DENGUE FEVER in INTERNATIONL TRAVELERS Eli Schwartz MD,DTMH The Center of Geographic Medicine & Tropical Diseases Sheba Medical Center, Tel-Hashomer Sackler Faculty of Medicine, Tel-Aviv univ. ISRAEL
World Distribution of Dengue - 1999 Areas infested with Aedes aegypti Dengue in 1960 Areas with Aedes aegypti and recent epidemic dengue CENTERS FOR DISEASE CONTROL ANN PREVENTION
DENGUE -PUBLICATIONS 1200 1000 1071 800 600 400 330 610 419 -general travelers reported cases 200 0 114 1 0 0 0 5 9 14 1960-69 1970-79 1980-89 1990-99
Travel & Dengue fever * Affects International travelers * Contributing factor in spread of dengue worldwide.
Why GeoSentinel? To augment existing public health systems by providing rapid and comprehensive global surveillance for a spectrum of diseases and syndromes amongst increasingly mobile populations days 400 350 300 250 200 150 100 50 0 1850 1900 1950 2000 500 450 400 350 300 250 200 150 100 50 0 millions Days to circle the globe International arrivals
Dengue Fever: Epidemiology in Travelers The Problems: Lack of true numerator Lack of denominator
MORBIDITY AND MORTALITY IN TRAVELERS TO DEVELOPING CONTRIES: RATES / MONTH OF STAY Travelers Diarrhea Malaria Acute febrile respiratory tract infections Hepatitis A Gonorrhea Hepatitis B Typhoid (India; N, NW-Africa) HIV-infection Legionellosis Typhoid (other areas) Poliomyelitis, asymptomatic 100% 100,000 10% 10,000 1% 1,000 0.1% 100 0.01% 10 0.001% 1 Cholera 0.0005% Paralytic poliomyelitis 0,00007% Any health problem: used medication or felt ill Felt subjectively ill Consulted doctor abroad or home Stayed in bed Incapacity of work after return Hospitalized abroad Air evacuation Died abroad (PVC) Died abroad (any traveler) Steffen in Manson s, 1999, p 407
Diagnosis of DF in returning travelers hospitalized with febrile illness Country Ref. Number of Travelers Dengue % Years of study Canada MacLean 587 2 1981-8 U.K Doherty 195 6 1991-3 et al Germany Jelinek 130 7 1995-6 et al Australia O'Brien 232 8 1997-9 et al Israel Schwartz et al 163 17 1999-03
Attack Rate of Dengue Fever among Israeli Travelers to Thailand,1998 Cohort No. Travelers Dengue cases Attack Rate SHARIV 5030 17 3.4/1000 All Visitors 58 000 52 0.9/1000 Schwartz E. et al: Eur. J. Clin Microbiol Infect Dis. 2000: 784-6
Dengue Seroconversion among Israeli Travelers to Tropical Countries Number 104 travelers Year of study-1998 Age (mean) 22 + 2 years Trip (average)- 6 (3-16) mo. Destination- S.E. Asia- 70 % S. America- 24 % Africa- 4% Combined-2% Potasman I, Srugo I, Schwartz E. : E.I.D; 1999,824-6
Dengue Seroconversion; Results: 7/104= 6.7 % (95% CI= 2.7-13.3%) 3/7- were asymptomatic Potasman I, Srugo I, Schwartz E. : E.I.D; 1999,824-6
Dengue Seroconversion /month of Exposure S.E Asia- 5/451= 1.1% (95% CI= 0.36-2.6%) S. America-1/159=0.6% (95% CI= 0.02-3.5%) Africa-1/25= 4% (95% CI= 0.1-20.3%) Potasman I, Srugo I, Schwartz E. : E.I.D; 1999,824-6
Dengue Seroconversion among Dutch Travelers to Asia 447 travelers to Asia Short-term (1 month) Study period during 1991-2 Cobelens FG et al; Trop Med Int Health 2002;7:331-8.
Dengue Seroconversion /month of Exposure Seroconversion rate of 2.9% The incidence was 30 per 1000 personmonths of travel (pmt). and 6.9 per 1000pmt for clinical infection. Cobelens FG et al; Trop Med Int Health 2002;7:331-8.
MORBIDITY AND MORTALITY IN TRAVELERS TO DEVELOPING CONTRIES: RATES / MONTH OF STAY Travelers Diarrhea Malaria Dengue Acute febrile respiratory tract infections Hepatitis A Gonorrhea Hepatitis B Typhoid (India; N, NW-Africa) HIV-infection Legionellosis Typhoid (other areas) Poliomyelitis, asymptomatic 100% 100,000 10% 10,000 1% 1,000 0.1% 100 0.01% 10 0.001% 1 Cholera 0.0005% Paralytic poliomyelitis 0,00007% Any health problem: used medication or felt ill Felt subjectively ill Consulted doctor abroad or home Stayed in bed Incapacity of work after return Hospitalized abroad Air evacuation Died abroad (PVC) Died abroad (any traveler) Steffen in Manson s, 1999, p 407
Year Dengue Fever - Israel Total-156 No. of Cases 40 35 34 30 25 20 18 15 10 11 10 9 10 5 4 3 0 1994 1995 1996 1997 1998 1999 2000 2001 2002
Year Dengue Fever - Thailand Total=87 No. of Cases 40 35 30 28 29 25 20 15 10 7 8 8 5 2 4 1 0 1995 1996 1997 1998 1999 2000 2001 2002
Distribution of dengue cases according to seasons. 1995-7 1998 2002 Rainy season 80% 48% 32 % Dry season 20% 52% 68 % Schwartz E. WHO, Dengue Bull. Dec.2002
GEOSENTINEL SURVEILLANCE SITES GeoSentinel The Global Surveillance Network of the ISTM and CDC A worldwide communications and data collections network of travel/tropical medicine clinics
Dengue Cases, Percent of Morbidity per Month 8 6 Percent of Morbidity 4 2 1.9% 9/97 1/98 5/98 9/98 1/99 5/99 9/99 1/00
Dengue Fever: Clinical Aspects *Asymptomatic infection *Classical Dengue fever *Complicated DF (DHF/DSS)
Dengue- Asymptomatic Infection In the endemic countries most infections are asymptomatic. Among travelers?
Asymptomatic Infection Israeli Study; 104 travelers Dutch study; 447 travelers 3/7- asymptomatic 8/13 asymptomatic Ratio- 1:0.75 Ratio- 1:3.3
Dengue Fever-Classical
D.F- Symptoms Europe Sweden USA Israel TropNet C.I.D 2002 E.I.D 2003 MMWR; 1993-2000 Am.J. Med 1996 Fever 86 % 100 % 95 % 100 % Headache 60 % 75 % 62 % 83 % Fatigue 43 % N.R N.R 100 % Myalgia 42 % 73 % 50 % 26 % Rash 29 % 62 % 53 % 44 % Hospitalization 25 % 66 % Average days 5 days 3 days
DHF/DSS
DHF/DSS in Travelers GeoSentinel Inern l Net EuropeTrop Net (C.I.D 2002) CDC MMWR 1993-2000 Number of Travelers 339 250 266 DHF/DSS 2% 2% 1.8% Death 0 0 2 cases =0.7% or=0.2%
Global Dengue Disease Burden Reported (1998) Estimates No. Dengue cases/year 1.2 million 51 million No. DHF/DSS cases/year No data 400,000 No. deaths/year 3,500 15,000 WHO/CDS
WHO/CDS Global Dengue Disease Burden Reported (1998) Estimates No. Dengue cases/year 1.2 million 51 million No. DHF/DSS cases/year No data 400,000 [=0.8%] No. deaths/year 3,500 [=0.3%] 15,000 [=0.03%]
Dengue infection-outcome Significant morbidity * Interruption of the trip * Dengue hemorrhagic fever (DHF) Dengue shock syndrome (DSS) * Death
Estimate rate of dengue infection and outcome in travelers to endemic area (S.E. Asia)/month 3-5-Death 12-14- DHF/DSS 175-460 hospitalization/ evacuation 700 symptomatic DF 3000-Dengue infection 100,000 travelers to endemic area
Diagnosis of DF in Travelers
Cross-reaction of Dengue Ab. Among Vaccinees with J.E & Y.F % IgG Positive 45 40 35 30 25 20 15 10 5 0 0 Control 11 J.E short 17 15 J.E long 44 Y.F short 42 Y.F long J.E+Y.F N=100 vaccinees Schwartz E. et al: J. Clin Virol. 2000,169-173
IgM seroconversion during Acute DF Patient 1 2 3 4 5 6 First day of IgM+ 5 6 5 6 8 8 Schwartz E. et al: J. Clin Virol. 2000,169-173
Dengue cross reactivity with West-Nile Fever patients IgM+ IgG+ 8/37= 22% 15/30= 50% Bin et al., National Ctr.for Arboviruses, CVL, MOH, Sheba Medical Ctr., Israel
Conclusions: D.F is a significant disease among travelers Travelers can be sentinels for changing epidemiology of the disease. The attack rate is similar to Hepatitis A (without vaccine), or to Malaria in Africa without prophylaxis. There is a need to improve diagnosis (rapid test of Ag. Detection). There is an urgent need for vaccine.
Dengue cross-reactivity (X-R) with West Nile fever patients Complete X-R Partial X-R No X-R IgM 5/37 (13.5%) 3/37 (8.1%) 29/37 (78.4%) IgG 10/30 (33.3%) 5/30 (16.7%) 15/30 (50%) Bin et al., National Ctr.for Arboviruses, CVL, MOH, Sheba Medical Ctr., Israel
Dengue Seroconversion among Israeli Travelers to Tropical Countries Number 104 travelers Age (mean) 22 + 2 years Trip (average)- 6 (3-16) mo. Destination- S.E. Asia- 70 % S. America- 24 % Africa- 4% Combined-2% Potasman I, Srugo I, Schwartz E. : E.I.D; 1999,824-6
Dengue Seroconversion; Results: 7/104= 6.7 % (95% CI= 2.7-13.3%) 4/104= 3.8 % ; IgM + 3/104= 2.8% ; IgG+ 3/7- were asymptomatic Potasman I, Srugo I, Schwartz E. : E.I.D; 1999,824-6
Distribution of dengue cases according to seasons. 1995-7 1998 2002 Rainy season 80% 48% 32 % Dry season 20% 52% 68 %
GeoSentinel Database CDC & ISTM List of most frequent diagnosis All Travelers N=26408 Dengue diagnosis# 22 Percent of morbidity- 0.9% ISRAEL N=1046 Dengue diagnosis# 6 Percent of morbidity- 5% Date: June,2002
Dengue Fever Break- bone fever Dandy fever Denguero fever Geraffe fever Polka fever 5-7 days fever Donkey fever
Israeli data 27 hospitalized 69 days ~ 3 days (2.6)
Thanks to the Central Virology Lab. staff At Sheba Medical Ctr. Dr. Ella Mendelson Dr. Hanna Bin Dr. Zehava Grossman Mr.Fernando Mileguir
Diagnosis of DF in returning travelers hospitalized with febrile illness Country Ref Total number of febrile pts. Number of DF cases/ % Year of study Canada MacLean (see below) 587 12 2% 1981-1988 UK Doherty (see below) 195 12 6.2% 1992-93 Germany Australia Jelinek(ref 27) Obrien (ref 40) 130 9 6.9% 1995-6? Please check I do not have the paper. 232 18 8% 1997-99 Israel Abst. (see below) 163 27 16.5 % 1999-2003
symptoms Europe (jelinek) Sweden (Lindback) US MMW R 1993-2000 No. travelers 250 74 266 18 Fever 86 100 95% 100 Headache 60% 78% 62% 83 Fatigue 43% Not reported Not reporte d Rash 29% 62% 53% 44 Israel Am.J.Med 96 100 Myalgia/arthralgi a 42% 73% 50% 28 Vomiting/nausea 8% 16% 25% 38 Hemorrhagic manifestation 28% 13% 22 DHF/DSS 2% 3+ (2 death) cases Death 0 0 2 cases 0 0 Hospitalization 25% Not reported 66%
World Distribution of Dengue - 1999 Areas infested with Aedes aegypti Dengue in 1960 Areas with Aedes aegypti and recent epidemic dengue CENTERS FOR DISEASE CONTROL ANN PREVENTION
GeoSentinel: The Global Surveillance Network of the ISTM and CDC A worldwide communications and data collection network of travel/tropical medicine clinics
Malaria Cases, Percent of Morbidity per Month 20 Percent of Morbidity 15 10 7% 5 9/97 1/98 5/98 9/98 1/99 5/99 9/99 1/00 Month of Office Visit, N=303 cases