Dengue

worldwide distribution of dengue

1. before 1970, only 9 countries had experienced severe dengue epidemics

2. now endemic in more than 100 countries in the Africa, Americas, Eastern Mediterranean, South-East Asia and the Western Pacific

3. Americans, South-East Asia and Western pacific the most affected

the flavivirus genus includes important human pathogens such

1. DENV Dengue virus

2. West Nile Virus (WNV)

3. yellow fever virus (YFV)

4. japanese encephalitis virus (JEV)

5. tick borne encephalitis (TBEV)

6. murray valley encephalitis virus

transmission of dengue

1. mosquito to human transmission- through bite of infected female mosquito primarily Aedes aegypti and secondary Aedes albopictus. After feeding DENV infected person virus replicates in the mosquito midgut . disseminates to secondary tissue including salivary glands

2. human to mosquito transmission- people are viremic 4 to 5 days. symptomatic presymptomatic and asymptomatic

vector ecology

1. Aedes aegypti lives in urban and like to breeds in man made containers

2. Day time feeder, peak bitting early in the morning and evening before sunset

3. frequently feed multiple times between each egg laying period. Once has laid eggs . these eggs remain viable for several months and will hatch when they in contact to water

4. highly adaptive and secondary vector in Asia

5. geographical spread because tolerance to colder conditions as an egg and adult

Flavivirus virions

1. enveloped spherical about 50 nm in diameter

2. surface protein arranged isohedral like symmetry

3. mature virions contain 2 virus encoded membrane protein M and E

4. there are 4 serotypes : DENV1 DENV2 DENV3 DENV4

genome flavivirus

1. monopartite , linear, ssRNA

2. virions RNA serves as both genome and viral messenger RNA . the whole genome translated in a polyprotein, which processed co and post-translationally by host and viral protease

NS1

1. Dengue non-structural protein 1 a secreted glycoprotein used as diagnostic marker of dengue infections

2. appear early in the serum before antibodies are generated

3. function as cofactor for viral RNA replications

4. trigger cytokine release and contribute to vascular leak through binding TLR4 and engaging the endothelial glcocalyx

5. some antibodies against NS1 cross react with endothelial cells and induced apoptosis contribute to endothelial dysfunction and vascular leak

6. prevent complement activation and neutralizations of DENV

disease characteristics

1. flu like illness affects infants, children and adult

2. symptoms last to 2-7 days

incubation period

4 to 10 days

dengue classification and symptoms

1. dengue- high fever (40 degree) accompanied by 2 following symptoms : severe headache, muscle and joint pains, nausea, vomiting, lymphadenopathy, rash( sea of red with white island), Retro-orbital pain (a hallmark symptom of dengue)

2. severe dengue- patient enter the critical phase about 3-7 days after illness onset, fever dropping (38degree)

why severe dengue can cause fatal complication

1. plasma leaking

2. fluid accumulation

3. respiratory distress

4. severe bleeding

5. organ impairment

mechanism contribution DENV NS1 cause thrombocytopenia and hemorrhage during infection

1. increase platelet destruction and clearance from peripheral blood

2. the other is decrease production of platelets in the bone marrow

warning sign

1. severe abdominal pain

2. persistent vomiting

3. rapid breathing

4. bleeding gums

5. fatigue

6. blood in vomit

previous categories of dengue

1. dengue fever

2. dengue hemorrhagic fever- acute continuous fever 2-7 days, hemorrhage associated with thrombocytopenia (100000cells/ml or less), hemoconcentration (>20)

3. dengue shock syndrome- severe increase vascular leakage with hypovolemic shock which lead to tissue injury and organ failure

Antibodies dependent enhancement

1. DENV infections by one serotype provides long-lasting protection against that specific serotypes and short lived protection against other serotype

2. overtime these antibody concentration will decline the make susceptibel to infection by other DENV

3. cross reactive antibodies present at the time secondary dengue virus infection bind to virions without neutralizing and than enhance the entry of the virus into monocytic cell that express immunoglobulin receptors on its membrane

diagnosis method

1. Virological method

2. Serological method

explain virological methods in diagnosis dengue

1. NSP1 test- testing for virus prodeced protein NS1, commercially produced rapid diagnostic test available takes only 20 mins and does not required specialized lab technique or equipment

2. RT-PCR

3. virus isolated from the blood during first few days

explain serological methods in diagnosis dengue

1. ELISA may confirm the presence of a recent or past infection with the detection of IgM and IgG anti-dengue antibodies

2. IgM detectable 1 week after infection and are highest at 2 to 4 weeks after onset (recent DENV infection)

3. IgG takes longer to develop than IgM but remain for years (past infection)

treatment

1. fever reducers and painkillers taken to control the symptoms of muscle aches and pains and fever

2. paracetamol

3. NSAIDs (ibuprofen and aspirin should be avoided) because cause thinning blood may exacerbate hemorrhage

4. maintain body fluid volume critical to severe dengue care

vaccination

1. dengvaxia december 2015 has now be approved in 20 countries

2. in 2017 analysis show who wre seronegative at time first vaccination have higher risk more sever dengue and hospitalization from dengue compared to people that unvaccinated

3. vaccine targeted for person living in endemic country 9-45 y/o have at least 1 documented dengue virus infection previously

prevention and control

1. avoid mosquito bites first week of illness

2. prevention of mosquito breeding -remove man made containers. appropriate insecticides to water storage outdoor containers

3. personal protection

4. community engagement- educating, and engaging

5. fooging

dengue in Sabah

1. increasing cases

2. kota kinabalu, tawau, sandakan, lahad datu severe dengue in east coast

3. all 4 serotypes are circulating in Sabah

4. no seasonal variations