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


Infectious diseases

4/5th Semester Classes on Infectious Diseases, 8-9AM, Tuesdays (LT-1)

Topics

1

Approach to Infectious Diseases and their prevention

2

Antibiotic stewardship practices

3

Community-Acquired Infections

4

Health Care?Associated Infections

5

Gram-Positive Bacteria (part-1)

6

Gram-Positive Bacteria (part-2)

7

Gram-Negative Bacteria (part-1)

8

Gram-Negative Bacteria (part-2)

9

Spirochetal Diseases

10

Diseases Caused by Atypical/Miscel aneous Bacterial Infections

11

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

12

Infections Due to DNA Viruses

1

13

Infections Due to RNA Viruses (part 1)

14

Infections Due to RNA Viruses (part 2)

15

HIV/AIDS ? part 1

16

HIV/AIDS ? part 2

17

Fungal Infections

18

Parasitic Infections (part 1)

19

Parasitic Infections (part 2)

20

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

Family

Common

virus

Picornaviridae

Polio

Entero

Calciviridae

Noro

Reoviridae

Rota

Orthomyxviridae

Influenza

Paramyxoviridae Measle

Mumps

Parainfluenza

Coronaviridae

SARS

MARS

Togaviridae

Rubel a

Chikungunya

Flaviviridae

Dengue

West nile

Filoviridae

Ebola

Rhabdoviridae

Rabies

Bunyaviridae

Hanta

Nairo (CCHF)

Retroviridae

HIV


RABIES

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

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

-human possibly

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

nodules called Babes nodules & Negri bodies (eosinophilic cytoplasmic

inclusions)

? Disease usually presents as atypical encephalitis with relative preservation of

consciousness

? Prodromal ? nonspecific, sometimes earliest specific neurologic symptoms that

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

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

? Autonomic dysfunction is common

and may result in hypersalivation,

gooseflesh, cardiac arrhythmia, and

priapism

? Episodes of hyperexcitability are

typical y followed by periods of

complete lucidity that become shorter

as the disease progresses

? Early brainstem involvement

(hydrophobia, aerophobia)

? In paralytic type, commonly

misdiagnosed as Guil ain-Barre

syndrome


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

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

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

from the neck, and brain tissue

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

regardless of immunization status

? Other methods: RT-PCR, Direct fluorescent antibody
? 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
? 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
? 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

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

gluteal) ? 0, 3, 7, and 14


Zoonotic viruses: Arthropod-Borne and

Rodent-Borne Virus Infections

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

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

? Intrinsic incubation, as per type of infections
? Seven families: Arenaviridae, Bunyaviridae, Flaviviridae, Orthomyxoviridae, Reoviridae,

Rhabdoviridae, and Togaviridae

? Arena and hanta viruses are rodent borne viruses
? 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
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

adenoviruses, enteroviruses, herpesviruses, and mumps virus

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

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

wrists; rarely large joints

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

rather than a maculopapular/petechial rash

? Maternal?fetal transmission has been reported
? 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
? Nonsteroidal anti-inflammatory drugs and sometimes chloroquine for refractory arthritis

ENCEPHALITIS

? Seasonal diseases, commonly occurring in the warmer months
? Japanese encephalitis is the most important viral encephalitis in

Asia

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

(attract the natural avian vertebrate hosts and provide abundant

breeding sites for mosquitoes such as Culex tritaeniorhynchus)

? Additional amplification host by pigs and horses

? Unspecific febrile presentation (nausea, vomiting, diarrhea,

cough)

? aseptic meningitis,
? meningoencephalitis,
? acute flaccid paralysis,
? severe encephalitis.
? 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
? 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
? It is characterized by high lethality in children

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

States
? Few cases are reported from India

FEVER AND MYALGIA

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

malaise; "influenza-like" symptoms

? The most clinically important flaviviruses that cause this syndrome are

dengue viruses 1?4

Hantavirus syndrome: It was in 1966 that Thottapalayam

virus, the first indigenous hantavirus species was isolated.
The Old World hantaviruses cause haemorrhagic fever

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

New World hantaviruses cause hantavirus

cardiopulmonary syndrome (HCPS) in the America.






Dengue

Agent- Dengue Virus

? Single stranded RNA Virus

? Family: Flaviviridae

? Genus: Flavivirus

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

DENV-3 and DENV-4

Vector- Mosquito

?Aedes aegypti , Aedes albopictus

?Day feeders, Recurrent biter,

Anthropophilic1

?Fresh water mosquitoes

?White bands or scale patterns on its

legs and thorax

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

DENV- Dengue virus



Dengue- An emerging disease

Mosquito

Travel

Temperature

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














Dengue- Seasonal Trends

2013-14

2014-15

2015-16

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

Man-Mosquito-Man Cycle

Mosquito

Intrinsic incubation period

with no

within the mosquito

dengue virus

8-12 days

Dengue infected

mosquito bites

Mosquito bites

healthy person and

and gets dengue

transmits the virus

virus in blood meal

Extrinsic incubation period

in the infected person

3-14 days

Febrile viremia in

a boy infected

with dengue virus

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










Immune-pathogenesis

The Original Antigenic Sin

The First Dengue Infection

T and B memory cells

Reinfection

B cells- Ab production &

T cell activation

Antibody dependent enhanced

replication

Chemical mediators

Ag-Ab complex formation with

Cytokine

complement activation

Mast cell mediated

Storm/Tsunami

Deposition on various tissues,

vascular pathology

vessels and platelets

Increased vascular

pathology

Thrombocytopenia bleeding

Vasculopathy capillary leakage

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

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

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

9 10

Course of Dengue

Febrile

Critical

Recovery

40C

Temperature

38C

Dehydration

Reabsorption and

Bleeding

Fluid Overload

Potential

clinical

Shock

problems

Organ Dysfunction

Capillary permeability

Platelet

Laboratory

parameters

WBC

Hematocrit

IgM/IgG

Virology &

Viremia

Serology

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








Dengue Case classification (2009)

Dengue +/- warning symptoms

Severe Dengue

1. Severe plasma

with

leakage

warning

2. Severe

signs

haemorrhage

Without

3. Severe organ

impairment

Criteria for Severe

Criteria for Dengue +/- warning symptoms

Dengue

Probable dengue

Severe plasma leakage

live in /travel to dengue endemic Warning signs*

leading to:

area.

? Abdominal pain or tenderness

? Shock (DSS)

Fever and 2 of the following

? Persistent vomiting

? Fluid accumulation with

criteria:

? Clinical fluid accumulation

respiratory distress

? Nausea, vomiting

? Mucosal bleed

? Rash

? Lethargy, restlessness

Severe bleeding as evaluated

? Aches and pains

? Liver enlargement >2 cm

by clinician

? Tourniquet test positive

? Laboratory: increase in HCT

? Leukopenia

concurrent with rapid decrease

Severe organ involvement

? Any warning sign

in platelet count

? Liver: AST or ALT >=1000

? CNS: Impaired

Laboratory-confirmed dengue *(requiring strict observation and

consciousness

(important when no sign of plasma

medical intervention)

leakage)

? Heart and other organs

DSS-Dengue shock syndrome

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

Clinical Features

Tourniquet test

? +ve when 10 or more petechia per

? Midpoint between SBP and 1 square inch area over forearm

DBP

? Definite positive test with 20

petechiae or more

? 5 minutes

SBP- systolic blood pressure

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

DBP- diastolic blood pressure


Confirming a case of Dengue

Isolation of Virus

Up to 6 days of

Have to process the sample

onset of illness

without delay.

Definite test

Takes 7-10 days

PCR

Up to 6 days of

RT-PCR, one step nested RT-

onset of illness

PCR, NASBA, real time RT-

PCR

ELISA and Dot blot for Up to 6 days of

EM and NS1 Ag

onset of illness

MAC ELISA

From day5 till day

60

IgG ELISA

Represents past infection

Hemagglutination

Not commonly used

Inhibition Test
Neutralisation test

Not commonly used

Rapid diagnostic tests

For anti dengue IgM, IgG,

NS1.high false positive

PCR- polymerase chain reaction, ELISA- Enzyme

linked immunosorbent assay, NASBA-

Management of Dengue

Group A- Sent Home

Group B

Group C

(all of the following)

(any of the following)

(any of the following)

?Getting adequate volumes of ?Has warning signs

?Severe plasma leakage

oral fluids

?Has coexisting conditions-

leading to dengue shock

?Passing urine at least once

diabetes mellitus, renal

and/or fluid accumulation

every six hours

failure, pregnant, infant or

with respiratory distress

?No warning signs

elderly

?Severe haemorrhages

?Stable hematocrit

?Has social circumstances:

?Severe organ impairment

?Hemodynamically stable

Living alone or living far

(hepatic damage, renal

away without reliable

impairment,

methods of transport

cardiomyopathy,

encephalopathy or

encephalitis)

1.Oral fluids- ORS, fruit

1.Inpatient care

1.Emergency treatment with

juices

2.Monitor Hct and

intesive care facility and

2.Paracetamol

hemodynamic stability

blood transfusion

3.Anticipatory guidance to

3.Use IV fluids judiciously

2.Fluid resuscitation

caregivers

4.Correct acidosis and

4.Follow up daily

electrolyte disturbances

5.Serial hemograms

6.Identify Warning signs

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

early










Use of Hematocrit

Hematocrit should be interpreted alongside clinical condition of the

patient

Observe closely for 24

Vitals

No

hrs, Hct should start

stable

requirement

of IV fluids

to fall as plasma

leakage resolve

Rising

Active

Hemodynamic

Further fluid

instability

plasma

leakage

replacement

Hematocrit

Hemodilution

Reduce IV fluids in a

Vitals

?Reabsorption

stepwise manner to

stable

of extravasated

prevent pulmonary

fluids

edema

Falling

Immediate

Hemodynamic

Major

instability

Hemorrhage

blood

transfusion

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

IV Fluids

? When to start?

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

? What fluids to be used?

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

? Which IV fluids to be avoided?

? Hypotonic saline, FFP, Dextrose solution, albumin solutions

? How much fluids to give and how fast?

? 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

? 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.

FFP- Fresh frozen plasma




Discharge criteria

? All of the following conditions must be present:

? Clinical

? No fever for 48 hours

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

haemodynamic status, urine output)

? No respiratory distress

? Laboratory

? Increasing trend of platelet count

? Stable haematocrit without intravenous fluids

Fever patient with history, symptoms and signs

of Dengue

Natural course of Dengue fever- Temperature,

Potential clinical problems, Lab parameters,

Virology/ Serology

Criteria for Dengue: Confirm the case, ?Warning

signs and coexisting conditions

Classify into Groups A, B, C for management

Management according to protocol

IV fluids <48hrs












Dengue Vaccine

? Most promising candidate is CYD-TDV vaccine/Dengvaxia

? Approval by WHO in Dec 2015

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

serotypes of dengue virus

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

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

? Short term safety profile encouraging

? Recently withdrawn from Philippines after 14 children death

Cure for Dengue?
THANK YOU

This post was last modified on 05 April 2022