Chapter 136. Meningococcal Infections (Part 1)

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Harrison's Internal Medicine Chapter 136. Meningococcal Infections Definition Neisseria meningitidis is the etiologic agent of two life-threatening diseases: meningococcal meningitis and fulminant meningococcemia. More rarely, meningococci cause pneumonia, septic arthritis, pericarditis, urethritis, and conjunctivitis. Most cases are potentially preventable by vaccination. Etiologic Agent Meningococci are gram-negative aerobic diplococci. Unlike the other neisseriae, they have a polysaccharide capsule. They are transmitted among humans—their only known habitat—via respiratory secretions. Colonization of the nasopharynx or pharynx is much more common than invasive disease. ...

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Chapter 136. Meningococcal Infections (Part 1) Harrison's Internal Medicine > Chapter 136. Meningococcal Infections Definition Neisseria meningitidis is the etiologic agent of two life-threatening diseases: meningococcal meningitis and fulminant meningococcemia. More rarely, meningococci cause pneumonia, septic arthritis, pericarditis, urethritis, and conjunctivitis. Most cases are potentially preventable by vaccination. Etiologic Agent Meningococci are gram-negative aerobic diplococci. Unlike the other neisseriae, they have a polysaccharide capsule. They are transmitted among humans—their only known habitat—via respiratory secretions. Colonization of the nasopharynx or pharynx is much more common than invasive disease. Microbiology and Classification
On the basis of genome sequencing, N. meningitidis is categorized as a β- proteobacterium related to Bordetella, Burkholderia, Kingella, and Methylomonas and—more distantly—to Vibrio, Haemophilus, and Escherichia coli. Meningococci are traditionally classified by serologic typing systems based on structural differences in capsule (serogroup), major outer-membrane protein (OMP) porin (PorB, serotype), minor porin (PorA, serosubtype), and lipooligosaccharide (LOS, immunotype). Thus, for example, the meningococcal strain designation B:2b:P1.5:L3,7,9 reflects the serogroup (B), serotype (2b), serosubtype (P1.5), and immunotype (L3,7,9). Meningococci are also differentiated from the other Neisseriaceae by their pattern of sugar fermentation. N. gonorrhoeae ferments only glucose; N. meningitidis ferments glucose and maltose; and N. lactamica ferments glucose, maltose, and lactose. Meningococci are classified into serogroups according to the antigenicity of their capsular polysaccharides, which reflects structural differences in these carbohydrates. Five serogroups (A, B, C, Y, and W-135; see below) are responsible for >90% of cases of meningococcal disease worldwide. One limitation of serogroup classification based on polysaccharide capsular structure is that the genes for capsule biosynthesis can be transferred from one strain to another, with consequent changes in the capsule structure of the recipient strain and therefore in its serogroup. Meningococcal serotypes and subtypes are defined by antigenic differences in specific OMPs. Thus, other methods for tracking
meningococcal strains have become increasingly useful. Multilocus enzyme electrophoresis classifies bacteria into electrophoretic types (ETs), and variations in ET are not based on antigenic variations or alterations in outer-membrane component structures. Other techniques for establishing strain identity or nonidentity—i.e., pulsed-field gel electrophoresis of large DNA fragments and amplification of bacterial genomic sequences by polymerase chain reaction (PCR)—are based on the genetic makeup of the strain. These techniques are used for identification of the strains associated with outbreaks of disease. For example, the virulent III-1 clonal complex of serogroup A was first recognized in Nepal in 1983–1984; it spread to Mecca, then to sub-Saharan Africa, and subsequently to temperate Africa. The serogroup B ET-5 complex was first identified in Norway in the 1970s and later caused outbreaks in Europe, Cuba, and South and North America (most recently, in the Pacific Northwest). Serogroup C ET-24 (the ET-37 complex) has caused sporadic cases and outbreaks in Canada and the United States; in some analyses, it has been associated with high rates of mortality and morbidity. Epidemiology Meningococcal disease occurs worldwide as isolated (sporadic) cases, institution- or community-based outbreaks, and large epidemics. Despite effective antibiotics and partially effective vaccines, N. meningitidis is still a leading global cause of meningitis and rapidly fatal sepsis, often in otherwise-healthy individuals.
N. meningitidis is unique among the major bacterial agents of meningitis in that it causes epidemic as well as endemic (sporadic) disease. In all, 300,000– 500,000 cases of meningococcal disease occur worldwide each year—numbers that frequently are increased by large epidemics. The annual incidence of meningococcal disease is 1–2 cases per 100,000 population for sporadic disease, 5–10 cases per 100,000 for hypersporadic disease (localized outbreaks and case clusters), and 10–>1000 cases per 100,000 for pandemic and epidemic disease (e.g., serogroup A epidemics). Serogroup A strains, which caused most of the large epidemics of meningococcal disease during the first half of the twentieth century, are now associated with recurring epidemics in sub-Saharan Africa (the African meningitis belt) and other locales in the developing world. In the largest meningococcal epidemic recorded, >300,000 cases and 30,000 deaths due to serogroup A N. meningitidis occurred in sub-Saharan Africa in 1996–1997. Serogroups B and C cause most cases of sporadic and epidemic meningococcal disease in industrialized countries. Since 1980, large serogroup B epidemics and/or outbreaks of serogroup A or C meningococcal disease have also occurred in Europe, the United States, Canada, China, Nepal, Mongolia, New Zealand, Cuba, Brazil, Chile, Saudi Arabia, and South Africa. In the United States and Canada during the 1990s, serogroup B was the most common cause of sporadic disease, while serogroup C was a more frequent cause of outbreaks. Serogroup Y has
recently been isolated from almost one-third of cases of meningococcal disease in the United States. In general, patients with serogroup Y disease are older and more likely to be African American or to have a chronic underlying illness than are patients with disease caused by other serogroups. Serogroups Y and W-135 are isolated more often than the other serogroups from patients with pneumonia. In 2000, 2001, and 2002, worldwide epidemics of serogroup W-135 meningococcal disease occurred in association with the Muslim pilgrimage to Mecca (the Hajj) and in the meningitis belt of sub-Saharan Africa.