1. Intern Case Report Nick Robell

2. Goals & Objectives Challenge the Audience Presenting a novel case Review a common infectious disease test Educate Epidemiology Disease pathogenesis Diagnosis and classification Management and treatment Entertain No Disclaimers

3. Weekday in September CAT 2 West

4. 34 yo m c/o fever

5. “Pt to prelim desk c/o fever, possible tooth infection. Pt had tooth extraction 1 week ago. Now having fever. AOx3. Resp even and unlabored. Skin w/d. MAE x4.” “Sent from Wayne State Campus for fever of unknown origin. Wearing mask.” T 39.5HR 119BP 99/65 RR 20SpO 2 98%

6. History Fever, headache and myalgia Vietnam for 1 mo, returned yesterday Tooth extracted 1 week ago

7. Physical Exam Negative for eye pain. Negative for rash. Positive for headache. Positive for myalgias. Negative for Neck stiffness. Negative for any GI, Resp or CV complaints Diaphoretic Oropharyneal exudates No meningismus No rash No focal neurologic deficits Review of Systems Past Medical History No Past Medical History No Past Surgical History No Family History

8. Initial Testing ED Blood Panel Imaging Other Testing Lumbar Puncture ID tests

9. 1329915 111 3.5221.15 3.4 14.1 3.4 140 85 0.6 0.1 49 100 Back Rapid Strep Negative Differential Neutro (T/%): 2.6/ 77 Lymphs (T/%): 0.50/ 15 Mono (T/%): 0.30/8 Baso (T/%): 0/0 Eos (T/%): 0/0 Bands (T/%): 0/0

10. FINDINGS: There is a metallic fixation rod in the midportion of the right scapula. Cardiomediastinal contours are normal. Lungs and pleural spaces are clear IMPRESSION: No pneumonia. No other significant finding FINDINGS: There are multiple prominent bilateral lymph nodes, which are likely reactive. IMPRESSION: 1. Absent left posterior mandibular molar level without surrounding inflammatory changes. However, cannot exclude an infected socket. No abscess. 2. May have an oro-antral fistula. Correlate clinically. Back SPOILER ALERT: NOT HELPFUL

11. Meanwhile… Patient remained tachycardic, 90-120s Spiked fevers multiple times despite antipyretics Blood pressures ranged from 100-120s/ 60-70s received 1 L of normal saline Normal respiratory rate Back

12. FINDINGS: Ventricles are normal in size and midline in location. No intra-axial or extra-axial fluid collections. Gray white differentiation is well maintained. Mucosal thickening right maxillary sinus and ethmoid air cells. IMPRESSION: No acute intracranial process Lumbar Puncture -Opening pressure 19.2 cm H 2 O -4 tubes of clear fluid -Cryptococcus -West Nile Virus -Mononucleosis

13. HIV Positive

14. Admit to F6/ Infectious Disease

15. HIV Testing Screening- ELISA Based on antibody testing Misses window period False-positive in healthy population, 0.06%-0.12% False Positive- Rheumatic, EtOH, Syphilis, IVIG, Dengue, Malaria & Hep B Confirmatory- WB Based on viral protein

16. HIV Testing Confirmatory Western Blot Based on viral protein Scored as negative, positive or indeterminate Indeterminate- Elevated bilirubin, SLE, hemolysis, RF, Polyclonal gammopathy, HD, HLA ab, HTLV-1, Schistosomiasis, Heterophile Ab, massive proteinuria

17. Hosp. Day 1 Leukopenia, Lymphopenia, Elevated LFTs, thrombocytopenia and febrile Hosp. Day 2-5 Negative HIV WB, cyclical fevers, + cryptococcus CSF, antibiotics & anti- fungals given Negative HIV WB, cyclical fevers, + cryptococcus CSF, antibiotics & anti- fungals given Hosp. Day 6, Discharge Antibiotics and anti-fungals discontinued, Dx confirmed, LFTs downtrended, Plts uptrending

18. The Febrile Traveler 34 yo male with no pmhx presents with fever and headache after being in Vietnam for 1 month with leukopenia, thrombocytopenia, transaminitis and positive HIV ELISA.

20. CDC Tropical Diseases in Travelers A.Malaria B.Typhoid Fever C.Leptospirosis D.Chikungunya E.West Nile Virus F.Measles G.Rubella H.Acute HIV conversion disease I.EBV J.Dengue K.Viral Hemorrhagic Fevers L.Rickettsial Diseases M.SARS

21. Day of Hospitalization Dengue Serology sent on Hospital Day 5 Performed Salt Lake City, UT Elevated IgM and IgG All antibiotics discontinued Follow-up with DMC providers

23. “Most rapidly spreading mosquito-borne viral disease in the world…”

25. Dengue Pandemic “Imperils” 2-5 billion people living in Tropical and sub-tropical countries 50-100 Million infected every year, 500,000 admitted to hospital, 25,000 deaths/ year 100 Countries world-wide 796 Cases in North America from 2001-2007 Outbreaks in Texas 2006, Hawaii 2002, Cuba 1977, Singapore 2006 and Florida today 16% of febrile travelers may have Dengue

26. Dengue RNA genome Flavivirus with Aedes vector Viral Syndrome Partial-immunity leads to more severe reactions to second infection (DHF/DSS) Hemorrhage, Third spacing and organ failure Shock-state due to venous pooling Serologic diagnosis with IgM and IgG Infants

28. DENV-1 DENV-2,3 and 4 Immune System T-cells Cytokines Antibodies Complements

29. Dengue Fever Viral Syndrome Hemorrhagic Fever Bleeding tendencies Shock Syndrome Circulatory collapseCirculatory collapse

30. WHO criteria dengue fever 1. Fever 2. Two or more of the following clinical symptoms 3. Positive serology or occurrence with same time and place as other confirmed cases of dengue. "HARMS" - Headache Hemolytic tendencies (Ecchymoses, purpura) Arthralgia Retro orbital pain Rash Myalgia Serology for dengue WHO criteria for dengue hemorrhagic fever 1. Thrombocytopenia (Platelets < 100,000/cu mm) 2. Evidence of plasma leakage (> 20% rise in hematocrit >20% drop following fluids Signs like pleural effusion, ascites, hypoproteinaema) 3. Signs of hemorrhagic tendencies (Positive tourniquet test Petechie, ecchymoses, purpura Bleeding from gums Hematemesis, melena) 4. Fever (Lasting for 2-7 days) WHO criteria for dengue shock syndrome All 4 for DHF signs of circulatory failure. The mnemonic is, "CHIRP" - C: Cold clammy skin H: Hypotension R: Restlessness Rapid and weak pulse P: Narrow pulse pressure

31. Dengue with warning signs -Abdominal pain or tenderness -Persistent vomiting -Clinical fluid accumulation (ascites, pleural effusion) -Mucosal bleeding -Lethargy, restlessness -Liver enlargement >2 cm -Laboratory: increase in HCT concurrent with rapid decrease in platelet count **requires strict observation and medical intervention Severe Dengue Severe Plasma Leakage leading to: – Shock (DSS) – Fluid accumulation with respiratory distress Severe Bleeding as evaluated by clinician Severe organ involvement – Liver: AST or ALT ≥ 1000 – CNS: impaired consciousness – Failure of heart and other organs Dengue without warning signs -Nausea, vomiting -Rash -Aches and pains -Leukopenia -Positive tourniquet test

32. Treatment Death from acute liver failure, hemorrhage, renal failure, brain edema and pulmonary edema No specific treatment available Supportive Measures (antipyretics, Oxygen, colloids > crystalloids, blood products) Monitor vitals, Monitor CBC and Fluid balance (avoid over hydration) WHO Guidelines available for fluid management Antivirals are being investigated CDC Indications for hospitalization Tachycardia Increased cap refill Cool Mottled or pale skin Decreased peripheral pulses Mental status changes Oliguria Sudden increase in hematocrit despite fluids Narrowing of pulse pressure (<20 mmHg) Hypotension

33. Summary ALL LOVE for 7 warning signs of Dengue Abdominal pain Lethargy Liver enlargement Low platelet & high hematocrit O – nil Vomiting persistently Extravasation of fluid Aedes vector Second infection is worse Defervescence Period DF/ DHF/ DSS Follow WHO guidelines Interferes with many immunologic –based tests

35. Sources 1.Dengue and Dengue Hemorrhagic Fever: Information for Health Care Practicioners. 2015. Centers for Disease Control and Prevention. 2.Treatment. Chapter 3. Dengue Haemorrhagic Fever. Centers for Disease Control and Prevention. 3.Laboratory Diagnosis. Chapter 4. Dengue Haemorrhagic Fever. Centers for Disease Control and Prevention 4.Raza, Ali. Variable Impacting Dengue Surveillance in Key West Florida. University of Arizona College of Medicine. 5.Messenger AM, Barr KL, Weppelman TA, Barnes AN, Anderson BD, Okech BA and Focks DA. 2015. Serological Evidence of Ongoing Transmission of Dengue Virus in Permanent Residents of Key West Florida. 6.Watt G, Chanbancherd P, and Brown AE. 2000. Human Immunodeficiency Virus Type 1 Test Results in Patients with Malaria and Dengue Infections. Clin Inf Dis 2000, 30: 819. 7.Weerakkody RM, Palangasinghe DR, Dalpatadu KPC, Rankothumbura JP, Cassim MRN, and Karunanayake P. 2014. Dengue Fever in a Liver-transplanted Patient: A Case Report. Journal of Medical Case Reports 2014, 8: 378. 8.Halstead SB. 2007. Dengue. Lancet 2007, 370: 1644-52. 9.Wilder-Smith A and Schwartz E. 2005. Dengue in Travelers. N Engl J Med 2005, 353: 924-32. 10.Effler et al. 2005. Dengue Fever, Hawaii, 2001-2002. Emerg Inf Dis 2005, 11 (5): 742-749. 11.Guzma et al. 2010. Dengue: A Continuing Global Threat. Nat Rev Microbiol 2010, 8 (120): S7-16.