Case # 64Lucia Rosas, Sandra Isnasious, Bita Bahrami

• 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.

• 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.

Classic Dengue fever

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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

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• 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.

•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

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.

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Main Figure:

Primary Research Article Primary Research Article Contributing to the Understanding of Contributing to the Understanding of this Diseasethis Disease

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.

Negative Control

DENV-1 antibodies +DENV-2 infection

DENV-2 infection

Positive Control

ELISA Virus Isolation

◦ Cell culture, ◦ Mosquito inoculation◦ Fluorescent antibody test

RT-PCR Tourniquet Test

Positive TourniquetTest

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• 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.

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• 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.

• 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.

•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.

• 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