FAQS

Disease:

Neisseria meningitidis or the meningococcus is a Gram negative bacterium occurring in pairs (diplococcus). The meningococci synthesise polysaccharides (chains of sugar molecules) that encapsulate the bacteria. Based on reactions with antisera, different polysaccharides have been identified as so-called serogroups, classifying at least 13 serogroups. Groups A, B and C account for about 90% of meningococcal disease, whereas groups Y and W-135 are relatively uncommon causes of meningococcal infection. Other serogroups are of little importance.

Transmission:

Most people may have carried potentially harmful meningococci in the throat for some time. Such carriage is usually harmless, but on rare occasions the meningococci invade the blood and cause disease. Meningococcal disease has two main manifestations, meningitis and septicaemia. Meningitis is an inflammation of the lining of the brain and spinal chord and can lead to rapid death or permanent brain damage, particularly in young children. Five to ten percent of those suffering from this manifestation of the disease die as a result of it. Septicaemia, on the other hand, results from an infection of the blood (bacteremia). Although less common than meningococcal meningitis it is more serious and has a mortality rate that may exceed 15-20 %.

Symptoms

The most common symptoms of meningococcal meningitis are vomiting, severe headache, a stiff neck and abnormal sensitivity to light. In infants and small children high fever, irritability and vomiting are often the only signs, and children are frequently not brought to the hospital until loss of consciousness or convulsions occur. If the blood is infected, the patient often experiences generalised malaise, headache, weakness and hypotension. A purplish skin rash similar to bruising may appear, a sign that the disease is already in an advanced state. This rash is characteristic in that it will not disappear when seen through a glass pressed against the skin. N. meningitidis is transmitted by saliva or by droplets from the nose and throat of an infected person. The period between infection and onset of the disease varies from 1 - 10 days, but is usually less than 4 days. Effective treatment will eliminate the possibility of meningococcal transmission within 24 hours.

Carriers

Transient nasopharyngeal carriage rather than disease is the normal outcome of meningococcal colonisation. A person may carry the organism for up to 2 years, the average being 9-10 months. Carriers are regarded as a source of infection and the risk of an epidemic increases with the percentage carriers in a population. Among healthy young children 5%-15% are carriers of meningococci whereas the corresponding number in adult populations is approximately 1%.

Who is at risk

Child care centres, schools, colleges, and military recruit camps are at particular risk of outbreaks. Information is incomplete with regard to the conditions influencing the balance between asymptomatic carriage and bacterial invasion, but they are likely to include factors such as virulence of the meningococcal strain, state of an individual's immune defence, nutritional status, environmental factors such as pollution (dust, smoking) and climatic conditions.

Diagnosis

The definitive diagnosis of invasive meningococcal infection requires the isolation of N. meningitidis from a normally sterile body fluid such as blood or cerebrospinal fluid (CSF). In general, the CSF seems a more reliable diagnostic, as more patients test positive when CSF is cultured. Even without clinical evidence of meningitis, bacteraemic patients may test positive for N. meningitidis in their CSF.

Treatment

Penicillin is used in order to treat meningococcal disease, whilst drugs such as the antibiotic rifampicin are administered as a preventive measure to those who have come into close contact with patients suffering from the disease.

Immunity

Serum antibodies are essential in the resistance to meningococcal disease whereas the role of the immune cells is poorly defined. The ability of the antibodies to mediate killing of the meningococci is regarded a pivotal property in protecting against disease. Such bactericidal antibodies are generally directed against the polysaccharides and confer protection in a serogroup specific manner. Furthermore, the bacterium possesses several proteins in its outer membrane. These proteins are targets for bactericidal antibodies and exhibit an even higher degree of variation than the polysaccharides. Thus, colonisation and carriage with different strains of N. meningitidis are essential elements in the natural immunization process that steadily broadens the protective abilities of the immune system in the children.

Prevalence

N. meningitidis is one of the most common causes of bacterial meningitis world-wide and the only bacterium capable of generating large epidemics of meningitis. Mainly affecting infants and young children it annually accounts for approximately 300 000 cases of bacterial meningitis and more than 30 000 deaths.

Although meningococcal disease frequently occurs as scattered, unrelated cases or in small outbreaks, in some regions this situation may alternate with devastating, unpredictable epidemics. The disease is widespread in the so-called "meningitis belt" to be found in sub-Saharan Africa, from Ethiopia in the east to Senegal in the west. In this area particularly, epidemic waves are seen every 8-14 years, killing many thousands of schoolchildren and young adults, and often leaving survivors with serious lasting effects. Incidence rates of up to 1000 cases per 100 000 inhabitants have been reported. In 1996, an epidemic involving several West African countries caused approximately 250 000 cases and 25 000 deaths. These epidemics usually start towards the end of the dry season (January-March) and end at the beginning of the rainy season a couple of months later. In temperate climates, meningococcal disease is most common during the winter and spring.

Progression of the disease

Rapid progression of meningococcal disease may result in death within less than one day of onset, or permanent neurological or mental disorders, even in countries where medical services are of a high standard. Antibiotics may be useful in the prevention of further cases where outbreaks are small, but are of little preventive value in large epidemics. Hence, immunization using safe and effective vaccines is the only rational approach to the control of meningococcal disease.

Vaccination

Meningococcal polysaccharide vaccines exist that are effective against Neisseria meningitidis groups A and C, the most important cause of epidemics in sub-Saharan Africa. They are used primarily in mass campaigns to bring major group A epidemics under control, although they may also eliminate the problem of group C disease in military camps and other communities where many people live closely together. Combined vaccines to protect against serogroups A, C, Y, and W-135 are also available. The serogroup B polysaccharide is not immunogenic in humans and thus unsuitable as a vaccine antigen.

Although safe and highly immunogenic in children older than 4 years of age and adults, the above vaccines are not very effective in the group at highest risk of meningococcal disease, namely children under two years of age. Additionally, the duration of vaccine induced protection is limited. For this reason, improved vaccines are being developed by conjugating (i.e. chemically coupling) the polysaccharides to a protein carrier. One such conjugate vaccine against serogroup C meningococci has been licensed in the United Kingdom. It is given intramuscularly at 2, 3 and 4 months of age and confers long lasting immunity with an excellent safety record so far. Children 5-12 months of age receive 2 doses one month apart, whereas children older than one year and adults are given one dose only.

Research is also ongoing to find a vaccine, which protects against Neisseria meningitidis serotype B - responsible for the majority of meningococcal meningitis cases outside of Africa. Already licensed in Cuba and used in Brazil is a vaccine based on vesicles prepared from protein containing outer membranes of serotype B meningococci. Alternative vaccines based on the same idea have been developed in Norway and in the United States.

Meningococcal polysaccharide vaccines are given as one single intramuscular dose and are effective against Neisseria meningitidis groups A, C, Y and W-135 for children older than four years of age and adults. In these age groups the vaccines provide protection for at least 3 years. Children younger than this are poorly protected by this vaccine. However, both group A and C vaccines have documented short-term efficacy levels of 85%-100% in children aged 2 years and above and in adults.

The outer membrane type B vaccine produced in Cuba and used in parts of South America and Asia has proved more than 80 % protective against meningococcal disease, and protective of 72 % of children aged four. At the age of two, the efficacy rate was below 50 % and almost non-existent in younger children. Similar vaccines from Norway and the United States have shown efficacy rates of 56 % and 50 %, respectively. However, the efficacy of these vaccines will depend on how their protein composition matches that of the prevailing meningococcal strains.

Meningococcal vaccine is mostly used in situations representing a high risk of transmission. An example is travel to highly endemic or epidemic areas. Persons residing in close contact communities such as military barracks should be vaccinated. The vaccine is administered in group A or group C outbreaks to reduce the risk of further spread of the disease. Mass vaccination against group A epidemics has proved very efficient in some African settings. Patients suffering from various types of impaired immune functions, including advanced HIV infection, asplenia, and inherited complement deficiencies should receive meningococcal vaccine.

Contraindications

Currently, the polysaccharide vaccines are not recommended for children younger than two years of age. It is not yet known whether the vaccine is safe for pregnant women and, in the absence of this information, pregnant women should only be immunised if the risk of infection is high.

WHO recommendations

WHO recommends the use of the currently available meningococcal vaccines for the control of epidemic outbreaks of group A and C meningococcal disease among persons older than 4 years of age.

These vaccines do not elicit effective immune responses in children under 2 years of age and are therefore not recommended for inclusion in national childhood immunization programmes.

High priority should be given to the development of new combined meningococcal vaccines that also protect against group B disease and are safe and effective in infants and young children.

Special issues Serogroup B meningococcal vaccine: Serogroup B is responsible for approximately 50% of endemic meningococcal infections in developed countries, but the group B polysaccharide is a poor antigen. Because some of the molecular structure is identical between meningococcal B polysaccharide and human brain tissue, safety concerns were raised on this cross-reactivity and a new approach has been taken using outer membrane protein (OMP) as potential candidate vaccine. OMP based vaccines have been developed in Norway (protective efficacy, PE, 57%) (10) and in Cuba (PE 80%), and in Brazil (74% in adults and 47% in children less than 4 years of age).

Conjugate A and C vaccines:There is clearly a need for improved group A and C meningococcal vaccines, which provide high-level and long-term protection in all age groups, including infants. Conjugate serogroup A and C vaccines are currently in advanced stages of development. In analogy with the recently developed conjugate Haemophilus influenzae b vaccine, conjugate meningococcal vaccines may show improved efficacy in the youngest age groups, and induce protection of longer duration. In future, improved vaccines, ideally combining the most important serogroups of N. meningitidis, may be included in routine childhood immunization programmes.

Therefore, an effective meningitis surveillance is needed to detect the emergence of an epidemic in order to institute immunization at the earliest possible time. Studies in Burkina Faso showed that meningitis incidence rate of 15 per 100 000 averaged over 2 weeks is a specific and predictive threshold for an epidemic and for initiating emergency immunization.

Source: WHO

Last updated: May 24, 2001

FAQS

DRUGS & TREATMENT
Penicillin is used in order to treat meningococcal disease, whilst drugs such as the antibiotic rifampicin are administered as a preventive measure to those who have come into close contact with patients suffering from the disease.

Meningitis
Related Links

The WHO Meningitis site

Meningitis in Africa - The International Federation of Red Cross and Red Crescent Societies