8/3/2019 Dengue 3y1 2

1/37

8/3/2019 Dengue 3y1 2

2/37

ArbovirusesThe Arboviruses are also called as Arthropod borne viruses,represent an ecological grounding of viruses with complextransmission cycles involving Arthropods

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

Dengue infection is caused by Arboviruses

8/3/2019 Dengue 3y1 2

3/37

History DengueThis disease was first described 1780, and the virus was

isolated by Sabin 1944. Dengue virus infection is the mostcommon arthropod-borne disease worldwide with an

increasing incidence in the tropical regions of Asia, Africa,and Central and South America. There are four serotypes ofthe virus. All are transmitted by mosquitoes, which are notaffected by the disease, although an infected mosquito may

infect others (not via man).

8/3/2019 Dengue 3y1 2

4/37

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

when Sri Lanka, India, and the Maldives Islands had theirfirst major DHF epidemics; Pakistan first reported an

epidemic of dengue fever in 1994. The epidemics in SriLanka and India were associated with multiple dengue virusserotypes, but DEN-3 was predominant and was geneticallydistinct from DEN-3 viruses previously isolated from

infected persons in those countries.

8/3/2019 Dengue 3y1 2

5/37

Prevalence of Dengue Infection

8/3/2019 Dengue 3y1 2

6/37

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, isat risk for contracting dengue virus. DENV infection cancause dengue fever, dengue hemorrhagic fever, dengueshock syndrome, and death.

8/3/2019 Dengue 3y1 2

7/37

Dengue

Mosquito transmitted Viral Infection

8/3/2019 Dengue 3y1 2

8/37

What causes Dengue

Dengue (DF) and dengue hemorrhagic fever (DHF) arecaused by one of four closely related, but antigenicallydistinct, virus serotypes (DEN-1, DEN-2, DEN-3, andDEN-4), of the genus Flavivirus. Infection with one of theseserotypes provides immunity to only that serotype for life,

8/3/2019 Dengue 3y1 2

9/37

Aedes aegypti

Vector

Aedes aegypti, a domestic, day-biting mosquito thatprefers to feed on humans, is the most commonAedesspecies. Infections produce a spectrum of clinicalillness ranging from a nonspecific viral syndrome tosevere and fatal hemorrhagic disease. Other species ofAedes can also transmit.

http://www.cdc.gov/ncidod/dvbid/dengue/ae-aegypti-feeding.htmhttp://www.cdc.gov/ncidod/dvbid/dengue/ae-aegypti-feeding.htmhttp://www.cdc.gov/ncidod/dvbid/dengue/ae-aegypti-feeding.htmhttp://www.cdc.gov/ncidod/dvbid/dengue/ae-aegypti-feeding.htm

8/3/2019 Dengue 3y1 2

10/37

Dengue VirusA Flavivirius Flavivirius are spherical and

40- 60 mm in diameter.

GenomePositive sense,single sense RNA,11kb in size

GenomeRNA infectious

Enveloped virus

Three structural polypeptides

two are glycosylatedReplication in cytoplasam

8/3/2019 Dengue 3y1 2

11/37

How Mosquitos spread the infectionThe disease starts during the rainy season, when vector

Mosquito Aedes aegypti is abundant

The Aedes breeds in the tropical or semitropicalclimates in water holding receptacles or in plants closeto human dwellings

A female Aedes acquires the infection feeding upon aviremic human.After a period of 814 days mosquitoes are infective

and remain infective for life. ( 1- 3 ) months.

8/3/2019 Dengue 3y1 2

12/37

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

than one dengue infection during their lifetime. DF andDHF are primarily diseases of tropical and sub tropicalareas, and the four different dengue serotypes aremaintained in a cycle that involves humans and the Aedesmosquito.

8/3/2019 Dengue 3y1 2

13/37

Clinical Manifestations

Any or few of the following events can occur.

Fever,

Severe head ache Muscle and joint pains

Nausea, vomiting,

Eye pain

8/3/2019 Dengue 3y1 2

14/37

How Dengue Infection starts and manifests

Incubation period 47 days ( 314 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 58 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.

8/3/2019 Dengue 3y1 2

15/37

Dengue with Rashes

8/3/2019 Dengue 3y1 2

16/37

Dengue Hemorrhagic Fever Common in children.

In children passively acquired contributed by the maternalantibodies transferred to the fetus.

In other ( Adults ) the presence of antibodies due toprevious infection with different serotype

Initially presents like classical Dengue infection

But patients condition abruptly worsens, an important causeof morbidity and mortality in Dengue

8/3/2019 Dengue 3y1 2

17/37

Risk factor for DHF Important risk factors for DHF include the strain of the

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

8/3/2019 Dengue 3y1 2

18/37

Dengue Hemorrhagic Syndrome Chateresied by shock and hemoconcentration

Contributed by circustantial evidence suggests secondary

infection with Dengue type 2 following type 1 infection inthe past.

8/3/2019 Dengue 3y1 2

19/37

Pathogenesis Presence of existing Dengue antibody, associated with fresh

viral infection with new serotype complexes and formswithin few days of the second dengue infection.

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

8/3/2019 Dengue 3y1 2

20/37

Dengue Hemorraghigic Syndrome DHS is caused due to release of,

1 Release of cytokines

2 Vasoactive mediators.3 Procoagulants

Manifest with disseminated

intravascular coagulation

8/3/2019 Dengue 3y1 2

21/37

Risk of Hemorrhagic FeverThe risk of hemorrhagic fever syndrome is about 0.2%

during the first attack

The second attack with different serotype increases therisk to ten fold

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

On few occasions patients condition abruptly worsensinto Dengue shock syndrome, a more severe form ofdisease characterized by shock and hemoconcentration.

8/3/2019 Dengue 3y1 2

22/37

DiagnosisIn resource rich establishments

1 Reverse transcriptase polymerase chain reaction methods

help rapid identification2 Isolation of virus is difficult

3 The current favored approach is inoculation of mosquitocell line with patient serum coupled with nucleic acid assay

to identify a recovered virus.

8/3/2019 Dengue 3y1 2

23/37

Dengue SerologyThe serology is limited with cross reactivity of IgG

antibodies to heterologus Flavivirius antigens

Most commonly used methods areViral protein specific capture IgM or IgG by ELISA

IgM antibodies develop within few days of illness

Neutralizing anti Hemagglutination inhibiting antibodiesappear within a week after onset of Dengue fever

8/3/2019 Dengue 3y1 2

24/37

Importance of paired sample testing in

Serology

Testing one sample for serum and reporting a negative testis fallacious

Analysis of paired acute andconvalescent sera to show significant

rise in antibody titer is the most reliableevidence of an active dengue infection.

8/3/2019 Dengue 3y1 2

25/37

Newer Diagnostic MethodsRT - PCR

RT PCR is a highlysensitive tool in

Diagnosis, withestablished highsensitivity in Diagnosisin Puzzles

Developing world lacksresources toimplement and utilizethe Scientific advances

8/3/2019 Dengue 3y1 2

26/37

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 ismore dangerous causes Dengue hemorrhagic fever.

8/3/2019 Dengue 3y1 2

27/37

Dengue a Reemerging Infection Dengue in 2005 identified as the most important mosquito

borne viral disease

An estimated 50 million or more cases occur annuallyworldwide

400,000 cases of dengue hemorrhagic fever.

Asian counties report major cases of childhood deaths

8/3/2019 Dengue 3y1 2

28/37

Treatment No Anti viral therapy available

Symptomatic management in Majority of cases

Dengue Hemorrhagic fever to be treated with suitable fluidreplacement

No Vaccine available, difficult in view of four serotypes.

PREVENT MULTIPLICATION OF

8/3/2019 Dengue 3y1 2

29/37

PREVENT MULTIPLICATION OF

MOSQUITOES

Mosquitoes which spread dengue live and breed in and aroundhouses.

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. whichhave 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.

8/3/2019 Dengue 3y1 2

30/37

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;

Repellentcare should be taken in using repellents on smallchildren and the elderly;

Use mosquito coils and electric vapour mats during the daytimeto prevent Dengue;

Use mosquito netsto 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 (pyrethroidinsecticide). Curtains (cloth or bamboo) can also be treated withinsecticide and hung at windows or doorways, to repel or killmosquitoes.

8/3/2019 Dengue 3y1 2

31/37

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 rapidurban population growth, over crowding and lax mosquitocontrol measures

8/3/2019 Dengue 3y1 2

32/37

Febrile Phase

In the early febrile phase, it is not possible to distinguish DFfrom 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 aserious 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

8/3/2019 Dengue 3y1 2

33/37

Afebrile Phase

Dengue Fever

Constitutional symptoms in patients with DF after the fallof fever are as during the febrile stage. Most patients willrecover without complication. Treatment should be carriedout as indicated

8/3/2019 Dengue 3y1 2

34/37

Afebrile Phase

Dengue Haemorrhagic Fever (DHF) Grades I and II

As in DF, during the afebrile phase of DHF Grades I and II, thepatient has the same symptoms as during the febrile phase. The clinicalsigns plus thrombocytopenia and hemoconcentration or rise inhematocrit 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 noseor gums, blue spots on the skin or tarry stools. If any of these signs areobserved, the patients should be brought to the hospital without delay.

The only difference between the DF and DHF Grade I is the presenceof thrombocytopenia and rise in hematocrit (>20%). Patients withDHF Grade I do not usually require intravenous fluid therapy and

ORT is sufficient. Intravenous fluid therapy may need to beadministered only when the patient is vomiting persistently or severely,or refusing to accept oral fluids. Patients with DHF Grade Iwho live faraway from the hospital or those who are not likely to beable to followthe medical advice should be kept in the hospital for observation .

8/3/2019 Dengue 3y1 2

35/37

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 concealedbleeding or to stop bleeding (by cold lavage) is notrecommended since it is hazardous.

8/3/2019 Dengue 3y1 2

36/37

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

8/3/2019 Dengue 3y1 2

37/37

Avoiding Mosquito bites

remain only way to prevent

DENGUE