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A Dengue Epidemic in Puerto Rico, 2010. LT Tyler M. Sharp, Ph.D. USPHS Scientific and Training Symposium June 21, 2011. National Center for Emerging and Zoonotic Infectious Diseases. Division of Vector-Borne Diseases — Dengue Branch. Dengue.
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A Dengue Epidemic in Puerto Rico, 2010 LT Tyler M. Sharp, Ph.D. USPHS Scientific and Training Symposium June 21, 2011 National Center for Emerging and Zoonotic Infectious Diseases Division of Vector-Borne Diseases — Dengue Branch
Dengue • Most important vector-borne viral disease worldwide • ~100 million infections/year • ~500,000 hospitalizations/year • ~25,000 deaths/year • Four dengue viruses (DENV1–4) cause an acute febrile illness • Common symptoms: fever, headache, myalgia, retro-orbital and joint pain, rash • Severe symptoms: hemorrhage, shock, death Photos credits: “Train-the-Trainer” course material, CDC 2010
Asymptomatic 75% Symptomatic 25% Severe dengue 1-5% Dengue Fever 95-99% Survive 95-99.5% Death 0.5 - 5% Dengue Virus Infections Infection Incidence ~ 5% / year Adapted from Vaccine 2002; 3043-3046
The Vicious Cycle of DENV Infections Mosquito acquires virus during feeding, virus replicates in mosquito Mosquito bites susceptible human, transfers DENV Mosquito bites susceptible human, transfers DENV Mosquito acquires virus during feeding, virus replicates in mosquito
Prevention and Control of Dengue • Surveillance • Disease • Vector • Primary prevention • Vector control • Vaccination • Secondary prevention • Clinical care • Anti-viral drugs Image: http://www.lafayettela.gov/eos/dpt122mosquitocontrol.asp
Puerto Rico and Dengue • 3.7 million individuals • Endemic • Seasonal • 7,000 – 24,000 cases/year • Passive surveillance Puerto Rico Image: http://www.caribbeanplanning.com/caribbean-map.htm
Recent Dengue Epidemics in Puerto Rico 1994 Mean
Recent Dengue Epidemics in Puerto Rico 1998 1994 Mean
Recent Dengue Epidemics in Puerto Rico 2007 1998 1994 Mean
Recent Dengue Epidemics in Puerto Rico 2010 2007 1998 1994 Mean
Recent Dengue Epidemics in Puerto Rico 2010 Mean
Diagnostics RT-PCR IgM ELISA • Positive: RT-PCR or IgM ELISA positive • Negative: RT-PCR and IgM ELISA negative • Indeterminate: negative RT-PCR, no convalescent specimen Acute Convalescent Virus IgG IgM 0 5 10 90 Day Post-Onset of Symptoms
Diagnostic Results, 2010 Suspected Cases (n = 23,622) Positive Cases (n = 10,947) Indeterminate 42.2%
Rates of Lab Positive Cases by Municipality, 2010 Lab positive cases per 1,000 persons 0.1-1.6 1.7-2.7 2.8-4.3 4.4-16.1 Overall incidence: 2.9 lab positive cases per 1,000 persons
Age Distribution of Lab Positive Cases, 2010 47% of cases were in adults Cases per 1,000 Individuals
Age distribution of serotypes, 2010 Percent Serotype
Lab Positive Cases and Lab Positive Deaths by Month, 2010 Suspected deaths: 123 Lab positive deaths: 38 Deaths
Age Distribution of Lab Positive Deaths, 2010 89% of deaths were in adults
Deaths by Serotype*, 2010 (n = 17) (n = 10) (n = 5) *32 of 38 deaths have a confirmed serotype.
First documented outbreak in Philadelphia in 1780 Dengue disappeared in the US following vector elimination due to concerns of yellow fever Travel-associated dengue has re-introduced the virus into the US History of Dengue in the United States
Dengue more common than malaria in some travelers Mosquito vector exists in US Imported outbreaks in TX, FL, HI In 2010, 702 cases reported from 38 states 18X under-reporting Re-emergence of Dengue in the United States Distribution of Aedes mosquitoes Mosquito surveillance data courtesy of Chester G. Moore, Colorado State University
Travel-associated Dengue in US, 2010 702 cases reported from 38 states 0 1-2 3-10 11-30 >30 Source: ArboNET
Travel-associated Dengue in US, 2010 • Puerto Rico, Dominican Republic, Haiti and other Caribbean Islands made up nearly half of all cases Cases Week of Report Source: ArboNET
Travel-associated Dengue in US, 2010 • Puerto Rico, Dominican Republic, Haiti and other Caribbean Islands made up nearly half of all cases Puerto Rico Cases Week of Report Source: ArboNET
Conclusions • Dengue is re-emerging • Large epidemic in PR in 2010 • 2.9 lab positive cases/1,000 individuals • Most lab positive deaths ever (n = 38) • 3.5 lab positive deaths/1,000 lab positive cases • 10–19 year olds most affected • 6.5 lab positive cases per 1,000 persons • Most deaths in adults • Median age: 44 years • Epidemics in PR overflow into the continental U.S.
Future Steps • Examine dengue deaths for: • Risk factors • Under-reporting and -recognition • Emphasize personal protection • Avoid mosquito bites • Educate physicians in clinical case management • 8,300 physicians and 2,500 nurses trained • Evaluation of clinical case management
Acknowledgements Aidsa Rivera, M.S. –Fatal case findings and PDSS oversight Rosa Rodriguez, Ph.D. – EDSS oversight Jorge L. Muñoz-Jordan, Ph.D. – Lab Chief, Molecular diagnostics and research Elizabeth Hunsperger, Ph.D. – Lab Chief, Serology diagnostics and research Luis Santiago, MPH – Statistical analysis and data processing LCDR FermínArgüello, M.D., MPH – Study design and analysis Hal Margolis, M.D. – Dengue Branch Chief CAPT Kay Tomashek, M.D., MPH – Epidemiology Chief National Center for Emerging and Zoonotic Infectious Diseases Division of Vector-Borne Diseases — Dengue Branch
Deaths per Population, 2010 Overall : 0.9 lab positive deaths per 100,000 individuals Deaths per 100,000 Individuals
Distribution of Aedes aegypti, 2007 Source: Chester G. Moore, Dept. of Microbiology, Immunology & Pathology, Colorado State University
Distribution of Aedes albopictus, 2007 Source: Chester G. Moore, Dept. of Microbiology, Immunology & Pathology, Colorado State University
Rates of Lab Positive Cases by Municipality, 2010 Fatalities 1 2 3
Under-reporting of Dengue in Puerto Rico • Lack of reporting • 10-27 symptomatic cases for every reported case in 1990’s • Failure of patients to present • Lack of clinical supicion • Failure of clinicians to report • Alternative methods of reporting • Category-1 form • Specimens sent off island for diagnostics (3 major companies) • Company A: ~2,000 from June-December, 2010 • Asymptomatic cases • ≤ 90% of all infections • In total, we estimate that 5-10% of Puerto Ricans were infected in 2010 • ~350,000 individuals
DHF Cases by Serotype, 2010 (n = 57) (n = 70) (n = 17)
DHF Cases by Serotype, 2010 (n = 92) (n = 52)
DHF Cases per Population Overall : 6.7 lab positive DHF cases per 100,000 individuals DHF Cases per 1,000 Individuals
DHF Cases per DF Cases Overall : 21.4 lab positive DHF cases per 1,000 lab positive cases DHF Cases per 1,000 DF Cases
Suspected and Confirmed Cases by Week, 2010 Outbreak declared Feb. 27, 2010
Clinical Course of Dengue Infection 1 to 3 days; usually <48 hrs Critical Phase Mosquito bite Range: 2 to 7 days; usually 3 to 5 days Usually 3 to 5 days Range: 3 to 14 d; usually 4 to 7 days Convalescent Phase Acute Febrile Phase Incubation Viremia -2 0 2 4 6 8 10 12 Day of Illness * Typically uncomplicated DHF/DSS lasts for 10 to 12 days
WHO Dengue Case Definitions (1997) Dengue fever (DF) Fever plus 2 of: headache, retro-orbital pain, myalgia, joint pain, bone pain, rash, bleeding, low WBC count Dengue hemorrhagic fever (DHF): Fever, hemorrhagic manifestation(s), thrombocytopenia (≤100,000 cells per mm³), plasma leakage Dengue shock syndrome (DSS): DHF plus rapid, weak pulse and narrow pulse pressure, OR DHF plus hypotension and cold, clammy skin and restlessness
Characteristics of the 2010 Epidemic * denominator varies due to data availability
Age Distribution of Hospitalized Cases, 2010 Percent Serotype
Infecting Serotypes in Non-Hospitalized and Hospitalized Individuals, 2010