Your SlideShare is downloading. ×
0
 Dengue Fever
 Dengue Fever
 Dengue Fever
 Dengue Fever
 Dengue Fever
 Dengue Fever
 Dengue Fever
 Dengue Fever
 Dengue Fever
 Dengue Fever
 Dengue Fever
 Dengue Fever
 Dengue Fever
 Dengue Fever
 Dengue Fever
 Dengue Fever
 Dengue Fever
 Dengue Fever
 Dengue Fever
 Dengue Fever
 Dengue Fever
 Dengue Fever
 Dengue Fever
Upcoming SlideShare
Loading in...5
×

Thanks for flagging this SlideShare!

Oops! An error has occurred.

×
Saving this for later? Get the SlideShare app to save on your phone or tablet. Read anywhere, anytime – even offline.
Text the download link to your phone
Standard text messaging rates apply

Dengue Fever

7,526

Published on

Published in: Health & Medicine
0 Comments
3 Likes
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total Views
7,526
On Slideshare
0
From Embeds
0
Number of Embeds
0
Actions
Shares
0
Downloads
397
Comments
0
Likes
3
Embeds 0
No embeds

Report content
Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
No notes for slide

Transcript

  • 1. Dengue Fever Prof: Nooruddin Jaffer HMC Karachi
  • 2. Dengue Fever <ul><li>Dengue virus </li></ul><ul><li>Most prevalent vector-borne viral illness in the world </li></ul><ul><li>Main mosquito vector is Aedes aegypti </li></ul><ul><li>Year round transmission </li></ul>
  • 3. Incidence <ul><li>50-100 million dengue fever infections per year globally </li></ul><ul><li>500,000 cases of severe dengue, dengue hemorrhagic fever or dengue shock syndrome </li></ul><ul><li>100-200 cases annually in U.S. </li></ul><ul><li>Average case fatality 5% </li></ul>
  • 4. Distribution <ul><li>Endemic in more than 100 tropical and subtropical countries </li></ul><ul><li>Pandemic began in Southeast Asia after WW II with subsequent global spread </li></ul><ul><li>Several epidemics since 1980s </li></ul><ul><li>Distribution is comparable to malaria </li></ul>
  • 5. Clinical Presentation <ul><li>Spectrum of illness </li></ul><ul><li>non-specific febrile illness </li></ul><ul><li>classic dengue </li></ul><ul><li>dengue hemorrhagic fever </li></ul><ul><li>dengue shock syndrome </li></ul><ul><li>other (CNS dysfunction, liver failure, myocarditis) </li></ul>
  • 6. Classic Dengue <ul><li>Acute febrile illness with headache, retro-orbital pain, myalgias, arthralgias </li></ul><ul><li>“ Break-bone fever” </li></ul><ul><li>High fever 5-7 days </li></ul><ul><li>Second fever for 1-2 days in 5% patients </li></ul><ul><li>Followed by marked fatigue days to weeks </li></ul><ul><li>Classic dengue 15-60% of infections </li></ul><ul><li>Nausea, vomiting, diarrhea (30%) </li></ul><ul><li>Macular or maculopapular confluent rash (50%) </li></ul><ul><li>Respiratory symptoms: cough, sore throat (30%) </li></ul>
  • 7. Dengue Hemorrhagic Fever <ul><li>WHO classification of DHF </li></ul><ul><li>Thrombocytopenia (platelet count &lt;100,000) </li></ul><ul><li>Fever 2-7 days </li></ul><ul><li>Hemorrhagic manifestations with a positive tourniquet test, petechiae, ecchymoses or mucosal bleeding. </li></ul><ul><li>Hemoconcentration or evidence of plasma leakage (ascites, effusion, decreased albumin) </li></ul>
  • 8. Dengue Hemorrhagic Fever <ul><li>Usually occurs in secondary infections after actively or passively (maternal) acquired immunity to a different viral serotype </li></ul><ul><li>Only 2-4% of secondary infections result in severe disease </li></ul><ul><li>Mortality is 10-20% if untreated, but decreases to &lt;1% if adequately treated </li></ul><ul><li>Plasma leakage may progress to dengue shock syndrome </li></ul>
  • 9. Physical Exam <ul><li>Nonspecific findings </li></ul><ul><li>Conjunctival injection, pharyngeal erythema, lymphadenopathy, hepatomegaly (20-50%) </li></ul><ul><li>Macular or maculopapular rash (50%) </li></ul>
  • 10. Laboratory Findings <ul><li>Leukopenia </li></ul><ul><li>Thrombocytopenia (&lt;100,000) </li></ul><ul><li>Modest liver enzyme elevation (2-5x nml) </li></ul><ul><li>Serology: </li></ul><ul><li>Acute phase serum IgM (+6-90 days) ELISA </li></ul><ul><li>Acute and convalescent IgG (99% sens, 96% spec) </li></ul><ul><li>Hemagglutination inhibition assay (HI) is gold standard. Paired acute and convalescent HI assay, positive if &gt;4 fold titer rise </li></ul>
  • 11. Virology <ul><li>Flavivirus family </li></ul><ul><li>Small enveloped viruses containing single stranded positive RNA </li></ul><ul><li>Four distinct viral serotypes (Den-1, Den-2, Den-3, Den-4) </li></ul>
  • 12. Pathophysiology <ul><li>Transmitted by the bite of Aedes mosquito (Aedes aegypti) </li></ul><ul><li>Incubation 3-14 days </li></ul><ul><li>Acute illness and viremia 3-7 days </li></ul><ul><li>Recovery or progression to leakage phase </li></ul>
  • 13. Pathophysiology <ul><li>Dengue virus enters and replicates within monocytes, mast cells, fibroblasts </li></ul><ul><li>Innate and adaptive immune response </li></ul><ul><li>Cytokine release: TNF-a, IL-2, IL-6, IL-8 </li></ul><ul><li>Compliment activation </li></ul><ul><li>Antibody dependent enhancement (ADE) thought to contribute to severe infections </li></ul><ul><li>T-cell activation: CD4 and CD8 cells cytokine production </li></ul>
  • 14. Pathophysiology <ul><li>Capillary Leak Syndrome: </li></ul><ul><li>Transient increased capillary permeability due to endothelial cell dysfunction </li></ul><ul><li>Widening of tight junctions </li></ul><ul><li>Cytokine release and complement activation </li></ul><ul><li>Leukopenia, Thrombocytopenia and Hemorrhagic diathesis: </li></ul><ul><li>Direct viral bone marrow suppression </li></ul><ul><li>Platelet destruction in DHF </li></ul><ul><li>?Molecular mimicry between viral protein and coagulation factors </li></ul>
  • 15. Disease Factors <ul><li>Dengue-2 serotype most virulent </li></ul><ul><li>Increased severity with secondary infections </li></ul><ul><li>Increased risk in children &lt;15 years and elderly. </li></ul><ul><li>Greatest risk of DHF in infants. </li></ul><ul><li>More severe in females </li></ul><ul><li>Increased mortality with comorbid conditions </li></ul><ul><li>Less common in malnourished children </li></ul>
  • 16. Differential Diagnosis <ul><li>Vira l : Influenza, HIV, Hepatitis A, Yellow Fever, Hantavirus, Measles, Rubella, Coxsackie and other enteroviruses, parvovirus B19, Chikungunya virus, EBV </li></ul><ul><li>Bacterial : Typhoid, Scarlet fever, Meningococcemia </li></ul><ul><li>Parasitic : Malaria, Leptospirosis, Rickettsial disease, Leishmaniasis, Chagas disease </li></ul><ul><li>Fungal: Cryptococcus, Blastomycosis, Histoplasmosis </li></ul><ul><li>Non-Infectious : Malignancy, rheumatic, vasculitis, drug fever, other miscellaneous </li></ul>
  • 17. Differential Diagnosis <ul><li>Mosquito Borne Illnesses </li></ul><ul><li>Protozoa : Malaria </li></ul><ul><li>Roundworm : Filariasis, dirofilariasis </li></ul><ul><li>Alphaviruses : Chikungunya fever, Mayaro fever, Ross River fever, Eastern, Western, and Venezuelan equine encephalitis </li></ul><ul><li>Flaviviruses : West Nile fever, Zika fever, St. Louis encephalitis, Japanese encephalitis, Yellow Fever </li></ul><ul><li>Bunyaviruses : LaCrosse encephalitis, Oropouche virus, Bwamba fever, California encephalitis </li></ul>
  • 18. Treatment <ul><li>No specific therapy </li></ul><ul><li>Supportive measures: </li></ul><ul><li>adequate hydration </li></ul><ul><li>acetaminophen (if no liver dysfunction) </li></ul><ul><li>avoid ASA and NSAIDs </li></ul><ul><li>DHF or DHF w/ shock: </li></ul><ul><li>IV fluid resuscitation and hospitalization </li></ul><ul><li>blood or platelet transfusion as needed </li></ul>
  • 19. Treatment <ul><li>Treatment with corticosteroids shown not to reduce mortality with severe dengue shock </li></ul><ul><li>2 studies of 63 and 92 pediatric DHF shock pts treated w/ hydrocortisone 50mg/kg x1 or methylprednisolone 30mg/kg x1 dose vs placebo. </li></ul><ul><li>Study of 95 pediatric DHF shock pts treated with carbazochrome sodium sulfate (AC-17) vs B vitamins for 3 days </li></ul><ul><li>Ribavirin very weak in vitro and in vivo activity against flaviviruses </li></ul>
  • 20. Vaccination <ul><li>No current dengue vaccine </li></ul><ul><li>Estimated availability in 5-10 years </li></ul><ul><li>Vaccine development is problematic as the vaccine must provide immunity to all 4 serotypes </li></ul><ul><li>Lack of dengue animal model </li></ul><ul><li>Live attenuated tetravalent vaccines under phase 2 trials </li></ul><ul><li>New approaches include infectious clone DNA and naked DNA vaccines </li></ul>
  • 21. Prevention <ul><li>Personal: </li></ul><ul><li>clothing to reduce exposed skin </li></ul><ul><li>insect repellent especially in early morning, late afternoon. Bed netting is of little utility. </li></ul><ul><li>Environmental: </li></ul><ul><li>reduced vector breeding sites </li></ul><ul><li>solid waste management </li></ul><ul><li>public education </li></ul>
  • 22. Prevention <ul><li>Biological: </li></ul><ul><li>Target larval stage of Aedes in large water storage containers </li></ul><ul><li>Larvivorous fish (Gambusia), endotoxin producing bacteria (Bacillus), copepod crustaceans (mesocyclops) </li></ul><ul><li>Chemical: </li></ul><ul><li>Insecticide treatment of water containers </li></ul><ul><li>Space spraying (thermal fogs) </li></ul>
  • 23. Public Health <ul><li>Major and escalating global public health problem </li></ul><ul><li>Global demographic changes: urbanization and population growth with substandard housing, water, and waster management systems </li></ul><ul><li>Deteriorating public health infrastructure with limited resources resulting in “crisis management” not prevention </li></ul><ul><li>Increased travel </li></ul><ul><li>Lack of effective mosquito control </li></ul>

×