DENGUE AND BLOOD SAFETY. Ester C Sabino, MD, PhD Dep. of Infectious Disease/Institute of Tropical Medicine University of São Paulo

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1 DENGUE AND BLOOD SAFETY Ester C Sabino, MD, PhD Dep. of Infectious Disease/Institute of Tropical Medicine University of São Paulo

2 Dengue virus Arbovirus (arthropod-borne virus) virus transmitted by mosquitoes: Flaviviridae, Flavivirus Dengue DENV-1 DENV-2 DENV-3 DENV-4 West Nile Virus Yellow Fever Jap. Encephalitis Some medically important flaviruses TBEV YFV WNV MVEV JEV SLEV DENV 1 DENV 3 DENV 2 DENV 4 Countries with dengue outbreaks 2012 DengueMap a CDC-HealthMap Collaboration (

3 Global Impact of dengue infection 2.5 billion people =40% of world population at risk >100 countries in Asia, the Pacific, Americas and Africa million cases/year 500,000 hospitalizations 25,000 fatalities/year Leading cause of childhood death in southeast Asia Significantly under-identified/reported throughout the world Reportable disease since 2010 in the U.S. Aedes aegypti Aedes albopictus Laughlin et al., JID 2012

4 Concerns over Dengue outbreaks in the U.S. and Europe Distribution of A. aegypti Distribution of A. albopictus Source: Chester G. Moore, Ph.D., Colorado State University Maps from the ECDC (European Centre for Disease Prevention and Control) network

5 Dengue clinical outcomes Asymptomatic 53-87% Symptomatic Vaccine 2002; DF 98-99% Survive 95% DHF/DSS 1-2% Risk factors: Viral titer 2 Infection Death 0.5-5%

6 Viral and Immune parameters Primary Infection Secondary Infection IgG IgG Virus Virus NS1 IgM NS1 IgM Days Days from onset of symptoms Incubation Fever Fever

7 Dengue RNA prevalence in blood donors Study Linnen (Transfusion 2008,48:1355) Honduras Sao Paulo(Brazil) Australia prevalence 0.37% 0.06% 0.00% Mohammed (Transfusion 2008,48:1348) Puerto Rico 0.07% Strammer (Transfusion 2012,52:1657) Puerto Rico 0.19% Dias (Transfusion 2012,52:1667) Ribeirao Preto (Brazil) 0.4%

8 Transfusion-Transmitted Dengue Case Reports Singapore (NEJM 2008;359) Donor symptomatic one day after donation Two recipients (RBCs, FFP) developed dengue-related illness and seroconverted Third recipient (platelet) asymptomatic but developed IgM/IgG antibodies Donor and two symptomatic recipients positive for DENV-2 RNA Hong Kong (ProMed: Oct 11, 2002) Donor symptomatic one day after donation One recipient (RBC) developed dengue-related illness and seroconverted Donor and recipient positive for DENV-1 RNA Puerto Rico (Transfusion 2012,52:1657) 29 RNA+ units 3 recipients were tested. 1 developed Dengue hemorragic fever. 8

9 Why only 3 documented clusters of TT dengue despite high viremia rates in donors? Lack of active surveillance in regions with high rates of mosquito transmission; Inhibition of infection by preexisting or co-transfused DENV antibodies; Differences in infectivity related to viral envelope glycosylation and/or role of mosquito saliva Reduced clinical symptoms in transfusion recipients due to immune suppression of underlying disease

10 DENGUE RNA AMONG BLOOD DONORS AND RECIPIENTS DURING LARGE EPIDEMICS OF DENV-4 IN RIO DE JANEIRO AND RECIFE, BRAZIL For the NHLBI Recipient Epidemiology and Donor Evaluation Study-III (REDS-III)

11 Overall Study Objectives: 1) Estimate rates of donor viremia and risk of DENV in recipients of components from viremic donors, and correlate transmission risk with donation and recipient dengue marker status 2) Evaluate occurrence of symptoms consistent with DENV infection in DENV infected vs. non-infected recipients and estimate proportion of symptomatic infections among recipients following DENV+ transfusions 3) Estimate incidence of new DENV infections among donors during the 2012 epidemic outbreaks; correlate seasonal incidence rates with rates of detection of DENV RNA+ donations and clinical dengue in communities

12 Methods: Period: peak dengue transmission season (Feb-Jun 2012) Accrual: All donors asked to participate in the study and extra PPT tubes collected from consenting donors. Consented donor units were prioritized to the study hospitals when possible. Recipients from 4 hospitals/transfusion centers were invited to participate and for those who consented blood samples were collected 3-10 days (mean 5 days, max 21 days) after transfusion (up to 4 samples) A dengue symptoms questionnaire was administered at the time of post-transfusion sample collection and 30 days after the last transfusion episode. Testing: Target-capture transcription-mediated amplification (TMA) assay (GP/NDx) 50% LOD ~5 RNA copies/ml All recipient post-transfusion samples (subsequent testing of pre-tx samples) All donor samples from Rio de Janeiro Donor samples linked to enrolled recipients from Recife

13 Dengue TMA Assay Analytical Sensitivity Detection of 4 Dengue Virus Serotypes 100 n = 152 % Reactive copies/ml Type 1 Type 2 Type 3 Type 4

14 REDS-III Dengue Study Sites and Epidemic Activity Recife and Rio de Janeiro Dengue Epidemics in Recife ( ) Dengue Epidemics in Rio de Janeiro ( ) Weeks