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Download MBBS General Medicine PPT 8 Rna Viruses Part II Lecture Notes

Download MBBS (Bachelor of Medicine, Bachelor of Surgery) General Medicine 2022 PPT 8 Rna Viruses Part II Lecture Notes

This post was last modified on 05 April 2022

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Topics

1

Approach to Infectious Diseases and their prevention

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2

Antibiotic stewardship practices

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3

Community-Acquired Infections

4

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Health Care?Associated Infections

5

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Gram-Positive Bacteria (part-1)

6

Gram-Positive Bacteria (part-2)

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7

Gram-Negative Bacteria (part-1)

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8

Gram-Negative Bacteria (part-2)

9

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Spirochetal Diseases

10

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Diseases Caused by Atypical/Miscel aneous Bacterial Infections

11

Revision-cum-exam on bacteria (Must to know type)

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12

Infections Due to DNA Viruses

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1

13

Infections Due to RNA Viruses (part 1)

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14

Infections Due to RNA Viruses (part 2)

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15

HIV/AIDS ? part 1

16

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HIV/AIDS ? part 2

17

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Fungal Infections

18

Parasitic Infections (part 1)

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19

Parasitic Infections (part 2)

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20

Revision-cum-exam on Virus, Fungal, and Parasite (Must to know type)

Family

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Common

virus

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Picornaviridae

Polio

Entero

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Calciviridae

Noro

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Reoviridae

Rota

Orthomyxviridae

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Influenza

Paramyxoviridae Measle

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Mumps

Parainfluenza

Coronaviridae

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SARS

MARS

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Togaviridae

Rubel a

Chikungunya

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Flaviviridae

Dengue

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West nile

Filoviridae

Ebola

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Rhabdoviridae

Rabies

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Bunyaviridae

Hanta

Nairo (CCHF)

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Retroviridae

HIV

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RABIES

? Zoonotic infection that occurs in a variety of mammals throughout the world

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except in Antarctica and on some islands

? Canine rabies continues to be a threat to humans; others ? bat/raccoon rabies
? IP: 20?90 days but in rare cases is as short as a few days or >1 year
? usually transmitted to humans by the bite; rarely aerosol, transplantation, human

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-human possibly

? Neuronal dysfunction--rather than neuronal death--is responsible; microglial

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nodules called Babes nodules & Negri bodies (eosinophilic cytoplasmic

inclusions)

? Disease usually presents as atypical encephalitis with relative preservation of

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consciousness

? Prodromal ? nonspecific, sometimes earliest specific neurologic symptoms that

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include paresthesias, pain, or pruritus near the site of the exposure

? Acute neurologic ? encephalitic (furious) in 80% and paralytic in 20%.
? Comatose -

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? Autonomic dysfunction is common

and may result in hypersalivation,

gooseflesh, cardiac arrhythmia, and

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priapism

? Episodes of hyperexcitability are

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typical y followed by periods of

complete lucidity that become shorter

as the disease progresses

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? Early brainstem involvement

(hydrophobia, aerophobia)

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? In paralytic type, commonly

misdiagnosed as Guil ain-Barre

syndrome

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? Diagnosis should be considered in patients presenting with acute atypical encephalitis

or acute flaccid paralysis, including those in whom Guillain-Barre syndrome is suspected

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? Diagnostically useful specimens include serum, CSF, fresh saliva, skin biopsy samples

from the neck, and brain tissue

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? Presence of rabies virus?specific antibodies in the CSF suggests rabies encephalitis,

regardless of immunization status

? Other methods: RT-PCR, Direct fluorescent antibody

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? DD: Anti-N-methyl-d-aspartate receptor (anti-NMDA) encephalitis, Postinfectious

(immune-mediated) encephalomyelitis, psychiatric disorder (Rabies hysteria)

? There is no established treatment for rabies

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? There are seven well-documented cases of survival from rabies
? Postexposure Prophylaxis (PEP) ?

? Healthy dogs, cats, or ferrets may be confined and observed for 10 days
? If an animal escapes after an exposure, it must be considered rabid, and PEP must be initiated

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? Includes local wound care and both active and passive immunization
? If anatomically feasible, the entire dose of RIG (20 IU/kg) should be infiltrated at the site of the

bite

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? Vaccines; Four 1-mL doses of rabies vaccine should be given IM in the deltoid area (NOT

gluteal) ? 0, 3, 7, and 14


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Zoonotic viruses: Arthropod-Borne and

Rodent-Borne Virus Infections

? Extrinsic incubation, typically lasts 1?3 weeks in mosquitoes; Arboviruses infect their vectors

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after ingestion of a blood meal from vertebrate; some arthropods by saliva-activated
transmission, Rarely transovarial transmission

? Intrinsic incubation, as per type of infections

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? Seven families: Arenaviridae, Bunyaviridae, Flaviviridae, Orthomyxoviridae, Reoviridae,

Rhabdoviridae, and Togaviridae

? Arena and hanta viruses are rodent borne viruses

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? Diagnosis; recognized history of mosquito bite or tick bite (more diagnostic) or rodent

exposure; serology; PCR;

Hantavirus infections differ from other viral infections in that severe acute disease is

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immunopathologic;
SYNDROMES - grouped into one of five broad categories
ARTHRITIS AND RASH

? D/D - hepatitis B, parvovirus B19 infection, and rubella, and occasionally due to

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adenoviruses, enteroviruses, herpesviruses, and mumps virus

? Chikungunya:
? Aedes albopictus was identified as the major vector with IP ? 2-10 DAYS

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? Abrupt onset of Fever (often severe) with a saddleback pattern and severe arthralgia

accompanied by chills and constitutional symptoms and signs, such as abdominal

pain, anorexia, conjunctival injection, headache, nausea, and photophobia

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? Migratory polyarthritis mainly affects the smal joints of the ankles, feet, hands, and

wrists; rarely large joints

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? Rashes often coincides with defervescence; Children also often develop a bullous

rather than a maculopapular/petechial rash

? Maternal?fetal transmission has been reported

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? petechiae are occasionally seen and epistaxis is not rare, but chikungunya virus should

not be considered a VHF agent

? Mildly decreased platelet counts may be seen

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? Nonsteroidal anti-inflammatory drugs and sometimes chloroquine for refractory arthritis

ENCEPHALITIS

? Seasonal diseases, commonly occurring in the warmer months

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? Japanese encephalitis is the most important viral encephalitis in

Asia

? The virus is particularly common in areas of irrigated rice fields

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(attract the natural avian vertebrate hosts and provide abundant

breeding sites for mosquitoes such as Culex tritaeniorhynchus)

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? Additional amplification host by pigs and horses

? Unspecific febrile presentation (nausea, vomiting, diarrhea,

cough)

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? aseptic meningitis,
? meningoencephalitis,
? acute flaccid paralysis,
? severe encephalitis.

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? Common findings in JE are cerebellar signs, cranial nerve palsies, and

cognitive and speech impairments

? Diagnosis by CSF/serum PCR study along with clinical features

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? Symptomatic treatment only
? Usually two intramuscular doses of the vaccine are given 28 days apart

Chandipura virus seems to be an emerging in India
? It is transmitted among hedgehogs by mosquitoes and sandflies

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? It is characterized by high lethality in children

West Nile virus is the primary cause of arboviral encephalitis in the United

States

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? Few cases are reported from India

FEVER AND MYALGIA

? Typically begins with the abrupt onset of fever, chills, intense myalgia, and

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malaise; "influenza-like" symptoms

? The most clinically important flaviviruses that cause this syndrome are

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dengue viruses 1?4

Hantavirus syndrome: It was in 1966 that Thottapalayam

virus, the first indigenous hantavirus species was isolated.

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The Old World hantaviruses cause haemorrhagic fever

with renal syndrome (HFRS) in Asia and Europe while the

New World hantaviruses cause hantavirus

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cardiopulmonary syndrome (HCPS) in the America.



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Dengue

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Agent- Dengue Virus

? Single stranded RNA Virus

? Family: Flaviviridae

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? Genus: Flavivirus

? 4 serotypes: DENV-1, DENV-2,

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DENV-3 and DENV-4

Vector- Mosquito

?Aedes aegypti , Aedes albopictus

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?Day feeders, Recurrent biter,

Anthropophilic1

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?Fresh water mosquitoes

?White bands or scale patterns on its

legs and thorax

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Gubler Djet al. New York: CAB International; 1997. p. 1?22.

DENV- Dengue virus

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Dengue- An emerging disease

Mosquito

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Travel

Temperature

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Urbanization

Source: WHO-TDR Guidelines for diagnosis, management, prevention and control of dengue 2009

Ref: Gubler DJ, Trop Med Health. 2011 December; 39(4 Suppl): 3?11

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Dengue- Seasonal Trends

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2013-14

2014-15

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2015-16

Source: Dengue Trends, https://www.google.org/denguetrends/intl/en_us/

Man-Mosquito-Man Cycle

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Mosquito

Intrinsic incubation period

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with no

within the mosquito

dengue virus

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8-12 days

Dengue infected

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mosquito bites

Mosquito bites

healthy person and

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and gets dengue

transmits the virus

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virus in blood meal

Extrinsic incubation period

in the infected person

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3-14 days

Febrile viremia in

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a boy infected

with dengue virus

Ref: WHO and TDR, Handbook for clinical management of dengue 2012.

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Immune-pathogenesis

The Original Antigenic Sin

The First Dengue Infection

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T and B memory cells

Reinfection

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B cells- Ab production &

T cell activation

Antibody dependent enhanced

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replication

Chemical mediators

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Ag-Ab complex formation with

Cytokine

complement activation

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Mast cell mediated

Storm/Tsunami

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Deposition on various tissues,

vascular pathology

vessels and platelets

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Increased vascular

pathology

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Thrombocytopenia bleeding

Vasculopathy capillary leakage

Ref: Mongkolsapaya J et al. 2003. Nat Med 9: 921?927

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Mathew A et al. 2008. Immunol Rev 225: 300?313

Day of illness 0 1 2 3 4 5 6 7 8

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9 10

Course of Dengue

Febrile

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Critical

Recovery

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40C

Temperature

38C

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Dehydration

Reabsorption and

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Bleeding

Fluid Overload

Potential

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clinical

Shock

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problems

Organ Dysfunction

Capillary permeability

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Platelet

Laboratory

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parameters

WBC

Hematocrit

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IgM/IgG

Virology &

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Viremia

Serology

Ref: WHO-TDR Guidelines for diagnosis, management, prevention and control of dengue 2009

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Dengue Case classification (2009)

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Dengue +/- warning symptoms

Severe Dengue

1. Severe plasma

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with

leakage

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warning

2. Severe

signs

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haemorrhage

Without

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3. Severe organ

impairment

Criteria for Severe

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Criteria for Dengue +/- warning symptoms

Dengue

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Probable dengue

Severe plasma leakage

live in /travel to dengue endemic Warning signs*

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leading to:

area.

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? Abdominal pain or tenderness

? Shock (DSS)

Fever and 2 of the following

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? Persistent vomiting

? Fluid accumulation with

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criteria:

? Clinical fluid accumulation

respiratory distress

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? Nausea, vomiting

? Mucosal bleed

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? Rash

? Lethargy, restlessness

Severe bleeding as evaluated

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? Aches and pains

? Liver enlargement >2 cm

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by clinician

? Tourniquet test positive

? Laboratory: increase in HCT

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? Leukopenia

concurrent with rapid decrease

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Severe organ involvement

? Any warning sign

in platelet count

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? Liver: AST or ALT >=1000

? CNS: Impaired

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Laboratory-confirmed dengue *(requiring strict observation and

consciousness

(important when no sign of plasma

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medical intervention)

leakage)

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? Heart and other organs

DSS-Dengue shock syndrome

Ref: WHO-TDR Guidelines for diagnosis, management, prevention and control of dengue 2009

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Clinical Features

Tourniquet test

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? +ve when 10 or more petechia per

? Midpoint between SBP and 1 square inch area over forearm

DBP

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? Definite positive test with 20

petechiae or more

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? 5 minutes

SBP- systolic blood pressure

Ref: National guidelines for clinical management of Dengue ,NVBDCP, 2014.

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DBP- diastolic blood pressure


Confirming a case of Dengue

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Isolation of Virus

Up to 6 days of

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Have to process the sample

onset of illness

without delay.

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Definite test

Takes 7-10 days

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PCR

Up to 6 days of

RT-PCR, one step nested RT-

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onset of illness

PCR, NASBA, real time RT-

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PCR

ELISA and Dot blot for Up to 6 days of

EM and NS1 Ag

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onset of illness

MAC ELISA

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From day5 till day

60

IgG ELISA

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Represents past infection

Hemagglutination

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Not commonly used

Inhibition Test
Neutralisation test

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Not commonly used

Rapid diagnostic tests

For anti dengue IgM, IgG,

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NS1.high false positive

PCR- polymerase chain reaction, ELISA- Enzyme

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linked immunosorbent assay, NASBA-

Management of Dengue

Group A- Sent Home

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Group B

Group C

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(all of the following)

(any of the following)

(any of the following)

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?Getting adequate volumes of ?Has warning signs

?Severe plasma leakage

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oral fluids

?Has coexisting conditions-

leading to dengue shock

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?Passing urine at least once

diabetes mellitus, renal

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and/or fluid accumulation

every six hours

failure, pregnant, infant or

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with respiratory distress

?No warning signs

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elderly

?Severe haemorrhages

?Stable hematocrit

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?Has social circumstances:

?Severe organ impairment

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?Hemodynamically stable

Living alone or living far

(hepatic damage, renal

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away without reliable

impairment,

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methods of transport

cardiomyopathy,

encephalopathy or

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encephalitis)

1.Oral fluids- ORS, fruit

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1.Inpatient care

1.Emergency treatment with

juices

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2.Monitor Hct and

intesive care facility and

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2.Paracetamol

hemodynamic stability

blood transfusion

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3.Anticipatory guidance to

3.Use IV fluids judiciously

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2.Fluid resuscitation

caregivers

4.Correct acidosis and

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4.Follow up daily

electrolyte disturbances

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5.Serial hemograms

6.Identify Warning signs

Ref: WHO and TDR, Handbook for clinical management of dengue 2012.

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early



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Use of Hematocrit

Hematocrit should be interpreted alongside clinical condition of the

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patient

Observe closely for 24

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Vitals

No

hrs, Hct should start

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stable

requirement

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of IV fluids

to fall as plasma

leakage resolve

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Rising

Active

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Hemodynamic

Further fluid

instability

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plasma

leakage

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replacement

Hematocrit

Hemodilution

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Reduce IV fluids in a

Vitals

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?Reabsorption

stepwise manner to

stable

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of extravasated

prevent pulmonary

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fluids

edema

Falling

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Immediate

Hemodynamic

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Major

instability

Hemorrhage

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blood

transfusion

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Ref: WHO and TDR, Handbook for clinical management of dengue 2012.

IV Fluids

? When to start?

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? In critical phase for 24-48 hrs
? In presence of features of shock
? In febrile phase if oral fluids are insufficient

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? What fluids to be used?

? Isotonic solutions like Ringer lactate and Normal saline
? Colloids used to restore blood pressure immediately

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? Which IV fluids to be avoided?

? Hypotonic saline, FFP, Dextrose solution, albumin solutions

? How much fluids to give and how fast?

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? Compensated shock: 5 to 10 ml/kg over one hour
? Hypotensive shock: 10 to 20 ml/kg over 15-30 minutes
? Maintenance fluids according to Holliday- Segar formula

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? 4ml/kg/hour for first 10 kg body weight
? 2ml/kg/hour for next 10 kg body weight
? 1ml/kg/hour for onward each kg body weight

Ref: WHO and TDR, Handbook for clinical management of dengue 2012.

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FFP- Fresh frozen plasma



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Discharge criteria

? All of the following conditions must be present:

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? Clinical

? No fever for 48 hours

? Improvement in clinical status (general well-being, appetite,

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haemodynamic status, urine output)

? No respiratory distress

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? Laboratory

? Increasing trend of platelet count

? Stable haematocrit without intravenous fluids

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Fever patient with history, symptoms and signs

of Dengue

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Natural course of Dengue fever- Temperature,

Potential clinical problems, Lab parameters,

Virology/ Serology

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Criteria for Dengue: Confirm the case, ?Warning

signs and coexisting conditions

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Classify into Groups A, B, C for management

Management according to protocol

IV fluids <48hrs

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Dengue Vaccine

? Most promising candidate is CYD-TDV vaccine/Dengvaxia

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? Approval by WHO in Dec 2015

? Each engineered to express surface envelope and membrane proteins of 4

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serotypes of dengue virus

? Administered as 3 doses (0/1/6 months)

? Striking benefit of reduction in hospitalizations among children > 9 years of age

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? Short term safety profile encouraging

? Recently withdrawn from Philippines after 14 children death

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Cure for Dengue?
THANK YOU