DENGUE FEVERDENGUE FEVER

Dr.T.V.Rao MDDr.T.V.Rao MD

Professor of MicrobiologyProfessor of Microbiology

ArbovirusesArboviruses

The Arboviruses are also called as The Arboviruses are also called as Arthropod borne viruses, represent an Arthropod borne viruses, represent an ecological grounding of viruses with ecological grounding of viruses with complex transmission cycles involving complex transmission cycles involving ArthropodsArthropods

These viruses have diverse physical and These viruses have diverse physical and chemical properties and are classified in chemical properties and are classified in several virus families.several virus families.

Dengue infection is caused by Dengue infection is caused by ArbovirusesArboviruses

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

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

Current TrendsCurrent Trends In the 1980s, DHF began a second In the 1980s, DHF began a second

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

Prevalence of Dengue Prevalence of Dengue InfectionInfection

Dengue Infection and Dengue Infection and ImplicationsImplications

Dengue virus (DENV) Dengue virus (DENV) infects 50 infects 50 million (WHO) to 100 million (NIH) million (WHO) to 100 million (NIH) people annually. Forty percent of the people annually. Forty percent of the world’s population, predominately in world’s population, predominately in the tropics and sub-tropics, is at risk the tropics and sub-tropics, is at risk for contracting  dengue virus. DENV for contracting  dengue virus. DENV infection can cause dengue fever, infection can cause dengue fever, dengue hemorrhagic fever, dengue dengue hemorrhagic fever, dengue shock syndrome, and death.shock syndrome, and death.

Dengue Dengue Mosquito traanmitted Viral Mosquito traanmitted Viral

InfectionInfection

What causes DengueWhat causes Dengue

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

Aedes aegypti – VectorAedes aegypti – Vector

Aedes aegyptiAedes aegypti, a domestic, day-, a domestic, day-biting mosquito that prefers to feed biting mosquito that prefers to feed on humans, is the most common on humans, is the most common AedesAedes species. Infections produce a species. Infections produce a spectrum of clinical illness ranging spectrum of clinical illness ranging from a nonspecific viral syndrome to from a nonspecific viral syndrome to severe and fatal hemorrhagic severe and fatal hemorrhagic disease. Other species of Aedes can disease. Other species of Aedes can also transmit.also transmit.

Dengue Virus – A Dengue Virus – A FlaviviriusFlavivirius

FlaviviriusFlavivirius are spherical are spherical and 40- 60 mm in and 40- 60 mm in diameter.diameter.

GenomeGenome – Positive sense, – Positive sense, single sense RNA,11kb in single sense RNA,11kb in size size

GenomeGenome – RNA infectious – RNA infectious

Enveloped virus Enveloped virus

Three structural Three structural polypeptides two are polypeptides two are glycosylatedglycosylated

Replication in cytoplasam Replication in cytoplasam

How Mosquitos spread the How Mosquitos spread the infectioninfection

The disease starts during the rainy season, The disease starts during the rainy season, when vector Mosquito Aedes aegypti is when vector Mosquito Aedes aegypti is abundant abundant

The Aedes breeds in the tropical or The Aedes breeds in the tropical or semitropical climates in water holding semitropical climates in water holding receptacles or in plants close to human receptacles or in plants close to human dwellingsdwellings

A female Aedes acquires the infection A female Aedes acquires the infection feeding upon a viremic human.feeding upon a viremic human.

After a period of 8 – 14 days mosquitoes After a period of 8 – 14 days mosquitoes are infective and remain infective for life. are infective and remain infective for life. ( 1- 3 ) months.( 1- 3 ) months.

Dengue - EndemicsDengue - Endemics

Persons living in a dengue-endemic Persons living in a dengue-endemic area can have more than one dengue area can have more than one dengue infection during their lifetime. DF infection during their lifetime. DF and DHF are primarily diseases of and DHF are primarily diseases of tropical and sub tropical areas, and tropical and sub tropical areas, and the four different dengue serotypes the four different dengue serotypes are maintained in a cycle that are maintained in a cycle that involves humans and the involves humans and the AedesAedes mosquito. mosquito.

Clinical ManifestationsClinical Manifestations

Any or few of the following events Any or few of the following events can occur.can occur.

Fever,Fever, Severe head acheSevere head ache Muscle and joint painsMuscle and joint pains Nausea, vomiting,Nausea, vomiting, Eye painEye pain

How Dengue Infection How Dengue Infection starts and manifestsstarts and manifests

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

muscular pain, pain in the eye ball.muscular pain, pain in the eye ball. Temperature may persist for 3 -5 days.Temperature may persist for 3 -5 days. On some occasions once again raises in about 5 – 8 On some occasions once again raises in about 5 – 8

days ( Saddle back fever )days ( Saddle back fever ) Myalgia may be severe with deep bone painMyalgia may be severe with deep bone pain ( Break bone fever ) characteristic of the Disease( Break bone fever ) characteristic of the Disease

On majority of the occasions a self limited On majority of the occasions a self limited condition,condition,

Subside on its ownSubside on its ownDeath is a rare eventDeath is a rare event..

Dengue with RashesDengue with Rashes

Dengue Hemorrhagic Dengue Hemorrhagic FeverFever

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

the maternal antibodies transferred to the the maternal antibodies transferred to the fetus.fetus.

In other ( Adults ) the presence of antibodies In other ( Adults ) the presence of antibodies due to previous infection with different due to previous infection with different serotypeserotype

Initially presents like classical Dengue Initially presents like classical Dengue infectioninfection

But patients condition abruptly worsens, an But patients condition abruptly worsens, an important cause of morbidity and mortality in important cause of morbidity and mortality in DengueDengue

Risk factor for DHFRisk factor for DHF

Important risk factors for DHF Important risk factors for DHF include the strain of the infecting include the strain of the infecting virus, as well as the age, and virus, as well as the age, and especially the prior dengue infection especially the prior dengue infection history of the patienthistory of the patient

Dengue Hemorrhagic Dengue Hemorrhagic SyndromeSyndrome

Chateresied by shock and Chateresied by shock and hemoconcentrationhemoconcentration

Contributed by circustantial Contributed by circustantial evidence suggests secondary evidence suggests secondary infection with Dengue type 2 infection with Dengue type 2 following type 1 infection in the following type 1 infection in the past.past.

PathogenesisPathogenesis

Presence of existing Dengue Presence of existing Dengue antibody, associated with fresh viral antibody, associated with fresh viral infection with new serotype infection with new serotype complexes and forms within few complexes and forms within few days of the second dengue infection.days of the second dengue infection.

Non neutralizing enhancing Non neutralizing enhancing antibodies promote infection of antibodies promote infection of higher number of Mononuclear cells.higher number of Mononuclear cells.

Dengue hemorraghigic Dengue hemorraghigic SyndromeSyndrome

DHS is caused due to release of,DHS is caused due to release of,

1 Release of cytokines1 Release of cytokines

2 Vasoactive mediators.2 Vasoactive mediators.

3 Procoagulants 3 Procoagulants

Manifest with disseminated Manifest with disseminated intravascular coagulationintravascular coagulation

Risk of Hemorrhagic Risk of Hemorrhagic FeverFever

The risk of hemorrhagic fever syndrome is The risk of hemorrhagic fever syndrome is about 0.2% during the first attackabout 0.2% during the first attack

The second attack with different serotype The second attack with different serotype increases the risk to ten foldincreases the risk to ten fold

The fatality rate with dengue hemorrhagic The fatality rate with dengue hemorrhagic fever can reach 15% but proper medical care fever can reach 15% but proper medical care and symptomatic mangement can reduce and symptomatic mangement can reduce mortality to less than 1%mortality to less than 1%

On few occasions patients condition abruptly On few occasions patients condition abruptly worsens into Dengue shock syndrome, a more worsens into Dengue shock syndrome, a more severe form of disease characterized by shock severe form of disease characterized by shock and hemoconcentration.and hemoconcentration.

DiagnosisDiagnosis

In resource rich establishmentsIn resource rich establishments 1 Reverse transcriptase polymerase 1 Reverse transcriptase polymerase

chain reaction methods help rapid chain reaction methods help rapid identificationidentification

2 Isolation of virus is difficult2 Isolation of virus is difficult

3 The current favored approach is 3 The current favored approach is inoculation of mosquito cell line with inoculation of mosquito cell line with patient serum coupled with nucleic acid patient serum coupled with nucleic acid assay to identify a recovered virus.assay to identify a recovered virus.

Dengue SerologyDengue Serology

The serology is limited with cross reactivity of The serology is limited with cross reactivity of IgG antibodies to heterologus Flavivirius IgG antibodies to heterologus Flavivirius antigensantigens

Most commonly used methods are Most commonly used methods are

Viral protein specific capture IgM or IgG by Viral protein specific capture IgM or IgG by ELISAELISA

IgM antibodies develop within few days of IgM antibodies develop within few days of illnessillness

Neutralizing anti Hemagglutination inhibiting Neutralizing anti Hemagglutination inhibiting antibodies appear within a week after onset of antibodies appear within a week after onset of Dengue feverDengue fever

Importance of paired Importance of paired sample testing in Serologysample testing in Serology

Testing one sample for serum and Testing one sample for serum and reporting a negative test is fallaciousreporting a negative test is fallacious

Analysis of paired acute and Analysis of paired acute and convalescent sera to show convalescent sera to show significant rise in antibody significant rise in antibody titer is the most reliable titer is the most reliable evidence of an active dengue evidence of an active dengue infectioninfection..

Newer Diagnostic MethodsNewer Diagnostic MethodsRT - PCRRT - PCR

RT PCR is a highly RT PCR is a highly sensitive tool in sensitive tool in Diagnosis, with Diagnosis, with established high established high sensitivity in sensitivity in Diagnosis in PuzzlesDiagnosis in Puzzles

Developing world Developing world lacks resources to lacks resources to implement and implement and utilize the Scientific utilize the Scientific advancesadvances

Immunology DengueImmunology Dengue

Four serotypes exist distinguished by Four serotypes exist distinguished by Molecular basis and Nt testsMolecular basis and Nt tests

Infection confers life long immunity Infection confers life long immunity But cross protection between But cross protection between

serotypes is of short duration.serotypes is of short duration. Reinfection with different serotype Reinfection with different serotype

after primary attack is more dangerous after primary attack is more dangerous causes causes Dengue hemorrhagic fever.Dengue hemorrhagic fever.

Treatment Treatment

No Anti viral therapy availableNo Anti viral therapy available Symptomatic management in Symptomatic management in

Majority of casesMajority of cases Dengue Hemorrhagic fever to be Dengue Hemorrhagic fever to be

treated with suitable fluid treated with suitable fluid replacementreplacement

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

Control of DengueControl of Dengue

Control of Mosquito breeding places.Control of Mosquito breeding places. Anti mosquito measures Anti mosquito measures Use of Insecticides. Use of Insecticides. Screened windows and doors can Screened windows and doors can

reduce exposure to vectors.reduce exposure to vectors.

Epidemiology - DengueEpidemiology - Dengue

Dengue virus are distributed world Dengue virus are distributed world wide in tropical regions.wide in tropical regions.

Where the Aedes vectors exist, are Where the Aedes vectors exist, are endemic areasendemic areas

Changing and increasing incidences Changing and increasing incidences are associated with rapid urban are associated with rapid urban population growth, over crowding population growth, over crowding and lax mosquito control measures and lax mosquito control measures

Dengue a Reemerging Dengue a Reemerging InfectionInfection

Dengue in 2005 identified as the most Dengue in 2005 identified as the most important mosquito borne viral diseaseimportant mosquito borne viral disease

An estimated 50 million or more cases An estimated 50 million or more cases occur annually worldwide occur annually worldwide

400,000 cases of dengue hemorrhagic 400,000 cases of dengue hemorrhagic fever.fever.

Asian counties report major cases of Asian counties report major cases of childhood deathschildhood deaths

Avoiding Mosquito bites Avoiding Mosquito bites remain only way to prevent remain only way to prevent

DengueDengue

Created for Created for Training Medical Training Medical and Health Careand Health Care

Workers in Workers in Developing World Developing World

Dr.T.V.Rao MDDr.T.V.Rao MD

EmailEmail

doctortvrao@gmail.doctortvrao@gmail.comcom