Medicine for Africa - Medical Information Service

ENINGITIS

Definition:

Meningitis is defined as an inflammation of the meninges, which are membranes (sheets of tissue) that protect the brain and spinal cord.

Meningeal inflammation is usually caused by an infection due to bacteria, viruses or less often, other microorganisms, e.g. fungi.

Bacterial meningitis is commonly caused by strains such as Streptococcus pneumoniae, Neisseria meningitides, Staphylococcus aureus, Escherichia coli and Staphylococcus epidermidis.  Haemophilus influenzae type b used to be the primary cause of bacterial meningitis until the 1990s, when the introduction of a widespread vaccination (the Hib vaccine) caused a significant reduction in the incidence of this type  of meningitis infection.

In newborn babies up to three months, or in premature babies, common bacteria causing meningitis include the group B streptococcus (subtype III) and normal residents of the digestive tract, such as E. coli (carrying the K1 antigen) and Listeria monocytogenes (type IVb); the latter two can also be found causing epidemics. 

Older children are more often infected by Neisseria meningitides (meningococcus), Strep. pneumoniae (serotypes 6,9,14,18,23) and Haemophilus influenzae typeB in children under five years of age (especially if not vaccinated – see Prevention).

Tuberculous meningitis caused by Mycobacterium tuberculosis predominantly occurs in countries where tuberculosis is still prevalent and in patients with HIV/AIDS or who are otherwise immune compromised (certain cancers, transplant patients)

Recurrent bacterial meningitis may be caused by certain anatomical defects, such as e.g. skull fractures or other causes (often congenital) resulting in leakage of cerebrospinal fluid (CSF), or, again due to disorders (congenital or acquired) of the immune system.

Viral meningitis is caused in about 90% of cases by anyone member of the enteroviruses (e.g. coxsackievirus, echovirus, or poliovirus); the remaining 10% of viral meningitis may be due to mumps, the herpesvirus (herpes simplex virus type 2, HSV-2), the human immunodeficiency virus (HIV), or the arboviruses, which are transmitted by insect bites. People who are not vaccinated against mumps can develop meningitis following a mumps infection in about 30% of cases.  

Meningitis can also be caused by certain cancers and drugs, or secondary to non-infectious diseases, such as:

• Widespread metastatic cancer (carcinomatosis);
• Parasite-contaminated water;
• Head injuries, including brain surgery or birth defects of the skull;
• Diseases such as sarcoidosis, systemic lupus erythematosus (SLE), certain forms of vasculitis, e.g. Behçet’s disease, and even migraine;
• Certain medications, such as some non-steroidal anti-inflammatory drugs (e.g. ibuprofen, naproxen) or certain antibiotics and intravenous immunoglobulins. 

Aseptic meningitis may be due to viruses or following partially treated bacterial meningitis. Other diseases that may cause aseptic meningitis include:

• Endocarditis – infection of the heart valves spreading clusters of bacteria through the bloodstream;
• Syphilis – via the disease causing spirochetes called Treponema palidum;
• Lyme disease – is a tick borne disease caused by Borrelia burgdorferi, and the most common tick-borne disease in the Northern hemisphere;
• Malaria – cerebral malaria
• Fungal diseases causing meningitis, e.g. due to Candida albicans, Cryptococcus neoformans or Histoplasma capsulatum; fungal meningitis often occurs as an opportunistic disease in HIV/AIDS patients or other severely immune compromised patients;
• Amoebic meningitis – is caused by amoebae such as Naegleria fowleri from freshwater sources (rivers, lakes).

Meningococcal meningitis occurs classically in epidemics in areas where people live close together, such as army barracks, college campuses, informal settlements such as townships and others (annual Hajj pilgrimage).  In sub-Saharan Africa, large epidemics often occur during the dry season, usually caused by Neisseria meningitides group A and C, while group W135 meningococci have recently been implicated for epidemics in Africa.

Symptoms:

Symptoms of bacterial meningitis usually development within just a few hours following infection and are dominated by fever, irritability, nausea and vomiting, and at times, a runny nose or sore throat.  Within 8 to 12 hours, these symptoms are followed by cold hands and feet, again followed by leg pain.

Acute bacterial meningitis can be fatal within hours, thus, it is important to seek medical attention as soon as possible.

In viral meningitis, symptoms may surface suddenly or develop slowly over days or weeks, depending on the virus involved and the overall health status of the patient.

Characteristic symptoms of both bacterial and viral meningitis are rather similar and include:

• Severe headache – most common symptom;
• Stiff neck – nuchal rigidity, second most common symptom, is the inability to flex the neck forward passively, due to increased muscle tone in the neck;
• Fever.

Sometimes, a dry cough, runny nose and congestion may precede the development of other symptoms and signs, such as:

• Petechial skin rashes – typical red and purple spots on the trunk, lower extremities, mucous membranes, conjunctiva of the eyes, and occasionally on hands and feet; points to an infection by Neisseria meningitides bacteria (meningococcal meningitis);
• Confusion or altered consciousness;
• Drowsiness;
• Lethargy;
• General joint pain;
• Nausea and vomiting;
• Seizures;
• Photophobia – sensitivity to light;
• Phonophobia – sensitivity to loud noise.

In young infants, typical symptoms may include:

• Bulging of the fontanels (soft areas between skull bones) on the head, due to increased intracranial pressure;
• Decreased activity;
• High pitched cry;
• Increased crying and irritability;
• Difficulty with nursing and eating;
• Excessive sleeping.

Complications of meningitis, especially in untreated cases or where treatment has been delayed may include ‘disseminated intravascular coagulation’ (DIC), a life-threatening blood clotting disorder, encephalitis (inflammation of brain tissues) with subsequent seizures, and the so-called ‘syndrome of inappropriate anti-diuretic hormone’ (SIADH), in which the excessive release of anti-diuretic hormone (ADH or vasopressin) results in fluid retention and overload.

Long term complications in cases that have not been treated promptly also increase the risk of brain damage with behavioral and personality changes; vision, speech and hearing loss (partial or total); cerebral palsy; learning disabilities and/or mental retardation, and partial or total paralysis.

Severe bacterial meningitis may result in coma and death.

 
Diagnosis:

The diagnosis of meningitis can well be suspected during a thorough physical examination of the patient, who describes the above listed symptoms of a stiff neck, severe headache and fever.  The diagnosis can be confirmed by examining the cerebrospinal fluid (CSF – envelops the brain and spinal cord) collected by way of a lumbar puncture (spinal tab).

Clinical signs for meningitis include:

• Kernig’s sign – the patient is assessed while lying supine (on his/her back) with both hips and knees flexed to 90 degrees; if ensuing pain limits the passive extension of the knee, Kernig’s sign is considered ‘positive’;

• Brudzinski’s sign – is considered positive, if flexion of the neck of the patient lying supine causes involuntary hip and knee flexion.

While the sensitivity of both tests is limited, they are very specific, that is, these tests are rarely positive in other diseases.  Thus, a positive test is a good inclination for the presence of meningitis. 

Laboratory tests should include a complete blood count (CBC) and setting up a blood culture. A lumbar puncture, or spinal tap, would be essential to determine the diagnosis, to identify the offending type of bacteria and to subsequently select and start an appropriate treatment scheme.

The CSF is examined as to its pressure (200-500 mm H2O is consistent with bacterial meningitis), the content and type of white blood cells (WBCs), red blood cells (RBCs), (presence of) protein content and the (increased) level of glucose.  Gram staining the CSF and examining it under the microscope can further identify the type of bacteria that caused the meningitis (in about 60% of cases); CSF cultures will definitely determine the offending bacteria.

Additional tests that could be performed with the CSF, if available, include the latex agglutination test, the limulus lysate test, and the highly sensitive polymerase chain reaction (PCR) test for identifying bacterial or viral DNA.

Other tests that may be done, if available, include a CT scan (computer tomography) and/or MRI (magnetic resonance imaging) of the brain to evaluate the brain and exclude other diseases that are part of the differential diagnosis of meningitis, such as other neurological diseases or tumors.


 
Treatment:

Meningitis is a potentially life-threatening disease and should be treated as soon as possible.  Treatment depends on the agent that caused the meningitis, i.e. whether the cause of the disease is bacterial, viral, fungal or parasitic.

Bacterial meningitis can be treated with a multi-drug regimen of antibiotics, given intravenously (i.v.) as soon as possible, in order to prevent complications and neurological damage.  If the clinical symptoms are already severe when the patient presents to the doctor or healthcare facility, treatment may be started prior to performing a lumbar puncture (spinal tap) for properly diagnosing the offending agent.

Thus, severely ill patients can be treated with an antibiotic combination of penicillin and one of the cephalosporin drugs.  Since some bacteria may be resistant to these drugs, vancomycin with/without the addition of rifampin, ampicillin and gentamicin may be added to cover resistant strains of pneumococcal bacteria and Listeria monocytogenes.

Once the results of the CSF gram stained smears and/or from the CSF culture have revealed the specific type of bacteria, the antibiotic treatment can be adjusted accordingly.

Viral meningitis requires primarily palliative care, such as symptom relief, including increased fluid intake (intravenous saline solution) to prevent dehydration, bed rest and pain relievers (aspirin, acetaminophen) which will ease body aches and reduce fever. The only antiviral medication that is available is acyclovir which can be used in meningitis that is caused by the herpes simplex virus or varicella zoster virus (which is also a type of herpes virus).

Fungal meningitis can be treated by amphotericin B and fluconazole, individually or combined, which are the drugs of choice for this type of meningitis.

Parasitic meningitis is best treated with antihelminthic agents such as benzimidazole or others.

Corticosteroids may be used in case of complications to reduce mortality, severe hearing loss and neurological damages due to the infection.  Corticosteroids have also shown some positive effects in tuberculous meningitis in patients with AIDS (acquired immune deficiency syndrome).


 
Prevention:

There are a number of vaccines available against various meningitis causing bacteria.

Immunization against Haemophilus influenzae type B bacteria has become part of the routine vaccination schemes for young children; since then, this pathogen has been all but eliminated as a cause for meningitis in young children.   Furthermore, childhood vaccination against mumps has also resulted in greatly reduced cases of meningitis caused by the mumps virus.

Regarding the meningococcal meningitis – there are individual vaccines, and now even a quadrivalent vaccine available against Neisseria meningitides groups A, C, W135 and Y.

There is also a vaccine against the group B meningococcus available, albeit with mixed results, as the vaccine cross-reacts with some normal human proteins, resulting in only a weak response from the immune system against this bacterium.

Meningitis caused by Streptococcus pneumoniae can partially be prevented by a ‘pneumococcal polysaccharide vaccine’, which covers one particular group of bacterial subtypes.  However, this vaccine is still rather expensive.

BCG (Bacillus Calmette-Guérin) vaccination against tuberculosis has also shown to have some effect against tuberculous meningitis, which, however, wanes in adulthood.

In summary, vaccines are available against:

• Haemophilus influenzae type b bacteria;
• Neisseria meningitides bacteria;
• Pneumococcal (children aged 2 and younger) bacteria;
• Streptococcus pneumoniae bacteria;
• MMR (measles, mumps, rubella) virus;
• Varicella (chickenpox) virus.

And finally, antibiotics may be used to prevent the development of bacterial meningitis in people exposed to the disease.

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