DENGUE FEVER

ARBOVIRAL ILLNESS VIRAL ZOONOSIS -the most rapidly spreading mosquito-borne viral disease in the world-

N. Negrut, MD, Infectious Disease Specialist, Teaching Assistant Faculty of Medicine and Pharmacy, University of Oradea

DENGUE VIRUS
FAM. FLAVIVIRIDAE GENUS FLAVIVIRUS RNA VIRUS 4 SEROTYPES TRANSMITTED THRU MOSQUITOES: Genus Aedes
(A. aeqypti, A. albopictus, A. polynesiensis )

The mosquito Aedes aegypti feeding off a human host

DISTRIBUTION

SUBTROPICAL AND TROPICAL AREAS 50 million dengue infections occur annually

DENV are efficiently transmitted between mosquitoes and humans. A sylvatic cycle for dengue transmission has been documented in western Africa and southeast Asia.

CLINICAL FEATURES
INCUBATION: 3 -14 days CLINICAL MANIFESTATION:
onset abrupt three phases -- febrile, critical and recovery

50-90% asimptomatic Non specific febrile illness Clasic Dengue fever (DF) Dengue hemorrhagie fever (DHF) Dengue shock syndrome (DSS)

Febrile phase
FEVER:41C Between 5-7 days +CHILLS +ERYTHEMATHOS MOTTLING OF THE SKIN +FACIAL FLUSHING SADDLEBACK PATTERN (the fever abates for a day and then returns) more commonly in children risk for development of DHF or DSS at time of defervescence HEADACHE, RETROORBITAL PAIN NAUSEA, VOMITING SORE THROAT, INJECTED PHARYNS, CONJUNCTIVAL INJECTION RASH: maculopapular/macular confluent rash face, thorax, and flexor surfaces, with islands of skin sparing typically begins on day 3 and persists 2-3 days MYALGIAS, ARTHRALGIAS HEMORRHAGIC MANIFESTATION: petechiae and mucosal membrane bleeding HEPATITIS

Critical phase

when the temperature drops, on days 37 of illness and lasts 2448 hours
Warning signs Dengue with warning signs 1. Abdominal pain or tenderness 2. Persistent vomiting 3. Clinical fluid accumulation 4. Mucosal bleed 5. Lethargy, restlessness 6. Liver enlargement >2 cm 7. haematocrit 8. T Can appears: - Pleural effusion - Ascites - Severe bleeding - Severe hepatitis - Encephalitis - Myocarditis Future evolution of dengue with warning signs: recover with early intravenous rehydration or severe dengue

Sequential infection or pre-existing antidengue antibodies increases the risk of DHF through antibody-dependent enhancement.

Recovery phase

after 24-48 hours

well-being improves, appetite returns, gastrointestinal symptoms abate, haemodynamic status stabilizes, diuresis ensues.

The course of dengue infection

Types of rash in dengue

DF
fever severe headache retro-orbital pain severe joint and muscle pain nausea and vomiting rash

DHF is characterised by four criteria:

acute onset of high fever haemorrhagic manifestations:
positive tourniquet test, skin haemorrhages, mucosal and gastrointestinal tract bleeding

thrombocytopenia plasma leakage:

rise or drop in haematocrit,

pleural effusions or ascites,

hypoproteinaemia.

Tourniquet test (Rumpel-Leede Capillary-Fragility Test or Capillary Fragility Test)

A blood pressure cuff is applied and inflated to a point between the systolic and diastolic blood pressures for 5 minutes. The test is positive > 10 petechiae per square inch.

A positive tourniquet test on the left side of the image.

DF-DHF-DSS
Criteria for severe evolution of DF: patient from an area of dengue risk + fever 27 days + plasma leakage:
high or progressively rising haematocrit; pleural effusions or ascites; circulatory compromise or shock.

one of the following:

significant bleeding. altered level of consciousness. severe gastrointestinal involvement. severe organ impairment (acute liver failure, acute renal failure, encephalopathy or encephalitis, or other unusual manifestations, cardiomyopathy) or other unusual manifestations.

WHO grading of severity of DHF

Grade I

Grade II

fever + non-specific constitutional symptoms; haemorrhagic manifestation: positive tourniquet test+/- easy bruising.
spontaneous bleeding manifestations of Grade I, usually in the form of skin and other haemorrhages circulatory failure (tachycardia, weak pulse and narrowing of pulse pressure or hypotension, cold, clammy skin,restlessness) profound shock (undetectable blood pressure or pulse).

Grade III = DSS

Grade IV = DSS

DF+thrombocytopenia +haemoconcentration= DHF grades I/II DHF grades III/IV = DSS.

Laboratory Studies
Complete blood cell count
WBC , Lym Hematocrit level rise of greater

than 20% = hemoconcentration should be monitored at 24 hours for early recognition of DHF 3-4 hours in severe cases of DHF or DSS.

T
<100,000 cells/L =DHF/DSS should be monitored at 24 hours for early recognition DHF

Basic metabolic panel

Liver injury panel

Na is the most common in DHF/DSS Metabolic acidosis DSS BUN levels - DSS ALAT, ASAT Albumin levels = hemoconcentration. Prothrombin time Fibrinogen and fibrin degradation product = DIC

Coagulation panel

Chest radiography, ultrasonography

Tests for confirmation:

detection of the virus in cell culture in the first 5 days (serum, plasma,circulating blood cells and other tissues) detection of viral RNA (nucleic acid amplification tests - NAAT) in the first 5 days detection of viral antigens
(ELISA/rapid test)

in the first 5 days

antibodies Anti-dengue IgM and IgG (A four-fold or greater increase in

antibody levels in paired sera (at 10 days) indicates an acute or recent flavivirus infection)- after 5th day of infection.

Differential Diagnoses
Meningococcal infections Hepatitis Influenza Rocky Mountain Spotted Fever Leptospirosis Sepsis Malaria Typhus Meningitis Yellow Fever Chikungunya virus infections Mayaro fever Ross River fever Sindbis virus infections Viral Hemorrhagic Fevers Severe acute respiratory syndrome (SARS)

Treatment self limited disease

Bed rest, fruit juice and other fluids containing electrolytes and sugar.
NO: IM
Acetylsalicylic acid (aspirin) Reyes Syndrome Non-steroidal anti-inflammatory agents (NSAIDs) Gastritis or bleeding.

Oral rehydration solution (ORS) IV fluid: Ringer lactate solution, Sodium Chloride Plasma expander (Dextran 40, Albumin 5%) Blood transfusion, fresh frozen plasma

Antipiretics: Paracetamol Supportive treatment Treatment of the complication.

Prevention
Reduce humanvector contact:
installing mosquito screening on windows, doors and other entry points; using mosquito nets while sleeping during daytime; avoid travel to areas where dengue is endemic; wear protective clothing; eliminate the mosquitoes.

Improvement of water supply and water-storage systems. No vaccine is currently available.

Bibliography
1. Mandell's Principles and Practice of Infectious Diseases, 5th edition, 2000 2. WHO-Dengue-Guideline for diagnosis, tretment, prevention and control New Edition, 2009 3. http://www.emedicine.com 4. http://www.niaid.nih.gov 5. http://www.denguefeverpictures.com 6. Stephen S. Whitehead, Joseph E. Blaney, Anna P. Durbin & Brian R. Murphy: Prospects for a dengue virus vaccine,Nature Reviews Microbiology 5, 518528 (July 2007).