PATHOGENESIS

AND
CLINICAL MANIFESTATIONS
OF MENINGITIS
- By Prachi Tete
Batch 2017
ETIOLOGICAL CLASSIFICATION
 ROUTES OF INFECTION

Hematogenous Anatomical defect

(CNS)
• Entry through choroid plexus of
other vessels of brain • Surgery (CSF shunts), trauma,
• Most common congenital defects

Direct spread Direct intraneural

spread
• Infected site close to meninges
(Otitis media, sinusitis, • Through nerves
mastoiditis, etc) • HSV, Rabies virus
 PREDISPOSING FACTORS :
HOST AND MICROBIAL FACTORS
AGE VACCINATION HIGH RISK GROUPS

• Neonates : highest • Children and infants

• Hib vaccines
prevalence • Pregnant women
• Immature immune • HIV/AIDS patients
system; permeability • Significant reduction
in incidence of H. • Immunocompromised
of BBB patients
influenzae meningitis
• Acquiring the • Frequent travelers,
colonized organisms migrants
from mother's birth • Meningococcal,
canal Pneumococcal
• (e.g. Listeria or Group vaccines
B Streptococcus)
■ Group setting: College campuses have reported
outbreaks of meningococcal disease, caused by N.
meningitidis.

■ Working with meningitis-causing pathogens:

Microbiologists routinely exposed to meningitis-causing
bacteria are at increased risk for meningitis.
Predisposing Factors…
■ Breach in blood brain barrier : organisms can enter through by
– Disruption of tight junctions
– Transport within → circulatory phagocytes and endothelial
cell vacuoles

■ Presence of CSF shunts : colonization and direct pathogen entry.

■ Microbial virulence factors : some common virulence factors

Factor Function
Capsular polysaccharide Antiphagocytic
IgA proteases Epithelial attachment; destroys
secretory IgA
Lipoteichoic acid Causes inflammation
Adhesion Adhesins and pili
Predisposing factors…
■ Factors promoting primary site infection:
– respiratory tract → the primary portal of entry.
↑RTI = ↑ meningitis incidence
– E.g. alcoholism, diabetes, immunosuppression,
splenectomy, etc.
 PATHOGENESIS
Enter body via:
Bacteria/virus - Nasopharynx Attach to
/ - Anatomical defect
mucosal Disrupt BBB;
fungi/parasite surface Invade meninges
- Other sources of
infection

Cerebral edema, Entry of blood Induce

CSF protein,
components in Vascular pathophysiolo
subarachnoid leakage gical changes
Glucose WBC space
in CSF

Neurological
Intracranial Ischemia dysfunction&
Hypertension injury
 F
1. Host acquires new organism (nasopharyngeal route mc)
• systemic invasion and development of a high-grade
bacteraemia.

2. Primary viremia or bacteremia

• introduces the virus or bacteria to the reticuloendothelial
organs.

3. Evasion of host immune response

• inhibiting neutrophil phagocytosis
• resisting classic complement-mediated bactericidal
activity.
4. Secondary bacteraemia/viremia and then CNS invasion
occurs.

5. Local immune response

• Production and/or release of virulence factors takes places
• stimulation of formation of inflammatory cytokines

6. Increased vascular permeability

• Allows protein and neutrophils to move into the
subarachnoid space.
• lymphocytes in case of viral and fungal; and eosinophils in
7. Intense subarachnoid space inflammatory response,
• Oozing of fluid exudate, inflammatory cells,
• Neutrophils migrate from capillaries → release toxins
• TNF-a and IL-β1 → activate macrophages and endothelial cells

8. Cerebral edema Increased ICP

9. Vasculitis bleeding and thromboses

• Hemorrhage andInfarction
10.Obstruction of CSF flow
• exudate formation can lead to obstruction and
hydrocephalous
• This in turn can lead to herniation of brain stem

11. Finally neuronal damage leading to their

degeneration
 CLINICAL
MANIFESTATIONS
Fever
Important symptoms Important Signs

• High grade fever • Neck rigidity

CLASSICA
• Vomiting • Kernig’s sign L TRIAD
(projectile)
• Intense headache • Brudzinski’s sign
Nuchal Altered
mental
• Photophobia/ rigidity status
Phonophobia
Associated
symptoms
• Rash,
• Sore throat,
• Swollen glands,
• Genitourinary
symptoms
Signs and symptoms:
INFANTS

■ Non-specific complaints ■ Brudzinski’s sign

(Fever, Nausea and ■ Kernig's sign
vomiting)
■ Bulging fontanelle
■ Lethargic, sleepy (raised ICP)
■ Irritability ■ Nuchal rigidity
■ Poor feeding ■ Altered mental status
Bulging fontanelle
Positive Kernig’s and Brudzinski's Signs
i.e., Meningismus (stiff neck + Brudzinski + Kernig signs)
Overview of Symptoms by Organs Affected
Signs and symptoms : Onset of
symptoms
■ Acute (<1 day)- common with S. pneumoniae and N.
meningitides

■ Subacute (2-3 days)- preceding URI like symptoms more

common with H. influenzae, other pathogens.

■ Chronic (symptoms evolving over more than one week) –

usually in immunocompromised, eg. Mycoplasma
tuberculosis
 Haemophilus influenzae Meningitis
• Occurs mostly in unvaccinated children
(6 months to 6 years)

• Gram-negative aerobic bacteria, normal

throat microbiota.

• Capsule antigen type b

• Prevented by Hib vaccine

Neisseria meningitidis Meningitis
■ Gram-negative aerobic cocci,
capsule

■ 10% of people are healthy

nasopharyngeal carriers

■ Begins as throat infection, rash.

■ Vaccination recommended for

college students.
Streptococcus pneumoniae Meningitis
■ in children and unvaccinated
adolescents and young adults;
■ Most common in children (1 month to 4
years)
■ Gram-positive diplococci
■ 70% of people are healthy
nasopharyngeal carriers
■ Prevented by vaccination
■ S. pneumoniae is found in recurrent
meningitis in patients with basilar skull
fractures.
Viral meningitis
■ Incubation period : 3 to 6 days (enterovirus)
: 2 to 15 days
(arbovirus)

■ Common in young children

(<5 years; incidence decreases with age)

■ Although most cases are self limiting

(approx. 7 to 10 days), morbidity may be
considerable
Viral meningitis…

■ In the absence of associated encephalitis, the

prognosis is usually good

■ Bacterial and viral meningitis cannot reliably be

differentiated clinically, lab tests on CSF
required.
A 32 year old woman presented with a three day history of headache, fever, and photophobia. She had perianal
tenderness, and her boyfriend had noticed a rash. On examination, unilateral herpetic lesions were seen.
Cerebrospinal fluid showed mononuclear pleocytosis (67×10^6/l) and protein 1.2 g/l and was positive for varicella
zoster virus DNA. She received oral valaciclovir 1 g eight hourly for seven days and opiates for severe headache.
Her symptoms gradually resolved over three weeks.

zoster associated with varicella zoster virus meningitis

Viral meningitis
■ Enterovirus (most common) ■ Measles virus
– Echovirus, Coxsackie ■ Influenza virus
virus
■ Arboviruses, such as West Nile
■ Mumps virus virus
■ Herpesviruses, ■ Lymphocytic choriomeningitis
– including Epstein-Barr virus
virus, herpes simplex
viruses, and varicella-
zoster virus
– can cause recurring
meningitis
complications
■ Hearing loss ■ Brain abscess
■ Due to raised ICP ■ Neurological deficits
– Herniation  Problems with
– hydrocephaly memory and
concentration;
■ Recurrent seizures
 Problems with
■ Vision loss movement and
■ Subdural effusion balance
(pressure effects)
Misc.
■ Gram-negative bacilli cause meningitis in
– acute head trauma and
– neurosurgical patients and neonates (encapsulated E
coli).

■ Mycobacterium tuberculosis can have a slow onset (chronic;

>7 days) in immunologically normal persons but progresses
more rapidly (subacute) in immunosuppressed persons such
as AIDS patients.

■ Naegleria species (free-living amoebas) occasionally cause

meningitis in persons with a recent history of swimming in
warm fresh water.