Microbiology
Pathogens
A patient presents to ED with a fever and a headache. You notice that in the patient’s notes it states they are particularly susceptible to infection with Neisseria meningitidis. Which of the following immunodeficiencies is this patient most likely to have?
Answer:
Immunity against N. meningitidis is dependent on complement activation and formation of the membrane attack complex (MAC), therefore individuals with complement deficiencies, particularly C5 - C9, have an increased risk of developing meningococcal bacteraemia. C1 inhibitor deficiency can result in hereditary angioedema.Neisseria Meningitidis
Microbiology / Pathogens / Neisseria
Last Updated: 21st April 2019
| Microorganism | Neisseria Meningitidis |
|---|---|
| Gram stain | Gram negative |
| Shape | Cocci (diplococci) |
| Oxygen requirements | Obligate aerobe |
| Additional features | Encapsulated, Ferments glucose and maltose |
| Reservoir | Nasopharynx |
| Transmission | Direct contact or respiratory droplet |
| Diseases | Meningitis and meningococcal sepsis (notifiable diseases) |
| Risk factors | Smoking, winter, complement deficiencies (C5 - C9) |
Transmission
Asymptomatic carriage of Neisseria meningitidis in the nasopharynx and upper respiratory tract is common (in about 5 - 10% of the population). Spread largely occurs from close (e.g. kissing) contact with saliva or respiratory secretions.
Epidemiology
Infection is most common in the winter, with epidemics occurring about every 10 - 12 years. Most invasive infections in the UK are caused by serogroups B or C, serogroup B most commonly since the introduction of the MenC vaccination in 1999. The new MenB vaccine was added to the UK routine immunisation schedule in September 2015.
Pathogenesis
N. meningitidis has three important virulence factors:
- A polysaccharide capsule that resists phagocytosis by PMNs (this capsule is the antigen that defines the serologic groups, that is detected in CSF and that is used in vaccines)
- Endotoxin (LPS) which activates complement and stimulates cytokine release resulting in fever and shock
- An IgA protease that helps the bacteria attach to the membranes of the upper respiratory tract by cleaving secretory IgA
Immunity against N. meningitidis is dependent on complement activation and formation of the membrane attack complex (MAC), therefore individuals with complement deficiencies, particularly C5 - C9, have an increased risk of developing meningococcal bacteraemia.
Risk Factors
Risk factors for disease:
- Environmental risk factors
- Overcrowding e.g. military recruits, university students
- Respiratory viral infections e.g. influenza
- Damage to the upper respiratory tract caused by smoking, low humidity, dust or trauma
- Winter season
- Host risk factors
- Infants and young children (highest incidence in infancy < 5 years, second smaller peak at 14 - 19 years)
- Older age (> 65 years)
- Complement deficiency
- Hyposplenia/asplenia
Clinical Disease
The two most important manifestations of disease are meningitis and meningococcal septicaemia. Meningococcal meningitis is characterised by fever, headache, neck stiffness, photophobia and reduced consciousness and meningococcal septicaemia by a non-blanching petechial rash and signs of septic shock.
Treatment
Treatment of meningococcal disease should be given as soon as the diagnosis is suspected, and without waiting for investigations.
If meningococcal disease is suspected out of hospital, patients should receive a single dose of parenteral (IM or IV) benzylpenicillin as soon as possible before urgent transfer to hospital (as long as this does not delay the transfer).
In hospital, benzylpenicillin or cefotaxime (or ceftriaxone) are the antibiotics of choice for meningococcal disease. Chloramphenicol may be considered in severe penicillin allergy.
To eliminate nasopharyngeal carriage, ciprofloxacin, or rifampicin, or ceftriaxone may be used.
Diagnosis
Definitive diagnosis is made from smear and cultures of blood and CSF aspirate; rapid antigen detection or NAAT of CSF and blood are sensitive and reliable.
CSF analysis typically shows:
- cloudy turbid appearance
- raised WCC
- predominantly neutrophils
- high protein
- low glucose (typically < 40% of serum glucose)
- Gram-negative diplococci seen under microscopy
Prevention
Prophylaxis against meningococcal disease should be considered with rifampicin or ciprofloxacin, regardless of meningococcal vaccination status, for all household and other intimate contacts of an index case and for individuals who have had transient close contact with an index case where they have been directly exposed to large particle droplets/secretions from the respiratory tract.
Vaccinations available against N. meningitidis are shown below:
| Serotype | Vaccine |
|---|---|
| MenB | 2, 4 and 12 months |
| MenC | 1 year |
| Men ACWY | 14 years |
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- Biochemistry
- Blood Gases
- Haematology
| Biochemistry | Normal Value |
|---|---|
| Sodium | 135 – 145 mmol/l |
| Potassium | 3.0 – 4.5 mmol/l |
| Urea | 2.5 – 7.5 mmol/l |
| Glucose | 3.5 – 5.0 mmol/l |
| Creatinine | 35 – 135 μmol/l |
| Alanine Aminotransferase (ALT) | 5 – 35 U/l |
| Gamma-glutamyl Transferase (GGT) | < 65 U/l |
| Alkaline Phosphatase (ALP) | 30 – 135 U/l |
| Aspartate Aminotransferase (AST) | < 40 U/l |
| Total Protein | 60 – 80 g/l |
| Albumin | 35 – 50 g/l |
| Globulin | 2.4 – 3.5 g/dl |
| Amylase | < 70 U/l |
| Total Bilirubin | 3 – 17 μmol/l |
| Calcium | 2.1 – 2.5 mmol/l |
| Chloride | 95 – 105 mmol/l |
| Phosphate | 0.8 – 1.4 mmol/l |
| Haematology | Normal Value |
|---|---|
| Haemoglobin | 11.5 – 16.6 g/dl |
| White Blood Cells | 4.0 – 11.0 x 109/l |
| Platelets | 150 – 450 x 109/l |
| MCV | 80 – 96 fl |
| MCHC | 32 – 36 g/dl |
| Neutrophils | 2.0 – 7.5 x 109/l |
| Lymphocytes | 1.5 – 4.0 x 109/l |
| Monocytes | 0.3 – 1.0 x 109/l |
| Eosinophils | 0.1 – 0.5 x 109/l |
| Basophils | < 0.2 x 109/l |
| Reticulocytes | < 2% |
| Haematocrit | 0.35 – 0.49 |
| Red Cell Distribution Width | 11 – 15% |
| Blood Gases | Normal Value |
|---|---|
| pH | 7.35 – 7.45 |
| pO2 | 11 – 14 kPa |
| pCO2 | 4.5 – 6.0 kPa |
| Base Excess | -2 – +2 mmol/l |
| Bicarbonate | 24 – 30 mmol/l |
| Lactate | < 2 mmol/l |
