This document discusses meningitis, including: 1) Meningitis is an infection of the membranes surrounding the brain and spinal cord called the meninges. 2) Causative organisms of acute meningitis include bacteria like Streptococcus pneumoniae and viruses like enteroviruses. Subacute and chronic meningitis are often caused by organisms like Mycobacterium tuberculosis and fungi. 3) Clinical manifestations include fever, headache, stiff neck, and altered mental status. Empiric antibiotic treatment depends on the suspected causative organism and includes drugs that cross the blood-brain barrier like ceftriaxone.

1. Dr / Eman Ahmed Abd-Elrhman
Lecturer of Medical Microbiology and Immunology
MENINGITIS

2. MENINGITIS
Definition: Meningitis is an infection of the
meninges, the membranes that line the brain and
spinal cord
Types
1) Acute(rapid progression hours to days)
2) Subacute & Chronic ( slaw progression days to
weeks)
Depending on the speed of onset of the initial
presentation and the rate of progression of the
illness.

3. MENINGITIS
Causative organisms based on the onset :
1) Acute meningitis is caused by :
a) Pyogenic bacteria, such as Streptococcus pneumoniae
, Neisseria meningitidis, Haemophilus influenzae (type b)
less common
Staphylococci, streptococci, pneumococci, E. coli,
Klebsiella, proteus, pseudomonas or anaerobes may be the
cause, after trauma or surgery
.

4. MENINGITIS
b) Viruses
The most common viral causes of acute meningitis are
1)Enteroviruses such as Coxsackie virus and echovirus.
2) Herpes simplex virus type 2 (HSV-2)
Enteroviral meningitis occurs primarily in young
children, and the peak incidence is in the summer and
fall seasons.
Note that HSV-2 typically causes meningitis, whereas
herpes simplex virus type1 causes viral encephalitis

5. Other causes of viral meningitis include :
Varicella-zoster virus, Mumps virus ( widespread use of
the mumps vaccine has greatly reduced its incidence)
MENINGITIS
Viral meningitis is often called aseptic meningitis
because routine cultures for bacterial pathogens are
negative

6. 2) Subacute and Chronic Meningitis
The most common causes of subacute and chronic
meningitis are:
a) M. tuberculosis
b) fungi such as Cryptococcus, Coccidioides, and
Histoplasma.
Cryptococcal meningitis occurs most commonly in
immunocompromised patients, such as those with
acquired immunodeficiency syndrome
(AIDS)
MENINGITIS

7. MENINGITIS
Causative organisms based on the onset :
1- In neonates
• Group B Streptococcus
• Escherichia coli
• Listeria monocytogenes
2- In adults
• Streptococcus pneumoniae
• Neisseria meningitidis causing epidemic
• Haemophilus influenzae (type b)

8. Pathophysiology
1. Hematogenous spread (i.e., bacteremia or viremia) is
the most common route by which organisms reach the
meninges.
2. Direct spread via adjacent infections, such as otitis
media and sinusitis
3. Trauma, such as a fracture of the cribriform plate,
occurs less frequently.
The importance of hematogenous spread is emphasized by the
success of the conjugate vaccines against S. pneumoniae, N.
meningitidis, and Haemophilus influenzae type B that induce
circulating IgG antibodies that neutralize the bacteria in the
blood.

9. Acute bacterial meningitis begins with nasopharygeal
colonization followed by local invasion, entry into the
bloodstream, and invasion of the meninges .
This is followed by an inflammatory response that causes
many of the clinical manifestations, especially the edema
resulting in increased intracranial pressure leading to
headache.
Pathophysiology

11. Clinical Manifestations
Fever
Headache
Stiff neck
Altered mental status also commonly occurs.
If untreated, meningitis may progress to vomiting,
seizures, photophobia, and focal neurologic deficits.
Neisseria meningitidis infection can be associated with
disseminated disease (meningococcemia) and result in
petechial rash and ultimately purpura fulminans

12. Purpura fulminans caused by Neisseria Meningitidis.

13. NEISSERIAE
Two members in the genus Neisseriae: N. meningitidis and N.
gonorrhoeae causing disease only in man.
Other members are commensals in naso-pharynx, and vagina.
Morphology:
• Gram negative diplococci with kidney shaped appearance
occur intracellularly in pus cells as well as extracellularly.
Cultural characters:
• N. gonorrhoeae and N. meningitidis are aerobes
• growth only on chocolate agar or the selective Modified
Thayer-Martin (MTM) medium in5-10% CO2 at 35-37°C.
All Neisseria are Oxidase test positive

14. The genus Neisseria includes:
1-Pathogenic: two species:
•N. gonorrhoeae Gonorrhea.
•N. meningitidis Epidemic cerebrospinal
meningitis.
2- Commensals: include N.Sicca, N.subflava,…etc, are
found in mouth, throat, pharynx and vagina.
GRAM NEGATIVE COCCI
Neisseria
Transmission:
The infection is transmitted by airborne droplets from
cases or carriers

15. GRAM NEGATIVE COCCI
Neisseria
Morphology:
Gram negative cocci arranged in pairs with flattened adjacent
sides, (kidney shaped appearance).
Detected intracellularly in the pathological specimens
Gram stained film of pathogenic Neisseria

16. Cultural Characters:
- N.gonorrhoeae and meningitidis are fastidious organisms;
grow only on enriched media e.g. chocolate, Thayer- Martin
and modified Thayer- Martin media at 37°C, in the presence
of 5-10% Co2, Its colony is smooth, translucent and non-
pigmented.
Neisseria culture on chocolate agar

17. Biochemical reactions:
•Oxidase test: All Neisseria give a positive
oxidase reaction.
•Sugar fermentation:
•N. gonorrhoeae ferments glucose only.
•N. meningitidis ferments glucose and maltose
Oxidase test

18. Virulence factors:
1- Capsule (polysaccharide and the most important)
According to which the meningococci are classified into
13 serogroups.
The most important serogroups associated with disease
are A, B, C, Y and W-135.
Properties of the polysaccharide capsule:
a- Anti phagocytic action
b- It is the antigen that defines the serologic groups
c- detected in the spinal fluid by latex agglutination
d- It induces protective antibodies

19. 2- Pili: mediate adherance to the nasopharyngeal mucosa.
3- Outer membrane proteins: mediate adherence
4- Lipopolysaccharide (endotoxin) is responsible for the
septic shock due to septicemia associated with
meningococcemia.
5- IgA1 protease hydrolyzes secretory IgA1, and helps the
attachment of the organism to the mucous membrane
(colonization).

20. Diagnosis of meningococcal carriers:-
•Nasopharyngeal swab is obtained and cultured on chocolate
agar and the isolated Gram negative diplococcic should be
differentiated from commensal Neisseria by using
meningococcal antisera.

21. Treatment :
Combination of antibiotics I.V. should be used.
Use of antibiotic whitch cross blood brain barrier.
Ampicillin + third generation cephalosporins e.g.
cefotaxime or ceftriaxone are recommended as a
first line of empirical treatment.
Chemoprophylaxis:
Rifampicin, 600 mg orally twice daily for 2 days

22. Prevention:
Vaccines:
1) A meningococcal polysaccharide vaccine (MPSV4)
2) A meningococcal conjugate vaccine (MCV4) both are
tetravalent and immunize against types A, C, Y and W-135.
Conjugation with protein increase effectiveness of vaccine.
MCV4 is recommended for those at increased risk for infection,
before high school, college freshmen living in dorms, the
military, travelers to crowded areas (e.g. Hajj), asplenic patients,
persons with complement deficiencies and microbiologists.
MPSV4 can be used as an alternative if MCV4 is not available.

23. Cryptococcus neoformans
• C. neoformans are yeast cells with a gelatinous capsule.
• It is found in soil contaminated with the excreta of birds specially
pigeons' faeces.
• It is an opportunistic pathogen affecting mainly
immunosuppressed individuals specially AIDS patients.
• Infection occurs by inhalation where it causes subclinical lung
affection or pneumonia.
• It may spread systemically to the CNS causing
meningoencephalitis.

24. Pathogenesis of Cryptococcus
neoformans

25. Morphology of Cryptococcus neoformans

26. Diagnosis of meningitis
 Chemical examination

27. •Specimen: CSF is obtained by lumber puncture,
centrifuged and the deposit is used.

28. Lab diagnosis of meningitis
• Bacteriologic examination: CSF is centrifuged and the deposit
is examined by:
• Direct smears stained by gram and by Ziehl Neelsen if
indicated or by India ink if cryptococcosis is suspected(India
ink, reveals large gelatinous capsule around budding yeast
cells in case of cryptococcus).
• Due to the need for rapid results to start treatment,
initiatative report can be given on the basis of gram stain.
• Cultures are made on blood and chocolate agar and
incubated aerobically and at 5-10% CO2 atmosphere.
• Culture for tuberculosis is done if indicated. Cultures for
fungi on sabaroud dextrose agar may be needed.

29. • Detection of bacterial antigens in CSF by coagglutination
and latex agglutination using antisera to the three
common organisms i.e. N. meningitides, H. influenzae
and Str. pneumoniae. Cryptoccocal antigens can be
detected by latex agglutination.
Lab diagnosis of meningitis

30. • Blood cultures should be done at the same time since
bacteraemia frequently occurs in pyogenic meningitis.
• PCR may be used for detection of viral or bacterial
nucleic acids in CSF or blood for rapid diagnosis.
• Serologic diagnosis of viral causes by detecting IgM or
IgG rising titre.
Lab diagnosis of meningitis

31. Treatment of meningitis
Empiric therapy for acute bacterial meningitis must include
drugs with excellent penetration into the CSF, are bactericidal,
and are active against the most common pathogens.
1) In older children and adults, ceftriaxone or cefotaxime
plus vancomycin is a common empiric regimen.
2) Ampicillin should be added if Listeria is a likely cause.
3)Empiric therapy for neonatal bacterial meningitis
includes ampicillin plus either ceftriaxone or cefotaxime,
with or without gentamicin.
4) Acyclovir is used for the treatment of HSV and VZV
infection.