Correspondence

Dengue Hemorrhagic Fever Transmitted by Blood Transfusion

N Engl J Med 2008; 359:1526-1527October 2, 2008

Article

To the Editor:

Dengue, the most common vectorborne viral infection worldwide,1 is predominantly transmitted by the Aedes aegypti mosquito. We describe a well-documented cluster of blood transfusion–associated dengue infections in Singapore, a country in which the disease is endemic.

A 52-year-old, asymptomatic, repeat blood donor gave blood on July 15, 2007. An investigation of all recipients of his blood products was initiated after he informed the blood bank that he had had a fever the day after donation. The stored serum sample was positive for dengue virus type 2, as ascertained by means of a polymerase-chain-reaction (PCR) assay.2

The recipient of the donor's red cells had fever and myalgia 2 days after transfusion. The recipient of the donor's fresh-frozen plasma had fever and worsening pleural effusions the day after transfusion. Both recipients were positive for dengue virus type 2 as detected with the use of a PCR assay, with serologic evidence of secondary dengue infections, and received supportive care and were discharged in good health. The recipient of the donor's platelets was asymptomatic but had serologic evidence of a recent secondary dengue infection on follow-up. Clinical and laboratory details of the patients are shown in Table 1Table 1Characteristics of the Donor and Recipients..

We cloned the PCR-amplified products from the donor and two recipients, by using a cloning protocol (Topo TA, Invitrogen). Direct sequencing of all available envelope glycoprotein gene-cloned segments 78 bp in length, by means of a sequencing kit (ABI PRISM 3100, Applied Biosystems), showed alignment with published sequences for dengue virus type 2 in the GenBank database that are highly conserved in local circulating strains; we were unable to perform whole-genome sequencing for definitive confirmation. Given the timing of the infections — soon after transfusion and, in the plasma recipient, during a prolonged stay in an air-conditioned mosquito-free intensive care unit — the evidence for transfusion-related transmission is convincing.

To our knowledge, transfusion-associated dengue is quite rare; there was a report from Hong Kong, where the disease is not endemic.3 Although it is transient, asymptomatic dengue viremia is a potential risk to the blood supply.4 Nucleic-acid testing has greatly improved blood safety; for example, the potential risk of transfusion-associated transmission of West Nile virus in the United States has been markedly reduced through stratified molecular screening.5 Although screening is expensive, confidence in the blood supply could outweigh cost-effectiveness considerations.

In our patients, prompt recognition through a donor callback system led to favorable clinical outcomes despite the advanced age and multiple coexisting conditions of the patients. This case illustrates the difficulties encountered when attempting to ensure a safe blood supply in the face of emerging flavivirus threats worldwide.

Paul A. Tambyah, M.B., B.S.
Evelyn S.C. Koay, F.R.C.Path.
Michelle L.M. Poon, M.R.C.P.
Raymond V.T.P. Lin, F.R.C.P.A.
Benjamin K.C. Ong, F.R.C.P.
National University of Singapore, Singapore 119074, Singapore
mdcpat@nus.edu.sg

for the Transfusion-Transmitted Dengue Infection Study Group

Dr. Tambyah reports receiving consulting fees from the Asia Pacific Influenza Advisory Committee and MerLion Pharma; lecture fees from Pfizer, Wyeth, and International Business Communications Asia; and grant support from Baxter, Interimmune, and Adamas. No other potential conflict of interest relevant to this letter was reported.

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