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Invasive meningococcal disease (IPD) is a severe systemic bacterial infection caused by Neisseria meningitidis. This infection may present as severe meningococcal sepsis associated with shock and disseminated intravascular coagulation (DIC). In the remaining cases, invasive meningococcal disease develops as sepsis or inflammation of the meninges and the brain, and in some patients sepsis and meningitis occur simultaneously.
Risk factors of invasive meningococcal disease
Meningococcal infections can also lead to localized (non-invasive) infections such as:
- conjunctiva,
- salivary glands,
- spit,
- sinuses
- middle ear,
- epiglottis,
- genitourinary system.
Risk factors for the development of invasive meningococcal disease include:
- patient’s age (from 3 months to 5 years and 15-24 years),
- deficiencies of terminal complement components (C5-C9),
- zaburzenia układu properdyny,
- functional and anatomical lack of spleen,
- smoking,
- preceding viral infections,
- falling ill in the immediate environment (400-800 times higher risk),
- staying in closed environments,
- poor social conditions related to congestion,
- certain climatic conditions and lifestyle (e.g. frequent attending discos, clubs, pubs).
Less common forms of invasive meningococcal disease are septic arthritis, septic arthritis, septic arthritis, inflammation of the lungs with bacteraemia, myocarditis, endocarditis and pericarditis, either on their own or accompanying sepsis.
Epidemiology of invasive meningococcal disease
In most cases, strains of N. meningitidis do not cause disease, but are only responsible for the asymptomatic carrier state, which in an endemic situation affects about 10% of the population. Meningococcal infections occur in people of all age groups, but the greatest number of them affects children under 5 years of age, especially children up to 1 year of age. The second peak in the incidence is in adolescents and young adults, which is related to lifestyle and higher carriage levels, with meningococcal serogroup C accounting for the majority of these cases.
The spread of meningococcal infections is usually mediated by asymptomatic carriers, less often sick, therefore attempts to establish the epidemiological chain are often unsuccessful. The level of carriage depends on age – it is highest in 15-24 year olds, lower in younger adolescents and lowest in children under 4 years of age. High carriage levels have been reported among military recruits and first-year students. A carrier may be short-term or may last for many months.
The meningococcal colonization of the nasopharynx induces an immune response in the form of the production of bactericidal antibodies. Every year, around 500 cases and over 000 deaths are reported worldwide due to infections caused by N. meningitidis strains. The incidence of IChM is very diverse and depends, inter alia, on on geographic location. In Europe, it is on average around 1,1 / 100 inhabitants, while in Africa, during an epidemic, the incidence may be as high as 000% of the population (1 / 1000). Comparing incidence across countries is difficult as some of them only record cases of meningococcal meningitis and others all record cases of invasive meningococcal disease. In Europe, in contrast to the number of vectors independent of the season, the highest number of cases of IChM occurs in the winter months. Outbreaks in the so-called in Africa’s “meningitis belt”, an area that extends south of the Sahara desert, begins during the dry season and ends with the onset of the rainy season.
Types of strains causing the meningococcal disease epidemic
Meningococcal infections may be rare, endemic, and may take the form of outbreaks, epidemics and pandemics. Outbreaks are mainly caused by strains of serogroups A, C and W135. The largest epidemics, caused mainly by serological group A, take place every few years in the “sub-Saharan belt”. After 2000, an increase in the number of cases and epidemics caused by strains belonging to the serogroup W-135 and X was observed in this region. In Europe, strains of two serological groups – B and C. Outbreaks and epidemics usually cause meningococcus serogupy C.
In the case of meningococcal infections, an epidemic is considered to be the occurrence of 3 or more cases for which an epidemiological link can be established. Outbreaks / outbreaks usually concern closed environments, such as:
- schools,
- before school,
- orphanages,
- academic,
- barracks,
- prisons,
- Nursing homes.
Until recently, serogroup Y meningococcal infections were only discussed in the context of the epidemiology of the United States of America, where they accounted for about 30% of meningococcal infections, mainly pneumonia in the elderly. However, for some time a high percentage of serogroup Y meningococcal infections has been observed in Sweden; there are also more infections in England and Wales and Finland. Although serogroup B strains are primarily associated with sporadic infections, they have also caused long-term epidemics in some parts of the world.
The appearance of serogroup C meningococci in a given area results in an overall increase in the number of invasive cases and a higher mortality. Countries with an increase in the number of infections or outbreaks / epidemics caused by meningococcal serogroup C include, among others
- Czech Republic,
- United States,
- Canada,
- Spain,
- Belgium,
- Anglia i Walia,
- France,
- Greece,
- Scotland,
- in the last decade also Poland.
In Poland, according to the data of the National Institute of Public Health of the National Institute of Hygiene, the incidence of invasive meningococcal disease in 2010 was 0,58 / 100. Since 000, there has been an increase in the percentage of meningococcal group C among invasive infections caused by this species in Poland . In previous years, each year, isolates of serogroup B were responsible for over 2002% of infections. Currently, 80-40% of cases are meningococci of serogroup C. In 50-2006 and 2007, several epidemic outbreaks caused by isolates of this particular serogroup were noted in Poland.
All these outbreaks were caused by meningococci belonging to the epidemic clonal complex ST-11, responsible for the most infections caused by serogroup C meningococci in the world.
The causes of invasive meningococcal disease
Invasive meningococcal disease it is caused by Gram-negative split Neisseria meningitidis (meningococcus, meningitis).
The structure of N. meningitidis does not differ significantly from other Gram-negative bacteria whose cells are surrounded by an outer membrane composed of lipids, outer membrane proteins (OMP) and lipopolysaccharides (LPS).
- Meningococcal lipopolysaccharides have shorter sugar chains and are therefore referred to as “lipooligosaccharides” (LOS).
- Under electron microscopy, the meningococcal cell has a characteristic morphology that is given by numerous vesicles filled with outer membrane proteins, endotoxin, phospholipids, and envelope polysaccharides.
- With few exceptions, meningococci that cause infections have a polysaccharide shell.
Based on differences in capsular structure among N. meningitidis species 12 serological groups were distinguished (A, B, C, X, Y, Z, W135, 29E, H, I, K and L). From the clinical and epidemiological point of view, the most important are strains belonging to five serogroups: A, B, C, Y and W-135 responsible for over 90% of infections. There are also non-enveloped strains that occur mainly in asymptomatic carriers and very rarely cause infections. Determining which serogroup of meningococcal infections is essential since the available vaccines are effective only against meningococcal groups A, C, Y and W-135.
Currently, the first protein vaccine against meningococcal serogroup B infections is awaiting registration, and another, also protein vaccine, is in the last stages of research. In addition to the division into serological groups, meningococcal types and serological subtypes can be distinguished on the basis of antigenic differences in outer membrane proteins (OMP). Class 1 (PorA) proteins form the basis of the division of meningococcus into serological subtypes, while proteins of classes 2 and 3 (PorB) allow division into serological types. The group, type and serological subtype of N. meningitidis define the phenotype of a given strain. Based on the antigenic diversity of the lipooligosaccharide, strains of N. meningitidis can be divided into 13 immunotypes.
Pathogenesis of invasive meningococcal disease
Meningokoki występują wyłącznie u ludzi, rezerwuarem jest chory lub bezobjawowy nosiciel. Microorganisms colonize the nasopharynx. They are transmitted by droplets or by direct contact from person to person. Invasive meningococcal infection occurs after N. meningitidis penetrates the nasopharyngeal epithelium and enters the bloodstream.
Colonization of the epithelium lining the nasopharynx is made possible by meningococcal IgA1 protease, pilom and outer membrane proteins. IgA1 proteases are produced by all strains belonging to the species N. meningitidis and they attenuate the local immune response on the host mucosa by digesting IgA. Pile (fimbriae) produced by strains of antigenically and structurally differentiated N. meningitidis are essential in the adhesion process to host cells. Pile, along with some of the outer membrane proteins, are the main factors enabling adherence to non-cystic epithelial cells of the nasopharynx. In addition, they take part in transformation processes.
Meningococci have the ability to regulate the production of dranks and other surface structures. Outer membrane proteins enable bacteria to adhere to host cells, interact with them and further invade the cells. The proteins PorA, PorB, undergoing phase change of the Opa protein, and the Opc protein also control the environment inside the host cell, e.g. by transporting ions to its interior.
After the adhesion phase, it takes place endocytosis of bacteria and their transport in vacuoles by cytoplasm of epithelial cells. The bacteria then enter the bloodstream. N. meningitidis has many virulence factors that play a key role in this stage of infection. They include, among others polysaccharide shell enabling the survival of bacteria in the blood bed and protecting them against phagocytosis. The phenomenon of capsule switching is associated with the shell of N. meningitidis strains. Under the influence of external factors (e.g. immunological pressure from vaccination), but mainly spontaneously, meningococci can take up genes encoding proteins responsible for envelope synthesis from another strain.
Another substance responsible for the virulence of N. meningitidis are lipooligosaccharides – they play an essential role in the pathogenesis of septic shock. The degree of their release is a characteristic feature of individual strains. The level of circulating endotoxin is believed to be proportional to the severity of the shock. Meningococci also have specific mechanisms that enable them to obtain nutrients, including obtaining iron from human lactoferrin, transferrin and hemoglobin.
Despite many years of research on the aforementioned virulence factors and the pathogenesis of meningococcal infections, it is not known so far why the same strains in one patient, without diagnosed disorders of the immune system, cause a lightning infection leading to death within a few hours, and in another they remain only at the stage of colonization.
Source: J. Cianciara, J. Juszczyk, Infectious and parasitic diseases; Czelej Publishing House