1. Flight Surgeon RSV Day I n t e g r i t y - S e r v i c e - E x c e l l e n c e ANGRC Joint Base Andrews UNCLASSIFIED

2. Tropical Medicine : Dengue Fever Bryan S. Delage MD COL MC FS SAS JFHQ North Dakota National Guard 26 July 2014 2

3. Dengue Fever I have no pharmaceutical bias or relationship to report 3

4. Patient Jim was a 61 y.o. male, who had returned from the Dominican Republic on vacation and presented to his primary care physician after a week of fever, and chills and not feeling well, with some fatigue myalgias and headache. His primary care physician sent blood work to rule out malaria, and then after the patient had left came to my office to ask the question – What do you think is going on with this guy ? Blood work returned normal, and the patient had defervesced, and had no further sequelae 4

5. What’s your Diagnosis So what would your answer be ? Obviously a definitive diagnosis cannot be had with limited laboratory testing, But ……. A case can be made for Dengue Fever! 5

6. 6 Tropical Medicine- Dengue Fever Dengue Fever – 1. Overview 2. Signs and Symptoms 3. Clinical Course 4. Diagnosis 5. Treatment and Management

7. Dengue Fever Overview: Dengue virus is one of the leading causes of illness and death in tropical and subtropical areas 400 million people are infected with the 4 strains of Dengue virus yearly It is caused by 4 distinct serotypes of the dengue virus (DENV, called DENV1,..2,..3,..4) Single stranded RNA virus A Flavivirus in the family Flaviviridae Other viruses in this group that are important (Yellow Fever Virus, West Nile Virus, Japanese and St. Louis Encephalitis viruses) 7

8. Dengue Fever Overview (cont.) : It is an arbovirus, which means it is arthropod- borne, and is transmitted primarily through an infected Aedes species of mosquito; but can be transmitted by blood transfusion, organ transplant, or by needle stick (all of these from an infected individual) 8

9. Dengue Fever Signs and Symptoms: Infection with Dengue virus can manifest in a spectrum of Dengue that ranges from an acute mild febrile illness to classic dengue fever, to the severe forms of the disease DHF ( Dengue Hemorrhagic Fever) and DSS ( Dengue Shock Syndrome) 9 About 75% of Dengue infections are asymptomatic, and 25% symptomatic, most symptomatic infections present as a mild to moderate acute febrile illness; up to 5% can develop severe life threatening disease.

10. Dengue Fever- Clinical Course The illness begins abruptly after an incubation of 4 – 7 days (range 3-14 days). It typically goes through 3 phases- febrile, critical and convalescent The Fever lasts 2 to 7 days, Signs and Symptoms include: severe headache, retro- orbital pain, muscle and joint, as well as bone pain. A macular or maculo-papular rash, and can include petechiae, ecchymosis, purpura, epistaxis, bleeding gums, hematuria 10

11. Dengue Fever – Clinical Course The severe forms of DHF and DSS tend to occur at the time of defervescence and on or about day 7, a high index of suspicion and early supportive care with fluid resuscitation and colloid replacement for the critical 24 to 48 hours can improve outcome. 11

12. Dengue Fever- Clinical Course Markers for more serious disease include severe abdominal pain, persistent nausea, and vomiting, bleeding mucosa, difficulty breathing (pulmonary edema), hypovolemic shock, abrupt thrombocytopenia, and increased hematocrit due to hemo-concentration. Patients will typically improve during this 24-48 hour critical phase, but patients with severe plasma leakage may have a marked drop in BP, and irreversible shock and death may occur. Also hemorrhagic complications including hematemesis, melena and hematochezia, or menorrhagia 12

13. Dengue Fever – Clinical Course If patients can be supported through this critical phase with fluids, colloid and transfusions, as the plasma leakage starts to subside, and fluid is re-absorbed their hemodynamics will stabilize, and a natural diuresis will typically start to reverse the fluid retention, and edema as well as ascites. Hematocrit may drop due to dilution effects as fluid is reabsorbed, and white count starts to rise, and then a slow recovery of platelets. During the convalescent phase the rash may desquamate and become pruritic. 13

14. Dengue Fever – Lab Findings There can be leukopenia, as well as thrombocytopenia, hyponatremia, AST, and ALT elevation, and sed rates typically remain stable. Lab confirmation can be made from a single acute phase serum specimen that is drawn early <= to 5 days from onset of fever; with Reverse Transcriptase – PCR for DENV genomic sequences, or immunoassay for DENV nonstructural protein 1 (NS 1) Later in the course ( 4 days or more after onset of fever) the PCR or NS1; and IgM anti- DENV may be confirmatory 14

15. Dengue Fever- Diagnosis The diagnosis of Dengue should be considered in a patient presenting with fever who was in an endemic area within 2 weeks of the onset of illness, that persists, and should be reported to the local health department; as it is nationally reportable As listed on the last slide confirmation by RT- PCR or Immunoassay for NS1 are confirmatory, and IgM- anti-DENV suggests a likely recent DENV infection 15

16. Dengue – Endemic Areas Dengue is a tropical and sub-tropical disease, and its distribution is throughout central and South America, the Caribbean, Southeast Asia and Africa, who’s range has increased over time. 16

17. Dengue Fever – Endemic Areas Africa 17

18. Dengue Fever- Endemic Areas Pacific and Asia 18

19. Treatment and Management There is no anti-viral medication that is effective for Dengue Treatment is aimed at symptoms, and Treatment of severe cases such as DHF or DSS, includes fluid replacement, treatment or coagulation disorders, and colloid, crystalloid and isotonic fluids until the symptoms start to abate. 19

20. Treatment and Management Close monitoring for development of more serious dengue, Avoidance of ASA, and other NSAID’s with the increased bleeding risk Confirmed or suspected cases need to be reported to the State Health Department and CDC. 20

21. Another Possibility ? 21

22. Chikungunya Virus Arbovirus Similar symptoms to Dengue Fever http://www.cdc.gov/me dia/DPK/2014/dpk- chikungunya.html?s_c id=cdc_homepage_wh atsnew_001 http://www.cdc.gov/me dia/DPK/2014/dpk- chikungunya.html?s_c id=cdc_homepage_wh atsnew_001 22

23. Chickungunya virus Transmitted by an Aedes mosquito, predominantly Aedes aegypti, and Aedes albopictus Humans are the primary host Blood borne transmission is possible, as well as in utero and is found in breast milk 23

24. Chikungunya Now there are cases found in the US Incubation is 3-7 days, Usually marked by the acute onset of fever and polyarthralgia Usually symptoms are bilateral, symmetric, and severe and debilitating Other symptoms include headache, myalgia, arthritis, nausea and vomiting, as well as a rash that is maculo-papular http://www.cdc.gov/chi kungunya/geo/united- states.html http://www.cdc.gov/chi kungunya/geo/united- states.html 24

25. Chikungunya Preliminary diagnosis is based on clinical feature’s, places and dates of travel; and activities Lab diagnosis by testing of serum or plasma for virus, viral nucleic acid or virus specific IgM Chikungunya testing is done at the CDC, a few state health departments, and one commercial laboratory Viral culture in the first 3 days of illness may be utilized Chikungunya virus antibodies normally develop toward the end of the first week of illness 25

26. Chikungunya Instructions for sending samples can be found on the CDC website There are no serious forms like in Dengue, no DHF or DSS variants There is some increased morbidity and mortality at the extremes of age Symptoms can persist, especially the arthralgia for prolonged periods of time http://www.cdc.gov/chi kungunya/geo/americ as.html http://www.cdc.gov/chi kungunya/geo/americ as.html 26

27. Summary Dengue Fever is an acute febrile illness seen throughout the tropics and subtropics Diagnosis can be done by RT- PCR less than 5 days and immunoassay for NS 1, as well as IgM for DENV later There are more serious manifestations that can result in increased morbidity and mortality (DHF and DSS) that typically occur about the 7 th day at about the time of defervescence, and need aggressive fluid management and possible transfusion of blood products, and management of bleeding Service members traveling to these areas especially the carribbean and other tropics need to be informed about the need to use protective measures to avoid infection, Also information on chikungunya and need to use measures to avoid infection with clothing and repellant in this case as well 27

28. Summary In both cases, suspected cases need to be reported to the CDC through the State Health Department. 28

29. Bibliography Dengue haemorrhagic fever; Diagnosis, treatment, prevention and control; 2 nd edition, World Health Organization, Geneva, 1997 CDC.gov http://www.cdc.gov/me dia/DPK/2014/dpk- chikungunya.html?s_c id=cdc_homepage_wh atsnew_001 29