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