Reed Final Dengue

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Information about Reed Final Dengue

Published on April 3, 2008

Author: Bernardo


Slide1:  DENGUE VIRUS: NO ONE IS SAFE Caitlin Reed Smith College April 29, 2005 Slide2:  OVERVIEW OF THEMES Background Information Clinical Presentation & Diagnosis Biology Vaccination Prospects Public Health WHAT IS DENGUE?:  WHAT IS DENGUE? Flavivirus (type of arbovirus) Transmitted from Aedes aegypti and Aedes albopictus mosquitoes Four Serotypes (Dengue 1-4) DENGUE (cont’d):  DENGUE (cont’d) Three Manifestations: 1. Dengue Fever 2. Dengue Hemorrhagic Fever 3. Dengue Shock Syndrome Leads to death in 5% of cases More dangerous if infected second time by different serotype WHY DO WE CARE ABOUT DENGUE?:  WHY DO WE CARE ABOUT DENGUE? CDC Category A Infectious Disease Infects 50-100 million people every year About half the world lives in a “hot zone” Very hard to create vaccine Mosquito evolution = threat to U.S. Global warming WHY NOW?:  WHY NOW? Failed eradication attempt in the Americas in 1970 Previously unestablished serotypes are establishing themselves in various countries Recent Outbreaks: 1. India, 2003 2. Hawaii, 2001 3. Taiwan, 2001 4. Puerto Rico, 1994-1995 WHERE IS DENGUE FOUND?:  WHERE IS DENGUE FOUND? DENGUE TRANSMISSION :  DENGUE TRANSMISSION Slide9:  Mosquitoes transmit dengue to human dendritic cells 2. Dengue targets areas with high WBC counts (liver, spleen, lymph nodes, bone marrow, and glands) 3. Dengue enters WBCs & lymphatic tissue 4. Dengue enters blood circulation HOW DENGUE SPREADS CLINICAL PRESENTATION OF DENGUE:  CLINICAL PRESENTATION OF DENGUE SYMPTOMS OF DHF:  SYMPTOMS OF DHF GRADE I: Fever with other symptoms such as vomiting, headache, muscle and joint pain: positive tourniquet test is the only evidence of hemorrhaging GRADE II: Grade I symptoms + spontaneous bleeding GRADE III*: Failure of circulatory system, clammy skin, rapid & weak pulse, restlessness GRADE IV*: Severe shock, no measurable blood pressure or pulse *Considered Dengue Shock Syndrome (DSS) DENGUE GRADATION:  DENGUE GRADATION Slide13: P E T E C H I A E Slide14:  P U R P U R A Slide15: E C C H Y M O S I S Slide16: NASAL HEMORRHAGING BIOLOGY OF DENGUE :  BIOLOGY OF DENGUE BASIC BIOLOGY:  BASIC BIOLOGY Single, positive-stranded RNA surrounded by an icosahedral core 90 glycoprotein E dimers overly M proteins Protein E is most important characteristic of dengue Modis, Ogata, Clements, et. al., 2004 BASIC DENGUE GENOME:  BASIC DENGUE GENOME FUSION PROTEIN E:  FUSION PROTEIN E Modis, Ogata, et. al., 2004. IMMUNE RESPONSE:  IMMUNE RESPONSE FIRST INFECTION:  FIRST INFECTION Humoral and cellular immune response - Ab serum neutralizing levels increase - T-lymphocytes activated by dendritic cells - Memory cells develop antibodies to fight off future infection of same serotype SECOND INFECTION:  SECOND INFECTION Antibody dependent enhancement - Enhancing immunoglobulin G (IgG) antibodies - Fc Receptors CELLULAR LEVEL OF DENGUE FUSION :  CELLULAR LEVEL OF DENGUE FUSION ENTRY INTO CELL:  ENTRY INTO CELL Dengue infection Endosome entry & pH change E protein conformational change Release of viral RNA into cell Replication & further infection Slide26:  PRE-FUSION POST-FUSION PROTEIN E CONFORMATIONAL CHANGE Modis, Ogata, et. al., 2004 PROTEIN E INSERTION INTO PM:  PROTEIN E INSERTION INTO PM Modis, Ogata, et. al., 2004. VIRAL REPLICATION:  VIRAL REPLICATION TO SUMMARIZE…:  TO SUMMARIZE… THE BODY’S RESPONSE TO A DENGUE INFECTION DENGUE IN THE CELL:  DENGUE IN THE CELL Dendritic cell infection  T-cell activation Previous infection = increase in viral load and decrease in incubation period ADE is problem for 20 years after first infection PATHOGENIC STRATEGIES OF DENGUE :  PATHOGENIC STRATEGIES OF DENGUE Invades circulatory system, causing: - vascular permeability - Disseminated intravascular coagulation - Potentially death DENGUE DIAGNOSIS:  DENGUE DIAGNOSIS LABORATORY DIAGNOSIS OF DENGUE:  LABORATORY DIAGNOSIS OF DENGUE METHODS: 1. Viral Isolation & Characterization 2. Genomic Sequencing 3. Antibody Detection VIRAL ISOLATION & CHARACTERIZATION:  VIRAL ISOLATION & CHARACTERIZATION Old “Gold Standard” Cell Culture (mammals & mosquitoes) -Indirect Immunofluorescence Useful to study basic virology, epidemiology, and pathogenesis Impractical for rapid diagnosis & treatment GENOMIC SEQUENCING:  GENOMIC SEQUENCING Quicker, more reliable means of diagnosis NASBA method (RNA-specific amplification assay) RT-PCR method to provide most accuracy, uses 5’-3’ nuclease oligonucleotide probe (which may not be able to distinguish among serotypes) – new “Gold Standard” Beware of false-positives due to contamination ANTIBODY DETECTION:  ANTIBODY DETECTION Most common methods 1. Hemagglutinin inhibition test (HI test) 2. ELISA 3. Rapid immunochromatography test (commercial kits available) STOPPING DENGUE:  VACCINE DEVELOPMENT AND PUBLIC HEALTH STRATEGIES STOPPING DENGUE MOST PROMISING VACCINE:  MOST PROMISING VACCINE ChimeriVax-Dengue - Tetravalent - Uses yellow fever vaccine as base - 92% of monkeys passed “virulent virus challenge” Guirakoo, Pugachev, and Zhang, 2004 WHAT ABOUT HUMANS?:  WHAT ABOUT HUMANS? Tetravalent vaccine ChimeriVax-Dengue? 20% seroconversion rate More research necessary! PUBLIC HEALTH STRATEGIES :  PUBLIC HEALTH STRATEGIES Vector Control Surveillance Preparation for outbreaks Research Slide41:  NON-BIOLOGICAL MEANS OF DECREASING THE INCIDENCE OF DENGUE MOSQUITO NETS: images/Bed%20net.jpg MOSQUITO NETS NO MORE MOSQUITOES!:  NO MORE MOSQUITOES! images/tincan.jpg Slide44: images/unsanitary.jpg ABOUT THAT STANDING WATER… Slide45:  “Children play in sewage in Nairobi's sprawling Mukuru Kaiyaba slum.” IMPEDIMENTS:  IMPEDIMENTS Still lack complete understanding of dengue virus virulence Social/socioeconomic Travel spreads different serotypes Demographic changes Decentralized and therefore weak public health systems REFERENCES:  REFERENCES “Arthropod-borne Viruses Infection” (accessed on April 2, 2005). “Bioterrorism Agents/Diseases” (2004). (accessed on April 12, 2005). “Bleeding Into the Skin.” (2003). (accessed on April 12, 2005). “Capillary Fragility Test.” (1998). (accessed on April 5, 2005). CDC Dengue Fever Homepage. (2005). (accessed on March 3, 2005). CDC Slideshow. (1999). “Dengue: Virus, Vector, and Epidemiology.” (accessed on April 1, 2005) Chambers, T.J., Y. Liang, D.A. Droll, J.J. Schlesinger, A.D. Davidson, P.J. Wright, X. Jiang (2003). Yellow Fever Virus/Dengue-2 Virus and Yellow Fever Virus/Dengue-4 Virus Chimeris: biological characterization, immunogenicity, and protection against dengue encephalitis in the mouse model. Journal of Virology. 77:3655-3668. “Dengue Triad.” (2005). (accessed on March 31, 2005). REFERENCES:  REFERENCES “Dengue Virus Profile.” (2000). (accessed on April 4, 2005). Guirakhoo, F., K Pugachev, Z. Zhang, G. Myers, I. Levenbook, K. Draper, J. Lang, S. Ocran, F. Mitchell, M. Parsons, N. Brown, S. Brandler, C. Fournier, B. Barrere, F. Rizvi, A. Travassos, R. Nichols, D. Trent, and T. Monath. (2004). Safety and efficacy of chimeric yellow fever-dengue virus tetravalent vaccine formulations in nonhuman primates. Journal of Virology. 78:4761-4775. Halstead, S.B. (1988). Pathogenesis or dengue: challenges to molecular biology. Science. 239:476-481. “Hemorrhagic Fevers.” 2005. (accessed on April 3, 2005). Ho, L., J. Wang, M Shaio, C. Kao, D. Chang, S. Han, and J. Lai. (2001). Infection of human dendritic cells by dengue virus causes cell maturation and cytokine production. The Journal of Immunology. 166:1499-1506. Kalayanarooj, S. (1999). Standardized clinical management: evidence of reduction in dengue hemorrhagic fever child fatality rate in Thailand. Dengue Bulletin. 23. (accessed on April 2, 2005). REFERENCES:  REFERENCES Kao, C., C. King, D. Chao, H. Wu, and G. Chang. (2005). Laboratory diagnosis of dengue virus infection: current and future perspectives in clinical diagnosis and public health. J. Microbiol. Immunol. Infect. 38: 5-16. Kuhn, R.J., W. Zhang, M.G. Rossmann, S.V. Pletney, J. Corver, E. Lenches, C.T. Jones, S. Mukhopadhyay, P.R. Chipman, E.G. Strauss, T.S. Baker, and J.H. Strauss. (2002). Structure of dengue virus: implications for flavivirus organization, maturation, and fusion. Cell Press. 108:717-725. Lai, P., S. Lee, C. Kao, Y. Chan, C. Huang, W. Lia, S. Wann, H. Lin, M Yen, and Y. Liu. (2004). Characteristics of a dengue hemorrhagic fever oubreak in 2001 in Kaohsiung. J. Microbiol. Immunolo. Infect. 37: 266-270. “Lymph Nodes.” (accessed on April 1, 2005). Mady, B.J., D.V. Erbe, I. Kurane, M.W. Fanger, and F.A. Ennis. (1991). Antibody-dependent enhancement of dengue virus infection mediated by bispecific antibodies against cell surface molecules other than Fc gamma receptors. Journal of Immunology. 147:3139- 3144. Modis, Y., S. Ogata., D. Clements, S. Harrison. (2004). Structure of the dengue virus envelope protein after membrane fusion. Nature. 427:313-318. Perez, J., A Vorndam, and G. Clark. (2001). The dengue and dengue hemorrhagic fever epidemic in Puerto Rico, 1994-1995. Am. J. Trop. Med. Hyg. 64: 67-74. “Petechiae.” (2001). (accessed on April 3, 2005). Shepherd, S., P. Hinfrey, and W.H. Shoff. (2002). Dengue Fever. (accessed April 12, 2005). Shrivastava, R. (2004). Dengue haemorrhagic fever: a global challenge. Indian Journal of Medical Microbiology. 22:5-6. REFERENCES:  REFERENCES Shu, P. and J. Huang. (2004). Current advances in dengue diagnosis. Clinical and Diagnostic Laboratory Immunology. 11:642-650. Stephenson, J. (2005). Understanding dengue pathogenesis: implications for vaccine design. Bulletin of the WHO. 83: 308-314. Sun, W., R. Edelman, N. Kanesa-Thasan, K.H. Eckels, J.R. Putnak, A.D. King, H. Houng, D. Tang, J. M. Scherer, C.H. Hoke, and B. Innis. 2003. Vaccination of human volunteers with monovalent and tetravalent live-attenuated dengue vaccine candidates. Am. J. Trop. Med. Hyg. 69: 24-31. “Thrombocytopenia.” (2005). (accessed on April 2, 2005). World Health Organization. (2002). Dengue: Strategic direction for research. (accessed on March 20, 2005). World Health Organization. (1999). Regional guidelines on dengue/DHF Prevention and Control: Clinical manifestations and diagnosis. (accessed on April 1, 2005). Wilson, M. and L. Chen. (2002). Dengue in the Americas. Dengue Bulletin. 26: 44-61.

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