15-year-old Male with Decreased Level of Consciousness

Clinical Case:

A previously healthy 15-year-old male presented to a community hospital with a decreased level of consciousness. Five days prior, he attended a community fair after which he developed a flu-like illness including fatigue, nausea and vomiting. The illness did not resolve and after three days his parents noticed red spots on his hands, arms and legs. On the day of admission, he was found to be delirious and becoming less responsive, so his parents brought him to the emergency department. All his routine vaccinations were up to date. His past medical history was significant only for recreational cannabis use. While he still lived at home with his parents, he frequently went to “sleep-overs” at his friends’ homes.

On presentation to the emergency, the patient was found to be afebrile with a temperature of 37.5°C, but hypotensive and tachycardic. He had a score of 8 on the Glascow Coma Scale. Physical examination revealed marked nuchal rigidity and petechiae on the face and limbs.

Laboratory investigations showed leucocytosis with a white blood cell count of 16.8 x 10⁹/L. The electrolytes were normal and the serum glucose was 7.7 mM. Lumbar puncture was attempted twice but unsuccessful. The patient was empirically started on vancomycin, ceftriaxone and decadron and transferred by helicopter to an intensive care unit at a tertiary-care hospital on the same day. Cerebral spinal fluid was finally obtained. It was turbid and contained 13,300 x 10⁶/L leucocytes (95% polymorphs). The protein was 4.4 g/L and glucose 1.4 mM. The Gram stain of the fluid showed many polymorphonuclear cells and gram-negative diplococci. With that result, the vancomycin was discontinued. The patient improved after a single day of antibiotics and was transferred to the regular ward. He subsequently made a full recovery after a full seven days of antibiotic therapy. Unfortunately there was no growth from his CSF or blood cultures to confirm the identity of the microorganism causing his disease.

Questions:

What are the most common organisms causing meningitis? How do these differ in different age groups?
Based on the results, which agent is most likely in this case? What are risk factors for acquiring this infection?
How is the identity of this organism confirmed in the laboratory? What other diagnostic tests are available to determine the presence of this organism?
What is the empiric treatment for meningitis? What is the treatment for meningitis caused by this organism? What about close contacts of the patient?
Could this infection have been prevented? How?

Discussion:

This is a case of meningitis caused by the aerobic bacterium, Neisseria meningitidis. Most Neisseria species are non-pathogenic and only N. meningitidis and N. gonorrheae are considered pathogenic for humans. N. meningitidis may asymptomatically colonize the nasopharynx and even the anogenital area of homosexual men. Transmission occurs by direct contact with contaminated respiratory secretions and droplets. The bacteria can disseminate from the nasopharynx to the blood and meninges, causing meningococcemia and/or menigitis. School-aged children and young adults, especially those residing in dormitories, are most at risk for meningococcal meningitis. Persons with inherited complement deficiencies are at risk for repeated episodes of meningococcal disease.

A petechial skin rash can occur in up to 75% of infected individuals. In severe infections, death can ensue within hours of the appearance of symptoms. Usually these patients have profound bacteremia and die of sepsis and the associated complications such as disseminated intravascular coagulopathy. Other infections include arthritis and rarely, conjunctivitis, sinusitis, endocarditis and pneumonia.

The presumptive identification of Neisseria may be made from the Gram stain showing gram-negative diplococci. Colonies appear smooth, grayish to white on blood and chocolate agar. After 18-24 hours incubation in a CO2-enriched, humid environment, the colonies reach 1-2 mm in diameter. Encapsulated strains may appear mucoid. Neisseria are oxidase positive. Confirmatory testing includes biochemical testing looking for acid production from various carbohydrates. N. meningitidis typically produces acid from glucose, and maltose, but not lactose, sucrose or fructose. N. gonorrheae only produces acid from glucose. Other biochemical tests include nitrate reduction, DNase and beta-lactamase. Latex agglutination tests are also available to detect meningococcal antigens in bodily fluids. A negative test does not exclude the diagnosis of meningococcal disease. PCR is also used for detecting meningococci but no tests are commercially available at this point.

13 serogroups of N. meningitidis are recognized: A, B, C, D, 29E, H, I, K, L, W135, X, Y, Z. The most common serogroups are A, B, C, Y and W135. Epidemics have most commonly been reported with groups A and C. Group B is endemic in our population. The most common serogroups causing disease in Canada are groups B and C.

Chromosomal and plasmid-mediated resistance to penicillin and tetracycline has been reported. Resistance to sulfonamides is also growing and these are also no longer recommended. The third generation cephalosporins have good activity against meningococci. Treatment of close contacts is imperative and rifampin, minocycline and ciprofloxacin have been used to reduce the carrier state.

Vaccination against meningococcal disease is available. Meningococcal polysaccharide vaccines against groups A, C, Y and W135 have been available for many years. These are not recommended for routine immunization because they induce a T-cell independent immune response, resulting in poor immunogenicity and protection in early childhood and a short duration of protection. Thus it is only recommended for use in high risk groups such as people with asplenia or complement deficiencies, travelers, military recruits and those working routinely with meningococci in the laboratory. It is also used in outbreak situations. The conjugate vaccine Menjugate (Chiron) was recently introduced for the prevention of meningococcal group C disease in adults and children as young as two months of age. It is recommended for infants, children less than five years of age, adolescents and young adults. Because of its conjugate formulation, it is the only vaccine against meningococcal group C disease that can be given as of two months of age.