Epidemiology
In 2014, annual invasive meningococcal disease (IMD) incidence across all age groups was approximately 1.2/100,000 in the UK.[7] Between January and March 2020 (inclusive), 169 laboratory-confirmed cases of IMD were reported in England; in the same time frame in 2021, there were 18 cases, and there were 57 cases in January to March 2022.[8] These lower numbers in 2021 and 2022 were observed across all capsular groups.[8] The UK government’s implementation of social distancing measures as part of the coronavirus disease 2019 (COVID-19) response from March 2020 and again in January 2021 likely led to this decreased incidence of IMD. Since July 2021 and withdrawal of COVID-19 control measures, overall rates of IMT in England have gradually increased.[8]
The epidemiology of IMD in children in the UK has changed dramatically since the introduction of meningococcal B (2015) and meningococcal C (1999) vaccination programmes.[8][9][10] Serogroup C was traditionally responsible for most invasive disease, but numbers fell from 883 laboratory confirmed cases in England in 1998/99 to 29 cases in 2017/18 in people aged 18 years and younger.[11][12] Meningococcal B infection is now the leading cause of IMD in the UK, with 278 laboratory confirmed cases in people aged 18 years and younger in 2017/18.[10]
In the US, rates of invasive meningococcal infection have been declining since the late 1990s to a low of 0.11 cases in 100,000 people in 2017.[13] Most infections are caused by serogroups B, C, and Y. Reduced incidence of meningococcal disease has been linked to the introduction of meningococcal conjugate vaccines.[14]
Most infections are sporadic, but about 5% of infections occur as part of outbreaks, caused predominantly by serogroups B, C, and Y. The increasing incidence of serogroup W infections in the US, Europe, and Australia has been associated with a hyper-virulent clonal strain.[15]
The highest rates of invasive infection are in children under 5 years of age, especially those under 1 year of age, with a second peak occurring in 11- to 24-year-olds and a third peak in people >65 years of age.[16] Infections in infants and children aged 1-5 are predominantly the result of serogroup B.[16]
In addition to social and geographical factors, seasonal variations are thought to affect meningococcal disease rates. Winter is associated with increased meningococcal disease in both Africa and Europe (the reasons for this are not clear).[10]
Risk factors
Bactericidal serum and mucosal antibodies elicited by nasopharyngeal colonisation with both Neisseria meningitidis and other Neisseria species increase over the first decade of life. In the third trimester of pregnancy these protective antibodies are transmitted transplacentally from mother to fetus. The highest rates of infection occur in children under 1 year of age, following the physiological waning of this maternally derived antibody.[4] Increased exposure to meningococcal carriers is probably responsible for a second peak in invasive infections in older adolescents.[24][25]
Hereditary or acquired deficiencies of the common complement pathway components C3, properdin, Factor D, Factor H, or C5-C9 are associated with high rates of invasive meningococcal infection and chronic meningococcaemia.[4][26] Serum from patients with these deficiencies kills bacteria poorly, implying that serum complement-dependent bactericidal activity is a critical host defence.
The prevalence of complement deficiency in patients with invasive meningococcal infections ranges from 0% to 25%, and is higher in patients with recurrent meningococcal infections and those with infections caused by unusual serogroups.[27]
There is an estimated 1000- to 2000-fold increase in the risk of meningococcal infection among patients taking eculizumab, even if vaccinated.[28] Experts believe that the use of ravulizumab also confers an increased risk of invasive infection.
Eculizumab and ravulizumab are complement inhibitors that may be used in the treatment of paroxysmal nocturnal haemoglobinuria, atypical haemolytic uraemic syndrome, and generalised myasthenia gravis.
Opsonophagocytic antibodies directed against the meningococcal capsular polysaccharide and against other bacterial antigens contribute to bacterial killing. Patients with congenital or acquired hypogammaglobulinaemia, IgG subclass deficiencies, or functional immunoglobulin deficiencies are more susceptible to meningococcal infections, although rates of meningococcal infection in these patients are not as high as those of Streptococcus pneumoniae or Haemophilus influenzae.
People with HIV infection, in particular those with a low CD4 count or high viral load, are at increased risk of meningococcal disease.[26][29][30][31] People with HIV (regardless of CD4 count) infection should receive immunisation against meningococcal disease in line with the routine vaccination schedule.[32][33][34]
People with anatomical or functional hyposplenia are at increased risk of severe meningococcal infections, although the risk is not as great as that for Streptococcus pneumoniae infections.[35]
Students in the US and UK are at significantly higher risk for meningococcal infection than similarly aged peers who do not attend university or college.[31][36][37] Rates in first-year students, however, and particularly those living in dormitories, are two- to fivefold higher than in other students.[4][38] This is presumably related to a rapid increase in rates of meningococcal colonisation during the first year of college.[25]
Over 95% of meningococcal infections are sporadic. However, secondary cases may occur in contacts of patients with meningococcal infections.[7] Household contacts of people with meningococcal infection have infection rates ranging from 0.25% to 3%.[18] Contacts in schools and the workplace have a lower risk of infection (0.04% to 2.5%), with the highest rates in adolescents and people living or working in crowded conditions. Most secondary cases are diagnosed within 2 weeks of the index case. Outbreaks can occur within communities, as seen in gay and bisexual men in Melbourne (Australia) in 2017, and in Florida (the US) in 2022.[39][40] People who are in a community affected by an outbreak are recommended to get vaccinated or receive booster vaccinations, depending on their individual risk factors and vaccination status.[32][33]
Household crowding is a risk factor for invasive meningococcal infection in children and adolescents, possibly because living close to others facilitates the transmission of bacteria between household members.[24]
Serogroups A and C meningococcal infections are hyperendemic in the sub-Saharan meningitis belt extending from Senegal to Ethiopia, especially in the December-to-June dry season. During epidemics, attack rates may be as high as 1000 in 100,000 people.[41] Epidemics caused by W-135 and Y strains have occurred in several African countries, and serogroup A epidemics have occurred in India.[42] Travellers to these regions have increased rates of meningococcal disease. Infections have also been reported in participants in the Hajj pilgrimage to Saudi Arabia, and their household contacts.
Clinical microbiologists who have occupational exposure to Neisseria meningitidis are at increased risk of infection.[24][43] In many cases, these people have reported activities that were likely to have exposed them to infectious droplets or aerosols, or had confirmed exposure in the form of handling a confirmed N meningitidis isolate or specimen in the 14 days prior to symptom onset.[43]
Both smoking and passive exposure to tobacco smoke are risk factors for meningococcal carriage and invasive meningococcal disease.[24][31][44] Tobacco smoke impairs physical barriers to bacterial colonisation, such as ciliary function and local cellular immune responses. It is toxic to respiratory epithelial cells, and bacteria may be better able to colonise and invade damaged respiratory epithelium.
People moving to a new living environment, particularly into a closed or semi-closed community such as a residential school, college dormitory, or military facility, have increased rates of meningococcal infection. Meningococcal carriage rates are high or increase rapidly in the first weeks of residence and are frequently sustained at elevated levels. The elevated risk of disease in these environments is likely to be related to higher rates of colonisation in susceptible people.
Up to 50% of people with invasive meningococcal infections have had recent symptoms of an upper respiratory infection, and many have identifiable respiratory co-pathogens.[45][46] Respiratory pathogens may promote bacterial colonisation by impairing local immunity or facilitating bacterial invasion. Coughing and sneezing may promote the transmission of Neisseria meningitidis to close contacts.
In adolescents and young adults, a risk factor for meningococcal disease is intimate kissing.[24] Smoking is a strong confounder in many studies.
Use of this content is subject to our disclaimer