sign in sign up
<<
Home , Dengue fever, Dengue virus, West Nile virus

BRIEF REPORT

Transmission of Dengue had recently returned from Peru; the presumed mechanism of was mucocutaneous exposure that occurred dur- without a : ing medical care. We describe both cases of dengue and Nosocomial Mucocutaneous review the ways that can be transmitted without mosquito vectors. Transmission and Other Routes Case reports. Patient 1, a 48-year-old female traveler, pres- of Transmission ented in November 2002 with a 5-day history of fever, , Downloaded from https://academic.oup.com/cid/article/39/6/e56/359683 by guest on 30 September 2021 and . She had recently returned from Iquitos, Peru Lin H. Chen1,2,3 and Mary E. Wilson1,3 (on a trip that lasted from 1 through 10 November), where 1Harvard Medical School, and 2Travel Medicine Center and 3Division of she worked as a nurse on a medical mission and traveled Infectious , Mount Auburn Hospital, Cambridge, Massachusetts through the Amazon jungles. She stayed in a hotel that had unscreened, open windows. The patient had received hepatitis A virus, hepatitis , and oral typhoid prior to We report a case of in a Boston-area health travel, and she took mefloquine hydrochloride for pro- care worker with no recent history of travel but with mu- phylaxis. She had received fever in 1997. cocutaneous exposure to infected blood from a febrile trav- At examination, the patient’s temperature was 37.9C. Ab- eler who had recently returned from Peru. Serologic tests normal findings included marked erythroderma, especially on confirmed acute dengue virus in both the traveler the patient’s back, and a maculopapular along her hairline. and the health care worker. We believe that this is the first She had generalized and a faint maculopapular con- documented case of dengue virus transmission via the mu- fluent rash on her arms, legs, and back. Laboratory results cocutaneous route. We present case reports and review other obtained on 18 November (i.e., day 2 of illness) are summarized ways that dengue virus has been transmitted without a mos- in table 1, along with the results of subsequent studies. quito vector. Patient 2, a 37-year-old health care worker, was seen on 19 December 2002 for residual , myalgia, headache, and Dengue fever, a mosquito-borne viral infection caused by 4 low-grade fever, which occurred after an acute illness that began antigenically distinct dengue virus in the family Fla- on 28 November 2002 and that included eye pain, nosebleeds, viviridae, is widespread in tropical and subtropical regions. In- and decreased appetite. Ten days prior to the onset of her fection is characterized by the abrupt onset of fever, myalgia, symptoms, the patient had contact with blood from patient 1. fatigue, and headache. Diffuse erythema may be present early While patient 2 was transferring blood from a syringe to a in the course of infection, and maculopapular eruption may bottle, the needle dislodged from the syringe, and be present later. Associated complications include dengue hem- she felt blood splash onto her face, including her eye, nose, orrhagic fever and dengue syndrome, which are diag- and mouth. She had a history of 2 previous occupational need- nosed on the basis of the presence of fever, , lestick exposures (in 1995 and 1999) and had been vaccinated hemorrhage, and excessive vascular permeability. Laboratory against hepatitis B virus in 1995. Results of tests for HIV were findings commonly include , thrombocytopenia,and negative after those incidents. Her only international travel was abnormalities in the results of function tests. to the Bahamas 20 years before the exposure occurred; she We report a case of dengue fever in a health care worker denied recent travel to Texas or Florida. with no recent history of travel outside of the northeastern Serum samples obtained from both patients were submitted United States. The source of her infection was a traveler who to the Dengue Branch of the Centers for Control and Prevention (CDC) in Puerto Rico. No virus was isolated from Received 15 March 2004; accepted 17 May 2004; electronically published 30 August 2004. patient 1 on day 6 of illness, but dengue virus IgM titers were Presented in part: Annual meeting of the American Society of and Hygiene, positive, and IgG titers were positive at 1:163,840. The con- , Pennsylvania, December 2003 (abstract 2002). Reprints or correspondence: Dr. Lin H. Chen, Div. of Infectious Diseases, Mount Auburn valescent-phase serum sample (obtained on day 23 after the Hospital, 330 Mount Auburn St., Cambridge, MA ([email protected]). onset of illness) was IgM positive. IgG titers were positive at Clinical Infectious Diseases 2004;39:e56–60 1:655,360, which is consistent with a secondary flavivirus in- 2004 by the Infectious Diseases Society of America. All rights reserved. 1058-4838/2004/3906-00E3$15.00 fection. A serum sample from patient 2 (obtained on day 8 of e56 • CID 2004:39 (15 September) • BRIEF REPORT Table 1. Pertinent laboratory values and findings for 2 patients infected with dengue virus in 2002, by date of illness.

Patient 1 Patient 2 Variable 18 Nov 20 Nov 22 Nov 26 Nov 10 Dec 5 Dec 19 Dec Day of illness 2 4 6 10 24 8 22 Laboratory values WBC counta, ϫ 103 cells/mm3 2.97 … 1.92 5.47 5.46 2.63 5.22 Hematocritb,% 37.7 … 44 43 34.8 44.6 39.1 countc, ϫ 103 /mm3 255 … 121 332 437 110 209 ALP leveld, U/L 52 … 61 59 48 131 129 ALT levele,U/L 107 … 108 91 35 88 55 AST levelf,U/L 227 … 104 65 21 75 36

Findings of serologic tests Downloaded from https://academic.oup.com/cid/article/39/6/e56/359683 by guest on 30 September 2021 Dengue virus Isolation …… Ϫ ………… IgM … Ϫ + … +++ IgG … ++g … +h Ϫ +i Neutralization ………… Serotypes 2 and 3 … 3

NOTE. Abnormal values or findings are in bold. ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; Ϫ, negative finding; +, positive finding. a Normal range, 4.0–10.8 ϫ 103 cells/mm3. b Normal range, 34%–40%. c Normal range, 150–350 ϫ 103 platelets/mm3. d Normal range, 50–136 U/L. e Normal range, 30–65 U/L. f Normal range, 15–37 U/L. g Titer of 1:163,840. h Titer of 1:655,360. i Titer of 1:2560. illness) was IgM positive and IgG negative. Virus isolation was take at least 1 week to perform. typically begins 2–3 not attempted. A convalescent-phase serum sample from pa- days before the onset of symptoms, and it continues for 4–5 tient 2 (obtained on day 22 of illness) was positive for IgM days during acute illness [4]. Hence, there is a limited period and IgG at titers of 1:2560. Neutralization tests during which the virus can be isolated. Among Thai children, showed antibodies against dengue serotype 2 and dengue se- viral RNA levels peaked 2 days before defervescence [5]. PCR rotype 3 in patient 1 and antibodies against dengue serotype 3 detects viral RNA [5, 6], can be performed more rapidly than in patient 2 (figure 1). can virus isolation but can detect viral RNA only during the Discussion. The usual mosquito vectors for dengue virus period of viremia, and has a sensitivity similar to that of viral are aegypti and, less frequently, . Vector culture. control programs initiated after World War II eliminated A. Because of the drawbacks of culture and PCR, testing paired aegypti from most parts of the Americas, but, after the cessation acute-phase and convalescent-phase serum samples by use of of the programs in the 1960s, A. aegypti reinfestation occurred ELISA has become the primary technique for the diagnosis of in most countries, including their urban areas. Dengue has dengue [7, 8]. Detection of IgM in acute-phase serum samples become widespread in the Americas, and its has been usually supports the diagnosis of dengue, although IgM may increasing [1]. be undetectable during the early stages of the infection. A 4- Although dengue epidemics occurred in the United States fold increase in the levels of antibodies in specimens obtained decades ago, most of the recent cases of dengue have occurred from the acute phase to the convalescent phase strongly sup- among international travelers. Autochthonous transmissioncan ports the diagnosis of acute dengue virus infection. However, occur in areas that have competent vectors, such as Texas and dengue virus antibodies cross-react with those of many other Florida. In 2001–2002, local transmission of dengue virus in flaviviruses, including , Japanese , Hawaii resulted in 1100 cases of infection [2]. and . Acute or past with other The diagnosis of dengue is confirmed by isolating the virus flaviviruses, or against them (in the case of yellow from serum either by inoculating live mosquitoes or by per- fever virus or ), can complicate the inter- forming cell cultures [3, 4]. Although these methods are spe- pretation of dengue serologic findings. cific, the sensitivity may be as low as 50%, and the procedures For patient 1 (the traveler), the results of ELISA performed

BRIEF REPORT • CID 2004:39 (15 September) • e57 Table 2. Details of published reports of dengue virus transmission without a mosquito vector.

Route of exposure Case report Reference Needlestick A nurse sustained a needlestick while drawing blood from a febrile traveler who had deWazieres [11] returned from the Ivory Coast. The injury occurred on day 8 of illness, and the nurse developed fever and myalgia 8 days after the event. Both patients were positive for den- gue virus IgM, serotype 2. Needlestick A medical student pricked a finger while drawing blood from a febrile traveler who had re- Langgartner [12] turned from India and Sri Lanka. The incident occurred on day 5 of illness, and the medical student became ill 6 days after the event. For the patient and the medical student, results of tests for dengue virus IgG and IgM were positive. Needlestick A health care worker who pricked her finger while drawing blood from a febrile traveler who Hirsch [13] had returned from became ill 6 days after the incident. Dengue virus serotype 2 was isolated from the traveler. Results of serologic testing for the health care worker were

consistent with acute flavivirus infection. Downloaded from https://academic.oup.com/cid/article/39/6/e56/359683 by guest on 30 September 2021 Needlestick A nurse sustained a needlestick while drawing blood from a febrile traveler who had Bauer [14] returned from Cambodia. The nurse developed headache, myalgia, and 4 days after the incident. For the patient, results of tests for dengue virus IgG were positive; fpr the nurse, results of serial tests for dengue virus IgMshowed seroconversion consistent with acute infection. A 6-year-old child from Puerto Rico developed fever 4 days after bone marrow transplanta- Rigau-Perez [15] transplantation tion and died 7 days later. Dengue virus serotype 4 was isolated from the child’s blood and tissues. The donor became febrile 2 days after the marrow was harvested, and results of tests for dengue virus IgM were positive when performed 3 weeks later, with serotype 4 being the most likely serotype. Intrapartum or Six days after birth, a newborn had a positive result of PCR for dengue virus serotype 2. His Rigau-Perez [15] vertical mother had a denguelike illness 1 day before a cesarean procedure was performed, and results of a test performed 5 days after delivery were positive for dengue virus IgM. Intrapartum or Two mothers had acute dengue virus infection develop 4 and 8 days before delivery, respec- Chye [16] vertical tively. One newborn was ill at birth, had an intracerebral hemorrhage, and died 6 days after birth. Dengue virus serotype 2 was isolated from the infant, and dengue virus IgM was detected in the mother’s blood. A newborn from the second mother was thrombo- cytopenic at birth. Dengue virus serotype 2 virus was isolated from the mother’s blood, and dengue virus IgM was detected in the newborn’s blood. Intrapartum or A 39-year-old pregnant woman presented with a 3-day history of fever and with thrombo- Kerdpanich [17] vertical cytopenia 5 days before childbirth, and a diagnosis of dengue hemorrhagic fever was es- tablished 2 days after presentation. An infant was delivered by cesarean section. Samples of maternal blood were positive for dengue virus IgM. Cord blood and the newborn’s blood were PCR positive for dengue virus serotype 2. Intrapartum or A 27-year-old woman delivered an infant prematurely at 33 weeks’ gestation. She developed Boussemart [18] vertical fever and headache 10 h later, which lasted for 4 days, and she was dengue virus IgM positive and IgG negative. The newborn developed thrombocytopenia and leukopenia on day 9 but recovered. The infant subsequently was found to be positive for dengue virus IgM. Intrapartum or A newborn became febrile 6 days after birth by cesarean section, and dengue virus serotype Thaithumyanon [19] vertical 2 was isolated from the newborn. His mother had fever for 2 days prior to surgery and experienced hemorrhage postoperatively. She was later determined to have acute dengue infection. on the acute-phase serum samples were dengue virus IgG pos- more straightforward because of the absence of past exposure itive, which could be attributed to past flavivirus infection or to flaviviruses. Although transmission of West Nile virus has to immunization against yellow fever [4]. Although no virus been occurring in the northeastern United States since 1999, was isolated from the serum samples obtained on day 6 of the December onset of illness for patient 2 occurred after the illness, a serum sample obtained on day 4 was IgM negative transmission season ended in Boston. The results of ELISA were but became IgM positive on day 6, which is consistent with positive for dengue virus IgM on day 7, strongly suggesting the previous reports on the timing of seroconversion [9]. In ad- diagnosis of acute dengue virus infection. Although the 2 dition, convalescent-phase serum samples tested positive for women were linked epidemiologically, positive results of viral both IgM and IgG, with a 4-fold increase in IgG titers, strongly cultures with genetically identical isolates from both would have supporting the diagnosis of acute dengue virus infection. been required for absolute proof of linked infections. For patient 2 (the health care worker), the diagnosis was Analysis of neutralizing antibodies against dengue viruses e58 • CID 2004:39 (15 September) • BRIEF REPORT transmission include needlestick injuries, bone marrow trans- plantation, and intrapartum and vertical transmission (table 2). A brief report on ProMed-mail described 2 suspected cases of dengue fever aquired through in Hong Kong; in both cases, the donor developed symptoms consistent with dengue 1 day after giving blood and tested positive for dengue infection [20]. Dengue virus presumably infected patient 2 via blood contact with mucous membranes. This is biologically plausible, given the well-documented nosocomial spread of multiple viruses (i.e., hepatitis B virus, virus, and HIV) after mu- cocutaneous contact with blood [21]. The mean volume of Downloaded from https://academic.oup.com/cid/article/39/6/e56/359683 by guest on 30 September 2021 blood delivered via a needlestick injury with a 22-gauge needle attached to a syringe containing 2 mL of blood has been found to be only 1.40 mL, yet transmission of many infections, in- cluding dengue, has occurred [22]. The amount of blood as- sociated with mucocutaneous transmission of has not been defined. Because the level of viremia can reach 109 RNA copies per milliliter of blood in acute dengue virus in- fections, it is plausible that blood splashed on broken skin or on a mucous membrane could deliver a sufficient amount of virus to cause infection [5]. Nosocomial transmission, including mucocutaneous trans- mission, may occur in areas of endemicity but is unlikely to be recognized in areas in which dengue virus circulates widely. Hemorrhage, a feature of dengue hemorrhagic fever, may in- crease the risk of nosocomial transmission. Assessing the mag- nitude of nosocomial dengue virus transmission in areas of endemicity is difficult because all health care workers are also potentially exposed to infective mosquitoes. It is not surprising that nosocomial transmission of dengue virus has been iden- tified primarily in areas of nonendemicity, in settings in which no other exposures to the virus are plausible. West Nile virus is transmissible via breastfeeding, as well as through blood transfusions, organ transplantations, stem cell transplantations, intrauterine exposure, and needlestick injuries [23–27]. It is possible that dengue virus could be transmitted Figure 1. Sequence of events in 2 cases of dengue virus infection also through breast milk, although no documented cases have that occurred in 2002; 1 case involved a traveler, and 1 case involved a been reported. health care worker who had mucocutaneous exposure to the traveler’s Health care workers have frequent exposures to blood. One blood. recently published survey found that 43% of physicians, 38.5% of registered nurses, 26.4% of licensed practical nurses, and identified serotypes 2 and 3 in patient 1 and serotype 3 in 24.5% of medical technologists reported at least 1 mucocuta- patient 2. The plaque reduction neutralization test uses refer- neous blood exposure within the previous 3 months [28]. Ad- ence viruses (expressed as plaque-forming units), which are herence to standard precautions was not ideal, and the under- mixed and incubated with diluted test sera in . An- reporting of incidents was common. Phlebotomy equipment tibodies that neutralize specific serotypes of the virus reduce that operates as a closed system could minimize the number the number of plaques formed [10]; therefore, the specific den- of blood-splash and needlestick exposures. gue serotype can often be determined. In summary, health care workers should be aware that nos- Although rarely documented, dengue virus transmission ocomial transmission of dengue virus can occur by mucocu- without a mosquito vector has been reported. The routes of taneous exposures, as well as by needlestick exposures. This

BRIEF REPORT • CID 2004:39 (15 September) • e59 may be especially relevant to health care workers who care for 11. de Wazieres B, Gil H, Vuitton DA, Dupond J-L. Nosocomial trans- mission of dengue from a needlestick injury. Lancet 1998; 351:498. patients with dengue with hemorrhage in resource-poor areas 12. Langgartner J, Audebert F, Scho¨lmerich J, et al. Dengue virus infection in which gloves and access to good infection-control measures transmitted by needle stick injury. J Infect 2002; 44:269–70. are limited. 13. Hirsch JF, Deschamps C, Lhuillier M. Transmission me´tropolitaine d’une dengue par inoculation accidentelle hospitalie`re. Ann Med In- terne (Paris) 1990; 141:629. Acknowledgments 14. Bauer TM, De With K, Eppinger S, Huzly D, Wagner D, Kern WV. Nosokomiale ubertragung von dengue-fieber. Infection 2003; 31(Suppl We thank the Dengue Branch of the Centers for Disease Control and 1):117. Prevention, for performing the dengue studies; Dr. Vance Vorndam, Dr. 15. Rigau-Perez JG, Vorndam AV, Clark GG. The dengue and dengue hem- Timothy Brewer, and Kerrie Dirosario, for reviewing the manuscript; and orrhagic fever epidemic in Puerto Rico, 1994–1995. Am J Trop Med Dr. Joycelyn Datu, Dr. Stanley Sagov, and Diane Boivin, for their helpful Hyg 2001; 64:67–74. comments. 16. Chye JK, Lim CT, Ng KB, Lim JMH, George R, Lam SK. Vertical Conflict of interest. All authors: No conflict. transmission of dengue. Clin Infect Dis 1997; 25:1374–77.

17. Kerdpanich A, Watanaveeradej V, Samakoses R, et al. Perinatal dengue Downloaded from https://academic.oup.com/cid/article/39/6/e56/359683 by guest on 30 September 2021 infection. Southeast Asian J Trop Med Public Health 2001; 32:488–93. References 18. Boussemart T, Babe P, Sibille G, Neyret C, Berchel C. Prenatal trans- mission of dengue: two new cases. J Perinatol 2001; 21:255–7. 1. Wilson ME, Chen LH. Dengue in the Americas. Dengue Bulletin 19. Thaithumyanon P, Thisyakorn U, Deerojnawong J, Innis BL. Dengue 2002; 26:44–61. infection complicated by severe hemorrhage and vertical transmission 2. Centers for Disease Control and Prevention. Notice: dengue fever, in a parturient woman. Clin Infect Dis 1994; 18:248–9. Hawaii. Released 2 October 2001; updated 4 March 2002. Available 20. ProMed-mail. Archive 20021011.5526. Dengue virus, transfusion trans- at: http://www.cdc.gov/travel/other/dengue-hawaii-oct2001.htm. Ac- mission—China (Hong Kong). ProMed 11 October 2002. Available at: cessed 12 March 2002. http://www.promedmail.org/pls/askus/f?pp2400:1202:1789808462154 3. Gubler DJ, Kuno G, Sather GE, Velez M, Oliver A. Mosquito cell 5356247::NO::F2400_P1202_CHECK_DISPLAY,F2400_P1202_PUB_ cultures and specific monoclonal antibodies in surveillance for dengue MAIL_ID:X,19530. Accessed 27 August 2004. viruses. Am J Trop Med Hyg 1984; 33:158–65. 21. Beltrami EM, Williams IT, Shapiro CN, Chamberland ME. Risk and 4. Guzman MG, Kouri G. Dengue diagnosis, advances and challenges. management of blood-borne infections in health care workers. Clin Int J Infect Dis 2004; 8:69–80. Microbiol Rev 2000; 13:385–407. 5. Sudiro TM, Zivny J, Ishiko H, et al. Analysis of plasma viral RNA 22. Napoli VM, McGowan JE Jr. How much blood is in a needlestick? J levels during acute dengue virus infection using quantitative competitor Infect Dis 1987; 155:828. reverse transcription-polymerase chain reaction. J Med Virol 2001; 63: 23. Centers for Disease Control and Prevention. Possible West Nile virus 29–34. transmission to an infant through breast-feeding—Michigan, 2002. 6. Lanciotti RS, Calisher CH, Gubler DJ, Chang GJ, Vorndam AV. Rapid MMWR Morb Mortal Wkly Rep 2002; 51:877–8. detection and typing of dengue viruses from clinical samples by using 24. Iwamoto M, Jernigan DB, Guasch A, et al. Transmission of West Nile reverse transcriptase-polymerase chain reaction. J Clin Microbiol virus from an organ donor to four transplant recipients. N Engl J Med 1992; 30:545–51. 2003; 348:2196–203. 7. Innis BL, Nisalak A, Nimmannitya S, et al. An enzyme-linked im- 25. Hong DS, Jacobson KL, Raad II, et al. West Nile encephalitis in 2 munosorbent assay to characterize dengue infections where dengue hematopoietic stem cell transplant recipients: case series and literature and Japanese encephalitis co-circulate. Am J Trop Med Hyg 1989; 40: review. Clin Infect Dis 2003; 37:1044–9. 418–27. 26. Centers for Disease Control and Prevention. Intrauterine West Nile 8. Miagostovich MP, Nogueira RM, dos Santos FB, Schatzmayr HG, Ar- virus infection—New York, 2002. MMWR Morb Mortal Wkly Rep aujo ES, Vorndam V. Evaluation of an IgG enzyme-linked immuno- 2002; 51:1135–6. sorbent assay for dengue diagnosis. J Clin Virol 1999; 14:183–9. 27. Centers for Disease Control and Prevention. Laboratory-acquired West 9. Schwartz E, Mileguir F, Grossman Z, Mendelson E. Evaluation of Nile virus infections—United States, 2002. MMWR Morb Mortal Wkly ELISA-based sero-diagnosis of dengue fever among travelers. J Clin Rep 2002; 51:1133–5. Virol 2000; 19:169–73. 28. Doebbeling BN, Vaughn TE, McCoy KD, et al. Percutaneous injury, 10. Russell PK, Nisalak A, Sukhavachana P, Vivona S. A plaque reduction blood exposure, and adherence to standard precautions: are hospital- test for dengue virus neutralizing antibodies. J Immunol 1967; 99: based health care providers still at risk? Clin Infect Dis 2003; 37: 291–6. 1006–13.

e60 • CID 2004:39 (15 September) • BRIEF REPORT