Case Study MICR 454L Emerging and Re-Emerging Infectious Diseases S2010

1. Case StudyMICR 454L Emerging and Re-Emerging Infectious DiseasesS2010 Case # 64 Lucia Rosas, Sandra Isnasious, Bita Bahrami

2. Case Summary • 30-year-old woman • Symptoms: fever, back aches and headache for 2 days, pain on moving her eyes, myalgias in the upper arms. • Exposure: Recent trip to El Salvador with high mosquito exposure • Physical exam: • Erythematous rash on face, arms, trunks and thighs (Fig. 1). • There was no enanthem, murmur, or splenomegaly. • White blood cell count was l,600/ml (normal 4,500-10,000/ml) • Platelet count was l40,000/ml (normal 150,000/ml-400,000/ml • Hemoglobin was 17.5 g/dl (normal 12-15.2g/dl) • Convalescent-phase antibodies to a mosquito-borne viral disease were diagnostic.

3. Key Information Pointing to Diagnosis • Symptoms: • Fever, Back ache and Headache • Myalgias in the upper arms: muscle and joint pain • Pain with the movement of the eyes • Recent Trip to El Salvador: tropical environment with Dengue endemic. • Exposure to Mosquitoes: female Aedes aegypti • Erythematous rash (petechiae). • Positive for mosquito viral borne antibodies.

4. The Diagnosis for Case # 64 Classic Dengue fever fabio93.wordpress.com

5. Microbiology of Dengue Virus • Family Falviviridae • Enveloped, single-stranded (+) RNA genome • The four distinct serotypes are DEN-1, DEN-2, DEN-3, and DEN-4.  • The female Aedes mosquito is this virus’ biological vector microbiologybytes.com biosingularity.wordpress.com

6. Pathogenesis of Classic Dengue Fever • Classic dengue primarily occurs in non-indigenous adults individuals • Symptoms begin after a 5 to 10 day incubation period and last 3 to 10 days. • Transmitted to humans via the bite of a mosquito. Not transmitted from human to human. • Majority of infected individuals are asymptomatic. • Individuals who do present with symptoms present: Fever, headache, muscle and joint pain, retro orbital pain, rash • A small percent of individuals can develop Dengue Hemorrhagic fever and can potentially develop Dengue Shock Syndrome. Both of these can lead to death.

7. Pathogenesis of Dengue Hemorrhagic Fever and Dengue Shock Syndrome • Necessary Criteria for DHF: • Fever or recent fever • Hemorrhagic manifestations • Low Platelet Count (100,000/ml) • Evidence of leaky capillaries • Symptoms: Gingival, nasal, gastro intestinal bleeding, hematuria, skin hemorrhages • Necessary Criteria for DSS: • 4 criteria for DHF • Evidence of circulatory failure • Both DHF and DSS lead to death. niaid.nih.gov

8. Pathogenesis

9. Primary Research Article Contributing to the Understanding of this Disease • Balsitis, Scott, et al. 2010, Lethal Antibody Enhancement of Dengue Mice is Prevented by Fc Modification, PLoS Pathogens 6: 1-13. • Experimental set up: Mice models with 4 groups. • Uninfected, infected with DENV-2 normal levels, infected with DENV-2 high levels, DENV-1 antibodies with DENV-2 infection. • What they found: • Secondary DENV infection results in enhanced infection or may offer some protection in vivo. • Can prevent enhanced infection by modifying Fc region of DENV antibody to prevent binding to Fc receptor. aalaslearninglibrary.org

10. Primary Research Article Contributing to the Understanding of this Disease Main Figure: Negative Control DENV-2 infection DENV-1 antibodies +DENV-2 infection Positive Control This article helps us understand how our patient is at risk for DHF and DSS upon secondary infection. It also shows that partial short-term cross-reactive protection can occur.

11. Diagnostic Tests for Dengue Virus • ELISA • Virus Isolation • Cell culture, • Mosquito inoculation • Fluorescent antibody test • RT-PCR • Tourniquet Test st.mahidol.ac.th omegahealthcare.co.uk thaitravelclinic.com Positive Tourniquet Test

12. Therapy and Prognosis for Classic Dengue Fever • No specific drugs to treat the virus. • Patient recommendations: • Get plenty of rest and stay hydrated. • You can take medication to reduce your fever but make sure to avoid NSAIDs. • Take precautions against mosquitos as you may be still infectious. • If you feel worse and develop vomiting and abdominal pain seek emergency medical treatment. • This is not the time to get any invasive procedures. • This should resolve itself within 2 weeks, you will be fine. www.buytylenol.net/

13. Prevention of Dengue virus • There is currently no vaccine available. • Targeting the mosquito vector can prevent infection. • Insecticides • When infected, early recognition and prompt supportive treatment can substantially lower the risk of developing severe disease leading to death. • Traveling recommendations: • Items that collect rainwater or to store should be covered or properly discarded. • Staying in screened or air-conditioned rooms • Spraying rooms with aerosol bomb insecticides to kill adult mosquitoes indoors using a repellent, DEET, on exposed skin. • Wearing protective clothing treated with repellant.

14. Epidemiology and Threats • Infection with one serotype does not protect against the others, and sequential infections put people at greater risk for dengue hemorraghic fever (DHF) and dengue shock syndrome (DSS). • With more than one-third of the world’s population living in endemic areas in Central America • Dengue infection is a leading cause of illness and death in the tropics and subtropics. As many as 100 million people are infected yearly. • These mosquito vectors are found here in the U.S. and there have been reported cases of dengue infections in Texas, Arizona, Hawaii. • Vectors can become resistant to insecticides.

15. Take Home Message • Dengue virus can manifest itself as: Classic Dengue Fever, DHF, DSS. • Classic Dengue fever symptoms include fever, rash, headache, muscle and joint pain. • Pathogen is an enveloped, (+) ssRNA virus known as the flavivirus. • Diagnostics include ELISA, RT-PCR and Tourniquet tests. • Therapy includes fluids, rest, and fever reducers. • Prognosis is good, most people recover completely within two weeks. Only 1% develop DHF or DSS which could lead to death. • Preventative measures: window screens, insect repellent and insecticides. No vaccine or drug is available. • Transmission is via the female Aedes aegypti mosquito. • Threats include 2.5% mortality, reports of infections in the U.S. and vector resistance.

16. References • Argüello A.F., Luxemburger C, Quiñones L, Muñoz J. L., Beatty M, Lang J., Tomashek K. M., 2008. Epidemiological and Clinical Observations on Patients with Dengue in Puerto Rico. Am. J. Trop. Med. Hyg., (79)123-127 • BalsitiS.J., Williams K.L., Lachica R., Flores D., Kyle J.L., Mehlhop E., Johnson S., Diamond M.S., Beatty P. R., and Harris E., 2010. Lethal Antibody Enhancement of Dengue Disease in Mice Is Prevented by Fc Modification, Plos pathogens, (6) issue 2. • Gubler D. J., 1998. Dengue and Dengue Hemorrhagic Fever Clin Microbiol Rev. (11) 480–496. • Johansson M.A., Dominici F., Glass G.E., 2009. Local and Global Effects of Climate on Dengue Transmission in Puerto Rico. Plos. (3) 382. • Muñoz-Jordán J., L.,Collins C.S., Vergne E., Gilberto A. Santiago, L Petersen L., Sun W., and Linnen J. M.,2009.Highly Sensitive Detection of Dengue Virus Nucleic Acid in Samples from Clinically Ill Patients Journal of Clinical Microbiology, (47) 27-931 • Wahala M.P.B., Donaldson E.F., Alwis R., Accavitti-Loper M.A., 2010. Natural Strain Variation and Antibody Neutralization of Dengue Serotype 3 Viruses. Plos Pathogens, (6) issue 3. • CDC (center for disease Control and Prevention) • Lecture