| A 10 year old child is brought
to the hospital with high fever, neck rigidity, and petechial rashes
on the body. The child had complained of severe headache and had
vomited before being brought in. Photophobia and an altered mental
status was also noted.
What is your diagnosis?
It could be a case of acute pyogenic meningitis with septicemia,
probably meningococcemia with meningitis.
Which are the bacteria that can cause pyogenic meningitis?
Neisseria meningitidis, Streptococcus pneumoniae, Escherichia
coli, Hemophilus influenzae, Streptococcus agalactiae and Listeria
monocytogenes can cause
acute bacterial meningitis.
What is meningitis?
Meningitis is the term to denote inflammation of the meninges. Depending
on the duration of symptoms, meningitis may be classified as acute
(hours to days) or chronic (weeks to months). Acute bacterial
meningitis is caused by bacteria and is characterized by an acute
onset of meningeal symptoms and neutrophilic pleocytosis. Aseptic
meningitis characteristically have an acute onset of meningeal
symptoms and cerebrospinal pleocytosis that is usually prominently
lymphocytic. While viruses cause most cases of aseptic meningitis,
it can also be caused by bacterial, fungal, mycobacterial, and
parasitic agents.
What is the pathogenesis of meningitis?
Initially, the infectious agent colonizes or establishes a
localized infection in the host. This may be in the form of
colonization or infection of the skin, nasopharynx, respiratory
tract, gastrointestinal tract, or genitourinary tract. Most
meningeal pathogens are transmitted through the respiratory route.
Both N. meningitidis and S. pneumoniae are known to colonize the
oropharynx. From this site, the organism gains access to the CNS
by invasion of the bloodstream and subsequent hematogenous seeding
of the CNS, a retrograde neuronal (ie, olfactory and peripheral
nerves) pathway or direct contiguous spread (ie, sinusitis, otitis
media). Once inside the CNS, the infectious agents likely survive
because host defenses (eg, immunoglobulins, neutrophils,
complement components) appear to be limited. Inflammation of
meninges is initiated by the presence of several bacterial
components such as lipopolysaccharide and teichoic acid
in the subarachnoid space. These components stimulates monocytes
and macrophages to produce cytokines such as TNF-α, IL-1 and IL-8.
The inflammatory response elicited by these cytokines are
responsible for clinical manifestations of meningitis. The
fundamental pathologic change in meningococcemia is widespread
vascular injury characterized by endothelial necrosis,
intraluminal thrombosis, and perivascular hemorrhage. Skin lesions
usually contain numerous meningococci undergoing phagocytosis by
neutrophils.
How is this condition diagnosed using laboratory techniques?
Since there is both meningitis and septicemia, both blood as well
as CSF must be collected. Laboratory diagnosis involves
microscopic examination of CSF smear, culture from blood & CSF as
well as detection of bacterial antigen.
Which are the specimens collected?
Approximately 3-5 ml Spinal fluid (CSF) is collected by spinal tap
(lumbar puncture) by inserting the needle between L3 and L4
vertebrae into a sterile container.
Only 3-5 ml of CSF must be collected and the rate of collection
should be slow(4-5 drops/second). Alternatively, 1 ml fluid each
may be collected in three separate containers. Five ml of venous
blood may be drawn by venipuncture for blood culture.
Which are the necessary investigations performed?
CSF should be subjected to cytological (cell type & cell count),
biochemical (glucose & protein level) and microbiological
investigations. In bacterial meningitis CSF is usually purulent
(>100 cells/mm2), containing polymorphonuclear
leucocytes and the glucose level is usually less than half the
serum level. Microbiological investigations include microscopy
(Gram stained smear), antigen detection and culture followed by
antibiotic susceptibility testing. If the CSF is clear, it should
be centrifuged and the deposit taken for microscopy and culture.
A loopful of CSF is inoculated on to Blood agar and Chocolate agar
and incubated at 37oC in the presence of 5-10% CO2
in a candle jar
and incubated overnight. CSF may be subjected to antigen detection
by latex agglutination, co-agglutination or counterimmuno-electrophoresis.
The blood may be subjected to
antigen detection and culture. Blood is inoculated into brain
heart infusion broth and incubated at 37oC,
it is then subcultured to Blood agar the following day.
What are your observations?
The gram stained smear shows plenty of pus cells and gram
negative diplococci (both intracellular and extracellular). Round,
smooth, moist, glistening, convex, greyish and unpigmented
colonies with an entire edge that may be 1-4 mm wide
are seen on blood
agar. Older cultures may sometimes cause the underlying agar to
turn dark. The gram stain of the colonies display gram negative
cocci in pairs. These colonies are oxidase positive.
Similar colonies are obtained from subculture of blood. The
isolate fermented glucose and maltose but not lactose or sucrose.
The isolate is identified as Neisseria meningitidis. Latex
agglutination test for Neisseria antigen in CSF and blood was also
positive.
How is this disease treated and prevented?
Meningococcal disease can be treated using antibiotics such as
Penicillin and ampicillin. However, due to emergence of drug
resistance, third generation cephalosporin such as ceftriaxone is
now preferred. MPSV4, a tetravalent polysaccharide vaccine
containing 50 μg each of purified bacterial capsular
polysaccharides (serogroups A,C,Y,W-135) is available as a
single-dose (0.5-mL) vaccine. Conjugate vaccines containing
oligosaccharide derived from serogroup C capsular polysaccharide,
conjugated to nontoxic mutant diphtheria toxin or tetanus toxoid
have been developed. MCV4 is a tetravalent meningococcal conjugate
vaccine containing 4 μg each of capsular polysaccharide from
serogroups A, C, Y, and W-135 conjugated to 48 μg of diphtheria
toxoid and is available as 0.5-mL single dose vaccine. Rifampin,
ciprofloxacin, and ceftriaxone are effective in reducing
nasopharyngeal carriage of N. meningitdis
and are all acceptable antimicrobial agents for chemoprophylaxis.
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