Neisseria and Moraxella Notes

Neisseria And Moraxella

Gram-negative cocci include Neisseria, Moraxella catarrhalis and Veillonella
Neisseriae are catalase and oxidase positive, non-motile, aerobic gram-negative diplococci:

• Two species are pathogenic to humans: N.meningitidis and N.gonorrhoeae
• Others are commensals of intestine, genital tract or oral cavity.

Read And Learn More: Micro Biology And Immunology Notes

Neisseria Meningitidis (Meningococcus)

Virulence Factors

Capsular polysaccharide: It prevents the bacteria from phagocytosis, can be typed into 13 serogroups:

• Only 6 serogroups account for the majority of cases: A, B, C, X, Y, and W135;
• Other capsular serotypes and non capsulated strains (16% of isolates are not capsulated) colonize the nasopharynx of asymptomatic carriers.
• Outer membrane proteins: OMP is used to classify serogroups to serotypes.
• Lipopolysaccharide and endotoxin: Causes endothelial injury leads to:
• Increased vascular permeability leading to loss of fluid and shock
• Intravascular thrombosis leading to disseminated intravascular coagulation (DIC)
• Waterhouse-Friderichsen syndrome
• Myocardial dysfunction
• IgA proteases—Cleave mucosal IgA
• Transferrin binding protein.
• Adhesins: Mediated by OPA protein and pili.

Epidemiology

Worldwide, nearly 5 lakh cases of meningococcal disease occur each year, and 10% of those die.

Patterns of disease: Ranges from sporadic infection, to endemic, hyperendemic and explosive epidemics

• High prevalence area: The sub-Saharan belt of Africa (from Ethiopia to Senegal) is the most prevalent area for meningococcal infections. Around 30,000 cases are still reported each year from this area.
• World: The serogroups distribution varies among various regions
• Group A: Was leading cause of epidemic meningitis worldwide, now reduced cases due to vaccination.
• Group B and C are currently the major serogroups causing invasive disease worldwide.
• Group B causes hyperendemic disease (>10 cases per 100,000 population) and Group C has caused a recent explosive outbreak in Nigeria in 2016–17 (>18,000 cases).
• Group X, Y and W are less commonly reported worldwide. Group W (formerly W 135) can cause outbreaks in mass gatherings; has caused the global outbreak in 2000 in Hajj pilgrimage.
• India: Sporadic cases have been occurring every year, mainly from North India with occasional outbreaks. Serogroup A has been reported from few places. In 2015, >12,000 cases were reported, maximum from Bihar (>8,000 cases)
• Seasonality: Common in winter and spring (cold and dry climate)
• Age: Meningitis is common in early childhood (3 months to 5 years) with a second peak occurring in adolescents (15–25 years of age)
• Risk factors that promote colonization include: Overcrowding and semiclosed communities
  (schools, military and refugee camps), travelers (Hajj pilgrims), Smoking, Viral and Mycoplasma infection of respiratory tract.
• Risk factors that promote disease include:
• Deficiency of terminal complement components (C5–C9)
• Eculizumab therapy—a terminal complement inhibitor
• Hypogammaglobulinemia and hyposplenism.

Pathogenesis

• Source: MC source of infection is human nasopharyngeal carriers (mainly children).
• Carrier rate may vary from 5–10% (during inter epidemic period) up to 70–80% (during epidemic).
• The mode of transmission is by droplet inhalation
• Spread of infection: From nasopharynx, meningococci reach the meninges either by:
• Hematogenous route (most common) or
• By direct olfactory nerve spread through cribriform plate or Rarely through conjunctiva.
• Mortality: It is high (>10%), reaches up to 50% when untreated and high frequency (>10%) of severe sequelae.

Clinical Manifestations

Asymptomatic colonization is the most common presentation.

Various manifestations include:

• Rashes: A nonblanching rash (petechial or purpuric) develops in > 80% of cases.
• Septicemia: It is attributed to endotoxin-induced endothelial injury
• Waterhouse-Friderichsen syndrome: It is a severe form of fulminant meningococcemia, characterized by large purpuric rashes (purpura fulminans), shock, DIC, bilateral adrenal hemorrhage and multi-organ failure.
• Pyogenic meningitis: Commonly affects young children (3–5 years of age).
• Chronic meningococcemia: Occurs rarely and characterized by petechial rash, fever, arthritis, and splenomegaly.
• Postmeningococcal reactive disease: Immune complexes develop 4–10 days later, lead to manifestations like arthritis, rash, iritis, pericarditis, polyserositis and fever.

Laboratory Diagnosis

• Specimen:
  • For cases: Blood and CSF
  • For carriers: Nasopharyngeal swab
• CSF examination:
  • First portion is centrifuged and used for:
  • Capsular antigen detection
  • Biochemical analysis: ↑ CSF pressure, ↑ protein and ↓ glucose in CSF
  • Gram staining: Pus cells with gram-negative diplococci, lens-shaped
  • Second portion: For culture on blood agar, chocolate agar
  • Third portion is enriched in BHI broth and incubated for 7 days
• Nasopharyngeal swab culture: On Thayer Martin medium
• Biochemical tests:
  • Oxidase and catalase positive
  • Ferment glucose and maltose but not sucrose
• Serogrouping: by latex agglutination test:
• Serology: Antibodies to capsular Ag (ELISA), Useful in retrospective diagnosis of disease
• Molecular diagnosis: By multiplex PCR.

• Meningococcal polysaccharide vaccines availables as bivalent (serogroups A and C) or quadrivalent (serogroups A, C, Y, and W135).
• Efficacy: It has a protective efficacy rate of >95%. The duration of protection lasts for 3–5 years
• Indication: It is recommended for high-risk people such as (1) contacts of patients during outbreaks, (2) splenic dysfunction, (3) terminal complement component deficiency, (4) taking eculizumab therapy, (5) laboratory staff at risk
• Dose 50 μg single dose, immunity starts in 10 days, lasts for 3 years
• Vaccine is indicated to travellers like Hajj pilgrimage
  Contraindications pregnancy and below 3 year (capsule being T independent, is poorly immunogenic<3 year).
• Capsular vaccine is not available for serogroup B as: Capsule of serogroup B (made up of sialic acid) is less immunogenic and it is also encephalitogenic due to expression of similar cross reactive antigens on neural cells.
• Conjugated vaccine is available, can be given to young children. Addition of a protein carrier (adjuvant) increases the immunogenicity of the capsular vaccine.
• Vaccine for Group B (MenB vaccine) Recently, recombinant vaccine for Group B Meningococcus has been licensed.
• Vaccine contains four recombinant proteins: adhesin A, heparin binding antigen, factor H binding protein and outer membrane vesicles (OMV)
• Indication: 16–25 years age.

Drug Resistance in Neisseria Gonorrhoeae

• Gonococci were initially susceptible to most antibiotics, such as sulfonamides, penicillins, quinolones, but because of their continual usage, resistance has emerged over the time.
• Though third-generation cephalosporins are the drugs of choice for gonococcal infections at present, some strains show reduced susceptibility to ceftriaxone and cefixime (termed as cephalosporin intermediate/resistant strains), which may be due to altered penicillin-binding protein 2.