Diseases

Meningococcal Meningitis

Meningococcal meningitis is a infection of the lining of the brain and spinal cord. A range of antibiotics and vaccines has reduced the devastating consequences it can cause. More medicines will follow.

What is meningococcal meningitis? Top

Meningococcal meningitis is an infection caused by Neisseria meningitidis. The meningococci infect the meninges, the thin lining that surrounds the brain and the spinal cord and the fluid around them. The outcome can be quite severe and may result in brain damage, hearing loss, or learning disability. High fever, severe headache, and stiff neck are common symptoms of the disease in anyone over the age of two years. The symptoms can develop over several hours, or they may take one or two days.

Other symptoms include nausea, vomiting, discomfort looking into bright light, confusion, and sleepiness. In newborns and small infants, the symptoms may be difficult to detect. As the disease progresses, patients of any age may have seizures. Early diagnosis and treatment are crucial and the patient should see a doctor immediately. The diagnosis is usually made by growing bacteria from a sample of cerebrospinal fluid. Meningococcal disease remains the most common infectious cause of death in children in the western world. Many of the patients deteriorate so rapidly that death from shock and multi-organ failure occurs before transfer to a specialist paediatric intensive care unit.

Meningococcal meningitis is contagious. The bacteria are spread through the exchange of respiratory and throat secretions. Fortunately, N. meningitidis is not as contagious as influenza virus, for example. Spreading does not occur by casual contact or by simply breathing the air where a person with meningitis has been. The natural habitat for the bacteria is the mucosal surfaces of the human nose and throat and, to a lesser extent, the urogenital tract. Approximately five to ten per cent adults are asymptomatic nasopharyngeal carriers. That number increases to as many as 60-80 per cent of members of closed populations, e.g. military recruits in camps.

Who does meningococcal meningitis affect? Top

Invasive disease depends on host factors. Infants are protected from meningococcal disease for the first few months of life by transferred maternal antibodies and low rate of meningococcal acquisition. Subsequently, susceptibility peaks at age 6-12 months. Later on, individuals acquire the infection if they are exposed to virulent bacteria and have no protective bactericidal antibodies. The disease most commonly affects individuals aged between three years and adolescence. It rarely occurs in individuals older than 50 years.

Crowding living conditions also facilitate disease spread, since individuals from different areas carry different strains. People at increased risk for whom routine vaccination is recommended are college students living in dormitories, microbiologists who are routinely exposed to meningococcal bacteria, military recruits, anyone who has a damaged spleen or whose spleen has been removed; anyone who is travelling to countries which have an outbreak of meningococcal disease, and those who might have been exposed to meningitis during an outbreak.

Meningococcal serogroups A, B, and C are responsible for most cases throughout the world. In Europe and the Americas, serogroup B is the predominant agent, followed in frequency by serogroup C. The incidence is at approximately 0.9-1.5 per 100,000 people per year. This equals some 6,000 cases in Europe every year. In children aged 2-5, the incidence is 1.7 per 100,000 and in the age group 18-23, the rate is 1.4. Most cases occur during winter and early spring.

Serogroup A is the predominant cause in Africa and Asia. In the African region of Savannah that extends from Ethiopia in the east to Senegal in the West, this disease frequently occurs in epidemics during the hot and dry weather from December to March. The recent meningococcal meningitis pandemic, which began in 1996, has resulted so far in approximately 300,000 cases being reported to the World Health Organisation (WHO). Morbidity and mortality rates from the disease remain high. Apart from epidemics, at least 500,000 cases of meningococcal meningitis are estimated to occur world-wide every year; 50,000 of them are fatal.

 

Electron-microscopic picture of Neisseria meningitidis

Present treatments Top

Meningococcal meningitis is treated effectively with a number of antibiotics. Standard therapy varies and includes a derivative of penicillin or a cephalosporin plus an amino glycoside. Intravenously given penicillin G is still the medicine of choice for the treatment of meningococcal meningitis and septicaemia. The speed with which the diagnosis is made, antibiotics administered, and the complications of shock and multi-organ failure treated is likely to be a major determinant of outcome. Appropriate antibiotic treatment reduces the risk of dying from meningitis to below 15 per cent. People who qualify as close contacts of a patient with meningococcal meningitis should receive antibiotics to prevent them from getting the disease.

For prophylaxis, several vaccines are available. Meningococcal polysaccharide (sugar) vaccine has been approved since 1981. Meningococcal conjugate vaccine was licensed in 2005 for people between the ages of 11 and 55. Both vaccines can prevent four types of meningococcal meningitis, including two of the three types most common in Europe (serogroup C, Y, and W-135) and strains that cause epidemics in Africa (serogroup A and W-135).

The advantage of the new diphtheria toxoid conjugate vaccine is that the immunity the vaccine provides is expected to last longer than that rendered by the polysaccharide product, which is effective for about three years. Further, the conjugate vaccine can be given as a booster several years after the initial inoculation. In addition, the new vaccine should provide “herd“ immunity to unvaccinated people when a large percentage, i.e. more than 60 per cent of a specific population, is inoculated.

The bacterial strain W-135 is a major threat to African countries. In 2002, when an epidemic took hold in Burkina Faso, the strain affected more than 13,000 people and killed at least 1,500. In 2003, some 3,500 deaths were attributable to the pathogen. In 2002, a pharmaceutical manufacturer was approached by the WHO and agreed to develop a vaccine against strain W-135, which was done in less than six months. The Bill and Melinda Gates Foundation gave funding for its development. The company has given the vaccine a low price of 1 per dose.

What’s in the development pipeline? Top

Extension studies with diphtheria toxoid conjugate vaccine are underway to see if children immunised at 11 years of age continue to show immunity when they reach college age. Phase 3 clinical trials are also running with children aged two to five years.

Research groups are looking into natural immunisation, i.e. administering experimental meningococcal vaccine through the nose. Specific meningococcal polysaccharides are studied to find out whether they enhance immune response in vaccinated people. Also the interaction between bacterial and human receptors is of major interest, as it may have implications for susceptibility and meningococcal vaccine design. Other studies include human and bacterial genes involved in carriage of the bacterium.

The longer-term future Top

Patients are still waiting for a type B vaccine. Serogroup B, which accounts for about one third of all meningococcal infections each year, is the only strain of N. meningitides not covered by either the conjugate or the polysaccharide-based vaccines. At the moment, a polysaccharide-based vaccine against all serogroup B strains is not feasible because the type B polysaccharide consists of the same macromolecule that is involved in neural coding of the human nervous system, which makes it an undesirable target for vaccine development.

The pathway to a vaccine for serogroup B has to take into account these protein types, of which there are nearly 100 variations. To identify potential antigens suitable for use in a multiunit vaccine, the genome sequences of N. meningitidis B strains that represent the most important disease-causing serotypes had to be scanned. Worldwide, there are few vaccines against B. A meningitis B vaccine is used in New Zealand. The possibility of a single dominant protein type exists only in an island situation.