A Sudden Seizure by a Demon… Dengue The Danger A Sudden Seizure by a Demon… Group no. 20 , 3rd year I.Ya. Horbachevsky Ternopil State Medical University.

INTRODUCTION Dengue is caused by 4 flavivirus serotypes (DEN1-4). The incidence of dengue fever (DF) & dengue hemorrhagic fever (DHF) has increased 30 fold globally in the last 4 decades and more than half the world’s population is now threatened with it’s infection. According to WHO 100 million attacks of DF, 2,50,000 DHF occur annually with 25,000 unfortunate deaths.

Epidemiological evidences show that DHF & DSS (dengue shock syndrome) occur more frequently on re-infection with a second serotype.

Epidemiology Since the 18th. Century, dengue has caused repeated epidemics worldwide. H.Graham in 1903 implicated Aedes aegypti as the vector for the disease and the virus was isolated in 1944 by Albert Sabin. DHF gained nosologic status in 1954 and subsequently became endemic in many areas of tropical world. Dengue now affects >100 countries all over the world except Europe.

world distribution of dengue in 2006

Some important data l In India, the first recorded outbreak was in 1812. l 60 outbreaks have been reported during the period 1956 to 2001. l 10252 cases and 423 deaths in the year 1996 in Delhi. l India, 2006: 12750 cases, 217 deaths

Dengue cases reported in india in september 2006 STATES Number of cases reported.

Dengue victim

A child with dengue hemorrhagic fever or dengue shock syndrome may present severely hypotensive with disseminated intravascular coagulation (DIC)

Etiology Causative agent: 4 dengue viruses within the genus flavivirus are found in India. Dengue virions are small particles with lipoprotein envelope containing E proteins and nucleocapsid of single stranded RNA genome. There is a close antigenic similarity among the 4 serotypes but cross protection in human is at best partial and transient. DEN-2 is more virulent than other 3 serotypes.

conceivable." Immature Dengue Virus

Mature Dengue Virus

A TEM micrograph showing dengue virus Virus classification Group:Group IV ((+)ssRNA) Family:Flaviviridae Genus:Flavivirus Species:Dengue virus

B) Transmission: Reservoir of infection is both man & mosquito. The transmission cycle is “Man-Mosquito-Man”. Aedes aegypti is the principal vector, other less important vectors being Aedes albopictus, Aedes polynesiensis and several species of Aedes scutellaris complex.

Incubation period E3-14 days with mosquitoes remaining infected for life. The outbreaks coincide with the monsoon.

A MOSQUITO LARVA

Female Aedes Albopictus

Female Aedes Aegypti (Tiger Mosquito)

Pathogenesis After the bite by an infected mosquito, the virus replicates in the regional lymph nodes of the affected individual and is disseminated via the lymph and blood to the other tissues.DHF & DSS are characterised by abnormally increased capillary permeability and disordered haemostasis. The DHF/DSS are primarily seen in the young(<12yrs.) & mostly in secondary infection.

Pathology The pathologic findings include: Depression of all haemopoietic cells including megakaryocytes in bone marrow. Active proliferation and lymphocytolysis in germinal centers in lymph nodes & spleen. Focal mid-zonal necrosis and fatty changes in liver. Occasionally glomerulonephritis ( immune- complex deposition).

Dengue virus infection Clinical spectrum of Dengue fever Dengue virus infection Asymptomatic symptomatic ↓ Dengue hemorrhagic fever (plasma leakage) ↓ Undifferentiated fever (viral syndrome) Dengue fever syndrome ↓ No shock DSS Without hemorrhage With unusual hemorrhage Dengue fever DHF

Clinical features Classic Dengue (“Break-bone fever”) Abrupt onset of fever ĉ chill, headache, retro-orbital pain & low backache. The fever is typically high and occasionally followed by remission lasting for a few hours to 2 days, comes again following appearance of rash (saddle-back fever) & lasts for 5-7 days. Transient generalized erythematous flush like or typical morbilliform rash appears on trunk spreading to face & extremities sparing palms &soles. It may be accompanied by itching.

Generalised myalgia, arthralgia. Constitutional symptoms like anorexia, nausea, vomiting may be present. Relative bradycardia, generalized lymphadenopathy. Convalescence may be accompanied by asthenia & bradycardia.

Morbilliform rash of Dengue (A,B)

Clinical feature (contd.) B) Dengue haemorrhagic fever (DHF): The critical stage is reached after 2-7 days when fever subsides & circulatory disturbances start appearing as - Ascites. Petechiae, purpura, echymoses. Epistaxis, gum bleeding, GI haemorrhage etc. Generalized abdominal pain with tenderness over right costal margin. Hepatomegaly.

Clinical feature (contd.) C) Dengue shock syndrome (DSS) Some patients of DHF manifest signs of restlessness, abdominal pain and shock (rapid weak pulse, cold clammy extremities, diaphoresis, circumoral cyanosis, irritability or drowsiness). These cases, known as DSS, are characterised by severe hypotension or undetectable BP & pulse. The duration of shock is very short & the patient may die ĉ in 12-24 hrs.

petechia

..Investigation.. A) Virus isolation From blood during febrile phase. Newer diagnostic techniques: RT-PCR (Reverse transcriptase polymerase chain reaction). Very sensitive & specific for detection of viral RNA. Hybridization probe- identification of viral nucleic acids. Immuno-cytochemical methods- for detecting Dengue virus antigen.

B) Serology Hemagglutination inhibition assays:- It is the WHO recommended reference test for dengue virus infection. Disadvantages of these tests are Time consuming Cannot identify specific serotypes Cross-reaction with other related flaviviruses.

Interpretation of hemagglutination inhibition test S1 (1st.sample taken on adm.) S2 (2nd.sample taken after 10-14 days) Interpretation <1:20 <1:1280 Primary Dengue >1:20 >1:1280 Secondary Dengue --- Presumptive e/o Secondary Dengue

Commercial Dengue blot assay: It is a rapid diagnostic test, which is as sensitive as haemagglutination inhibition assay in diagnosing a secondary dengue infection but not so in case of primary infection.

ELISA The IgM antibody– Capture ELISA (MAC-ELISA) is specially useful in diagnosis of recent infection. IgG ELISA has results and interpretation same as haemagglutination inhibition assay.

GUAIAC TEST Signs of early coagulopathy may be as subtle as a guaiac test positive for occult blood in the stool. This test should be performed on all patients in whom dengue virus infection is suspected.

Other associated lab. Findings WBC count- May be normal but leucopenia is common. Neutropenia occurs towards end of febrile phase. Relative lymphocytosis ĉ >15% atypical lymphocytes is common in DHF/DSS. Thrombocytopenia Rising haematocrit Hypoproteinaemia/ mild albuminuria

..Treatment.. A) Classical Dengue Treatment of dengue fever is symptomatic only. Bed rest, sponging, Paracetamol,oral rehydration, which is most important from day1. B) Dengue haemorrhagic fever (grade I & II) The patient should be hospitalized. Management of fever is same as classic dengue Fluid replacement is through IV line.

Prognosis The case fatality rate varies greatly on the condition of the patient at admission and the quality of available treatment. However, most DHF/DSS patients respond well to supportive therapy, and overall mortality in an experienced center is as low as 1%.

Measures to control outbreaks Initiate vector control measures (eg. Residual spraying). Ensure community participation. Assess facilities for case management of patients with haemorrhagic shock. Alert health personnel to report increase /clustering of cases. Measures for prevention of mosquito bites to be conveyed to general population:

Measures (contd.) Wear clothes that cover full arms & legs Mandatory use of mosquito nets/repellants Keep patients protected from mosquito bite in acute phase Elimination of mosquito breeding places: Empty water tanks once a week Cover & seal septic tanks and soak away pits. Regular removal of rubbish Change water of coolers & other stagnant domestic water sources etc.

Mosquito breeding grounds

Eradication of mosquito breeding grounds by spraying of insecticides

..Immunisation.. Tetravalent vaccines are in advanced stage (phase III) of development in Thailand and are expected to be available in near future (within 5-10yrs).

..Conclusion.. Though Dengue fever is usually a self-limiting disease, lack of proper monitoring and adequate volume replacement may lead to fatal outcome. In view of emerging outbreaks of dengue fever in various states of India, it becomes imperative for primary care physicians to have an updated knowledge of its early diagnosis and recent management guidelines.

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Ayan Pratim Chakraborty COMPILED BY: Ira Bisawas Ayan Pratim Chakraborty YYYYYYYYYYYYYY