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Letter
Polymerase Chain Reaction
for Screening Blood Donors at Risk for Malaria: Safe and Useful?
Suggested
citation for this article: Hänscheid
T, Valadas E, Grobusch MP. Polymerase chain reaction for screening blood
donors at risk for malaria: safe and useful? Emerg Infect Dis
[serial online] 2002 Aug [date cited];8. Available from: URL: http://www.cdc.gov/ncidod/EID/vol8no8/02-0025.htm
To the Editor: Transfusion-transmitted malaria, although extremely
uncommon in most countries not endemic for malaria, may have fatal consequences
if undetected (1,2). Benito and Rubio (3)
addressed this timely issue by presenting data on screening of blood donors
at risk for malaria in Spain with a seminested polymerase chain reaction
(SNM-PCR). Of 125 donors at risk (immigrants from malarious areas), these
researchers identified five cases of Plasmodium falciparum by using
SNM-PCR with a 5-mL EDTA blood sample. Benito and Rubio’s conclusion was
that the SNM-PCR could serve as the reference test for screening blood
(3). Obviously, this conclusion implies the potential
use of blood donations from donors who were at risk but whose PCR results
were negative. We believe that this practice would be dangerous and could
lead to the administration of unsafe blood.
The PCR, like any method based on direct detection of the parasite, does
have a shortcoming: the amount of specimen processed determines the limit
of detection. Even if the described PCR method detected a single parasite
in the 5-mL blood sample used by the authors (3) (hypothetical
sensitivity 0.0002 parasites/µL), a standard 450-mL blood donation could
still contain <90 parasites and have a negative PCR result.
However, with the “best” sensitivity reported by Benito and Rubio (3)
of 0.004 parasites/µL, a standard 450-mL blood donation could contain
<1,800 parasites and still be tested negative by SNM-PCR. Surely, <1,800
parasites is enough to cause disease in a blood recipient. As few as 10
parasites per donation (perhaps even fewer) may cause disease. Theoretically,
any method would have to detect a single parasite per unit of blood to
be safe, thus requiring a hypothetical detection limit of 2.2x10-6
parasites/µL. However, a sample equal to the unit of donated blood (450
mL) would have to be processed to achieve this level. In addition, one
would have to assume that parasites are equally distributed in the peripheral
blood at the time of donation.
Little is known about the frequency of very low parasitemias. No large-scale
epidemiologic studies have been conducted in which large amounts of blood
(e.g., the equivalent of a blood donation or 450 mL) were collected. The
authors (3) could not confirm the PCR-positive cases
by microscopy. This finding suggests very low levels of parasitemia, below
the sensitivity of thick smears, in the range of 1–20 parasites per mL
(4). Similar results were observed in blood donors associated
with transfusion-transmitted malaria in the United States, in which malaria
smears were positive in only 17 of 49 donors (1). PCR
is similar to microscopy in screening donors at risk, even if the detection
limits are different. Hommel and Gilles report in Topley and Wilson that
for disease-endemic countries “the use of PCR… …is not, despite its much
increased sensitivity, a complete guarantee of safe blood, because the
absence of parasites in a 20-µL sample does not exclude the possibility
of infection in the remaining volume of the 450 mL blood unit” (5).
On the other hand, one might argue that screening the whole blood supply
for malaria by PCR may detect the rare blood donation with undetected
malaria, with higher parasitemias. However, the generally accepted deferral
criteria for blood donors at risk seem highly efficient. In the United
States, only 14 cases of transfusion-transmitted malaria were reported
from 1990 through 1999 (1). The same authors estimate
that this deferral policy led to 50,000 rejected donations in a total
of 13 million per year (0.3%). At an estimated expense of $2.00–$3.00
per PCR, a general screening program would cost more than $20 million–$30
million per year. Each case of malaria prevented would therefore cost
in excess of several million U.S. dollars.
Several novel diagnostic methods have been developed recently (6).
However, we agree with Mungai et al. (1). These methods,
including PCR, have still not been shown to detect the lowest possible
parasitemia that can cause malaria. Showing that a method is able to detect
donors at risk for malaria, as done by Benito and Rubio (3),
is insufficient. On the contrary, the only convincing study design would
be to show that donors at risk who have a negative PCR result also do
not harbor parasites and cannot transmit the disease. Accordingly, careful
screening of blood donors in nondisease-endemic countries, in accordance
with the established exclusion criteria, remains the best way to prevent
transmission of malaria (1,2).
T. Hänscheid,* E. Valadas,* and M.P. Grobusch†
*Faculty of Medicine, Hospital de Santa Maria, Lisboa, Portugal; and
†Institute of Tropical Medicine, Tuebingen, Germany
References
- Mungai M, Tegtmeier G, Chamberland M, Parise M. Transfusion-transmitted
malaria in the United States from 1963 through 1999. N Engl J Med
2001;344:1973–8.
- Slinger R, Giulivi A, Bodie-Collins M, Hindieh F, St. John R, Goldman
M, et al. Transfusion-transmitted
malaria in Canada. CMAJ 2001;164:377–9.
- Benito A, Rubio JM. Usefulness
of seminested polymerase chain reaction for screening blood donors at
risk for malaria in Spain. Emerg Infect Dis 2001;7:1068.
- Dowling MAC, Shute GT. A
comparative study of thick and thin blood films in the diagnosis of
scanty malaria parasitaemia. Bull World Health Organ 1966;34:249–67.
- Hommel M, Gilles HM. Malaria. In: Collier L, Balows A, Sussman M,
editors. Topley and Wilson’s microbiology and microbial infections.
Vol. 4, Parasitology. London: Arnold; 1998. p. 384–409.
- Hänscheid T. Diagnosis
of malaria: review of alternatives to conventional microscopy. Clin
Lab Haematol 1999;21:235–45.
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