1. Case Study: Dengue Virus Virology 516 Fall 2007 Milette Mahinan, Suzi Sanchez, Olayinka Taiwo

2. Dengue Virus Morphology Dengue virus is a small, spherical,single stranded enveloped RNA virus Dengue virus is a small, spherical,single stranded enveloped RNA virus Belongs to the family Flaviviridae Belongs to the family Flaviviridae Http://news.uns.purdue.edu/html4ever/030618.Rossmann.immature.html

3. Case Study Information Victim: a 30 year old woman Victim: a 30 year old woman Symptoms: fever, backache, headache, myalgias in the upper arms, pain on moving her eyes, blanching erythematous rash on face, arms, trunk, and thighs, Symptoms: fever, backache, headache, myalgias in the upper arms, pain on moving her eyes, blanching erythematous rash on face, arms, trunk, and thighs, Possible exposure area: had returned home from trip to El Salvador where she had extensive exposure to mosquitoes Possible exposure area: had returned home from trip to El Salvador where she had extensive exposure to mosquitoes Other physical characteristics: no enanthem, murmur, of splenomegaly Other physical characteristics: no enanthem, murmur, of splenomegaly White blood cell count 1600/µl with a normal differential White blood cell count 1600/µl with a normal differential Platlet count 140,000/µl Platlet count 140,000/µl Hemoglobin 17.5g/dl Hemoglobin 17.5g/dl Convalescent phase antibodies tested positive for dengue virus Convalescent phase antibodies tested positive for dengue virus

4. By what type of mosquito is this virus transmitted? Aedes aegypti mosquito Aedes aegypti mosquito Small in comparison to other mosquitoes Small in comparison to other mosquitoes Found in the tropics (dengue is the second most frequent cause of hospitalization among travelers returning from the tropics) Found in the tropics (dengue is the second most frequent cause of hospitalization among travelers returning from the tropics) Some presence in the lower half of Florida Some presence in the lower half of Florida

5. Dengue Hemorrhagic Fever (DHF) Dengue may appear as a severe and fatal disease called DHF. Dengue may appear as a severe and fatal disease called DHF. DHF is defined by 4 criteria according to the world health organization: DHF is defined by 4 criteria according to the world health organization: 1) fever or history of fever lasting 2-7 days 1) fever or history of fever lasting 2-7 days 2) a hemorrhagic tendency shown by a positive tourniquet test or spontaneous bleeding 2) a hemorrhagic tendency shown by a positive tourniquet test or spontaneous bleeding 3) thrombocytopenia (platelet count <100x10 9 cells/L) 3) thrombocytopenia (platelet count <100x10 9 cells/L) 4) evidence of plasma leakage shown by hemoconcentration with substantial changes in serial measurements, or by packed cell volume 4) evidence of plasma leakage shown by hemoconcentration with substantial changes in serial measurements, or by packed cell volume Note: hemorrhagic manifestations without capillary leakage do not constitute DHF Note: hemorrhagic manifestations without capillary leakage do not constitute DHF Wilder-Smith, Ananth Tambyah (2007) Wilder-Smith, Ananth Tambyah (2007)

6. Other clinical Manifestations Petichial rash on extremities such as, the forehead Petichial rash on extremities such as, the forehead the capillaries become excessively permeable, may lead to plasma leakage the capillaries become excessively permeable, may lead to plasma leakage Shock- due to rapid and weak pulse, may lead to DSS Shock- due to rapid and weak pulse, may lead to DSS Hapatomegaly (enlargement of the liver)- observed mostly in children living in Thailand. Hapatomegaly (enlargement of the liver)- observed mostly in children living in Thailand. In severe cases, circulatory failure, which if left untreated can result in death within 12-24hrs In severe cases, circulatory failure, which if left untreated can result in death within 12-24hrs nevertheless, people can recover following appropriate volume replacement therapy of the circulating fluid in the body nevertheless, people can recover following appropriate volume replacement therapy of the circulating fluid in the body

7. Dengue has 4 serotypes These are known as DEN-1,DEN-2,DEN-3, and DEN4 These are known as DEN-1,DEN-2,DEN-3, and DEN4 A viral serotype is distinguished by protein or a protein component that determines its antigenic specificity A viral serotype is distinguished by protein or a protein component that determines its antigenic specificity Each viral serotype has characteristics that determine the nature of the epidemic and disease severity Each viral serotype has characteristics that determine the nature of the epidemic and disease severity Nisalak et al.(2003) Nisalak et al.(2003)

8. Secondary Infection It is common to see more serious symptoms related to secondary infection It is common to see more serious symptoms related to secondary infection Secondary infection occurs when a person is infected with a serotype distinct from the one that caused the initial infection Secondary infection occurs when a person is infected with a serotype distinct from the one that caused the initial infection The predominant serotype causing an epidemic may vary by year and geographic location The predominant serotype causing an epidemic may vary by year and geographic location DEN-1,2,3 are associated with moderately severe epidemic years DEN-1,2,3 are associated with moderately severe epidemic years Only DEN-3 is associated with severe epidemic years Only DEN-3 is associated with severe epidemic years DEN-2,3 are associated with severe symptoms, DHF DEN-2,3 are associated with severe symptoms, DHF Epidemics by multiple serotypes= hyperendemicity Epidemics by multiple serotypes= hyperendemicity Nisalak et al.(2003) Nisalak et al.(2003) http://en.wikipedia.org/wiki/Dengue_fever http://en.wikipedia.org/wiki/Dengue_fever

9. Subcutaneous hemorrhage on a DHF patient Subcutaneous hemorrhage on a DHF patient http://www.med.sc.edu:85/mhunt/arbo.htm

10. Will primary infection confer immunity to other serotypes???? It is known that immunity to the same serotype is long lasting (refers to the serotype causing the initial infection) It is known that immunity to the same serotype is long lasting (refers to the serotype causing the initial infection) Immunity to a second serotype is at best transient Immunity to a second serotype is at best transient Based on the current information, it can be predicted that immunity to one serotype does NOT confer immunity to others that exist, or new ones that may arise Based on the current information, it can be predicted that immunity to one serotype does NOT confer immunity to others that exist, or new ones that may arise Rothman(2007) Rothman(2007)

11. Dengue endemic regions The disease is now endemic in more than 100 countries in: The disease is now endemic in more than 100 countries in: Eastern Mediterranean Eastern Mediterranean South-east Asia South-east Asia Pacific Islands Pacific Islands Central and South America Central and South America Carribean Carribean Africa Africa WHO currently estimates that there may be 50 million cases of dengue infection worldwide every year WHO currently estimates that there may be 50 million cases of dengue infection worldwide every year http://www.who.int/mediacentre/factsheets/fs117/en/ http://www.who.int/mediacentre/factsheets/fs117/en/

13. Preventive measures for travelers Use mosquito repellents containing DEET Use mosquito repellents containing DEET Use mosquito nets Use mosquito nets Insecticides Insecticides Wear protective clothing Wear protective clothing Avoid being outdoors during the early morning and late afternoon (feeding times of the Aedes aegypti mosquitoes) Avoid being outdoors during the early morning and late afternoon (feeding times of the Aedes aegypti mosquitoes)

14. Thank You!!!!!