Assist Prof Microbiology
Dr. Syed Yousaf Kazmi
LEARNING OBJECTIVES
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1. List the causes of encephalitis and meningo-encephalitis
2. Discuss pathogenesis of HSV encephalitis, rabies
encephalitis and Primary Amoebic meningoencephalitis
3. Explain mechanism of transmission of HSV, rabies and
Primary Amoebic meningoencephalitis
4. Discuss laboratory diagnosis of rabies encephalitis and
meningo-encephalitis
5. Explain the role of immunization in primary and
secondary prevention in rabies encephalitis
ENCEPHALITIS & MENINGOENCEPHALITIS-ETIOLOGY
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FAMILY
EXAMPLES
DISEASE
Herpesvirus
Herpes simplex virus 1 &2 Herpes virus encephalitis
Enterovirus
Enterovirus
Viral Encephalitis
Retroviruses
HIV
HIV Dementia
Arboviruses
West Nile virus, St Louis
Encephalitis
Rhabdoviridea
Rhabdovirus
Rabies encephalitis
Protozoa
Naegleria fowleri,
Acanthamoeba
Primary amoebic
meningo-encephalitis
Others
Measles, Mumps, Rubella,
Polio, Influenza ,VZV
Post infectious encephalitis
Bacterial causes
Syphilis, Mycobacterium,
Lyme disease
Bacterial encephalitis
HERPES SIMPLEX
INTRODUCTION
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HSV 1 & 2 belongs to Herpes virus (DNA Virus)
Sexually Transmitted Infection usually
HSV1 usually above waist (gingivo-stomatitis, keratitis,
encephalitis) while HSV2 below waist(genital herpes)
Notorious for Latent Infection
Genome in human DNA in sensory ganglion
Primary infection & Recurrent illness
Herpes labialis very common recurrent disease
HERPES SIMPLEX ENCEPHALITIS
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 TRANSMISSION
 Through saliva, skin blisters,
genital sores
 Active lesions important
 Asymptomatic virus shredding
also common
 Sexual as well as intimate contact
e.g. kissing on skin with herpes
lesion
Herpes labialis
HERPES SIMPLEX
ENCEPHALITIS
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 PATHOGENESIS
 Virus multiplies in skin/
mucous membrane
 Migrates up the neuron by
retrograde axonal flow
 Becomes latent in sensory
nerve ganglion (usually
Trigeminal ganglion)
 Viral DNA in cytoplasm of
ganglion during latency
HERPES SIMPLEX
ENCEPHALITIS
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 Reactivation factors-sunlight,
hormonal changes (e.g.
menstruation), trauma, stress, and
fever
 Reactivation-viral particles migrate
down neuron and produce skin
lesions
 In certain cases, virus enters brain
during reactivation period producing
encephalitis
 Primary infection can directly infect
brain producing encephalitis
HERPES SIMPLEX
ENCEPHALITIS
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HSV encephalitis is very severe illness
Diagnosis is aided by past history of HSV infection or
active lesion
CSF findings are same as viral meningitis except 10–500
RBCs/mm3
PCR for HSV RNA in CSF is positive
High mortality rate and severe neurological damage in
survivor
RABIES
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Rabies is caused by Enveloped RNA Virus
Rhabdoviridea family, Lyssavirus genus
Single antigenic type
Extremely sensitive to sunlight, uv light, heat, lipid
solvents (e.g., ether), alcohol, detergents, soap
 Sylvatic cycle-foxes, coyotes, wolves, skunks,
raccoons, opossums, hyaena, dogs, cats etc. and bats
 Urban cycle-dogs, cats, monkeys, camel, horses, etc.




RABIES-TRANSMISSION
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 All warm blooded animals including humans can be
infected
 Virus is present in saliva of animal with rabies
 Encephalitis affects limbic system-emotionally
unstable- important in transmission of disease
 Rabid animal bites unprovoked
 Virus transmitted through wound via saliva
 Also transmitted by organ transplants e.g. cornea,
kidney etc.
RABIES-PATHOGENESIS
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 Binds Acetylcholine receptor
 Multiplies in muscle/ connective tissue locally
 Enters sensory nerves-moves by axonal transport to
the central nervous system
 Sheltered from immune system
 Encephalitis –diffuse demyelination and neuron
death- Negri bodies
 Travels down the peripheral nerves to salivary
gland, kidney, heart etc.
RABIES-PATHOGENESIS
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 Incubation period is variable (2 -16 weeks or >)
 Bites on face/ head, children, multiple deep wounds
short incubation period
 nonspecific symptoms such as fever, anorexia, and
changes in sensation at the bite site
 confusion, lethargy, and increased salivation develop
 Hydrophobia-painful spasm of throat muscles
 Emotional, violent, aggressive, hellucination
 Death is inevitable once symptoms of rabies develop
RABIES-LAB DIAGNOSIS
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RABIES ANTIGENS OR NUCLEIC ACIDS
 Immunofluorescence or
immunoperoxidase staining
 Biopsy specimen -skin of the neck at the
hairline
 Impression preparations of brain or
cornea tissue
 Negri bodies in the brain-80% positivity
 RT-PCR test on brain tissue specimen
Negri Body
VIRAL ISOLATION
 tissue is inoculated intra-cerebrally into
suckling mice
SEROLOGY
 Serum/ CSF anti-rabies Ab by
immunofluorescence
ANIMAL OBSERVATION
Rabies
immunofluorescence test
RABIES-PROPHYLAXIS
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PRE-EXPOSURE PROPHYLAXIS
 HDCV (Human Diploid Cell Vaccine) Inactivated virus
 High-risk groups e.g. Veterinarians, Zookeepers, and
Travelers to areas of hyper-endemic infection
 Three doses given on days 0, 7, and 21 or 28
POST EXPOSURE PROPHYLAXIS
 After person is exposed to virus
 Thorough cleaning of wound by soap/ detergent/ alcohol/
povidon iodine etc. THIS MAY BE LIFE SAVING ACT
RABIES-PROPHYLAXIS
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 HDCV given in Deltoid region, anterolateral thigh but never in
gluteal region
 Intramuscular/ Intradermal routes
 0,3,7,21,28 (optional at 90 day)
 Antibody titers checked for efficacy
RABIES IMMUNE GLOBULIN, HUMAN (HRIG)
 The nature of the biting animal, the availability of the
animal for laboratory examination, the existence of rabies
in the area, the manner of attack (provoked or
unprovoked), severity of the bite
 20 IU/kg, half infiltrated around wound and half I/M
SHORT MOVIE
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PRIMARY AMOEBIC
MENINGO-ENCEPHALITIS
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 Free living ameoba-Naegleria fowleri, Acanthamoeba
 Fresh water, lakes, ponds, un-chlorinated swimming
pools, other warm water sources
 Do not require any human/ animal host for completion of
life cycle
 Human infection is accidental
 Rare but serious disease of meninges and brain
 Around and more than 90 % fatal even with timely
diagnosis and treatment
PRIMARY AMOEBIC
MENINGO-ENCEPHALITIS
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TRANSMISSION
 Swimming, diving, other sports
activity in fresh water of ponds,
lakes etc.
 Trophozoites/ flaggellate form
in fresh warm water
 World wide distribution
 Young immuno-competent
individuals
 Forceful entry of water in
nostrils
 No human to human cases
PRIMARY AMOEBIC
MENINGO-ENCEPHALITIS
PATHOGENESIS

 Amoeba enters nose and through
cribriform plate pass into brain
 Very thin bone
 Causes meningo-encephalitis
 Brain oedema
 Brain pathology is indistinguishable
from other encephalitis/ meningitis
PRIMARY AMOEBIC
MENINGO-ENCEPHALITIS
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LABORATORY DIAGNOSIS
 Clinical suspicion very important
 CSF findings may be equivocal or
similar to other cases of bacterial/
viral meningitis
 Cells may be Neutrophils and
lymphocytes/ monocytes
 Trophozoites might be read as
monocytes by electronic counter
 Fresh CSF wet film examination
will show motile trophozoites/
flagellate form
Wet film exam of CSF
showing Naegleria
SHORT VIDEO
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