INFECTIONS OF THE EYES AND THE

CENTRAL NERVOUS SYSTEM

JOAN E. CERRADA, M.D.

MICROBIOLOGY
The Blood-Brain barrier
The blood barrier is
created by the tight
apposition of
endothelial cells lining
blood vessels in the
brain preventing easy
passage of large
macromolecules and
pathogens between the
circulation and the brain
The Blood-CSF Barrier
The blood—CSF
barrier is at the
choroid plexus
epithelial cells,
which are joined
together by tight
junctions.
Microvilli are
present on the
CSF-facing surface
• Blood—CSF barrier. The capillaries in the choroid plexus differ
from those of the brain in that there is free movement of
molecules across the endothelial cell through fenestrations
and intercellular gaps. The blood—CSF barrier is at the
choroid plexus epithelial cells, which are joined together by
tight junctions. Microvilli are present on the CSF-facing
surface. These greatly increase the surface area of the apical
membrane and may aid in fluid secretion. Diffusion,
facilitated diffusion and active transport into CSF, as well as
active transport of metabolites from CSF to blood, have been
demonstrated in the choroid plexus.
• From: Blood—Cerebrospinal Fluid Barrier
 INVASION OF THE CENTRAL NERVOUS SYSTEM

• Blood-borne invasion Blood-borne infections:

-Across the BBB = encephalitis
• Invasion via peripheral
nerves -Across the blood-csf barrier =
Invasion via peripheral nerves: meningitis
-Herpes simplex
-VZV
-Rabies

Blood-borne infections: organisms can traverse the barriers by

1. Growing across, infecting the cells that comprise the barriers
2. Being passively transported across the intracellular vacuoles
3. Carried across by infected white blood cells
The response to invasion: CSF changes
cells /uL Protein Glucose Causes
(mg/dl) (mg/dl)

Normal 0-5 15-45 45-85

Septic 200-20,000 High <45 Bacterial
Mainly (>100) meningitis
neutrophils Brain abscess
(bacterial/amebi
c)

Aseptic 100-1000 Mod. High Normal** Viruses

Mainly (50-100) TB
mononuclears Leptospira
Fungi
Partially-treated
bacterial
meningitis

** low (<45) in TB, fungi, leptospira

 INFECTIONS OF THE CNS
• Meningitis
• Encephalomyelitis
• Brain Abscess
• Slow virus infections
BACTERIAL MENINGITIS
 BACTERIAL MENINGITIS
• Neisseria meningitidis
• Haemophilus influenzae
• Streptococcus pneumoniae
• Escherichia coli
• Group B streptococci
• Listeria monocytogenes
 BACTERIAL MENINGITIS
• Neisseria meningitidis
– Meningococcal meningitis
– Gram-negative diplococci
– Presence of polysaccharide capsule
– May be carried asymptomatically in up to 20%
of the population (nasopharynx)
– Person-to-person spread by droplet infection
 BACTERIAL MENINGITIS
• Neisseria meningitidis clinical features
– IP = 1-3 days
– Sudden onset headache, sore throat, fever
followed by drowsiness, irritability with neck
stiffness
– Hemorrhagic rash
– In 1/3 of patients: fulminating infection with DIC,
endotoxemia, shock and renal failure
– Most severe cases: Addisonian crisis: bleeding
into the brain and adrenals (Waterhouse-
Friederichsen syndrome)
– MR = 100% if untreated; 10% if treated
 BACTERIAL MENINGITIS
• Neisseria meningitidis diagnosis
– Clinical
– Culture of blood and CSF; CSF gram staining
 BACTERIAL MENINGITIS
• Neisseria meningitidis treatment
– Medical emergency
– Appropriate antibiotics:
• Penicillin
• Ampicillin
• Ceftriaxone
• Chloramphenicol
• Cefotaxime
 BACTERIAL MENINGITIS
• Neisseria meningitidis prevention
– Primary vaccination (polysaccharide vaccine;
poor protection against group B)
– Prophylaxis for close contacts only
• Rifampicin
• Ciprofloxacin
 BACTERIAL MENINGITIS
• Haemophilus influenzae
– Gram negative coccobacilli
– Serotype a to f
– Serotype b most significantly causes disease
 BACTERIAL MENINGITIS
• Haemophilus influenzae clinical features
– IP: 5-6 days
– Insiduous in onset
– Serious sequelae: hearing loss, delayed
speech, mental retardation, seizures
 BACTERIAL MENINGITIS
• Haemophilus influenzae diagnosis
– CSF gram staining and culture
– blood culture
 BACTERIAL MENINGITIS
• Haemophilus influenzae treatment and
prevention
– Hib vaccination
– Appropriate antibiotics for treatment:
• Ampicillin
• Chloramphenicol
• Cefotaxime
• Ceftriaxone
 BACTERIAL MENINGITIS
– Streptococcus pneumoniae
• Encapsulated gram-positive cocci
• More common in the very young and the elderly,
those with sickle cell disease, head trauma and
asplenia
 BACTERIAL MENINGITIS
– Streptococcus pneumoniae clinical features
• Acute onset
• May follow pneumonia in the elderly
 BACTERIAL MENINGITIS
– Streptococcus pneumoniae treatment and
prevention
• Pneumococcal vaccine (?)
– Appropriate antibiotics for treatment:
• Penicillin
• Ampicillin
• Chloramphenicol
• Cefotaxime
• Ceftriaxone
 BACTERIAL MENINGITIS

VIRULENCE N. H. S.
FACTORS meningitidis influenzae pneumoniae
Capsule + + +
IgA protease + + +
Pili + + -
Endotoxin + + -
OMPs ? + -
 BACTERIAL MENINGITIS
• Listeria monocytogenes
– Gram positive coccobacilli
– Important cause of meningitis in
immunocompromised adults
– Diagnosis:
• Gram staining CSF and culture
– Treatment:
• Ampicillin + Gentamycin
• PCN + Gentamycin
 BACTERIAL MENINGITIS
• Group B streptococci and E. coli
– Common causes of neonatal meningitis
– High incidence of complications/sequelae
TUBERCULOUS MENINGITIS
 TUBERCULOUS MENINGITIS
• Mycobacterium tuberculosis
– Associated with miliary TB in >50% of cases
– Gradual onset of generalized illness and fever
– Later with neck stiffness and impairment of
consciousness
– Diagnosis
• CSF AFB smear, TB culture, TB PCR
– Treatment
• 2HRZE/12HR or more
FUNGAL MENINGITIS
 FUNGAL MENINGITIS
• Cryptococcus neoformans
– Occurs in those with depressed cell-mediated
immunity
– Insiduous onset of signs and symptoms:
headaches and behavioral change common
– Diagnosis: india ink CSF; CALAS CSF
– Treatment: Amphotericin B + Flucytosine

Lungs  blood  brain = meningitis

 FUNGAL MENINGITIS
– Coccidioides immitis
• Same signs and symptoms as in Cryptococcal
meningitis
• Diagnosis: CF serum
• Treatment: Amphotericin B

Lungs  blood  brain = meningitis

PROTOZOAL MENINGITIS
 PROTOZOAL MENINGITIS
– Naegleria or Hartmanella sp
• Can multiply in stagnant fresh waters
• Reach the meninges via the olfactory tract and
cribriform plate
• High mortality rate
VIRAL MENINGITIS
 VIRAL MENINGITIS
• The commonest type of meningitis
• Milder disease than bacterial meningitis
• Headache, fever with less neck stiffness
 VIRAL MENINGITIS
VIRUS VIRUS GROUP COMMENTS
Herpes simplex Alpha herpes virus Uncommon
Mumps Paramyxovirus Common
complication
Lymphocytic Arenavirus Uncommon
choriomeningitis
Polio, coxsackie Picornavirus Common
Japanese Togavirus India, SE Asia,
encephalitis Japan
E and W equine Togavirus E and W USA
encephalitis
VIRAL ENCEPHALITIS
 VIRAL ENCEPHALITIS
• Abnormal behaviour, seizures, altered
consciousness, often with nausea, vomiting
and fever
• Causes:
– Herpes simplex
– Poliovirus
– Mumps
– Rabies
– Togaviruses
– HIV
 VIRAL ENCEPHALITIS
• Herpes simplex
– Commonest cause of severe sporadic
encephalitis
– In adults, it is due to virus reactivation in the
trigeminal ganglia to the temporal lobe of the
brain
– Skin lesions may be present
– Diagnosis is indicated by signs and symptoms of
a space occupying lesion in the temporal lobe
– 70% MR in untreated patients
– Diagnosis: brain scan/CT scan
– Treatment: Acyclovir
 VIRAL ENCEPHALITIS
• Poliovirus
– Initial 1-4 days fever, sore throat malaise followed
by CNS involvement,
motor neuron involvement
then paralysis
– Common sequela:
paralysis of 1 leg of 1 leg
– Prevention: poliovirus
vaccine (OPV)
 VIRAL ENCEPHALITIS
• Mumps virus:
– Common cause of mild encephalitis
– Often seen without parotitis
– Treatment: supportive
 VIRAL ENCEPHALITIS
• Rabies
– Rhabdovirus: bullet-shaped single-stranded RNA
virus
– Excreted in sliva of dogs, cats, foxes, some bats
and transmitted via bite or contamination of
mucosa
– Can infect all warm-blooded animals
– IP: 4-13 weeks (may be as long as 6 months
– The virus travels up peripheral nerves. The
farther the bite from the CNS, the longer is the
incubation period
 VIRAL ENCEPHALITIS
• Rabies
– Pathogenesis:
• The virus travels up the axons of motor and
sensory neurons
• Once in the brain, the virus travels from cell to cell
with little cytopathic effect
• Dysfunction of the infected cells
• Virus invasion of the limbic system = bahavioral
change
 VIRAL ENCEPHALITIS
• Rabies
– Diagnosis:
• Clinical
• Detection of viral antigen by IF on skin biopsies,
corneal impression smears, brain biopsy =
intracytoplasmic inclusions (Negri bodies)
– Clinical manifestations:
• Sore throat, headache, fever, discomfort at site of bite
• Hydrophobia and aerophobia
• Patient becomes excited with muscle spasms and
convulsions
• fatal
 VIRAL ENCEPHALITIS
• Rabies
– Treatment and prevention:
• Supportive
• Preventive wound management
 VIRAL ENCEPHALITIS
• Togaviruses
– Western equine encephalitis
– St. Louis encephalitis
– Japanese encephalitis
 VIRAL ENCEPHALITIS
• Japanese encephalitis
– Japanese encephalitis virus (JEV), a flavivirus
(single-stranded ribonucleic acid RNA),
represents the most significant etiology of
arboviral encephalitis worldwide.
– spread throughout mostly rural areas of Asia
by culicine mosquitoes, most often Culex
tritaeniorhynchus
 VIRAL ENCEPHALITIS
• Japanese encephalitis
– attachment of the Japanese encephalitis virus
(JEV) to a host cell membrane  local
membrane disruption  entry of the virus into the
cell
– viremia develops  inflammatory changes in the
heart, lungs, liver, and reticuloendothelial system
– Most infections are cleared before the virus can
invade the central nervous system (CNS), leading
to subclinical disease.
 VIRAL ENCEPHALITIS
• Japanese encephalitis
– Due to the neurotropic character of JEV,
neurologic invasion can develop, possibly by
growth of the virus across vascular endothelial
cells, leading to involvement of large areas of the
brain, including the thalamus, basal ganglia, brain
stem, cerebellum (especially the destruction of
the cerebellar Purkinje cells), hippocampus, and
cerebral cortex.
– Persistent infection and congenital transmission
may occur.
 VIRAL ENCEPHALITIS
• Japanese encephalitis
– transmitted to humans via the bite of infected
Culex mosquitoes: They prefer to bite outdoors
and are extremely active in the evening and night,
when the risk of infection is greatest
– Mosquitoes breed in collections of water (typically
rice paddies), increasing the risk of infection in
rural areas.
– Humans and other mammals (eg, horses) are
end hosts (low-grade, short-term viremia).
 VIRAL ENCEPHALITIS
• Japanese encephalitis
– Pigs and aquatic birds (eg, egrets, herons) serve as
amplifying hosts. They develop persistent, high-grade
viremia and represent the main vertebrate hosts as
the principal reservoir for the virus.
– There are 4 main genotypic variants :
• JEV type I isolates have been ideentified in China, India,
Japan, Nepal, Sri Lanka, Taiwan, and Vietnam
• JEV type II isolates have been identified in Cambodia and
northern Thailand
• JEV type III isolates have been identified in Indonesia,
Malaysia, and southern Thailand; this genotype appears to
have had the greatest spread
• JEV type IV isolates were also identified in the Indonesian
and Malaysian regions
 VIRAL ENCEPHALITIS
• Japanese encephalitis
– The virus initially propagates at the site of the bite
and in regional lymph nodes.
– Two cellular characteristics are critical to the
pathogenesis:
• (1) the M protein, that help to anchor the virus onto the
host cell
• (2) the E protein, which is the principal immunogenic
feature and which is expressed on the membrane of
infected cells. The E protein mediates membrane fusion
of the viral envelope and the cellular membrane,
promoting viral entry into the host cell.
 VIRAL ENCEPHALITIS
• Japanese encephalitis
– Only 1 per 250 Japanese encephalitis virus (JEV) infections
results in symptomatic disease.
– Proven risk factors for death include demonstration of virus in
the CSF, low levels of IgG/IgM in the CSF or serum, and a
decreased sensorium.
– Approximately 33-50% of survivors of symptomatic disease
have major neurologic sequelae at 1 year, including seizure
disorders, motor or cranial nerve paresis, or movement
disorders. At 5 years, nearly 75% of such patients score lower
on standardized tests than control subjects.
– Mortality rates with intensive care capabilities are 5-10%. In
less-developed areas, mortality rates may exceed 35%.
 VIRAL ENCEPHALITIS
• Japanese encephalitis
– Clinical manifestations
• IP 6-8 days, with a range of 4-15 days
• prodromal period is characterized by fever,
headache, nausea, diarrhea, vomiting, and
myalgia, which may last for several days.
• Altered mental status follows, which can range
from mild confusion to agitation to overt coma.
Seizures develop in 66% of infected persons, most
often in children, while headache and
meningismus are more common in adults.
 VIRAL ENCEPHALITIS
• Japanese encephalitis
– Diagnosis:
• Viral isolation: tissue, blood, or CSF
• Immunoglobulin M antibody: may be found even within
7 days of symptoms.
• MRI and CT scanning: bilateral thalamic lesions with
hemorrhage; MRI being more sensitive.
• Electroencephalography: diffuse, continuous delta
slowing; a diffuse delta pattern with spikes; theta waves;
and burst suppression.
• Histologic findings: include focal neuronal degeneration
with diffuse and focal microglial proliferation and
lymphocytic perivascular cuffing in the thalamus,
substantia nigra, brain stem, hippocampus, cerebellum,
and spinal cord
• Immunoassays
 VIRAL ENCEPHALITIS
• Japanese encephalitis
– Diagnosis:
• Lumbar puncture:
– The opening pressure is usually normal but
may be raised.
– CSF protein levels are mildly elevated in most
cases, often less than 900 mg/dL
– CSF glucose levels are often normal.
– Between 10 and several hundred mononuclear
white blood cells may be observed on cell
count.
 VIRAL ENCEPHALITIS
• Japanese encephalitis
Treatment and preventive management:
supportive
Three Japanese encephalitis vaccines are used
worldwide:
1. inactivated mouse brain vaccine
(Nakayama and Beijing-1 strains)
2. inactivated primary hamster kidney cell
vaccine (P3 strains)
3. live attenuated primary hamster kidney cell
vaccine (SA14 -14-2 strain
BRAIN ABSCESS
 BRAIN ABSCESS
• Predisposing factors:
– Trauma
– Surgery
– Infection from contiguous site
– Hematogenous spread
– Embolisation
• Lumbar puncture is contraindicated
• Diagnosis: CT scan
• Treatment by surgical drainage and anti-
infectives
 BRAIN ABSCESS
INFECTIONS THAT MAY MANIFEST AS CHRONIC
MENINGITIS OR BRAIN ABSCESS
BACTERIAL
Tuberculosis Syphilis
Brucellosis Lyme Disease
Nocardiosis Actinomycosis
FUNGAL
Cryptococcosis Cossidioidomycosis
Histoplasmosis Candidiasis
Balstomycosis
PARASITIC
Tosoplasmosis
Cysticercosis
 INFECTIONS OF THE EYE
• Conjunctivitis
• Blepharitis
• Stye, Hordeolum
• Toxoplasmosis
• CMV
 INFECTIONS OF THE EYE
• Microbial invasions of the conjunctiva
– Adenovirus
– Measles
– VZV
– Enteroviruses
– Chlamydia trachomatis
– Neisseria gonorrhea
– Staphylococcus aureus
 INFECTIONS OF THE EYE
• Conjunctivitis:
– Chlamydia
– Streptococci
– Haemophilus
– Neisseria
– Staphylococci
– Pseudomonas
– Acanthamoeba
 INFECTIONS OF THE EYE
• Chlamydia trachomatis:
– Have surface molecules that bind specifically to
receptors of host cells
– Transmission: contact
– Diagnosis:
• Conjunctival fluid or scrapings examinations
 INFECTIONS OF THE EYE
• Blepharitis, Stye, Hordeolum
– Blepharitis is the inflammation that affects the eyelids,
usually involving the part where the eyelashes grow
– Blepharitis occurs when tiny oil glands located near the
base of the eyelashes malfunction
– Blepharitis is often a chronic condition that is difficult to
treat but it usually doesn't cause permanent damage to
eyesight
 INFECTIONS OF THE EYE
• Blepharitis, Stye, Hordeolum, chalazion
– Styes and chalazia are lumps in or along the edge of an eyelid
– A stye is an infection that occur along the edge of the eyelid
– When a stye occurs inside the eyelid, it is called an internal hordeolum
– A chalazion is a lump in the eyelid
• Usually the bacteria grow in the root (follicle) of an eyelash. An
internal hordeolum is caused by infection in one of the oil glands
inside the eyelid.
• A chalazion develops when an oil gland in the eyelid becomes
blocked. If an internal hordeolum doesn't drain and heal, it can turn
into a chalazion.
INFECTIONS OF THE EYE
Toxoplasmosis
– choreoretinitis
– Protozoan infection
– Serious when acquired in utero or with
immunosuppression
– Occurs by swallowing oocysts released by
infected cats
INFECTIONS OF THE EYE
Toxoplasmosis
INFECTIONS OF THE EYE
Toxoplasmosis
 INFECTIONS OF THE EYE
Toxoplasmosis
Cerebral toxoplasmosis:
Axial T1-weighted MRI scan
reveals multiple foci of high
signal in the basal ganglia
consistent with
hemorrhage.