Case of the Month

August 2013

Linda de Gouveia and Colleen Bamford - SASCM

A 19-year-old female university student was admitted to casualty with a 26-hour history of high fever, chills, severe headache and a stiff neck. Soon after arriving at casualty she vomited twice. She had received all appropriate immunizations and was otherwise healthy. No travel history was available.

  • Temp: 39.9° C
  • Pulse 124/minute
  • respiratory rate 20/minute
  • BP 105/71 mmHg
  • No rash

Question 1: What is the clinical diagnosis?

Answer to Q1

The clinical diagnosis is one of acute meningitis. The main differential diagnosis would be an intracranial bleed The signs and symptoms of meningitis are variable and often depend on the patient’s age. In infants and the elderly, the clinical presentation of meningitis is often non-specific and may consist primarily of altered mental status, whereas in older children and adults, a classic triad of fever, headache, and nuchal rigidity is the most common manifestation. Nausea and vomiting are common at any age.

Petechiae or purpura are noted in ~50% of adults with meningococcal meningitis. Seizures are noted in ~30% of patients before admission or early in the course of the illness.

Several anatomic barriers exist that effectively prevent organism entry into the central nervous system; the most obvious being the scalp and skull, which protect the brain from external elements. Three meninges surround and protect the brain and spinal cord. The outermost, dura mater, (a thick membrane that is adherent to the periosteum of the skull), the arachnoid, (loosely surrounds the brain), and the pia mater, (contiguous with the external surface of the brain. Finally, the blood-brain barrier prevents organisms from entering the CNS.

Depending on where these CNS infections occur, they are usually grouped as meningitis, encephalitis, brain abscess, or myelitis (infection of the spinal cord). The subarachnoid space is the site where meningitis develops. Most infections of the CNS are relatively acute and demand prompt diagnostic and therapeutic attention.

A lumber puncture was performed.

CSF appearanceTurbid
Polymorphonuclear cells4 200 /µl
Lymphocytes410 / µl
Erythrocytes300 / µl
Protein2 g/l
Glucose1.8 mmol/l

Question 2: What is the diagnosis and what are the likely causative organisms of this patient’s illness?

Answer to Q2

The diagnosis is most compatible with bacterial meningitis

Aetiological differential diagnosis
Streptococcus pneumoniae
Neisseria meningitidis
Listeria monocytogenes
Streptococcus agalactiae (Group B streptococcus)
Haemophilus influenzae type b (Hib)

The most common causes of meningitis are viruses, which are associated with the ‘aseptic meningitis’ syndrome. Enteroviruses account for the majority of cases, although mumps, herpes, and HIV are also common causes. Typical symptoms are fever, headache, neck stiffness, and photophobia, sometimes accompanied by upper respiratory symptoms. Beyond the neonatal period, viral meningitis is rarely fatal.

Life-threatening bacterial meningitis is caused primarily by a small group of pathogens, including Streptococcus pneumoniae, Neisseria meningitidis, Listeria monocytogenes, and Streptococcus agalactiae which affect different age groups with some overlap. Until the introduction of the highly effective Hib vaccine in children < 5 years of age, haemophilus influenzae type b (hib) was the most common cause of bacterial meningitis.

Question 3: What laboratory examination/s can assist in confirming the diagnosis?

Answer to Q3

Gram stain and culture of CSF Blood culture [Antigen detection test or PCR on CSF]

Gram stain is a quick, cheap, simple and widely used in meningitis, with a sensitivity of 60% to 90% in cases of bacterial meningitis. If the CSF is clear, smears should be prepared from centrifuged deposit, but if CSF is turbid, smears should be prepared directly from unspun CSF.

Blood culture –Although sensitivity is limited, blood culture is a valuable diagnostic tool, particularly in situations where lumbar puncture is delayed for any reason.

Bacterial latex antigen test (1-3) - Antigen detection of pathogens in specimens may provide a useful adjunct to culture-based diagnosis and allows for the rapid detection of a number of specific bacterial antigens, namely S. agalactiae, S. pneumoniae, N. meningitidis, and H. influenzae type b (Hib), in body fluids (mostly CSF and blood). However, these tests, do have limited sensitivity and specificity, and interpretation of results can be subjective. The kits are also are expensive and have a short shelf life.

There are a number of literature reviews regarding the role for bacterial antigen kits for diagnosing bacterial meningitis. Most suggest that Gram stain remains the primary diagnostic test, and if done properly provides the most valuable information. Antigen detection may be done in consultation with the clinician or when the patient has had prior antibiotic use or the Gram stain is hard to read. Extreme care should be taken in performing and interpreting results so that these are both accurate and meaningful.

PCR – Molecular confirmation of pathogen/s, where DNA is extracted, amplified and detected. Although previously limited to reference laboratories because of cost and complexity, recent development of realtime methods for testing multiple pathogens simultaneously means that molecular testing may become part of routine diagnostic testing in the future. This would be a great advantage, particularly in patients who have received prior antibiotics. The rapid detection of common viral pathogens would also reduce unnecessary antibiotic therapy in such patients.

Question 4: The laboratory reports the presence of scanty Gram-negative diplococci on the Gram stain. What is the most likely pathogen, and what are its microbiologic and phenotypic properties?

Answer to Q4

Neisseria meningitidis

  • Gram-negative coffee-bean shaped diplococci, that occur both intracellularly (in polymorphonucleocytes) and extracellularly
  • Cocci have a thin capsule forming a halo which may be visible microscopically
  • Strains grow on blood agar (unpigmented, round, smooth, moist glistening colonies) and boiled blood agar (large, colourless-to-grey opaque colonies) and require a CO2 enriched atmosphere for incubation and growth
  • Isolates are oxidase positive, ferment glucose and maltose, but not lactose and sucrose.
  • Encapsulated clinical isolates may be agglutinated by specific serogrouping antisera into the common serogroups: A, B, C, Y and W. (Serogroup W135 has been renamed and is now referred to as N. meningitidis serogroup W)(4).

Question 5: What are the clinical and public health implications? What infection control measures need to be implemented?

Answer to Q5

As bacterial meningitis has a rapid progression (within minutes to hours), aggressive management is critical to improving patient outcome. Therefore these patients should be managed as a medical emergency in order to reduce morbidity and mortality and started on empirical antibiotics as soon as possible. If lumbar puncture is delayed, a blood culture should be obtained, and antibiotics administered. Delays in therapy are associated with worsened outcomes. There should be a high index of suspicion for meningococcal disease in patients who present with nonspecific early signs and symptoms.

Interventions should include the administration of post-exposure chemoprophylaxis (PEP) to individuals exposed to the case.

All cases of suspected meningococcal disease (meningitis and sepsis) should be notified to the Department of Health, on clinical suspicion alone, not necessarily based on laboratory confirmation.

Sporadic cases of meningococcal disease are reported across South Africa; however the numbers usually peak during the months of August to October, (winter and spring seasons), with diverse serogroups seen across the country (6-7). Recent South African data can be found at: here

Outcomes of the case

The patient was treated with intravenous penicillin and a cephalosporin immediately on admission. The headache and stiff neck persisted for an additional two days. Five days later the cephalosporin was discontinued, but the intravenous penicillin continued for 10 days. By then the signs and symptoms of her illness had disappeared and she was discharged in a state of good health.

Post-exposure chemoprophylaxis (PEP) was given to her immediate close contacts, as well as other university attendees. No further cases were reported. This was an isolated case.

Lessons Learned
  • Clinicians should have a high index of suspicion for meningococcal disease in patients who present with acute febrile illness.
  • Disease typically has a rapid progression and should be managed as a medical emergency, requiring urgent antibiotics in order to reduce morbidity and mortality.

All cases of suspected meningococcal disease (meningitis and sepsis) should be notified telephonically to the Department of Health


  1. Hayden RT, Frenkel LD. More laboratory testing: greater cost but not necessarily better. Pediatr Infect Dis J 2000;19:290-292.
  2. Tarafdar K, Rao S, Recco RA, Zaman MM. Lack of sensitivity of the latex agglutination test to detect bacterial antigen in the cerebrospinal fluid of patients with culture-negative meningitis. Clin Infect Dis 2001;33:406-8.
  3. Tunkel AR, Hartman BJ, Kaplan SL, Kaufman BA, Roos KL, Scheld WM, Whitley RJ. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis 2004;39:1267-84.
  4. Harrison OB et al, Description and nomenclature of Neisseria meningitidis capsule locus. Emerg. Infect Dis 2013: 19;566-573
  5. http://nicd.ac.za/?page=alerts&id=5&rid=180
  6. http://nicd.ac.za/?page=publications&id=48

Useful Resources:

  • Guidelines for the management, prevention and control of meningococcal disease in South Africa 2011 Department of Health, South Africa. www.doh.gov.za
  • Boyles T, Bamford C, Bateman K, Blumberg L, Dramowski A, Karstaedt A, Korsman S, le Roux D, Maartens G, Madhi S, Naidoo R, Nuttall J, Reubenson G, Taljaard, J, Thomas J, van Zyl G, von Gottberg A, Whitelaw A, Mendelson M. Guidelines for the management of acute meningitis in children and adults in South Africa. South African Journal of Epidemiology and Infection 2013;28(1):5-15
  • initial csf findings in viral meningitis may show a polymorphonuclear predominance, particularly in enteroviral meningitits, which can also be associated with low csf glucose.

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