desilva

Dengue Epidemics from South Asia to the Americas: 

Dengue Epidemics from South Asia to the Americas Aravinda de Silva, MPH, PhD Associate Professor Department of Microbiology and Immunology University of North Carolina School of Medicine Chapel Hill, USA Vector-borne Diseases Of The Southeastern United States, May 2007, Searle Center, Duke University- Durham, NC.

Slide2: 

The Dengue Viruses + sense RNA virus; approx. 11kb genome Infections are asymptomatic or symptomatic (DF or DHF) Four closely related but distinct viruses Designated D-1, D-2, D-3, D-4 Infected individuals develop life long immunity to the infecting serotype but they can be infected by a different serotype. People exposed to secondary infections are at greater risk of developing severe disease.

Slide3: 

Non-human primates Non-human primates Humans Humans SYLVATIC DENGUE (Africa, Asia) URBAN DENGUE Aedes aegypti Aedes sp ~500 yrs ago *Semi urban or rural cycle with Aedes albopictus as Vector?

Slide4: 

3 Billion people at risk, with approximately 50 million cases of which 500,000 develop DHF.

Why is dengue emerging?: 

Why is dengue emerging? Urbanization Use of non-biodegradable containers Rural to urban migration of people Break down in vector control and public health infrastructure Increased global movement of people and goods

Slide6: 

D1-D4 have been circulating in Sri Lanka since at least 1966.

DF and DHF cases in Sri LankaData from the Epidemiology Unit, MOH, Sri Lanka: 

DF and DHF cases in Sri Lanka Data from the Epidemiology Unit, MOH, Sri Lanka

Dengue transmission before and after the emergence of DHF in Sri Lanka (Messer, W.B., et al. (2002) Epidemiology Of Dengue In Sri Lanka Before And After The Emergence Of Epidemic Dengue Hemorrhagic Fever. AJTMH 66:765-773.): 

Dengue transmission before and after the emergence of DHF in Sri Lanka (Messer, W.B., et al. (2002) Epidemiology Of Dengue In Sri Lanka Before And After The Emergence Of Epidemic Dengue Hemorrhagic Fever. AJTMH 66:765-773.) School cohort study 1980-1985 (Pre-DHF): Dengue sero-prevalence 50% (7000 5-7 year olds) Fever surveillance: 1980-1985 (pre DHF): 583 cases (14% dengue) 1997-1998 (Post DHF): 166 cases (18% dengue) Similar proportion of secondary cases during pre and post DHF period DEN3 responsible for DHF cases in Sri Lanka (Pre DHF data from Vitarana and Gubler)

Slide9: 

34 isolates D1 6%, D2 65% D3 3%, D4 26% 249 isolates D1 8%, D2 35% D3 49%, D4 8% Desilva, Kanakaratne and Wahala, unpublished data

The relationship of Sri Lankan D3 isolates pre and post-DHF: 

The relationship of Sri Lankan D3 isolates pre and post-DHF Post DHF emergence in Sri Lanka Pre-DHF Emergence in Sri Lanka Subtype III Subtype II Subtype IV Subtype I Results No evidence for introduction of a new D3 subtype into Sri Lanka. Sri Lankan D3, Subtype III isolates form 2 distinct groups, associated, temporally, with the presence or absence of DHF. Post DHF group is most closely related to isolates from East Africa and India. 99 99 100 75 82

Summary of dengue in Sri Lanka: 

Summary of dengue in Sri Lanka Before 1989 dengue viruses were common with co-circulation of all 4 serotypes. However, severe disease was rare. After 1989 clinically apparent dengue including DHF common. Hypothesis: A new genotype of DEN3 is responsible for the emergence of severe disease

Dengue 3 In Central America: 

Dengue 3 In Central America Before 1994, D2 responsible for severe disease. D3 undetected in human cases for 17 years (1977-1994). D3, subtype III introduced in 1994 in Nicaragua and Panama, associated with severe disease (Lanciotti and Gubler, Wkly Epidemiol Rec 1995;70:41-3 ).

Slide13: 

Spread of DEN3 subtype III in the Americas

Conclusions: 

Conclusions A DEN3 subtype III virus from South Asia/East Africa was introduced to Panama or Nicaragua. Virus has spread throughout Central America, the Caribbean, and into parts of South America. DEN3 subtype III viruses responsible for severe disease in the Indian subcontinent and in Latin America are very closely related.

Slide15: 

Dengue in the SE USA Current distribution of Aedes agypti in the Americas (Figure adapted from CDC, DVBID, Website)

Slide16: 

Distribution of Aedes albopictus in the USA

Recent Dengue in the U.S.A. (Texas): 

Recent Dengue in the U.S.A. (Texas) Dengue epidemics occurred in the USA in the 1800s and the first half of the 1900s Recent indigenous transmission 1980: 23 cases, first locally acquired since 1945 1986: 9 cases 1995: 7 cases 1997: 3 cases 1998: 1 case 1999: 18 cases Data and slide from CDC, DVBID

Slide18: 

Compared dengue in Nuevo Laredo, Mexico and in Laredo, Texas. Vector (Ades aegypti) more prevalent in Laredo compared to Nuevo Laredo. Dengue IgM seroprevalence 16% in Nuevo Laredo and only 1.3% in Laredo. Life style and economic factors restrict dengue transmission on the US side. Not having AC was a significant risk factor for dengue antibody. EID, 9:86-89 (2003)

Risk of established dengue transmission in the Southeastern US: 

Risk of established dengue transmission in the Southeastern US Urban dengue with humans as the primary reservoir unlikely to become established in the region. Mutations that change host range of dengue to a non-human host found in the USA could pose a problem in the future. More research is needed to understand the basis of the narrow host range of dengue (Vector and Vertebrate host).

Collaborators: 

Collaborators UNC: William Messer CDC: Duane Gubler Sri Lanka: MRI: Tissa Vitarana, Nalini Withana, Kamala Sivananthan Genetech: Late Maya Gunasekera, Nalaka Kankaratne Support: UNC, NIH (Fogarty), Government of Sri Lanka.

Slide21: 

Makenzie, Gubler and Peterson