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Dengue Hemorrhagic Fever Transmitted by Blood Transfusion

N Engl J Med 2008; 359:1526-1527October 2, 2008 Article Citing Articles (26)

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 transfusionassociated 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 1

Characteristics 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 genecloned 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 wholegenome 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. 5 References 1. Gubler DJ. Epidemic dengue/dengue hemorrhagic fever as a public health, social and economic problem in the 21st century. Trends Microbiol 2002;10:100-103 CrossRef | Medline 2. Johnson BW, Russell BJ, Lanciotti RS. Serotype-specific detection of dengue viruses in a fourplex real-time reverse transcriptase PCR assay. J Clin Microbiol 2005;43:4977-4983 CrossRef | Web of Science | Medline 3. Chuang VW, Wong TY, Leung YH, et al. Review of dengue fever cases in Hong Kong during 1998 to 2005. Hong Kong Med J 2008;14:170-177 Medline 4. Linnen JM, Vinelli E, Sabino EC, et al. Dengue viremia in blood donors from Honduras, Brazil, and Australia. Transfusion 2008;48:1355-1362 CrossRef | Web of Science | Medline 5. West Nile virus transmission through blood transfusion -- South Dakota, 2006. MMWR Morb Mortal Wkly Rep 2007;56:76-79 Medline http://www.nejm.org/doi/full/10.1056/NEJMc0708673

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Dengue fever: Vector control is important!

25 November 2009

I read with interest Teixeira et als recent excellent clinical review on the 'Diagnosis and management of dengue'. [1] However, when Texeira et al under the subheading of How might dengue be prevented? state that the reduction of the vector population has low or no effectiveness in reducing levels of dengue transmission, they perhaps leave the impression that vector control measures- that are aimed at keeping the mosquito population at a low level- are ineffective in reducing the incidence of dengue infections. Indeed, the Aedes aegypti mosquito, the main vector for dengue, is well adapted to living in urban environments and natural breeding habitats are created as quickly as they are eliminated, and there is no evidence that the use of chemical insecticides in an area after cases have already been detected are effective. However, the experience in Singapore shows that a well-conducted vector control system based on entolomogic surveillance and larval source reduction aiming to control the mosquito population before disease is detected in an area can be successful. [2] In this instance, this strategy of keeping the vector population low was successful in bringing about a 15-year period of low dengue incidence. Dengue infections are currently on a rapid rise globally. This has been attributed to population growth, a proliferation of breeding sites for mosquitos with uncontrolled urbanization, difficulties in implementing successful vector control and a rapid increase in international travel. [3] In fact, the recent resurgence in Singapore itself has been partly

attributed to the shift in the emphasis in prevention from vector surveillance towards responding to detected cases of dengue, and increasing travel. [2} With treatment for dengue fever and dengue haemorrhagic fever being at best supportive and an effective vaccine still at the stage of phase III trials, [4] then continued diligence towards holistic and effective vector control measures aimed at keeping the Aedes aegypti population low cannot and should not be neglected. References 1. Teixeira MG, Barreto ML. Diagnosis and management of dengue. BMJ 2009; 39: b4338. 2. Ooi EE, Goh KT, Gubler DJ. Dengue prevention and 35 ears of vector control in Singapore. Emerg infect Dis 2006; 12(6): 887-93. 3. Kyle JL, Harris E. Global spread and persistence of dengue. Annu Rev Microbiol 2008; 62: 7192. 4. Webster DP, Farrar J, Rowland-Jones S. Progress towards a dengue vaccine. Lancet Infect Dis. 2009 Nov;9(11):678-87. Competing interests: None declared Competing interests: None declared http://www.bmj.com/rapid-response/2011/11/02/dengue-fever-vector-control-important