Meningococcal Infection

Clinical Description

Identification

An acute bacterial disease, characterized by sudden onset of fever, intense headache, nausea and often vomiting, stiff neck and photophobia. A petechial rash with pink macules or occasionally vesicles may be observed in Europe and North America, but rarely in Africa. Case fatality rates formerly exceeded 50%. Antibiotics, intensive care units and improved supportive measures have decreased this, but case fatality remains high at 8%–15%. In addition, 10%–20% of survivors will suffer long-term sequelae, including mental retardation, hearing loss, and loss of limb use. Invasive disease is characterized by one or more clinical syndromes including bacteremia, sepsis, or meningitis, the latter being the most common presentation. Meningococcemia, or meningococcal sepsis, is the most severe form of infection, with petechial rash, hypotension, disseminated intravascular coagulation and multi-organ failure. Other forms of meningococcal disease, such as pneumonia, purulent arthritis, and pericarditis, are less common.

Infectious Agents

Neisseria meningitidis, the meningococcus, is a Gram-negative, aerobic diplococcus. Neisseria are divided into serogroups according to the immunological reactivity of their capsular polysaccharide. Group A, B, and C organisms account for at least 90% of cases, although the proportion of groups Y and W135 is increasing in several regions. In most European and many Latin American countries, serogroups B and C cause the majority of disease, while serogroup A causes the majority of disease in Africa and Asia. Serogroups A, B, C, Y, W-135 and X are all capable of causing outbreaks—most characteristically serogroup A, which is responsible for major epidemics, particularly in the so-called African meningitis belt (see Occurrence). Outbreaks of N. meningitidis are usually caused by closely related strains. Molecular subtyping of isolates (multi-locus enzyme electrophoresis or pulsed-field gel electrophoresis of enzyme-restricted DNA fragments) may allow identification of an “outbreak strain” and assist in better differentiation of outbreaks from endemic disease.


Diagnosis

The gold standard for diagnosis is recovery of meningococci from a sterile site, primarily cerebrospinal fluid (CSF) or blood; however, the sensitivity of culture, especially in patients who have received antibiotics, is low. In culture-negative cases, identification of group-specific meningococcal polysaccharides in CSF by latex agglutination is of help but false-negative results are common, especially for serogroup B. Polymerase chain reaction offers the advantage of detecting meningococcal DNA in CSF or plasma and not requiring live organisms; it is not yet widely available in many countries. Microscopic examination of Gram-stained smears from petechiae may show Neisseria.


Epidemiology

Mode of Transmission

Direct contact, including respiratory droplets from noses and throats of infected people; infection usually causes only a subclinical mucosal infection. Up to 5%–10% of people may be asymptomatic carriers with nasopharyngeal colonization by N. meningitidis. Less than 1% of those colonized will progress to invasive disease. Carrier rates of 25% have been documented in some populations in the absence of any cases of meningococcal disease. In contrast, during some meningococcal outbreaks in industrialized countries, no carriers of the “outbreak stain” have been identified. Fomite transmission is insignificant.

Incubation Period

2 to 10 days, commonly 3 to 4 days.

Period of Communicability

Until live meningococci are no longer present in discharges from nose and mouth. Meningococci usually disappear from the nasopharynx within 24 hours after institution of antimicrobial treatment to which the organisms are sensitive, and with substantial concentrations in oronasopharyngeal secretions. Penicillin will temporarily suppress the organisms, but does not usually eradicate them from the oronasopharynx.

Reservoir

Humans.

Susceptibility

Susceptibility to the clinical disease is low and decreases with age; this induces a high ratio of carriers to cases. Persons deficient in certain complement components are especially prone to recurrent disease; splenectomized persons are susceptible to bacteremic illness. Group-specific immunity of unknown duration follows even subclinical infections.

Occurrence

In Europe and North America the incidence of meningococcal disease is higher during winter and spring; in Sub-Saharan Africa the disease classically peaks during the dry season. Infants have the highest risk of meningococcal disease. Rates of disease decrease after infancy and then increase in adolescence and young adulthood. In addition to age, other individual risk factors for meningococcal disease include underlying immune deficiencies, such as asplenia, properdin deficiency, and a deficiency of terminal complement components. Crowding, low socioeconomic status, active or passive exposure to tobacco smoke and concurrent upper respiratory tract infections increase the risk of meningococcal disease. In some countries males are at higher risk than females. New military recruits have also been consistently found to have higher risk of disease; it may be similar reasons that cause increased risk among university students living in dormitories.

The highest burden of the disease undoubtedly lies in the African meningitis belt, a large area that stretches from Senegal to Ethiopia and affects all or part of 21 countries. In this region, high rates of sporadic infections (1–20 cases per 100 000 population) occur in annual cycles, with periodical superimposition of large-scale epidemics (usually caused by serogroup A, occasionally serogroup C, and more recently by serogroup W-135). In the countries of the African meningitis belt, epidemics with incidence rates as high as 1 000 cases per 100 000 population have occurred every 8–12 years over at least the past 50 years. In addition, major epidemics have occurred in adjacent countries not usually considered part of the African meningitis belt (such as Kenya and the United Republic of Tanzania).

In 2000, an epidemic of serogroup W-135 meningococcal disease associated with the Hajj occurred in Saudi Arabia; in 2000 and 2001, in several countries, cases of serogroup W-135 occurred among returning pilgrims and their close contacts. In 2002, the first major serogroup W-135 epidemic occurred in Burkina Faso, with over 13 000 cases and 1 400 deaths reported.

During the 1980s and 1990s, serogroup B has emerged as the most common cause of disease in Europe and most of the Americas. Epidemics characterized by a 5- to 10-fold increase in incidence for 10–20 years have been reported from many countries in Europe, Central and South America, and most recently in New Zealand and the US Pacific northwest. Community outbreaks of group C disease have occurred with increasing frequency in Canada and the USA since 1990. During the late 1990s, group Y disease has become as common as groups B and C in parts of the USA.


Prevention and Control

1) Preventive measures:

a) Educate the public on the need to reduce direct contact and exposure to droplet infection.

b) Reduce overcrowding in living quarters and workplaces, such as barracks, schools, camps and ships.

c) Vaccines containing groups A, C, Y and W-135 meningococcal polysaccharides are available; two polysaccharide vaccines are currently available on the market (quadrivalent ACYW-135 vaccine, and bivalent AC). Bivalent polysaccharide meningococcal vaccines against serogroups A and C are safe and effective in adults and children over 2, but do not elicit long-term protection, particularly in children under 5. The serogroup A polysaccharide can induce antibodies in children as young as 3 months, but the C polysaccharide is poorly immunogenic and ineffective in children under 2. Serogroup Y and W135 polysaccharides are also immunogenic in adults and children over 2, but immunogenicity and clinical protection have not been fully documented. Meningococcal polysaccharide vaccines are effective for outbreak control and for prevention among high-risk groups, such as travelers to countries where disease is epidemic, Hajj pilgrims, military groups, and individuals with underlying immune dysfunctions. Because these vaccines are often poorly immunogenic in young children and have limited duration of efficacy, they are not generally used in routine childhood immunization programs. Re-immunization may be considered within 3–5 years if indications still exist. No vaccine effective against group B meningococci is currently licensed, although several have been developed and show some efficacy in older children and adults.

2) Control of patient, contacts and the immediate environment:

a) Report to local health authority: Obligatory case report in most countries, Class 2.

b) Isolation: Respiratory isolation for 24 hours after start of chemotreatment.

c) Concurrent disinfection: Of discharges from the nose and throat and articles soiled therewith. Terminal cleaning.

d) Quarantine: Not applicable.

e) Protection of contacts: Close surveillance of household, day care, and other intimate contacts for early signs of illness, especially fever, to initiate appropriate therapy without delay; prophylactic administration of an effective chemotherapeutic agent to intimate contacts (household contacts, military personnel sharing the same sleeping space and people socially close enough to have shared eating utensils, e.g. close friends at school but not the whole class). Younger children in day care centers, even if not close friends, should all be given prophylaxis after an index case is identified. Rifampicin, ceftriaxone and ciprofloxacin are equally effective prophylactic agents. Rifampicin is administered twice daily for 2 days: adults 600 mg per dose; children over 1 month old, 10 mg/kg; under 1 month, 5 mg/kg. Rifampicin should not be given to pregnant women and may reduce the effectiveness of oral contraceptives.

For adults, ceftriaxone, 250 mg IM, given in a single dose, is effective; 125 mg IM for children under 15. Ciprofloxacin, 500 mg PO, may be given as a single dose to adults. Because in most countries 50% of N. meningitidis isolates are resistant to sulfadiazine, the latter is rarely used for prophylaxis. If the organisms have been shown to be sensitive to sulfadiazine, it may be given to adults and older children at a dosage of 1 gram every 12 hours for 4 doses; for infants and children, the dosage is 125–150 mg/kg/day divided into 4 equal doses, on each of 2 consecutive days. Health care personnel are rarely at risk even when caring for infected patients; only intimate exposure to nasopharyngeal secretions (e.g. as in mouth-to-mouth resuscitation) warrants prophylaxis. Because of the efficacy of prophylaxis, immunization is generally not recommended.

f) Investigation of contacts and source of infection: Throat or nasopharyngeal cultures are of no value in deciding who should receive prophylaxis, since carriage is variable, and there is no consistent relationship between that found in the normal population and that found in an epidemic.

g) Specific treatment: Penicillin given parenterally in adequate doses is the drug of choice for proven meningococcal disease; ampicillin and chloramphenicol are also effective. Penicillin-resistant strains have been reported in many countries, including Spain, the UK and the USA; strains resistant to chloramphenicol have been reported in France and in Viet Nam. Treatment should start as soon as the presumptive clinical diagnosis is made, even before meningococci have been identified. In children, until the specific agent has been identified, the drug chosen must be effective against Haemophilus influenzae type b (Hib) as well as Streptococcus pneumoniae. While ampicillin is the drug of choice for both as long as the organisms are ampicillin-sensitive, it should be combined with a third-generation cephalosporin, or chloramphenicol or vancomycin should be substituted in the many places where ampicillin-resistant H. influenzae b or penicillin-resistant S. pneumoniae strains are known to occur. Patients with meningococcal or Hib disease should receive rifampicin prior to discharge if neither a third-generation cephalosporin nor ciprofloxacin was given as treatment, to ensure elimination of the organism.

3) Epidemic measures:

a) When an outbreak occurs, major emphasis must be placed on careful surveillance, early diagnosis, and immediate treatment of suspected cases. A high index of suspicion is necessary. A threshold approach tailored to the epidemiology of the country is used in many developing countries to differentiate endemic disease from outbreaks. Thresholds (alert and epidemic) from a country with high rates of endemic disease (African meningitis belt) are given here as an example. When thresholds are passed, immunization campaigns must be implemented.

5 cases/100 000 population or increase in relation to previous non-epidemic years. Once alert threshold is reached: mandatory investigation, confirmation of agent, reinforcing of surveillance, enhancing of preparedness, and treatment of patients.

10 cases/100 000 population and alert threshold crossed early in meningitis season or weekly doubling of cases each week during a three week period or 15 cases/100 000 population or 2 cases at a mass gathering or among refugees or displaced persons. Once epidemic threshold is reached: mass vaccination, provision of drugs to health units, treatment of cases and public education.

In some industrialized countries, the following steps are used to decide whether to declare an outbreak and initiate vaccination:

i) Determine whether it is an organization-based outbreak (e.g. school, university, prison) or a community-based outbreak (town, city, county)

ii) Investigate links between cases, because secondary or co-primary cases are excluded from calculations

iii) Calculate attack rates with the outbreak strain among the population at risk

iv) Subtype N. meningitidis isolates, if available, from cases of disease, using molecular typing methods.

If at least 3 cases have occurred during a 3 month period, the attack rate exceeds 10 cases per 100 000 in the population at risk, and the strain is vaccine-preventable (serogroup A, C, Y or W-135), immunization of those in the group at risk should be considered.

b) Reduce overcrowding and ventilate living and sleeping quarters for all people exposed to infection because of living conditions (e.g. soldiers, miners and prisoners).

c) Mass chemoprophylaxis is usually not effective in controlling outbreaks; in outbreaks involving small populations (e.g. a single school), chemoprophylaxis to all members of the community may be considered, especially if the outbreak is caused by a serogroup not included in the available vaccine. If undertaken, chemoprophylaxis should be administered to all members at the same time. Intimate contacts should all be considered for prophylaxis, regardless of whether the entire small population is treated.

d) The use of vaccine in all age groups affected is strongly recommended if an outbreak occurs in a large institutional or community setting in which the cases are due to groups A, C, W-135 or Y. Meningococcal vaccine has been very effective in halting epidemics due to A and C serogroups.
In countries where large-scale epidemics occur, mass vaccination of the entire population in affected areas should be considered when vaccine supply and administrative facilities allow. Geographical distribution of cases, age-specific attack rates and available resources all must be considered in estimating the target population. Decisions about vaccination should consider where the intervention is likely to have the largest impact in preventing disease and death.

4) Disaster implications:

Epidemics may develop in situations of forced crowding.

5) International measures:

WHO Collaborating Centres provide support as required. More information can be found at: http://www.who.int/collaboratingcentres/database/en/

6) Although the disease is not covered by International Health Regulations, some countries may require a valid certificate of immunization against meningococcal meningitis as a condition of entry, e.g. Saudi Arabia for Hajj pilgrims. For further information, please see: http://www.who.int/topics/meningitis/en/

Source: Heymann (Ed.). (2008). Control of Communicable Diseases Manual, 19th edition. Washington, DC: American Public Health Association.


Available Vaccines

WHO-Prequalified meningococcal infection vaccines
 
 
Common Disease Taxonomy: