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dengue; bone break fever; dandy fever; Duengero fever; 7 day fever

Mosquito-transmitted arbovirus infection. Epidemiology: 1) transmitted by mosquito Aedes aegypti - not sexually transmitted [4] 2) hemorrhagic fever & shock uncommon in patients > 12 years of age 3) females affected > males 4) white affected > blacks 5) diagnosed in the U.S. almost exclusively among travelers returning from tropical areas 6) cases have emerged in Florida, New Mexico [5,11] 7) 390 million cases worldwide each year [8] 8) most prevalent mosquito-borne infection in the world [4,9] 9) endemic areas include Southeast Asia, South Pacific, Central America, South America, & the Carribbean [4] 10) Phillipines declares National dengue epidemic Aug 2019 [19] 11) U.S. travelers most often acquire Dengue in the Caribbean, Southeast Asia, & Oceania [20] 12) reported cases up 8-fold since 2000 with 4.2 million cases reported in 2022 [21] 13) countries in the Americas have reported more than 9.7 million dengue cases in 2024, twice as many as in all of 2023; none reported in the United States [23] 14) 3036 cases reported in the US & its territories in 2023 [23] - 2 cases of locally acquired dengue in Southern Calfornio October 2023 [24] - 1498 cases reported in Puerto Rico in 1st half of 2024 [23] - 2 locally acquired cases reported in Florida Keys 7/2/24 [23] 15) climate change made 2024 the deadliest year of dengue [24] Pathology: 1) incubation period 3-15 days (4-7 days) [4] (4-10 days) [22] 2) 4 antigenically similar serotypes a) immunity to 1 serotype may not confer immunity to another b) sequential infection with different serotypes may increase risk of hemorrhagic fever & shock c) serotype 2 is most pathogenic d) sequence of infection: - serotype 1 followed by serotype 2 has a higher morbidity than serotype 4 followed by serotype 2 3) macrophage/monocyte infection 4) malnutrition is protective Clinical manifestations: 1) incubation period of 4-7 days 2) may be asymptomatic [4] - 1st time infection tends to be mild [17] - 2nd infection can be more serious symptoms with hemorrhagic fever 3) abrupt onset of symptoms a) remitting after 3-4 days b) relapsing fever 1-3 days later in some patients 4) fever/chills (high fever) 5) pain a) frontal headache b) retro-orbital pain [4] c) arthralgias d) severe mylagias e) bone pain - especially severe in the lumbar spine, thus "bone-break fever" (low back pain) 6) gastrointestinal or respiratory symptoms may predominate [4] 7) erythematous morbilliform, punctate or petechial rash a) begins on dorsal surface of hands & feet b) spreads centrally to trunk c) spares the palms & the soles [4,9] d) rash often develops 3-4 days after onset, corresponding to initial remission of fever e) muscosal ulcerations [13] 8) minor spontaneous hemorrhage variable [4] - bleeding common 56-75%, plasma leakage 14-30% [20] 9) petechial rash following inflation of blood pressure cuff (positive tourniquet test) distal arm a sign of microvascular fragility 10) hemorrhagic fever & shock may occur with sequential infection with different serotypes 11) liver disease 46-79% [20] 12) manifestations similar to chikungunya & Zika Laboratory: 1) complete blood count: a) leukopenia, neutropenia b) thrombocytopenia 2) alanine aminotransferase in serum (serum ALT) is elevated 3) isolation of virus from blood early - Dengue virus RNA* - dengue + chikungunya + zika virus RNA 4) dengue virus antigen - NS1 tests detect the non-structural protein 1 (NS1) of dengue virus - NS1 is secreted into the blood during a dengue infection - presence of NS1 in blood is consistent with acute phase dengue infection 5) positive complement-fixation & neutralizing antibodies after 1st week 6) dengue virus IgM in serum (positive 3-5 days after onset of fever) 7) blood cultures are negative 8) negative peripheral blood smears 9) see ARUP consult [5] * also loincs for dengue virus DNA CDC recommendations in areas where both Zika & dengue are endemic [18] - nucleic acid amplification testing (NAAT) for dengue & Zika on serum samples collected <= 7 days after symptoms begin. - when NAAT results are negative, or serum samples are collected > 7 days after symptom onset, IgM antibody testing should be performed - if IgM antibody results are positive & NAAT results are negative, neutralizing antibody testing as indicated - for pregnant women: - serum & urine samples should be collected as soon as possible within 12 weeks of symptom onset for simultaneous NAAT & IgM serology for dengue & Zika - if IgM antibody results are positive & NAAT results are negative, neutralizing antibody testing as indicated [18] Special laboratory: - positive tourniquet test - ophthalmoscopy: abnormalities seen in 23% of primary infections [20] Complications: - hemorrhagic encephalitis - dengue shock syndrome [7] - vasculopathy - thrombocytopenia - coagulopathy - hemophagocytic lymphohistiocytosis [11] Differential diagnosis: - Chikungunya incubation is 48-72 hours [22] - Zika incubation is 3-14 days [22] - rash not as prominent as Chikungunya or Zika - myalgia more prominent than Chikungunya or Zika - arthralgia less prominent than Chikungunya or Zika - bleeding not a feature of Chikungunya or Zika - shock not a feature of Chikungunya or Zika - conjunctivitis not a feature of dengue or Chikungunya - typhoid fever - negative blood cultures & absence of GI symptoms distinguishing features from typhoid fever - malaria - thrombocytopenia, abnormal liver function tests & negative peripheral blood smears render malaria unlikely Management: 1) treatment is supportive 2) prednisone not effective [7] 3) prevention: - mosquito avoidance, insect repellant - Dengue virus vaccine for secondary prevention in children & adolescents with laboratory-confirmed prior dengue infection [12,17]

Related

Aedes aegypti (Asian tiger mosquito) dengue virus dengue virus vaccine (Dengvaxia)

General

viral infection

References

  1. DeGowin & DeGowin's Diagnostic Examination, 6th edition, RL DeGowin (ed), McGraw Hill, NY 1994, pg 878
  2. C. Panosian, UCLA School of Medicine, Laboratory Medicine lecture, Oct 1, 2001
  3. Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 1145
  4. Medical Knowledge Self Assessment Program (MKSAP) 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 2009, 2012, 2015, 2018, 2021.
  5. ARUP Consult: Mosquito-Borne Arboviruses The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/mosquito-borne-arboviruses
  6. Centers for Disease Control and Prevention (CDC) Locally Acquired Dengue - Key West, Florida, 2009-2010 MMWR 2010;59:577 PMID: 20489680 http://www.cdc.gov/mmwr/PDF/wk/mm5919.pdf
  7. Tam DTH et al. Effects of short-course oral corticosteroid therapy in early dengue infection in Vietnamese patients: A randomized, placebo-controlled trial. Clin Infect Dis 2012 Nov 1; 55:1216 PMID: 22865871Capeding
  8. Bhatt S et al The global distribution and burden of dengue. Nature. April 7, 2013 PMID: 23563266 http://www.nature.com/nature/journal/vaop/ncurrent/full/nature12060.html
  9. Ross TM. Dengue virus. Clin Lab Med. 2010 Mar;30(1):149-60 PMID: 20513545
  10. Teixeira MG, Barreto ML. Diagnosis and management of dengue. BMJ. 2009 Nov 18;339:b4338 PMID: 19923152
  11. Centers for Disease Control and Prevention. Sharp TM et al Fatal Hemophagocytic Lymphohistiocytosis Associated with Locally Acquired Dengue Virus Infection - New Mexico and Texas, 2012. MMWR. January 24, 2014 / 63(03);49-54 http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6303a1.htm
  12. Capeding MR et al Clinical efficacy and safety of a novel tetravalent dengue vaccine in healthy children in Asia: a phase 3, randomised, observer-masked, placebo-controlled trial. The Lancet, Early Online Publication, 11 July 2014 PMID: 25018116 http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2814%2961060-6/abstract - Wilder-Smith A Dengue vaccines: dawning at last? The Lancet, Early Online Publication, 11 July 2014 PMID: 25018119 http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2814%2961142-9/fulltext
  13. Hyle EP, Alame D Case records of the Massachusetts General Hospital. Case 13-2015. A 27-year-old woman with arthralgias and a rash. N Engl J Med 2015; 372:1657-1664April 23, 2015 PMID: 25901430 http://www.nejm.org/doi/full/10.1056/NEJMcpc1415172
  14. Ratnam I, Leder K, Black J, Torresi J. Dengue fever and international travel. J Travel Med. 2013 Nov-Dec;20(6):384-93. Review. PMID: 24165383 Free Article
  15. Simmons CP, Farrar JJ, Nguyen vV, Wills B. Dengue. N Engl J Med. 2012 Apr 12;366(15):1423-32. PMID: 22494122
  16. Centers for Disease Control and Prevention (CDC) Clinical Assessment. Tourniquet Test handout https://www.cdc.gov/dengue/training/cme/ccm/page73112.html
  17. Young K. Sofair A FDA Approves First Dengue Vaccine in U.S. Physician's First Watch, May 3, 2019 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org
  18. Sharp TM, Fischer M, Munoz-Jordan JL, et al. Dengue and Zika Virus Diagnostic Testing for Patients with a Clinically Compatible Illness and Risk for Infection with Both Viruses. MMWR Recomm Rep 2019;68(No. RR-1):1-10 https://www.cdc.gov/mmwr/volumes/68/rr/rr6801a1.htm
  19. Phillipines Department of Health. Aug 2019 DOH DECLARES NATIONAL DENGUE EPIDEMIC https://www.doh.gov.ph/press-release/DOH-DECLARES-NATIONAL-DENGUE-EPIDEMIC
  20. Huits R et al. Clinical characteristics and outcomes among travelers with severe dengue: A GeoSentinel analysis. Ann Intern Med 2023 Jun 20; [e-pub] PMID: 37335991 https://www.acpjournals.org/doi/10.7326/M23-0721
  21. Farge E, Harrison M WHO Warns of Dengue Risk as Global Warming Pushes Cases Near Historic Highs. Medscape. July 24, 2023 https://www.medscape.com/s/viewarticle/994626
  22. Bronze MS Fast Five Quiz: Dengue Medscape. August 22, 2022 https://reference.medscape.com/viewarticle/995704
  23. CDC Health Alert Network. June 25, 2024 Increased Risk of Dengue Virus Infections in the United States https://emergency.cdc.gov/han/2024/han00511.asp - Acevedo N Health officials in the Florida Keys issue a dengue fever alert The Florida Department of Health in Monroe County reported two cases of locally acquired dengue fever. NBC News. July 2, 2024 https://www.nbcnews.com/health/health-news/health-officials-florida-keys-issue-local-dengue-fever-alert-rcna159931
  24. Thiagarajan K. How climate change made 2024 the deadliest year of dengue. BMJ. 2024 Nov 6;387:q2391. PMID: 39505398
  25. Dengue County of Los Angeles Public Health http://publichealth.lacounty.gov/acd/VectorDengue.htm
  26. Dengue Centers for Disease Control and Prevention (CDC) http://www.cdc.gov/dengue/