Arboviruses

The Arboviruses are also called as Arthropod borne viruses,

represent an ecological grounding of viruses with complex transmission cycles involving Arthropods These viruses have diverse physical and chemical properties and are classified in several virus families. Dengue infection is caused by Arboviruses

History Dengue
This disease was first described 1780, and the virus was

isolated by Sabin 1944. Dengue virus infection is the most common arthropod-borne disease worldwide with an increasing incidence in the tropical regions of Asia, Africa, and Central and South America. There are four serotypes of the virus. All are transmitted by mosquitoes, which are not affected by the disease, although an infected mosquito may infect others (not via man).

Current Trends
In the 1980s, DHF began a second expansion into Asia

when Sri Lanka, India, and the Maldives Islands had their first major DHF epidemics; Pakistan first reported an epidemic of dengue fever in 1994. The epidemics in Sri Lanka and India were associated with multiple dengue virus serotypes, but DEN-3 was predominant and was genetically distinct from DEN-3 viruses previously isolated from infected persons in those countries.

Prevalence of Dengue Infection

Dengue Infection and Implications

Dengue virus (DENV) infects 50 million (WHO) to 100

million (NIH) people annually. Forty percent of the worlds population, predominately in the tropics and sub-tropics, is at risk for contracting dengue virus. DENV infection can cause dengue fever, dengue hemorrhagic fever, dengue shock syndrome, and death.

Dengue Mosquito transmitted Viral Infection

What causes Dengue

Dengue (DF) and dengue hemorrhagic fever (DHF) are

caused by one of four closely related, but antigenically distinct, virus serotypes (DEN-1, DEN-2, DEN-3, and DEN-4), of the genus Flavivirus. Infection with one of these serotypes provides immunity to only that serotype for life,

Aedes aegypti Vector

Aedes aegypti, a domestic, day-biting mosquito that

prefers to feed on humans, is the most common Aedes species. Infections produce a spectrum of clinical illness ranging from a nonspecific viral syndrome to severe and fatal hemorrhagic disease. Other species of Aedes can also transmit.

Dengue Virus A Flavivirius

Flavivirius are spherical and

40- 60 mm in diameter. Genome Positive sense, single sense RNA,11kb in size Genome RNA infectious Enveloped virus Three structural polypeptides two are glycosylated Replication in cytoplasam

How Mosquitos spread the infection

The disease starts during the rainy season, when vector Mosquito Aedes aegypti is abundant The Aedes breeds in the tropical or semitropical

climates in water holding receptacles or in plants close to human dwellings A female Aedes acquires the infection feeding upon a viremic human. After a period of 8 14 days mosquitoes are infective and remain infective for life. ( 1- 3 ) months.

Dengue - Endemics
Persons living in a dengue-endemic area can have more

than one dengue infection during their lifetime. DF and DHF are primarily diseases of tropical and sub tropical areas, and the four different dengue serotypes are maintained in a cycle that involves humans and the Aedes mosquito.

Clinical Manifestations
Any or few of the following events can occur.
Fever, Severe head ache

Muscle and joint pains

Nausea, vomiting, Eye pain

How Dengue Infection starts and manifests

Incubation period 4 7 days ( 3 14 days) Fever may start with, Malise,chills,head ache Soon leads to severe back ache, joint pains, muscular pain, pain in

the eye ball. Temperature may persist for 3 -5 days. On some occasions once again raises in about 5 8 days ( Saddle back fever ) Myalgia may be severe with deep bone pain ( Break bone fever ) characteristic of the Disease

On majority of the occasions a self limited condition, Subside on its own Death is a rare event.

Dengue with Rashes

Dengue Hemorrhagic Fever

Common in children. In children passively acquired contributed by the maternal

antibodies transferred to the fetus. In other ( Adults ) the presence of antibodies due to previous infection with different serotype Initially presents like classical Dengue infection But patients condition abruptly worsens, an important cause of morbidity and mortality in Dengue

Risk factor for DHF

Important risk factors for DHF include the strain of the

infecting virus, as well as the age, and especially the prior dengue infection history of the patient

Dengue Hemorrhagic Syndrome

Chateresied by shock and hemoconcentration
Contributed by circustantial evidence suggests secondary

infection with Dengue type 2 following type 1 infection in the past.

Pathogenesis
Presence of existing Dengue antibody, associated with fresh

viral infection with new serotype complexes and forms within few days of the second dengue infection. Non neutralizing enhancing antibodies promote infection of higher number of Mononuclear cells.

Dengue Hemorraghigic Syndrome

DHS is caused due to release of,

1 Release of cytokines 2 Vasoactive mediators. 3 Procoagulants

Manifest with disseminated intravascular coagulation

Risk of Hemorrhagic Fever

The risk of hemorrhagic fever syndrome is about 0.2% during the first attack The second attack with different serotype increases the risk to ten fold The fatality rate with dengue hemorrhagic fever can reach 15% but proper medical care and symptomatic mangement can reduce mortality to less than 1% On few occasions patients condition abruptly worsens into Dengue shock syndrome, a more severe form of disease characterized by shock and hemoconcentration.

Diagnosis
In resource rich establishments
1 Reverse transcriptase polymerase chain reaction methods help rapid identification 2 Isolation of virus is difficult 3 The current favored approach is inoculation of mosquito cell line with patient serum coupled with nucleic acid assay to identify a recovered virus.

Dengue Serology
The serology is limited with cross reactivity of IgG antibodies to heterologus Flavivirius antigens
Most commonly used methods are

Viral protein specific capture IgM or IgG by ELISA IgM antibodies develop within few days of illness Neutralizing anti Hemagglutination inhibiting antibodies appear within a week after onset of Dengue fever

Importance of paired sample testing in Serology

Testing one sample for serum and reporting a negative test

is fallacious

Analysis of paired acute and

convalescent sera to show significant rise in antibody titer is the most reliable evidence of an active dengue infection.

Newer Diagnostic Methods RT - PCR

RT PCR is a highly sensitive tool in Diagnosis, with established high sensitivity in Diagnosis in Puzzles Developing world lacks resources to implement and utilize the Scientific advances

Immunology in Dengue
Four serotypes exist distinguished by Molecular basis and Nt

tests Infection confers life long immunity But cross protection between serotypes is of short duration. Reinfection with different serotype after primary attack is more dangerous causes Dengue hemorrhagic fever.

Dengue a Reemerging Infection

Dengue in 2005 identified as the most important mosquito

borne viral disease An estimated 50 million or more cases occur annually worldwide 400,000 cases of dengue hemorrhagic fever. Asian counties report major cases of childhood deaths

Treatment
No Anti viral therapy available
Symptomatic management in Majority of cases Dengue Hemorrhagic fever to be treated with suitable fluid

replacement No Vaccine available, difficult in view of four serotypes.

PREVENT MULTIPLICATION OF MOSQUITOES

Mosquitoes which spread dengue live and breed in and around houses. Drain water from coolers, tanks, barrels, drums and buckets, etc.; There should be no water in coolers when not in use; Remove from the house all objects, e.g. plant saucers, etc. which have water collected in them; Remove water from refrigerator drip pans every other day; All stored water containers should be kept covered all the time; Discard solid waste and objects where water collects, e.g. bottles, tins, tyres, etc.

PREVENT MOSQUITO BITES

Dengue mosquitoes bite during the daytime. Protect yourself

from the bite. Wear full sleeve clothes and long dresses to cover the limbs; Repellent care should be taken in using repellents on small children and the elderly; Use mosquito coils and electric vapour mats during the daytime to prevent Dengue; Use mosquito nets to protect babies, old people and others, who may rest during the day. The effectiveness of such nets can be improved by treating them with permethrin (pyrethroid insecticide). Curtains (cloth or bamboo) can also be treated with insecticide and hung at windows or doorways, to repel or kill mosquitoes.

Epidemiology - Dengue
Dengue virus are distributed world wide in tropical regions.
Where the Aedes vectors exist, are endemic areas Changing and increasing incidences are associated with rapid

urban population growth, over crowding and lax mosquito control measures

Febrile Phase
In the early febrile phase, it is not possible to distinguish DF

from DHF. Their treatments during the febrile phase are the same, i.e. symptomatic and supportive: Rest. Do not give Aspirin or Brufen. Aspirin can cause gastritis and/or bleeding. In children, Reyes syndrome (encephalopathy) may be a serious complication. Do not give antibiotics as these do not help. Oral rehydration therapy2 is recommended for patients with moderate dehydration caused by vomiting and high temperature. Food should be given according to appetite. Paracetamol (not more than 4 times in 24 hours) according: Age Dose(tablet 250 mg) Mg/Dose

Afebrile Phase
Dengue Fever
Constitutional symptoms in patients with DF after the fall

of fever are as during the febrile stage. Most patients will recover without complication. Treatment should be carried out as indicated

Afebrile Phase
Dengue Haemorrhagic Fever (DHF) Grades I and II As in DF, during the afebrile phase of DHF Grades I and II, the

patient has the same symptoms as during the febrile phase. The clinical signs plus thrombocytopenia and hemoconcentration or rise in hematocrit are sufficient to establish a clinical diagnosis of DHF. During this phase, the patients should be observed for at least 2-3 days after the fall in temperature, for rashes on the skin, bleeding from nose or gums, blue spots on the skin or tarry stools. If any of these signs are observed, the patients should be brought to the hospital without delay. The only difference between the DF and DHF Grade I is the presence of thrombocytopenia and rise in hematocrit (>20%). Patients with DHF Grade I do not usually require intravenous fluid therapy and ORT is sufficient. Intravenous fluid therapy may need to be administered only when the patient is vomiting persistently or severely, or refusing to accept oral fluids. Patients with DHF Grade Iwho live far away from the hospital or those who are not likely to beable to follow the medical advice should be kept in the hospital for observation.

What not to do
Do not

give Aspirin or Brufen for treatment of fever. Avoid giving intravenous therapy before there is evidence of hemorrhage and bleeding. Avoid giving blood transfusion unless indicated, reduction in hematocrit or severe bleeding. Avoid giving steroids. They do not show any benefit. Do not use antibiotics Do not changes the speed of fluid rapidly, i.e. avoid rapidly increasing or rapidly slowing the speed of fluids. Insertion of nasogastric tube to determine concealed bleeding or to stop bleeding (by cold lavage) is not recommended since it is hazardous.

Signs of Recovery
Stable pulse, blood pressure and breathing rate
Normal temperature No evidence of external or internal bleeding

Return of appetite
No vomiting Good urinary output Stable haematocrit Convalescent confluent petechiae rash

Avoiding Mosquito bites remain only way to prevent DENGUE