Dengue Presentation

What is Dengue Fever?

Dengue Fever History

Why is Dengue Important?

Epidemiology

• Serotype location and prevalence
• Vector
• Transmission Cycle

Endemic to...

Serotype locations

• All four serotypes now circulate through many at risk countries

• This is dramatically different than 20-30 years ago where most countries were hypoendemic (one serotype present)

• This increase in hyperendemicity (many serotypes present) has led to epidemic Dengue Hemorrhagic Fever in all at risk countries

Vector

The cause of widespread Dengue

• The vectors of Dengue Fever include Aedes aegypti (Top Right) and Aedes albopictus (Bottom Right)

• A.aegypti has a worldwide distribution in tropical areas

• The lack of population control of these vectors has increased the transmission of Dengue Fever and led to increased outbreaks around the world

Transmission Cycle

From Vector to Humans

• There are two distinct transmission cycles,

an rural/urban epidemic cycle and a tropic

epidemic cycle

• The tropic epidemic cycle involves primates

and A. aegypti mosquitos, this cycle rarely

leaves the tropics and is maintained in rural

villages in forests or islands outside urban

areas

• The urban epidemic cycle co-circulates between Aedes mosquitos and the human population often involving infrequent epidemics

Symptoms

Disease Progression

Pathogenesis

Prevention

Treatment

Control

Treatment, Prevention and Control

• No vaccine or drugs are available to treat Dengue

• The epidemic potential of Dengue makes prevention difficult, some methods include:

• The movement of people and increased mosquito populations are hard to contain

• Complications vary depending on immunological status and age

• Vaccination: a tetravalent vaccine is being developed

• Proper mosquito control techniques can greatly reduce transmission

How can we stop the spread of Dengue?

• Laboratory based surveillance

• Severe complications can be mitigated through heavy intravenous hydration therapy

• Giving travellers and residents proper knowledge of mosquito life cycles can reduce epidemics

• Disease prevention programs including education of medical community

Laboratory Diagnostic Techniques

There are multiple methods with which to detect Dengue Fever

1. Molecular detection methods through RNA isolation and PCR amplification

2. Serological diagnosis through antibody detection

3. Virus isolation in cell culture

Blood samples must be taken at the acute phase of infection for accurate detection using these methods

Serological Methods

There are 5 routine serological tests for antibody detection:

1. Hemaglutination Inhibition (HI)

2. Complement Fixation (CF)

3. Neutralization Test (NT)

4. Immunoglobulin-M (IgM) capture enzyme-linked

immunosorbent assay (MAC-ELISA)

5. Indirect Immunoglobulin-G (IgG) ELISA

The most common serological detection method IgG and IgM ELISA. ELISA is useful in detection as it is an inexpensive, quick and accurate test for Dengue antibodies. Although there are differences in Dengue IgM accumulation times, it can be difficult to say when the patient is infected, or give a false-negative if no IgM has accumulated. Not specific for serotype.

Dengue antibodies are highly cross-reactive within the flavirius family so specificity is difficult.

Virus Isolation

There are four different types of virus isolation methods:

1. Intracerebral inoculation into baby mice

2. Isolation into a mammalian cell culture

3. Inoculation into a live mosquito host

4. Inoculation of a live mosquito cell culture

Virus isolation is very labour intensive, costly, and slow. It is not a very effective diagnostic tool; however, it is useful for research purposes and direct identification of serotype.

Of these techniques, mosquito inoculation is the most widely used technique and is by far the best in terms of viral titre and culture methods.

Molecular Methods

Real-Time Reverse Transcription PCR

• Real-time reverse transcription PCR is the fastest and most sensitive way to test for Dengue

• Can be used to differentiate between serotypes of infected individuals

• This is a great tool for rapid diagnostics as well as surveillence of Dengue outbreaks and serotypes

Contributing Factors of Increased Dengue

Contributing Factors

There are many different causes for the rise of dengue, these include:

1) Societal issues: increased population and rapid urbanization increase vector prevalence

2) Control methods: Lack of effective vector control in endemic areas and increased geographic distribution of vectors, with increased temperature this rate my increase even faster

3) Faster travel: Rapid tranport between countries is the best way to increase dengue transmission, people can bring it back with them unknowingly

4) Declining health facility infrastructure and with that, declining health policies

Global Burden of Dengue

Global Burden

• Dengue has a severe health burden and economic burden on many of the countries it affects.

• It is estimated that more than 4 billion people are at risk around the world of dengue infection.

• Public health awareness and a lack of serious symptoms causes dengue to go under-reported, leading to more infections.

• If more surveillence and faster screening techniques aren't utilized in affected countries dengue will only become more severe.

References

1) Gubler DJ. Dengue and dengue hemorrhagic fever. Clin Microbiol Rev. 1998;11:480–96.

2)Guzman MC, Halstead SB, Artsob H, Buchy P, Jeremy F, Gubler DJ, et al. Dengue: a continuing global threat. Nat Rev Microbiol. 2010;8:S7–16. doi: 10.1038/nrmicro2460

3) Bhatt, S, Gething, PW, Brady, OJ et al. The global distribution and burden of dengue. Nature. 2013; 496: 504–507

4) Stanaway, Jeffrey D. et al. “The Global Burden of Dengue: An Analysis from the Global Burden of Disease Study 2013.” The Lancet. Infectious diseases 16.6 (2016): 712–723. PMC. Web. 10 Apr. 2018.

5)Shu P-Y, et al. (2003) Development of group- and serotype-specific one-step SYBR green I-based real-time reverse transcription-PCR assay for dengue virus. J Clin Microbiol 41(6):2408–2416.. Clin. Microbiol. June 2003 vol. 41 no. 6 2408-2416

References