning. This is 16 Warhurst DC, Williams JE: Laboratory diagnosis of malaria – ACP clearly a cumulative problem that, if malaria risk leads to Broadsheet no 148, July 1996. J Clin Pathol 1996; 49:533–538
permanent deferral, is likely to erode significantly the donor 17 Moody A: Rapid diagnostic tests for malaria parasites. Clin base. Therefore, an effective strategy with comprehensive Microbiol Rev 2002; 15:66–78
and effective guidelines for both the management of donors 18 Milne LM, Kyi MS, Chiodini PL, Warhurst DC: Accuracy of and the screening of donations needs to be put into place to routine laboratory diagnosis of malaria in the United Kingdom.
safeguard both the safety and sufficiency of the blood supply J Clin Pathol 1994; 47:740–742
in the face of an ever-growing threat. Finally, it must be 19 Baird JK, Purnomo, Jones TR: Diagnosis of malaria in the field recognized that cases of TTM will still occur, albeit rarely.
by fluorescence microscopy of QBC capillary tubes. Trans R Soc Although no set of guidelines is perfect, appropriate deferral Trop Med Hyg 1992; 86:3–5
strategies, providing that they are properly applied, with the 20 Benito A, Roche J, Molina R, Amela C, Alvar J: Application and evaluation of QBC malaria diagnosis in a holoendemic area.
appropriate laboratory screening, will reduce this risk to a Appl Parasitol 1994; 35:266–272
21 Bosch I, Bracho C, Perez HA: Diagnosis of malaria by acridine orange fluorescent microscopy in an endemic area of venezuela.
References
Mem Inst Oswaldo Cruz 1996; 91:83–86
22 Davidson N, Woodfield G, Henry S: Malaria antibodies in 1 Bruce-Chwatt LJ: Transfusion malaria. Bull WHO 1974; Auckland blood donors. NZ Med J 1999; 112:181–183
50:337–346
23 Draper C, Sirr SS: Serological investigations in retrospective 2 Bruce-Chwatt LJ: Transfusion malaria revisited. Trop Dis Bull diagnosis of malaria. BMJ 1980; 1575–1576 1982; 79:827–840
24 Kitchen AD, Lowe PHJ, Lalloo K, Chiodini PL: Evaluation of a 3 De Silva M, Contreras M, Barbara J: Two cases of transfusion- malarial antibody assay for use in the screening of blood and transmitted malaria (TTM) in the UK [letter]. Transfusion 1988; tissue products for clinical use. Vox Sang 2004; 87:150–155
25 Huong NM, Davis TM, Hewitt S, Huong NV, Uyen TT, Nhan DH, 4 Chiodini PL, Hartley S, Hewitt PE, Barbara JAJ, Lalloo K, Bligh Cong le D: Comparison of three antigen detection methods for J, Voller A: Evaluation of a malaria antibody ELISA and its value diagnosis and therapeutic monitoring of malaria: a field study in reducing potential wastage of red cell donations from blood from southern Vietnam. Trop Med Int Health 2002; 7:304–308
donors exposed to malaria, with a note on a case of transfusion- 26 Silvie O, Thellier M, Rosenheim M, Datry A, Lavigne P, Danis M, transmitted malaria. Vox Sang 1997; 73:143–148
Mazier D: Potential value of Plasmodium falciparum-associated 2006 Blackwell Publishing Ltd. Vox Sanguinis (2006) 90, 77– 84
antigen and antibody detection for screening of blood donors to 32 Thellier M, Lusina D, Guiguen C, Delamaire M, Lkegros F, prevent transfusion-transmitted malaria. Transfusion 2002; Ciceron L, Klerlein M, Danis M, Mazier D: Is airport malaria 42:357–362
a transfusion-transmitted malaria risk? Transfusion 2001; 27 Seed C, Cheng A, Keller A: Comparison of the efficacy of two 41:301–302
malarial antibody enzyme immunoassays for targeted blood 33 Rickman LS, Jones TR, Long GW, Paparello S, Schneider I, Paul donor screening. Transfusion 2004; 44:99A [Abstract]
CF, Beaudoin RL, Hoffman SL: Plasmodium falciparum-infected 28 Perandin F, Manca N, Calderaro A, Piccolo G, Galati L, Ricci L, Anopheles stephensi inconsistently transmit malaria to humans.
Medici MC, Arcangeletti MC, Snounou G, Dettori G, Chezzi C: Am J Trop Med Hyg 1990; 43:441–445
Development of a real-time PCR assay for detection of Plasmo- 34 Timms R, Colegrave N, Chan BHK, Read AF: The effect of para- dium falciparum, Plasmodium vivax and Plasmodium ovale for site dose on disease severity in the rodent malaria Plasmodium routine clinical diagnosis. J Clin Microbiol 2004; 42:1214–1219
chabaudi. Parasitology 2001; 123:1–11
29 McNamara DT, Thomson JM, Kasehagen LJ, Zimmerman PA: 35 Shehata N, Kohli M, Detsky A: The cost-effectiveness of screen- Development of a multiplex PCR-ligase detection reaction assay ing blood donors for malaria by PCR. Transfusion 2004; 44:217–
for diagnosis of infection by the four parasite species causing malaria in humans. J Clin Microbiol 2004; 42:2403–2410
36 Hang VT, Be TV, Tran PN, Thanh LT, Hien LV, O’Brien E, Morris 30 Rubio JM, Benito A, Berzosa PJ, Roche J, Puente S, Subirats M, GE: Screening donor blood for malaria by polymerase chain Lopez-Velez R, Garcia L, Alvar J: Usefulness of seminested reaction. Trans R Soc Trop Med Hyg 1995; 89:44–47
multiplex PCR in surveillance of imported malaria in Spain.
37 Ndao M, Bandyayera E, Kokoskin E, Gyorkos TW, MacLean JD, J Clin Microbiol 1999; 37:3260–3264
Ward BJ: Comparison of blood smear, antigen detection and 31 Benito A, Rubio JM: Usefulness of seminested polymerase chain nested-PCR methods for screening refugees from regions where reaction for screening blood donors at risk for malaria in Spain.
malaria is endemic after a malaria outbreak in Quebec. Canada.
Emerg Infect Dis 2001; 7:1068 [Letter]
J Clin Microbiol 2004; 42:2694–2700
2006 Blackwell Publishing Ltd. Vox Sanguinis (2006) 90, 77– 84

Source: http://www.blutspenden-zh.ch/Media/File/Malaria%20and%20Blood%20transfusion.pdf