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Dengue in Travelers
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     To the Editor: Wilder-Smith and Schwartz (Sept. 1 issue)1 mention that serotypes of dengue virus are distinguishable by the plaque-reduction neutralization test.2 But they neglect to include this test in Table 2 of the article, which lists laboratory tests for the diagnosis of dengue. The concept that the plaque-reduction neutralization test is more specific than other serologic assays for the diagnosis of dengue and other flavivirus infections3 is confirmed by recent experience at the Wadsworth Center, operated by the New York State Department of Health. Since 1999, with the introduction of West Nile virus into the United States, the plaque-reduction neutralization test has been particularly helpful in distinguishing this flavivirus from the closely related St. Louis encephalitis virus and in substantiating the diagnosis of dengue, particularly in the absence of isolation of the virus or data from the reverse-transcriptase polymerase chain reaction. Of the other serologic tests listed in Table 2 of the article, hemagglutination inhibition lacks specificity,4 and the IgM enzyme-linked immunosorbent assay at times yields false positive reactions that are not confirmed by the plaque-reduction neutralization test.

    Stephen J. Seligman, M.D.

    New York Medical College

    Valhalla, NY 10595

    stephen_seligman@nymc.edu

    Laura D. Kramer, Ph.D.

    Wadsworth Center

    Slingerlands, NY 12159

    References

    Wilder-Smith A, Schwartz E. Dengue in travelers. N Engl J Med 2005;353:924-932.

    Russell PK, Nisalak A. Dengue virus identification by the plaque reduction neutralization test. J Immunol 1967;99:291-296.

    Burke DS, Monath TP. Flaviviruses. In: Knipe DM, Howley PM, eds. Fields virology. 4th ed. Philadelphia: Lippincott Williams & Wilkins, 2001:1043-126.

    Yamada K, Takasaki T, Nawa M, Yabe S, Kurane I. Antibody responses determined for Japanese dengue fever patients by neutralization and hemagglutination inhibition assays demonstrate cross-reactivity between dengue and Japanese encephalitis viruses. Clin Diagn Lab Immunol 2003;10:725-728.

    To the Editor: Wilder-Smith and Schwartz note that dengue is an emerging disease in the Caribbean; however, the status of these islands is not indicated on the accompanying map. Island outbreaks are common,1 and there is now an epidemic in the French Antilles.2 Since more than 5 million U.S. travelers visit the Caribbean annually, vigilance with respect to dengue in returning travelers from this area, particularly during the months of July through November, cannot be overemphasized. Florida, which was the site of an outbreak 70 years ago, is an entry portal to the southeastern United States, to which travelers return and where the vectors reside.3 Accordingly, the Walter Reed Army Institute of Research, with the Department of Defense and the Centers for Disease Control and Prevention, has partnered with the Caribbean Epidemiology Centre to enhance the Caribbean's current dengue surveillance.4 It's only a hop, skip, and a jump away.

    Thomas R. Roesel, M.D., Ph.D.

    Walter Reed Army Medical Center

    Washington, DC 20307

    thomas.roesel@na.amedd.army.mil

    References

    Campione-Piccardo J, Ruben M, Vaughan H, Morris-Glasgow V. Dengue viruses in the Caribbean: twenty years of dengue virus isolates from the Caribbean Epidemiology Centre. West Indian Med J 2003;52:191-198.

    ProMED-mail. Dengue/DHF update 2005 (27): ProMED-mail post. Archive no. 20050831.2569. August 31, 2005. (Accessed November 15, 2005, at http://www.promedmail.org.)

    Gill J, Stark LM, Clark GG. Dengue surveillance in Florida, 1997-98. Emerg Infect Dis 2000;6:30-35.

    Writer JV, Kelley PW, Boisson EV, Hospedales J. Caribbean Public Health Laboratory Surveillance Project: a Department of Defense-sponsored humanitarian mission. Mil Med 2003;168:843-8.

    To the Editor: Wilder-Smith and Schwartz do not mention ultrasonography in the diagnostic workup of dengue. Ultrasonography can be useful in making a provisional diagnosis of dengue fever in children as well as adults.1,2,3,4 The reported findings include thickening of the gallbladder wall and the presence of pericholecystic fluid, pleural effusion, ascites, pericardial effusion, hepatomegaly, and splenomegaly. Pleural effusion may be right-sided, left-sided, or bilateral. Such features may be noted even before seroconversion takes place. These findings have been reported during dengue epidemics as well as in zones in which dengue is endemic and could be used to screen travelers to such zones.

    Akshay Kumar Saxena, M.D.

    Post Graduate Institute of Medical Education and Research

    Chandigarh 160012, India

    fatakshay@yahoo.com

    References

    Venkata Sai PM, Dev B, Krishnan R. Role of ultrasound in dengue fever. Br J Radiol 2005;78:416-418.

    Wu KL, Changchien CS, Kuo CH, et al. Early abdominal sonographic findings in patients with dengue fever. J Clin Ultrasound 2004;32:386-388.

    Gupta S, Singh SK, Taneja V, Goulatia RK, Bhagat A, Puliyel JM. Gall bladder wall edema in serology proven pediatric dengue hemorrhagic fever: a useful diagnostic finding which may help in prognostication. J Trop Pediatr 2000;46:179-181.

    Thulkar S, Sharma S, Srivastava DN, Sharma SK, Berry M, Pandey RM. Sonographic findings in grade III dengue hemorrhagic fever in adults. J Clin Ultrasound 2000;28:34-37.

    The authors reply: With regard to comments by Seligman and Kramer: the plaque-reduction neutralization test1 is indeed one of the most specific and sensitive tests for dengue, and it can be used to identify the infecting virus serotype in primary dengue infection. In secondary and tertiary infections, however, the infecting viral serotype cannot be reliably determined. Because of the long persistence of neutralizing antibodies, the test can also be used for seroepidemiologic studies. The major disadvantages are the expense, the time needed to perform the test, its technical difficulty, and the need for live virus in the laboratory.2 The test is therefore mainly used in research settings, rather than in routine clinical practice.

    Saxena correctly points out the potential value of ultrasonography in the diagnosis of dengue. The technique is not routinely used in the diagnostic workup in countries in which dengue is endemic and is also not one of the diagnostic criteria for dengue used by the World Health Organization (WHO). Although thickening of the gallbladder wall is a frequent ultrasonographic finding in dengue fever, this finding also occurs in many other viral infections, is nonspecific, and can therefore be used only as an adjunct test to the clinical and laboratory profile in the diagnosis of dengue fever.3 Ultrasonography is more sensitive and accurate in the early diagnosis of capillary leakage than is clinical examination.3 Our concern is that ultrasonography may be too sensitive and may lead to overdiagnosis of dengue hemorrhagic fever, as compared with use of the WHO criteria, which are based on clinical signs and laboratory findings. Prospective studies are needed to determine whether earlier diagnosis on the basis of ultrasonographic findings would have an effect on earlier institution of fluid therapy and be associated with a better prognosis for patients with dengue hemorrhagic fever. The value of ultrasonography in the workup of possible dengue in returning travelers needs to be examined, given that the majority of travelers present with mild-to-moderate dengue fever, rather than with dengue hemorrhagic fever.

    Roesel's comments on emerging dengue in the Caribbean highlight our concern about the geographic expansion of dengue, with the risk of reintroduction into areas that previously had endemic disease or introduction into areas where dengue is not endemic but where the vector exists. The publication of maps on the endemicity of dengue cannot keep up with the evolving epidemic.

    We propose that dengue has become the leading emerging disease among travelers to the tropics and subtropical areas during the past 20 years. The development of a dengue vaccine and specific antiviral therapy should be expedited, since such efforts would benefit not only travelers, but more important, people who live in areas where dengue is endemic.

    Annelies Wilder-Smith, M.D., Ph.D.

    Travellers' Health and Vaccination Center

    Singapore 308433, Singapore

    epvws@pacific.net.sg

    Eli Schwartz, M.D.

    Chaim Sheba Medical Center

    52621 Tel Hashomer, Israel

    References

    Russell PK, Nisalak A, Sukhavachana P, Vivona S. A plaque reduction test for dengue virus neutralizing antibodies. J Immunol 1967;99:285-290.

    Laboratory diagnosis. (Accessed November 15, 2005, at http://www.who.int/csr/resources/publications/dengue/034-47.pdf.)

    Venkata Sai PM, Dev B, Krishnan R. Role of ultrasound in dengue fever. Br J Radiol 2005;78:416-418.