Dengue clinical phenotypes + pathophysiology

Question 1

incubation time

Answer 1

4-7 day average, but 3-14 day range

Question 2

“breakbone fever” symptoms

Answer 2

15-60% of patients 
myalgias
arthralgias 
headache (retro-orbital pain) 
rash 
nausea, vomiting, abdominal pain

Question 3

Dengue Tourniquet Test

Answer 3

measures capillary fragility and may serve as a severe disease predictor

Question 4

WHO case definition of dengue fever (DF)

Answer 4

acute febrile illness + fever and at least 2:
retro-orbital/ocular pain, headache, rash myalgia, arthralgia, leukopenia, or hemorrhagic manifestations but not meeting the case definition of DHF

Question 5

WHO case definition of dengue hemorrhagic fever (DHF)

Answer 5

DF + all below:

fever 2-7 days, hemorrhagic manifestation or a positive tourniquet test, thrombocytopenia, evidence of plasma leakage

Question 6

WHO case definition of Dengue Shock Syndrome (DSS)

Answer 6

DF + DHF + circulatory failure

Question 7

Where does the virus replicate in humans first?

primary infection

Answer 7

local lymph tissues

Question 8

After 2-3 days how does the virus disseminate to the rest of the body? (primary infection)

Answer 8

macrophages/B cells, T cells

Question 9

What increases the risk of a severe infection?

Answer 9

secondary infection with a different serotype

Question 10

Heterotypic antibodies

Answer 10

protect against all 4 serotypes for a brief period post infection (3 months)

Question 11

Antibody Dependent Enhancement

Answer 11

**Replication in Fc receptor-bearing cells
Serotype sequence and virus genotype may be impt
DENV1 followed by DENV2 (Asian genotype)
Host Specific
3rd or more heterotypic infections = less severe disease
Multiple serotypes/genotypes are usually circulating in one area

Question 12

Dengue Shock Syndrome (DSS)

Answer 12

Associated with immune activation

Question 13

immune activation of DSS

Answer 13

Increased sTNFR/75, IL-8 and IFN-gamma
local endothelial production of IL-8 RANTES with apoptotic cell death
Immune complex formation activates complement, increases C3a and C5a

Question 14

Secondary Infection (immunology)

Answer 14

Increased TNF-alpha, soluble CD8, soluble IL-2
Reinforced by IFN-gamma, lymphokines
increased infected target cells by IFN-gamma upreg

Question 15

review Mechanism overview

Answer 15

slide 83 (clinical microbiology reviews, 2009)
doi: 10.1128/CMR.00035-09

Question 16

review mechanism overview

Answer 16

slide 84