- Email: [email protected]
Imported dengue fever in Austria 1990–2005
ARTICLE IN PRESS Travel Medicine and Infectious Disease (2006) 4, 319–323
www.elsevierhealth.com/journals/tmid
Imported dengue fever in Austria 1990–2005 H. Laferl, M. Szell, E. Bischof, C. Wenisch 4th Medical Department with Infectious Diseases & Tropical Medicine, Kaiser Franz Josef - Hospital, Kundratstraße 3, A-1100, Vienna, Austria Received 4 August 2005; received in revised form 3 October 2005; accepted 6 October 2005 Available online 5 December 2005
KEYWORDS Travel-associated fever; Dengue; Austria; Travel medicine
Summary Dengue is the most important human viral disease transmitted by an arthropod vector. The steadily increasing numbers of tourists visiting endemic areas coupled with the present resurgence of dengue, raises the risk of exposure for large numbers of travelers and imported dengue cases are increasingly observed in nonendemic countries. We aimed to study the epidemiology, clinical manifestations and laboratory findings in imported dengue at a City of Vienna hospital. Medical records of 93 patients (age: 17–68 years, 43 f, 50 m) with imported dengue in Vienna between 1990 and April 2005 were analyzed retrospectively. Fortyeight (52%) were classified as confirmed and 45 (48%) as probable dengue, according to the CDC criteria. The patients acquired the infection in South East Asia (56%), the Indian subcontinent (18%), Africa (10%) and Oceania (3%). The most important symptoms were fever, headache, arthralgia and myalgia, nausea and vomiting, diarrhea, chills, extreme fatigue and dizziness. A rash was observed in 43%, and lymphadenopathy in 22%. Laboratory findings were thrombocytopenia, leukopenia and elevated hepatic enzymes. Eighteen patients showed hemorrhagic manifestations, and 7 fulfilled the criteria of dengue hemorrhagic fever; 1 of them had dengue shock syndrome. Case fatality rate was nil. Dengue has to be considered in all febrile travelers returning from endemic areas. Prompt diagnosis and symptomatic treatment is warranted and should prevent patients from unnecessary and potentially harmful diagnostic and therapeutic procedures. & 2005 Elsevier Ltd. All rights reserved.
Introduction Corresponding author. Tel.: +43 1 60191 2407;
fax: +43 1 60191 2419. E-mail address: [email protected] (C. Wenisch).
Dengue is the most important human viral disease transmitted by an arthropod vector (Aedes sp.). Worldwide there are 50–100 million cases of dengue fever (DF), and 250 000–500 000 cases of
1477-8939/$ - see front matter & 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.tmaid.2005.10.001
ARTICLE IN PRESS 320
been traveling to endemic areas, 9 (10%) were immigrants returning from a visit to their country of origin. The median duration of travel was 23.5 days Table 1
Second sample
Number
Confirmed cases (IgG X4-fold titer rise), total 48 cases Neg. X1280 8 10 X1280 6 20 X1280 3 40 X1280 5 80 X1280 11 160 X1280 5 360 X1280 7 640 10 240 2 1280 10 240 1
Patients and methods
Probable cases, total 45 IgM positive IgM and single IgG X1280 Single high titer (X1280)
8 5 32
16 Dengue Patients per Year
14 12 10 8 6 4 2
5
04
in co
m
pl
.2
00
03
20
02
20
01
20
00
20
99
20
98
19
97
19
96
19
95
19
94
19
93
19
92
19
91
19
90
0 19
A probable case is defined as a clinically compatible illness with supportive serologic findings (a reciprocal hemagglutination-inhibition IgG titer of X1280 (in house assay, which was done as described earlier6 or a positive IgM antibody test (IgM capture ELISA, Focus Technologies, Cypress, California 90630, USA) on a single, late-acute or convalescent-phase serum specimen to 1 or more dengue virus antigens). A confirmed diagnosis was distinguished by a 4-fold or greater rise or fall in reciprocal IgG or IgM antibody titers to 1 or more dengue virus antigens in paired serum samples. Following parameters were analyzed: clinical history and travel history, symptoms and signs assessment, physical exam, routine laboratory values, blood cultures, malaria tests, medication, and as indicated ultrasound of liver/spleen, stool culture, ECG. Defervescence time was defined as the time from onset of fever until the body temperature was falling and remaining ato37.5 1C.
Serological data of the patients.
First sample
19
dengue hemorrhagic fever (DHF) per year.1,2 Currently A. aegypti and dengue viruses are endemic in every continent except Europe and Antarctica.1 The steadily increasing numbers of tourists visiting endemic areas, coupled with the present resurgence of dengue, raises the risk of exposure for large numbers of travelers and imported dengue cases are increasingly observed in non-endemic European countries.3–5 In this study the epidemiology, clinical manifestations and laboratory findings of 93 cases of imported DF at a City of Vienna hospital during 1990–2005 were analyzed retrospectively.
H. Laferl et al.
Results
Figure 1 Number of imported dengue in Vienna 1990–2005 per year.
Epidemiology Number of Patients
25
There were 48 confirmed (52%) and 45 probable cases (48%). Table 1 depicts the serological data of the patients. Fourteen patients were IgM negative during the first 6 days after the beginning of the illness. These patients were confirmed subsequently by the hemagglutination-inhibition test on paired samples (Table 1).7,8 The median age of patients was 32.5 years (range 17–68), 43 (46%) were female, 50 (54%) male. Figure 1 shows the annual number of imported dengue patients and Fig. 2 shows the age distribution. The majority (90%) were Austrians who had
20 15 10 5 0 1620
2125
2630
3135
3640
4145
4650
5155
5660
6165
6670
Figure 2 Age distribution of imported dengue in Vienna 1990–2005 per year.
ARTICLE IN PRESS Imported dengue fever in Austria 1990–2005
321
(9–455). In 52 patients (56%) infection was associated with travel to South East Asia (SEA)—Thailand 23, Philippines 10, Indonesia 8, Malaysia 5, Myanmar 4 and Vietnam 2–17 (18%) had visited the Indian subcontinent—India 10, Sri Lanka 3, Pakistan 2, Bangladesh 2–12 (13%) had been to the Americas—Caribbean 3, Mexico 2, Brazil 2, Venezuela 2, Nicaragua 1, Honduras 1, Paraguay 1–9 (10%) had contracted their infection in Africa—Seychelles 3, Mauritius 2, Madagascar 1, Kenya 1, Ghana 1, Senegal 1— and 3 patients had acquired infection in oceania—Fiji 1, Tonga 1, roundtrip 1. The onset of symptoms preceded the return in 54 (58%) patients; 16 (17%) fell ill during their flight back home. In 39 cases (42%) disease started after a median of 2 days (1–7) after their return to Austria. Eighteen patients (19%) had taken oral antibiotics prior to admission: 4 had received chloramphenicol, 3 patients had received ciprofloxacin for suspected typhoid fever. Betalactams (4), doxycycline (3), clarithromycin (1), trimethoprim/sulfamethoxazole (1), and unknown antibiotics (2) were given for various, unspecified reasons. Sixty-three patients (68%) were hospitalized, 30 (32%) treated as outpatients. The median length of stay in the hospital was 6 days (1–23).
Patients Table 2 depicts the clinical symptoms and signs of the patients and Table 3 shows the laboratory data of the patients. A diagnostic work-up for gastrointestinal bacterial and parasitic infection was done in 19 of the 28 patients who had diarrhea or gave a history of diarrheal illness prior to presentation. It was negative in 15 patients, but revealed Table 2
concomitant campylobacteriosis in 3 patients, and shigellosis plus giardiasis in another 1. Lymphadenopathy was detected in 20 patients (22%). Abdominal sonography was performed in 27 patients, and revealed splenomegaly in 7 patients, hepatic steatosis in 2, and ascites in 1 patient with DHF. A chest-X-ray was performed in 72 patients. It gave normal results in 97%, and showed a pneumonic infiltrate in 1, and bilateral pleural effusions in 1 patient with DHF. An ECG was done in 65 patients, and was normal in 54 (83%) of them. Eleven patients (17%), however, showed transient abnormalities, most commonly T-wave negativity in leads II, III and aVF (6), in the chest leads V1–V4 (2), in III and V1 (1), isolated in III (1), and 1 patient with known WPW-syndrome had transient bigeminus. Eighteen patients (19%) showed some kind of hemorrhagic manifestations but only 7 of them fulfilled the WHO criteria for DHF.9 One of these 7 DHF cases had dengue shock syndrome.10 None of the patients in this study had jaundice, and case fatality rate was nil. Treatment was symptomatic, 81% of the admitted patients received intravenous fluids, and 39% were given paracetamol. One patient had undergone bone marrow biopsy because of unexplained leukopenia and thrombocytopenia in another hospital prior to admission to our department.
Discussion We analyzed retrospectively 93 patients with dengue attending our clinic for tropical disease after return from tropical travel from 1990 to 2005. Eighty-six had classic DF, 7 fulfilled the criteria of
Clinical characteristics of 93 serologically confirmed dengue cases in Vienna, Austria, 1990–2005.
Symptoms/signs
Number (%)
Symptoms/signs
Number (%)
(History of) Fever: no. (%) Headache: no. (%) Arthralgia: no. (%) Myalgia: no. (%) Nausea: no. (%) Diarrhea: no. (%) Chills: no. (%) Vomiting: no. (%) Extreme fatigue: no. (%) Dizziness: no. (%) Abdominal pain: no. (%) Pharyngeal inject.: no.(%) Sore throat: no. (%)
93/93 (100) 62/93 (67) 59/93 (63) 59/93 (63) 32/93 (34) 28/93 (30) 33/93 (35) 18/93 (19) 24/93 (26) 18/93 (19) 14/93 (15) 24/92 (26) 8/93 (9)
Temp. max.: 1C median (range) Days of fever:median (range) Defervescence time: median (range) Rash: no. (%) Petechial rash: no. (%) Lymphadenopathy: no. (%) Any haemorrhage:no. (%) Positive tourniquet test: no. (%) Pruritus: no. (%) Epistaxis: no. (%) Melena: no. (%) Haematemesis: no. (%) Metrorrhagia: no. (%)
39.3 (38–40.1) 4 (1–21) 6 (1–23) 40/93 (43) 12/93 (13) 20/93 (22) 18/93 (19) 8/22 (36) 5/93 (5) 7/93 (8) 2/93 (2) 1/93 (1) 1/50 (1)
Until presentation at clinic. Including positive tourniquet test and petechial rash.
ARTICLE IN PRESS 322 Table 3
H. Laferl et al. Laboratory findings in 93 serologically confirmed dengue cases in Vienna, Austria, 1990–2005.
Laboratory value (Unit)
Result
Reference value
p-value
PLT median (range) PLTo100 000/ml: no. (%) WBC min: median, (range) WBCo4000/ml: no. (%) HKT max: median (range) HKT min: median (range) Hemoconcentration:no. (%) ESR: median (range) CRP median (range) AST max: median (range) AST4ULN: no. (%) ALT max: median (range) ALT4ULN: no. (%) LDH max: median (range) LDH4ULN: no. (%) CK max: median (range) CK4ULN: no. (%)
66 000 (8000–428 000) 65/90 (72) 2280 (900–15 500) 80/90 (89) 43.9 (28.5–56) 40.1 (23.4–45.9) 7/91 (8) 8 (1–90) 10.8 (0.5–130) 2.51 (0.5–19) 70/89 (79) 2.22 (0.41–16.3) 62/88 (70) 1.31 (0.5–4.8) 65/89 (73) 0.7 (0.2–46.4) 25/63 (40)
140 000–440 000 cells/ml
o0.025
4000–10 000 cells/ml
o0.05
42–52% 42–52%
40.05 40.05
6–20 mm/h 0.5–8 mg/l ULN
40.05 40.05 o0.01
ULN
o0.01
ULN
o0.01 40.05
Note: PLT, platelet count; WBC, white blood cell count; HKT, hematocrit; AST, aspartate aminotransferase; ALT, alanine aminotransferase; LDH, lactic dehydrogenase; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; ULN, upper limit of normal. Hematocrit increased by at least one-fifth or decreased by the same amount after intravenous fluid therapy. Wilcoxon rank sum test.
dengue hemorrhagic fever and 1 of them had dengue shock syndrome. The most common symptoms and signs were fever, rash, thrombocytopenia, leukopenia, and elevated transminases with a frequency rate in the range of published series.11 In contrast to patients of Puerto Rico,11 the frequency and intensity of symptoms was not influenced by the patient’s age and sex in this study. This could be due to higher portion of primary infection in travelers compared to Puerto Ricans. The physical examination in patients with dengue was generally nonspecific. However, conjunctival injection and hepatomegaly was seen less frequently in our patients than in military personnel.12 Laboratory findings typical of dengue were found in our patients in the reported range.13 Recently, more than 2200 German citizens were studied after they returned from dengue-endemic countries from 1996 to 2004.5 The authors note that fluctuations might lead to misinterpretation of probable trends if data are derived only from short-term observations (see also Fig. 1 with respect to the outbreak in SEA). In addition, this variability underscores the importance of tourists’ seeking information before traveling to dengueendemic areas. Fever in the returned traveler can be a manifestation of a minor, self-limited process or can herald
a progressive, life-threatening illness. Within the wide differential diagnosis malaria is the most important febrile illness to exclude, in particular in the outpatient setting. Initial findings may not distinguish between trivial and serious infections.14,15 The assessment of these patients is often hampered by the clinician’s lack of familiarity with the types of infections that the patient may have encountered while traveling. A systematic approach to the evaluation of febrile patients should include basic information about the geographic distribution of infections in the locations where the person has lived and travelled.16 The tempo and intensity of the initial work-up will be influenced by both the clinical findings and by the types of infections that are possible. When dengue virus infection (DF or DHF) is suspected on clinical grounds, the patient should be treated empirically as appropriate for the symptoms and signs present.9,17–19 The recommended approach to confirm the diagnosis includes an acute phase serum sample, if a reference laboratory is readily available, and the IgM immunoassay (MAC-ELISA or equivalent) for rapid confirmation of the diagnosis. A convalescent phase serum sample should be obtained at least 10–14 days after the acute phase serum. The acute and convalescent specimens should be analyzed together by HI assay or IgG immunoassay to provide definitive serologic testing
ARTICLE IN PRESS Imported dengue fever in Austria 1990–2005
Figure 3 Rash in dengue.
for acute dengue virus infection. Virus isolation and RT-PCR should generally be performed only when needed for epidemiologic purposes or as part of clinical research studies.9,17–20 In conclusion, dengue has to be considered in all febrile travelers who recently returned from endemic areas, especially from SEA.21–24 Apart from typical symptoms like fever, headache, myalgia and rash (Fig. 3), diarrhea is not uncommon on presentation in patients with dengue. Prompt diagnosis, orientated by negative malaria smears, and symptomatic treatment is warranted and should prevent patients from unnecessary and potentially harmful diagnostic and therapeutic procedures. The risk for dengue infection among travelers can be reduced by use of repellents and by avoiding exposure to mosquitoes.25
References 1. Pinheiro FP, Corber A. Global situation of dengue and dengue haemorrhagic fever, and its emergence in the Americas. World Health Stat Q 1997;50:161–9. 2. Anonymous. Imported dengue—United States, 1997 and 1998. MMWR 2000;49:248–53. 3. Jelinek T, Muhlberger N, Harms G, Corachan M, Grobusch MP, Knobloch J, et al. European network on imported infectious disease surveillance. Epidemiology and clinical features of imported dengue fever in Europe: sentinel surveillance data from TropNetEurop. Clin Infect Dis 2002;35:1047–52. 4. Jelinek T, Dobler G, Holscher M, Loscher T, Nothdurft HD. Prevalence of infection with dengue virus among international travellers. Arch Intern Med 1997;157:2367–70. 5. Wichmann O, Lauschke A, Frank C, Shu P-Y, Niedrig M, Huang J-H, et al. Dengue antibody prevalence in German travelers. Emerg Infect Dis 2005;11:762–5.
323 6. Holzmann H, Kundi M, Stiasny K, Clement J, McKenna P, Kunz C, et al. Correlation between ELISA, hemagglutination inhibition, and neutralization tests after vaccination against tick-borne encephalitis. J Med Virol 1996;48:102–7. 7. Gubler DJ. Dengue and dengue hemorrhagic fever. Clin Microbiol Rev 1998;11:480–96. 8. Stephan C, Allwinn R, Brodt HR, Knupp B, Preiser W, JustNu ¨bling G. Travel-acquired dengue infection: clinical spectrum and diagnostic aspects. Infection 2002;30:225–8. 9. World Health Organization (WHO). Dengue haemorrhagic fever: diagnosis, treatment and control, 2nd ed. Geneva: World Health Organization; 1997. p. 12–23. 10. Laferl H. Pleural effusion and ascites on return from Pakistan. Lancet 1997;350:1072. 11. Cobra C, Rigau-Perez JG, Kuno G, Vorndam V. Symptoms of dengue fever in relation to host immunologic response and virus serotype, Puerto Rico, 1990–1991. Am J Epidemiol 1995;142:1204–11. 12. Trofa AF, DeFraites RF, Smoak BL, Kanesa-Thasan N, King AD, Burrous JM, et al. Dengue fever in US military personnel in Haiti. JAMA 1997;277:1546–8. 13. Kalayanarooj S, Vaughn DW, Nimmannitya S, Green S, Suntayakorn S, Kunentrasai N, et al. Early clinical and laboratory indicators of acute dengue illness. J Infect Dis 1997;176:313–21. 14. Bruni M, Steffen R. Impact of travel-related health impairments. J Travel Med 1997;4:61–4. 15. O’Brien D, Tobin S, Brown GV, Torresi J. Fever in returned travelers: review of hospital admissions for a 3-year period. Clin Infect Dis 2001;33:603–9. 16. Ryan ET, Wilson ME, Kain KC. Illness after international travel. N Engl J Med 2002;347:505–16. 17. Rigau-Perez JG, Clark GG, Gubler DJ, Reiter P, Sanders EJ, Vorndam AV. Dengue and dengue haemorrhagic fever. Lancet 1998;352:971–7. 18. Rigau-Perez JG, Gubler DJ, Vorndam AV, Clark GG. Dengue surveillance—United States, 1986–1992. MMWR CDC Surveill Summ 1994;43:7–19. 19. CDC. Case definitions for infectious conditions under public health surveillance. MMWR 1997;46(RR-10):45–6. 20. Lindegren G, Vene S, Lundkvist A, Falk KI. Optimized diagnosis of acute dengue fever in Swedish travelers by a combination of reverse transcription-PCR and immunoglobulin M detection. J Clin Microbiol 2005;43:2850–5. 21. Helbok R, Dent W, Gattringer K, Innerebner M, Schmutzhard E. Imported dengue fever presenting with febrile diarrhoea: report of two cases. Wien Klin Wochenschr 2004;116(Suppl 4):58–60. 22. Shirtcliffe P, Cameron E, Nicholson KG, Wiselka MJ. Don’t forget dengue! Clinical features of dengue fever in returning travellers. J R Coll Physicians Lond 1998;32:235–7. 23. Teichmann D, Gobels K, Niedrig M, Grobusch MP. Dengue virus infection in travellers returning to Berlin, Germany: clinical, laboratory, and diagnostic aspects. Acta Trop 2004;90:87–95. 24. Teichmann D, Gobels K, Niedrig M, Sim-Brandenburg JW, Lage-Stehr J, Grobusch MP. Virus isolation for diagnosing dengue virus infections in returning travelers. Eur J Clin Microbiol Infect Dis 2003;22:697–700. 25. Centers for disease control prevention (CDC). Travelassociated dengue infections—United States, 2001–2004. MMWR 2005;54:556–8.
www.elsevierhealth.com/journals/tmid
Imported dengue fever in Austria 1990–2005 H. Laferl, M. Szell, E. Bischof, C. Wenisch 4th Medical Department with Infectious Diseases & Tropical Medicine, Kaiser Franz Josef - Hospital, Kundratstraße 3, A-1100, Vienna, Austria Received 4 August 2005; received in revised form 3 October 2005; accepted 6 October 2005 Available online 5 December 2005
KEYWORDS Travel-associated fever; Dengue; Austria; Travel medicine
Summary Dengue is the most important human viral disease transmitted by an arthropod vector. The steadily increasing numbers of tourists visiting endemic areas coupled with the present resurgence of dengue, raises the risk of exposure for large numbers of travelers and imported dengue cases are increasingly observed in nonendemic countries. We aimed to study the epidemiology, clinical manifestations and laboratory findings in imported dengue at a City of Vienna hospital. Medical records of 93 patients (age: 17–68 years, 43 f, 50 m) with imported dengue in Vienna between 1990 and April 2005 were analyzed retrospectively. Fortyeight (52%) were classified as confirmed and 45 (48%) as probable dengue, according to the CDC criteria. The patients acquired the infection in South East Asia (56%), the Indian subcontinent (18%), Africa (10%) and Oceania (3%). The most important symptoms were fever, headache, arthralgia and myalgia, nausea and vomiting, diarrhea, chills, extreme fatigue and dizziness. A rash was observed in 43%, and lymphadenopathy in 22%. Laboratory findings were thrombocytopenia, leukopenia and elevated hepatic enzymes. Eighteen patients showed hemorrhagic manifestations, and 7 fulfilled the criteria of dengue hemorrhagic fever; 1 of them had dengue shock syndrome. Case fatality rate was nil. Dengue has to be considered in all febrile travelers returning from endemic areas. Prompt diagnosis and symptomatic treatment is warranted and should prevent patients from unnecessary and potentially harmful diagnostic and therapeutic procedures. & 2005 Elsevier Ltd. All rights reserved.
Introduction Corresponding author. Tel.: +43 1 60191 2407;
fax: +43 1 60191 2419. E-mail address: [email protected] (C. Wenisch).
Dengue is the most important human viral disease transmitted by an arthropod vector (Aedes sp.). Worldwide there are 50–100 million cases of dengue fever (DF), and 250 000–500 000 cases of
1477-8939/$ - see front matter & 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.tmaid.2005.10.001
ARTICLE IN PRESS 320
been traveling to endemic areas, 9 (10%) were immigrants returning from a visit to their country of origin. The median duration of travel was 23.5 days Table 1
Second sample
Number
Confirmed cases (IgG X4-fold titer rise), total 48 cases Neg. X1280 8 10 X1280 6 20 X1280 3 40 X1280 5 80 X1280 11 160 X1280 5 360 X1280 7 640 10 240 2 1280 10 240 1
Patients and methods
Probable cases, total 45 IgM positive IgM and single IgG X1280 Single high titer (X1280)
8 5 32
16 Dengue Patients per Year
14 12 10 8 6 4 2
5
04
in co
m
pl
.2
00
03
20
02
20
01
20
00
20
99
20
98
19
97
19
96
19
95
19
94
19
93
19
92
19
91
19
90
0 19
A probable case is defined as a clinically compatible illness with supportive serologic findings (a reciprocal hemagglutination-inhibition IgG titer of X1280 (in house assay, which was done as described earlier6 or a positive IgM antibody test (IgM capture ELISA, Focus Technologies, Cypress, California 90630, USA) on a single, late-acute or convalescent-phase serum specimen to 1 or more dengue virus antigens). A confirmed diagnosis was distinguished by a 4-fold or greater rise or fall in reciprocal IgG or IgM antibody titers to 1 or more dengue virus antigens in paired serum samples. Following parameters were analyzed: clinical history and travel history, symptoms and signs assessment, physical exam, routine laboratory values, blood cultures, malaria tests, medication, and as indicated ultrasound of liver/spleen, stool culture, ECG. Defervescence time was defined as the time from onset of fever until the body temperature was falling and remaining ato37.5 1C.
Serological data of the patients.
First sample
19
dengue hemorrhagic fever (DHF) per year.1,2 Currently A. aegypti and dengue viruses are endemic in every continent except Europe and Antarctica.1 The steadily increasing numbers of tourists visiting endemic areas, coupled with the present resurgence of dengue, raises the risk of exposure for large numbers of travelers and imported dengue cases are increasingly observed in non-endemic European countries.3–5 In this study the epidemiology, clinical manifestations and laboratory findings of 93 cases of imported DF at a City of Vienna hospital during 1990–2005 were analyzed retrospectively.
H. Laferl et al.
Results
Figure 1 Number of imported dengue in Vienna 1990–2005 per year.
Epidemiology Number of Patients
25
There were 48 confirmed (52%) and 45 probable cases (48%). Table 1 depicts the serological data of the patients. Fourteen patients were IgM negative during the first 6 days after the beginning of the illness. These patients were confirmed subsequently by the hemagglutination-inhibition test on paired samples (Table 1).7,8 The median age of patients was 32.5 years (range 17–68), 43 (46%) were female, 50 (54%) male. Figure 1 shows the annual number of imported dengue patients and Fig. 2 shows the age distribution. The majority (90%) were Austrians who had
20 15 10 5 0 1620
2125
2630
3135
3640
4145
4650
5155
5660
6165
6670
Figure 2 Age distribution of imported dengue in Vienna 1990–2005 per year.
ARTICLE IN PRESS Imported dengue fever in Austria 1990–2005
321
(9–455). In 52 patients (56%) infection was associated with travel to South East Asia (SEA)—Thailand 23, Philippines 10, Indonesia 8, Malaysia 5, Myanmar 4 and Vietnam 2–17 (18%) had visited the Indian subcontinent—India 10, Sri Lanka 3, Pakistan 2, Bangladesh 2–12 (13%) had been to the Americas—Caribbean 3, Mexico 2, Brazil 2, Venezuela 2, Nicaragua 1, Honduras 1, Paraguay 1–9 (10%) had contracted their infection in Africa—Seychelles 3, Mauritius 2, Madagascar 1, Kenya 1, Ghana 1, Senegal 1— and 3 patients had acquired infection in oceania—Fiji 1, Tonga 1, roundtrip 1. The onset of symptoms preceded the return in 54 (58%) patients; 16 (17%) fell ill during their flight back home. In 39 cases (42%) disease started after a median of 2 days (1–7) after their return to Austria. Eighteen patients (19%) had taken oral antibiotics prior to admission: 4 had received chloramphenicol, 3 patients had received ciprofloxacin for suspected typhoid fever. Betalactams (4), doxycycline (3), clarithromycin (1), trimethoprim/sulfamethoxazole (1), and unknown antibiotics (2) were given for various, unspecified reasons. Sixty-three patients (68%) were hospitalized, 30 (32%) treated as outpatients. The median length of stay in the hospital was 6 days (1–23).
Patients Table 2 depicts the clinical symptoms and signs of the patients and Table 3 shows the laboratory data of the patients. A diagnostic work-up for gastrointestinal bacterial and parasitic infection was done in 19 of the 28 patients who had diarrhea or gave a history of diarrheal illness prior to presentation. It was negative in 15 patients, but revealed Table 2
concomitant campylobacteriosis in 3 patients, and shigellosis plus giardiasis in another 1. Lymphadenopathy was detected in 20 patients (22%). Abdominal sonography was performed in 27 patients, and revealed splenomegaly in 7 patients, hepatic steatosis in 2, and ascites in 1 patient with DHF. A chest-X-ray was performed in 72 patients. It gave normal results in 97%, and showed a pneumonic infiltrate in 1, and bilateral pleural effusions in 1 patient with DHF. An ECG was done in 65 patients, and was normal in 54 (83%) of them. Eleven patients (17%), however, showed transient abnormalities, most commonly T-wave negativity in leads II, III and aVF (6), in the chest leads V1–V4 (2), in III and V1 (1), isolated in III (1), and 1 patient with known WPW-syndrome had transient bigeminus. Eighteen patients (19%) showed some kind of hemorrhagic manifestations but only 7 of them fulfilled the WHO criteria for DHF.9 One of these 7 DHF cases had dengue shock syndrome.10 None of the patients in this study had jaundice, and case fatality rate was nil. Treatment was symptomatic, 81% of the admitted patients received intravenous fluids, and 39% were given paracetamol. One patient had undergone bone marrow biopsy because of unexplained leukopenia and thrombocytopenia in another hospital prior to admission to our department.
Discussion We analyzed retrospectively 93 patients with dengue attending our clinic for tropical disease after return from tropical travel from 1990 to 2005. Eighty-six had classic DF, 7 fulfilled the criteria of
Clinical characteristics of 93 serologically confirmed dengue cases in Vienna, Austria, 1990–2005.
Symptoms/signs
Number (%)
Symptoms/signs
Number (%)
(History of) Fever: no. (%) Headache: no. (%) Arthralgia: no. (%) Myalgia: no. (%) Nausea: no. (%) Diarrhea: no. (%) Chills: no. (%) Vomiting: no. (%) Extreme fatigue: no. (%) Dizziness: no. (%) Abdominal pain: no. (%) Pharyngeal inject.: no.(%) Sore throat: no. (%)
93/93 (100) 62/93 (67) 59/93 (63) 59/93 (63) 32/93 (34) 28/93 (30) 33/93 (35) 18/93 (19) 24/93 (26) 18/93 (19) 14/93 (15) 24/92 (26) 8/93 (9)
Temp. max.: 1C median (range) Days of fever:median (range) Defervescence time: median (range) Rash: no. (%) Petechial rash: no. (%) Lymphadenopathy: no. (%) Any haemorrhage:no. (%) Positive tourniquet test: no. (%) Pruritus: no. (%) Epistaxis: no. (%) Melena: no. (%) Haematemesis: no. (%) Metrorrhagia: no. (%)
39.3 (38–40.1) 4 (1–21) 6 (1–23) 40/93 (43) 12/93 (13) 20/93 (22) 18/93 (19) 8/22 (36) 5/93 (5) 7/93 (8) 2/93 (2) 1/93 (1) 1/50 (1)
Until presentation at clinic. Including positive tourniquet test and petechial rash.
ARTICLE IN PRESS 322 Table 3
H. Laferl et al. Laboratory findings in 93 serologically confirmed dengue cases in Vienna, Austria, 1990–2005.
Laboratory value (Unit)
Result
Reference value
p-value
PLT median (range) PLTo100 000/ml: no. (%) WBC min: median, (range) WBCo4000/ml: no. (%) HKT max: median (range) HKT min: median (range) Hemoconcentration:no. (%) ESR: median (range) CRP median (range) AST max: median (range) AST4ULN: no. (%) ALT max: median (range) ALT4ULN: no. (%) LDH max: median (range) LDH4ULN: no. (%) CK max: median (range) CK4ULN: no. (%)
66 000 (8000–428 000) 65/90 (72) 2280 (900–15 500) 80/90 (89) 43.9 (28.5–56) 40.1 (23.4–45.9) 7/91 (8) 8 (1–90) 10.8 (0.5–130) 2.51 (0.5–19) 70/89 (79) 2.22 (0.41–16.3) 62/88 (70) 1.31 (0.5–4.8) 65/89 (73) 0.7 (0.2–46.4) 25/63 (40)
140 000–440 000 cells/ml
o0.025
4000–10 000 cells/ml
o0.05
42–52% 42–52%
40.05 40.05
6–20 mm/h 0.5–8 mg/l ULN
40.05 40.05 o0.01
ULN
o0.01
ULN
o0.01 40.05
Note: PLT, platelet count; WBC, white blood cell count; HKT, hematocrit; AST, aspartate aminotransferase; ALT, alanine aminotransferase; LDH, lactic dehydrogenase; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; ULN, upper limit of normal. Hematocrit increased by at least one-fifth or decreased by the same amount after intravenous fluid therapy. Wilcoxon rank sum test.
dengue hemorrhagic fever and 1 of them had dengue shock syndrome. The most common symptoms and signs were fever, rash, thrombocytopenia, leukopenia, and elevated transminases with a frequency rate in the range of published series.11 In contrast to patients of Puerto Rico,11 the frequency and intensity of symptoms was not influenced by the patient’s age and sex in this study. This could be due to higher portion of primary infection in travelers compared to Puerto Ricans. The physical examination in patients with dengue was generally nonspecific. However, conjunctival injection and hepatomegaly was seen less frequently in our patients than in military personnel.12 Laboratory findings typical of dengue were found in our patients in the reported range.13 Recently, more than 2200 German citizens were studied after they returned from dengue-endemic countries from 1996 to 2004.5 The authors note that fluctuations might lead to misinterpretation of probable trends if data are derived only from short-term observations (see also Fig. 1 with respect to the outbreak in SEA). In addition, this variability underscores the importance of tourists’ seeking information before traveling to dengueendemic areas. Fever in the returned traveler can be a manifestation of a minor, self-limited process or can herald
a progressive, life-threatening illness. Within the wide differential diagnosis malaria is the most important febrile illness to exclude, in particular in the outpatient setting. Initial findings may not distinguish between trivial and serious infections.14,15 The assessment of these patients is often hampered by the clinician’s lack of familiarity with the types of infections that the patient may have encountered while traveling. A systematic approach to the evaluation of febrile patients should include basic information about the geographic distribution of infections in the locations where the person has lived and travelled.16 The tempo and intensity of the initial work-up will be influenced by both the clinical findings and by the types of infections that are possible. When dengue virus infection (DF or DHF) is suspected on clinical grounds, the patient should be treated empirically as appropriate for the symptoms and signs present.9,17–19 The recommended approach to confirm the diagnosis includes an acute phase serum sample, if a reference laboratory is readily available, and the IgM immunoassay (MAC-ELISA or equivalent) for rapid confirmation of the diagnosis. A convalescent phase serum sample should be obtained at least 10–14 days after the acute phase serum. The acute and convalescent specimens should be analyzed together by HI assay or IgG immunoassay to provide definitive serologic testing
ARTICLE IN PRESS Imported dengue fever in Austria 1990–2005
Figure 3 Rash in dengue.
for acute dengue virus infection. Virus isolation and RT-PCR should generally be performed only when needed for epidemiologic purposes or as part of clinical research studies.9,17–20 In conclusion, dengue has to be considered in all febrile travelers who recently returned from endemic areas, especially from SEA.21–24 Apart from typical symptoms like fever, headache, myalgia and rash (Fig. 3), diarrhea is not uncommon on presentation in patients with dengue. Prompt diagnosis, orientated by negative malaria smears, and symptomatic treatment is warranted and should prevent patients from unnecessary and potentially harmful diagnostic and therapeutic procedures. The risk for dengue infection among travelers can be reduced by use of repellents and by avoiding exposure to mosquitoes.25
References 1. Pinheiro FP, Corber A. Global situation of dengue and dengue haemorrhagic fever, and its emergence in the Americas. World Health Stat Q 1997;50:161–9. 2. Anonymous. Imported dengue—United States, 1997 and 1998. MMWR 2000;49:248–53. 3. Jelinek T, Muhlberger N, Harms G, Corachan M, Grobusch MP, Knobloch J, et al. European network on imported infectious disease surveillance. Epidemiology and clinical features of imported dengue fever in Europe: sentinel surveillance data from TropNetEurop. Clin Infect Dis 2002;35:1047–52. 4. Jelinek T, Dobler G, Holscher M, Loscher T, Nothdurft HD. Prevalence of infection with dengue virus among international travellers. Arch Intern Med 1997;157:2367–70. 5. Wichmann O, Lauschke A, Frank C, Shu P-Y, Niedrig M, Huang J-H, et al. Dengue antibody prevalence in German travelers. Emerg Infect Dis 2005;11:762–5.
323 6. Holzmann H, Kundi M, Stiasny K, Clement J, McKenna P, Kunz C, et al. Correlation between ELISA, hemagglutination inhibition, and neutralization tests after vaccination against tick-borne encephalitis. J Med Virol 1996;48:102–7. 7. Gubler DJ. Dengue and dengue hemorrhagic fever. Clin Microbiol Rev 1998;11:480–96. 8. Stephan C, Allwinn R, Brodt HR, Knupp B, Preiser W, JustNu ¨bling G. Travel-acquired dengue infection: clinical spectrum and diagnostic aspects. Infection 2002;30:225–8. 9. World Health Organization (WHO). Dengue haemorrhagic fever: diagnosis, treatment and control, 2nd ed. Geneva: World Health Organization; 1997. p. 12–23. 10. Laferl H. Pleural effusion and ascites on return from Pakistan. Lancet 1997;350:1072. 11. Cobra C, Rigau-Perez JG, Kuno G, Vorndam V. Symptoms of dengue fever in relation to host immunologic response and virus serotype, Puerto Rico, 1990–1991. Am J Epidemiol 1995;142:1204–11. 12. Trofa AF, DeFraites RF, Smoak BL, Kanesa-Thasan N, King AD, Burrous JM, et al. Dengue fever in US military personnel in Haiti. JAMA 1997;277:1546–8. 13. Kalayanarooj S, Vaughn DW, Nimmannitya S, Green S, Suntayakorn S, Kunentrasai N, et al. Early clinical and laboratory indicators of acute dengue illness. J Infect Dis 1997;176:313–21. 14. Bruni M, Steffen R. Impact of travel-related health impairments. J Travel Med 1997;4:61–4. 15. O’Brien D, Tobin S, Brown GV, Torresi J. Fever in returned travelers: review of hospital admissions for a 3-year period. Clin Infect Dis 2001;33:603–9. 16. Ryan ET, Wilson ME, Kain KC. Illness after international travel. N Engl J Med 2002;347:505–16. 17. Rigau-Perez JG, Clark GG, Gubler DJ, Reiter P, Sanders EJ, Vorndam AV. Dengue and dengue haemorrhagic fever. Lancet 1998;352:971–7. 18. Rigau-Perez JG, Gubler DJ, Vorndam AV, Clark GG. Dengue surveillance—United States, 1986–1992. MMWR CDC Surveill Summ 1994;43:7–19. 19. CDC. Case definitions for infectious conditions under public health surveillance. MMWR 1997;46(RR-10):45–6. 20. Lindegren G, Vene S, Lundkvist A, Falk KI. Optimized diagnosis of acute dengue fever in Swedish travelers by a combination of reverse transcription-PCR and immunoglobulin M detection. J Clin Microbiol 2005;43:2850–5. 21. Helbok R, Dent W, Gattringer K, Innerebner M, Schmutzhard E. Imported dengue fever presenting with febrile diarrhoea: report of two cases. Wien Klin Wochenschr 2004;116(Suppl 4):58–60. 22. Shirtcliffe P, Cameron E, Nicholson KG, Wiselka MJ. Don’t forget dengue! Clinical features of dengue fever in returning travellers. J R Coll Physicians Lond 1998;32:235–7. 23. Teichmann D, Gobels K, Niedrig M, Grobusch MP. Dengue virus infection in travellers returning to Berlin, Germany: clinical, laboratory, and diagnostic aspects. Acta Trop 2004;90:87–95. 24. Teichmann D, Gobels K, Niedrig M, Sim-Brandenburg JW, Lage-Stehr J, Grobusch MP. Virus isolation for diagnosing dengue virus infections in returning travelers. Eur J Clin Microbiol Infect Dis 2003;22:697–700. 25. Centers for disease control prevention (CDC). Travelassociated dengue infections—United States, 2001–2004. MMWR 2005;54:556–8.