Bacterial Meningitis Diagnosis

Essentials of Medical Microbiology by Apurba S Sastry © Jaypee Brothers Medical Publishers
INTRODUCTION
▰ Meningitis is a life-threatening infection of the leptomeninges (arachnoid
and pia mater) surrounding the brain and spinal cord, with involvement
of the subarachnoid space. The disease can be
▰ Caused by several pathogens including bacteria, viruses, fungi or
parasites.
▰ Highest global burden is seen with bacterial meningitis.
2

ACUTE BACTERIAL MENINGITIS
▰ Acute bacterial meningitis (also called as pyogenic meningitis), is an acute
purulent infection within the subarachnoid space. It is
▰ Characterized by elevated polymorphonuclear cells in CSF.
4

(Cont..)
▰ Agents implicated in pyogenic meningitis - vary according to the age.
▰ Overall: Streptococcus pneumoniae - most common. Other agents include
meningococcus, Streptococcus agalactiae, Listeria and Haemophilus
influenzae.
5

(Cont..)
▰ Neonates: Streptococcus agalactiae, gram-negative bacilli - Escherichia coli
and Klebsiella, and Listeria monocytogenes.
▰ Elderly (>60 years): Streptococcus agalactiae and Listeria monocytogenes.
6

PATHOGENESIS
▰ Transmitted from person-to-person through droplets of respiratory
secretions from cases or nasopharyngeal carriers.
▰ Close and prolonged contact—kissing, sneezing or coughing on someone -
with an infected person facilitate the spread of the disease.
8

Routes of Infection
▰ Hematogenous spread
▰ Direct spread from an infected site
▰ Anatomical defect in central nervous system (CNS)
9

Predisposing Factors
▰ Age: Neonates have the highest prevalence of meningitis
▰ Vaccination: Widespread vaccination is shown to reduce the incidence of
meningitis
▰ Factors that promote infection at primary site: Because respiratory tract
is the primary portal of entry for many etiological agents of meningitis
10

CLINICAL MANIFESTATIONS
▰ Average incubation period - 4 days, range 2 and 10 days.
▰ Important symptoms - fever, vomiting, intense headache, altered consciousness
and occasionally photophobia.
▰ Signs of meningism (meningeal irritation):
 Nuchal rigidity (“stiff neck”)
 Kernig’s sign
 Brudzinski’s sign
12

Signs seen in meningitis
13
A. Kernig’s sign;
B. Brudzinski’s sign.

Specimen Collection and Transport
▰ CSF - most ideal specimen for pyogenic meningitis.
▰ Blood culture - another useful specimen for culture.
▰ CSF collection: Lumbar puncture under strict aseptic conditions.
▰ It is divided into three sterile containers; one each for cell count,
biochemical analysis and bacteriological examination
15

Specimen Collection and Transport
(Cont..)
▰ CSF transport: Should be examined immediately
▰ When the bacteriological examination (culture) is required - CSF should
never be refrigerated - if a delay is expected - kept in an incubator at 37°C.
▰ For molecular diagnosis - CSF can be kept inside the freezer.
16

Cytological and Biochemical Analysis
17
Characteristics Normal individual Pyogenic meningitis Tuberculous meningitis Viral meningitis
CSF pressure (mm of
water)
Normal (50–150) Highly elevated (>180) Moderately elevated Slightly elevated/normal
Total leukocyte count
(per mm3)
0–5 100–10,000 10–500 25–500
Predominant cell type Lymphocytes Neutrophils Lymphocytes Lymphocytes
Glucose (mg%) 40–70 <40 mg/dL (decreased
to absent)
20–40 mg/dL (slightly
decreased)
Normal
Total proteins (mg%) 15–45 >45 mg/dL (usually
>250; markedly
increased)
100–500 mg/dL
(moderate to markedly
increased)
20–80 mg/dL (normal
or slightly elevated)

CSF Microscopy (Gram Staining)
18
Appearance in CSF gram stain Suggestive of
Gram-positive cocci in pair, capsulated, flame or
lanceolate-shaped
Gram-positive diplococci, flame or lanceolate-shaped
with clear halo (capsulated)
Streptococcus pneumoniae
Gram-negative diplococci, capsulated, with adjacent
sides flattened (lens or half-moon shaped)
Neisseria meningitidis
Pleomorphic gram-negative coccobacilli, capsulated Haemophilus influenzae
Gram-negative bacilli, arranged singly Escherichia coli or others
Gram-positive cocci in short chain Streptococcus agalactiae
Gram-positive short bacilli Listeria monocytogenes

Direct Antigen Detection
▰ From CSF: After centrifugation – supernatant - used for antigen detection.
Latex agglutination test - performed using latex beads coated with anti-
capsular antibodies
▰ From urine: Useful for pneumococcal meningitis.
Immunochromatographic test (ICT) - detect the C-polysaccharide antigen
of S. pneumoniae in urine
19

Culture
▰ Ideal media for bacteriological culture of CSF are enriched media like
chocolate agar and blood agar, and differential media like MacConkey agar
▰ Enriching: As the bacterial load is very low - part of the CSF - inoculated
into enriched media - blood culture bottles at the bed side (preferred) or
brain heart infusion (BHI) broth in the laboratory
20

Culture (Cont..)
▰ Blood culture can be collected in conventional blood culture bottles - BHI
broth/agar or preferably in automated blood cultures (e.g. BacT/ALERT)
▰ Culture plates (blood agar and chocolate agar) are incubated at 37°C,
preferably in candle jar (provides 5% CO2) for 48 hours
21

Culture and identification properties of common
bacterial agents of pyogenic meningitis
22
Streptococcus pneumoniae
 Culture: It produces α-hemolytic colonies on blood agar, described as
draughtsman-shaped or carrom coin appearance
 Biochemical identification: It shows bile soluble, ferments inulin and
sensitive to optochin
Neisseria meningitidis
 It produces non- hemolytic colonies on blood agar, which on smear
shows gram-negative diplococci
 Biochemical identification: Meningococci are catalase and oxidase
positive. They ferment glucose and maltose but not sucrose
 Serogrouping: Slide agglutination serogrouping (SASG) test is done to
identify the serogroups of meningococci isolates by using appropriate
antisera

bacterial agents of pyogenic meningitis (Cont..)
23
Haemophilus influenzae
 Culture: Blood agar with S. aureus streak line shows satellitism.
 Biochemical identification: Disk test for X and V factor requirement
shows growth surrounding combined XV disk
Streptococcus agalactiae
 Culture: It produces β-hemolytic colonies on blood agar, which on
smear shows gram-positive cocci in short chain
 Biochemical identification: It shows CAMP test positive and resistance
to bacitracin
 Serogrouping with group specific antisera shows Lancefield group B

bacterial agents of pyogenic meningitis (Cont..)
24
Gram-negative bacilli meningitis
 Escherichia coli and Klebsiella produce lactose-fermenting colonies on MacConkey
agar; identified by ICUT tests
 Non-fermenters: Pseudomonas is oxidase positive, whereas Acinetobacter is oxidase
negative. They produce non-lactose fermenting colonies; identified by ICUT tests
Listeria monocytogenes
 Motility: It shows tumbling type of motility at 25°C but nonmotile at 37°C (called
differential motility, which is due to temperature dependent flagella expression)
 Culture: It grows on blood agar (β-hemolytic colonies), and chocolate agar.
Note: Selective media such as PALC AM agar (containing mixture of antibiotics) may be
useful for isolation of Listeria from specimens such as food and environmental samples.

Culture (Cont..)
▰ Antimicrobial susceptibility test: done to initiate definitive antimicrobial
therapy.
▰ Sensitivity: CSF and blood cultures - take >48 hours for identification –
Sensitivity drops rapidly - prior antimicrobial therapy or delay in processing
▰ Rapid diagnostic tests: antigen detection or molecular test - considered to
determine the bacterial etiology of pyogenic meningitis.
25

Serology
▰ Antibodies to capsular antigens of meningococci - detected in patient’s
serum by ELISA.
▰ Useful to study sero prevalence and to know the response to vaccination;
not for diagnosis.
26

Molecular Methods
▰ Molecular tests - highly sensitive, detect even few bacteria in CSF with less
turnaround time than culture and also help in serogroup identification.
▰ Multiplex PCR and multiplex real-time PCR.
▰ BioFire FilmArray
27

Treatment of Pyogenic meningitis
▰ The mortality of pyogenic meningitis is very high (~20% for pneumococci)
and among the survivors, up to 50% develop complications - treatment
should be initiated as early as possible.
▰ The choice of antimicrobial agent - based on the type of organism
suspected and good CSF penetration ability of the agent
28

(Cont.. )
▰ Empirical therapy comprises of:
▰ Adult: IV cefotaxime or ceftriaxone and vancomycin. If Listeria is
suspected, IV ampicillin - added to the regimen
▰ For neonates: IV ampicillin plus gentamicin
▰ IV dexamethasone - added to the regimen to reduce intracranial pressure.
29

(Cont.. )
▰ Definitive therapy:
▰ After the culture report is available - empirical therapy is modified based
on the organism isolated and its antimicrobial susceptibility pattern
30

AGENTS OF PYOGENIC
MENINGITIS
31

Pneumococcal Meningitis
▰ Streptococcus pneumoniae (or pneumococcus) - leading cause of
meningitis in adults (>20 years of age),
▰ Also the most common agent of pneumonia.
▰ Present as commensals in human nasopharynx - spread locally to cause
otitis media or pneumonia – bloodstream to distant sites - invasive
pneumococcal disease - bacteremia and meningitis
32

Pneumococcal Meningitis (Cont..)
▰ Principle virulence factors – capsular polysaccharide, C-carbohydrate
antigen, pneumolysin and autolysin.
▰ Risk factors: Underlying pneumococcal pneumonia (most important) or
otitis media, alcoholism, diabetes, splenectomy, complement deficiency,
hypogammaglobulinemia, and head trauma
33

Meningococcal Meningitis
▰ Caused by Neisseria meningitidis
(or meningococcus) - capsulated
gram-negative diplococci with
adjacent sides flattened
(lens-shaped/half-moon shaped)
34

Meningococcal Meningitis (Cont..)
▰ N. gonorrhoeae - causes gonorrhea.
▰ Other species are commensals of the genital tract or oral cavity - N.
lactamica, N. flavescens, N. mucosa, N. sicca, N. subflava, etc.; although
they can be occasionally pathogenic to humans.
35

Differences between Neisseria meningitidis and
Neisseria gonorrhoeae
36
N. meningitidis N. gonorrhoeae
Capsulated Noncapsulated
Lens-shaped/half moon-shaped
(diplococci with adjacent sides flattened)
Kidney-shaped (diplococci with
adjacent sides concave)
Ferments glucose and maltose Ferments only glucose
Rarely have plasmids Usually possess plasmids, coding
for drug-resistant genes
Exist in both intra- and
extracellular forms
Predominantly exist in
intracellular form
Habitat—nasopharynx Habitat—genital tract (urethra,
cervix), rarely pharynx

Virulence Factors
Capsular Polysaccharide:
▰ 13 serogroups - A, B, C, X, Y & W135 - account for the majority of cases of
invasive disease.
▰ Other capsular serogroups and noncapsulated meningococci - commonly
colonize the nasopharynx of asymptomatic carriers
37

Pathogenesis
▰ Source – Only Humans, nasopharyngeal carriers (mainly children) – MC
▰ Mode of transmission- droplet inhalation
 portal of entry - nasopharynx
38

Pathogenesis (Cont..)
▰ Spread of infection from nasopharynx to meninges
 Hematogenous route causing septicemia (most common)
 Direct spread along olfactory nerve through cribriform plate
 Through conjunctiva - rare
39

Clinical Manifestations
▰ Rashes: A non-blanching rash (petechial or purpuric) – 80%
▰ Septicemia - endotoxin induced endothelial injury - increased vascular
permeability and intravascular thrombosis
▰ Waterhouse–Friderichsen syndrome - fulminant meningococcemia - large
purpuric rashes, shock, DIC, bilateral adrenal hemorrhage and multiorgan
failure
40

Clinical Manifestations (Cont..)
▰ Pyogenic meningitis
 3–5 years of age - fever, vomiting, headache, neck
▰ Chronic meningococcemia – rare - repeated episodes of petechial rash,
fever, arthritis, and splenomegaly
▰ Postmeningococcal reactive disease - Immune complexes develop 4–10
days later - arthritis, rash, iritis, pericarditis, polyserositis, and fever
41

Treatment of Meningococcal meningitis
▰ Third-generation cephalosporins – DOC
▰ Penicillin can also be given; however, reduced sensitivity reported from
few countries
▰ Symptomatic treatment - aggressive fluid resuscitation (for shock) and
measures to decrease intracranial pressure.
42

Chemoprophylaxis
▰ Indicated to the close contacts of primary cases.
▰ Close contacts - household contacts and others who are directly exposed
to patient’s oral secretions, in the 7 days before symptom onset.
▰ Ceftriaxone (single dose, IM) - drug of choice
▰ Alternatively, rifampicin or ciprofloxacin can be given.
43

Vaccine Prophylaxis
▰ Polysaccharide vaccine:
 Bivalent (A & C) or Quadrivalent (A,C,Y, & W135)
 Two doses - children of 3–18 months Single dose to > 2 yrs
 Efficacy >95%
 Duration of protection - 3–5 years
44

Vaccine Prophylaxis (Cont..)
▰ Capsular vaccine is not available for serogroup B as:
 Capsule of serogroup B (made up of sialic acid) is less immunogenic
 Encephalitogenic due to expression of similar cross reactive antigens
on neural cells.
 Not given below 3 years
45

Vaccine Prophylaxis (Cont..)
Conjugated vaccine:
▰ Given to young children.
▰ Addition of a protein carrier (adjuvant) increases the immunogenicity of
the capsular vaccine.
46

Haemophilus influenzae Meningitis
▰ Virulence factor: Capsular polysaccharide - acts by inhibiting phagocytosis
▰ Hib: Out of the six capsular serotypes, H. influenzae serotype b (Hib) -
most virulent types – responsible for pneumonia - spread by
hematogenous route - meningitis
47

Haemophilus influenzae Meningitis
(Cont..)
▰ CNS infections:
 Pyogenic meningitis: Children less than 2 years of age
 Subdural effusion: Common complication following meningitis -
seizures or hemiparesis
 Mortality rate - high if untreated.
48

Group B Streptococcal (S. agalactiae meningitis)
▰ Major cause of neonatal sepsis and meningitis.
▰ Early-onset: Occurs in the first week of life , transmission of organism from
the maternal genital tract during or before birth
▰ Late-onset: Occurs from 7-90 days of birth, transmitted by contact with a
colonized mother or nursing personnel.
49

Treatment of Group B Streptococcal meningitis
▰ Meningitis should be treated with penicillin for a duration of 14 days, as
shorter courses may lead to relapse.
50

Gram-negative Bacilli Meningitis
▰ Gram-negative bacilli cause meningitis in individuals with chronic and
debilitating diseases - diabetes, cirrhosis, or alcoholism and in those with
chronic UTI.
▰ Gram-negative meningitis - occur secondary to neurosurgical procedures,
particularly craniotomy, and head trauma with CSF rhinorrhea or otorrhea.
51

Gram-negative Bacilli Meningitis
(Cont..)
▰ Escherichia coli and Klebsiella – common cause of pyogenic meningitis in
neonates
▰ Pseudomonas - meningitis in postoperative or post-traumatic patients
(head trauma with CSF rhinorrhea or otorrhea)
▰ Acinetobacter – postneurosurgical meningitis
▰ Elizabethkingia meningosepticum – meningitis in neonates.
52

Listeriosis
▰ Caused by Listeria monocytogenes - food-borne pathogen that can cause
serious infections, particularly in neonates, pregnant women and elderly
people.
▰ Also a ubiquitous saprophyte, known to cause epizootic disease in birds
and animals
53

Human Infection
▰ Mode of transmission: through contaminated food, vertical transmission.
▰ Age: Extremes of age (neonate and old age)
▰ Use of proton pump inhibitors increases risk
▰ Other risk factors: Pregnant women & immunocompromised individuals
54

▰ Depends on the age of the patient and other risk factors
▰ Common serotypes 1/2a,1/2b & 4
▰ Neonatal listeriosis: early-onset and late-onset neonatal disease
▰ In pregnant women:
 Fetal complications - abortion, preterm delivery - early onset disease
 Maternal complications - flu-like symptoms, bacteremia and rarely meningitis
55

▰ Adults:
 Bacteremia and meningitis
 Risk factors - immunosuppression (steroid therapy, HIV, diabetes,
malignancy)
 Gastroenteritis following consumption of contaminated milk, meat and
salads.
56

Treatment of Listeriosis
▰ Meningitis: Ampicillin - drug of choice, given for 2–3 weeks in combination
with gentamicin for synergistic effect
▰ Cotrimoxazole is given for patients with penicillin allergy
▰ In febrile gastroenteritis - Amoxicillin is recommended in
immunocompromised, elderly or pregnant patients.
57

Staphylococcal meningitis
▰ S. aureus and coagulase-negative staphylococci – cause meningitis
following invasive neurosurgical procedures, particularly ventricular
shunting
58

CHRONIC BACTERIAL
MENINGITIS
59

CHRONIC BACTERIAL MENINGITIS
▰ Bacterial agents causing chronic meningitis include the following:
 Partially treated pyogenic meningitis
 Parameningeal infections (e.g. otitis media)
 Mycobacterium tuberculosis
 Borrelia burgdorferi (Lyme disease)
 Treponema pallidum (tertiary syphilis)
 Rare bacterial agents - Nocardia, Actinomyces, Tropheryma whipplei,
Leptospira and Brucella
60

▰ Persistent headache and neck or back pain/stiffness (similar to pyogenic
meningitis)
▰ Hydrocephalus: Accumulation of CSF - ventricles - increased pressure
inside the skull
▰ Cranial neuropathies: Facial weakness, double vision, diminished vision,
papilledema, optic atrophy, hearing loss
61

▰ Myelopathy or radiculopathy: Leads to arm or leg weakness or numbness,
urinary retention/incontinence
▰ Changes in the personality - altered mental status—drowsiness,
inattention, disorientation, and memory loss
62

AGENTS OF CHRONIC
MENINGITIS
63

Mycobacterium tuberculosis Infections of CNS
▰ Tuberculosis of the CNS - ~5% of extrapulmonary cases. It is
▰ Seen most often in young children but also develops in adults - infected
with HIV.
▰ Presents in two clinical forms: tuberculous meningitis and tuberculoma.
64

Tuberculous Meningitis (TBM)
▰ TBM results from the hematogenous spread of primary or post-primary
pulmonary TB.
▰ Disease evolves over 1–2 weeks or longer
65

Clinical Features
▰ Headache, slight mental changes, low-grade fever, malaise, night sweat,
anorexia, and irritability.
▰ Evolve acutely with severe headache, confusion, lethargy, altered
sensorium, and neck rigidity
▰ Cranial nerves paresis (ocular nerves in particular) - frequent finding.
66

Clinical Features (Cont..)
▰ Stroke - due to involvement of cerebral arteritis
▰ Ultimately - progresses towards coma, with hydrocephalus and intracranial
hypertension.
67

Laboratory Diagnosis
CSF analysis:
▰ High leukocyte count (up to 1,000/μL), mostly lymphocytic.
▰ Neutrophils – elevated in the early stage
▰ Protein content of 100–800 mg/dL
▰ Low glucose concentration.
68

Laboratory Diagnosis (Cont..)
▰ Cobweb coagulum: When CSF is kept in a tube for 12 hours - coagulum
forms in the form of a cobweb - higher fibrin content in the fluid
▰ Acid-fast staining of CSF: Direct smear of CSF sediment - long slender
beaded acid-fast bacilli.
69

▰ Culture of CSF - Gold standard test. Time consuming, takes 4–8 weeks by
Lowenstein-Jensen medium and 2-3 weeks by automated liquid culture -
Mycobacteria Growth Indicator Tube (MGIT).
▰ GeneXpert assay: Automated real-time PCR, sensitivity of up to 80%
70

▰ Imaging studies (CT and MRI) – hydrocephalus and abnormal
enhancement of basal cisterns
71

Treatment of Tuberculous meningitis
▰ Treatment - initiated immediately upon a positive GeneXpert MTB/RIF
result.
▰ Negative result does not exclude a diagnosis of TB and requires further
diagnostic workup
▰ Responds well to anti-tubercular therapy, if started early.
▰ Adjunctive glucocorticoids - used to reduce the CSF pressure, resulting in
faster resolution
72

Tuberculoma (or Tuberculous Granulomas)
▰ Uncommon manifestation of tubercular infection of CNS; presents as
space-occupying lesions (firm nodule with central caseous necrosis) -
causes seizures and focal signs.
▰ CT or MRI - contrast-enhanced ring lesions, but biopsy is necessary to
establish the diagnosis and to differentiate it from malignancies.
73

Neuroborreliosis (Lyme Disease)
▰ Lyme disease - caused by Borrelia burgdorferi, transmitted by tick bite.
▰ Cutaneous lesions and arthritis; CNS infections.
▰ Manifestations: Meningitis, subtle encephalitic signs, cranial neuritis
(including bilateral facial palsy), and radiculoneuropathy.
74

Neuroborreliosis (Lyme Disease)
(Cont..)
▰ Treatment: IV ceftriaxone for 14–28 days
▰ Alternatively IV cefotaxime or IV penicillin G can be given
75

Neurosyphilis (Treponema pallidum)
▰ Neurosyphilis - tertiary form of syphilis - develops in about10% of
untreated patients.
▰ Sexually transmitted disease
▰ Invasion of CNS - early within first few weeks of infection, followed by
years of asymptomatic period.
76

▰ CSF analysis: Increased lymphocytes (>5/μL), and increased protein level
(>45 mg/dL)
▰ CSF VDRL test: Nontreponemal test, detects antibodies against cardiolipin
antigen derived from bovine heart.
▰ FTA-ABS test (fluorescent treponemal antibody absorption)
▰ PCR-based tests
77

Treatment of Neurosyphilis
▰ Aqueous crystalline or procaine penicillin G is given for 10– 14 days for
neurosyphilis
▰ Re-treatment if non-treponemal titres in CSF do not decrease by four-folds
within 2 years of completion of treatment
▰ Patients with penicillin allergy, desensitization to penicillin has to be done,
following which penicillin is administered.
78

VIRAL MENINGITIS
▰ Viral meningitis, inflammation of subarachnoid space due to viral etiology.
▰ Second most common type of meningitis, next to acute bacterial
meningitis.
▰ Often less severe than bacterial meningitis.
▰ Better prognosis.
80

ETIOLOGY
▰ Enteroviruses - most common cause of viral meningitis.
▰ Other less common viral agents are:
 Herpesviruses
 Arboviruses
 LCM virus
 Other causes: Mumps virus, measles virus, influenza virus and human
immunodeficiency virus (HIV).
81

CLINICAL MANIFESTATIONS
▰ Common symptoms in children and adults - fever, headache (frontal or
retro-orbital), stiff neck (milder than bacterial meningitis), photophobia,
sleepiness or trouble in waking up from sleep, nausea, irritability,
vomiting, lack of appetite (poor eating in babies), and lethargy.
82

CSF Analysis (Cytological and Biochemical)
▰ Normal or slightly elevated protein level (20–80 mg/dL)
▰ Normal glucose level
▰ Normal or mildly elevated CSF pressure (100–350 mm H2O)
▰ Cell count - 25–500/μL, in some viral meningitis (e.g. LCM virus and
mumps) the cell counts of several thousands/μL may be seen.
84

CSF Analysis (Cytological and Biochemical)
(Cont..)
▰ Pleocytosis: Lymphocytes – predominant cell type, although neutrophils
may predominate in the first 48 h of illness in some viral meningitis (e.g.
West Nile virus)
▰ Organisms are not seen on Gram staining of CSF.
85

Molecular Methods
▰ Amplification of specific viral DNA or RNA from CSF by PCR
▰ PCR of throat washings or stool specimen - enterovirus infections
▰ Formats: Multiplex PCR and multiplex real-time PCR
▰ BioFire FilmArray
86

Viral Culture
▰ Sensitivity of CSF cultures - generally poor.
▰ In addition to CSF, specific viruses – isolated from throat swabs, stool,
blood, and urine
▰ Isolation of enteroviruses from stool – not diagnostic
87

Oligoclonal Gamma Globulin Bands
▰ They may be detected in CSF in a number of viral infections.
▰ Can also be raised in other conditions – Lyme disease and multiple
sclerosis.
88

Treatment of Viral meningitis
▰ Primarily symptomatic - use of analgesics, antipyretics, antiemetics and
fluid and electrolyte replacement.
▰ Oral or intravenous acyclovir - HSV-1 or 2 , severe EBV or VZV infection
▰ Patients with HIV meningitis - highly active antiretroviral therapy.
89

AGENTS CAUSING VIRAL
MENINGITIS
90

Non-polio Enterovirus Infections
▰ Non-polio enteroviruses - most common cause of viral meningitis.
▰ Cases - sporadic or occur in clusters
▰ Examples - Coxsackieviruses, echoviruses, parechoviruses and Enterovirus
71.
91

Taxonomy (Picornaviridae) (Cont..)
Enteroviruses :
▰ Transmitted by feco-oral route.
▰ Multiply in the intestine - do not cause any intestinal manifestations.
▰ Associated with various systemic manifestations
▰ Divided into several (>115) human serotypes
92

Enteroviruses (Cont..) :
▰ Polioviruses—cause myelitis
▰ Coxsackieviruses, echoviruses, parechoviruses and Enterovirus 71—
cause aseptic meningitis
93

Rhinoviruses :
▰ Comprise of >100 antigenic types.
▰ Transmitted by respiratory route and cause common cold
94

Coxsackieviruses
▰ Coxsackieviruses (named after the place of discovery; Coxsackie village in
USA).
▰ Divided into two groups, A and B, based on their pathogenic potentials for
suckling mice.
▰ Serotypes- Coxsackieviruses group A are typed into serotypes 1–24
(except 15, 18 and 23) and group B are typed into serotypes 1–6.
95

▰ Coxsackieviruses - spread through an infected person’s nasal and throat
secretions, fluid from blisters or scabs.
▰ Produce a variety of clinical illnesses in humans associated with different
serotypes.
▰ Incubation period - 2 to 9 days.
96

▰ Aseptic meningitis
▰ Herpangina
▰ Hand-foot-and-mouth disease
▰ Pleurodynia (also known as Bornholm disease or epidemic myalgia)
▰ Cardiac: Myocarditis and pericarditis
▰ Respiratory: Coxsackieviruses A and B - associated with common colds
97

▰ Acute hemorrhagic conjunctivitis: Caused by coxsackievirus A24 and
enterovirus 70.
▰ Generalized disease of infants
▰ Pancreatitis leading to juvenile diabetes mellitus
98

▰ Specimen collection: Throat swabs, stool and CSF.
▰ Isolation of the Virus- Coxsackie viruses can be recovered by Intra-
cerebral inoculation into suckling mice-
 Coxsackie - A produce flaccid paralysis
 Coxsackie - B produce spastic paralysis
99

▰ Inoculating into tissue culture - Cytopathic effect can be observed within
5-14 days.
▰ PCR targeting specific genes (e.g. VP1) is highly useful as it is rapid, more
sensitive and serotype-specific
▰ Serology is performed to detect neutralizing antibodies.
100

Echoviruses
▰ Echoviruses (enteric cytopathogenic human orphan viruses) infect
humans by feco-oral route.
▰ Echoviruses - further typed into serotypes 1–33 (there are no types—8,
10, 22, 23 or 34), but not all cause human illness.
▰ Associated with aseptic meningitis, encephalitis, rashes, common cold,
and ocular disease
101

Parechoviruses
▰ Parechoviruses have 16 serotypes:
▰ 1. Serotype 1 and 2 - classified as echoviruses 22 and 23 respectively
▰ 2. Their capsid consists of three viral proteins
▰ 3. Rarely associated with aseptic meningitis, respiratory and neonatal
diseases.
102

Enterovirus 71
▰ Enterovirus 71 - caused large epidemic of meningitis in Southeast Asia.
▰ Also cause encephalitis, hand-foot-and-mouth disease and herpangina
(similar to coxsackieviruses) and paralysis resembling poliomyelitis.
103

Herpesvirus Meningitis
▰ A number herpesviruses can cause meningitis.
▰ Common agents are herpes simplex viruses, varicella zoster virus (VZV)
and Epstein-Barr virus (EBV)
▰ Rare causes - cytomegalovirus and human herpesvirus 6.
104

HSV Meningitis
▰ Herpes simplex viruses (HSV) - second most common cause of viral
meningitis, next to enteroviruses.
▰ Adults are commonly affected than children.
▰ HSV-2 - more frequent cause of meningitis than HSV-1.
105

HSV Meningitis (Cont..)
▰ Other neurological manifestations caused by HSV:
 HSV encephalitis
 Bell’s palsy
 Autonomous system involvement
 Transverse myelitis
 Guillain-Barre syndrome
 Peripheral nervous system involvement
106

Other Herpesviruses
▰ VZV meningitis
▰ EBV meningitis
107

Arboviral Meningitis
▰ The encephalitic arboviruses - sometime cause meningitis, especially in
individuals – recently travelled to the areas where these viruses are endemic.
▰ Transmitted by the bite of their arthropod vectors.
 West Nile virus
 Saint Louis encephalitis virus
 Tick-borne encephalitis
 California encephalitis virus
108

HIV Meningitis
▰ Meningitis in HIV infection may occur following primary infection in 5–10%
of cases and less commonly at later stages of illness.
▰ Cranial nerve palsies - involving cranial nerves V, VII, or VIII, are more
common in HIV meningitis than in other viral infections.
109

Mumps Meningitis
▰ Mumps mainly cause parotitis.
▰ Meningitis in mumps - secondary to parotitis.
▰ Mumps meningitis - more common in the late winter or early spring,
especially in unvaccinated children with a male preponderance.
110

LCM Virus Meningitis
▰ Lymphocytic choriomeningitis (LCM) virus affects people with history of
contact with rodent droppings or urine.
▰ Some patients have an associated rash, pulmonary infiltrates, alopecia,
parotitis, orchitis, or myopericarditis.
111

Bacterial Meningitis Diagnosis

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