applied cases

Neisseria meningitidis: meningitis

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. Physical examination showed Kernig's and Brudzinski's signs to be positive.

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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