Infections of the central nervous system
As the cerebrospinal fluid is devoid of effective antimicrobial defences, generalized infection rapidly sets in when pyogenic organisms enter the subarachnoid space and the cerebrospinal fluid. This may be caused by:
■ direct spread due to trauma and resultant breach of the integuments of the central nervous system
■ seeding via blood from a peripheral infective focus.
Inflammation of the meninges, the membranes that cover the brain and spinal cord, is classified according to the aetiological agent, as:
■ bacterial meningitis (also called pyogenic or polymorphonuclear meningitis)
■ viral meningitis (also called aseptic or lymphocytic meningitis).
Bacterial meningitis is more severe than the viral type and remains a serious cause of morbidity and mortality despite antibiotic therapy. Prompt diagnosis is of the essence in preventing disabling sequelae of infection and death.
Symptoms include severe headache, fever, vomiting, photophobia and convulsions leading to drowsiness and unconsciousness. Signs are mainly those of meningeal irritation, i.e., neck and spinal stiffness, and Kernig's sign (pain and resistance on extending the knee when the thigh is flexed). These cardinal signs and symptoms may be absent in neonatal meningitis and meningitis in the elderly and the immunocompromised.
Sequelae include encephalopathy (altered cerebral function), cranial nerve palsies, cerebral abscess, obstructive hydrocephalus and subdural effusion of sterile or infected fluid.
The common types of bacterial meningitis and the major agents are:
■ meningococcal meningitis: Neisseria meningitidis
■ haemophilus meningitis: Haemophilus influenzae, capsulated (Pittman type b)
■ pneumococcal meningitis: Streptococcus pneumoniae
■ tuberculous meningitis: Mycobacterium tuberculosis and other mycobacteria.
Epidemiology, treatment and prevention
N. meningitidis (the meningococcus) is the main agent of meningitis in the UK and USA and most infections are caused by group B strains. The disease is common in children and young adults. Penicillin is the drug of choice: cefotaxime and chloramphenicol are alternatives. Haemophilus meningitis is mostly seen in children between 1 month and 4 years old and is treated with chloramphenicol or cefotaxime. Pneumococcal infection, common in older patients and those without a functioning spleen, is treated with penicillin. Tuberculous infection is managed by 'triple therapy', as described in Chapter 23.
Meningitis may spread quickly in close household contacts. Avoiding overcrowding in living and working conditions is helpful. Chemoprophylaxis with antibiotics (e.g., rifampicin) in meningococcal infection can eliminate the carrier state, which may develop in some.
Meningitis due to other organisms
Rarely, other organisms, such as Listeria monocytogenes, Leptospira interrogans and Cryptococcus neoformans (a fungus), may cause meningitis.
Examination of the cerebrospinal fluid, usually obtained by a lumbar puncture, is essential. Changes that occur in the cerebrospinal fluid, depending on whether the aetiology is acute pyogenic, tuberculous or viral, dictate appropriate and timely therapy (Table 25.1). Cerebrospinal fluid should also be centrifuged and the deposit Gram-stained and cultured to isolate and identify the causative agent. Blood cultures are also useful in the diagnosis of bacterial meningitis.
Treatment is dictated by the causative organism and its antibiotic sensitivity; because of the serious nature of the illness, empirical therapy with two or three antibiotic drugs is given immediately.
Viral or aseptic meningitis can be caused by many agents, as shown in Table 25.2.
The major routes of viral entry into the body are the respiratory and gastrointestinal tracts. From these portals, they spread to the central nervous system by direct migration via the olfactory nerves or indirectly via blood. Cells involved in viral spread include capillary endothelial cells, epithelial cells of the choroid plexus and infected leukocytes.
Children and young adults are the most affected.
Viral meningitis is a benign, self-limiting condition and requires only symptomatic treatment. No antiviral drugs are indicated as the condition resolves in 1-2 weeks.
Infection of the brain substance (as opposed to the meninges) is called encephalitis. This is a somewhat artificial division as patients often show signs and symptoms of meningitis and encephalitis at the same time.
The most frequently involved viruses are herpes simplex virus, mumps virus and arboviruses.
Encephalitis occurs after childhood illnesses such as measles, chickenpox and rubella, and rarely after immunization with vaccines such as pertussis. Affected patients often die or have debilitating sequelae.
In contrast to viral meningitis, encephalitis is a very serious disease that needs prompt and specific antiviral therapy such as intravenous aciclovir.
Poliomyelitis is caused by poliovirus types 1-3, belonging to the Picornaviridae.
The portal of infection is the mouth, and the virus multiplies in the lymphoid tissue of the pharynx and the intestine. It then enters the blood stream and causes a viraemia, with resulting spread into the central nervous system, causing neurological disease. The disease is an influenza-like illness, with meningitis and encephalitis. In some, damage to the anterior horn cells of the spinal cord leads to respiratory failure (requiring artificial ventilation) or permanent lower motor neuron weakness and paralytic poliomyelitis.
Epidemiology and prevention
Although epidemics of poliomyelitis were common in the past, it is now rare in the West, owing to effective polio vaccine. However, the disease is still prevalent in developing countries, where universal vaccination programmes are difficult to implement, despite the goal of the World Health Organization to eradicate the disease by the year 2000. The polio vaccines are of two types: the killed (Salk) vaccine and the live attenuated (Sabin) vaccine (Chapter 37).
Many bacteria may cause brain abscesses. These include streptococci (Streptococcus milleri and Streptococcus pneumoniae) enterococci (Enterococcus faecalis), staphylococci, anaerobic cocci and coliforms. The infections are mostly polymicrobial in nature (i.e., mixed infections).
The infective agent may reach the brain in the blood or by direct extension. In the latter case, a brain abscess may result as a direct extension of sinus infection caused by oral bacteria or, rarely, as a complication of acute or chronic dental infection. Infection may also follow traumatic injury to the maxillofacial region.
Operative drainage and excision of the abscess (if well encapsulated) is supplemented by antibiotic therapy. β-Lactam group antibiotics and gentamicin are very popular; metronidazole is also used because of its good penetration into abscesses, and as anaerobes are frequently involved.
Tetanus is caused by infection with Clostridium tetani (drumstick bacillus).
After an incubation period of 5-15 days, the exotoxins produced by the organisms precipitate severe and painful muscle spasms:
■ lockjaw—spasm of masseter muscles
■ risus sardonicus—facial grimace due to spasm of facial muscles
■ opisthotonos—arched body due to spasm of the more powerful extensor muscles of the body (see Fig. 13.4).
Contamination of wounds with tetanus spores derived from dust, manured soil or rusty objects results in spore germination and release of the powerful exotoxins tetanospasmin and tetanolysin (see Chapters 5 and 13). Although the bacteria remain localized at the site of infection, the exotoxins are absorbed at the motor nerve endings and diffuse centripetally towards the anterior horn cells of the spinal cord, blocking the normal inhibitory impulses that control motor nerve function, with resultant sustained contraction of the muscles. Wounds of the face, neck and upper extremities are more dangerous than those of the lower extremities as they have a shorter incubation period and result in more severe disease.
The main source of spores is animal faeces. The incidence is higher in the developing world because of lack of immunization and poor standards of wound care. Although tetanus is commonly associated with deep penetrating wounds, it can often result from superficial abrasions (e.g., thorn pricks). Neonatal tetanus due to infection of the umbilical stump is common in rural areas of developing countries.
Diagnosis is mainly clinical as bacteriological confirmation frequently fails. Swab or exudate from the wound typically shows 'drumstick bacilli'; biochemical identification and confirmation by mouse pathogenicity are described in Chapter 13.
1. Supportive treatment: muscle relaxants to control spasms, sedation and artificial ventilation (for respiratory muscle paralysis).
2. Antitoxin: given intravenously in large doses to neutralize the toxin; it is of little use in the late stage of disease.
3. Antibiotics: penicillin or tetracycline to prevent further toxin production.
4. Debridement: excision and cleaning of the wound.
Active immunization with adsorbed tetanus vaccine, also called toxoid (a component of diphtheria-tetanus-pertussis vaccine), should be given in childhood (during the first year of life and before school or nursery-school entry).
Prophylaxis of wounded patients
■ If the patient is immune, a booster dose of toxoid or adsorbed tetanus vaccine should be given if the primary course (or booster dose) was given more than 10 years previously, and human antitetanus immunoglobulin if the wound is dirty and more than 24 h old.
■ If the patient is non-immune, human antitetanus immunoglobulin should be given, followed by a full course of tetanus toxoid by injection.
Penicillin may be given as prophylaxis, not only to prevent tetanus but also to avoid pyogenic infection.
Booster doses of toxoid 10 years after the primary course and again 10 years later maintain a satisfactory level of protection. Any adult who has received five doses is likely to have lifelong immunity.
Infections of the locomotor system
The two major infections associated with the locomotor system (i.e., bones and joints) are acute septic arthritis and osteomyelitis. Natural defences in the locomotor system include:
■ specialized macrophages in the synovial membranes of joints (highly phagocytic)
■ a few mononuclear cells, complement and lysozyme of synovial fluid
■ a rich vascular plexus traversing the medulla and cortex of bone with integral defences.
Important pathogens are listed in Fig. 25.1.
Acute septic arthritis
Commonly associated bacteria are Staphylococcus aureus, H. influenzae, Streptococcus pneumoniae and other streptococci,
Fig. 25.1 Major infectious agents of the locomotor system.
Neisseria gonorrhoeae and non-sporing anaerobes such as Bacteroides spp. Other infrequent but notable agents are M. tuberculosis, Salmonella spp. and Brucella spp.
Limitation of movement with swelling, redness and severe pain are the cardinal symptoms; usually, only a single joint is involved. Crippling and permanent joint damage may result despite antibiotic therapy.
The condition may result from:
■ traumatic injury through the joint capsule
■ haematogenous spread, usually as a complication of septicaemia
■ extension of osteomyelitis or spread of infection from an adjacent septic focus
■ complication of rheumatoid arthritis
■ infection of joint prosthesis.
Acute septic arthritis occurs most commonly in children. Sources of infection are many and include sepsis of the skin, nasopharynx, sinuses, lungs, peritoneum and genital tract. The source of infection of artificial joints could be the patient, the operating team or the theatre air.
Diagnosis is by direct film observation and culture of aspirated joint fluid; blood culture; culture of specimens from the suspected primary focus of infection, e.g., throat, genital tract; and serological tests for salmonellosis and brucellosis, if suspected.
Initial antibiotic therapy is given on an empirical or 'best-guess' basis. Early administration of antibiotics, immediately after the specimen is taken, is essential to prevent chronic sequelae. Antibiotics may be injected directly into the joint or given systemically.
Reactive arthritis is the term given to acute arthritis affecting one or more joints; it develops 1-4 weeks after infection of the genital (post-sexual reactive arthritis) or gastrointestinal tract (post-dysenteric reactive arthritis). The causative agent in post-sexual reactive arthritis is Chlamydia trachomatis; almost all patients are men. Post-dysenteric reactive arthritis may follow infections with Salmonella, Shigella, Yersinia or Campylobacter.
Reactive arthritis should be differentiated from septic arthritis as it is not due to joint infection. It is thought to be mediated by immunological mechanisms, and there is an apparent genetic predisposition to the disease.
Osteomyelitis can be divided into acute and chronic forms. Acute infection usually occurs in children under 10 years old, whereas the chronic variety is more common in adults.
Mostly Staphylococcus aureus (some 75% of cases); other agents include H. influenzae (in preschool children), Streptococcus pyogenes, Streptococcus pneumoniae and other streptococci; Salmonella, Brucella and non-sporing anaerobes rarely.
Staphylococcus aureus is most common; rarely M. tuberculosis, Pseudomonas aeruginosa, Salmonella and Brucella spp.
Any septic lesion can be the source of the organism (e.g., a boil or pustule); spread to bone is usually haematogenous. Infection at all ages may be a result of major trauma (e.g., compound fracture) that exposes bone tissue to the environment.
Diagnosis is by blood culture (a number of cultures may be required to isolate the infective agent(s), which circulate in the blood in very small numbers); culture of pus from the bony focus—pus may be obtained by needle aspiration or by open surgery; and by specimens from the related infective focus, e.g., 'cold abscess' pus in tuberculosis.
Antibiotics alone are helpful if started early in the disease, by the parenteral route first and the oral route later. Penicillinaseresistant penicillin (such as flucloxacillin) should be given first if culture results are not available as Staphylococcus aureus is the predominant agent. Drugs that penetrate bone well (such as fusidic acid and clindamycin) are alternatives. Erythromycin is an alternative in patients who are hypersensitive to penicillin.
Surgery may be needed to drain pus and remove sequestra, if any.
Osteomyelitis of the jaws
Osteomyelitis of the jaws (see also Chapter 34) is uncommon owing to the relatively high vascularity of the jaws, especially the maxilla; therefore, the mandible is more commonly affected than the maxilla. The following predisposing conditions are noteworthy:
■ bone disease, such as Paget's disease or osteopetrosis, fibrous dysplasia, bone tumours
■ irradiation of the jaws for cancer therapy (e.g., nasopharyngeal carcinoma)
■ trauma superimposed on debilitating conditions such as malnutrition, and immunocompromised states.
• The cerebrospinal fluid is sterile and devoid of effective antimicrobial defences; it may be infected either directly from a contiguous focus (e.g., due to trauma) or indirectly via blood from a peripheral infective focus.
• Meningitis, defined as the inflammation of the meninges, can be broadly categorized as bacterial meningitis (also called pyogenic or polymorphonuclear meningitis) or viral meningitis (also called aseptic or lymphocytic meningitis).
• The common types (and agents) of bacterial meningitis are meningococcal meningitis (Neisseria meningitidis), haemophilus meningitis (Haemophilus influenzae), pneumococcal meningitis (Streptococcus pneumoniae) and tuberculous meningitis (Mycobacterium tuberculosis and others).
• Examination of the cerebrospinal fluid, obtained by a lumbar puncture, is mandatory for diagnosis of the different types of bacterial meningitis.
• Viral or aseptic meningitis can be caused by many agents and the major routes of entry are the respiratory and gastrointestinal tracts.
• Viral meningitis is usually benign and self-limiting, requiring only symptomatic treatment; no antiviral therapy is indicated.
• Polio vaccine is of two types: the killed (Salk) vaccine and the live attenuated (Sabin) vaccine; the latter given orally is the more popular.
Contamination of wounds with Clostridium tetani spores derived from dust, manured soil or rusty objects results in spore germination and release of the powerful exotoxins tetanospasmin and tetanolysin to cause tetanus.
Tetanus is managed by supportive measures (e.g., muscle relaxants, sedation and artificial ventilation), antitoxin, antibiotics (penicillin or tetracycline) and wound debridement.
Tetanus-preventive measures are active immunization with formol toxoid (a component of diphtheria-tetanus-pertussis (DTP) vaccine given in childhood) and booster doses of toxoid once every 10 years for risk groups.
Osteomyelitis can be divided into acute (seen in children under 10 years old) and chronic osteomyelitis (common in adults). The acute form is mostly caused by Staphylococcus aureus (some 75% of cases); in chronic osteomyelitis, Staphylococcus aureus is most common; rarely M. tuberculosis, Salmonella and Brucella spp.
Osteomyelitis of the jaws is uncommon owing to their high vascularity (especially the maxilla).
Predisposing conditions that result in osteomyelitis of the jaws include bone disease (e.g., Paget’s disease, osteopetrosis, fibrous dysplasia, bone tumours), irradiation and trauma superimposed on debilitating conditions such as malnutrition, and immunocompromised states.
Review questions (answers on p. 366)
Please indicate which answers are true, and which are false.
25.1 Common causative agents of acute bacterial meningitis include:
A. Neisseria meningitidis
B. Non-typable Haemophilus influenzae
C. Streptococcus pneumoniae
D. Staphylococcus aureus
E. Leptospira interrogans
25.2 Signs and symptoms of acute bacterial meningitis include:
B. Nuchal rigidity
E. All of the above
25.3 Aseptic meningitis:
A. Commonly has a viral aetiology
B. Can be easily differentiated from pyogenic meningitis at presentation
C. Has a seasonal incidence
D. Cerebrospinal fluid cultures often become positive
E. Cerebrospinal fluid examination usually shows an elevated lymphocyte count
A. Is caused by an RNA virus
B. Spreads by the faecal-oral route
C. Leads to flaccid paralysis
D. Causes death due to cardiac failure
E. Can be prevented using a live vaccine
25.5 Cerebral abscesses:
A. Are often due to monomicrobial infections
B. May follow traumatic injury to the maxillofacial region
C. Can manifest with focal neurological signs
D. May rarely need surgical drainage
E. May be caused by oral flora
A. Is the result of direct invasion of the anterior horn cells by Clostridium tetani
B. Results in painful muscle spasms and spastic paralysis
C. Patient may present to the dentist with trismus
D. Treatment of the acute case is with toxoid and penicillin
E. Could be prevented by a single dose of tetanus toxoid
25.7 Osteomyelitis of the jaw:
A. Is relatively uncommon
B. Is more common than those of long bones
C. Anaerobes are the common causative agents
D. Is a complication of irradiation therapy
E. May be complicated by pre-existing bone disease
Shanson, D. C. (1999). Infections of the central nervous system. In Microbiology in clinical practice (3rd ed.). Ch. 11. Oxford: Butterworth-Heinemann.
Shanson, D. C. (1999). Bone and joint infections. In Microbiology in clinical practice (3rd ed.). Ch. 18. Oxford: Butterworth- Heinemann.