Meningitis is an inflammation of the meninges, which are the protective membranes that cover the brain and spinal cord. Bacteria can reach the meninges through the bloodstream, direct contact from a site of infection like the sinuses or ears, or iatrogenically through procedures like lumbar puncture. Symptoms include fever, headache, neck stiffness, and altered mental status. Diagnosis involves analyzing cerebrospinal fluid obtained via lumbar puncture for signs of infection like increased white blood cells. The most common causes of bacterial meningitis are Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae.

1. MENINGITIS
Deogratias katabalo
U56/80217/2012

2. DEFINATION
The brain and spinal cord are covered by connective tissue layers
collectively called the meninges which form the blood-brain barrier.
• Dura mater,( pachymeninges)- lies directly beneath and is adherent to the
skull.
• Arachnoid (leptomeninges)- the middle layer, lies between the dura mater
and the pia mater.
• Pia mater (leptomeninges)- lies directly over brain tissue
The meninges contain cerebrospinal fluid (CSF)-In subarachnoid space
Meningitis is an inflammation of the meninges, which, if severe, may
become encephalitis, an inflammation of the brain.

4. MODE OF INFECTION
• The CNS is normally sterile. Bacteria gain access to the CNS by three
main routes:
• direct spread from an adjacent focus of infection, such as the
paranasal sinuses or middle ear; or by direct spread from outside the
body, e.g. head injury with open skull fractures
• blood-borne spread, which can occur as a consequence of
septicaemia
• iatrogenic infection, following introduction of organisms into the CSF
at lumbar puncture.

5. CSF
The CSF is normally is clear, with a
• protein content <50 mg/dL,
• Glucose concentration approximately 50% to 66% of the
simultaneous peripheral serum glucose concentration
• pH approximately 7.4.
• It typically contains <5 white blood cells (WBCs) per cubic millimeter,
all of which should be lymphocytes
• As meninges become inflamed, the constituency of the CSF changes
and these changes can be used diagnostically as markers of Infection.

6. EPIDEMIOLOGY
• Meningitis occurs sporadically throughout the world, but the vast majority
of cases and deaths are in Africa.
• Epidemics regularly hit countries in the area referred to as the African
"meningitis belt," which stretches across the continent from Senegal to
Ethiopia.Kenya & Uganda included
• The most affected countries in the region are Burkina Faso, Chad, Ethiopia,
and Niger. They accountable for 65% of all cases in Africa.
• Over 1.2 million cases of bacterial meningitis are estimated to occur
worldwide each year
• Without treatment, the case-fatality rate can be as high as 70 percent, and
one in five survivors of bacterial meningitis may be left with permanent
sequelae including hearing loss, neurologic disability, or loss of a limb

7. ETIOLOGY
- Bacterial Infections
- Viral Infections-
(Mumps, Influenza, Varicella zoster, HIV)
- Fungal Infections
(Cryptococcus neoformans Coccidiodes immitus)
- Protozoa and Parasites
(Toxoplasma, Amoeba, Cysticerus)
- Inflammatory diseases- (SLE)
- Cancer
- Trauma to head or spine.

8. PATHOPHYSIOLOGY
In bacterial meningitis, bacteria reach the meninges by one of two
main routes:
• Through the bloodstream or
• Through direct contact between the meninges and either the nasal
cavity or the skin.

9. Through the bloodstream
• Follows invasion of the bloodstream by organisms that live
upon mucous surfaces such as the nasal cavity. This often precedes a
viral infection, which breaks down the normal barrier provided by the
mucous surfaces.
• Once bacteria have entered the bloodstream, they enter the
subarachnoid space in places where the blood–brain barrier is
vulnerable—such as the choroid plexus.
• Meningitis occurs in 25% of newborns with bloodstream infections
due to group B streptococci; this phenomenon is less common in
adults.

10. • Direct contamination of the CSF may arise from indwelling devices,
skull fractures, or infections of the nasopharynx or the nasal sinuses
that have formed a tract with the subarachnoid space).
• The inflammation that occurs in the subarachnoid space during
meningitis is not a direct result of bacterial infection but, the
response of the immune system to the entry of bacteria into the CNS.
• When components of the bacterial cell membrane are identified by
the immune cells of the brain (astrocytes and microglia), they
respond by releasing large amounts of cytokines,that recruit other
immune cells and stimulate other tissues to participate in an immune
response.
Through direct contact

11. ….Through direct contact
• The BBB becomes more permeable, leading to "vasogenic" cerebral
edema (swelling of the brain due to fluid leakage from blood vessels).
• Large numbers of WBCs enter the CSF, causing inflammation of the
meninges and leading to "interstitial" edema (swelling due to fluid
between the cells).
• In addition, the walls of the blood vessels themselves become inflamed
(cerebral vasculitis), which leads to decreased blood flow and a third type
of edema, "cytotoxic" edema
• This 3 forms of cerebral edema all lead to increased intracranial pressure &
lowered B.P (encountered in acute infection),thus harder for blood to enter
the brain
• Consequently brain cells are deprived of oxygen and undergo apoptosis.

12. …Through direct contact
• Administration of antibiotics may initially worsen the process outlined
above, by increasing the amount of bacterial cell membrane products
released through the destruction of bacteria.
• Particular treatments, such as the use of corticosteroids, are aimed at
dampening the immune system's response to this phenomenon.

14. Clinical signs & Symptoms
• sudden high fever
• Nuchal rigidity (the inability to flex the neck forward passively)
• Altered mental status
• severe headache-90% of cases of bacterial meningitis
• Photophobia
• Phonophobia
• Fontanelle can bulge in infants aged up to 6 months.
• Small children often do not exhibit the aforementioned symptoms, and may
only be irritable and look unwell
• Leg pain, cold extremities, and an abnormal skin color(Distinguishes
meningitis from severe illness in children)
The classic triad
of diagnostic
signs

15. …Clinical signs & Symptoms
• +ve Kerning's sign- assessed with the person lying supine, with the hip and
knee flexed to 90 degrees.Pain limits passive extension of the knee
• +ve Brudziński sign- flexion of the neck causes involuntary flexion of the
knee and hip.
• jolt accentuation maneuver" -A person is asked to rapidly rotate the head
horizontally; if this does not make the headache worse, meningitis is
unlikely
• Rapidly spreading petechial rash (numerous small, irregular purple or red
spots on the trunk, lower extremities, mucous membranes, conjuctiva, and
(occasionally) the palms of the hands or soles of the feet. – Mainly seen in
Neisseria meningitidis
• The rash is typically non-blanching; the redness does not disappear when
pressed with a finger or a glass tumbler.

16. Nuchal rigidity

17. Severe stiffness of the hamstrings causes an inability to
straighten the leg when the hip is flexed to 90 degrees.
.Severe neck stiffness causes a patient's hips and knees to flex
when the neck is flexed

21. DIAGNOSIS
Blood tests and imaging-
• for markers of inflammation (e.g. C-reactive protein, complete blood count) &
blood cultures
Lumbar puncture(L.P)- CSF analysis
• L.P is contraindicated if there is a mass in the brain (tumor or abscess) or
the intracranial pressure (ICP) is elevated, as it may lead to brain herniation.
• Gram staining of the CSF sample may demonstrate bacteria in bacterial meningitis,
absence of bacteria does not exclude bacterial meningitis as they are only seen in
60% of cases; this figure is reduced by a further 20% if antibiotics were
administered before the sample was taken.
• Microbiological culture of the sample is more sensitive (it identifies the organism in
70–85% of cases) but results can take up to 48 hours to become available
• Raised ICP- recent head injury, a known immune system problem, localizing
neurological signs, or evidence on examination of a raised ICP

22. • The "opening pressure" of the
CSF is measured using
a manometer, normally between
6 and 18 cm water (cmH2O);
• Bacterial meningitis- ICP is
usually elevated.
• Cryptococcal meningitis-ICP is
markedly elevated.
• Cloudy CSF indicates higher
levels of protein, white and red
blood cells and/or bacteria, and
therefore may suggest Bacterial
meningitis

23. ….DIAGNOSIS
TYPE NORMAL BACTERIAL VIRAL FUNGAL TUBERCULOSIS
WBC(Cells/mm3) <5 1000-5000 100-100 40-400 100-500
Cell type Lymphocytes Polymorphs Lymphocytes Lymphocytes Polymorphs/Lympoc
yes/Mixed
Protein (mg/dl) <50 100-500(Normal or
elevated)
30-150(Normal) 40-150(Elevated) Elevated
Glucose(mg/dl) >60% of blood
glucose
Low Normal Low Low
As meninges become inflamed, the constituency of the CSF changes and these changes can be used diagnostically as
markers of Infection.

24. CSF ANALYSIS
The type of WBC predominantly present indicates type of
meningitis is
• Bacterial (usually Neutrophil-predominant) or
• Viral (usually lymphocyte-predominant), although at the beginning of
the disease this is not always a reliable indicator.,
• Fungal & Parasitic - Eosinophils predominate,
• High levels of lactate in CSF(>35mg/l) indicate a higher likelihood of
bacterial meningitis, as does a higher WBC count

25. …DIAGNOSIS
• Polymerase chain reaction (PCR) is a technique used to amplify small
traces of bacterial DNA in order to detect the presence of bacterial or
viral DNA in CSF; it is a highly sensitive and specific test since only
trace amounts of the infecting agent's DNA is required.
• Serology (identification of antibodies to viruses) may be useful in viral
meningitis
• India ink stain of the CSF- diagnosis of cryptococcal meningitis

26. Bacterial meningitis…..
Etiological Agents:
• Pneumococcal, Streptococcus pneumoniae (38%)
• Meningococcal, Neisseria meningitidis (14%)
• Haemophilus influenzae (4%)
• Staphylococcal, Staphylococcus aureus (5%)
• Tuberculous, Mycobacterium tuberculosis

27. Bacterial meningitis
• One million cases per year world wide. 200,000 die annually.
• Can affect all age groups but some are at higher risk.
• Pneumococcal meningitis is the most common type. Approximately
6,000 cases/yr
• Haemophilus meningitis: Since 1985 Incidence has declined by 95%
due to the introduction of Haemophilus influenza b vaccine.
• Other bacterial meningitis caused by E-Coli K-1, Klebsiella species and
Enterobacter species are less common overall, but may be more
prevalent in newborns, pregnant women, the elderly and
immunocompromised hosts

28. Neisseria meningitidis (Meningococcal)
Etiological Agent: Neisseria meningitidis
Clinical Features: sudden onset. Fever,Headache,N,V
N. meningitidis can also cause a severe bacteremia, called meningococcemia.
Reservoir: Humans only. 5-15% healthy carriers
Mode of transmission: direct contact with patients oral or nasal secretions. Saliva.
Incubation period: 1-10 days. Usually 2-4 days
Infectious period: as long as meningococci are present in oral secretions or until 24
hrs of effective antibiotic therapy
Epidemiology:
Sporadic cases worldwide.
“Meningitis belt” –sub-Saharan Africa into India/Nepal.
Children under five and adolescent most susceptible. Overcrowding e.g.
dormitories and military training camps predispose to spread of infection.

29. Haemophilus influenzae
• H. influenzae meningitis is rare in adolescents and adults, rates of
meningitis due to Hib are highest in children less than five years of
age
• The incidence of which has decreased dramatically since the
introduction of the Hib vaccine
• H. influenzae is also an important cause of pneumonia as well as
epiglottitis.

30. Streptococcus pneumoniae
• Meningitis due to S. pneumoniae occurs most commonly in the very
young and the very old, with an estimated incidence rate of 17 cases
per 100,000 population in children <5 yrs of age
• The case fatality rate for meningitis due to S. pneumoniae in children
less than five years of age exceeds 73% in some parts of the world.

31. T.B MENINGITIS
• Mycobacterium tuberculosis infection of the meninges
• It is the most common form of CNS tuberculosis
• Inflammation is concentrated towards the base of the brain.
• Cranial nerve roots may be affected by the inflammation. The
symptoms will mimic those of space-occupying lesions.
• Infection begins in the lungs and may spread to the meninges by a
variety of routes.
• Blood-borne spread certainly occurs.
• 25% of patients with miliary TB have TB meningitis, presumably by
crossing the blood–brain barrier

32. Diagnosis
• Cerebrospinal fluid collected by lumbar puncture(preferably 5 to
10ml).
• CSF composition: high protein, low glucose and a raised number of
lymphocytes.
• Acid-fast bacilli are sometimes seen on a CSF smear, but more
commonly, M. tuberculosis is grown in culture.
• A spiderweb clot in the collected CSF is characteristic of TB
meningitis, but is a rare finding.
• The culture of TB from CSF takes a minimum of two weeks, and
therefore the majority of patients with TB meningitis are started on
treatment before the diagnosis is confirmed.

33. TREATMENT
• Isoniazid, Rifampicin, Pyrazinamide and ethambutol – 2 months,
• Followed by isoniazid and rifampicin alone for a further 10 months.
• Steroids are always used in the first six weeks of treatment (and
sometimes for longer).
• A few patients may require immunomodulatory agents such
as thalidomide.
• Hydrocephalus occurs as a complication in about a third of patients
with TB meningitis and will require a ventricular shunt

34. CRYPTOCOCCAL MENENGITIS
• Is a potentially fatal fungal disease.
• It is caused by one of two species; Cryptococcus neoformans
and Cryptococcus gattii
• Acquired by inhalation of the infectious propagule from the
environment.
• It is a defining opportunistic infection for AIDS.
• Other conditions which pose an increased risk include
certain lymphomas (Hodgkin's lymphoma), sarcoidosis, liver
cirrhosis and patients on long-term corticosteroid therapy.

35. TREATMENT
Non-AIDS patients –
• IV Amphotericin B(0.7-1.0 mg/kg/day )X 1WK combined + oral flucytosine.
• Every attempt should be made to reduce the amount of
immunosuppressive medication until the infection is resolved.
• Where flucytosine (5FC) is not available, fluconazole 800-1200mg/day
should be used adjunctively with amphotericin B (1mg/kg/day)
• Amphotericin-based induction therapy has much greater microbiologic
activity than fluconazole monotherapy with 30% better survival at 10-
weeks

36. Aseptic (viral) Meningitis
Definition: A syndrome characterized by acute onset of meningeal symptoms, fever, and cerebrospinal
fluid pleocytosis (white cells in the spinal fluid), with bacteriologically sterile cultures.
Confirmed: a clinically compatible illness diagnosed as aseptic meningitis,
with no laboratory evidence of bacterial or fungal meningitis
Laboratory criteria for diagnosis:
CSF showing ≥ 5 WBC/cu mm
No evidence of bacterial or fungal meningitis.
Case classification
Confirmed: a clinically compatible illness diagnosed by a physician as aseptic meningitis, with no
laboratory evidence of bacterial or fungal meningitis
Aseptic meningitis is a syndrome of multiple etiologies, but most cases are caused by a viral agent

37. Aseptic (viral) Meningitis
Etiological Agents:
Enteroviruses (Coxsackie's and echovirus): most common.
-Adenovirus
-Arbovirus
-Measles virus
-Herpes Simplex Virus
-Varicella
Reservoirs:
-Humans for Enteroviruses, Adenovirus, Measles, Herpes Simplex, and Varicella
-Natural reservoir for arbovirus birds, rodents etc.
Modes of transmission:
-Primarily person to person and arthopod vectors for Arboviruses
Incubation Period:
-Variable. For enteroviruses 3-6 days, for arboviruses 2-15 days
Treatment: No specific treatment available.
Most patients recover completely on their own.

38. Non-infective meningitis
• Meningeal inflammation can be caused by meningeal infiltration by
malignant cells (leukaemia, lymphoma, other tumours);
• chemical meningitis (intrathecal drugs, contaminants);
• drugs (NSAIDs, trimethoprim);
• sarcoidosis;
• SLE.

39. MANAGEMENT
• Treatment with broad-spectrum antibiotics should not be delayed while
confirmatory tests are being conducted.
• If meningococcal disease is suspected in primary care, guidelines
recommend that benzyl penicillin be administered before transfer to
hospital.
• Intravenous fluids should be administered if hypotension or shock are
present.
• Mechanical ventilation may be needed if the level of consciousness is very
low, or if there is evidence of respiratory failure
• signs of raised intracranial pressure- ICP with medication e.g mannitol
• Seizures are treated with anticonvulsants- phenytoin (20mg/kg over one
hour)
• Hydrocephalus may require insertion of a temporary or long-term drainage
device, such as a cerebral shunt

40. Bacterial meningitis:
Empiric antibiotics
• should be started immediately, even before the results of the LP &
CSF analysis are known.
• Changes in CSF after administration of antibiotics occurs after 12-24
hrs.

41. Management algorithm for infants and children with suspected bacterial meningitis. “Stat” indicates that the
intervention should be done emergently.

42. Management algorithm for adults with suspected bacterial meningitis

43. Recommendations for antimicrobial therapy in adult patients with presumptive pathogen identification by positive
Gram stain.

44. Recommendations for empirical antimicrobial therapy for purulent meningitis based on patient age and specific
predisposing condition (A-III).

45. Duration of antimicrobial therapy for bacterial meningitis based on isolated pathogen

46. Recommended dosages of antimicrobial therapy in patients with bacterial meningitis (A-III).

47. Steroids
• Has shown some benefits, such as a reduction of hearing loss, and
better short term neurological outcomes
• Dexamethasone, 0.15mg/kg/dose qid *4/7, age>2/12 in bacterial
meningitis with ↑ bacterial load & ↑ICP (15 minutes prior to
parenteral antibiotics)
• Professional guidelines therefore recommend the commencement of
dexamethasone or a similar corticosteroid just before the first dose of
antibiotics is given, and continued for four days.
• MOA: suppression of overactive inflammation.
• Benefit is greatest in cases of H. influenza meningitis

48. Monitor:
• Neurological observations including blood pressure should be
performed every 15 minutes for the first two hours and then at
intervals determined by the conscious state.
• Electrolytes and glucose should be checked 6-12 hourly until the
serum sodium is normal
• Ensure adequate analgesia

49. Fluid management in suspected or confirmed
bacterial meningitis
Assess for all of the following:
• signs of shock
• raised intracranial pressure
• signs of dehydration.
• If present, correct dehydration using intravenous isotonic fluids (for
example, sodium chloride 0.9% with glucose 5%.
Do not restrict fluids unless there is evidence of:
• raised intracranial pressure, or
• increased antidiuretic hormone secretion
• Give full-volume maintenance fluids to avoid hypoglycaemia and maintain
electrolyte balance.

50. PREVENTION & CONTROL
Vaccines are the cornerstone of prevention and control of bacterial meningitis
• Serogroup A meningococcal conjugate vaccine-result in higher levels of
protection, longer duration of protection, protection of children less than 2 yrs of
age, and may interrupt nasopharyngeal carriage and transmission, resulting in
herd immunity.
• Haemophilus influenzae type b (Hib) vaccine. are available for young
children.These vaccines have dramatically decreased the burden of Hib meningitis
and virtually eliminated it as a public health problem through direct effects and
induction of herd immunity without significant strain replacement
• A 23-valent polysaccharide vaccine for S. pneumoniae - not effective in children
younger than two years of age.
• Newer polysaccharide-protein conjugate vaccines(7 valent,10 valent,13valent
pneumococcal conjugate vaccines) have been introduced- dramatic declines in
pneumococcal meningitis in infants and young children and in adults through
induction of herd immunity

51. PENETRATION OF ANTINFECTIVES INTO THE CSF
• Drugs that achieve therapeutic levels: sulfonamides, CAF,
metronidazole, RHZ.
• Drugs that achieve therapeutic levels on meningeal inflammation:
penicillins, 3rd generation cephalosporins, vancomycin, ciprofloxacin,
fluconazole, acyclovir, cefuroxime.
• Drugs that don’t achieve therapeutic levels: 1st &2nd generation
cephalosporins, aminoglycosides, clindamycin.

52. PROGNOSIS
• Untreated, bacterial meningitis is almost always fatal. Viral meningitis, in
contrast, tends to resolve spontaneously and is rarely fatal.
• Of newborns, 20–30% may die from an episode of bacterial meningitis. This
risk is much lower in older children, whose mortality is about 2%, but rises
again to about 19–37% in adults
• Meningitis caused by H. influenzae and meningococci has a better
prognosis than cases caused by group B streptococci, coliforms and S.
pneumonia
• Potential disabilities in children which may result from damage to the
nervous system, including sensorineural hearing loss, epilepsy, learning and
behavioral difficulties, as well as decreased intelligence.occur in about 15%
of survivors. Some of the hearing loss may be reversible

53. REFERENCES
• http://www.cdc.gov/meningitis/lab-manual/chpt02-epi.html
• Dipiro Pharmacotherapy
• Pathologic Basis of Disease, Robbins & cotran
• Davidson”s principles and practice of medicine